Beta-hydroxy-beta-methyl-butyrate blunts negative age-related changes in body composition, functionality and myofiber dimensions in rats

PubMed Central

2012-01-01

Purpose To determine the effects of 16 wk. of beta-hydroxy-beta-methylbutyrate (HMB) administration on age-related changes in functionality and diffusion tensor imaging (DTI) determined myofiber dimensions. Methods Twelve young (44 wk.), 6 middle-aged (60 wk.), 10 old (86 wk.), and 5 very old (102 wk.) male Fisher-344 rat's body composition and grip strength were assessed at baseline. Following, 6 young, 6 middle-aged, 5 old and 5 very old rats were sacrificed for baseline myofiber dimensions and gene transcript factor expression in the soleus (SOL) and gastrocnemius (GAS). The remaining 6 young and 5 old rats were given HMB for 16 wk. and then sacrificed. Results Fat mass increased in the middle-aged control condition (+49%) but not the middle-aged HMB condition. In addition, fat mass declined (-56%) in the old HMB condition but not the old control condition. Normalized strength declined and maintained respectively in the control and HMB conditions from 44 to 60 wk. and increased (+23%) (p < 0.05) from 86 to 102 wk. in only the HMB condition. Declines occurred in myofiber size in all muscles from 44 to 102 wk. in the control condition(-10 to -15%), but not HMB condition. Atrogin-1 mRNA expression in the SOL and GAS muscles was greater in the 102-wk control condition than all other conditions: SOL (+45%) and GAS (+100%). This elevation was blunted by HMB in the 102 wk. old SOL. There was a condition effect in the SOL for myogenin, which significantly increased (+40%) only in the 102-wk. HMB group relative to the 44-wk. group. Conclusions HMB may blunt age-related losses of strength and myofiber dimensions, possibly through attenuating the rise in protein breakdown. PMID:22512917

Metabolic and functional effects of beta-hydroxy-beta-methylbutyrate (HMB) supplementation in skeletal muscle.

PubMed

Pinheiro, Carlos Hermano da Justa; Gerlinger-Romero, Frederico; Guimarães-Ferreira, Lucas; de Souza, Alcione Lescano; Vitzel, Kaio Fernando; Nachbar, Renato Tadeu; Nunes, Maria Tereza; Curi, Rui

2012-07-01

Beta-hydroxy-beta-methylbutyrate (HMB) is a metabolite derived from leucine. The anti-catabolic effect of HMB is well documented but its effect upon skeletal muscle strength and fatigue is still uncertain. In the present study, male Wistar rats were supplemented with HMB (320 mg/kg per day) for 4 weeks. Placebo group received saline solution only. Muscle strength (twitch and tetanic force) and resistance to acute muscle fatigue of the gastrocnemius muscle were evaluated by direct electrical stimulation of the sciatic nerve. The content of ATP and glycogen in red and white portions of gastrocnemius muscle were also evaluated. The effect of HMB on citrate synthase (CS) activity was also investigated. Muscle tetanic force was increased by HMB supplementation. No change was observed in time to peak of contraction and relaxation time. Resistance to acute muscle fatigue during intense contractile activity was also improved after HMB supplementation. Glycogen content was increased in both white (by fivefold) and red (by fourfold) portions of gastrocnemius muscle. HMB supplementation also increased the ATP content in red (by twofold) and white (1.2-fold) portions of gastrocnemius muscle. CS activity was increased by twofold in red portion of gastrocnemius muscle. These results support the proposition that HMB supplementation have marked change in oxidative metabolism improving muscle strength generation and performance during intense contractions.

DMN Operational Synchrony Relates to Self-Consciousness: Evidence from Patients in Vegetative and Minimally Conscious States.

PubMed

Fingelkurts, Andrew A; Fingelkurts, Alexander A; Bagnato, Sergio; Boccagni, Cristina; Galardi, Giuseppe

2012-01-01

The default mode network (DMN) has been consistently activated across a wide variety of self-related tasks, leading to a proposal of the DMN's role in self-related processing. Indeed, there is limited fMRI evidence that the functional connectivity within the DMN may underlie a phenomenon referred to as self-awareness. At the same time, none of the known studies have explicitly investigated neuronal functional interactions among brain areas that comprise the DMN as a function of self-consciousness loss. To fill this gap, EEG operational synchrony analysis [1, 2] was performed in patients with severe brain injuries in vegetative and minimally conscious states to study the strength of DMN operational synchrony as a function of self-consciousness expression. We demonstrated that the strength of DMN EEG operational synchrony was smallest or even absent in patients in vegetative state, intermediate in patients in minimally conscious state and highest in healthy fully self-conscious subjects. At the same time the process of ecoupling of operations performed by neuronal assemblies that comprise the DMN was highest in patients in vegetative state, intermediate in patients in minimally conscious state and minimal in healthy fully self-conscious subjects. The DMN's frontal EEG operational module had the strongest decrease in operational synchrony strength as a function of selfconsciousness loss, when compared with the DMN's posterior modules. Based on these results it is suggested that the strength of DMN functional connectivity could mediate the strength of self-consciousness expression. The observed alterations similarly occurred across EEG alpha, beta1 and beta2 frequency oscillations. Presented results suggest that the EEG operational synchrony within DMN may provide an objective and accurate measure for the assessment of signs of self-(un)consciousness in these challenging patient populations. This method therefore, may complement the current diagnostic procedures for patients with severe brain injuries and, hence, the planning of a rational rehabilitation intervention.

DMN Operational Synchrony Relates to Self-Consciousness: Evidence from Patients in Vegetative and Minimally Conscious States

PubMed Central

Fingelkurts, Andrew A; Fingelkurts, Alexander A; Bagnato, Sergio; Boccagni, Cristina; Galardi, Giuseppe

2012-01-01

The default mode network (DMN) has been consistently activated across a wide variety of self-related tasks, leading to a proposal of the DMN’s role in self-related processing. Indeed, there is limited fMRI evidence that the functional connectivity within the DMN may underlie a phenomenon referred to as self-awareness. At the same time, none of the known studies have explicitly investigated neuronal functional interactions among brain areas that comprise the DMN as a function of self-consciousness loss. To fill this gap, EEG operational synchrony analysis [1, 2] was performed in patients with severe brain injuries in vegetative and minimally conscious states to study the strength of DMN operational synchrony as a function of self-consciousness expression. We demonstrated that the strength of DMN EEG operational synchrony was smallest or even absent in patients in vegetative state, intermediate in patients in minimally conscious state and highest in healthy fully self-conscious subjects. At the same time the process of ecoupling of operations performed by neuronal assemblies that comprise the DMN was highest in patients in vegetative state, intermediate in patients in minimally conscious state and minimal in healthy fully self-conscious subjects. The DMN’s frontal EEG operational module had the strongest decrease in operational synchrony strength as a function of selfconsciousness loss, when compared with the DMN’s posterior modules. Based on these results it is suggested that the strength of DMN functional connectivity could mediate the strength of self-consciousness expression. The observed alterations similarly occurred across EEG alpha, beta1 and beta2 frequency oscillations. Presented results suggest that the EEG operational synchrony within DMN may provide an objective and accurate measure for the assessment of signs of self-(un)consciousness in these challenging patient populations. This method therefore, may complement the current diagnostic procedures for patients with severe brain injuries and, hence, the planning of a rational rehabilitation intervention. PMID:22905075

Failure of the gross theory of beta decay in neutron deficient nuclei

DOE PAGES

Firestone, R. B.; Schwengner, R.; Zuber, K.

2015-05-28

The neutron deficient isotopes 117-121Xe, 117-124Cs, and 122-124Ba were produced by a beam of 28Si from the LBNL SuperHILAC on a target of natMo. The isotopes were mass separated and their beta decay schemes were measured with a Total Absorption Spectrometer (TAS). The beta strengths derived from these data decreased dramatically to levels above ≈1 MeV for the even-even decays; 3–4 MeV for even-Z, odd-N decays; 4–5 MeV for the odd-Z, even-N decays; and 7–8 MeV for the odd-Z, odd-N decays. The decreasing strength to higher excitation energies in the daughters contradicts the predictions of the Gross Theory of Betamore » Decay. The integrated beta strengths are instead found to be consistent with shell model predictions where the single-particle beta strengths are divided amoung many low-lying levels. The experimental beta strengths determined here have been used calculate the half-lives of 143 neutron deficient nuclei with Z=51–64 to a precision of 20% with respect to the measured values.« less

Preparation and characterization of calcium phosphate ceramics and composites as bone substitutes

NASA Astrophysics Data System (ADS)

Zhang, Xing

Marine CaCO3 skeletons have tailored architectures created by nature, which give them structural support and other functions. For example, seashells have dense lamellar structures, while coral, cuttlebone and sea urchin spines have interconnected porous structures. In our experiments, seashells, coral and cuttlebone were hydrothermally converted to hydroxyapatite (HAP), and sea urchin spines were converted to Mg-substituted tricalcium phosphate (beta-TCMP), while maintaining their original structures. Partially converted shell samples have mechanical strength, which is close to that of compact human bone. After implantation of converted shell and spine samples in rat femoral defects for 6 weeks, there was newly formed bone growth up to and around the implants. Some new bone was found to migrate through the pores of converted spine samples and grow inward. These results show good bioactivity and osteoconductivity of the implants, indicating the converted shell and spine samples can be used as bone defect fillers. Calcium phosphate powders were prepared through different synthesis methods. Micro-size HAP rods were synthesized by hydrothermal method through a nucleation-growth mechanism. On the other hand, HAP particles, which have good crystallinity, were prepared by wet precipitation with further hydrothermal treatment. beta-TCP or beta-TCMP powders were prepared by a two-step process: wet precipitation of apatitic tricalcium phosphate ('precursor') and calcination of the precursor at 800°C for 3 hours. beta-TCMP or beta-TCP powders were also prepared by solid-state reactions from CaHPO4 and CaCO 3 with/without MgO. Biphasic calcium phosphate, which is mixture of HAP and beta-TCP, can be prepared though mechanical mixing of HAP and beta-TCP powders synthesized as above. Dense beta-TCP and beta-TCMP ceramics can be produced by pressing green bodies at 100MPa and further sintering above 1100°C for 2 hours. beta-TCMP ceramics ˜99.4% relative dense were prepared by this method. Dense beta-TCP ceramics have average strength up to 540MPa. Macroporous beta-TCMP ceramics were produced with sucrose as the porogen following a two-step pressing method. Porous beta-TCMP ceramics were also prepared by replication of polyurethane sponge. beta-TCMP ceramics with porous structures in the center surrounded by dense structures were created. The outside dense structures give the scaffold mechanical strength, while the central porous structures enable cells migration and vascular infiltration, and finally in-growth of new bone into the scaffold.

Childhood cardiorespiratory fitness, muscular fitness and adult measures of glucose homeostasis.

PubMed

Fraser, Brooklyn J; Blizzard, Leigh; Schmidt, Michael D; Juonala, Markus; Dwyer, Terence; Venn, Alison J; Magnussen, Costan G

2018-02-14

To assess whether childhood cardiorespiratory fitness (CRF) and muscular fitness phenotypes (strength, power, endurance) predict adult glucose homeostasis measures. Prospective longitudinal study. Study examining participants who had physical fitness measured in childhood (aged 7-15 years) and who attended follow-up clinics approximately 20 years later and provided a fasting blood sample which was tested for glucose and insulin. Physical fitness measurements included muscular strength (right and left grip, shoulder flexion, shoulder and leg extension), power (standing long jump distance) and endurance (number of push-ups in 30s), and CRF (1.6km run duration). In adulthood, fasting glucose and insulin levels were used to derive glucose homeostasis measures of insulin resistance (HOMA2-IR) and beta cell function (HOMA2-β). A standard deviation increase in childhood CRF or muscular strength (males) was associated with fasting glucose (CRF: β=-0.06mmol/L), fasting insulin (CRF: β=-0.73mU/L; strength: β=-0.40mU/L), HOMA2-IR (CRF: β=-0.06; strength: β=-0.05) and HOMA2-β (CRF: β=-3.06%; strength: β=-2.62%) in adulthood, independent of the alternative fitness phenotype (all p<0.01). Adjustment for childhood waist circumference reduced the effect by 17-35% for CRF and 0-15% for muscular strength (males) and statistical significance remained for all associations expect between CRF, fasting glucose and HOMA2-β (p>0.06). CRF and muscular fitness in childhood were inversely associated with measures of fasting insulin, insulin resistance and beta cell function in adulthood. Childhood CRF and muscular fitness could both be potential independent targets for strategies to help reduce the development of adverse glucose homeostasis. Copyright © 2018 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Measurements of the {sup 116}Cd(p,n) and {sup 116}Sn(n,p) reactions at 300 MeV for studying Gamow-Teller transition strengths in the intermediate nucleus of the {sup 116}Cd double-{beta} decay

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

Sasano, M.; Kuboki, H.; Sekiguchi, K.

2009-11-09

The double differential cross sections for the {sup 116}Cd(p,n) and {sup 116}Sn(n,p) reactions at 300 MeV have been measured over a wide excitation-energy region including Gamow-Teller (GT) giant resonance (GTGR) for studying GT transition strengths in the intermediate nucleus of the {sup 116}Cd double-{beta} decay, namely {sup 116}In. A large amount of the strengths in the {beta}{sup +} direction has been newly found in the energy region up to 30 MeV, which may imply that the GT strengths in the GTGR region contribute to the nuclear matrix element of the two-neutrino double-{beta} decay.

Controlled synthesis and inclusion ability of a hyaluronic acid derivative bearing beta-cyclodextrin molecules.

PubMed

Charlot, Aurélia; Heyraud, Alain; Guenot, Pierre; Rinaudo, Marguerite; Auzély-Velty, Rachel

2006-03-01

A new synthetic route to beta-cyclodextrin-linked hyaluronic acid (HA-CD) was developed. This was based on the preparation of a HA derivative selectively modified with adipic dihydrazide (HA-ADH) and a beta-cyclodextrin derivative possessing an aldehyde function on the primary face, followed by their coupling by a reductive amination-type reaction. The CD-polysaccharide was fully characterized in terms of chemical integrity and purity by high-resolution NMR spectroscopy. The complexation ability of the grafted CD was further demonstrated by isothermal titration calorimetry using sodium adamantane acetate (ADAc) and Ibuprofen as model guest molecules. The thermodynamic parameters for the complexation of these negatively charged guest molecules by the beta-CD grafted on negatively charged HA were shown to be largely influenced by the ionic strength of the aqueous medium.

Biochemical changes in response to intensive resistance exercise training in the elderly.

PubMed

Bautmans, Ivan; Njemini, Rose; Vasseur, Sabine; Chabert, Hans; Moens, Lisa; Demanet, Christian; Mets, Tony

2005-01-01

It is assumed that low-grade inflammation, characterized by increased circulating IL-6 and TNF-alpha, is related to the development of sarcopenia. Physical exercise, especially high intensity resistance training, has been shown to be effective in restoring the strength deficit in the elderly. Intensive exercise is accompanied by significant release of IL-6 and TNF-alpha into the blood circulation, but does not result in muscle wasting. Exercise-induced changes in heat-shock protein (Hsp), responsible for cellular protection during stressful situations, might interfere with the acute phase reaction and muscle adaptation. To investigate if intensive strength training in elderly persons induces changes in Hsp70 expression, and if these changes are related to changes in the acute phase reaction or muscle adaptation. 31 elderly persons (aged 68.4+/-5.4 years) performed 6 weeks' intensive strength training. At baseline and after 6 weeks, muscle strength, functional performance (physical activity profile, 6-min walk, 30- second chair stand, grip strength, chair sit & reach and back scratch), linear isokinetic leg extension, circulating IL-6, TNF-alpha, IL-10 and TGF-beta, and Hsp70 in monocytes (M) and lymphocytes (L) immediately after sampling (IAS), after incubation at 37 and 42 degrees C were determined. In 12 participants, cytokines were determined in untrained and trained conditions before and after a single training session. After 6 weeks' training, muscle strength and functional performance improved significantly, together with decreased Hsp70 IAS and Hsp70 37 degrees C and increased Hsp70 42 degrees C (all p<0.05). Strength gains correlated positively with baseline Hsp70 37 degrees C and training-induced changes of Hsp70 42 degrees C in M and L. In an untrained condition, training induced an increase of IL-6 (p<0.05) and a tendency of IL-10 to decrease (p=0.06). In a trained condition the decrease of IL-10 disappeared. Baseline physical activity and 6-min walk distance correlated negatively with circulating IL-6 (p<0.05); except for a negative correlation between TGF-beta and Hsp70 37 degrees C L (p<0.05), no significant relationships were found between cytokines and Hsp70. After the training program, Hsp70 37 degrees C was negatively related to circulating TNF-alpha, IL-10 and TGF-beta. Strength training in the elderly induces changes in Hsp70 expression, associated to strength gains and circulating cytokines. Copyright (c) 2005 S. Karger AG, Basel.

Effect of complex configurations on the description of properties of {sup 132}Sn beta decay

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

Severyukhin, A. P., E-mail: sever@theor.jinr.ru; Sushenok, E. O.

2015-07-15

Gamow–Teller transitions in the beta decay of the {sup 132}Sn neutron-rich nucleus was described microscopically. The coupling of one- and two-phonon components of the wave functions was taken into account on the basis of Skyrme interactions featuring various contributions of the tensor component. A separable approximation of the particle—hole interaction made it possible tohole interaction perform calculations in a large configuration space. It was shown that an increase in the strength of the neutron—proton tensor interaction led to an increase in the energy of Gamow—Teller transitions. In addition, a decrease in the {sup 132}Sn half-life with respect to beta decaymore » was obtained.« less

Hot hardness of nickel-rich nickel-chromium-aluminum alloys

NASA Technical Reports Server (NTRS)

Levine, S. R.

1976-01-01

Rockwell A hardness of cast nickel-chromium-aluminum (NiCrAl) alloys was examined from ambient to 1150 K and compared to cast NiAl and IN-100. Alloy constitution was either gamma, gamma prime + gamma or gamma + beta + alpha + gamma prime. Below 1000 K beta containing NiCrAl alloys have hardnesses comparable to IN-100; above 1000 K they soften faster than IN-100. At 1150 K the hardness of beta-containing NiCrAl alloys decreases with increasing beta-content. The beta-containing NiCrAl alloys were harder than beta-NiAl. The ultimate tensile strengths of the NiCrAl alloys were estimated. The effects of NiCrAl coatings on strength and fatigue life of cooled turbine components were deduced.

Multiscale Information Transfer in Functional Corticomuscular Coupling Estimation Following Stroke: A Pilot Study

PubMed Central

Chen, Xiaoling; Xie, Ping; Zhang, Yuanyuan; Chen, Yuling; Yang, Fangmei; Zhang, Litai; Li, Xiaoli

2018-01-01

Recently, functional corticomuscular coupling (FCMC) between the cortex and the contralateral muscle has been used to evaluate motor function after stroke. As we know, the motor-control system is a closed-loop system that is regulated by complex self-regulating and interactive mechanisms which operate in multiple spatial and temporal scales. Multiscale analysis can represent the inherent complexity. However, previous studies in FCMC for stroke patients mainly focused on the coupling strength in single-time scale, without considering the changes of the inherently directional and multiscale properties in sensorimotor systems. In this paper, a multiscale-causal model, named multiscale transfer entropy, was used to quantify the functional connection between electroencephalogram over the scalp and electromyogram from the flexor digitorum superficialis (FDS) recorded simultaneously during steady-state grip task in eight stroke patients and eight healthy controls. Our results showed that healthy controls exhibited higher coupling when the scale reached up to about 12, and the FCMC in descending direction was stronger at certain scales (1, 7, 12, and 14) than that in ascending direction. Further analysis showed these multi-time scale characteristics mainly focused on the beta1 band at scale 11 and beta2 band at scale 9, 11, 13, and 15. Compared to controls, the multiscale properties of the FCMC for stroke were changed, the strengths in both directions were reduced, and the gaps between the descending and ascending directions were disappeared over all scales. Further analysis in specific bands showed that the reduced FCMC mainly focused on the alpha2 at higher scale, beta1 and beta2 across almost the entire scales. This study about multi-scale confirms that the FCMC between the brain and muscles is capable of complex and directional characteristics, and these characteristics in functional connection for stroke are destroyed by the structural lesion in the brain that might disrupt coordination, feedback, and information transmission in efferent control and afferent feedback. The study demonstrates for the first time the multiscale and directional characteristics of the FCMC for stroke patients, and provides a preliminary observation for application in clinical assessment following stroke. PMID:29765351

Relationship between neighborhood context, family management practices and alcohol use among urban, multi-ethnic, young adolescents.

PubMed

Tobler, Amy L; Komro, Kelli A; Maldonado-Molina, Mildred M

2009-12-01

We examined relationships between alcohol-related neighborhood context, protective home and family management practices, and alcohol use among urban, racial/ethnic minority, adolescents. The sample comprised 5,655 youth who were primarily low SES (72%), African American (43%) and Hispanic (29%). Participants completed surveys in 2002-2005 (ages 11-14 years). Items assessed alcohol use, accessibility of alcohol at home and parental family management practices. Neighborhood context measures included: (1) alcohol outlet density; (2) commercial alcohol accessibility; (3) alcohol advertisement exposure; and (4) perceived neighborhood strength, reported by parents and community leaders. Structural equation modeling was used to assess direct and indirect relationships between alcohol-related neighborhood context at baseline, home alcohol access and family management practices in seventh grade, and alcohol use in eighth grade. Neighborhood strength was negatively associated with alcohol use (beta = -0.078, p < or = 0.05) and exposure to alcohol advertisements was positively associated with alcohol use (beta = 0.043, p < or = 0.05). Neighborhood strength and commercial alcohol access were associated with home alcohol access (beta = 0.050, p

Skeletal phenotype of growing transgenic mice that express a function-perturbing form of beta1 integrin in osteoblasts

NASA Technical Reports Server (NTRS)

Globus, R. K.; Amblard, D.; Nishimura, Y.; Iwaniec, U. T.; Kim, J-B; Almeida, E. A. C.; Damsky, C. D.; Wronski, T. J.; van der Meulen, M. C. H.

2005-01-01

Skeletal modeling entails the deposition of large amounts of extracellular matrix (ECM) to form structures tailored to withstand increasing mechanical loads during rapid growth. Specific ECM molecules bind to integrin receptors on the cell surface, thereby triggering a cascade of signaling events that affect critical cell functions. To evaluate the role of integrins during skeletal growth, transgenic mice were engineered to express a function-perturbing fragment of beta1 integrin consisting of the transmembrane domain and cytoplasmic tail under the control of the osteocalcin promoter (TG mice). Thus, transgene expression was targeted to mature cells of the osteoblast lineage, and herein we show that cultured cells resembling osteocytes from 90-day-old TG mice display impaired adhesion to collagen I, a ligand for beta1 integrin. To determine the influence of beta1 integrin on bones that are responsible for providing structural support during periods of rapid growth, we examined the phenotype of the appendicular skeleton in TG mice compared to wild type (WT) mice. According to radiographs, bones from mice of both genotypes between 14 and 90 days of age appeared similar in gross structure and density, although proximal tibiae from 35-90 days old TG mice were less curved than those of WT mice (72-92% TG/WT). Although there were only mild and transient differences in absolute bone mass and strength, once normalized to body mass, the tibial dry mass (79.1% TG/WT females), ash mass (78.5% TG/WT females), and femoral strength in torsion (71.6% TG/WT females) were reduced in TG mice compared to WT mice at 90 days of age. Similar effects of genotype on bone mass and curvature were observed in 1-year-old retired breeders, indicating that these phenotypic differences between TG and WT mice were stable well into adulthood. Effects of genotype on histomorphometric indices of cancellous bone turnover were minimal and evident only transiently during growth, but when present they demonstrated differences in osteoblast rather than osteoclast parameters. Together, these results suggest that integrin signals generated during growth enhance the acquisition of a skeletal mass, structure, and strength to withstand the mechanical loads generated by weight-bearing.

The Relationships Between Microstructure, Tensile Properties and Fatigue Life in Ti-5Al-5V-5Mo-3Cr-0.4Fe (Ti-5553)

NASA Astrophysics Data System (ADS)

Foltz, John W., IV

beta-titanium alloys are being increasingly used in airframes as a way to decrease the weight of the aircraft. As a result of this movement, Ti-5Al-5V-5Mo-3Cr-0.4Fe (Timetal 555), a high-strength beta titanium alloy, is being used on the current generation of landing gear. This alloy features good combinations of strength, ductility, toughness and fatigue life in alpha+beta processed conditions, but little is known about beta-processed conditions. Recent work by the Center for the Accelerated Maturation of Materials (CAMM) research group at The Ohio State University has improved the tensile property knowledge base for beta-processed conditions in this alloy, and this thesis augments the aforementioned development with description of how microstructure affects fatigue life. In this work, beta-processed microstructures have been produced in a Gleeble(TM) thermomechanical simulator and subsequently characterized with a combination of electron and optical microscopy techniques. Four-point bending fatigue tests have been carried out on the material to characterize fatigue life. All the microstructural conditions have been fatigue tested with the maximum test stress equal to 90% of the measured yield strength. The subsequent results from tensile tests, fatigue tests, and microstructural quantification have been analyzed using Bayesian neural networks in an attempt to predict fatigue life using microstructural and tensile inputs. Good correlation has been developed between lifetime predictions and experimental results using microstructure and tensile inputs. Trained Bayesian neural networks have also been used in a predictive fashion to explore functional dependencies between these inputs and fatigue life. In this work, one section discusses the thermal treatments that led to the observed microstructures, and the possible sequence of precipitation that led to these microstructures. The thesis then describes the implications of microstructure on fatigue life and implications of tensile properties on fatigue life. Several additional experiments are then described that highlight possible causes for the observed dependence of microstructure on fatigue life, including fractographic evidence to provide support of microstructural dependencies.

Dipole strength distributions from HIGS Experiments

NASA Astrophysics Data System (ADS)

Werner, V.; Cooper, N.; Goddard, P. M.; Humby, P.; Ilieva, R. S.; Rusev, G.; Beller, J.; Bernards, C.; Crider, B. P.; Isaak, J.; Kelley, J. H.; Kwan, E.; Löher, B.; Peters, E. E.; Pietralla, N.; Romig, C.; Savran, D.; Scheck, M.; Tonchev, A. P.; Tornow, W.; Yates, S. W.; Zweidinger, M.

2015-05-01

A series of photon scattering experiments has been performed on the double-beta decay partners 76Ge and 76Se, in order to investigate their dipole response up to the neutron separation threshold. Gamma-ray beams from bremsstrahlung at the S-DALINAC and from Compton-backscattering at HIGS have been used to measure absolute cross sections and parities of dipole excited states, respectively. The HIGS data allows for indirect measurement of averaged branching ratios, which leads to significant corrections in the observed excitation cross sections. Results are compared to statistical calculations, to test photon strength functions and the Axel-Brink hypothesis

Cross-frequency synchronization connects networks of fast and slow oscillations during visual working memory maintenance.

PubMed

Siebenhühner, Felix; Wang, Sheng H; Palva, J Matias; Palva, Satu

2016-09-26

Neuronal activity in sensory and fronto-parietal (FP) areas underlies the representation and attentional control, respectively, of sensory information maintained in visual working memory (VWM). Within these regions, beta/gamma phase-synchronization supports the integration of sensory functions, while synchronization in theta/alpha bands supports the regulation of attentional functions. A key challenge is to understand which mechanisms integrate neuronal processing across these distinct frequencies and thereby the sensory and attentional functions. We investigated whether such integration could be achieved by cross-frequency phase synchrony (CFS). Using concurrent magneto- and electroencephalography, we found that CFS was load-dependently enhanced between theta and alpha-gamma and between alpha and beta-gamma oscillations during VWM maintenance among visual, FP, and dorsal attention (DA) systems. CFS also connected the hubs of within-frequency-synchronized networks and its strength predicted individual VWM capacity. We propose that CFS integrates processing among synchronized neuronal networks from theta to gamma frequencies to link sensory and attentional functions.

Effective axial-vector strength and β-decay systematics

NASA Astrophysics Data System (ADS)

Delion, D. S.; Suhonen, J.

2014-09-01

We use the weak axial-vector coupling strength g_{\\text{A}} as a key parameter to reproduce simultaneously the available data for both the Gamow-Teller \\beta^- and \\beta^+/\\text{EC} decay rates in nine triplets of isobars with mass numbers A=70,78,100,104,106,110,116,128,130 . We use the proton-neutron quasiparticle random-phase approximation (pnQRPA) with schematic dipole interaction containing particle-particle and particle-hole parts with mass-dependent strengths. Our analysis points to a strongly quenched effective value g_{\\text{A}}\\approx 0.3 , with a relative error of 28%. We then perform a systematic computation of 218 experimentally known \\beta^- and \\beta^+/\\text{EC} decays with quite a remarkable success. The presently extracted value of g_{\\text{A}} should be taken as an effective one, specific for a given nuclear theory framework. Present studies suggest that the effective g_{\\text{A}} is suitable for the description of decay transitions to 1^+ states at moderate excitation, below the Gamow-Teller giant resonance region.

Particle Orbit Analysis in the Finite Beta Plasma of the Large Helical Device using Real Coordinates

NASA Astrophysics Data System (ADS)

Seki, Ryousuke; Matsumoto, Yutaka; Suzuki, Yasuhiro; Watanabe, Kiyomasa; Itagaki, Masafumi

High-energy particles in a finite beta plasma of the Large Helical Device (LHD) are numerically traced in a real coordinate system. We investigate particle orbits by changing the beta value and/or the magnetic field strength. No significant difference is found in the particle orbit classifications between the vacuum magnetic field and the finite beta plasma cases. The deviation of a banana orbit from the flux surfaces strongly depends on the beta value, although the deviation of the orbit of a passing particle is independent of the beta value. In addition, the deviation of the orbit of the passing particle, rather than that of the banana-orbit particles, depends on the magnetic field strength. We also examine the effect of re-entering particles, which repeatedly pass in and out of the last closed flux surface, in the finite beta plasma of the LHD. It is found that the number of re-entering particles in the finite beta plasma is larger than that in the vacuum magnetic field. As a result, the role of reentering particles in the finite beta plasma of the LHD is more important than that in the vacuum magnetic field, and the effect of the charge-exchange reaction on particle confinement in the finite beta plasma is large.

Genetic effect of interleukin-1 beta (C-511T) polymorphism on the structural covariance network and white matter integrity in Alzheimer's disease.

PubMed

Huang, Chi-Wei; Hsu, Shih-Wei; Tsai, Shih-Jen; Chen, Nai-Ching; Liu, Mu-En; Lee, Chen-Chang; Huang, Shu-Hua; Chang, Weng-Neng; Chang, Ya-Ting; Tsai, Wan-Chen; Chang, Chiung-Chih

2017-01-18

Inflammatory processes play a pivotal role in the degenerative process of Alzheimer's disease. In humans, a biallelic (C/T) polymorphism in the promoter region (position-511) (rs16944) of the interleukin-1 beta gene has been significantly associated with differences in the secretory capacity of interleukin-1 beta. In this study, we investigated whether this functional polymorphism mediates the brain networks in patients with Alzheimer's disease. We enrolled a total of 135 patients with Alzheimer's disease (65 males, 70 females), and investigated their gray matter structural covariance networks using 3D T1 magnetic resonance imaging and their white matter macro-structural integrities using fractional anisotropy. The patients were classified into two genotype groups: C-carriers (n = 108) and TT-carriers (n = 27), and the structural covariance networks were constructed using seed-based analysis focusing on the default mode network medial temporal or dorsal medial subsystem, salience network and executive control network. Neurobehavioral scores were used as the major outcome factors for clinical correlations. There were no differences between the two genotype groups in the cognitive test scores, seed, or peak cluster volumes and white matter fractional anisotropy. The covariance strength showing C-carriers > TT-carriers was the entorhinal-cingulum axis. There were two peak clusters (Brodmann 6 and 10) in the salience network and four peak clusters (superior prefrontal, precentral, fusiform, and temporal) in the executive control network that showed C-carriers < TT-carriers in covariance strength. The salience network and executive control network peak clusters in the TT group and the default mode network peak clusters in the C-carriers strongly predicted the cognitive test scores. Interleukin-1 beta C-511 T polymorphism modulates the structural covariance strength on the anterior brain network and entorhinal-interconnected network which were independent of the white matter tract integrity. Depending on the specific C-511 T genotype, different network clusters could predict the cognitive tests.

Isokinetic Extension Strength Is Associated With Single-Leg Vertical Jump Height.

PubMed

Fischer, Felix; Blank, Cornelia; Dünnwald, Tobias; Gföller, Peter; Herbst, Elmar; Hoser, Christian; Fink, Christian

2017-11-01

Isokinetic strength testing is an important tool in the evaluation of the physical capacities of athletes as well as for decision making regarding return to sports after anterior cruciate ligament (ACL) reconstruction in both athletes and the lay population. However, isokinetic testing is time consuming and requires special testing equipment. A single-jump test, regardless of leg dominance, may provide information regarding knee extension strength through the use of correlation analysis of jump height and peak torque of isokinetic muscle strength. Cross-sectional study; Level of evidence, 3. A total of 169 patients who underwent ACL reconstruction were included in this study. Isokinetic testing was performed on the injured and noninjured legs. Additionally, a single-leg countermovement jump was performed to assess jump height using a jump accelerometer sensor. Extension strength values were used to assess the association between isokinetic muscle strength and jump height. The sample consisted of 60 female (mean age, 20.8 ± 8.3 years; mean weight, 61.7 ± 6.5 kg; mean height, 167.7 ± 5.3 cm) and 109 male (mean age, 23.2 ± 7.7 years; mean weight, 74.6 ± 10.2 kg; mean height, 179.9 ± 6.9 cm) patients. Bivariate correlation analysis showed an association ( r = 0.56, P < .001) between jump height and isokinetic extension strength on the noninvolved side as well as an association ( r = 0.52, P < .001) for the involved side. Regression analysis showed that in addition to jump height (beta = 0.49, P < .001), sex (beta = -0.17, P = .008) and body mass index (beta = 0.37, P < .001) affected isokinetic strength. The final model explained 51.1% of the variance in isokinetic muscle strength, with jump height having the strongest impact (beta = 0.49, P < .001) and explaining 31.5% of the variance. Initial analysis showed a strong association between isokinetic strength and jump height. The study population encompassed various backgrounds, skill levels, and activity profiles, which might have affected the outcome. Even after controlling for age and sex, isokinetic strength was still moderately associated with jump height. Therefore, the jump technique and type of sport should be considered in future research.

Cross-frequency synchronization connects networks of fast and slow oscillations during visual working memory maintenance

PubMed Central

Siebenhühner, Felix; Wang, Sheng H; Palva, J Matias; Palva, Satu

2016-01-01

Neuronal activity in sensory and fronto-parietal (FP) areas underlies the representation and attentional control, respectively, of sensory information maintained in visual working memory (VWM). Within these regions, beta/gamma phase-synchronization supports the integration of sensory functions, while synchronization in theta/alpha bands supports the regulation of attentional functions. A key challenge is to understand which mechanisms integrate neuronal processing across these distinct frequencies and thereby the sensory and attentional functions. We investigated whether such integration could be achieved by cross-frequency phase synchrony (CFS). Using concurrent magneto- and electroencephalography, we found that CFS was load-dependently enhanced between theta and alpha–gamma and between alpha and beta-gamma oscillations during VWM maintenance among visual, FP, and dorsal attention (DA) systems. CFS also connected the hubs of within-frequency-synchronized networks and its strength predicted individual VWM capacity. We propose that CFS integrates processing among synchronized neuronal networks from theta to gamma frequencies to link sensory and attentional functions. DOI: http://dx.doi.org/10.7554/eLife.13451.001 PMID:27669146

Effects of six weeks of beta-hydroxy-beta-methylbutyrate (HMB) and HMB/creatine supplementation on strength, power, and anthropometry of highly trained athletes.

PubMed

O'Connor, Donna M; Crowe, Melissa J

2007-05-01

This study investigated the effects of 6 weeks of dietary supplementation of beta-hydroxy-beta-methylbutyrate (HMB) and HMB combined with creatine monohydrate (HMBCr) on the muscular strength and endurance, leg power, and anthropometry of elite male rugby league players. The subjects were divided into a control group (n = 8), a HMB group (n = 11; 3 g.d(-1)) or a HMBCr group (n = 11; 12 g.d(-1) with 3 g HMB, 3 g Cr, 6 g carbohydrates). Three repetition maximum lifts on bench press, deadlifts, prone row, and shoulder press, maximum chin-up repetitions, 10-second maximal cycle test, body mass, girths, and sum of skinfolds were assessed pre- and postsupplementation. Statistical analysis revealed no effect of HMB or HMBCr on any parameter compared with presupplementation measures or the control group. HMB and HMBCr were concluded to have no ergogenic effect on muscular strength and endurance, leg power, or anthropometry when taken orally by highly trained male athletes over 6 weeks.

The effects of surface finish and grain size on the strength of sintered silicon carbide

NASA Technical Reports Server (NTRS)

You, Y. H.; Kim, Y. W.; Lee, J. G.; Kim, C. H.

1985-01-01

The effects of surface treatment and microstructure, especially abnormal grain growth, on the strength of sintered SiC were studied. The surfaces of sintered SiC were treated with 400, 800 and 1200 grit diamond wheels. Grain growth was induced by increasing the sintering times at 2050 C. The beta to alpha transformation occurred during the sintering of beta-phase starting materials and was often accompanied by abnormal grain growth. The overall strength distributions were established using Weibull statistics. The strength of the sintered SiC is limited by extrinsic surface flaws in normal-sintered specimens. The finer the surface finish and grain size, the higher the strength. But the strength of abnormal sintering specimens is limited by the abnormally grown large tabular grains. The Weibull modulus increases with decreasing grain size and decreasing grit size for grinding.

Complexation of Nd(III) with tetraborate ion and its effect on actinide (III) solubility in WIPP brine

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

Borkowski, Marian; Richmann, Michael K; Reed, Donald T

2010-01-01

The potential importance of tetraborate complexation on lanthanide(III) and actinide(III) solubility is recognized in the literature but a systematic study of f-element complexation has not been performed. In neodymium solubility studies in WIPP brines, the carbonate complexation effect is not observed since tetraborate ions form a moderately strong complex with neodymium(III). The existence of these tetraborate complexes was established for low and high ionic strength solutions. Changes in neodymium(III) concentrations in undersaturation experiments were used to determine the neodymium with tetraborate stability constants as a function of NaCl ionic strength. As very low Nd(III) concentrations have to be measured, itmore » was necessary to use an extraction pre-concentration step combined with ICP-MS analysis to extend the detection limit by a factor of 50. The determined Nd(III) with borate stability constants at infinite dilution and 25 C are equal to log {beta}{sub 1} = 4.55 {+-} 0.06 using the SIT approach, equal to log {beta}{sub 1} = 4.99 {+-} 0.30 using the Pitzer approach, with an apparent log {beta}{sub 1} = 4.06 {+-} 0.15 (in molal units) at I = 5.6 m NaCl. Pitzer ion-interaction parameters for neodymium with tetraborate and SIT interaction coefficients were also determined and reported.« less

Beta-hydroxy-beta-methylbutyrate supplementation and skeletal muscle in healthy and muscle-wasting conditions.

PubMed

Holeček, Milan

2017-08-01

Beta-hydroxy-beta-methylbutyrate (HMB) is a metabolite of the essential amino acid leucine that has been reported to have anabolic effects on protein metabolism. The aims of this article were to summarize the results of studies of the effects of HMB on skeletal muscle and to examine the evidence for the rationale to use HMB as a nutritional supplement to exert beneficial effects on muscle mass and function in various conditions of health and disease. The data presented here indicate that the beneficial effects of HMB have been well characterized in strength-power and endurance exercise. HMB attenuates exercise-induced muscle damage and enhances muscle hypertrophy and strength, aerobic performance, resistance to fatigue, and regenerative capacity. HMB is particularly effective in untrained individuals who are exposed to strenuous exercise and in trained individuals who are exposed to periods of high physical stress. The low effectiveness of HMB in strength-trained athletes could be due to the suppression of the proteolysis that is induced by the adaptation to training, which may blunt the effects of HMB. Studies performed with older people have demonstrated that HMB can attenuate the development of sarcopenia in elderly subjects and that the optimal effects of HMB on muscle growth and strength occur when it is combined with exercise. Studies performed under in vitro conditions and in various animal models suggest that HMB may be effective in treatment of muscle wasting in various forms of cachexia. However, there are few clinical reports of the effects of HMB on muscle wasting in cachexia; in addition, most of these studies evaluated the therapeutic potential of combinations of various agents. Therefore, it has not been possible to determine whether HMB was effective or if there was a synergistic effect. Although most of the endogenous HMB is produced in the liver, there are no reports regarding the levels and the effects of HMB supplementation in subjects with liver disease. Several studies have suggested that anabolic effects of HMB supplementation on skeletal muscle do not occur in healthy, non-exercising subjects. It is concluded that (i) HMB may be applied to enhance increases in the mass and strength of skeletal muscles in subjects who exercise and in the elderly and (ii) studies examining the effects of HMB administered alone are needed to obtain conclusions regarding the specific effectiveness in attenuating muscle wasting in various muscle-wasting disorders. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

Interaction of Beta-Hydroxy-Beta-Methylbutyrate Free Acid and Adenosine Triphosphate on Muscle Mass, Strength, and Power in Resistance Trained Individuals.

PubMed

Lowery, Ryan P; Joy, Jordan M; Rathmacher, John A; Baier, Shawn M; Fuller, John C; Shelley, Mack C; Jäger, Ralf; Purpura, Martin; Wilson, Stephanie M C; Wilson, Jacob M

2016-07-01

Lowery, RP, Joy, JM, Rathmacher, JA, Baier, SM, Fuller, JC Jr, Shelley, MC II, Jäger, R, Purpura, M, Wilson, SMC, and Wilson, JM. Interaction of beta-hydroxy-beta-methylbutyrate free acid and adenosine triphosphate on muscle mass, strength, and power in resistance trained individuals. J Strength Cond Res 30(7): 1843-1854, 2016-Adenosine-5'-triphosphate (ATP) supplementation helps maintain performance under high fatiguing contractions and with greater fatigue recovery demands also increase. Current evidence suggests that the free acid form of β-hydroxy-β-methylbutyrate (HMB-FA) acts by speeding regenerative capacity of skeletal muscle after high-intensity or prolonged exercise. Therefore, we investigated the effects of 12 weeks of HMB-FA (3 g) and ATP (400 mg) administration on lean body mass (LBM), strength, and power in trained individuals. A 3-phase double-blind, placebo-, and diet-controlled study was conducted. Phases consisted of an 8-week periodized resistance training program (phase 1), followed by a 2-week overreaching cycle (phase 2), and a 2-week taper (phase 3). Lean body mass was increased by a combination of HMB-FA/ATP by 12.7% (p < 0.001). In a similar fashion, strength gains after training were increased in HMB-FA/ATP-supplemented subjects by 23.5% (p < 0.001). Vertical jump and Wingate power were increased in the HMB-FA/ATP-supplemented group compared with the placebo-supplemented group, and the 12-week increases were 21.5 and 23.7%, respectively. During the overreaching cycle, strength and power declined in the placebo group (4.3-5.7%), whereas supplementation with HMB-FA/ATP resulted in continued strength gains (1.3%). In conclusion, HMB-FA and ATP in combination with resistance exercise training enhanced LBM, power, and strength. In addition, HMB-FA plus ATP blunted the typical response to overreaching, resulting in a further increase in strength during that period. It seems that the combination of HMB-FA/ATP could benefit those who continuously train at high levels such as elite athletes or military personnel.

Intermediate Nuclear Structure for 2v 2{beta} Decay of {sup 48}Ca Studied by (p, n) and (n, p) Reactions at 300 MeV

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

Sakai, H.; Yako, K.

2009-08-26

Angular distributions of the double differential cross sections for the {sup 48}Ca(p,n) and the {sup 48}Ti(n,p) reactions were measured at 300 MeV. A multipole decomposition technique was applied to the spectra to extract the Gamow-Teller (GT) transition strengths. In the (n, p) spectrum beyond 8 MeV excitation energy extra B(GT{sup +}) strengths which are not predicted by the shell model calculation. This extra B(GT{sup +}) strengths significantly contribute to the nuclear matrix element of the 2v2{beta}-decay.

Amyloid-beta aggregation: selective inhibition of aggregation in mixtures of amyloid with different chain lengths.

PubMed Central

Snyder, S W; Ladror, U S; Wade, W S; Wang, G T; Barrett, L W; Matayoshi, E D; Huffaker, H J; Krafft, G A; Holzman, T F

1994-01-01

One of the clinical manifestations of Alzheimer's disease is the deposition of the 39-43 residue amyloid-beta (A beta) peptide in aggregated fibrils in senile plaques. Characterization of the aggregation behavior of A beta is one of the critical issues in understanding the role of A beta in the disease process. Using solution hydrodynamics, A beta was observed to form three types of species in phosphate-buffered saline: insoluble aggregates with sedimentation coefficients of approximately 50,000 S and molecular masses of approximately 10(9) Da, "soluble aggregates" with sedimentation coefficients of approximately 30 S and masses of approximately 10(6) Da, and monomer. When starting from monomer, the aggregation kinetics of A beta 1-40 (A beta 40) and A beta 1-42 (A beta 42), alone and in combination, reveal large differences in the tendency of these peptides to aggregate as a function of pH and other solution conditions. At pH 4.1 and 7.0-7.4, aggregation is significantly slower than at pH 5 and 6. Under all conditions, aggregation of the longer A beta 42 was more rapid than A beta 40. Oxidation of Met-35 to the sulfoxide in A beta 40 enhances the aggregation rate over that of the nonoxidized peptide. Aggregation was found to be dependent upon temperature and to be strongly dependent on peptide concentration and ionic strength, indicating that aggregation is driven by a hydrophobic effect. When A beta 40 and A beta 42 are mixed together, A beta 40 retards the aggregation of A beta 42 in a concentration-dependent manner. Shorter fragments have a decreasing ability to interfere with A beta 42 aggregation. Conversely, the rate of aggregation of A beta 40 can be significantly enhanced by seeding slow aggregating solutions with preformed aggregates of A beta 42. Taken together, the inhibition of A beta 42 aggregation by A beta 40, the seeding of A beta 40 aggregation by A beta 42 aggregates, and the chemical oxidation of A beta 40 suggest that the relative abundance and rates of production of different-length A beta and its exposure to radical damage may be factors in the accumulation of A beta in plaques in vivo. Images FIGURE 6 PMID:7811936

Isokinetic Extension Strength Is Associated With Single-Leg Vertical Jump Height

PubMed Central

Fischer, Felix; Blank, Cornelia; Dünnwald, Tobias; Gföller, Peter; Herbst, Elmar; Hoser, Christian; Fink, Christian

2017-01-01

Background: Isokinetic strength testing is an important tool in the evaluation of the physical capacities of athletes as well as for decision making regarding return to sports after anterior cruciate ligament (ACL) reconstruction in both athletes and the lay population. However, isokinetic testing is time consuming and requires special testing equipment. Hypothesis: A single-jump test, regardless of leg dominance, may provide information regarding knee extension strength through the use of correlation analysis of jump height and peak torque of isokinetic muscle strength. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 169 patients who underwent ACL reconstruction were included in this study. Isokinetic testing was performed on the injured and noninjured legs. Additionally, a single-leg countermovement jump was performed to assess jump height using a jump accelerometer sensor. Extension strength values were used to assess the association between isokinetic muscle strength and jump height. Results: The sample consisted of 60 female (mean age, 20.8 ± 8.3 years; mean weight, 61.7 ± 6.5 kg; mean height, 167.7 ± 5.3 cm) and 109 male (mean age, 23.2 ± 7.7 years; mean weight, 74.6 ± 10.2 kg; mean height, 179.9 ± 6.9 cm) patients. Bivariate correlation analysis showed an association (r = 0.56, P < .001) between jump height and isokinetic extension strength on the noninvolved side as well as an association (r = 0.52, P < .001) for the involved side. Regression analysis showed that in addition to jump height (beta = 0.49, P < .001), sex (beta = –0.17, P = .008) and body mass index (beta = 0.37, P < .001) affected isokinetic strength. The final model explained 51.1% of the variance in isokinetic muscle strength, with jump height having the strongest impact (beta = 0.49, P < .001) and explaining 31.5% of the variance. Conclusion: Initial analysis showed a strong association between isokinetic strength and jump height. The study population encompassed various backgrounds, skill levels, and activity profiles, which might have affected the outcome. Even after controlling for age and sex, isokinetic strength was still moderately associated with jump height. Therefore, the jump technique and type of sport should be considered in future research. PMID:29147670

Mechanical and biological evaluations of beta-tricalcium phosphate/silicone rubber composite as a novel soft-tissue implant.

PubMed

Zhang, Yi-ming; Wang, Shao-liang; Lei, Ze-yuan; Fan, Dong-li

2009-09-01

Although silicone rubber (SR) implants are most commonly used and effective for soft-tissue augmentation, they still have been implicated in many adverse reactions. To overcome this problem, a novel composite beta-tricalcium phosphate/silicone rubber (beta-TCP/SR) was prepared by adding beta-TCP into a SR matrix. This study was to evaluate its application potential by investigating the mechanical properties and biocompatibility of beta-TCP/SR. Mechanical properties, including Shore A hardness and tensile strength, were evaluated with 3-mm-thick samples and a universal testing machine. Cytocompatibility tests were conducted in vitro using 0.2-mm-thick beta-TCP/SR samples by seeding fibroblasts onto different samples. Soft-tissue response to beta-TCP/SR and pull-out measurements were investigated 4 weeks and 24 weeks after implantation. The main mechanical properties were all significantly changed after mixing beta-TCP into the SR matrix, except for tearing strength. The cytocompatibility test showed enhanced adhesion and proliferation of fibroblasts onto beta-TCP/SR. Fibrous tissue ingrowth after resorption of beta-TCP was observed by in vivo histologic analysis. The peri-implant capsules in the beta-TCP/SR group were thinner than in the SR group 24 weeks after implantation. In a 24-week test, the maximum force required to pull out the beta-TCP/SR sheet was about six times greater than that needed for SR. Although some mechanical properties were significantly changed, the results of the cytocompatibility test and in vivo animal study still suggest that beta-TCP/SR may be more suitable as a soft-tissue implant than SR and has the potential to be used in plastic surgery.

Gamow-Teller strength observed in the 48Ti(n, p) 48Sc reaction: Implications for the double beta decay of 48Ca

NASA Astrophysics Data System (ADS)

Alford, W. P.; Helmer, R. L.; Abegg, R.; Celler, A.; Frekers, D.; Green, P.; Häusser, O.; Henderson, R.; Hicks, K.; Jackson, K. P.; Jeppesen, R.; Miller, C. A.; Trudel, A.; Vetterli, M.; Yen, S.; Pourang, R.; Watson, J.; Brown, B. A.; Engel, J.

1990-07-01

Cross sections for the 48Ti(n, p) reaction have been measured at angles of 0°, 6°, and 12° at an energy of 200 MeV. The measurements are compared with results of DWIA calculations to obtain estimates of transition strengths for L = 0, 1, and ⩾2 up to an excitation energy of 25 MeV. Gamow-Teller strength ( L = 0) is peaked between 3 and 4 MeV excitation energy, with a significant distribution extending to about 12 MeV. The L = 1 strength is found mainly between 6 and 20 MeV while the cross section for transitions with L ⩾2 increases from 10 MeV to the upper limit of the measurements. The distribution of Gamow-Teller strength is in poor agreement with theoretical distributions used to calculate the lifetime for double beta decay of 48Ca.

Nanomechanical strength mechanisms of hierarchical biological materials and tissues.

PubMed

Buehler, Markus J; Ackbarow, Theodor

2008-12-01

Biological protein materials (BPMs), intriguing hierarchical structures formed by assembly of chemical building blocks, are crucial for critical functions of life. The structural details of BPMs are fascinating: They represent a combination of universally found motifs such as alpha-helices or beta-sheets with highly adapted protein structures such as cytoskeletal networks or spider silk nanocomposites. BPMs combine properties like strength and robustness, self-healing ability, adaptability, changeability, evolvability and others into multi-functional materials at a level unmatched in synthetic materials. The ability to achieve these properties depends critically on the particular traits of these materials, first and foremost their hierarchical architecture and seamless integration of material and structure, from nano to macro. Here, we provide a brief review of this field and outline new research directions, along with a review of recent research results in the development of structure-property relationships of biological protein materials exemplified in a study of vimentin intermediate filaments.

[The relationship of quality of life (QOL) with physical fitness, competence and stress response in elderly in Japan].

PubMed

Uemura, Shinichi; Machida, Kazuhiki

2003-09-01

In order to evaluate the relationship of quality of life (QOL) with physical fitness, competence and stress response in the elderly population in Japan, a cross sectional field survey of elderly subjects was conducted. This survey was taken in Naguri village, Saitama. The data collected included physical fitness, competence, stress response and QOL in addition to demographic variables. As for physical fitness indexes, grip strength (GS), single leg balance with eyes closed (SLB), bar grip ping reaction time (RT), trunk flexion (RF), ten-meter walking time (WT) and vital capacity (VC) were measured. The SF-36 was used for QOL assessment. A total of 120 elderly subjected participated to the survey. There were 42 males (73.5 +/- 5.74 years) and 78 females (74.2 +/- 6.17 years). The associations between physical health parameters in SF-36 and WT were highly significant: physical functioning (beta = -2.96, p < 0.001), role physical (beta = -3.64, p < 0.001), bodily pain (beta = -3.27, p < 0.001) and general health (beta = -3.14, p = 0.001). Psychological stress response had a negative correlation with social functioning (beta = -0.74, p = 0.024), role-emotional (beta = -2.34, p < 0.007) and mental health (beta = -0.97, p = 0.024) as determined by multiple regression analysis. The goodness-of-fit indexes of the structural equation model describing the relationships among physical fitness, competence, stress response and QOL indicated excellent fit to the data with GFI = 0.95 and AGFI = 0.88. Stress response showed relatively stronger influence on QOL than physical fitness or competence. Although there were slight differences in degree of influence, physical fitness, stress response and competence were found to be clearly related to QOL in elderly subjects. To keep good QOL status, it is important to maintain good physical fitness and level of competence and to reduce stress response.

Effect of magnetic field on beta processes in a relativistic moderately degenerate plasma

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

Ognev, I. S., E-mail: ognev@uniyar.ac.ru

The effect of a magnetic field of arbitrary strength on the beta decay and crossing symmetric processes is analyzed. A covariant calculation technique is used to derive the expression for the squares of S-matrix elements of these reactions, which is also valid in reference frames in which the medium moves as a single whole along magnetic field lines. Simple analytic expressions obtained for the neutrino and antineutrino emissivities for a moderately degenerate plasma fully characterize the emissivity and absorbability of the studied medium. It is shown that the approximation used here is valid for core collapse supernovae and accretion disksmore » around black holes; beta processes in these objects are predominantly neutrino reactions. The analytic expressions obtained for the emissivities can serve as a good approximation for describing the interaction of electron neutrinos and antineutrinos with the medium of the objects in question and hold for an arbitrary magnetic field strength. Due to their simplicity, these expressions can be included in the magnetohydrodynamic simulation of supernovae and accretion disks to calculate neutrino and antineutrino transport in them. The rates of beta processes and the energy and momentum emitted in them are calculated for an optically transparent matter. It is shown that the macroscopic momentum transferred in the medium increases linearly with the magnetic field strength and can substantially affect the dynamics of supernovae and accretion disks in the regions of a degenerate matter. It is also shown that the rates of beta processes and the energy emission for a magnetic field strength of B ≲ 10{sup 15} G typical of supernovae and accretion disks are lower than in the absence of field. This suppression is stronger for reactions with neutrinos.« less

Structure-property relationship of cast Ti-Nb alloys.

PubMed

Lee, C M; Ju, C P; Chern Lin, J H

2002-04-01

The present work is a study of the microstructure, mechanical properties and corrosion behaviour of a series of binary Ti-Nb alloys with Nb contents up to 35 wt%, with emphasis placed on the structure-property relationship of the alloys. The results indicate that crystal structure and morphology of the Ti-Nb alloys are sensitive to the Nb content. The cast c.p. Ti has a hexagonal alpha phase with a lath type morphology. The alloys containing 15 wt% or less Nb are dominated by a hexagonal alpha' phase with an acicular, martensitic structure. When containing 17.5-25 wt% Nb, the alloys are primarily comprised of an orthorhombic alpha" phase. With 27.5 wt% Nb, metastable beta phase starts to be retained. With Nb contents higher than 30 wt%, the equi-axed beta phase is almost entirely retained. Small amounts of omega phase are detected in alloys containing 27.5 and 30 wt% Nb. Among all present alloys, Ti-10Nb and Ti-27.5Nb exhibit the highest strengths, while the alpha"-dominated (17.5 and 20Nb) and beta-dominated (> 30Nb) alloys have the lowest moduli. All Ti-Nb alloys show excellent corrosion resistance in Hank's solution at 37 degrees C. From the present data, the microhardness, bending strength and modulus of the various phases in Ti-Nb alloys are compared and tentatively summarized as follows: Microhardness: omega > alpha' > alpha" > beta > alpha (c.p. Ti) Bending strength: omega > alpha' > alpha" > beta > alpha (c.p. Ti) Bending modulus: omega > alpha (c.p. Ti) > alpha' > alpha" > beta

Chemical factors determine olfactory system beta oscillations in waking rats.

PubMed

Lowry, Catherine A; Kay, Leslie M

2007-07-01

Recent studies have pointed to olfactory system beta oscillations of the local field potential (15-30 Hz) and their roles both in learning and as specific responses to predator odors. To describe odorant physical properties, resultant behavioral responses and changes in the central olfactory system that may induce these oscillations without associative learning, we tested rats with 26 monomolecular odorants spanning 6 log units of theoretical vapor pressure (estimate of relative vapor phase concentration) and 10 different odor mixtures. We found odorant vapor phase concentration to be inversely correlated with investigation time on the first presentation, after which investigation times were brief and not different across odorants. Analysis of local field potentials from the olfactory bulb and anterior piriform cortex shows that beta oscillations in waking rats occur specifically in response to the class of volatile organic compounds with vapor pressures of 1-120 mmHg. Beta oscillations develop over the first three to four presentations and are weakly present for some odorants in anesthetized rats. Gamma oscillations show a smaller effect that is not restricted to the same range of odorants. Olfactory bulb theta oscillations were also examined as a measure of effective afferent input strength, and the power of these oscillations did not vary systematically with vapor pressure, suggesting that it is not olfactory bulb drive strength that determines the presence of beta oscillations. Theta band coherence analysis shows that coupling strength between the olfactory bulb and piriform cortex increases linearly with vapor phase concentration, which may facilitate beta oscillations above a threshold.

Mechanical properties of calcium phosphate scaffolds fabricated by robocasting.

PubMed

Miranda, Pedro; Pajares, Antonia; Saiz, Eduardo; Tomsia, Antoni P; Guiberteau, Fernando

2008-04-01

The mechanical behavior under compressive stresses of beta-tricalcium phosphate (beta-TCP) and hydroxyapatite (HA) scaffolds fabricated by direct-write assembly (robocasting) technique is analyzed. Concentrated colloidal inks prepared from beta-TCP and HA commercial powders were used to fabricate porous structures consisting of a 3-D tetragonal mesh of interpenetrating ceramic rods. The compressive strength and elastic modulus of these model scaffolds were determined by uniaxial testing to compare the relative performance of the selected materials. The effect of a 3-week immersion in simulated body fluid (SBF) on the strength of the scaffolds was also analyzed. The results are compared with those reported in the literature for calcium phosphate scaffolds and human bone. The robocast calcium phosphate scaffolds were found to exhibit excellent mechanical performances in terms of strength, especially the HA structures after SBF immersion, indicating a great potential of this type of scaffolds for use in load-bearing bone tissue engineering applications. Copyright 2007 Wiley Periodicals, Inc.

Directionally solidified eutectic alloy gamma-beta

NASA Technical Reports Server (NTRS)

Tewari, S. N.

1977-01-01

A pseudobinary eutectic alloy composition was determined by a previously developed bleed-out technique. The directionally solidified eutectic alloy with a composition of Ni-37.4Fe-10.0Cr-9.6Al (in wt%) had tensile strengths decreasing from 1,090 MPa at room temperature to 54 MPa at 1,100 C. The low density, excellent microstructural stability, and oxidation resistance of the alloy during thermal cycling suggest that it might have applicability as a gas turbine vane alloy while its relatively low high temperature strength precludes its use as a blade alloy. A zirconium addition increased the 750 C strength, and a tungsten addition was ineffective. The gamma=beta eutectic alloys appeared to obey a normal freezing relation.

Effects of nine weeks of beta-hydroxy-beta- methylbutyrate supplementation on strength and body composition in resistance trained men.

PubMed

Thomson, Jasmine S; Watson, Patricia E; Rowlands, David S

2009-05-01

The dietary supplement beta-hydroxy-beta-methylbutyrate (HMB) is claimed to increase strength, lean body mass, and decrease fat mass when used in conjunction with resistance training. Although there is some support for these claims, the evidence is not conclusive, and it is even less so for resistance trained individuals. Therefore, we aimed to further elucidate the effects of HMB supplementation in trained men. A randomized, double-blind, controlled study design was used to investigate the effects of supplementing 22 resistance trained men with 3 g.d of HMB or corn starch placebo for 9 weeks with resistance training. The effect of HMB on strength was determined using the 1-repetition maximum (1RM) method for the lower body (leg extension) and upper body (bench press, bicep preacher curl) at baseline and after the supplementation period. Body composition was assessed by skinfolds and bioelectrical impedance analysis (BIA). Overall, 9 weeks' HMB supplementation resulted in a clear-cut, trivial increase in combined averaged strength measures of 1.6% (90% confidence limits: +/-4.3%). When considered in isolation, however, leg extension 1RM increased by a substantial 9.1% (90% confidence limits: +/-7.5%), but the effect on upper-body strength was inconclusive (bench press: -1.9 +/- 9.3%; bicep curl: -1.7 +/- 4.7%). Based on BIA estimates, HMB had a decreasing (although inconclusive) influence on fat mass of -9 +/- 14%, but it had a clear, trivial effect on fat-free mass of 0.2 +/- 2.2%. The magnitude of change in body mass was trivial, but the probability of substantial reductions in skinfold thicknesses ranged from negligible to likely. In previously trained men, supplementation of HMB in conjunction with resistance training provides a substantial benefit to lower-body strength, but it has negligible effects on body composition.

Influence of different functional ingredients on physical properties, rheology, tribology, and oral perceptions of no fat stirred yoghurt.

PubMed

Ng, Sophia Bao Xian; Nguyen, Phuong T M; Bhandari, Bhesh; Prakash, Sangeeta

2018-06-01

Effects of adding four functional ingredients: inulin, pectin, galacto-oligosaccharides (GOS), and beta glucan on physical, rheology, tribology, and sensory characteristics of skim (0.1% fat) stirred yoghurt were studied. Three levels of each ingredient were chosen: inulin (7, 8, and 9%), pectin (0.2, 0.25, and 0.3%), GOS (9.1, 11.3, and 13.6%), and beta glucan (0.1, 0.2, and 0.3%). Among the investigated ingredients, inulin and GOS appeared to be preferable choices due to their ability to both reduce syneresis and slightly increase sample lubrication while maintaining texture, rheology, and sensory characteristics of skim yoghurt. Pectin and beta glucan, conversely, increased viscosity and gel strength, slightly increased sample lubrication for the skim yoghurt but created large particles (i.e., greater than 100 μm) in the product body. This led to the increase in lumpiness and residual coating while reducing smoothness and creaminess of the sample. The observed tribology behaviors of the stirred yoghurts were similar to the previous study of pot-set yoghurt whose friction curves comprised four friction zones (Nguyen, Kravchuk, Bhandari, and Prakash). The sensory characteristics of six selected samples for various texture and mouthfeel attributes obtained from a trained panel were in agreement with particle size, rheology, and tribology characteristics of the yoghurt samples. With the increasing demand for low fat and functional food, there is a need to understand the impact of adding functional ingredients in low fat yoghurt to satisfy consumers' requirements. This study investigates the effects of these functional ingredients at different dosages on physical, rheology, tribology, and sensory characteristics of skim (0.1% fat) stirred yoghurt. The results from this study may guide use of functional ingredients in yoghurt production. © 2017 Wiley Periodicals, Inc.

Microporous pure beta-tricalcium phosphate implants for press-fit fixation of anterior cruciate ligament grafts: strength and healing in a sheep model.

PubMed

Mayr, Hermann O; Dietrich, Markwart; Fraedrich, Franz; Hube, Robert; Nerlich, Andreas; von Eisenhart-Rothe, Rüdiger; Hein, Werner; Bernstein, Anke

2009-09-01

A sheep study was conducted to test a press-fit technique using microporous pure beta-tricalcium phosphate (beta-TCP) dowels for fixation of the anterior cruciate ligament (ACL) graft. Microporous (5 mum) cylindrical plugs of beta-TCP (diameter, 7 mm; length, 25 mm) with interconnecting pores were used. The material featured a novel configuration of structure and surface geometry. Implants were tested by use of press-fit fixation of ACL grafts with and without bone blocks in 42 sheep over a period of 24 weeks. Biomechanical, radiologic, histologic, and immunohistochemical evaluations were performed. In load-to-failure tests at 6, 12, and 24 weeks after surgery, the intra-articular graft always failed, not the fixation. Grafts showed bony fixation in the tunnel at 6 weeks and primary healing at the junction of the tunnel and joint after 24 weeks. Tricalcium phosphate was resorbed and simultaneously replaced by bone. Remodeling was still incomplete at 24 weeks. In the sheep model microporous beta-TCP implants used with press-fit fixation of ACL grafts permit early functional rehabilitation. After 6 weeks, the graft is fixed by woven bone or bony integration. Implanted microporous tricalcium phosphate is resorbed and replaced by bone. In a sheep model we showed that primary healing of ACL grafts with resorption and bony replacement of the fixating implant can be achieved by means of press-fit fixation with pure beta-TCP.

Beta-alanine supplementation improves isometric, but not isotonic or isokinetic strength endurance in recreationally strength-trained young men.

PubMed

Bassinello, Diogo; de Salles Painelli, Vitor; Dolan, Eimear; Lixandrão, Manoel; Cajueiro, Monique; de Capitani, Mariana; Saunders, Bryan; Sale, Craig; Artioli, Guilherme G; Gualano, Bruno; Roschel, Hamilton

2018-06-15

β-Alanine (BA) supplementation may be ergogenic during high-intensity exercise, primarily due to the buffering of hydrogen cations, although the effects of beta-alanine supplementation on strength endurance are equivocal. The aim of the study was to determine the effects of 4 weeks of beta-alanine supplementation on skeletal muscle endurance using a battery of performance tests. This study employed a parallel group, repeated measures, randomised, double-blinded and placebo-controlled design. Twenty recreationally strength-trained healthy males completed tests of isotonic strength endurance (repeated bench and leg press), along with tests of isometric and isokinetic endurance conducted using an isokinetic dynamometer. Tests were performed before and after a 4 week intervention, comprising an intake of 6.4 g day -1 of BA (n = 9) or placebo (maltodextrin, n = 11). Time-to-exhaustion during the isometric endurance test improved by ~ 17% in the BA group (p < 0.01), while PL remained unchanged. No significant within-group differences (p > 0.1) were shown for any of the performance variables in the isokinetic test (peak torque, fatigue index, total work) nor for the total number of repetitions performed in the isotonic endurance tests (leg or bench press). Four weeks of BA supplementation (6.4 g day -1 ) improved isometric, but not isokinetic or isotonic endurance performance.

Probing the N˜Z line via β decay

NASA Astrophysics Data System (ADS)

Oinonen, Markku

1999-11-01

This contribution reports several beta-decay studies performed at ISOLDE On-line Mass Separator at CERN recently for nuclei close to N=Z line. Beta decay of 58Zn provides a possibility to compare Gamow-Teller strength extracted from complementary beta-decay studies and charge-exchange reactions. Measurement on beta-decay half-life of 70Kr shows importance of experimental information in modelling the path of the astrophysical rp process. Decay of 71Kr is an example of a mirror beta decay and extends the systematics of these particular decays towards highly deformed region close to A=80.

Clenbuterol, a beta(2)-agonist, retards atrophy in denervated muscles

NASA Technical Reports Server (NTRS)

Zeman, Richard J.; Ludemann, Robert; Etlinger, Joseph D.

1987-01-01

The effects of a beta(2) agonist, clenbuterol, on the protein content as well as on the contractile strength and the muscle fiber cross-sectional area of various denervated muscles from rats were investigated. It was found that denervated soleus, anterior tibialis, and gastrocnemius muscles, but not the extensor digitorum longus, of rats treated for 2-3 weeks with clenbuterol contained 95-110 percent more protein than denervated controls. The twofold difference in the protein content of denervated solei was paralleled by similar changes in contractile strength and muscle fiber cross-sectional area.

Hydrogen bonds between the alpha and beta subunits of the F1-ATPase allow communication between the catalytic site and the interface of the beta catch loop and the gamma subunit.

PubMed

Boltz, Kathryn W; Frasch, Wayne D

2006-09-19

F(1)-ATPase mutations in Escherichia coli that changed the strength of hydrogen bonds between the alpha and beta subunits in a location that links the catalytic site to the interface between the beta catch loop and the gamma subunit were examined. Loss of the ability to form the hydrogen bonds involving alphaS337, betaD301, and alphaD335 lowered the k(cat) of ATPase and decreased its susceptibility to Mg(2+)-ADP-AlF(n) inhibition, while mutations that maintain or strengthen these bonds increased the susceptibility to Mg(2+)-ADP-AlF(n) inhibition and lowered the k(cat) of ATPase. These data suggest that hydrogen bonds connecting alphaS337 to betaD301 and betaR323 and connecting alphaD335 to alphaS337 are important to transition state stabilization and catalytic function that may result from the proper alignment of catalytic site residues betaR182 and alphaR376 through the VISIT sequence (alpha344-348). Mutations betaD301E, betaR323K, and alphaR282Q changed the rate-limiting step of the reaction as determined by an isokinetic plot. Hydrophobic mutations of betaR323 decreased the susceptibility to Mg(2+)-ADP-AlF(n)() inhibition and lowered the number of interactions required in the rate-limiting step yet did not affect the k(cat) of ATPase, suggesting that betaR323 is important to transition state formation. The decreased rate of ATP synthase-dependent growth and decreased level of lactate-dependent quenching observed with alphaD335, betaD301, and alphaE283 mutations suggest that these residues may be important to the formation of an alternative set of hydrogen bonds at the interface of the alpha and beta subunits that permits the release of intersubunit bonds upon the binding of ATP, allowing gamma rotation in the escapement mechanism.

Beta-decay strength and isospin mixing studies in the sd and fp-shells

NASA Astrophysics Data System (ADS)

Jokinen, A.; ńystö, J.; Dendooven, P.; Honkanen, A.; Lipas, P.; Peräjärvi, K.; Oinonen, M.; Siiskonen, T.

1998-12-01

We have studied beta decays of MT<0 nuclei in sd and fp shells. The decay of 41Ti shows a large, 10(8) %, isospin mixing of IAS and the Gamow-Teller strength is observed to be quenched by a factor of q2=0.64. These results can be reproduced qualitatively in our shell model calculations. We have observed for the first time proton and gamma decay of the isobaric analogue state in 23Mg. Our results on the isospin mixing of the isobaric analogue state agrees well with the shell model calculations. The obtained proton branch of the IAS is used to extract the transition strength for the reaction 22Na(p,γ)23Mg.

The electronic structure and second-order nonlinear optical properties of donor-acceptor acetylenes - A detailed investigation of structure-property relationships

NASA Technical Reports Server (NTRS)

Stiegman, A. E.; Graham, Eva; Khundkar, Lutfur R.; Perry, Joseph W.; Cheng, L.-T.; Perry, Kelly J.

1991-01-01

A series of donor-acceptor acetylene compounds was synthesized in which systematic changes in both the conjugation length and the donor-acceptor strength were made. The effect of these structural changes on the spectroscopic and electronic properties of the molecules and, ultimately, on the measured second-order molecular hyperpolarizabilities (beta) was investigated. It was found that increases in the donor-acceptor strength resulted in increases in the magnitude of beta. For this class of molecules, the increase is dominated by the energy of the intramolecular charge-transfer transition, while factors such as the ground to excited-state dipole moment change and the transition-moment integral are much less important. Increasing the conjugation length from one to two acetylene linkers did not result in an increase in the value of beta; however, beta increased sharply in going from two acetylenes to three. This increase is attributed to the superposition of several nearly isoenergetic excited states.

Effect of nipradilol, a beta-adrenergic blocker with vasodilating activity, on oxotremorine-induced tremor in mice.

PubMed

Iwata, S; Nomoto, M; Fukuda, T

1996-10-01

The effect of nipradilol, a nonselective beta-adrenergic receptor blocker with nitroglycerin-like vasodilating activity, on oxotremorine-induced tremor was studied in mice. General tremor in mice was elicited by 0.5 mg/kg oxotremorine. The tremor was quantified using a capacitance transducer, then analyzed by a signal processor. The strength of the tremor was expressed in "points". The point values of the tremor (mean +/- SE) in control mice for 5 mg/kg (+/-)-propranolol, 2.5 mg/kg arotinolol, 0.5 mg/kg nipradilol, 1.0 mg/kg nipradilol and 2.5 mg/kg nipradilol were 87 +/- 16, 42 +/- 6, 38 +/- 6, 99 +/- 28, 28 +/- 6 and 31 +/- 7, respectively. The strength of the tremor was reduced by all beta-blockers. Although 1.0 mg/kg nipradilol significantly reduced the tremor, further inhibition of the tremor was not obtained with dosages up to 2.5 mg/kg of the drug. In conclusion, nipradilol was effective for suppressing oxotremorine-induced tremor, as were other beta-blockers.

Gamow-Teller Strength Distributions in {sup 48}Sc by the {sup 48}Ca(p,n) and {sup 48}Ti(n,p) Reactions and Two-Neutrino Double-beta Decay Nuclear Matrix Elements

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

Yako, K.; Sasano, M.; Miki, K.

2009-07-03

The double-differential cross sections for the {sup 48}Ca(p,n) and {sup 48}Ti(n,p) reactions were measured at 300 MeV. A multipole decomposition technique was applied to the spectra to extract the Gamow-Teller (GT) components. The integrated GT strengths up to an excitation energy of 30 MeV in {sup 48}Sc are 15.3+-2.2 and 2.8+-0.3 in the (p,n) and (n,p) spectra, respectively. In the (n,p) spectra additional GT strengths were found above 8 MeV where shell models within the fp shell-model space predict almost no GT strengths, suggesting that the present shell-model description of the nuclear matrix element of the two-neutrino double-beta decay ismore » incomplete.« less

Characterizing components of the Saw Palmetto Berry Extract (SPBE) on prostate cancer cell growth and traction.

PubMed

Scholtysek, Carina; Krukiewicz, Aleksandra A; Alonso, José-Luis; Sharma, Karan P; Sharma, Pal C; Goldmann, Wolfgang H

2009-02-13

Saw Palmetto Berry Extract (SPBE) is applied for prostate health and treatment of urinary tract infections, nonbacterial prostitis and Benign Prostatic Hyperplasia (BPH) in man. An assumption is that SPBE affects tumor cell progression and migration in breast and prostate tissue. In this work, DU-145 cells were used to demonstrate that SPBE and its sterol components, beta-sitosterol and stigmasterol, inhibit prostate cancer growth by increasing p53 protein expression and also inhibit carcinoma development by decreasing p21 and p27 protein expression. In the presence of cholesterol, these features are not only reversed but increased significantly. The results show for the first time the potential of SPBE, beta-sitosterol and stigmasterol as potential anti-tumor agents. Since the protein p53 is also regarded as nuclear matrix protein facilitating actin cytoskeletal binding, 2D tractions were measured. The cell adhesion strength in the presence of SPBE, beta-sitosterol and cholesterol and the observation was that the increase in p53 expression triggered an increase in the intracellular force generation. The results suggest a dual function of p53 in cells.

Stabilization of model beverage cloud emulsions using protein-polysaccharide electrostatic complexes formed at the oil-water interface.

PubMed

Harnsilawat, Thepkunya; Pongsawatmanit, Rungnaphar; McClements, David J

2006-07-26

The potential of utilizing interfacial complexes, formed through the electrostatic interactions of proteins and polysaccharides at oil-water interfaces, to stabilize model beverage cloud emulsions has been examined. These interfacial complexes were formed by mixing charged polysaccharides with oil-in-water emulsions containing oppositely charged protein-coated oil droplets. Model beverage emulsions were prepared that consisted of 0.1 wt % corn oil droplets coated by beta-lactoglobulin (beta-Lg), beta-Lg/alginate, beta-Lg/iota-carrageenan, or beta-Lg/gum arabic interfacial layers (pH 3 or 4). Stable emulsions were formed when the polysaccharide concentration was sufficient to saturate the protein-coated droplets. The emulsions were subjected to variations in pH (from 3 to 7), ionic strength (from 0 to 250 mM NaCl), and thermal processing (from 30 or 90 degrees C), and the influence on their stability was determined. The emulsions containing alginate and carrageenan had the best stability to ionic strength and thermal processing. This study shows that the controlled formation of protein-polysaccharide complexes at droplet surfaces may be used to produce stable beverage emulsions, which may have important implications for industrial applications.

Directionally solidified eutectic gamma plus beta nickel-base superalloys

NASA Technical Reports Server (NTRS)

Jackson, M. R. (Inventor)

1977-01-01

A directionally solidified multivariant eutectic gamma + beta nickel-base superalloy casting having improved high temperature strength and oxidation resistance properties is provided. This comprises a two phase eutectic structure containing, on a weight percent basis, 5.0-15.0 tungsten, 8.5-14.5 aluminum, 0.0-35.0 cobalt and the balance being nickel. Embedded within the gamma phase nickel-base matrix are aligned eutectic beta phase (primarily (NiCo)Al reinforcing lamellae.

Error Correction for the JLEIC Ion Collider Ring

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

Wei, Guohui; Morozov, Vasiliy; Lin, Fanglei

2016-05-01

The sensitivity to misalignment, magnet strength error, and BPM noise is investigated in order to specify design tolerances for the ion collider ring of the Jefferson Lab Electron Ion Collider (JLEIC) project. Those errors, including horizontal, vertical, longitudinal displacement, roll error in transverse plane, strength error of main magnets (dipole, quadrupole, and sextupole), BPM noise, and strength jitter of correctors, cause closed orbit distortion, tune change, beta-beat, coupling, chromaticity problem, etc. These problems generally reduce the dynamic aperture at the Interaction Point (IP). According to real commissioning experiences in other machines, closed orbit correction, tune matching, beta-beat correction, decoupling, andmore » chromaticity correction have been done in the study. Finally, we find that the dynamic aperture at the IP is restored. This paper describes that work.« less

Frontal delta-beta cross-frequency coupling in high and low social anxiety: An index of stress regulation?

PubMed

Poppelaars, Eefje S; Harrewijn, Anita; Westenberg, P Michiel; van der Molen, Melle J W

2018-05-17

Cross-frequency coupling (CFC) between frontal delta (1-4 Hz) and beta (14-30 Hz) oscillations has been suggested as a candidate neural correlate of social anxiety disorder, a disorder characterized by fear and avoidance of social and performance situations. Prior studies have used amplitude-amplitude correlation (AAC) as a CFC measure and hypothesized it as a candidate neural mechanism of affective control. However, using this metric has yielded inconsistent results regarding the direction of CFC, and the functional significance of coupling strength is uncertain. To offer a better understanding of CFC in social anxiety, we compared frontal delta-beta AAC with phase-amplitude coupling (PAC) - a mechanism for information transfer through neural circuits. Twenty high socially anxious (HSA) and 32 low socially anxious (LSA) female undergraduates participated in a social performance task (SPT). Delta-beta PAC and AAC were estimated during the resting state, as well as the anticipation and recovery conditions. Results showed significantly more AAC in LSA than HSA participants during early anticipation, as well as significant values during all conditions in LSA participants only. PAC did not distinguish between LSA and HSA participants, and instead was found to correlate with state nervousness during early anticipation, but in LSA participants only. Together, these findings are interpreted to suggest that delta-beta AAC is a plausible neurobiological index of adaptive stress regulation and can distinguish between trait high and low social anxiety during stress, while delta-beta PAC might be sensitive enough to reflect mild state anxiety in LSA participants.

The effects of 12 weeks of beta-hydroxy-beta-methylbutyrate free acid supplementation on muscle mass, strength, and power in resistance-trained individuals: a randomized, double-blind, placebo-controlled study.

PubMed

Wilson, Jacob M; Lowery, Ryan P; Joy, Jordan M; Andersen, J C; Wilson, Stephanie M C; Stout, Jeffrey R; Duncan, Nevine; Fuller, John C; Baier, Shawn M; Naimo, Marshall A; Rathmacher, John

2014-06-01

Studies utilizing beta-hydroxy-beta-methylbutyrate (HMB) supplementation in trained populations are limited. No long-term studies utilizing HMB free acid (HMB-FA) have been conducted. Therefore, we investigated the effects of 12 weeks of HMB-FA supplementation on skeletal muscle hypertrophy, body composition, strength, and power in trained individuals. We also determined the effects of HMB-FA on muscle damage and performance during an overreaching cycle. A three-phase double-blind, placebo- and diet-controlled randomized intervention study was conducted. Phase 1 was an 8-week-periodized resistance-training program; Phase 2 was a 2-week overreaching cycle; and Phase 3 was a 2-week taper. Muscle mass, strength, and power were examined at weeks 0, 4, 8, and 12 to assess the chronic effects of HMB-FA; and assessment of these, as well as cortisol, testosterone, and creatine kinase (CK) was performed at weeks 9 and 10 of the overreaching cycle. HMB-FA resulted in increased total strength (bench press, squat, and deadlift combined) over the 12-week training (77.1 ± 18.4 vs. 25.3 ± 22.0 kg, p < 0.001); a greater increase in vertical jump power (991 ± 168 vs. 630 ± 167 W, p < 0.001); and increased lean body mass gain (7.4 ± 4.2 vs. 2.1 ± 6.1 kg, p < 0.001) in HMB-FA- and placebo-supplemented groups, respectively. During the overreaching cycle, HMB-FA attenuated increases in CK (-6 ± 91 vs. 277 ± 229 IU/l, p < 0.001) and cortisol (-0.2 ± 2.9 vs. 4.5 ± 1.7 μg/dl, p < 0.003) in the HMB-FA- and placebo-supplemented groups, respectively. These results suggest that HMB-FA enhances hypertrophy, strength, and power following chronic resistance training, and prevents decrements in performance following the overreaching.

Deformation and fracture behavior of titanium-aluminum-niobium-(chromium,molybdenum) alloys with a gamma+sigma microstructure at ambient temperature

NASA Astrophysics Data System (ADS)

Kesler, Michael Steiner

Titanium aluminides are of interest as a candidate material for aerospace turbine applications due to their high strength to weight ratio. gamma-TiAl + alpha2-Ti3Al alloys have recently been incorporated in the low pressure turbine region but their loss of strength near 750C limits their high temperature use. Additions of Nb have been shown to have several beneficial effects in gamma+alpha2 alloys, including enhancements in strength and ductility of the gamma-phase, along with the stabilization of the cubic BCC beta-phase at forging temperatures allowing for thermomechanical processing. In the ternary Ti-Al-Nb system at high Nb-contents above approximately 10at%, there exists a two-phase gamma-TiAl + sigma-Nb2Al region at and above current service temperature for the target application. Limited research has been conducted on the mechanical properties of alloys with this microstructure, though they have demonstrated excellent high temperature strength, superior to that of gamma+alpha2 alloys. Because the sigma-phase does not deform at room temperature, high volume fractions of this phase result in poor toughness and no tensile elongation. Controlling the microstructural morphology by disconnecting the brittle matrix through heat treatments has improved the toughness at room temperature. In this study, attempts to further improve the mechanical properties of these alloys were undertaken by reducing the volume fraction of the sigma-phase and controlling the scale of the gamma+sigma microstructure through the aging of a meta-stable parent phase, the beta- phase, that was quenched-in to room temperature. Additions of beta-stabilizing elements, Cr and Mo, were needed in order to quench-in the beta-phase. The room temperature mechanical properties were evaluated by compression, Vickers' indentation and single edge notch bend tests at room temperature. The formation of the large gamma-laths at prior beta- phase grain boundaries was found to be detrimental to ductility due to strain localization in this coarsened region of the microstructure. Furthermore, samples aged from beta- phase single crystals proved to have excellent combinations of strength and ductility under compression. In the single crystals, microcracking did not develop until much larger plastic strains were reached. Lowering the volume fraction of the sigma-phase proved to enhance the fracture toughness in these alloys. (Full text of this dissertation may be available via the University of Florida Libraries web site. Please check http://www.uflib.ufl.edu/etd.html)

Effect of Oral Beta-Hydroxy-Beta-Methylbutyrate (HMB) Supplementation on Physical Performance in Healthy Old Women Over 65 Years: An Open Label Randomized Controlled Trial.

PubMed

Berton, Linda; Bano, Giulia; Carraro, Sara; Veronese, Nicola; Pizzato, Simona; Bolzetta, Francesco; De Rui, Marina; Valmorbida, Elena; De Ronch, Irene; Perissinotto, Egle; Coin, Alessandra; Manzato, Enzo; Sergi, Giuseppe

2015-01-01

Although older people are particularly liable to sarcopenia, limited research is available on beta-hydroxy-beta-methylbutyrate (HMB) supplementation in this population, particularly in healthy subjects. In this parallel-group, randomized, controlled, open-label trial, we aimed to evaluate whether an oral supplement containing 1.5 g of calcium HMB for 8 weeks could improve physical performance and muscle strength parameters in a group of community-dwelling healthy older women. Eighty healthy women attending a twice-weekly mild fitness program were divided into two equal groups of 40, and 32 of the treated women and 33 control completed the study. We considered a change in the Short Physical Performance Battery (SPPB) score as the primary outcome and changes in the peak torque (PT) isometric and isokinetic strength of the lower limbs, 6-minute walking test (6MWT), handgrip strength and endurance as secondary outcomes. Body composition was assessed with dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computerized tomography (pQCT). The mean difference between the two groups on pre-post change were finally calculated (delta) for each outcome. After 8 weeks, there were no significant differences between the groups’ SPPB, handgrip strength or DXA parameters. The group treated with HMB scored significantly better than the control group for PT isokinetic flexion (delta = 1.56±1.56 Nm; p = 0.03) and extension (delta = 3.32±2.61 Nm; p = 0.03), PT isometric strength (delta = 9.74±3.90 Nm; p = 0.02), 6MWT (delta = 7.67±8.29 m; p = 0.04), handgrip endurance (delta = 21.41±16.28 s; p = 0.02), and muscle density assessed with pQCT. No serious adverse effects were reported in either group. In conclusion, a nutritional supplement containing 1.5 g of calcium HMB for 8 weeks in healthy elderly women had no significant effects on SPPB, but did significantly improve several muscle strength and physical performance parameters. ClinicalTrials.gov NCT02118181.

[Sarcopenia intervention with progressive resistance training and protein nutritional supplements].

PubMed

Palop Montoro, M Victoria; Párraga Montilla, Juan Antonio; Lozano Aguilera, Emilio; Arteaga Checa, Milagros

2015-04-01

Aging is accompanied by changes in body composition among which is a progressive reduction in muscle mass, which may contribute to the development of functional limitations in older people, and where the lifestyle plays a particularly important role. To test the effectiveness of progressive resistance training, protein nutritional supplements and both interventions combined in the treatment of sarcopenia. Review of literature in Medline, ScienceDirect, CINAHL, ISI WOK and PEDro data by combining the descriptors of Medical Subject Headings (MeSH) concerning sarcopenia, progressive resistance training, protein supplements and seniors. A total of 147 studies were found which resistance exercise performed by sessions 45-60 minutes, 2-3 times a week, and 3-4 sets of 8 repetitions, to an increasing intensity. This exercise resulted in increased muscle mass and strength, and increased skeletal muscle protein synthesis and muscle fiber size. Nutritional supplements such as beta-hydroxy-beta-methylbutyrate, leucine and essential amino acids produced gains in muscle mass. All supplements increased strength, especially when combined with resistance exercise. The combination of progressive resistance training and protein included in the diet, either in the form of nutritional supplements, strengthens the impact that each of these interventions can have on the treatment of sarcopenia in the elderly. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Doping in sport: effects, harm and misconceptions.

PubMed

Birzniece, V

2015-03-01

Doping in sport is a widespread problem not just among elite athletes, but even more so in recreational sports. In scientific literature, major emphasis is placed on doping detection, whereas detrimental effects of doping agents on athletes' health are seldom discussed. Androgenic anabolic steroids are well known for their positive effects on muscle mass and strength. Human growth hormone also increases muscle mass, although the majority of that is an increase in extracellular fluid and not the functional muscle mass. In recreational athletes, growth hormone does not have major effect on muscle strength, power or aerobic capacity, but stimulates anaerobic exercise capacity. Erythropoietin administration increases oxygen-carrying capacity of blood improving endurance measures, whereas systemic administration of beta-adrenergic agonists may have positive effect on sprint capacity, and beta-adrenergic antagonists reduce muscle tremor. Thus, there are certain drugs that can improve selective aspects of physical performance. However, most of the doping agents exert serious side-effects, especially when used in combination, at high doses and for a long duration. The extent of long-term health consequences is difficult to predict, but likely to be substantial, especially when gene doping is considered. This review summarises the main groups of doping agents used by athletes, with the main focus on their effects on athletic performance and adverse effects. © 2014 Royal Australasian College of Physicians.

Gamma and Beta Oscillations Define a Sequence of Neurocognitive Modes Present in Odor Processing

PubMed Central

Frederick, Donald E.; Brown, Austin; Brim, Elizabeth; Mehta, Nisarg; Vujovic, Mark

2016-01-01

Olfactory system beta (15–35 Hz) and gamma (40–110 Hz) oscillations of the local field potential in mammals have both been linked to odor learning and discrimination. Gamma oscillations represent the activity of a local network within the olfactory bulb, and beta oscillations represent engagement of a systemwide network. Here, we test whether beta and gamma oscillations represent different cognitive modes using the different demands of go/no-go and two-alternative choice tasks that previously were suggested to favor beta or gamma oscillations, respectively. We reconcile previous studies and show that both beta and gamma oscillations occur in both tasks, with gamma dominating the early odor sampling period (2–4 sniffs) and beta dominating later. The relative power and coherence of both oscillations depend separately on multiple factors within both tasks without categorical differences across tasks. While the early/gamma-associated period occurs in all trials, rats can perform above chance without the later/beta-associated period. Longer sampling, which includes beta oscillations, is associated with better performance. Gamma followed by beta oscillations therefore represents a sequence of cognitive and neural states during odor discrimination, which can be separately modified depending on the demands of a task and odor discrimination. Additionally, fast (85 Hz) and slow (70 Hz) olfactory bulb gamma oscillation sub-bands have been hypothesized to represent tufted and mitral cell networks, respectively (Manabe and Mori, 2013). We find that fast gamma favors the early and slow gamma the later (beta-dominated) odor-sampling period and that the relative contributions of these oscillations are consistent across tasks. SIGNIFICANCE STATEMENT Olfactory system gamma (40–110 Hz) and beta (15–35 Hz) oscillations of the local field potential indicate different neural firing statistics and functional circuits. We show that gamma and beta oscillations occur in stereotyped sequence during odor sampling in associative tasks, with local gamma dominating the first 250 ms of odor sniffing, followed by systemwide beta as behavioral responses are prepared. Oscillations and coupling strength between brain regions are modulated by task, odor, and learning, showing that task features can dramatically adjust the dynamics of a cortical sensory system, which changes state every ∼250 ms. Understanding cortical circuits, even at the biophysical level, depends on careful use of multiple behavioral contexts and stimuli. PMID:27445151

Gamma and Beta Oscillations Define a Sequence of Neurocognitive Modes Present in Odor Processing.

PubMed

Frederick, Donald E; Brown, Austin; Brim, Elizabeth; Mehta, Nisarg; Vujovic, Mark; Kay, Leslie M

2016-07-20

Olfactory system beta (15-35 Hz) and gamma (40-110 Hz) oscillations of the local field potential in mammals have both been linked to odor learning and discrimination. Gamma oscillations represent the activity of a local network within the olfactory bulb, and beta oscillations represent engagement of a systemwide network. Here, we test whether beta and gamma oscillations represent different cognitive modes using the different demands of go/no-go and two-alternative choice tasks that previously were suggested to favor beta or gamma oscillations, respectively. We reconcile previous studies and show that both beta and gamma oscillations occur in both tasks, with gamma dominating the early odor sampling period (2-4 sniffs) and beta dominating later. The relative power and coherence of both oscillations depend separately on multiple factors within both tasks without categorical differences across tasks. While the early/gamma-associated period occurs in all trials, rats can perform above chance without the later/beta-associated period. Longer sampling, which includes beta oscillations, is associated with better performance. Gamma followed by beta oscillations therefore represents a sequence of cognitive and neural states during odor discrimination, which can be separately modified depending on the demands of a task and odor discrimination. Additionally, fast (85 Hz) and slow (70 Hz) olfactory bulb gamma oscillation sub-bands have been hypothesized to represent tufted and mitral cell networks, respectively (Manabe and Mori, 2013). We find that fast gamma favors the early and slow gamma the later (beta-dominated) odor-sampling period and that the relative contributions of these oscillations are consistent across tasks. Olfactory system gamma (40-110 Hz) and beta (15-35 Hz) oscillations of the local field potential indicate different neural firing statistics and functional circuits. We show that gamma and beta oscillations occur in stereotyped sequence during odor sampling in associative tasks, with local gamma dominating the first 250 ms of odor sniffing, followed by systemwide beta as behavioral responses are prepared. Oscillations and coupling strength between brain regions are modulated by task, odor, and learning, showing that task features can dramatically adjust the dynamics of a cortical sensory system, which changes state every ∼250 ms. Understanding cortical circuits, even at the biophysical level, depends on careful use of multiple behavioral contexts and stimuli. Copyright © 2016 the authors 0270-6474/16/367750-18$15.00/0.

Relationships of pancreatic beta-cell function with microalbuminuria and glomerular filtration rate in middle-aged and elderly population without type 2 diabetes mellitus: a Chinese community-based analysis.

PubMed

Fu, Shihui; Zhou, Shanjing; Luo, Leiming; Ye, Ping

2017-01-01

Relationships of pancreatic beta-cell function abnormality with microalbuminuria (MA) and glomerular filtration rate (GFR) may differ by age, ethnicity and accompanied diseases. Previous studies were generally conducted in Western adult patients with type 2 diabetes mellitus (T2DM), and it is uncertain whether pancreatic beta-cell function is associated with MA and GFR in Chinese community-dwelling middle-aged and elderly population without T2DM. We therefore examined the relationships of pancreatic beta-cell function with two indices of renal damage, MA and GFR, in Chinese community-dwelling middle-aged and elderly population without T2DM. This analysis focused on 380 Beijing residents older than 45 years who were free of T2DM and completed the evaluation of pancreatic beta-cell function. Median age was 67 (49-80) years. Levels of triglyceride, diastolic blood pressure and homeostasis model assessment-beta (HOMA-beta) index were positively related to urine microalbumin ( P <0.05 for all). Age, low-density lipoprotein cholesterol levels and HOMA-beta index were inversely correlated with GFR, while high-density lipoprotein cholesterol levels were positively correlated with GFR ( P <0.05 for all). In all three adjustment models, there was a significant positive association between HOMA-beta index and MA; subjects with higher beta-cell function had higher odds of MA ( P <0.05 for all). There was no association between HOMA-beta index and GFR <60 mL/min/1.73 m 2 in any model ( P >0.05 for all). Modeling the pancreatic beta-cell function with different adjusted variables provided the same conclusion of association with MA; beta-cell function was positively associated with MA. Additionally, there was a specific difference in the adjusted associations of pancreatic beta-cell function with MA and GFR <60 mL/min/1.73 m 2 ; beta-cell function was not independently associated with GFR <60 mL/min/1.73 m 2 . This result indicated that abnormal pancreatic beta-cell function plays an important role in the development of MA.

Formation of thermally induced aggregates of the soya globulin beta-conglycinin.

PubMed

Mills, E N; Huang, L; Noel, T R; Gunning, A P; Morris, V J

2001-06-11

The effect of ionic strength (I) on the formation of thermally induced aggregates by the 7S globular storage protein of soya, beta-conglycinin, has been studied using atomic force microscopy. Aggregates were only apparent when I> or =0.1, and had a fibrous appearance, with a height (diameter) of 8-11 nm. At high ionic strength (I=1.0) the aggregates appeared to associate into clumps. When aggregate formation was studied at I=0.2, it was clear that aggregation only began at temperatures above the main thermal transition for the protein at 75 degrees C, as determined by differential scanning calorimetry. This coincided with a small change in secondary structure, as indicated by circular dichroism spectroscopy, suggesting that a degree of unfolding was necessary for aggregation to proceed. Despite prolonged heating the size of the aggregates did not increase indefinitely, suggesting that certain beta-conglycinin isoforms were able to act as chain terminators. At higher protein concentrations (1% w/v) the linear aggregates appeared to form large macroaggregates, which may be the precursors of protein gel formation. The ability of beta-conglycinin to form such distinctive aggregates is discussed in relation to the presence of acidic inserts in certain of the beta-conglycinin subunits, which may play an important role in limiting aggregate length.

Investigation on the Size Effect in Large-Scale Beta-Processed Ti-17 Disks Based on Quantitative Metallography

NASA Astrophysics Data System (ADS)

Zhang, Saifei; Zeng, Weidong; Gao, Xiongxiong; Zhao, Xingdong; Li, Siqing

2017-10-01

The present study investigates the mechanical properties of large-scale beta-processed Ti-17 forgings because of the increasing interest in beta thermal-mechanical processing method for fabricating compressor disks or blisks in aero-engines due to its advantage in damage tolerance performance. Three Ti-17 disks with different weights of 57, 250 and 400 kg were prepared by beta processing techniques firstly for comparative study. The results reveal a significant `size effect' in beta-processed Ti-17 disks, i.e., dependences of high cycle fatigue, tensile properties and fracture toughness of beta-processed Ti-17 disks on disk size (or weight). With increasing disk weight from 57 to 400 kg, the fatigue limit (fatigue strength at 107 cycles, R = -1) was reduced from 583 to 495 MPa, tensile yield strength dropped from 1073 to 1030 MPa, while fracture toughness ( K IC) rose from 70.9 to 95.5 MPaṡm1/2. Quantitative metallography analysis shows that the `size effect' of mechanical properties can be attributed to evident differences between microstructures of the three disk forgings. With increasing disk size, nearly all microstructural components in the basket-weave microstructure, including prior β grain, α layers at β grain boundaries (GB- α) and α lamellas at the interior of the grains, get coarsened to different degrees. Further, the microstructural difference between the beta-processed disks is proved to be the consequence of longer pre-forging soaking time and lower post-forging cooling rate for large disks than small ones. Finally, suggestions are made from the perspective of microstructural control on how to improve mechanical properties of large-scale beta-processed Ti-17 forgings.

Reduced beta connectivity during emotional face processing in adolescents with autism.

PubMed

Leung, Rachel C; Ye, Annette X; Wong, Simeon M; Taylor, Margot J; Doesburg, Sam M

2014-01-01

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social cognition. The biological basis of deficits in social cognition in ASD, and their difficulty in processing emotional face information in particular, remains unclear. Atypical communication within and between brain regions has been reported in ASD. Interregional phase-locking is a neurophysiological mechanism mediating communication among brain areas and is understood to support cognitive functions. In the present study we investigated interregional magnetoencephalographic phase synchronization during the perception of emotional faces in adolescents with ASD. A total of 22 adolescents with ASD (18 males, mean age =14.2 ± 1.15 years, 22 right-handed) with mild to no cognitive delay and 17 healthy controls (14 males, mean age =14.4 ± 0.33 years, 16 right-handed) performed an implicit emotional processing task requiring perception of happy, angry and neutral faces while we recorded neuromagnetic signals. The faces were presented rapidly (80 ms duration) to the left or right of a central fixation cross and participants responded to a scrambled pattern that was presented concurrently on the opposite side of the fixation point. Task-dependent interregional phase-locking was calculated among source-resolved brain regions. Task-dependent increases in interregional beta synchronization were observed. Beta-band interregional phase-locking in adolescents with ASD was reduced, relative to controls, during the perception of angry faces in a distributed network involving the right fusiform gyrus and insula. No significant group differences were found for happy or neutral faces, or other analyzed frequency ranges. Significant reductions in task-dependent beta connectivity strength, clustering and eigenvector centrality (all P <0.001) in the right insula were found in adolescents with ASD, relative to controls. Reduced beta synchronization may reflect inadequate recruitment of task-relevant networks during emotional face processing in ASD. The right insula, specifically, was a hub of reduced functional connectivity and may play a prominent role in the inability to effectively extract emotional information from faces. These findings suggest that functional disconnection in brain networks mediating emotional processes may contribute to deficits in social cognition in this population.

Beta-propellers: associated functions and their role in human diseases.

PubMed

Pons, Tirso; Gómez, Raú; Chinea, Glay; Valencia, Alfonso

2003-03-01

The beta-propeller fold appears as a very fascinating architecture based on four-stranded antiparallel and twisted beta-sheets, radially arranged around a central tunnel. Similar to the alpha/beta-barrel (TIM-barrel) fold, the beta-propeller has a wide range of different functions, and is gaining substantial attention. Some proteins containing beta-propeller domains have been implicated in the pathogenesis of a variety of diseases such as cancer, Alzheimer, Huntington, arthritis, familial hypercholesterolemia, retinitis pigmentosa, osteogenesis, hypertension, and microbial and viral infections. This article reviews some aspects of 3D structure, amino acids sequence regularities, and biological functions of the proteins containing beta-propeller domains. Major emphasis has been laid on beta-propellers whose functions are associated to human diseases. Recent research efforts reported in the fields of protein engineering, drug design, and protein structure-function relationship studies, concerning the beta-propeller architecture, have also been discussed.

Forecasting Sensorimotor Adaptability from Baseline Inter-Trial Correlations

NASA Technical Reports Server (NTRS)

Beaton, K. H.; Bloomberg, J. J.

2014-01-01

One of the greatest challenges surrounding adaptation to the spaceflight environment is the large variability in symptoms, and corresponding functional impairments, from one crewmember to the next. This renders preflight training and countermeasure development difficult, as a "one-size-fits-all" approach is inappropriate. Therefore, it would be highly advantageous to know ahead of time which crewmembers might have more difficulty adjusting to the novel g-levels inherent to spaceflight. Such knowledge could guide individually customized countermeasures, which would enable more efficient use of crew time, both preflight and inflight, and provide better outcomes. The primary goal of this project is to look for a baseline performance metric that can forecast sensorimotor adaptability without exposure to an adaptive stimulus. We propose a novel hypothesis that considers baseline inter-trial correlations, the trial-to-trial fluctuations in motor performance, as a predictor of individual sensorimotor adaptive capabilities. To-date, a strong relationship has been found between baseline inter-trial correlations and adaptability in two oculomotor systems. For this project, we will explore an analogous predictive mechanism in the locomotion system. METHODS: Baseline Inter-trial Correlations: Inter-trial correlations specify the relationships among repeated trials of a given task that transpire as a consequence of correcting for previous performance errors over multiple timescales. We can quantify the strength of inter-trial correlations by measuring the decay of the autocorrelation function (ACF), which describes how rapidly information from past trials is "forgotten." Processes whose ACFs decay more slowly exhibit longer-term inter-trial correlations (longer memory processes), while processes whose ACFs decay more rapidly exhibit shorterterm inter-trial correlations (shorter memory processes). Longer-term correlations reflect low-frequency activity, which is more easily measured in the frequency domain. Therefore, we use the power spectrum (PS), which is the Fourier transform of the ACF, to describe our inter-trial correlations. The decay of the PS yields a straight line on a log-log frequency plot, which we quantify by Beta = - (slope of PS on log-log axes). Hence, Beta is a measure of the strength of inter- trial correlations in the baseline data. Larger Beta values are indicative of longer inter-trial correlations. Experimental Approach: We will begin by performing a retrospective analysis of treadmill-gait adaptation data previously collected by Dr. Bloomberg and colleagues. Specifically, we will quantify the strength of inter-trial correlations in the baseline step cadence and heart rate data and compare it to the locomotor adaptability performance results already described by these investigators. Incorporating these datasets will also allow us to explore the applicability of (and potential limitations surrounding) the use of Beta in forecasting physiological performance. We will also perform a new experiment, in which Beta will be derived from baseline data collected during over-ground (non-treadmill) walking, which will enable us to consider locomotor performance, through the parameter Beta, under the most functionallyrelevant, natural gait condition. This experiment will incorporate two baseline and five post-training over-ground locomotion tests to explore the consistency and potential adaptability of the Beta values themselves. HYPOTHESES: We hypothesize that the strength of baseline inter-trial correlations of step cadence and heart rate will relate to locomotor adaptability. Specifically, we anticipate that individuals who show weaker longer-term inter-trial correlations in baseline step cadence data will be the better adaptors, as step cadence can be modified in real-time (i.e., online corrections are an inherent property of the locomotor system; analogous to results observed in the VOR). Conversely, because heart rate is not altered mid-beat, we expect that individuals who demonstrate stronger longer-term correlations in heart rate will be the better adaptors (analogous to results observed in the saccadic system). CONCLUSIONS: At the conclusion of this project we hope to uncover a baseline predictor of locomotor adaptability. If our hypotheses hold true, our results will demonstrate that the temporal structure of baseline behavioral data contains important information that may aid in forecasting adaptive capacities. The ability to predict such adaptability in the sensorimotor system has significant implications for spaceflight, where astronauts must adjust their motor programs following a change in g-level to retain movement accuracy.

Beta delayed neutrons for nuclear structure and astrophysics

NASA Astrophysics Data System (ADS)

Grzywacz, Robert

2014-09-01

Beta-delayed neutron emission (β xn) is a significant or even dominant decay channel for the majority of very neutron-rich nuclei, especially for those on the r-process path. The recent theoretical models predicts that it may play more significant role then previously expected for astrophysics and this realization instigated a renewed experimental interest in this topic as a part of a larger scope of research on beta-decay strength distribution. Because studies of the decay strength directly probe relevant physics on the microscopic level, energy-resolved measurements of the beta-decay strength distribution is a better test of nuclear models than traditionally used experimental observables like half-lives and neutron branching ratios. A new detector system called the Versatile Array of Neutron Detectors at Low Energy (VANDLE) was constructed to directly address this issue. In its first experimental campaign at the Holifield Radioactive Ion Beam Facility neutron energy spectra in key regions of the nuclear chart were measured: near the shell closures at 78Ni and 132Sn, and for the deformed nuclei near 100Rb. In several cases, unexpectedly intense and concentrated, resonant-like, high-energy neutron structures were observed. These results were interpreted within shell model framework which clearly indicated that these neutron emission is driven by nuclear structure effects and are due to large Gamow-Teller type transition matrix elements. This research was sponsored in part by the National Nuclear Security Administration under the Stewardship Science Academic Alliances program through DOE Cooperative Agreement No. DE-FG52-08NA28552.

The novel acidophilic structure of the killer toxin from halotolerant yeast demonstrates remarkable folding similarity with a fungal killer toxin.

PubMed

Kashiwagi, T; Kunishima, N; Suzuki, C; Tsuchiya, F; Nikkuni, S; Arata, Y; Morikawa, K

1997-01-15

Several strains of yeasts and fungi produce proteinous substances, termed killer toxins, which kill sensitive strains. The SMK toxin, secreted by the halotolerant yeast Pichia farinosa KK1 strain, uniquely exhibits its maximum killer activity under conditions of acidic pH and high salt concentration. The toxin is composed of two distinct subunits, alpha and beta, which tightly interact with each other under acidic conditions. However, they are easily dissociated under neutral conditions and lose the killer activity. The three-dimensional structure of the SMK toxin will provide a better understanding of the mechanism of toxicity of this protein and the cause of its unique pH-dependent stability. Two crystal structures of the SMK toxin have been determined at 1.8 A resolution in different ionic strength conditions. The two subunits, alpha and beta, are jointly folded into an ellipsoidal, single domain structure belonging to the alpha/beta-sandwich family. The folding topology of the SMK toxin is essentially the same as that of the fungal killer toxin, KP4. This shared topology contains two left-handed split betaalphabeta motifs, which are rare in the other proteins. Many acidic residues are clustered at the bottom of the SMK toxin molecule. Some of the carboxyl sidechains interact with each other through hydrogen bonds. The ionic strength difference induces no evident structural change of the SMK toxin except that, in the high ionic strength crystal, a number of sulfate ions are electrostatically bound near the basic residues which are also locally distributed at the bottom of the toxin molecule. The two killer toxins, SMK and KP4, share a unique folding topology which contains a rare structural motif. This observation may suggest that these toxins are evolutionally and/or functionally related. The pH-dependent stability of the SMK toxin is a result of the intensive interactions between the carboxyl groups. This finding is important for protein engineering, for instance, towards stabilization of the toxin molecule in a broader pH range. The present crystallographic study revealed that the structure of the SMK toxin itself is hardly affected by the ionic strength, implying that a high salt concentration affects the sensitivity of the cell against the toxin.

[Mechanical properties of polylactic acid/beta-tricalcium phosphate composite scaffold with double channels based on three-dimensional printing technique].

PubMed

Lian, Qin; Zhuang, Pei; Li, Changhai; Jin, Zhongmin; Li, Dichen

2014-03-01

To improve the poor mechanical strength of porous ceramic scaffold, an integrated method based on three-dimensional (3-D) printing technique is developed to incorporate the controlled double-channel porous structure into the polylactic acid/beta-tricalcium phosphate (PLA/beta-TCP) reinforced composite scaffolds (double-channel composite scaffold) to improve their tissue regeneration capability and the mechanical properties. The designed double-channel structure inside the ceramic scaffold consisted of both primary and secondary micropipes, which parallel but un-connected. The set of primary channels was used for cell ingrowth, while the set of secondary channels was used for the PLA perfusion. Integration technology of 3-D printing technique and gel-casting was firstly used to fabricate the double-channel ceramic scaffolds. PLA/beta-TCP composite scaffolds were obtained by the polymer gravity perfusion process to pour PLA solution into the double-channel ceramic scaffolds through the secondary channel set. Microscope, porosity, and mechanical experiments for the standard samples were used to evaluate the composite properties. The ceramic scaffold with only the primary channel (single-channel scaffold) was also prepared as a control. Morphology observation results showed that there was no PLA inside the primary channels of the double-channel composite scaffolds but a dense interface layer between PLA and beta-TCP obviously formed on the inner wall of the secondary channels by the PLA penetration during the perfusion process. Finite element simulation found that the compressive strength of the double-channel composite scaffold was less than that of the single-channel scaffold; however, mechanical tests found that the maximum compressive strength of the double-channel composite scaffold [(21.25 +/- 1.15) MPa] was higher than that of the single-channel scaffold[ (9.76 +/- 0.64) MPa]. The double-channel composite scaffolds fabricated by 3-D printing technique have controlled complex micropipes and can significantly enhance mechanical properties, which is a promising strategy to solve the contradiction of strength and high-porosity of the ceramic scaffolds for the bone tissue engineering application.

Finite-Temperature Relativistic Time-Blocking Approximation for Nuclear Strength Functions

NASA Astrophysics Data System (ADS)

Wibowo, Herlik; Litvinova, Elena

2017-09-01

This work presents an extension of the relativistic nuclear field theory (RNFT) developed throughout the last decade as an approach to the nuclear many-body problem, based on QHD meson-nucleon Lagrangian and relativistic field theory. The unique feature of RNFT is a consistent connection of the high-energy scale of heavy mesons, the medium-energy range of pion, and the low-energy domain of emergent collective vibrations (phonons). RNFT has demonstrated a very good performance in various nuclear structure calculations across the nuclear chart and, in particular, provides a consistent input for description of the two phases of r-process nucleosynthesis: neutron capture and beta decay. Further inclusion of finite temperature effects presented here allows for an extension of the method to highly excited compound nuclei. The covariant response theory in the relativistic time-blocking approximation (RTBA) is generalized for thermal effects, adopting the Matsubara Green's function formalism to the RNFT framework. The finite-temperature RTBA is implemented numerically to calculate multipole strength functions in medium-mass and heavy nuclei. The obtained results will be discussed in comparison to available experimental data and in the context of possible consequences for astrophysics.

Immune Reactions against Gene Gun Vaccines Are Differentially Modulated by Distinct Dendritic Cell Subsets in the Skin

PubMed Central

Deressa, Tekalign; Strandt, Helen; Florindo Pinheiro, Douglas; Mittermair, Roberta; Pizarro Pesado, Jennifer; Thalhamer, Josef; Hammerl, Peter; Stoecklinger, Angelika

2015-01-01

The skin accommodates multiple dendritic cell (DC) subsets with remarkable functional diversity. Immune reactions are initiated and modulated by the triggering of DC by pathogen-associated or endogenous danger signals. In contrast to these processes, the influence of intrinsic features of protein antigens on the strength and type of immune responses is much less understood. Therefore, we investigated the involvement of distinct DC subsets in immune reactions against two structurally different model antigens, E. coli beta-galactosidase (betaGal) and chicken ovalbumin (OVA) under otherwise identical conditions. After epicutaneous administration of the respective DNA vaccines with a gene gun, wild type mice induced robust immune responses against both antigens. However, ablation of langerin+ DC almost abolished IgG1 and cytotoxic T lymphocytes against betaGal but enhanced T cell and antibody responses against OVA. We identified epidermal Langerhans cells (LC) as the subset responsible for the suppression of anti-OVA reactions and found regulatory T cells critically involved in this process. In contrast, reactions against betaGal were not affected by the selective elimination of LC, indicating that this antigen required a different langerin+ DC subset. The opposing findings obtained with OVA and betaGal vaccines were not due to immune-modulating activities of either the plasmid DNA or the antigen gene products, nor did the differential cellular localization, size or dose of the two proteins account for the opposite effects. Thus, skin-borne protein antigens may be differentially handled by distinct DC subsets, and, in this way, intrinsic features of the antigen can participate in immune modulation. PMID:26030383

Approaches for optimizing the first electronic hyperpolarizability of conjugated organic molecules

NASA Technical Reports Server (NTRS)

Marder, S. R.; Beratan, D. N.; Cheng, L.-T.

1991-01-01

Conjugated organic molecules with electron-donating and -accepting moieties can exhibit large electronic second-order nonlinearities, or first hyperpolarizabilities, beta. The present two-state, four-orbital independent-electron analysis of beta leads to the prediction that its absolute value will be maximized at a combination of donor and acceptor strengths for a given conjugated bridge. Molecular design strategies for beta optimization are proposed which give attention to the energetic manipulations of the bridge states. Experimental results have been obtained which support the validity of this approach.

Method of producing .beta.-spodumene bodies

DOEpatents

Chyung, Kenneth; Day, J. Paul; Holleran, Louis M.; Olszewski, Anthony R.

1999-01-01

Beta-spodumene bodies and method of preparing the bodies that involves providing a uniform plastic batch of inorganic raw materials, organic binder, and vehicle, wherein the inorganic raw materials are composed of, in percent by weight, about 75% to 95% minerals, and about 5% to 25% glass. The batch is formed into a green body that is fired to produce a body composed substantially of beta-spodumene, and having a thermal expansion coefficient of <10.times.10.sup.-7 /.degree.C.(0-800.degree. C.), and a strength of .gtoreq.4 Ksi.

The effect of plant water stress approach on the modelled energy-, water and carbon balance for Mediterranean vegetation; implications for (agro)meteorological applications.

NASA Astrophysics Data System (ADS)

Verhoef, Anne; Egea, Gregorio; Garrigues, Sebastien; Vidale, Pier Luigi; Balan Sarojini, Beena

2017-04-01

Current land surface schemes in many crop, weather and climate models make use of the coupled photosynthesis-stomatal conductance (A-gs) models of plant function to determine the transpiration flux and gross primary productivity. Vegetation exchange is controlled by many environmental factors, and soil moisture control on root water uptake and stomatal function is a primary pathway for feedbacks in sub-tropical to temperate ecosystems. Representations of the above process of soil moisture control on plant function (often referred to as a 'beta' factor) vary among models. This matters because the simulated energy, water and carbon balances are very sensitive to the representation of water stress in these models. Building on Egea et al. (2011) and Verhoef and Egea (2014), we tested a range of 'beta' approaches in a leaf-level A-gs model (compatible with models such as JULES, CHTESSEL, ISBA, CLM), as well as some beta-approaches borrowed from the agronomic, and plant physiological communities (a combined soil-plant hydraulic approach, see Verhoef and Egea, 2014). Root zone soil moisture was allowed to limit plant function via individual routes (via CO2 assimilation, stomatal conductance, or mesophyll conductance) as well as combinations of that. The simulations were conducted for a typical Mediterranean field site (Avignon, France; Garrigues et al., 2015) which provides 14 years of near-continuous measurements of soil moisture and atmospheric driving data. Daytime (8-16 hrs local time) data between April-September were used. This allowed a broad range of atmospheric and soil moisture/vegetation states to be explored. A number of crops and tree types were investigated in this way. We evaluated the effect of choice of beta-function for Mediterranean climates in relation to stomatal conductance, transpiration, photosynthesis, and leaf surface temperature. We also studied the implications for a range of widely used agro-/micro-meteorological indicators such as Bowen ratio and the omega decoupling coefficient (which quantifies the degree of the aerodynamic coupling between a vegetated surface and the atmospheric boundary layer; Jacobs and de Bruin, 1992); and applications (e.g. the use of surface temperature based water stress indices). Results showed that choice of 'beta' function has far-reaching consequences. For certain widely used 'beta'-models the predicted key fluxes and state variables, predominantly compared using kernel density functions, showed considerable 'clumping' around narrow data ranges. This will have implications for the strength of land-surface feedback predicted by these models, and for any agrometeorological applications they are used for. Recommendations as to the most suitable 'beta'-functions, and related parameter sets, for Mediterranean climates were made. References Garrigues, S. et al. (2015) Evaluation of land surface model simulations of evapotranspiration over a 12-year crop succession: impact of soil hydraulic and vegetation properties, Hydrol. Earth Syst. Sci., 19, 3109-3131; Jacobs, C. M. J. and de Bruin, H. A. R. (1992) The sensitivity of regional transpiration to land-surface characteristics: Significance of feedback, J. Climate, 5(7), 683-698; Verhoef, A. and Egea, G. (2014) Agriculture and Forest Meteorology, 191, 22-32; Egea, G., Verhoef, A., and Vidale, P. L. (2011) Agricultural and Forest Meteorology, 151, 1370-1384

Human APC sequesters beta-catenin even in the absence of GSK-3beta in a Drosophila model.

PubMed

Rao, P R; Makhijani, K; Shashidhara, L S

2008-04-10

There have been conflicting reports on the requirement of GSK-3beta-mediated phosphorylation of the tumor suppressor adenomatous polyposis coli (APC) vis-à-vis its ability to bind and degrade beta-catenin. Using a unique combination of loss of function for Shaggy/GSK-3beta and a gain of function for human APC in Drosophila, we show that misexpressed human APC (hAPC) can still sequester Armadillo/beta-catenin. In addition, human APC could suppress gain of Wnt/Wingless phenotypes associated with loss of Shaggy/GSK-3beta activity, suggesting that sequestered Armadillo/beta-catenin is non-functional. Based on these studies, we propose that binding per se of beta-catenin by APC does not require phosphorylation by GSK-3beta.

A comparative evaluation of laser and GTA welds in a high-strength titanium alloy -- Ti-6-22-22S

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

Baeslack, W.A. III; Hurley, J.; Paskell, T.

1994-12-31

Titanium alloy Ti-6Al-2Sn-2Zr-2Mo-2Cr-025Si (hereafter designated Ti-6-22-22S)is an alpha-beta titanium alloy developed for deep hardenability, high strength, intermediate temperature creep resistance, and moderate toughness. As a potential structural material for next-generation aircraft and aerospace systems, the weldability of Ti-6-22-22S has recently become a subject of increasing importance and concern. In the welding of titanium sheet, achieving satisfactory ductility is the principal limitation to alloy weldability, with poor ductility promoted by a coarse beta grain structure in the weld fusion and near-heat-affected zones. Square-butt welds were produced in 1.6 mm thick Ti-6-22-22S sheet using automatic GTA and CO{sub 2} laser welding systems.more » Microstructure analysis and DPH hardness traverses were performed on mounted. polished and etched specimens. Three-point bend and tensile tests were performed on transverse-weld and longitudinal-weld oriented specimens. Microstructure analysis of the laser welds revealed a fine, columnar fusion zone beta grain macrostructure and a fully-martensitic transformed-beta microstructure. Consistent with the microstructural similarities, fusion zone hardnesses of the laser welds were comparable (385 and 390 DPG, respectively) and greater than that of the base metal (330 DPH). In general, laser welds did not exhibit markedly superior ductilities relative to the GTAW, which was attributed to differences in the nature of the intragranular transformed-beta microstructures, being coarser and softer for the GTAW, the response of these as-welded microstructures to heat treatment, and interactions between the transformed-beta microstructure and the beta grain macrostructure.« less

Beta-1-Selective Beta-Blockers and Cognitive Functions in Patients With Coronary Artery Disease: A Cross-Sectional Study.

PubMed

Burkauskas, Julius; Noreikaite, Aurelija; Bunevicius, Adomas; Brozaitiene, Julija; Neverauskas, Julius; Mickuviene, Narseta; Bunevicius, Robertas

2016-01-01

The association between current beta-1-selective beta-blocker use and cognitive function was evaluated in 722 patients with coronary artery disease without dementia. Beta-1-selective beta-blocker use was associated with worse incidental learning independently of sociodemographic characteristics, clinical coronary artery disease severity, and depression/anxiety.

Use of additives to improve microstructures and fracture resistance of silicon nitride ceramics

DOEpatents

Becher, Paul F [Oak Ridge, TN; Lin, Hua-Tay [Oak Ridge, TN

2011-06-28

A high-strength, fracture-resistant silicon nitride ceramic material that includes about 5 to about 75 wt-% of elongated reinforcing grains of beta-silicon nitride, about 20 to about 95 wt-% of fine grains of beta-silicon nitride, wherein the fine grains have a major axis of less than about 1 micron; and about 1 to about 15 wt-% of an amorphous intergranular phase comprising Si, N, O, a rare earth element and a secondary densification element. The elongated reinforcing grains have an aspect ratio of 2:1 or greater and a major axis measuring about 1 micron or greater. The elongated reinforcing grains are essentially isotropically oriented within the ceramic microstructure. The silicon nitride ceramic exhibits a room temperature flexure strength of 1,000 MPa or greater and a fracture toughness of 9 MPa-m.sup.(1/2) or greater. The silicon nitride ceramic exhibits a peak strength of 800 MPa or greater at 1200 degrees C. Also included are methods of making silicon nitride ceramic materials which exhibit the described high flexure strength and fracture-resistant values.

Time-resolved FT EPR and optical spectroscopy study on photooxidation of aliphatic alpha-amino acids in aqueous solutions; electron transfer from amino vs carboxylate functional group.

PubMed

Tarabek, Peter; Bonifacić, Marija; Beckert, Dieter

2006-06-08

Using time-resolved Fourier transform electron paramagnetic resonance, FT EPR, and optical spectroscopy, the photooxidation of glycine, alpha-alanine, alpha-aminoisobutyric acid, and model compounds beta-alanine, methylamine and sodium acetate, by excited triplets of anthraquinone-2,6-disulfonate dianion was studied in aqueous solutions in the pH range 5-13. Anthraquinone radical trianions showing strong emissive spin-polarization (CIDEP) were formed, indicating fast electron transfer from the quenchers to the spin-polarized quinone triplet as the primary reaction. None of the primary radicals formed upon one-electron oxidation of quenchers could be detected at the nanosecond time scale of FT EPR measurements because of their very fast transformation into secondary products. The latter were identified to be decarboxylated alpha-aminoalkyl radicals for alpha-amino acids anions and zwitterions, beta-aminoalkyl radicals for beta-alanine zwitterions, and methyl radicals for acetate anions; corresponding aminyl radicals were the first EPR detectable products from beta-alanine anions and methylamine. Thus, anthraquinone-2,6-disulfonate triplet can take an electron from both NH(2)- and -CO(2)(-) functional groups forming aminium ((+*)NH(2)-) and acyloxyl (-CO(2)(*)) radicals, respectively. Aminium radicals derived from beta-alanine anions and CH(3)-NH(2) stabilize by deprotonation into aminyl radicals, whereas these derived from alpha-amino acids anions are known to suffer ultrafast decarboxylation (tau approximately 10 ps). Analysis of the polarization patterns revealed that decarboxylation from acyloxyl radicals are considerably slower (ns < tau < 0.1 micros). Therefore, in the case of alpha-amino acids, the isoelectronic structures NH(2)-CR(2)-CO(2)(*) and (+*)NH(2)-CR(2)-CO(2)(-) probably do not constitute resonance mesomeric forms of one and the same species and the decarboxylation of aminium radicals is not preceded by the intramolecular carboxylate to amino group electron transfer. Absolute triplet quenching rate constants at zero ionic strength were in the range of 2 x 10(8) to 2 x 10(9) M(-1) s(-1) for R-NH(2) and 2 x 10(7) to 10(8) M(-1) s(-1) for R-CO(2)(-) type of electron donors, reflecting in principle their standard reduction potentials. The strengths of acids: (+)NH(3)-(*)CH(2), (+)NH(3)-(*)C(CH(3))H, and (+)NH(3)-(*)C(CH(3))(2), pK(a) <4, >6, and >7, respectively, were found to be remarkably strongly dependent on alpha-C substitution. The conjugate bases of these alpha-aminoalkyl radicals reduce anthraquinone-2,6-disulfonate dianion ground state with k(sec) = 3 x 10(9) M(-1) s(-1).

COMMERCIALLY PURE TITANIUM-ARSENIC ALLOYS. CONSTITUTION AND ROOM- TEMPERATURE TENSILE PROPERTIES

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

Haynes, R.

1960-02-01

Titanium--arsenic alloys undergo a peritectoid reaction at approximately 900 deg C, in which beta solid solution reacts with a compound, shown to be Ti/sub 4/As, to form alpha phase containing approximately 0.05 wt.% (0.03 at.%) arsenic. Solubility of arsenic in beta phase increases slowly with temperature, reaching a maximum of approximately 1.6 wt.% (1 at.%) at the eutectic temperature, 1351 plus or minus 15 deg C. The eutectic composition is approximately 17.5 wt.% (12 at.%) arsenic. Up to 1 wt.% arsenic exerts only a slight strengthening effect on commercially pure titanium, accompanied by a small loss in ductility. Solution-treatment atmore » temperatures in the beta field increases the strength above the level obtained by annealing in the ( alpha + Ti/ sub 4/As) field and this strengthening can be further enhanced by ageing at 550 deg C. Optimum properties obtainable are similar to those of low-strength titunium alloys. (auth)« less

Catalytic performance of Metal-Organic-Frameworks vs. extra-large pore zeolite UTL in condensation reactions

PubMed Central

Shamzhy, Mariya; Opanasenko, Maksym; Shvets, Oleksiy; Čejka, Jiří

2013-01-01

Catalytic behavior of isomorphously substituted B-, Al-, Ga-, and Fe-containing extra-large pore UTL zeolites was investigated in Knoevenagel condensation involving aldehydes, Pechmann condensation of 1-naphthol with ethylacetoacetate, and Prins reaction of β-pinene with formaldehyde and compared with large-pore aluminosilicate zeolite beta and representative Metal-Organic-Frameworks Cu3(BTC)2 and Fe(BTC). The yield of the target product over the investigated catalysts in Knoevenagel condensation increases in the following sequence: (Al)beta < (Al)UTL < (Ga)UTL < (Fe)UTL < Fe(BTC) < (B)UTL < Cu3(BTC)2 being mainly related to the improving selectivity with decreasing strength of active sites of the individual catalysts. The catalytic performance of Fe(BTC), containing the highest concentration of Lewis acid sites of the appropriate strength is superior over large-pore zeolite (Al)beta and B-, Al-, Ga-, Fe-substituted extra-large pore zeolites UTL in Prins reaction of β-pinene with formaldehyde and Pechmann condensation of 1-naphthol with ethylacetoacetate. PMID:24790940

Synthesis of plastic scintillation microspheres: alpha/beta discrimination.

PubMed

Santiago, L M; Bagán, H; Tarancón, A; Garcia, J F

2014-11-01

Plastic scintillation microspheres (PSm) have been developed as an alternative for liquid scintillation cocktails due to their ability to avoid the mixed waste, besides other strengths in which the possibility for alpha/beta discrimination is included. The aim of this work was to evaluate the capability of PSm containing two combinations of fluorescence solutes (PPO/POPOP and pT/Bis-MSB) and variable amounts of a second organic solvent (naphthalene) to enhance the alpha/beta discrimination. Two commercial detectors with different Pulse Shape Discrimination performances (Quantulus and Triathler) were used to evaluate the alpha/beta discrimination. An optimal discrimination of alpha/beta particles was reached, with very low misclassification values (2% for beta particles and 0.5% for alpha particles), when PSm containing PPO/POPOP and between 0.6 and 2.0 g of naphthalene were evaluated using Triathler and the appropriate programme for data processing. Copyright © 2014 Elsevier Ltd. All rights reserved.

Developmental cardiovascular physiology of the olive ridley sea turtle (Lepidochelys olivacea).

PubMed

Crossley, Dane Alan; Crossley, Janna Lee; Smith, Camilla; Harfush, Martha; Sánchez-Sánchez, Hermilo; Garduño-Paz, Mónica Vanessa; Méndez-Sánchez, José Fernando

2017-09-01

Our understanding of reptilian cardiovascular development and regulation has increased substantially for two species the American alligator (Alligator mississippiensis) and the common snapping turtle (Chelydra serpentina) during the past two decades. However, what we know about cardiovascular maturation in many other species remains poorly understood or unknown. Embryonic sea turtles have been studied to understand the maturation of metabolic function, but these studies have not addressed the cardiovascular system. Although prior studies have been pivotal in characterizing development, and factors that influence it, the development of cardiovascular function, which supplies metabolic function, is unknown in sea turtles. During our investigation we focused on quantifying how cardiovascular morphological and functional parameters change, to provide basic knowledge of development in the olive ridley sea turtle (Lepidochelys olivacea). Embryonic mass, as well as mass of the heart, lungs, liver, kidney, and brain increased during turtle embryo development. Although heart rate was constant during this developmental period, arterial pressure approximately doubled. Further, while embryonic olive ridley sea turtles lacked cholinergic tone on heart rate, there was a pronounced beta adrenergic tone on heart rate that decreased in strength at 90% of incubation. This beta adrenergic tone may be partially originating from the sympathetic nervous system at 90% of incubation, with the majority originating from circulating catecholamines. Data indicates that olive ridley sea turtles share traits of embryonic functional cardiovascular maturation with the American alligator (Alligator mississippiensis) but not the common snapping turtle (Chelydra serpentina). Copyright © 2017 Elsevier Inc. All rights reserved.

Physical, mechanical, and flexural properties of 3 orthodontic wires: an in-vitro study.

PubMed

Juvvadi, Shubhaker Rao; Kailasam, Vignesh; Padmanabhan, Sridevi; Chitharanjan, Arun B

2010-11-01

Understanding the biologic requirements of orthodontic patients requires proper characterization studies of new archwire alloys. The aims of this study were to evaluate properties of wires made of 2 new materials and to compare their properties with those of stainless steel. The sample consisted of 30 straight lengths of 3 types of wires: stainless steel, titanium-molybdenum alloy, and beta-titanium alloy. Eight properties were evaluated: wire dimension, edge bevel, composition, surface characteristics, frictional characteristics, ultimate tensile strength (UTS), modulus of elasticity (E), yield strength (YS), and load deflection characteristics. A toolmaker's microscope was used to measure the edge bevel, and x-ray fluorescence was used for composition analysis. Surface profilometry and scanning electron microscopy were used for surface evaluation. A universal testing machine was used to evaluate frictional characteristics, tensile strength, and 3-point bending. Stainless steel was the smoothest wire; it had the lowest friction and spring-back values and high values for stiffness, E, YS, and UTS. The titanium-molybdenum alloy was the roughest wire; it had high friction and intermediate spring-back, stiffness, and UTS values. The beta-titanium alloy was intermediate for smoothness, friction, and UTS but had the highest spring-back. The beta-titanium alloy with increased UTS and YS had a low E value, suggesting that it would have greater resistance to fracture, thereby overcoming a major disadvantage of titanium-molybdenum alloy wires. The beta-titanium alloy wire would also deliver gentler forces. Copyright © 2010 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Prenatal programming of skeletal development in the offspring: effects of maternal treatment with beta-hydroxy-beta-methylbutyrate (HMB) on femur properties in pigs at slaughter age.

PubMed

Tatara, Marcin R; Sliwa, Ewa; Krupski, Witold

2007-06-01

Alteration in fetal growth and development in response to prenatal environmental conditions such as nutrition has long-term or permanent effects during postnatal life. The aim of this study was to investigate effects of beta-hydroxy-beta-methylbutyrate (HMB) treatment of sows during the last 2 weeks of pregnancy on programming of skeletal development in the offspring. The study was performed on 141 pigs born by 12 sows of Polish Landrace breed. Two weeks before delivery, pregnant sows were divided into two groups. The first group consisted of control sows (N=6) that were treated with placebo. Sows that were orally treated with beta-hydroxy-beta-methylbutyrate (N=6) at the dosage of 0.05 g/kg of body weight per day belonged to the second group. Newborn piglets were weighed and subjected to blood collection for determination of serum levels of growth hormone (GH), insulin-like growth factor-1 (IGF-1), insulin, leptin, glucose and bone alkaline phosphatase (BAP) activity and lipid profile. At the age of 6 months, the piglets were slaughtered, their femur was isolated for analysis and assessment of lean meat content of carcasses was performed. The effects of maternal administration with HMB on skeletal properties in the offspring were evaluated in relation to bone mineral density and geometrical and mechanical properties. Maternal treatment with HMB increased serum levels of GH, IGF-1 and BAP activity in the newborns by 38.0%, 20.0% and 26.0%, respectively (P<0.01). HMB administration significantly increased volumetric bone mineral density of the trabecular and cortical bone of femur in the offspring at the age of 6 months (P<0.001). The weight of femur and geometrical parameters such as cross-sectional area, second moment of inertia, mean relative wall thickness and cortical index were significantly increased after HMB treatment (P<0.05). HMB induced higher values of maximum elastic strength and ultimate strength of femur (P<0.01). Furthermore, lean meat content of carcass was significantly increased in the females born by HMB-treated sows (P<0.05). The obtained results showed that maternal administration with HMB has positive long-term effects on bone tissue and improves volumetric bone mineral density, geometrical and mechanical properties of femur in the offspring. These effects were connected with increased level of GH and IGF-1 in the newborns indicating involvement of improved somatotrophic axis function in prenatal programming of skeletal development in pigs.

Mood states, sympathetic activity, and in vivo beta-adrenergic receptor function in a normal population.

PubMed

Yu, Bum-Hee; Kang, Eun-Ho; Ziegler, Michael G; Mills, Paul J; Dimsdale, Joel E

2008-01-01

The purpose of this study was to examine the relationship between mood states and beta-adrenergic receptor function in a normal population. We also examined if sympathetic nervous system activity is related to mood states or beta-adrenergic receptor function. Sixty-two participants aged 25-50 years were enrolled in this study. Mood states were assessed using the Profile of Mood States (POMS). Beta-adrenergic receptor function was determined using the chronotropic 25 dose isoproterenol infusion test. Level of sympathetic nervous system activity was estimated from 24-hr urine norepinephrine excretion. Higher tension-anxiety, depression-dejection, and anger-hostility were related to decreased beta-adrenergic receptor sensitivity (i.e., higher chronotropic 25 dose values), but tension-anxiety was the only remaining independent predictor of beta-adrenergic receptor function after controlling for age, gender, ethnicity, and body mass index (BMI). Urinary norepinephrine excretion was unrelated to either mood states or beta-adrenergic receptor function. These findings replicate previous reports that anxiety is related to decreased (i.e., desensitized) beta-adrenergic receptor sensitivity, even after controlling for age, gender, ethnicity, and body mass index.

Peripheral and central changes combine to induce motor behavioral deficits in a moderate repetition task.

PubMed

Coq, Jacques-Olivier; Barr, Ann E; Strata, Fabrizio; Russier, Michael; Kietrys, David M; Merzenich, Michael M; Byl, Nancy N; Barbe, Mary F

2009-12-01

Repetitive motion disorders, such as carpal tunnel syndrome and focal hand dystonia, can be associated with tasks that require prolonged, repetitive behaviors. Previous studies using animal models of repetitive motion have correlated cortical neuroplastic changes or peripheral tissue inflammation with fine motor performance. However, the possibility that both peripheral and central mechanisms coexist with altered motor performance has not been studied. In this study, we investigated the relationship between motor behavior changes associated with repetitive behaviors and both peripheral tissue inflammation and cortical neuroplasticity. A rat model of reaching and grasping involving moderate repetitive reaching with negligible force (MRNF) was used. Rats performed the MRNF task for 2 h/day, 3 days/week for 8 weeks. Reach performance was monitored by measuring reach rate/success, daily exposure, reach movement reversals/patterns, reach/grasp phase times, grip strength and grooming function. With cumulative task exposure, reach performance, grip strength and agility declined while an inefficient food retrieval pattern increased. In S1 of MRNF rats, a dramatic disorganization of the topographic forepaw representation was observed, including the emergence of large receptive fields located on both the wrist/forearm and forepaw with alterations of neuronal properties. In M1, there was a drastic enlargement of the overall forepaw map area, and of the cortex devoted to digit, arm-digits and elbow-wrist responses. In addition, unusually low current amplitude evoked digit movements. IL-1 beta and TNF-alpha increased in forearm flexor muscles and tendons of MRNF animals. The increases in IL-1 beta and TNF-alpha negatively correlated with grip strength and amount of current needed to evoke forelimb movements. This study provides strong evidence that both peripheral inflammation and cortical neuroplasticity jointly contribute to the development of chronic repetitive motion disorders.

A de novo designed 11 kDa polypeptide: model for amyloidogenic intrinsically disordered proteins.

PubMed

Topilina, Natalya I; Ermolenkov, Vladimir V; Sikirzhytski, Vitali; Higashiya, Seiichiro; Lednev, Igor K; Welch, John T

2010-07-01

A de novo polypeptide GH(6)[(GA)(3)GY(GA)(3)GE](8)GAH(6) (YE8) has a significant number of identical weakly interacting beta-strands with the turns and termini functionalized by charged amino acids to control polypeptide folding and aggregation. YE8 exists in a soluble, disordered form at neutral pH but is responsive to changes in pH and ionic strength. The evolution of YE8 secondary structure has been successfully quantified during all stages of polypeptide fibrillation by deep UV resonance Raman (DUVRR) spectroscopy combined with other morphological, structural, spectral, and tinctorial characterization. The YE8 folding kinetics at pH 3.5 are strongly dependent on polypeptide concentration with a lag phase that can be eliminated by seeding with a solution of folded fibrillar YE8. The lag phase of polypeptide folding is concentration dependent leading to the conclusion that beta-sheet folding of the 11-kDa amyloidogenic polypeptide is completely aggregation driven.

The influence of drawing parameters on the mechanical properties of two beta-titanium alloys.

PubMed

Shastry, C V; Goldberg, A J

1983-10-01

The total cold reduction and reduction per pass used during the drawing of fine wires affected the mechanical properties of two beta-titanium alloys. Both Ti-11.5Mo-6Zr-4.5Sn and Ti-13V-11Cr-3Al showed increased yield strengths and low moduli of elasticity, which resulted in wires appropriate for orthodontic application.

The lifespan trajectory of neural oscillatory activity in the motor system.

PubMed

Heinrichs-Graham, Elizabeth; McDermott, Timothy J; Mills, Mackenzie S; Wiesman, Alex I; Wang, Yu-Ping; Stephen, Julia M; Calhoun, Vince D; Wilson, Tony W

2018-04-01

Numerous studies connect beta oscillations in the motor cortices to volitional movement, and beta is known to be aberrant in multiple movement disorders. However, the dynamic interplay between these beta oscillations, motor performance, and spontaneous beta power (e.g., during rest) in the motor cortices remains unknown. This study utilized magnetoencephalography (MEG) to investigate these three parameters and their lifespan trajectory in 57 healthy participants aged 9-75 years old. Movement-related beta activity was imaged using a beamforming approach, and voxel time series data were extracted from the peak voxels in the primary motor cortices. Our results indicated that spontaneous beta power during rest followed a quadratic lifespan trajectory, while movement-related beta oscillations linearly increased with age. Follow-on analyses showed that spontaneous beta power and the beta minima during movement, together, significantly predicted task performance above and beyond the effects of age. These data are the first to show lifespan trajectories among measures of beta activity in the motor cortices, and suggest that the healthy brain compensates for age-related increases in spontaneous beta activity by increasing the strength of beta oscillations within the motor cortices which, when successful, enables normal motor performance into later life. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Measurements of 2νββ decay-matrix elements for mass A=64,76 and A=96 through charge-exchange reactions

NASA Astrophysics Data System (ADS)

Grewe, E.-W.; Frekers, D.

2006-07-01

We have used the (d,He2) charge-exchange reaction to obtain GT +-strength distributions in the nuclei 64Cu, 76As and 96Nb. These nuclei are the intermediate nuclei in the second-order perturbative description of the 64Zn double-beta plus ( β+β+) and the 76Ge and 96Zr double-beta minus ( β-β-) decays. By means of charge-exchange reactions on parent and daughter nucleus the double-beta decay matrix element can be deduced. In this contribution the measured excitation energy spectra are presented.

Beta Function Quintessence Cosmological Parameters and Fundamental Constants I: Power and Inverse Power Law Dark Energy Potentials

NASA Astrophysics Data System (ADS)

Thompson, Rodger I.

2018-04-01

This investigation explores using the beta function formalism to calculate analytic solutions for the observable parameters in rolling scalar field cosmologies. The beta function in this case is the derivative of the scalar ϕ with respect to the natural log of the scale factor a, β (φ )=d φ /d ln (a). Once the beta function is specified, modulo a boundary condition, the evolution of the scalar ϕ as a function of the scale factor is completely determined. A rolling scalar field cosmology is defined by its action which can contain a range of physically motivated dark energy potentials. The beta function is chosen so that the associated "beta potential" is an accurate, but not exact, representation of the appropriate dark energy model potential. The basic concept is that the action with the beta potential is so similar to the action with the model potential that solutions using the beta action are accurate representations of solutions using the model action. The beta function provides an extra equation to calculate analytic functions of the cosmologies parameters as a function of the scale factor that are that are not calculable using only the model action. As an example this investigation uses a quintessence cosmology to demonstrate the method for power and inverse power law dark energy potentials. An interesting result of the investigation is that the Hubble parameter H is almost completely insensitive to the power of the potentials and that ΛCDM is part of the family of quintessence cosmology power law potentials with a power of zero.

Beta function quintessence cosmological parameters and fundamental constants - I. Power and inverse power law dark energy potentials

NASA Astrophysics Data System (ADS)

Thompson, Rodger I.

2018-07-01

This investigation explores using the beta function formalism to calculate analytic solutions for the observable parameters in rolling scalar field cosmologies. The beta function in this case is the derivative of the scalar φ with respect to the natural log of the scale factor a, β (φ)=d φ/d ln (a). Once the beta function is specified, modulo a boundary condition, the evolution of the scalar φ as a function of the scale factor is completely determined. A rolling scalar field cosmology is defined by its action which can contain a range of physically motivated dark energy potentials. The beta function is chosen so that the associated `beta potential' is an accurate, but not exact, representation of the appropriate dark energy model potential. The basic concept is that the action with the beta potential is so similar to the action with the model potential that solutions using the beta action are accurate representations of solutions using the model action. The beta function provides an extra equation to calculate analytic functions of the cosmologies parameters as a function of the scale factor that are not calculable using only the model action. As an example, this investigation uses a quintessence cosmology to demonstrate the method for power and inverse power law dark energy potentials. An interesting result of the investigation is that the Hubble parameter H is almost completely insensitive to the power of the potentials and that Λ cold dark matter is part of the family of quintessence cosmology power-law potentials with a power of zero.

FIRST MAGNETIC FIELD MODELS FOR RECENTLY DISCOVERED MAGNETIC {beta} CEPHEI AND SLOWLY PULSATING B STARS

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

Hubrig, S.; Ilyin, I.; Schoeller, M.

2011-01-01

In spite of recent detections of magnetic fields in a number of {beta} Cephei and slowly pulsating B (SPB) stars, their impact on stellar rotation, pulsations, and element diffusion has not yet been sufficiently studied. The reason for this is the lack of knowledge of rotation periods, the magnetic field strength distribution and temporal variability, and the field geometry. New longitudinal field measurements of four {beta} Cephei and candidate {beta} Cephei stars, and two SPB stars were acquired with FORS 2 at the Very Large Telescope. These measurements allowed us to carry out a search for rotation periods and tomore » constrain the magnetic field geometry for four stars in our sample.« less

Use of a mixture of n-dodecyl-beta-D-maltoside and sodium dodecyl sulfate in poly(dimethylsiloxane) microchips to suppress adhesion and promote separation of proteins.

PubMed

Huang, Bo; Kim, Samuel; Wu, Hongkai; Zare, Richard N

2007-12-01

Dynamic modification of poly(dimethylsiloxane) channels using a mixture of n-dodecyl-beta-D-maltoside (DDM) and sodium dodecyl sulfate (SDS) is able to suppress analyte adsorption and control electroosmotic flow (EOF). In this mixed surfactant system, the nonionic surfactant DDM functions as a surface blocking reagent, whereas the anionic surfactant SDS introduces negative charges to the channel walls. Changing the DDM/SDS mixing ratio tunes the surface charge density and the strength of EOF. Using 0.1% (w/v) DDM and 0.03% (w/v) SDS, Alexa Fluor 647 labeled streptavidin can be analyzed according to the charges added by the fluorophores. Protein molecules with different numbers of fluorophores are well resolved. DDM and SDS also form negatively charged mixed micelles, which act as a separation medium. The low critical micellar concentration of DDM/SDS mixed micelles also allows the use of SDS at a nondenaturing concentration, which enables the analysis of proteins in their native state. The immunocomplex between a membrane protein, beta2 adrenergic receptor, and anti-FLAG antibody has been fully separated using 0.1% (w/v) DDM and 0.03% (w/v) SDS. We have also analyzed the composition of light-harvesting protein-chromophore complexes in cyanobacteria.

Assignment of the {beta}-arrestin 1 gene (ARRB1) to human chromosome 11q13

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

Calabrese, G.; Morizio, E.; Palka, G.

1994-11-01

Two types of proteins play a major role in determining homologous desensitization of G-coupled receptors: {beta}-adrenergic receptor kinase ({beta}ARK), which phosphorylates the agonist-occupied receptor, and its functional cofactor, {beta}-arrestin. {beta}ARK is a member of a multigene family, consisting of six known subtypes, which have also been named G-protein-coupled receptor kinases (GRK 1 to 6) due to the apparently unique functional association of such kinases with this receptor family. The gene for {beta}ARK1 has been localized to human chromosome 11q13. The four members of the arrestin/{beta}-arrestin gene family identified so far are arrestin, X-arrestin, {beta}-arrestin 1, and {beta}-arrestin 2. Here themore » authors report the chromosome mapping of the human gene for {beta}-arrestin 1 (ARRB1) to chromosome 11q13 by fluorescence in situ hybridization (FISH). Two-color FISH confirmed that the two genes coding for the functionally related proteins {beta}ARK1 and {beta}arrestin 1 both map to 11q13. 16 refs., 1 fig., 1 tab.« less

Temporal dynamics of sensorimotor integration in speech perception and production: independent component analysis of EEG data

PubMed Central

Jenson, David; Bowers, Andrew L.; Harkrider, Ashley W.; Thornton, David; Cuellar, Megan; Saltuklaroglu, Tim

2014-01-01

Activity in anterior sensorimotor regions is found in speech production and some perception tasks. Yet, how sensorimotor integration supports these functions is unclear due to a lack of data examining the timing of activity from these regions. Beta (~20 Hz) and alpha (~10 Hz) spectral power within the EEG μ rhythm are considered indices of motor and somatosensory activity, respectively. In the current study, perception conditions required discrimination (same/different) of syllables pairs (/ba/ and /da/) in quiet and noisy conditions. Production conditions required covert and overt syllable productions and overt word production. Independent component analysis was performed on EEG data obtained during these conditions to (1) identify clusters of μ components common to all conditions and (2) examine real-time event-related spectral perturbations (ERSP) within alpha and beta bands. 17 and 15 out of 20 participants produced left and right μ-components, respectively, localized to precentral gyri. Discrimination conditions were characterized by significant (pFDR < 0.05) early alpha event-related synchronization (ERS) prior to and during stimulus presentation and later alpha event-related desynchronization (ERD) following stimulus offset. Beta ERD began early and gained strength across time. Differences were found between quiet and noisy discrimination conditions. Both overt syllable and word productions yielded similar alpha/beta ERD that began prior to production and was strongest during muscle activity. Findings during covert production were weaker than during overt production. One explanation for these findings is that μ-beta ERD indexes early predictive coding (e.g., internal modeling) and/or overt and covert attentional/motor processes. μ-alpha ERS may index inhibitory input to the premotor cortex from sensory regions prior to and during discrimination, while μ-alpha ERD may index sensory feedback during speech rehearsal and production. PMID:25071633

Resting-state EEG coupling analysis of amnestic mild cognitive impairment with type 2 diabetes mellitus by using permutation conditional mutual information.

PubMed

Wen, Dong; Bian, Zhijie; Li, Qiuli; Wang, Lei; Lu, Chengbiao; Li, Xiaoli

2016-01-01

This study was meant to explore whether the coupling strength and direction of resting-state electroencephalogram (rsEEG) could be used as an indicator to distinguish the patients of type 2 diabetes mellitus (T2DM) with or without amnestic mild cognitive impairment (aMCI). Permutation conditional mutual information (PCMI) was used to calculate the coupling strength and direction of rsEEG signals between different brain areas of 19 aMCI and 20 normal control (NC) with T2DM on 7 frequency bands: Delta, Theta, Alpha1, Alpha2, Beta1, Beta2 and Gamma. The difference in coupling strength or direction of rsEEG between two groups was calculated. The correlation between coupling strength or direction of rsEEG and score of different neuropsychology scales were also calculated. We have demonstrated that PCMI can calculate effectively the coupling strength and directionality of EEG signals between different brain regions. The significant difference in coupling strength and directionality of EEG signals was found between the patients of aMCI and NC with T2DM on different brain regions. There also existed significant correlation between sex or age and coupling strength or coupling directionality of EEG signals between a few different brain regions from all subjects. The coupling strength or directionality of EEG signals calculated by PCMI are significantly different between aMCI and NC with T2DM. These results showed that the coupling strength or directionality of EEG signals calculated by PCMI might be used as a biomarker in distinguishing the aMCI from NC with T2DM. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Preparation of novel beta-cyclodextrin functionalized monolith and its application in chiral separation.

PubMed

Lv, Yongqin; Mei, Danping; Pan, Xinxin; Tan, Tianwei

2010-09-15

A novel beta-cyclodextrin (beta-CD) functionalized organic polymer monolith was prepared by covalently bonding ethylenediamine-beta-CD (EDA-beta-CD) to poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) (poly(GMA-co-EGDMA)) monolith via ring opening reaction of epoxy groups. SEM characterization was performed to confirm the homogeneity of the monolithic polymer. The resulting monolith was then characterized by DSC and XPS elemental analysis to study the thermal stability of the monolith, and to prove the successful immobilization of beta-CD on the polymer substrate. The beta-CD ligand density of 0.68 mmol g(-1) was obtained for the modified monolith, indicating the high reactivity and efficiency of the EDA-beta-CD modifier. The ethylenediamine-beta-CD functionalized monoliths were used for the chiral separation of ibuprofen racemic mixture and showed promising results. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Structure-Property Correlations in Al-Li Alloy Integrally Stiffened Extrusions

NASA Technical Reports Server (NTRS)

Hales, Stephen J.; Hafley, Robert A.

2001-01-01

The objective of this investigation was to establish the relationship between mechanical property anisotropy, microstructure and crystallographic texture in integrally 'T'-stiffened extruded panels fabricated from the Al-Li alloys 2195, 2098 and 2096. In-plane properties were measured as a function of orientation at two locations in the panels, namely mid-way between (Skin), and directly beneath (Base), the integral 'T' stiffeners. The 2195 extrusion exhibited the best combination of strength and toughness, but was the most anisotropic. The 2098 extrusion exhibited lower strength and comparable toughness, but was more isotropic than 2195. The 2096 extrusion exhibited the lowest strength and poor toughness, but was the most isotropic. All three alloys exhibited highly elongated grain structures and similar location-dependent variations in grain morphology. The textural characteristics comprised a beta + <100> fiber texture, similar to rolled product, in the Skin regions and alpha <111> + <100> fiber texture, comparable to axisymmetric extruded product, in the Base regions. In an attempt to quantitatively correlate texture with yield strength anisotropy, the original 'full constraint' Taylor model and a variant of the 'relaxed constraint' model, explored by Wert et al., were applied to the data. A comparison of the results revealed that the Wert model was consistently more accurate than the Taylor model.

Multifunctional Beta Ti Alloy with Improved Specific Strength

NASA Astrophysics Data System (ADS)

Park, Chan Hee; Hong, Jae-Keun; Lee, Sang Won; Yeom, Jong-Taek

2017-12-01

Gum metals feature properties such as ultrahigh strength, ultralow elastic modulus, superelasticity, and superplasticity. They are composed of elements from Groups 4 and 5 of the periodic table and exist when the valance electron concentration (\\overline{e/a}) is 4.24; the bond order (\\overline{Bo}) is 2.87; and the "d" electron-orbital energy level (\\overline{Md}) is 2.45 eV. Typical compositions include Ti-23Nb-2Zr-0.7Ta-O and Ti-12Ta-9Nb-6Zr-3 V-O, which contain large amounts of heavy Group-5 elements such as Nb and Ta. In the present study, to improve the specific strength of a multifunctional beta Ti alloy, three alloys (Ti-20Nb-5Zr-1Fe-O, Ti-12Zr-10Mo-4Nb-O, and Ti-24Zr-9Cr-3Mo-O) were designed by satisfying the above three requirements while adding Fe, Mo, and Cr, which are not only lightweight but also have strong hardening effects. Microstructural and mechanical property analyses revealed that Ti-20Nb-5Zr-1Fe-O has a 25% higher specific strength than gum metal while maintaining an ultralow elastic modulus.

A thymosin beta15-like peptide promotes intersegmental myotome extension in the chicken embryo.

PubMed

Chankiewitz, Verena; Morosan-Puopolo, Gabriela; Yusuf, Faisal; Rudloff, Stefan; Pröls, Felicitas; Kleff, Veronika; Hofmann, Dietrich Kurt; Brand-Saberi, Beate

2014-03-01

Beta-thymosins constitute a group of small actin-sequestering peptides. These highly conserved peptides are involved in cytoskeleton dynamics and can influence different cell properties such as motility, substrate adhesion, shape and chemotaxis. As a marker for tumour metastasis, the mammalian thymosin beta15 is believed to have an important diagnostic relevance in cancer prognosis, although little is known about its physiological function. In order to study the role of thymosin beta15(avian) in embryogenesis, we cloned the chicken and quail orthologues of thymosin beta15 and used the chicken as a model for vertebrate development. Avian thymosin beta15, the first known non-mammalian thymosin beta15-like gene, encodes a peptide that possesses a cysteine at position one after the methionine which is a significant difference compared to its mammalian counterparts. Thymosin beta15(avian) expression starts at an early stage of development. The expression pattern changes rapidly with development and differs from that of the related thymosin beta4 gene. The most prominent expression domain is seen in developing muscles of limbs and trunk. Gain-of-function experiments revealed that thymosin beta15(avian) has a function in normal myotome development. Ectopic over-expression of thymosin beta15(avian) leads to premature elongation of myotome cells trespassing segment borders. We conclude that thymosin beta15(avian) has a still undescribed function in promoting myocyte elongation.

A combination of cytokines EGF and CNTF protects the functional beta cell mass in mice with short-term hyperglycaemia.

PubMed

Lemper, Marie; De Groef, Sofie; Stangé, Geert; Baeyens, Luc; Heimberg, Harry

2016-09-01

When the beta cell mass or function declines beyond a critical point, hyperglycaemia arises. Little is known about the potential pathways involved in beta cell rescue. As two cytokines, epidermal growth factor (EGF) and ciliary neurotrophic factor (CNTF), restored a functional beta cell mass in mice with long-term hyperglycaemia by reprogramming acinar cells that transiently expressed neurogenin 3 (NGN3), the current study assesses the effect of these cytokines on the functional beta cell mass after an acute chemical toxic insult. Glycaemia and insulin levels, pro-endocrine gene expression and beta cell origin, as well as the role of signal transducer and activator of transcription 3 (STAT3) signalling, were assessed in EGF+CNTF-treated mice following acute hyperglycaemia. The mice were hyperglycaemic 1 day following i.v. injection of the beta cell toxin alloxan, when the two cytokines were applied. One week later, 68.6 ± 4.6% of the mice had responded to the cytokine treatment and increased their insulin(+) cell number to 30% that of normoglycaemic control mice, resulting in restoration of euglycaemia. Although insulin(-) NGN3(+) cells appeared following acute EGF+CNTF treatment, genetic lineage tracing showed that the majority of the insulin(+) cells originated from pre-existing beta cells. Beta cell rescue by EGF+CNTF depends on glycaemia rather than on STAT3-induced NGN3 expression in acinar cells. In adult mice, EGF+CNTF allows the rescue of beta cells in distress when treatment is given shortly after the diabetogenic insult. The rescued beta cells restore a functional beta cell mass able to control normal blood glucose levels. These findings may provide new insights into compensatory pathways activated early after beta cell loss.

First total-absorption spectroscopy measurement on the neutron-rich Cu isotopes

NASA Astrophysics Data System (ADS)

Naqvi, F.; Spyrou, A.; Liddick, S. N.; Larsen, A. C.; Guttormsen, M.; Bleuel, D. L.; Campo, L. C.; Couture, A.; Crider, B. P.; Dombos, A. C.; Ginter, T.; Lewis, R.; Mosby, S.; Perdikakis, G.; Prokop, C. P.; Quinn, S. J.; Renstrom, T.; Rubio, B.; Siem, S.

2015-10-01

The first beta-decay studies of 73-71Cu isotopes using the Total Absorption Spectroscopy (TAS) will be reported. The Cu isotopes have one proton outside the Z = 28 shell and hence are good candidates to probe the single-particle structure in the region.Theories predict weakening of the Z = 28 shell gap due to the tensor interaction between the valence πν single-particle orbitals. Comparing the beta-decay strength distributions in the daughter Zn isotopes to the theoretical calculations will provide a stringent test of the predictions. The experiment was performed at the National Superconducting Cyclotron Laboratory (NSCL) employing the TAS technique with the Summing NaI(Tl) detector, while beta decays were measured in the NSCL beta-counting system. The experimentally obtained total absorption spectra for the neutron-rich Cu isotopes will be presented and the implications of the extracted beta-feeding intensities will be discussed.

Determination of the Alfvén Speed and Plasma-beta Using the Seismology of Sunspot Umbra

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

Cho, I.-H.; Moon, Y.-J.; Nakariakov, V. M.

For 478 centrally located sunspots observed in the optical continuum with Solar Dynamics Observatory /Helioseismic Magnetic Imager, we perform seismological diagnostics of the physical parameters of umbral photospheres. The new technique is based on the theory of slow magnetoacoustic waves in a non-isothermally stratified photosphere with a uniform vertical magnetic field. We construct a map of the weighted frequency of three-minute oscillations inside the umbra and use it for the estimation of the Alfvén speed, plasma-beta, and mass density within the umbra. We find the umbral mean Alfvén speed ranges between 10.5 and 7.5 km s{sup −1} and is negativelymore » correlated with magnetic field strength. The umbral mean plasma-beta is found to range approximately between 0.65 and 1.15 and does not vary significantly from pores to mature sunspots. The mean density ranges between (1–6) × 10{sup −4} kg m{sup −3} and shows a strong positive correlation with magnetic field strength.« less

The interaction of methanol dehydrogenase and cytochrome cL in the acidophilic methylotroph Acetobacter methanolicus.

PubMed Central

Chan, H T; Anthony, C

1991-01-01

The quinoprotein methanol dehydrogenase (MDH) of Acetobacter methanolicus has an alpha 2 beta 2 structure. By contrast with other MDHs, the beta-subunit (approx. 8.5 kDa) does not contain the five lysine residues previously proposed to be involved in ionic interactions with the electron acceptor cytochrome cL. That electrostatic interactions are involved was confirmed by the demonstration that methanol:cytochrome cL oxidoreductase activity was inhibited by high ionic strength (I), the strength of interaction being inversely related to the square root of I. Specific modifiers of arginine residues on MDH inhibited this reaction but not the dye-linked MDH activity. Modification of lysine residues on MDH that altered its charge had no effect on the dye-linked activity but inhibited reaction with cytochrome cL. When the charge was retained on modification of lysine residues, little effect on either activity was observed. Cross-linking experiments confirmed that lysine residues on the alpha-subunit, but not the beta-subunit, are involved in the 'docking' process between the proteins. Images Fig. 4. PMID:1660263

The Effect of Beta Adrenergic Blockade on Ratings of Perceived Exertion.

DTIC Science & Technology

1984-01-01

exrcis is uvo Hughson, et al. (47) investigated the effect of beta blockade using a single, 100-mg oral dose of metoprolol or matched placebo on 12...administered either placebo, propranolol (80 mug) or metoprolol (100 mug) in a double- blind, randomised manner. Before the muscle-strength tests were...The non-selective BABA propranolol and the selective agent metoprolol were compared with a placebo in a double blind cross-over design. Measurements

Transforming growth factor beta-independent shuttling of Smad4 between the cytoplasm and nucleus.

PubMed

Pierreux, C E; Nicolás, F J; Hill, C S

2000-12-01

Smad4 plays a pivotal role in all transforming growth factor beta (TGF-beta) signaling pathways. Here we describe six widely expressed alternatively spliced variants of human Smad4 with deletions of different exons in the linker, the region of Smad4 that separates the two well-conserved MH1 and MH2 domains. All these Smad4 variants form complexes with activated Smad2 and Smad3 and are incorporated into DNA-binding complexes with the transcription factor Fast-1, regardless of the amount of linker they contain. However, sequences encoded by exons 5 to 7 in the linker are essential for transcriptional activation. Most importantly, our observation that different Smad4 isoforms have different subcellular localizations has led us to the identification of a functional CRM1-dependent nuclear export signal in the Smad4 linker and a constitutively active nuclear localization signal in the N-terminal MH1 domain. In the absence of TGF-beta signaling, we conclude that Smad4 is rapidly and continuously shuttling between the nucleus and the cytoplasm, the distribution of Smad4 between the nucleus and the cytoplasm being dictated by the relative strengths of the nuclear import and export signals. We demonstrate that inhibition of CRM1-mediated nuclear export by treatment of cells with leptomycin B results in endogenous Smad4 accumulating very rapidly in the nucleus. Endogenous Smad2 and Smad3 are completely unaffected by leptomycin B treatment, indicating that the nucleocytoplasmic shuttling is specific for Smad4. We propose that, upon TGF-beta signaling, complex formation between Smad4 and activated Smad2 or -3 leads to nuclear accumulation of Smad4 through inhibition of its nuclear export. We demonstrate that after prolonged TGF-beta signaling Smad2 becomes dephosphorylated and Smad2 and Smad4 accumulate back in the cytoplasm.

Beta-diversity of ectoparasites at two spatial scales: nested hierarchy, geography and habitat type.

PubMed

Warburton, Elizabeth M; van der Mescht, Luther; Stanko, Michal; Vinarski, Maxim V; Korallo-Vinarskaya, Natalia P; Khokhlova, Irina S; Krasnov, Boris R

2017-06-01

Beta-diversity of biological communities can be decomposed into (a) dissimilarity of communities among units of finer scale within units of broader scale and (b) dissimilarity of communities among units of broader scale. We investigated compositional, phylogenetic/taxonomic and functional beta-diversity of compound communities of fleas and gamasid mites parasitic on small Palearctic mammals in a nested hierarchy at two spatial scales: (a) continental scale (across the Palearctic) and (b) regional scale (across sites within Slovakia). At each scale, we analyzed beta-diversity among smaller units within larger units and among larger units with partitioning based on either geography or ecology. We asked (a) whether compositional, phylogenetic/taxonomic and functional dissimilarities of flea and mite assemblages are scale dependent; (b) how geographical (partitioning of sites according to geographic position) or ecological (partitioning of sites according to habitat type) characteristics affect phylogenetic/taxonomic and functional components of dissimilarity of ectoparasite assemblages and (c) whether assemblages of fleas and gamasid mites differ in their degree of dissimilarity, all else being equal. We found that compositional, phylogenetic/taxonomic, or functional beta-diversity was greater on a continental rather than a regional scale. Compositional and phylogenetic/taxonomic components of beta-diversity were greater among larger units than among smaller units within larger units, whereas functional beta-diversity did not exhibit any consistent trend regarding site partitioning. Geographic partitioning resulted in higher values of beta-diversity of ectoparasites than ecological partitioning. Compositional and phylogenetic components of beta-diversity were higher in fleas than mites but the opposite was true for functional beta-diversity in some, but not all, traits.

What Is the Role of Nutritional Supplements in Support of Total Hip Replacement and Total Knee Replacement Surgeries? A Systematic Review.

PubMed

Burgess, Louise C; Phillips, Stuart M; Wainwright, Thomas W

2018-06-25

Nutritional supplements can influence outcomes for individuals undergoing major surgery, particularly in older persons whose functional reserve is limited. Accelerating recovery from total hip replacement (THR) and total knee replacement (TKR) may offer significant benefits. Therefore, we explored the role of nutritional supplements in improving recovery following THR and TKR. A systematic review was conducted to source randomized clinical trials that tested nutritional supplements in cohorts of THR or TKR patients. Our search yielded nine relevant trials. Intake of a carbohydrate-containing fluid is reported to improve insulin-like growth factor levels, reduce hunger, nausea, and length of stay, and attenuate the decrease in whole-body insulin sensitivity and endogenous glucose release. Amino acid supplementation is reported to reduce muscle atrophy and accelerate return of functional mobility. One paper reported a suppressive effect of beta-hydroxy beta-methylbutyrate, L-arginine, and L-glutamine supplementation on muscle strength loss following TKR. There is limited evidence for nutritional supplementation in THR and TKR pathways; however, the low risk profile and potential benefits to adjunctive treatment methods, such as exercise programs, suggest nutritional supplements may have a role. Optimizing nutritional status pre-operatively may help manage the surgical stress response, with a particular benefit for undernourished, frail, or elderly individuals.

The effect of microstructure on the fracture toughness of titanium alloys

NASA Technical Reports Server (NTRS)

Vanstone, R. H.; Low, J. R., Jr.; Shannon, J. L., Jr.

1974-01-01

The microstructure of the alpha titanium alloy Ti-5Al-2.5Sn and the metastable beta titanium alloy Beta 3 was examined. The material was from normal and extra low interstitial grade plates which were either air-cooled or furnace-cooled from an annealing treatment. Beta 3 was studied in alpha-aged and omega-aged plates which were heat treated to similar strength levels. Tensile and plane strain fracture toughness tests were conducted at room temperature on the alpha-aged material. The microstructure and fracture mechanisms of alloys were studied using optical metallography, electron microscopy, microprobe analyses, and texture pole figures. Future experiments are described.

Characterization and inhibition of beta-adrenergic receptor kinase in intact myocytes.

PubMed

Laugwitz, K L; Kronsbein, K; Schmitt, M; Hoffmann, K; Seyfarth, M; Schömig, A; Ungerer, M

1997-08-01

beta-Adrenergic receptor kinase (beta ARK) phosphorylates and thereby inactivates agonist-occupied beta-adrenergic receptors (beta AR). beta ARK is thought to play an important role in the regulation of cardiac function. Therefore, we studied beta ARK activation and its inhibition in intact smooth muscle cells and in cardiomyoblasts. beta AR agonist-stimulated translocation of beta ARK was monitored by immunofluorescence labelling with specific antibodies and confocal laser scanning microscopy in DDT-MF 2 hamster smooth muscle cells and in H9c2 rat cardiomyoblasts. In unstimulated cells. beta ARK was mainly located in the cytosol. After beta AR agonist stimulation, the beta ARK signal was partially translocated to the membranes. Liposomal gene transfer of the COOH-terminus of beta ARK ('beta ARKmini') as a beta ARK inhibitor led to functional expression of this protein in both cell lines with high efficiency. Western blots with beta ARK antibodies showed a gene concentration-dependent immunoreactivity of the 'beta ARKmini' protein. 'beta ARKmini'-transfected myocytes demonstrated reduced membrane targeting of the beta ARK immuno-fluorescence signal. Additionally, the effect of 'beta ARKmini' on beta AR-induced desensitization of myocytic cAMP accumulation was investigated. In control cells, desensitization with isoproterenol led to a subsequent reduction of beta AR-induced cAMP accumulation. In 'beta ARKmini'-transfected myocytes, this beta AR-induced desensitization was significantly diminished, whereas normal beta AR-induced cAMP accumulation was unaffected. A gene concentration of 2 micrograms 'beta ARKmini' DNA/100,000 cardiomyoblasts, and of 0.7 microgram 'beta ARKmini' DNA/100,000 DDT-MF2 smooth muscle cells led to approximately 5.9- and approximately 5.6-fold overexpressions of 'beta ARKmini' vs. native beta ARK, respectively. These gene doses proved sufficient to attenuate beta-adrenergic desensitization significantly. (1) beta ARK translocation was evidenced in DDT-MF2 smooth muscle cells and in cardiomyoblasts by confocal laser scanning microscopy. (2) Feasibility of 'beta ARKmini' gene transfer to myocytes was demonstrated, and necessary gene doses for beta ARK inhibition were titered. (3) Overexpression of 'beta ARKmini' functionally interacted with endogenous beta-adrenergic signal transduction, leading to sustained cAMP accumulation after prolonged beta-adrenergic stimulation.

Tensile and creep properties of titanium-vanadium, titanium-molybdenum, and titanium-niobium alloys

NASA Technical Reports Server (NTRS)

Gray, H. R.

1975-01-01

Tensile and creep properties of experimental beta-titanium alloys were determined. Titanium-vanadium alloys had substantially greater tensile and creep strength than the titanium-niobium and titanium-molybdenum alloys tested. Specific tensile strengths of several titanium-vanadium-aluminum-silicon alloys were equivalent or superior to those of commercial titanium alloys to temperatures of 650 C. The Ti-50V-3Al-1Si alloy had the best balance of tensile strength, creep strength, and metallurgical stability. Its 500 C creep strength was far superior to that of a widely used commercial titanium alloy, Ti-6Al-4V, and almost equivalent to that of newly developed commercial titanium alloys.

Both conditional ablation and overexpression of E2 SUMO-conjugating enzyme (UBC9) in mouse pancreatic beta cells result in impaired beta cell function.

PubMed

He, Xiaoyu; Lai, Qiaohong; Chen, Cai; Li, Na; Sun, Fei; Huang, Wenting; Zhang, Shu; Yu, Qilin; Yang, Ping; Xiong, Fei; Chen, Zhishui; Gong, Quan; Ren, Boxu; Weng, Jianping; Eizirik, Décio L; Zhou, Zhiguang; Wang, Cong-Yi

2018-04-01

Post-translational attachment of a small ubiquitin-like modifier (SUMO) to the lysine (K) residue(s) of target proteins (SUMOylation) is an evolutionary conserved regulatory mechanism. This modification has previously been demonstrated to be implicated in the control of a remarkably versatile regulatory mechanism of cellular processes. However, the exact regulatory role and biological actions of the E2 SUMO-conjugating enzyme (UBC9)-mediated SUMOylation function in pancreatic beta cells has remained elusive. Inducible beta cell-specific Ubc9 (also known as Ube2i) knockout (KO; Ubc9 Δbeta ) and transgenic (Ubc9 Tg ) mice were employed to address the impact of SUMOylation on beta cell viability and functionality. Ubc9 deficiency or overexpression was induced at 8 weeks of age using tamoxifen. To study the mechanism involved, we closely examined the regulation of the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) through SUMOylation in beta cells. Upon induction of Ubc9 deficiency, Ubc9 Δbeta islets exhibited a 3.5-fold higher accumulation of reactive oxygen species (ROS) than Ubc9 f/f control islets. Islets from Ubc9 Δbeta mice also had decreased insulin content and loss of beta cell mass after tamoxifen treatment. Specifically, at day 45 after Ubc9 deletion only 40% of beta cell mass remained in Ubc9 Δbeta mice, while 90% of beta cell mass was lost by day 75. Diabetes onset was noted in some Ubc9 Δbeta mice 8 weeks after induction of Ubc9 deficiency and all mice developed diabetes by 10 weeks following tamoxifen treatment. In contrast, Ubc9 Tg beta cells displayed an increased antioxidant ability but impaired insulin secretion. Unlike Ubc9 Δbeta mice, which spontaneously developed diabetes, Ubc9 Tg mice preserved normal non-fasting blood glucose levels without developing diabetes. It was noted that SUMOylation of NRF2 promoted its nuclear expression along with enhanced transcriptional activity, thereby preventing ROS accumulation in beta cells. SUMOylation function is required to protect against oxidative stress in beta cells; this mechanism is, at least in part, carried out by the regulation of NRF2 activity to enhance ROS detoxification. Homeostatic SUMOylation is also likely to be essential for maintaining beta cell functionality.

Osteocalcin protects pancreatic beta cell function and survival under high glucose conditions

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

Kover, Karen, E-mail: kkover@cmh.edu; University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108; Yan, Yun

Diabetes is characterized by progressive beta cell dysfunction and loss due in part to oxidative stress that occurs from gluco/lipotoxicity. Treatments that directly protect beta cell function and survival in the diabetic milieu are of particular interest. A growing body of evidence suggests that osteocalcin, an abundant non-collagenous protein of bone, supports beta cell function and proliferation. Based on previous gene expression data by microarray, we hypothesized that osteocalcin protects beta cells from glucose-induced oxidative stress. To test our hypothesis we cultured isolated rat islets and INS-1E cells in the presence of normal, high, or high glucose ± osteocalcin for up tomore » 72 h. Oxidative stress and viability/mitochondrial function were measured by H{sub 2}O{sub 2} assay and Alamar Blue assay, respectively. Caspase 3/7 activity was also measured as a marker of apoptosis. A functional test, glucose stimulated insulin release, was conducted and expression of genes/protein was measured by qRT-PCR/western blot/ELISA. Osteocalcin treatment significantly reduced high glucose-induced H{sub 2}O{sub 2} levels while maintaining viability/mitochondrial function. Osteocalcin also significantly improved glucose stimulated insulin secretion and insulin content in rat islets after 48 h of high glucose exposure compared to untreated islets. As expected sustained high glucose down-regulated gene/protein expression of INS1 and BCL2 while increasing TXNIP expression. Interestingly, osteocalcin treatment reversed the effects of high glucose on gene/protein expression. We conclude that osteocalcin can protect beta cells from the negative effects of glucose-induced oxidative stress, in part, by reducing TXNIP expression, thereby preserving beta cell function and survival. - Highlights: • Osteocalcin reduces glucose-induced oxidative stress in beta cells. • Osteocalcin preserves beta cell function and survival under stress conditions. • Osteocalcin reduces glucose-induced TXNIP expression in beta cells.« less

Entrainment of prefrontal beta oscillations induces an endogenous echo and impairs memory formation.

PubMed

Hanslmayr, Simon; Matuschek, Jonas; Fellner, Marie-Christin

2014-04-14

Brain oscillations across all frequency bands play a key role for memory formation. Specifically, desynchronization of local neuronal assemblies in the left inferior prefrontal cortex (PFC) in the beta frequency (∼18 Hz) has been shown to be central for encoding of verbal memories. However, it remains elusive whether prefrontal beta desynchronization is causally relevant for memory formation and whether these endogenous beta oscillations can be entrained by external stimulation. By using combined EEG-TMS (transcranial magnetic stimulation), we here address these fundamental questions in human participants performing a word-list learning task. Confirming our predictions, memory encoding was selectively impaired when the left inferior frontal gyrus (IFG) was driven at beta (18.7 Hz) compared to stimulation at other frequencies (6.8 Hz and 10.7 Hz) and to ineffective sham stimulation (18.7 Hz). Furthermore, a sustained oscillatory "echo" in the left IFG, which outlasted the stimulation period by approximately 1.5 s, was observed solely after beta stimulation. The strength of this beta echo was related to memory impairment on a between-subjects level. These results show endogenous oscillatory entrainment effects and behavioral impairment selectively in beta frequency for stimulation of the left IFG, demonstrating an intimate causal relationship between prefrontal beta desynchronization and memory formation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparison of the dynamic fatigue behavior of two monolithic SiC and an Al{sub 2}O{sub 3}/SiC composite

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

Breder, K.; Tennery, V.J.

1994-09-01

Two monolithic silicon carbides, NT230 siliconized SiC from Norton Saint Gobain and sintered {beta}-SiC from Coors, and a silicon carbide particulate reinforced alumina ceramic composite from Lanxide, which all are candidate materials for pressurized heat exchangers in coal-fired power plants have been evaluated. The fast fracture flexure strength was measured as a function of temperature. All candidate materials retained a sufficient strength level up to 1400C. The susceptibility to slow crack growth (SCG) was evaluated by the dynamic fatigue method at 1100C and 1400C. None of the materials exhibited SCG at 1100C. At 1400C the siliconized SiC ceramic showed limitedmore » SCG and the composite ceramic exhibited creep damage when stressed to 50% of fast fracture strength at the intermediate and slow stressing rates. This prevented the evaluation of the SCG properties of this material at 1400C. Fractography supported the mechanical observations and with the exception of the specimens which exhibited creep damage, only the siliconized SiC showed a small SCG damage zone at long times at 1400C.« less

Fragrant dioxane derivatives identify beta1-subunit-containing GABAA receptors.

PubMed

Sergeeva, Olga A; Kletke, Olaf; Kragler, Andrea; Poppek, Anja; Fleischer, Wiebke; Schubring, Stephan R; Görg, Boris; Haas, Helmut L; Zhu, Xin-Ran; Lübbert, Hermann; Gisselmann, Günter; Hatt, Hanns

2010-07-30

Nineteen GABA(A) receptor (GABA(A)R) subunits are known in mammals with only a restricted number of functionally identified native combinations. The physiological role of beta1-subunit-containing GABA(A)Rs is unknown. Here we report the discovery of a new structural class of GABA(A)R positive modulators with unique beta1-subunit selectivity: fragrant dioxane derivatives (FDD). At heterologously expressed alpha1betaxgamma2L (x-for 1,2,3) GABA(A)R FDD were 6 times more potent at beta1- versus beta2- and beta3-containing receptors. Serine at position 265 was essential for the high sensitivity of the beta1-subunit to FDD and the beta1N286W mutation nearly abolished modulation; vice versa the mutation beta3N265S shifted FDD sensitivity toward the beta1-type. In posterior hypothalamic neurons controlling wakefulness GABA-mediated whole-cell responses and GABAergic synaptic currents were highly sensitive to FDD, in contrast to beta1-negative cerebellar Purkinje neurons. Immunostaining for the beta1-subunit and the potency of FDD to modulate GABA responses in cultured hypothalamic neurons was drastically diminished by beta1-siRNA treatment. In conclusion, with the help of FDDs we reveal a functional expression of beta1-containing GABA(A)Rs in the hypothalamus, offering a new tool for studies on the functional diversity of native GABA(A)Rs.

The effect of smoking cessation pharmacotherapies on pancreatic beta cell function

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

Woynillowicz, Amanda K.; Raha, Sandeep; Nicholson, Catherine J.

The goal of our study was to evaluate whether drugs currently used for smoking cessation (i.e., nicotine replacement therapy, varenicline [a partial agonist at nicotinic acetylcholine receptors (nAChR)] and bupropion [which acts in part as a nAChR antagonist]) can affect beta cell function and determine the mechanism(s) of this effect. INS-1E cells, a rat beta cell line, were treated with nicotine, varenicline and bupropion to determine their effects on beta cell function, mitochondrial electron transport chain enzyme activity and cellular/oxidative stress. Treatment of INS-1E cells with equimolar concentrations (1 μM) of three test compounds resulted in an ablation of normalmore » glucose-stimulated insulin secretion by the cells. This disruption of normal beta cell function was associated with mitochondrial dysfunction since all three compounds tested significantly decreased the activity of mitochondrial electron transport chain enzyme activity. These results raise the possibility that the currently available smoking cessation pharmacotherapies may also have adverse effects on beta cell function and thus glycemic control in vivo. Therefore whether or not the use of nicotine replacement therapy, varenicline and bupropion can cause endocrine changes which are consistent with impaired pancreatic function warrants further investigation. -- Highlights: ► Smoking cessation drugs have the potential to disrupt beta cell function in vitro. ► The effects of nicotine, varenicline and bupropion are similar. ► The impaired beta cell function is mediated by mitochondrial dysfunction. ► If similar effects are seen in vivo, these drugs may increase the risk of diabetes.« less

Preparation Of Strong, Dense Potassium Beta''-Alumina Ceramic

NASA Technical Reports Server (NTRS)

Williams, Roger M.; Jeffries-Nakamura, Barbara; Ryan, Margaret A.; O'Connor, Dennis E.; Kisor, Adam; Kikkert, Stanley J.; Losey, Robert; Suitor, Jerry W.

1995-01-01

Improved process for making mechanically strong, dense, phase-pure potassium beta''-alumina solid electrolyte (K-BASE) results in material superior to all previous K-BASE preparations and similar to commercial Na-BASE in strength, phase purity and high-temperature ionic conductivity. Potassium-based alkali-metal thermal-to-electric conversion (AMTEC) cells expected to operate efficiently at lower heat-input temperatures and lower rejection temperatures than sodium-based AMTEC cells, making them appropriate for somewhat different applications.

International Society of Sports Nutrition Position Stand: beta-hydroxy-beta-methylbutyrate (HMB).

PubMed

Wilson, Jacob M; Fitschen, Peter J; Campbell, Bill; Wilson, Gabriel J; Zanchi, Nelo; Taylor, Lem; Wilborn, Colin; Kalman, Douglas S; Stout, Jeffrey R; Hoffman, Jay R; Ziegenfuss, Tim N; Lopez, Hector L; Kreider, Richard B; Smith-Ryan, Abbie E; Antonio, Jose

2013-02-02

Position Statement: The International Society of Sports Nutrition (ISSN) bases the following position stand on a critical analysis of the literature on the use of beta-hydroxy-beta-methylbutyrate (HMB) as a nutritional supplement. The ISSN has concluded the following. 1. HMB can be used to enhance recovery by attenuating exercise induced skeletal muscle damage in trained and untrained populations. 2. If consuming HMB, an athlete will benefit from consuming the supplement in close proximity to their workout. 3. HMB appears to be most effective when consumed for 2 weeks prior to an exercise bout. 4. Thirty-eight mg·kg·BM-1 daily of HMB has been demonstrated to enhance skeletal muscle hypertrophy, strength, and power in untrained and trained populations when the appropriate exercise prescription is utilized. 5. Currently, two forms of HMB have been used: Calcium HMB (HMB-Ca) and a free acid form of HMB (HMB-FA). HMB-FA may increase plasma absorption and retention of HMB to a greater extent than HMB-CA. However, research with HMB-FA is in its infancy, and there is not enough research to support whether one form is superior. 6. HMB has been demonstrated to increase LBM and functionality in elderly, sedentary populations. 7. HMB ingestion in conjunction with a structured exercise program may result in greater declines in fat mass (FM). 8. HMB's mechanisms of action include an inhibition and increase of proteolysis and protein synthesis, respectively. 9. Chronic consumption of HMB is safe in both young and old populations.

International Society of Sports Nutrition Position Stand: beta-hydroxy-beta-methylbutyrate (HMB)

PubMed Central

2013-01-01

Position Statement: The International Society of Sports Nutrition (ISSN) bases the following position stand on a critical analysis of the literature on the use of beta-hydroxy-beta-methylbutyrate (HMB) as a nutritional supplement. The ISSN has concluded the following. 1. HMB can be used to enhance recovery by attenuating exercise induced skeletal muscle damage in trained and untrained populations. 2. If consuming HMB, an athlete will benefit from consuming the supplement in close proximity to their workout. 3. HMB appears to be most effective when consumed for 2 weeks prior to an exercise bout. 4. Thirty-eight mg·kg·BM-1 daily of HMB has been demonstrated to enhance skeletal muscle hypertrophy, strength, and power in untrained and trained populations when the appropriate exercise prescription is utilized. 5. Currently, two forms of HMB have been used: Calcium HMB (HMB-Ca) and a free acid form of HMB (HMB-FA). HMB-FA may increase plasma absorption and retention of HMB to a greater extent than HMB-CA. However, research with HMB-FA is in its infancy, and there is not enough research to support whether one form is superior. 6. HMB has been demonstrated to increase LBM and functionality in elderly, sedentary populations. 7. HMB ingestion in conjunction with a structured exercise program may result in greater declines in fat mass (FM). 8. HMB’s mechanisms of action include an inhibition and increase of proteolysis and protein synthesis, respectively. 9. Chronic consumption of HMB is safe in both young and old populations. PMID:23374455

Extraction and characterization of beta-D-glucan from oat for industrial utilization.

PubMed

Ahmad, Asif; Anjum, Faqir Muhammad; Zahoor, Tahir; Nawaz, Haq; Ahmed, Zaheer

2010-04-01

Oat beta-D-glucan is a valuable functional ingredient having numerous industrial, nutritional and health benefits. Its extraction needs careful attention as extraction process may affect the physiochemical and functional properties of extracted beta-D-glucan. The present study aimed at analyzing the effect of extraction of beta-D-glucan gum pellets from oat cultivar followed by detailed chemical and functional analysis. Enzymatic extraction process resulted in highest yield and recovery. Chemical analysis revealed protein as a dominating impurity. The water binding capacity of the beta-D-glucan ranged between 3.14 and 4.52 g g(-1) of sample. beta-D-Glucan exhibited ideal foaming stability when appropriate extraction technique was used. The viscosity of beta-D-glucan gum ranged between 35.6 and 56.16 cp. The color analysis showed L* value of beta-D-glucan gum pellet ranged between 72.18 and 83.54. Phosphorus, potassium and calcium appeared as major minerals in beta-D-glucan gum whereas iron, manganese and copper appeared as minor minerals. FTIR spectroscopy also confirms the presence of beta-D-glucan, protein and other components in extracted beta-D-glucan gum pellets. Overall, extracted beta-D-glucan showed a good potential for industrial usage. Copyright 2010 Elsevier B.V. All rights reserved.

A comparison of heart function and arrhythmia in clinically asymptomatic patients with beta thalassemia intermedia and beta thalassemia major.

PubMed

Amoozgar, Hamid; Zeighami, Samaneh; Haghpanah, Sezaneh; Karimi, Mehran

2017-01-01

The goal of this study was to compare heart function and arrhythmia in clinically asymptomatic patients with beta thalassemia intermedia and beta thalassemia major. In this cross-sectional study, 60 patients with beta thalassemia major and 60 patients with beta thalassemia intermedia who had clinically no symptoms of arrhythmia and clinically normal heart function were evaluated using 24-hour ambulatory electrocardiogram monitoring and echocardiography. For data analysis SPSS ver.20 software was used. A P-value of less than 0.05 was considered statistically significant. The mean age of the beta thalassemia intermedia patients was 24.18 ± 7.9 years and the mean age in beta thalassemia major was 24.38 ± 7.7 years (P>0.05). Premature atrial contractions (PACs) were observed in 14 (23.3%) patients with beta thalassemia intermedia and in 22 (36.6%) beta thalassemia major patients. Premature ventricular contractions (PVCs) were detected in 8 (13.3%) patients in the beta thalassemia intermediate group and 16 (26.6) patients in the beta thalassemia major group, respectively. The left ventricular diastolic dimension, end-diastolic volume, and stroke volume were significantly higher in beta thalassemia intermedia group (P<0.05). Pulmonary acceleration time as an indicator of pulmonary pressure was lower in beta thalassemia intermedia group. Both atrial and ventricular arrhythmias were more common in the beta thalassemia major group. Higher end-diastolic volume and stroke volume were detected in the beta thalassemia intermedia group. Pulmonary acceleration time was lower in the beta thalassemia intermedia group, which can be an indicator of higher pulmonary pressure.

Inequalities of extended beta and extended hypergeometric functions.

PubMed

Mondal, Saiful R

2017-01-01

We study the log-convexity of the extended beta functions. As a consequence, we establish Turán-type inequalities. The monotonicity, log-convexity, log-concavity of extended hypergeometric functions are deduced by using the inequalities on extended beta functions. The particular cases of those results also give the Turán-type inequalities for extended confluent and extended Gaussian hypergeometric functions. Some reverses of Turán-type inequalities are also derived.

Interleukin 1 beta inhibits synaptic strength and long-term potentiation in the rat CA1 hippocampus.

PubMed

Bellinger, F P; Madamba, S; Siggins, G R

1993-11-19

Cytokines such as interleukin-1 beta (IL-1 beta) are released in the nervous system following inflammation or infection. Recently, IL-1 beta was shown to enhance synaptic inhibitory mechanisms. We therefore investigated the effect of IL-1 beta superfusion on long-term potentiation (LTP), the cellular model of memory and learning, evoked in the CA1 region by tetanic stimulation of the stratum radiatum in the rat hippocampal slice. IL-1 beta (150 pM-1.5 nM) superfused 10 min before tetanic stimulation significantly reduced LTP of the slope of the population excitatory postsynaptic potential (pEPSP) and the population spike (PS) amplitude in CA1 in a concentration-dependent manner. IL-1 beta (1.5 nM) applied for 10 min 1 h before tetanus significantly inhibited LTP of the PS amplitude and pEPSP slope and reduced pEPSP and PS values before tetanus as well, although the PS returned to control values before tetanus. Heat-inactivated IL-1 beta had no effect on pre-tetanus pEPSP or PS values or the induction of LTP. These data demonstrate that IL-1 beta modulates synaptic potentials and reduces LTP. These findings have important implications for the role of IL-1 beta in neuronal disorders following infection, perhaps best exemplified by HIV-1-associated dementia.

Refractive index effects on the oscillator strength and radiative decay rate of 2,3-diazabicyclo[2.2.2]oct-2-ene.

PubMed

Mohanty, Jyotirmayee; Nau, Werner M

2004-01-01

The photophysical properties of 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO) were determined in 15 solvents, two supramolecular hosts (cucurbit[7]uril and beta-cyclodextrin) as well as in the gas phase. The oscillator strength and radiative decay rate of DBO as a function of refractive index i.e. polarizability have been analyzed. The oscillator strength increases by a factor of 10 upon going from the gas phase to the most polarizable carbon disulfide, while the corresponding radiative decay rates increase by a factor of 40. There is a good empirical correlation between the oscillator strength of the weakly allowed n,pi* transition of DBO and the reciprocal bulk polarizability, which can be employed to assess the polarizability of unknown microheterogeneous environments. A satisfactory correlation between the radiative decay rate and the square of the refractive index is also found, as previously documented for chromophores with allowed transitions. However, the correlation improves significantly when the oscillator strength is included in the correlation, which demonstrates the importance of this factor in the Strickler-Berg equation for chromophores with forbidden or weakly allowed transitions, for which the oscillator strength may be strongly solvent dependent. The radiative decay rate of DBO in two supramolecular assemblies has been determined, confirming the very low polarizability inside the cucurbituril cavity, in between perfluorohexane and the gas phase. The fluorescence quantum yield of DBO in the gas phase has been remeasured (5.1 +/- 0.5%) and was found to fall one full order of magnitude below a previously reported value.

Investigation of crystalline morphology in poly (ether ether ketone) using dielectric relaxation spectroscopy

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

Kalika, D.S.; Krishnaswamy, R.K.

1993-12-31

The relaxation behavior of poly (ether ether ketone) [PEEK] has been investigated using dielectric relaxation spectroscopy; the glass-rubber ({alpha}) relaxation and a sub-glass ({beta}) relaxation were examined for the amorphous material and both cold-crystallized and melt-crystallized specimens. Analysis of the data using the Cole-Cole modification of the Debye equation allowed determination of the dielectric relaxation strength and relaxation broadening parameter for both transitions as a function of material crystallization history. The crystallized specimens displayed a positive offset in isochronal loss temperature for both the {alpha} and {beta} relaxations, with the {alpha} relaxation broadened significantly. The measured dipolar response was interpretedmore » using a three-phase morphological model encompassing a crystalline phase, a mobile amorphous phase, and a rigid amorphous phase. Determination of phase fractions based on dipolar mobilization across the glass-rubber relaxation revealed a finite rigid amorphous phase fraction for both the cold-crystallized specimens which was relatively insensitive to thermal history and degree of crystallinity (W{sub RAP}40.20).« less

Electroencephalogram–Electromyography Coupling Analysis in Stroke Based on Symbolic Transfer Entropy

PubMed Central

Gao, Yunyuan; Ren, Leilei; Li, Rihui; Zhang, Yingchun

2018-01-01

The coupling strength between electroencephalogram (EEG) and electromyography (EMG) signals during motion control reflects the interaction between the cerebral motor cortex and muscles. Therefore, neuromuscular coupling characterization is instructive in assessing motor function. In this study, to overcome the limitation of losing the characteristics of signals in conventional time series symbolization methods, a variable scale symbolic transfer entropy (VS-STE) analysis approach was proposed for corticomuscular coupling evaluation. Post-stroke patients (n = 5) and healthy volunteers (n = 7) were recruited and participated in various tasks (left and right hand gripping, elbow bending). The proposed VS-STE was employed to evaluate the corticomuscular coupling strength between the EEG signal measured from the motor cortex and EMG signal measured from the upper limb in both the time-domain and frequency-domain. Results showed a greater strength of the bi-directional (EEG-to-EMG and EMG-to-EEG) VS-STE in post-stroke patients compared to healthy controls. In addition, the strongest EEG–EMG coupling strength was observed in the beta frequency band (15–35 Hz) during the upper limb movement. The predefined coupling strength of EMG-to-EEG in the affected side of the patient was larger than that of EEG-to-EMG. In conclusion, the results suggested that the corticomuscular coupling is bi-directional, and the proposed VS-STE can be used to quantitatively characterize the non-linear synchronization characteristics and information interaction between the primary motor cortex and muscles. PMID:29354091

Local-scale Partitioning of Functional and Phylogenetic Beta Diversity in a Tropical Tree Assemblage.

PubMed

Yang, Jie; Swenson, Nathan G; Zhang, Guocheng; Ci, Xiuqin; Cao, Min; Sha, Liqing; Li, Jie; Ferry Slik, J W; Lin, Luxiang

2015-08-03

The relative degree to which stochastic and deterministic processes underpin community assembly is a central problem in ecology. Quantifying local-scale phylogenetic and functional beta diversity may shed new light on this problem. We used species distribution, soil, trait and phylogenetic data to quantify whether environmental distance, geographic distance or their combination are the strongest predictors of phylogenetic and functional beta diversity on local scales in a 20-ha tropical seasonal rainforest dynamics plot in southwest China. The patterns of phylogenetic and functional beta diversity were generally consistent. The phylogenetic and functional dissimilarity between subplots (10 × 10 m, 20 × 20 m, 50 × 50 m and 100 × 100 m) was often higher than that expected by chance. The turnover of lineages and species function within habitats was generally slower than that across habitats. Partitioning the variation in phylogenetic and functional beta diversity showed that environmental distance was generally a better predictor of beta diversity than geographic distance thereby lending relatively more support for deterministic environmental filtering over stochastic processes. Overall, our results highlight that deterministic processes play a stronger role than stochastic processes in structuring community composition in this diverse assemblage of tropical trees.

Pathways linking regional hyperintensities in the brain and slower gait.

PubMed

Bolandzadeh, Niousha; Liu-Ambrose, Teresa; Aizenstein, Howard; Harris, Tamara; Launer, Lenore; Yaffe, Kristine; Kritchevsky, Stephen B; Newman, Anne; Rosano, Caterina

2014-10-01

Cerebral white matter hyperintensities (WMHs) are involved in the evolution of impaired mobility and executive functions. Executive functions and mobility are also associated. Thus, WMHs may impair mobility directly, by disrupting mobility-related circuits, or indirectly, by disrupting circuits responsible for executive functions. Understanding the mechanisms underlying impaired mobility in late life will increase our capacity to develop effective interventions. To identify regional WMHs most related to slower gait and to examine whether these regional WMHs directly impact mobility, or indirectly by executive functions. Cross-sectional study. Twenty-one WMH variables (i.e., total WMH volume and WMHs in 20 tracts), gait speed, global cognition (Modified Mini-Mental State Examination; 3MS), and executive functions and processing speed (Digit-Symbol Substitution Test; DSST) were assessed. An L1-L2 regularized regression (i.e., Elastic Net model) identified the WMH variables most related to slower gait. Multivariable linear regression models quantified the association between these WMH variables and gait speed. Formal tests of mediation were also conducted. Community-based sample. Two hundred fifty-three adults (mean age: 83years, 58% women, 41% black). Gait speed. In older adults with an average gait speed of 0.91m/sec, total WMH volume, WMHs located in the right anterior thalamic radiation (ATRR) and frontal corpuscallosum (CCF) were most associated with slower gait. There was a >10% slower gait for each standard deviation of WMH in CCF, ATRR or total brain (standardized beta in m/sec [p value]: -0.11 [p=0.046], -0.15 [p=0.007] and -0.14 [p=0.010], respectively). These associations were substantially and significantly attenuated after adjustment for DSST. This effect was stronger for WMH in CCF than for ATRR or total WMH (standardized beta in m/sec [p value]: -0.07 [p=0.190], -0.12 [p=0.024] and -0.10 [p=0.049], respectively). Adjustment for 3MS did not change these associations. The mediation analyses also found that DSST significantly mediated the associations between WMHs and gait speed. Our models were adjusted for age, sex, BMI, quadriceps strength, years of education, standing height, and prevalent hypertension. The impact, direct or indirect, of WMHs on gait speed depended on their location and was mediated by executive function. Thus, multi-faceted interventions targeting executive control functions as well as motor functions, such as balance and strength training, are candidates to the maintenance of mobility across the lifespan. Copyright © 2014 Elsevier Inc. All rights reserved.

Tetraspanin CD151 regulates alpha6beta1 integrin adhesion strengthening

NASA Technical Reports Server (NTRS)

Lammerding, Jan; Kazarov, Alexander R.; Huang, Hayden; Lee, Richard T.; Hemler, Martin E.

2003-01-01

The tetraspanin CD151 molecule associates specifically with laminin-binding integrins, including alpha6beta1. To probe strength of alpha6beta1-dependent adhesion to laminin-1, defined forces (0-1.5 nN) were applied to magnetic laminin-coated microbeads bound to NIH 3T3 cells. For NIH 3T3 cells bearing wild-type CD151, adhesion strengthening was observed, as bead detachment became more difficult over time. In contrast, mutant CD151 (with the C-terminal region replaced) showed impaired adhesion strengthening. Static cell adhesion to laminin-1, and detachment of beads coated with fibronectin or anti-alpha6 antibody were all unaffected by CD151 mutation. Hence, CD151 plays a key role in selectively strengthening alpha6beta1 integrin-mediated adhesion to laminin-1.

MST1 is a key regulator of beta cell apoptosis and dysfunction in diabetes.

PubMed

Ardestani, Amin; Paroni, Federico; Azizi, Zahra; Kaur, Supreet; Khobragade, Vrushali; Yuan, Ting; Frogne, Thomas; Tao, Wufan; Oberholzer, Jose; Pattou, Francois; Conte, Julie Kerr; Maedler, Kathrin

2014-04-01

Apoptotic cell death is a hallmark of the loss of insulin-producing beta cells in all forms of diabetes mellitus. Current treatments fail to halt the decline in functional beta cell mass, and strategies to prevent beta cell apoptosis and dysfunction are urgently needed. Here, we identified mammalian sterile 20-like kinase-1 (MST1) as a critical regulator of apoptotic beta cell death and function. Under diabetogenic conditions, MST1 was strongly activated in beta cells in human and mouse islets and specifically induced the mitochondrial-dependent pathway of apoptosis through upregulation of the BCL-2 homology-3 (BH3)-only protein BIM. MST1 directly phosphorylated the beta cell transcription factor PDX1 at T11, resulting in the latter's ubiquitination and degradation and thus in impaired insulin secretion. MST1 deficiency completely restored normoglycemia, beta cell function and survival in vitro and in vivo. We show MST1 as a proapoptotic kinase and key mediator of apoptotic signaling and beta cell dysfunction and suggest that it may serve as target for the development of new therapies for diabetes.

GARP (LRRC32) is essential for the surface expression of latent TGF-beta on platelets and activated FOXP3+ regulatory T cells.

PubMed

Tran, Dat Q; Andersson, John; Wang, Rui; Ramsey, Heather; Unutmaz, Derya; Shevach, Ethan M

2009-08-11

TGF-beta family members are highly pleiotropic cytokines with diverse regulatory functions. TGF-beta is normally found in the latent form associated with latency-associated peptide (LAP). This latent complex can associate with latent TGFbeta-binding protein (LTBP) to produce a large latent form. Latent TGF-beta is also found on the surface of activated FOXP3(+) regulatory T cells (Tregs), but it is unclear how it is anchored to the cell membrane. We show that GARP or LRRC32, a leucine-rich repeat molecule of unknown function, is critical for tethering TGF-beta to the cell surface. We demonstrate that platelets and activated Tregs co-express latent TGF-beta and GARP on their membranes. The knockdown of GARP mRNA with siRNA prevented surface latent TGF-beta expression on activated Tregs and recombinant latent TGF-beta1 is able to bind directly with GARP. Confocal microscopy and immunoprecipitation strongly support their interactions. The role of TGF-beta on Tregs appears to have dual functions, both for Treg-mediated suppression and infectious tolerance mechanism.

Heterocellular interaction enhances recruitment of {alpha} and {beta}-catenins and ZO-2 into functional gap-junction complexes and induces gap junction-dependant differentiation of mammary epithelial cells

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

Talhouk, Rabih S.; Mroue, Rana; Mokalled, Mayssa

2008-11-01

Gap junctions (GJ) are required for mammary epithelial differentiation. Using epithelial (SCp2) and myoepithelial-like (SCg6) mouse-derived mammary cells, the role of heterocellular interaction in assembly of GJ complexes and functional differentiation ({beta}-casein expression) was evaluated. Heterocellular interaction is critical for {beta}-casein expression, independent of exogenous basement membrane or cell anchoring substrata. Functional differentiation of SCp2, co-cultured with SCg6, is more sensitive to GJ inhibition relative to homocellular SCp2 cultures differentiated by exogenous basement membrane. Connexin (Cx)32 and Cx43 levels were not regulated across culture conditions; however, GJ functionality was enhanced under differentiation-permissive conditions. Immunoprecipitation studies demonstrated association of junctional complexmore » components ({alpha}-catenin, {beta}-catenin and ZO-2) with Cx32 and Cx43, in differentiation conditions, and additionally with Cx30 in heterocellular cultures. Although {beta}-catenin did not shuttle between cadherin and GJ complexes, increased association between connexins and {beta}-catenin in heterocellular cultures was observed. This was concomitant with reduced nuclear {beta}-catenin, suggesting that differentiation in heterocellular cultures involves sequestration of {beta}-catenin in GJ complexes.« less

Factors Affecting the Strength and Toughness of Ultra-Low Carbon Steel Weld Metal

DTIC Science & Technology

1999-12-01

ferrite or martensite due to its strength and toughness, respectively. Ferrite with non-aligned second phase is associated with ferrite completely...with interphase carbides and pearlite. It forms at high temperatures and slow cooling rates than ferrite with secondary phase or martensite . It is...therefore termed a diffusionless transformation . In low carbon steels, the transformation occurs from fccy (austenite) to beta’ ( martensite ),

Functional overload increases beta-MHC promoter activity in rodent fast muscle via the proximal MCAT (betae3) site.

PubMed

Giger, Julia M; Haddad, Fadia; Qin, Anqi X; Baldwin, Kenneth M

2002-03-01

Functional overload (OL) of the rat plantaris muscle by the removal of synergistic muscles induces a shift in the myosin heavy chain (MHC) isoform expression profile from the fast isoforms toward the slow type I, or, beta-MHC isoform. Different length rat beta-MHC promoters were linked to a firefly luciferase reporter gene and injected in control and OL plantaris muscles. Reporter activities of -3,500, -914, -408, and -215 bp promoters increased in response to 1 wk of OL. The smallest -171 bp promoter was not responsive to OL. Mutation analyses of putative regulatory elements within the -171 and -408 bp region were performed. The -408 bp promoters containing mutations of the betae1, distal muscle CAT (MCAT; betae2), CACC, or A/T-rich (GATA), were still responsive to OL. Only the proximal MCAT (betae3) mutation abolished the OL response. Gel mobility shift assays revealed a significantly higher level of complex formation of the betae3 probe with nuclear protein from OL plantaris compared with control plantaris. These results suggest that the betae3 site functions as a putative OL-responsive element in the rat beta-MHC gene promoter.

Stability of human interferon-beta 1: oligomeric human interferon-beta 1 is inactive but is reactivated by monomerization.

PubMed

Utsumi, J; Yamazaki, S; Kawaguchi, K; Kimura, S; Shimizu, H

1989-10-05

Human interferon-beta 1 is extremely stable is a low ionic strength solution of pH 2 such as 10 mM HCl at 37 degrees C. However, the presence of 0.15 M NaCl led to a remarkable loss of antiviral activity. The molecular-sieve high-performance liquid chromatography revealed that, whereas completely active human interferon-beta 1 eluted as a 25 kDa species (monomeric form), the inactivated preparation eluted primarily as a 90 kDa species (oligomeric form). The specific activity (units per mg protein) of the oligomeric form was approx. 10% of that of the monomeric form. This observation shows that oligomeric human interferon-beta 1 is apparently in an inactive form. When the oligomeric eluate was resolved by polyacrylamide gel containing sodium dodecyl sulphate (SDS), it appeared to be monomeric under non-reducing conditions. Monomerization of the oligomeric human interferon-beta 1 by treatment with 1% SDS, fully regenerated its antiviral activity. These results suggest that the inactivation of the human interferon-beta 1 preparation was caused by its oligomerization via hydrophobic interactions without the formation of intermolecular disulphide bonds. These oligomers can be dissociated by SDS to restore biological activity.

Function and CO binding properties of the NiFe complex in carbon monoxide dehydrogenase from Clostridium thermoaceticum.

PubMed

Shin, W; Lindahl, P A

1992-12-29

Adding 1,10-phenanthroline to carbon monoxide dehydrogenase from Clostridium thermoaceticum results in the complete loss of the NiFeC EPR signal and the CO/acetyl-CoA exchange activity. Other EPR signals characteristic of the enzyme (the gav = 1.94 and gav = 1.86 signals) and the CO oxidation activity are completely unaffected by the 1,10-phenanthroline treatment. This indicates that there are two catalytic sites on the enzyme; the NiFe complex is required for catalyzing the exchange and acetyl-CoA synthase reactions, while some other site is responsible for CO oxidation. The strength of CO binding to the NiFe complex was examined by titrating dithionite-reduced enzyme with CO. During the titration, the NiFeC EPR signal developed to a final spin intensity of 0.23 spin/alpha beta. The resulting CO titration curve (NiFeC spins/alpha beta vs CO pha beta) was fitted using two reactions: binding of CO to the oxidized NiFe complex, and reduction of the CO-bound species to a form that exhibits the NiFeC signal. Best fits yielded apparent binding constants between 6000 and 14,000 M-1 (Kd = 70-165 microM). This sizable range is due to uncertainty whether CO binds to all or only a small fraction (approximately 23%) of the NiFe complexes. Reduction of the CO-bound NiFe complex is apparently required to activate it for catalysis. The electron used for this reduction originates from the CO oxidation site, suggesting that delivery of a low-potential electron to the CO-bound NiFe complex is the physiological function of the CO oxidation reaction catalyzed by this enzyme.

[Renal handling of beta2 microglobulin. Its significance in carriers of adolescent nephronophthisis (NPH3)].

PubMed

Fernández, Carmen; Araque, Carolina; Méndez, Jorge; Angulo, Luisa; Fargier, Bernardo

2007-06-01

The adolescent nephronophthisis (NPH3) is a variant of the nephronophthisis. In Venezuela, one to three patients have been registered each year, all of them belonging to the same family tree. The objective of this study was to evaluate the function of the proximal convoluted tubule in NPHP3 carriers; using the beta2M as biological marker. Eight carriers, 7 heterozygotes and 1 homozygote, with normal renal function were compared with a 10 healthy subjects (control group). Serum beta2 microglobulin (beta2M), urinary beta2M, the quotient urinary beta2M/urinary creatinine and the beta2M fractional excretion were determinated. The filtered beta2M and the percentage of reabsortion were calculated. We observed an increase in the plasmatic concentration of beta2M but not related with a decrease of the glomerular filtration. The urinary beta2M, the beta2M/urinary creatinine relation and the fractional excretion of beta2M were normal. The filtered load of beta2M was elevated without increase in the excretion or percentage of reabsortion. We conclude that in our group of NPH3 carriers, functional changes in the proximal convoluted tubule, when measured by urinary excretion of beta2M, were absent. This finding suggests the existence of other mechanism of uptake or degradation of the substance in the proximal convoluted tubule, which have yet to be elucidated.

Nickel hydroxide electrode. 3: Thermogravimetric investigations of nickel (II) hydroxides

NASA Technical Reports Server (NTRS)

Dennstedt, W.; Loeser, W.

1982-01-01

Water contained in Ni hydroxide influences its electrochemical reactivity. The water content of alpha and beta Ni hydroxides is different with respect to the amount and bond strength. Thermogravimetric experiments show that the water of the beta Ni hydroxides exceeding the stoichiometric composition is completely removed at 160 deg. The water contained in the interlayers of the beta hydroxide, however, is removed only at higher temperatures, together with the water originating from the decomposition of the hydroxide. These differences are attributed to the formation of II bonds within the interlayers and between interlayers and adjacent main layers. An attempt is made to explain the relations between water content and the oxidizability of the Ni hydroxides.

Improved silicon carbide for advanced heat engines

NASA Technical Reports Server (NTRS)

Whalen, T. J.; Winterbottom, W. L.

1986-01-01

Work performed to develop silicon carbide materials of high strength and to form components of complex shape and high reliability is described. A beta-SiC powder and binder system was adapted to the injection molding process and procedures and process parameters developed capable of providing a sintered silicon carbide material with improved properties. The initial effort has been to characterize the baseline precursor materials (beta silicon carbide powder and boron and carbon sintering aids), develop mixing and injection molding procedures for fabricating test bars, and characterize the properties of the sintered materials. Parallel studies of various mixing, dewaxing, and sintering procedures have been carried out in order to distinguish process routes for improving material properties. A total of 276 MOR bars of the baseline material have been molded, and 122 bars have been fully processed to a sinter density of approximately 95 percent. The material has a mean MOR room temperature strength of 43.31 ksi (299 MPa), a Weibull characteristic strength of 45.8 ksi (315 MPa), and a Weibull modulus of 8.0. Mean values of the MOR strengths at 1000, 1200, and 14000 C are 41.4, 43.2, and 47.2 ksi, respectively. Strength controlling flaws in this material were found to consist of regions of high porosity and were attributed to agglomerates originating in the initial mixing procedures. The mean stress rupture lift at 1400 C of five samples tested at 172 MPa (25 ksi) stress was 62 hours and at 207 MPa (30 ksi) stress was 14 hours. New fluid mixing techniques have been developed which significantly reduce flaw size and improve the strength of the material. Initial MOR tests indicate the strength of the fluid-mixed material exceeds the baseline property by more than 33 percent.

Three-Dimensional Bioreactor Technologies for the Cocultivation of Human Mesenchymal Stem/Stromal Cells and Beta Cells

PubMed Central

Petry, Florian; Weidner, Tobias; Salzig, Denise

2018-01-01

Diabetes is a prominent health problem caused by the failure of pancreatic beta cells. One therapeutic approach is the transplantation of functional beta cells, but it is difficult to generate sufficient beta cells in vitro and to ensure these cells remain viable at the transplantation site. Beta cells suffer from hypoxia, undergo apoptosis, or are attacked by the host immune system. Human mesenchymal stem/stromal cells (hMSCs) can improve the functionality and survival of beta cells in vivo and in vitro due to direct cell contact or the secretion of trophic factors. Current cocultivation concepts with beta cells are simple and cannot exploit the favorable properties of hMSCs. Beta cells need a three-dimensional (3D) environment to function correctly, and the cocultivation setup is therefore more complex. This review discusses 3D cultivation forms (aggregates, capsules, and carriers) for hMSCs and beta cells and strategies for large-scale cultivation. We have determined process parameters that must be balanced and considered for the cocultivation of hMSCs and beta cells, and we present several bioreactor setups that are suitable for such an innovative cocultivation approach. Bioprocess engineering of the cocultivation processes is necessary to achieve successful beta cell therapy. PMID:29731775

Environmentally Assisted Cracking of High Strength Beta Titanium Alloys

DTIC Science & Technology

1993-11-01

financially supported by the Virginia Center for Innovative Technology TDC on Electrochemical Science and Engineering (Grant CIT- TDC -88-01) and by the Office...Material Behayir, N.R. Moody and A.W. Thompson, eds., TMS -AIME, Warrendale, PA, p. 891(1990). 18. 0. Vosikovsky, J.Tt. EyaL, Vol. 6, p. 175 (1978). 19...acknowledged. 3 23 REFERENCES 1. Beta Titanium Alloys in the 80’s R.R. Boyer and H.W. Rosenberg, eds., TMS -AIME,3 Warrendale, PA. pp. 209-229, 1983. 2

An acoustic method for predicting relative strengths of cohesive sediment deposits

NASA Astrophysics Data System (ADS)

Reed, A. H.; Sanders, W. M.

2017-12-01

Cohesive sediment dynamics are fundamentally determined by sediment mineralogy, organic matter composition, ionic strength of water, and currents. These factors work to bind the cohesive sediments and to determine depositional rates. Once deposited the sediments exhibit a nonlinear response to stress and they develop increases in shear strength. Shear strength is critically important in resuspension, transport, creep, and failure predictions. Typically, shear strength is determined by point measurements, both indirectly from free-fall penetrometers or directly on cores with a shear vane. These values are then used to interpolate over larger areas. However, the remote determination of these properties would provide continuos coverage, yet it has proven difficult with sonar systems. Recently, findings from an acoustic study on cohesive sediments in a laboratory setting suggests that cohesive sediments may be differentiated using parametric acoustics; this method pulses two primary frequencies into the sediment and the resultant difference frequency is used to determine the degree of acoustic nonlinearity within the sediment. In this study, two marine clay species, kaolinite and montmorillonite, and two biopolymers, guar gum and xanthan gum were mixed to make nine different samples. The samples were evaluated in a parametric acoustic measurement tank. From the parametric acoustic measurements, the quadratic nonlinearity coefficient (beta) was determined. beta was correlated with the cation exchange capacity (CEC), an indicator of shear strength. The results indicate that increased acoustic nonlinearity correlates with increased CEC. From this work, laboratory measurements indicate that this correlation may be used evaluate geotechnical properties of cohesive sediments and may provide a means to predict sediment weakness in subaqueous environments.

Analytical functions for beta and gamma absorbed fractions of iodine-131 in spherical and ellipsoidal volumes.

PubMed

Mowlavi, Ali Asghar; Fornasier, Maria Rossa; Mirzaei, Mohammd; Bregant, Paola; de Denaro, Mario

2014-10-01

The beta and gamma absorbed fractions in organs and tissues are the important key factors of radionuclide internal dosimetry based on Medical Internal Radiation Dose (MIRD) approach. The aim of this study is to find suitable analytical functions for beta and gamma absorbed fractions in spherical and ellipsoidal volumes with a uniform distribution of iodine-131 radionuclide. MCNPX code has been used to calculate the energy absorption from beta and gamma rays of iodine-131 uniformly distributed inside different ellipsoids and spheres, and then the absorbed fractions have been evaluated. We have found the fit parameters of a suitable analytical function for the beta absorbed fraction, depending on a generalized radius for ellipsoid based on the radius of sphere, and a linear fit function for the gamma absorbed fraction. The analytical functions that we obtained from fitting process in Monte Carlo data can be used for obtaining the absorbed fractions of iodine-131 beta and gamma rays for any volume of the thyroid lobe. Moreover, our results for the spheres are in good agreement with the results of MIRD and other scientific literatures.

Deficiency of bone marrow beta3-integrin enhances non-functional neovascularization.

PubMed

Watson, Alan R; Pitchford, Simon C; Reynolds, Louise E; Direkze, Natalie; Brittan, Mairi; Alison, Malcolm R; Rankin, Sara; Wright, Nicholas A; Hodivala-Dilke, Kairbaan M

2010-03-01

beta3-Integrin is a cell surface adhesion and signalling molecule important in the regulation of tumour angiogenesis. Mice with a global deficiency in beta3-integrin show increased pathological angiogenesis, most likely due to increased vascular endothelial growth factor receptor 2 expression on beta3-null endothelial cells. Here we transplanted beta3-null bone marrow (BM) into wild-type (WT) mice to dissect the role of BM beta3-integrin deficiency in pathological angiogenesis. Mice transplanted with beta3-null bone marrow show significantly enhanced angiogenesis in subcutaneous B16F0 melanoma and Lewis lung carcinoma (LLC) cell models and in B16F0 melanoma lung metastasis when compared with tumours grown in mice transplanted with WT bone marrow. The effect of bone marrow beta3-integrin deficiency was also assessed in the RIPTAg mouse model of pancreatic tumour growth. Again, angiogenesis in mice lacking BM beta3-integrin was enhanced. However, tumour weight between the groups was not significantly altered, suggesting that the enhanced blood vessel density in the mice transplanted with beta3-null bone marrow was not functional. Indeed, we demonstrate that in mice transplanted with beta3-null bone marrow a significant proportion of tumour blood vessels are non-functional when compared with tumour blood vessels in WT-transplanted controls. Furthermore, beta3-null-transplanted mice showed an increased angiogenic response to VEGF in vivo when compared with WT-transplanted animals. BM beta3-integrin deficiency affects the mobilization of progenitor cells to the peripheral circulation. We show that VEGF-induced mobilization of endothelial progenitor cells is enhanced in mice transplanted with beta3-null bone marrow when compared with WT-transplanted controls, suggesting a possible mechanism underlying the increased blood vessel density seen in beta3-null-transplanted mice. In conclusion, although BM beta3-integrin is not required for pathological angiogenesis, our studies demonstrate a role for BM beta3-integrin in VEGF-induced mobilization of bone marrow-derived cells to the peripheral circulation and for the functionality of those vessels in which BM-derived cells become incorporated.

Changes in intrinsic functional connectivity and group relevant salience: The case of sport rivalry.

PubMed

Moradi, Zargol; Mantini, Dante; Yankouskaya, Alla; Hewstone, Miles; Humphreys, Glyn W

2017-08-14

Studies have shown that attending to salient group relevant information could increase the BOLD activity across distributed neural networks. However, it is unclear how attending to group relevant information changes the functional connectivity across these networks. We investigated this issue combining resting states and task-based fMRI experiment. The task involved football fans learning associations between arbitrary geometric shapes and the badges of in-group, the rival and the neutral football teams. Upon learning, participants viewed different badge/shape pairs and their task was to judge whether the viewed pair was a match or a mismatch. For whole brain analyses increased activity was found in the IFG, DLPFC, AI, fusiform gyrus, precuneus and pSTS (all in the left hemisphere) for the rival over the in-group mismatch. Further, the ROI analyses revealed larger beta-values for the rival badge in the left pSTS, left AI and the left IFG. However, larger beta-values were found in the left pSTS and the left IFG (but not AI) for the in-group shape. The intrinsic functional connectivity analyses revealed that compare to the pre-task, post task functional connectivity was decreased between the left DLPFC and the left AI. In contrast, it was increased between the left IFG and the left AI and this was correlated with the difference in RT for the rival vs. in-group team. Our findings suggest that attending to group relevant information differentially affects the strength of functional coupling in attention networks and this can be explained by the saliency of the group relevant information. Copyright © 2017 Elsevier B.V. All rights reserved.

AGS vertical beta function measurements for Run 15

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

Harper, C.; Ahrens, L.; Huang, H.

2016-10-07

One key parameter for running the AGS efficiently is by maintaining a low emittance. To measure emittance, one needs to measure the beta function throughout the cycle. This can be done by measuring the beta function at the ionization profile monitors (IPM) in the AGS. This tech note delves into the motivation, the measurement, and some strides that were made throughout Run15.

Beta-cell function, incretin effect, and incretin hormones in obese youth along the span of glucose tolerance from normal to prediabetes to Type 2 diabetes

USDA-ARS?s Scientific Manuscript database

Using the hyperglycemic and euglycemic clamp, we demonstrated impaired Beta-cell function in obese youth with increasing dysglycemia. Herein we describe oral glucose tolerance test (OGTT)-modeled Beta-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. Bet...

Inhibition of glycogen synthase kinase 3beta during heart failure is protective.

PubMed

Hirotani, Shinichi; Zhai, Peiyong; Tomita, Hideharu; Galeotti, Jonathan; Marquez, Juan Pablo; Gao, Shumin; Hong, Chull; Yatani, Atsuko; Avila, Jesús; Sadoshima, Junichi

2007-11-26

Glycogen synthase kinase (GSK)-3, a negative regulator of cardiac hypertrophy, is inactivated in failing hearts. To examine the histopathological and functional consequence of the persistent inhibition of GSK-3beta in the heart in vivo, we generated transgenic mice with cardiac-specific overexpression of dominant negative GSK-3beta (Tg-GSK-3beta-DN) and tetracycline-regulatable wild-type GSK-3beta. GSK-3beta-DN significantly reduced the kinase activity of endogenous GSK-3beta, inhibited phosphorylation of eukaryotic translation initiation factor 2B epsilon, and induced accumulation of beta-catenin and myeloid cell leukemia-1, confirming that GSK-3beta-DN acts as a dominant negative in vivo. Tg-GSK-3beta-DN exhibited concentric hypertrophy at baseline, accompanied by upregulation of the alpha-myosin heavy chain gene and increases in cardiac function, as evidenced by a significantly greater Emax after dobutamine infusion and percentage of contraction in isolated cardiac myocytes, indicating that inhibition of GSK-3beta induces well-compensated hypertrophy. Although transverse aortic constriction induced a similar increase in hypertrophy in both Tg-GSK-3beta-DN and nontransgenic mice, Tg-GSK-3beta-DN exhibited better left ventricular function and less fibrosis and apoptosis than nontransgenic mice. Induction of the GSK-3beta transgene in tetracycline-regulatable wild-type GSK-3beta mice induced left ventricular dysfunction and premature death, accompanied by increases in apoptosis and fibrosis. Overexpression of GSK-3beta-DN in cardiac myocytes inhibited tumor necrosis factor-alpha-induced apoptosis, and the antiapoptotic effect of GSK-3beta-DN was abrogated in the absence of myeloid cell leukemia-1. These results suggest that persistent inhibition of GSK-3beta induces compensatory hypertrophy, inhibits apoptosis and fibrosis, and increases cardiac contractility and that the antiapoptotic effect of GSK-3beta inhibition is mediated by myeloid cell leukemia-1. Thus, downregulation of GSK-3beta during heart failure could be compensatory.

Oral supplement enriched in HMB combined with pulmonary rehabilitation improves body composition and health related quality of life in patients with bronchiectasis (Prospective, Randomised Study).

PubMed

Olveira, Gabriel; Olveira, Casilda; Doña, Esperanza; Palenque, Francisco Javier; Porras, Nuria; Dorado, Antonio; Godoy, Ana M; Rubio-Martínez, Elehazara; Rojo-Martínez, Gemma; Martín-Valero, Rocío

2016-10-01

Pulmonary Rehabilitation (PR) is recommended for bronchiectasis but there is no data about its effect on body composition. The aim of this study is to assess the effect of Pulmonary Rehabilitation (PR) for 12 weeks in normally-nourished non-cystic-fibrosis bronchiectasis patients compared with the effect of PR plus a hyperproteic oral nutritional supplement enriched with beta-hydroxy-beta-methylbutyrate (HMB) on body composition, muscle strength, quality of life and serum biomarkers. single center randomized controlled trial, parallel treatment design: Participants were randomly assigned to receive PR for 12 weeks or PR plus ONS (PRONS) (one can per day). Outcome assessments were performed at baseline, 12 weeks and 24 weeks: body composition (Dual-energy X-Ray Absorptiometry (DEXA), mid-arm muscle circumference (MAMC), phase angle by Bio-impedance), health related quality of life (Spanish QOL-B-V3.0, Physical Functioning Scale), handgrip strength, diet questionnaire, and plasma levels of prealbumin, myostatin and somatomedin-c. Thirty patients were randomized (15 per group) without differences in clinical and respiratory variables. In the PRONS group bone mineral density (BMD), mean and maximum handgrip dynamometry, MAMC, QOLB and prealbumin were significantly increased from baseline at 12 and 24 weeks and Fat free Mass (FFM) and FFM index, at 12 weeks. In the PR group only mean handgrip dynamometry and prealbumin were significantly increased at 12 and 24 weeks. In both groups plasma myostatin was reduced at 12 weeks (without significant differences). The addition of a hyperproteic ONS enriched with HMB to Pulmonary Rehabilitation could improve body composition, BMD, muscle strength and health related quality of life in bronchiectasis patients. Clinical Trials Number NCT02048397. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Use of a purified and functional recombinant calcium-channel beta4 subunit in surface-plasmon resonance studies.

PubMed Central

Geib, Sandrine; Sandoz, Guillaume; Mabrouk, Kamel; Matavel, Alessandra; Marchot, Pascale; Hoshi, Toshinori; Villaz, Michel; Ronjat, Michel; Miquelis, Raymond; Lévêque, Christian; de Waard, Michel

2002-01-01

Native high-voltage-gated calcium channels are multi-subunit complexes comprising a pore-forming subunit Ca(v) and at least two auxiliary subunits alpha(2)delta and beta. The beta subunit facilitates cell-surface expression of the channel and contributes significantly to its biophysical properties. In spite of its importance, detailed structural and functional studies are hampered by the limited availability of native beta subunit. Here, we report the purification of a recombinant calcium-channel beta(4) subunit from bacterial extracts by using a polyhistidine tag. The purified protein is fully functional since it binds on the alpha1 interaction domain, its main Ca(v)-binding site, and regulates the activity of P/Q calcium channel expressed in Xenopus oocytes in a similar way to the beta(4) subunit produced by cRNA injection. We took advantage of the functionality of the purified material to (i) develop an efficient surface-plasmon resonance assay of the interaction between two calcium channel subunits and (ii) measure, for the first time, the affinity of the recombinant His-beta(4) subunit for the full-length Ca(v)2.1 channel. The availability of this purified material and the development of a surface-plasmon resonance assay opens two immediate research perspectives: (i) drug screening programmes applied to the Ca(v)/beta interaction and (ii) crystallographic studies of the calcium-channel beta(4) subunit. PMID:11988102

Functional Connectivity in Islets of Langerhans from Mouse Pancreas Tissue Slices

PubMed Central

Stožer, Andraž; Gosak, Marko; Dolenšek, Jurij; Perc, Matjaž; Marhl, Marko; Rupnik, Marjan Slak; Korošak, Dean

2013-01-01

We propose a network representation of electrically coupled beta cells in islets of Langerhans. Beta cells are functionally connected on the basis of correlations between calcium dynamics of individual cells, obtained by means of confocal laser-scanning calcium imaging in islets from acute mouse pancreas tissue slices. Obtained functional networks are analyzed in the light of known structural and physiological properties of islets. Focusing on the temporal evolution of the network under stimulation with glucose, we show that the dynamics are more correlated under stimulation than under non-stimulated conditions and that the highest overall correlation, largely independent of Euclidean distances between cells, is observed in the activation and deactivation phases when cells are driven by the external stimulus. Moreover, we find that the range of interactions in networks during activity shows a clear dependence on the Euclidean distance, lending support to previous observations that beta cells are synchronized via calcium waves spreading throughout islets. Most interestingly, the functional connectivity patterns between beta cells exhibit small-world properties, suggesting that beta cells do not form a homogeneous geometric network but are connected in a functionally more efficient way. Presented results provide support for the existing knowledge of beta cell physiology from a network perspective and shed important new light on the functional organization of beta cell syncitia whose structural topology is probably not as trivial as believed so far. PMID:23468610

Synthetic alleles at position 121 define a functional domain of human interleukin-1 beta.

PubMed

Ambrosetti, D C; Palla, E; Mirtella, A; Galeotti, C; Solito, E; Navarra, P; Parente, L; Melli, M

1996-06-01

The non-conservative substitution of the tyrosine residue at position 121 of human interleukin-1 beta (IL-1 beta) generates protein mutants showing strong reduction of the capacity to induce (a) prostaglandin E2 (PGE2) release from fibroblasts and smooth muscle cells, (b) murine T-cells proliferation and (c) activation of interleukin-6 (IL-6) gene expression. It is generally accepted that these functions are mediated by the type-I interleukin-1 receptor (IL-1RI). However, the mutant proteins maintain the binding affinity to the types-I and II IL-1 receptors, which is the same as the control IL-1 beta, suggesting that this amino acid substitution does not alter the structure of the molecule, except locally. Thus we have identified a new functional site of IL-1 beta different from the known receptor binding region, responsible for fundamental IL-1 beta functions. Moreover, we show that the same mutants maintain at least two hypothalamic functions, that is, the in vitro short-term PGE2 release from rat hypothalamus and the induction of fever in rabbits. This result suggests that there is yet another site of the molecule responsible for the hypothalamic functions, implying that multiple active sites on the IL-1 beta molecule, possibly binding to more than one receptor chain, trigger different signals.

Contrasting species and functional beta diversity in montane ant assemblages.

PubMed

Bishop, Tom R; Robertson, Mark P; van Rensburg, Berndt J; Parr, Catherine L

2015-09-01

Beta diversity describes the variation in species composition between sites and can be used to infer why different species occupy different parts of the globe. It can be viewed in a number of ways. First, it can be partitioned into two distinct patterns: turnover and nestedness. Second, it can be investigated from either a species identity or a functional-trait point of view. We aim to document for the first time how these two aspects of beta diversity vary in response to a large environmental gradient. Maloti-Drakensberg Mountains, southern Africa. We sampled ant assemblages along an extensive elevational gradient (900-3000 m a.s.l.) twice yearly for 7 years, and collected functional-trait information related to the species' dietary and habitat-structure preferences. We used recently developed methods to partition species and functional beta diversity into their turnover and nestedness components. A series of null models were used to test whether the observed beta diversity patterns differed from random expectations. Species beta diversity was driven by turnover, but functional beta diversity was composed of both turnover and nestedness patterns at different parts of the gradient. Null models revealed that deterministic processes were likely to be responsible for the species patterns but that the functional changes were indistinguishable from stochasticity. Different ant species are found with increasing elevation, but they tend to represent an increasingly nested subset of the available functional strategies. This finding is unique and narrows down the list of possible factors that control ant existence across elevation. We conclude that diet and habitat preferences have little role in structuring ant assemblages in montane environments and that some other factor must be driving the non-random patterns of species turnover. This finding also highlights the importance of distinguishing between different kinds of beta diversity.

The mechanism of chromosome 7 inversion in human lymphocytes expressing chimeric gamma beta TCR.

PubMed

Retière, C; Halary, F; Peyrat, M A; Le Deist, F; Bonneville, M; Hallet, M M

1999-01-15

Functional chimeric TCR chains, encoded by V gamma J gamma C beta or V gamma J beta C beta hybrid gene TCR, are expressed at the surface of a small fraction of alpha beta T lymphocytes in healthy individuals. Their frequency is dramatically increased in patients with ataxia-telangiectasia, a syndrome associated with inherited genomic instability. As the TCR gamma and beta loci are in an inverted orientation on chromosome 7, the generation of such hybrid genes requires at least an inversion event. Until now, neither the sequences involved in this genetic mechanism nor the number of recombinations leading to the formation of functional transcriptional units have been characterized. In this manuscript, we demonstrate that at least two rearrangements, involving classical recombination signal sequence and the V(D)J recombinase complex, lead to the formation of productive hybrid genes. A primary inversion 7 event between D beta and J gamma genic segments generates C gamma V beta and C beta V gamma hybrid loci. Within the C gamma V beta locus, secondary rearrangements between V gamma and J gamma or V gamma and J beta elements generate functional genes. Besides, our results suggest that secondary rearrangements were blocked in the C beta V gamma locus of normal but not ataxia-telangiectasia T lymphocytes. We also provide formal evidence that the same D beta-3' recombination signal sequence can be used in successive rearrangements with J gamma and J beta genic segments, thus showing that a signal joint has been involved in a secondary recombination event.

Programmed disorders of beta-cell development and function as one cause for type 2 diabetes? The GK rat paradigm.

PubMed

Portha, Bernard

2005-01-01

Now that the reduction in beta-mass has been clearly established in humans with type 2 diabetes mellitus (T2DM) 1-4, the debate focuses on the possible mechanisms responsible for decreased beta-cell number and impaired beta-cell function and their multifactorial etiology. Appropriate inbred rodent models are essential tools for identification of genes and environmental factors that increase the risk of abnormal beta-cell function and of T2DM. The information available in the Goto-Kakizaki (GK) rat, one of the best characterized animal models of spontaneous T2DM, are reviewed in such a perspective. We propose that the defective beta-cell mass and function in the GK model reflect the complex interactions of three pathogenic players: (1) several independent loci containing genes causing impaired insulin secretion; (2) gestational metabolic impairment inducing a programming of endocrine pancreas (decreased beta-cell neogenesis) which is transmitted to the next generation; and (3) secondary (acquired) loss of beta-cell differentiation due to chronic exposure to hyperglycemia (glucotoxicity). An important message is that the 'heritable' determinants of T2DM are not simply dependant on genetic factors, but probably involve transgenerational epigenetic responses. Copyright (c) 2005 John Wiley & Sons, Ltd.

HMB supplementation: clinical and athletic performance-related effects and mechanisms of action.

PubMed

Zanchi, Nelo Eidy; Gerlinger-Romero, Frederico; Guimarães-Ferreira, Lucas; de Siqueira Filho, Mário Alves; Felitti, Vitor; Lira, Fabio Santos; Seelaender, Marília; Lancha, Antonio Herbert

2011-04-01

Amino acids such as leucine and its metabolite α-ketoisocaproate (KIC), are returning to be the focus of studies, mainly because of their anti-catabolic properties, through inhibition of muscle proteolysis and enhancement of protein synthesis. It is clear that these effects may counteract catabolic conditions, as well as enhance skeletal muscle mass and strength in athletes. Moreover, beta-hydroxy-beta-methylbutyrate (HMB) has been shown to produce an important effect in reducing muscle damage induced by mechanical stimuli of skeletal muscle. This review aims to describe the general scientific evidence of KIC and HMB supplementation clinical relevance, as well as their effects (e.g., increases in skeletal muscle mass and/or strength), associated with resistance training or other sports. Moreover, the possible mechanisms of cell signaling regulation leading to increases and/or sparing (during catabolic conditions) of skeletal muscle mass are discussed in detail based on the recent literature.

Elevated-temperature flow strength, creep resistance and diffusion welding characteristics of Ti-gAl-2Nb-1Ta-0.8Mo

NASA Technical Reports Server (NTRS)

Whittenberger, J. D.; Moore, T. J.

1977-01-01

A study of the flow strength, creep resistance and diffusion welding characteristics of the titanium alloy Ti-6Al-2Nb-1Ta-0.8Mo was conducted. Two mill-processed forms of this alloy were examined. The forged material was essentially processed above the beta transus while the rolled form was subjected to considerable work below the beta transus. Between 1150 and 1250 K, the forged material was stronger and more creep resistant than the rolled alloy. Both forms exhibit superplastic characteristics in this temperature range. Strain measurements during diffusion welding experiments at 1200 K reveal that weld interfaces have no measurable effect on the overall creep deformation. Significant deformation appears to be necessary to produce a quality diffusion weld between superplastic materials. A 'soft' interlayer inserted between faying surfaces would seemingly allow manufacture of quality diffusion welds with little overall deformation.

The 3 micron spectrum of the classical Be star Beta Monocerotis A

NASA Technical Reports Server (NTRS)

Sellgren, K.; Smith, R. G.

1992-01-01

A 3.1-3.7-micron spectrum of the classical Be star Beta Mon A is presented at a resolution of lambda/Delta-lambda of 700-800. The spectrum shows strong hydrogen recombination lines, including Pf-delta and a series of Humphreys lines from Hu 19 to Hu 28. The relative recombination line strengths suggest that Pf-delta has a large optical depth. The Humphreys lines have relative strengths consistent with case B and may be optically thin. The line widths observed are broader than the Balmer lines and similar in width to Fe II lines, consistent with a disk model in which optically thinner lines arise primarily from a faster rotating inner disk, while optically thicker lines come mainly from a slower rotating outer disk. The apparent lack of Stark broadening of the Humphreys lines is used to place an upper limit on the circumstellar electron density of about 10 exp 12/cu cm.

NEW MEMBERS OF THE SCORPIUS-CENTAURUS COMPLEX AND AGES OF ITS SUB-REGIONS

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

Song, Inseok; Zuckerman, B.; Bessell, M. S.

2012-07-15

We have spectroscopically identified {approx}100 G-, K-, and M-type members of the Scorpius-Centaurus complex. To deduce the age of these young stars we compare their Li {lambda}6708 absorption line strengths against those of stars in the TW Hydrae association and {beta} Pictoris moving group. These line strengths indicate that Sco-Cen stars are younger than {beta} Pic stars whose ages of {approx}12 Myr have previously been derived from a kinematic traceback analysis. Our derived age, {approx}10 Myr, for stars in the Lower Centaurus Crux and Upper Centaurus Lupus subgroups of ScoCen is younger than previously published ages based on the movingmore » cluster method and upper main-sequence fitting. The discrepant ages are likely due to an incorrect (or lack of) cross-calibration between model-dependent and model-independent age-dating methods.« less

Properties of low-lying intruder states in 34Al and 34Si populated in the beta-decay of 34Mg

NASA Astrophysics Data System (ADS)

Licǎ, R.; Rotaru, F.; Negoitǎ, F.; Grévy, S.; Mǎrginean, N.; Desagne, Ph.; Stora, T.; Borcea, C.; Borcea, R.; Cǎlinescu, S.; Daugas, J. M.; Filipescu, D.; Kuti, I.; Fraile, L. M.; Franchoo, S.; Gheorghe, I.; Ghitǎ, D. G.; Mǎrginean, R.; Mihai, C.; Mourface, P.; Morel, P.; Mrazek, J.; Negret, A.; Pietreanu, D.; Sava, T.; Sohler, D.; Stǎnoiu, M.; Stefan, I.; Şuvǎilǎ, R.; Toma, S.; Ur, C. A.

2015-02-01

The results of the IS530 experiment at ISOLDE revealed new information concerning several nuclei close to the N ≈ 20 'Island of Inversion' - 34Mg , 34Al , 34Si . The half-life of 34Mg was found to be three times larger than the adopted value (63(1) ms instead of 20(10) ms). The beta-gamma spectroscopy of 34Mg performed for the first time in this experiment, led to the first experimental level scheme for 34Al , also showing that the full beta strength goes through the predicted 1+ isomer in 34Al [1] and/or excited states that deexcite to it. The subsequent beta-decay of the 1+ isomer in 34Al allowed the observation of new gamma lines in 34Si , (tentatively) associated with low-spin high-energy excited states previously unobserved.

High shear mixing granulation of ibuprofen and beta-cyclodextrin: effects of process variables on ibuprofen dissolution.

PubMed

Ghorab, Mohamed K; Adeyeye, Moji Christianah

2007-10-19

The aims of the study were to evaluate the effect of high shear mixer (HSM) granulation process parameters and scale-up on wet mass consistency and granulation characteristics. A mixer torque rheometer (MTR) was employed to evaluate the granulating solvents used (water, isopropanol, and 1:1 vol/vol mixture of both) based on the wet mass consistency. Gral 25 and mini-HSM were used for the granulation. The MTR study showed that the water significantly enhanced the beta-cyclodextrin (beta CD) binding tendency and the strength of liquid bridges formed between the particles, whereas the isopropanol/water mixture yielded more suitable agglomerates. Mini-HSM granulation with the isopropanol/water mixture (1:1 vol/vol) showed a reduction in the extent of torque value rise by increasing the impeller speed as a result of more breakdown of agglomerates than coalescence. In contrast, increasing the impeller speed of the Gral 25 resulted in higher torque readings, larger granule size, and consequently, slower dissolution. This was due to a remarkable rise in temperature during Gral granulation that reduced the isopropanol/water ratio in the granulating solvent as a result of evaporation and consequently increased the beta CD binding strength. In general, the HSM granulation retarded ibuprofen dissolution compared with the physical mixture because of densification and agglomeration. However, a successful HSM granulation scale-up was not achieved due to the difference in the solvent mixture's effect from 1 scale to the other.

Studies of insulin secretory responses and of arachidonic acid incorporation into phospholipids of stably transfected insulinoma cells that overexpress group VIA phospholipase A2 (iPLA2beta ) indicate a signaling rather than a housekeeping role for iPLA2beta.

PubMed

Ma, Z; Ramanadham, S; Wohltmann, M; Bohrer, A; Hsu, F F; Turk, J

2001-04-20

A cytosolic 84-kDa group VIA phospholipase A(2) (iPLA(2)beta) that does not require Ca(2+) for catalysis has been cloned from several sources, including rat and human pancreatic islet beta-cells and murine P388D1 cells. Many potential iPLA(2)beta functions have been proposed, including a signaling role in beta-cell insulin secretion and a role in generating lysophosphatidylcholine acceptors for arachidonic acid incorporation into P388D1 cell phosphatidylcholine (PC). Proposals for iPLA(2)beta function rest in part on effects of inhibiting iPLA(2)beta activity with a bromoenol lactone (BEL) suicide substrate, but BEL also inhibits phosphatidate phosphohydrolase-1 and a group VIB phospholipase A(2). Manipulation of iPLA(2)beta expression by molecular biologic means is an alternative approach to study iPLA(2)beta functions, and we have used a retroviral construct containing iPLA(2)beta cDNA to prepare two INS-1 insulinoma cell clonal lines that stably overexpress iPLA(2)beta. Compared with parental INS-1 cells or cells transfected with empty vector, both iPLA(2)beta-overexpressing lines exhibit amplified insulin secretory responses to glucose and cAMP-elevating agents, and BEL substantially attenuates stimulated secretion. Electrospray ionization mass spectrometric analyses of arachidonic acid incorporation into INS-1 cell PC indicate that neither overexpression nor inhibition of iPLA(2)beta affects the rate or extent of this process in INS-1 cells. Immunocytofluorescence studies with antibodies directed against iPLA(2)beta indicate that cAMP-elevating agents increase perinuclear fluorescence in INS-1 cells, suggesting that iPLA(2)beta associates with nuclei. These studies are more consistent with a signaling than with a housekeeping role for iPLA(2)beta in insulin-secreting beta-cells.

The pleiotropic roles of transforming growth factor beta inhomeostasis and carcinogenesis of endocrine organs.

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

Fleisch, Markus C.; Maxwell, Christopher A.; Barcellos-Hoff,Mary-Helen

2006-01-13

Transforming growth factor beta (TGF-beta) is a ubiquitous cytokine that plays a critical role in numerous pathways regulating cellular and tissue homeostasis. TGF-beta is regulated by hormones and is a primary mediator of hormone response in uterus, prostate and mammary gland. This review will address the role of TGF-beta in regulating hormone dependent proliferation and morphogenesis. The subversion of TGF-beta regulation during the processes of carcinogenesis, with particular emphasis on its effects on genetic stability and epithelial to mesenchymal transition (EMT), will also be examined. An understanding of the multiple and complex mechanisms of TGF-beta regulation of epithelial function, andmore » the ultimate loss of TGF-beta function during carcinogenesis, will be critical in the design of novel therapeutic interventions for endocrine-related cancers.« less

The quest to make fully functional human pancreatic beta cells from embryonic stem cells: climbing a mountain in the clouds.

PubMed

Johnson, James D

2016-10-01

The production of fully functional insulin-secreting cells to treat diabetes is a major goal of regenerative medicine. In this article, I review progress towards this goal over the last 15 years from the perspective of a beta cell biologist. I describe the current state-of-the-art, and speculate on the general approaches that will be required to identify and achieve our ultimate goal of producing functional beta cells. The need for deeper phenotyping of heterogeneous cultures of stem cell derived islet-like cells in parallel with a better understanding of the heterogeneity of the target cell type(s) is emphasised. This deep phenotyping should include high-throughput single-cell analysis, as well as comprehensive 'omics technologies to provide unbiased characterisation of cell products and human beta cells. There are justified calls for more detailed and well-powered studies of primary human pancreatic beta cell physiology, and I propose online databases of standardised human beta cell responses to physiological stimuli, including both functional and metabolomic/proteomic/transcriptomic profiles. With a concerted, community-wide effort, including both basic and applied scientists, beta cell replacement will become a clinical reality for patients with diabetes.

Milk whey proteins and xanthan gum interactions in solution and at the air-water interface: a rheokinetic study.

PubMed

Perez, Adrián A; Sánchez, Cecilio Carrera; Patino, Juan M Rodríguez; Rubiolo, Amelia C; Santiago, Liliana G

2010-11-01

In this contribution, we present experimental information about the effect of xanthan gum (XG) on the adsorption behaviour of two milk whey protein samples (MWP), beta-lactoglobulin (beta-LG) and whey protein concentrate (WPC), at the air-water interface. The MWP concentration studied corresponded to the protein bulk concentration which is able to saturate the air-water interface (1.0 wt%). Temperature, pH and ionic strength of aqueous systems were kept constant at 20 degrees C, pH 7 and 0.05 M, respectively, while the XG bulk concentration varied in the range 0.00-0.25 wt%. Biopolymer interactions in solution were analyzed by extrinsic fluorescence spectroscopy using 1-anilino-8-naphtalene sulphonic acid (ANS) as a protein fluorescence probe. Interfacial biopolymer interactions were evaluated by dynamic tensiometry and surface dilatational rheology. Adsorption behaviour was discussed from a rheokinetic point of view in terms of molecular diffusion, penetration and conformational rearrangement of adsorbed protein residues at the air-water interface. Differences in the interaction magnitude, both in solution and at the interface vicinity, and in the adsorption rheokinetic parameters were observed in MWP/XG mixed systems depending on the protein type (beta-LG or WPC) and biopolymer relative concentration. beta-LG adsorption in XG presence could be promoted by mechanisms based on biopolymer segregative interactions and thermodynamic incompatibility in the interface vicinity, resulting in better surface and viscoelastic properties. The same mechanism could be responsible of WPC interfacial adsorption in the presence of XG. The interfacial functionality of WPC was improved by the synergistic interactions with XG, although WPC chemical complexity might complicate the elucidation of molecular events that govern adsorption dynamics of WPC/XG mixed systems at the air-water interface. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Highly stereoselective three-component reactions of phenylselenomagnesium bromide, acetylenic sulfones, and saturated aldehydes/ketones or alpha,beta-unsaturated enals or enones.

PubMed

Huang, Xian; Xie, Meihua

2002-12-13

beta-Phenylseleno-alpha-tolylsulfonyl-substituted alkenes were synthesized via the three-component conjugate-nucleophilic addition of acetylenic sulfones, phenylselenomagnesium bromide, and carbonyl compounds, such as aldehydes, aliphatic ketones, or alpha,beta-unsaturated enals or enones. The reaction is highly regio- and stereoselective with moderate to good yields. Functionalized allylic alcohols were obtained in the case of aldehydes and aliphatic ketones. In the case of alpha,beta-unsaturated enones, functionalized allylic alcohols or functionalized gamma,delta-unsaturated ketones were obtained, depending on the structures of the ketones.

Structural domains required for channel function of the mouse transient receptor potential protein homologue TRP1beta.

PubMed

Engelke, Michael; Friedrich, Olaf; Budde, Petra; Schäfer, Christina; Niemann, Ursula; Zitt, Christof; Jüngling, Eberhard; Rocks, Oliver; Lückhoff, Andreas; Frey, Jürgen

2002-07-17

Transient receptor potential proteins (TRP) are supposed to participate in the formation of store-operated Ca(2+) influx channels by co-assembly. However, little is known which domains facilitate the interaction of subunits. Contribution of the N-terminal coiled-coil domain and ankyrin-like repeats and the putative pore region of the mouse TRP1beta (mTRP1beta) variant to the formation of functional cation channels were analyzed following overexpression in HEK293 (human embryonic kidney) cells. MTRP1beta expressing cells exhibited enhanced Ca(2+) influx and enhanced whole-cell membrane currents compared to mTRP1beta deletion mutants. Using a yeast two-hybrid assay only the coiled-coil domain facilitated homodimerization of the N-terminus. These results suggest that the N-terminus of mTRP1beta is required for structural organization thus forming functional channels.

To improve the flame resistance of spandex elastic elastomeric fiber

NASA Technical Reports Server (NTRS)

1972-01-01

Strength characteristics of fibers were improved to pass the 70% oxygen/30% nitrogen specification. Spinning techniques and information about incorporating these fibers in fabric structures using wrapping materials of Beta Fiberglas, Nomex, and PBI were developed.

Effect of beta-blockers on exacerbation rate and lung function in chronic obstructive pulmonary disease (COPD).

PubMed

Duffy, Sean; Marron, Robert; Voelker, Helen; Albert, Richard; Connett, John; Bailey, William; Casaburi, Richard; Cooper, J Allen; Curtis, Jeffrey L; Dransfield, Mark; Han, MeiLan K; Make, Barry; Marchetti, Nathaniel; Martinez, Fernando; Lazarus, Stephen; Niewoehner, Dennis; Scanlon, Paul D; Sciurba, Frank; Scharf, Steven; Reed, Robert M; Washko, George; Woodruff, Prescott; McEvoy, Charlene; Aaron, Shawn; Sin, Don; Criner, Gerard J

2017-06-19

Beta-blockers are commonly prescribed for patients with cardiovascular disease. Providers have been wary of treating chronic obstructive pulmonary disease (COPD) patients with beta-blockers due to concern for bronchospasm, but retrospective studies have shown that cardio-selective beta-blockers are safe in COPD and possibly beneficial. However, these benefits may reflect symptom improvements due to the cardiac effects of the medication. The purpose of this study is to evaluate associations between beta-blocker use and both exacerbation rates and longitudinal measures of lung function in two well-characterized COPD cohorts. We retrospectively analyzed 1219 participants with over 180 days of follow up from the STATCOPE trial, which excluded most cardiac comorbidities, and from the placebo arm of the MACRO trial. Primary endpoints were exacerbation rates per person-year and change in spirometry over time in association with beta blocker use. Overall 13.9% (170/1219) of participants reported taking beta-blockers at enrollment. We found no statistically significant differences in exacerbation rates with respect to beta-blocker use regardless of the prevalence of cardiac comorbidities. In the MACRO cohort, patients taking beta-blockers had an exacerbation rate of 1.72/person-year versus a rate of 1.71/person-year in patients not taking beta-blockers. In the STATCOPE cohort, patients taking beta-blockers had an exacerbation rate of 1.14/person-year. Patients without beta-blockers had an exacerbation rate of 1.34/person-year. We found no detrimental effect of beta blockers with respect to change in lung function over time. We found no evidence that beta-blocker use was unsafe or associated with worse pulmonary outcomes in study participants with moderate to severe COPD.

Value of the intravenous and oral glucose tolerance tests for detecting subtle impairments in insulin sensitivity and beta-cell function in former gestational diabetes.

PubMed

Tura, A; Mari, A; Prikoszovich, T; Pacini, G; Kautzky-Willer, A

2008-08-01

Women with former gestational diabetes mellitus (fGDM) often show defects in both insulin sensitivity and beta-cell function but it is not clear which defect plays the major role or which appears first. This might be because fGDM women are often studied as a unique group and not divided according to their glucose tolerance. Different findings might also be the result of using different tests. Our aim was to study insulin sensitivity and beta-cell function with two independent glucose tolerance tests in fGDM women divided according to their glucose tolerance. A total of 108 fGDM women divided into normal glucose tolerance (IGT; N = 82), impaired glucose metabolism (IGM; N = 20) and overt type 2 diabetes (T2DM; N = 6) groups, and 38 healthy control women (CNT) underwent intravenous (IVGTT) and oral glucose tolerance tests (OGTT). Measurements Insulin sensitivity and beta-cell function were assessed by both the IVGTT and the OGTT. Both tests revealed impaired insulin sensitivity in the normotolerant group compared to controls (IVGTT: 4.2 +/- 0.3 vs. 5.4 +/- 0.4 10(-4) min(-1) (microU/ml)(-1); OGTT: 440 +/- 7 vs. 472 +/- 9 ml min(-1) m(-2)). Conversely, no difference was found in beta-cell function from the IVGTT. However, some parameters of beta-cell function by OGTT modelling analysis were found to be impaired: glucose sensitivity (106 +/- 5 vs. 124 +/- 7 pmol min(-1) m(-2) mm(-1), P = 0.0407) and insulin secretion at 5 mm glucose (168 +/- 9 vs. 206 +/- 10 pmol min(-1) m(-2), P = 0.003). Both insulin sensitivity and beta-cell function are impaired in normotolerant fGDM but the subtle defect in beta-cell function is disclosed only by OGTT modelling analysis.

Arsenic Exposure and Calpain-10 Polymorphisms Impair the Function of Pancreatic Beta-Cells in Humans: A Pilot Study of Risk Factors for T2DM

PubMed Central

Díaz-Villaseñor, Andrea; Cruz, Laura; Cebrián, Arturo; Hernández-Ramírez, Raúl U.; Hiriart, Marcia; García-Vargas, Gonzálo; Bassol, Susana; Sordo, Monserrat; Gandolfi, A. Jay; Klimecki, Walter T.; López-Carillo, Lizbeth; Cebrián, Mariano E.; Ostrosky-Wegman, Patricia

2013-01-01

The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide and diverse environmental and genetic risk factors are well recognized. Single nucleotide polymorphisms (SNPs) in the calpain-10 gene (CAPN-10), which encodes a protein involved in the secretion and action of insulin, and chronic exposure to inorganic arsenic (iAs) through drinking water have been independently associated with an increase in the risk for T2DM. In the present work we evaluated if CAPN-10 SNPs and iAs exposure jointly contribute to the outcome of T2DM. Insulin secretion (beta-cell function) and insulin sensitivity were evaluated indirectly through validated indexes (HOMA2) in subjects with and without T2DM who have been exposed to a gradient of iAs in their drinking water in northern Mexico. The results were analyzed taking into account the presence of the risk factor SNPs SNP-43 and -44 in CAPN-10. Subjects with T2DM had significantly lower beta-cell function and insulin sensitivity. An inverse association was found between beta-cell function and iAs exposure, the association being more pronounced in subjects with T2DM. Subjects without T2DM who were carriers of the at-risk genotype SNP-43 or -44, also had significantly lower beta-cell function. The association of SNP-43 with beta-cell function was dependent on iAs exposure, age, gender and BMI, whereas the association with SNP-44 was independent of all of these factors. Chronic exposure to iAs seems to be a risk factor for T2DM in humans through the reduction of beta-cell function, with an enhanced effect seen in the presence of the at-risk genotype of SNP-43 in CAPN-10. Carriers of CAPN-10 SNP-44 have also shown reduced beta-cell function. PMID:23349674

Evaluation of suitable porosity for sintered porous {beta}-tricalcium phosphate as a bone substitute

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

Park, Jin-Hong; Bae, Ji-Yong; Shim, Jaebum

2012-09-15

Structural and mechanical characterization is performed for sintered porous beta tricalcium phosphate ({beta}-TCP) to determine the appropriate porosity for use as a bone substitute. Four different types of porous {beta}-TCP specimen with different porosities are fabricated through a sintering process. For structural characterization, scanning electron microscopy and a Microfocus X-ray computed tomography system are used to investigate the pore openings on the specimen's surface, pore size, pore distribution, and pore interconnections. Compression tests of the specimens are performed, and mechanical properties such as the elastic modulus and compressive strength are obtained. Also, the geometric shape and volume of the {beta}-TCPmore » around the contact region of two pores, which need to be initially resolved after implantation in order to increase the size of the pore openings, are evaluated through simple calculations. The results show that porous {beta}-TCP with 42.1% porosity may be a suitable bone substitute candidate in terms of sustaining external loads, and inducing and cultivating bone cells. - Highlights: Black-Right-Pointing-Pointer Structural and mechanical characterization was performed for sintered porous {beta}-TCP specimens. Black-Right-Pointing-Pointer For structural characterization, SEM and Microfocus X-ray CT system were used. Black-Right-Pointing-Pointer For mechanical characterization, compression tests were performed. Black-Right-Pointing-Pointer Porous {beta}-TCP with 42.1% porosity may be a suitable bone substitute.« less

Oscillator strengths for ionized iron and manganese

NASA Technical Reports Server (NTRS)

De Boer, K. S.; Pottasch, S. R.; Morton, D. C.; York, D. G.

1974-01-01

The observed strengths of interstellar absorption lines of Fe II and Mn II in the spectra of alpha Vir, beta Cen, pi Sco, and zeta Oph along with laboratory f values of some of these lines between 2343 and 2606 A have been used to determine curves of growth for these ions and the f-values of ten lines of Fe II and three lines of Mn II between 1055 and 1261 A. The Fe and Mn abundances are derived.

Double Charge Exchange Reactions and Double Beta Decay

NASA Astrophysics Data System (ADS)

Auerbach, N.

2018-05-01

The subject of this presentation is at the forefront of nuclear physics, namely double beta decay. In particular one is most interested in the neutrinoless process of double beta decay, when the decay proceeds without the emission of two neutrinos. The observation of such decay would mean that the lepton conservation symmetry is violated and that the neutrinos are of Majorana type, meaning that they are their own anti-particles. The life time of this process has two unknowns, the mass of the neutrino and the nuclear matrix element. Determining the nuclear matrix element and knowing the cross-section well will set limits on the neutrino mass. There is a concentrated effort among the nuclear physics community to calculate this matrix element. Usually these matrix elements are a very small part of the total strength of the transition operators involved in the process. There is no simple way to “calibrate” the nuclear double beta decay matrix element. The double beta decay is a double charge exchange process, therefore it is proposed that double charge exchange reactions using ion projectiles on nuclei that are candidates for double beta decay, will provide additional necessary information about the nuclear matrix elements.

Gene Editing and Human Pluripotent Stem Cells: Tools for Advancing Diabetes Disease Modeling and Beta-Cell Development.

PubMed

Millette, Katelyn; Georgia, Senta

2017-10-05

This review will focus on the multiple approaches to gene editing and address the potential use of genetically modified human pluripotent stem cell-derived beta cells (SC-β) as a tool to study human beta-cell development and model their function in diabetes. We will explore how new variations of CRISPR/Cas9 gene editing may accelerate our understanding of beta-cell developmental biology, elucidate novel mechanisms that establish and regulate beta-cell function, and assist in pioneering new therapeutic modalities for treating diabetes. Improvements in CRISPR/Cas9 target specificity and homology-directed recombination continue to advance its use in engineering stem cells to model and potentially treat disease. We will review how CRISPR/Cas9 gene editing is informing our understanding of beta-cell development and expanding the therapeutic possibilities for treating diabetes and other diseases. Here we focus on the emerging use of gene editing technology, specifically CRISPR/Cas9, as a means of manipulating human gene expression to gain novel insights into the roles of key factors in beta-cell development and function. Taken together, the combined use of SC-β cells and CRISPR/Cas9 gene editing will shed new light on human beta-cell development and function and accelerate our progress towards developing new therapies for patients with diabetes.

Milk composition and lactation of beta-casein-deficient mice.

PubMed Central

Kumar, S; Clarke, A R; Hooper, M L; Horne, D S; Law, A J; Leaver, J; Springbett, A; Stevenson, E; Simons, J P

1994-01-01

beta-Casein is a major protein component of milk and, in conjunction with the other caseins, it is assembled into micelles. The casein micelles determine many of the physical characteristics of milk, which are important for stability during storage and for milk-processing properties. There is evidence that suggests that beta-casein may also possess other, nonnutritional functions. To address the function of beta-casein, the mouse beta-casein gene was disrupted by gene targeting in embryonic stem cells. Homozygous beta-casein mutant mice are viable and fertile; females can lactate and successfully rear young. beta-Casein was expressed at a reduced level in heterozygotes and was completely absent from the milk of homozygous mutant mice. Despite the deficiency of beta-casein, casein micelles were assembled in heterozygous and homozygous mutants, albeit with reduced diameters. The absence of beta-casein expression was reflected in a reduced total protein concentration in milk, although this was partially compensated for by an increased concentration of other proteins. The growth of pups feeding on the milk of homozygous mutants was reduced relative to those feeding on the milk of wild-type mice. Various genetic manipulations of caseins have been proposed for the qualitative improvement of cow's milk composition. The results presented here demonstrate that beta-casein has no essential function and that the casein micelle is remarkably tolerant of changes in composition. Images PMID:8016126

V(D)J recombination and allelic exclusion of a TCR beta-chain minilocus occurs in the absence of a functional promoter.

PubMed

Alvarez, J D; Anderson, S J; Loh, D Y

1995-08-01

Transcriptional activation of rearranging Ag receptor gene segments has been hypothesized to regulate their accessibility to V(D)J recombination. We analyzed the role of a functional promoter in the rearrangement of the murine TCR beta-chain locus using two transgenic minilocus constructs. These miniloci each contain an unrearranged V beta 8.3 gene. One has a wild-type V beta 8.3 gene, but the other has a V beta 8.3 gene with a promoter mutation that was previously shown to abrogate transcription in tissue culture. FACS analysis of thymus and lymph node cells from transgenic mouse lines showed that only the lines with the wild-type V beta 8.3 gene promoter express an 8.3 TCR beta-chain. Consistent with the protein expression data, V beta 8.3 gene transcripts were found only in the transgenic lines with the wild-type promoter. Using a quantitative PCR-based assay, it was shown that both types of transgenic lines recombine the V beta 8.3 gene at similar levels. Rearrangement of the transgenes was normal with respect to thymic development and junctional reading frame. Interestingly, both types of miniloci also underwent allelic exclusion in that recombination was blocked by the expression of a rearranged TCR beta-chain transgene. We conclude that a functional V beta gene promoter is not necessary for proper V(D)J recombination to occur.

The insulin and islet amyloid polypeptide genes contain similar cell-specific promoter elements that bind identical beta-cell nuclear complexes.

PubMed Central

German, M S; Moss, L G; Wang, J; Rutter, W J

1992-01-01

The pancreatic beta cell makes several unique gene products, including insulin, islet amyloid polypeptide (IAPP), and beta-cell-specific glucokinase (beta GK). The functions of isolated portions of the insulin, IAPP, and beta GK promoters were studied by using transient expression and DNA binding assays. A short portion (-247 to -197 bp) of the rat insulin I gene, the FF minienhancer, contains three interacting transcriptional regulatory elements. The FF minienhancer binds at least two nuclear complexes with limited tissue distribution. Sequences similar to that of the FF minienhancer are present in the 5' flanking DNA of the human IAPP and rat beta GK genes and also the rat insulin II and mouse insulin I and II genes. Similar minienhancer constructs from the insulin and IAPP genes function as cell-specific transcriptional regulatory elements and compete for binding of the same nuclear factors, while the beta GK construct competes for protein binding but functions poorly as a minienhancer. These observations suggest that the patterns of expression of the beta-cell-specific genes result in part from sharing the same transcriptional regulators. Images PMID:1549125

The complex roles of space and environment in structuring functional, taxonomic and phylogenetic beta diversity of frogs in the Atlantic Forest

PubMed Central

Luiz, Amom Mendes; Sawaya, Ricardo J.

2018-01-01

Ecological communities are complex entities that can be maintained and structured by niche-based processes such as environmental conditions, and spatial processes such as dispersal. Thus, diversity patterns may be shaped simultaneously at different spatial scales by very distinct processes. Herein we assess whether and how functional, taxonomic, and phylogenetic beta diversities of frog tadpoles are explained by environmental and/or spatial predictors. We implemented a distance–based redundancy analysis to explore variation in components of beta diversity explained by pure environmental and pure spatial predictors, as well as their interactions, at both fine and broad spatial scales. Our results indicated important but complex roles of spatial and environmental predictors in structuring phylogenetic, taxonomic and functional beta diversities. The pure fine-scales spatial fraction was more important in structuring all beta diversity components, especially to functional and taxonomical spatial turnover. Environmental variables such as canopy cover and vegetation structure were important predictors of all components, but especially to functional and taxonomic beta diversity. We emphasize that distinct factors related to environment and space are affecting distinct components of beta diversity in different ways. Although weaker, phylogenetic beta diversity, which is structured more on biogeographical scales, and thus can be represented by spatially structured processes, was more related to broad spatial processes than other components. However, selected fine-scale spatial predictors denoted negative autocorrelation, which may be revealing the existence of differences in unmeasured habitat variables among samples. Although overall important, local environmental-based processes explained better functional and taxonomic beta diversity, as these diversity components carry an important ecological value. We highlight the importance of assessing different components of diversity patterns at different scales by spatially explicit models in order to improve our understanding of community structure and help to unravel the complex nature of biodiversity. PMID:29672575

Role of beta-alanine supplementation on muscle carnosine and exercise performance.

PubMed

Artioli, Guilherme Giannini; Gualano, Bruno; Smith, Abbie; Stout, Jeffrey; Lancha, Antonio Herbert

2010-06-01

In this narrative review, we present and discuss the current knowledge available on carnosine and beta-alanine metabolism as well as the effects of beta-alanine supplementation on exercise performance. Intramuscular acidosis has been attributed to be one of the main causes of fatigue during intense exercise. Carnosine has been shown to play a significant role in muscle pH regulation. Carnosine is synthesized in skeletal muscle from the amino acids l-histidine and beta-alanine. The rate-limiting factor of carnosine synthesis is beta-alanine availability. Supplementation with beta-alanine has been shown to increase muscle carnosine content and therefore total muscle buffer capacity, with the potential to elicit improvements in physical performance during high-intensity exercise. Studies on beta-alanine supplementation and exercise performance have demonstrated improvements in performance during multiple bouts of high-intensity exercise and in single bouts of exercise lasting more than 60 s. Similarly, beta-alanine supplementation has been shown to delay the onset of neuromuscular fatigue. Although beta-alanine does not improve maximal strength or VO2max, some aspects of endurance performance, such as anaerobic threshold and time to exhaustion, can be enhanced. Symptoms of paresthesia may be observed if a single dose higher than 800 mg is ingested. The symptoms, however, are transient and related to the increase in plasma concentration. They can be prevented by using controlled release capsules and smaller dosing strategies. No important side effect was related to the use of this amino acid so far. In conclusion, beta-alanine supplementation seems to be a safe nutritional strategy capable of improving high-intensity anaerobic performance.

Mechanical properties of a biodegradable bone regeneration scaffold

NASA Technical Reports Server (NTRS)

Porter, B. D.; Oldham, J. B.; He, S. L.; Zobitz, M. E.; Payne, R. G.; An, K. N.; Currier, B. L.; Mikos, A. G.; Yaszemski, M. J.

2000-01-01

Poly (Propylene Fumarate) (PPF), a novel, bulk erosion, biodegradable polymer, has been shown to have osteoconductive effects in vivo when used as a bone regeneration scaffold (Peter, S. J., Suggs, L. J., Yaszemski, M. J., Engel, P. S., and Mikos, A. J., 1999, J. Biomater. Sci. Polym. Ed., 10, pp. 363-373). The material properties of the polymer allow it to be injected into irregularly shaped voids in vivo and provide mechanical stability as well as function as a bone regeneration scaffold. We fabricated a series of biomaterial composites, comprised of varying quantities of PPF, NaCl and beta-tricalcium phosphate (beta-TCP), into the shape of right circular cylinders and tested the mechanical properties in four-point bending and compression. The mean modulus of elasticity in compression (Ec) was 1204.2 MPa (SD 32.2) and the mean modulus of elasticity in bending (Eb) was 1274.7 MPa (SD 125.7). All of the moduli were on the order of magnitude of trabecular bone. Changing the level of NaCl from 20 to 40 percent, by mass, did not decrease Ec and Eb significantly, but did decrease bending and compressive strength significantly. Increasing the beta-TCP from 0.25 g/g PPF to 0.5 g/g PPF increased all of the measured mechanical properties of PPF/NVP composites. These results indicate that this biodegradable polymer composite is an attractive candidate for use as a replacement scaffold for trabecular bone.

Infrared and Raman Study of the Recluse Spider Silk

NASA Astrophysics Data System (ADS)

Wang, S. L.; Wang, Qijue; Xing, Zhen; Schniepp, H. C.; Qazilbash, M. M.

Spider silk exhibits remarkable mechanical properties, such as high tensile strength and toughness. We want to gain insight into the composition and structure of spider silk to discover the origin of these properties. We are especially interested in the organization of the crystalline beta sheets that are expected to contribute to the high strength of the silk from the recluse spider, Loxosceles laeta. The recluse spider produces a silk that has a unique geometry amongst arachnids. We measure the silk's optical properties, particularly the infrared-active and Raman-active vibrations. Broadband infrared transmission spectra were collected in the spectral range between 600 cm-1 and 4000 cm-1, with light polarized parallel and perpendicular to the long axis of the silk. Raman micro-spectroscopy was performed in the spectral range 500 cm-1 and 4000 cm- 1 with a 514 nm laser. The infrared and Raman vibrational modes are fit with Lorentzian and pseudo-Voigt functions. The vibrational modes are assigned to specific structures and electronic bonds in the silk. This work was supported by NASA/ Virginia Space Grant Consortium.

Integrin-mediated transforming growth factor-beta activation regulates homeostasis of the pulmonary epithelial-mesenchymal trophic unit.

PubMed

Araya, Jun; Cambier, Stephanie; Morris, Alanna; Finkbeiner, Walter; Nishimura, Stephen L

2006-08-01

Trophic interactions between pulmonary epithelial and mesenchymal cell types, known as the epithelial-mesenchymal trophic unit (EMTU), are crucial in lung development and lung disease. Transforming growth factor (TGF)-beta is a key factor in mediating these interactions, but it is expressed in a latent form that requires activation to be functional. Using intact fetal tracheal tissue and primary cultures of fetal tracheal epithelial cells and fibroblasts, we demonstrate that a subset of integrins, alpha(v)beta(6) and alpha(v)beta(8), are responsible for almost all of the TGF-beta activation in the EMTU. Both alpha(v)beta(8) and alpha(v)beta(6) contribute to fetal tracheal epithelial activation of TGF-beta, whereas only alpha(v)beta(8) contributes to fetal tracheal fibroblast activation of TGF-beta. Interestingly, fetal tracheal epithelial alpha(v)beta(8)-mediated TGF-beta activation can be enhanced by phorbol esters, likely because of the increased activity of MT1-MMP, an essential co-factor in alpha(v)beta(8)-mediated activation of TGF-beta. Autocrine alpha(v)beta(8)-mediated TGF-beta activation by fetal tracheal fibroblasts results in suppression of both transcription and secretion of hepatocyte growth factor, which is sufficient to affect phosphorylation of the airway epithelial hepatocyte growth factor receptor, c-Met, as well as airway epithelial proliferation in a co-culture model of the EMTU. These findings elucidate the function and complex regulation of integrin-mediated activation of TGF-beta within the EMTU.

Double gene deletion reveals the lack of cooperation between PPAR{alpha} and PPAR{beta} in skeletal muscle

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

Bedu, E.; Desplanches, D.; Pequignot, J.

2007-06-15

The peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of most of the pathways linked to lipid metabolism. PPAR{alpha} and PPAR{beta} isotypes are known to regulate muscle fatty acid oxidation and a reciprocal compensation of their function has been proposed. Herein, we investigated muscle contractile and metabolic phenotypes in PPAR{alpha}-/-, PPAR{beta}-/-, and double PPAR{alpha}-/- {beta}-/- mice. Heart and soleus muscle analyses show that the deletion of PPAR{alpha} induces a decrease of the HAD activity ({beta}-oxidation) while soleus contractile phenotype remains unchanged. A PPAR{beta} deletion alone has no effect. However, these mild phenotypes are not due to a reciprocal compensationmore » of PPAR{beta} and PPAR{alpha} functions since double gene deletion PPAR{alpha}-PPAR{beta} mostly reproduces the null PPAR{alpha}-mediated reduced {beta}-oxidation, in addition to a shift from fast to slow fibers. In conclusion, PPAR{beta} is not required for maintaining skeletal muscle metabolic activity and does not compensate the lack of PPAR{alpha} in PPAR{alpha} null mice.« less

Evidence for Intramolecular Antiparallel Beta-Sheet Structure in Alpha-Synuclein Fibrils from a Combination of Two-Dimensional Infrared Spectroscopy and Atomic Force Microscopy

NASA Astrophysics Data System (ADS)

Roeters, Steven J.; Iyer, Aditya; Pletikapić, Galja; Kogan, Vladimir; Subramaniam, Vinod; Woutersen, Sander

2017-01-01

The aggregation of the intrinsically disordered protein alpha-synuclein (αS) into amyloid fibrils is thought to play a central role in the pathology of Parkinson’s disease. Using a combination of techniques (AFM, UV-CD, XRD, and amide-I 1D- and 2D-IR spectroscopy) we show that the structure of αS fibrils varies as a function of ionic strength: fibrils aggregated in low ionic-strength buffers ([NaCl] ≤ 25 mM) have a significantly different structure than fibrils grown in higher ionic-strength buffers. The observations for fibrils aggregated in low-salt buffers are consistent with an extended conformation of αS molecules, forming hydrogen-bonded intermolecular β-sheets that are loosely packed in a parallel fashion. For fibrils aggregated in high-salt buffers (including those prepared in buffers with a physiological salt concentration) the measurements are consistent with αS molecules in a more tightly-packed, antiparallel intramolecular conformation, and suggest a structure characterized by two twisting stacks of approximately five hydrogen-bonded intermolecular β-sheets each. We find evidence that the high-frequency peak in the amide-I spectrum of αS fibrils involves a normal mode that differs fundamentally from the canonical high-frequency antiparallel β-sheet mode. The high sensitivity of the fibril structure to the ionic strength might form the basis of differences in αS-related pathologies.

Evidence for Intramolecular Antiparallel Beta-Sheet Structure in Alpha-Synuclein Fibrils from a Combination of Two-Dimensional Infrared Spectroscopy and Atomic Force Microscopy

PubMed Central

Roeters, Steven J.; Iyer, Aditya; Pletikapić, Galja; Kogan, Vladimir; Subramaniam, Vinod; Woutersen, Sander

2017-01-01

The aggregation of the intrinsically disordered protein alpha-synuclein (αS) into amyloid fibrils is thought to play a central role in the pathology of Parkinson’s disease. Using a combination of techniques (AFM, UV-CD, XRD, and amide-I 1D- and 2D-IR spectroscopy) we show that the structure of αS fibrils varies as a function of ionic strength: fibrils aggregated in low ionic-strength buffers ([NaCl] ≤ 25 mM) have a significantly different structure than fibrils grown in higher ionic-strength buffers. The observations for fibrils aggregated in low-salt buffers are consistent with an extended conformation of αS molecules, forming hydrogen-bonded intermolecular β-sheets that are loosely packed in a parallel fashion. For fibrils aggregated in high-salt buffers (including those prepared in buffers with a physiological salt concentration) the measurements are consistent with αS molecules in a more tightly-packed, antiparallel intramolecular conformation, and suggest a structure characterized by two twisting stacks of approximately five hydrogen-bonded intermolecular β-sheets each. We find evidence that the high-frequency peak in the amide-I spectrum of αS fibrils involves a normal mode that differs fundamentally from the canonical high-frequency antiparallel β-sheet mode. The high sensitivity of the fibril structure to the ionic strength might form the basis of differences in αS-related pathologies. PMID:28112214

Association of T-cell reactivity with beta-cell function in recent onset type 1 diabetes patients.

PubMed

Pfleger, Christian; Meierhoff, Guido; Kolb, Hubert; Schloot, Nanette C

2010-03-01

The aim of the current study was to investigate whether autoantigen directed T-cell reactivity relates to beta-cell function during the first 78 weeks after diagnosis of type 1 diabetes. 50 adults and 49 children (mean age 27.3 and 10.9 years respectively) with recent onset type 1 diabetes who participated in a placebo-controlled trial of immune intervention with DiaPep277 were analyzed. Secretion of interferon (IFN)-gamma, interleukin (IL)-5, IL-13 and IL-10 by single peripheral mononuclear cells (PBMC) upon stimulation with islet antigens GAD65, heat shock protein 60 (Hsp60) protein-tyrosine-phosphatase-like-antigen (pIA2) or tetanus toxoid (TT) was determined applying ELISPOT; beta-cell function was evaluated by glucagon stimulated C-peptide. Multivariate regression analysis was applied. In general, number of islet antigen-reactive cells decreased over 78 weeks in both adults and children, whereas reactivity to TT was not reduced. In addition, there was an association between the quality of immune cell responses and beta-cell function. Overall, increased responses by IFN-gamma secreting cells were associated with lower beta-cell function whereas IL-5, IL-13 and IL-10 cytokine responses were positively associated with beta-cell function in adults and children. Essentially, the same results were obtained with three different models of regression analysis. The number of detectable islet-reactive immune cells decreases within 1-2 years after diagnosis of type 1 diabetes. Cytokine production by antigen-specific PBMC reactivity is related to beta-cell function as measured by stimulated C-peptide. Cellular immunity appears to regress soon after disease diagnosis and begin of insulin therapy. Copyright 2009 Elsevier Ltd. All rights reserved.

The nonlinear light output of NaI(Tl) detectors in the Modular Total Absorption Spectrometer

DOE PAGES

Rasco, B. C.; Fijałkowska, A.; Karny, M.; ...

2015-04-08

New detector array, the Modular Total Absorption Spectrometer (MTAS),was commissioned at the Holifield Radioactive Ion Beam Facility (HRIBF) at Oak Ridge National Lab(ORNL).Total absorption gamma spectra measured with MTAS are expected to improve beta-feeding patterns and beta strength functions in fission products.MTAS is constructed out of hexagonal NaI(Tl) detectors with a unique central module surrounded by 18 identical crystals assembled in three rings. The total NaI(Tl) mass of MTAS is over1000 kg.The response of the central and other 18 MTAS modules to -radiation was simulated using the GEANT4 tool kit modified to analyze the nonlinear light output of NaI(Tl).A detailedmore » description oftheGEANT4modifications madeisdiscussed.SimulatedenergyresolutionofMTAS modules is found to agree well with the measurements for single transitions of 662keV (137Cs) with 8.2% full width half maximum (FWHM),835keV (54Mn) with FWHM of 7.5% FWHM, and 1115keV (65Zn) with FWHM of 6.5%.Simulations of single and multiple -rays from 60Co are also discussed.« less

The changes in beta-adrenoceptor-mediated cardiac function in experimental hypothyroidism: the possible contribution of cardiac beta3-adrenoceptors.

PubMed

Arioglu, E; Guner, S; Ozakca, I; Altan, V M; Ozcelikay, A T

2010-02-01

Thyroid hormone deficiency has been reported to decrease expression and function of both beta(1)- and beta(2)-adrenoceptor in different tissues including heart. The purpose of this study was to examine the possible contribution of beta(3)-adrenoceptors to cardiac dysfunction in hypothyroidism. In addition, effect of this pathology on beta(1)- and beta(2)-adrenoceptor was investigated. Hypothyroidism was induced by adding methimazole (300 mg/l) to drinking water of rats for 8 weeks. Cardiac hemodynamic parameters were measured in anesthetised rats in vivo. Responses to beta-adrenoceptor agonists were examined in rat papillary muscle in vitro. We also studied the effect of hypotyroidism on mRNA expression of beta-adrenoceptors, Gialpha, GRK, and eNOS in rat heart. All of the hemodynamic parameters (systolic, diastolic and mean arterial pressure, left ventricular pressure, heart rate, +dp/dt, and -dp/dt) were significantly reduced by the methimazole treatment. The negative inotropic effect elicited by BRL 37344 (a beta(3)-adrenoceptor preferential agonist) and positive inotropic effects produced by isoprenaline and noradrenaline, respectively, were significantly decreased in papillary muscle of hypothyroid rats as compared to those of controls. On the other hand, hypothyroidism resulted in increased cardiac beta(2)- and beta(3)-adrenoceptor, Gialpha(2), Gialpha(3), GRK3, and eNOS mRNA expressions. However, beta(1)-adrenoceptor and GRK2 mRNA expressions were not changed significantly in this pathology. These results show that mRNA expression of beta(3)-adrenoceptors as well as the signalling pathway components mediated through beta(3)-adrenoceptors are significantly increased in hypothyroid rat heart. Since we could not correlate these alternates with the decreased negative inotropic response mediated by this receptor subtype, it is not clear whether these changes are important for hypothyroid induced reduction in cardiac function.

Expression of beta 3-adrenoceptor mRNA in rat tissues.

PubMed

Evans, B A; Papaioannou, M; Bonazzi, V R; Summers, R J

1996-01-01

1. This study examines the expression of beta 3-adrenoceptor messenger RNA (beta 3-AR mRNA) in rat tissues to allow comparison with atypical beta-adrenoceptors determined by functional and radioligand binding techniques. 2. A reverse transcription/polymerase chain reaction protocol has been developed for determining the relative amounts of beta 3-AR mRNA in rat tissues. 3. Measurement of adipsin and uncoupling protein (UCP) mRNA was used to examine all tissues for the presence of white and brown adipose tissue which may contribute beta 3-AR mRNA. 4. The beta 3-AR mRNA is expressed at high levels in brown and white adipose tissue, stomach fundus, the longitudinal/circular smooth muscle of both colon and ileum, and colon submucosa. There was substantial expression of adipsin in colon submucosa and moderate expression in fundus, suggesting that in these regions at least some of the beta 3-AR signal may be contributed by fat. Pylorus and colon mucosa showed moderate levels of beta 3-AR mRNA with lower levels of adipsin. Ileum mucosa and submucosa showed low but readily detectable levels of beta 3-AR. 5. Expression of adipsin in rat skeletal muscles coupled to very low levels of beta 3-AR mRNA indicates that the observed beta 3-AR may be due to the presence of intrinsic fat. beta 3-AR mRNA was virtually undetectable in heart, lung and liver. These results raise the possibility that the atypical beta-AR demonstrated by functional and/or binding studies in muscle and in heart is not the beta 3-AR. 6. By use of two different sets of primers for amplification of beta 3-AR cDNA, no evidence was found for differential splicing of the mRNA in any of the tissues examined. 7. The detection of beta 3-AR mRNA in the gut mucosa and submucosa suggests that in addition to its established roles in lipolysis, thermogenesis and regulation of gut motility beta 3-AR may subserve other functions in the gastrointestinal tract. The absence of beta 3-AR mRNA in rat heart or its presence with adipsin in skeletal muscle suggests that atypical beta-adrenoceptor responses in heart and skeletal muscle are unlikely to be mediated by beta 3-AR.

HNF1(beta) is required for mesoderm induction in the Xenopus embryo.

PubMed

Vignali, R; Poggi, L; Madeddu, F; Barsacchi, G

2000-04-01

XHNF1(&bgr;) is a homeobox-containing gene initially expressed at the blastula stage in the vegetal part of the Xenopus embryo. We investigated its early role by functional ablation, through mRNA injection of an XHNF1(beta)/engrailed repressor fusion construct (XHNF1(beta)/EngR). Dorsal injections of XHNF1(beta)/EngR mRNA abolish dorsal mesoderm formation, leading to axial deficiencies; ventral injections disrupt ventral mesoderm formation without affecting axial development. XHNF1(beta)/EngR phenotypic effects specifically depend on the DNA-binding activity of its homeodomain and are fully rescued by coinjection of XHNF1(beta) mRNA. Vegetal injection of XHNF1(beta)/EngR mRNA blocks the mesoderm-inducing ability of vegetal explants. Both B-Vg1 and VegT maternal determinants trigger XHNF1(beta) expression in animal caps. XHNF1(beta)/EngR mRNA blocks B-Vg1-mediated, but not by eFGF-mediated, mesoderm induction in animals caps. However, wild-type XHNF1(beta) mRNA does not trigger Xbra expression in animal caps. We conclude that XHNF1(beta) function is essential, though not sufficient, for mesoderm induction in the Xenopus embryo.

Isolation and functional characterization of a lycopene beta-cyclase gene that controls fruit colour of papaya (Carica papaya L.).

PubMed

Devitt, Luke C; Fanning, Kent; Dietzgen, Ralf G; Holton, Timothy A

2010-01-01

The colour of papaya fruit flesh is determined largely by the presence of carotenoid pigments. Red-fleshed papaya fruit contain lycopene, whilst this pigment is absent from yellow-fleshed fruit. The conversion of lycopene (red) to beta-carotene (yellow) is catalysed by lycopene beta-cyclase. This present study describes the cloning and functional characterization of two different genes encoding lycopene beta-cyclases (lcy-beta1 and lcy-beta2) from red (Tainung) and yellow (Hybrid 1B) papaya cultivars. A mutation in the lcy-beta2 gene, which inactivates enzyme activity, controls lycopene production in fruit and is responsible for the difference in carotenoid production between red and yellow-fleshed papaya fruit. The expression level of both lcy-beta1 and lcy-beta2 genes is similar and low in leaves, but lcy-beta2 expression increases markedly in ripe fruit. Isolation of the lcy-beta2 gene from papaya, that is preferentially expressed in fruit and is correlated with fruit colour, will facilitate marker-assisted breeding for fruit colour in papaya and should create possibilities for metabolic engineering of carotenoid production in papaya fruit to alter both colour and nutritional properties.

Beta-globin locus activation regions: conservation of organization, structure, and function.

PubMed Central

Li, Q L; Zhou, B; Powers, P; Enver, T; Stamatoyannopoulos, G

1990-01-01

The human beta-globin locus activation region (LAR) comprises four erythroid-specific DNase I hypersensitive sites (I-IV) thought to be largely responsible for activating the beta-globin domain and facilitating high-level erythroid-specific globin gene expression. We identified the goat beta-globin LAR, determined 10.2 kilobases of its sequence, and demonstrated its function in transgenic mice. The human and goat LARs share 6.5 kilobases of homologous sequences that are as highly conserved as the epsilon-globin gene promoters. Furthermore, the overall spatial organization of the two LARs has been conserved. These results suggest that the functionally relevant regions of the LAR are large and that in addition to their primary structure, the spatial relationship of the conserved elements is important for LAR function. Images PMID:2236034

Chemical rescue of cleft palate and midline defects in conditional GSK-3beta mice.

PubMed

Liu, Karen J; Arron, Joseph R; Stankunas, Kryn; Crabtree, Gerald R; Longaker, Michael T

2007-03-01

Glycogen synthase kinase-3beta (GSK-3beta) has integral roles in a variety of biological processes, including development, diabetes, and the progression of Alzheimer's disease. As such, a thorough understanding of GSK-3beta function will have a broad impact on human biology and therapeutics. Because GSK-3beta interacts with many different pathways, its specific developmental roles remain unclear. We have discovered a genetic requirement for GSK-3beta in midline development. Homozygous null mice display cleft palate, incomplete fusion of the ribs at the midline and bifid sternum as well as delayed sternal ossification. Using a chemically regulated allele of GSK-3beta (ref. 6), we have defined requirements for GSK-3beta activity during discrete temporal windows in palatogenesis and skeletogenesis. The rapamycin-dependent allele of GSK-3beta produces GSK-3beta fused to a tag, FRB* (FKBP/rapamycin binding), resulting in a rapidly destabilized chimaeric protein. In the absence of drug, GSK-3beta(FRB)*(/FRB)* mutants appear phenotypically identical to GSK-3beta-/- mutants. In the presence of drug, GSK-3betaFRB* is rapidly stabilized, restoring protein levels and activity. Using this system, mutant phenotypes were rescued by restoring endogenous GSK-3beta activity during two distinct periods in gestation. This technology provides a powerful tool for defining windows of protein function during development.

Structure function and splice site analysis of the synaptogenic activity of the neurexin-1 beta LNS domain.

PubMed

Graf, Ethan R; Kang, Yunhee; Hauner, Anna M; Craig, Ann Marie

2006-04-19

Recent findings suggest that the neurexin-neuroligin link promotes both GABAergic and glutamatergic synaptogenesis, but the mechanism by which neurexins influence the clustering of appropriate neuroligins and postsynaptic differentiation remains unclear. Previous studies suggested that the presence or absence of alternatively spliced residues at splice site 4 (S4) in the neurexin LNS domain may regulate neurexin function. We demonstrate that addition of the S4 insert selectively reduces the ability of neurexin-1beta to cluster neuroligin-1/3/4 and glutamatergic postsynaptic proteins, although clustering of neuroligin-2 and GABAergic postsynaptic proteins remain strong. Furthermore, addition of the S4 insert decreases the binding affinity of neurexin-1beta to neuroligins-1 and -4 but has little effect on binding to neuroligins-2 and -3. Additional structure-function studies reveal the neurexin binding interface mediating synaptogenic activity to be composed primarily of residues in the beta2beta3, beta6beta7, and beta10beta11 loops on one rim of the LNS domain beta sandwich. Mutation of two predicted Ca(2+)-binding residues disrupts postsynaptic protein clustering and binding to neuroligins, consistent with previous findings that neurexin-neuroligin binding is Ca2+ dependent. Glutamatergic postsynaptic clustering was more readily disrupted by the mutagenesis than GABAergic postsynaptic protein clustering. Perhaps neurexins-neuroligins, or neurexin-1beta at least, is most important for GABA synapse formation or controlling the balance of GABA and glutamate synapses. These results suggest that differential neurexin-neuroligin binding affinities and splice variations may play an instructive role in postsynaptic differentiation.

Specific beta1-adrenergic receptor silencing with small interfering RNA lowers high blood pressure and improves cardiac function in myocardial ischemia.

PubMed

Arnold, Anne-Sophie; Tang, Yao Liang; Qian, Keping; Shen, Leping; Valencia, Valery; Phillips, Michael Ian; Zhang, Yuan Clare

2007-01-01

Beta-blockers are widely used and effective for treating hypertension, acute myocardial infarction (MI) and heart failure, but they present side-effects mainly due to antagonism of beta2-adrenergic receptor (AR). Currently available beta-blockers are at best selective but not specific for beta1 or beta2-AR. To specifically inhibit the expression of the beta1-AR, we developed a small interfering RNA (siRNA) targeted to beta1-AR. Three different sequences of beta1 siRNA were delivered into C6-2B cells with 90% efficiency. One of the three sequences reduced the level of beta1-AR mRNA by 70%. The siRNA was highly specific for beta1-AR inhibition with no overlap with beta2-AR. To test this in vivo, systemic injection of beta1 siRNA complexed with liposomes resulted in efficient delivery into the heart, lung, kidney and liver, and effectively reduced beta1-AR expression in the heart without altering beta2-AR. beta1 siRNA significantly lowered blood pressure of spontaneously hypertensive rats (SHR) for at least 12 days and reduced cardiac hypertrophy following a single injection. Pretreatment with beta1 siRNA 3 days before induction of MI in Wistar rats significantly improved cardiac function, as demonstrated by dP/dt and electrocardiogram following the MI. The protective mechanism involved reduction of cardiomyocyte apoptosis in the beta1 siRNA-treated hearts. The present study demonstrates the possibility of using siRNA for treating cardiovascular diseases and may represent a novel beta-blocker specific for beta1-AR.

Selective Ring Opening of 1-Methylnaphthalene Over NiW-Supported Catalyst Using Dealuminated Beta Zeolite.

PubMed

Kim, Eun-Sang; Lee, You-Jin; Kim, Jeong-Rang; Kim, Joo-Wan; Kim, Tae-Wan; Chae, Ho-Jeong; Kim, Chul-Ung; Lee, Chang-Ha; Jeong, Soon-Yong

2016-02-01

Nanoporous Beta zeolite was dealuminated by weak acid treatment for reducing the acidity. Bi-functional catalysts were prepared using commercial Beta zeolites and the dealuminated zeolites for acidic function, NiW for metallic function. 1-Methylnaphthalene was selected as a model compound for multi-ring aromatics in heavy oil, and its selective ring opening reaction has been investigated using the prepared bi-functional catalysts with different acidity in fixed bed reaction system. The dealuminated Beta zeolites, which crystal structure and nanoporosity were maintained, showed the higher SiO2/Al2O3 ratio and smaller acidity than their original zeolite. NiW-supported catalyst using the dealuminated Beta zeolite with SiO2/Al203 mole ratio of 55 showed the highest performance for the selective ring opening. The acidity of catalyst seemed to play an important role as active sites for the selective ring opening of 1-methylnaphthalene but there should be some optimum catalyst acidity for the reaction. The acidity of Beta zeolite could be controlled by the acid treatment and the catalyst with the optimum acidity for the selective ring opening could be prepared.

Asymptotic expansions of the kernel functions for line formation with continuous absorption

NASA Technical Reports Server (NTRS)

Hummer, D. G.

1991-01-01

Asymptotic expressions are obtained for the kernel functions M2(tau, alpha, beta) and K2(tau, alpha, beta) appearing in the theory of line formation with complete redistribution over a Voigt profile with damping parameter a, in the presence of a source of continuous opacity parameterized by beta. For a greater than 0, each coefficient in the asymptotic series is expressed as the product of analytic functions of a and eta. For Doppler broadening, only the leading term can be evaluated analytically.

Beta-Cryptoxanthin as a source of Vitamin A.

USDA-ARS?s Scientific Manuscript database

Beta-cryptoxanthin is a common carotenoid that is found in fruit, and in human blood and tissues. Foods that are rich in beta-cryptoxanthin include tangerines, persimmons, and oranges. Beta-cryptoxanthin has several functions that are important for human health, including roles in antioxidant defens...

Incretin hormone receptors are required for normal beta cell development and function in female mice.

PubMed

Omar, Bilal; Ahlkvist, Linda; Yamada, Yuchiro; Seino, Yutaka; Ahrén, Bo

2016-05-01

The incretin hormones, glucose dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), potentiate insulin secretion and are responsible for the majority of insulin secretion that occurs after a meal. They may also, however, have a fundamental role in pancreatic beta cell development and function, independently of their role in potentiating insulin secretion after a meal. This has led to observations that a loss of GIP or GLP-1 action affects normal beta cell function, however each one of the incretin hormones may compensate when the action of the other is lost and therefore the overall impact of the incretin hormones on beta cell function is not known. We therefore utilized a mouse line deficient in both the GLP-1 and GIP receptor genes, the double incretin receptor knockout (DIRKO), to determine the consequences of a lifelong, complete lack of incretin hormone action on beta cell function, in vivo, in intact animals. We found that DIRKO mice displayed impaired glucose tolerance and insulin secretion in response to both oral glucose and mixed meal tolerance tests compared to wild-type mice. Assessment of beta cell function using the hyperglycemic clamp technique revealed an 80% decrease in first phase insulin response in DIRKO mice, but a normal second phase insulin secretion. A similar decline was seen when wild-type mice were given acute intravenous injection of glucose together with the GLP-1 receptor antagonist Ex9-39. Ex vivo assessments of the pancreas revealed significantly fewer islets in the pancreata of DIRKO mice despite no differences in total pancreatic mass. Insulin secretion from isolated islets of DIRKO mice was impaired to a similar extent to that seen during the hyperglycemic clamp. Insulin secretion in wild-type islets was impaired by acute treatment with Ex9-39 to a similar extent as the in vivo intravenous glucose tolerance tests. In conclusion, a loss of the action of both incretin hormones results in direct impairment of beta cell function both in vivo and in vitro in a process that appears to be independent of the intestinally secreted incretin hormones. We therefore conclude that the incretin hormones together significantly impact both beta-cell function and beta-cell development. Copyright © 2016. Published by Elsevier Inc.

Functionalization of DNA Nanostructures for Cell Signaling Applications

NASA Astrophysics Data System (ADS)

Pedersen, Ronnie O.

Transforming growth factor beta (TGF-beta) is an important cytokine responsible for a wide range of different cellular functions including extracellular matrix formation, angiogenesis and epithelial-mesenchymal transition. We have sought to use self-assembling DNA nanostructures to influence TGF-beta signaling. The predictable Watson Crick base pairing allows for designing self-assembling nanoscale structures using oligonucleotides. We have used the method of DNA origami to assemble structures functionalized with multiple peptides that bind TGF-beta receptors outside the ligand binding domain. This allows the nanostructures to cluster TGF-beta receptors and lower the energy barrier of ligand binding thus sensitizing the cells to TGF-beta stimulation. To prove efficacy of our nanostructures we have utilized immunofluorescent staining of Smad2/4 in order to monitor TGF-beta mediated translocation of Smad2/4 to the cell nucleus. We have also utilized Smad2/4 responsive luminescence constructs that allows us to quantify TGF-beta stimulation with and without nanostructures. To functionalize our nanostructures we relied on biotin-streptavidin linkages. This introduces a multivalency that is not necessarily desirable in all designs. Therefore we have investigated alternative means of functionalization. The first approach is based on targeting DNA nanostructure by using zinc finger binding proteins. Efficacy of zinc finger binding proteins was assayed by the use of enzyme-linked immunosorbent (ELISA) assay and atomic force microscopy (AFM). While ELISA indicated a relative specificity of zinc finger proteins for target DNA sequences AFM showed a high degree of non-specific binding and insufficient affinity. The second approach is based on using peptide nucleic acid (PNA) incorporated in the nanostructure through base pairing. PNA is a synthetic DNA analog consisting of a backbone of repeating N-(2-aminoethyl)-glycine units to which purine and pyrimidine bases are linked by amide bonds. The solid phase synthesis of PNA allows for convenient extension of the backbone into a peptide segment enabling peptide functionalization of DNA nanostructures. We have investigated how the neutral character of PNA alters the incorporation in DNA based nanostructures compared to a DNA control using biotinylation and AFM. Results indicate that PNA can successfully be used as a way of functionalizing DNA nanostructures. Additionally we have shown that functionalized nanostructures are capable of sensitizing cells to TGF-beta stimulation.

The rate of transient beta frequency events predicts behavior across tasks and species

PubMed Central

Law, Robert; Tsutsui, Shawn; Moore, Christopher I; Jones, Stephanie R

2017-01-01

Beta oscillations (15-29Hz) are among the most prominent signatures of brain activity. Beta power is predictive of healthy and abnormal behaviors, including perception, attention and motor action. In non-averaged signals, beta can emerge as transient high-power 'events'. As such, functionally relevant differences in averaged power across time and trials can reflect changes in event number, power, duration, and/or frequency span. We show that functionally relevant differences in averaged beta power in primary somatosensory neocortex reflect a difference in the number of high-power beta events per trial, i.e. event rate. Further, beta events occurring close to the stimulus were more likely to impair perception. These results are consistent across detection and attention tasks in human magnetoencephalography, and in local field potentials from mice performing a detection task. These results imply that an increased propensity of beta events predicts the failure to effectively transmit information through specific neocortical representations. PMID:29106374

MicroRNA-29a is up-regulated in beta-cells by glucose and decreases glucose-stimulated insulin secretion

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

Bagge, Annika; Clausen, Trine R.; Larsen, Sylvester

Highlights: Black-Right-Pointing-Pointer MicroRNA-29a (miR-29a) levels are increased by glucose in human and rat islets and INS-1E cells. Black-Right-Pointing-Pointer miR-29a increases proliferation of INS-1E beta-cells. Black-Right-Pointing-Pointer Forced expression of miR-29a decreases glucose-stimulated insulin secretion (GSIS). Black-Right-Pointing-Pointer Depletion of beta-cell miR-29a improves GSIS. Black-Right-Pointing-Pointer miR-29a may be a mediator of glucose toxicity in beta-cells. -- Abstract: Chronically elevated levels of glucose impair pancreatic beta-cell function while inducing beta-cell proliferation. MicroRNA-29a (miR-29a) levels are increased in several tissues in diabetic animals and mediate decreased insulin-stimulated glucose-transport of adipocytes. The aim was to investigate the impact of glucose on miR-29a levels in INS-1E beta-cellsmore » and in human islets of Langerhans and furthermore to evaluate the impact of miR-29a on beta-cell function and proliferation. Increased glucose levels up-regulated miR-29a in beta-cells and human and rat islets of Langerhans. Glucose-stimulated insulin-secretion (GSIS) of INS-1E beta-cells was decreased by forced expression of miR-29a, while depletion of endogenous miR-29a improved GSIS. Over-expression of miR-29a increased INS-1E proliferation. Thus, miR-29a up-regulation is involved in glucose-induced proliferation of beta-cells. Furthermore, as depletion of miR-29a improves beta-cell function, miR-29a is a mediator of glucose-induced beta-cell dysfunction. Glucose-induced up-regulation of miR-29a in beta-cells could be implicated in progression from impaired glucose tolerance to type 2 diabetes.« less

Neural mechanisms of transient neocortical beta rhythms: Converging evidence from humans, computational modeling, monkeys, and mice.

PubMed

Sherman, Maxwell A; Lee, Shane; Law, Robert; Haegens, Saskia; Thorn, Catherine A; Hämäläinen, Matti S; Moore, Christopher I; Jones, Stephanie R

2016-08-16

Human neocortical 15-29-Hz beta oscillations are strong predictors of perceptual and motor performance. However, the mechanistic origin of beta in vivo is unknown, hindering understanding of its functional role. Combining human magnetoencephalography (MEG), computational modeling, and laminar recordings in animals, we present a new theory that accounts for the origin of spontaneous neocortical beta. In our MEG data, spontaneous beta activity from somatosensory and frontal cortex emerged as noncontinuous beta events typically lasting <150 ms with a stereotypical waveform. Computational modeling uniquely designed to infer the electrical currents underlying these signals showed that beta events could emerge from the integration of nearly synchronous bursts of excitatory synaptic drive targeting proximal and distal dendrites of pyramidal neurons, where the defining feature of a beta event was a strong distal drive that lasted one beta period (∼50 ms). This beta mechanism rigorously accounted for the beta event profiles; several other mechanisms did not. The spatial location of synaptic drive in the model to supragranular and infragranular layers was critical to the emergence of beta events and led to the prediction that beta events should be associated with a specific laminar current profile. Laminar recordings in somatosensory neocortex from anesthetized mice and awake monkeys supported these predictions, suggesting this beta mechanism is conserved across species and recording modalities. These findings make several predictions about optimal states for perceptual and motor performance and guide causal interventions to modulate beta for optimal function.

Clinical characteristics and beta cell function in Chinese patients with newly diagnosed type 2 diabetes mellitus with different levels of serum triglyceride.

PubMed

Zheng, Shuang; Zhou, Huan; Han, Tingting; Li, Yangxue; Zhang, Yao; Liu, Wei; Hu, Yaomin

2015-04-29

To explore clinical characteristics and beta cell function in Chinese patients with newly diagnosed drug naive type 2 diabetes mellitus (T2DM) with different levels of serum triglyceride (TG). Patients with newly diagnosed T2DM (n = 624) were enrolled and divided into different groups according to levels of serum TG. All patients underwent oral glucose tolerance tests and insulin releasing tests. Demographic data, lipid profiles, glucose levels, and insulin profiles were compared between different groups. Basic insulin secretion function index (homeostasis model assessment for beta cell function index, HOMA-β), modified beta cell function index (MBCI), glucose disposition indices (DI), and early insulin secretion function index (insulinogenic index, IGI) were used to evaluate the beta cell function. Patients of newly diagnosed T2DM with hypertriglyceridemia were younger, fatter and had worse lipid profiles, glucose profiles, and high insulin levels than those with normal TG. There is no difference in early phase insulin secretion among groups of newly diagnosed T2DM patients with different TG levels. The basal beta cell function (HOMA-β and MBCI) initially increased along rising TG levels and then decreased as the TG levels rose further. The insulin sensitivity was relatively high in patients with a low level of TG and low with a high level of TG. Hypertriglyceridemia influences clinical characteristics and β cell function of Chinese patients with newly diagnosed T2DM. A better management of dyslipidemia may, to some extent, reduce the effect of lipotoxicity, thereby improving glucose homeostasis in patients with newly diagnosed T2DM.

The effect of microstructure on the deformation modes and mechanical properties of Ti-6Al-2Nb-1Ta-0.8Mo: Part II. Equiaxed structures

NASA Astrophysics Data System (ADS)

Lin, Fu-Shiong; Starke, E. A.; Gysler, A.

1984-10-01

The Ti-6Al-2Nb-lTa-0.8Mo alloy was processed to develop both near-basal and transverse textures. Samples were annealed at different temperatures to vary the equiaxed alpha grain size and the thick-ness of the grain boundary beta, and subsequently quenched in order to transform the beta phase to either martensite, tempered martensite, or Widmanstätten alpha + beta. The effect of microstructure and texture on tensile properties and on fracture toughness was investigated. In addition, yield locus diagrams were constructed in order to study the texture strengthening effect. The yield strength was found to be strongly dependent on the thickness and Burgers relationship of the transformed beta phase surrounding the alpha grains. A texture hardening effect as large as 60 pct was found for the basal-texture material but only 15 pct for the transverse texture material. These variations are asso-ciated with differences in deformation behavior.

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

Lopes, E.S.N.; Cremasco, A.; Afonso, C.R.M.

Aging heat treatment can be a good way to optimize mechanical properties, changing the microstructure, and hence, the mechanical behavior of Ti alloys. The effects of aging heat treatments on {beta}-type Ti-30Nb alloy were investigated to evaluate the kinetics of {alpha}'' {yields} {alpha} + {beta} transformation. The results obtained from differential scanning calorimetry and high-temperature X-ray diffraction experiments indicated the complete decomposition of orthorhombic {alpha}'' phase at close to 300 deg. C, followed by {alpha} phase precipitation at 470 deg. C. The aging heat treatments also enabled us to observe a transformation sequence {alpha}'' {yields} {beta} + {omega} {yields} {beta}more » + {omega} + {alpha}, indicating martensite decomposition and {omega} phase precipitation at 260 deg. C after 2 h, followed by {alpha} phase nucleation after heating at 400 deg. C for 1 h. The elastic modulus and Vickers hardness of Ti-30Nb alloy were found to be very sensitive to the microstructural changes caused by heat treatment. - Highlights: {yields} DSC and XRD shed light on the {alpha}'' decomposition and nucleation of {omega} and {alpha} phases. {yields} Aging allows for {alpha}''{yields}{beta} transformation and nucleation of {omega} dispersed in the {beta} matrix. {yields} During aging, {alpha}'' interplanar distances are reduced to enable {beta} phase nucleation. {yields} Mechanical behavior is dependent on the microstructure and the phases in the alloy. {yields} It is not possible to obtain high strength and low elastic modulus by applying aging.« less

Multi-subject hierarchical inverse covariance modelling improves estimation of functional brain networks.

PubMed

Colclough, Giles L; Woolrich, Mark W; Harrison, Samuel J; Rojas López, Pedro A; Valdes-Sosa, Pedro A; Smith, Stephen M

2018-05-07

A Bayesian model for sparse, hierarchical, inver-covariance estimation is presented, and applied to multi-subject functional connectivity estimation in the human brain. It enables simultaneous inference of the strength of connectivity between brain regions at both subject and population level, and is applicable to fMRI, MEG and EEG data. Two versions of the model can encourage sparse connectivity, either using continuous priors to suppress irrelevant connections, or using an explicit description of the network structure to estimate the connection probability between each pair of regions. A large evaluation of this model, and thirteen methods that represent the state of the art of inverse covariance modelling, is conducted using both simulated and resting-state functional imaging datasets. Our novel Bayesian approach has similar performance to the best extant alternative, Ng et al.'s Sparse Group Gaussian Graphical Model algorithm, which also is based on a hierarchical structure. Using data from the Human Connectome Project, we show that these hierarchical models are able to reduce the measurement error in MEG beta-band functional networks by 10%, producing concomitant increases in estimates of the genetic influence on functional connectivity. Copyright © 2018. Published by Elsevier Inc.

TGF-beta1 inhibits Cx43 expression and formation of functional syncytia in cultured smooth muscle cells from human detrusor.

PubMed

Neuhaus, Jochen; Heinrich, Marco; Schwalenberg, Thilo; Stolzenburg, Jens-Uwe

2009-02-01

Human detrusor smooth muscle cells (hBSMCs) are coupled by connexin 43 (Cx43)-positive gap junctions to form functional syncytia. Gap junctional communication likely is necessary for synchronised detrusor contractions and is supposed to be altered in voiding disturbances. Other authors have shown that the pleiotropic cytokine TGF-beta1 upregulates Cx43 expression in human aortic smooth muscle cells. In this study, we examined the TGF-beta1 effects on Cx43 expression in cultured hBSMCs. hBSMC cultures, established from patients undergoing cystectomy, were treated with recombinant human TGF-beta1. Cx43 expression was then examined by Western blotting, real-time PCR, and immunocytochemistry. Dye-injection experiments were used to study the size of functional syncytia. Dye-coupling experiments revealed stable formation of functional syncytia in passaged cell cultures (P1-P4). Stimulation with TGF-beta1 led to significant reduction of Cx43 immunoreactivity and coupling. Cx43 protein expression was significantly downregulated and Cx43 mRNA was only 30% of the control level. Interestingly, low phosphorylation species of Cx43 were particularly affected. Our experiments demonstrated a significant down regulation of connexin 43 by TGF-beta1 in cultured hBSMCs. These findings support the view that TGF-beta1 is involved in the pathophysiology of urinary bladder dysfunction.

Elevated temperature flow strength, creep resistance and diffusion welding characteristics of Ti-6Al-2Nb-1Ta-0.8Mo

NASA Technical Reports Server (NTRS)

Whittenberger, J. D.; Moore, T. J.

1979-01-01

A study of the flow strength, creep resistance and diffusion welding characteristics of the titanium alloy Ti-6Al-2Nb-1Ta-0.8Mo has been conducted. Two mill-processed forms of this alloy were examined. The forged material had been processed above the beta transus (approximately 1275 K) while the rolled form had been subjected to work below the beta transus. Between 1150 and 1250 K, the forged material was stronger and more creep resistant than the rolled alloy. Both forms exhibit superplastic characteristics in this temperature range. Strain measurements during diffusion welding experiments at 1200 K reveal that weld interfaces have no measurable effect on the overall creep deformation. Significant deformation appears to be necessary to produce a quality diffusion weld between superplastic materials. A 'soft' interlayer inserted between faying surfaces would seemingly allow manufacture of quality diffusion welds with little overall deformation.

Fatigue behaviour of boron free and boron containing heat treated Ti-13Zr-13Nb alloy for biomedical applications

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

Majumdar, P., E-mail: m.pallab@gmail.com; Singh, S.B.; Chakraborty, M.

2010-12-15

Fatigue behaviour of heat treated Ti-13Zr-13Nb (TZN) and Ti-13Zr-13Nb-0.5B (TZNB) alloys for biomedical implants has been investigated by rotating bending test. It was found that fatigue strength of TZN and TZNB alloys is comparable with that of conventionally used biomedical titanium alloys. Addition of boron to TZN alloy deteriorates fatigue strength. - Research Highlights: {yields}The microstructure of the aged TZN consists of {alpha} phase in {beta} matrix. {yields}Addition of boron to TZN leads to the formation of dispersed acicular TiB. {yields}Presence of TiB deteriorates the fatigue strength of TZN alloy. {yields}Fatigue strength of aged TZN/TZNB alloys is comparable with biomedicalmore » Ti-alloys.« less

SIRT6-mediated transcriptional suppression of Txnip is critical for pancreatic beta cell function and survival in mice.

PubMed

Qin, Kunhua; Zhang, Ning; Zhang, Zhao; Nipper, Michael; Zhu, Zhenxin; Leighton, Jake; Xu, Kexin; Musi, Nicolas; Wang, Pei

2018-04-01

Better understanding of how genetic and epigenetic components control beta cell differentiation and function is key to the discovery of novel therapeutic approaches to prevent beta cell dysfunction and failure in the progression of type 2 diabetes. Our goal was to elucidate the role of histone deacetylase sirtuin 6 (SIRT6) in beta cell development and homeostasis. Sirt6 endocrine progenitor cell conditional knockout and beta cell-specific knockout mice were generated using the Cre-loxP system. Mice were assayed for islet morphology, glucose tolerance, glucose-stimulated insulin secretion and susceptibility to streptozotocin. Transcriptional regulatory functions of SIRT6 in primary islets were evaluated by RNA-Seq analysis. Reverse transcription-quantitative (RT-q)PCR and immunoblot were used to verify and investigate the gene expression changes. Chromatin occupancies of SIRT6, H3K9Ac, H3K56Ac and active RNA polymerase II were evaluated by chromatin immunoprecipitation. Deletion of Sirt6 in pancreatic endocrine progenitor cells did not affect endocrine morphology, beta cell mass or insulin production but did result in glucose intolerance and defective glucose-stimulated insulin secretion in mice. Conditional deletion of Sirt6 in adult beta cells reproduced the insulin secretion defect. Loss of Sirt6 resulted in aberrant upregulation of thioredoxin-interacting protein (TXNIP) in beta cells. SIRT6 deficiency led to increased acetylation of histone H3 lysine residue at 9 (H3K9Ac), acetylation of histone H3 lysine residue at 56 (H3K56Ac) and active RNA polymerase II at the promoter region of Txnip. SIRT6-deficient beta cells exhibited a time-dependent increase in H3K9Ac, H3K56Ac and TXNIP levels. Finally, beta cell-specific SIRT6-deficient mice showed increased sensitivity to streptozotocin. Our results reveal that SIRT6 suppresses Txnip expression in beta cells via deacetylation of histone H3 and plays a critical role in maintaining beta cell function and viability. Sequence data have been deposited in the National Institutes of Health (NIH) Gene Expression Omnibus (GEO) with the accession code GSE104161.

High Integrity Castings: Proceedings of the Conference on Advances in High Integrity Castings Held in Conjunction with the 1988 World Materials Congress, Chicago, Illinois, USA, 24-30 September 1988

DTIC Science & Technology

1988-01-01

above design requirements. The The first cast parts used in this higher strength standard chemistry parts application were of the Extra Low...present work was to study the use of beta THE HIGH COST OF TITANIUM alloys can limit their titanium alloys in the cast form. Beta or use to applications ...refractory as was is intended to achieve a pouring stream su- used with the nozzles for steel applications . perior to conventional nozzle designs , and this

Extrusion-based, three-dimensional printing of calcium-phosphate scaffolds

NASA Astrophysics Data System (ADS)

Witek, Lukasz

Small or large bone defects, can occur due to a variety of reasons: congenital disorders, infections, tumors, or traumas which can lead to significant disabilities. There is an assortment of bone grafting procedures, each having their own respective advantages and disadvantages and exhibiting certain essential characteristics. Among the available grafts, autogenous (autograft), allograft, xenograft, and alloplasts, all exhibit a minimum of two-thirds of the essential characteristics and have been proven useful in fully or partially repairing skeletal defects. However, different host-to-grafting material responses have been reported and should be taken into consideration when determining treatment options. A large range of physical and chemical properties can be achieved with calcium phosphate based materials, which possess two of the ideal characteristics for grafting procedures: osteoconduction and osseointegration. Calcium phosphate based scaffolds composed of hydroxyapatite (HA), beta-tri-calcium phosphate (beta-TCP), or a combination of both (HA/beta-TCP) were investigated as materials for three-dimensional printing process to create layer-by-layer structures for use as bone regeneration scaffolds. Different calcium-phosphate phases will result in different degrees of in vivo dissolution and/or cell-mediated resorption. There has been a growing interest in BCP because it has been shown that this material improves the formation of new bone inside the implanted scaffold. The literature indicates that the faster dissolution rate of ?-TCP would be greatly responsible of this enhancement. However, in vitro tests indicate that fast dissolution can decrease the mechanical strength of BCP scaffolds. Furthermore, studies reported that HA has higher mechanical strength and lower degradation rate than beta-TCP. Therefore, the HA/beta-TCP ratio is a key parameter controlling the performance of the scaffold for bone repair applications, since it determines degradation rate, calcium (Ca2+) and phosphate (PO4) release and mechanical properties of the material.

The effect of perioperative beta-blockade on the pulmonary function of patients undergoing major arterial surgery.

PubMed

Kieran, S M; Cahill, R A; Browne, I; Sheehan, S J; Mehigan, D; Barry, M C

2006-09-01

Concern about the potential detrimental side-effects of beta-blockade on pulmonary function often dissuades against their perioperative use in patients undergoing major arterial surgery (especially in those with chronic obstructive pulmonary disease (COPD)). In this study we aimed to establish prospectively the clinical relevance of these concerns. After ethics committee approval and individual informed consent, the pulmonary function of twenty patients (mean age 68.7 years (range 43-82), 11 males) scheduled to undergo non-emergency major vascular surgery was studied by recording symptoms and spirometry before and after institution of effective beta-blockade. Fifteen patients (75%) had significant smoking histories (mean pack years/patient=50), while 12 (60%) had COPD. All patients tolerated effective beta-blockade satisfactorily without developing either subjective deterioration in symptoms or significant change on spirometry. The mean change in FEV1 following adequate beta-blockade was 0.05+/-0.24 liters (95% CI -0.06 to +1.61), p=0.35, giving a mean percentage change of 3.18%+/-11.66 (95% CI -2.26 to 8.62). Previously held concerns about worsening pulmonary function through the short-term use of beta-blockers should not dissuade their perioperative usage in patients with peripheral vascular disease. Furthermore, the accuracy of pulmonary function tests in preoperative assessment and risk stratification also appears unaffected by this therapy.

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

Rahman, Shaikh M., E-mail: rmizanoor@hotmail.com; Choudhury, Mahua; Janssen, Rachel C.

Highlights: Black-Right-Pointing-Pointer LXR agonist activation increases liver TG accumulation by increasing lipogenesis. Black-Right-Pointing-Pointer C/EBP{beta}{sup -/-} mouse prevents LXR activation-mediated induction of hepatic lipogenesis. Black-Right-Pointing-Pointer C/EBP{beta} deletion increases mitochondrial transport chain function. Black-Right-Pointing-Pointer Beneficial effects of LXR activation on liver cholesterol metabolism did not change. Black-Right-Pointing-Pointer C/EBP{beta} inhibition might have important therapeutic potential. -- Abstract: Drugs designed specifically to activate liver X receptors (LXRs) have beneficial effects on lowering cholesterol metabolism and inflammation but unfortunately lead to severe hepatic steatosis. The transcription factor CCAAT/enhancer binding protein beta (C/EBP{beta}) is an important regulator of liver gene expression but little is known aboutmore » its involvement in LXR-based steatosis and cholesterol metabolism. The present study investigated the role of C/EBP{beta} expression in LXR agonist (T0901317)-mediated alteration of hepatic triglyceride (TG) and lipogenesis in mice. C/EBP{beta} deletion in mice prevented LXR agonist-mediated induction of lipogenic gene expression in liver in conjunction with significant reduction of liver TG accumulation. Surprisingly, C/EBP{beta}{sup -/-} mice showed a major increase in liver mitochondrial electron chain function compared to WT mice. Furthermore, LXR activation in C/EBP{beta}{sup -/-} mice increased the expression of liver ATP-binding cassette transporter ABCG1, a gene implicated in cholesterol efflux and reducing blood levels of total and LDL-cholesterol. Together, these findings establish a central role for C/EBP{beta} in the LXR-mediated steatosis and mitochondrial function, without impairing the influence of LXR activation on lowering LDL and increasing HDL-cholesterol. Inactivation of C/EBP{beta} might therefore be an important therapeutic strategy to prevent LXR activation-mediated adverse effects on liver TG metabolism without disrupting its beneficial effects on cholesterol metabolism.« less

Genetic models rule out a major role of beta cell glycogen in the control of glucose homeostasis.

PubMed

Mir-Coll, Joan; Duran, Jordi; Slebe, Felipe; García-Rocha, Mar; Gomis, Ramon; Gasa, Rosa; Guinovart, Joan J

2016-05-01

Glycogen accumulation occurs in beta cells of diabetic patients and has been proposed to partly mediate glucotoxicity-induced beta cell dysfunction. However, the role of glycogen metabolism in beta cell function and its contribution to diabetes pathophysiology remain poorly understood. We investigated the function of beta cell glycogen by studying glucose homeostasis in mice with (1) defective glycogen synthesis in the pancreas; and (2) excessive glycogen accumulation in beta cells. Conditional deletion of the Gys1 gene and overexpression of protein targeting to glycogen (PTG) was accomplished by Cre-lox recombination using pancreas-specific Cre lines. Glucose homeostasis was assessed by determining fasting glycaemia, insulinaemia and glucose tolerance. Beta cell mass was determined by morphometry. Glycogen was detected histologically by periodic acid-Schiff's reagent staining. Isolated islets were used for the determination of glycogen and insulin content, insulin secretion, immunoblots and gene expression assays. Gys1 knockout (Gys1 (KO)) mice did not exhibit differences in glucose tolerance or basal glycaemia and insulinaemia relative to controls. Insulin secretion and gene expression in isolated islets was also indistinguishable between Gys1 (KO) and controls. Conversely, despite effective glycogen overaccumulation in islets, mice with PTG overexpression (PTG(OE)) presented similar glucose tolerance to controls. However, under fasting conditions they exhibited lower glycaemia and higher insulinaemia. Importantly, neither young nor aged PTG(OE) mice showed differences in beta cell mass relative to age-matched controls. Finally, a high-fat diet did not reveal a beta cell-autonomous phenotype in either model. Glycogen metabolism is not required for the maintenance of beta cell function. Glycogen accumulation in beta cells alone is not sufficient to trigger the dysfunction or loss of these cells, or progression to diabetes.

Loss of c-myc repression coincides with ovarian cancer resistance to transforming growth factor beta growth arrest independent of transforming growth factor beta/Smad signaling.

PubMed

Baldwin, Rae Lynn; Tran, Hang; Karlan, Beth Y

2003-03-15

Many epithelial carcinomas, including ovarian, are refractory to the antiproliferative effects of transforming growth factor (TGF) beta. In some cancers, TGF-beta resistance has been linked to TGF-beta receptor II (TbetaR-II) and Smad4 mutations; however, in ovarian cancer, the mechanism of resistance remains unclear. Primary ovarian epithelial cell cultures were used as a model system to determine the mechanisms of TGF-beta resistance. To simulate in vivo responses to TGF-beta, primary cultures derived from normal human ovarian surface epithelium (HOSE) and from ovarian carcinomas (CSOC) were grown on collagen I gel, the predominant matrix molecule in the ovarian tumor milieu. When treated with 5 ng/ml TGF-beta for 72 h, HOSE (n = 11) proliferation was inhibited by 20 +/- 21% on average. In contrast, CSOC (n = 10) proliferation was stimulated 5 +/- 10% in response to TGF-beta (a statistically significant difference in response when compared with HOSE; P = 0.001). To dissect the TGF-beta/Smad signaling pathway we used a quantitative RNase protection assay (RPA) for measuring mRNA levels of TGF-beta pathway components in 20 HOSE and 20 CSOC cultures. Basal mRNA levels of TGF-beta receptors I and II, downstream signaling components Smad2, 3, 4, 6, 7, and the transcriptional corepressors Ski and SnoN did not show a statistically significant difference between HOSE and CSOC, and cannot explain their differential susceptibility to TGF-beta-induced cell cycle arrest. To assess functional differences of the TGF-beta pathway in TGF-beta-sensitive HOSE and TGF-beta-resistant CSOC, we measured Smad2/4 and 3/4 complex induction after TGF-beta treatment. HOSE and CSOC showed equivalent Smad2/4 and 3/4 complex induction after TGF-beta exposure for 0, 0.5, 2, and 4 h. It has been proposed that SnoN and Ski are corepressors of the TGF-beta/Smad pathway and undergo TGF-beta-induced degradation followed by reinduction of SnoN mRNA. However, our data show equivalent SnoN degradation in HOSE and CSOC, and equivalent SnoN mRNA induction after TGF-beta treatment. Surprising, TGF-beta-induced Ski degradation was not observed in HOSE or CSOC, suggesting that Ski may not function as a TGF-beta/Smad corepressor in ovarian epithelial cells. These data implied that the TGF-beta/Smad pathway remains functional in CSOC, although CSOC cells are resistant to antimitogenic TGF-beta effects. CSOC resistance to TGF-beta coincided with the loss of c-myc down-regulation. These data suggest that TGF-beta/Smad signaling is blocked downstream of Smad complex formation or that an alternate signaling pathway other than TGF-beta/Smad may transmit TGF-beta-induced cell cycle arrest in the ovarian epithelium.

Capture cross sections on unstable nuclei

NASA Astrophysics Data System (ADS)

Tonchev, A. P.; Escher, J. E.; Scielzo, N.; Bedrossian, P.; Ilieva, R. S.; Humby, P.; Cooper, N.; Goddard, P. M.; Werner, V.; Tornow, W.; Rusev, G.; Kelley, J. H.; Pietralla, N.; Scheck, M.; Savran, D.; Löher, B.; Yates, S. W.; Crider, B. P.; Peters, E. E.; Tsoneva, N.; Goriely, S.

2017-09-01

Accurate neutron-capture cross sections on unstable nuclei near the line of beta stability are crucial for understanding the s-process nucleosynthesis. However, neutron-capture cross sections for short-lived radionuclides are difficult to measure due to the fact that the measurements require both highly radioactive samples and intense neutron sources. Essential ingredients for describing the γ decays following neutron capture are the γ-ray strength function and level densities. We will compare different indirect approaches for obtaining the most relevant observables that can constrain Hauser-Feshbach statistical-model calculations of capture cross sections. Specifically, we will consider photon scattering using monoenergetic and 100% linearly polarized photon beams. Challenges that exist on the path to obtaining neutron-capture cross sections for reactions on isotopes near and far from stability will be discussed.

Biocompatibility of a functionally graded bioceramic coating made by wide-band laser cladding.

PubMed

Weidong, Zhu; Qibin, Liu; Min, Zheng; Xudong, Wang

2008-11-01

The application of plasma spray is the most popular method by which a metal-bioceramic surface composite can be prepared for the repair of biological hard-tissue, but this method has disadvantages. These disadvantages include poor coating-to-substrate adhesion, low mechanical strength, and brittleness of the coating. In the investigation described in this article, a gradient bioceramic coating was prepared on a Ti-6Al-4V titanium alloy surface using a gradient composite design and wide-band laser cladding techniques. Using a trilayer-structure composed of a substratum, an alloy and bioceramics, the coating was chemically and metallurgically bonded with the substratum. The coating, which contains beta-tricalcium phosphate and hydroxyapatite, showed favorable biocompatibility with the bone tissue and promoted in vivo osteogenesis.

Lack of the central nervous system- and neural crest-expressed forkhead gene Foxs1 affects motor function and body weight.

PubMed

Heglind, Mikael; Cederberg, Anna; Aquino, Jorge; Lucas, Guilherme; Ernfors, Patrik; Enerbäck, Sven

2005-07-01

To gain insight into the expression pattern and functional importance of the forkhead transcription factor Foxs1, we constructed a Foxs1-beta-galactosidase reporter gene "knock-in" (Foxs1beta-gal/beta-gal) mouse, in which the wild-type (wt) Foxs1 allele has been inactivated and replaced by a beta-galactosidase reporter gene. Staining for beta-galactosidase activity reveals an expression pattern encompassing neural crest-derived cells, e.g., cranial and dorsal root ganglia as well as several other cell populations in the central nervous system (CNS), most prominently the internal granule layer of cerebellum. Other sites of expression include the lachrymal gland, outer nuclear layer of retina, enteric ganglion neurons, and a subset of thalamic and hypothalamic nuclei. In the CNS, blood vessel-associated smooth muscle cells and pericytes stain positive for Foxs1. Foxs1beta-gal/beta-gal mice perform significantly better (P < 0.01) on a rotating rod than do wt littermates. We have also noted a lower body weight gain (P < 0.05) in Foxs1beta-gal/lbeta-gal males on a high-fat diet, and we speculate that dorsomedial hypothalamic neurons, expressing Foxs1, could play a role in regulating body weight via regulation of sympathetic outflow. In support of this, we observed increased levels of uncoupling protein 1 mRNA in Foxs1beta-gal/beta-gal mice. This points toward a role for Foxs1 in the integration and processing of neuronal signals of importance for energy turnover and motor function.

Extension arm facilitated pegylation of alphaalpha-hemoglobin with modifications targeted exclusively to amino groups: functional and structural advantages of free Cys-93(beta) in the PEG-Hb adduct.

PubMed

Li, Dongxia; Hu, Tao; Manjula, Belur N; Acharya, Seetharama A

2009-11-01

Cys-93(beta) of hemoglobin (Hb) was reversibly protected as a mixed disulfide with thiopyridine during extension arm facilitated (EAF) PEGylation and its influence on the structural and functional properties of the EAF-PEG-Hb has been investigated. Avoiding PEGylation of Cys-93(beta) in the EAF-PEG-Hb lowers the level of perturbation of heme pocket, alpha1beta2 interface, autoxidation, heme loss, and the O(2) affinity, as compared to the EAF-PEG-Hb with PEGylation of Cys-93(beta).The structural and functional advantages of reversible protection of Cys-93(beta) during EAF PEGylation of oxy-Hb has been compared with Euro PEG-Hb generated by EAF PEGylation of deoxy Hb where Cys-93(beta) is free in the final product. The alphaalpha-fumaryl cross-linking and EAF PEGylation targeted exclusively to Lys residues has been combined together for generation of second-generation EAF-PEG-Hb with lower oxygen affinity. The PEG chains engineered on Lys as well as PEGylation of Cys-93(beta) independently contribute to the stabilization of oxy conformation of Hb and hence increase the oxygen affinity of Hb. However, oxygen affinity of the EAF-PEG-alphaalpha-Hb is more sensitive to the presence of PEGylation on Cys-93(beta) than that of the EAF-PEG-Hb. The present modified EAF PEGylation platform is expected to facilitate the design of novel versions of the EAF-PEG-Hbs that can now integrate the advantages of avoiding PEGylation of Cys-93(beta).

Time-dependent fiber bundles with local load sharing. II. General Weibull fibers.

PubMed

Phoenix, S Leigh; Newman, William I

2009-12-01

Fiber bundle models (FBMs) are useful tools in understanding failure processes in a variety of material systems. While the fibers and load sharing assumptions are easily described, FBM analysis is typically difficult. Monte Carlo methods are also hampered by the severe computational demands of large bundle sizes, which overwhelm just as behavior relevant to real materials starts to emerge. For large size scales, interest continues in idealized FBMs that assume either equal load sharing (ELS) or local load sharing (LLS) among fibers, rules that reflect features of real load redistribution in elastic lattices. The present work focuses on a one-dimensional bundle of N fibers under LLS where life consumption in a fiber follows a power law in its load, with exponent rho , and integrated over time. This life consumption function is further embodied in a functional form resulting in a Weibull distribution for lifetime under constant fiber stress and with Weibull exponent, beta. Thus the failure rate of a fiber depends on its past load history, except for beta=1 . We develop asymptotic results validated by Monte Carlo simulation using a computational algorithm developed in our previous work [Phys. Rev. E 63, 021507 (2001)] that greatly increases the size, N , of treatable bundles (e.g., 10(6) fibers in 10(3) realizations). In particular, our algorithm is O(N ln N) in contrast with former algorithms which were O(N2) making this investigation possible. Regimes are found for (beta,rho) pairs that yield contrasting behavior for large N. For rho>1 and large N, brittle weakest volume behavior emerges in terms of characteristic elements (groupings of fibers) derived from critical cluster formation, and the lifetime eventually goes to zero as N-->infinity , unlike ELS, which yields a finite limiting mean. For 1/21 but with 0

Beta 1D integrin displaces the beta 1A isoform in striated muscles: localization at junctional structures and signaling potential in nonmuscle cells.

PubMed

Belkin, A M; Zhidkova, N I; Balzac, F; Altruda, F; Tomatis, D; Maier, A; Tarone, G; Koteliansky, V E; Burridge, K

1996-01-01

The cytoplasmic domains of integrins provide attachment of these extracellular matrix receptors to the cytoskeleton and play a critical role in integrin-mediated signal transduction. In this report we describe the identification, expression, localization, and initial functional characterization of a novel form of beta 1 integrin, termed beta 1D. This isoform contains a unique alternatively spliced cytoplasmic domain of 50 amino acids, with the last 24 amino acids encoded by an additional exon. Of these 24 amino acids, 11 are conserved when compared to the beta 1A isoform, but 13 are unique (Zhidkova, N. I., A. M. Belkin, and R. Mayne. 1995. Biochem. Biophys. Res. Commun. 214:279-285; van der Flier, A., I. Kuikman, C. Baudoin, R, van der Neuf, and A. Sonnenberg. 1995. FEBS Lett. 369:340-344). Using an anti-peptide antibody against the beta 1D integrin subunit, we demonstrated that the beta 1D isoform is synthesized only in skeletal and cardiac muscles, while very low amounts of beta 1A were detected by immunoblot in striated muscles. Whereas beta 1A could not be detected in adult skeletal muscle fibers and cardiomyocytes by immunofluorescence, beta 1D was localized to the sarcolemma of both cell types. In skeletal muscle, beta 1D was concentrated in costameres, myotendinous, and neuromuscular junctions. In cardiac muscle this beta 1 isoform was found in costamers and intercalated discs. beta 1D was associated with alpha 7A and alpha 7B in adult skeletal muscle. In cardiomyocytes of adult heart, alpha 7B was the major partner for the beta 1D isoform. beta 1D could not be detected in proliferating C2C12 myoblasts, but it appeared immediately after myoblast fusion and its amount continued to rise during myotube growth and maturation. In contrast, expression of the beta 1A isoform was downregulated during myodifferentiation in culture and it was completely displaced by beta 1D in mature differentiated myotubes. We also analyzed some functional properties of the beta 1D integrin subunit. Expression of human beta 1D in CHO cells led to its localization at focal adhesions. Clustering of this integrin isoform on the cell surface stimulated tyrosine phosphorylation of pp125FAK (focal adhesion kinase) and caused transient activation of mitogen-activated protein (MAP) kinases. These data indicate that beta 1D and beta 1A integrin isoforms are functionally similar with regard to integrin-mediated signaling.

Beta-delayed neutron emission from 94Rb at CARIBU

NASA Astrophysics Data System (ADS)

Wilson, Gemma; Chowdhury, P.; Lister, C.; Brown, T.; Chillery, T.; Copp, P.; Doucet, E.; Carpenter, M.; Savard, G.; Zhu, S.; Mitchell, Aj

2017-09-01

Beta-delayed neutron emission studies are important in the astrophysical r-process, nuclear structure and for nuclear reactor safety and design. The probability of β-delayed neutron emission in 94Sr is 10.2(2)%. Many of the γ rays in 94Sr are misplaced, and an estimated 26% are thought to be missing. Recently, substantial γ strength from above the neutron separation energy in 94Sr has been reported. An experiment to understand this high-lying γ strength was performed with the X-Array (a high-efficiency HPGe clover array), SCANS (Small CLYC Array for Neutron Scattering) and the SATURN decay station (Scintillator And Tape Using Radioactive Nuclei) for γ, fast-neutron and β-particle detection, respectively. Data from β decay of 94Rb ions delivered from CARIBU were collected in a triggerless digital data acquisition system, with detected β, n, and γ events correlated offline. A new 94Sr level scheme will be presented, with confirmation of new levels and transitions, in addition to evidence of γ strength above the neutron separation energy. NNSA Stewardship Science Academic Alliance Program through USDOE under Grant DE-NA0002932; USDOE, Office of Nucl Phys, under Contract No. DE-FG02-96ER40978; Louisiana State Board of Regents RCS LEQSF(2016-19)-RD-A-09; DE-AC02-06CHI1357.

Fabrication of low-cost beta-type Ti-Mn alloys for biomedical applications by metal injection molding process and their mechanical properties.

PubMed

Santos, Pedro Fernandes; Niinomi, Mitsuo; Liu, Huihong; Cho, Ken; Nakai, Masaaki; Itoh, Yoshinori; Narushima, Takayuki; Ikeda, Masahiko

2016-06-01

Titanium and its alloys are suitable for biomedical applications owing to their good mechanical properties and biocompatibility. Beta-type Ti-Mn alloys (8-17 mass% Mn) were fabricated by metal injection molding (MIM) as a potential low cost material for use in biomedical applications. The microstructures and mechanical properties of the alloys were evaluated. For up to 13 mass% Mn, the tensile strength (1162-938MPa) and hardness (308-294HV) of the MIM fabricated alloys are comparable to those of Ti-Mn alloys fabricated by cold crucible levitation melting. Ti-9Mn exhibits the best balance of ultimate tensile strength (1046MPa) and elongation (4.7%) among the tested alloys, and has a Young's modulus of 89GPa. The observed low elongation of the alloys is attributed to the combined effects of high oxygen content, with the presence of interconnected pores and titanium carbides, the formation of which is due to carbon pickup during the debinding process. The elongation and tensile strength of the alloys decrease with increasing Mn content. The Ti-Mn alloys show good compressive properties, with Ti-17Mn showing a compressive 0.2% proof stress of 1034MPa, and a compressive strain of 50%. Copyright © 2016 Elsevier Ltd. All rights reserved.

Novel function of STAT1beta in B cells: induction of cell death by a mechanism different from that of STAT1alpha.

PubMed

Najjar, Imen; Schischmanoff, Pierre Olivier; Baran-Marszak, Fanny; Deglesne, Pierre-Antoine; Youlyouz-Marfak, Ibtissam; Pampin, Mathieu; Feuillard, Jean; Bornkamm, Georg W; Chelbi-Alix, Mounira K; Fagard, Remi

2008-12-01

Alternate splicing of STAT1 produces two isoforms: alpha, known as the active form, and beta, previously shown to act as a dominant-negative factor. Most studies have dealt with STAT1alpha, showing its involvement in cell growth control and cell death. To examine the specific function of either isoform in cell death, a naturally STAT1-deficient human B cell line was transfected to express STAT1alpha or STAT1beta. STAT1alpha, expressed alone, enhanced cell death, potentiated the fludarabine-induced apoptosis, and enhanced the nuclear location, the phosphorylation, and the transcriptional activity of p53. Unexpectedly, STAT1beta, expressed alone, induced cell death through a mechanism that was independent of the nuclear function of p53. Indeed, in STAT1beta-expressing B cells, p53 was strictly cytoplasmic where it formed clusters, and there was no induction of the transcriptional activity of p53. These data reveal a novel role of STAT1beta in programmed cell death, which is independent of p53.

Immunohistochemical detection of active transforming growth factor-beta in situ using engineered tissue

NASA Technical Reports Server (NTRS)

Barcellos-Hoff, M. H.; Ehrhart, E. J.; Kalia, M.; Jirtle, R.; Flanders, K.; Tsang, M. L.; Chatterjee, A. (Principal Investigator)

1995-01-01

The biological activity of transforming growth factor-beta 1 (TGF-beta) is governed by dissociation from its latent complex. Immunohistochemical discrimination of active and latent TGF-beta could provide insight into TGF-beta activation in physiological and pathological processes. However, evaluation of immunoreactivity specificity in situ has been hindered by the lack of tissue in which TGF-beta status is known. To provide in situ analysis of antibodies to differentiate between these functional forms, we used xenografts of human tumor cells modified by transfection to overexpress latent TGF-beta or constitutively active TGF-beta. This comparison revealed that, whereas most antibodies did not differentiate between TGF-beta activation status, the immunoreactivity of some antibodies was activation dependent. Two widely used peptide antibodies to the amino-terminus of TGF-beta, LC(1-30) and CC(1-30) showed marked preferential immunoreactivity with active TGF-beta versus latent TGF-beta in cryosections. However, in formalin-fixed, paraffin-embedded tissue, discrimination of active TGF-beta by CC(1-30) was lost and immunoreactivity was distinctly extracellular, as previously reported for this antibody. Similar processing-dependent extracellular localization was found with a neutralizing antibody raised to recombinant TGF-beta. Antigen retrieval recovered cell-associated immunoreactivity of both antibodies. Two antibodies to peptides 78-109 showed mild to moderate preferential immunoreactivity with active TGF-beta only in paraffin sections. LC(1-30) was the only antibody tested that discriminated active from latent TGF-beta in both frozen and paraffin-embedded tissue. Thus, in situ discrimination of active versus latent TGF-beta depends on both the antibody and tissue preparation. We propose that tissues engineered to express a specific form of a given protein provide a physiological setting in which to evaluate antibody reactivity with specific functional forms of a protein.

Gaussian membership functions are most adequate in representing uncertainty in measurements

NASA Technical Reports Server (NTRS)

Kreinovich, V.; Quintana, C.; Reznik, L.

1992-01-01

In rare situations, like fundamental physics, we perform experiments without knowing what their results will be. In the majority of real-life measurement situations, we more or less know beforehand what kind of results we will get. Of course, this is not the precise knowledge of the type 'the result will be between alpha - beta and alpha + beta,' because in this case, we would not need any measurements at all. This is usually a knowledge that is best represented in uncertain terms, like 'perhaps (or 'most likely', etc.) the measured value x is between alpha - beta and alpha + beta.' Traditional statistical methods neglect this additional knowledge and process only the measurement results. So it is desirable to be able to process this uncertain knowledge as well. A natural way to process it is by using fuzzy logic. But, there is a problem; we can use different membership functions to represent the same uncertain statements, and different functions lead to different results. What membership function do we choose? In the present paper, we show that under some reasonable assumptions, Gaussian functions mu(x) = exp(-beta(x(exp 2))) are the most adequate choice of the membership functions for representing uncertainty in measurements. This representation was efficiently used in testing jet engines to airplanes and spaceships.

Improved performance of silicon nitride-based high temperature ceramics

NASA Technical Reports Server (NTRS)

Ashbrook, R. L.

1977-01-01

Recent progress in the production of Si3N4 based ceramics is reviewed: (1) high temperature strength and toughness of hot pressed Si3N4 were improved by using high purity powder and a stabilized ZrO2 additive, (2) impact resistance of hot pressed Si3N4 was increased by the use of a crushable energy absorbing layer, (3) the oxidation resistance and strength of reaction sintered Si3N4 were increased by impregnating reaction sintered silicon nitride with solutions that oxidize to Al2O3 or ZrO2, (4) beta prime SiA1ON compositions and sintering aids were developed for improved oxidation resistance or improved high temperature strength.

An investigation of proton pair correlations relevant to the neutrinoless double beta decay of 76Ge

NASA Astrophysics Data System (ADS)

Ticehurst, David R.

The observation of neutrinoless double beta decay (0nubetabeta ) would demonstrate that the neutrino is a Majorana particle and allow determination of its mass by comparing the measured decay rate to the calculated rate. The main uncertainty in the calculation of the 0 nubetabeta rate is due to uncertainties in the nuclear structure models used in the computation of the nuclear matrix elements for the decay process. This project tested the validity of using wavefunctions for the nuclear states involved in the 0nubetabeta process that are based on a first-order application of the Bardeen-Cooper-Schrieffer (BCS) theory of superconductivity. In the BCS approximation, most of the strength for two-nucleon transfer reactions should be for transitions to the 0 + ground state of the final nucleus (i.e., little strength should go to the 0+ excited states). This experiment measured the strength to the first 0+ excited state for the 74Ge( 3He,n)76Se and 76Ge( 3He,n)78Se reactions relative to the strength for transition to the 0+ ground state in selenium. For both nuclei, and at 3He beam energies of 15 and 21 MeV, the observed relative strength for transfer to the first 0+ excited state was less than 13%. This result supports the validity of using the BCS approximation to describe the ground state of both 76Se and 78Se and is consistent with the results of recent ( 3He,n) cross section measurements on 74Ge and 76Ge. In addition, the magnitude and shape of the measured angular distributions suggest that contribution of the sequential two-nucleon transfer process, which is an indicator of long-range nucleon-nucleon correlations, is over-predicted by the DWBA code FRESCO.

Generalized Jastrow Variational Method for Liquid HELIUM-3-HELIUM-4 Mixtures at T = 0 K.

NASA Astrophysics Data System (ADS)

Mirabbaszadeh, Kavoos

Microscopic theory of dilute liquid { ^3 He}-{^4 He} mixtures is of great interest, because it provides a physical realization of a nearly degenerate weakly interacting Fermion system. An understanding of properties of the mixtures has received considerable attention both theoretically and experimentally over the past thirty years. We present here a variational procedure based on the Jastrow function for the ground state of {^3 He}- {^4 He} mixtures by minimizing the total energy of the mixture using the hypernetted-chain (HNC) approximation and the Percus-Yevick (PY) approximation for the two body correlation functions. Our goal is to compute from first principles the internal energy of the system and the various two body correlation functions at various densities and compare the results with experiment. The Jastrow variational method for the ground state energy of liquid {^4 He} consists of the following ansatz for the wave function Psi_alpha {rm(vec r_{1 alpha},} {vec r_{2alpha},} dots, {vec r_{N _alpha})} = prod _{rm i < j} {rm f_ {alphaalpha}(r_{ij}). } For a {^3 He } system the corresponding ansatz is Psi_beta {rm( vec r_{1beta},} {vec r_{2beta },} dots, {vec r_{N_beta})} = {[prod _{i < j} f_{betabeta }(r_{ij})]} Phi {rm( vec r_{1beta},} {vec r_{2beta },} dots, {vec r_{Nbeta}),} where Phi is a Slater determinant of plane waves for the ground state of the Fermion system. The total energy per particle can be written in the form: E = x_sp{alpha}{2} E_{alphaalpha} + x_sp{beta}{2 }E_{betabeta } + 2x_{alpha} x_{beta}E _{alphabeta}, where E_{alphaalpha} , E_{betabeta} , E_{alphabeta} are unknown parameters to be determined from a microscopic theory. Using the Jastrow wave function Psi for the mixture, a general expression is given for the ground state energy in terms of the two body potential and two and three body correlation functions. The Kirkwood Super-position Approximation (KSA) is used for the three-body correlation functions. The antisymmetry of the wave function for Fermions is incorporated following the procedure given earlier by Lado, Inguva and Smith. This procedure for treating the antisymmetry of the wave function simplifies the equations for the two-body correlation functions considerably. The equations for the correlation functions are solved in the hypernetted-chain approximation. Once the two-particle correlation functions for the mixture ( ^3He-^4He) have been obtained, the energy is minimized with respect to the variational parameters involved in the Jastrow wave function. The binding energy and the optimal correlation functions are then obtained as a function of the concentration of ^3He atoms in the mixture. (Abstract shortened with permission of author.).

Gamma Rhythm Simulations in Alzheimer's Disease

NASA Astrophysics Data System (ADS)

Montgomery, Samuel; Perez, Carlos; Ullah, Ghanim

The different neural rhythms that occur during the sleep-wake cycle regulate the brain's multiple functions. Memory acquisition occurs during fast gamma rhythms during consciousness, while slow oscillations mediate memory consolidation and erasure during sleep. At the neural network level, these rhythms are generated by the finely timed activity within excitatory and inhibitory neurons. In Alzheimer's Disease (AD) the function of inhibitory neurons is compromised due to an increase in amyloid beta (A β) leading to elevated sodium leakage from extracellular space in the hippocampus. Using a Hodgkin-Huxley formalism, heightened sodium leakage current into inhibitory neurons is observed to compromise functionality. Using a simple two neuron system it was observed that as the conductance of the sodium leakage current is increased in inhibitory neurons there is a significant decrease in spiking frequency regarding the membrane potential. This triggers a significant increase in excitatory spiking leading to aberrant network behavior similar to that seen in AD patients. The next step is to extend this model to a larger neuronal system with varying synaptic densities and conductance strengths as well as deterministic and stochastic drives.

Integrin beta1-mediated matrix assembly and signaling are critical for the normal development and function of the kidney glomerulus.

PubMed

Kanasaki, Keizo; Kanda, Yoshiko; Palmsten, Kristin; Tanjore, Harikrishna; Lee, Soo Bong; Lebleu, Valerie S; Gattone, Vincent H; Kalluri, Raghu

2008-01-15

The human kidneys filter 180 l of blood every day via about 2.5 million glomeruli. The three layers of the glomerular filtration apparatus consist of fenestrated endothelium, specialized extracellular matrix known as the glomerular basement membrane (GBM) and the podocyte foot processes with their modified adherens junctions known as the slit diaphragm (SD). In this study we explored the contribution of podocyte beta1 integrin signaling for normal glomerular function. Mice with podocyte specific deletion of integrin beta1 (podocin-Cre beta1-fl/fl mice) are born normal but cannot complete postnatal renal development. They exhibit detectable proteinuria on day 1 and die within a week. The kidneys of podocin-Cre beta1-fl/fl mice exhibit normal glomerular endothelium but show severe GBM defects with multilaminations and splitting including podocyte foot process effacement. The integrin linked kinase (ILK) is a downstream mediator of integrin beta1 activity in epithelial cells. To further explore whether integrin beta1-mediated signaling facilitates proper glomerular filtration, we generated mice deficient of ILK in the podocytes (podocin-Cre ILK-fl/fl mice). These mice develop normally but exhibit postnatal proteinuria at birth and die within 15 weeks of age due to renal failure. Collectively, our studies demonstrate that podocyte beta1 integrin and ILK signaling is critical for postnatal development and function of the glomerular filtration apparatus.

Beta-Delayed Neutron Spectroscopy of 72Co with VANDLE

NASA Astrophysics Data System (ADS)

Keeler, Andrew; Grzywacz, Robert; King, Thomas; Taylor, Steven; Paulauskas, Stanley; Zachary, Christopher; Vandle Collaboration

2017-09-01

Measurements of simple, closed-shell isotopes far from stability provide important benchmarks for nuclear models and are a key constraint in r-process calculations. In particular, r-process models are sensitive to beta decay lifetimes and branching ratios of these neutron-rich isotopes. In this experiment, the Versatile Array of Neutron Detectors at Low Energy (VANDLE) was used to observe decays of nuclei produced by the fragmentation of 82Se at the National Superconducting Cyclotron Laboratory (NSCL). The neutron and gamma emissions of 72Co were measured to map the beta strength distribution (S_beta) above the neutron separation energy and infer the size of the Z = 28 shell gap in the 78Ni region. An implantation detector made of a radiation-hardened, inorganic scintillator was used to correlate implanted ions with beta decays as well as provide a start signal for the neutron Time of Flight measurement. Funded by the National Nuclear Security Administration under the Stewardship Science Academic Alliances program through DOE Award No. DE-NA0002132 and by the Office of Nuclear Physics, U.S. Department of Energy under Awards No. DE-FG02-96ER40983 (UTK).

The amyloid precursor protein and postnatal neurogenesis/neuroregeneration

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

Chen Yanan; Tang, Bor Luen

2006-03-03

The amyloid precursor protein (APP) is the source of amyloid-beta (A{beta}) peptide, produced via its sequential cleavage {beta}- and {gamma}-secretases. Various biophysical forms of A{beta} (and the mutations of APP which results in their elevated levels) have been implicated in the etiology and early onset of Alzheimer's disease. APP's evolutionary conservation and the existence of APP-like isoforms (APLP1 and APLP2) which lack the A{beta} sequence, however, suggest that these might have important physiological functions that are unrelated to A{beta} production. Soluble N-terminal fragments of APP have been known to be neuroprotective, and the interaction of its cytoplasmic C-terminus with amore » myriad of proteins associates it with diverse processes such as axonal transport and transcriptional regulation. The notion for an essential postnatal function of APP has been demonstrated genetically, as mice deficient in both APP and APLP2 or all three APP isoforms exhibit early postnatal lethality and neuroanatomical abnormalities. Recent findings have also brought to light two possible functions of the APP family in Brain-regulation of neural progenitor cell proliferation and axonal outgrowth after injury. Interestingly, these two apparently related neurogenic/neuroregenerative functions of APP involve two separate domains of the molecule.« less

Linear optics measurements and corrections using an AC dipole in RHIC

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

Wang, G.; Bai, M.; Yang, L.

2010-05-23

We report recent experimental results on linear optics measurements and corrections using ac dipole. In RHIC 2009 run, the concept of the SVD correction algorithm is tested at injection energy for both identifying the artificial gradient errors and correcting it using the trim quadrupoles. The measured phase beatings were reduced by 30% and 40% respectively for two dedicated experiments. In RHIC 2010 run, ac dipole is used to measure {beta}* and chromatic {beta} function. For the 0.65m {beta}* lattice, we observed a factor of 3 discrepancy between model and measured chromatic {beta} function in the yellow ring.

Effect of beta blockers (carvedilol or metoprolol XL) in patients with transposition of great arteries and dysfunction of the systemic right ventricle.

PubMed

Doughan, Abdul Rahman K; McConnell, Michael E; Book, Wendy M

2007-03-01

This study evaluated the effects of beta blockers (carvedilol and metoprolol XL) on New York Heart Association functional class and systemic right ventricular (RV) function in patients with complete transposition of the great arteries who had systemic RV dysfunction late after atrial inflow correction. A significant improvement in New York Heart Association functional class was found after 4 months of therapy with beta blockers. Functional recovery was significant mostly in those patients with pacemakers who received higher maintenance doses of carvedilol. RV end-diastolic area was significantly greater in untreated patients at the end of the follow-up period, whereas it was unchanged in treated patients. In conclusion, beta blockers prevent RV remodeling, with a concomitant improvement in exercise tolerance in patients with complete transposition of the great arteries and systemic RV dysfunction.

New developments and prospective applications for beta (1,3) glucans.

PubMed

Laroche, Celine; Michaud, Philippe

2007-01-01

Publications and patents relative to newly observed functions of beta-(1,3)-D-glucans have notably increased in the last few years with the exploitation of their biological activities. The term beta-(1,3)-D-glucans includes a very large number of polysaccharides from bacterial, fungal and vegetable sources. Their structures have a common backbone of beta-(1,3) linked glucopyranosyl residues but the polysaccharidic chain can be beta-(1,6) branched with glucose or integrate some beta-(1,4) linked glucopyranosyl residues in the main chain. Except for the curdlan, a bacterial linear beta-(1,3)-D-glucans, and for the scleroglucan produced by Sclerotium rolfsii, the main drawback limiting the development of these polysaccharides is the lack of efficient processes for their extraction and purification and their cost. However new applications in agronomy, foods, cosmetic and therapeutic could in a next future accentuate the effort of research for their development. So this review focuses on these beta-(1,3)-D-glucans with the objective to detail the strategies employed for their extraction and the relation structure-functions identified when they induce biological activities.

Control of yeast mating signal transduction by a mammalian. beta. sub 2 -adrenergic receptor and G sub s. alpha. subunit

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

King, K.; Caron, M.G.; Lefkowitz, R.J.

1990-10-05

To facilitate functional and mechanistic studies of receptor-G protein interactions by expression of the human {beta}{sub 2}-adrenergic receptor (h{beta}-AR) has been expressed in Saccharomyces cerevisiae. This was achieved by placing a modified h{beta}-AR gene under control of the galactose-inducible GAL1 promoter. After induction by galactose, functional h{beta}-AR was expressed at a concentration several hundred times as great as that found in any human tissue. As determined from competitive ligand binding experiments, h{beta}-AR expressed in yeast displayed characteristic affinities, specificity, and stereoselectivity. Partial activation of the yeast pheromone response pathway by {beta}-adrenergic receptor agonists was achieved in cells coexpressing h{beta}-AR andmore » a mammalian G protein (G{sub s}) {alpha} subunit - demonstrating that these components can couple to each other and to downstream effectors when expressed in yeast. This in vivo reconstitution system provides a new approach for examining ligand binding and G protein coupling to cell surface receptors.« less

Functionally essential, invariant glutamate near the C-terminus of strand beta 5 in various (alpha/beta)8-barrel enzymes as a possible indicator of their evolutionary relatedness.

PubMed

Janecek, S; Baláz, S

1995-08-01

Twelve different (alpha/beta)8-barrel enzymes belonging to three structurally distinct families were found to contain, near the C-terminus of their strand beta 5, a conserved invariant glutamic acid residue that plays an important functional role in each of these enzymes. The search was based on the idea that a conserved sequence region of an (alpha/beta)8-barrel enzyme should be more or less conserved also in the equivalent part of the structure of the other enzymes with this folding motif owing to their mutual evolutionary relatedness. For this purpose, the sequence region around the well conserved fifth beta-strand of alpha-amylase containing catalytic glutamate (Glu230, Aspergillus oryzae alpha-amylase numbering), was used as the sequence-structural template. The isolated sequence stretches of the 12 (alpha/beta)8-barrels are discussed from both the sequence-structural and the evolutionary point of view, the invariant glutamate residue being proposed to be a joining feature of the studied group of enzymes remaining from their ancestral (alpha/beta)8-barrel.

Highly mesoporous single-crystalline zeolite beta synthesized using a nonsurfactant cationic polymer as a dual-function template.

PubMed

Zhu, Jie; Zhu, Yihan; Zhu, Liangkui; Rigutto, Marcello; van der Made, Alexander; Yang, Chengguang; Pan, Shuxiang; Wang, Liang; Zhu, Longfeng; Jin, Yinying; Sun, Qi; Wu, Qinming; Meng, Xiangju; Zhang, Daliang; Han, Yu; Li, Jixue; Chu, Yueying; Zheng, Anmin; Qiu, Shilun; Zheng, Xiaoming; Xiao, Feng-Shou

2014-02-12

Mesoporous zeolites are useful solid catalysts for conversion of bulky molecules because they offer fast mass transfer along with size and shape selectivity. We report here the successful synthesis of mesoporous aluminosilicate zeolite Beta from a commercial cationic polymer that acts as a dual-function template to generate zeolitic micropores and mesopores simultaneously. This is the first demonstration of a single nonsurfactant polymer acting as such a template. Using high-resolution electron microscopy and tomography, we discovered that the resulting material (Beta-MS) has abundant and highly interconnected mesopores. More importantly, we demonstrated using a three-dimensional electron diffraction technique that each Beta-MS particle is a single crystal, whereas most previously reported mesoporous zeolites are comprised of nanosized zeolitic grains with random orientations. The use of nonsurfactant templates is essential to gaining single-crystalline mesoporous zeolites. The single-crystalline nature endows Beta-MS with better hydrothermal stability compared with surfactant-derived mesoporous zeolite Beta. Beta-MS also exhibited remarkably higher catalytic activity than did conventional zeolite Beta in acid-catalyzed reactions involving large molecules.

Fear conditioning is associated with altered integration of PLC and ERK signaling in the hippocampus.

PubMed

Buckley, Colin T; Caldwell, Kevin K

2004-12-01

The extracellular signal-regulated protein kinases (ERKs) are proline-directed, serine/threonine kinases that regulate a variety of cellular functions, including proliferation, differentiation, and plasticity. In the present report, we provide evidence that ERK2 and phosphatidylinositol-specific phospholipase C (PLC)-beta and -gamma isozymes interact in the rat hippocampal formation. We found that anti-PLC-beta1a, -beta2, -beta4, -gamma1 and -gamma2, but not -beta3, immune complexes isolated from rat hippocampal formation postnuclear fractions contain anti-ERK2 immunoreactivity. Further, we show that PLC catalytic activity is associated with anti-ERK2 immunoprecipitates isolated from the hippocampal formation, and that the amount of enzyme activity is significantly increased following fear-conditioned learning. The observed interactions may be mediated by consensus sequences conforming to an ERK2 docking site, termed a D-domain, that we identified in PLC-beta1a, -beta2, -beta4 -gamma1 and -gamma2. Based on these results, we propose that PLC-beta and PLC-gamma isozymes form signaling complexes with ERK2 in rat brain, and these complexes play critical roles in learning and memory, as well as a variety of other neuronal functions.

An ancient role for nuclear beta-catenin in the evolution of axial polarity and germ layer segregation

NASA Technical Reports Server (NTRS)

Wikramanayake, Athula H.; Hong, Melanie; Lee, Patricia N.; Pang, Kevin; Byrum, Christine A.; Bince, Joanna M.; Xu, Ronghui; Martindale, Mark Q.

2003-01-01

The human oncogene beta-catenin is a bifunctional protein with critical roles in both cell adhesion and transcriptional regulation in the Wnt pathway. Wnt/beta-catenin signalling has been implicated in developmental processes as diverse as elaboration of embryonic polarity, formation of germ layers, neural patterning, spindle orientation and gap junction communication, but the ancestral function of beta-catenin remains unclear. In many animal embryos, activation of beta-catenin signalling occurs in blastomeres that mark the site of gastrulation and endomesoderm formation, raising the possibility that asymmetric activation of beta-catenin signalling specified embryonic polarity and segregated germ layers in the common ancestor of bilaterally symmetrical animals. To test whether nuclear translocation of beta-catenin is involved in axial identity and/or germ layer formation in 'pre-bilaterians', we examined the in vivo distribution, stability and function of beta-catenin protein in embryos of the sea anemone Nematostella vectensis (Cnidaria, Anthozoa). Here we show that N. vectensis beta-catenin is differentially stabilized along the oral-aboral axis, translocated into nuclei in cells at the site of gastrulation and used to specify entoderm, indicating an evolutionarily ancient role for this protein in early pattern formation.

Mechanical properties of {beta}-SiC pressureless sintered with Al{sub 2}O{sub 3} additions

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

Mulla, M.A.; Krstic, V.D.

1994-01-01

Mechanical properties of pressureless sintered SiC with Al{sub 2}O{sub 3}addition were measured. The increase in fracture toughness and strength is attributed to the presence of a liquid phase which results in the formation of platelets of an {alpha}-SiC. The highest values for flexural strength and toughness were measured on samples with {approximately}10%Al{sub 2}O{sub 3} addition. Pull out, crack bridging and crack deflection are identified as the major strengthening and toughening mechanisms.

Persistent suppression of subthalamic beta-band activity during rhythmic finger tapping in Parkinson's disease.

PubMed

Joundi, Raed A; Brittain, John-Stuart; Green, Alex L; Aziz, Tipu Z; Brown, Peter; Jenkinson, Ned

2013-03-01

The function of synchronous oscillatory activity at beta band (15-30Hz) frequencies within the basal ganglia is unclear. Here we sought support for the hypothesis that beta activity has a global function within the basal ganglia and is not directly involved in the coding of specific biomechanical parameters of movement. We recorded local field potential activity from the subthalamic nuclei of 11 patients with Parkinson's disease during a synchronized tapping task at three different externally cued rates. Beta activity was suppressed during tapping, reaching a minimum that differed little across the different tapping rates despite an increase in velocity of finger movements. Thus beta power suppression was independent of specific motor parameters. Moreover, although beta oscillations remained suppressed during all tapping rates, periods of resynchronization between taps were markedly attenuated during high rate tapping. As such, a beta rebound above baseline between taps at the lower rates was absent at the high rate. Our results demonstrate that beta desynchronization in the region of the subthalamic nucleus is independent of motor parameters and that the beta resynchronization is differentially modulated by rate of finger tapping, These findings implicate consistent beta suppression in the facilitation of continuous movement sequences. Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Fabry disease and enzyme replacement therapy in classic patients with same mutation: different formulations--different outcome?

PubMed

Politei, J; Schenone, A B; Cabrera, G; Heguilen, R; Szlago, M

2016-01-01

We describe the results of the multidisciplinary evaluation in patients with Fabry disease and the same genetic mutation and their outcomes using different approved enzyme replacement therapy (ERT). We measured baseline data and serial results of neuropathic pain assessment and renal, cardiac and cerebrovascular functioning. Pain scale showed improvement in all male cases treated with agalsidasa beta. A mild improvement was detected in agalsidasa alfa-treated patients after 1 year with posterior increase. During the agalsidase beta shortage, two male patients were switched to agalsidasa alfa, after 1 year both cases presented an increase in scale values. Renal evolution showed a tendency toward a decrease in proteinuria in patients using agalsidase beta and worsening with agalsidase alfa. We found improvement in two females using agalsidase beta and no changes in the other cases regarding cardiac functioning. Brain magnetic resonance imaging (MRI) showed increase of white matter lesions in four patients. Improvement and stabilization in neuropathic pain, renal and cardiac functioning and brain MRI were found mainly in patients treated with agalsidase beta. Following the reported recommendations on reintroduction of agalsidase beta after the enzyme shortage, we decided to switch all patients to agalsidase beta. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of metoprolol on the beta-adrenoceptor density of lymphocytes in patients with dilated cardiomyopathy.

PubMed

Ishida, S; Makino, N; Masutomo, K; Hata, T; Yanaga, T

1993-05-01

We investigated the effect of the beta 1-selective blocker metoprolol on the beta-adrenergic receptor density of circulating lymphocytes in patients with dilated cardiomyopathy. Nine men in New York Heart Association functional classes II (six patients) and III were given metoprolol for 6 months (mean dose 45.6 +/- 18.1 mg). Their cardiac function was assessed by echocardiography. Although there was no difference in the heart rate or pressure rate products, the end-systolic and end-diastolic dimensions significantly decreased in six patients after metoprolol treatment. The ejection fraction, fractional shortening, and mean left ventricular circumferential shortening were significantly increased after the treatment. beta-Adrenoceptor densities of lymphocytes, examined by iodine 125-labeled iodocyanopindolol, were reduced in patients at entry but recovered to normal levels after the metoprolol treatment. The dissociation constants did not differ at any stage of the disease. The relationship between beta-adrenoceptor densities in lymphocytes and echocardiographic parameters showed a positive correlation with the plasma norepinephrine concentration. This study thus provides evidence that long-term metoprolol therapy for dilated cardiomyopathy is associated with beta-receptor up-regulation, and the restoration of myocardial beta-receptor density may be associated with the improved cardiac function as determined by echocardiography.

Cortical Amyloid Beta in Cognitively Normal Elderly Adults is Associated with Decreased Network Efficiency within the Cerebro-Cerebellar System

PubMed Central

Steininger, Stefanie C.; Liu, Xinyang; Gietl, Anton; Wyss, Michael; Schreiner, Simon; Gruber, Esmeralda; Treyer, Valerie; Kälin, Andrea; Leh, Sandra; Buck, Alfred; Nitsch, Roger M.; Prüssmann, Klaas P.; Hock, Christoph; Unschuld, Paul G.

2014-01-01

Background: Deposition of cortical amyloid beta (Aβ) is a correlate of aging and a risk factor for Alzheimer disease (AD). While several higher order cognitive processes involve functional interactions between cortex and cerebellum, this study aims to investigate effects of cortical Aβ deposition on coupling within the cerebro-cerebellar system. Methods: We included 15 healthy elderly subjects with normal cognitive performance as assessed by neuropsychological testing. Cortical Aβ was quantified using (11)carbon-labeled Pittsburgh compound B positron-emission-tomography late frame signals. Volumes of brain structures were assessed by applying an automated parcelation algorithm to three dimensional magnetization-prepared rapid gradient-echo T1-weighted images. Basal functional network activity within the cerebro-cerebellar system was assessed using blood-oxygen-level dependent resting state functional magnetic resonance imaging at the high field strength of 7 T for measuring coupling between cerebellar seeds and cerebral gray matter. A bivariate regression approach was applied for identification of brain regions with significant effects of individual cortical Aβ load on coupling. Results: Consistent with earlier reports, a significant degree of positive and negative coupling could be observed between cerebellar seeds and cerebral voxels. Significant positive effects of cortical Aβ load on cerebro-cerebellar coupling resulted for cerebral brain regions located in inferior temporal lobe, prefrontal cortex, hippocampus, parahippocampal gyrus, and thalamus. Conclusion: Our findings indicate that brain amyloidosis in cognitively normal elderly subjects is associated with decreased network efficiency within the cerebro-cerebellar system. While the identified cerebral regions are consistent with established patterns of increased sensitivity for Aβ-associated neurodegeneration, additional studies are needed to elucidate the relationship between dysfunction of the cerebro-cerebellar system and risk for AD. PMID:24672483

Cortical Amyloid Beta in Cognitively Normal Elderly Adults is Associated with Decreased Network Efficiency within the Cerebro-Cerebellar System.

PubMed

Steininger, Stefanie C; Liu, Xinyang; Gietl, Anton; Wyss, Michael; Schreiner, Simon; Gruber, Esmeralda; Treyer, Valerie; Kälin, Andrea; Leh, Sandra; Buck, Alfred; Nitsch, Roger M; Prüssmann, Klaas P; Hock, Christoph; Unschuld, Paul G

2014-01-01

Deposition of cortical amyloid beta (Aβ) is a correlate of aging and a risk factor for Alzheimer disease (AD). While several higher order cognitive processes involve functional interactions between cortex and cerebellum, this study aims to investigate effects of cortical Aβ deposition on coupling within the cerebro-cerebellar system. We included 15 healthy elderly subjects with normal cognitive performance as assessed by neuropsychological testing. Cortical Aβ was quantified using (11)carbon-labeled Pittsburgh compound B positron-emission-tomography late frame signals. Volumes of brain structures were assessed by applying an automated parcelation algorithm to three dimensional magnetization-prepared rapid gradient-echo T1-weighted images. Basal functional network activity within the cerebro-cerebellar system was assessed using blood-oxygen-level dependent resting state functional magnetic resonance imaging at the high field strength of 7 T for measuring coupling between cerebellar seeds and cerebral gray matter. A bivariate regression approach was applied for identification of brain regions with significant effects of individual cortical Aβ load on coupling. Consistent with earlier reports, a significant degree of positive and negative coupling could be observed between cerebellar seeds and cerebral voxels. Significant positive effects of cortical Aβ load on cerebro-cerebellar coupling resulted for cerebral brain regions located in inferior temporal lobe, prefrontal cortex, hippocampus, parahippocampal gyrus, and thalamus. Our findings indicate that brain amyloidosis in cognitively normal elderly subjects is associated with decreased network efficiency within the cerebro-cerebellar system. While the identified cerebral regions are consistent with established patterns of increased sensitivity for Aβ-associated neurodegeneration, additional studies are needed to elucidate the relationship between dysfunction of the cerebro-cerebellar system and risk for AD.

Structural and molecular characterization of the prefoldin beta subunit from Thermococcus strain KS-1.

PubMed

Kida, Hiroshi; Sugano, Yuri; Iizuka, Ryo; Fujihashi, Masahiro; Yohda, Masafumi; Miki, Kunio

2008-11-14

Prefoldin (PFD) is a heterohexameric molecular chaperone that is found in eukaryotic cytosol and archaea. PFD is composed of alpha and beta subunits and forms a "jellyfish-like" structure. PFD binds and stabilizes nascent polypeptide chains and transfers them to group II chaperonins for completion of their folding. Recently, the whole genome of Thermococcus kodakaraensis KOD1 was reported and shown to contain the genes of two alpha and two beta subunits of PFD. The genome of Thermococcus strain KS-1 also possesses two sets of alpha (alpha1 and alpha2) and beta subunits (beta1 and beta2) of PFD (TsPFD). However, the functions and roles of each of these PFD subunits have not been investigated in detail. Here, we report the crystal structure of the TsPFD beta1 subunit at 1.9 A resolution and its functional analysis. TsPFD beta1 subunits form a tetramer with four coiled-coil tentacles resembling the jellyfish-like structure of heterohexameric PFD. The beta hairpin linkers of beta1 subunits assemble to form a beta barrel "body" around a central fourfold axis. Size-exclusion chromatography and multi-angle light-scattering analyses show that the beta1 subunits form a tetramer at pH 8.0 and a dimer of tetramers at pH 6.8. The tetrameric beta1 subunits can protect against aggregation of relatively small proteins, insulin or lysozyme. The structural and biochemical analyses imply that PFD beta1 subunits act as molecular chaperones in living cells of some archaea.

Cerebrospinal fluid levels of corticotropin-releasing hormone in women with functional hypothalamic amenorrhea.

PubMed

Berga, S L; Loucks-Daniels, T L; Adler, L J; Chrousos, G P; Cameron, J L; Matthews, K A; Marcus, M D

2000-04-01

Women with functional hypothalamic amenorrhea are anovulatory because of reduced gonadotropin-releasing hormone drive. Several studies have documented hypercortisolemia, which suggests that functional hypothalamic amenorrhea is stress-induced. Further, with recovery (resumption of ovulation), cortisol decreased and gonadotropin-releasing hormone drive increased. Corticotropin-releasing hormone can increase cortisol and decrease gonadotropin-releasing hormone. To determine its role in functional hypothalamic amenorrhea, we measured corticotropin-releasing hormone in cerebrospinal fluid along with arginine vasopressin, another potent adrenocorticotropic hormone secretagog, and beta-endorphin, which is released by corticotropin-releasing hormone and can inhibit gonadotropin-releasing hormone. Corticotropin-releasing hormone, vasopressin, and beta-endorphin levels were measured in cerebrospinal fluid from 14 women with eumenorrhea and 15 women with functional hypothalamic amenorrhea. Levels of corticotropin-releasing hormone in cerebrospinal fluid and of vasopressin were comparable and beta-endorphin levels were lower in women with functional hypothalamic amenorrhea. In women with established functional hypothalamic amenorrhea, increased cortisol and reduced gonadotropin-releasing hormone are not sustained by elevated cerebrospinal-fluid corticotropin-releasing hormone, vasopressin, or beta-endorphin. These data do not exclude a role for these factors in the initiation of functional hypothalamic amenorrhea.

[Correlates of change in cognitive function during a two-year follow-up period in a comprehensive health examination for the community-dwelling elderly for the prevention of geriatric syndromes and bed-ridden state].

PubMed

Iwasa, Hajime; Suzuki, Takao; Yoshida, Yuko; Kwon, Jinhee; Yoshida, Hideyo; Kim, Hunkyung; Sugiura, Miho; Furuna, Taketo

2006-11-01

We explored correlates of change in cognitive function during a two-year follow-up period among the community-dwelling elderly in Japan, using a population-based prospective approach. The participants analyzed in the present study were 260 men and 222 women aged 70 to 84 years at baseline, living in an urban Japanese community. Data such as change in cognitive function during two years (calculated by subtracting baseline Mini-Mental State Examination [MMSE] score from follow-up MMSE score: a negative value means a decrease in MMSE scores during the two-year period) as an outcome variable, age, education, hearing and vision problems, IADL deficit (measured by the Tokyo Metropolitan Institute of Gerontology of Index of Competence), problems related to memory complaint, living alone, hemoglobin level, as explanatory variables, and the baseline MMSE score, depressive status (measured by the Mini-International Neuropsychiatric Interview), chronic conditions (hypertension, stroke, and diabetes mellitus) as covariates, were collected during a comprehensive health examination survey for the elderly. We conducted multivariate regression analysis by genders to explore correlates of change in cognitive function. The results showed that higher age (beta = -0.18), presence of hearing problem (beta = -0.21), presence of IADL deficit (beta = -0.15), and memory complaint (beta = -0.20) in men, and higher age (beta = -0.27), low education level (beta = -0.25) and lower hemoglobin level (beta = 0.16) in women, were significantly associated with change in cognitive function when adjusting for the potential confounders. These factors may be reliable predictors for cognitive decline.

Beta-Actin Is Required for Proper Mouse Neural Crest Ontogeny

PubMed Central

Tondeleir, Davina; Noelanders, Rivka; Bakkali, Karima; Ampe, Christophe

2014-01-01

The mouse genome consists of six functional actin genes of which the expression patterns are temporally and spatially regulated during development and in the adult organism. Deletion of beta-actin in mouse is lethal during embryonic development, although there is compensatory expression of other actin isoforms. This suggests different isoform specific functions and, more in particular, an important function for beta-actin during early mammalian development. We here report a role for beta-actin during neural crest ontogeny. Although beta-actin null neural crest cells show expression of neural crest markers, less cells delaminate and their migration arrests shortly after. These phenotypes were associated with elevated apoptosis levels in neural crest cells, whereas proliferation levels were unchanged. Specifically the pre-migratory neural crest cells displayed higher levels of apoptosis, suggesting increased apoptosis in the neural tube accounts for the decreased amount of migrating neural crest cells seen in the beta-actin null embryos. These cells additionally displayed a lack of membrane bound N-cadherin and dramatic decrease in cadherin-11 expression which was more pronounced in the pre-migratory neural crest population, potentially indicating linkage between the cadherin-11 expression and apoptosis. By inhibiting ROCK ex vivo, the knockout neural crest cells regained migratory capacity and cadherin-11 expression was upregulated. We conclude that the presence of beta-actin is vital for survival, specifically of pre-migratory neural crest cells, their proper emigration from the neural tube and their subsequent migration. Furthermore, the absence of beta-actin affects cadherin-11 and N-cadherin function, which could partly be alleviated by ROCK inhibition, situating the Rho-ROCK signaling in a feedback loop with cadherin-11. PMID:24409333

cGMP may have trophic effects on beta cell function comparable to those of cAMP, implying a role for high-dose biotin in prevention/treatment of diabetes.

PubMed

McCarty, Mark F

2006-01-01

Incretin hormones have trophic effects on beta cell function that can aid prevention and treatment of diabetes. cAMP is the primary mediator of these effects, and has been shown to potentiate glucose-stimulated insulin secretion, promote proper beta cells differentiation by increasing expression of the crucial transcription factor PDX-1, and prevent beta cell apoptosis. cGMP's role in beta cell function has received far less scrutiny, but there is emerging evidence that it may have a trophic impact on beta cell function analogous to that of cAMP. An increase in plasma glucose boosts beta cell production of cGMP, which acts as a feed-forward mediator to enhance glucose-stimulated insulin secretion. cGMP also has an anti-apoptotic effect in beta cells, and there is now indirect evidence that it promotes expression of PDX-1. Supraphysiological concentrations of biotin can directly activate guanylate cyclase, and there is limited evidence that high intakes of this vitamin can be therapeutically beneficial in diabetics and in rodent models of diabetes. Beneficial effects of cGMP on muscle insulin sensitivity and on control of hepatic glucose output may contribute to biotin's utility in diabetes. The fact that nitric oxide/cGMP exert a range of favorable effects on vascular health should further encourage exploration of biotin's preventive and therapeutic potential. If an appropriate high-dose biotin regimen could achieve a modest systemic increase in guanylate cyclase activity, without entailing unacceptable side effects or risks, such a regimen might have considerable potential for promoting vascular health and preventing or managing diabetes.

A methodology for efficiency optimization of betavoltaic cell design using an isotropic planar source having an energy dependent beta particle distribution.

PubMed

Theirrattanakul, Sirichai; Prelas, Mark

2017-09-01

Nuclear batteries based on silicon carbide betavoltaic cells have been studied extensively in the literature. This paper describes an analysis of design parameters, which can be applied to a variety of materials, but is specific to silicon carbide. In order to optimize the interface between a beta source and silicon carbide p-n junction, it is important to account for the specific isotope, angular distribution of the beta particles from the source, the energy distribution of the source as well as the geometrical aspects of the interface between the source and the transducer. In this work, both the angular distribution and energy distribution of the beta particles are modeled using a thin planar beta source (e.g., H-3, Ni-63, S-35, Pm-147, Sr-90, and Y-90) with GEANT4. Previous studies of betavoltaics with various source isotopes have shown that Monte Carlo based codes such as MCNPX, GEANT4 and Penelope generate similar results. GEANT4 is chosen because it has important strengths for the treatment of electron energies below one keV and it is widely available. The model demonstrates the effects of angular distribution, the maximum energy of the beta particle and energy distribution of the beta source on the betavoltaic and it is useful in determining the spatial profile of the power deposition in the cell. Copyright © 2017. Published by Elsevier Ltd.

INJECTION OPTICS FOR THE JLEIC ION COLLIDER RING

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

Morozov, Vasiliy; Derbenev, Yaroslav; Lin, Fanglei

2016-05-01

The Jefferson Lab Electron-Ion Collider (JLEIC) will accelerate protons and ions from 8 GeV to 100 GeV. A very low beta function at the Interaction Point (IP) is needed to achieve the required luminosity. One consequence of the low beta optics is that the beta function in the final focusing (FF) quadrupoles is extremely high. This leads to a large beam size in these magnets as well as strong sensitivity to errors which limits the dynamic aperture. These effects are stronger at injection energy where the beam size is maximum, and therefore very large aperture FF magnets are required tomore » allow a large dynamic aperture. A standard solution is a relaxed injection optics with IP beta function large enough to provide a reasonable FF aperture. This also reduces the effects of FF errors resulting in a larger dynamic aperture at injection. We describe the ion ring injection optics design as well as a beta-squeeze transition from the injection to collision optics.« less

Treatment of prediabetes

PubMed Central

Kanat, Mustafa; DeFronzo, Ralph A; Abdul-Ghani, Muhammad A

2015-01-01

Progression of normal glucose tolerance (NGT) to overt diabetes is mediated by a transition state called impaired glucose tolerance (IGT). Beta cell dysfunction and insulin resistance are the main defects in type 2 diabetes mellitus (type 2 DM) and even normoglycemic IGT patients manifest these defects. Beta cell dysfunction and insulin resistance also contribute to the progression of IGT to type 2 DM. Improving insulin sensitivity and/or preserving functions of beta-cells can be a rational way to normalize the GT and to control transition of IGT to type 2 DM. Loosing weight, for example, improves whole body insulin sensitivity and preserves beta-cell function and its inhibitory effect on progression of IGT to type 2 DM had been proven. But interventions aiming weight loss usually not applicable in real life. Pharmacotherapy is another option to gain better insulin sensitivity and to maintain beta-cell function. In this review, two potential treatment options (lifestyle modification and pharmacologic agents) that limits the IGT-type 2 DM conversion in prediabetic subjects are discussed. PMID:26464759

Structure of a Trypanosoma Brucei Alpha/Beta--Hydrolase Fold Protein With Unknown Function

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

Merritt, E.A.; Holmes, M.; Buckner, F.S.

2009-05-26

The structure of a structural genomics target protein, Tbru020260AAA from Trypanosoma brucei, has been determined to a resolution of 2.2 {angstrom} using multiple-wavelength anomalous diffraction at the Se K edge. This protein belongs to Pfam sequence family PF08538 and is only distantly related to previously studied members of the {alpha}/{beta}-hydrolase fold family. Structural superposition onto representative {alpha}/{beta}-hydrolase fold proteins of known function indicates that a possible catalytic nucleophile, Ser116 in the T. brucei protein, lies at the expected location. However, the present structure and by extension the other trypanosomatid members of this sequence family have neither sequence nor structural similaritymore » at the location of other active-site residues typical for proteins with this fold. Together with the presence of an additional domain between strands {beta}6 and {beta}7 that is conserved in trypanosomatid genomes, this suggests that the function of these homologs has diverged from other members of the fold family.« less

Control of the immune response by DHEA and its metabolites.

PubMed

Loria, R M; Padgett, D A

1998-06-01

The 17 keto steroid, Dehydroepiandrosterone (5-androsten-3 beta-17-one, DHEA) has been shown to protect mice from a variety of lethal infections. This includes, but is not limited to, infection with viruses (herpesvirus type 2, coxsackievirus B4-CVB4),bacteria (Enterococcus faecalis, Pseudomonas aeruginosa), and a parasite (Cryptosporidium parvum). We have reported that androstenediol (5-androsten-3 beta-17 beta-diol, beta AED), which is derived from DHEA, is at least 100x more effective in up-regulating systemic resistance against CVB4-infection than its precursor. Furthermore, androstenetriol (5-androstene-3 beta-7 beta-17 beta-triol beta AET) which is formed by 7 beta hydroxylation of beta AED, was more effective against CVB4-infection than its precursor beta AED. Neither steroid however has shown any significant direct antiviral effects. The in-vitro influences of DHEA, beta AED, and beta AET on a mitogen-induced mixed splenocyte proliferation assay were determined. The results showed that DHEA suppressed the proliferation of concanavalin A (Con A) or lipopolysaccharide (LPS) activated cultures in a dose dependent manner. beta AED had little influence on the activation response. However, beta AET potentiated the response to both mitogens significantly above control. The regulation of interleukin-2 and interleukin-3 secretion from Con A-activated lymphocytes was analogous to these observations. These functions were suppressed by DHEA, unaffected by beta AED, and potently increased by beta AET. Moreover, the classic immuno-suppressive effects of hydro-cortisone on Con A-induced lymphocyte proliferation, as well as IL-2 and IL-3 production were unaffected by co-cultured with DHEA and only minimally counteracted by beta AED. In contrast, beta AET significantly counteracted the effect of hydrocortisone when co-cultured together. These results show that while in-vivo, DHEA, beta AED, and beta AET each function in a similar manner. In-vitro, their effects are dramatically different from one another with only beta AET potentiating the cellular response by increasing lymphocyte activation and counteracting the immuno-suppressive activity of hydrocortisone.

Beta-lactam antibiotics modulate T-cell functions and gene expression via covalent binding to cellular albumin.

PubMed

Mor, Felix; Cohen, Irun R

2013-02-19

Recent work has suggested that beta-lactam antibiotics might directly affect eukaryotic cellular functions. Here, we studied the effects of commonly used beta-lactam antibiotics on rodent and human T cells in vitro and in vivo on T-cell-mediated experimental autoimmune diseases. We now report that experimental autoimmune encephalomyelitis and adjuvant arthritis were significantly more severe in rats treated with cefuroxime and other beta-lactams. T cells appeared to mediate the effect: an anti-myelin basic protein T-cell line treated with cefuroxime or penicillin was more encephalitogenic in adoptive transfer experiments. The beta-lactam ampicillin, in contrast to cefuroxime and penicillin, did not enhance encephalomyelitis, but did inhibit the autoimmune diabetes developing spontaneously in nonobese diabetic mice. Gene expression analysis of human peripheral blood T cells showed that numerous genes associated with T helper 2 (Th2) and T regulatory (Treg) differentiation were down-regulated in T cells stimulated in the presence of cefuroxime; these genes were up-regulated in the presence of ampicillin. The T-cell protein that covalently bound beta-lactam antibiotics was found to be albumin. Human and rodent T cells expressed albumin mRNA and protein, and penicillin-modified albumin was taken up by rat T cells, leading to enhanced encephalitogenicity. Thus, beta-lactam antibiotics in wide clinical use have marked effects on T-cell behavior; beta-lactam antibiotics can function as immunomodulators, apparently through covalent binding to albumin.

The electrophysiologic properties of esmolol, a short acting beta-blocker.

PubMed

Greenspan, A M; Spielman, S R; Horowitz, L N; Laddu, A; Senior, S

1988-04-01

Although beta-blockers have established efficacy in treating ventricular ectopy and PSVT, their applicability for acute antiarrhythmic interventions in patients with organic heart disease or COPD, is frequently limited by negative inotropic or bronchospastic side effects. The development of an ultrashort acting beta-blocker with rapid reversibility of its side effects would widen their applicability. Therefore, we tested the electrophysiologic properties of such a new short acting beta-blocker, esmolol, in 14 patients (10 with organic heart disease) with a mean EF of 47.6 +/- 17%, undergoing standard clinical electrophysiologic studies for various indications. Like most other beta-blockers, esmolol's major direct effects were on sinus node function and AV nodal conduction characteristics; significantly prolonging sinus cycle length, cycle length to Wenckebach and AH interval in sinus rhythm and at a paced cycle length of 600 ms. In contrast to most other beta-blockers, following termination of its infusion, esmolol shortened parameters of sinus node function and AV nodal refractoriness, with respect to the control values, suggesting a possible rebound phenomena. These effects occurred within 5 min of terminating the intravenous drug infusion. Esmolol had no significant effect on systolic blood pressure, electrocardiographic intervals and had rare adverse reactions. We conclude that esmolol is an ultra-short acting beta-blocker, with typical direct electrophysiologic effects on sinus node and AV nodal function, and a possible rebound phenomena following its discontinuation that may make it particularly suited to acute antiarrhythmic interventions in patients susceptible to adverse beta-blocker side effects.

Source analysis of beta-synchronisation and cortico-muscular coherence after movement termination based on high resolution electroencephalography.

PubMed

Muthuraman, Muthuraman; Tamás, Gertrúd; Hellriegel, Helge; Deuschl, Günther; Raethjen, Jan

2012-01-01

We hypothesized that post-movement beta synchronization (PMBS) and cortico-muscular coherence (CMC) during movement termination relate to each other and have similar role in sensorimotor integration. We calculated the parameters and estimated the sources of these phenomena.We measured 64-channel EEG simultaneously with surface EMG of the right first dorsal interosseus muscle in 11 healthy volunteers. In Task1, subjects kept a medium-strength contraction continuously; in Task2, superimposed on this movement, they performed repetitive self-paced short contractions. In Task3 short contractions were executed alone. Time-frequency analysis of the EEG and CMC was performed with respect to the offset of brisk movements and averaged in each subject. Sources of PMBS and CMC were also calculated.High beta power in Task1, PMBS in Task2-3, and CMC in Task1-2 could be observed in the same individual frequency bands. While beta synchronization in Task1 and PMBS in Task2-3 appeared bilateral with contralateral predominance, CMC in Task1-2 was strictly a unilateral phenomenon; their main sources did not differ contralateral to the movement in the primary sensorimotor cortex in 7 of 11 subjects in Task1, and in 6 of 9 subjects in Task2. In Task2, CMC and PMBS had the same latency but their amplitudes did not correlate with each other. In Task2, weaker PMBS source was found bilaterally within the secondary sensory cortex, while the second source of CMC was detected in the premotor cortex, contralateral to the movement. In Task3, weaker sources of PMBS could be estimated in bilateral supplementary motor cortex and in the thalamus. PMBS and CMC appear simultaneously at the end of a phasic movement possibly suggesting similar antikinetic effects, but they may be separate processes with different active functions. Whereas PMBS seems to reset the supraspinal sensorimotor network, cortico-muscular coherence may represent the recalibration of cortico-motoneuronal and spinal systems.

Physical association and functional interaction between beta1 integrin and CD98 on human T lymphocytes

NASA Technical Reports Server (NTRS)

Miyamoto, Yuko J.; Mitchell, Jason S.; McIntyre, Bradley W.

2003-01-01

CD98 is a cell surface protein previously characterized as a cell activation marker, an amino acid transporter, and has recently been implicated in integrin-related functions. Integrins are cell surface proteins, important for homotypic cell aggregation, cell adhesion, and coactivation of T lymphocytes. We have previously shown that the anti-CD98 mAb 80A10, when coimmobilized with anti-CD3 mAb OKT3, is able to mediate human T cell coactivation that is inhibited by anti-beta1 integrin specific mAb 18D3. These results indicated a functional association of CD98 and beta1 integrin signaling but left open the question of a physical association. We now show the induction of homotypic aggregation through CD98 among human T cells and this aggregation was inhibited by anti-beta1 integrin mAb. Therefore, CD98-dependent lymphocyte proliferation and adhesion may involve integrins. Competitive binding assays and fluorescence colocalization analysis suggested that CD98 and beta1 integrin were physically associated. Differential extraction techniques and immunoprecipitations provided the first evidence that the alpha4beta1 integrin and CD98 are specifically associated on human T lymphocytes.

ROS signaling, oxidative stress and Nrf2 in pancreatic beta-cell function

PubMed Central

Pi, Jingbo; Zhang, Qiang; Fu, Jingqi; Woods, Courtney G.; Hou, Yongyong; Corkey, Barbara E; Collins, Sheila; Andersen, Melvin E.

2009-01-01

This review focuses on the emerging evidence that reactive oxygen species (ROS) derived from glucose metabolism, such as H2O2, act as metabolic signaling molecules for glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells. Particular emphasis is placed on the potential inhibitory role of endogenous antioxidants, which rise in response to oxidative stress, in glucose-triggered ROS and GSIS. We propose that cellular adaptive response to oxidative stress challenge, such as nuclear factor E2-related factor 2 (Nrf2)-mediated antioxidant induction, plays paradoxical roles in pancreatic beta-cell function. On the one hand, induction of antioxidant enzymes protects beta-cells from oxidative damage and possible cell death, thus minimizing oxidative damage-related impairment of insulin secretion. On the other hand, the induction of antioxidant enzymes by Nrf2 activation blunts glucose-triggered ROS signaling, thus resulting in reduced GSIS. These two premises are potentially relevant to impairment of beta-cells occurring in the late and early stage of Type 2 diabetes, respectively. In addition, we summarized our recent findings that persistent oxidative stress due to absence of uncoupling protein 2 activates cellular adaptive response which is associated with impaired pancreatic beta-cell function. PMID:19501608

Systematic evaluation of a tissue-engineered bone for maxillary sinus augmentation in large animal canine model.

PubMed

Wang, Shaoyi; Zhang, Zhiyuan; Xia, Lunguo; Zhao, Jun; Sun, Xiaojuan; Zhang, Xiuli; Ye, Dongxia; Uludağ, Hasan; Jiang, Xinquan

2010-01-01

The objective of this study is to systematically evaluate the effects of a tissue-engineered bone complex for maxillary sinus augmentation in a canine model. Twelve sinus floor augmentation surgeries in 6 animals were performed bilaterally and randomly repaired with the following 3 groups of grafts: group A consisted of tissue-engineered osteoblasts/beta-TCP complex (n=4); group B consisted of beta-TCP alone (n=4); group C consisted of autogenous bone obtained from iliac crest as a positive control (n=4). All dogs had uneventful healings following the surgery. Sequential polychrome fluorescent labeling, maxillofacial CT, microhardness tests, as well as histological and histomorphometric analyses indicated that the tissue-engineered osteoblasts/beta-TCP complex dramatically promoted bone formation and mineralization and maximally maintained the height and volume of elevated maxillary sinus. By comparison, both control groups of beta-TCP or autologous iliac bone showed considerable resorption and replacement by fibrous or fatty tissue. We thus conclude that beta-TCP alone could barely maintain the height and volume of the elevated sinus floor, and that the transplantation of autogenous osteoblasts on beta-TCP could promote earlier bone formation and mineralization, maximally maintain height, volume and increase the compressive strength of augmented maxillary sinus. This tissue engineered bone complex might be a better alternative to autologous bone for the clinical edentulous maxillary sinus augmentation. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Conformational stability of apoflavodoxin.

PubMed Central

Genzor, C. G.; Beldarraín, A.; Gómez-Moreno, C.; López-Lacomba, J. L.; Cortijo, M.; Sancho, J.

1996-01-01

Flavodoxins are alpha/beta proteins that mediate electron transfer reactions. The conformational stability of apoflavodoxin from Anaboena PCC 7119 has been studied by calorimetry and urea denaturation as a function of pH and ionic strength. At pH > 12, the protein is unfolded. Between pH 11 and pH 6, the apoprotein is folded properly as judged from near-ultraviolet (UV) circular dichroism (CD) and high-field 1H NMR spectra. In this pH interval, apoflavodoxin is a monomer and its unfolding by urea or temperature follows a simple two-state mechanism. The specific heat capacity of unfolding for this native conformation is unusually low. Near its isoelectric point (3.9), the protein is highly insoluble. At lower pH values (pH 3.5-2.0), apoflavodoxin adopts a conformation with the properties of a molten globule. Although apoflavodoxin at pH 2 unfolds cooperatively with urea in a reversible fashion and the fluorescence and far-UV CD unfolding curves coincide, the transition midpoint depends on the concentration of protein, ruling out a simple two-state process at acidic pH. Apoflavodoxin constitutes a promising system for the analysis of the stability and folding of alpha/beta proteins and for the study of the interaction between apoflavoproteins and their corresponding redox cofactors. PMID:8819170

Fabrication and evaluation of cold/formed/weldbrazed beta-titanium skin-stiffened compression panels

NASA Technical Reports Server (NTRS)

Royster, D. M.; Bales, T. T.; Davis, R. C.; Wiant, H. R.

1983-01-01

The room temperature and elevated temperature buckling behavior of cold formed beta titanium hat shaped stiffeners joined by weld brazing to alpha-beta titanium skins was determined. A preliminary set of single stiffener compression panels were used to develop a data base for material and panel properties. These panels were tested at room temperature and 316 C (600 F). A final set of multistiffener compression panels were fabricated for room temperature tests by the process developed in making the single stiffener panels. The overall geometrical dimensions for the multistiffener panels were determined by the structural sizing computer code PASCO. The data presented from the panel tests include load shortening curves, local buckling strengths, and failure loads. Experimental buckling loads are compared with the buckling loads predicted by the PASCO code. Material property data obtained from tests of ASTM standard dogbone specimens are also presented.

Functional characterization of the beta-adrenergic receptor subtypes expressed by CA1 pyramidal cells in the rat hippocampus.

PubMed

Hillman, Kristin L; Doze, Van A; Porter, James E

2005-08-01

Recent studies have demonstrated that activation of the beta-adrenergic receptor (AR) using the selective beta-AR agonist isoproterenol (ISO) facilitates pyramidal cell long-term potentiation in the cornu ammonis 1 (CA1) region of the rat hippocampus. We have previously analyzed beta-AR genomic expression patterns of 17 CA1 pyramidal cells using single cell reverse transcription-polymerase chain reaction, demonstrating that all samples expressed the beta2-AR transcript, with four of the 17 cells additionally expressing mRNA for the beta1-AR subtype. However, it has not been determined which beta-AR subtypes are functionally expressed in CA1 for these same pyramidal neurons. Using cell-attached recordings, we tested the ability of ISO to increase pyramidal cell action potential (AP) frequency in the presence of subtype-selective beta-AR antagonists. ICI-118,551 [(+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol] and butoxamine [alpha-[1-(t-butylamino)ethyl]-2,5-dimethoxybenzyl alcohol) hydrochloride], agents that selectively block the beta2-AR, produced significant parallel rightward shifts in the concentration-response curves for ISO. From these curves, apparent equilibrium dissociation constant (K(b)) values of 0.3 nM for ICI-118,551 and 355 nM for butoxamine were calculated using Schild regression analysis. Conversely, effective concentrations of the selective beta1-AR antagonists CGP 20712A [(+/-)-2-hydroxy-5-[2-([2-hydroxy-3-(4-[1-methyl-4-(trifluoromethyl)-1H-imidazol-2-yl]phenoxy)propyl]amino)ethoxy]-benzamide methanesulfonate] and atenolol [4-[2'-hydroxy-3'-(isopropyl-amino)propoxy]phenylacetamide] did not significantly affect the pyramidal cell response to ISO. However, at higher concentrations, atenolol significantly decreased the potency for ISO-mediated AP frequencies. From these curves, an apparent atenolol K(b) value of 3162 nM was calculated. This pharmacological profile for subtype-selective beta-AR antagonists indicates that beta2-AR activation is mediating the increased AP frequency. Knowledge of functional AR expression in CA1 pyramidal neurons will aid future long-term potentiation studies by allowing selective manipulation of specific beta-AR subtypes.

Parallel beta/alpha-barrels of alpha-amylase, cyclodextrin glycosyltransferase and oligo-1,6-glucosidase versus the barrel of beta-amylase: evolutionary distance is a reflection of unrelated sequences.

PubMed

Janecek, S

1994-10-17

The structures of functionally related beta/alpha-barrel starch hydrolases, alpha-amylase, beta-amylase, cyclodextrin glycosyltransferase and oligo-1,6-glucosidase, are discussed, their mutual sequence similarities being emphasized. Since these enzymes (except for beta-amylase) along with the predicted set of more than ten beta/alpha-barrels from the alpha-amylase enzyme superfamily fulfil the criteria characteristic of the products of divergent evolution, their unrooted distance tree is presented.

Development of Tough, Strong, and Pest-Resistant MoSi2-(Beta)Si3N4 Composites for High-Temperature Structural Applications

NASA Technical Reports Server (NTRS)

Hebsur, M. G.; Choi, S. R.; Whittenberger, J. D.; Salem, J. A.; Noebe, R. D.

2001-01-01

A new MoSi2-base composite was developed that contains in-situ reinforcement of whisker-type beta-Si3N4 grains in a MoSi2 matrix. The advantages of this in-situ reinforced MoSi2-Si3N4 are lower density, higher fracture toughness and better strength than typical MoSi2 alloys, combined with excellent environmental and pest resistance. The average fracture toughness of the in-situ reinforced material determined by one technique was 12.2 MPa.m(exp 1/2) compared to 4.9 to 5.5 MPa.m(exp 1/2) for similar materials with the exception that the beta-Si3N4 had a blocky morphology as opposed to the whisker-like morphology typical of the in-situ toughened material. This MoSi2-(beta)Si3N4 was also resistant to pesting at intermediate temperatures (400 to 600 C) even when precracked or under applied load; conditions that would quickly reduce typical MoSi2 alloys to oxidized powder.

On ripple-load, stress-corrosion, and sustained-load cracking behavior in a high strength beta titanium alloy

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

Pao, P.S.; Meyn, D.A.; Bayles, R.A.

1997-06-01

Both overaged and peakaged TIMETAL 21S beta titanium alloys exhibit significant ripple-load cracking susceptibility in salt water and in ambient air environments. At R = 0.90, the ripple-load cracking thresholds of the overaged alloy are 67% and 72% lower than the stress-corrosion cracking and sustained-load cracking thresholds. For the peakaged alloy, the reductions are 55% and 61%. The stress-corrosion cracking threshold in salt water and the sustained-load cracking threshold in air of peakaged TIMETAL 21S are significantly lower while the ripple-load cracking threshold is slightly lower than those of the overaged alloy. The stress-corrosion cracking, sustained-load cracking, and ripple-load crackingmore » resistance of peakaged TIMETAL 21S are significantly inferior to those of both beta-annealed Ti-6Al-4V and Ti-15V-3Cr-3Al-3Sn. The ripple-load cracking resistance of overaged TIMETAL 21S, though better than Ti-15V-3Cr-3Al-3Sn, is still inferior than that of beta-annealed Ti-6Al-4V.« less

Spontaneous sensorimotor cortical activity is suppressed by deep brain stimulation in patients with advanced Parkinson's disease.

PubMed

Luoma, Jarkko; Pekkonen, Eero; Airaksinen, Katja; Helle, Liisa; Nurminen, Jussi; Taulu, Samu; Mäkelä, Jyrki P

2018-06-22

Advanced Parkinson's disease (PD) is characterized by an excessive oscillatory beta band activity in the subthalamic nucleus (STN). Deep brain stimulation (DBS) of STN alleviates motor symptoms in PD and suppresses the STN beta band activity. The effect of DBS on cortical sensorimotor activity is more ambiguous; both increases and decreases of beta band activity have been reported. Non-invasive studies with simultaneous DBS are problematic due to DBS-induced artifacts. We recorded magnetoencephalography (MEG) from 16 advanced PD patients with and without STN DBS during rest and wrist extension. The strong magnetic artifacts related to stimulation were removed by temporal signal space separation. MEG oscillatory activity at 5-25 Hz was suppressed during DBS in a widespread frontoparietal region, including the sensorimotor cortex identified by the cortico-muscular coherence. The strength of suppression did not correlate with clinical improvement. Our results indicate that alpha and beta band oscillations are suppressed at the frontoparietal cortex by STN DBS in PD. Copyright © 2018. Published by Elsevier B.V.

Shock wave response of a zirconium-based bulk metallic glass and its composite

NASA Astrophysics Data System (ADS)

Zhuang, Shiming; Lu, Jun; Ravichandran, Guruswami

2002-06-01

A zirconium-based bulk metallic glass, Zr41.2Ti13.8Cu12.5Ni10Be22.5 (Vit 1), and its composite, Zr56.3Ti13.8Cu6.9Ni5.6Nb5.0Be12.5 (beta-Vit), were subjected to planar impact loading. A surprisingly low amplitude elastic precursor and bulk wave, corresponding to the elastic response of the "frozen structure" of the intact metallic glasses, were observed to precede the rate-dependent large deformation shock wave. A concave downward curvature after the initial increase of the Us-Up shock Hugoniots suggests that a phase-change-like transition occurred during shock compression. Further, compression damage occurred due to the shear localization. The spalling in Vit 1 was induced by shear localization, while in beta-Vit, it was due to debonding of the beta-phase boundary from the matrix. The spall strengths at strain rate of 2 x106 s-1 were determined to be 2.35 and 2.11 GPa for Vit 1 and beta-Vit, respectively.

A recombinant tail-less integrin beta 4 subunit disrupts hemidesmosomes, but does not suppress alpha 6 beta 4-mediated cell adhesion to laminins

PubMed Central

1995-01-01

To examine the function of the alpha 6 beta 4 integrin we have determined its ligand-binding ability and overexpressed two potentially dominant negative mutant beta 4 subunits, lacking either the cytoplasmic or extracellular domain, in bladder epithelial 804G cells. The results of cell adhesion and radioligand-binding assays showed that alpha 6 beta 4 is a receptor for several laminin isoforms, including laminin 1, 2, 4, and 5. Overexpression of the tail-less or head-less mutant beta 4 subunit did not suppress alpha 6 beta 4-mediated adhesion to laminins, as both types of transfectants adhered to these ligands in the presence of blocking anti-beta 1 antibodies as well as the controls. However, immunofluorescence experiments indicated that the endogenous alpha 6 beta 4 integrin and other hemidesmosomal markers were not concentrated in hemidesmosomes in cells overexpressing tail- less beta 4, while the distribution of these molecules was not altered in cells overexpressing the head-less subunit. Electron microscopic studies confirmed that cells overexpressing tail-less beta 4 had a drastically reduced number of hemidesmosomes, while cells expressing the head-less subunit had a normal number of these structures. Thus, expression of a tail-less, but not a head-less mutant beta 4 subunit leads to a dominant negative effect on hemidesmosome assembly without suppressing initial adhesion to laminins. We conclude that the alpha 6 beta 4 integrin binds to several laminins and plays an essential role in the assembly and/or stability of hemidesmosomes, that alpha 6 beta 4- mediated adhesion and hemidesmosome assembly have distinct requirements, and that it is possible to use a dominant negative approach to selectively interfere with a specific function of an integrin. PMID:7721947

Increased androgen levels in rats impair glucose-stimulated insulin secretion through disruption of pancreatic beta cell mitochondrial function.

PubMed

Wang, Hongdong; Wang, Xiaping; Zhu, Yunxia; Chen, Fang; Sun, Yujie; Han, Xiao

2015-11-01

Although insulin resistance is recognized to contribute to the reproductive and metabolic phenotypes of polycystic ovary syndrome (PCOS), pancreatic beta cell dysfunction plays an essential role in the progression from PCOS to the development of type 2 diabetes. However, the role of insulin secretory abnormalities in PCOS has received little attention. In addition, the precise changes in beta cells and the underlying mechanisms remain unclear. In this study, we therefore attempted to elucidate potential mechanisms involved in beta cell alterations in a rat model of PCOS. Glucose-induced insulin secretion was measured in islets isolated from DHT-treated and control rats. Oxygen consumption rate (OCR), ATP production, and mitochondrial copy number were assayed to evaluate mitochondrial function. Glucose-stimulated insulin secretion is significantly decreased in islets from DHT-treated rats. On the other hand, significant reductions are observed in the expression levels of several key genes involved in mitochondrial biogenesis and in mitochondrial OCR and ATP production in DHT-treated rat islets. Meanwhile, we found that androgens can directly impair beta cell function by inducing mitochondrial dysfunction in vitro in an androgen receptor dependent manner. For the first time, our study demonstrates that increased androgens in female rats can impair glucose-stimulated insulin secretion partly through disruption of pancreatic beta cell mitochondrial function. This work has significance for hyperandrogenic women with PCOS: excess activation of the androgen receptor by androgens may provoke beta cell dysfunction via mitochondrial dysfunction. Copyright © 2015 Elsevier Ltd. All rights reserved.

Human beta-cell precursors mature into functional insulin-producing cells in an immunoisolation device: implications for diabetes cell therapies.

PubMed

Lee, Seung-Hee; Hao, Ergeng; Savinov, Alexei Y; Geron, Ifat; Strongin, Alex Y; Itkin-Ansari, Pamela

2009-04-15

Islet transplantation is limited by the need for chronic immunosuppression and the paucity of donor tissue. As new sources of human beta-cells are developed (e.g., stem cell-derived tissue), transplanting them in a durable device could obviate the need for immunosuppression, while also protecting the patient from any risk of tumorigenicity. Here, we studied (1) the survival and function of encapsulated human beta-cells and their progenitors and (2) the engraftment of encapsulated murine beta-cells in allo- and autoimmune settings. Human islets and human fetal pancreatic islet-like cell clusters were encapsulated in polytetrafluorethylene devices (TheraCyte) and transplanted into immunodeficient mice. Graft survival and function was measured by immunohistochemistry, circulating human C-peptide levels, and blood glucose levels. Bioluminescent imaging was used to monitor encapsulated neonatal murine islets. Encapsulated human islet-like cell clusters survived, replicated, and acquired a level of glucose responsive insulin secretion sufficient to ameliorate hyperglycemia in diabetic mice. Bioluminescent imaging of encapsulated murine neonatal islets revealed a dynamic process of cell death followed by regrowth, resulting in robust long-term allograft survival. Further, in the non-obese diabetic (NOD) mouse model of type I diabetes, encapsulated primary beta-cells ameliorated diabetes without stimulating a detectable T-cell response. We demonstrate for the first time that human beta-cells function is compatible with encapsulation in a durable, immunoprotective device. Moreover, our study suggests that encapsulation of beta-cells before terminal differentiation will be a successful approach for new cell-based therapies for diabetes, such as those derived from stem cells.

NLC Luminosity as a Function of Beam Parameters

NASA Astrophysics Data System (ADS)

Nosochkov, Y.

2002-06-01

Realistic calculation of NLC luminosity has been performed using particle tracking in DIMAD and beam-beam simulations in GUINEA-PIG code for various values of beam emittance, energy and beta functions at the Interaction Point (IP). Results of the simulations are compared with analytic luminosity calculations. The optimum range of IP beta functions for high luminosity was identified.

Gauge coupling beta functions in the standard model to three loops.

PubMed

Mihaila, Luminita N; Salomon, Jens; Steinhauser, Matthias

2012-04-13

In this Letter, we compute the three-loop corrections to the beta functions of the three gauge couplings in the standard model of particle physics using the minimal subtraction scheme and taking into account Yukawa and Higgs self-couplings.

Regulation of pancreatic islet beta-cell mass by growth factor and hormone signaling.

PubMed

Huang, Yao; Chang, Yongchang

2014-01-01

Dysfunction and destruction of pancreatic islet beta cells is a hallmark of diabetes. Better understanding of cellular signals in beta cells will allow development of therapeutic strategies for diabetes, such as preservation and expansion of beta-cell mass and improvement of beta-cell function. During the past several decades, the number of studies analyzing the molecular mechanisms, including growth factor/hormone signaling pathways that impact islet beta-cell mass and function, has increased exponentially. Notably, somatolactogenic hormones including growth hormone (GH), prolactin (PRL), and insulin-like growth factor-1 (IGF-1) and their receptors (GHR, PRLR, and IGF-1R) are critically involved in beta-cell growth, survival, differentiation, and insulin secretion. In this chapter, we focus more narrowly on GH, PRL, and IGF-1 signaling, and GH-IGF-1 cross talk. We also discuss how these signaling aspects contribute to the regulation of beta-cell proliferation and apoptosis. In particular, our novel findings of GH-induced formation of GHR-JAK2-IGF-1R protein complex and synergistic effects of GH and IGF-1 on beta-cell signaling, proliferation, and antiapoptosis lead to a new concept that IGF-1R may serve as a proximal component of GH/GHR signaling. © 2014 Elsevier Inc. All rights reserved.

Role of beta1-adrenoceptor in the basolateral amygdala of rats with anxiety-like behavior.

PubMed

Fu, Ailing; Li, Xiaorong; Zhao, Baoquan

2008-05-23

There are evidence suggesting that the function of adrenergic receptor is affected in the amygdala of animals with anxiety-like behavior. However, beta-adrenoceptor (beta-AR) subtypes, consisting of three subtypes, exert different effects on anxiety regulation. In order to determine the function of the beta1-AR subtype in anxiety-like behavior, we investigated the change of beta1-AR expression by immunostaining in the basolateral amygdala (BLA) of rats treated by conditional fear training. The results indicated that the level of beta1-AR was significantly increased in the BLA of fear-conditioned animals as compared that of controls. In animal behavioral tests, animals treated with selective beta1-AR antagonist metoprolol before conditional fear training exhibited a significant attenuation of anxiety-like behavior characterized by increased percentage of time spent and percentage of entries in the open arms, and increased number of head-dips in the elevated plus-maze (EPM) test compared with the animals treated with only saline. Furthermore, the rats pretreated with metoprolol in the conditional fear training significantly decreased the freezing behavior in the test compared with the controls. The results suggested that the beta1-AR played an important role in anxiety-like behavior, and inhibition of the beta1-AR in the BLA could produce anxiolytic effect.

Role of Jumonji c-domain containing protein 6 (JMJD6) in infectivity of foot-and-mouth disease virus

USDA-ARS?s Scientific Manuscript database

Foot-and-mouth disease virus (FMDV) can utilize as many as three distinct groups of receptor molecules to attach and enter a susceptible host cell. Four integrin heterodimers (alphavBeta1, alphavBeta3, alphavBeta6, and alphavBeta8) can function as the primary receptor for FMDV field strains. FMDV ...

Base induced chemical conversion of 3-carbamoyl-2-isoxazolines.

PubMed

Nishiwaki, Nagatoshi; Maki, Asaka; Ariga, Masahiro

2009-01-01

3-Carbamoyl-2-isoxazolines, prepared by cycloaddition of functionalized nitrile oxide, serve as masked 3-unsubstituted isoxazolines to afford 2-isoxazoline-3-carboxylic acid, beta-cyanoalcohol, alpha,beta-unsaturated nitrile, and alpha,beta-unsaturated amide upon heating in the alkaline solution. The present reaction is also applicable to synthesis of 3,4-difunctionalized isoxazoles and beta-hydroxy-gamma-lactone.

Neurotensin protects pancreatic beta cells from apoptosis.

PubMed

Coppola, Thierry; Béraud-Dufour, Sophie; Antoine, Aurélie; Vincent, Jean-Pierre; Mazella, Jean

2008-01-01

The survival of pancreatic beta cells depends on the balance between external cytotoxic and protective molecular systems. The neuropeptide neurotensin (NT) has been shown to regulate certain functions of the endocrine pancreas including insulin and glucagon release. However, the mechanism of action of NT as well as the identification of receptors involved in the pancreatic functions of the peptide remained to be studied. We demonstrate here that NT is an efficient protective agent of pancreatic beta cells against cytotoxic agents. Both beta-TC3 and INS-1E cell lines and the mouse pancreatic islet cells express the three known NT receptors. The incubation of beta cells with NT protects cells from apoptosis induced either by staurosporine or by IL-1beta. In beta-TC3 cells, NT activates both MAP and PI-3 kinases pathways and strongly reduces the staurosporine or the Il-1beta-induced caspase-3 activity by a mechanism involving Akt activation. The NTSR2 agonist levocabastine displays the same protective effect than NT whereas the NTSR1 antagonist is unable to block the effect of NT suggesting the predominant involvement of the NTSR2 in the action of NT on beta cells. These results clearly indicate for the first time that NT is able to protect endocrine beta cells from external cytotoxic agents, a role well correlated with its release in the circulation after a meal.

Structure, function, and fate of the BlaR signal transducer involved in induction of beta-lactamase in Bacillus licheniformis.

PubMed Central

Zhu, Y; Englebert, S; Joris, B; Ghuysen, J M; Kobayashi, T; Lampen, J O

1992-01-01

The membrane-spanning protein BlaR is essential for the induction of beta-lactamase in Bacillus licheniformis. Its nature and location were confirmed by the use of an antiserum specific for its carboxy-terminal penicillin sensor, its function was studied by genetic dissection, and the structure of the penicillin sensor was derived from hydrophobic cluster analysis of the amino acid sequence by using, as a reference, the class A beta-lactamases with known three-dimensional structures. During the first 2 h after the addition of the beta-lactam inducer, full-size BlaR, bound to the plasma membrane, is produced, and then beta-lactamase is produced. By 2 h after induction, BlaR is present in various (membrane-bound and cytosolic) forms, and there is a gradual decrease in beta-lactamase production. The penicillin sensors of BlaR and the class D beta-lactamases show strong similarities in primary structures. They appear to have the same basic spatial disposition of secondary structures as that of the class A beta-lactamases, except that they lack several alpha helices and, therefore, have a partially uncovered five-stranded beta sheet and a more readily accessible active site. Alterations of BlaR affecting conserved secondary structures of the penicillin sensor and specific sites of the transducer annihilate beta-lactamase inducibility. Images PMID:1400165

Beta cell function after weight loss: a clinical trial comparing gastric bypass surgery and intensive lifestyle intervention

PubMed Central

Hofsø, D; Jenssen, T; Bollerslev, J; Ueland, T; Godang, K; Stumvoll, M; Sandbu, R; Røislien, J; Hjelmesæth, J

2011-01-01

Objective The effects of various weight loss strategies on pancreatic beta cell function remain unclear. We aimed to compare the effect of intensive lifestyle intervention (ILI) and Roux-en-Y gastric bypass surgery (RYGB) on beta cell function. Design One year controlled clinical trial (ClinicalTrials.gov identifier NCT00273104). Methods One hundred and nineteen morbidly obese participants without known diabetes from the MOBIL study (mean (s.d.) age 43.6 (10.8) years, body mass index (BMI) 45.5 (5.6) kg/m2, 84 women) were allocated to RYGB (n=64) or ILI (n=55). The patients underwent repeated oral glucose tolerance tests (OGTTs) and were categorised as having either normal (NGT) or abnormal glucose tolerance (AGT). Twenty-nine normal-weight subjects with NGT (age 42.6 (8.7) years, BMI 22.6 (1.5) kg/m2, 19 women) served as controls. OGTT-based indices of beta cell function were calculated. Results One year weight reduction was 30 % (8) after RYGB and 9 % (10) after ILI (P<0.001). Disposition index (DI) increased in all treatment groups (all P<0.05), although more in the surgery groups (both P<0.001). Stimulated proinsulin-to-insulin (PI/I) ratio decreased in both surgery groups (both P<0.001), but to a greater extent in the surgery group with AGT at baseline (P<0.001). Post surgery, patients with NGT at baseline had higher DI and lower stimulated PI/I ratio than controls (both P<0.027). Conclusions Gastric bypass surgery improved beta cell function to a significantly greater extent than ILI. Supra-physiological insulin secretion and proinsulin processing may indicate excessive beta cell function after gastric bypass surgery. PMID:21078684

Capture cross sections on unstable nuclei

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

Tonchev, A. P.; Escher, J. E.; Scielzo, N.

2017-09-13

Accurate neutron-capture cross sections on unstable nuclei near the line of beta stability are crucial for understanding the s-process nucleosynthesis. However, neutron-capture cross sections for short-lived radionuclides are difficult to measure due to the fact that the measurements require both highly radioactive samples and intense neutron sources. Essential ingredients for describing the γ decays following neutron capture are the γ-ray strength function and level densities. We will compare different indirect approaches for obtaining the most relevant observables that can constrain Hauser-Feshbach statistical-model calculations of capture cross sections. Specifically, we will consider photon scattering using monoenergetic and 100% linearly polarized photonmore » beams. Here, challenges that exist on the path to obtaining neutron-capture cross sections for reactions on isotopes near and far from stability will be discussed.« less

Proliferation of Estrogen Receptor alpha Positive Mammary Epithelial Cells is Restrained by TGFbeta1 in Adult Mice

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

Ewan, Kenneth B.R.; Oketch-Rabah, Hellen A.; Ravani, Shraddha A.

2005-03-03

Transforming growth factor {beta}1 (TGF{beta}1) is a potent inhibitor of mammary epithelial proliferation. In human breast, estrogen receptor {alpha} (ER{alpha}) cells rarely co-localize with markers of proliferation, but their increased frequency correlates with breast cancer risk. To determine whether TGF{beta}1 is necessary for the quiescence of ER{alpha}-positive population, we examined mouse mammary epithelial gland at estrus. Approximately 35% of cells showed TGF{beta}1 activation, which co-localized with nuclear receptor-phosphorylated Smad 2/3, indicating that TGF{beta} signaling is autocrine. Furthermore, nuclear Smad co-localized with nuclear ER{alpha}. To test whether TGF{beta} was functional, we examined genetically engineered mice with different levels of TGF{beta}1. ER{alpha}more » co-localization with markers of proliferation (i.e. Ki-67 or BrdU) at estrus was significantly increased in the mammary glands of Tgf{beta}1 C57/bl/129SV heterozygote mice. This relationship was maintained following pregnancy, but was absent at puberty. Conversely, mammary epithelial expression of constitutively active TGF{beta}1 via the MMTV promoter suppressed proliferation of ER{alpha} positive cells. Thus, TGF{beta}1 activation functionally restrains ER{alpha} positive cells from proliferating in adult mammary gland. Accordingly, we propose that TGF{beta}1 dysregulation may promote proliferation of ER{alpha} positive cells associated with breast cancer risk in humans.« less

Function of Several Critical Amino Acids in Human Pyruvate Dehydrogenase Revealed by Its Structure

NASA Technical Reports Server (NTRS)

Korotchkina, Lioubov G.; Ciszak, E.; Patel, M.

2004-01-01

Pyruvate dehydrogenase (E1), an alpha 2 beta 2 tetramer, catalyzes the oxidative decarboxylation of pyruvate and reductive acetylation of lipoyl moieties of the dihydrolipoamide acetyltransferase. The roles of beta W135, alpha P188, alpha M181, alpha H15 and alpha R349 of E1 determined by kinetic analysis were reassessed by analyzing the three-dimensional structure of human E1. The residues identified above are found to play a structural role rather than being directly involved in catalysis: beta W135 is the center residue in the hydrophobic interaction between beta and beta' subunits; alpha P188 and alpha M181 are critical for the conformation of the TPP-binding motif and interaction between alpha and beta subunits; alpha H15, is necessary for the organization of the N-terminus of alpha and alpha'; subunits and alpha R349 supports the interaction of the C-terminus of the alpha subunits with the beta subunits. Analysis of several critical E1 residues confirms the importance of residues distant from the active site for subunit interactions and enzyme function.

Conversion of Short-Term Potentiation to Long-Term Potentiation in Mouse CA1 by Coactivation of [beta]-Adrenergic and Muscarinic Receptors

ERIC Educational Resources Information Center

Connor, Steven A.; Maity, Sabyasachi; Roy, Birbickram; Ali, Declan W.; Nguyen, Peter V.

2012-01-01

Encoding new information requires dynamic changes in synaptic strength. The brain can boost synaptic plasticity through the secretion of neuromodulatory substances, including acetylcholine and noradrenaline. Considerable effort has focused on elucidating how neuromodulatory substances alter synaptic properties. However, determination of the…

Heterodimerization with beta2-adrenergic receptors promotes surface expression and functional activity of alpha1D-adrenergic receptors.

PubMed

Uberti, Michelle A; Hague, Chris; Oller, Heide; Minneman, Kenneth P; Hall, Randy A

2005-04-01

The alpha1D-adrenergic receptor (alpha1D-AR) is a G protein-coupled receptor (GPCR) that is poorly trafficked to the cell surface and largely nonfunctional when heterologously expressed by itself in a variety of cell types. We screened a library of approximately 30 other group I GPCRs in a quantitative luminometer assay for the ability to promote alpha1D-AR cell surface expression. Strikingly, these screens revealed only two receptors capable of inducing robust increases in the amount of alpha1D-AR at the cell surface: alpha1B-AR and beta2-AR. Confocal imaging confirmed that coexpression with beta2-AR resulted in translocation of alpha1D-AR from intracellular sites to the plasma membrane. Additionally, coimmunoprecipitation studies demonstrated that alpha1D-AR and beta2-AR specifically interact to form heterodimers when coexpressed in HEK-293 cells. Ligand binding studies revealed an increase in total alpha1D-AR binding sites upon coexpression with beta2-AR, but no apparent effect on the pharmacological properties of the receptors. In functional studies, coexpression with beta2-AR significantly enhanced the coupling of alpha1D-AR to norepinephrine-stimulated Ca2+ mobilization. Heterodimerization of beta2-AR with alpha1D-AR also conferred the ability of alpha1D-AR to cointernalize upon beta2-AR agonist stimulation, revealing a novel mechanism by which these different adrenergic receptor subtypes may regulate each other's activity. These findings demonstrate that the selective association of alpha1D-AR with other receptors is crucial for receptor surface expression and function and also shed light on a novel mechanism of cross talk between alpha1- and beta2-ARs that is mediated through heterodimerization and cross-internalization.

EPConDB: a web resource for gene expression related to pancreatic development, beta-cell function and diabetes.

PubMed

Mazzarelli, Joan M; Brestelli, John; Gorski, Regina K; Liu, Junmin; Manduchi, Elisabetta; Pinney, Deborah F; Schug, Jonathan; White, Peter; Kaestner, Klaus H; Stoeckert, Christian J

2007-01-01

EPConDB (http://www.cbil.upenn.edu/EPConDB) is a public web site that supports research in diabetes, pancreatic development and beta-cell function by providing information about genes expressed in cells of the pancreas. EPConDB displays expression profiles for individual genes and information about transcripts, promoter elements and transcription factor binding sites. Gene expression results are obtained from studies examining tissue expression, pancreatic development and growth, differentiation of insulin-producing cells, islet or beta-cell injury, and genetic models of impaired beta-cell function. The expression datasets are derived using different microarray platforms, including the BCBC PancChips and Affymetrix gene expression arrays. Other datasets include semi-quantitative RT-PCR and MPSS expression studies. For selected microarray studies, lists of differentially expressed genes, derived from PaGE analysis, are displayed on the site. EPConDB provides database queries and tools to examine the relationship between a gene, its transcriptional regulation, protein function and expression in pancreatic tissues.

Limit cycles and conformal invariance

NASA Astrophysics Data System (ADS)

Fortin, Jean-François; Grinstein, Benjamín; Stergiou, Andreas

2013-01-01

There is a widely held belief that conformal field theories (CFTs) require zero beta functions. Nevertheless, the work of Jack and Osborn implies that the beta functions are not actually the quantites that decide conformality, but until recently no such behavior had been exhibited. Our recent work has led to the discovery of CFTs with nonzero beta functions, more precisely CFTs that live on recurrent trajectories, e.g., limit cycles, of the beta-function vector field. To demonstrate this we study the S function of Jack and Osborn. We use Weyl consistency conditions to show that it vanishes at fixed points and agrees with the generator Q of limit cycles on them. Moreover, we compute S to third order in perturbation theory, and explicitly verify that it agrees with our previous determinations of Q. A byproduct of our analysis is that, in perturbation theory, unitarity and scale invariance imply conformal invariance in four-dimensional quantum field theories. Finally, we study some properties of these new, "cyclic" CFTs, and point out that the a-theorem still governs the asymptotic behavior of renormalization-group flows.

Excitation Mechanism of O I Lines in Herbig Ae/Be Stars

NASA Astrophysics Data System (ADS)

Mathew, Blesson; Manoj, P.; Narang, Mayank; Banerjee, D. P. K.; Nayak, Pratheeksha; Muneer, S.; Vig, S.; Pramod Kumar, S.; Paul, K. T.; Maheswar, G.

2018-04-01

We have investigated the role of a few prominent excitation mechanisms viz. collisional excitation, recombination, continuum fluorescence, and Lyman beta fluorescence on the O I line spectra in Herbig Ae/Be stars. The aim is to understand which of them is the central mechanism that explains the observed O I line strengths. The study is based on an analysis of the observed optical spectra of 62 Herbig Ae/Be stars and near-infrared spectra of 17 Herbig Ae/Be stars. The strong correlation observed between the line fluxes of O I λ8446 and O I λ11287, as well as a high positive correlation between the line strengths of O I λ8446 and Hα suggest that Lyman beta fluorescence is the dominant excitation mechanism for the formation of O I emission lines in Herbig Ae/Be stars. Furthermore, from an analysis of the emission line fluxes of O I λλ7774, 8446, and comparing the line ratios with those predicted by theoretical models, we assessed the contribution of collisional excitation in the formation of O I emission lines.

Formation of proteoglycan and collagen-rich scaffold-free stiff cartilaginous tissue using two-step culture methods with combinations of growth factors.

PubMed

Miyazaki, Tatsuya; Miyauchi, Satoshi; Matsuzaka, Satoshi; Yamagishi, Chie; Kobayashi, Kohei

2010-05-01

Tissue-engineered cartilage may be expected to serve as an alternative to autologous chondrocyte transplantation treatment. Several methods for producing cartilaginous tissue have been reported. In this study, we describe the production of scaffold-free stiff cartilaginous tissue of pig and human, using allogeneic serum and growth factors. The tissue was formed in a mold using chondrocytes recovered from alginate bead culture and maintained in a medium with transforming growth factor-beta and several other additives. In the case of porcine tissue, the tear strength of the tissue and the contents of proteoglycan (PG) and collagen per unit of DNA increased dose-dependently with transforming growth factor-beta. The length of culture was significantly and positively correlated with thickness, tear strength, and PG and collagen contents. Tear strength showed positive high correlations with both PG and collagen contents. A positive correlation was also seen between PG content and collagen content. Similar results were obtained with human cartilaginous tissue formed from chondrocytes expanded in monolayer culture. Further, an in vivo pilot study using pig articular cartilage defect model demonstrated that the cartilaginous tissue was well integrated with surrounding tissue at 13 weeks after the implantation. In conclusion, we successfully produced implantable scaffold-free stiff cartilaginous tissue, which characterized high PG and collagen contents.

Effects of species' similarity and dominance on the functional and phylogenetic structure of a plant meta-community.

PubMed

Chalmandrier, L; Münkemüller, T; Lavergne, S; Thuiller, W

2015-01-01

Different assembly processes drive the spatial structure of meta-communities (beta-diversity). Recently, functional and phylogenetic diversities have been suggested as indicators of these assembly processes. Assuming that diversity is a good proxy for niche overlap, high beta-diversity along environmental gradients should be the result of environmental filtering while low beta-diversity should stem from competitive interactions. So far, studies trying to disentangle the relative importance of these assembly processes have provided mixed results. One reason for this may be that these studies often rely on a single measure of diversity and thus implicitly make a choice on how they account for species relative abundances and how species similarities are captured by functional traits or phylogeny. Here, we tested the effect of gradually scaling the importance of dominance (the weight given to dominant vs. rare species) and species similarity (the weight given to small vs. large similarities) on resulting beta-diversity patterns of an alpine plant meta-community. To this end, we combined recent extensions of the Hill numbers framework with Pagel's phylogenetic tree transformation approach. We included functional (based on the leaf-height-seed spectrum) and phylogenetic facets of beta-diversity in our analysis and explicitly accounted for effects of environmental and spatial covariates. We found that functional beta-diversity, was high when the same weight was given to dominant vs. rare species and to large vs. small species' similarities. In contrast, phylogenetic beta-diversity was low when greater weight was given to dominant species and small species' similarities. Those results suggested that different environments along the gradients filtered different species according to their functional traits, while, the same competitive lineages dominated communities across the gradients. Our results highlight that functional vs. phylogenetic facets, presence-absence vs. abundance structure and different weights of species' dissimilarity provide complementary and important information on the drivers of meta-community structure. By utilizing the full extent of information provided by the flexible frameworks of Hill numbers and Pagel's tree transformation, we propose a new approach to disentangle the patterns resulting from different assembly processes.

A low-cost hierarchical nanostructured beta-titanium alloy with high strength

PubMed Central

Devaraj, Arun; Joshi, Vineet V.; Srivastava, Ankit; Manandhar, Sandeep; Moxson, Vladimir; Duz, Volodymyr A.; Lavender, Curt

2016-01-01

Lightweighting of automobiles by use of novel low-cost, high strength-to-weight ratio structural materials can reduce the consumption of fossil fuels and in turn CO2 emission. Working towards this goal we achieved high strength in a low cost β-titanium alloy, Ti–1Al–8V–5Fe (Ti185), by hierarchical nanostructure consisting of homogenous distribution of micron-scale and nanoscale α-phase precipitates within the β-phase matrix. The sequence of phase transformation leading to this hierarchical nanostructure is explored using electron microscopy and atom probe tomography. Our results suggest that the high number density of nanoscale α-phase precipitates in the β-phase matrix is due to ω assisted nucleation of α resulting in high tensile strength, greater than any current commercial titanium alloy. Thus hierarchical nanostructured Ti185 serves as an excellent candidate for replacing costlier titanium alloys and other structural alloys for cost-effective lightweighting applications. PMID:27034109

Discovery of novel acetanilide derivatives as potent and selective beta3-adrenergic receptor agonists.

PubMed

Maruyama, Tatsuya; Onda, Kenichi; Hayakawa, Masahiko; Matsui, Tetsuo; Takasu, Toshiyuki; Ohta, Mitsuaki

2009-06-01

In the search for potent and selective human beta3-adrenergic receptor (AR) agonists as potential drugs for the treatment of obesity and noninsulin-dependent (type II) diabetes, a novel series of acetanilide-based analogues were prepared and their biological activities were evaluated at the human beta3-, beta2-, and beta1-ARs. Among these compounds, 2-pyridylacetanilide (2f), pyrimidin-2-ylacetanilide (2u), and pyrazin-2-ylacetanilide (2v) derivatives exhibited potent agonistic activity at the beta3-AR with functional selectivity over the beta1- and beta2-ARs. In particular, compound 2u was found to be the most potent and selective beta3-AR agonist with an EC(50) value of 0.11 microM and no agonistic activity for either the beta1- or beta2-AR. In addition, 2f, 2u, and 2v showed significant hypoglycemic activity in a rodent diabetic model.

Tuning peptide amphiphile supramolecular structure for biomedical applications

NASA Astrophysics Data System (ADS)

Pashuck, Eugene Thomas, III

The use of biomaterials in regenerative medicine has been an active area of research for more than a decade. Peptide amphiphiles, which are short peptide sequences coupled to alkyl tails, have been studied in the Stupp group since the beginning of the decade and been used for a variety of biomedical applications. Most of the work has focused on the bioactive epitopes places on the periphery of the PA molecules, but the interior amino acids, known as the beta-sheet region, give the PA nanofiber gel much of its mechanical strength. To study the important parameters in the beta-sheet region, six PA molecules were constructed to determine the influence of beta-sheet length and order of the amino acids in the beta-sheet. It was found that having beta-sheet forming amino acids near the center of the fiber improves PA gel stiffness, and that having extra amino acids that have preferences for other secondary structures, like alpha-helix decreased the gels stiffness. Using FTIR and circular dichroism it was found that the mechanical properties are influenced by the amount of twist in the beta-sheet, and PAs that have more twisted beta-sheets form weaker gels. The effect amino acid properties have on peptide amphiphile self-assembly where studied by synthesizining molecules with varying side group size and hydrophobicity. It was found that smaller amino acids lead to stiffer gels and when two amino acids had the same size the amino acid with the larger beta-sheet propensity lead to a stiffer gel. Furthermore, small changes in peptide structure were found to lead to big changes in nanostructure, as leucine and isoleucine, which have the same size but slightly different structures, form flat ribbons and cylindrical nanofibers, respectively. Phenylalanine and alanine were studied more indepth because they represent the effects of adding an aromatic group to amino acids in the beta-sheet regon. These phenylalanine PAs formed short, twisted ribbons when freshly dissolved in water that rapdily elongate to form long twisted ribbons. After being aged for two weeks half of these twisted ribbons turn into helical ribbons and by one month all of them have formed this new nanostructure. As a target in regenerative medicine, spinal cord injury repair presents a daunting challenge that has so far eluded successful pharmaceutical treatment. Previous work showing that PAs bearing the IKVAV epitope were found to increase functional recovery in mice paved the way for the more complex systems studied here. By making a PA that bound growth factors like neurotrophin-3 (NT-3) and glial cell line derived neurotrophic factor (GDNF) in with the PA matrix, it was found that the release of NT-3 could be significantly slowed from an IKVAV with the presence of a novel binding epitope, and that including GDNF into the gel significantly increased neurite outgrowth compared to the standard IKVAV PA.

Latent transforming growth factor beta1 activation in situ: quantitative and functional evidence after low-dose gamma-irradiation

NASA Technical Reports Server (NTRS)

Ehrhart, E. J.; Segarini, P.; Tsang, M. L.; Carroll, A. G.; Barcellos-Hoff, M. H.; Chatterjee, A. (Principal Investigator)

1997-01-01

The biological activity of transforming growth factor beta1 (TGF-beta) is controlled by its secretion as a latent complex in which it is noncovalently associated with latency-associated peptide (LAP). Activation is the extracellular process in which TGF-beta is released from LAP, and is considered to be a primary regulatory control. We recently reported rapid and persistent changes in TGF-beta immunoreactivity in conjunction with extracellular matrix remodeling in gamma-irradiated mouse mammary gland. Our hypothesis is that these specific changes in immunoreactivity are indicative of latent TGF-beta activation. In the present study, we determined the radiation dose response and tested whether a functional relationship exists between radiation-induced TGF-beta and collagen type III remodeling. After radiation exposures as low as 0.1 Gy, we detected increased TGF-beta immunoreactivity in the mammary epithelium concomitant with decreased LAP immunostaining, which are events consistent with activation. Quantitative image analysis demonstrated a significant (P=0.0005) response at 0.1 Gy without an apparent threshold and a linear dose response to 5 Gy. However, in the adipose stroma, loss of LAP demonstrated a qualitative threshold at 0.5 Gy. Loss of LAP paralleled induction of collagen III immunoreactivity in this tissue compartment. We tested whether TGF-beta mediates collagen III expression by treating animals with TGF-beta panspecific monoclonal antibody, 1D11.16, administered i.p. shortly before irradiation. Radiation-induced collagen III staining in the adipose stroma was blocked in an antibody dose-dependent manner, which persisted through 7 days postirradiation. RNase protection assay revealed that radiation-induced elevation of total gland collagen III mRNA was also blocked by neutralizing antibody treatment. These data provide functional confirmation of the hypothesis that radiation exposure leads to latent TGF-beta activation, support our interpretation of the reciprocal shift in immunoreactivity as evidence of activation, and implicate TGF-beta as a mediator of tissue response to ionizing radiation. The sensitivity of activation to low radiation doses points to a potential role for TGF-beta in orchestrating tissue response to oxidative stress. As such, radiation may be useful as a probe to delineate the consequences of latent TGF-beta activation in situ.

Rematching AGS Booster synchrotron injection lattice for smaller transverse beam emittances

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

Liu, C.; Beebe-Wang, J.; Brown, K.

2017-01-25

The polarized proton beam is injected into the booster via the charge-exchange (H- to H+) scheme. The emittance growth due to scattering at the stripping foil is proportional to the beta functions at the foil. It was demonstrated that the current scheme of reducing the beta functions at the stripping foil preserves the emittance better; however the betatron tunes are above but very close to half integer. Due to concern of space charge and half integer in general, options of lattice designs aimed towards reducing the beta functions at the stripping foil with tunes at more favorable places are explored.

Beta-hydroxy-beta-methyl butyrate (HMB): From experimental data to clinical evidence in sarcopenia.

PubMed

Cruz-Jentoft, Alfonso J

2017-05-28

β-hydroxy-β-methylbutyrate (HMB) is a metabolite derived from leucine and its ketoacid alpha-ketoisocaproate. Leucine has a role in regulating protein synthesis in muscle cells, and HMB seems to be a key active metabolite in such regulation. HMB has been shown to modulate muscle protein degradation by inhibiting the ubiquitin-proteasome proteolytic pathway, to up-regulate protein synthesis via the mTOR pathway, and to stabilize cell membranes via the rate limiting enzyme to cholesterol synthesis HMG- coenzyme A reductase. It can also decrease cell apoptosis, therefore improving cell survival; and increase proliferation and differentiation of muscle stem cell, via the MAPK/ERK and PI3K/Akt pathways. HMB is widely used as an ergogenic supplement by athletes and bodybuilders, usually combined with exercise training, to increase muscle mass and strength. Some studies have explored the role of HMB in chronic diseases associated with muscle wasting (cancer, acquired immunodeficiency syndrome, chronic obstructive pulmonary disease) This review focuses on the role of HMB in the management of sarcopenia (age or disease-related loss of muscle mass and function) in older persons. A small number of studies have shown increases in lean (muscle) mass and some muscle function and physical performance parameters in older people with or without resistance exercise, and preservation of muscle mass during bed rest. However, heterogeneous methodological approaches preclude solid conclusions, and more studies are needed to confirm the role of HMB as a promising agent to treat sarcopenia. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Perturbations of Jacobi polynomials and piecewise hypergeometric orthogonal systems

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

Neretin, Yu A

2006-12-31

A family of non-complete orthogonal systems of functions on the ray [0,{infinity}] depending on three real parameters {alpha}, {beta}, {theta} is constructed. The elements of this system are piecewise hypergeometric functions with singularity at x=1. For {theta}=0 these functions vanish on [1,{infinity}) and the system is reduced to the Jacobi polynomials P{sub n}{sup {alpha}}{sup ,{beta}} on the interval [0,1]. In the general case the functions constructed can be regarded as an interpretation of the expressions P{sub n+{theta}}{sup {alpha}}{sup ,{beta}}. They are eigenfunctions of an exotic Sturm-Liouville boundary-value problem for the hypergeometric differential operator. The spectral measure for this problem ismore » found.« less

Identification of beta-2 as a key cell adhesion molecule in PCa cell neurotropic behavior: a novel ex vivo and biophysical approach.

PubMed

Jansson, Keith H; Castillo, Deborah G; Morris, Joseph W; Boggs, Mary E; Czymmek, Kirk J; Adams, Elizabeth L; Schramm, Lawrence P; Sikes, Robert A

2014-01-01

Prostate cancer (PCa) is believed to metastasize through the blood/lymphatics systems; however, PCa may utilize the extensive innervation of the prostate for glandular egress. The interaction of PCa and its nerve fibers is observed in 80% of PCa and is termed perineural invasion (PNI). PCa cells have been observed traveling through the endoneurium of nerves, although the underlying mechanisms have not been elucidated. Voltage sensitive sodium channels (VSSC) are multimeric transmembrane protein complexes comprised of a pore-forming α subunit and one or two auxiliary beta (β) subunits with inherent cell adhesion molecule (CAM) functions. The beta-2 isoform (gene SCN2B) interacts with several neural CAMs, while interacting putatively with other prominent neural CAMs. Furthermore, beta-2 exhibits elevated mRNA and protein levels in highly metastatic and castrate-resistant PCa. When overexpressed in weakly aggressive LNCaP cells (2BECFP), beta-2 alters LNCaP cell morphology and enhances LNCaP cell metastasis associated behavior in vitro. We hypothesize that PCa cells use beta-2 as a CAM during PNI and subsequent PCa metastasis. The objective of this study was to determine the effect of beta-2 expression on PCa cell neurotropic metastasis associated behavior. We overexpressed beta-2 as a fusion protein with enhanced cyan fluorescence protein (ECFP) in weakly aggressive LNCaP cells and observed neurotropic effects utilizing our novel ex vivo organotypic spinal cord co-culture model, and performed functional assays with neural matrices and atomic force microscopy. With increased beta-2 expression, PCa cells display a trend of enhanced association with nerve axons. On laminin, a neural CAM, overexpression of beta-2 enhances PCa cell migration, invasion, and growth. 2BECFP cells exhibit marked binding affinity to laminin relative to LNECFP controls, and recombinant beta-2 ectodomain elicits more binding events to laminin than BSA control. Functional overexpression of VSSC beta subunits in PCa may mediate PCa metastatic behavior through association with neural matrices.

Effect of metal surface topography on mechanical bonding at simulated total hip stem-cement interfaces.

PubMed

Chen, C Q; Scott, W; Barker, T M

1999-01-01

Bonding and loosening mechanisms between bone cement and joint prostheses have not been well identified. In this study, the effects of simulated hip stem surface topography on the interfacial shear strength were examined. Six different surface topographies were used. They were described by several surface characterization parameters that may directly relate to the interfacial bonding strength: average surface roughness R(a), root mean square slope R(Deltaq), correlation length beta, and fluid retention index R(ri). The shear strengths between Palacos E bone cement and stainless steel rods were measured using an Instron materials testing machine. We found that cement can "flow" into the surface microtopography and establish good contact with the metal surface. The results show that the interfacial strength increases monotonically with the increase of R(Deltaq) instead of with R(a). The relationship between interfacial strength and surface parameters shows that a metal stem with an isotropic surface texture, higher R(Deltaq), and greater R(ri) gives a higher interfacial strength. Copyright 1999 John Wiley & Sons, Inc.

Controlling microstructure and mechanical properties of the new microelectronic interconnect alloys

NASA Astrophysics Data System (ADS)

Mutuku, Francis M.

An in-depth understanding of the physics of solidification could lead to the optimization of the properties of micro-electronic interconnects. Sn is the base material in the billions of interconnects in devices such as smart phones. These interconnects are formed by melting and solidifying a solder alloy (e.g. SnAgCu) in situ. But Sn has a low symmetry structure, Sn nucleation from the solder melt is complex and the morphology of the Sn and Sn alloys precipitates that form during solidification can vary tremendously (along with resultant mechanical properties). The effect of processing parameters on the solidification behavior, microstructure, and properties must be carefully addressed. Strong evidence adduced in this study shows that under many conditions, when cooling near eutectic SnAgCu from the melt, Ag3Sn nucleates before beta-Sn. The difficulty in the nucleation of beta-Sn provides a window of time between the nucleation of Ag3Sn precipitates and of beta-Sn solidification within which the Ag3Sn precipitate morphology can be manipulated. Thus distinct variations in precipitate number density, and inter-particle spacing were observed for different thermal histories, e.g. for different cooling rates. The average number density of Ag3Sn particles and the area of the pseudo-eutectic phase were observed to increase with increase in the Ag concentration, and with increase in the cooling rate. The shear strength and shear fatigue life increased with increase in the area fraction of the pseudo-eutectic phase. Upon aging of SnAgCu solder joints at an elevated temperature, the Ag3Sn particles coarsened, and became less effective in impeding dislocation motion. Consequently, the shear strength and shear fatigue performance degraded. On the other hand, alloys with constituents that formed solid solutions in Sn, such as small concentrations of Bi or Sb registered less degradation in both shear strength and shear fatigue life upon aging.

Diving behaviour and haemoglobin function: the primary structure of the alpha- and beta-chains of the sea turtle (Caretta caretta) and its functional implications.

PubMed

Petruzzelli, R; Aureli, G; Lania, A; Galtieri, A; Desideri, A; Giardina, B

1996-06-15

The amino acid sequence of the alpha- and beta-chains of haemoglobin (Hb) from the loggerhead sea turtle (Caretta caretta) has been determined. Comparison with that of human Hb shows differences in several residues involved in both alpha 1 beta 1 and alpha 1 beta 2 packing contacts. On the whole, in spite of the mutations, the essential characteristics of both interfaces seem to be maintained. The functional properties of the sea turtle Hb have been investigated at different temperatures and as a function of proton, chloride and organic phosphate concentrations. In addition to overall similarities shared with most of the vertebrate Hbs previously described, this molecule shows significant differences which could be related to the life behaviour of the turtle. In fact, while the shape of the Bohr-effect curve is well adapted for gas exchange during prolonged dives, the very small enthalpy change for O2 binding ensures that O2 delivery becomes essentially insensitive to the temperature changes of the environment. Moreover, and similarly to the case of emperor penguin Hb, the small alkaline Bohr effect appears to be only choride-linked, since the pH dependence of the O2 affinity is abolished in the absence of this ion. These functional characteristics are discussed on the basis of the primary structure of alpha- and beta-chains.

Disturbance, neutral theory, and patterns of beta diversity in soil communities.

PubMed

Maaß, Stefanie; Migliorini, Massimo; Rillig, Matthias C; Caruso, Tancredi

2014-12-01

Beta diversity describes how local communities within an area or region differ in species composition/abundance. There have been attempts to use changes in beta diversity as a biotic indicator of disturbance, but lack of theory and methodological caveats have hampered progress. We here propose that the neutral theory of biodiversity plus the definition of beta diversity as the total variance of a community matrix provide a suitable, novel, starting point for ecological applications. Observed levels of beta diversity (BD) can be compared to neutral predictions with three possible outcomes: Observed BD equals neutral prediction or is larger (divergence) or smaller (convergence) than the neutral prediction. Disturbance might lead to either divergence or convergence, depending on type and strength. We here apply these ideas to datasets collected on oribatid mites (a key, very diverse soil taxon) under several regimes of disturbances. When disturbance is expected to increase the heterogeneity of soil spatial properties or the sampling strategy encompassed a range of diverging environmental conditions, we observed diverging assemblages. On the contrary, we observed patterns consistent with neutrality when disturbance could determine homogenization of soil properties in space or the sampling strategy encompassed fairly homogeneous areas. With our method, spatial and temporal changes in beta diversity can be directly and easily monitored to detect significant changes in community dynamics, although the method itself cannot inform on underlying mechanisms. However, human-driven disturbances and the spatial scales at which they operate are usually known. In this case, our approach allows the formulation of testable predictions in terms of expected changes in beta diversity, thereby offering a promising monitoring tool.

Inactivation properties of voltage-gated K+ channels altered by presence of beta-subunit.

PubMed

Rettig, J; Heinemann, S H; Wunder, F; Lorra, C; Parcej, D N; Dolly, J O; Pongs, O

1994-05-26

Structural and functional diversity of voltage-gated Kv1-type potassium channels in rat brain is enhanced by the association of two different types of subunits, the membrane-bound, poreforming alpha-subunits and a peripheral beta-subunit. We have cloned a beta-subunit (Kv beta 1) that is specifically expressed in the rat nervous system. Association of Kv beta 1 with alpha-subunits confers rapid A-type inactivation on non-inactivating Kv1 channels (delayed rectifiers) in expression systems in vitro. This effect is mediated by an inactivating ball domain in the Kv beta 1 amino terminus.

Lubrol-RAFTs in melanoma cells: a molecular platform for tumor-promoting ephrin-B2-integrin-beta1 interaction.

PubMed

Meyer, Stefanie; Orsó, Evelyn; Schmitz, Gerd; Landthaler, Michael; Vogt, Thomas

2007-07-01

Ephrins control cell motility and matrix adhesion. These functions play a pivotal role in cancer progression, for example, in malignant melanomas. We have previously shown that the ephrin-B2-tumor-promoting action is partly mediated by integrin-beta1 interaction. However, the subcellular prerequisites for molecular interaction like molecular proximity and co-compartmentalization have not been elucidated yet. Specific cholesterol-rich microdomains, termed lipid rafts (RAFTs), are known to be essential for functional ephrin-B2 signalling and integrin-mediated effects. Therefore, we addressed the question whether RAFT co-compartmentalization of both molecules could provide the molecular platform for their tumor-promoting interaction. In this study, we show that overexpressed ephrin-B2 is not only compartmentalized to classical Triton X-100 RAFTs in B16 melanoma cells, but also to the recently defined Lubrol-RAFTs. Interestingly, in the melanoma cells investigated, integrin-beta1 is also preferentially detected in such Lubrol-RAFTs. Accordingly, the presence of ephrin-B2 and integrin-beta1 in RAFTs and their function in cell migration and matrix attachment are highly sensitive to RAFT disruption by cholesterol depletion. Confocal fluorescence microscopy analyses also support the concept of a close molecular proximity and functional interplay of ephrin-B2 and integrin-beta1 in the plasma membrane. We conclude that Lubrol-RAFTs probably represent the platform for tumor-promoting ephrin-B2-integrin-beta1 interaction, which could become an interesting target for future antitumoral therapies.

Alpha cells secrete acetylcholine as a non-neuronal paracrine signal priming human beta cell function

PubMed Central

Rodriguez-Diaz, Rayner; Dando, Robin; Jacques-Silva, M. Caroline; Fachado, Alberto; Molina, Judith; Abdulreda, Midhat; Ricordi, Camillo; Roper, Stephen D.; Berggren, Per-Olof; Caicedo, Alejandro

2011-01-01

Acetylcholine is a neurotransmitter that plays a major role in the function of the insulin secreting pancreatic beta cell1,2. Parasympathetic innervation of the endocrine pancreas, the islets of Langerhans, has been shown to provide cholinergic input to the beta cell in several species1,3,4, but the role of autonomic innervation in human beta cell function is at present unclear. Here we show that, in contrast to mouse islets, cholinergic innervation of human islets is sparse. Instead, we find that the alpha cells of the human islet provide paracrine cholinergic input to surrounding endocrine cells. Human alpha cells express the vesicular acetylcholine transporter and release acetylcholine when stimulated with kainate or a lowering in glucose concentration. Acetylcholine secretion by alpha cells in turn sensitizes the beta cell response to increases in glucose concentration. Our results demonstrate that in human islets acetylcholine is a paracrine signal that primes the beta cell to respond optimally to subsequent increases in glucose concentration. We anticipate these results to revise models about neural input and cholinergic signaling in the endocrine pancreas. Cholinergic signaling within the islet represents a potential therapeutic target in diabetes5, highlighting the relevance of this advance to future drug development. PMID:21685896

Anxiety and beta-adrenergic receptor function in a normal population.

PubMed

Kang, Eun-Ho; Yu, Bum-Hee

2005-06-01

Many studies have shown a close relationship between anxiety and beta-adrenergic receptor function in patients with anxiety disorders. This study examined the relationship between beta-adrenergic receptor function and anxiety levels in a normal population. Subjects for this study included 36 men and 44 women between the ages of 20 and 40 years whose Body Mass Index (BMI) was between 18 and 26. All of them were healthy subjects who had no previous history of medical or psychiatric illnesses. The authors measured the Spielberger State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI), and Chronotropic 25 Dose (CD25) of isoproterenol, previously developed to assess in vivo beta-adrenergic receptor sensitivity. We also examined correlations between log normalized CD25 and mood states. The mean of CD25 was 2.64+/-1.37 mug and the mean of CD25 in men was significantly higher (i.e., lower beta-adrenergic receptor sensitivity) than that of women (3.26+/-1.35 vs. 2.14+/-1.17 microg; t = 3.99, p < 0.001). CD25 showed negative correlations with STAI state anxiety (r = -0.344, p = 0.002), trait anxiety (r = -0.331, p = 0.003), and BDI (r = -0.283, p = 0.011). CD25 was positively correlated with BMI (r = 0.423, p < 0.001) and age (r = 0.271, p = 0.015). In stepwise multiple regression analyses, 34% of the variance in CD25 was accounted for by sex, state anxiety, and BMI. The sensitivity of beta-adrenergic receptors increased as anxiety levels became higher in a normal population. Thus, the relationship between anxiety and beta-adrenergic receptor function in healthy subjects may be different from that of patients with anxiety disorders.

Metabolomic profiling of amino acids and beta-cell function relative to insulin sensitivity in youth

USDA-ARS?s Scientific Manuscript database

In longitudinal studies of adults, elevated amino acid (AA) concentrations predicted future type 2 diabetes mellitus (T2DM). The aim of the present investigation was to examine whether increased plasma AA concentrations are associated with impaired beta-cell function relative to insulin sensitivity ...

Renormalization of loop functions for all loops

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

Brandt, R.A.; Neri, F.; Sato, M.

1981-08-15

It is shown that the vacuum expectation values W(C/sub 1/,xxx, C/sub n/) of products of the traces of the path-ordered phase factors P exp(igcontour-integral/sub C/iA/sub ..mu../(x)dx/sup ..mu../) are multiplicatively renormalizable in all orders of perturbation theory. Here A/sub ..mu../(x) are the vector gauge field matrices in the non-Abelian gauge theory with gauge group U(N) or SU(N), and C/sub i/ are loops (closed paths). When the loops are smooth (i.e., differentiable) and simple (i.e., non-self-intersecting), it has been shown that the generally divergent loop functions W become finite functions W when expressed in terms of the renormalized coupling constant and multipliedmore » by the factors e/sup -K/L(C/sub i/), where K is linearly divergent and L(C/sub i/) is the length of C/sub i/. It is proved here that the loop functions remain multiplicatively renormalizable even if the curves have any finite number of cusps (points of nondifferentiability) or cross points (points of self-intersection). If C/sub ..gamma../ is a loop which is smooth and simple except for a single cusp of angle ..gamma.., then W/sub R/(C/sub ..gamma../) = Z(..gamma..)W(C/sub ..gamma../) is finite for a suitable renormalization factor Z(..gamma..) which depends on ..gamma.. but on no other characteristic of C/sub ..gamma../. This statement is made precise by introducing a regularization, or via a loop-integrand subtraction scheme specified by a normalization condition W/sub R/(C-bar/sub ..gamma../) = 1 for an arbitrary but fixed loop C-bar/sub ..gamma../. Next, if C/sub ..beta../ is a loop which is smooth and simple except for a cross point of angles ..beta.., then W(C/sub ..beta../) must be renormalized together with the loop functions of associated sets S/sup i//sub ..beta../ = )C/sup i//sub 1/,xxx, C/sup i//sub p/i) (i = 2,xxx,I) of loops C/sup i//sub q/ which coincide with certain parts of C/sub ..beta../equivalentC/sup 1//sub 1/. Then W/sub R/(S/sup i//sub ..beta../) = Z/sup i/j(..beta..)W(S/sup j//sub ..beta../) is finite for a suitable matrix Z/sup i/j(..beta..).« less

Topologically heterogeneous beta cell adaptation in response to high-fat diet in mice.

PubMed

Ellenbroek, Johanne H; Töns, Hendrica A; de Graaf, Natascha; Loomans, Cindy J; Engelse, Marten A; Vrolijk, Hans; Voshol, Peter J; Rabelink, Ton J; Carlotti, Françoise; de Koning, Eelco J

2013-01-01

Beta cells adapt to an increased insulin demand by enhancing insulin secretion via increased beta cell function and/or increased beta cell number. While morphological and functional heterogeneity between individual islets exists, it is unknown whether regional differences in beta cell adaptation occur. Therefore we investigated beta cell adaptation throughout the pancreas in a model of high-fat diet (HFD)-induced insulin resistance in mice. C57BL/6J mice were fed a HFD to induce insulin resistance, or control diet for 6 weeks. The pancreas was divided in a duodenal (DR), gastric (GR) and splenic (SR) region and taken for either histology or islet isolation. The capacity of untreated islets from the three regions to adapt in an extrapancreatic location was assessed by transplantation under the kidney capsule of streptozotocin-treated mice. SR islets showed 70% increased beta cell proliferation after HFD, whereas no significant increase was found in DR and GR islets. Furthermore, isolated SR islets showed twofold enhanced glucose-induced insulin secretion after HFD, as compared with DR and GR islets. In contrast, transplantation of islets isolated from the three regions to an extrapancreatic location in diabetic mice led to a similar decrease in hyperglycemia and no difference in beta cell proliferation. HFD-induced insulin resistance leads to topologically heterogeneous beta cell adaptation and is most prominent in the splenic region of the pancreas. This topological heterogeneity in beta cell adaptation appears to result from extrinsic factors present in the islet microenvironment.

Analysis of methods for determining high cycle fatigue strength of a material with investigation of titanium-aluminum-vanadium gigacycle fatigue behavior

NASA Astrophysics Data System (ADS)

Pollak, Randall D.

Today, aerospace engineers still grapple with the qualitative and quantitative understanding of fatigue behavior in the design and testing of turbine-driven jet engines. The Department of Defense has taken a very active role in addressing this problem with the formation of the National High Cycle Fatigue Science & Technology Program in 1994. The primary goal of this program is to further the understanding of high cycle fatigue (HCF) behavior and develop methods in order to mitigate the negative impact of HCF on aerospace operations. This research supports this program by addressing the fatigue strength testing guidance currently provided by the DoD to engine manufacturers, with the primary goal to investigate current methods and recommend a test strategy to characterize the fatigue strength of a material at a specified number of cycles, such as the 109 design goal specified by MIL-HDBK-1783B, or range of cycles. The research utilized the benefits of numerical simulation to initially investigate the staircase method for use in fatigue strength testing. The staircase method is a commonly used fatigue strength test, but its ability to characterize fatigue strength variability is extremely suspect. A modified staircase approach was developed and shown to significantly reduce bias and scatter in estimates for fatigue strength variance. Experimental validation of this proposed test strategy was accomplished using a dual-phase Ti-6Al-4V alloy. The HCF behavior of a second material with a very different microstructure (beta annealed Ti-6Al-4V) was also investigated. The random fatigue limit (RFL) model, a recently developed analysis tool, was investigated to characterize stress-life behavior but found to have difficulty representing fatigue life curves with sharp transitions. Two alternative models (bilinear and hyperbolic) were developed based on maximum likelihood methods to better characterize the Ti-6Al-4V fatigue life behavior. These models provided a good fit to the experimental data for the dual-phase Ti-6Al-4V and were applied to the beta annealed variant in order to estimate stress-life behavior using a small-sample approach. Based on this research, designers should be better able to make reliable estimates of fatigue strength parameters using small-sample testing.

Exercise training improves autonomic function and inflammatory pattern in women with polycystic ovary syndrome (PCOS).

PubMed

Giallauria, Francesco; Palomba, Stefano; Maresca, Luigi; Vuolo, Laura; Tafuri, Domenico; Lombardi, Gaetano; Colao, Annamaria; Vigorito, Carlo; Francesco, Orio

2008-11-01

Polycystic ovary syndrome (PCOS) is a common female reproductive-age endocrine disease predominantly characterized by chronic anovulation, hyperandrogenism, insulin-resistance and low-grade inflammatory status. Exercise training (ET) favourably modulates cardiopulmonary function and insulin-sensitivity markers in PCOS women. The present study investigated the effects of ET on autonomic function and inflammatory pattern in PCOS women. Prospective baseline uncontrolled clinical study. One-hundred and eighty five PCOS women referred to our department were screened for the inclusion into the study protocol from March 2004 to July 2007. One-hundred and twenty four PCOS women met the criteria for the inclusion into the study protocol and were subdivided into two groups each composed of 62 patients: PCOS-T (trained) group underwent 3-month ET program, whereas PCOS-UnT (untrained) group did not. At baseline and at 3-month follow-up, hormonal and metabolic profile, cardiopulmonary parameters, autonomic function (as expressed by heart rate recovery, HRR) and inflammatory pattern [as expressed by C-reactive protein (CRP) and white blood cells (WBCs) count] were evaluated. PCOS-T showed a significant (P < 0.05) improvement in maximal oxygen consumption (VO(2max)) and in post-exercise HRR, and a significant (P < 0.001) decrease in CRP and WBCs; whereas no statistically significant changes of the same parameters were observed in PCOS-UnT. Multiple linear regression analysis showed that 3-month HRR is linearly related to the inclusion in training group (beta = 0.316, P < 0.001), VO(2max) (beta = 0.151, P = 0.032) and the ratio between glucose and insulin area under curve (AUC) (beta = 0.207, P = 0.003), and inversely related to body mass index (beta = -0.146, P = 0.046), insulin AUC (beta = -0.152, P = 0.032), CRP (beta = -0.165, P < 0.021), and WBCs count (beta = -0.175, P = 0.039). Exercise training improves autonomic function and inflammatory pattern in PCOS women.

Different downstream signalling of CCK1 receptors regulates distinct functions of CCK in pancreatic beta cells.

PubMed

Ning, Shang-lei; Zheng, Wen-shuai; Su, Jing; Liang, Nan; Li, Hui; Zhang, Dao-lai; Liu, Chun-hua; Dong, Jun-hong; Zhang, Zheng-kui; Cui, Min; Hu, Qiao-Xia; Chen, Chao-chao; Liu, Chang-hong; Wang, Chuan; Pang, Qi; Chen, Yu-xin; Yu, Xiao; Sun, Jin-peng

2015-11-01

Cholecystokinin (CCK) is secreted by intestinal I cells and regulates important metabolic functions. In pancreatic islets, CCK controls beta cell functions primarily through CCK1 receptors, but the signalling pathways downstream of these receptors in pancreatic beta cells are not well defined. Apoptosis in pancreatic beta cell apoptosis was evaluated using Hoechst-33342 staining, TUNEL assays and Annexin-V-FITC/PI staining. Insulin secretion and second messenger production were monitored using ELISAs. Protein and phospho-protein levels were determined by Western blotting. A glucose tolerance test was carried out to examine the functions of CCK-8s in streptozotocin-induced diabetic mice. The sulfated carboxy-terminal octapeptide CCK26-33 amide (CCK-8s) activated CCK1 receptors and induced accumulation of both IP3 and cAMP. Whereas Gq -PLC-IP3 signalling was required for the CCK-8s-induced insulin secretion under low-glucose conditions, Gs -PKA/Epac signalling contributed more strongly to the CCK-8s-mediated insulin secretion in high-glucose conditions. CCK-8s also promoted formation of the CCK1 receptor/β-arrestin-1 complex in pancreatic beta cells. Using β-arrestin-1 knockout mice, we demonstrated that β-arrestin-1 is a key mediator of both CCK-8s-mediated insulin secretion and of its the protective effect against apoptosis in pancreatic beta cells. The anti-apoptotic effects of β-arrestin-1 occurred through cytoplasmic late-phase ERK activation, which activates the 90-kDa ribosomal S6 kinase-phospho-Bcl-2-family protein pathway. Knowledge of different CCK1 receptor-activated downstream signalling pathways in the regulation of distinct functions of pancreatic beta cells could be used to identify biased CCK1 receptor ligands for the development of new anti-diabetic drugs. © 2015 The British Pharmacological Society.

Rationale and design of a multicentre, randomized, placebo-controlled trial of mirabegron, a Beta3-adrenergic receptor agonist on left ventricular mass and diastolic function in patients with structural heart disease Beta3-left ventricular hypertrophy (Beta3-LVH).

PubMed

Pouleur, Anne-Catherine; Anker, Stefan; Brito, Dulce; Brosteanu, Oana; Hasenclever, Dirk; Casadei, Barbara; Edelmann, Frank; Filippatos, Gerasimos; Gruson, Damien; Ikonomidis, Ignatios; Lhommel, Renaud; Mahmod, Masliza; Neubauer, Stefan; Persu, Alexandre; Gerber, Bernhard L; Piechnik, Stefan; Pieske, Burkert; Pieske-Kraigher, Elisabeth; Pinto, Fausto; Ponikowski, Piotr; Senni, Michele; Trochu, Jean-Noël; Van Overstraeten, Nancy; Wachter, Rolf; Balligand, Jean-Luc

2018-06-22

Progressive left ventricular (LV) remodelling with cardiac myocyte hypertrophy, myocardial fibrosis, and endothelial dysfunction plays a key role in the onset and progression of heart failure with preserved ejection fraction. The Beta3-LVH trial will test the hypothesis that the β 3 adrenergic receptor agonist mirabegron will improve LV hypertrophy and diastolic function in patients with hypertensive structural heart disease at high risk for developing heart failure with preserved ejection fraction. Beta3-LVH is a randomized, placebo-controlled, double-blind, two-armed, multicentre, European, parallel group study. A total of 296 patients will be randomly assigned to receive either mirabegron 50 mg daily or placebo over 12 months. The main inclusion criterion is the presence of LV hypertrophy, that is, increased LV mass index (LVMi) or increased wall thickening by echocardiography. The co-primary endpoints are a change in LVMi by cardiac magnetic resonance imaging and a change in LV diastolic function (assessed by the E/e' ratio). Secondary endpoints include mirabegron's effects on cardiac fibrosis, left atrial volume index, maximal exercise capacity, and laboratory markers. Two substudies will evaluate mirabegron's effect on endothelial function by pulse amplitude tonometry and brown fat activity by positron emission tomography using 17F-fluorodeoxyglucose. Morbidity and mortality as well as safety aspects will also be assessed. Beta3-LVH is the first large-scale clinical trial to evaluate the effects of mirabegron on LVMi and diastolic function in patients with LVH. Beta3-LVH will provide important information about the clinical course of this condition and may have significant impact on treatment strategies and future trials in these patients. © 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.

Sequence specificity, statistical potentials, and three-dimensional structure prediction with self-correcting distance geometry calculations of beta-sheet formation in proteins.

PubMed Central

Zhu, H.; Braun, W.

1999-01-01

A statistical analysis of a representative data set of 169 known protein structures was used to analyze the specificity of residue interactions between spatial neighboring strands in beta-sheets. Pairwise potentials were derived from the frequency of residue pairs in nearest contact, second nearest and third nearest contacts across neighboring beta-strands compared to the expected frequency of residue pairs in a random model. A pseudo-energy function based on these statistical pairwise potentials recognized native beta-sheets among possible alternative pairings. The native pairing was found within the three lowest energies in 73% of the cases in the training data set and in 63% of beta-sheets in a test data set of 67 proteins, which were not part of the training set. The energy function was also used to detect tripeptides, which occur frequently in beta-sheets of native proteins. The majority of native partners of tripeptides were distributed in a low energy range. Self-correcting distance geometry (SECODG) calculations using distance constraints sets derived from possible low energy pairing of beta-strands uniquely identified the native pairing of the beta-sheet in pancreatic trypsin inhibitor (BPTI). These results will be useful for predicting the structure of proteins from their amino acid sequence as well as for the design of proteins containing beta-sheets. PMID:10048326

17{beta}-Hydroxysteroid dehydrogenase type 13 is a liver-specific lipid droplet-associated protein

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

Horiguchi, Yuka; Araki, Makoto; Motojima, Kiyoto

2008-05-30

17{beta}-Hydroxysteroid dehydrogenase (17{beta}HSD) type 13 is identified as a new lipid droplet-associated protein. 17{beta}HSD type 13 has an N-terminal sequence similar to that of 17{beta}HSD type 11, and both sequences function as an endoplasmic reticulum and lipid droplet-targeting signal. Localization of native 17{beta}HSD type 13 on the lipid droplets was confirmed by subcellular fractionation and Western blotting. In contrast to 17{beta}HSD type 11, however, expression of 17{beta}HSD type 13 is largely restricted to the liver and is not enhanced by peroxisome proliferator-activated receptor {alpha} and its ligand. Instead the expression level of 17{beta}HSD type 13 in the receptor-null mice wasmore » increased several-fold. 17{beta}HSD type 13 may have a distinct physiological role as a lipid droplet-associated protein in the liver.« less

Normal T lymphocytes can express two different T cell receptor beta chains: implications for the mechanism of allelic exclusion

PubMed Central

1995-01-01

We have examined the extent of allelic exclusion at the T cell receptor (TCR) beta locus using monoclonal antibodies specific for V beta products. A small proportion (approximately 1%) of human peripheral blood T cells express two V beta as determined by flow cytometric analysis, isolation of representative clones, and sequencing of the corresponding V beta chains. Dual beta T cells are present in both the CD45R0+ and CD45R0- subset. These results indicate that dual beta expression is compatible with both central and peripheral selection. They also suggest that the substantial degree of TCR beta allelic exclusion is dependent only on asynchronous rearrangements at the beta locus, whereas the role of the pre-TCR is limited to signaling the presence of at least one functional beta protein. PMID:7699339

Relationship of low plasma klotho with poor grip strength in older community-dwelling adults: the InCHIANTI study

PubMed Central

Semba, Richard D.; Cappola, Anne R.; Sun, Kai; Bandinelli, Stefania; Dalal, Mansi; Crasto, Candace; Guralnik, Jack M.; Ferrucci, Luigi

2012-01-01

Handgrip strength is a strong indicator of total body muscle strength and is a predictor of poor outcomes in older adults. The aging suppressor gene klotho encodes a single-pass transmembrane protein that is secreted as a circulating hormone. In mice, disruption of klotho expression results in a syndrome that includes sarcopenia, atherosclerosis, osteoporosis, and shortened lifespan, and conversely, overexpression of klotho leads to a greater longevity. The objective was to determine whether plasma klotho levels are related to skeletal muscle strength in humans. We measured plasma klotho in 804 adults, ≥65 years, in the InCHIANTI study, a longitudinal population-based study of aging in Tuscany, Italy. Grip strength was positively correlated with plasma klotho at threshold <681 pg/mL. After adjusting for age, sex, education, smoking, physical activity, cognition, and chronic diseases, plasma klotho (per 1 standard deviation increase) was associated with grip strength (beta = 1.20, standard error = 0.35, P = 0.0009) in adults with plasma klotho <681 pg/mL. These results suggest that older adults with lower plasma klotho have poor skeletal muscle strength. PMID:21769735

Attenuated Response to Methamphetamine Sensitization and Deficits in Motor Learning and Memory after Selective Deletion of [beta]-Catenin in Dopamine Neurons

ERIC Educational Resources Information Center

Diaz-Ruiz, Oscar; Zhang, YaJun; Shan, Lufei; Malik, Nasir; Hoffman, Alexander F.; Ladenheim, Bruce; Cadet, Jean Lud; Lupica, Carl R.; Tagliaferro, Adriana; Brusco, Alicia; Backman, Cristina M.

2012-01-01

In the present study, we analyzed mice with a targeted deletion of [beta]-catenin in DA neurons (DA-[beta]cat KO mice) to address the functional significance of this molecule in the shaping of synaptic responses associated with motor learning and following exposure to drugs of abuse. Relative to controls, DA-[beta]cat KO mice showed significant…

[Predictive factors associated with severity of asthma exacerbations].

PubMed

Atiş, Sibel; Kaplan, Eylem Sercan; Ozge, Cengiz; Bayindir, Suzan

2008-01-01

Several factors have been accused for asthma exacerbations, however, very few studies have evaluated whether different factors predict severity of asthma exacerbation. We aimed to determine the predictive factors for severity of asthma exacerbation. Retrospective analysis of data on 93 patients visited our emergency-department because of asthma exacerbation was reviewed. Hospitalization in intensive care unit and/or intubation because of asthma was accepted as the criteria for severe exacerbation. Logistic regression analysis estimated the strength of association of each variable, potentially related to severe asthmatic exacerbation, with severe/very severe as compared to mild/moderate asthmatic exacerbation. Independent variables included in the analysis were age, sex, smoking history, inhaler steroid using, compliance with medication, chronic asthma severity, presence of additional atopic diseases, prick test positivity, provocative factors, number of short-acting beta(2)-agonist using, number of visits to emergency department for asthma over one year period, previous severe exacerbation, pulmonary functions, and blood eosinophil count. 20 were severe/very severe and 73 mild/moderate asthmatic exacerbation. Frequent using of short-acting beta(2)-agonist (OR= 1.5, 95% CI= 1.08-5.3, p= 0.003), noncompliance with medication (OR= 3.6, 95% CI= 1.3-9.9, p= 0.013), previous severe asthmatic exacerbation (OR= 3.8, 95% CI= 1.48-10.01, p= 0.005) and recent admission to hospital (OR= 2.9, 95% CI= 1.07-8.09, p= 0.037) were found to be predictive factors for severe asthmatic exacerbation. Different predictive factors, in particular frequent using of short-acting beta(2)-agonist and noncompliance with medication may be associated with severe asthma exacerbations compared to milder exacerbations. This suggests different mechanisms are responsible for severity of asthma exacerbation.

Role of residual kidney function and convective volume on change in beta2-microglobulin levels in hemodiafiltration patients.

PubMed

Penne, E Lars; van der Weerd, Neelke C; Blankestijn, Peter J; van den Dorpel, Marinus A; Grooteman, Muriel P C; Nubé, Menso J; Ter Wee, Piet M; Lévesque, Renée; Bots, Michiel L

2010-01-01

Removal of beta2-microglobulin (beta2M) can be increased by adding convective transport to hemodialysis (HD). The aim of this study was to investigate the change in beta2M levels after 6-mo treatment with hemodiafiltration (HDF) and to evaluate the role of residual kidney function (RKF) and the amount of convective volume with this change. Predialysis serum beta2M levels were evaluated in 230 patients with and 176 patients without RKF from the CONvective TRAnsport STudy (CONTRAST) at baseline and 6 mo after randomization for online HDF or low-flux HD. In HDF patients, potential determinants of change in beta2M were analyzed using multivariable linear regression models. Mean serum beta2M levels decreased from 29.5 +/- 0.8 (+/-SEM) at baseline to 24.3 +/- 0.6 mg/L after 6 mo in HDF patients and increased from 31.9 +/- 0.9 to 34.4 +/- 1.0 mg/L in HD patients, with the difference of change between treatment groups being statistically significant (regression coefficient -7.7 mg/L, 95% confidence interval -9.5 to -5.6, P < 0.001). This difference was more pronounced in patients without RKF as compared with patients with RKF. In HDF patients, beta2M levels remained unchanged in patients with GFR >4.2 ml/min/1.73 m2. The beta2M decrease was not related to convective volume. This study demonstrated effective lowering of beta2M levels by HDF, especially in patients without RKF. The role of the amount of convective volume on beta2M decrease appears limited, possibly because of resistance to beta2M transfer between body compartments.

Thermoelectric effects in decaying homogeneous magneto-gas turbulence

NASA Technical Reports Server (NTRS)

Shebalin, John V.

1991-01-01

In the formulation of compressible MHD (i.e., magneto-gas dynamics), a 'generalized Ohm's law is required. In particular, an electron pressure term and a 'Hall effect' term may appear as non-negligible additions to the Ohm's law that is conventionally used for incompressible MHD. In 'high-beta' (i.e., relatively low magnetic energy) situations, the Hall term may be neglected (at least initially) but, as it turns out, the electron pressure term cannot be neglected. Here, three-dimensional, high-beta, homogeneous, decaying, magneto-gas turbulence is examined with regard to this additional term. Through numerical simulation, it is found that 'thermoelectric effects' are produced that significantly alter the evolution of the magnetic field and electric current strengths.

Observed departures from LTE ionization equilibrium in late-type giants

NASA Technical Reports Server (NTRS)

Ramsey, L. W.

1977-01-01

Photoelectric scans of the Ca I line at 6572 A and the forbidden Ca II transition at 7323 A are studied in the K giant alpha Tau, the M supergiant alpha Ori, and the M giants beta And, alpha Cet, mu Gem, and beta Peg. The relative strengths of these lines are shown to be indicative of the ratio of the relative number densities of the neutral and ionized species in the photosphere. The analysis indicates an overionization relative to LTE in qualitative agreement with the theoretical calculations of Auman and Woodrow for the K and M giants. The M supergiant alpha Ori exhibits a large overionization relative to LTE.

Slurry-pressing consolidation of silicon nitride

NASA Technical Reports Server (NTRS)

Sanders, William A.; Kiser, James D.; Freedman, Marc R.

1988-01-01

A baseline slurry-pressing method for a silicon nitride material is developed. The Si3N4 composition contained 5.8 wt percent SiO2 and 6.4 wt percent Y2O3. Slurry-pressing variables included volume percent solids, application of ultrasonic energy, and pH. Twenty vol percent slurry-pressed material was approximately 11 percent stronger than both 30 vol percent slurry-pressed and dry-pressed materials. The Student's t-test showed the difference to be significant at the 99 percent confidence level. Twenty volume percent (300 h) slurry-pressed test bars exhibited strengths as high as 980 MPa. Large, columnar beta-Si3N4 grains caused failure in the highest strength specimens. The improved strength correlated with better structural uniformity as determined by radiography, optical microscopy, and image analysis.

Scaling in tournaments

NASA Astrophysics Data System (ADS)

Ben-Naim, E.; Redner, S.; Vazquez, F.

2007-02-01

We study a stochastic process that mimics single-game elimination tournaments. In our model, the outcome of each match is stochastic: the weaker player wins with upset probability q<=1/2, and the stronger player wins with probability 1-q. The loser is eliminated. Extremal statistics of the initial distribution of player strengths governs the tournament outcome. For a uniform initial distribution of strengths, the rank of the winner, x*, decays algebraically with the number of players, N, as x*~N-β. Different decay exponents are found analytically for sequential dynamics, βseq=1-2q, and parallel dynamics, \\beta_par=1+\\frac{\\ln (1-q)}{\\ln 2} . The distribution of player strengths becomes self-similar in the long time limit with an algebraic tail. Our theory successfully describes statistics of the US college basketball national championship tournament.

High temperature compounds for turbine vanes

NASA Technical Reports Server (NTRS)

Rhodes, W. H.; Cannon, R. M., Jr.

1972-01-01

Fabrication and microstructure control studies were conducted on SiC, Si3N4, and composites based on these compounds. Charpy mode impact testing to 2400 F established that beta-spodumene, lithium aluminum silicate, coated Si3N4, Si3N4 derived from alpha-Si3N4 powder, and SiC containing 5-25 v/o chopped C fibers had the most promising strengths. Several other composite systems had excellent microstructures and could prove interesting materials in the future. Stress-rupture testing on Si3N4 established that increasing 2000 F - 100 hour strengths were obtained for increasing grain size to at least 5 micrometers, increasing density and possibly increasing phase purity. These parameters became less important at 2400 F where it is thought a grain boundary phase controls strength.

Effects of Beta-Alanine Supplementation on Brain Homocarnosine/Carnosine Signal and Cognitive Function: An Exploratory Study

PubMed Central

Hobson, Ruth M; Artioli, Guilherme G.; Otaduy, Maria C.; Roschel, Hamilton; Robertson, Jacques; Martin, Daniel; S. Painelli, Vitor; Harris, Roger C.; Gualano, Bruno

2015-01-01

Objectives Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d-1 on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1) and on cognitive function before and after exercise in trained cyclists (Study 2). Methods In Study 1, seven healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation), with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task) being performed before and after exercise on each occasion. Results In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99) or omnivores (p = 0.27); nor was there any effect when data from both groups were pooled (p = 0.19). Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27). In study 2, exercise improved cognitive function across all tests (P<0.05), although there was no effect (P>0.05) of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise. Conclusion 28 d of beta-alanine supplementation at 6.4g d-1 appeared not to influence brain homocarnosine/carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists. PMID:25875297

Arsenic-gene interactions and beta-cell function in the Strong Heart Family Study.

PubMed

Balakrishnan, Poojitha; Navas-Acien, Ana; Haack, Karin; Vaidya, Dhananjay; Umans, Jason G; Best, Lyle G; Goessler, Walter; Francesconi, Kevin A; Franceschini, Nora; North, Kari E; Cole, Shelley A; Voruganti, V Saroja; Gribble, Matthew O

2018-06-01

We explored arsenic-gene interactions influencing pancreatic beta-cell activity in the Strong Heart Family Study (SHFS). We considered 42 variants selected for associations with either beta-cell function (31 variants) or arsenic metabolism (11 variants) in the SHFS. Beta-cell function was calculated as homeostatic model - beta corrected for insulin resistance (cHOMA-B) by regressing homeostatic model - insulin resistance (HOMA-IR) on HOMA-B and adding mean HOMA-B. Arsenic exposure was dichotomized at the median of the sum of creatinine-corrected inorganic and organic arsenic species measured by high performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS). Additive GxE models for cHOMA-B were adjusted for age and ancestry, and accounted for family relationships. Models were stratified by center (Arizona, Oklahoma, North Dakota and South Dakota) and meta-analyzed. The two interactions between higher vs. lower arsenic and SNPs for cHOMA-B that were nominally significant at P < 0.05 were with rs10738708 (SNP overall effect -3.91, P = 0.56; interaction effect with arsenic -31.14, P = 0.02) and rs4607517 (SNP overall effect +16.61, P = 0.03; interaction effect with arsenic +27.02, P = 0.03). The corresponding genes GCK and TUSC1 suggest oxidative stress and apoptosis as possible mechanisms for arsenic impacts on beta-cell function. No interactions were Bonferroni-significant (1.16 × 10 -3 ). Our findings are suggestive of oligogenic moderation of arsenic impacts on pancreatic β-cell endocrine function, but were not Bonferroni-significant. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of beta-alanine supplementation on brain homocarnosine/carnosine signal and cognitive function: an exploratory study.

PubMed

Solis, Marina Yazigi; Cooper, Simon; Hobson, Ruth M; Artioli, Guilherme G; Otaduy, Maria C; Roschel, Hamilton; Robertson, Jacques; Martin, Daniel; S Painelli, Vitor; Harris, Roger C; Gualano, Bruno; Sale, Craig

2015-01-01

Two independent studies were conducted to examine the effects of 28 d of beta-alanine supplementation at 6.4 g d(-1) on brain homocarnosine/carnosine signal in omnivores and vegetarians (Study 1) and on cognitive function before and after exercise in trained cyclists (Study 2). In Study 1, seven healthy vegetarians (3 women and 4 men) and seven age- and sex-matched omnivores undertook a brain 1H-MRS exam at baseline and after beta-alanine supplementation. In study 2, nineteen trained male cyclists completed four 20-Km cycling time trials (two pre supplementation and two post supplementation), with a battery of cognitive function tests (Stroop test, Sternberg paradigm, Rapid Visual Information Processing task) being performed before and after exercise on each occasion. In Study 1, there were no within-group effects of beta-alanine supplementation on brain homocarnosine/carnosine signal in either vegetarians (p = 0.99) or omnivores (p = 0.27); nor was there any effect when data from both groups were pooled (p = 0.19). Similarly, there was no group by time interaction for brain homocarnosine/carnosine signal (p = 0.27). In study 2, exercise improved cognitive function across all tests (P < 0.05), although there was no effect (P>0.05) of beta-alanine supplementation on response times or accuracy for the Stroop test, Sternberg paradigm or RVIP task at rest or after exercise. 28 d of beta-alanine supplementation at 6.4 g d(-1) appeared not to influence brain homocarnosine/carnosine signal in either omnivores or vegetarians; nor did it influence cognitive function before or after exercise in trained cyclists.

Conservation of Oxidative Protein Stabilization in an Insect Homologue of Parkinsonism-Associated Protein DJ-1

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

Lin, Jiusheng; Prahlad, Janani; Wilson, Mark A.

2012-08-21

DJ-1 is a conserved, disease-associated protein that protects against oxidative stress and mitochondrial damage in multiple organisms. Human DJ-1 contains a functionally essential cysteine residue (Cys106) whose oxidation is important for regulating protein function by an unknown mechanism. This residue is well-conserved in other DJ-1 homologues, including two (DJ-1{alpha} and DJ-1{beta}) in Drosophila melanogaster. Because D. melanogaster is a powerful model system for studying DJ-1 function, we have determined the crystal structure and impact of cysteine oxidation on Drosophila DJ-1{beta}. The structure of D. melanogaster DJ-1{beta} is similar to that of human DJ-1, although two important residues in the humanmore » protein, Met26 and His126, are not conserved in DJ-1{beta}. His126 in human DJ-1 is substituted with a tyrosine in DJ-1{beta}, and this residue is not able to compose a putative catalytic dyad with Cys106 that was proposed to be important in the human protein. The reactive cysteine in DJ-1 is oxidized readily to the cysteine-sulfinic acid in both flies and humans, and this may regulate the cytoprotective function of the protein. We show that the oxidation of this conserved cysteine residue to its sulfinate form (Cys-SO{sub 2{sup -}}) results in considerable thermal stabilization of both Drosophila DJ-1{beta} and human DJ-1. Therefore, protein stabilization is one potential mechanism by which cysteine oxidation may regulate DJ-1 function in vivo. More generally, most close DJ-1 homologues are likely stabilized by cysteine-sulfinic acid formation but destabilized by further oxidation, suggesting that they are biphasically regulated by oxidative modification.« less

Chromosome mapping of the human arrestin (SAG), {beta}-arrestin 2 (ARRB2), and {beta}-adrenergic receptor kinase 2 (ADRBK2) genes

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

Calabrese, G.; Sallese, M.; Stornaiuolo, A.

1994-09-01

Two types of proteins play a major role in determining homologous desensitization of G-coupled receptors: {beta}-adrenergic receptor kinase ({beta}ARK), which phosphorylates the agonist-occupied receptor and its functional cofactor, {beta}-arrestin. Both {beta}ARK and {beta}-arrestin are members of multigene families. The family of G-protein-coupled receptor kinases includes rhodopsin kinase, {beta}ARK1, {beta}ARK2, IT11-A (GRK4), GRK5, and GRK6. The arrestin/{beta}-arrestin gene family includes arrestin (also known as S-antigen), {beta}-arrestin 1, and {beta}-arrestin 2. Here we report the chromosome mapping of the human genes for arrestin (SAG), {beta}arrestin 2 (ARRB2), and {beta}ARK2 (ADRBK2) by fluorescence in situ hybridization (FISH). FISH results confirmed the assignment ofmore » the gene coding for arrestin (SAG) to chromosome 2 and allowed us to refine its localization to band q37. The gene coding for {beta}-arrestin 2 (ARRB2) was mapped to chromosome 17p13 and that coding for {beta}ARK2 (ADRBK2) to chromosome 22q11. 17 refs., 1 fig.« less

Structural and metabolic relationships between goldfish brain glycoproteins participating in functional plasticity of the central nervous system.

PubMed

Schmidt, R; Shashoua, V E

1983-03-01

Ependymins beta and gamma (MW 32,000 and 26,000 daltons) are two secreted goldfish brain glycoproteins that exhibit a specifically enhanced turnover rate when the animals successfully acquire a new pattern of swimming behaviour. Both proteins are bound identically to concanavalin A and can be isolated from brain extracellular fluid and from brain cytoplasm by lectin affinity chromatography. Radioimmunoassay data, using purified 125I-labeled ependymins and antisera directed against ependymin beta or ependymin gamma, show complete cross-reactivity between the two proteins. It is demonstrated by Scatchard-plot analysis that the antisera recognize identical immunological determinants in both proteins. The amino acid composition of the ependymins is similar, and several identical polypeptide fragments are obtained after limited proteolysis with Staphylococcus aureus protease. The proteins are capable of forming complexes of the compositions gamma 2, beta gamma, and beta 2. A protease present in the extracellular fluid of goldfish brain promotes proteolysis of ependymin beta to ependymin gamma. The finding that ependymin gamma is physiologically derived from ependymin beta suggests the possibility that ependymin beta might exert its biological function during consolidation of new behavioural patterns via smaller polypeptide fragments.

EBSCO's Usage Consolidation Attempts to Streamline Gathering, Storage, and Reporting of Usage Statistics

ERIC Educational Resources Information Center

Remy, Charlie

2012-01-01

This paper provides an overview of EBSCO's new Usage Consolidation product designed to streamline the harvesting, storage, and analysis of usage statistics from electronic resources. Strengths and weaknesses of the product are discussed as well as an early beta partner's experience. In the current atmosphere of flat or declining budgets, libraries…

Functional properties of an isolated. cap alpha beta. heterodimeric human placenta insulin-like growth factor 1 receptor complex

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

Feltz, S.M.; Swanson, M.L.; Wemmie, J.A.

1988-05-03

Treatment of human placenta membranes at pH 8.5 in the presence of 2.0 mM dithiothreitol (DTT) for 5 min, followed by the simultaneous removal of the DTT and pH adjustment of pH 7.6, resulted in the formation of a functional ..cap alpha beta.. heterodimeric insulin-like growth factor 1 (IGF-1) receptor complex from the native ..cap alpha../sub 2/..beta../sub 2/ heterotetrameric disulfide-linked state. The membrane-bound ..cap alpha beta.. heterodimeric complex displayed similar curvilinear /sup 125/I-IGF-1 equilibrium binding compared to the ..cap alpha../sub 2/..beta../sub 2/ heterotetrameric complex. /sup 125/I-IGF-1 binding to both the isolated ..cap alpha../sub 2/..beta../sub 2/ heterotetrameric and ..cap alpha beta..more » heterodimeric complexes demonstrated a marked straightening of the Scatchard plots, compared to the placenta membrane-bound IGF-1 receptors, with a 2-fold increase in the high-affinity binding component. IGF-1 stimulation of IGF-1 receptor autophosphorylation indicated that the ligand-dependent activation of ..cap alpha beta.. heterodimeric protein kinase activity occurred concomitant with the reassociation into a covalent ..cap alpha../sub 2/..beta../sub 2/ heterotetrameric state. These data demonstrate that (i) a combination of alkaline pH and DTT treatment of human placenta membranes results in the formation of an ..cap alpha beta.. heterodimeric IGF-1 receptor complex, (ii) unlike the insulin receptor, high-affinity homogeneous IGF-1 binding occurs in both the ..cap alpha../sub 2/..beta../sub 2/ heterotetrameric and ..cap alpha beta.. heterodimeric complexes, and (iii) IGF-1-dependent autophosphorylation of the ..cap alpha beta.. heterodimeric IGF-1 receptor complex correlates wit an IGF-1 dependent covalent reassociation into an ..cap alpha../sub 2/..beta../sub 2/ heterotetrameric disulfide-linked state.« less

17-Beta-estradiol inhibits transforming growth factor-beta signaling and function in breast cancer cells via activation of extracellular signal-regulated kinase through the G protein-coupled receptor 30.

PubMed

Kleuser, Burkhard; Malek, Daniela; Gust, Ronald; Pertz, Heinz H; Potteck, Henrik

2008-12-01

Breast cancer development and breast cancer progression involves the deregulation of growth factors leading to uncontrolled cellular proliferation, invasion and metastasis. Transforming growth factor (TGF)-beta plays a crucial role in breast cancer because it has the potential to act as either a tumor suppressor or a pro-oncogenic chemokine. A cross-communication between the TGF-beta signaling network and estrogens has been postulated, which is important for breast tumorigenesis. Here, we provide evidence that inhibition of TGF-beta signaling is associated with a rapid estrogen-dependent nongenomic action. Moreover, we were able to demonstrate that estrogens disrupt the TGF-beta signaling network as well as TGF-beta functions in breast cancer cells via the G protein-coupled receptor 30 (GPR30). Silencing of GPR30 in MCF-7 cells completely reduced the ability of 17-beta-estradiol (E2) to inhibit the TGF-beta pathway. Likewise, in GPR30-deficient MDA-MB-231 breast cancer cells, E2 achieved the ability to suppress TGF-beta signaling only after transfection with GPR30-encoding plasmids. It is most interesting that the antiestrogen fulvestrant (ICI 182,780), which possesses agonistic activity at the GPR30, also diminished TGF-beta signaling. Further experiments attempted to characterize the molecular mechanism by which activated GPR30 inhibits the TGF-beta pathway. Our results indicate that GPR30 induces the stimulation of the mitogen-activated protein kinases (MAPKs), which interferes with the activation of Smad proteins. Inhibition of MAPK activity prevented the ability of E2 from suppressing TGF-beta signaling. These findings are of great clinical relevance, because down-regulation of TGF-beta signaling is associated with the development of breast cancer resistance in response to antiestrogens.

Identification of functional domains within the alpha and beta subunits of beta-hexosaminidase A through the expression of alpha-beta fusion proteins.

PubMed

Tse, R; Wu, Y J; Vavougios, G; Hou, Y; Hinek, A; Mahuran, D J

1996-08-20

There are three human beta-hexosaminidase isozymes which are composed of all possible dimeric combinations of an alpha and/or a beta subunit; A (alpha beta), and B (beta beta), and S (alpha alpha). The amino acid sequences of the two subunits are 60% identical. The homology between the two chains varies with the middle > the carboxy-terminal > > the amino-terminal portions. Although dimerization is required for activity, each subunit contains its own active site and differs in its substrate specificity and thermal stability. The presence of the beta subunit in hexosaminidase A also influences the substrate specificity of the alpha subunit; e.g., in vivo only the A heterodimer can hydrolyze GM2 ganglioside. In this report, we localize functional regions in the two subunits by cellular expression of alpha/beta fusion proteins joined at adjacently aligned residues. First, a chimeric alpha/beta chain was made by replacing the least well-conserved amino-terminal section of the beta chain with the corresponding alpha section. The biochemical characteristics of this protein were nearly identical to hexosaminidase B. Therefore, the most dissimilar regions in the subunits are not responsible for their dissimilar biochemical properties. A second fusion protein was made that also included the more homologous middle section of the alpha chain. This protein expressed the substrate specificity unique to isozymes containing an alpha subunit (A and S). We conclude that the region responsible for the ability of the alpha subunit to bind negatively charged substrates is located within residues alpha 132-283. Interestingly, the remaining carboxy-terminal section from the beta chain, beta 316-556, was sufficient to allow this chimera to hydrolyze GM2 ganglioside with 10% the specific activity of heterodimeric hexosaminidase A. Thus, the carboxy-terminal section of each subunit is likely involved in subunit-subunit interactions.

Deconfinement and the Hagedorn transition in string theory.

PubMed

Chaudhuri, S

2001-03-05

We introduce a new definition of the thermal partition function in string theory. With this new definition, the thermal partition functions of all of the string theories obey thermal duality relations with self-dual Hagedorn temperature beta(2)(H) = 4pi(2)alpha('). A beta-->beta(2)(H)/beta transformation maps the type I theory into a new string theory (type I) with thermal D p-branes, spatial hypersurfaces supporting a p-dimensional finite temperature non-Abelian Higgs-gauge theory for p< or =9. We demonstrate a continuous phase transition in the behavior of the static heavy quark-antiquark potential for small separations r(2)(*)

Boldenone, boldione, and milk replacers in the diet of veal calves: the effects of phytosterol content on the urinary excretion of boldenone metabolites.

PubMed

Gallina, G; Ferretti, G; Merlanti, R; Civitareale, C; Capolongo, F; Draisci, R; Montesissa, C

2007-10-03

Twenty-six veal calves were split into two groups and fed two milk replacers with a different content of phytosterols for 26 days; then, 14 calves (7 animals from each diet) were kept as controls and 12 calves (6 per diet) received daily, per os, a combination of 17beta-boldenone (17beta-Bol) and androsta-1,4-dien-3,17-dione (ADD) for 38 days. The urinary elimination of 17 alpha-/17beta-boldenone conjugates (17 alpha/beta-Bol) and androsta-1,4-dien-3,17-dione (ADD) was followed by liquid chromatography-tandem mass spectrometry from all of the animals until slaughtering. In urine from treated animals, 17 alpha-Bol concentrations, despite a great variability, were greater than 17beta-Bol, both detected always as conjugates. At days 1, 2, and 3, the mean urine concentration of 17 alpha-Bol was higher than 12 ng/mL. A remarkable decrease was observed during the following days, but the 17 alpha-Bol concentration was still higher than the attention level of 2 ng/mL in 58% of the samples; the concentration of 17beta-Bol was around the action level of 1 ng/mL; two days after treatment withdrawal, no 17beta-Bol was detected in the urine. In urine from control animals, the 17 alpha-Bol concentration was strictly related to the phytosterol content of the diet, while, in urine from treated animals, the much higher 17 alpha-Bol levels were not modified by the production from diet precursors. The results confirmed that a 17 alpha-Bol level higher than 2 ng/mL should be considered as evidence of suspected illegal treatment and that the urinary excretion of 17beta-Bol is due to exogenous administration of 17beta-Bol. The discontinuous rate of elimination of both 17 alpha- and 17beta-Bol, despite the daily administration of 17beta-Bol plus ADD, indicates the necessity for further research to detect other urinary boldenone metabolites to strength surveillance strategy.

Temperature Dependence of Positron Annihilation in beta-Cyclodextrin and beta-Cyclodextrin Complexes

NASA Astrophysics Data System (ADS)

Hu, Y.; Hsu Hadley, F. H., Jr.; Trinh, T.

1996-11-01

The effects of temperature on positron annihilation in beta-cyclodextrin and beta-cyclodextrin complexed with benzyl salicylate, benzyl acetate, ethyl salicylate, geraniol, linalool and nerol were studied. Samples were prepared by slurry, air-dried and freeze-dried methods. Lifetime spectra were measured as a function of temperature for each sample. Comparison of the annihilation rate and intensity of the longer-lived component showed that positronium formation was affected by guest molecules, preparation methods and temperature variations. Results can be used to explain beta-cyclodextrin complex formation with different guest molecules.

[Role of Ski/SnoN protein in the regulation of TGF-beta signal pathway].

PubMed

Lu, Zhao-hui; Chen, Jie

2003-04-01

TGF-beta signal pathway plays an important role in the cell growth, differentiation, formation of extracellular matrix, embryo development and carcinogenesis, etc. However, the regulation of TGF-beta pathway is not totally understood. In 1999, three independent research groups found that Ski/SnoN protein could inhibit the TGF-beta mediated transcription by recruiting N-CoR, a transcription co-repressor. Later studies suggested that TGF-beta and SMADs degraded the Ski/SnoN protein by mediating ubiquitin linkage, showing negative feedback regulation. The important findings in Ski/SnoN laid the theoretical foundation for demonstrating the function of TGF-beta signal pathway.

Bilateral Functional Connectivity of the Basal Ganglia in Patients with Parkinson’s Disease and Its Modulation by Dopaminergic Treatment

PubMed Central

Little, Simon; Tan, Huiling; Anzak, Anam; Pogosyan, Alek; Kühn, Andrea; Brown, Peter

2013-01-01

Parkinson’s disease is characterised by excessive subcortical beta oscillations. However, little is known about the functional connectivity of the two basal ganglia across hemispheres and specifically the role beta plays in this. We recorded local field potentials from the subthalamic nucleus bilaterally in 23 subjects with Parkinson’s disease at rest, on and off medication. We found suppression of low beta power in response to levodopa (t22 = −4.4, p<0.001). There was significant coherence between the two sides in the beta range in 19 of the subjects. Coherence was selectively attenuated in the low beta range following levodopa (t22 = −2.7; p = 0.01). We also separately analysed amplitude co-modulation and phase synchronisation in the beta band and found significant amplitude co-modulation and phase locking values in 17 and 16 subjects respectively, off medication. There was a dissociable effect of levodopa on these measures, with a significant suppression only in low beta phase locking value (t22 = −2.8, p = 0.01) and not amplitude co-modulation. The absolute mean values of amplitude co-modulation (0.40±0.03) and phase synchronisation (0.29±0.02) off medication were, however, relatively low, suggesting that the two basal ganglia networks may have to be approached separately with independent sensing and stimulation during adaptive deep brain stimulation. In addition, our findings highlight the functional distinction between the lower and upper beta frequency ranges and between amplitude co-modulation and phase synchronization across subthalamic nuclei. PMID:24376574

The assembly of ecological communities inferred from taxonomic and functional composition

Treesearch

Eric R. Sokol; E.F. Benfield; Lisa K. Belden; H. Maurice. Valett

2011-01-01

Among-site variation in metacommunities (beta diversity) is typically correlated with the distance separating the sites (spatial lag). This distance decay in similarity pattern has been linked to both niche-based and dispersal-based community assembly hypotheses. Here we show that beta diversity patterns in community composition, when supplemented with functional-trait...

Measuring beta-cell function relative to insulin sensitivity in youth: Does the hyperglycemic clamp suffice?

USDA-ARS?s Scientific Manuscript database

To compare beta-cell function relative to insulin sensitivity, disposition index (DI), calculated from two clamps (2cDI, insulin sensitivity from the hyperinsulinemic-euglycemic clamp and first-phase insulin from the hyperglycemic clamp) with the DI calculated from the hyperglycemic clamp alone (hcD...

Predicting hand function in older adults: evaluations of grip strength, arm curl strength, and manual dexterity.

PubMed

Liu, Chiung-Ju; Marie, Deana; Fredrick, Aaron; Bertram, Jessica; Utley, Kristen; Fess, Elaine Ewing

2017-08-01

Hand function is critical for independence in activities of daily living for older adults. The purpose of this study was to examine how grip strength, arm curl strength, and manual dexterous coordination contributed to time-based versus self-report assessment of hand function in community-dwelling older adults. Adults aged ≥60 years without low vision or neurological disorders were recruited. Purdue Pegboard Test, Jamar hand dynamometer, 30-second arm curl test, Jebsen-Taylor Hand Function Test, and the Late-Life Function and Disability Instrument were administered to assess manual dexterous coordination, grip strength, arm curl strength, time-based hand function, and self-report of hand function, respectively. Eighty-four adults (mean age = 72 years) completed the study. Hierarchical multiple regressions show that older adults with better arm curl strength (β = -.25, p < .01) and manual dexterous coordination (β = -.52, p < .01) performed better on the time-based hand function test. In comparison, older adults with better grip strength (β = .40, p < .01), arm curl strength (β = .23, p < .05), and manual dexterous coordination (β = .23, p < .05) were associated with better self-report of upper extremity function. The relationship between grip strength and hand function may be test-specific. Grip strength becomes a significant factor when the test requires grip strength to successfully complete the test tasks. Arm curl strength independently contributed to hand function in both time-based and self-report assessments, indicating that strength of extrinsic muscles of the hand are essential for hand function.

Beta Adrenergic Blocking Medications for Aggressive or Self-Injurious Mentally Retarded Persons.

ERIC Educational Resources Information Center

Ruedrich, Stephen L.; And Others

1990-01-01

Literature is reviewed and a case report is presented concerning blockers of the beta-adrenergic function of the sympathetic nervous system, postulated to have efficacy in treatment of aggressive or self-injurious syndromes in persons with mental retardation. Concerns are raised regarding endorsement of beta-blocking medications before they have…

31Cl beta decay and the 30P31S reaction rate in nova nucleosynthesis

NASA Astrophysics Data System (ADS)

Bennett, Michael; Wrede, C.; Brown, B. A.; Liddick, S. N.; Pérez-Loureiro, D.; NSCL e12028 Collaboration

2016-03-01

The 30P31S reaction rate is critical for modeling the final isotopic abundances of ONe nova nucleosynthesis, identifying the origin of presolar nova grains, and calibrating proposed nova thermometers. Unfortunately, this rate is essentially experimentally unconstrained because the strengths of key 31S proton capture resonances are not known, due to uncertainties in their spins and parities. Using a 31Cl beam produced at the National Superconducting Cyclotron Laboratory, we have populated several 31S states for study via beta decay and devised a new decay scheme which includes updated beta feedings and gamma branchings as well as multiple states previously unobserved in 31Cl beta decay. Results of this study, including the unambiguous identification due to isospin mixing of a new l = 0 , Jπ = 3 /2+ 31S resonance directly in the middle of the Gamow Window, will be presented, and significance to the evaluation of the 30P31S reaction rate will be discussed. Work supported by U.S. Natl. Sci. Foundation (Grants No. PHY-1102511, PHY-1404442, PHY-1419765, and PHY-1431052); U.S. Dept. of Energy, Natl. Nucl. Security Administration (Award No. DE-NA0000979); Nat. Sci. and Eng. Research Council of Canada.

Effect of grain growth of [beta]-silicon nitride on strength, Weibull modulus, and fracture toughness

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

Hirosaki, Naota; Akimune, Yoshio; Mitomo, Mamoru

1993-07-01

[beta]-Si[sub 3]N[sub 4] powder containing 1 mol% of equimolar Y[sub 2]O[sub 3]-Nd[sub 2]O[sub 3] was gas-pressure sintered at 2,000C for 2 h (SN2), 4 h (SN4), and 8 h (SN8) in 30-MPa nitrogen gas. These materials had a microstructure of in-situ composites'' as a result of exaggerated grain growth of some [beta]-Si[sub 3]N[sub 4] grains during firing. Growth of elongated grains was controlled by the sintering time, so that the desired microstructures were obtained. SN2 had a Weibull modulus as high as 53 because of the uniform size and spatial distribution of its large grains. SN4 had a fracture toughnessmore » of 10.3 MPa[center dot]m[sup 1/2] because of toughening provided by the bridging of elongated grains, whereas SN8 showed a lower fracture toughness, possibly caused by extensive microcracking resulting from excessively large grains. Gas-pressure sintering of [beta]-Si[sub 3]N[sub 4] powder was shown to be effective in fostering selective grain growth for obtaining the desired composite microstructure.« less

Simulation studies for surfaces and materials strength

NASA Technical Reports Server (NTRS)

Halicioglu, T.

1985-01-01

From intermolecular force studies, it is now known that the overall non-additive contribution to the lattice enegy is positive so that analysis based on only pairwise additivity suggests a shallower intermolecular potential than the true value. Two body contributions alone are also known to be categorically unable to even qualitatively describe some configurations of molecular clusters in the gas phase or the general relaxation and reconstruction of fcc crystal surfaces. In addition, the many-body contribution was shown to play a key role in the stability of certain crystal structures. In these recent analyses, a relatively simple potential energy function (PEF), comprising only a two-body Mie-type potential plus a three-body Axilrod-Teller-type potential, was found to be extremely effective. This same parametric PEF is applied to describe the bulk stability and surface energy for the diamond cubic structure. To test the stability condition, the FCC, BCC, diamond cubic, graphite and beta-tin structures were considered.

Scale magnetic effect in quantum electrodynamics and the Wigner-Weyl formalism

NASA Astrophysics Data System (ADS)

Chernodub, M. N.; Zubkov, M. A.

2017-09-01

The scale magnetic effect (SME) is the generation of electric current due to a conformal anomaly in an external magnetic field in curved spacetime. The effect appears in a vacuum with electrically charged massless particles. Similarly to the Hall effect, the direction of the induced anomalous current is perpendicular to the direction of the external magnetic field B and to the gradient of the conformal factor τ , while the strength of the current is proportional to the beta function of the theory. In massive electrodynamics the SME remains valid, but the value of the induced current differs from the current generated in the system of massless fermions. In the present paper we use the Wigner-Weyl formalism to demonstrate that in accordance with the decoupling property of heavy fermions the corresponding anomalous conductivity vanishes in the large-mass limit with m2≫|e B | and m ≫|∇τ | .

[Chronic heart failure].

PubMed

Gosch, Markus

2008-08-01

As a consequence of the increasing life expectancy the number of patients suffering from chronic heart failure has been growing continuously in the past few decades, especially in the group of the old and oldest. Frailty is a clinical syndrome that geriatricians attach great importance to. Like many other diseases chronic heart failure can cause frailty. Based on the experience that we see only a small correlation between the functional capacity of patients with heart failure and the results of cardiological findings, the model of peripheral myopathy in chronic heart failure was developed. Different pathophysiological changes may cause the increasing exercise intolerance in patients with chronic heart failure. We can already consider different experimental approaches to the therapy of frailty caused by chronic heart failure. At the moment we have to focus our efforts on an optimal therapy of heart failure, especially with angiotensin-converting-enzyme inhibitors and beta-blockers, and on individual endurance and strength training.

Variation in flexural properties of photo-pultruded composite archwires: analyses of round and rectangular profiles.

PubMed

Fallis, D W; Kusy, R P

2000-11-01

Prototype continuous, unidirectional, fiber-reinforced composite archwires were manufactured into round and rectangular profiles utilizing a photo-pultrusion process. Both 0.022 inch (0.56 mm) diameter and 0.021 x 0.028 inch (0.53 x 0.71 mm) rectangular composites were formed utilizing commercially available S2-glass reinforcement within a polymeric matrix. Reinforcement was varied according to the number, denier and twists per inch (TPI) of four S2-glass yarns to volume levels of 32-74% for round and 41-61% for rectangular profiles. Cross-sectional geometry was evaluated via light microscopy to determine loading characteristics; whereas two flexural properties (the elastic moduli and flexural strengths) were determined by 3-point bending tests. Morphological evaluation of samples revealed that as the TPI increased from 1 to 8, the yarns were more separated from one another and distributed more peripherally within a profile. For round and rectangular profiles utilizing 1 TPI fibers, moduli increased with fiber content approaching theoretical values. For round profiles utilizing 1 TPI and 4 TPI fibers, flexural strengths increased until the loading geometry was optimized. In contrast, the flexural strengths of composites that were pultruded with 8 TPI fibers were not improved at any loading level. Doubling the denier of the yarn, without altering the loading, increased both the moduli and flexural strengths in rectangular samples; whereas, the increases observed in round samples were not statistically significant. At optimal loading the maximum mean moduli and strengths equaled 53.6 +/- 2.0 and 1.36 +/- 0.17 GPa for round wire and equaled 45.7 +/- 0.8 and 1.40 +/- 0.05 GPa for rectangular wires, respectively. These moduli were midway between that of martensitic NiTi (33.4 GPa) and beta-titanium (72.4 GPa), and produced about one-quarter the force of a stainless steel wire per unit of activation. Values of strengths placed this composite material in the range of published values for beta-titanium wires (1.3-1.5 GPa). Copyright 2000 Kluwer Academic Publishers

The relationship between health-related fitness and quality of life in postmenopausal women from Southern Taiwan

PubMed Central

Hsu, Wei-Hsiu; Chen, Chi-lung; Kuo, Liang Tseng; Fan, Chun-Hao; Lee, Mel S; Hsu, Robert Wen-Wei

2014-01-01

Background Health-related fitness has been reported to be associated with improved quality of life (QoL) in the elderly. Health-related fitness is comprised of several dimensions that could be enhanced by specific training regimens. It has remained unclear how various dimensions of health-related fitness interact with QoL in postmenopausal women. Objective The purpose of the current study was to investigate the relationship between the dimensions of health-related fitness and QoL in elderly women. Methods A cohort of 408 postmenopausal women in a rural area of Taiwan was prospectively collected. Dimensions of health-related fitness, consisting of muscular strength, balance, cardiorespiratory endurance, flexibility, muscle endurance, and agility, were assessed. QoL was determined using the Short Form Health Survey (SF-36). Differences between age groups (stratified by decades) were calculated using a one-way analysis of variance (ANOVA) and multiple comparisons using a Scheffé test. A Spearman’s correlation analysis was performed to examine differences between QoL and each dimension of fitness. Multiple linear regression with forced-entry procedure was performed to evaluate the effects of health-related fitness. A P-value of <0.05 was considered statistically significant. Results Age-related decreases in health-related fitness were shown for sit-ups, back strength, grip strength, side steps, trunk extension, and agility (P<0.05). An age-related decrease in QoL, specifically in physical functioning, role limitation due to physical problems, and physical component score, was also demonstrated (P<0.05). Multiple linear regression analyses demonstrated that back strength significantly contributed to the physical component of QoL (adjusted beta of 0.268 [P<0.05]). Conclusion Back strength was positively correlated with the physical component of QoL among the examined dimensions of health-related fitness. Health-related fitness, as well as the physical component of QoL, declined with increasing age. PMID:25258526

Precision PEP-II optics measurement with an SVD-enhanced Least-Square fitting

NASA Astrophysics Data System (ADS)

Yan, Y. T.; Cai, Y.

2006-03-01

A singular value decomposition (SVD)-enhanced Least-Square fitting technique is discussed. By automatic identifying, ordering, and selecting dominant SVD modes of the derivative matrix that responds to the variations of the variables, the converging process of the Least-Square fitting is significantly enhanced. Thus the fitting speed can be fast enough for a fairly large system. This technique has been successfully applied to precision PEP-II optics measurement in which we determine all quadrupole strengths (both normal and skew components) and sextupole feed-downs as well as all BPM gains and BPM cross-plane couplings through Least-Square fitting of the phase advances and the Local Green's functions as well as the coupling ellipses among BPMs. The local Green's functions are specified by 4 local transfer matrix components R12, R34, R32, R14. These measurable quantities (the Green's functions, the phase advances and the coupling ellipse tilt angles and axis ratios) are obtained by analyzing turn-by-turn Beam Position Monitor (BPM) data with a high-resolution model-independent analysis (MIA). Once all of the quadrupoles and sextupole feed-downs are determined, we obtain a computer virtual accelerator which matches the real accelerator in linear optics. Thus, beta functions, linear coupling parameters, and interaction point (IP) optics characteristics can be measured and displayed.

Functional characterization of recombinant prefoldin complexes from a hyperthermophilic archaeon, Thermococcus sp. strain KS-1.

PubMed

Iizuka, Ryo; Sugano, Yuri; Ide, Naoki; Ohtaki, Akashi; Yoshida, Takao; Fujiwara, Shinsuke; Imanaka, Tadayuki; Yohda, Masafumi

2008-03-28

Prefoldin is a heterohexameric molecular chaperone complex that is found in the eukaryotic cytosol and also in archaea. It captures a nonnative protein and subsequently delivers it to a group II chaperonin for proper folding. Archaeal prefoldin is a heterocomplex containing two alpha subunits and four beta subunits with the structure of a double beta-barrel assembly, with six long coiled coils protruding from it like a jellyfish with six tentacles. We have studied the protein folding mechanism of group II chaperonin using those of Thermococcus sp. strain KS-1 (T. KS-1) because they exhibit high protein folding activity in vitro. We have also demonstrated functional cooperation between T. KS-1 chaperonins and prefoldin from Pyrococcus horikoshii OT3. Recent genome analysis has shown that Thermococcus kodakaraensis KOD1 contains two pairs of prefoldin subunit genes, correlating with the existence of two different chaperonin subunits. In this study, we characterized four different recombinant prefoldin complexes composed of two pairs of prefoldin subunits (alpha1, alpha2, beta1, and beta2) from T. KS-1. All of them (alpha1-beta1, alpha2-beta1, alpha1-beta2, and alpha2-beta2) exist as alpha(2)beta(4) heterohexamers and can protect several proteins from forming aggregates with different activities. We have also compared the collaborative activity between the prefoldin complexes and the cognate chaperonins. Prefoldin complexes containing the beta1 subunit interacted with the chaperonins more strongly than those with the beta2 subunit. The results suggest that Thermococcus spp. express different prefoldins for different substrates or conditions as chaperonins.

Nanoscale organization of {beta}{sub 2}-adrenergic receptor-Venus fusion protein domains on the surface of mammalian cells

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

Vobornik, Dusan; Rouleau, Yanouchka; Haley, Jennifer

2009-04-24

Adrenergic receptors are a key component of nanoscale multiprotein complexes that are responsible for controlling the beat rate in a mammalian heart. We demonstrate the ability of near-field scanning optical microscopy (NSOM) to visualize {beta}{sub 2}-adrenergic receptors ({beta}{sub 2}AR) fused to the GFP analogue Venus at the nanoscale on HEK293 cells. The expression of the {beta}{sub 2}AR-Venus fusion protein was tightly controlled using a tetracycline-induced promoter. Both the size and density of the observed nanoscale domains are dependent on the level of induction and thus the level of protein expression. At concentrations between 100 and 700 ng/ml of inducer doxycycline,more » the size of domains containing the {beta}{sub 2}AR-Venus fusion protein appears to remain roughly constant, but the number of domains per cell increase. At 700 ng/ml doxycycline the functional receptors are organized into domains with an average diameter of 150 nm with a density similar to that observed for the native protein on primary murine cells. By contrast, larger micron-sized domains of {beta}{sub 2}AR are observed in the membrane of the HEK293 cells that stably overexpress {beta}{sub 2}AR-GFP and {beta}{sub 2}AR-eYFP. We conclude that precise chemical control of gene expression is highly advantageous for the use {beta}{sub 2}AR-Venus fusion proteins as models for {beta}{sub 2}AR function. These observations are critical for designing future cell models and assays based on {beta}{sub 2}AR, since the receptor biology is consistent with a relatively low density of nanoscale receptor domains.« less

“Too Many betas do not Spoil the Broth”: The Role of Beta Brain Oscillations in Language Processing

PubMed Central

Weiss, Sabine; Mueller, Horst M.

2012-01-01

Over the past 20 years, brain oscillations have proven to be a gateway to the understanding of cognitive processes. It has been shown that different neurocognitive aspects of language processing are associated with brain oscillations at various frequencies. Frequencies in the beta range (13–30 Hz) turned out to be particularly important with respect to cognitive and linguistic manipulations during language processing. Beta activity has been involved in higher-order linguistic functions such as the discrimination of word categories and the retrieval of action semantics as well as semantic memory, and syntactic binding processes, which support meaning construction during sentence processing. From a neurophysiological point of view, the important role of the beta frequencies for such a complex cognitive task as language processing seems reasonable. Experimental evidence suggests that frequencies in the beta range are ideal for maintaining and preserving the activity of neuronal assemblies over time. In particular, recent computational and experimental evidence suggest that beta frequencies are important for linking past and present input and the detection of novelty of stimuli, which are essential processes for language perception as well as production. In addition, the beta frequency’s role in the formation of cell assemblies underlying short-term memory seems indispensable for language analysis. Probably the most important point is the well-known relation of beta oscillations with motor processes. It can be speculated that beta activities reflect the close relationship between language comprehension and motor functions, which is one of the core claims of current theories on embodied cognition. In this article, the importance of beta oscillations for language processing is reviewed based both on findings in psychophysiological and neurophysiological literature. PMID:22737138

Dissociation between cardiomyocyte function and remodeling with beta-adrenergic receptor blockade in isolated canine mitral regurgitation.

PubMed

Pat, Betty; Killingsworth, Cheryl; Denney, Thomas; Zheng, Junying; Powell, Pamela; Tillson, Michael; Dillon, A Ray; Dell'Italia, Louis J

2008-12-01

The low-pressure volume overload of isolated mitral regurgitation (MR) is associated with increased adrenergic drive, left ventricular (LV) dilatation, and loss of interstitial collagen. We tested the hypothesis that beta1-adrenergic receptor blockade (beta1-RB) would attenuate LV remodeling after 4 mo of MR in the dog. beta1-RB did not attenuate collagen loss or the increase in LV mass in MR dogs. Using MRI and three-dimensional (3-D) analysis, there was a 70% increase in the LV end-diastolic (LVED) volume-to-LV mass ratio, a 23% decrease in LVED midwall circumferential curvature, and a >50% increase in LVED 3-D radius/wall thickness in MR dogs that was not attenuated by beta1-RB. However, beta1-RB caused a significant increase in LVED length from the base to apex compared with untreated MR dogs. This was associated with an increase in isolated cardiomyocyte length (171+/-5 microm, P<0.05) compared with normal (156+/-3 microm) and MR (165+/-4 microm) dogs. Isolated cardiomyocyte fractional shortening was significantly depressed in MR dogs compared with normal dogs (3.73+/-0.31 vs. 5.02+/-0.26%, P<0.05) and normalized with beta1-RB (4.73+/-0.48%). In addition, stimulation with the beta-adrenergic receptor agonist isoproterenol (25 nM) increased cardiomyocyte fractional shortening by 215% (P<0.05) in beta1-RB dogs compared with normal (56%) and MR (50%) dogs. In summary, beta1-RB improved LV cardiomyocyte function and beta-adrenergic receptor responsiveness despite further cell elongation. The failure to attenuate LV remodeling associated with MR could be due to a failure to improve ultrastructural changes in extracellular matrix organization.

Respiratory effect of beta-blocker eye drops in asthma: population-based study and meta-analysis of clinical trials.

PubMed

Morales, Daniel R; Dreischulte, Tobias; Lipworth, Brian J; Donnan, Peter T; Jackson, Cathy; Guthrie, Bruce

2016-09-01

To measure the prevalence of beta-blocker eye drop prescribing and respiratory effect of ocular beta-blocker administration in people with asthma. We measured the prevalence of ocular beta-blocker prescribing in people with asthma and ocular hypertension, and performed a nested case-control study (NCCS) measuring risk of moderate exacerbations (rescue steroids in primary care) and severe exacerbations (asthma hospitalization) using linked data from the UK Clinical Practice Research Datalink. We then performed a systematic review and meta-analysis of clinical trials evaluating changes in lung function following ocular beta-blocker administration in people with asthma. From 2000 to 2012, the prevalence of non-selective and selective beta-blocker eye drop prescribing in people with asthma and ocular hypertension fell from 23.0% to 13.4% and from 10.5% to 0.9% respectively. In the NCCS, the relative incidence (IRR) of moderate exacerbations increased significantly with acute non-selective beta-blocker eye drop exposure (IRR 4.83, 95% CI 1.56-14.94) but not with chronic exposure. In the meta-analysis, acute non-selective beta-blocker eye drop exposure caused significant mean falls in FEV1 of -10.9% (95% CI -14.9 to -6.9), and falls in FEV1 of ≥20% affecting one in three. Corresponding values for selective beta-blockers in people sensitive to ocular non-selective beta-blockers was -6.3% (95% CI -11.7 to -0.8), and a non-significant increase in falls in FEV1 of ≥20%. Non-selective beta-blocker eye drops significantly affect lung function and increase asthma morbidity but are still frequently prescribed to people with asthma and ocular hypertension despite safer agents being available. © 2016 The British Pharmacological Society.

Meta-analysis of studies with bivariate binary outcomes: a marginal beta-binomial model approach

PubMed Central

Chen, Yong; Hong, Chuan; Ning, Yang; Su, Xiao

2018-01-01

When conducting a meta-analysis of studies with bivariate binary outcomes, challenges arise when the within-study correlation and between-study heterogeneity should be taken into account. In this paper, we propose a marginal beta-binomial model for the meta-analysis of studies with binary outcomes. This model is based on the composite likelihood approach, and has several attractive features compared to the existing models such as bivariate generalized linear mixed model (Chu and Cole, 2006) and Sarmanov beta-binomial model (Chen et al., 2012). The advantages of the proposed marginal model include modeling the probabilities in the original scale, not requiring any transformation of probabilities or any link function, having closed-form expression of likelihood function, and no constraints on the correlation parameter. More importantly, since the marginal beta-binomial model is only based on the marginal distributions, it does not suffer from potential misspecification of the joint distribution of bivariate study-specific probabilities. Such misspecification is difficult to detect and can lead to biased inference using currents methods. We compare the performance of the marginal beta-binomial model with the bivariate generalized linear mixed model and the Sarmanov beta-binomial model by simulation studies. Interestingly, the results show that the marginal beta-binomial model performs better than the Sarmanov beta-binomial model, whether or not the true model is Sarmanov beta-binomial, and the marginal beta-binomial model is more robust than the bivariate generalized linear mixed model under model misspecifications. Two meta-analyses of diagnostic accuracy studies and a meta-analysis of case-control studies are conducted for illustration. PMID:26303591

Al{sub 2}TiO{sub 5}-Al{sub 2}O{sub 3}-TiO{sub 2} nanocomposite: Structure, mechanical property and bioactivity studies

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

Kalita, Samar Jyoti, E-mail: Samar.Kalita@und.nodak.edu; Somani, Vikas

2010-12-15

Novel biomaterials are of prime importance in tissue engineering. Here, we developed novel nanostructured Al{sub 2}TiO{sub 5}-Al{sub 2}O{sub 3}-TiO{sub 2} composite as a biomaterial for bone repair. Initially, nanocrystalline Al{sub 2}O{sub 3}-TiO{sub 2} composite powder was synthesized by a sol-gel process. The powder was cold compacted and sintered at 1300-1500 {sup o}C to develop nanostructured Al{sub 2}TiO{sub 5}-Al{sub 2}O{sub 3}-TiO{sub 2} composite. Nano features were retained in the sintered structures while the grains showed irregular morphology. The grain-growth and microcracking were prominent at higher sintering temperatures. X-ray diffraction peak intensity of {beta}-Al{sub 2}TiO{sub 5} increased with increasing temperature. {beta}-Al{sub 2}TiO{submore » 5} content increased from 91.67% at 1300 {sup o}C to 98.83% at 1500 {sup o}C, according to Rietveld refinement. The density of {beta}-Al{sub 2}TiO{sub 5} sintered at 1300 {sup o}C, 1400 {sup o}C and 1500 {sup o}C were computed to be 3.668 g cm{sup -3}, 3.685 g cm{sup -3} and 3.664 g cm{sup -3}, respectively. Nanocrystalline grains enhanced the flexural strength. The highest flexural strength of 43.2 MPa was achieved. Bioactivity and biomechanical properties were assessed in simulated body fluid. Electron microscopy confirmed the formation of apatite crystals on the surface of the nanocomposite. Spectroscopic analysis established the presence of Ca and P ions in the crystals. Results throw light on biocompatibility and bioactivity of {beta}-Al{sub 2}TiO{sub 5} phase, which has not been reported previously.« less

On the effect of incremental forming on alpha phase precipitation and mechanical behavior of beta-Ti-10V-2Fe-3Al

NASA Astrophysics Data System (ADS)

Winter, S.; F-X Wagner, M.

2016-03-01

A combination of good ductility and fatigue resistance makes β-titanium alloys interesting for many current and potential future applications. The mechanical behavior is primarily determined by microstructural parameters like (beta phase) grain size, morphology and volume fraction of primary / secondary α-phase precipitates, and this allows changing and optimizing their mechanical properties across a wide range. In this study, we investigate the possibility to modify the microstructure of the high-strength beta titanium alloy Ti-10V-2Fe-3Al, with a special focus on shape and volume fraction of primary α-phase. In addition to the conventional strategy for precipitation of primary α, a special thermo-mechanical processing is performed; this processing route combines the conventional heat treatment with incremental forming during the primary α-phase annealing. After incremental forming, considerable variations in terms of microstructure and mechanical properties can be obtained for different thermo-mechanical processing routes. The microstructures of the deformed samples are characterized by globular as well as lamellar (bimodal) α precipitates, whereas conventional annealing only results in the formation of lamellar precipitates. Because of the smaller size, and the lower amount, of α-phase after incremental forming, tensile strength is not as high as after the conventional strategy. However, high amounts of grain boundary α and lamellar αp-phase in the undeformed samples lead to a significantly lower ductility in comparison to the matrix with bimodal structures obtained by thermo-mechanical processing. These results illustrate the potential of incremental forming during the annealing to modify the microstructure of the beta titanium Ti-10V-2Fe-3Al in a wide range of volume fractions and morphologies of the primary α phase, which in turn leads to considerably changes, and improved, mechanical properties.

Inhibition of myostatin does not ameliorate disease features of severe spinal muscular atrophy mice.

PubMed

Sumner, Charlotte J; Wee, Claribel D; Warsing, Leigh C; Choe, Dong W; Ng, Andrew S; Lutz, Cathleen; Wagner, Kathryn R

2009-09-01

There is currently no treatment for the inherited motor neuron disease, spinal muscular atrophy (SMA). Severe SMA causes lower motor neuron loss, impaired myofiber development, profound muscle weakness and early mortality. Myostatin is a transforming growth factor-beta family member that inhibits muscle growth. Loss or blockade of myostatin signaling increases muscle mass and improves muscle strength in mouse models of primary muscle disease and in the motor neuron disease, amyotrophic lateral sclerosis. In this study, we evaluated the effects of blocking myostatin signaling in severe SMA mice (hSMN2/delta7SMN/mSmn(-/-)) by two independent strategies: (i) transgenic overexpression of the myostatin inhibitor follistatin and (ii) post-natal administration of a soluble activin receptor IIB (ActRIIB-Fc). SMA mice overexpressing follistatin showed little increase in muscle mass and no improvement in motor function or survival. SMA mice treated with ActRIIB-Fc showed minimal improvement in motor function, and no extension of survival compared with vehicle-treated mice. Together these results suggest that inhibition of myostatin may not be a promising therapeutic strategy in severe forms of SMA.

Functionalized polymers for binding to solutes in aqueous solutions

DOEpatents

Smith, Barbara F.; Robison, Thomas W.

2006-11-21

A functionalized polymer for binding a dissolved molecule in an aqueous solution is presented. The polymer has a backbone polymer to which one or more functional groups are covalently linked. The backbone polymer can be such polymers as polyethylenimine, polyvinylamine, polyallylamine, and polypropylamine. These polymers are generally water-soluble, but can be insoluble when cross-linked. The functional group can be for example diol derivatives, polyol derivatives, thiol and dithiol derivatives, guest-host groups, affinity groups, beta-diphosphonic acids, and beta-diamides

Impaired compensatory beta-cell function and growth in response to high-fat diet in LDL receptor knockout mice

PubMed Central

Oliveira, Ricardo B d; Carvalho, Carolina P d F; Polo, Carla C; Dorighello, Gabriel d G; Boschero, Antônio C; Oliveira, Helena C F d; Collares-Buzato, Carla B

2014-01-01

In this study, we investigated the effect of low density lipoprotein receptor (LDLr) deficiency on gap junctional connexin 36 (Cx36) islet content and on the functional and growth response of pancreatic beta-cells in C57BL/6 mice fed a high-fat (HF) diet. After 60 days on regular or HF diet, the metabolic state and morphometric islet parameters of wild-type (WT) and LDLr−/− mice were assessed. HF diet-fed WT animals became obese and hypercholesterolaemic as well as hyperglycaemic, hyperinsulinaemic, glucose intolerant and insulin resistant, characterizing them as prediabetic. Also they showed a significant decrease in beta-cell secretory response to glucose. Overall, LDLr−/− mice displayed greater susceptibility to HF diet as judged by their marked cholesterolaemia, intolerance to glucose and pronounced decrease in glucose-stimulated insulin secretion. HF diet induced similarly in WT and LDLr−/− mice, a significant decrease in Cx36 beta-cell content as revealed by immunoblotting. Prediabetic WT mice displayed marked increase in beta-cell mass mainly due to beta-cell hypertrophy/replication. Nevertheless, HF diet-fed LDLr−/− mice showed no significant changes in beta-cell mass, but lower islet–duct association (neogenesis) and higher beta-cell apoptosis index were seen as compared to controls. The higher metabolic susceptibility to HF diet of LDLr−/− mice may be explained by a deficiency in insulin secretory response to glucose associated with lack of compensatory beta-cell expansion. PMID:24853046

Difference between beta1-adrenoceptor autoantibodies of human and animal origin-Limitations detecting beta1-adrenoceptor autoantibodies using peptide based ELISA technology.

PubMed

Wenzel, Katrin; Schulze-Rothe, Sarah; Müller, Johannes; Wallukat, Gerd; Haberland, Annekathrin

2018-01-01

Cell-based analytics for the detection of the beta1-adrenoceptor autoantibody (beta1-AAB) are functional, yet difficult to handle, and should be replaced by easily applicable, routine lab methods. Endeavors to develop solid-phase-based assays such as ELISA to exploit epitope moieties for trapping autoantibodies are ongoing. These solid-phase-based assays, however, are often unreliable when used with human patient material, in contrast to animal derived autoantibodies. We therefore tested an immunogen peptide-based ELISA for the detection of beta1-AAB, and compared commercially available goat antibodies against the 2nd extracellular loop of human beta1-adrenoceptor (ADRB1-AB) to autoantibodies enriched from patient material. The functionality of these autoantibodies was tested in a cell based assay for comparison and their structural appearance was investigated using 2D gel electrophoresis. The ELISA showed a limit of detection for ADRB1-AB of about 1.5 nmol antibody/L when spiked in human control serum and only about 25 nmol/L when spiked in species identical (goat) matrix material. When applied to samples of human origin, the ELISA failed to identify the specific beta1-AABs. A low concentration of beta1-AAB, together with structural inconsistency of the patient originated samples as seen from the 2D Gel appearance, might contribute to the failure of the peptide based ELISA technology to detect human beta1-AABs.

Sensitivity Analysis of Geometrical Parameters on the Aerodynamic Performance of Closed-Box Girder Bridges.

PubMed

Yang, Yongxin; Zhou, Rui; Ge, Yaojun; Du, Yanliang; Zhang, Lihai

2018-06-27

In this study, the influence of two critical geometrical parameters (i.e., angles of wind fairing, α; and lower inclined web, β) in the aerodynamic performance of closed-box girder bridges was systematically investigated through conducting a theoretical analysis and wind tunnel testing using laser displacement sensors. The results show that, for a particular inclined web angle β, a closed-box girder with a sharper wind fairing angle of α = 50° has better flutter and vortex-induced vibration (VIV) performance than that with α = 60°, while an inclined web angle of β = 14° produces the best VIV performance. In addition, the results from particle image velocimetry (PIV) tests indicate that a wind fairing angle of α = 50° produces a better flutter performance by inducing a single vortex structure and a balanced distribution of the strength of vorticity in both upper and lower parts of the wake region. Furthermore, two-dimensional three-degrees-of-freedom (2D-3DOF) analysis results demonstrate that the absolute values of Part A (with a reference of flutter derivative A ₂ * ) and Part D (with a reference of A ₁ * H ₃ * ) generally decrease with the increase of β, while the change of the participation level of heaving degrees of freedom (DOF) in torsion-dominated coupled flutter initially increases, reaches its peak, and then decreases with the increase of β.

The Influence of Magnetosheath Beta and Ionospheric Conductivity in the Structure of the Lobes Near Solstice

NASA Astrophysics Data System (ADS)

Wilder, F. D.; Eriksson, S.; Wiltberger, M. J.

2017-12-01

The saturation of the cross-polar cap potential (CPCP) is an unexplained phenomenon in magnetosphere-ionosphere system science. In the present study, we expand upon the Alfvén Wing model of CPCP saturation by investigating its impact on the magnetosphere-ionosphere current system, particularly the cusp-mantle dynamo associated with lobe field lines. In this expansion of the Alfven wing model, the ability of open flux tubes to deform in response to the fluid stress from the magnetosheath is governed by the magnetosheath plasma beta, which in turn reduces the Maxwell stress imposed on the ionospheric plasma to accelerate it against ion-neutral collisional drag. We perform 32 simulations using the Lyon-Fedder-Mobarry (LFM) Magnetohydrodynamic (MHD) model with varying solar wind density and IMF strength, as well as a dipole tilt of 25 degrees to investigate the relative importance of both magnetosheath plasma beta and ionospheric conductivity in the formation of Alfvén wing-like structures and the saturation of the CPCP. We find that the plasma beta in the magnetosheath is different in each hemisphere and dependent on the stagnation point location. We also show that the lobes become more bent in the summer hemisphere with higher ionospheric conductivity. We find that higher ionospheric conductivity also makes the summer hemisphere lobes more sensitive to changes in the magnetosheath beta.

Beta-catenin signaling plays a disparate role in different phases of fracture repair: implications for therapy to improve bone healing.

PubMed

Chen, Yan; Whetstone, Heather C; Lin, Alvin C; Nadesan, Puviindran; Wei, Qingxia; Poon, Raymond; Alman, Benjamin A

2007-07-31

Delayed fracture healing causes substantial disability and usually requires additional surgical treatments. Pharmacologic management to improve fracture repair would substantially improve patient outcome. The signaling pathways regulating bone healing are beginning to be unraveled, and they provide clues into pharmacologic management. The beta-catenin signaling pathway, which activates T cell factor (TCF)-dependent transcription, has emerged as a key regulator in embryonic skeletogenesis, positively regulating osteoblasts. However, its role in bone repair is unknown. The goal of this study was to explore the role of beta-catenin signaling in bone repair. Western blot analysis showed significant up-regulation of beta-catenin during the bone healing process. Using a beta-Gal activity assay to observe activation during healing of tibia fractures in a transgenic mouse model expressing a TCF reporter, we found that beta-catenin-mediated, TCF-dependent transcription was activated in both bone and cartilage formation during fracture repair. Using reverse transcription-PCR, we observed that several WNT ligands were expressed during fracture repair. Treatment with DKK1 (an antagonist of WNT/beta-catenin pathway) inhibited beta-catenin signaling and the healing process, suggesting that WNT ligands regulate beta-catenin. Healing was significantly repressed in mice conditionally expressing either null or stabilized beta-catenin alleles induced by an adenovirus expressing Cre recombinase. Fracture repair was also inhibited in mice expressing osteoblast-specific beta-catenin null alleles. In stark contrast, there was dramatically enhanced bone healing in mice expressing an activated form of beta-catenin, whose expression was restricted to osteoblasts. Treating mice with lithium activated beta-catenin in the healing fracture, but healing was enhanced only when treatment was started subsequent to the fracture. These results demonstrate that beta-catenin functions differently at different stages of fracture repair. In early stages, precise regulation of beta-catenin is required for pluripotent mesenchymal cells to differentiate to either osteoblasts or chondrocytes. Once these undifferentiated cells have become committed to the osteoblast lineage, beta-catenin positively regulates osteoblasts. This is a different function for beta-catenin than has previously been reported during development. Activation of beta-catenin by lithium treatment has potential to improve fracture healing, but only when utilized in later phases of repair, after mesenchymal cells have become committed to the osteoblast lineage.

Unpredicted Pitch Modulates Beta Oscillatory Power during Rhythmic Entrainment to a Tone Sequence.

PubMed

Chang, Andrew; Bosnyak, Dan J; Trainor, Laurel J

2016-01-01

Extracting temporal regularities in external stimuli in order to predict upcoming events is an essential aspect of perception. Fluctuations in induced power of beta band (15-25 Hz) oscillations in auditory cortex are involved in predictive timing during rhythmic entrainment, but whether such fluctuations are affected by prediction in the spectral (frequency/pitch) domain remains unclear. We tested whether unpredicted (i.e., unexpected) pitches in a rhythmic tone sequence modulate beta band activity by recording EEG while participants passively listened to isochronous auditory oddball sequences with occasional unpredicted deviant pitches at two different presentation rates. The results showed that the power in low-beta (15-20 Hz) was larger around 200-300 ms following deviant tones compared to standard tones, and this effect was larger when the deviant tones were less predicted. Our results suggest that the induced beta power activities in auditory cortex are consistent with a role in sensory prediction of both "when" (timing) upcoming sounds will occur as well as the prediction precision error of "what" (spectral content in this case). We suggest, further, that both timing and content predictions may co-modulate beta oscillations via attention. These findings extend earlier work on neural oscillations by investigating the functional significance of beta oscillations for sensory prediction. The findings help elucidate the functional significance of beta oscillations in perception.

A synergistic role for IL-1beta and TNFalpha in monocyte-derived IFNgamma inducing activity.

PubMed

Raices, Raquel M; Kannan, Yashaswini; Sarkar, Anasuya; Bellamkonda-Athmaram, Vedavathi; Wewers, Mark D

2008-11-01

Although much is known about classic IFNgamma inducers, little is known about the IFNgamma inducing capability of inflammasome-activated monocytes. In this study, supernatants from LPS/ATP-stimulated human monocytes were analyzed for their ability to induce IFNgamma production by KG-1 cells. Unexpectedly, monocyte-derived IFN inducing activity was detected, but it was completely inhibited by IL-1beta, not IL-18 blockade. Moreover, size-fractionation of the monocyte conditioned media dramatically reduced the IFNgamma inducing activity of IL-1beta, suggesting that IL-1beta requires a cofactor to induce IFNgamma production in KG-1 cells. Because TNFalpha is known to synergize with IL-1beta for various gene products, it was studied as the putative IL-1beta synergizing factor. Although recombinant TNFalpha (rTNFalpha) alone had no IFNgamma inducing activity, neutralization of TNFalpha in the monocyte conditioned media inhibited the IFNgamma inducing activity. Furthermore, rTNFalpha restored the IFNgamma inducing activity of the size-fractionated IL-1beta. Finally, rTNFalpha synergized with rIL-1beta, as well as with rIL-1alpha and rIL-18, for KG-1 IFNgamma release. These studies demonstrate a synergistic role between TNFalpha and IL-1 family members in the induction of IFNgamma production and give caution to interpretations of KG-1 functional assays designed to detect functional IL-18.

Unpredicted Pitch Modulates Beta Oscillatory Power during Rhythmic Entrainment to a Tone Sequence

PubMed Central

Chang, Andrew; Bosnyak, Dan J.; Trainor, Laurel J.

2016-01-01

Extracting temporal regularities in external stimuli in order to predict upcoming events is an essential aspect of perception. Fluctuations in induced power of beta band (15–25 Hz) oscillations in auditory cortex are involved in predictive timing during rhythmic entrainment, but whether such fluctuations are affected by prediction in the spectral (frequency/pitch) domain remains unclear. We tested whether unpredicted (i.e., unexpected) pitches in a rhythmic tone sequence modulate beta band activity by recording EEG while participants passively listened to isochronous auditory oddball sequences with occasional unpredicted deviant pitches at two different presentation rates. The results showed that the power in low-beta (15–20 Hz) was larger around 200–300 ms following deviant tones compared to standard tones, and this effect was larger when the deviant tones were less predicted. Our results suggest that the induced beta power activities in auditory cortex are consistent with a role in sensory prediction of both “when” (timing) upcoming sounds will occur as well as the prediction precision error of “what” (spectral content in this case). We suggest, further, that both timing and content predictions may co-modulate beta oscillations via attention. These findings extend earlier work on neural oscillations by investigating the functional significance of beta oscillations for sensory prediction. The findings help elucidate the functional significance of beta oscillations in perception. PMID:27014138

Monte Carlo calculated TG-60 dosimetry parameters for the {beta}{sup -} emitter {sup 153}Sm brachytherapy source

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

Sadeghi, Mahdi; Taghdiri, Fatemeh; Hamed Hosseini, S.

Purpose: The formalism recommended by Task Group 60 (TG-60) of the American Association of Physicists in Medicine (AAPM) is applicable for {beta} sources. Radioactive biocompatible and biodegradable {sup 153}Sm glass seed without encapsulation is a {beta}{sup -} emitter radionuclide with a short half-life and delivers a high dose rate to the tumor in the millimeter range. This study presents the results of Monte Carlo calculations of the dosimetric parameters for the {sup 153}Sm brachytherapy source. Methods: Version 5 of the (MCNP) Monte Carlo radiation transport code was used to calculate two-dimensional dose distributions around the source. The dosimetric parameters ofmore » AAPM TG-60 recommendations including the reference dose rate, the radial dose function, the anisotropy function, and the one-dimensional anisotropy function were obtained. Results: The dose rate value at the reference point was estimated to be 9.21{+-}0.6 cGy h{sup -1} {mu}Ci{sup -1}. Due to the low energy beta emitted from {sup 153}Sm sources, the dose fall-off profile is sharper than the other beta emitter sources. The calculated dosimetric parameters in this study are compared to several beta and photon emitting seeds. Conclusions: The results show the advantage of the {sup 153}Sm source in comparison with the other sources because of the rapid dose fall-off of beta ray and high dose rate at the short distances of the seed. The results would be helpful in the development of the radioactive implants using {sup 153}Sm seeds for the brachytherapy treatment.« less

Deletion of CXCR4 in cardiomyocytes exacerbates cardiac dysfunction following isoproterenol administration

PubMed Central

Wang, ER; Jarrah, AA; Benard, L; Chen, J; Schwarzkopf, M; Hadri, L; Tarzami, ST

2014-01-01

Altered alpha- and beta-adrenergic receptor signaling is associated with cardiac hypertrophy and failure. Stromal cell-derived factor-1α (SDF-1α) and its cognate receptor CXCR4 have been reported to mediate cardioprotection after injury through the mobilization of stem cells into injured tissue. However, little is known regarding whether SDF-1/CXCR4 induces acute protection following pathological hypertrophy and if so, by what molecular mechanism. We have previously reported that CXCR4 physically interacts with the beta-2 adrenergic receptor and modulates its down stream signaling. Here we have shown that CXCR4 expression prevents beta-adrenergic receptor induced hypertrophy. Cardiac beta-adrenergic receptors were stimulated with the implantation of a subcutaneous osmotic pump administrating isoproterenol and CXCR4 expression was selectively abrogated in cardiomyocytes using Cre-loxP-mediated gene recombination. CXCR4 knockout mice showed worsened fractional shortening and ejection fraction. CXCR4 ablation increased susceptibility to isoproterenol-induced heart failure, by upregulating apoptotic markers and reducing mitochondrial function; cardiac function decreases while fibrosis increases. Additionally, CXCR4 expression was rescued with the use of cardiotropic Adeno-associated viral-9 (AAV9) vectors. CXCR4 gene transfer reduced cardiac apoptotic signaling, improved mitochondrial function and resulted in a recovered cardiac function. Our results represent the first evidence that SDF-1/CXCR4 signaling mediates acute cardioprotection through modulating beta-adrenergic receptor signaling in vivo. PMID:24646609

The role of alpha3beta1 integrin in determining the supramolecular organization of laminin-5 in the extracellular matrix of keratinocytes.

PubMed

deHart, Gregory W; Healy, Kevin E; Jones, Jonathan C R

2003-02-01

Analyses of mice with targeted deletions in the genes for alpha3 and beta1 integrin suggest that the alpha3beta1 integrin heterodimer likely determines the organization of the extracellular matrix within the basement membrane of skin. Here we tested this hypothesis using keratinocytes derived from alpha3 integrin-null mice. We have compared the organizational state of laminin-5, a ligand of alpha3beta1 integrin, in the matrix of wild-type keratinocytes with that of laminin-5 in the matrix of alpha3 integrin-null cells. Laminin-5 distributes diffusely in arc structures in the matrix of wild-type mouse keratinocytes, whereas laminin-5 is organized into linear, spike-like arrays by the alpha3 integrin-null cells. The fact that alpha3 integrin-null cells are deficient in their ability to assemble a proper laminin-5 matrix is also shown by their failure to remodel laminin-5 when plated onto surfaces coated with purified laminin-5 protein. In sharp contrast, wild-type keratinocytes organize exogenously added laminin-5 into discrete ring-like organizations. These findings led us next to assess whether differences in laminin-5 organization in the matrix of the wild-type and alpha3 integrin-null cells impact cell behavior. Our results indicate that alpha3 integrin-null cells are more motile than their wild-type counterparts and leave extensive trails of laminin-5 over the surface on which they move. Moreover, HEK 293 cells migrate significantly more on the laminin-5-rich matrix derived from the alpha3 integrin-null cells than on the wild-type keratinocyte laminin-5 matrix. In addition, alpha3 integrin-null cells show low strength of adhesion to surfaces coated with purified laminin-5 compared to wild-type cells although both the wild type and the alpha3 integrin-null keratinocytes adhere equally strongly to laminin-5 that has been organized into arrays by other epithelial cells. These data suggest: (1) that alpha3beta1 integrin plays an important role in determining the incorporation of laminin-5 into its proper higher-order structure within the extracellular matrix of keratinocytes and (2) that the organizational state of laminin-5 has an influence on laminin-5 matrix function. Copyright 2003 Elsevier Science (USA)

Immunomodulatory effects of beta-glucan on neutrophil function in fathead minnows (Pimephales promelas Rafinesque, 1820).

PubMed

Palić, Dusan; Andreasen, Claire B; Herolt, Dawn M; Menzel, Bruce W; Roth, James A

2006-01-01

Stimulatory effects of yeast beta-1,3-1,6-glucans on neutrophils have long been recognized, but effects of glucans on degranulation of primary granules in fish neutrophils have not been previously reported. Neutrophil function was monitored during in vitro and in vivo application of glucans to non- (NS), acute- (AS) and chronically stressed (CS) fish. beta-Glucan proved to be a strong and quick (80%, 2 min) stimulant of degranulation. Dietary glucan increased degranulation in NS fish, and prevented a decrease in AS fish. Degranulation in CS fish returned to NS levels 3 days after the glucan diet was fed. Fathead minnows appear to be a useful model to investigate neutrophil degranulation in fish exposed to different environmental conditions and immunomodulators. Use of beta-glucans in fish diets prior to AS and during chronic stress can enhance neutrophil function, potentially increasing disease resistance and survival rates after transportation or exposure to poor water quality.

Neurotensin receptor-2 and -3 are crucial for the anti-apoptotic effect of neurotensin on pancreatic beta-TC3 cells.

PubMed

Béraud-Dufour, Sophie; Coppola, Thierry; Massa, Fabienne; Mazella, Jean

2009-12-01

The neuropeptide neurotensin (NT) has been recently shown to protect pancreatic beta cells from toxic agents-induced apoptosis through interaction with the NT receptor-2 (NTSR2) and activation of the phosphatidylinositol-3 kinase pathway. However, expression of the NT receptor-3/sortilin (NTSR3) in the mouse pancreatic beta cell line -TC3 led us to investigate its possible functional role in these cells. By using siRNA, immunoprecipitation, co-localization and caspase-3 assays,we provide evidence for a functional endogenous interaction between NTSR2 and NTSR3. Expression of both receptors is necessary for the protective action of NT on staurosporine-induced caspase-3 activity in -TC3 cells. Moreover, NTSR2 and NTSR3 co-immunoprecipitate and are co-localized at the plasma membrane. Thus, the NT response in beta cells is controlled by the formation of a functional complex between NTSR2 and NTSR3.

Double beta decays of {sup 106}Cd

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

Suhonen, Jouni

2011-12-16

The two-neutrino (2{nu}2{beta}) and neutrinoless (0{nu}2{beta}) double beta decays of {sup 106}Cd are studied for the transitions to the ground state 0{sub gs}{sup +} and 0{sup +} and 2{sup +} excited states in {sup 106}Pd by using realistic many-body wave functions calculated in the framework of the quasiparticle random-phase approximation. Effective, G-matrix-derived nuclear forces are used in realistic single-particle model spaces. All the possible channels, {beta}{sup +}{beta}{sup +}, {beta}{sup +}EC, and ECEC, are discussed for both the 2{nu}2{beta} and 0{nu}2{beta} decays. The associated half-lives are computed and particular attention is devoted to the study of the detectability of the resonantmore » neutrinoless double electron capture (R0{nu}ECEC) process in {sup 106}Cd. The calculations of the present article constitute the thus far most complete and up-to-date investigation of the double-beta-decay properties of {sup 106}Cd.« less

BetaTPred: prediction of beta-TURNS in a protein using statistical algorithms.

PubMed

Kaur, Harpreet; Raghava, G P S

2002-03-01

beta-turns play an important role from a structural and functional point of view. beta-turns are the most common type of non-repetitive structures in proteins and comprise on average, 25% of the residues. In the past numerous methods have been developed to predict beta-turns in a protein. Most of these prediction methods are based on statistical approaches. In order to utilize the full potential of these methods, there is a need to develop a web server. This paper describes a web server called BetaTPred, developed for predicting beta-TURNS in a protein from its amino acid sequence. BetaTPred allows the user to predict turns in a protein using existing statistical algorithms. It also allows to predict different types of beta-TURNS e.g. type I, I', II, II', VI, VIII and non-specific. This server assists the users in predicting the consensus beta-TURNS in a protein. The server is accessible from http://imtech.res.in/raghava/betatpred/

[Associations of insulin resistance and pancreatic beta-cell function with plasma glucose level in type 2 diabetes].

PubMed

Nian, Xiaoping; Sun, Gaisheng; Dou, Chunmei; Hou, Hongbo; Fan, Xiuping; Yu, Hongmei; Ma, Ling; He, Bingxian

2002-06-10

To investigate the influence of insulin resistance and pancreatic beta-cell function on plasma glucose level in type 2 diabetes so as to provide theoretical basis for reasonable selection of hypoglycemic agents. The plasma non-specific insulin (NSINS), true insulin (TI) and glucose in eight-one type 2 diabetics, 38 males and 43 females, with a mean age of 53 years, were examined 0, 30, 60 and 120 minutes after they had 75 grams of instant noodles. The patients were divided into two groups according to their fasting plasma glucose (FPG): group A (FPG < 8.89 mmol/L) and group B (FPG> = 8.89 mmol/L). The insulin resistance was evaluated by HOMA-IR, the beta-cell function was evaluated by HOMA-beta formula and the formula deltaI(30)/deltaG(30) = (deltaI(30)-deltaI(0))/(deltaG(30)-deltaG(0)). The insulin area under curve (INSAUC) was evaluated by the formula INSAUC=FINS/2+INS(30)+INS(60)+INS(120)/2. The mean FPG was 6.23 mmol/L in group A and 12.6 mmol/L in group B. PG2H was 11.7 mmol/L in group A and 19.2 mmol/L in group B. The TI levels in group B at 0, 30, 60, 120 min during standard meal test were significantly higher than those in group A: 6.15 +/- 1.06 vs 4.77 +/- 1.06, 9.76 +/- 1.1 vs 5.88 +/- 1.1,14.68 +/- 1.11 vs 6.87 +/- 1.1 and 17.13 +/- 1.12 vs 8.0 +/- 1.1 microU/dl (all P< 0.01). The NSINS showed the same trend. The insulin resistance in group B was 1.5 times that in group A. With the insulin resistance adjusted, the beta cell function in group A was 5 to 6 times that in group B. The INSAUC in group A was 1.66 times larger than that in group B, especially the INSAUC for true insulin (2 times larger). The contribution of insulin resistance and beta cell function to PG2H was half by half in group A and 1:8 in group B. beta cell function calculated by insulin (Homa-beta) explained 41% of the plasma glucose changes in group A and 54% of the plasma glucose changes in group B. The contribution of insulin deficiency to plasma glocose was 3.3.times that of insulin resistance in group A and was 9.5 times that of insulin resistance in group B. Insulin sensitivity explained 12% of the plasma glucose changes in group A, and only 5.7% of the plasma glucose changes in group B. Diabetics with FPG greater than 8.89 mmol/L have both higher insulin resistance and poorer beta-cell function, their hyperglycemia being caused mainly by beta-cell failure, The combined use of insulin sensitizer and insulin or insulintropic agents during the initial stage of treatment is effective.

Constraints on the magnetic fields in galaxies implied by the infrared-to-radio correlation

NASA Technical Reports Server (NTRS)

Helou, George; Bicay, M. D.

1990-01-01

A physical model is proposed for understanding the tight correlation between far-IR and nonthermal radio luminosities in star-forming galaxies. The approach suggests that the only constraint implied by the correlation is a universal relation whereby magnetic field strength scales with gas density to a power beta between 1/3 and 2/3, inclusive.

Beta-blockers for the treatment of problematic hemangiomas

PubMed Central

Sharma, Vishal K; Fraulin, Frankie OG; Dumestre, Danielle O; Walker, Lori; Harrop, A Robertson

2013-01-01

OBJECTIVE: To examine treatment indications, efficacy and side effects of oral beta-blockers for the treatment of problematic hemangiomas. METHODS: A retrospective review of patients with hemangiomas presenting to the Alberta Children’s Hospital Vascular Birthmark Clinic (Calgary, Alberta) between 2009 and 2011 was conducted. The subset of patients treated with oral beta-blockers was further characterized, investigating indication for treatment, response to treatment, time to resolution of indication, duration of treatment, occurrence of rebound growth and side effects of therapy. RESULTS: Between 2009 and 2011, 311 new patients with hemangiomas were seen, of whom 105 were treated with oral beta-blockers. Forty-five patients completed beta-blocker treatment while the remainder continue to receive therapy. Indications for treatment were either functional concerns (68.6%) or disfigurement (31.4%). Functional concerns included ulceration (29.5%), periocular location with potential for visual interference (28.6%), airway interference (4.8%), PHACES syndrome (3.8%), auditory interference (0.95%) and visceral location with congestive heart failure (0.95%). The median age at beta-blocker initiation was 3.3 months; median duration of therapy was 10.6 months; and median maximal treatment dose was 1.5 mg/kg/day for propranolol and 1.6 mg/kg/day for atenolol. Ninety-nine patients (94.3%) responded to therapy with size reduction, colour changes, softened texture and/or healing of ulceration. Rebound growth requiring an additional course of therapy was observed in 23 patients. Side effects from beta-blockers included cool extremities (26.7%), irritability (17.1%), lower gastrointestinal upset (14.3%), emesis (11.4%), hypotension (10.5%), poor feeding (7.6%), lethargy (4.8%), bronchospasm (0.95%) and rash (0.95%). Side effects did not result in complete discontinuation of beta-blocker treatment in any case; however, they prompted a switch to a different beta-blocker preparation in some cases. Resolution of the primary indication, requiring a median time of three months, occurred in 87 individuals (82.9%). CONCLUSIONS: Treatment of infantile hemangiomas with oral beta-blocker therapy is highly effective and well tolerated, with more than 94% of patients demonstrating a response to treatment and 90% showing resolution of the primary functional indication for treatment. PMID:24431932

Targeting Cellular Calcium Homeostasis to Prevent Cytokine-Mediated Beta Cell Death.

PubMed

Clark, Amy L; Kanekura, Kohsuke; Lavagnino, Zeno; Spears, Larry D; Abreu, Damien; Mahadevan, Jana; Yagi, Takuya; Semenkovich, Clay F; Piston, David W; Urano, Fumihiko

2017-07-17

Pro-inflammatory cytokines are important mediators of islet inflammation, leading to beta cell death in type 1 diabetes. Although alterations in both endoplasmic reticulum (ER) and cytosolic free calcium levels are known to play a role in cytokine-mediated beta cell death, there are currently no treatments targeting cellular calcium homeostasis to combat type 1 diabetes. Here we show that modulation of cellular calcium homeostasis can mitigate cytokine- and ER stress-mediated beta cell death. The calcium modulating compounds, dantrolene and sitagliptin, both prevent cytokine and ER stress-induced activation of the pro-apoptotic calcium-dependent enzyme, calpain, and partly suppress beta cell death in INS1E cells and human primary islets. These agents are also able to restore cytokine-mediated suppression of functional ER calcium release. In addition, sitagliptin preserves function of the ER calcium pump, sarco-endoplasmic reticulum Ca 2+ -ATPase (SERCA), and decreases levels of the pro-apoptotic protein thioredoxin-interacting protein (TXNIP). Supporting the role of TXNIP in cytokine-mediated cell death, knock down of TXNIP in INS1-E cells prevents cytokine-mediated beta cell death. Our findings demonstrate that modulation of dynamic cellular calcium homeostasis and TXNIP suppression present viable pharmacologic targets to prevent cytokine-mediated beta cell loss in diabetes.

Subthalamic nucleus phase–amplitude coupling correlates with motor impairment in Parkinson’s disease

PubMed Central

van Wijk, Bernadette C.M.; Beudel, Martijn; Jha, Ashwani; Oswal, Ashwini; Foltynie, Tom; Hariz, Marwan I.; Limousin, Patricia; Zrinzo, Ludvic; Aziz, Tipu Z.; Green, Alexander L.; Brown, Peter; Litvak, Vladimir

2016-01-01

Objective High-amplitude beta band oscillations within the subthalamic nucleus are frequently associated with Parkinson’s disease but it is unclear how they might lead to motor impairments. Here we investigate a likely pathological coupling between the phase of beta band oscillations and the amplitude of high-frequency oscillations around 300 Hz. Methods We analysed an extensive data set comprising resting-state recordings obtained from deep brain stimulation electrodes in 33 patients before and/or after taking dopaminergic medication. We correlated mean values of spectral power and phase–amplitude coupling with severity of hemibody bradykinesia/rigidity. In addition, we used simultaneously recorded magnetoencephalography to look at functional interactions between the subthalamic nucleus and ipsilateral motor cortex. Results Beta band power and phase–amplitude coupling within the subthalamic nucleus correlated positively with severity of motor impairment. This effect was more pronounced within the low-beta range, whilst coherence between subthalamic nucleus and motor cortex was dominant in the high-beta range. Conclusions We speculate that the beta band might impede pro-kinetic high-frequency activity patterns when phase–amplitude coupling is prominent. Furthermore, results provide evidence for a functional subdivision of the beta band into low and high frequencies. Significance Our findings contribute to the interpretation of oscillatory activity within the cortico-basal ganglia circuit. PMID:26971483

Developing radiopure copper alloys for high strength low background applications

NASA Astrophysics Data System (ADS)

Suriano, A. M.; Howard, S. M.; Christofferson, C. D.; Arnquist, I. J.; Hoppe, E. W.

2018-01-01

High purity copper continues to play an important role for ultra-low-background detectors. Measurements of rare nuclear decays, e.g. neutrinoless double-beta decay, and searches for dark matter can require construction materials that have high thermal and electrical conductivity with bulk radiopurity less than one micro-Becquerel per kilogram. However, experiments currently using components constructed of radiopure electroformed copper struggle with design of structural and mechanical parts due to the physical properties of pure copper. A higher strength material which possesses many of the favorable attributes of copper yet remains radiopure is desired. A number of copper alloying candidates which may provide improved mechanical performance and adequate radiopurity were considered. Development of an electrodeposited copper-chrome alloy from additive-free electrolyte systems is discussed. The resulting material is shown to possess high strength and meets the aforementioned radiopurity goals.

Beta-lactamase induction and cell wall metabolism in Gram-negative bacteria

PubMed Central

Zeng, Ximin; Lin, Jun

2013-01-01

Production of beta-lactamases, the enzymes that degrade beta-lactam antibiotics, is the most widespread and threatening mechanism of antibiotic resistance. In the past, extensive research has focused on the structure, function, and ecology of beta-lactamases while limited efforts were placed on the regulatory mechanisms of beta-lactamases. Recently, increasing evidence demonstrate a direct link between beta-lactamase induction and cell wall metabolism in Gram-negative bacteria. Specifically, expression of beta-lactamase could be induced by the liberated murein fragments, such as muropeptides. This article summarizes current knowledge on cell wall metabolism, beta-lactam antibiotics, and beta-lactamases. In particular, we comprehensively reviewed recent studies on the beta-lactamase induction by muropeptides via two major molecular mechanisms (the AmpG–AmpR–AmpC pathway and BlrAB-like two-component regulatory system) in Gram-negative bacteria. The signaling pathways for beta-lactamase induction offer a broad array of promising targets for the discovery of new antibacterial drugs used for combination therapies. Therefore, to develop effective mitigation strategies against the widespread beta-lactam resistance, examination of the molecular basis of beta-lactamase induction by cell wall fragment is highly warranted. PMID:23734147

Glassy aging with modified Kohlrausch-Williams-Watts form

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

Sen Gupta, Bhaskar; Das, Shankar P.

2007-12-15

In this paper, we address the question of whether aging in the nonequilibrium glassy state is controlled by the equilibrium {alpha}-relaxation process, which occurs at temperatures above T{sub g}. Recently, Lunkenheimer et al. [Phys. Rev. Lett. 95, 055702 (2005)] proposed a model for the glassy aging data of dielectric relaxation using a modified Kohlrausch-Williams-Watts form exp[-(t{sub age}/{tau}{sub age}){sup {beta}{sub age}}]. The aging time t{sub age} dependence of the relaxation time {tau}{sub age} is defined by these authors through a functional relation involving the corresponding frequency {nu}(t{sub age})=1/(2{pi}{tau}{sub age}), but the stretching exponent {beta}{sub age} is the same as {beta}{sub {alpha}},more » the {alpha}-relaxation stretching exponent. We present here an alternative functional form for {tau}{sub age}(t{sub age}) directly involving the relaxation time itself. The proposed model fits the data of Lunkenheimer et al. perfectly with a stretching exponent {beta}{sub age} different from {beta}{sub {alpha}}.« less

Material transport in laser-heated diamond anvil cell melting experiments

NASA Technical Reports Server (NTRS)

Campbell, Andrew J.; Heinz, Dion L.; Davis, Andrew M.

1992-01-01

A previously undocumented effect in the laser-heated diamond anvil cell, namely, the transport of molten species through the sample chamber, over distances large compared to the laser beam diameter, is presented. This effect is exploited to determine the melting behavior of high-pressure silicate assemblages of olivine composition. At pressures where beta-spinel is the phase melted, relative strengths of partitioning can be estimated for the incompatible elements studied. Iron was found to partition into the melt from beta-spinel less strongly than calcium, and slightly more strongly than manganese. At higher pressures, where a silicate perovskite/magnesiowuestite assemblage is melted, it is determined that silicate perovskite is the liquidus phase, with iron-rich magnesiowuestite accumulating at the end of the laser-melted stripe.

Reaction diffusion in the nickel-chromium-aluminum and cobalt-chromium-aluminum systems

NASA Technical Reports Server (NTRS)

Levine, S. R.

1977-01-01

The effects of MCrAl coating-substrate interdiffusion on oxidation life and the general mutliphase, multicomponent diffusion problem were examined. Semi-infinite diffusion couples that had sources representing coatings and sinks representing gas turbine alloys were annealed at 1,000, 1,095, 1,150, or 1,205 C for as long as 500 hours. The source and sink aluminum and chromium contents and the base metal (cobalt or nickel) determined the parabolic diffusion rate constants of the couples and predicted finite coating lives. The beta source strength concept provided a method (1) for correlating beta recession rate constants with composition; (2) for determining reliable average total, diffusion, and constitutional activation energies; and (3) for calculating interdiffusion coefficients.

A low-cost hierarchical nanostructured beta-titanium alloy with high strength

DOE PAGES

Devaraj, Arun; Joshi, Vineet V.; Srivastava, Ankit; ...

2016-04-01

Lightweighting of automobiles by use of novel low-cost, high strength-to-weight ratio structural materials can reduce the consumption of fossil fuels and in turn CO 2 emission. Working towards this goal we achieved high strength in a low cost β-titanium alloy, Ti-1Al-8V-5Fe (Ti185), by hierarchical nanostructure consisting of homogenous distribution of micron-scale and nanoscale α-phase precipitates within the β-phase matrix. The sequence of phase transformation leading to this hierarchical nanostructure is explored using electron microscopy and atom probe tomography. Our results suggest that the high number density of nanoscale α-phase precipitates in the β-phase matrix is due to ω assisted nucleationmore » of α resulting in high tensile strength, greater than any current commercial titanium alloy. Furthermore hierarchical nanostructured Ti185 serves as an excellent candidate for replacing costlier titanium alloys and other structural alloys for cost-effective lightweighting applications.« less

A low-cost hierarchical nanostructured beta-titanium alloy with high strength

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

Devaraj, Arun; Joshi, Vineet V.; Srivastava, Ankit

Lightweighting of automobiles by use of novel low-cost, high strength-to-weight ratio structural materials can reduce the consumption of fossil fuels and in turn CO 2 emission. Working towards this goal we achieved high strength in a low cost β-titanium alloy, Ti-1Al-8V-5Fe (Ti185), by hierarchical nanostructure consisting of homogenous distribution of micron-scale and nanoscale α-phase precipitates within the β-phase matrix. The sequence of phase transformation leading to this hierarchical nanostructure is explored using electron microscopy and atom probe tomography. Our results suggest that the high number density of nanoscale α-phase precipitates in the β-phase matrix is due to ω assisted nucleationmore » of α resulting in high tensile strength, greater than any current commercial titanium alloy. Furthermore hierarchical nanostructured Ti185 serves as an excellent candidate for replacing costlier titanium alloys and other structural alloys for cost-effective lightweighting applications.« less

Predictors of hospital CEO affiliation with a professional association.

PubMed

Khaliq, Amir A; Walston, Stephen L

2012-01-01

Based on a 2008 cross-sectional survey of 582 hospital CEOs in the United States, this study reports the findings of two logistic regression models designed to identify CEO and hospital characteristics associated with Member and Fellow status in the American College of Healthcare Executives (ACHE). The purpose of the study was to understand the personal and organizational characteristics of those CEOs who choose to be Members and Fellows of a professional association such as ACHE. The results showed that most (74 percent) of the respondents considered ACHE to be their primary professional association. The results also revealed that a master's degree in health administration [beta = .88, t(427) = 5.35, p < .0001], male gender [beta = .59, t(427) = 3.01, p = .002], and financial incentives provided by the parent hospital [beta = .25, t(427) = 2.73, p = .006] were statistically positively linked with Member status in ACHE. A master's degree in health administration [beta = .81, t(424) = 5.79, p < .0001], male gender [beta = .39, t(424) = 2.25, p = .02], and age [beta = .02, t(424) 2.32, p = .02] were also statistically positively associated with Fellow status in ACHE. Notably, organizational factors such as size, geographic location, for-profit status, and financial strength of the hospital do not seem to play an important role in the CEOs' decision to become a Member or Fellow of ACHE. The implication of these findings is that membership and fellowship at a professional association are influenced by characteristics of the individual, and incentives provided by employers can encourage employees to get involved with their professional associations.

Electroencephalographic identifiers of motor adaptation learning

NASA Astrophysics Data System (ADS)

Özdenizci, Ozan; Yalçın, Mustafa; Erdoğan, Ahmetcan; Patoğlu, Volkan; Grosse-Wentrup, Moritz; Çetin, Müjdat

2017-08-01

Objective. Recent brain-computer interface (BCI) assisted stroke rehabilitation protocols tend to focus on sensorimotor activity of the brain. Relying on evidence claiming that a variety of brain rhythms beyond sensorimotor areas are related to the extent of motor deficits, we propose to identify neural correlates of motor learning beyond sensorimotor areas spatially and spectrally for further use in novel BCI-assisted neurorehabilitation settings. Approach. Electroencephalographic (EEG) data were recorded from healthy subjects participating in a physical force-field adaptation task involving reaching movements through a robotic handle. EEG activity recorded during rest prior to the experiment and during pre-trial movement preparation was used as features to predict motor adaptation learning performance across subjects. Main results. Subjects learned to perform straight movements under the force-field at different adaptation rates. Both resting-state and pre-trial EEG features were predictive of individual adaptation rates with relevance of a broad network of beta activity. Beyond sensorimotor regions, a parieto-occipital cortical component observed across subjects was involved strongly in predictions and a fronto-parietal cortical component showed significant decrease in pre-trial beta-powers for users with higher adaptation rates and increase in pre-trial beta-powers for users with lower adaptation rates. Significance. Including sensorimotor areas, a large-scale network of beta activity is presented as predictive of motor learning. Strength of resting-state parieto-occipital beta activity or pre-trial fronto-parietal beta activity can be considered in BCI-assisted stroke rehabilitation protocols with neurofeedback training or volitional control of neural activity for brain-robot interfaces to induce plasticity.

Post-Movement Beta Activity in Sensorimotor Cortex Indexes Confidence in the Estimations from Internal Models.

PubMed

Tan, Huiling; Wade, Cian; Brown, Peter

2016-02-03

Beta oscillations are a dominant feature of the sensorimotor system. A transient and prominent increase in beta oscillations is consistently observed across the sensorimotor cortical-basal ganglia network after cessation of voluntary movement: the post-movement beta synchronization (PMBS). Current theories about the function of the PMBS have been focused on either the closure of motor response or the processing of sensory afferance. Computational models of sensorimotor control have emphasized the importance of the integration between feedforward estimation and sensory feedback, and therefore the putative motor and sensory functions of beta oscillations may reciprocally interact with each other and in fact be indissociable. Here we show that the amplitude of sensorimotor PMBS is modulated by the history of visual feedback of task-relevant errors, and negatively correlated with the trial-to-trial exploratory adjustment in a sensorimotor adaptation task in young healthy human subjects. The PMBS also negatively correlated with the uncertainty associated with the feedforward estimation, which was recursively updated in light of new sensory feedback, as identified by a Bayesian learning model. These results reconcile the two opposing motor and sensory views of the function of PMBS, and suggest a unifying theory in which PMBS indexes the confidence in internal feedforward estimation in Bayesian sensorimotor integration. Its amplitude simultaneously reflects cortical sensory processing and signals the need for maintenance or adaptation of the motor output, and if necessary, exploration to identify an altered sensorimotor transformation. For optimal sensorimotor control, sensory feedback and feedforward estimation of a movement's sensory consequences should be weighted by the inverse of their corresponding uncertainties, which require recursive updating in a dynamic environment. We show that post-movement beta activity (13-30 Hz) over sensorimotor cortex in young healthy subjects indexes the evaluation of uncertainty in feedforward estimation. Our work contributes to the understanding of the function of beta oscillations in sensorimotor control, and provides further insight into how aberrant beta activity can contribute to the pathophysiology of movement disorders. Copyright © 2016 Tan et al.

Synthesis and pharmacological characterization of beta2-adrenergic agonist enantiomers: zilpaterol.

PubMed

Kern, Christopher; Meyer, Thorsten; Droux, Serge; Schollmeyer, Dieter; Miculka, Christian

2009-03-26

The beta-adrenergic agonist 1 (zilpaterol) is used as production enhancer in cattle. Binding experiments of separated enantiomers on recombinant human beta(2)-adrenergic and mu-opioid receptors and functional studies showed that the (-)-1 enantiomer accounts for essentially all the beta(2)-adrenergic agonist activity and that it exhibits less affinity toward the mu-opioid receptor than (+)-1, which is a mu-opioid receptor antagonist. X-ray crystallography revealed the absolute configuration of (-)-1 to be 6R,7R.

Affective attitudes to face images associated with intracerebral EEG source location before face viewing.

PubMed

Pizzagalli, D; Koenig, T; Regard, M; Lehmann, D

1999-01-01

We investigated whether different, personality-related affective attitudes are associated with different brain electric field (EEG) sources before any emotional challenge (stimulus exposure). A 27-channel EEG was recorded in 15 subjects during eyes-closed resting. After recording, subjects rated 32 images of human faces for affective appeal. The subjects in the first (i.e., most negative) and fourth (i.e., most positive) quartile of general affective attitude were further analyzed. The EEG data (mean=25+/-4. 8 s/subject) were subjected to frequency-domain model dipole source analysis (FFT-Dipole-Approximation), resulting in 3-dimensional intracerebral source locations and strengths for the delta-theta, alpha, and beta EEG frequency band, and for the full range (1.5-30 Hz) band. Subjects with negative attitude (compared to those with positive attitude) showed the following source locations: more inferior for all frequency bands, more anterior for the delta-theta band, more posterior and more right for the alpha, beta and 1.5-30 Hz bands. One year later, the subjects were asked to rate the face images again. The rating scores for the same face images were highly correlated for all subjects, and original and retest affective mean attitude was highly correlated across subjects. The present results show that subjects with different affective attitudes to face images had different active, cerebral, neural populations in a task-free condition prior to viewing the images. We conclude that the brain functional state which implements affective attitude towards face images as a personality feature exists without elicitors, as a continuously present, dynamic feature of brain functioning. Copyright 1999 Elsevier Science B.V.

Validity, prognostic value and optimal cutoff of respiratory muscle strength in patients with chronic heart failure changes with beta-blocker treatment.

PubMed

Frankenstein, Lutz; Nelles, Manfred; Meyer, F Joachim; Sigg, Caroline; Schellberg, Dieter; Remppis, B Andrew; Katus, Hugo A; Zugck, Christian

2009-08-01

Training studies frequently use maximum inspiratory mouth occlusion pressure (PImax) as a therapeutic target and surrogate marker. For patients on beta-blocker (BBL), prognostic data allowing this extrapolation do not exist. Furthermore, the effects of BBL, mainstay of modern chronic heart failure therapy, on respiratory muscle function remain controversial. Finally, no proper separate cutoff according to treatment exists. Prospective, observational inclusion of patients with stable systolic chronic heart failure and recording of 1 year and all-time mortality for endpoint analysis. In 686 patients, 81% men, 494 patients on BBL, PImax was measured along with clinical evaluation. The median follow-up was 50 months (interquartile range: 26-75 months). Patients with or without BBL did not differ significantly for PImax, percentage of predicted PImax or other marker of disease severity. PImax was a significant (hazard ratio: 0.925; 95% confidence interval: 0.879-0.975; chi(2): 8.62) marker of adverse outcome, independent of BBL-status or aetiology. Percentage of predicted PImax was not independent of PImax. The cutoff identified through receiver-operated characteristics for 1-year mortality was 4.14 kPa for patients on BBL and 7.29 kPa for patients not on BBL. When separated accordingly, 1-year mortality was 8.5 versus 21.4%, P=0.02, for patients not on BBL and 4.3 versus 16.2%, P<0.001, for patients on BBL. This study fills the gap between trials targeting respiratory muscle on a functional basis and the resultant prognostic information with regard to BBL. BBL lowered the optimal PImax cutoff values for risk stratification without changing the measured values of PImax. This should be considered at inclusion and evaluation of trials and interpretation of exercise parameters.

Absence of association of a single-nucleotide polymorphism in the TERT-CLPTM1L locus with age-related phenotypes in a large multicohort study: the HALCyon programme.

PubMed

Alfred, Tamuno; Ben-Shlomo, Yoav; Cooper, Rachel; Hardy, Rebecca; Cooper, Cyrus; Deary, Ian J; Elliott, Jane; Gunnell, David; Harris, Sarah E; Kivimaki, Mika; Kumari, Meena; Martin, Richard M; Power, Chris; Sayer, Avan Aihie; Starr, John M; Kuh, Diana; Day, Ian N M

2011-06-01

Several age-related traits are associated with shorter telomeres, the structures that cap the end of linear chromosomes. A common polymorphism near the telomere maintenance gene TERT has been associated with several cancers, but relationships with other aging traits such as physical capability have not been reported. As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, men and women aged between 44 and 90 years from nine UK cohorts were genotyped for the single-nucleotide polymorphism (SNP) rs401681. We then investigated relationships between the SNP and 30 age-related phenotypes, including cognitive and physical capability, blood lipid levels and lung function, pooling within-study genotypic effects in meta-analyses. No significant associations were found between the SNP and any of the cognitive performance tests (e.g. pooled beta per T allele for word recall z-score = 0.02, 95% CI: -0.01 to 0.04, P-value = 0.12, n = 18,737), physical performance tests (e.g. pooled beta for grip strength = -0.02, 95% CI: -0.045 to 0.006, P-value = 0.14, n = 11,711), blood pressure, lung function or blood test measures. Similarly, no differences in observations were found when considering follow-up measures of cognitive or physical performance after adjusting for its measure at an earlier assessment. The lack of associations between SNP rs401681 and a wide range of age-related phenotypes investigated in this large multicohort study suggests that while this SNP may be associated with cancer, it is not an important contributor to other markers of aging. © 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.

The Synthesis of N-Acetyllactosamine Functionalized Dendrimers, and the Functionalization of Silica Surfaces Using Tunable Dendrons and beta-Cyclodextrins

NASA Astrophysics Data System (ADS)

Ennist, Jessica Helen

Galectin-3 is beta-galactoside binding protein which is found in many healthy cells. In cancer, the galectin-3/tumor-associated Thomsen-Friedenreich antigen (TF antigen) interaction has been implicated in heterotypic and homotypic cellular adhesion and apoptotic signaling pathways. However, a stronger mechanistic understanding of the role of galectin-3 in these processes is needed. N-acetyllactosamine (LacNAc) is a non-native ligand for galectin-3 which binds with comparable affinity to the TF antigen and therefore an important ligand to study galectin-3 mediated processes. To study galectin-3 mediated homotypic cellular aggregation, four generations of polyamidoamine (PAMAM) dendrimers were functionalized with N-acetyllactosamine using a four-step chemoenzymatic route. The enzymatic step controlled the regiochemistry of the galactose addition to N-acetylglucosamine functionalized dendrimers using a recombinant beta-1,4-Galactosyltransferase-/UDP-4'-Gal Epimerase Fusion Protein (lgtB-galE). Homotypic cellular aggregation, which is promoted by the presence of galectin-3 as it binds to glycosides at the cell surface, was studied using HT-1080 fibrosarcoma, A549 lung, and DU-145 prostate cancer cell lines. In the presence of small LacNAc functionalized PAMAM dendrimers, galectin-3 induced cancer cellular aggregation was inhibited. However, the larger glycodendrimers induced homotypic cellular aggregation. Additionally, novel poly(aryl ether) dendronized silica surfaces designed for reversible adsorbtion of targeted analytes were synthesized, and characterization using X-ray Photoelectron Spectroscopy (XPS) was performed. Using a Cu(I) mediated cycloaddition "click" reaction, beta-cyclodextrin was appended to dendronized surfaces via triazole formation and also to a non-dendronized surface for comparison purposes. First generation G(1) dendrons have more than 6 times greater capacity to adsorb targeted analytes than slides functionalized with monomeric beta-cyclodextrin and are 2 times greater than slides functionalized with larger generation dendrons. This study reported beta-cyclodextrin functionalized surfaces can undergo a triggered release of the adsorbent, but otherwise retained the targeted analyte through multiple aqueous washes. Therefore, a new generation of G(1) dendronized surfaces capable of reversible adsorption were developed by heterogeneously appending sulfonic acid/pyridine end-groups. Auger Electron Spectroscopy (AES) was used to quantify the ratio of groups installed. Furthermore, G(1) dendronized surfaces were functionalized homogenously with sulfonic acid and pyridine for comparison and with chiral amino acids for chiral recognition studies.

Basal Ganglia Beta Oscillations Accompany Cue Utilization

PubMed Central

Leventhal, Daniel K.; Gage, Gregory J.; Schmidt, Robert; Pettibone, Jeffrey R.; Case, Alaina C.; Berke, Joshua D.

2012-01-01

SUMMARY Beta oscillations in cortical-basal ganglia (BG) circuits have been implicated in normal movement suppression and motor impairment in Parkinson’s disease. To dissect the functional correlates of these rhythms we compared neural activity during four distinct variants of a cued choice task in rats. Brief beta (~20 Hz) oscillations occurred simultaneously throughout the cortical-BG network, both spontaneously and at precise moments of task performance. Beta phase was rapidly reset in response to salient cues, yet increases in beta power were not rigidly linked to cues, movements, or movement suppression. Rather, beta power was enhanced after cues were used to determine motor output. We suggest that beta oscillations reflect a postdecision stabilized state of cortical-BG networks, which normally reduces interference from alternative potential actions. The abnormally strong beta seen in Parkinson’s Disease may reflect overstabilization of these networks, producing pathological persistence of the current motor state. PMID:22325204

Apparatus and method for closed-loop control of reactor power in minimum time

DOEpatents

Bernard, Jr., John A.

1988-11-01

Closed-loop control law for altering the power level of nuclear reactors in a safe manner and without overshoot and in minimum time. Apparatus is provided for moving a fast-acting control element such as a control rod or a control drum for altering the nuclear reactor power level. A computer computes at short time intervals either the function: .rho.=(.beta.-.rho.).omega.-.lambda..sub.e '.rho.-.SIGMA..beta..sub.i (.lambda..sub.i -.lambda..sub.e ')+l* .omega.+l* [.omega..sup.2 +.lambda..sub.e '.omega.] or the function: .rho.=(.beta.-.rho.).omega.-.lambda..sub.e .rho.-(.lambda..sub.e /.lambda..sub.e)(.beta.-.rho.)+l* .omega.+l* [.omega..sup.2 +.lambda..sub.e .omega.-(.lambda..sub.e /.lambda..sub.e).omega.] These functions each specify the rate of change of reactivity that is necessary to achieve a specified rate of change of reactor power. The direction and speed of motion of the control element is altered so as to provide the rate of reactivity change calculated using either or both of these functions thereby resulting in the attainment of a new power level without overshoot and in minimum time. These functions are computed at intervals of approximately 0.01-1.0 seconds depending on the specific application.

Left ventricular diastolic function in patients with treated haemochromatosis.

PubMed

Davidsen, Einar Skulstad; Omvik, Per; Hervig, Tor; Gerdts, Eva

2009-02-01

We recently demonstrated reduced exercise capacity in phlebotomy treated genetic haemochromatosis in spite of normal systolic function. The present objective was to investigate diastolic function at rest. Diastolic function was echocardiographically assessed in 132 phlebotomy treated genetic haemochromatosis patients and 50 controls. Patients had higher body mass index and heart rate, higher transmitral early (E) (11.2+/-2.6 versus 10.4+/-2.2 cm) and atrial (A) (5.7+/-1.6 versus 5.0+/-1.6) velocity time integrals, pulmonary venous systolic peak velocity (0.58+/-0.12 versus 0.54+/-0.13 m/s) and ratio of E to spectral tissue Doppler E' velocity (6.3+/-1.6 versus 5.6+/-1.4, all p <0.05). Independently of age, heart rate, systolic blood pressure and body weight, having haemochromatosis remained statistically significantly associated with higher E (beta=0.27) and A (beta =0.18) velocity time integrals, pulmonary venous systolic peak velocity (beta =0.21), and E/E'-ratio (beta=0.25) in separate multivariate analyses (all p <0.05). In the youngest age tertile, patients had longer isovolumic relaxation time and lower E' than controls. Our findings are compatible with mildly impaired diastolic function in treated haemochromatosis, with delayed relaxation in the younger tertile, and an elevated filling pressure and pseudonormalisation with increasing age.

Amyloid-beta oligomers impair fear conditioned memory in a calcineurin-dependent fashion in mice.

PubMed

Dineley, Kelly T; Kayed, Rakez; Neugebauer, Volker; Fu, Yu; Zhang, Wenru; Reese, Lindsay C; Taglialatela, Giulio

2010-10-01

Soluble oligomeric aggregates of the amyloid-beta (A beta) peptide are believed to be the most neurotoxic A beta species affecting the brain in Alzheimer disease (AD), a terminal neurodegenerative disorder involving severe cognitive decline underscored by initial synaptic dysfunction and later extensive neuronal death in the CNS. Recent evidence indicates that A beta oligomers are recruited at the synapse, oppose expression of long-term potentiation (LTP), perturb intracellular calcium balance, disrupt dendritic spines, and induce memory deficits. However, the molecular mechanisms behind these outcomes are only partially understood; achieving such insight is necessary for the comprehension of A beta-mediated neuronal dysfunction. We have investigated the role of the phosphatase calcineurin (CaN) in these pathological processes of AD. CaN is especially abundant in the CNS, where it is involved in synaptic activity, LTP, and memory function. Here, we describe how oligomeric A beta treatment causes memory deficits and depresses LTP expression in a CaN-dependent fashion. Mice given a single intracerebroventricular injection of A beta oligomers exhibited increased CaN activity and decreased pCREB, a transcription factor involved in proper synaptic function, accompanied by decreased memory in a fear conditioning task. These effects were reversed by treatment with the CaN inhibitor FK506. We further found that expression of hippocampal LTP in acutely cultured rodent brain slices was opposed by A beta oligomers and that this effect was also reversed by FK506. Collectively, these results indicate that CaN activation may play a central role in mediating synaptic and memory disruption induced by acute oligomeric A beta treatment in mice. (c) 2010 Wiley-Liss, Inc.

β-Arrestin2 plays a key role in the modulation of the pancreatic beta cell mass in mice.

PubMed

Ravier, Magalie A; Leduc, Michele; Richard, Joy; Linck, Nathalie; Varrault, Annie; Pirot, Nelly; Roussel, Morgane M; Bockaert, Joël; Dalle, Stéphane; Bertrand, Gyslaine

2014-03-01

Beta cell failure due to progressive secretory dysfunction and limited expansion of beta cell mass is a key feature of type 2 diabetes. Beta cell function and mass are controlled by glucose and hormones/neurotransmitters that activate G protein-coupled receptors or receptor tyrosine kinases. We have investigated the role of β-arrestin (ARRB)2, a scaffold protein known to modulate such receptor signalling, in the modulation of beta cell function and mass, with a specific interest in glucagon-like peptide-1 (GLP-1), muscarinic and insulin receptors. β-arrestin2-knockout mice and their wild-type littermates were fed a normal or a high-fat diet (HFD). Glucose tolerance, insulin sensitivity and insulin secretion were assessed in vivo. Beta cell mass was evaluated in pancreatic sections. Free cytosolic [Ca(2+)] and insulin secretion were determined using perifused islets. The insulin signalling pathway was evaluated by western blotting. Arrb2-knockout mice exhibited impaired glucose tolerance and insulin secretion in vivo, but normal insulin sensitivity compared with wild type. Surprisingly, the absence of ARRB2 did not affect glucose-stimulated insulin secretion or GLP-1- and acetylcholine-mediated amplifications from perifused islets, but it decreased the islet insulin content and beta cell mass. Additionally, there was no compensatory beta cell mass expansion through proliferation in response to the HFD. Furthermore, Arrb2 deletion altered the islet insulin signalling pathway. ARRB2 is unlikely to be involved in the regulation of insulin secretion, but it is required for beta cell mass plasticity. Additionally, we provide new insights into the mechanisms involved in insulin signalling in beta cells.

Meta-analysis of studies with bivariate binary outcomes: a marginal beta-binomial model approach.

PubMed

Chen, Yong; Hong, Chuan; Ning, Yang; Su, Xiao

2016-01-15

When conducting a meta-analysis of studies with bivariate binary outcomes, challenges arise when the within-study correlation and between-study heterogeneity should be taken into account. In this paper, we propose a marginal beta-binomial model for the meta-analysis of studies with binary outcomes. This model is based on the composite likelihood approach and has several attractive features compared with the existing models such as bivariate generalized linear mixed model (Chu and Cole, 2006) and Sarmanov beta-binomial model (Chen et al., 2012). The advantages of the proposed marginal model include modeling the probabilities in the original scale, not requiring any transformation of probabilities or any link function, having closed-form expression of likelihood function, and no constraints on the correlation parameter. More importantly, because the marginal beta-binomial model is only based on the marginal distributions, it does not suffer from potential misspecification of the joint distribution of bivariate study-specific probabilities. Such misspecification is difficult to detect and can lead to biased inference using currents methods. We compare the performance of the marginal beta-binomial model with the bivariate generalized linear mixed model and the Sarmanov beta-binomial model by simulation studies. Interestingly, the results show that the marginal beta-binomial model performs better than the Sarmanov beta-binomial model, whether or not the true model is Sarmanov beta-binomial, and the marginal beta-binomial model is more robust than the bivariate generalized linear mixed model under model misspecifications. Two meta-analyses of diagnostic accuracy studies and a meta-analysis of case-control studies are conducted for illustration. Copyright © 2015 John Wiley & Sons, Ltd.

Opposite effects of dihydrosphingosine 1-phosphate and sphingosine 1-phosphate on transforming growth factor-beta/Smad signaling are mediated through the PTEN/PPM1A-dependent pathway.

PubMed

Bu, Shizhong; Kapanadze, Bagrat; Hsu, Tien; Trojanowska, Maria

2008-07-11

Transforming growth factor-beta (TGF-beta) is an important regulator of physiological connective tissue biosynthesis and plays a central role in pathological tissue fibrosis. Previous studies have established that a biologically active lipid mediator, sphingosine 1-phosphate (S1P), mimics some of the profibrotic functions of TGF-beta through cross-activation of Smad signaling. Here we report that another product of sphingosine kinase, dihydrosphingosine 1-phosphate (dhS1P), has an opposite role in the regulation of TGF-beta signaling. In contrast to S1P, dhS1P inhibits TGF-beta-induced Smad2/3 phosphorylation and up-regulation of collagen synthesis. The effects of dhS1P require a lipid phosphatase, PTEN, a key modulator of cell growth and survival. dhS1P stimulates phosphorylation of the C-terminal domain of PTEN and its subsequent translocation into the nucleus. We demonstrate a novel function of nuclear PTEN as a co-factor of the Smad2/3 phosphatase, PPM1A. Complex formation of PTEN with PPM1A does not require the lipid phosphatase activity but depends on phosphorylation of the serine/threonine residues located in the C-terminal domain of PTEN. Upon complex formation with PTEN, PPM1A is protected from degradation induced by the TGF-beta signaling. Consequently, overexpression of PTEN abrogates TGF-beta-induced Smad2/3 phosphorylation. This study establishes a novel role for nuclear PTEN in the stabilization of PPM1A. PTEN-mediated cross-talk between the sphingolipid and TGF-beta signaling pathways may play an important role in physiological and pathological TGF-beta signaling.

The complexity of selection at the major primate beta-defensin locus.

PubMed

Semple, Colin A M; Maxwell, Alison; Gautier, Philippe; Kilanowski, Fiona M; Eastwood, Hayden; Barran, Perdita E; Dorin, Julia R

2005-05-18

We have examined the evolution of the genes at the major human beta-defensin locus and the orthologous loci in a range of other primates and mouse. For the first time these data allow us to examine selective episodes in the more recent evolutionary history of this locus as well as the ancient past. We have used a combination of maximum likelihood based tests and a maximum parsimony based sliding window approach to give a detailed view of the varying modes of selection operating at this locus. We provide evidence for strong positive selection soon after the duplication of these genes within an ancestral mammalian genome. Consequently variable selective pressures have acted on beta-defensin genes in different evolutionary lineages, with episodes both of negative, and more rarely positive selection, during the divergence of primates. Positive selection appears to have been more common in the rodent lineage, accompanying the birth of novel, rodent-specific beta-defensin genes. These observations allow a fuller understanding of the evolution of mammalian innate immunity. In both the rodent and primate lineages, sites in the second exon have been subject to positive selection and by implication are important in functional diversity. A small number of sites in the mature human peptides were found to have undergone repeated episodes of selection in different primate lineages. Particular sites were consistently implicated by multiple methods at positions throughout the mature peptides. These sites are clustered at positions predicted to be important for the specificity of the antimicrobial or chemoattractant properties of beta-defensins. Surprisingly, sites within the prepropeptide region were also implicated as being subject to significant positive selection, suggesting previously unappreciated functional significance for this region. Identification of these putatively functional sites has important implications for our understanding of beta-defensin function and for novel antibiotic design.

Disrupted resting-state functional connectivity in minimally treated chronic schizophrenia.

PubMed

Wang, Xijin; Xia, Mingrui; Lai, Yunyao; Dai, Zhengjia; Cao, Qingjiu; Cheng, Zhang; Han, Xue; Yang, Lei; Yuan, Yanbo; Zhang, Yong; Li, Keqing; Ma, Hong; Shi, Chuan; Hong, Nan; Szeszko, Philip; Yu, Xin; He, Yong

2014-07-01

The pathophysiology of chronic schizophrenia may reflect long term brain changes related to the disorder. The effect of chronicity on intrinsic functional connectivity patterns in schizophrenia without the potentially confounding effect of antipsychotic medications, however, remains largely unknown. We collected resting-state fMRI data in 21 minimally treated chronic schizophrenia patients and 20 healthy controls. We computed regional functional connectivity strength for each voxel in the brain, and further divided regional functional connectivity strength into short-range regional functional connectivity strength and long-range regional functional connectivity strength. General linear models were used to detect between-group differences in these regional functional connectivity strength metrics and to further systematically investigate the relationship between these differences and clinical/behavioral variables in the patients. Compared to healthy controls, the minimally treated chronic schizophrenia patients showed an overall reduced regional functional connectivity strength especially in bilateral sensorimotor cortex, right lateral prefrontal cortex, left insula and right lingual gyrus, and these regional functional connectivity strength decreases mainly resulted from disruption of short-range regional functional connectivity strength. The minimally treated chronic schizophrenia patients also showed reduced long-range regional functional connectivity strength in the bilateral posterior cingulate cortex/precuneus, and increased long-range regional functional connectivity strength in the right lateral prefrontal cortex and lingual gyrus. Notably, disrupted short-range regional functional connectivity strength mainly correlated with duration of illness and negative symptoms, whereas disrupted long-range regional functional connectivity strength correlated with neurocognitive performance. All of the results were corrected using Monte-Carlo simulation. This exploratory study demonstrates a disruption of intrinsic functional connectivity without long-term exposure to antipsychotic medications in chronic schizophrenia. Furthermore, this disruption was connection-distance dependent, thus raising the possibility for differential neural pathways in neurocognitive impairment and psychiatric symptoms in schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.

Bone sialoprotein mediates the tumor cell-targeted prometastatic activity of transforming growth factor beta in a mouse model of breast cancer.

PubMed

Nam, Jeong-Seok; Suchar, Adam M; Kang, Mi-Jin; Stuelten, Christina H; Tang, Binwu; Michalowska, Aleksandra M; Fisher, Larry W; Fedarko, Neal S; Jain, Alka; Pinkas, Jan; Lonning, Scott; Wakefield, Lalage M

2006-06-15

Transforming growth factor betas (TGF-beta) play a dual role in carcinogenesis, functioning as tumor suppressors early in the process, and then switching to act as prometastatic factors in late-stage disease. We have previously shown that high molecular weight TGF-beta antagonists can suppress metastasis without the predicted toxicities. To address the underlying mechanisms, we have used the 4T1 syngeneic mouse model of metastatic breast cancer. Treatment of mice with a monoclonal anti-TGF-beta antibody (1D11) significantly suppressed metastasis of 4T1 cells to the lungs. When metastatic 4T1 cells were recovered from lungs of 1D11-treated and control mice, the most differentially expressed gene was found to be bone sialoprotein (Bsp). Immunostaining confirmed the loss of Bsp protein in 1D11-treated lung metastases, and TGF-beta was shown to regulate and correlate with Bsp expression in vitro. Functionally, knockdown of Bsp in 4T1 cells reduced the ability of TGF-beta to induce local collagen degradation and invasion in vitro, and treatment with recombinant Bsp protected 4T1 cells from complement-mediated lysis. Finally, suppression of Bsp in 4T1 cells reduced metastasis in vivo. We conclude that Bsp is a plausible mediator of at least some of the tumor cell-targeted prometastatic activity of TGF-beta in this model and that Bsp expression in metastases can be successfully suppressed by systemic treatment with anti-TGF-beta antibodies.

Bioinformatics Knowledge Map for Analysis of Beta-Catenin Function in Cancer

PubMed Central

Arighi, Cecilia N.; Wu, Cathy H.

2015-01-01

Given the wealth of bioinformatics resources and the growing complexity of biological information, it is valuable to integrate data from disparate sources to gain insight into the role of genes/proteins in health and disease. We have developed a bioinformatics framework that combines literature mining with information from biomedical ontologies and curated databases to create knowledge “maps” of genes/proteins of interest. We applied this approach to the study of beta-catenin, a cell adhesion molecule and transcriptional regulator implicated in cancer. The knowledge map includes post-translational modifications (PTMs), protein-protein interactions, disease-associated mutations, and transcription factors co-activated by beta-catenin and their targets and captures the major processes in which beta-catenin is known to participate. Using the map, we generated testable hypotheses about beta-catenin biology in normal and cancer cells. By focusing on proteins participating in multiple relation types, we identified proteins that may participate in feedback loops regulating beta-catenin transcriptional activity. By combining multiple network relations with PTM proteoform-specific functional information, we proposed a mechanism to explain the observation that the cyclin dependent kinase CDK5 positively regulates beta-catenin co-activator activity. Finally, by overlaying cancer-associated mutation data with sequence features, we observed mutation patterns in several beta-catenin PTM sites and PTM enzyme binding sites that varied by tissue type, suggesting multiple mechanisms by which beta-catenin mutations can contribute to cancer. The approach described, which captures rich information for molecular species from genes and proteins to PTM proteoforms, is extensible to other proteins and their involvement in disease. PMID:26509276

Investigation on the individual contributions of N-H...O=C and C-H...O=C interactions to the binding energies of beta-sheet models.

PubMed

Wang, Chang-Sheng; Sun, Chang-Liang

2010-04-15

In this article, the binding energies of 16 antiparallel and parallel beta-sheet models are estimated using the analytic potential energy function we proposed recently and the results are compared with those obtained from MP2, AMBER99, OPLSAA/L, and CHARMM27 calculations. The comparisons indicate that the analytic potential energy function can produce reasonable binding energies for beta-sheet models. Further comparisons suggest that the binding energy of the beta-sheet models might come mainly from dipole-dipole attractive and repulsive interactions and VDW interactions between the two strands. The dipole-dipole attractive and repulsive interactions are further obtained in this article. The total of N-H...H-N and C=O...O=C dipole-dipole repulsive interaction (the secondary electrostatic repulsive interaction) in the small ring of the antiparallel beta-sheet models is estimated to be about 6.0 kcal/mol. The individual N-H...O=C dipole-dipole attractive interaction is predicted to be -6.2 +/- 0.2 kcal/mol in the antiparallel beta-sheet models and -5.2 +/- 0.6 kcal/mol in the parallel beta-sheet models. The individual C(alpha)-H...O=C attractive interaction is -1.2 +/- 0.2 kcal/mol in the antiparallel beta-sheet models and -1.5 +/- 0.2 kcal/mol in the parallel beta-sheet models. These values are important in understanding the interactions at protein-protein interfaces and developing a more accurate force field for peptides and proteins. 2009 Wiley Periodicals, Inc.

Defining a Role for the Oncogene Beta-Catenin in Prostate Epithelial Growth and Invasion

DTIC Science & Technology

2011-07-01

receptor function. To determine in increased or decreased Wnt signaling can affect androgen receptor function, we harvested E15.5 UGSs from Esr1 -Cre x...beta-cateninfl/fl and Esr1 -Cre APCfl/fl embryos and treated them with 2 uM tamoxifen and zero, low, normal, or high androgen to determine if high

Differences in beta-cell function and insulin secretion in Black vs. White obese adolescents: Do incretin hormones play a role?

USDA-ARS?s Scientific Manuscript database

Black youth are at higher risk for type 2 diabetes (T2D) than their White peers. Previously we demonstrated that for the same degree of insulin sensitivity, Black youth have an upregulated beta-cell function and insulin hypersecretion, in response to intravenous (IV) glucose, compared with Whites. T...

Beta cell function and BMI in ethnically diverse children with newly diagnosed autoimmune type 1 diabetes

USDA-ARS?s Scientific Manuscript database

The objective of our study was to examine the relationship between BMI and beta-cell function at diagnosis of autoimmune type 1 diabetes (T1D) in a large group of ethnically diverse children. Cross-sectional analysis of 524 children (60.8% White, 19.5% Hispanic, 14.5% African-American, 5.2% other n...

Field Tolerances for the Triplet Quadrupoles of the LHC High Luminosity Lattice

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

Nosochkov, Yuri; Cai, Y.; Jiao, Y.

2012-06-25

It has been proposed to implement the so-called Achromatic Telescopic Squeezing (ATS) scheme in the LHC high luminosity (HL) lattice to reduce beta functions at the Interaction Points (IP) up to a factor of 8. As a result, the nominal 4.5 km peak beta functions reached in the Inner Triplets (IT) at collision will be increased by the same factor. This, therefore, justifies the installation of new, larger aperture, superconducting IT quadrupoles. The higher beta functions will enhance the effects of the triplet quadrupole field errors leading to smaller beam dynamic aperture (DA). To maintain the acceptable DA, the effectsmore » of the triplet field errors must be re-evaluated, thus specifying new tolerances. Such a study has been performed for the so-called '4444' collision option of the HL-LHC layout version SLHCV3.01, where the IP beta functions are reduced by a factor of 4 in both planes with respect to a pre-squeezed value of 60 cm at two collision points. The dynamic aperture calculations were performed using SixTrack. The impact on the triplet field quality is presented.« less

Functional Expression of Two Neuronal Nicotinic Acetylcholine Receptors from cDNA Clones Identifies a Gene Family

NASA Astrophysics Data System (ADS)

Boulter, Jim; Connolly, John; Deneris, Evan; Goldman, Dan; Heinemann, Steven; Patrick, Jim

1987-11-01

A family of genes coding for proteins homologous to the α subunit of the muscle nicotinic acetylcholine receptor has been identified in the rat genome. These genes are transcribed in the central and peripheral nervous systems in areas known to contain functional nicotinic receptors. In this paper, we demonstrate that three of these genes, which we call alpha3, alpha4, and beta2, encode proteins that form functional nicotinic acetylcholine receptors when expressed in Xenopus oocytes. Oocytes expressing either alpha3 or alpha4 protein in combination with the beta2 protein produced a strong response to acetylcholine. Oocytes expressing only the alpha4 protein gave a weak response to acetylcholine. These receptors are activated by acetylcholine and nicotine and are blocked by Bungarus toxin 3.1. They are not blocked by α -bungarotoxin, which blocks the muscle nicotinic acetylcholine receptor. Thus, the receptors formed by the alpha3, alpha4, and beta2 subunits are pharmacologically similar to the ganglionic-type neuronal nicotinic acetylcholine receptor. These results indicate that the alpha3, alpha4, and beta2 genes encode functional nicotinic acetylcholine receptor subunits that are expressed in the brain and peripheral nervous system.

Dynamic radioactive particle source

DOEpatents

Moore, Murray E; Gauss, Adam Benjamin; Justus, Alan Lawrence

2012-06-26

A method and apparatus for providing a timed, synchronized dynamic alpha or beta particle source for testing the response of continuous air monitors (CAMs) for airborne alpha or beta emitters is provided. The method includes providing a radioactive source; placing the radioactive source inside the detection volume of a CAM; and introducing an alpha or beta-emitting isotope while the CAM is in a normal functioning mode.

In vitro differentiation of rat bone marrow mesenchymal stem cells into hepatocytes.

PubMed

Feng, Zhihui; Li, Changying; Jiao, Shuxian; Hu, Bin; Zhao, Lin

2011-01-01

To investigate the mechanism and regulation of differentiation from bone marrow mesenchymal stem cells (BMSCs) into hepatocytes and to find a new source for therapies of hepatic diseases. We isolated BMSCs for subsequent differentiation in the presence of hepatocyte growth factor (HGF) or beta-nerve growth factor (beta-NGF). Cell morphology was observed and cell surface phenotypings were detected by flow cytometry. a1-antitrypsin (AAT) expression of the hepatocytes was confirmed by immunocytochemistry and albumin expression was validated by real time PCR and western blotting. The expression of high-affinity nerve growth factor receptor (TrkA) and the activation of Erk pathway were detected by western blotting. Hepatocyte functional activity was confirmed by uptake of indocyanine green (ICG) assay. Small round cells appeared in the presence of HGF on day 10 or beta-NGF on day 12. Differentiated cells expressed albumin and had functional characteristics of hepatocytes, such as uptake of ICG. BMSCs were positive for TrkA. HGF and beta-NGF significantly upregulated the protein levels of phospho-Erk. BMSCs could differentiate into hepatocytes in the differentiation media including HGF or beta-NGF. Combination of HGF and beta-NGF significantly increased the efficiency of hepatic differentiation.

Meprin A and meprin {alpha} generate biologically functional IL-1{beta} from pro-IL-1{beta}

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

Herzog, Christian; University of Arkansas for Medical Sciences, Department of Medicine, Little Rock, AR 72205; Haun, Randy S.

The present study demonstrates that both oligomeric metalloendopeptidase meprin A purified from kidney cortex and recombinant meprin {alpha} are capable of generating biologically active IL-1{beta} from its precursor pro-IL-1{beta}. Amino-acid sequencing analysis reveals that meprin A and meprin {alpha} cleave pro-IL-1{beta} at the His{sup 115}-Asp{sup 116} bond, which is one amino acid N-terminal to the caspase-1 cleavage site and five amino acids C-terminal to the meprin {beta} site. The biological activity of the pro-IL-1{beta} cleaved product produced by meprin A, determined by proliferative response of helper T-cells, was 3-fold higher to that of the IL-1{beta} product produced by meprin {beta}more » or caspase-1. In a mouse model of sepsis induced by cecal ligation puncture that results in elevated levels of serum IL-1{beta}, meprin inhibitor actinonin significantly reduces levels of serum IL-1{beta}. Meprin A and meprin {alpha} may therefore play a critical role in the production of active IL-1{beta} during inflammation and tissue injury.« less

Analysis of Voyager spectra of the beta Cephei star nu Eridani

NASA Technical Reports Server (NTRS)

Porri, A.; Stalio, R.; Ali, B.; Polidan, R. S.; Morossi, C.

1994-01-01

Voyager 500-1700 A spectrophotometric observations of the beta Cephei star nu Eri are presented and discussed. The Voyager observations were obtained in 1981 and cover six pulsation cycles of the star. These data are supplemented with a set of nine International Ultraviolet Explorer (IUE) SWP high-resolution observations covering one, earlier epoch, pulsation cycle. Light curves are derived from the Voyager data at 1055 and 1425 A. These light curves are found to be consistent in both shape and period with published optical curves. The 1055 A light curve also exhibits a phenomenon not seen in the optical curves: a small but highly significant systematic increase in the flux of the maximum light phases while maintaining a constant minimum light level over the interval of observation. Substantially larger errors in the longer wavelength data preclude discussion of this phenomenon in the 1425 A light curve. Examination of the far-UV continuum in nu Eri during this period shows that the color temperature is lower for the brighter maxima. Analysis of the far-UV continuum at maximum and minimum light yields an effective temperature difference between these two phases of 2200 + or - 750 K. Spectroscopically, three prominent features are seen in the Voyager data: a feature at 985 A mostly due to a blend of C III 977 A, H I Ly gamma 972 A, and N III 990 A; a feature at 1030 A due to H I Ly beta 1026 A and C II 1037 A; and the Si IV resonance doublet near 1400 A. A comparison of the 912-1700 A spectral region in nu Eri with a set of standard, i.e., nonpulsating stars, shows that nu Eri closely resembles the standard both in continuum shape and spectral line strengths with the possible exception of a slight flux excess between 912 and 975 A. The equivalent width of the 985 A feature is shown to vary in strength over the pulsation cycle in antiphase with the light curve and variations seen in the C IV 1548-1551 lines from the IUE data. This behavior of the 985 A feature is most likely caused by variations in the strength of the Ly gamma component of the blend. Comparisons are also made between nu Eri and the only other beta Cephei star studied in the far-UV, BW Vul, with the most notable differences between the two stars being the much larger delta(T(sub eff)) for BW Vul and the almost total absence of abnormalities in observed spectrum of nu Eri.

Function of beta 2-adrenergic receptors in chronic localized myalgia.

PubMed

Maekawa, Kenji; Kuboki, Takuo; Inoue, Eitoku; Inoue-Minakuchi, Mami; Suzuki, Koji; Yatani, Hirofumi; Clark, Glenn T

2003-01-01

To investigate alteration of beta 2-adrenergic receptor (beta 2 AR) function in chronic localized myalgia subjects by evaluating levels of the beta 2 AR second messenger, cyclic adenosine monophosphate (cAMP), in mononuclear cells after beta AR-agonist stimulation. Eleven chronic localized myalgia subjects and 21 matched healthy controls participated in this study. Peripheral blood (30 cc) was drawn from the subjects' anterocubital vein. Mononuclear cells were isolated from the total blood by using the Ficoll-Hypaque gradient technique. Basal and stimulated intracellular cAMP levels were determined by enzyme immunoassay using a commercially available kit. Aliquots of 5 x 10(6) cells were incubated with or without stimulation of the beta AR-agonist isoproterenol for 5 minutes. Five different concentrations of isoproterenol (10(-3) M to 10(-7) M) were utilized. cAMP levels in both groups were tested statistically by a 2-way repeated-measures ANOVA with 2 predictors, group difference and isoproterenol concentration difference. As with isoproterenol stimulation, the cAMP responses to forskolin, which activates adenylyl cyclase directly and produces cAMP, bypassing the cell surface receptors were also measured. The basal cAMP levels in both groups (myalgia: 0.33 +/- 0.02 pmol/5 x 10(6) cells; control: 0.43 +/- 0.10 pmol/5 x 10(6) cells) were almost identical, and isoproterenol-produced cAMP levels increased dose-dependently in both groups. No significant differences in the mean cAMP levels were observed between the groups (P = .909). Significant increases were observed according to the isoproterenol concentration increase (P < .0001). The cAMP responses to forskolin stimulation also showed no significant group difference (P = .971). These results suggest that beta 2 AR function is not different between localized myalgia subjects and healthy individuals.

Oncogenic mechanisms of Evi-1 protein.

PubMed

Hirai, H; Izutsu, K; Kurokawa, M; Mitani, K

2001-08-01

Although Evi-1 is thought to promote growth or block differentiation in some cell types, its biological functions have not been elucidated. To explore the mechanisms underlying Evi-1-induced oncogenesis, we investigated whether Evi-1 affects the signaling of transforming growth factor beta (TGF-beta), which inhibits proliferation of a wide range of cell types and is one of the most studied growth regulatory factors. We demonstrated that Evi-1 represses TGF-beta signaling and antagonizes its growth-inhibitory effects. Two separate regions of Evi-1 are responsible for this repression, one of which is the first zinc-finger domain. Through this domain, Evi-1 physically interacts with Smad3, an intracellular mediator of TGF-beta signaling, thereby suppressing the transcriptional activity of Smad3. These results define a novel function of Evi-1 as a repressor of signaling components of TGF-beta. We also demonstrated that Evi-1 represses Smad-induced transcriptional activation by recruiting CtBP as a corepressor. Evi-1 associates with CtBP1 through one of the CtBP-binding consensus motifs within the region from amino acid 544 to 607, and this association is required for the efficient inhibition of TGF-beta signaling. A specific histone deacetylase (HDAc) inhibitor, trichostatin A (TSA), alleviates Evi-1-mediated repression of TGF-beta signaling, suggesting that HDAc is involved in transcriptional repression by Evi-1. This identifies a novel function of Evi-1 as a member of corepressor complexes and suggests that aberrant recruitment of corepressors is one of the mechanisms involved in Evi-1-induced leukemogenesis. These results indicate that specific HDAc inhibitors may be useful in the treatment of Evi-1-induced neoplastic tumors, including myeloid leukemias.

Development of magnetic resonance imaging based detection methods for beta amyloids via sialic acid-functionalized magnetic nanoparticles

NASA Astrophysics Data System (ADS)

Kouyoumdjian, Hovig

The development of a non-invasive method for the detection of Alzheimer's disease is of high current interest, which can be critical in early diagnosis and in guiding preventive treatment of the disease. The aggregates of beta amyloids are a pathological hallmark of Alzheimer's disease. Carbohydrates such as sialic acid terminated gangliosides have been shown to play significant roles in initiation of amyloid aggregation. Herein, we report a biomimetic approach using sialic acid coated iron oxide superparamagnetic nanoparticles for in vitro detection in addition to the assessment of the in vivo mouse-BBB (Blood brain barrier) crossing of the BSA (bovine serum albumin)-modified ones. The sialic acid functionalized dextran nanoparticles were shown to bind with beta amyloids through several techniques including ELISA (enzyme linked immunosorbent assay), MRI (magnetic resonance imaging), TEM (transmission electron microscopy), gel electrophoresis and tyrosine fluorescence assay. The superparamagnetic nature of the nanoparticles allowed easy detection of the beta amyloids in mouse brains in both in vitro and ex vivo model by magnetic resonance imaging. Furthermore, the sialic acid nanoparticles greatly reduced beta amyloid induced cytotoxicity to SH-SY5Y neuroblastoma cells, highlighting the potential of the glyconanoparticles for detection and imaging of beta amyloids. Sialic acid functionalized BSA (bovine serum albumin) nanoparticles also showed significant binding to beta amyloids, through ELISA and ex vivo mouse brain MRI experiments. Alternatively, the BBB crossing was demonstrated by several techniques such as confocal microscopy, endocytosis, exocytosis assays and were affirmed by nanoparticles transcytosis assays through bEnd.3 endothelial cells. Finally, the BBB crossing was confirmed by analyzing the MRI signal of nanoparticle-injected CD-1 mice.

The role of beta-arrestin2 in shaping fMRI BOLD responses to dopaminergic stimulation.

PubMed

Sahlholm, Kristoffer; Ielacqua, Giovanna D; Xu, Jinbin; Jones, Lynne A; Schlegel, Felix; Mach, Robert H; Rudin, Markus; Schroeter, Aileen

2017-07-01

The dopamine D 2 receptor (D 2 R) couples to inhibitory G i/o proteins and is targeted by antipsychotic and antiparkinsonian drugs. Beta-arrestin2 binds to the intracellular regions of the agonist-occupied D 2 R to terminate G protein activation and promote internalization, but also to initiate downstream signaling cascades which have been implicated in psychosis. Functional magnetic resonance imaging (fMRI) has proven valuable for measuring dopamine receptor-mediated changes in neuronal activity, and might enable beta-arrestin2 function to be studied in vivo. The present study examined fMRI blood oxygenation level dependent (BOLD) signal changes elicited by a dopamine agonist in wild-type (WT) and beta-arrestin2 knockout (KO) mice, to investigate whether genetic deletion of beta-arrestin2 prolongs or otherwise modifies D 2 R-dependent responses. fMRI BOLD data were acquired on a 9.4 T system. During scans, animals received 0.2 mg/kg apomorphine, i.v. In a subset of experiments, animals were pretreated with 2 mg/kg of the D 2 R antagonist, eticlopride. Following apomorphine administration, BOLD signal decreases were observed in caudate/putamen of WT and KO animals. The time course of response decay in caudate/putamen was significantly slower in KO vs. WT animals. In cingulate cortex, an initial BOLD signal decrease was followed by a positive response component in WT but not in KO animals. Eticlopride pretreatment significantly reduced apomorphine-induced BOLD signal changes. The prolonged striatal response decay rates in KO animals might reflect impaired D 2 R desensitization, consistent with the known function of beta-arrestin2. Furthermore, the apomorphine-induced positive response component in cingulate cortex may depend on beta-arrestin2 signaling downstream of D 2 R.

Designing Allosteric Control into Enzymes by Chemical Rescue of Structure

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

Deckert, Katelyn; Budiardjo, S. Jimmy; Brunner, Luke C.

2012-08-07

Ligand-dependent activity has been engineered into enzymes for purposes ranging from controlling cell morphology to reprogramming cellular signaling pathways. Where these successes have typically fused a naturally allosteric domain to the enzyme of interest, here we instead demonstrate an approach for designing a de novo allosteric effector site directly into the catalytic domain of an enzyme. This approach is distinct from traditional chemical rescue of enzymes in that it relies on disruption and restoration of structure, rather than active site chemistry, as a means to achieve modulate function. We present two examples, W33G in a {beta}-glycosidase enzyme ({beta}-gly) and W492Gmore » in a {beta}-glucuronidase enzyme ({beta}-gluc), in which we engineer indole-dependent activity into enzymes by removing a buried tryptophan side chain that serves as a buttress for the active site architecture. In both cases, we observe a loss of function, and in both cases we find that the subsequent addition of indole can be used to restore activity. Through a detailed analysis of {beta}-gly W33G kinetics, we demonstrate that this rescued enzyme is fully functionally equivalent to the corresponding wild-type enzyme. We then present the apo and indole-bound crystal structures of {beta}-gly W33G, which together establish the structural basis for enzyme inactivation and rescue. Finally, we use this designed switch to modulate {beta}-glycosidase activity in living cells using indole. Disruption and recovery of protein structure may represent a general technique for introducing allosteric control into enzymes, and thus may serve as a starting point for building a variety of bioswitches and sensors.« less

Beneficial effect of 17{beta}-estradiol on hyperglycemia and islet {beta}-cell functions in a streptozotocin-induced diabetic rat model

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

Yamabe, Noriko; Kang, Ki Sung; Zhu Baoting, E-mail: BTZhu@kumc.ed

2010-11-15

The modulating effect of estrogen on glucose homeostasis remains a controversial issue at present. In this study, we sought to determine the beneficial effect of 17{beta}-estradiol (E{sub 2}) on hyperglycemia and islet {beta}-cell functions in streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats were injected i.p. with STZ to induce a relatively mild diabetic condition. The rats were then treated with E{sub 2} orally at 500 {mu}g/kg body weight/day for 15 days to evaluate the modulating effect on hyperglycemia, insulin secretion, and islet {beta}-cell proliferation. E{sub 2} administration for 10 days significantly lowered plasma glucose levels, increased plasma insulin levels, andmore » improved glucose tolerance by attenuating insulin response to oral glucose loading. These beneficial effects of E{sub 2} were accompanied by increases in islet number and volume, rate of islet cell proliferation, and the amount of insulin secreted. The growth-stimulatory effect of E{sub 2} on islet cells was linked to the functions of the estrogen receptor {alpha}. Notably, these protective effects of E{sub 2} on diabetic conditions were basically not observed when the STZ-treated rats had a more severe degree of islet damage and hyperglycemia. Taken together, we conclude that E{sub 2} can promote the regeneration of damaged pancreatic islets by stimulating {beta}-cell proliferation in diabetic rats, and this effect is accompanied by improvements in glucose tolerance and a decrease in plasma glucose levels. These findings suggest that oral administration of E{sub 2} may be beneficial in diabetic patients with an accelerated loss of islet {beta}-cells.« less

Functional desensitization to isoproterenol without reducing cAMP production in canine failing cardiocytes.

PubMed

Laurent, C E; Cardinal, R; Rousseau, G; Vermeulen, M; Bouchard, C; Wilkinson, M; Armour, J A; Bouvier, M

2001-02-01

To corroborate alterations in the functional responses to beta-adrenergic receptor (beta-AR) stimulation with changes in beta-AR signaling in failing cardiomyocytes, contractile and L-type Ca(2+) current responses to isoproterenol along with stimulated cAMP generation were compared among cardiomyocytes isolated from canines with tachycardia-induced heart failure or healthy hearts. The magnitude of shortening of failing cardiomyocytes was significantly depressed (by 22 +/- 4.4%) under basal conditions, and the maximal response to isoproterenol was significantly reduced (by 45 +/- 18%). Similar results were obtained when the responses in the rate of contraction and rate of relaxation to isoproterenol were considered. The L-type Ca(2+) current amplitude measured in failing cardiomyocytes under basal conditions was unchanged, but the responses to isoproterenol were significantly reduced compared with healthy cells. Isoproterenol-stimulated cAMP generation was similar in sarcolemmal membranes derived from the homogenates of failing (45 +/- 6.8) and healthy cardiomyocytes (52 +/- 8.5 pmol cAMP. mg protein(-1). min(-1)). However, stimulated cAMP generation was found to be significantly reduced when the membranes were derived from the homogenates of whole tissue (failing: 67 +/- 8.1 vs. healthy: 140 +/- 27.8 pmol cAMP. mg protein(-1). min(-1)). Total beta-AR density was not reduced in membranes derived from either whole tissue or isolated cardiomyocyte homogenates, but the beta(1)/beta(2) ratio was significantly reduced in the former (failing: 45/55 vs. healthy: 72/28) without being altered in the latter (failing: 72/28, healthy: 77/23). We thus conclude that, in tachycardia-induced heart failure, reduction in the functional responses of isolated cardiomyocytes to beta-AR stimulation may be attributed to alterations in the excitation-contraction machinery rather than to limitation of cAMP generation.

Low-dose oral rapamycin treatment reduces fibrogenesis, improves liver function, and prolongs survival in rats with established liver cirrhosis.

PubMed

Neef, Markus; Ledermann, Monika; Saegesser, Hans; Schneider, Vreni; Reichen, Juerg

2006-12-01

Mammalian target of rapamycin (mTOR) signalling is central in the activation of hepatic stellate cells (HSCs), the key source of extracellular matrix (ECM) in fibrotic liver. We tested the therapeutic potential of the mTOR inhibitor rapamycin in advanced cirrhosis. Cirrhosis was induced by bile duct-ligation (BDL) or thioacetamide injections (TAA). Rats received oral rapamycin (0.5 mg/kg/day) for either 14 or 28 days. Untreated BDL and TAA-rats served as controls. Liver function was quantified by aminopyrine breath test. ECM and ECM-producing cells were quantified by morphometry. MMP-2 activity was measured by zymography. mRNA expression of procollagen-alpha1, transforming growth factor-beta1 (TGF-beta1) and beta2 was quantified by RT-PCR. Fourteen days of rapamycin improved liver function. Accumulation of ECM was decreased together with numbers of activated HSCs and MMP-2 activity in both animal models. TGF-beta1 mRNA was downregulated in TAA, TGF-beta2 mRNA was downregulated in BDL. 28 days of rapamycin treatment entailed a survival advantage of long-term treated BDL-rats. Low-dose rapamycin treatment is effectively antifibrotic and attenuates disease progression in advanced fibrosis. Our results warrant the clinical evaluation of rapamycin as an antifibrotic drug.

Effects of 18beta-glycyrrhetinic acid on the junctional complex and steroidogenesis in rat adrenocortical cells.

PubMed

Huang, Shih-Horng; Wu, Jiahn-Chun; Hwang, Ra-Der; Yeo, Hui-Lin; Wang, Seu-Mei

2003-09-01

Cellular junctions play important roles in cell differentiation, signal transduction, and cell function. This study investigated their function in steroid secretion by adrenal cells. Immunofluorescence staining revealed the presence of gap junctions and adherens junctions between adrenal cells. The major gap junction protein, connexin43, was seen as a linear dotted pattern of the typical gap junction plaques, in contrast to alpha-, beta-, and gamma-catenin, which were seen as continuous, linear staining of cell-cell adherens junction. Treatment with 18beta-glycyrrhetinic acid, a gap junction inhibitor, reduced the immunoreactivity of these proteins in a time- and dose-dependent manner, and caused the gap junction and adherens junction to separate longitudinally from the cell-cell contact sites, indicating the structural interdependency of these two junctions. Interestingly, 18beta-glycyrrhetinic acid stimulated a two- to three-fold increase in steroid production in these adrenal cells lacking intact cell junctions. These data raise the question of the necessity for cell communication for the endocrine function of adrenal cells. Pharmacological analyses indicated that the steroidogenic effect of 18beta-glycyrrhetinic acid was partially mediated by extracellular signal-related kinase and calcium/calmodulin-dependent kinase, a pathway distinct from the protein kinase A signaling pathway already known to mediate steroidogenesis in adrenal cells. Copyright 2003 Wiley-Liss, Inc.

Noncommutative QED+QCD and the {beta} function for QED

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

Ettefaghi, M. M.; Haghighat, M.; Mohammadi, R.

2010-11-15

QED based on {theta}-unexpanded noncomutative space-time in contrast with the noncommutative QED based on {theta}-expanded U(1) gauge theory via the Seiberg-Witten map is one-loop renormalizable. Meanwhile it suffers from asymptotic freedom that is not in agreement with the experiment. We show that the QED part of the U{sub *}(3)xU{sub *}(1) gauge group as an appropriate gauge group for the noncommutative QED+QCD is not only one-loop renormalizable but also has a {beta} function that can be positive, negative and even zero. In fact the {beta} function depends on the mixing parameter {delta}{sub 13} as a free parameter and it will bemore » equal to its counterpart in the ordinary QED for {delta}{sub 13}=0.367{pi}.« less

Correlation between increased urinary sodium excretion and decreased left ventricular diastolic function in patients with type 2 diabetes mellitus.

PubMed

Kagiyama, Shuntaro; Koga, Tokushi; Kaseda, Shigeru; Ishihara, Shiro; Kawazoe, Nobuyuki; Sadoshima, Seizo; Matsumura, Kiyoshi; Takata, Yutaka; Tsuchihashi, Takuya; Iida, Mitsuo

2009-10-01

Increased salt intake may induce hypertension, lead to cardiac hypertrophy, and exacerbate heart failure. When elderly patients develop heart failure, diastolic dysfunction is often observed, although the ejection fraction has decreased. Diabetes mellitus (DM) is an established risk factor for heart failure. However, little is known about the relationship between cardiac function and urinary sodium excretion (U-Na) in patients with DM. We measured 24-hour U-Na; cardiac function was evaluated directly during coronary catheterization in type 2 DM (n = 46) or non-DM (n = 55) patients with preserved cardiac systolic function (ejection fraction > or = 60%). Cardiac diastolic and systolic function was evaluated as - dp/dt and + dp/dt, respectively. The average of U-Na was 166.6 +/- 61.2 mEq/24 hour (mean +/- SD). In all patients, stepwise multivariate regression analysis revealed that - dp/dt had a negative correlation with serum B-type natriuretic peptide (BNP; beta = - 0.23, P = .021) and U-Na (beta = - 0.24, P = .013). On the other hand, + dp/dt negatively correlated with BNP (beta = - 0.30, P < .001), but did not relate to U-Na. In the DM-patients, stepwise multivariate regression analysis showed that - dp/dt still had a negative correlation with U-Na (beta = - 0.33, P = .025). The results indicated that increased urinary sodium excretion is associated with an impairment of cardiac diastolic function, especially in patients with DM, suggesting that a reduction of salt intake may improve cardiac diastolic function.

Solution Structures of 2 : 1 And 1 : 1 DNA Polymerase - DNA Complexes Probed By Ultracentrifugation And Small-Angle X-Ray Scattering

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

Tang, K.H.; /Ohio State U.; Niebuhr, M.

2009-04-30

We report small-angle X-ray scattering (SAXS) and sedimentation velocity (SV) studies on the enzyme-DNA complexes of rat DNA polymerase {beta} (Pol {beta}) and African swine fever virus DNA polymerase X (ASFV Pol X) with one-nucleotide gapped DNA. The results indicated formation of a 2 : 1 Pol {beta}-DNA complex, whereas only 1 : 1 Pol X-DNA complex was observed. Three-dimensional structural models for the 2 : 1 Pol {beta}-DNA and 1 : 1 Pol X-DNA complexes were generated from the SAXS experimental data to correlate with the functions of the DNA polymerases. The former indicates interactions of the 8 kDamore » 5{prime}-dRP lyase domain of the second Pol {beta} molecule with the active site of the 1 : 1 Pol {beta}-DNA complex, while the latter demonstrates how ASFV Pol X binds DNA in the absence of DNA-binding motif(s). As ASFV Pol X has no 5{prime}-dRP lyase domain, it is reasonable not to form a 2 : 1 complex. Based on the enhanced activities of the 2 : 1 complex and the observation that the 8 kDa domain is not in an optimal configuration for the 5{prime}-dRP lyase reaction in the crystal structures of the closed ternary enzyme-DNA-dNTP complexes, we propose that the asymmetric 2 : 1 Pol {beta}-DNA complex enhances the function of Pol {beta}.« less

Design and Optimization of Resorbable Silk Internal Fixation Devices

NASA Astrophysics Data System (ADS)

Haas, Dylan S.

Limitations of current material options for internal fracture fixation devices have resulted in a large gap between user needs and hardware function. Metal systems offer robust mechanical strength and ease of implantation but require secondary surgery for removal and/or result in long-term complications (infection, palpability, sensitivity, etc.). Current resorbable devices eliminate the need for second surgery and long-term complications but are still associated with negative host response as well as limited functionality and more difficult implantation. There is a definitive need for orthopedic hardware that is mechanically capable of immediate fracture stabilization and fracture fixation during healing, can safely biodegrade while allowing complete bone remodeling, can be resterilized for reuse, and is easily implantable (self-tapping). Previous work investigated the use of silk protein to produce resorbable orthopedic hardware for non- load bearing fracture fixation. In this study, silk orthopedic hardware was further investigated and optimized in order to better understand the ability of silk as a fracture fixation system and more closely meet the unfulfilled market needs. Solvent-based and aqueous-based silk processing formulations were cross-linked with methanol to induce beta sheet structure, dried, autoclaved and then machined to the desired device/geometry. Silk hardware was evaluated for dry, hydrated and fatigued (cyclic) mechanical properties, in vitro degradation, resterilization, functionalization with osteoinductive molecules and implantation technique for fracture fixation. Mechanical strength showed minor improvements from previous results, but remains comparable to current resorbable fixation systems with the advantages of self-tapping ability for ease of implantation, full degradation in 10 months, ability to be resterilized and reused, and ability to release molecules for osteoinudction. In vivo assessment confirmed biocompatibility, showed improved bone deposition and remodeling with functionalization and showed promising feasibility of fracture fixations with minor adjustments to geometry. The proposed silk orthopedic hardware exhibits high potential as a resorbable fixation system that can bridge the gap between the current materials for internal fixation devices.

Probing conformational changes in the I-like domain and the cysteine-rich repeat of human beta 3 integrins following disulfide bond disruption by cysteine mutations: identification of cysteine 598 involved in alphaIIbbeta3 activation.

PubMed

Chen, P; Melchior, C; Brons, N H; Schlegel, N; Caen, J; Kieffer, N

2001-10-19

We have investigated receptor function and epitope expression of recombinant alpha(IIb)beta(3) mutated at Cys(177) or Cys(273) in the I-like domain as well as Cys(598), located in the fourth repeat of the membrane-proximal cysteine-rich region and mutated in a Glanzmann's thrombasthenia type II patient. The beta(3) mutants beta(3)C177A, beta(3)C273A, and beta(3)C598Y exhibited a decreased electrophoretic mobility in SDS-polyacrylamide gel electrophoresis under nonreducing conditions, confirming the disruption of the respective disulfide loops. Despite reduced surface expression, the alpha(IIb)beta(3)C177A, alpha(IIb)beta(3)C273A, and alpha(IIb)beta(3)C598Y receptors mediated cell adhesion to immobilized fibrinogen and translocated into focal adhesion plaques. The beta(3)C598Y mutation, but not the beta(3)C177A or beta(3)C273A mutations, induced spontaneous binding of the ligand mimetic monoclonal antibody PAC-1, while the beta(3)C177A and beta(3)C273A mutants exhibited reduced complex stability in the absence of Ca(2+). Epitope mapping of function-blocking monoclonal antibodies (mAbs) allowed the identification of two distinct subgroups; mAbs A2A9, pl2-46, 10E5, and P256 did not interact with alpha(IIb)beta(3)C273A and bound only weakly to alpha(IIb)beta(3)C177A, while mAbs AP2, LM609 and 7E3 bound normally to mutant alpha(IIb)beta(3)C273A, but interacted only weakly with mutant alpha(IIb)beta(3)C177A. Furthermore, a cryptic epitope recognized by mAb 4D10G3 and not exposed on wild type alpha(IIb)beta(3) became accessible only on mutant alpha(IIb)beta(3)C177A and was mapped to the 60-kDa chymotrypsin fragment of beta(3). Finally, the ligand-induced binding site (LIBS) epitopes AP5, D3, LIBS1, and LIBS2 were spontaneously expressed on all three mutants independent of RGDS or dithiothreitol treatment. Our results provide evidence that disruption of a single cysteine disulfide bond in the cysteine-rich repeat domain, but not in the I-like domain, activates integrin alpha(IIb)beta(3). In contrast, disruption of each of the disulfide bonds in the two long insertions of the I-like domain predicted to be in close contact with the alpha subunit beta-propeller domain affect the stability of the alpha(IIb)beta(3) heterodimer and inhibit complex-specific mAb binding without affecting the RGD binding capacity of the metal ion-dependent adhesion site-like domain.

Test-retest reliability and cross validation of the functioning everyday with a wheelchair instrument.

PubMed

Mills, Tamara L; Holm, Margo B; Schmeler, Mark

2007-01-01

The purpose of this study was to establish the test-retest reliability and content validity of an outcomes tool designed to measure the effectiveness of seating-mobility interventions on the functional performance of individuals who use wheelchairs or scooters as their primary seating-mobility device. The instrument, Functioning Everyday With a Wheelchair (FEW), is a questionnaire designed to measure perceived user function related to wheelchair/scooter use. Using consumer-generated items, FEW Beta Version 1.0 was developed and test-retest reliability was established. Cross-validation of FEW Beta Version 1.0 was then carried out with five samples of seating-mobility users to establish content validity. Based on the content validity study, FEW Version 2.0 was developed and administered to seating-mobility consumers to examine its test-retest reliability. FEW Beta Version 1.0 yielded an intraclass correlation coefficient (ICC) Model (3,k) of .92, p < .001, and the content validity results revealed that FEW Beta Version 1.0 captured 55% of seating-mobility goals reported by consumers across five samples. FEW Version 2.0 yielded ICC(3,k) = .86, p < .001, and captured 98.5% of consumers' seating-mobility goals. The cross-validation study identified new categories of seating-mobility goals for inclusion in FEW Version 2.0, and the content validity of FEW Version 2.0 was confirmed. FEW Beta Version 1.0 and FEW Version 2.0 were highly stable in their measurement of participants' seating-mobility goals over a 1-week interval.

The H,K-ATPase beta-subunit can act as a surrogate for the beta-subunit of Na,K-pumps.

PubMed

Horisberger, J D; Jaunin, P; Reuben, M A; Lasater, L S; Chow, D C; Forte, J G; Sachs, G; Rossier, B C; Geering, K

1991-10-15

Na,K-ATPase and H,K-ATPase are the only members of the P-type ATPases in which a glycosylated beta-subunit is part of the purified active enzyme. In this study, we have followed the synthesis and the posttranslational processing of the beta-subunit of H,K-ATPase (beta HK) in Xenopus oocytes injected with beta HK cRNA and have tested whether it can act as a surrogate for the beta-subunit of Na,K-ATPase (beta NaK) to support the functional expression of Na,K-pumps. In Xenopus oocytes, beta HK is processed from an Endo H-sensitive 51-kDa coreglycosylated form to an Endo H-resistant 71-kDa fully glycosylated form. Similar to beta NaK, beta HK can stabilize and increase the trypsin resistance of alpha-subunits of Na,K-ATPase (alpha NaK). Finally, expression of beta HK together with alpha NaK leads to an increased number of ouabain binding sites at the plasma membrane accompanied by an increased Rb+ uptake and Na,K-pump current. Our data suggest that beta HK, similar to beta NaK, can assemble to alpha NaK, support the structural maturation and the intracellular transport of catalytic alpha NaK, and ultimately form active alpha NaK-beta HK complexes with Na,K-pump transport properties.

[Experimental therapy of cardiac remodeling with quercetin-containing drugs].

PubMed

Kuzmenko, M A; Pavlyuchenko, V B; Tumanovskaya, L V; Dosenko, V E; Moybenko, A A

2013-01-01

It was shown that continuous beta-adrenergic hyperstimulation resulted in cardiac function disturbances and fibrosis of cardiac tissue. Treatment with quercetin-containing drugs, particularly, water-soluble corvitin and tableted quertin exerted favourable effect on cardiac hemodynamics, normalized systolic and diastolic function in cardiac remodeling, induced by sustained beta-adrenergic stimulation. It was estimated that conducted experimental therapy limited cardiac fibrosis area almost three-fold, that could be associated with first and foremost improved cardiac distensibility, characteristics of diastolic and also pump function in cardiac remodeling.

The multicategory case of the sequential Bayesian pixel selection and estimation procedure

NASA Technical Reports Server (NTRS)

Pore, M. D.; Dennis, T. B. (Principal Investigator)

1980-01-01

A Bayesian technique for stratified proportion estimation and a sampling based on minimizing the mean squared error of this estimator were developed and tested on LANDSAT multispectral scanner data using the beta density function to model the prior distribution in the two-class case. An extention of this procedure to the k-class case is considered. A generalization of the beta function is shown to be a density function for the general case which allows the procedure to be extended.

[Impact of frailty over the functional state of hospitalized elderly].

PubMed

García-Cruz, Juan Carlos; García-Peña, Carmen

2016-01-01

Frailty in elderly results from impaired physiological reserve in multiple systems. Establishing if frail elderly inpatients develop more functional impairment at discharge, will allow the development of strategies for preventing or limiting the deterioration in this vulnerable group. Prospective cohort in 133 elderly inpatients. At admission, frailty, functional status, comorbidity and comprehensive geriatric evaluation were determined. The main outcome was functional state at hospital discharge. 64 patients presented frailty (48.1%) and 69 did not present that state (51.9%), with a mean age of 73 and 68 years, respectively. Mean decrement in functional state at discharge was -8.06 % (IC 95 % -10.38 to -5.74), from 97.97 % to 89.91 % (p < 0.001) in patients who did not present frailty, and -21.18 % (IC 95 % -24.97 to -17.38), from 87.52 % to 66.34 % (p < 0.001) in frail patients. The difference between groups at discharge was -14.37 % (IC 95 % -16.80 to -11.94, p < 0.001) to the detriment of the frail. Frailty was associated with functional impairment in the univariated and multivariated analysis, beta -13.11 % (IC 95 % -17.45 to -8.78, p < 0.001) and beta -17.27 (IC 95 % -23.27 to -11.28, p < 0.001), respectively. In the final model, frailty (beta -14.73, IC 95 % -19.39 to -10.07, p < 0.001) and cognitive impairment (beta -8.19, IC 95 % -15.28 to -1.10, p = 0.024) predict functional decrement. Frailty independently predicts functional impairment at hospital discharge.

Function of the two Xenopus smad4s in early frog development.

PubMed

Chang, Chenbei; Brivanlou, Ali H; Harland, Richard M

2006-10-13

Signals from the transforming growth factor beta family members are transmitted in the cell through specific receptor-activated Smads and a common partner Smad4. Two Smad4 genes (alpha and beta/10, or smad4 and smad4.2) have been isolated from Xenopus, and conflicting data are reported for Smad4beta/10 actions in mesodermal and neural induction. To further understand the functions of the Smad4s in early frog development, we analyzed their activities in detail. We report that Smad10 is a mutant form of Smad4beta that harbors a missense mutation of a conserved arginine to histidine in the MH1 domain. The mutation results in enhanced association of Smad10 with the nuclear transcription corepressor Ski and leads to its neural inducing activity through inhibition of bone morphogenetic protein (BMP) signaling. In contrast to Smad10, both Smad4alpha and Smad4beta enhanced BMP signals in ectodermal explants. Using antisense morpholino oligonucleotides (MOs) to knockdown endogenous Smad4 protein levels, we discovered that Smad4beta was required for both activin- and BMP-mediated mesodermal induction in animal caps, whereas Smad4alpha affected only the BMP signals. Neither Smad4 was involved directly in neural induction. Expression of Smad4beta-MO in early frog embryos resulted in reduction of mesodermal markers and defects in axial structures, which were rescued by either Smad4alpha or Smad4beta. Smad4alpha-MO induced only minor deficiency at late stages. As Smad4beta, but not Smad4alpha, is expressed at high levels maternally and during early gastrulation, our data suggest that although Smad4alpha and Smad4beta may have similar activities, they are differentially utilized during frog embryogenesis, with only Smad4beta being essential for mesoderm induction.

Beta oscillations reflect supramodal information during perceptual judgment.

PubMed

Haegens, Saskia; Vergara, José; Rossi-Pool, Román; Lemus, Luis; Romo, Ranulfo

2017-12-26

Previous work on perceptual decision making in the sensorimotor system has shown population dynamics in the beta band, corresponding to the encoding of stimulus properties and the final decision outcome. Here, we asked how oscillatory dynamics in the medial premotor cortex (MPC) contribute to supramodal perceptual decision making. We recorded local field potentials (LFPs) and spikes in two monkeys trained to perform a tactile-acoustic frequency discrimination task, including both unimodal and crossmodal conditions. We studied the role of oscillatory activity as a function of stimulus properties (frequency and sensory modality), as well as decision outcome. We found that beta-band power correlated with relevant stimulus properties: there was a significant modulation by stimulus frequency during the working-memory (WM) retention interval, as well as modulation by stimulus modality-the latter was observed only in the case of a purely unimodal task, where modality information was relevant to prepare for the upcoming second stimulus. Furthermore, we found a significant modulation of beta power during the comparison and decision period, which was predictive of decision outcome. Finally, beta-band spike-field coherence (SFC) matched these LFP observations. In conclusion, we demonstrate that beta power in MPC is reflective of stimulus features in a supramodal, context-dependent manner, and additionally reflects the decision outcome. We propose that these beta modulations are a signature of the recruitment of functional neuronal ensembles, which encode task-relevant information.

Identification and comparative expression analysis of interleukin 2/15 receptor B chain in chickens infected with E. tenella

USDA-ARS?s Scientific Manuscript database

Background: Interleukin (IL) 2 and IL15 receptor beta chain (IL2/15Receptor beta, CD122) play critical roles in signal transduction for the biological activities of IL2 and IL15. Increased knowledge of non-mammalian IL2/15Receptor beta will enhance the understanding of IL2 and IL15 functions. Meth...

Crystal Structure of the Passenger Domain of the Escherichia coli Autotransporter EspP

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

Khan, Shekeb; Mian, Hira S.; Sandercock, Linda E.

2013-03-07

Autotransporters represent a large superfamily of known and putative virulence factors produced by Gram-negative bacteria. They consist of an N-terminal 'passenger domain' responsible for the specific effector functions of the molecule and a C-terminal '{beta}-domain' responsible for translocation of the passenger across the bacterial outer membrane. Here, we present the 2.5-{angstrom} crystal structure of the passenger domain of the extracellular serine protease EspP, produced by the pathogen Escherichia coli O157:H7 and a member of the serine protease autotransporters of Enterobacteriaceae (SPATEs). Like the previously structurally characterized SPATE passenger domains, the EspP passenger domain contains an extended right-handed parallel {beta}-helix precededmore » by an N-terminal globular domain housing the catalytic function of the protease. Of note, however, is the absence of a second globular domain protruding from this {beta}-helix. We describe the structure of the EspP passenger domain in the context of previous results and provide an alternative hypothesis for the function of the {beta}-helix within SPATEs.« less

Requirement for Pdx1 in specification of latent endocrine progenitors in zebrafish

PubMed Central

2011-01-01

Background Insulin-producing beta cells emerge during pancreas development in two sequential waves. Recently described later-forming beta cells in zebrafish show high similarity to second wave mammalian beta cells in developmental capacity. Loss-of-function studies in mouse and zebrafish demonstrated that the homeobox transcription factors Pdx1 and Hb9 are both critical for pancreas and beta cell development and discrete stage-specific requirements for these genes have been uncovered. Previously, exocrine and endocrine cell recovery was shown to follow loss of pdx1 in zebrafish, but the progenitor cells and molecular mechanisms responsible have not been clearly defined. In addition, interactions of pdx1 and hb9 in beta cell formation have not been addressed. Results To learn more about endocrine progenitor specification, we examined beta cell formation following morpholino-mediated depletion of pdx1 and hb9. We find that after early beta cell reduction, recovery occurs following loss of either pdx1 or hb9 function. Unexpectedly, simultaneous knockdown of both hb9 and pdx1 leads to virtually complete and persistent beta cell deficiency. We used a NeuroD:EGFP transgenic line to examine endocrine cell behavior in vivo and developed a novel live-imaging technique to document emergence and migration of late-forming endocrine precursors in real time. Our data show that Notch-responsive progenitors for late-arising endocrine cells are predominantly post mitotic and depend on pdx1. By contrast, early-arising endocrine cells are specified and differentiate independent of pdx1. Conclusions The nearly complete beta cell deficiency after combined loss of hb9 and pdx1 suggests functional cooperation, which we clarify as distinct roles in early and late endocrine cell formation. A novel imaging approach permitted visualization of the emergence of late endocrine cells within developing embryos for the first time. We demonstrate a pdx1-dependent progenitor population essential for the formation of duct-associated, second wave endocrine cells. We further reveal an unexpectedly low mitotic activity in these progenitor cells, indicating that they are set aside early in development. PMID:22034951

Interaction of Hb South Florida (codon 1; GTG-->ATG) and HbE, with beta-thalassemia (IVS1-1; G-->A): expression of different clinical phenotypes.

PubMed

Tan, Jin-Ai Mary Anne; Tan, Kim-Lian; Omar, Khairul Zaman; Chan, Lee-Lee; Wee, Yong-Chui; George, Elizabeth

2009-09-01

Interactions of different hemoglobin variants with thalassemia alleles can result in various clinical phenotypes. HbE-beta-thalassemia generally manifests with severe anemia where individuals exhibit beta-thalassemia major with regular blood transfusions or beta-thalassemia intermedia with periodic blood transfusions. This study presents a unique Malay family with three beta-globin gene defects-HbE, Hb South Florida, and IVS1-1 (G-->A). HbE activates a cryptic splice site that produces non-functional mRNAs. Hb South Florida is a rare beta-hemoglobin variant, and its interactions with other beta-thalassemia alleles have not been reported. IVS1-1 is a Mediterranean mutation that affects mRNA processing giving rise to beta(o)-thalassemia. Fifteen mutations along the beta-globin gene complex were analyzed using the amplification refractory mutation system. Hb South Florida was identified by direct sequencing using genomic DNA. The affected child with HbE/IVS1-1 produced a beta-thalassemia major phenotype. Compound heterozygosity for Hb South Florida/IVS1-1 produced a beta-thalassemia carrier phenotype in the mother.

Correlation of Shear Strength Between Longitudial and Transverse Specimens

DTIC Science & Technology

2012-05-17

Transverse Specimens" (2012). University of New Orleans Theses and Dissertations. Paper 1435. http://scholarworks.uno.edu/ td /1435 Report Documentation... ATI ) and they were  the sole providers of this metal during this project.  ATI  called the alloy:  ATI  425; it is very similar  in its properties to...Nie, C.; Dong, P.. Traction Stress Based Shear Strength Definition of Fillet Welds. Pending  Publishing.  [5] ATI  38‐644 Beta Titanium Alloy. Technical

Functional Connectivity and Quantitative EEG in Women with Alcohol Use Disorders: A Resting-State Study.

PubMed

Herrera-Díaz, Adianes; Mendoza-Quiñones, Raúl; Melie-Garcia, Lester; Martínez-Montes, Eduardo; Sanabria-Diaz, Gretel; Romero-Quintana, Yuniel; Salazar-Guerra, Iraklys; Carballoso-Acosta, Mario; Caballero-Moreno, Antonio

2016-05-01

This study was aimed at exploring the electroencephalographic features associated with alcohol use disorders (AUD) during a resting-state condition, by using quantitative EEG and Functional Connectivity analyses. In addition, we explored whether EEG functional connectivity is associated with trait impulsivity. Absolute and relative powers and Synchronization Likelihood (SL) as a measure of functional connectivity were analyzed in 15 AUD women and fifteen controls matched in age, gender and education. Correlation analysis between self-report impulsivity as measured by the Barratt impulsiveness Scale (BIS-11) and SL values of AUD patients were performed. Our results showed increased absolute and relative beta power in AUD patients compared to matched controls, and reduced functional connectivity in AUD patients predominantly in the beta and alpha bands. Impaired connectivity was distributed at fronto-central and occipito-parietal regions in the alpha band, and over the entire scalp in the beta band. We also found that impaired functional connectivity particularly in alpha band at fronto-central areas was negative correlated with non-planning dimension of impulsivity. These findings suggest that functional brain abnormalities are present in AUD patients and a disruption of resting-state EEG functional connectivity is associated with psychopathological traits of addictive behavior.

Development of New Open-Shell Perturbation and Coupled-Cluster Theories Based on Symmetric Spin Orbitals

NASA Technical Reports Server (NTRS)

Lee, Timothy J.; Arnold, James O. (Technical Monitor)

1994-01-01

A new spin orbital basis is employed in the development of efficient open-shell coupled-cluster and perturbation theories that are based on a restricted Hartree-Fock (RHF) reference function. The spin orbital basis differs from the standard one in the spin functions that are associated with the singly occupied spatial orbital. The occupied orbital (in the spin orbital basis) is assigned the delta(+) = 1/square root of 2(alpha+Beta) spin function while the unoccupied orbital is assigned the delta(-) = 1/square root of 2(alpha-Beta) spin function. The doubly occupied and unoccupied orbitals (in the reference function) are assigned the standard alpha and Beta spin functions. The coupled-cluster and perturbation theory wave functions based on this set of "symmetric spin orbitals" exhibit much more symmetry than those based on the standard spin orbital basis. This, together with interacting space arguments, leads to a dramatic reduction in the computational cost for both coupled-cluster and perturbation theory. Additionally, perturbation theory based on "symmetric spin orbitals" obeys Brillouin's theorem provided that spin and spatial excitations are both considered. Other properties of the coupled-cluster and perturbation theory wave functions and models will be discussed.

A critical role for transcription factor Smad4 in T cell function independent of transforming growth factor beta receptor signaling

PubMed Central

Gu, Ai-Di; Zhang, Song; Wang, Yunqi; Xiong, Hui; Curtis, Thomas A.; Wan, Yisong Y.

2014-01-01

Summary Transforming growth factor-beta (TGF-β) suppresses T cell function to maintain self-tolerance and to promote tumor immune evasion. Yet how Smad4, a transcription factor component of TGF-β signaling, regulates T cell function remains unclear. Here we have demonstrated an essential role for Smad4 in promoting T cell function during autoimmunity and anti-tumor immunity. Smad4 deletion rescued the lethal autoimmunity resulting from transforming growth factor-beta receptor (TGF-βR) deletion and compromised T-cell-mediated tumor rejection. While Smad4 was dispensable for T cell generation, homeostasis and effector function, it was essential for T cell proliferation following activation in vitro and in vivo. The transcription factor Myc was identified to mediate Smad4-controlled T cell proliferation. This study thus reveals a requirement of Smad4 for T-cell-mediated autoimmunity and tumor rejection, which is beyond the current paradigm. It highlights a TGF-βR-independent role for Smad4 in promoting T cell function, autoimmunity and anti-tumor immunity. PMID:25577439

Mechanical properties and grindability of dental cast Ti-Nb alloys.

PubMed

Kikuchi, Masafumi; Takahashi, Masatoshi; Okuno, Osamu

2003-09-01

Aiming at developing a dental titanium alloy with better mechanical properties and machinability than unalloyed titanium, a series of Ti-Nb alloys with Nb concentrations up to 30% was made. They were cast into magnesia-based molds using a dental casting machine and the mechanical properties and grindability of the castings were examined. The hardness of the alloys with Nb concentrations of 5% and above was significantly higher than that of titanium. The yield strength and tensile strength of the alloys with Nb concentrations of 10% and above were significantly higher than those of titanium, while the elongation was significantly lower. A small addition of niobium to titanium did not contribute to improving the grindability of titanium. The Ti-30% Nb alloy exhibited significantly better grindability at low grinding speed with higher hardness, strength, and Young's modulus than titanium, presumably due to precipitation of the omega phase in the beta matrix.

Compressive Failure of Fiber Composites under Multi-Axial Loading

NASA Technical Reports Server (NTRS)

Basu, Shiladitya; Waas, Anthony M.; Ambur, Damodar R.

2006-01-01

This paper examines the compressive strength of a fiber reinforced lamina under multi-axial stress states. An equilibrium analysis is carried out in which a kinked band of rotated fibers, described by two angles, is sandwiched between two regions in which the fibers are nominally straight. Proportional multi-axial stress states are examined. The analysis includes the possibility of bifurcation from the current equilibrium state. The compressive strength of the lamina is contingent upon either attaining a load maximum in the equilibrium response or satisfaction of a bifurcation condition, whichever occurs first. The results show that for uniaxial loading a non-zero kink band angle beta produces the minimum limit load. For multi-axial loading, different proportional loading paths show regimes of bifurcation dominated and limit load dominated behavior. The present results are able to capture the beneficial effect of transverse compression in raising the composite compressive strength as observed in experiments.

Regulated binding of PTP1B-like phosphatase to N-cadherin: control of cadherin-mediated adhesion by dephosphorylation of beta-catenin

PubMed Central

1996-01-01

Cadherins are a family of cell-cell adhesion molecules which play a central role in controlling morphogenetic movements during development. Cadherin function is regulated by its association with the actin containing cytoskeleton, an association mediated by a complex of cytoplasmic proteins, the catenins: alpha, beta, and gamma. Phosphorylated tyrosine residues on beta-catenin are correlated with loss of cadherin function. Consistent with this, we find that only nontyrosine phosphorylated beta-catenin is associated with N-cadherin in E10 chick retina tissue. Moreover, we demonstrate that a PTP1B-like tyrosine phosphatase associates with N-cadherin and may function as a regulatory switch controlling cadherin function by dephosphorylating beta-catenin, thereby maintaining cells in an adhesion-competent state. The PTP1B-like phosphatase is itself tyrosine phosphorylated. Moreover, both direct binding experiments performed with phosphorylated and dephosphorylated molecules, and treatment of cells with tyrosine kinase inhibitors indicate that the interaction of the PTP1B-like phosphatase with N-cadherin depends on its tyrosine phosphorylation. Concomitant with the tyrosine kinase inhibitor-induced loss of the PTP1B-like phosphatase from its association with N-cadherin, phosphorylated tyrosine residues are retained on beta-catenin, the association of N- cadherin with the actin containing cytoskeleton is lost and N-cadherin- mediated cell adhesion is prevented. Tyrosine phosphatase inhibitors also result in the accumulation of phosphorylated tyrosine residues on beta-catenin, loss of the association of N-cadherin with the actin- containing cytoskeleton, and prevent N-cadherin mediated adhesion, presumably by directly blocking the function of the PTP1B-like phosphatase. We previously showed that the binding of two ligands to the cell surface N-acetylgalactosaminylphosphotransferase (GalNAcPTase), the monoclonal antibody 1B11 and a proteoglycan with a 250-kD core protein, results in the accumulation of phosphorylated tyrosine residues on beta-catenin, uncoupling of N-cadherin from its association with the actin containing cytoskeleton, and loss of N- cadherin function. We now report that binding of these ligands to the GalNAcPTase results in the absence of the PTP1B-like phosphatase from its association with N-cadherin as well as the loss of the tyrosine kinase and tyrosine phosphatase activities that otherwise co- precipitate with N-cadherin. Control antibodies and proteoglycans have no such effect. This effect is similar to that observed with tyrosine kinase inhibitors, suggesting that the GalNAcPTase/proteoglycan interaction inhibits a tyrosine kinase, thereby preventing the phosphorylation of the PTP1B-like phosphatase, and its association with N-cadherin. Taken together these data indicate that a PTP1B-like tyrosine phosphatase can regulate N-cadherin function through its ability to dephosphorylate beta-catenin and that the association of the phosphatase with N-cadherin is regulated via the interaction of the GalNAcPTase with its proteoglycan ligand. In this manner the GalNAcPTase-proteoglycan interaction may play a major role in morphogenetic cell and tissue interactions during development. PMID:8707857

Expression of S100 beta in sensory and secretory cells of the vertebrate inner ear

NASA Technical Reports Server (NTRS)

Fermin, C. D.; Martin, D. S.

1995-01-01

We evaluated anti-S100 beta expression in the chick (Gallus domesticus) inner ear and determined that: 1) the monomer anti-S100 beta is expressed differentially in the vestibular and auditory perikarya; 2) expression of S100 beta in the afferent nerve terminals is time-related to synapse and myelin formation; 3) the expression of the dimer anti-S100 alpha alpha beta beta and monomer anti-S100 beta overlaps in most inner ear cell types. Most S100 alpha alpha beta beta positive cells express S100 beta, but S100 beta positive cells do not always express S100 alpha alpha beta beta. 4) the expression of S100 beta is diffused over the perikaryal cytoplasm and nuclei of the acoustic ganglia but is concentrated over the nuclei of the vestibular perikarya. 6) S100 beta is expressed in secretory cells, and it is co-localized with GABA in sensory cells. 7) Color thresholding objective quantitation indicates that the amount of S100 beta was higher (mean 22, SD +/- 4) at E19 than at E9 (mean 34, SD +/- 3) in afferent axons. 8) Moreover, S100 beta was unchanged between E11-E19 in the perikaryal cytoplasm, but did change over the nuclei. At E9, 74%, and at E21, 5% of vestibular perikarya were positive. The data suggest that S100 beta may be physically associated with neuronal and ionic controlling cells of the vertebrate inner ear, where it could provide a dual ionic and neurotrophic modulatory function.

Molecular biology of the 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase gene family.

PubMed

Simard, Jacques; Ricketts, Marie-Louise; Gingras, Sébastien; Soucy, Penny; Feltus, F Alex; Melner, Michael H

2005-06-01

The 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4) isomerase (3beta-HSD) isoenzymes are responsible for the oxidation and isomerization of Delta(5)-3beta-hydroxysteroid precursors into Delta(4)-ketosteroids, thus catalyzing an essential step in the formation of all classes of active steroid hormones. In humans, expression of the type I isoenzyme accounts for the 3beta-HSD activity found in placenta and peripheral tissues, whereas the type II 3beta-HSD isoenzyme is predominantly expressed in the adrenal gland, ovary, and testis, and its deficiency is responsible for a rare form of congenital adrenal hyperplasia. Phylogeny analyses of the 3beta-HSD gene family strongly suggest that the need for different 3beta-HSD genes occurred very late in mammals, with subsequent evolution in a similar manner in other lineages. Therefore, to a large extent, the 3beta-HSD gene family should have evolved to facilitate differential patterns of tissue- and cell-specific expression and regulation involving multiple signal transduction pathways, which are activated by several growth factors, steroids, and cytokines. Recent studies indicate that HSD3B2 gene regulation involves the orphan nuclear receptors steroidogenic factor-1 and dosage-sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome gene 1 (DAX-1). Other findings suggest a potential regulatory role for STAT5 and STAT6 in transcriptional activation of HSD3B2 promoter. It was shown that epidermal growth factor (EGF) requires intact STAT5; on the other hand IL-4 induces HSD3B1 gene expression, along with IL-13, through STAT 6 activation. However, evidence suggests that multiple signal transduction pathways are involved in IL-4 mediated HSD3B1 gene expression. Indeed, a better understanding of the transcriptional factors responsible for the fine control of 3beta-HSD gene expression may provide insight into mechanisms involved in the functional cooperation between STATs and nuclear receptors as well as their potential interaction with other signaling transduction pathways such as GATA proteins. Finally, the elucidation of the molecular basis of 3beta-HSD deficiency has highlighted the fact that mutations in the HSD3B2 gene can result in a wide spectrum of molecular repercussions, which are associated with the different phenotypic manifestations of classical 3beta-HSD deficiency and also provide valuable information concerning the structure-function relationships of the 3beta-HSD superfamily. Furthermore, several recent studies using type I and type II purified enzymes have elegantly further characterized structure-function relationships responsible for kinetic differences and coenzyme specificity.

Sensory and motor peripheral nerve function and longitudinal changes in quadriceps strength.

PubMed

Ward, Rachel E; Boudreau, Robert M; Caserotti, Paolo; Harris, Tamara B; Zivkovic, Sasa; Goodpaster, Bret H; Satterfield, Suzanne; Kritchevsky, Stephen; Schwartz, Ann V; Vinik, Aaron I; Cauley, Jane A; Newman, Anne B; Strotmeyer, Elsa S

2015-04-01

Poor peripheral nerve function is common in older adults and may be a risk factor for strength decline, although this has not been assessed longitudinally. We assessed whether sensorimotor peripheral nerve function predicts strength longitudinally in 1,830 participants (age = 76.3 ± 2.8, body mass index = 27.2 ± 4.6kg/m(2), strength = 96.3 ± 34.7 Nm, 51.0% female, 34.8% black) from the Health ABC study. Isokinetic quadriceps strength was measured semiannually over 6 years. Peroneal motor nerve conduction amplitude and velocity were recorded. Sensory nerve function was assessed with 10-g and 1.4-g monofilaments and average vibration detection threshold at the toe. Lower-extremity neuropathy symptoms were self-reported. Worse vibration detection threshold predicted 2.4% lower strength in men and worse motor amplitude and two symptoms predicted 2.5% and 8.1% lower strength, respectively, in women. Initial 10-g monofilament insensitivity predicted 14.2% lower strength and faster strength decline in women and 6.6% lower strength in men (all p < .05). Poor nerve function predicted lower strength and faster strength decline. Future work should examine interventions aimed at preventing declines in strength in older adults with impaired nerve function. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Preoperative Beta Cell Function Is Predictive of Diabetes Remission After Bariatric Surgery.

PubMed

Souteiro, Pedro; Belo, Sandra; Neves, João Sérgio; Magalhães, Daniela; Silva, Rita Bettencourt; Oliveira, Sofia Castro; Costa, Maria Manuel; Saavedra, Ana; Oliveira, Joana; Cunha, Filipe; Lau, Eva; Esteves, César; Freitas, Paula; Varela, Ana; Queirós, Joana; Carvalho, Davide

2017-02-01

Bariatric surgery can improve glucose metabolism in obese patients with diabetes, but the factors that can predict diabetes remission are still under discussion. The present study aims to examine the impact of preoperative beta cell function on diabetes remission following surgery. We investigated a cohort of 363 obese diabetic patients who underwent bariatric surgery. The impact of several preoperative beta cell function indexes on diabetes remission was explored through bivariate logistic regression models. Postoperative diabetes remission was achieved in 39.9 % of patients. Younger patients (p < 0.001) and those with lower HbA1c (p = 0.001) at the baseline evaluation had higher odds of diabetes remission. Use of oral anti-diabetics and insulin therapy did not reach statistical significance when they were adjusted for age and HbA1c. Among the evaluated indexes of beta cell function, higher values of insulinogenix index, Stumvoll first- and second-phase indexes, fasting C-peptide, C-peptide area under the curve (AUC), C-peptide/glucose AUC, ISR (insulin secretion rate) AUC, and ISR/glucose AUC predicted diabetes remission even after adjustment for age and HbA1c. Among them, C-peptide AUC had the higher discriminative power (AUC 0.76; p < 0.001). Patients' age and preoperative HbA1c can forecast diabetes remission following surgery. Unlike other studies, our group found that the use of oral anti-diabetics and insulin therapy were not independent predictors of postoperative diabetes status. Preoperative beta cell function, mainly C-peptide AUC, is useful in predicting diabetes remission, and it should be assessed in all obese diabetic patients before bariatric or metabolic surgery.

Pancreas-Specific Sirt1-Deficiency in Mice Compromises Beta-Cell Function without Development of Hyperglycemia.

PubMed

Pinho, Andreia V; Bensellam, Mohammed; Wauters, Elke; Rees, Maxine; Giry-Laterriere, Marc; Mawson, Amanda; Ly, Le Quan; Biankin, Andrew V; Wu, Jianmin; Laybutt, D Ross; Rooman, Ilse

2015-01-01

Sirtuin 1 (Sirt1) has been reported to be a critical positive regulator of glucose-stimulated insulin secretion in pancreatic beta-cells. The effects on islet cells and blood glucose levels when Sirt1 is deleted specifically in the pancreas are still unclear. This study examined islet glucose responsiveness, blood glucose levels, pancreatic islet histology and gene expression in Pdx1Cre; Sirt1ex4F/F mice that have loss of function and loss of expression of Sirt1 specifically in the pancreas. We found that in the Pdx1Cre; Sirt1ex4F/F mice, the relative insulin positive area and the islet size distribution were unchanged. However, beta-cells were functionally impaired, presenting with lower glucose-stimulated insulin secretion. This defect was not due to a reduced expression of insulin but was associated with a decreased expression of the glucose transporter Slc2a2/Glut2 and of the Glucagon like peptide-1 receptor (Glp1r) as well as a marked down regulation of endoplasmic reticulum (ER) chaperones that participate in the Unfolded Protein Response (UPR) pathway. Counter intuitively, the Sirt1-deficient mice did not develop hyperglycemia. Pancreatic polypeptide (PP) cells were the only other islet cells affected, with reduced numbers in the Sirt1-deficient pancreas. This study provides new mechanistic insights showing that beta-cell function in Sirt1-deficient pancreas is affected due to altered glucose sensing and deregulation of the UPR pathway. Interestingly, we uncovered a context in which impaired beta-cell function is not accompanied by increased glycemia. This points to a unique compensatory mechanism. Given the reduction in PP, investigation of its role in the control of blood glucose is warranted.

Efficacy of quercetin flavonoid in recovering the postbleaching bond strength of orthodontic brackets: A preliminary study.

PubMed

Shamsedin, Mana; Arash, Valiollah; Jahromi, Masoud Babaei; Moghadamnia, Ali Akbar; Kamel, Manouchehr Rahmati; Ezoji, Fariba; Bijani, Ali; Kavoli, Samira; Ghasemi, Tania; Ramezani, Gholamhossein

2017-01-01

To evaluate comparatively the effect of quercetin on postbleaching shear bond strength (SBS) and adhesive remnant index (ARI). Intact maxillary premolars were divided randomly into 12 groups of 10 each: (1) bonding the bracket immediately after bleaching, (2) bonding 1 week after bleaching, (3-8) application of three experimental concentrations of quercetin (0.1%, 0.5%, and 1%) at two time durations (5 and 10 min), (9-10) application of the solvent of quercetin at two time periods (5 and 10 min), (11) application of 10% sodium ascorbate for 10 min, and (12) bonding the brackets on nonbleached teeth. Bleaching was performed using 15% carbamide peroxide gel for 5 days (6 h daily). After incubation and thermocycling, the SBS of brackets was measured. The ARI too was recorded at ×20. The data were analyzed statistically (α =0.05). Bleaching reduced the SBS below 10 Megapascal (MPa) level ( P < 0.05) while all the postbleaching treatments (except the application of the solvent of quercetin) recovered the SBS back to values greater than 10 MPa ( P < 0.05) and also back to nonbleached SBS levels ( P > 0.01). All eight postbleaching treatments had rather similar efficacies ( P = 0.1396). The concentration of quercetin (beta = 0.259, P = 0.042) but not its duration (beta = 0.213, P = 0.093) significantly improved its efficacy. Bleaching can weaken the bond strength of orthodontic brackets below acceptable levels. The application of quercetin or Vitamin C or delaying the bracket bonding improved the postbleaching SBS.

In vivo IL-10 and TGF-beta production by PBMC from long-term kidney transplant recipients with excellent graft function: a possible feedback mechanism participating in immunological stability.

PubMed

Alberú, Josefina; Richaud-Patin, Yvonne; Vázquez-Lavista, Luis Gabriel; de Leo, Claudia; Guzmán-Rodríguez, Hugo; Mancilla, Eduardo; Correa-Rotter, Ricardo; Chew-Wong, Alfredo; Llorente, Luis

2004-04-01

Interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) are Th2-derived multifunctional cytokines that exhibit potent immunoregulatory and anti-inflammatory properties which might prolong graft survival. The aim of this study was to explore whether spontaneous production of IL-10 and TGF-beta by blood mononuclear cells correlates with excellent long-term graft function. A cross-sectional study was carried out in 32 kidney transplant recipients, without albuminuria, treated with azathioprine and prednisone. Spontaneous IL-10 and TGF-beta were measured by enzyme-linked immunosorbent assay in supernatants from 24 h cultured unstimulated peripheral blood mononuclear cells. Both cytokines were also determined in 10 healthy kidney donors. There was no correlation between IL-10 or TGF-beta with any variable tested, namely age, SCr, histocompatibility, and post-transplant follow-up. In vivo IL-10 production displayed a statistical trend to be higher in transplant recipients than in controls (362.3 +/- 465, range 12.5-1929.3 pg/ml, and 189 +/- 170, range 4.17-485.7 pg/ml, respectively; p = 0.08), whereas no difference was observed in TGF-beta among the same groups (134.7 +/- 79.2, range 68-421 pg/ml, and 121.4 +/- 25.8, range 75-151 pg/ml, respectively). Interestingly, a statistically significant inverse correlation was observed between IL-10 and TGF-beta in kidney transplant recipients (p = 0.03). The higher IL-10 production observed in long-term kidney transplant recipients supports the notion that this cytokine contributes in decreasing allogenic immune responses and allows prolongation of allograft survival. The balance between TGF-beta and IL-10 may be of paramount importance in graft acceptance.

Alterations induced by E-cadherin and beta-catenin antibodies during the development of Bufo arenarum (Anura-Bufonidae).

PubMed

Izaguirre, M F; Adur, J F; Soler, A P; Casco, V H

2001-10-01

E(epithelial)-cadherin is a member of a calcium-dependent family of cell surface glycoproteins involved in cell-cell adhesion and morphogenesis. Catenins are a large family of proteins that connect the cadherins to the cytoskeleton. They are important for cadherin function and for transducing signals involved in specification of cell fate during embryogenesis. The best characterized catenins include alpha-, beta-, gamma-, and p120-catenin. Using specific antibodies, we studied the expression and distribution of E-cadherin, and alpha- and beta-catenin in developmental stages of Bufo arenarum toad. The three proteins were found co-localized in stages 19 to 41 of development. Surprisingly, E-cadherin was the only of these three proteins found earlier than stage 19. To test whether E-cadherin and beta-catenin have a functional role in Bufo arenarum embryogenesis, stage 17 whole embryos were incubated with anti-E-cadherin and beta-catenin antibodies. Both anti-E-cadherin and anti-beta-catenin antibodies induced severe morphological alterations. However, while alterations produced by the anti-beta-catenin antibody, showed some variability from the most severe (neural tube and notochord duplication) to a simple delay in development, the alterations with anti-E-cadherin were homogeneous. These observations suggest a critical role for E-cadherin and beta-catenin in the early embryonic development of the Bufo arenarum toad. Our results are consistent with the developmental role of these proteins in other species. One of the most surprising findings was the blockage with the anti-beta-catenin antibodies on later embryo stages, and we hypothesize that the partial axes duplication could be mediated by the notochord induction.

The molecular biology of the group VIA Ca2+-independent phospholipase A2.

PubMed

Ma, Z; Turk, J

2001-01-01

The group VIA PLA2 is a member of the PLA2 superfamily. This enzyme, which is cytosolic and Ca2+-independent, has been designated iPLA2beta to distinguish it from another recently cloned Ca2+-independent PLA2. Features of iPLA2beta molecular structure offer some insight into possible cellular functions of the enzyme. At least two catalytically active iPLA2beta isoforms and additionalsplicing variants are derived from a single gene that consists of at least 17 exons located on human chromosome 22q13.1. Potential tumor suppressor genes also reside at or near this locus. Structural analyses reveal that iPLA2beta contains unique structural features that include a serine lipase consensus motif (GXSXG), a putative ATP-binding domain, an ankyrin-repeat domain, a caspase-3 cleavage motif DVTD138Y/N, a bipartite nuclear localization signal sequence, and a proline-rich region in the human long isoform. iPLA2beta is widely expressed among mammalian tissues, with highest expression in testis and brain. iPLA2beta prefers to hydrolyze fatty acid at the sn-2 fatty acid substituent but also exhibits phospholipase A1, lysophospholipase, PAF acetylhydrolase, and transacylase activities. iPLA2beta may participate in signaling, apoptosis, membrane phospholipid remodeling, membrane homeostasis, arachidonate release, and exocytotic membrane fusion. Structural features and the existence of multiple splicing variants of iPLA2beta suggest that iPLA2beta may be subject to complex regulatory mechanisms that differ among cell types. Further study of its regulation and interaction with other proteins may yield insight into how its structural features are related to its function.

Receptor protection studies comparing recombinant and native nicotinic receptors: Evidence for a subpopulation of mecamylamine-sensitive native alpha3beta4* nicotinic receptors.

PubMed

Free, R Benjamin; Kaser, Daniel J; Boyd, R Thomas; McKay, Dennis B

2006-01-09

Studies involving receptor protection have been used to define the functional involvement of specific receptor subtypes in tissues expressing multiple receptor subtypes. Previous functional studies from our laboratory demonstrate the feasibility of this approach when applied to neuronal tissues expressing multiple nicotinic acetylcholine receptors (nAChRs). In the current studies, the ability of a variety of nAChR agonists and antagonists to protect native and recombinant alpha3beta4 nAChRs from alkylation were investigated using nAChR binding techniques. Alkylation of native alpha3beta4* nAChRs from membrane preparations of bovine adrenal chromaffin cells resulted in a complete loss of specific [(3)H]epibatidine binding. This loss of binding to native nAChRs was preventable by pretreatment with the agonists, carbachol or nicotine. The partial agonist, cytisine, produced partial protection. Several nAChR antagonists were also tested for their ability to protect. Hexamethonium and decamethonium were without protective activity while mecamylamine and tubocurarine were partially effective. Addition protection studies were performed on recombinant alpha3beta4 nAChRs. As with native alpha3beta4* nAChRs, alkylation produced a complete loss of specific [(3)H]epibatidine binding to recombinant alpha3beta4 nAChRs which was preventable by pretreatment with nicotine. However, unlike native alpha3beta4* nAChRs, cytisine and mecamylamine, provide no protection for alkylation. These results highlight the differences between native alpha3beta4* nAChRs and recombinant alpha3beta4 nAChRs and support the use of protection assays to characterize native nAChR subpopulations.

Structural Aspects for Evolution of [beta]-Lactamases from Penicillin-Binding Proteins

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

Meroueh, Samy O.; Minasov, George; Lee, Wenlin

Penicillin-binding proteins (PBPs), biosynthetic enzymes of bacterial cell wall assembly, and {beta}-lactamases, resistance enzymes to {beta}-lactam antibiotics, are related to each other from an evolutionary point of view. Massova and Mobashery (Antimicrob. Agents Chemother. 1998, 42, 1-17) have proposed that for {beta}-lactamases to have become effective at their function as antibiotic resistance enzymes, they would have had to undergo structure alterations such that they would not interact with the peptidoglycan, which is the substrate for PBPs. A cephalosporin analogue, 7{beta}-[N-Acetyl-L-alanyl-{gamma}-D-glutamyl-L-lysine]-3-acetoxymethyl-3-cephem-carboxylic acid (compound 6), was conceived and synthesized to test this notion. The X-ray structure of the complex of this cephalosporinmore » bound to the active site of the deacylation-deficient Q120L/Y150E variant of the class C AmpC {beta}-lactamase from Escherichia coli was solved at 1.71 {angstrom} resolution. This complex revealed that the surface for interaction with the strand of peptidoglycan that acylates the active site, which is present in PBPs, is absent in the {beta}-lactamase active site. Furthermore, insertion of a peptide in the {beta}-lactamase active site at a location where the second strand of peptidoglycan in some PBPs binds has effectively abolished the possibility for such interaction with the {beta}-lactamase. A 2.6 ns dynamics simulation was carried out for the complex, which revealed that the peptidoglycan surrogate (i.e., the active-site-bound ligand) undergoes substantial motion and is not stabilized for binding within the active site. These factors taken together disclose the set of structure modifications in the antibiotic resistance enzyme that prevent it from interacting with the peptidoglycan, en route to achieving catalytic proficiency for their intended function.« less

N-terminal tyrosine phosphorylation of caveolin-2 negates anti-proliferative effect of transforming growth factor beta in endothelial cells

PubMed Central

Abel, Britain; Willoughby, Cara; Jang, Sungchan; Cooper, Laura; Xie, Leike; Vo-Ransdell, Chi; Sowa, Grzegorz

2012-01-01

Here we show that tyrosine phosphorylation of caveolin-2 (Cav-2) negatively regulates the anti-proliferative function of transforming growth factor beta (TGF-beta) in endothelial cells. In contrast to wild-type-Cav-2, retroviral re-expression of Y19/27F-Cav-2 in Cav-2 knockout endothelial cells did not affect anti-proliferative effect of TGF-beta compared to empty vector. Conversely, although less effective than wild-type, re-expression of S23/36A-Cav-2 reduced the effect of TGF-beta compared to empty vector. This differential effect of tyrosine and serine phosphorylation mutants of Cav-2 correlated with TGF-beta-induced Smad3 phosphorylation and transcriptional activation of plasminogen activator inhibitor-1. Thus tyrosine-phosphorylated Cav-2 counteracts anti-proliferative effect of TGF-beta in endothelial cells. PMID:22819829

Transforming growth factor-beta1 mediates cellular response to DNA damage in situ

NASA Technical Reports Server (NTRS)

Ewan, Kenneth B.; Henshall-Powell, Rhonda L.; Ravani, Shraddha A.; Pajares, Maria Jose; Arteaga, Carlos; Warters, Ray; Akhurst, Rosemary J.; Barcellos-Hoff, Mary Helen

2002-01-01

Transforming growth factor (TGF)-beta1 is rapidly activated after ionizing radiation, but its specific role in cellular responses to DNA damage is not known. Here we use Tgfbeta1 knockout mice to show that radiation-induced apoptotic response is TGF-beta1 dependent in the mammary epithelium, and that both apoptosis and inhibition of proliferation in response to DNA damage decrease as a function of TGF-beta1 gene dose in embryonic epithelial tissues. Because apoptosis in these tissues has been shown previously to be p53 dependent, we then examined p53 protein activation. TGF-beta1 depletion, by either gene knockout or by using TGF-beta neutralizing antibodies, resulted in decreased p53 Ser-18 phosphorylation in irradiated mammary gland. These data indicate that TGF-beta1 is essential for rapid p53-mediated cellular responses that mediate cell fate decisions in situ.

The Golgi localization of phosphatidylinositol transfer protein beta requires the protein kinase C-dependent phosphorylation of serine 262 and is essential for maintaining plasma membrane sphingomyelin levels.

PubMed

van Tiel, Claudia M; Westerman, Jan; Paasman, Marten A; Hoebens, Martha M; Wirtz, Karel W A; Snoek, Gerry T

2002-06-21

Recombinant mouse phosphatidylinositol transfer protein (PI-TP)beta is a substrate for protein kinase C (PKC)-dependent phosphorylation in vitro. Based on site-directed mutagenesis and two-dimensional tryptic peptide mapping, Ser(262) was identified as the major site of phosphorylation and Ser(165) as a minor phosphorylation site. The phospholipid transfer activities of wild-type PI-TP beta and PI-TP beta(S262A) were identical, whereas PI-TP beta(S165A) was completely inactive. PKC-dependent phosphorylation of Ser(262) also had no effect on the transfer activity of PI-TP beta. To investigate the role of Ser(262) in the functioning of PI-TP beta, wtPI-TP beta and PI-TP beta(S262A) were overexpressed in NIH3T3 fibroblast cells. Two-dimensional PAGE analysis of cell lysates was used to separate PI-TP beta from its phosphorylated form. After Western blotting, wtPI-TP beta was found to be 85% phosphorylated, whereas PI-TP beta(S262A) was not phosphorylated. In the presence of the PKC inhibitor GF 109203X, the phosphorylated form of wtPI-TP beta was strongly reduced. Immunolocalization showed that wtPI-TP beta was predominantly associated with the Golgi membranes. In the presence of the PKC inhibitor, wtPI-TP beta was distributed throughout the cell similar to what was observed for PI-TP beta(S262A). In contrast to wtPI-TP beta overexpressors, cells overexpressing PI-TP beta(S262A) were unable to rapidly replenish sphingomyelin in the plasma membrane upon degradation by sphingomyelinase. This implies that PKC-dependent association with the Golgi complex is a prerequisite for PI-TP beta to express its effect on sphingomyelin metabolism.

Functional analysis of multiple carotenogenic genes from Lycium barbarum and Gentiana lutea L. for their effects on beta-carotene production in transgenic tobacco.

PubMed

Ji, Jing; Wang, Gang; Wang, Jiehua; Wang, Ping

2009-02-01

Carotenoids are red, yellow and orange pigments, which are widely distributed in nature and are especially abundant in yellow-orange fruits and vegetables and dark green leafy vegetables. Carotenoids are essential for photosynthesis and photoprotection in plant life and also have different beneficial effects in humans and animals (van den Berg et al. 2000). For example, beta-carotene plays an essential role as the main dietary source of vitamin A. To obtain further insight into beta-carotene biosynthesis in two important economic plant species, Lycium barbarum and Gentiana lutea L., and to investigate and prioritize potential genetic engineering targets in the pathway, the effects of five carotenogenic genes from these two species, encoding proteins including geranylgeranyl diphosphate synthase, phytoene synthase and delta-carotene desaturase gene, lycopene beta-cyclase, lycopene epsilon-cyclase were functionally analyzed in transgenic tobacco (Nicotiana tabacum) plants. All transgenic tobacco plants constitutively expressing these genes showed enhanced beta-carotene contents in their leaves and flowers to different extents. The addictive effects of co-ordinate expression of double transgenes have also been investigated.

Integrating Taxonomic, Functional and Phylogenetic Beta Diversities: Interactive Effects with the Biome and Land Use across Taxa.

PubMed

Corbelli, Julian Martin; Zurita, Gustavo Andres; Filloy, Julieta; Galvis, Juan Pablo; Vespa, Natalia Isabel; Bellocq, Isabel

2015-01-01

The spatial distribution of species, functional traits and phylogenetic relationships at both the regional and local scales provide complementary approaches to study patterns of biodiversity and help to untangle the mechanisms driving community assembly. Few studies have simultaneously considered the taxonomic (TBD), functional (FBD) and phylogenetic (PBD) facets of beta diversity. Here we analyze the associations between TBD, FBD, and PBD with the biome (representing different regional species pools) and land use, and investigate whether TBD, FBD and PBD were correlated. In the study design we considered two widely used indicator taxa (birds and ants) from two contrasting biomes (subtropical forest and grassland) and land uses (tree plantations and cropfields) in the southern Neotropics. Non-metric multidimensional scaling showed that taxonomic, functional and phylogenetic distances were associated to biome and land use; study sites grouped into four groups on the bi-dimensional space (cropfields in forest and grassland, and tree plantations in forest and grassland), and that was consistent across beta diversity facets and taxa. Mantel and PERMANOVA tests showed that TBD, FBD and PBD were positively correlated for both bird and ant assemblages; in general, partial correlations were also significant. Some of the functional traits considered here were conserved along phylogeny. Our results will contribute to the development of sound land use planning and beta diversity conservation.

Integrating Taxonomic, Functional and Phylogenetic Beta Diversities: Interactive Effects with the Biome and Land Use across Taxa

PubMed Central

Corbelli, Julian Martin; Zurita, Gustavo Andres; Filloy, Julieta; Galvis, Juan Pablo; Vespa, Natalia Isabel; Bellocq, Isabel

2015-01-01

The spatial distribution of species, functional traits and phylogenetic relationships at both the regional and local scales provide complementary approaches to study patterns of biodiversity and help to untangle the mechanisms driving community assembly. Few studies have simultaneously considered the taxonomic (TBD), functional (FBD) and phylogenetic (PBD) facets of beta diversity. Here we analyze the associations between TBD, FBD, and PBD with the biome (representing different regional species pools) and land use, and investigate whether TBD, FBD and PBD were correlated. In the study design we considered two widely used indicator taxa (birds and ants) from two contrasting biomes (subtropical forest and grassland) and land uses (tree plantations and cropfields) in the southern Neotropics. Non-metric multidimensional scaling showed that taxonomic, functional and phylogenetic distances were associated to biome and land use; study sites grouped into four groups on the bi-dimensional space (cropfields in forest and grassland, and tree plantations in forest and grassland), and that was consistent across beta diversity facets and taxa. Mantel and PERMANOVA tests showed that TBD, FBD and PBD were positively correlated for both bird and ant assemblages; in general, partial correlations were also significant. Some of the functional traits considered here were conserved along phylogeny. Our results will contribute to the development of sound land use planning and beta diversity conservation. PMID:25978319

A Multifunctional Bread Rich in Beta Glucans and Low in Starch Improves Metabolic Control in Type 2 Diabetes: A Controlled Trial

PubMed Central

Tessari, Paolo; Lante, Anna

2017-01-01

Design: Functional foods may be useful for people with diabetes. The soluble fibers beta glucans can modify starch digestion and improve postprandial glucose response. We analyzed the metabolic effects of a specifically designed ‘functional’ bread, low in starch, rich in fibers (7 g/100 g), with a beta glucan/starch ratio of (7.6:100, g/g), in people with type 2 diabetes mellitus. Methods: Clinical and metabolic data from two groups of age-, sex- and glycated hemoglobin-matched diabetic subjects, taking either the functional bread or regular white bread, over a roughly six-month observation period, were retrieved. Results: Bread intake did not change during the trial. The functional bread reduced glycated hemoglobin by ~0.5% (absolute units) vs. pre-treatment values (p = 0.028), and by ~0.6% vs. the control group (p = 0.027). Post-prandial and mean plasma glucose was decreased in the treatment group too. Body weight, blood pressure and plasma lipids did not change. The acceptance of the functional bread was good in the majority of subjects, except for taste. Conclusions: A starch-restricted, fiber-rich functional bread, with an increased beta glucan/starch ratio, improved long term metabolic control, and may be indicated in the dietary treatment of type 2 diabetes. PMID:28304350