New type IIB backgrounds and aspects of their field theory duals

NASA Astrophysics Data System (ADS)

Caceres, Elena; Macpherson, Niall T.; Núñez, Carlos

2014-08-01

In this paper we study aspects of geometries in Type IIA and Type IIB String theory and elaborate on their field theory dual pairs. The backgrounds are associated with reductions to Type IIA of solutions with G 2 holonomy in eleven dimensions. We classify these backgrounds according to their G-structure, perform a non-Abelian T-duality on them and find new Type IIB configurations presenting dynamical SU(2)-structure. We study some aspects of the associated field theories defined by these new backgrounds. Various technical details are clearly spelled out.

Bayesian phylogeny of sucrose transporters: ancient origins, differential expansion and convergent evolution in monocots and dicots

PubMed Central

Peng, Duo; Gu, Xi; Xue, Liang-Jiao; Leebens-Mack, James H.; Tsai, Chung-Jui

2014-01-01

Sucrose transporters (SUTs) are essential for the export and efficient movement of sucrose from source leaves to sink organs in plants. The angiosperm SUT family was previously classified into three or four distinct groups, Types I, II (subgroup IIB), and III, with dicot-specific Type I and monocot-specific Type IIB functioning in phloem loading. To shed light on the underlying drivers of SUT evolution, Bayesian phylogenetic inference was undertaken using 41 sequenced plant genomes, including seven basal lineages at key evolutionary junctures. Our analysis supports four phylogenetically and structurally distinct SUT subfamilies, originating from two ancient groups (AG1 and AG2) that diverged early during terrestrial colonization. In both AG1 and AG2, multiple intron acquisition events in the progenitor vascular plant established the gene structures of modern SUTs. Tonoplastic Type III and plasmalemmal Type II represent evolutionarily conserved descendants of AG1 and AG2, respectively. Type I and Type IIB were previously thought to evolve after the dicot-monocot split. We show, however, that divergence of Type I from Type III SUT predated basal angiosperms, likely associated with evolution of vascular cambium and phloem transport. Type I SUT was subsequently lost in monocots along with vascular cambium, and independent evolution of Type IIB coincided with modified monocot vasculature. Both Type I and Type IIB underwent lineage-specific expansion. In multiple unrelated taxa, the newly-derived SUTs exhibit biased expression in reproductive tissues, suggesting a functional link between phloem loading and reproductive fitness. Convergent evolution of Type I and Type IIB for SUT function in phloem loading and reproductive organs supports the idea that differential vascular development in dicots and monocots is a strong driver for SUT family evolution in angiosperms. PMID:25429293

On the stability of non-supersymmetric supergravity solutions

NASA Astrophysics Data System (ADS)

Imaanpur, Ali; Zameni, Razieh

2017-09-01

We examine the stability of some non-supersymmetric supergravity solutions that have been found recently. The first solution is AdS5 ×M6, for M6 an stretched CP3. We consider breathing and squashing mode deformations of the metric, and find that the solution is stable against small fluctuations of this kind. Next we consider type IIB solution of AdS2 ×M8, where the compact space is a U (1) bundle over N (1 , 1). We study its stability under the deformation of M8 and the 5-form flux. In this case we also find that the solution is stable under small fluctuation modes of the corresponding deformations.

A geometrical upper bound on the inflaton range

NASA Astrophysics Data System (ADS)

Cicoli, Michele; Ciupke, David; Mayrhofer, Christoph; Shukla, Pramod

2018-05-01

We argue that in type IIB LVS string models, after including the leading order moduli stabilisation effects, the moduli space for the remaining flat directions is compact due the Calabi-Yau Kähler cone conditions. In cosmological applications, this gives an inflaton field range which is bounded from above, in analogy with recent results from the weak gravity and swampland conjectures. We support our claim by explicitly showing that it holds for all LVS vacua with h 1,1 = 3 obtained from 4-dimensional reflexive polytopes. In particular, we first search for all Calabi-Yau threefolds from the Kreuzer-Skarke list with h 1,1 = 2, 3 and 4 which allow for LVS vacua, finding several new LVS geometries which were so far unknown. We then focus on the h 1,1 = 3 cases and show that the Kähler cones of all toric hypersurface threefolds force the effective 1-dimensional LVS moduli space to be compact. We find that the moduli space size can generically be trans-Planckian only for K3 fibred examples.

New class of de Sitter vacua in string theory compactifications

NASA Astrophysics Data System (ADS)

Achúcarro, Ana; Ortiz, Pablo; Sousa, Kepa

2016-10-01

String theory contains few known working examples of de Sitter vacua, four-dimensional universes with a positive cosmological constant. A notorious obstacle is the stabilization of a large number—sometimes hundreds—of moduli fields that characterize the compact dimensions. We study the stability of a class of supersymmetric moduli (the complex structure moduli and dilaton in type-IIB flux compactifications) in the regime where the volume of the compact space is large but not exponentially large. We show that, if the number of moduli is very large, random matrix theory provides a new stability condition, a lower bound on the volume. We find a new class of stable vacua where the mass spectrum of these supersymmetric moduli is gapped, without requiring a large mass hierarchy between moduli sectors or any fine-tuning of the superpotential. We provide the first explicit example of this class of vacua in the P[1,1 ,1 ,6 ,9 ] 4 model. A distinguishing feature is that all fermions in the supersymmetric sector are lighter than the gravitino.

Effects of carbon and hafnium concentrations in wrought powder-metallurgy superalloys based on NASA 2B-11 alloy

NASA Technical Reports Server (NTRS)

Miner, R. V., Jr.

1976-01-01

A candidate alloy for advanced-temperature turbine engine disks, and four modifications of that alloy with various C and Hf concentrations were produced as cross-rolled disks from prealloyed powder that was hot isostatically compacted. The mechanical properties, microstructures, and phase relations of the alloys are discussed in terms of their C and Hf concentrations. A low-C and high-Hf modification of IIB-11 had the best balance of mechanical properties for service below about 750 C. Because of their finer grain sizes, none of the powder-metallurgy alloys produced had the high-temperature rupture strength of conventionally cast and wrought IIB-11.

IIB duals of D = 3 {N} = 4 circular quivers

NASA Astrophysics Data System (ADS)

Assel, Benjamin; Bachas, Costas; Estes, John; Gomis, Jaume

2012-12-01

We construct the type-IIB AdS4 ⋉ K supergravity solutions which are dual to the three-dimensional {N} = 4 superconformal field theories that arise as infrared fixed points of circular-quiver gauge theories. These superconformal field theories are labeled by a triple ( {ρ, hat{ρ},L} ) subject to constraints, where ρ and hat{ρ} are two partitions of a number N, and L is a positive integer. We show that in the limit of large L the localized five- branes in our solutions are effectively smeared, and these type-IIB solutions are dual to the near-horizon geometry of M-theory M2-branes at a {{{{{{C}}^4}}} / {{( {{Z_k}× {Z_{widehat{k}}}} )}} .} orbifold singularity. Our IIB solutions resolve the singularity into localized five-brane throats, without breaking the conformal symmetry. The constraints satisfied by the triple ( {ρ, hat{ρ},L} ) , together with the enhanced non-abelian flavour symmetries of the superconformal field theories are precisely reproduced by the type-IIB supergravity solutions. As a bonus, we uncover a novel type of "orbifold equivalence" between different quantum field theories and provide quantitative evidence for this equivalence.

Integral group actions on symmetric spaces and discrete duality symmetries of supergravity theories

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

Carbone, Lisa; Murray, Scott H.; Sati, Hisham

For G = G(ℝ), a split, simply connected, semisimple Lie group of rank n and K the maximal compact subgroup of G, we give a method for computing Iwasawa coordinates of K∖G using the Chevalley generators and the Steinberg presentation. When K∖G is a scalar coset for a supergravity theory in dimensions ≥3, we determine the action of the integral form G(ℤ) on K∖G. We give explicit results for the action of the discrete U-duality groups SL{sub 2}(ℤ) and E{sub 7}(ℤ) on the scalar cosets SO(2)∖SL{sub 2}(ℝ) and [SU(8)/( ± Id)]∖E{sub 7(+7)}(ℝ) for type IIB supergravity in ten dimensions andmore » 11-dimensional supergravity reduced to D = 4 dimensions, respectively. For the former, we use this to determine the discrete U-duality transformations on the scalar sector in the Borel gauge and we describe the discrete symmetries of the dyonic charge lattice. We determine the spectrum-generating symmetry group for fundamental BPS solitons of type IIB supergravity in D = 10 dimensions at the classical level and we propose an analog of this symmetry at the quantum level. We indicate how our methods can be used to study the orbits of discrete U-duality groups in general.« less

[Type IIb primary hyperlipoproteinemia. An homogenous series of 412 cases].

PubMed

Rouffy, J; Loeper, J; Dreux, C; Lemogne, M; Loeper, J; Pestel, M; Dakkak, R

1976-03-20

On the basis of a homogeneous series of 412 cases of type IIb primary hyperlipoproteinaemia, the authors compare their experience with findings in the literature. The prevalence of this type of hyperlipoproteinaemia in the general population has been underestimated at 3%. Biological diagnosis remains simple (identification of a double and distinct excess in beta and pre beta lipoproteins). Extravascular lipid deposits (gerontoxon, xanthelasma, tendon xanthomata) are not type specific. Hyperlipidaemic syndrome is rare. Above all, the importance of type IIb in atheromatous disease in the young subject now seems obvious. The mode of hereditary transmission of the familial anomaly is not certain but would appear to be often associated with a double heterozygote condition.

Platelet adhesion via glycoprotein IIb integrin is critical for atheroprogression and focal cerebral ischemia: an in vivo study in mice lacking glycoprotein IIb.

PubMed

Massberg, Steffen; Schürzinger, Katrin; Lorenz, Michael; Konrad, Ildiko; Schulz, Christian; Plesnila, Nikolaus; Kennerknecht, Elisabeth; Rudelius, Martina; Sauer, Susanne; Braun, Siegmund; Kremmer, Elisabeth; Emambokus, Nikla R; Frampton, Jon; Gawaz, Meinrad

2005-08-23

The platelet glycoprotein (GP) IIb/IIIa integrin binds to fibrinogen and thereby mediates platelet aggregation. Here, we addressed the role of GP IIb for platelet adhesion and determined the relevance of platelet GP IIb for the processes of atherosclerosis and cerebral ischemia-reperfusion (I/R) injury. GP IIb(-/-) mice were generated and bred with ApoE(-/-) animals to create GP IIb(-/-)ApoE(-/-) mice. Platelet adhesion to the mechanically injured or atherosclerotic vessel wall was monitored by in vivo video fluorescence microscopy. In the presence of GP IIb, vascular injury and early atherosclerosis induced platelet adhesion in the carotid artery (CA). In contrast, platelet adhesion was significantly reduced in the absence of GP IIb integrin (P<0.05). To address the contribution of platelet GP IIb to atheroprogression, we determined atherosclerotic lesion formation in the CA and aortic arch (AA) of GP IIb(+/+)ApoE(-/-) or GP IIb(-/-)ApoE(-/-) mice. Interestingly, the absence of GP IIb attenuated lesion formation in CA and AA, indicating that platelets, via GP IIb, contribute substantially to atherosclerosis. Next, we assessed the implication of GP IIb for cerebral I/R injury. We observed that after occlusion of the middle cerebral artery, the cerebral infarct size was drastically reduced in mice lacking GP IIb compared with wild-types. These findings show for the first time in vivo that GP IIb not only mediates platelet aggregation but also triggers platelet adhesion to exposed extracellular matrices and dysfunctional endothelial cells. In a process strictly involving GP IIb, platelets, which are among the first blood cells to arrive at the scene of endothelial dysfunction, contribute essentially to atherosclerosis and cerebral I/R injury.

Progenitor constraints for core-collapse supernovae from Chandra X-ray observations

NASA Astrophysics Data System (ADS)

Heikkilä, T.; Tsygankov, S.; Mattila, S.; Eldridge, J. J.; Fraser, M.; Poutanen, J.

2016-03-01

The progenitors of hydrogen-poor core-collapse supernovae (SNe) of Types Ib, Ic and IIb are believed to have shed their outer hydrogen envelopes either by extremely strong stellar winds, characteristic of classical Wolf-Rayet stars, or by binary interaction with a close companion star. The exact nature of the progenitors and the relative importance of these processes are still open questions. One relatively unexplored method to constrain the progenitors is to search for high-mass X-ray binaries (HMXBs) at SN locations in pre-explosion X-ray observations. In an HMXB, one star has already exploded as a core-collapse SN, producing a neutron star or a stellar mass black hole. It is likely that the second star in the system will also explode as an SN, which should cause a detectable long-term change in the system's X-ray luminosity. In particular, a pre-explosion detection of an HMXB coincident with an SN could be informative about the progenitor's nature. In this paper, we analyse pre-explosion ACIS observations of 18 nearby Type Ib, Ic and IIb SNe from the Chandra X-ray observatory public archive. Two sources that could potentially be associated with the SN are identified in the sample. Additionally we make similar post-explosion measurements for 46 SNe. Although our modelling indicates that progenitor systems with compact binary companions are probably quite rare, studies of this type can in the future provide more stringent constraints as the number of discovered nearby SNe and suitable pre-explosion X-ray data are both increasing.

Clavicle hook plate fixation for distal-third clavicle fracture (Neer type II): comparison of clinical and radiologic outcomes between Neer types IIA and IIB.

PubMed

Lee, Wonyong; Choi, Chong-Hyuk; Choi, Yun-Rak; Lim, Kyung-Han; Chun, Yong-Min

2017-07-01

The purpose of this study was to investigate clinical and radiologic outcomes of clavicle hook plate fixation for distal-third clavicle fracture (Neer type II) and to compare the clinical and radiologic outcomes and complications between Neer type IIA and type IIB. We retrospectively reviewed 35 patients who underwent open reduction and internal fixation with AO hook locking compression plate (LCP) for distal clavicle fracture, including 13 patients with Neer type IIA and 22 patients with type IIB. Visual analog scale pain score, shoulder scores (subjective shoulder value, University of California-Los Angeles shoulder score, American Shoulder and Elbow Surgeons score), and active range of motion were evaluated to determine clinical outcome. Coracoclavicular distance was measured, and that of the injured side at last follow-up was compared with that of the uninjured side to evaluate radiologic outcomes. AO hook LCP fixation for distal-third clavicle fracture (Neer type II) produced satisfactory radiologic outcomes, including high union rates (100%) and coracoclavicular distance maintenance, as well as satisfactory clinical outcomes, including visual analog scale score for pain, shoulder scores (subjective shoulder value, University of California-Los Angeles shoulder score, American Shoulder and Elbow Surgeons score), and active range of motion. There were no significant differences between Neer type IIA and type IIB. With regard to complications, 22.9% of patients experienced shoulder stiffness and 17.1% had subacromial erosion; however, there were no significant differences between the 2 groups. The AO hook LCP is a suitable choice for Neer type IIA and type IIB distal-third clavicle fracture fixation. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Remarks on non-BPS string amplitudes and their all order α' contact interactions in IIB, IIA

NASA Astrophysics Data System (ADS)

Hatefi, Ehsan

2017-03-01

We explore the entire form of S-Matrix elements of a potential C n-1 Ramond-Ramond (RR) form field, a tachyon and two transverse scalar fields on both world volume and transverse directions of type IIB and IIA superstring theories. Apart from < {V}_{C^{-2}}{V}_{φ^0}{V}_{φ^0}{V}_{T^0}\\rangle the other scattering amplitude, namely < {V}_{C^{-1}}{V}_{φ^{-1}}{V}_{φ^0}{V}_{T^0}\\rangle is also revealed. We then start to compare all singularity structures of symmetric and asymmetric analysis, generating all infinite singularity structures as well as all order α' contact interactions on the whole directions. This leads to deriving various new contact terms and several new restricted Bianchi identities in both type IIB and IIA. It is also shown that just some of the new couplings of type IIB (IIA) string theory can be re-verified in an Effective Field Theory (EFT) by pull-back of branes. To construct the rest of S-matrix elements one needs to first derive restricted world volume (or bulk) Bianchi identities and then discover new EFT couplings in both type IIB and IIA. Finally the presence of commutator of scalar fields inside the exponential of Wess-Zumino action for non-BPS branes has been confirmed as well.

Does the Modified Gartland Classification Clarify Decision Making?

PubMed

Leung, Sophia; Paryavi, Ebrahim; Herman, Martin J; Sponseller, Paul D; Abzug, Joshua M

2018-01-01

The modified Gartland classification system for pediatric supracondylar fractures is often utilized as a communication tool to aid in determining whether or not a fracture warrants operative intervention. This study sought to determine the interobserver and intraobserver reliability of the Gartland classification system, as well as to determine whether there was agreement that a fracture warranted operative intervention regardless of the classification system. A total of 200 anteroposterior and lateral radiographs of pediatric supracondylar humerus fractures were retrospectively reviewed by 3 fellowship-trained pediatric orthopaedic surgeons and 2 orthopaedic residents and then classified as type I, IIa, IIb, or III. The surgeons then recorded whether they would treat the fracture nonoperatively or operatively. The κ coefficients were calculated to determine interobserver and intraobserver reliability. Overall, the Wilkins-modified Gartland classification has low-moderate interobserver reliability (κ=0.475) and high intraobserver reliability (κ=0.777). A low interobserver reliability was found when differentiating between type IIa and IIb (κ=0.240) among attendings. There was moderate-high interobserver reliability for the decision to operate (κ=0.691) and high intraobserver reliability (κ=0.760). Decreased interobserver reliability was present for decision to operate among residents. For fractures classified as type I, the decision to operate was made 3% of the time and 27% for type IIa. The decision was made to operate 99% of the time for type IIb and 100% for type III. There is almost full agreement for the nonoperative treatment of Type I fractures and operative treatment for type III fractures. There is agreement that type IIb fractures should be treated operatively and that the majority of type IIa fractures should be treated nonoperatively. However, the interobserver reliability for differentiating between type IIa and IIb fractures is low. Our results validate the Gartland classfication system as a method to help direct treatment of pediatric supracondylar humerus fractures, although the modification of the system, IIa versus IIb, seems to have limited reliability and utility. Terminology based on decision to treat may lead to a more clinically useful classification system in the evaluation and treatment of pediatric supracondylar humerus fractures. Level III-diagnostic studies.

Toll-Like Receptor 2 Mediates Cellular Activation by the B Subunits of Type II Heat-Labile Enterotoxins

PubMed Central

Hajishengallis, George; Tapping, Richard I.; Martin, Michael H.; Nawar, Hesham; Lyle, Elizabeth A.; Russell, Michael W.; Connell, Terry D.

2005-01-01

The type II heat-labile enterotoxins (LT-IIa and LT-IIb) of Escherichia coli have an AB5 subunit structure similar to that of cholera toxin (CT) and other type I enterotoxins, despite significant differences in the amino acid sequences of their B subunits and different ganglioside receptor specificities. LT-II holotoxins and their nontoxic B subunits display unique properties as immunological adjuvants distinct from those of CT and its B subunits. In contrast to type II holotoxins, the corresponding pentameric B subunits, LT-IIaB and LT-IIbB, stimulated cytokine release in both human and mouse cells dependent upon Toll-like receptor 2 (TLR2). Induction of interleukin-1β (IL-1β), IL-6, IL-8, or tumor necrosis factor alpha in human THP-1 cells by LT-IIaB or LT-IIbB was inhibited by anti-TLR2 but not by anti-TLR4 antibody. Furthermore, transient expression of TLR1 and TLR2 in human embryonic kidney 293 cells resulted in activation of a nuclear factor-κB-dependent luciferase gene in response to LT-IIaB or LT-IIbB. Moreover, peritoneal macrophages from TLR2-deficient mice failed to respond to LT-IIaB or LT-IIbB, in contrast to wild-type or TLR4-deficient cells. These results demonstrate that besides their established binding to gangliosides, the B subunits of type II enterotoxins also interact with TLR2. Although a ganglioside-nonbinding mutant (T34I) of LT-IIaB effectively induced cytokine release, a phenotypically similar point mutation (T13I) in LT-IIbB abrogated cytokine induction, suggesting a variable requirement for gangliosides as coreceptors in TLR2 agonist activity. TLR2-dependent activation of mononuclear cells by type II enterotoxin B subunits appears to be a novel mechanism whereby these molecules may exert their immunomodulatory and adjuvant activities. PMID:15731031

GUTs on Compact Type IIB Orientifolds

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

Blumenhagen, Ralph; /Munich, Max Planck Inst.; Braun, Volker

We systematically analyze globally consistent SU(5) GUT models on intersecting D7-branes in genuine Calabi-Yau orientifolds with O3- and O7-planes. Beyond the well-known tadpole and K-theory cancellation conditions there exist a number of additional subtle but quite restrictive constraints. For the realization of SU(5) GUTs with gauge symmetry breaking via U(1)Y flux we present two classes of suitable Calabi-Yau manifolds defined via del Pezzo transitions of the elliptically fibred hypersurface P{sub 1,1,1,6,9}[18] and of the Quintic P{sub 1,1,1,1,1}[5], respectively. To define an orientifold projection we classify all involutions on del Pezzo surfaces. We work out the model building prospects of thesemore » geometries and present five globally consistent string GUT models in detail, including a 3-generation SU(5) model with no exotics whatsoever. We also realize other phenomenological features such as the 10 10 5{sub H} Yukawa coupling and comment on the possibility of moduli stabilization, where we find an entire new set of so-called swiss-cheese type Calabi-Yau manifolds. It is expected that both the general constrained structure and the concrete models lift to F-theory vacua on compact Calabi-Yau fourfolds.« less

The Relationship between Muscle Fiber Type-Specific PGC-1α Content and Mitochondrial Content Varies between Rodent Models and Humans

PubMed Central

Gouspillou, Gilles; Sgarioto, Nicolas; Norris, Brandon; Barbat-Artigas, Sébastien; Aubertin-Leheudre, Mylène; Morais, Jose A.; Burelle, Yan; Taivassalo, Tanja; Hepple, Russell T.

2014-01-01

PGC-1α regulates critical processes in muscle physiology, including mitochondrial biogenesis, lipid metabolism and angiogenesis. Furthermore, PGC-1α was suggested as an important regulator of fiber type determination. However, whether a muscle fiber type-specific PGC-1α content exists, whether PGC-1α content relates to basal levels of mitochondrial content, and whether such relationships are preserved between humans and classically used rodent models are all questions that have been either poorly addressed or never investigated. To address these issues, we investigated the fiber type-specific content of PGC-1α and its relationship to basal mitochondrial content in mouse, rat and human muscles using in situ immunolabeling and histochemical methods on muscle serial cross-sections. Whereas type IIa fibers exhibited the highest PGC-1α in all three species, other fiber types displayed a hierarchy of type IIx>I>IIb in mouse, type I = IIx> IIb in rat, and type IIx>I in human. In terms of mitochondrial content, we observed a hierarchy of IIa>IIx>I>IIb in mouse, IIa >I>IIx> IIb in rat, and I>IIa> IIx in human skeletal muscle. We also found in rat skeletal muscle that type I fibers displayed the highest capillarization followed by type IIa >IIx>IIb. Finally, we found in human skeletal muscle that type I fibers display the highest lipid content, followed by type IIa>IIx. Altogether, our results reveal that (i) the fiber type-specific PGC-1α and mitochondrial contents were only matched in mouse, (ii) the patterns of PGC-1α and mitochondrial contents observed in mice and rats do not correspond to that seen in humans in several respects, and (iii) the classical phenotypes thought to be regulated by PGC-1α do not vary exclusively as a function of PGC-1α content in rat and human muscles. PMID:25121500

Remarks on non-BPS string amplitudes and their all order α' contact interactions in IIB, IIA

DOE PAGES

Hatefi, Ehsan

2017-03-06

Here, we explore the entire form of S-Matrix elements of a potential C n–1 Ramond-Ramond (RR) form field, a tachyon and two transverse scalar fields on both world volume and transverse directions of type IIB and IIA superstring theories. Apart from V C–2V Φ0V Φ0V T0 the other scattering amplitude, namely V C–1V Φ–1V Φ0V T0 is also revealed. We then start to compare all singularity structures of symmetric and asymmetric analysis, generating all infinite singularity structures as well as all order α' contact interactions on the whole directions. This leads to deriving various new contact terms and several newmore » restricted Bianchi identities in both type IIB and IIA. It is also shown that just some of the new couplings of type IIB (IIA) string theory can be re-verified in an Effective Field Theory (EFT) by pull-back of branes. To construct the rest of S-matrix elements one needs to first derive restricted world volume (or bulk) Bianchi identities and then discover new EFT couplings in both type IIB and IIA. Finally the presence of commutator of scalar fields inside the exponential of Wess-Zumino action for non-BPS branes has been confirmed as well.« less

Differences in sodium voltage-gated channel properties according to myosin heavy chain isoform expression in single muscle fibres.

PubMed

Rannou, F; Droguet, M; Giroux-Metges, M A; Pennec, Y; Gioux, M; Pennec, J P

2009-11-01

The myosin heavy chain (MHC) isoform determines the characteristics and shortening velocity of muscle fibres. The functional properties of the muscle fibre are also conditioned by its membrane excitability through the electrophysiological properties of sodium voltage-gated channels. Macropatch-clamp is used to study sodium channels in fibres from peroneus longus (PL) and soleus (Sol) muscles (Wistar rats, n = 8). After patch-clamp recordings, single fibres are identified by SDS-PAGE electrophoresis according to their myosin heavy chain isoform (slow type I and the three fast types IIa, IIx, IIb). Characteristics of sodium currents are compared (Student's t test) between fibres exhibiting only one MHC isoform. Four MHC isoforms are identified in PL and only type I in Sol single fibres. In PL, maximal sodium current (I(max)), maximal sodium conductance (g(Na,max)) and time constants of activation and inactivation ((m) and (h)) increase according to the scheme I-->IIa-->IIx-->IIb (P < 0.05). (m) values related to sodium channel type and/or function, are similar in Sol I and PL IIb fibres (P = 0.97) despite different contractile properties. The voltage dependence of activation (V(a,1/2)) shows a shift towards positive potentials from Sol type I to IIa, IIx and finally IIb fibres from PL (P < 0.05). These data are consistent with the earlier recruitment of slow fibres in a fast-mixed muscle like PL, while slow fibres of postural muscle such as soleus could be recruited in the same ways as IIb fibres in a fast muscle.

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

Liu, Yu-Qian; Modjaz, Maryam; Bianco, Federica B.

Using the largest spectroscopic data set of stripped-envelope core-collapse supernovae (stripped SNe), we present a systematic investigation of spectral properties of Type IIb SNe (SNe IIb), Type Ib SNe (SNe Ib), and Type Ic SNe (SNe Ic). Prior studies have been based on individual objects or small samples. Here, we analyze 242 spectra of 14 SNe IIb, 262 spectra of 21 SNe Ib, and 207 spectra of 17 SNe Ic based on the stripped SN data set of Modjaz et al. and other published spectra of individual SNe. Each SN in our sample has a secure spectroscopic ID, a datemore » of V -band maximum light, and most have multiple spectra at different phases. We analyze these spectra as a function of subtype and phase in order to improve the SN identification scheme and constrain the progenitors of different kinds of stripped SNe. By comparing spectra of SNe IIb with those of SNe Ib, we find that the strength of H α can be used to quantitatively differentiate between these two subtypes at all epochs. Moreover, we find a continuum in observational properties between SNe IIb and Ib. We address the question of hidden He in SNe Ic by comparing our observations with predictions from various models that either include hidden He or in which He has been burnt. Our results favor the He-free progenitor models for SNe Ic. Finally, we construct continuum-divided average spectra as a function of subtype and phase to quantify the spectral diversity of the different types of stripped SNe.« less

Volatile anesthetics, not intravenous anesthetic propofol bind to and attenuate the activation of platelet receptor integrin αIIbβ3.

PubMed

Yuki, Koichi; Bu, Weiming; Shimaoka, Motomu; Eckenhoff, Roderic

2013-01-01

In clinical reports, the usage of isoflurane and sevoflurane was associated with more surgical field bleeding in endoscopic sinus surgeries as compared to propofol. The activation of platelet receptor αIIbβ3 is a crucial event for platelet aggregation and clot stability. Here we studied the effect of isoflurane, sevoflurane, and propofol on the activation of αIIbβ3. The effect of anesthetics on the activation of αIIbβ3 was probed using the activation sensitive antibody PAC-1 in both cell-based (platelets and αIIbβ3 transfectants) and cell-free assays. The binding sites of isoflurane on αIIbβ3 were explored using photoactivatable isoflurane (azi-isoflurane). The functional implication of revealed isoflurane binding sites were studied using alanine-scanning mutagenesis. Isoflurane and sevoflurane diminished the binding of PAC-1 to wild-type αIIbβ3 transfectants, but not to the high-affinity mutant, β3-N305T. Both anesthetics also impaired PAC-1 binding in a cell-free assay. In contrast, propofol did not affect the activation of αIIbβ3. Residues adducted by azi-isoflurane were near the calcium binding site (an important regulatory site termed SyMBS) just outside of the ligand binding site. The mutagenesis experiments demonstrated that these adducted residues were important in regulating integrin activation. Isoflurane and sevoflurane, but not propofol, impaired the activation of αIIbβ3. Azi-isoflurane binds to the regulatory site of integrin αIIbβ3, thereby suggesting that isoflurane blocks ligand binding of αIIbβ3 in not a competitive, but an allosteric manner.

Myosin heavy chain isoform composition and Ca(2+) transients in fibres from enzymatically dissociated murine soleus and extensor digitorum longus muscles.

PubMed

Calderón, Juan C; Bolaños, Pura; Caputo, Carlo

2010-01-01

Electrically elicited Ca(2+) transients reported with the fast Ca(2+) dye MagFluo-4 AM and myosin heavy chain (MHC) electrophoretic patterns were obtained in intact, enzymatically dissociated fibres from adult mice extensor digitorum longus (EDL) and soleus muscles. Thirty nine fibres (23 from soleus and 16 from EDL) were analysed by both fluorescence microscopy and electrophoresis. These fibres were grouped as follows: group 1 included 13 type I and 4 type IC fibres; group 2 included 2 type IIC, 3 IIA and 1 I/IIA/IIX fibres; group 3 included 4 type IIX and 1 type IIX/IIB fibres; group 4 included 2 type IIB/IIX and 9 type IIB fibres. Ca(2+) transients obtained in groups 1, 2, 3 and 4 had the following kinetic parameters (mean +/- s.e.m.): amplitude (F/F): 0.61 +/- 0.05, 0.53 +/- 0.08, 0.61 +/- 0.06 and 0.61 +/- 0.03; rise time (ms): 1.64 +/- 0.05, 1.35 +/- 0.05, 1.18 +/- 0.06 and 1.14 +/- 0.04; half-amplitude width (ms): 19.12 +/- 1.85, 11.86 +/- 3.03, 4.62 +/- 0.31 and 4.23 +/- 0.37; and time constants of decay (tau(1) and tau(2), ms): 3.33 +/- 0.13 and 52.48 +/- 3.93, 2.69 +/- 0.22 and 41.06 +/- 9.13, 1.74 +/- 0.06 and 12.88 +/- 1.93, and 1.56 +/- 0.11 and 9.45 +/- 1.03, respectively. The statistical differences between the four groups and the analysis of the distribution of the parameters of Ca(2+) release and clearance show that there is a continuum from slow to fast, that parallels the MHC continuum from pure type I to pure IIB. However, type IIA fibres behave more like IIX and IIB fibres regarding Ca(2+) release but closer to type I fibres regarding Ca(2+) clearance. In conclusion, we show for the first time the diversity of Ca(2+) transients for the whole continuum of fibre types and correlate this functional diversity with the structural and biochemical diversity of the skeletal muscle fibres.

Common errors in textbook descriptions of muscle fiber size in nontrained humans.

PubMed

Chalmers, Gordon R; Row, Brandi S

2011-09-01

Exercise science and human anatomy and physiology textbooks commonly report that type IIB muscle fibers have the largest cross-sectional area of the three fiber types. These descriptions of muscle fiber sizes do not match with the research literature examining muscle fibers in young adult nontrained humans. For men, most commonly type IIA fibers were significantly larger than other fiber types (six out of 10 cases across six different muscles). For women, either type I, or both I and IIA muscle fibers were usually significantly the largest (five out of six cases across four different muscles). In none of these reports were type IIB fibers significantly larger than both other fiber types. In 27 studies that did not include statistical comparisons of mean fiber sizes across fiber types, in no cases were type IIB or fast glycolytic fibers larger than both type I and IIA, or slow oxidative and fast oxidative glycolytic fibers. The likely reason for mistakes in textbook descriptions of human muscle fiber sizes is that animal data were presented without being labeled as such, and without any warning that there are interspecies differences in muscle fiber properties. Correct knowledge of muscle fiber sizes may facilitate interpreting training and aging adaptations.

The role of myostatin and activin receptor IIB in the regulation of unloading-induced myofiber type-specific skeletal muscle atrophy.

PubMed

Babcock, Lyle W; Knoblauch, Mark; Clarke, Mark S F

2015-09-15

Chronic unloading induces decrements in muscle size and strength. This adaptation is governed by a number of molecular factors including myostatin, a potent negative regulator of muscle mass. Myostatin must first be secreted into the circulation and then bind to the membrane-bound activin receptor IIB (actRIIB) to exert its atrophic action. Therefore, we hypothesized that myofiber type-specific atrophy observed after hindlimb suspension (HLS) would be related to myofiber type-specific expression of myostatin and/or actRIIB. Wistar rats underwent HLS for 10 days, after which the tibialis anterior was harvested for frozen cross sectioning. Simultaneous multichannel immunofluorescent staining combined with differential interference contrast imaging was employed to analyze myofiber type-specific expression of myostatin and actRIIB and myofiber type cross-sectional area (CSA) across fiber types, myonuclei, and satellite cells. Hindlimb suspension (HLS) induced significant myofiber type-specific atrophy in myosin heavy chain (MHC) IIx (P < 0.05) and MHC IIb myofibers (P < 0.05). Myostatin staining associated with myonuclei was less in HLS rats compared with controls, while satellite cell staining for myostatin remained unchanged. In contrast, the total number myonuclei and satellite cells per myofiber was reduced in HLS compared with ambulatory control rats (P < 0.01). Sarcoplasmic actRIIB staining differed between myofiber types (I < IIa < IIx < IIb) independent of loading conditions. Myofiber types exhibiting the greatest cytoplasmic staining of actRIIB corresponded to those exhibiting the greatest degree of atrophy following HLS. Our data suggest that differential expression of actRIIB may be responsible for myostatin-induced myofiber type-selective atrophy observed during chronic unloading. Copyright © 2015 the American Physiological Society.

Mapping of a microbial protein domain involved in binding and activation of the TLR2/TLR1 heterodimer.

PubMed

Liang, Shuang; Hosur, Kavita B; Lu, Shanyun; Nawar, Hesham F; Weber, Benjamin R; Tapping, Richard I; Connell, Terry D; Hajishengallis, George

2009-03-01

The pentameric B subunit of type IIb Escherichia coli enterotoxin (LT-IIb-B(5)), a doughnut-shaped oligomeric protein from enterotoxigenic E. coli, activates the TLR2/TLR1 heterodimer (TLR2/1). We investigated the molecular basis of the LT-IIb-B(5) interaction with TLR2/1 to define the structure-function relationship of LT-IIb-B(5) and, moreover, to gain an insight into how TLR2/1 recognizes large, nonacylated protein ligands that cannot fit within its lipid-binding pockets, as previously shown for the Pam(3)CysSerLys(4) (Pam(3)CSK(4)) lipopeptide. We first identified four critical residues in the upper region of the LT-IIb-B(5) pore. Corresponding point mutants (M69E, A70D, L73E, S74D) were defective in binding TLR2 or TLR1 and could not activate APCs, despite retaining full ganglioside-binding capacity. Point mutations in the TLR2/1 dimer interface, as determined in the crystallographic structure of the TLR2/1-Pam(3)CSK(4) complex, resulted in diminished activation by both Pam(3)CSK(4) and LT-IIb-B(5). Docking analysis of the LT-IIb-B(5) interaction with this apparently predominant activation conformation of TLR2/1 revealed that LT-IIb-B(5) might primarily contact the convex surface of the TLR2 central domain. Although the TLR1/LT-IIb-B(5) interface is relatively smaller, the leucine-rich repeat motifs 9-12 in the central domain of TLR1 were found to be critical for cooperative TLR2-induced cell activation by LT-IIb-B(5). Moreover, the putative LT-IIb-B(5) binding site overlaps partially with that of Pam(3)CSK(4); consistent with this, Pam(3)CSK(4) suppressed TLR2 binding of LT-IIb-B(5), albeit not as potently as self-competitive inhibition. We identified the upper pore region of LT-IIb-B(5) as a TLR2/1 interactive domain, which contacts the heterodimeric receptor at a site that is distinct from, although it overlaps with, that of Pam(3)CSK(4).

Binding to Gangliosides Containing N-Acetylneuraminic Acid Is Sufficient To Mediate the Immunomodulatory Properties of the Nontoxic Mucosal Adjuvant LT-IIb(T13I) ▿

PubMed Central

Nawar, Hesham F.; Berenson, Charles S.; Hajishengallis, George; Takematsu, Hiromu; Mandell, Lorrie; Clare, Ragina L.; Connell, Terry D.

2010-01-01

By use of a mouse mucosal immunization model, LT-IIb(T13I), a nontoxic mutant type II heat-labile enterotoxin, was shown to have potent mucosal and systemic adjuvant properties. In contrast to LT-IIb, which binds strongly to ganglioside receptors decorated with either N-acetylneuraminic acid (NeuAc) or N-glycolylneuraminic acid (NeuGc), LT-IIb(T13I) binds NeuAc gangliosides much less well. Rather, LT-IIb(T13I) binds preferentially to NeuGc gangliosides. To determine if the adjuvant properties of LT-IIb(T13I) are altered in the absence of NeuGc ganglioside receptors, experiments were conducted using a Cmah-null mouse line which is deficient in the synthesis of NeuGc gangliosides. Several immunomodulatory properties of LT-IIb(T13I) were shown to be dependent on NeuGc gangliosides. LT-IIb(T13I) had reduced binding activity for NeuGc-deficient B cells and macrophages; binding to NeuGc-deficient T cells and dendritic cells (DC) was essentially undetectable. Treatment of Cmah-null macrophages with LT-IIb(T13I), however, upregulated the transcription of interleukin-4 (IL-4), IL-6, IL-17, and gamma interferon (IFN-γ), four cytokines important for promoting immune responses. The production of mucosal IgA and serum IgG against an immunizing antigen was augmented in NeuGc-deficient mice administered LT-IIb(T13I) as a mucosal adjuvant. Notably, NeuGc gangliosides are not expressed in humans. Still, treatment of human monocytes with LT-IIb(T13I) induced the secretion of IL-6, an inflammatory cytokine that mediates differential control of leukocyte activation. These results suggested that NeuAc gangliosides are sufficient to mediate the immunomodulatory properties of LT-IIb(T13I) in mice and in human cells. The nontoxic mutant enterotoxin LT-IIb(T13I), therefore, is potentially a new and safe human mucosal adjuvant. PMID:20392887

Topoisomerase VI senses and exploits both DNA crossings and bends to facilitate strand passage

PubMed Central

Wendorff, Timothy J

2018-01-01

Type II topoisomerases manage DNA supercoiling and aid chromosome segregation using a complex, ATP-dependent duplex strand passage mechanism. Type IIB topoisomerases and their homologs support both archaeal/plant viability and meiotic recombination. Topo VI, a prototypical type IIB topoisomerase, comprises two Top6A and two Top6B protomers; how these subunits cooperate to engage two DNA segments and link ATP turnover to DNA transport is poorly understood. Using multiple biochemical approaches, we show that Top6B, which harbors the ATPase activity of topo VI, recognizes and exploits the DNA crossings present in supercoiled DNA to stimulate subunit dimerization by ATP. Top6B self-association in turn induces extensive DNA bending, which is needed to support duplex cleavage by Top6A. Our observations explain how topo VI tightly coordinates DNA crossover recognition and ATP binding with strand scission, providing useful insights into the operation of type IIB topoisomerases and related meiotic recombination and GHKL ATPase machineries. PMID:29595473

Analysis of type IIb synthetic diamond using FTIR spectrometry

NASA Astrophysics Data System (ADS)

Klepikov, I. V.; Koliadin, A. V.; Vasilev, E. A.

2017-12-01

Analysis of internal structure in large IIb-type high pressure-high temperature (HPHT) synthetic single-crystal diamond are presented. The concentration of boron impurity in different growth sectors varies from 0.02 to 10.3 ppm. It is shown that in the manufacturing of synthetic diamond plates, internal inhomogeneities of the diamond should be taken into account; plates with different characteristics can be cut from one diamond, each of which can be used for its own purpose.

Rapid actions of aldosterone revisited: Receptors in the limelight.

PubMed

Wehling, Martin

2018-02-01

Steroid hormones like aldosterone have been conclusively shown to elicit both late genomic and rapid, nongenomically initiated responses. Aldosterone was among the first for which rapid, clinically relevant effects were even shown in humans. Yet, after over 30 years of research, the nature of receptors involved in rapid actions of aldosterone is still unclear. Such effects may be assigned to the classical, intracellular steroid receptors, in this case mineralocorticoid receptors (MR, class IIa action Mannheim classification). They typically disappear in knockout models and are blocked by MR-antagonists such as spironolactone, as shown for several cellular and physiological, e.g. renal or cardiovascular effects. In contrast, there is also consistent evidence suggesting type IIb effects involving structurally different receptors ("membrane receptors") being insensitive to classic antagonists and persistent in knockout models; IIb effects have lately even been confirmed by atomic force detection of surface receptors which bind aldosterone but not spironolactone. Type IIa and b may coexist in the same cell with IIa often augmenting early IIb effects. So far cloning of IIb receptors was unsuccessful; therefore results on G-protein coupled estrogen receptor 1 (GPER1) being potentially involved in rapid aldosterone action raised considerable interest. Surprisingly, GPER1 does not bind aldosterone. Though under these circumstances GPER1 should not yet be considered as IIb-receptor, it might be an intermediary signaling enhancer of mineralocorticoid action as shown for epithelial growth factor receptors reconciling those results. We still seem to be left without IIb-receptors whose identification would however be highly desirable and essential for clinical translation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Risk reductions for cardiovascular disease with pravastatin treatment by dyslipidemia phenotype: a post hoc analysis of the MEGA Study.

PubMed

Nishiwaki, Masato; Ikewaki, Katsunori; Ayaori, Makoto; Mizuno, Kyoichi; Ohashi, Yasuo; Ohsuzu, Fumitaka; Ishikawa, Toshitsugu; Nakamura, Haruo

2013-03-01

The beneficial effect of statins for cardiovascular disease (CVD) prevention has been well established. However, the effectiveness among different phenotypes of dyslipidemia has not been confirmed. We evaluated the effect of pravastatin on the incidence of CVD in relation to the phenotype of dyslipidemia. The MEGA Study evaluated the effect of low-dose pravastatin on primary prevention of CVD in 7832 Japanese patients, who were randomized to diet alone or diet plus pravastatin and followed for more than 5 years. These patients were classified into phenotype IIa (n=5589) and IIb (n=2041) based on the electrophoretic pattern for this post hoc analysis. In the diet group there was no significant difference in the incidence of coronary heart disease (CHD), stroke, CVD, and total mortality between the two phenotypes. Phenotype IIb patients, compared to phenotype IIa, had lower levels of high-density lipoprotein cholesterol (HDL-C) and a significantly higher incidence of CVD in relation to a low HDL-C level (<47.5mg/dL; p=0.02). Furthermore, pravastatin decreased the relative risk for each major endpoint in both type IIa and type IIb dyslipidemia. Significant risk reductions were observed for CHD by 38% (p=0.04) and CVD by 31% (p=0.02) in type IIa dyslipidemia but not in phenotype IIb. Pravastatin therapy provided significant risk reductions for CHD and CVD in patients with phenotype IIa dyslipidemia, but not in those with phenotype IIb dyslipidemia. Copyright © 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Late-time spectroscopy of envelope-stripped SNe: Figuring the central engine

NASA Astrophysics Data System (ADS)

Kawabata, Koji

2012-01-01

We propose to perform late-time spectroscopy of envelope-stripped core-collapse supernovae (SNe), i.e., Type Ib/c/IIb SNe. We aim to examine the explosion physics and its dependence on the progenitor mass. The key information is the asphericity and the chemical composition of the inner atmosphere, which can be explored by late-time observations. The difference in [O I] line profiles indicates that GRB-associated energetic SNe Ic (like SN 1998bw) and non-GRB energetic SNe Ic (2003jd) are intrinsically similar aspherical explosions that are differently viewed (pole-on for 1998bw and nearly edge-on for 2003jd). Our continuing study suggests that the asphericity is rather common characteristic even for normal energy SNe without a GRB. However, it is still unclear how the intermediate types of SNe (SNe Ib/IIb) are produced and how they connected with other types of core-collapse SNe. High-quality late-time spectra of SNe Ib/Ic/IIb are still lacking. We propose to obtain a larger number of nebular spectra of envelope-stripped SNe including SNe IIb so that we examine the degree of the asphericity explosion energy, amount of synthesized ^56Ni and the physical properties of the central remnant as a function of the progenitor's mass.

The Type II Heat-Labile Enterotoxins LT-IIa and LT-IIb and Their Respective B Pentamers Differentially Induce and Regulate Cytokine Production in Human Monocytic Cells

PubMed Central

Hajishengallis, George; Nawar, Hesham; Tapping, Richard I.; Russell, Michael W.; Connell, Terry D.

2004-01-01

The type II heat-labile enterotoxins, LT-IIa and LT-IIb, exhibit potent adjuvant properties. However, little is known about their immunomodulatory activities upon interaction with innate immune cells, unlike the widely studied type I enterotoxins that include cholera toxin (CT). We therefore investigated interactions of LT-IIa and LT-IIb with human monocytic THP-1 cells. We found that LT-II enterotoxins were inactive in stimulating cytokine release, whereas CT induced low levels of interleukin-1β (IL-1β) and IL-8. However, all three enterotoxins potently regulated cytokine induction in cells activated by bacterial lipopolysaccharide or fimbriae. Induction of proinflammatory (tumor necrosis factor α [TNF-α]) or chemotactic (IL-8) cytokines was downregulated, whereas induction of cytokines with anti-inflammatory (IL-10) or mucosal adjuvant properties (IL-1β) was upregulated by the enterotoxins. These effects appeared to depend on their A subunits, because isolated B-pentameric subunits lacked regulatory activity. Enterotoxin-mediated inhibition of proinflammatory cytokine induction in activated cells was partially attributable to synergism for endogenous production of IL-10 and to an IL-10-independent inhibition of nuclear factor κB (NF-κB) activation. In sharp contrast to the holotoxins, the B pentamers (LT-IIaB and, to a greater extent, LT-IIbB) stimulated cytokine production, suggesting a link between the absence of the A subunit and increased proinflammatory properties. In this regard, the ability of LT-IIbB to activate NF-κB and induce TNF-α and IL-8 was antagonized by the LT-IIb holotoxin. These findings support distinct immunomodulatory roles for the LT-II holotoxins and their respective B pentamers. Moreover, the anti-inflammatory properties of the holotoxins may serve to suppress innate immunity and promote the survival of the pathogen. PMID:15501764

Two hybridization events define the population structure of Trypanosoma cruzi.

PubMed

Westenberger, Scott J; Barnabé, Christian; Campbell, David A; Sturm, Nancy R

2005-10-01

Genetic variation in Trypanosoma cruzi is likely a key determinant in transmission and pathogenesis of Chagas disease. We have examined nine loci as markers for the extant T. cruzi strains. Four distinct alleles were found for each locus, corresponding to the sequence classes present in the homozygous discrete typing units (DTUs) I, IIa, IIb, and IIc. The alleles in DTUs IIa and IIc showed a spectrum of polymorphism ranging from DTU I-like to DTU IIb-like, in addition to DTU-specific sequence variation. DTUs IId and IIe were indistinguishable, showing DTU homozygosity at one locus and heterozygosity with DTU IIb and IIc allelic sequences at eight loci. Recombination between the DTU IIb and IIc alleles is evidenced from mosaic polymorphisms. These data imply that two discrete hybridization events resulted in the formation of the current DTUs. We propose a model in which a fusion between ancestral DTU I and IIb strains gave rise to a heterozygous hybrid that homogenized its genome to become the homozygous progenitor of DTUs IIa and IIc. The second hybridization between DTU IIb and IIc strains that generated DTUs IId and IIe resulted in extensive heterozygosity with subsequent recombination of parental genotypes.

Differential Muscle Hypertrophy Is Associated with Satellite Cell Numbers and Akt Pathway Activation Following Activin Type IIB Receptor Inhibition in Mtm1 p.R69C Mice

PubMed Central

Lawlor, Michael W.; Viola, Marissa G.; Meng, Hui; Edelstein, Rachel V.; Liu, Fujun; Yan, Ke; Luna, Elizabeth J.; Lerch-Gaggl, Alexandra; Hoffmann, Raymond G.; Pierson, Christopher R.; Buj-Bello, Anna; Lachey, Jennifer L.; Pearsall, Scott; Yang, Lin; Hillard, Cecilia J.; Beggs, Alan H.

2015-01-01

X-linked myotubular myopathy is a congenital myopathy caused by deficiency of myotubularin. Patients often present with severe perinatal weakness, requiring mechanical ventilation to prevent death from respiratory failure. We recently reported that an activin receptor type IIB inhibitor produced hypertrophy of type 2b myofibers and modest increases of strength and life span in the severely myopathic Mtm1δ4 mouse model of X-linked myotubular myopathy. We have now performed a similar study in the less severely symptomatic Mtm1 p.R69C mouse in hopes of finding greater treatment efficacy. Activin receptor type IIB inhibitor treatment of Mtm1 p.R69C animals produced behavioral and histological evidence of hypertrophy in gastrocnemius muscles but not in quadriceps or triceps. The ability of the muscles to respond to activin receptor type IIB inhibitor treatment correlated with treatment-induced increases in satellite cell number and several muscle-specific abnormalities of hypertrophic signaling. Treatment-responsive Mtm1 p.R69C gastrocnemius muscles displayed lower levels of phosphorylated ribosomal protein S6 and higher levels of phosphorylated eukaryotic elongation factor 2 kinase than were observed in Mtm1 p.R69C quadriceps muscle or in muscles from wild-type littermates. Hypertrophy in the Mtm1 p.R69C gastrocnemius muscle was associated with increased levels of phosphorylated ribosomal protein S6. Our findings indicate that muscle-, fiber type-, and mutation-specific factors affect the response to hypertrophic therapies that will be important to assess in future therapeutic trials. PMID:24726641

Differential muscle hypertrophy is associated with satellite cell numbers and Akt pathway activation following activin type IIB receptor inhibition in Mtm1 p.R69C mice.

PubMed

Lawlor, Michael W; Viola, Marissa G; Meng, Hui; Edelstein, Rachel V; Liu, Fujun; Yan, Ke; Luna, Elizabeth J; Lerch-Gaggl, Alexandra; Hoffmann, Raymond G; Pierson, Christopher R; Buj-Bello, Anna; Lachey, Jennifer L; Pearsall, Scott; Yang, Lin; Hillard, Cecilia J; Beggs, Alan H

2014-06-01

X-linked myotubular myopathy is a congenital myopathy caused by deficiency of myotubularin. Patients often present with severe perinatal weakness, requiring mechanical ventilation to prevent death from respiratory failure. We recently reported that an activin receptor type IIB inhibitor produced hypertrophy of type 2b myofibers and modest increases of strength and life span in the severely myopathic Mtm1δ4 mouse model of X-linked myotubular myopathy. We have now performed a similar study in the less severely symptomatic Mtm1 p.R69C mouse in hopes of finding greater treatment efficacy. Activin receptor type IIB inhibitor treatment of Mtm1 p.R69C animals produced behavioral and histological evidence of hypertrophy in gastrocnemius muscles but not in quadriceps or triceps. The ability of the muscles to respond to activin receptor type IIB inhibitor treatment correlated with treatment-induced increases in satellite cell number and several muscle-specific abnormalities of hypertrophic signaling. Treatment-responsive Mtm1 p.R69C gastrocnemius muscles displayed lower levels of phosphorylated ribosomal protein S6 and higher levels of phosphorylated eukaryotic elongation factor 2 kinase than were observed in Mtm1 p.R69C quadriceps muscle or in muscles from wild-type littermates. Hypertrophy in the Mtm1 p.R69C gastrocnemius muscle was associated with increased levels of phosphorylated ribosomal protein S6. Our findings indicate that muscle-, fiber type-, and mutation-specific factors affect the response to hypertrophic therapies that will be important to assess in future therapeutic trials. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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.

(2,2) and (0,4) supersymmetric boundary conditions in 3d N =4 theories and type IIB branes

NASA Astrophysics Data System (ADS)

Chung, Hee-Joong; Okazaki, Tadashi

2017-10-01

The half-BPS boundary conditions preserving N =(2 ,2 ) and N =(0 ,4 ) supersymmetry in 3d N =4 supersymmetric gauge theories are examined. The BPS equations admit decomposition of the bulk supermultiplets into specific boundary supermultiplets of preserved supersymmetry. Nahm-like equations arise in the vector multiplet BPS boundary condition preserving N =(0 ,4 ) supersymmetry, and Robin-type boundary conditions appear for the hypermultiplet coupled to the vector multiplet when N =(2 ,2 ) supersymmetry is preserved. The half-BPS boundary conditions are realized in the brane configurations of type IIB string theory.

Increased serum butyrylcholinesterase activity in type IIb hyperlipidaemic patients.

PubMed

Kálmán, János; Juhász, Anna; Rakonczay, Zoltán; Abrahám, György; Zana, Marianna; Boda, Krisztina; Farkas, Tibor; Penke, Botond; Janka, Zoltán

2004-07-23

The inheritance of the apolipoprotein E4 (APOE4) allele has been shown to increase the plasma cholesterol level, but little information is as concerns the association of the APOE genotype and hyperlipidaemia and the activities of two serum enzymes, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Blood samples from 55 type IIb hyperlipidaemic, non-demented patients and 55 age- and sex-matched controls were therefore examined in this pilot study. A significantly increased BChE activity was found in the serum of type IIb hyperlipidaemic patients, but the AChE activity did not differ significantly as compared with that in the control group. The APOE4 allele was significantly overrepresented among the hyperlipidaemic probands, but neither serum cholinesterase activity was affected by the dosage of the APOE4 gene. Our results point to a possible association between an abnormal lipid metabolism and the BChE activity and might have implications as regards the pathomechanism of both Alzheimer's and vascular dementias and the cholinesterase inhibitor therapy of dementing disorders.

S-duality in twistor space

NASA Astrophysics Data System (ADS)

Alexandrov, Sergei; Pioline, Boris

2012-08-01

In type IIB string compactifications on a Calabi-Yau threefold, the hypermultiplet moduli space {{M}_H} must carry an isometric action of the modular group SL(2 , {Z} ), inherited from the S-duality symmetry of type IIB string theory in ten dimensions. We investigate how this modular symmetry is realized at the level of the twistor space of {{M}_H} , and construct a general class of SL(2 , {Z} )-invariant quaternion-Kähler metrics with two commuting isometries, parametrized by a suitably covariant family of holomorphic transition functions. This family should include {{M}_H} corrected by D3-D1-D(-1)-instantons (with five-brane corrections ignored) and, after taking a suitable rigid limit, the Coulomb branch of five-dimensional {N} = {2} gauge theories compactified on a torus, including monopole string instantons. These results allow us to considerably simplify the derivation of the mirror map between type IIA and IIB fields in the sector where only D1-D(-1)-instantons are retained.

Complex Langevin analysis of the spontaneous symmetry breaking in dimensionally reduced super Yang-Mills models

NASA Astrophysics Data System (ADS)

Anagnostopoulos, Konstantinos N.; Azuma, Takehiro; Ito, Yuta; Nishimura, Jun; Papadoudis, Stratos Kovalkov

2018-02-01

In recent years the complex Langevin method (CLM) has proven a powerful method in studying statistical systems which suffer from the sign problem. Here we show that it can also be applied to an important problem concerning why we live in four-dimensional spacetime. Our target system is the type IIB matrix model, which is conjectured to be a nonperturbative definition of type IIB superstring theory in ten dimensions. The fermion determinant of the model becomes complex upon Euclideanization, which causes a severe sign problem in its Monte Carlo studies. It is speculated that the phase of the fermion determinant actually induces the spontaneous breaking of the SO(10) rotational symmetry, which has direct consequences on the aforementioned question. In this paper, we apply the CLM to the 6D version of the type IIB matrix model and show clear evidence that the SO(6) symmetry is broken down to SO(3). Our results are consistent with those obtained previously by the Gaussian expansion method.

Muscle hypertrophy and fast fiber type conversions in heavy resistance-trained women.

PubMed

Staron, R S; Malicky, E S; Leonardi, M J; Falkel, J E; Hagerman, F C; Dudley, G A

1990-01-01

Twenty-four women completed a 20-week heavy-resistance weight training program for the lower extremity. Workouts were twice a week and consisted of warm-up exercises followed by three sets each of full squats, vertical leg presses, leg extensions, and leg curls. All exercises were performed to failure using 6-8 RM (repetition maximum). Weight training caused a significant increase in maximal isotonic strength (1 RM) for each exercise. After training, there was a decrease in body fat percentage (p less than 0.05), and an increase in lean body mass (p less than 0.05) with no overall change in thigh girth. Biopsies were obtained before and after training from the superficial portion of the vastus lateralis muscle. Sections were prepared for histological and histochemical examination. Six fiber types (I, IC, IIC, IIA, IIAB, and IIB) were distinguished following routine myofibrillar adenosine triphosphatase histochemistry. Areas were determined for fiber types I, IIA, and IIAB + IIB. The heavy-resistance training resulted in significant hypertrophy of all three groups: I (15%), IIA (45%), and IIAB + IIB (57%). These data are similar to those in men and suggest considerable hypertrophy of all major fiber types is also possible in women if exercise intensity and duration are sufficient. In addition, the training resulted in a significant decrease in the percentage of IIB with a concomitant increase in IIA fibers, suggesting that strength training may lead to fiber conversions.

Coracoclavicular stabilization using a suture button device for Neer type IIB lateral clavicle fractures.

PubMed

Cho, Chul-Hyun; Jung, Jae-Hoon; Kim, Beom-Soo

2017-05-01

The purpose of this study was to evaluate the radiologic and clinical outcomes of coracoclavicular (CC) stabilization using a suture button device for Neer type IIB lateral clavicle fractures. Eighteen consecutive patients with Neer type IIB fractures were treated with CC stabilization using a TightRope device (Arthrex, Naples, FL, USA). The mean follow-up period was 46.6 months (range, 24-75 months). Radiologic outcomes were assessed using serial plain radiographs. Clinical outcomes were evaluated using the visual analog scale pain score; University of California, Los Angeles score; American Shoulder and Elbow Surgeons score; and subjective shoulder value. Intraoperative and postoperative complications were also evaluated. Of the 18 cases, 17 (94.4%) showed complete bony union. The mean final visual analog scale pain score was 1.1; University of California, Los Angeles score, 31.3; American Shoulder and Elbow Surgeons score, 88.6; and subjective shoulder value, 88.5%. Four complications were observed: (1) intraoperative coracoid process fracture, (2) nonunion, (3) delayed union, and (4) shoulder stiffness. The case with a coracoid process fracture during coracoid tunnel generation was converted to the K-wire tension band technique. CC stabilization using a suture button device for Neer type IIB lateral clavicle fractures yielded satisfactory radiologic and clinical outcomes. The major advantage of this technique is that implant removal is not required. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Disulfide bond exchanges in integrins αIIbβ3 and αvβ3 are required for activation and post-ligation signaling during clot retraction.

PubMed

Mor-Cohen, Ronit; Rosenberg, Nurit; Averbukh, Yulia; Seligsohn, Uri; Lahav, Judith

2014-05-01

Integrin αIIbβ3 mediates platelet adhesion, aggregation and fibrin clot retraction. These processes require activation of αIIbβ3 and post-ligation signaling. Disulfide bond exchanges are involved in αIIbβ3 and αvβ3 activation. In order to investigate the role of integrin activation and disulfide bond exchange during αIIbβ3- and αvβ3-mediated clot retraction, we co-expressed in baby hamster kidney cells wild-type (WT) human αIIb and WT or mutated human β3 that contain single or double cysteine substitutions disrupting C523-C544 or C560-C583 bonds. Flow cytometry was used to measure surface expression and activation state of the integrins. Time-course of fibrin clot retraction was examined. Cells expressed WT or mutated human αIIbβ3 as well as chimeric hamster/human αvβ3. The αIIbβ3 mutants were constitutively active and the thiol blocker dithiobisnitrobenzoic acid (DTNB) did not affect their activation state. WT cells retracted the clot and addition of αvβ3 inhibitors decreased the retraction rate. The active mutants and WT cells activated by anti-LIBS6 antibody retracted the clot faster than untreated WT cells, particularly in the presence of αvβ3 inhibitor. DTNB substantially inhibited clot retraction by WT or double C523S/C544S mutant expressing cells, but minimally affected single C523S, C544S or C560S mutants. Anti-LIBS6-enhanced clot retraction was significantly inhibited by DTNB when added prior to anti-LIBS6. Both αIIbβ3 and αvβ3 contribute to clot retraction without prior activation of the integrins. Activation of αIIbβ3, but not of αvβ3 enhances clot retraction. Both αIIbβ3 activation and post-ligation signaling during clot retraction require disulfide bond exchange. Copyright © 2014 Elsevier Ltd. All rights reserved.

Diversity and regulation of plant Ca2+ pumps: insights from expression in yeast

NASA Technical Reports Server (NTRS)

Sze, H.; Liang, F.; Hwang, I.; Curran, A. C.; Harper, J. F.; Evans, M. L. (Principal Investigator)

2000-01-01

The spatial and temporal regulation of calcium concentration in plant cells depends on the coordinate activities of channels and active transporters located on different organelles and membranes. Several Ca2+ pumps have been identified and characterized by functional expression of plant genes in a yeast mutant (K616). This expression system has opened the way to a genetic and biochemical characterization of the regulatory and catalytic features of diverse Ca2+ pumps. Plant Ca(2+)-ATPases fall into two major types: AtECA1 represents one of four or more members of the type IIA (ER-type) Ca(2+)-ATPases in Arabidopsis, and AtACA2 is one of seven or more members of the type IIB (PM-type) Ca(2+)-ATPases that are regulated by a novel amino terminal domain. Type IIB pumps are widely distributed on membranes, including the PM (plasma membrane), vacuole, and ER (endoplasmic reticulum). The regulatory domain serves multiple functions, including autoinhibition, calmodulin binding, and sites for modification by phosphorylation. This domain, however, is considerably diverse among several type IIB ATPases, suggesting that the pumps are differentially regulated. Understanding of Ca2+ transporters at the molecular level is providing insights into their roles in signaling networks and in regulating fundamental processes of cell biology.

Regulation of contractile protein gene expression in unloaded mouse skeletal muscle

NASA Technical Reports Server (NTRS)

Criswell, D. S.; Carson, J. A.; Booth, F. W.

1996-01-01

Hindlimb unloading was performed on mice in an effort to study the regulation of contractile protein genes. In particular, the regulation of myosin heavy chain IIb was examined. During unloading, muscle fibers undergo a type conversion. Preliminary data from this study does not support the hypothesis that the fiber type conversion is due to an increase in promoter activity of fast isoform genes, such as myosin heavy chain IIb. The consequences of this finding are examined, with particular focus on other factors controlling gene regulation.

Reactive codoping of GaAlInP compound semiconductors

DOEpatents

Hanna, Mark Cooper [Boulder, CO; Reedy, Robert [Golden, CO

2008-02-12

A GaAlInP compound semiconductor and a method of producing a GaAlInP compound semiconductor are provided. The apparatus and method comprises a GaAs crystal substrate in a metal organic vapor deposition reactor. Al, Ga, In vapors are prepared by thermally decomposing organometallic compounds. P vapors are prepared by thermally decomposing phospine gas, group II vapors are prepared by thermally decomposing an organometallic group IIA or IIB compound. Group VIB vapors are prepared by thermally decomposing a gaseous compound of group VIB. The Al, Ga, In, P, group II, and group VIB vapors grow a GaAlInP crystal doped with group IIA or IIB and group VIB elements on the substrate wherein the group IIA or IIB and a group VIB vapors produced a codoped GaAlInP compound semiconductor with a group IIA or IIB element serving as a p-type dopant having low group II atomic diffusion.

ADAP interactions with talin and kindlin promote platelet integrin αIIbβ3 activation and stable fibrinogen binding

PubMed Central

Kang, Jian; Kahner, Bryan; Ye, Feng; Ginsberg, Mark H.; Shattil, Sanford J.

2014-01-01

ADAP is a hematopoietic-restricted adapter protein that promotes integrin activation and is a carrier for other adapter proteins, Src kinase–associated phosphoprotein 1 (SKAP1) and SKAP2. In T lymphocytes, SKAP1 is the ADAP-associated molecule that activates integrins through direct linkages with Rap1 effectors (regulator of cell adhesion and polarization enriched in lymphoid tissues; Rap1-interacting adapter molecule). ADAP also promotes integrin αIIbβ3 activation in platelets, which lack SKAP1, suggesting an ADAP integrin–regulatory pathway different from those in lymphocytes. Here we characterized a novel association between ADAP and 2 essential integrin-β cytoplasmic tail-binding proteins involved in αIIbβ3 activation, talin and kindlin-3. Glutathione S-transferase pull-downs identified distinct regions in ADAP necessary for association with kindlin or talin. ADAP was physically proximal to talin and kindlin-3 in human platelets, as assessed biochemically, and by immunofluorescence microscopy and proximity ligation. Relative to wild-type mouse platelets, ADAP-deficient platelets exhibited reduced co-localization of talin with αIIbβ3, and reduced irreversible fibrinogen binding in response to a protease activated receptor 4 (PAR4) thrombin receptor agonist. When ADAP was heterologously expressed in Chinese hamster ovary cells co-expressing αIIbβ3, talin, PAR1, and kindlin-3, it associated with an αIIbβ3/talin complex and enabled kindlin-3 to promote agonist-dependent ligand binding to αIIbβ3. Thus, ADAP uniquely promotes activation of and irreversible fibrinogen binding to platelet αIIbβ3 through interactions with talin and kindlin-3. PMID:24523237

Muscle fiber characteristics and performance correlates of male Olympic-style weightlifters.

PubMed

Fry, Andrew C; Schilling, Brian K; Staron, Robert S; Hagerman, Fredrick C; Hikida, Robert S; Thrush, John T

2003-11-01

Biopsies fro the vastus lateralis muscle of male weightlifters (WL; n=6; X +/- SE, age=27.0 +/- 2.1 years), and non-weight-trained men (CON; n=7; age=27.0 +/- 2.0 years) were compared for fiber types, myosin heavy chain (MHC) and titin content, and fiber type-specific capillary density. Differences (p<0.05) were observed for percent fiber types IIC (WL=0.4 +/- 0.2, CON=2.4 +/- 0.8); IIA (WL=50.5 +/- 3.2, CON=26.9 +/- 3.7); and IIB (WL=1.7 +/- 1.4, CON=21.0 +/- 5.3), as well as percent MHC IIa (WL=65.3 +/- 2.4, CON=52.1 +/- 4.2) and percent MHC IIB (WL=0.9 +/- 0.9; CON=18.2 +/- 6.1). All WL exhibited only the titin-1 isoform. Capillary density (caps.mm(-2)) for all fiber types combined was greater for the CON subjects (WL=192.7 +/- 17.3; CON=262.9 +/- 26.3), due primarily to a greater capillary density in the IIA fibers. Weightlifting performances and vertical jump power were correlated with type II fiber characteristics. These results suggest that successful weightlifting performance is not dependent on IIB fibers, and that weightlifters exhibit large percentages of type IIA muscle fibers and MHC IIa isoform content.

Exercise increases the plasma membrane content of the Na+ -K+ pump and its mRNA in rat skeletal muscles.

PubMed

Tsakiridis, T; Wong, P P; Liu, Z; Rodgers, C D; Vranic, M; Klip, A

1996-02-01

Muscle fibers adapt to ionic challenges of exercise by increasing the plasma membrane Na+-K+ pump activity. Chronic exercise training has been shown to increase the total amount of Na+-K+ pumps present in skeletal muscle. However, the mechanism of adaptation of the Na+-K+ pump to an acute bout of exercise has not been determined, and it is not known whether it involves alterations in the content of plasma membrane pump subunits. Here we examine the effect of 1 h of treadmill running (20 m/min, 10% grade) on the subcellular distribution and expression of Na+-K+ pump subunits in rat skeletal muscles. Red type I and IIa (red-I/IIa) and white type IIa and IIb (white-IIa/IIb) hindlimb muscles from resting and exercised female Sprague-Dawley rats were removed for subcellular fractionation. By homogenization and gradient centrifugation, crude membranes and purified plasma membranes were isolated and subjected to gel electrophoresis and immunoblotting by using pump subunit-specific antibodies. Furthermore, mRNA was isolated from specific red type I (red-I) and white type IIb (white-IIb) muscles and subjected to Northern blotting by using subunit-specific probes. In both red-I/IIa and white-IIa/IIb muscles, exercise significantly raised the plasma membrane content of the alpha1-subunit of the pump by 64 +/- 24 and 55 +/- 22%, respectively (P < 0.05), and elevated the alpha2-polypeptide by 43 +/- 22 and 94 +/- 39%, respectively (P < 0.05). No significant effect of exercise could be detected on the amount of these subunits in an internal membrane fraction or in total membranes. In addition, exercise significantly increased the alpha1-subunit mRNA in red-I muscle (by 50 +/- 7%; P < 0.05) and the beta2-subunit mRNA in white-IIb muscles (by 64 +/- 19%; P < 0.01), but the alpha2- and beta1-mRNA levels were unaffected in this time period. We conclude that increased presence of alpha1- and alpha2-polypeptides at the plasma membrane and subsequent elevation of the alpha1- and beta2-subunit mRNAs may be mechanisms by which acute exercise regulates the Na+-K+ pump of skeletal muscle.

Phosphoinositide 3-Kinase p110β Regulates Integrin αIIbβ3 Avidity and the Cellular Transmission of Contractile Forces*

PubMed Central

Schoenwaelder, Simone M.; Ono, Akiko; Nesbitt, Warwick S.; Lim, Joanna; Jarman, Kate; Jackson, Shaun P.

2010-01-01

Phosphoinositide (PI) 3-kinase (PI3K) signaling processes play an important role in regulating the adhesive function of integrin αIIbβ3, necessary for platelet spreading and sustained platelet aggregation. PI3K inhibitors are effective at reducing platelet aggregation and thrombus formation in vivo and as a consequence are currently being evaluated as novel antithrombotic agents. PI3K regulation of integrin αIIbβ3 activation (affinity modulation) primarily occurs downstream of Gi-coupled and tyrosine kinase-linked receptors linked to the activation of Rap1b, AKT, and phospholipase C. In the present study, we demonstrate an important role for PI3Ks in regulating the avidity (strength of adhesion) of high affinity integrin αIIbβ3 bonds, necessary for the cellular transmission of contractile forces. Using knock-out mouse models and isoform-selective PI3K inhibitors, we demonstrate that the Type Ia p110β isoform plays a major role in regulating thrombin-stimulated fibrin clot retraction in vitro. Reduced clot retraction induced by PI3K inhibitors was not associated with defects in integrin αIIbβ3 activation, actin polymerization, or actomyosin contractility but was associated with a defect in integrin αIIbβ3 association with the contractile cytoskeleton. Analysis of integrin αIIbβ3 adhesion contacts using total internal reflection fluorescence microscopy revealed an important role for PI3Ks in regulating the stability of high affinity integrin αIIbβ3 bonds. These studies demonstrate an important role for PI3K p110β in regulating the avidity of high affinity integrin αIIbβ3 receptors, necessary for the cellular transmission of contractile forces. These findings may provide new insight into the potential antithrombotic properties of PI3K p110β inhibitors. PMID:19940148

Addition of a suture anchor for coracoclavicular fixation to a superior locking plate improves stability of type IIB distal clavicle fractures.

PubMed

Madsen, Wes; Yaseen, Zaneb; LaFrance, Russell; Chen, Tony; Awad, Hani; Maloney, Michael; Voloshin, Ilya

2013-06-01

The purpose of this study was to determine the effect of coracoclavicular (CC) fixation on biomechanical stability in type IIB distal clavicle fractures fixed with plate and screws. Twelve fresh-frozen matched cadaveric specimens were used to create type IIB distal clavicle fractures. Dual-energy x-ray absorptiometry (DEXA) scans ensured similar bone quality. Group 1 (6 specimens) was stabilized with a superior precontoured distal clavicle locking plate and supplemental suture anchor CC fixation. Group 2 (6 specimens) followed the same construct without CC fixation. Each specimen was cyclically loaded in the coronal plane at 40 to 80 N for 17,500 cycles. Load-to-failure testing was performed on the specimens that did not fail cyclic loading. Outcome measures included mode of failure and the number of cycles or load required to create 10 mm of displacement in the construct. All specimens (12 of 12) completed cyclic testing without failure and underwent load-to-failure testing. Group 1 specimens failed at a mean of 808.5 N (range, 635.4 to 952.3 N), whereas group 2 specimens failed at a mean of 401.3 N (range, 283.6 to 656.0 N) (P = .005). Group 1 specimens failed by anchor pullout without coracoid fracture (4 of 6) and distal clavicle fracture fragment fragmentation (1 of 6); one specimen did not fail at the maximal load the materials testing machine was capable of exerting (1,000 N). Group 2 specimens failed by distal clavicle fracture fragment fragmentation (3 of 6) and acromioclavicular (AC) joint displacement (1 of 6); 2 specimens did not fail at the maximal load of the materials testing machine. During cyclic loading, type IIB distal clavicle fractures with and without CC fixation remain stable. CC fixation adds stability to type IIB distal clavicle fractures fixed with plate and screws when loaded to failure. CC fixation for distal clavicle fractures is a useful adjunct to plate-and-screw fixation to augment stability of the fracture. Copyright © 2013 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Altered inhibition in Tuberous Sclerosis and Type IIb cortical dysplasia

PubMed Central

Talos, Delia M.; Sun, Hongyu; Kosaras, Bela; Joseph, Annelise; Folkerth, Rebecca D.; Poduri, Annapurna; Madsen, Joseph R.; Black, Peter M.; Jensen, Frances E.

2012-01-01

Objective The most common neurological symptom of tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) is early-life refractory epilepsy. As previous studies have shown enhanced excitatory glutamatergic neurotransmission in TSC and FCD brains, we hypothesized that neurons associated with these lesions may also express altered GABAA receptor (GABAAR)-mediated inhibition. Methods Expression of the GABAAR subunitsα1 and α4, the Na+-K+-2Cl− (NKCC1), and the K+−Cl− (KCC2) transporters in human TSC and FCD Type II specimens were analyzed by Western blot and double label immunocytochemistry. GABAAR responses in dysplastic neurons from a single case of TSC were measured by perforated-patch recording and compared to normal-appearing cortical neurons from a non-TSC epilepsy case. Results TSC and FCD Type IIb lesions demonstrated decreased expression of the GABAAR α1, increased NKCC1 and decreased KCC2 levels. In contrast, FCD Type IIa lesions showed decreased α4, and increased expression of both NKCC1 and KCC2 transporters. Patch clamp recordings from dysplastic neurons in acute slices from TSC tubers demonstrated excitatory GABAAR responses that were significantly attenuated by the NKCC1 inhibitor bumetanide, in contrast to hyperpolarizing GABAAR-mediated currents in normal neurons from non-TSC cortical slices. Interpretation Expression and function of GABAARs in TSC and FCD IIb suggests the relative benzodiazepine insensitivity and more excitatory action of GABA compared to FCD IIa. These factors may contribute to resistance of seizure activity to anticonvulsants that increase GABAergic function, and may justify add-on trials of the NKCC1 inhibitor bumetanide for the treatment of TSC and FCD Type IIb related epilepsy. PMID:22447678

Ultraviolet Detection of the Binary Companion to the Type IIb SN 2001ig

NASA Astrophysics Data System (ADS)

Ryder, Stuart D.; Van Dyk, Schuyler D.; Fox, Ori D.; Zapartas, Emmanouil; de Mink, Selma E.; Smith, Nathan; Brunsden, Emily; Azalee Bostroem, K.; Filippenko, Alexei V.; Shivvers, Isaac; Zheng, WeiKang

2018-03-01

We present HST/WFC3 ultraviolet imaging in the F275W and F336W bands of the Type IIb SN 2001ig at an age of more than 14 years. A clear point source is detected at the site of the explosion, with m F275W = 25.39 ± 0.10 and m F336W = 25.88 ± 0.13 mag. Despite weak constraints on both the distance to the host galaxy NGC 7424 and the line-of-sight reddening to the supernova, this source matches the characteristics of an early B-type main-sequence star with 19,000 < T eff < 22,000 K and {log}({L}bol}/{L}ȯ )=3.92+/- 0.14. A BPASS v2.1 binary evolution model, with primary and secondary masses of 13 M ⊙ and 9 M ⊙, respectively, is found to simultaneously resemble, in the Hertzsprung–Russell diagram, both the observed location of this surviving companion, and the primary star evolutionary endpoints for other Type IIb supernovae. This same model exhibits highly variable late-stage mass loss, as expected from the behavior of the radio light curves. A Gemini/GMOS optical spectrum at an age of 6 years reveals a narrow He II λ4686 emission line, indicative of continuing interaction with a dense circumstellar medium at large radii from the progenitor. We review our findings on SN 2001ig in the context of binary evolution channels for stripped-envelope supernovae. Owing to the uncrowded nature of its environment in the ultraviolet, this study of SN 2001ig represents one of the cleanest detections to date of a surviving binary companion to a Type IIb supernova.

The role of protein disulfide isomerase in the post-ligation phase of β3 integrin-dependent cell adhesion.

PubMed

Leader, Avi; Mor-Cohen, Ronit; Ram, Ron; Sheptovitsky, Vera; Seligsohn, Uri; Rosenberg, Nurit; Lahav, Judith

2015-12-01

Protein disulfide isomerase (PDI) catalyzes disulfide bond exchange. It is crucial for integrin-mediated platelet adhesion and aggregation and disulfide bond exchange is necessary for αIIbβ3 and αvβ3 activation. However, the role of disulfide bond exchange and PDI in the post-ligation phase of αIIbβ3 and αvβ3 mediated cell adhesion has yet to be determined. To investigate a possible such role, we expressed wild type (WT) human αIIb and either WT human β3, or β3 harboring single or double cysteine to serine substitutions disrupting Cys473-Cys503 or Cys523-Cys544 bonds, in baby hamster kidney (BHK) cells, leading to expression of both human αIIbβ3 and a chimeric hamster/human αvβ3. Adhesion to fibrinogen-coated wells was studied in the presence or absence of bacitracin, a PDI inhibitor, with and without an αvβ3 blocker. Flow cytometry showed WT and mutant αIIbβ3 expression in BHK cells and indicated that mutated αIIbβ3 receptors were constitutively active while WT αIIbβ3 was inactive. Both αIIbβ3 and αvβ3 integrins, WT and mutants, mediated adhesion to fibrinogen as shown by reduced but still substantial adhesion following treatment with the αvβ3 blocker. Mutated αIIbβ3 integrins disrupted in the Cys523-Cys544 bond still depended on PDI for adhesion as shown by the inhibitory effect of bacitracin in the presence of the αvβ3 blocker. Mutated integrins disrupted in the Cys473-Cys503 bond showed a similar trend. PDI-mediated disulfide bond exchange plays a pivotal role in the post-ligation phase of αIIbβ3-mediated adhesion to fibrinogen, while this step in αvβ3-mediated adhesion is independent of disulfide exchange. Copyright © 2015 Elsevier Ltd. All rights reserved.

Type IIB flux vacua from G-theory II

NASA Astrophysics Data System (ADS)

Candelas, Philip; Constantin, Andrei; Damian, Cesar; Larfors, Magdalena; Morales, Jose Francisco

2015-02-01

We find analytic solutions of type IIB supergravity on geometries that locally take the form Mink × M 4 × ℂ with M 4 a generalised complex manifold. The solutions involve the metric, the dilaton, NSNS and RR flux potentials (oriented along the M 4) parametrised by functions varying only over ℂ. Under this assumption, the supersymmetry equations are solved using the formalism of pure spinors in terms of a finite number of holomorphic functions. Alternatively, the solutions can be viewed as vacua of maximally supersymmetric supergravity in six dimensions with a set of scalar fields varying holomorphically over ℂ. For a class of solutions characterised by up to five holomorphic functions, we outline how the local solutions can be completed to four-dimensional flux vacua of type IIB theory. A detailed study of this global completion for solutions with two holomorphic functions has been carried out in the companion paper [1]. The fluxes of the global solutions are, as in F-theory, entirely codified in the geometry of an auxiliary K3 fibration over ℂℙ1. The results provide a geometric construction of fluxes in F-theory.

Non-topological cycloops

NASA Astrophysics Data System (ADS)

Lake, Matthew; Thomas, Steven; Ward, John

2010-01-01

We propose a mechanism for the creation of cosmic string loops with dynamically stabilised windings in the internal space. Assuming a velocity correlations regime in the post-inflationary epoch, such windings are seen to arise naturally in string networks prior to loop formation. The angular momentum of the string in the compact space may then be sufficient to ensure that the windings remain stable after the loop chops off from the network, even if the internal manifold is simply connected. For concreteness we embed our model in the Klebanov-Strassler geometry, which provides a natural mechanism for brane inflation, as well a being one of the best understood compactification schemes in type IIB string theory. We see that the interaction of angular momentum with the string tension causes the loop to oscillate between phases of expansion and contraction. This, in principle, should give rise to a distinct gravitational wave signature, the future detection of which could provide indirect evidence for the existence of extra dimensions.

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

Finn, Kieran; Bianco, Federica B.; Modjaz, Maryam

We compare the diversity of spectral line velocities in a large sample of type IIb supernovae (SNe IIb) with the expected asphericity in the explosion, as measured from the light echoes (LEs) of Cassiopeia A (Cas A), which was a historical galactic SN IIb. We revisit the results of Rest et al., who used LEs to observe Cas A from multiple lines of sight and hence determine its asphericity, as seen in the velocity of three spectral lines (He i λ 5876, H α , and the Ca ii near-infrared (NIR) triplet). We confirm and improve on this measurement bymore » reproducing the effect of the LEs in the spectra of several extragalactic SNe IIb found in the literature as well as mean SN IIb spectra recently created by Liu et al. and comparing these to the observed light echo spectra of Cas A, including their associated uncertainties. In order to quantify the accuracy of this comparison, we smooth the light echo spectra of Cas A using Gaussian processes and use a Monte Carlo method to measure the absorption velocities of these three features in the spectra. We then test the hypothesis that the diversity of ejecta velocities seen in SNe IIb can be explained by asphericity. We do this by comparing the range of velocities seen in the different LEs, and hence different lines of sight, of Cas A to that seen in the population of SNe IIb. We conclude that these two ranges are of the same order and thus asphericity could be enough to explain the diversity in the expansion velocity alone.« less

Synergistic ablation does not affect atrophy or altered myosin heavy chain expression in the non-weight bearing soleus muscle

NASA Technical Reports Server (NTRS)

Linderman, J. K.; Talmadge, R. J.; Gosselink, K. L.; Tri, P. N.; Roy, R. R.; Grindeland, R. E.

1996-01-01

The purpose of this study was to investigate whether the soleus muscle undergoes atrophy and alterations in myosin heavy chain (MHC) composition during non-weight bearing in the absence of synergists. Thirty-two female rats were randomly assigned to four groups: control (C), synergistic ablation (ABL) of the gastrocnemius and plantaris muscles to overload the soleus muscle, hindlimb suspension (HLS), or a combination of synergistic ablation and hindlimb suspension (HLS-ABL). After 28 days of hindlimb suspension, soleus atrophy was more pronounced in HLS (58%) than in HLS-ABL (43%) rats. Compared to C rats, non-weight bearing decreased mixed and myofibrillar protein contents and Type I MHC 49%, 45%, and 7%, respectively, in HLS animals. In addition, de novo expression of fast Type IIx and Type IIb MHC (5% and 2%, respectively) was observed in HLS animals. Similarly, when compared to C rats, mixed and myofibrillar protein contents and Type I MHC decreased 43%, 46%, and 4%, respectively, in HLS-ABL animals. Also, de novo expression of Type IIx (4%) and IIb (1%) MHC was observed. Collectively, these data indicate that the loss of muscle protein and Type I MHC, and the de novo expression of Type IIx and Type IIb MHC in the rat soleus occur independently of the presence of synergists during non-weight bearing. Furthermore, these results confirm the contention that soleus mass and MHC expression are highly sensitive to alterations in mechanical load.

Scale invariance of the η-deformed AdS5 × S5 superstring, T-duality and modified type II equations

NASA Astrophysics Data System (ADS)

Arutyunov, G.; Frolov, S.; Hoare, B.; Roiban, R.; Tseytlin, A. A.

2016-02-01

We consider the ABF background underlying the η-deformed AdS5 ×S5 sigma model. This background fails to satisfy the standard IIB supergravity equations which indicates that the corresponding sigma model is not Weyl invariant, i.e. does not define a critical string theory in the usual sense. We argue that the ABF background should still define a UV finite theory on a flat 2d world-sheet implying that the η-deformed model is scale invariant. This property follows from the formal relation via T-duality between the η-deformed model and the one defined by an exact type IIB supergravity solution that has 6 isometries albeit broken by a linear dilaton. We find that the ABF background satisfies candidate type IIB scale invariance conditions which for the R-R field strengths are of the second order in derivatives. Surprisingly, we also find that the ABF background obeys an interesting modification of the standard IIB supergravity equations that are first order in derivatives of R-R fields. These modified equations explicitly depend on Killing vectors of the ABF background and, although not universal, they imply the universal scale invariance conditions. Moreover, we show that it is precisely the non-isometric dilaton of the T-dual solution that leads, after T-duality, to modification of type II equations from their standard form. We conjecture that the modified equations should follow from κ-symmetry of the η-deformed model. All our observations apply also to η-deformations of AdS3 ×S3 ×T4and AdS2 ×S2 ×T6models.

Displaced Neer Type IIB distal-third clavicle fractures-Long-term clinical outcome after plate fixation and additional screw augmentation for coracoclavicular instability.

PubMed

Tiefenboeck, Thomas M; Boesmueller, Sandra; Binder, Harald; Bukaty, Adam; Tiefenboeck, Michael M; Joestl, Julian; Hofbauer, Marcus; Ostermann, Roman C

2017-01-23

Unstable Neer Type IIB fractures require meticulous surgical treatment. Thus, the aim of this study was to present long-term outcomes after plate fixation and minimally invasive coracoclavicular (CC) stabilization using screw fixation. A consecutive series of patients with unstable Neer Type IIB displaced clavicle fractures, treated by open reduction and internal fixation (ORIF) with a plate and additional screw fixation for coracoclavicular ligament instability, was reviewed in order to determine long-term clinical and radiological outcome. Seven patients, six males and one female, with a mean age of 37 ± 8 years (median: 36 years; range, 28-51 years), were evaluated. At latest follow-up, after a mean of 67 months (range, 11-117 months), patients presented with the following mean scores: DASH: 0.57, ASES: 98.81, UCLA: 34.29, VAS: 0.43, Simple Shoulder Test: 11.57. However, two complications were observed: one case of implant loosening and one non-union. There were no differences observed between the CC distances comparing postoperative X-rays to those in final follow-up. In 25% of our patients early postoperative complications occurred. In all patients reoperation was necessary to remove the implanted screw. The results of the present study indicate that the treatment of Neer Type IIB lateral clavicle fractures with ORIF using a plate and additional CC screw fixation, leads to satisfying clinical and radiological outcomes in the long-term. However, considering an early postoperative complication rate of 25% and a 100% rate of secondary surgery due to removal of the CC screw does not seem to justify this technique anymore.

Scale invariance of the η-deformed AdS 5 × S 5 superstring, T-duality and modified type II equations

DOE PAGES

Arutyunov, G.; Frolov, S.; Hoare, B.; ...

2015-12-23

We consider the ABF background underlying the η-deformed AdS 5 × S 5 sigma model. This background fails to satisfy the standard IIB supergravity equations which indicates that the corresponding sigma model is not Weyl invariant, i.e. does not define a critical string theory in the usual sense. We argue that the ABF background should still define a UV finite theory on a flat 2d world-sheet implying that the η-deformed model is scale invariant. This property follows from the formal relation via T-duality between the η-deformed model and the one defined by an exact type IIB supergravity solution that hasmore » 6 isometries albeit broken by a linear dilaton. We find that the ABF background satisfies candidate type IIB scale invariance conditions which for the R–R field strengths are of the second order in derivatives. Surprisingly, we also find that the ABF background obeys an interesting modification of the standard IIB supergravity equations that are first order in derivatives of R–R fields. These modified equations explicitly depend on Killing vectors of the ABF background and, although not universal, they imply the universal scale invariance conditions. Moreover, we show that it is precisely the non-isometric dilaton of the T-dual solution that leads, after T-duality, to modification of type II equations from their standard form. We conjecture that the modified equations should follow from κ-symmetry of the η-deformed model. All our observations apply also to η-deformations of AdS 3 × S 3 × T 4 and AdS 2 × S 2 × T 6 models.« less

Precision holography for N={2}^{\\ast } on S 4 from type IIB supergravity

NASA Astrophysics Data System (ADS)

Bobev, Nikolay; Gautason, Friðrik Freyr; van Muiden, Jesse

2018-04-01

We find a new supersymmetric solution of type IIB supergravity which is holographically dual to the planar limit of the four-dimensional N={2}^{\\ast } supersymmetric Yang-Mills theory on S 4. We study a probe fundamental string in this background which is dual to a supersymmetric Wilson loop in the N={2}^{\\ast } theory. Using holography we calculate the expectation value of this line operator to leading order in the 't Hooft coupling. The result is a non-trivial function of the mass parameter of the N={2}^{\\ast } theory that precisely matches the result from supersymmetric localization.

Implementing odd-axions in dimensional oxidation of 4D non-geometric type IIB scalar potential

NASA Astrophysics Data System (ADS)

Shukla, Pramod

2016-01-01

In a setup of type IIB superstring compactification on an orientifold of a T6 /Z4 sixfold, the presence of geometric flux (ω) and non-geometric fluxes (Q, R) is implemented along with the standard NS-NS and RR three-form fluxes (H, F). After computing the F/D-term contributions to the N = 1 four dimensional effective scalar potential, we rearrange the same into 'suitable' pieces by using a set of new generalized flux orbits. Subsequently, we dimensionally oxidize the various pieces of the total four dimensional scalar potential to guess their ten-dimensional origin.

Light Curve and Spectral Evolution of Type IIb Supernovae

NASA Astrophysics Data System (ADS)

Gangopadhyay, Anjasha; Misra, Kuntal; Pastorello, Andrea; Sahu, Devendra Kumar; Singh, Mridweeka; Dastidar, raya; Anapuma, Gadiyara Chakrapani; Kumar, Brijesh; Pandey, Shashi Bhushan

2018-04-01

Stripped-Envelope Supernovae constitute the sub-class of core-collapse supernovae that strip off their outer hydrogen envelope due to high stellar winds or due to interaction with a binary companion where mass transfer occurs as a result of Roche lobe overflow. We present here the photometric and spectroscopic analysis of a member of this class : SN 2015as classified as a type IIb supernova. Light curve features are similar to those of SN 2011fu while spectroscopic features are quite similar to those of SN 2008ax and SN 2011dh. Early epoch spectra have been modelled with SYN++ which indicates a photospheric velocity of 8500 km sec-1 and temperature of 6500K. Spectroscopic lines show transitioning from H to He features confirming it to be a type IIb supernova. Prominent oxygen and calcium emission features are indicative of the asymmetry of the ejecta. We also estimate the signal to noise ratio of the 3.6m telescope data. This telescope is located at ARIES, Devasthal, Nainital at an altitude of 2450m. We also show the comparison plots of spectra taken with a 2m and 4m class telescopes to enlighten the importance of spectral features displayed by bigger diameter telescopes.

Warped AdS 6 × S 2 in Type IIB supergravity III. Global solutions with seven-branes

NASA Astrophysics Data System (ADS)

D'Hoker, Eric; Gutperle, Michael; Uhlemann, Christoph F.

2017-11-01

We extend our previous construction of global solutions to Type IIB super-gravity that are invariant under the superalgebra F(4) and are realized on a spacetime of the form AdS 6 × S 2 warped over a Riemann surface Σ by allowing the supergravity fields to have non-trivial SL(2, ℝ) monodromy at isolated punctures on Σ. We obtain explicit solutions for the case where Σ is a disc, and the monodromy generators are parabolic elements of SL(2, ℝ) physically corresponding to the monodromy allowed in Type IIB string theory. On the boundary of Σ the solutions exhibit singularities at isolated points which correspond to semi-infinite five-branes, as is familiar from the global solutions without monodromy. In the interior of Σ, the solutions are everywhere regular, except at the punctures where SL(2, ℝ) monodromy resides and which physically correspond to the locations of [ p, q] seven-branes. The solutions have a compelling physical interpretation corresponding to fully localized five-brane intersections with additional seven-branes, and provide candidate holographic duals to the five-dimensional superconformal field theories realized on such intersections.

Late-time spectral line formation in Type IIb supernovae, with application to SN 1993J, SN 2008ax, and SN 2011dh

NASA Astrophysics Data System (ADS)

Jerkstrand, A.; Ergon, M.; Smartt, S. J.; Fransson, C.; Sollerman, J.; Taubenberger, S.; Bersten, M.; Spyromilio, J.

2015-01-01

We investigate line formation processes in Type IIb supernovae (SNe) from 100 to 500 days post-explosion using spectral synthesis calculations. The modelling identifies the nuclear burning layers and physical mechanisms that produce the major emission lines, and the diagnostic potential of these. We compare the model calculations with data on the three best observed Type IIb SNe to-date - SN 1993J, SN 2008ax, and SN 2011dh. Oxygen nucleosynthesis depends sensitively on the main-sequence mass of the star and modelling of the [O I] λλ6300, 6364 lines constrains the progenitors of these three SNe to the MZAMS = 12-16 M⊙ range (ejected oxygen masses 0.3-0.9 M⊙), with SN 2011dh towards the lower end and SN 1993J towards the upper end of the range. The high ejecta masses from MZAMS ≳ 17 M⊙ progenitors give rise to brighter nebular phase emission lines than observed. Nucleosynthesis analysis thus supports a scenario of low-to-moderate mass progenitors for Type IIb SNe, and by implication an origin in binary systems. We demonstrate how oxygen and magnesium recombination lines may be combined to diagnose the magnesium mass in the SN ejecta. For SN 2011dh, a magnesium mass of 0.02-0.14 M⊙ is derived, which gives a Mg/O production ratio consistent with the solar value. Nitrogen left in the He envelope from CNO burning gives strong [N II] λλ6548, 6583 emission lines that dominate over Hα emission in our models. The hydrogen envelopes of Type IIb SNe are too small and dilute to produce any noticeable Hα emission or absorption after ~150 days, and nebular phase emission seen around 6550 Å is in many cases likely caused by [N II] λλ6548, 6583. Finally, the influence of radiative transport on the emergent line profiles is investigated. Significant line blocking in the metal core remains for several hundred days, which affects the emergent spectrum. These radiative transfer effects lead to early-time blueshifts of the emission line peaks, which gradually disappear as the optical depths decrease with time. The modelled evolution of this effect matches the observed evolution in SN 2011dh. Appendices are available in electronic form at http://www.aanda.org

A seamless phase IIB/III adaptive outcome trial: design rationale and implementation challenges.

PubMed

Chen, Y H Joshua; Gesser, Richard; Luxembourg, Alain

2015-02-01

The licensed four-valent prophylactic human papillomavirus vaccine is highly efficacious in preventing cervical, vulvar, vaginal, and anal cancers and related precancers caused by human papillomavirus types 6, 11, 16, and 18. These four types account for approximately 70% of cervical cancers. A nine-valent human papillomavirus vaccine, including the four original types (6, 11, 16, and 18) plus the next five most prevalent types in cervical cancer (31, 33, 45, 52, and 58) could provide approximately 90% overall cervical cancer coverage. To expedite the nine-valent human papillomavirus vaccine clinical development, an adaptive, seamless Phase IIB/III outcome trial with ∼ 15,000 subjects was conducted to facilitate dose formulation selection and provide pivotal evidence of safety and efficacy for regulatory registrations. We discuss the design rationale and implementation challenges of the outcome trial, focusing on the adaptive feature of the seamless Phase IIB/III design. Subjects were enrolled in two parts (Part A and Part B). Approximately 1240 women, 16-26 years of age, were enrolled in Part A for Phase IIB evaluation and equally randomized to one of three dose formulations of the nine-valent human papillomavirus vaccine or the four-valent human papillomavirus vaccine (active control). Based on an interim analysis of immunogenicity and safety, one dose formulation of the nine-valent human papillomavirus vaccine was selected for evaluation in the Phase III part of the study. Subjects enrolled in Part A who received the selected dose formulation of the nine-valent human papillomavirus vaccine or four-valent human papillomavirus vaccine continued to be followed up and contributed to the final efficacy and safety analyses. In addition, ∼ 13,400 women 16-26 years of age were enrolled in Part B, randomized to nine-valent human papillomavirus vaccine at the selected dose formulation or four-valent human papillomavirus vaccine, and followed for immunogenicity, efficacy, and safety. A seamless Phase IIB/III design was justified by the extensive pre-existing knowledge of the licensed four-valent human papillomavirus vaccine and the development objectives for the nine-valent human papillomavirus vaccine. Subjects enrolled in Part A who received either the selected nine-valent human papillomavirus formulation or four-valent human papillomavirus vaccine contributed ∼ 10% of person-years of follow-up due to its earlier start-thereby maximizing the overall efficiency of the trial. Some of the challenges encountered in the implementation of the adaptive design included practical considerations during Phase IIB formulation selection by internal and external committees, End-of-Phase II discussion with health authorities and managing changes in the assay for immunological endpoints. Application of the experience and lesson learned from this seamless adaptive design to other clinical programs may depend on case-by-case consideration. A seamless Phase IIB/III adaptive design was successfully implemented in this large outcome study. The development time of the second-generation nine-valent human papillomavirus vaccine was shortened due to improved statistical efficiency. © The Author(s) 2014.

Spontaneous Intramuscular Hematomas of the Abdomen and Pelvis: A New Multilevel Algorithm to Direct Transarterial Embolization and Patient Management.

PubMed

Popov, Milen; Sotiriadis, Charalampos; Gay, Frederique; Jouannic, Anne-Marie; Lachenal, Yann; Hajdu, Steven D; Doenz, Francesco; Qanadli, Salah D

2017-04-01

To report our experience using a multilevel patient management algorithm to direct transarterial embolization (TAE) in managing spontaneous intramuscular hematoma (SIMH). From May 2006 to January 2014, twenty-seven patients with SIMH had been referred for TAE to our Radiology department. Clinical status and coagulation characteristics of the patients are analyzed. An algorithm integrating CT findings is suggested to manage SIMH. Patients were classified into three groups: Type I, SIMH with no active bleeding (AB); Type II, SIMH with AB and no muscular fascia rupture (MFR); and Type III, SIMH with MFR and AB. Type II is furthermore subcategorized as IIa, IIb and IIc. Types IIb, IIc and III were considered for TAE. The method of embolization as well as the material been used are described. Continuous variables are presented as mean ± SD. Categorical variables are reported as percentages. Technical success, clinical success, complications and 30-day mortality (d30 M) were analyzed. Two patients (7.5%) had Type IIb, four (15%) Type IIc and 21 (77.5%) presented Type III. The detailed CT and CTA findings, embolization procedure and materials used are described. Technical success was 96% with a complication rate of 4%. Clinical success was 88%. The bleeding-related thirty-day mortality was 15% (all with Type III). TAE is a safe and efficient technique to control bleeding that should be considered in selected SIMH as soon as possible. The proposed algorithm integrating CT features provides a comprehensive chart to select patients for TAE. 4.

Selective neck irradiation for supraglottic cancer: focus on Sublevel IIb omission.

PubMed

Kanayama, Naoyuki; Nishiyama, Kinji; Kawaguchi, Yoshifumi; Konishi, Koji; Ogawa, Kazuhiko; Suzuki, Motoyuki; Yoshii, Tadashi; Fujii, Takashi; Yoshino, Kunitoshi; Teshima, Teruki

2016-01-01

To estimate selective neck irradiation omitting surgical Sublevel IIb. Bilateral necks of 47 patients (94 necks) were subjected to definitive radiotherapy for supraglottic cancer. Sixty-nine and 25 necks were clinically node negative (cN-) and clinically node positive (cN+), respectively. We subdivided Sublevel IIb by the international consensus guideline for radiotherapy into Sublevel IIb/a, directly posterior to the internal jugular vein, and Sublevel IIb/b, which was behind Sublevel IIb/a and coincided with surgical Sublevel IIb. Bilateral (Sub)levels IIa, III, IV and IIb/a were routinely irradiated, whereas Sublevel IIb/b was omitted from the elective clinical target volume in 73/94 treated necks (78%). Two patients presented with ipsilateral Sublevel IIb/a metastases. No Sublevel IIb/b metastasis was observed. Five patients experienced cervical lymph node recurrence; Sublevel IIb/a recurrence developed in two patients, whereas no Sublevel IIb/b recurrence occurred even in the cN- necks of cN+ patients or cN0 patients. The 5-year regional control rates were 91.5% for Sublevel IIb/b-omitted patients and 77.8% for Sublevel IIb/b treated patients. Selective neck irradiation omitting Sublevel IIb/b did not compromise regional control and could be indicated for cN- neck of supraglottic cancer. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

High phosphorus diet-induced changes in NaPi-IIb phosphate transporter expression in the rat kidney: DNA microarray analysis.

PubMed

Suyama, Tatsuya; Okada, Shinji; Ishijima, Tomoko; Iida, Kota; Abe, Keiko; Nakai, Yuji

2012-01-01

The mechanism by which phosphorus levels are maintained in the body was investigated by analyzing changes in gene expression in the rat kidney following administration of a high phosphorus (HP) diet. Male Wistar rats were divided into two groups and fed a diet containing 0.3% (control) or 1.2% (HP) phosphorous for 24 days. Phosphorous retention was not significantly increased in HP rats, but fractional excretion of phosphorus was significantly increased in the HP group compared to controls, with an excessive amount of the ingested phosphorus being passed through the body. DNA microarray analysis of kidney tissue from both groups revealed changes in gene expression profile induced by a HP diet. Among the genes that were upregulated, Gene Ontology (GO) terms related to ossification, collagen fibril organization, and inflammation and immune response were significantly enriched. In particular, there was significant upregulation of type IIb sodium-dependent phosphate transporter (NaPi-IIb) in the HP rat kidney compared to control rats. This upregulation was confirmed by in situ hybridization. Distinct signals for NaPi-IIb in both the cortex and medulla of the kidney were apparent in the HP group, while the corresponding signals were much weaker in the control group. Immunohistochemical analysis showed that NaPi-IIb localized to the basolateral side of kidney epithelial cells surrounding the urinary duct in HP rats but not in control animals. These data suggest that NaPi-IIb is upregulated in the kidney in response to the active excretion of phosphate in HP diet-fed rats.

Dependence of cross-bridge kinetics on myosin light chain isoforms in rabbit and rat skeletal muscle fibres.

PubMed

Andruchov, Oleg; Andruchova, Olena; Wang, Yishu; Galler, Stefan

2006-02-15

Cross-bridge kinetics underlying stretch-induced force transients was studied in fibres with different myosin light chain (MLC) isoforms from skeletal muscles of rabbit and rat. The force transients were induced by stepwise stretches (< 0.3% of fibre length) applied on maximally Ca2+-activated skinned fibres. Fast fibre types IIB, IID (or IIX) and IIA and the slow fibre type I containing the myosin heavy chain isoforms MHC-IIb, MHC-IId (or MHC-IIx), MHC-IIa and MHC-I, respectively, were investigated. The MLC isoform content varied within fibre types. Fast fibre types contained the fast regulatory MLC isoform MLC2f and different proportions of the fast alkali MLC isoforms MLC1f and MLC3f. Type I fibres contained the slow regulatory MLC isoform MLC2s and the slow alkali MLC isoform MLC1s. Slow MLC isoforms were also present in several type IIA fibres. The kinetics of force transients differed by a factor of about 30 between fibre types (order from fastest to slowest kinetics: IIB > IID > IIA > I). The kinetics of the force transients was not dependent on the relative content of MLC1f and MLC3f. Type IIA fibres containing fast and slow MLC isoforms were about 1.2 times slower than type IIA fibres containing only fast MLC isoforms. We conclude that while the cross-bridge kinetics is mainly determined by the MHC isoforms present, it is affected by fast and slow MLC isoforms but not by the relative content of MLC1f and MLC3f. Thus, the physiological role of fast and slow MLC isoforms in type IIA fibres is a fine-tuning of the cross-bridge kinetics.

Spontaneous Intramuscular Hematomas of the Abdomen and Pelvis: A New Multilevel Algorithm to Direct Transarterial Embolization and Patient Management

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

Popov, Milen; Sotiriadis, Charalampos; Gay, Frederique

PurposeTo report our experience using a multilevel patient management algorithm to direct transarterial embolization (TAE) in managing spontaneous intramuscular hematoma (SIMH).Materials and MethodsFrom May 2006 to January 2014, twenty-seven patients with SIMH had been referred for TAE to our Radiology department. Clinical status and coagulation characteristics of the patients are analyzed. An algorithm integrating CT findings is suggested to manage SIMH. Patients were classified into three groups: Type I, SIMH with no active bleeding (AB); Type II, SIMH with AB and no muscular fascia rupture (MFR); and Type III, SIMH with MFR and AB. Type II is furthermore subcategorized asmore » IIa, IIb and IIc. Types IIb, IIc and III were considered for TAE. The method of embolization as well as the material been used are described. Continuous variables are presented as mean ± SD. Categorical variables are reported as percentages. Technical success, clinical success, complications and 30-day mortality (d30 M) were analyzed.ResultsTwo patients (7.5%) had Type IIb, four (15%) Type IIc and 21 (77.5%) presented Type III. The detailed CT and CTA findings, embolization procedure and materials used are described. Technical success was 96% with a complication rate of 4%. Clinical success was 88%. The bleeding-related thirty-day mortality was 15% (all with Type III).ConclusionTAE is a safe and efficient technique to control bleeding that should be considered in selected SIMH as soon as possible. The proposed algorithm integrating CT features provides a comprehensive chart to select patients for TAE.Level of Evidence4.« less

Late-time spectroscopy of envelope-stripped SNe: Figuring the central engine

NASA Astrophysics Data System (ADS)

Kawabata, Koji

2011-01-01

We propose to perform late-time spectroscopy of envelope-stripped core-collapse supernovae (SNe), i.e., Type Ib/c/IIb SNe. We aim to examine the explosion physics and its dependence on the progenitor mass. The key information is the asphericity and the chemical composition of the inner atmosphere, which can be explored by late-time observations. The difference in [O I] line profiles indicates that GRB-associated energetic SNe Ic (like SN 1998bw) and non-GRB energetic SNe Ic (2003jd) are intrinsically similar aspherical explosions that are differently viewed (pole-on for 1998bw and nearly edge-on for 2003jd). Our continuing study suggests that the asphericity is rather common characteristic even for normal energy SNe without a GRB. However, it is still unclear how the intermediate types of SNe (SNe Ib/IIb) are produced and how they connected with other types of core-collapse SNe. High-quality late-time spectra of SNe Ib/Ic/IIb are still lacking. We propose to obtain a larger number of nebular spectra of envelope-stripped SNe so that we examine the degree of the asphericity as a function of the progenitor's mass, explosion energy, amount of synthesized ^56Ni, and the physical properties of the central remnant.

Spectropolarimetry of SN 2011dh in M51: geometric insights on a Type IIb supernova progenitor and explosion

NASA Astrophysics Data System (ADS)

Mauerhan, Jon C.; Williams, G. Grant; Leonard, Douglas C.; Smith, Paul S.; Filippenko, Alexei V.; Smith, Nathan; Hoffman, Jennifer L.; Huk, Leah; Clubb, Kelsey I.; Silverman, Jeffrey M.; Cenko, S. Bradley; Milne, Peter; Gal-Yam, Avishay; Ben-Ami, Sagi

2015-11-01

We present seven epochs of spectropolarimetry of the Type IIb supernova (SN IIb) 2011dh in M51, spanning 86 d of its evolution. The first epoch was obtained 9 d after the explosion, when the photosphere was still in the depleted hydrogen layer of the stripped-envelope progenitor. Continuum polarization is securely detected at the level of P ≈ 0.5 per cent through day 14 and appears to diminish by day 30, which is different from the prevailing trends suggested by studies of other core-collapse SNe. Time-variable modulations in P and position angle are detected across P-Cygni line features. H α and He I polarization peak after 30 d and exhibit position angles roughly aligned with the earlier continuum, while O I and Ca II appear to be geometrically distinct. We discuss several possibilities to explain the evolution of the continuum and line polarization, including the potential effects of a tidally deformed progenitor star, aspherical radioactive heating by fast-rising plumes of 56Ni from the core, oblique shock breakout, or scattering by circumstellar material. While these possibilities are plausible and guided by theoretical expectations, they are not unique solutions to the data. The construction of more detailed hydrodynamic and radiative-transfer models that incorporate complex aspherical geometries will be required to further elucidate the nature of the polarized radiation from SN 2011dh and other SNe IIb.

Comparative Adjuvant Effects of Type II Heat-Labile Enterotoxins in Combination with Two Different Candidate Ricin Toxin Vaccine Antigens.

PubMed

Vance, David J; Greene, Christopher J; Rong, Yinghui; Mandell, Lorrie M; Connell, Terry D; Mantis, Nicholas J

2015-12-01

Type II heat-labile enterotoxins (HLTs) constitute a promising set of adjuvants that have been shown to enhance humoral and cellular immune responses when coadministered with an array of different proteins, including several pathogen-associated antigens. However, the adjuvant activities of the four best-studied HLTs, LT-IIa, LT-IIb, LT-IIb(T13I), and LT-IIc, have never been compared side by side. We therefore conducted immunization studies in which LT-IIa, LT-IIb, LT-IIb(T13I), and LT-IIc were coadministered by the intradermal route to mice with two clinically relevant protein subunit vaccine antigens derived from the enzymatic A subunit (RTA) of ricin toxin, RiVax and RVEc. The HLTs were tested with low and high doses of antigen and were assessed for their abilities to stimulate antigen-specific serum IgG titers, ricin toxin-neutralizing activity (TNA), and protective immunity. We found that all four HLTs tested were effective adjuvants when coadministered with RiVax or RVEc. LT-IIa was of particular interest because as little as 0.03 μg when coadministered with RiVax or RVEc proved effective at augmenting ricin toxin-specific serum antibody titers with nominal evidence of local inflammation. Collectively, these results justify the need for further studies into the mechanism(s) underlying LT-IIa adjuvant activity, with the long-term goal of evaluating LT-IIa's activity in humans. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Are the binary typology models of alcoholism valid in polydrug abusers?

PubMed

Pombo, Samuel; da Costa, Nuno F; Figueira, Maria L

2015-01-01

To evaluate the dichotomy of type I/II and type A/B alcoholism typologies in opiate-dependent patients with a comorbid alcohol dependence problem (ODP-AP). The validity assessment process comprised the information regarding the history of alcohol use (internal validity), cognitive-behavioral variables regarding substance use (external validity), and indicators of treatment during 6-month follow-up (predictive validity). ODP-AP subjects classified as type II/B presented an early and much more severe drinking problem and a worse clinical prognosis when considering opiate treatment variables as compared with ODP-AP subjects defined as type I/A. Furthermore, type II/B patients endorse more general positive beliefs and expectancies related to the effect of alcohol and tend to drink heavily across several intra- and interpersonal situations as compared with type I/A patients. These findings confirm two different forms of alcohol dependence, recognized as a low-severity/vulnerability subgroup and a high-severity/vulnerability subgroup, in an opiate-dependent population with a lifetime diagnosis of alcohol dependence.

Novel single skeletal muscle fiber analysis reveals a fiber type-selective effect of acute exercise on glucose uptake.

PubMed

Cartee, Gregory D; Arias, Edward B; Yu, Carmen S; Pataky, Mark W

2016-11-01

One exercise session can induce subsequently elevated insulin sensitivity that is largely attributable to greater insulin-stimulated glucose uptake by skeletal muscle. Because skeletal muscle is a heterogeneous tissue comprised of diverse fiber types, our primary aim was to determine exercise effects on insulin-independent and insulin-dependent glucose uptake by single fibers of different fiber types. We hypothesized that each fiber type featuring elevated insulin-independent glucose uptake immediately postexercise (IPEX) would be characterized by increased insulin-dependent glucose uptake at 3.5 h postexercise (3.5hPEX). Rat epitrochlearis muscles were isolated and incubated with 2-[ 3 H]deoxyglucose. Muscles from IPEX and sedentary (SED) controls were incubated without insulin. Muscles from 3.5hPEX and SED controls were incubated ± insulin. Glucose uptake (2-[ 3 H]deoxyglucose accumulation) and fiber type (myosin heavy chain isoform expression) were determined for single fibers dissected from the muscles. Major new findings included the following: 1) insulin-independent glucose uptake was increased IPEX in single fibers of each fiber type (types I, IIA, IIB, IIBX, and IIX), 2) glucose uptake values from insulin-stimulated type I and IIA fibers exceeded the values for the other fiber types, 3) insulin-stimulated glucose uptake for type IIX exceeded IIB fibers, and 4) the 3.5hPEX group vs. SED had greater insulin-stimulated glucose uptake in type I, IIA, IIB, and IIBX but not type IIX fibers. Insulin-dependent glucose uptake was increased at 3.5hPEX in each fiber type except for IIX fibers, although insulin-independent glucose uptake was increased IPEX in all fiber types (including type IIX). Single fiber analysis enabled the discovery of this fiber type-related difference for postexercise, insulin-stimulated glucose uptake. Copyright © 2016 the American Physiological Society.

76 FR 4271 - Approval and Promulgation of State Implementation Plans; State of Colorado Regulation Number 3...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-25

... action on the revision to APEN exemption II.D.1.uuu., because we proposed approval of the revision in the....uuu; II.D.1.eeee. No Action--Un-Revised Provisions.. II.B; II.B.1.a; II.B.3.b; II.B.4; II.B.5; II.B.6...

Interaction of chronic reatine depletion and muscle unloading effects on postural and locomotor muscles

NASA Technical Reports Server (NTRS)

Adams, Gregory R.; Haddad, Fadia; Baldwin, Kenneth M.

1994-01-01

In this study, creatine depletion was induced separately and in combination with non-weight-bearing activity to determine if the response to lowering this metabolite would counter the MHC transitions expected from non-weight-bearing. Creatine depletion was induced by feeding rats a diet supplemented with the creatine analogue beta-guanidinopropionic acid (beta-GPA). Animals were fed a diet containing the creatine analogue for 68 days. Hindlimb non-weight-bearing in BS and NS animals was accomplished by tail suspension for the final 30 days of this period. Beta-GPA feeding lowered the creatine content of muscles sampled by 65%. Creatine depletion resulted in a 16% increase in citrate synthase activity in the soleus (SOL) and a 24% increase in the plantaris (PLN). In two postural muscles, the SOL and vastus intermedius (VI), tail suspension resulted in large decreases in the type I MHC expression and increases in type IIx and IIb MHCs. In two locomotor muscles, the PLN and medial gastrocnemius, type I MHC declined and type IIb increased with suspension. Creatine depletion did not prevent the suspension-induced decline in type I MHC in any of these muscles. The increase in type IIb MHC was either prevented or reduced by creatine depletion before and during suspension in the SOL, VI, and PLN. Creatine depletion alone resulted in small increases in type I and IIa MHCs in the two locomotor muscles, but it had no effect on the MHC profile of the postural muscles studied. These results indicate that the mechanical signal generated by the hindlimb non-weight-bearing state dominated over the metabolic stimulus of creatine depletion with respect to the primary adaptation involving a reduction in type I MHC.

Mode of complement activation by acidic heteroglycans from the leaves of Artemisia princeps PAMP.

PubMed

Yamada, H; Nagai, T; Cyong, J C; Otsuka, Y

1991-08-01

The mode of action of the anti-complementary acidic heteroglycans, AAF-IIb-2 and IIb-3 which consisted of rhamnogalacturonan core and arabinogalactan moieties, purified from the leaves of Artemisia princeps PAMP (Japanese name = Gaiyo) were investigated. The anti-complementary activities of AAF-IIb-2 and IIb-3 were reduced partially in the absence of Ca2+ ions. A marked consumption of C4 was observed to have occurred when serum was incubated with both polysaccharides in the presence of Ca2+ ions. AAF-IIb-2 showed more potent C4 consumption than IIb-3. After the incubation of the serum with AAF-IIb-2 in the absence of Ca2+ ions, a cleavage of C3 in the serum was detected by immunoelectrophoresis. AAF-IIb-2 showed more significant consumption of the complement than IIb-3 when rabbit erythrocytes were used in the assay system in the absence of Ca2+ ions. These results indicate that AAF-IIb-2 activates the complement via both the alternative and classical pathways, whereas IIb-3 mainly activates the complement via the classical pathway. The absorption of serum with Protein A-Sepharose results in a decrease of the activity of AAF-IIb-2 and IIb-3. However, the decrease of the activity was restored by the replacement of the immunoglobulin G (IgG) fraction after its recovery from the Protein A-Sepharose. These results suggest that IgG dependent mechanisms are both involved in the anti-complementary activity of AAF-IIb-2 and IIb-3.

Polyclonal antibody against a complement-activating pectin from the roots of Angelica acutiloba.

PubMed

Wang, N L; Kiyohara, H; Matsumoto, T; Otsuka, H; Hirano, M; Yamada, H

1994-10-01

Anti-sera against a complement-activating pectin (AR-2IIb), which was purified from the roots of Angelica acutiloba Kitagawa, were obtained by immunization of rabbits, and a polyclonal anti-AR-2IIb antibody of the IgG class was purified by affinity chromatography on AR-2IIb-immobilized Sepharose and Protein G-Sepharose. Periodate oxidation of AR-2IIb significantly reduced its inhibitory activity on the reactivity of AR-2IIb to anti-AR-2IIb-IgG, but pronase digestion of AR-2IIb did not affect its inhibitory activity. Other pharmacologically active pectins from A. autiloba, Bupleurum falcatum, and Glycyrrhiza uralensis and the complement-activating pectic arabinogalactan from A. autiloba also showed significant inhibitory activities on the reactivity of AR-2IIb to anti-AR-2IIb-IgG, but these inhibitory activities were lower than that of AR-2IIb. Other pectins, polygalacturonic acid, arabinogalactan, galactan, and araban tested had negligible inhibitory activity. Endo-a-(1-->4)-polygalacturonase digestion of AR-2IIb indicated that its "ramified" region (rhamnogalacturonan core possessing neutral oligosaccharide side-chains) contained epitopes for anti-AR-2IIb-IgG, but that 2-keto-3-deoxyoctulosonic acid (KDO)-containing regions and oligogalacturonides obtained from AR-2IIb were not recognized by anti-AR-2IIb-IgG. Although carboxyl-reduction of galacturonic acid in the "ramified" region decreased the inhibitory activity of the "ramified" on its reactivity to anti-AR-2IIb, an acidic tetrasaccharide unit in the rhamnogalacturonan core had negligible inhibitory activity.

Type IIB Colliding Plane Waves

NASA Astrophysics Data System (ADS)

Gutperle, M.; Pioline, B.

2003-09-01

Four-dimensional colliding plane wave (CPW) solutions have played an important role in understanding the classical non-linearities of Einstein's equations. In this note, we investigate CPW solutions in 2n+2-dimensional Einstein gravity with a n+1-form flux. By using an isomorphism with the four-dimensional problem, we construct exact solutions analogous to the Szekeres vacuum solution in four dimensions. The higher-dimensional versions of the Khan-Penrose and Bell-Szekeres CPW solutions are studied perturbatively in the vicinity of the light-cone. We find that under small perturbations, a curvature singularity is generically produced, leading to both space-like and time-like singularities. For n = 4, our results pertain to the collision of two ten-dimensional type-IIB Blau-Figueroa o'Farrill-Hull-Papadopoulos plane waves.

On asymptotic freedom and confinement from type-IIB supergravity

NASA Astrophysics Data System (ADS)

Kehagias, A.; Sfetsos, K.

1999-06-01

We present a new type-IIB supergravity vacuum that describes the strong coupling regime of a non-supersymmetric gauge theory. The latter has a running coupling such that the theory becomes asymptotically free in the ultraviolet. It also has a running theta angle due to a non-vanishing axion field in the supergravity solution. We also present a worm-hole solution, which has finite action per unit four-dimensional volume and two asymptotic regions, a flat space and an AdS5xS5. The corresponding N=2 gauge theory, instead of being finite, has a running coupling. We compute the quark-antiquark potential in this case and find that it exhibits, under certain assumptions, an area-law behaviour for large separations.

Immunohistochemical analysis of MCT1 and CD147 in equine skeletal muscle fibres.

PubMed

Mykkänen, A K; Hyyppä, S; Pösö, A R; Ronéus, N; Essén-Gustavsson, B

2010-12-01

Monocarboxylate transporter 1 (MCT1) and its ancillary protein CD147 facilitate efflux of lactate from the muscle. Expression of MCT1 and CD147 were studied with immunohistochemistry in type I, IIA, IIAB and IIB fibres of equine gluteal muscle. Staining intensity of MCT1 in the cytoplasm as well as in the membranes of fibre types decreased in the order I=IIA>IIAB>IIB and correlated with the oxidative capacity. Capillaries were pronounced in the MCT1 staining. CD147 antibody stained plasma membranes of all fibre types evenly, whereas the staining in the cytoplasm followed that of MCT1. In the middle gluteal muscle the expression of MCT1 follows the oxidative capacity of muscle fibres, but the expression of CD147 in sarcolemma does not vary among fibre types. The use of horse specific MCT1 and CD147 antibodies can in future studies help to evaluate lactate efflux from different muscle fibre types. Copyright © 2010 Elsevier Ltd. All rights reserved.

Skeletal muscle myostatin mRNA expression is fiber-type specific and increases during hindlimb unloading

NASA Technical Reports Server (NTRS)

Carlson, C. J.; Booth, F. W.; Gordon, S. E.

1999-01-01

Transgenic mice lacking a functional myostatin (MSTN) gene demonstrate greater skeletal muscle mass resulting from muscle fiber hypertrophy and hyperplasia (McPherron, A. C., A. M. Lawler, and S. -J. Lee. Nature 387: 83-90, 1997). Therefore, we hypothesized that, in normal mice, MSTN may act as a negative regulator of muscle mass. Specifically, we hypothesized that the predominately slow (type I) soleus muscle, which demonstrates greater atrophy than the fast (type II) gastrocnemius-plantaris complex (Gast/PLT), would show more elevation in MSTN mRNA abundance during hindlimb unloading (HU). Surprisingly, MSTN mRNA was not detectable in weight-bearing or HU soleus muscle, which atrophied 42% by the 7th day of HU in female ICR mice. In contrast, MSTN mRNA was present in weight-bearing Gast/PLT muscle and was significantly elevated (67%) at 1 day but not at 3 or 7 days of HU. However, the Gast/PLT muscle had only atrophied 17% by the 7th day of HU. Because the soleus is composed only of type I and IIa fibers, whereas the Gast/PLT expresses type IId/x and IIb in addition to type I and IIa, it was necessary to perform a more careful analysis of the relationship between MSTN mRNA levels and myosin heavy-chain (MHC) isoform expression (as a marker of fiber type). A significant correlation (r = 0.725, P < 0. 0005) was noted between the percentage of MHC isoform IIb expression and MSTN mRNA abundance in several muscles of the mouse hindlimb. These results indicate that MSTN expression is not strongly associated with muscle atrophy induced by HU; however, it is strongly associated with MHC isoform IIb expression in normal muscle.

Generalizations of holographic renormalization group flows

NASA Astrophysics Data System (ADS)

Suh, Minwoo

The AdS/CFT correspondence conjectures the duality between type IIB supergravity on AdS5 × S5 and N = 4 super Yang-Mills theory. Mass deformations of N = 4 super Yang-Mills theory drive renormalization group (RG) flows. Holographic RG flows are described by domain wall solutions interpolating between AdS5 geometries at critical points of N = 8 gauged supergravity in five dimensions. In this thesis we study two directions of generalizations of holographic RG flows. First, motivated by the Janus solutions, we study holographic RG flows with dilaton and axion fields. To be specific, we consider the SU (3)-invariant flow with dilaton and axion fields, and discover the known supersymmetric Janus solution in five dimensions. Then, by employing the lift ansatz, we uplift the supersymmetric Janus solution of the SU(3)-invariant truncation with dilaton and axion fields to a solution of type IIB supergravity. We identify the uplifted solution to be one of the known supersymmetric Janus solution in type IIB supergravity. Furthermore, we consider the SU(2) × U(1)-invariant N = 2 and N = 1 supersymmetric flows with dilaton and axion fields. Second, motivated by the development in AdS/CMT, we study holographic RG flows with gauge fields. We consider the SU(3)-invariant flow with electric potentials or magnetic fields, and find first-order systems of flow equations for each case.

Effects of 1alpha-hydroxycholecalciferol on growth performance, parameters of tibia and plasma, meat quality, and type IIb sodium phosphate cotransporter gene expression of one- to twenty-one-day-old broilers.

PubMed

Han, J C; Yang, X D; Zhang, T; Li, H; Li, W L; Zhang, Z Y; Yao, J H

2009-02-01

This experiment was conducted to investigate the effects of 1alpha-hydroxycholecalciferol (1alpha-OH D3) on the growth performance, tibia and plasma parameters, nutrient utilization, meat quality of the breast and thigh, and type IIb sodium phosphate cotranspoter gene expression of broilers. A total of 96 males of 1-d-old Arbor Acres broilers were randomly assigned to 8 cages of 12 birds each. Two dietary treatments were applied to 4 cages each. Diet 1 was prepared as the basal diet (nonphytate phosphorus, 0.21%), whereas diet 2 was the basal diet supplemented with 5 microg/kg of 1alpha-OH D3. Results showed that supplementation of the basal diet with 1alpha-OH D3 increased growth performance, tibia ash and strength, plasma inorganic phosphate concentration, utilization of total phosphorus and nonphytate phosphorus, lightness and yellowness of the breast and thigh meat, and intestinal type IIb sodium phosphate cotranspoter mRNA expression, whereas it decreased the shear force and water-holding capacity of the thigh meat. These data suggest that the addition of 1alpha-OH D3 might improve growth performance, tibia development, and meat quality in 1- to 21-d-old broilers by increasing the absorption and retention of phosphorus.

Multi-Wavelength Observations of the Type IIb Supernova 2009mg

NASA Technical Reports Server (NTRS)

Oates, S. R.; Bayless, A. J.; Stritzinger, M. D.; Prichard, T.; Prieto, J. L.; Immler, S.; Brown, P. J.; Breeveld, A. A.; DePasquale, M.; Kuin, N. P. M.;

The B2 Alternatively Spliced Isoform of Nonmuscle Myosin II-B Lacks Actin-activated MgATPase Activity and In Vitro Motility

PubMed Central

Kim, Kye-Young; Kawamoto, Sachiyo; Bao, Jianjun; Sellers, James R.; Adelstein, Robert S.

2008-01-01

We report the initial biochemical characterization of an alternatively spliced isoform of nonmuscle heavy meromyosin (HMM) II-B2 and compare it with HMM II-B0, the non-spliced isoform. HMM II-B2 is the HMM derivative of an alternatively spliced isoform of endogenous nonmuscle myosin (NM) II-B, which has 21-amino acids inserted into loop 2, near the actin-binding region. NM II-B2 is expressed in the Purkinje cells of the cerebellum as well as in other neuronal cells (Ma et al., Mol. Biol. Cell 15 (2006) 2138-2149). In contrast to any of the previously described isoforms of NM II (II-A, II-B0, II-B1, II-C0 and II-C1) or to smooth muscle myosin, the actin-activated MgATPase activity of HMM II-B2 is not significantly increased from a low, basal level by phosphorylation of the 20 kDa myosin light chain (MLC-20). Moreover, although HMM II-B2 can bind to actin in the absence of ATP and is released in its presence, it cannot propel actin in the sliding actin filament assay following MLC-20 phosphorylation. Unlike HMM II-B2, the actin-activated MgATPase activity of a chimeric HMM with the 21-amino acids II-B2 sequence inserted into the homologous location in the heavy chain of HMM II-C is increased following MLC-20 phosphorylation. This indicates that the effect of the II-B2 insert is myosin heavy chain specific. PMID:18060863

Peptides derived from central turn motifs within integrin αIIb and αV cytoplasmic tails inhibit integrin activation.

PubMed

Li, Xinlei; Liu, Yongqing; Haas, Thomas A

2014-12-01

We previously found that peptides derived from the full length of integrin αIIb and αV cytoplasmic tails inhibited their parent integrin activation, respectively. Here we showed that the cell-permeable peptides corresponding to the conserved central turn motif within αIIb and αV cytoplasmic tails, myr-KRNRPPLEED (αIIb peptide) and myr-KRVRPPQEEQ (αV peptide), similarly inhibited both αIIb and αV integrin activation. Pre-treatment with αIIb or αV peptides inhibited Mn(2+)-activated αIIbβ3 binding to soluble fibrinogen as well as the binding of αIIbβ3-expressing Chinese Hamster Ovary cells to immobilized fibrinogen. Our turn peptides also inhibited adhesion of two breast cancer cell lines (MDA-MB-435 and MCF7) to αV ligand vitronectin. These results suggest that αIIb and αV peptides share a same mechanism in regulating integrin function. Using αIIb peptide as a model, we found that replacement of RPP with AAA significantly attenuated the inhibitory activity of αIIb peptide. Furthermore, we found that αIIb peptide specifically bound to β-tubulin in cells. Our work suggests that the central motif of α tails is an anchoring point for cytoskeletons during integrin activation and integrin-mediated cell adhesion, and its function depends on the turn structure at RPP. However, post-treatment of peptides derived from the full-length tail or from the turn motif did not reverse αIIb and αV integrin activation. Copyright © 2014 Elsevier Inc. All rights reserved.

Muscle glycogen depletion patterns during draught work in Standardbred horses.

PubMed

Gottlieb, M

1989-03-01

Muscle fibre recruitment was investigated during draught loaded exercise by studying glycogen depletion patterns from histochemical stains of muscle biopsies from the gluteus and semitendinosus muscles. Three Standardbred trotters performed several intervals of draught loaded exercise on a treadmill with 34 kp at a trot (7 m/sec) and with 34 and 80 kp, respectively at a walk (2m/sec). Exercise was continued until the horses were unwilling to continue. Glycogen depletion was seen in all three fibre types when trotting with 34 kp for 5 or 10 mins. When an equal weight resistance was pulled at a walk, glycogen depletion was first seen in type I fibres only, then followed by a small percentage of type IIA fibres after at least 1 h. When 80 kp was pulled at a walk both type I and IIA fibres showed glycogen depletion, and after at least 30 mins exercise a small percentage of type IIB fibres was also depleted. These results indicate that the muscle fibres are depleted, in order, from type I through IIA to IIB as the intensity or duration of draught work increases.

U-folds as K3 fibrations

NASA Astrophysics Data System (ADS)

Braun, Andreas P.; Fucito, Francesco; Morales, Jose Francisco

2013-10-01

We study four-dimensional flux vacua describing intrinsic non- perturbative systems of 3 and 7 branes in type IIB string theory. The solutions are described as compactifications of a G(ravity) theory on a Calabi Yau threefold which consists of a fibration of an auxiliary K3 surface over an S 2 base. In the spirit of F-theory, the complex structure of the K3 surface varying over the base codifies the details of the fluxes, the dilaton and the warp factors in type IIB string theory. We discuss in detail some simple examples of geometric and non-geometric solutions where the precise flux/geometry dictionary can be explicitly worked out. In particular, we describe non-geometric T-fold solutions exhibiting non-trivial T-duality monodromies exchanging 3- and 7-branes.

SESNPCA: Principal Component Analysis Applied to Stripped-Envelope Core-Collapse Supernovae

NASA Astrophysics Data System (ADS)

Williamson, Marc; Bianco, Federica; Modjaz, Maryam

2018-01-01

In the new era of time-domain astronomy, it will become increasingly important to have rigorous, data driven models for classifying transients, including supernovae (SNe). We present the first application of principal component analysis (PCA) to stripped-envelope core-collapse supernovae (SESNe). Previous studies of SNe types Ib, IIb, Ic, and broad-line Ic (Ic-BL) focus only on specific spectral features, while our PCA algorithm uses all of the information contained in each spectrum. We use one of the largest compiled datasets of SESNe, containing over 150 SNe, each with spectra taken at multiple phases. Our work focuses on 49 SNe with spectra taken 15 ± 5 days after maximum V-band light where better distinctions can be made between SNe type Ib and Ic spectra. We find that spectra of SNe type IIb and Ic-BL are separable from the other types in PCA space, indicating that PCA is a promising option for developing a purely data driven model for SESNe classification.

A quantitative study of the histochemical and morphometric characteristics of the human cricopharyngeus muscle.

PubMed Central

Brownlow, H; Whitmore, I; Willan, P L

1989-01-01

Samples of human cricopharyngeus muscles obtained at postmortem were assessed for fibre type composition and fibre size. Fibre type was determined using serial cryostat sections exposed to several histochemical reactions; narrow fibre diameter and fibre area were measured from photomicrographs using a digitiser interfaced to a microcomputer. Results were compared with values from samples of vastus lateralis obtained from the same subjects. Cricopharyngeus muscle, in comparison with vastus lateralis, contained significantly more oxidative fibres but fewer glycolytic fibres and significantly more Type I fibres but fewer Type IIB. Cricopharyngeal fibres were significantly smaller than the fibres in vastus lateralis and in neither muscle were fibre sizes normally distributed. In each muscle most Type I fibres were oxidative, and the ratio of oxidative: glycolytic fibres was similar for Type IIA and IIB fibres. The fibre type proportions and fibre sizes in cricopharyngeus did not vary significantly with age or between males and females. The composition of cricopharyngeus--mostly Type I oxidative fibres and few Type II glycolytic fibres--correlated well with the functions of sustained tonicity to prevent aerophagia and occasional forceful contraction during deglutition. Images Fig. 1 PMID:2621147

Effects of a traditional Chinese medicine formula and its extraction on muscle fiber characteristics in finishing pigs, porcine cell proliferation and isoforms of myosin heavy chain gene expression in myocytes

PubMed Central

Yu, Qin Ping; Feng, Ding Yuan; He, Xiao Jun; Wu, Fan; Xia, Min Hao; Dong, Tao; Liu, Yi Hua; Tan, Hui Ze; Zou, Shi Geng; Zheng, Tao; Ou, Xian Hua; Zuo, Jian Jun

2017-01-01

Objective This study evaluated the effects of a traditional Chinese medicine formula (TCMF) on muscle fiber characteristics in finishing pigs and the effects of the formula’s extract (distilled water, ethyl acetate and petroleum ether extraction) on porcine cell proliferation and isoforms of myosin heavy chain (MyHC) gene expression in myocytes. Methods In a completely randomized design, ninety pigs were assigned to three diets with five replications per treatment and six pigs per pen. The diets included the basal diet (control group), TCMF1 (basal diet+2.5 g/kg TCMF) and TCMF2 (basal diet+5 g/kg TCMF). The psoas major muscle was obtained from pigs at the end of the experiment. Muscle fiber characteristics in the psoas major muscle were analyzed using myosin ATPase staining. Cell proliferation was measured using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) dye and cytometry. Isoforms of MyHC gene expression were detected by real-time quantitative polymerase chain reaction. Results The final body weight and carcass weight of finishing pigs were increased by TCMF1 (p<0.05), while the psoas major muscle cross-sectional area was increased by TCMF (p<0.05). The cross-sectional area and diameter of psoas major muscle fiber I, IIA, and IIB were increased by TCMF2 (p<0.05). The cross-sectional area and fiber diameter of psoas major muscle fiber IIA and IIB were increased by diet supplementation with TCMF1 (p<0.05). Psoas major muscle fiber IIA and IIB fiber density from the pigs fed the TCMF1 diet and the type IIB fiber density from the pigs fed the TCMF2 diet were lower compared to pigs fed the control diet (p<0.05). Pigs fed TCMF2 had a higher composition of type I fiber and a lower percentage of type IIB fiber in the psoas major muscle (p<0.05). The expression levels of MyHC I, MyHC IIa, and MyHC IIx mRNA increased and the amount of MyHC IIb mRNA decreased in the psoas major muscle from TCMF2, whereas MyHC I and MyHC IIx mRNA increased in the psoas major muscle from TCMF1 (p<0.05). Peroxisome proliferator-activated receptor γ coactivator-1α and CaN mRNA expression in the psoas major muscle were up-regulated by TCMF (p<0.05). Porcine skeletal muscle satellite cell proliferation was promoted by 4 μg/mL and 20 μg/mL TCMF water extraction (p<0.05). Both 1 μg/mL and 5 μg/mL of TCMF water extraction increased MyHC IIa, MyHC IIb, and MyHC IIx mRNA expression in porcine myocytes (p<0.05), while MyHC I mRNA expression in porcine myocytes was decreased by 5 μg/mL TCMF water extraction (p<0.05). Porcine myocyte MyHC I and MyHC IIx mRNA expression were increased, and MyHC IIa and MyHC IIb mRNA expression were down-regulated by 5 μg/mL TCMF ethyl acetate extraction (p<0.05). MyHC I and MyHC IIa mRNA expression in porcine myocytes were increased, and the MyHC IIb mRNA expression was decreased by 1 μg/mL TCMF ethyl acetate extraction (p<0.05). Four isoforms of MyHC mRNA expression in porcine myocytes were reduced by 5 μg/mL TCMF petroleum ether extraction (p<0.05). MyHC IIa mRNA expression in porcine myocytes increased and MyHC IIb mRNA expression decreased by 1 μg/mL in a TCMF petroleum ether extraction (p<0.05). Conclusion These results indicated that TCMF amplified the psoas major muscle cross-sectional area through changing muscle fiber characteristics in finishing pigs. This effect was confirmed as TCMF extraction promoted porcine cell proliferation and affected isoforms of MyHC gene expression in myocytes. PMID:28728382

Structural characterization of anti-complementary polysaccharides from the leaves of Artemisia princeps.

PubMed

Yamada, H; Otsuka, Y; Omura, S

1986-08-01

Structural characterizations of the anti-complementary acidic heteroglycans, AAF IIb-2 and IIb-3, obtained from the leaves of Artemisia princeps pamp have been studied. AAF IIb-2 consists of rhamnose, xylose, arabinose, galactose, glucose and uronic acids (glucuronic acid and galacturonic acid) in the molar ratio of 7.6:7.6:13.0:10.9:3.0:57.9, and AAF IIb-3 consists of the same sugars in the ratio of 3.9:2.6:24.7:19.7:2.6:46.5. Methylation analysis including carboxyl-reduction and also selective enzymolysis using EXO-alpha- L-arabinofuranosidase suggested that AAF IIb-3 has a main chain consisting of (1-->4)-linked galacturonic acid and (1-->2)-linked rhamnose mostly substituted at the O-4 position. AAF IIb-3 also contained arabino-3,6-galactan moiety and most of the arabinose was present as an alpha- L-furanosyl residue in the non-reducing terminals and highly branched side chains which mostly attached to the O-3 position of (1-->6)-linked galactopyranosyl residue. The basic structure of AAF IIb-2 is similar to that of AAF IIb-3, but IIb-3 has a higher arabinogalactan content than IIb-2.

Modulation of Muscle Fiber Compositions in Response to Hypoxia via Pyruvate Dehydrogenase Kinase-1

PubMed Central

Nguyen, Daniel D.; Kim, Gyuyoup; Pae, Eung-Kwon

2016-01-01

Muscle fiber-type changes in hypoxic conditions in accordance with pyruvate dehydrogenase kinase (Pdk)-1 and hypoxia inducible factor (Hif)-1α were investigated in rats. Hif-1α and its down-stream molecule Pdk-1 are well known for readily response to hypoxia. We questioned their roles in relation to changes in myosin heavy chain (MyHC) composition in skeletal muscles. We hypothesize that the level of Pdk-1 with respect to the level of Hif-1α determines MyHC composition of the muscle in rats in hypoxia. Young male rats were housed in a chamber maintained at 11.5% (for sustained hypoxia) or fluctuating between 11.5 and 20.8% (for intermittent hypoxia or IH) oxygen levels. Then, muscle tissues from the geniohyoid (GH), soleus, and anterior tibialis (TA) were obtained at the end of hypoxic conditionings. After both hypoxic conditionings, protein levels of Pdk-1 and Hif-1 increased in GH muscles. GH muscles in acute sustained hypoxia favor an anaerobic glycolytic pathway, resulting in an increase in glycolytic MyHC IIb protein-rich fibers while maintain original fatigue-resistant MyHC IIa protein in the fibers; thus, the numbers of IIa- and IIb MyHC co-expressing fibers increased. Exogenous Pdk-1 over-expression using plasmid vectors elevated not only the glycolytic MyHC IIb, but also IIx as well as IIa expressions in C2C12 myotubes in ambient air significantly. The increase of dual expression of IIa- and IIb MyHC proteins in fibers harvested from the geniohyoid muscle has a potential to improve endurance as shown in our fatigability tests. By increasing the Pdk-1/Hif-1 ratio, a mixed-type muscle could alter endurance within the innate characteristics of the muscle toward more fatigue resistant. We conclude that an increased Pdk-1 level in skeletal muscle helps maintain MyHC compositions to be a fatigue resistant mixed-type muscle. PMID:28018235

Lineage Analysis of Circulating Trypanosoma cruzi Parasites and Their Association with Clinical Forms of Chagas Disease in Bolivia

PubMed Central

del Puerto, Ramona; Nishizawa, Juan Eiki; Kikuchi, Mihoko; Iihoshi, Naomi; Roca, Yelin; Avilas, Cinthia; Gianella, Alberto; Lora, Javier; Gutierrez Velarde, Freddy Udalrico; Renjel, Luis Alberto; Miura, Sachio; Higo, Hiroo; Komiya, Norihiro; Maemura, Koji; Hirayama, Kenji

2010-01-01

Background The causative agent of Chagas disease, Trypanosoma cruzi, is divided into 6 Discrete Typing Units (DTU): Tc I, IIa, IIb, IIc, IId and IIe. In order to assess the relative pathogenicities of different DTUs, blood samples from three different clinical groups of chronic Chagas disease patients (indeterminate, cardiac, megacolon) from Bolivia were analyzed for their circulating parasites lineages using minicircle kinetoplast DNA polymorphism. Methods and Findings Between 2000 and 2007, patients sent to the Centro Nacional de Enfermedades Tropicales for diagnosis of Chagas from clinics and hospitals in Santa Cruz, Bolivia, were assessed by serology, cardiology and gastro-intestinal examinations. Additionally, patients who underwent colonectomies due to Chagasic magacolon at the Hospital Universitario Japonés were also included. A total of 306 chronic Chagas patients were defined by their clinical types (81 with cardiopathy, 150 without cardiopathy, 100 with megacolon, 144 without megacolon, 164 with cardiopathy or megacolon, 73 indeterminate and 17 cases with both cardiopathy and megacolon). DNA was extracted from 10 ml of peripheral venous blood for PCR analysis. The kinetoplast minicircle DNA (kDNA) was amplified from 196 out of 306 samples (64.1%), of which 104 (53.3%) were Tc IId, 4 (2.0%) Tc I, 7 (3.6%) Tc IIb, 1 (0.5%) Tc IIe, 26 (13.3%) Tc I/IId, 1 (0.5%) Tc I/IIb/IId, 2 (1.0%) Tc IIb/d and 51 (25.9%) were unidentified. Of the 133 Tc IId samples, three different kDNA hypervariable region patterns were detected; Mn (49.6%), TPK like (48.9%) and Bug-like (1.5%). There was no significant association between Tc types and clinical manifestations of disease. Conclusions None of the identified lineages or sublineages was significantly associated with any particular clinical manifestations in the chronic Chagas patients in Bolivia. PMID:20502516

Arsenic processing of yeast isolates IIB-As1 & IIB-As2 and production of glutathione under stress conditions.

PubMed

Muneer, Bushra; Lali, Tayyaba; Iqbal, Muhammad J; Shakoori, Farah R; Shakoori, Abdul R

2016-10-01

Four arsenic resistant yeast were isolated from the industrial wastewater. Two strains IIB-As1 and IIB-As2 identified as Candida tropicalis and Saccharomyces cerevisiae, respectively. IIB-As1 and IIB-As2 showed maximum arsenic resistance. IIB-As1 showed maximum growth at 35 °C whereas it was 30 °C for IIB-As2. The yeast isolate showed typical growth curves, but arsenic extended the lag phase. Glutathione plays an important role in metal tolerance. In the present study, As increased the level glutathione and non-protein thiols in yeast isolates. Removal of As from supernatant was analyzed using the atomic absorption spectrophotometer. They removed arsenic from the medium after 72 h of incubation. Both yeast strains efficiently removed arsenic from the industrial effluent when used individually or in consortia. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Microvascular oxygen pressures in muscles comprised of different fiber types: Impact of dietary nitrate supplementation

PubMed Central

Ferguson, Scott K.; Holdsworth, Clark T.; Wright, Jennifer L.; Fees, Alex J.; Allen, Jason D.; Jones, Andrew M.; Musch, Timothy I.; Poole, David C.

2014-01-01

Nitrate (NO3−) supplementation via beetroot juice (BR) preferentially improves vascular conductance and O2 delivery to contracting skeletal muscles comprised predominantly of type IIb + d/x (i.e. highly glycolytic) fibers following its reduction to nitrite and nitric oxide (NO). To address the mechanistic basis for NO3− to improve metabolic control we tested the hypothesis that increased NO bioavailability via BR supplementation would elevate microvascular PO2 (PO2mv) in fast twitch but not slow twitch muscle. Twelve young adult male Sprague-Dawley rats were administered BR ([NO3−] 1 mmol/kg/day, n=6) or water (control, n=6) for 5 days. PO2mv (phosphorescence quenching) was measured at rest and during 180s of electrically induced 1-Hz twitch contractions (6–8 V) of the soleus (9% type IIb +d/x) and mixed portion of the gastrocnemius (MG, 91% type IIb + d/x) muscles. In the MG, but not the soleus, BR elevated contracting steady state PO2mv by ~43% (control: 13.7 ± 0.5, BR: 19 ± 1.6 mmHg, (P<0.05). This higher PO2mv represents a greater blood-myocyte O2 driving force during muscle contractions thus providing a potential mechanism by which NO3− supplementation via BR improves metabolic control in fast twitch muscle. Recruitment of higher order type II muscle fibers is thought to play a role in the development of the V.O2 slow component which is inextricably linked to the fatigue process. These data therefore provide a putative mechanism for the BR-induced improvements in high-intensity exercise performance seen in humans. PMID:25280991

Microvascular oxygen pressures in muscles comprised of different fiber types: Impact of dietary nitrate supplementation.

PubMed

Ferguson, Scott K; Holdsworth, Clark T; Wright, Jennifer L; Fees, Alex J; Allen, Jason D; Jones, Andrew M; Musch, Timothy I; Poole, David C

2015-08-01

Nitrate (NO3(-)) supplementation via beetroot juice (BR) preferentially improves vascular conductance and O2 delivery to contracting skeletal muscles comprised predominantly of type IIb + d/x (i.e. highly glycolytic) fibers following its reduction to nitrite and nitric oxide (NO). To address the mechanistic basis for NO3(-) to improve metabolic control we tested the hypothesis that BR supplementation would elevate microvascular PO2 (PO2mv) in fast twitch but not slow twitch muscle. Twelve young adult male Sprague-Dawley rats were administered BR ([NO3(-)] 1 mmol/kg/day, n = 6) or water (control, n = 6) for 5 days. PO2mv (phosphorescence quenching) was measured at rest and during 180 s of electrically-induced 1-Hz twitch contractions (6-8 V) of the soleus (9% type IIb +d/x) and mixed portion of the gastrocnemius (MG, 91% type IIb + d/x) muscles. In the MG, but not the soleus, BR elevated contracting steady state PO2mv by ~43% (control: 14 ± 1, BR: 19 ± 2 mmHg (P < 0.05)). This higher PO2mv represents a greater blood-myocyte O2 driving force during muscle contractions thus providing a potential mechanism by which NO3(-) supplementation via BR improves metabolic control in fast twitch muscle. Recruitment of higher order type II muscle fibers is thought to play a role in the development of the VO2 slow component which is inextricably linked to the fatigue process. These data therefore provide a putative mechanism for the BR-induced improvements in high-intensity exercise performance seen in humans. Copyright © 2014 Elsevier Inc. All rights reserved.

Protein expression changes during human triple negative breast cancer cell line progression to lymph node metastasis in a xenografted model in nude mice

PubMed Central

Roberti, María Paula; Arriaga, Juan Martín; Bianchini, Michele; Quintá, Héctor Ramiro; Bravo, Alicia Inés; Levy, Estrella Mariel; Mordoh, José; Barrio, María Marcela

2012-01-01

Triple negative breast cancers (TNBC) lacking hormone receptors and HER-2 amplification are very aggressive tumors. Since relevant differences between primary tumors and metastases could arise during tumor progression as evidenced by phenotypic discordances reported for hormonal receptors or HER-2 expression, in this analysis we studied changes that occurred in our TNBC model IIB-BR-G throughout the development of IIB-BR-G-MTS6 metastasis to the lymph nodes (LN) in nude mice, using an antibody-based protein array to characterize their expression profile. We also analyzed their growth kinetics, migration, invasiveness and cytoskeleton structure in vitro and in vivo. In vitro IIB-BR-G-MTS6 cells grew slower but showed higher anchorage independent growth. In vivo IIB-BR-G-MTS6 tumors grew significantly faster and showed a 100% incidence of LN metastasis after s.c. inoculation, although no metastasis was observed for IIB-BR-G. CCL3, IL1β, CXCL1, CSF2, CSF3, IGFBP1, IL1α, IL6, IL8, CCL20, PLAUR, PlGF and VEGF were strongly upregulated in IIB-BR-G-MTS6 while CCL4, ICAM3, CXCL12, TNFRSF18, FIGF were the most downregulated proteins in the metastatic cell line. IIB-BR-G-MTS6 protein expression profile could reflect a higher NFκB activation in these cells. In vitro, IIB-BR-G displayed higher migration but IIB-BR-G-MTS6 had more elevated matrigel invasion ability. In agreement with that observation, IIB-BR-G-MTS6 had an upregulated expression of MMP1, MMP9, MMP13, PLAUR and HGF. IIB-BR-G-MTS6 tumors presented also higher local lymphatic invasion than IIB-BR-G but similar lymphatic vessel densities. VEGFC and VEGFA/B expression were higher both in vitro and in vivo for IIB-BR-G-MTS6. IIB-BR-G-MTS6 expressed more vimentin than IB-BR-G cells, which was mainly localized in the cellular extremities and both cell lines are E-cadherin negative. Our results suggest that IIB-BR-G-MTS6 cells have acquired a pronounced epithelial-to-mesenchymal transition phenotype. Protein expression changes observed between primary tumor-derived IIB-BR-G and metastatic IIB-BR-G-MTS6 TNBC cells suggest potential targets involved in the control of metastasis. PMID:22825326

Effect of chronic ethanol ingestion and exercise training on skeletal muscle in rat.

PubMed

Vila, L; Ferrando, A; Voces, J; Cabral de Oliveira, C; Prieto, J G; Alvarez, A I

2001-09-01

The aim of this study was to investigate the interactive effects of exercise training and chronic ethanol consumption on metabolism, capillarity, and myofibrillar composition in rat limb muscles. Male Wistar rats were treated in separate groups as follows: non exercised-control; ethanol (15%) in animals' drinking water for 12 weeks; exercise training in treadmill and ethanol administration plus exercise for 12 weeks. Ethanol administration decreased capillarity and increased piruvate kinase and lactate dehydrogenase activities in white gastrocnemius; in plantaris muscle, ethanol increased citrate synthase activity and decreased cross-sectional area of type I, IIa, and IIb fibres. Exercise increased capillarity in all four limb muscles and decreased type I fibre area in plantaris. The decreased capillarity effect induced by ethanol in some muscles, was ameliorated when alcohol was combined with exercise. While alcoholic myopathy affects predominantly type IIb fibres, ethanol administration and aerobic exercise in some cases can affect type I and type IIa fibre areas. The exercise can decrease some harmful effects produced by ethanol in the muscle, including the decrease in the fibre area and capillary density.

Equine endometrial fibrosis correlates with 11beta-HSD2, TGF-beta1 and ACE activities.

PubMed

Ganjam, V K; Evans, T J

2006-03-27

Endometrial periglandular fibrosis (EPF) contributes to embryonic and fetal loss in mares. Equine EPF correlates inversely with conception and successful gestation. In the modified Kenney endometrial biopsy classification system, EPF categories I, IIA, IIB, and III correspond to minimal, mild, moderate, and severe fibrosis (+/-inflammation), respectively. Paraffin sections of biopsy specimens were stained with H&E, and picrosirius red (specific for fibrillar collagens types I and III), to determine %EPCVF. Endometrial ACE-binding activity, TGF-beta1 and 11beta-HSD2 activities were also measured. Ultrastructural changes in EPF categories IIB and III endometria strongly suggested myofibroblastic transformation. ACE-binding activity was highest in EPF category IIB; however, endometrial TGF-beta1 and 11beta-HSD2 activities were significantly correlated to the severity of EPF (P<0.05). We conclude that, locally generated angiotensin II initiates the expression of TGF-beta1 resulting in myofibroblastic transformation. 11Beta-HSD2 in concert appears to modulate the severity of endometrial fibrosis.

Kinetic mechanism of non-muscle myosin IIB: functional adaptations for tension generation and maintenance.

PubMed

Wang, Fei; Kovacs, Mihaly; Hu, Aihua; Limouze, John; Harvey, Estelle V; Sellers, James R

2003-07-25

Besides driving contraction of various types of muscle tissue, conventional (class II) myosins serve essential cellular functions and are ubiquitously expressed in eukaryotic cells. Three different isoforms in the human myosin complement have been identified as non-muscle class II myosins. Here we report the kinetic characterization of a human non-muscle myosin IIB subfragment-1 construct produced in the baculovirus expression system. Transient kinetic data show that most steps of the actomyosin ATPase cycle are slowed down compared with other class II myosins. The ADP affinity of subfragment-1 is unusually high even in the presence of actin filaments, and the rate of ADP release is close to the steady-state ATPase rate. Thus, non-muscle myosin IIB subfragment-1 spends a significantly higher proportion of its kinetic cycle strongly attached to actin than do the muscle myosins. This feature is even more pronounced at slightly elevated ADP levels, and it may be important in carrying out the cellular functions of this isoform working in small filamentous assemblies.

DIS off glueballs from string theory: the role of the chiral anomaly and the Chern-Simons term

NASA Astrophysics Data System (ADS)

Kovensky, Nicolas; Michalski, Gustavo; Schvellinger, Martin

2018-04-01

We calculate the structure function F 3( x, q 2) of the hadronic tensor of deep inelastic scattering (DIS) of charged leptons from glueballs of N=4 SYM theory at strong coupling and at small values of the Bjorken parameter in the gauge/string theory duality framework. This is done in terms of type IIB superstring theory scattering amplitudes. From the AdS5 perspective, the relevant part of the scattering amplitude comes from the five-dimensional non-Abelian Chern-Simons terms in the SU(4) gauged supergravity obtained from dimensional reduction on S 5. From type IIB superstring theory we derive an effective Lagrangian describing the four-point interaction in the local approximation. The exponentially small regime of the Bjorken parameter is investigated using Pomeron techniques.

The large N limit of superconformal field theories and supergravity

NASA Astrophysics Data System (ADS)

Maldacena, Juan

1999-07-01

We show that the large N limit of certain conformal field theories in various dimensions include in their Hilbert space a sector describing supergravity on the product of Anti-deSitter spacetimes, spheres and other compact manifolds. This is shown by taking some branes in the full M/string theory and then taking a low energy limit where the field theory on the brane decouples from the bulk. We observe that, in this limit, we can still trust the near horizon geometry for large N. The enhanced supersymmetries of the near horizon geometry correspond to the extra supersymmetry generators present in the superconformal group (as opposed to just the super-Poincare group). The 't Hooft limit of 3+1N=4 super-Yang-Mills at the conformal point is shown to contain strings: they are IIB strings. We conjecture that compactifications of M/string theory on various Anti-deSitter spacetimes is dual to various conformal field theories. This leads to a new proposal for a definition of M-theory which could be extended to include five non-compact dimensions.

Single-fiber myosin heavy chain polymorphism during postnatal development: modulation by hypothyroidism

NASA Technical Reports Server (NTRS)

di Maso, N. A.; Caiozzo, V. J.; Baldwin, K. M.

2000-01-01

The primary objective of this study was to follow the developmental time course of myosin heavy chain (MHC) isoform transitions in single fibers of the rodent plantaris muscle. Hypothyroidism was used in conjunction with single-fiber analyses to better describe a possible linkage between the neonatal and fast type IIB MHC isoforms during development. In contrast to the general concept that developmental MHC isoform transitions give rise to muscle fibers that express only a single MHC isoform, the single-fiber analyses revealed a very high degree of MHC polymorphism throughout postnatal development. In the adult state, MHC polymorphism was so pervasive that the rodent plantaris muscles contained approximately 12-15 different pools of fibers (i.e., fiber types). The degree of polymorphism observed at the single-fiber level made it difficult to determine specific developmental schemes analogous to those observed previously for the rodent soleus muscle. However, hypothyroidism was useful in that it confirmed a possible link between the developmental regulation of the neonatal and fast type IIB MHC isoforms.

NAVAIR Progress in Assessing, Validating and Implementing Non-Chromate Primers (Briefing charts)

DTIC Science & Technology

2011-02-09

logistics for any new coating or coating system NAVAIR Application Areas for Hexavalent Chromium Alternatives: Status Components/ Structure... Hexavalent chromium alternatives Sacrificial Coating Post Treatment MIL-A-8625 Anodize Avionics/ Electronics Magnesium/Titanium Conversion Aluminum Anodizing...Aluminum Pretreatment Type IC Seal Type IIB Seal Type II Seal Phosphating Rinse (Aluminum)Rinse (Steel) Cadmium Zinc-Nickel Aluminum Bonding Chrome

Role of G protein signaling in the formation of the fibrin(ogen)-integrin αIIbβ3-actin cytoskeleton complex in platelets.

PubMed

Budnik, Ivan; Shenkman, Boris; Savion, Naphtali

2016-09-01

Effective platelet function requires formation of a physical link between fibrin(ogen), integrin αIIbβ3, and cytoplasmic actin filaments. We investigated the role of the Gαq, Gαi, and Gα12/13 families of heterotrimeric GTP-binding proteins (G proteins) in the assembly of a ligand-αIIbβ3-actin cytoskeleton complex. Selective and combined activation of the G proteins was achieved by using combinations of various platelet agonists and inhibitors. Formation and stability of fibrinogen-αIIbβ3 interaction were evaluated by the extent of platelet aggregation and the rate of eptifibatide-induced platelet disaggregation; association of αIIbβ3 with the cytoskeleton was analyzed by western blot. Formation of the fibrin-αIIbβ3-actin cytoskeleton complex was evaluated by rotational thromboelastometry assay in which clot formation was induced by the mixture of reptilase and factor XIIIa. We demonstrated that involvement of heterotrimeric G proteins in the formation of the ligand-αIIbβ3-cytoskeleton complex depends on whether fibrinogen or fibrin serves as the integrin ligand. Formation of the fibrinogen-αIIbβ3-cytoskeleton complex requires combined activation of at least two G protein pathways while the maximal αIIbβ3-cytoskeleton association and the strongest αIIbβ3-fibrinogen binding supporting irreversible platelet aggregation require combined activation of all three-Gαq, Gαi, and Gα12/13-G protein families. In contrast, formation of the fibrin-αIIbβ3-cytoskeleton complex mediating clot retraction is critically dependent on the activation of the Gαi family, especially on the activation of Gαz.

The Interaction of Integrin αIIbβ3 with Fibrin Occurs through Multiple Binding Sites in the αIIb β-Propeller Domain*

PubMed Central

Podolnikova, Nataly P.; Yakovlev, Sergiy; Yakubenko, Valentin P.; Wang, Xu; Gorkun, Oleg V.; Ugarova, Tatiana P.

2014-01-01

The currently available antithrombotic agents target the interaction of platelet integrin αIIbβ3 (GPIIb-IIIa) with fibrinogen during platelet aggregation. Platelets also bind fibrin formed early during thrombus growth. It was proposed that inhibition of platelet-fibrin interactions may be a necessary and important property of αIIbβ3 antagonists; however, the mechanisms by which αIIbβ3 binds fibrin are uncertain. We have previously identified the γ370–381 sequence (P3) in the γC domain of fibrinogen as the fibrin-specific binding site for αIIbβ3 involved in platelet adhesion and platelet-mediated fibrin clot retraction. In the present study, we have demonstrated that P3 can bind to several discontinuous segments within the αIIb β-propeller domain of αIIbβ3 enriched with negatively charged and aromatic residues. By screening peptide libraries spanning the sequence of the αIIb β-propeller, several sequences were identified as candidate contact sites for P3. Synthetic peptides duplicating these segments inhibited platelet adhesion and clot retraction but not platelet aggregation, supporting the role of these regions in fibrin recognition. Mutant αIIbβ3 receptors in which residues identified as critical for P3 binding were substituted for homologous residues in the I-less integrin αMβ2 exhibited reduced cell adhesion and clot retraction. These residues are different from those that are involved in the coordination of the fibrinogen γ404–411 sequence and from auxiliary sites implicated in binding of soluble fibrinogen. These results map the binding of fibrin to multiple sites in the αIIb β-propeller and further indicate that recognition specificity of αIIbβ3 for fibrin differs from that for soluble fibrinogen. PMID:24338009

Cervical level IIb metastases in squamous cell carcinoma of the oral cavity: a systematic review and meta-analysis.

PubMed

Kou, Yurong; Zhao, Tengfei; Huang, Shaohui; Liu, Jie; Duan, Weiyi; Wang, Yunjing; Wang, Zechen; Li, Delong; Ning, Chunliu; Sun, Changfu

2017-01-01

The aim of this study was to clarify whether level IIb dissection should be performed or avoided in the treatment of oral squamous cell carcinoma by meta-analysis. Articles that were published before June 2017 were searched electronically in four databases (Web of Science, PubMed, Ovid and China National Knowledge Infrastructure) without any date or language restrictions by two independent reviewers. Abstracts and full-text papers which investigated the cervical metastases to level IIb from primary head and neck cancers and were deemed potentially relevant were screened. Data were analyzed using RevMan 5.3. Four hundred and fifty-five abstracts and 129 full-text papers were screened, and 22 studies were included in the analysis. Among the 2001 patients included, 112 patients had level IIb metastases, the pooled frequency of which was 6% (95% confidence interval [CI]: 4.0-7.0). Among the 400 patients with tongue squamous cell carcinoma from 12 studies, 37 patients had level IIb metastases, the pooled incidence of which was 7% (95% CI: 5.0-10.0). Metastases to level IIb always went together with level IIa, and only three patients were found to have isolated level IIb metastases without involving the other levels. Due to the low frequency of level IIb nodal metastases in oral squamous cell carcinoma patients and rare occurrence of isolated level IIb, level IIb dissection could be avoided when the primary lesions were in early stages (T1 and T2), with the exception of tongue cancer. It is recommended to dissect level IIb tongue cancers without considering the stages of primary lesions and the lymph nodes status. It is also suggested that level IIb dissection should be performed in patients preoperatively or intraoperatively found with multilevel neck metastasis, especially level IIa metastasis.

Active and adaptive Legionella CRISPR-Cas reveals a recurrent challenge to the pathogen.

PubMed

Rao, Chitong; Guyard, Cyril; Pelaz, Carmen; Wasserscheid, Jessica; Bondy-Denomy, Joseph; Dewar, Ken; Ensminger, Alexander W

2016-10-01

Clustered regularly interspaced short palindromic repeats with CRISPR-associated gene (CRISPR-Cas) systems are widely recognized as critical genome defense systems that protect microbes from external threats such as bacteriophage infection. Several isolates of the intracellular pathogen Legionella pneumophila possess multiple CRISPR-Cas systems (type I-C, type I-F and type II-B), yet the targets of these systems remain unknown. With the recent observation that at least one of these systems (II-B) plays a non-canonical role in supporting intracellular replication, the possibility remained that these systems are vestigial genome defense systems co-opted for other purposes. Our data indicate that this is not the case. Using an established plasmid transformation assay, we demonstrate that type I-C, I-F and II-B CRISPR-Cas provide protection against spacer targets. We observe efficient laboratory acquisition of new spacers under 'priming' conditions, in which initially incomplete target elimination leads to the generation of new spacers and ultimate loss of the invasive DNA. Critically, we identify the first known target of L. pneumophila CRISPR-Cas: a 30 kb episome of unknown function whose interbacterial transfer is guarded against by CRISPR-Cas. We provide evidence that the element can subvert CRISPR-Cas by mutating its targeted sequences - but that primed spacer acquisition may limit this mechanism of escape. Rather than generally impinging on bacterial fitness, this element drives a host specialization event - with improved fitness in Acanthamoeba but a reduced ability to replicate in other hosts and conditions. These observations add to a growing body of evidence that host range restriction can serve as an existential threat to L. pneumophila in the wild. © 2016 The Authors Cellular Microbiology Published by John Wiley & Sons Ltd.

On pp wave limit for η deformed superstrings

NASA Astrophysics Data System (ADS)

Roychowdhury, Dibakar

2018-05-01

In this paper, based on the notion of plane wave string/gauge theory duality, we explore the pp wave limit associated with the bosonic sector of η deformed superstrings propagating in ( AdS 5 × S 5) η . Our analysis reveals that in the presence of NS-NS and RR fluxes, the pp wave limit associated to full ABF background satisfies type IIB equations in its standard form. However, the beta functions as well as the string Hamiltonian start receiving non trivial curvature corrections as one starts probing beyond pp wave limit which thereby takes solutions away from the standard type IIB form. Furthermore, using uniform gauge, we also explore the BMN dynamics associated with short strings and compute the corresponding Hamiltonian density. Finally, we explore the Penrose limit associated with the HT background and compute the corresponding stringy spectrum for the bosonic sector.

Level IIB Neck Dissection in Oral Squamous Cell Carcinoma: Science or Myth?

PubMed

Ghantous, Yasmine; Akrish, Sharon; Abd-Elraziq, Morad; El-Naaj, Imad Abu

2016-06-01

Selective neck dissection enables us to reduce the morbidity of neck dissection while maintaining the same oncological results, mainly in clinically negative neck N0. The most common morbidity associated with selective neck dissection is spinal accessory nerve dysfunction and related shoulder disability, which are encountered during dissection of level IIB.The aim of authors' study is to evaluate the incidence of sublevel IIB lymphatic metastasis in clinically N0 oral squamous cell carcinoma (OSCC) patients.The study group comprised 48 men (68%) and 22 women (32%). The median number of the lymph nodes removed from level IIB was 6.5. All the investigated necks were clinically classified as N0, of which 14 (20%) turned out to have an occult nodal metastasis, including only 1 patient (1.42%) of level IIB occult metastasis, which originated from the primary tumor located in the tongue and also metastasized to level IIA. The most associated morbidity was shoulder pain and dysfunction, which presented in 60% of the patients.Also, an electronic search was conducted to find relevant studies investigating the prevalence of level IIB metastasis in OSCC. Ten studies were included for full text review, including the current study. The overall incidence of level IIB metastasis is 4% (17 patients); of these 17 patients, only 4 patients had isolated level IIB nodal metastases (2%).To conclude, neck dissecting, including dissecting level IIB, remains the keystone of treating OSCC. Its prognostic and therapeutic value exceeds its associated morbidity; therefore, dissecting level IIB is recommended in treating OSCC in clinically N0 patients.

Specific Molecular Signatures for Type II Crustins in Penaeid Shrimp Uncovered by the Identification of Crustin-Like Antimicrobial Peptides in Litopenaeus vannamei

PubMed Central

Barreto, Cairé; Coelho, Jaqueline da Rosa; Yuan, Jianbo; Xiang, Jianhai; Perazzolo, Luciane Maria

2018-01-01

Crustins form a large family of antimicrobial peptides (AMPs) in crustaceans composed of four sub-groups (Types I-IV). Type II crustins (Type IIa or “Crustins” and Type IIb or “Crustin-like”) possess a typical hydrophobic N-terminal region and are by far the most representative sub-group found in penaeid shrimp. To gain insight into the molecular diversity of Type II crustins in penaeids, we identified and characterized a Type IIb crustin in Litopenaeus vannamei (Crustin-like Lv) and compared Type II crustins at both molecular and transcriptional levels. Although L. vannamei Type II crustins (Crustin Lv and Crustin-like Lv) are encoded by separate genes, they showed a similar tissue distribution (hemocytes and gills) and transcriptional response to the shrimp pathogens Vibrio harveyi and White spot syndrome virus (WSSV). As Crustin Lv, Crustin-like Lv transcripts were found to be present early in development, suggesting a maternal contribution to shrimp progeny. Altogether, our in silico and transcriptional data allowed to conclude that (1) each sub-type displays a specific amino acid signature at the C-terminal end holding both the cysteine-rich region and the whey acidic protein (WAP) domain, and that (2) shrimp Type II crustins evolved from a common ancestral gene that conserved a similar pattern of transcriptional regulation. PMID:29337853

Geology and mineral deposits of an area in the Departments of Antioquia and Caldas (Subzone IIB), Colombia

USGS Publications Warehouse

Feininger, Tomas; Barrero L., Dario; Castro, Nestor; Hall, R.B.

1973-01-01

The Inventario Minero National (IMN), a four-year cooperative geologic mapping and mineral resources appraisal project, was accomplished under an agreement between the Republic of Colombia and the U. S. Agency for International Development from 1964 through 1969. Subzone IIB, consisting essentially of the east half of Zone comprises nearly 20,000 km2 principally in the Department of Antioquia but including also small parts of the Departments of Caldas and Tolima. The rocks in IIB range from Precambrian to Holocene. Precambrian feldspar-quartz gneiss occupies a mosaic of fault-bounded blocks intruded by igneous rocks between the Oto fault and the Rio Magdalena. Paleozoic rocks are extensive, and include lightly metamorphosed graptolite-bearing Ordovician shale at Cristalina, and a major suite of graphitic quartz-mica schist, feldspathic and aluminous gneiss, quartzite, marble, amphibolite, and other rocks. Syntectonic intrusive gneiss included many of the older rocks during a late Paleozoic(?) orogeny, which was accompanied by Abukuma-type metamorphosing from lowermost greenschist to upper amphibolite facies. A Jurassic diorite pluton bounded by faults cuts volcanic rocks of unknown age east of the Otu fault. Cretaceous rocks are major units. Middle Cretaceous carbonaceous shale, sandstone, graywacke, conglomerate, and volcanic rocks are locally prominent. The Antioquian batholith (quartz diorite) of Late Cretaceous age cuts the middle Cretaceous and older rocks. A belt of Tertiary nonmarine clastic sedimentary rocks crops out along the Magdalena Valley. Patches of Tertiary alluvium are locally preserved in the mountains. Quaternary alluvium, much of it auriferous, is widespread in modern stream valleys. Structurally IIB constitutes part of a vast complex synclinorium intruded concordantly by syntectonic catazonal or mesozonal felsic plutons, and by the later epizonal post-tectonic Antioquian batholith. Previously unrecognized major wrench faults are outstanding structural features of IIB. Some are traceable for several hundred kilometers and probably have displacements measurable in kilometers, although only the Palestina fault, with right-lateral displacement of 27.7 km, is accurately documented. Correlations of rocks mapped in IIB with those of outlying areas including neighboring IIA are discussed.

Proflavine acts as a Rev inhibitor by targeting the high-affinity Rev binding site of the Rev responsive element of HIV-1.

PubMed

DeJong, Eric S; Chang, Chia-en; Gilson, Michael K; Marino, John P

2003-07-08

Rev is an essential regulatory HIV-1 protein that binds the Rev responsive element (RRE) within the env gene of the HIV-1 RNA genome, activating the switch between viral latency and active viral replication. Previously, we have shown that selective incorporation of the fluorescent probe 2-aminopurine (2-AP) into a truncated form of the RRE sequence (RRE-IIB) allowed the binding of an arginine-rich peptide derived from Rev and aminoglycosides to be characterized directly by fluorescence methods. Using these fluorescence and nuclear magnetic resonance (NMR) methods, proflavine has been identified, through a limited screen of selected small heterocyclic compounds, as a specific and high-affinity RRE-IIB binder which inhibits the interaction of the Rev peptide with RRE-IIB. Direct and competitive 2-AP fluorescence binding assays reveal that there are at least two classes of proflavine binding sites on RRE-IIB: a high-affinity site that competes with the Rev peptide for binding to RRE-IIB (K(D) approximately 0.1 +/- 0.05 microM) and a weaker binding site(s) (K(D) approximately 1.1 +/- 0.05 microM). Titrations of RRE-IIB with proflavine, monitored using (1)H NMR, demonstrate that the high-affinity proflavine binding interaction occurs with a 2:1 (proflavine:RRE-IIB) stoichiometry, and NOEs observed in the NOESY spectrum of the 2:1 proflavine.RRE-IIB complex indicate that the two proflavine molecules bind specifically and close to each other within a single binding site. NOESY data further indicate that formation of the 2:1 proflavine.RRE-IIB complex stabilizes base pairing and stacking within the internal purine-rich bulge of RRE-IIB in a manner analogous to what has been observed in the Rev peptide.RRE-IIB complex. The observation that proflavine competes with Rev for binding to RRE-IIB by binding as a dimer to a single high-affinity site opens the possibility for rational drug design based on linking and modifying it and related compounds.

Mapping of a Microbial Protein Domain Involved in Binding and Activation of the TLR2/TLR1 Heterodimer 1

PubMed Central

Liang, Shuang; Hosur, Kavita B.; Lu, Shanyun; Nawar, Hesham F.; Weber, Benjamin R.; Tapping, Richard I.; Connell, Terry D.; Hajishengallis, George

2009-01-01

LT-IIb-B5, a doughnut-shaped oligomeric protein from enterotoxigenic Escherichia coli, is known to activate the TLR2/TLR1 heterodimer (TLR2/1). We investigated the molecular basis of the LT-IIb-B5 interaction with TLR2/1 in order to define the structure-function relationship of LT-IIb-B5 and, moreover, to gain an insight into how TLR2/1 recognizes large, non-acylated protein ligands that cannot fit within its lipid-binding pockets, as previously shown for the Pam3CSK4 lipopeptide. We first identified four critical residues in the upper region of the LT-IIb-B5 pore: Corresponding point mutants (M69E, A70D, L73E, S74D) were defective in binding TLR2 or TLR1 and could not activate antigen-presenting cells, despite retaining full ganglioside-binding capacity. Point mutations in the TLR2/1 dimer interface, as determined in the crystallographic structure of the TLR2/1-Pam3CSK4 complex, resulted in diminished activation by both Pam3CSK4 and LT-IIb-B5. Docking analysis of the LT-IIb-B5 interaction with this apparently “predominant” activation conformation of TLR2/1 revealed that LT-IIb-B5 may primarily contact the convex surface of the TLR2 central domain. Although the TLR1/LT-IIb-B5 interface is relatively smaller, the leucine-rich repeat motifs 9–12 in the central domain of TLR1 were found to be critical for cooperative TLR2-induced cell activation by LT-IIb-B5. Moreover, the putative LT-IIb-B5 binding site overlaps partially with that of Pam3CSK4; consistent with this, Pam3CSK4 suppressed TLR2 binding of LT-IIb-B5, albeit not as potently as self-competitive inhibition. In conclusion, we identified the upper pore region of LT-IIb-B5 as a TLR2/1 interactive domain, which contacts the heterodimeric receptor at a site that is distinct from, though overlaps with, that of Pam3CSK4. PMID:19234193

GpIIb/IIIa+ subpopulation of rat megakaryocyte progenitor cells exhibits high responsiveness to human thrombopoietin.

PubMed

Kato, T; Horie, K; Hagiwara, T; Maeda, E; Tsumura, H; Ohashi, H; Miyazaki, H

1996-08-01

The recently cloned factor thrombopoietin (TPO) has been shown to exhibit megakaryocyte colony-stimulating activity in vitro. In this investigation, to further evaluate the action of TPO on megakaryocyte progenitor cells (colony-forming units-megakaryocyte [CFU-MK]), GpIIb/IIIa+ and GpIIb/IIIa- populations of CFU-MK were prepared from rat bone marrow cells based on their reactivity with P55 antibody, a monoclonal antibody against rat GpIIb/IIIa, and their responsiveness to recombinant human TPO (rhTPO) and recombinant rat interleukin-3 (rrIL-3) was examined using a megakaryocyte colony-forming assay (Meg-CSA). rhTPO supported only megakaryocyte colony growth from both fractions in a dose-dependent fashion. The mean colony size observed with the GpIIb/IIIa+ population was smaller than that seen with the GpIIb/IIIa- population. With the optimal concentration of either rhTPO or rrIL-3, similar numbers of megakaryocyte colonies were formed from the GpIIb/IIIa+ population previously shown to be highly enriched for CFU-MK. In contrast, the maximum number of megakaryocyte colonies from the GpIIb/IIIa- population stimulated by rhTPO was only 24.2% of that achieved with rrIL-3. Morphologic analysis of rhTPO-promoted megakaryocyte colonies from the GpIIb/IIIa+ population showed that the average colony size was smaller but that the mean diameter of individual megakaryocytes was larger than in megakaryocyte colonies promoted with rrIL-3. rhTPO plus rrIL-3, each at suboptimal concentrations, had an additive effect on proliferation of CFU-MK in the GpIIb/IIIa+ fraction, whereas rhTPO plus murine IL-6 or murine granulocyte-macrophage colony-stimulating factor (mG-M-CSF) modestly but significantly reduced megakaryocyte colony growth. These results indicate that TPO preferentially acts on GpIIb/IIIa+ late CFU-MK with lower proliferative capacity and interacts with some other cytokines in CFU-MK development.

Dual mechanism of integrin αIIbβ3 closure in procoagulant platelets.

PubMed

Mattheij, Nadine J A; Gilio, Karen; van Kruchten, Roger; Jobe, Shawn M; Wieschhaus, Adam J; Chishti, Athar H; Collins, Peter; Heemskerk, Johan W M; Cosemans, Judith M E M

2013-05-10

Inactivation of integrin αIIbβ3 reverses platelet aggregate formation upon coagulation. Platelets from patient (Scott) and mouse (Capn1(-/-) and Ppif(-/-)) blood reveal a dual mechanism of αIIbβ3 inactivation: by calpain-2 cleavage of integrin-associated proteins and by cyclophilin D/TMEM16F-dependent phospholipid scrambling. These data provide novel insight into the switch mechanisms from aggregating to procoagulant platelets. Aggregation of platelets via activated integrin αIIbβ3 is a prerequisite for thrombus formation. Phosphatidylserine-exposing platelets with a key role in the coagulation process disconnect from a thrombus by integrin inactivation via an unknown mechanism. Here we show that αIIbβ3 inactivation in procoagulant platelets relies on a sustained high intracellular Ca(2+), stimulating intracellular cleavage of the β3 chain, talin, and Src kinase. Inhibition of calpain activity abolished protein cleavage, but only partly suppressed αIIbβ3 inactivation. Integrin αIIbβ3 inactivation was unchanged in platelets from Capn1(-/-) mice, suggesting a role of the calpain-2 isoform. Scott syndrome platelets, lacking the transmembrane protein TMEM16F and having low phosphatidylserine exposure, displayed reduced αIIbβ3 inactivation with the remaining activity fully dependent on calpain. In platelets from Ppif(-/-) mice, lacking mitochondrial permeability transition pore (mPTP) formation, agonist-induced phosphatidylserine exposure and αIIbβ3 inactivation were reduced. Treatment of human platelets with cyclosporin A gave a similar phenotype. Together, these data point to a dual mechanism of αIIbβ3 inactivation via calpain(-2) cleavage of integrin-associated proteins and via TMEM16F-dependent phospholipid scrambling with an assistant role of mPTP formation.

Three-dimensional Model of Human Platelet Integrin αIIbβ3 in Solution Obtained by Small Angle Neutron Scattering*

PubMed Central

Nogales, Aurora; García, Carolina; Pérez, Javier; Callow, Phil; Ezquerra, Tiberio A.; González-Rodríguez, José

2010-01-01

Integrin αIIbβ3 is the major membrane protein and adhesion receptor at the surface of blood platelets, which after activation plays a key role in platelet plug formation in hemostasis and thrombosis. Small angle neutron scattering (SANS) and shape reconstruction algorithms allowed formation of a low resolution three-dimensional model of whole αIIbβ3 in Ca2+/detergent solutions. Model projections after 90° rotation along its long axis show an elongated and “arched” form (135°) not observed before and a “handgun” form. This 20-nm-long structure is well defined, despite αIIbβ3 multidomain nature and expected segmental flexibility, with the largest region at the top, followed by two narrower and smaller regions at the bottom. Docking of this SANS envelope into the high resolution structure of αIIbβ3, reconstructed from crystallographic and NMR data, shows that the solution structure is less constrained, allows tentative assignment of the disposition of the αIIb and β3 subunits and their domains within the model, and points out the structural analogies and differences of the SANS model with the crystallographic models of the recombinant ectodomains of αIIbβ3 and αVβ3 and with the cryo-electron microscopy model of whole αIIbβ3. The ectodomain is in the bent configuration at the top of the model, where αIIb and β3 occupy the concave and convex sides, respectively, at the arched projection, with their bent knees at its apex. It follows the narrower transmembrane region and the cytoplasmic domains at the bottom end. αIIbβ3 aggregated in Mn2+/detergent solutions, which impeded to get its SANS model. PMID:19897481

Key role of integrin α(IIb)β (3) signaling to Syk kinase in tissue factor-induced thrombin generation.

PubMed

van der Meijden, Paola E J; Feijge, Marion A H; Swieringa, Frauke; Gilio, Karen; Nergiz-Unal, Reyhan; Hamulyák, Karly; Heemskerk, Johan W M

2012-10-01

The fibrin(ogen) receptor, integrin α(IIb)β(3), has a well-established role in platelet spreading, aggregation and clot retraction. How α(IIb)β(3) contributes to platelet-dependent coagulation is less well resolved. Here, we demonstrate that the potent suppressing effect of clinically used α(IIb)β(3) blockers on tissue factor-induced thrombin generation is linked to diminished platelet Ca(2+) responses and phosphatidylserine (PS) exposure. The same blockers suppress these responses in platelets stimulated with collagen and thrombin receptor agonists, whereas added fibrinogen potentiates these responses. In platelets spreading on fibrinogen, outside-in α(IIb)β(3) signaling similarly enhances thrombin-induced Ca(2+) rises and PS exposure. These responses are reduced in α(IIb)β(3)-deficient platelets from patients with Glanzmann's thrombasthenia. Furthermore, the contribution of α(IIb)β(3) to tissue factor-induced platelet Ca(2+) rises, PS exposure and thrombin generation in plasma are fully dependent on Syk kinase activity. Tyrosine phosphorylation analysis confirms a key role of Syk activation, which is largely but not exclusively dependent on α(IIb)β(3) activation. It is concluded that the majority of tissue factor-induced procoagulant activity of platelets relies on Syk activation and ensuing Ca(2+) signal generation, and furthermore that a considerable part of Syk activation relies on α(IIb)β(3) signaling. These results hence point to a novel role of Syk in integrin-dependent thrombin generation.

Variation in One Residue Associated with the Metal Ion-Dependent Adhesion Site Regulates αIIbβ3 Integrin Ligand Binding Affinity

PubMed Central

Wu, Xue; Xiu, Zhilong; Li, Guohui; Luo, Bing-Hao

2013-01-01

The Asp of the RGD motif of the ligand coordinates with the β I domain metal ion dependent adhesion site (MIDAS) divalent cation, emphasizing the importance of the MIDAS in ligand binding. There appears to be two distinct groups of integrins that differ in their ligand binding affinity and adhesion ability. These differences may be due to a specific residue associated with the MIDAS, particularly the β3 residue Ala252 and corresponding Ala in the β1 integrin compared to the analogous Asp residue in the β2 and β7 integrins. Interestingly, mutations in the adjacent to MIDAS (ADMIDAS) of integrins α4β7 and αLβ2 increased the binding and adhesion abilities compared to the wild-type, while the same mutations in the α2β1, α5β1, αVβ3, and αIIbβ3 integrins demonstrated decreased ligand binding and adhesion. We introduced a mutation in the αIIbβ3 to convert this MIDAS associated Ala252 to Asp. By combination of this mutant with mutations of one or two ADMIDAS residues, we studied the effects of this residue on ligand binding and adhesion. Then, we performed molecular dynamics simulations on the wild-type and mutant αIIbβ3 integrin β I domains, and investigated the dynamics of metal ion binding sites in different integrin-RGD complexes. We found that the tendency of calculated binding free energies was in excellent agreement with the experimental results, suggesting that the variation in this MIDAS associated residue accounts for the differences in ligand binding and adhesion among different integrins, and it accounts for the conflicting results of ADMIDAS mutations within different integrins. This study sheds more light on the role of the MIDAS associated residue pertaining to ligand binding and adhesion and suggests that this residue may play a pivotal role in integrin-mediated cell rolling and firm adhesion. PMID:24116162

Contour variations of the body and tail of the pancreas: evaluation with MDCT.

PubMed

Omeri, Ahmad Khalid; Matsumoto, Shunro; Kiyonaga, Maki; Takaji, Ryo; Yamada, Yasunari; Kosen, Kazuhisa; Mori, Hiromu; Miyake, Hidetoshi

2017-06-01

To analyze morphology/contour variations of the pancreatic body and tail in subjects free of pancreatic disease. We retrospectively reviewed triple-phase, contrast-enhanced multi-detector row computed tomography (3P-CE-MDCT) examinations of 449 patients who had no clinical or CT evidence of pancreatic diseases. These patients were evaluated for morphologic/contour variations of the pancreatic body and tail, which were classified into two types. In Type I, a portion of normal pancreatic parenchyma protrudes >1 cm in maximum diameter from the body or tail (Ia-anteriorly; Ib-posteriorly). Type II was defined as a morphologic anomaly of the pancreatic tail (IIa-globular; IIb-lobulated; IIc-tapered; IId-bifid). Thirty-eight (8.5%) out of 449 patients had body or tail variations. Of those, 23 patients showed Type I variant: Ia in 21 and Ib in two. Type II variant was identified in 15 patients: IIa in eight, IIb in two, IIc in two and IId in three. Protrusion of the anterior surface of the normal pancreas, especially in the tail, was the most frequently occurring variant. Recognizing the types and subtypes of morphology/contour variations of the pancreatic body and tail could help prevent misinterpretation of normal variants as pancreatic tumors on unenhanced MDCT.

Lnk regulates integrin αIIbβ3 outside-in signaling in mouse platelets, leading to stabilization of thrombus development in vivo

PubMed Central

Takizawa, Hitoshi; Nishimura, Satoshi; Takayama, Naoya; Oda, Atsushi; Nishikii, Hidekazu; Morita, Yohei; Kakinuma, Sei; Yamazaki, Satoshi; Okamura, Satoshi; Tamura, Noriko; Goto, Shinya; Sawaguchi, Akira; Manabe, Ichiro; Takatsu, Kiyoshi; Nakauchi, Hiromitsu; Takaki, Satoshi; Eto, Koji

2009-01-01

The nature of the in vivo cellular events underlying thrombus formation mediated by platelet activation remains unclear because of the absence of a modality for analysis. Lymphocyte adaptor protein (Lnk; also known as Sh2b3) is an adaptor protein that inhibits thrombopoietin-mediated signaling, and as a result, megakaryocyte and platelet counts are elevated in Lnk–/– mice. Here we describe an unanticipated role for Lnk in stabilizing thrombus formation and clarify the activities of Lnk in platelets transduced through integrin αIIbβ3–mediated outside-in signaling. We equalized platelet counts in wild-type and Lnk–/– mice by using genetic depletion of Lnk and BM transplantation. Using FeCl3- or laser-induced injury and in vivo imaging that enabled observation of single platelet behavior and the multiple steps in thrombus formation, we determined that Lnk is an essential contributor to the stabilization of developing thrombi within vessels. Lnk–/– platelets exhibited a reduced ability to fully spread on fibrinogen and mediate clot retraction, reduced tyrosine phosphorylation of the β3 integrin subunit, and reduced binding of Fyn to integrin αIIbβ3. These results provide new insight into the mechanism of αIIbβ3-based outside-in signaling, which appears to be coordinated in platelets by Lnk, Fyn, and integrins. Outside-in signaling modulators could represent new therapeutic targets for the prevention of cardiovascular events. PMID:20038804

On supersymmetric AdS6 solutions in 10 and 11 dimensions

NASA Astrophysics Data System (ADS)

Gutowski, J.; Papadopoulos, G.

2017-12-01

We prove a non-existence theorem for smooth, supersymmetric, warped AdS 6 solutions with connected, compact without boundary internal space in D = 11 and (massive) IIA supergravities. In IIB supergravity we show that if such AdS 6 solutions exist, then the NSNS and RR 3-form fluxes must be linearly independent and certain spinor bilinears must be appropriately restricted. Moreover we demonstrate that the internal space admits an so(3) action which leaves all the fields invariant and for smooth solutions the principal orbits must have co-dimension two. We also describe the topology and geometry of internal spaces that admit such a so(3) action and show that there are no solutions for which the internal space has topology F × S 2, where F is an oriented surface.

[New varieties of lateral metatarsophalangeal dislocations of the great toe].

PubMed

Bousselmame, N; Rachid, K; Lazrak, K; Galuia, F; Taobane, H; Moulay, I

2001-04-01

We report seven cases of traumatic dislocation of the great toe, detailing the anatomy, the mechanism of injury and the radiographic diagnosis. We propose an additional classification based on three hereto unreported cases. Between october 1994 and october 1997, we treated seven patients with traumatic dislocation of the first metatarso-phalangeal joint of the great toe. There were six men and one woman, mean age 35 years (range 24 - 44 years). Dislocation was caused by motor vehicle accidents in four cases and by falls in three. Diagnosis was made on anteroposterior, lateral and medial oblique radiographs. According to Jahss' classification, there was one type I and three type IIB dislocations. There was also one open lateral dislocation and two dorsomedial dislocations. Only these dorsomedial dislocations required open reduction, done via a dorsal approach. Mean follow-up was 17.5 months (range 9 - 24 months) in six cases. One patient was lost to follow-up. The outcome was good in six cases and poor in one (dorsomedial dislocation). Dislocation of the first metatarso-phalangeal joint of the great toe is an uncommon injury. In 1980, Jahss reported two cases and reviewed three others described in the literature. He proposed three types of dislocation based on the feasibility of closed reduction (type I, II and IIB). In 1991, Copeland and Kanat reported a unique case in which there was an association of IIA and IIB lesions. They proposed an addition to the classification (type IIC). In 1994, Garcia Mata et al. reported another case which had not been described by Jahss and proposed another addition. All dislocations reported to date have been sagittal dislocations. Pathological alteration of the collateral ligaments has not been previously reported. In our experience, we have seen one case of open lateral dislocation due, at surgical exploration, to medial ligament rupture and two cases of dorsomedial dislocation due, at surgical exploration, to lateral ligament rupture. We propose another additional classification with pure lateral dislocation (type III) and dorso-lateral dislocation (type IL or IIL+), which are related to the formerly described variants.

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

Steiner, B.; Cousot, D.; Trzeciak, A.

The platelet glycoprotein IIb-IIIa complex (GP IIb-IIIa) is a member of the integrin receptor family that recognizes adhesive proteins containing the Arg-Gly-Asp (RGD) sequence. In the present study the binding characteristics of the synthetic hexapeptide Tyr-Asn-Arg-Gly-Asp-Ser (YNRGDS, a sequence present in the fibrinogen alpha-chain at position 570-575) to purified GP IIb-IIIa were determined by equilibrium dialysis. The binding of 125I-YNRGDS to GP IIb-IIIa was specific, saturable, and reversible. The apparent dissociation constant was 1.0 +/- 0.2 microM, and the maximal binding capacity was 0.92 +/- 0.02 mol of 125I-YNRGDS/mol of GP IIb-IIIa, indicating that GP IIb-IIIa contains a single bindingmore » site for RGD peptides. The binding of 125I-YNRGDS to purified GP IIb-IIIa showed many of the characteristics of fibrinogen binding to activated platelets: the binding was inhibited by fibrinogen, by the monoclonal antibody A2A9, and by the dodecapeptide from the C terminus of the fibrinogen gamma-chain. In addition, the binding of 125I-YNRGDS to GP IIb-IIIa was divalent cation-dependent. Our data suggest that two divalent cation binding sites must be occupied for YNRGDS to bind: one site is specific for calcium and is saturated at 1 microM free Ca2+, whereas the other site is less specific and reaches saturation at millimolar concentrations of either Ca2+ or Mg2+. The results of the present study support the hypothesis that the RGD domains within the adhesive proteins are responsible for their binding to GP IIb-IIIa.« less

AdS6 solutions of type II supergravity

NASA Astrophysics Data System (ADS)

Apruzzi, Fabio; Fazzi, Marco; Passias, Achilleas; Rosa, Dario; Tomasiello, Alessandro

2014-11-01

Very few AdS6 × M 4 supersymmetric solutions are known: one in massive IIA, and two IIB solutions dual to it. The IIA solution is known to be unique; in this paper, we use the pure spinor approach to give a classification for IIB supergravity. We reduce the problem to two PDEs on a two-dimensional space Σ. M 4 is then a fibration of S 2 over Σ; the metric and fluxes are completely determined in terms of the solution to the PDEs. The results seem likely to accommodate near-horizon limits of ( p, q)-fivebrane webs studied in the literature as a source of CFT5's. We also show that there are no AdS6 solutions in eleven-dimensional supergravity.

Comparison of Muscle Fiber and Meat Quality Characteristics in Different Japanese Quail Lines

PubMed Central

Choi, Y. M.; Hwang, S.; Lee, K.

2016-01-01

The aim of this study was to compare the growth performance, fiber characteristics of the pectoralis major muscle, and meat quality characteristics in the heavy weight (HW) and random bred control (RBC) quail lines and genders. The HW male exhibited more than two times greater body (245.7 vs 96.1 g, p<0.05) and pectoralis major muscle (PMW; 37.1 vs 11.1 g, p<0.05) weights compared to the RBC female. This growth performance in the HW line was associated with a greater muscle fiber area (1,502 vs 663.0 μm2, p<0.001) compared to the RBC line. Greater muscle mass of the HW male was accompanied by a higher percentage of type IIB fiber compared to the HW female (64.0% vs 51.0%, p<0.05). However, muscle fiber hyperplasia (increase in fiber number) has had a somewhat limited effect on PMW between the two lines. On the other hand, the HW line harboring a higher proportion of type IIB fiber showed rapid pH decline at the early postmortem period (6.23 vs 6.41, p<0.05) and lighter meat surface (53.5 vs 47.3, p<0.05) compared to the RBC line harboring a lower proportion of type IIB fiber. There were no significant differences observed in the measurement of water-holding capacity including drip loss (2.74% vs 3.07%, p>0.05) and cooking loss (21.9% vs 20.4%, p>0.05) between the HW and RBC lines. Therefore, the HW quail line developed by selection from the RBC quail, was slightly different in the meat quality characteristics compared to the RBC line, and a marked difference was found in growth performance between the two quail lines. PMID:27383804

[Comparison between Endoscopic Therapy and Medical Therapy in Peptic Ulcer Patients with Adherent Clot: A Multicenter Prospective Observational Cohort Study].

PubMed

Kim, Si Hye; Jung, Jin Tae; Kwon, Joong Goo; Kim, Eun Young; Lee, Dong Wook; Jeon, Seong Woo; Park, Kyung Sik; Lee, Si Hyung; Park, Jeong Bae; Ha, Chang Yoon; Park, Youn Sun

2015-08-01

The optimal management of bleeding peptic ulcer with adherent clot remains controversial. The purpose of this study was to compare clinical outcome between endoscopic therapy and medical therapy. We also evaluated the risk factors of rebleeding in Forrest type IIB peptic ulcer. Upper gastrointestinal (UGI) bleeding registry data from 8 hospitals in Korea between February 2011 and December 2013 were reviewed and categorized according to the Forrest classification. Patients with acute UGI bleeding from peptic ulcer with adherent clots were enrolled. Among a total of 1,101 patients diagnosed with peptic ulcer bleeding, 126 bleedings (11.4%) were classified as Forrest type IIB. Of the 126 patients with adherent clots, 84 (66.7%) received endoscopic therapy and 42 (33.3%) were managed with medical therapy alone. The baseline characteristics of patients in two groups were similar except for higher Glasgow Blatchford Score and pre-endoscopic Rockall score in medical therapy group. Bleeding related mortality (1.2% vs.10%; p=0.018) and all cause mortality (3.7% vs. 20.0%; p=0.005) were significantly lower in the endoscopic therapy group. However, there was no difference between endoscopic therapy and medical therapy regarding rebleeding (7.1% vs. 9.5%; p=0.641). In multivariate analysis, independent risk factors of rebleeding were previous medication with aspirin and/or NSAID (OR, 13.1; p=0.025). In patients with Forrest type IIB peptic ulcer bleeding, endoscopic therapy was associated with a significant reduction in bleeding related mortality and all cause mortality compared with medical therapy alone. Important risk factor of rebleeding was use of aspirin and/or NSAID.

Preferential motor unit loss in the SOD1G93A transgenic mouse model of amyotrophic lateral sclerosis

PubMed Central

Hegedus, J; Putman, C T; Tyreman, N; Gordon, T

2008-01-01

The present study investigated motor unit (MU) loss in a murine model of familial amyotrophic lateral sclerosis (ALS). The fast-twitch tibialis anterior (TA) and medial gastrocnemius (MG) muscles of transgenic SOD1G93A and SOD1WT mice were studied during the presymptomatic phase of disease progression at 60 days of age. Whole muscle maximum isometric twitch and tetanic forces were 80% lower (P < 0.01) in the TA muscles of SOD1G93A compared to SOD1WT mice. Enumeration of total MU numbers within TA muscles showed a 60% reduction (P < 0.01) within SOD1G93A mice (38 ± 7) compared with SOD1WT controls (95 ± 12); this was attributed to a lower proportion of the most forceful fast-fatigable (FF) MU in SOD1G93A mice, as seen by a significant (P < 0.01) leftward shift in the cumulative frequency histogram of single MU forces. Similar patterns of MU loss and corresponding decreases in isometric twitch force were observed in the MG. Immunocytochemical analyses of the entire cross-sectional area (CSA) of serial sections of TA muscles stained with anti-neural cell adhesion molecule (NCAM) and various monoclonal antibodies for myosin heavy chain (MHC) isoforms showed respective 65% (P < 0.01) and 28% (P < 0.05) decreases in the number of innervated IIB and IID/X muscle fibres in SOD1G93A, which paralleled the 60% decrease (P < 0.01) in the force generating capacity of individual fibres. The loss of fast MUs was partially compensated by activity-dependent fast-to-slower fibre type transitions, as determined by increases (P < 0.04) in the CSA and proportion of IIA fibres (from 4% to 14%) and IID/X fibres (from 31% to 39%), and decreases (P < 0.001) in the CSA and proportion of type IIB fibres (from 65% to 44%). We conclude that preferential loss of IIB fibres is incomplete at 60 days of age, and is consistent with a selective albeit gradual loss of FF MUs that is not fully compensated by sprouting of the remaining motoneurons that innervate type IIA or IID/X muscle fibres. Our findings indicate that disease progression in fast-twitch muscles of SOD1G93A mice involves parallel processes: (1) gradual selective motor axon die-back of the FF motor units that contain large type IIB muscle fibres, and of fatigue-intermediate motor units that innervate type IID/X muscle fibres, and (2) activity-dependent conversion of motor units to those innervated by smaller motor axons innervating type IIA fatigue-resistant muscle fibres. PMID:18467368

Integrin αIIb (CD41) plays a role in the maintenance of hematopoietic stem cell activity in the mouse embryonic aorta

PubMed Central

Boisset, Jean-Charles; Clapes, Thomas; Van Der Linden, Reinier; Dzierzak, Elaine; Robin, Catherine

2013-01-01

Summary Integrins are transmembrane receptors that play important roles as modulators of cell behaviour through their adhesion properties and the initiation of signaling cascades. The αIIb integrin subunit (CD41) is one of the first cell surface markers indicative of hematopoietic commitment. αIIb pairs exclusively with β3 to form the αIIbβ3 integrin. β3 (CD61) also pairs with αv (CD51) to form the αvβ3 integrin. The expression and putative role of these integrins during mouse hematopoietic development is as yet unknown. We show here that hematopoietic stem cells (HSCs) differentially express αIIbβ3 and αvβ3 integrins throughout development. Whereas the first HSCs generated in the aorta at mid-gestation express both integrins, HSCs from the placenta only express αvβ3, and most fetal liver HSCs do not express either integrin. By using αIIb deficient embryos, we show that αIIb is not only a reliable HSC marker but it also plays an important and specific function in maintaining the HSC activity in the mouse embryonic aorta. PMID:23789102

DNA G-segment bending is not the sole determinant of topology simplification by type II DNA topoisomerases.

PubMed

Thomson, Neil H; Santos, Sergio; Mitchenall, Lesley A; Stuchinskaya, Tanya; Taylor, James A; Maxwell, Anthony

2014-08-21

DNA topoisomerases control the topology of DNA. Type II topoisomerases exhibit topology simplification, whereby products of their reactions are simplified beyond that expected based on thermodynamic equilibrium. The molecular basis for this process is unknown, although DNA bending has been implicated. To investigate the role of bending in topology simplification, the DNA bend angles of four enzymes of different types (IIA and IIB) were measured using atomic force microscopy (AFM). The enzymes tested were Escherichia coli topo IV and yeast topo II (type IIA enzymes that exhibit topology simplification), and Methanosarcina mazei topo VI and Sulfolobus shibatae topo VI (type IIB enzymes, which do not). Bend angles were measured using the manual tangent method from topographical AFM images taken with a novel amplitude-modulated imaging mode: small amplitude small set-point (SASS), which optimises resolution for a given AFM tip size and minimises tip convolution with the sample. This gave improved accuracy and reliability and revealed that all 4 topoisomerases bend DNA by a similar amount: ~120° between the DNA entering and exiting the enzyme complex. These data indicate that DNA bending alone is insufficient to explain topology simplification and that the 'exit gate' may be an important determinant of this process.

DNA G-segment bending is not the sole determinant of topology simplification by type II DNA topoisomerases

NASA Astrophysics Data System (ADS)

Thomson, Neil H.; Santos, Sergio; Mitchenall, Lesley A.; Stuchinskaya, Tanya; Taylor, James A.; Maxwell, Anthony

2014-08-01

DNA topoisomerases control the topology of DNA. Type II topoisomerases exhibit topology simplification, whereby products of their reactions are simplified beyond that expected based on thermodynamic equilibrium. The molecular basis for this process is unknown, although DNA bending has been implicated. To investigate the role of bending in topology simplification, the DNA bend angles of four enzymes of different types (IIA and IIB) were measured using atomic force microscopy (AFM). The enzymes tested were Escherichia coli topo IV and yeast topo II (type IIA enzymes that exhibit topology simplification), and Methanosarcina mazei topo VI and Sulfolobus shibatae topo VI (type IIB enzymes, which do not). Bend angles were measured using the manual tangent method from topographical AFM images taken with a novel amplitude-modulated imaging mode: small amplitude small set-point (SASS), which optimises resolution for a given AFM tip size and minimises tip convolution with the sample. This gave improved accuracy and reliability and revealed that all 4 topoisomerases bend DNA by a similar amount: ~120° between the DNA entering and exiting the enzyme complex. These data indicate that DNA bending alone is insufficient to explain topology simplification and that the `exit gate' may be an important determinant of this process.

Tiny graviton matrix theory/SYM correspondence: Analysis of BPS states

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

Ali-Akbari, M.; Torabian, M.; Department of Physics, Sharif University of Technology, P.O. Box 11365-9161, Tehran

2006-09-15

In this paper we continue analysis of the Matrix theory describing the DLCQ of type IIB string theory on AdS{sub 5}xS{sup 5} (and/or the plane-wave) background, i.e. the tiny graviton matrix theory (TGMT) [M. M. Sheikh-Jabbari, J. High Energy Phys. 09 (2004) 017.]. We study and classify 1/2, 1/4, and 1/8 BPS solutions of the TGMT which are generically of the form of rotating three-brane giants. These are branes whose shape are deformed three-spheres and hyperboloids. In lack of a classification of such ten-dimensional type IIb supergravity configurations, we focus on the dual N=4 four-dimensional 1/2, 1/4, and one 1/8more » BPS operators and show that they are in one-to-one correspondence with the states of the same set of quantum numbers in TGMT. This provides further evidence in support of the matrix theory.« less

Platelet glycoprotein IIb/IIIa receptor inhibition in non-ST-elevation acute coronary syndromes: early benefit during medical treatment only, with additional protection during percutaneous coronary intervention.

PubMed

Boersma, E; Akkerhuis, K M; Théroux, P; Califf, R M; Topol, E J; Simoons, M L

1999-11-16

Glycoprotein (GP) IIb/IIIa receptor blockers prevent life-threatening cardiac complications in patients with acute coronary syndromes without ST-segment elevation and protect against thrombotic complications associated with percutaneous coronary interventions (PCIs). The question arises as to whether these 2 beneficial effects are independent and additive. We analyzed data from the CAPTURE, PURSUIT, and PRISM-PLUS randomized trials, which studied the effects of the GP IIb/IIIa inhibitors abciximab, eptifibatide, and tirofiban, respectively, in acute coronary syndrome patients without persistent ST-segment elevation, with a period of study drug infusion before a possible PCI. During the period of pharmacological treatment, each trial demonstrated a significant reduction in the rate of death or nonfatal myocardial infarction in patients randomized to the GP IIb/IIIa inhibitor compared with placebo. The 3 trials combined showed a 2.5% event rate in this period in the GP IIb/IIIa inhibitor group (N=6125) versus 3.8% in placebo (N=6171), which implies a 34% relative reduction (P<0.001). During study medication, a PCI was performed in 1358 patients assigned GP IIb/IIIa inhibition and 1396 placebo patients. The event rate during the first 48 hours after PCI was also significantly lower in the GP IIb/IIIa inhibitor group (4. 9% versus 8.0%; 41% reduction; P<0.001). No further benefit or rebound effect was observed beyond 48 hours after the PCI. There is conclusive evidence of an early benefit of GP IIb/IIIa inhibitors during medical treatment in patients with acute coronary syndromes without persistent ST-segment elevation. In addition, in patients subsequently undergoing PCI, GP IIb/IIIa inhibition protects against myocardial damage associated with the intervention.

Topological charges in SL(2,R) covariant massive 11-dimensional and type IIB supergravity

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

Callister, Andrew K.; Smith, Douglas J.

2009-12-15

In this paper we construct closed expressions that correspond to the topological charges of the various 1/2-BPS states of the maximal 10- and 11-dimensional supergravity theories. These expressions are related to the structure of the supersymmetry algebras in curved spacetimes. We mainly focus on IIB supergravity and 11-dimensional supergravity in a double M9-brane background, with an emphasis on the SL(2,R) multiplet structure of the charges and how these map between theories. This includes the charges corresponding to the multiplets of 7- and 9-branes in IIB. We find that examining the possible multiplet structures of the charges provides another tool formore » exploring the spectrum of BPS states that appear in these theories. As a prerequisite to constructing the charges we determine the field equations and multiplet structure of the 11-dimensional gauge potentials, extending previous results on the subject. The massive gauge transformations of the fields are also discussed. We also demonstrate how these massive gauge transformations are compatible with the construction of an SL(2,R) covariant kinetic term in the 11-dimensional Kaluza-Klein monopole worldvolume action.« less

Antioxidant and immunological activities of polysaccharides from Gentiana scabra Bunge roots.

PubMed

Wang, Zhanyong; Wang, Chenyu; Su, Tingting; Zhang, Jing

2014-11-04

Two polysaccharide fractions, GSP I-a and GSP II-b, were isolated from Gentiana scabra Bunge roots. Both GSP I-a and GSP II-b comprised seven monosaccharides: fructose, mannose, rhamnose, galacturonic acid, glucose, galactose, and fucose. Ultraviolet and infrared analyses show that GSP I-a and GSP II-b are proteoglycans. In vitro evaluation of the antioxidant activity suggests that GSP I-a and GSP II-b scavenge 1,1-diphenyl-2-picrylhydrazyl radicals. However, the scavenging activity of the latter is stronger than that of the former. GSP I-a and GSP II-b have relatively low reducing powers and scavenging activities toward superoxide anions and hydroxyls. GSP I-a and GSP II-b significantly increase lymphocyte proliferation when lipopolysaccharide is used as a mitogen for lymphocytes, but only GSP I-a can significantly increase lymphocyte proliferation within the test-dosage range when concanavalin A is used as a mitogen. Copyright © 2014 Elsevier Ltd. All rights reserved.

Creatine Supplementation Induces Alteration in Cross-Sectional Area in Skeletal Muscle Fibers of Wistar Rats Under Swimming Training

PubMed Central

Santos, Fernando Farias Dos; Moura, José A. A.; Curi, Rui; Fernandes, Luiz C.

2002-01-01

Creatine has been shown to increase the total muscle mass. In this study, we investigated the effect of oral creatine monohydrate supplementation on cross-sectional area of type I, IIA and IIB fibers of gastrocnemius, extensor digitorum longus - EDL and soleus muscles from male Wistar rats subjected to swimming training for 33 days. Four groups were set up: sedentary with no supplementation (CON), sedentary with creatine supplementation (3.3 mg creatine per g chow) (CR), exercised with no supplementation (EX) and exercised with supplementation (CREX). The rats performed in a special swimming pool and swam five times a week for 1 hour each day, with a extra lead weight corresponding to 15% of their body weight. At the end of 33 days, skeletal muscles of the animals were dissected and the samples got immediately frozen using liquid nitrogen. Muscle samples were allocated to slices of 10 μm by a cryostat at -20°C, which was followed by histochemical analysis in order to identify fiber types of the muscles, and morphometrical analysis to calculate the muscle fiber areas. All groups gained body weight at the end of 33 days but there was no statistical difference among them. The EX and CREX rats had a larger food intake than the sedentary groups (CON and CR), and the CREX group had a larger food intake than CR rats. The cross-sectional area of type I and IIA fibers of the soleus muscle, type IIA and IIB fibers of EDL muscle and type IIA and IIB fibers of the white portion of gastrocnemius muscle were greater in the EX and CREX groups in comparison to sedentary rats. In addition, these fibers were greater in the CREX rats than in the EX group. There was no change in the cross sectional area of type I fibers in EDL muscle among all groups studied. Our results suggest that creatine supplementation enhances the exercise related muscle fiber hypertrophy in rodents. PMID:24701129

Constraints on the Progenitor System of SN 2016gkg from a Comprehensive Statistical Analysis

NASA Astrophysics Data System (ADS)

Sravan, Niharika; Marchant, Pablo; Kalogera, Vassiliki; Margutti, Raffaella

2018-01-01

Type IIb supernovae (SNe) present a unique opportunity for understanding the progenitors of stripped-envelope SNe because the stellar progenitor of several SNe IIb have been identified in pre-explosion images. In this paper, we use Bayesian inference and a large grid of non-rotating solar-metallicity single and binary stellar models to derive the associated probability distributions of single and binary progenitors of the SN IIb 2016gkg using existing observational constraints. We find that potential binary star progenitors have smaller pre-SN hydrogen-envelope and helium-core masses than potential single-star progenitors typically by 0.1 M ⊙ and 2 M ⊙, respectively. We find that, a binary companion, if present, is a main-sequence or red-giant star. Apart from this, we do not find strong constraints on the nature of the companion star. We demonstrate that the range of progenitor helium-core mass inferred from observations could help improve constraints on the progenitor. We find that the probability that the progenitor of SN 2016gkg was a binary is 22% when we use constraints only on the progenitor luminosity and effective temperature. Imposing the range of pre-SN progenitor hydrogen-envelope mass and radius inferred from SN light curves, the probability that the progenitor is a binary increases to 44%. However, there is no clear preference for a binary progenitor. This is in contrast to binaries being the currently favored formation channel for SNe IIb. Our analysis demonstrates the importance of statistical inference methods to constrain progenitor channels.

Disease Burden of Invasive Listeriosis and Molecular Characterization of Clinical Isolates in Taiwan, 2000-2013.

PubMed

Huang, Yu-Tsung; Ko, Wen-Chien; Chan, Yu-Jiun; Lu, Jang-Jih; Tsai, Hsih-Yeh; Liao, Chun-Hsing; Sheng, Wang-Huei; Teng, Lee-Jene; Hsueh, Po-Ren

2015-01-01

The information about disease burden and epidemiology of invasive listeriosis in Asia is scarce. From 2000 to 2013, a total of 338 patients with invasive listeriosis (bacteremia, meningitis, and peritonitis) were treated at four medical centers in Taiwan. The incidence (per 10,000 admissions) of invasive listeriosis increased significantly during the 14-year period among the four centers (0.15 in 2000 and >1.25 during 2010-2012) and at each of the four medical centers. Among these patients, 45.9% were elderly (>65 years old) and 3.3% were less than one year of age. More than one-third (36.7%) of the patients acquired invasive listeriosis in the spring (April to June). Among the 132 preserved Listeria monocytogenes isolates analyzed, the most frequently isolated PCR serogroup-sequence type (ST) was IIb-ST87 (23.5%), followed by IIa-ST378 (19.7%) and IIa-ST155 (12.1%). Isolation of PCR serogroups IIb and IVb increased significantly with year, with a predominance of IIb-ST87 isolates (23.5%) and IIb-ST 228 isolates emerging in 2013. A total of 12 different randomly amplified polymorphic DNA (RAPD) patterns (Patterns I to XII) were identified among the 112 L. monocytogenes isolates belonging to eight main PCR serogroup-STs. Identical RAPD patterns were found among the isolates exhibiting the same PCR serogroup-ST. In conclusion, our study revealed that during 2000-2013, listeriosis at four medical centers in Taiwan was caused by heterogeneous strains and that the upsurge in incidence beginning in 2005 was caused by at least two predominant clones.

Muscle mechanics: adaptations with exercise-training.

PubMed

Fitts, R H; Widrick, J J

1996-01-01

Based on the MHC isoform pattern, adult mammalian limb skeletal muscles contain two and, in some species, three types of fast fibers (Type IIa, IIx, and IIb), and one slow fiber (Type I). Slow muscles, such as the soleus, contain primarily the slow Type I fiber, whereas fast-twitch muscles are composed primarily of a mixture of the fast myosin isozymes. Force generation involves cross-bridge interaction and transition from a weakly bound, low-force state (AM-ADP-P(i)) to the strongly bound, high-force state (AM-ADP). This transition is thought to be rate limiting in terms of dP/dt, and the high-force state is the dominant cross-bridge form during a peak isometric contraction. Intact fast and slow skeletal muscles generate approximately the same amount of peak force (Po) of between 200 and 250 kN.m-2. However, the rate of transition from the low- to high-force state shows Ca2+ sensitivity and is 7-fold higher in fast-twitch, as compared to slow-twitch, skeletal muscle fibers. Fiber Vo or the maximal cross-bridge cycle rate is highly correlated with and thought to be dependent on the specific activity of the myosin or myofibrillar ATPase. The hierarchy for Vo is the Type IIb > IIx > IIa > I. This functional difference for the fast fiber types explains the higher Vo observed in the predominantly Type IIb SVL vs. the mixed fast Type IIa and IIb EDL muscle. A plot of Vo vs. species size demonstrates that an inverse relationship exists between Vo and body mass. From the standpoint of work capacity, the important property is power output. An analysis of individual muscles indicates that peak power is obtained at loads considerably below 50% of Po. Individuals with a high percentage of fast-twitch fibers generate a greater torque and higher power at a given velocity than those with predominantly slow-twitch fibers. In humans, mean peak power occurred in a ratio of 10:5:1 for the Type IIb, IIa, and I fibers. The in vivo measurement of the torque-velocity relationship and Vmax in human muscle is difficult because of limitations inherent in the equipment used and the inability to study the large limb muscles independently. Nevertheless, the in vivo torque-velocity relationships are similar to those measured in vitro in animals. This observation suggests that little central nervous system inhibition exists and that healthy subjects are able to achieve maximal activation of their muscles. Although peak isometric tension is not dependent on fiber type distribution, a positive correlation exists between the percentage of fast fibers and peak torque output at moderate-to-high angular isokinetic velocities. Consequently, peak power output is substantially greater in subjects possessing a predominance of fast fibers. The mechanical properties of slow and fast muscles do adapt to programs of regular exercise. Endurance exercise training has been shown to increase the Vo of the slow soleus by 20%. This increase could have been caused by either a small increase in all, or most, of the fibers, or to a conversion of a few fibers from slow to fast. Recently, the increase was shown to be caused by the former, as the individual slow Type I fibers of the soleus showed a 20% increase in Vo, but there was little or no change in the percentage of fast fibers. The increased Vo was correlated with, and likely caused by, an increased fiber ATPase. We hypothesize that the increased ATPase and cross-bridge cycling speed might be attributable to an increased expression of fast MLCs in the slow Type I fibers (Fig. 14.10). This hypothesis is based on the fact that light chains have been shown to be involved in the power stroke, and removal of light chains depresses force and velocity. Regular endurance exercise training had no effect on fiber size, but with prolonged durations of daily training it depressed Po and peak power. When the training is maintained over prolonged periods, it may even induce atrophy of the slow Type I and fast Type IIa fibers. (ABSTRACT TRUNCATED)

Morphometry, ultrastructure, myosin isoforms, and metabolic capacities of the "mini muscles" favoured by selection for high activity in house mice.

PubMed

Guderley, Helga; Houle-Leroy, Philippe; Diffee, Gary M; Camp, Dana M; Garland, Theodore

2006-07-01

Prolonged selective breeding of mice (Mus musculus) for high levels of voluntary wheel running has favoured an unusual phenotype ("mini muscles"), apparently caused by a single Mendelian recessive allele, in which most hind-limb muscles are markedly reduced in mass, but have increased mass-specific activities of mitochondrial enzymes. We examined whether these changes reflect changes in fibre size, number or ultrastructure in normal and "mini-muscle" mice within the two (of four) selectively bred lines (lab designations L3 and L6) that exhibit the phenotype at generations 26 and 27. In both lines, the gastrocnemius and plantaris muscles are smaller in mass (by >50% and 20%, respectively) in affected individuals. The mass-specific activities of mitochondrial enzymes in the gastrocnemius and plantaris muscles were increased in the mini phenotype in both lines, with stronger effects in the gastrocnemius muscle. In the gastrocnemius, the % myosin heavy chain (MHC) IIb was reduced by 50% in L3 and by 30% in L6, whereas the % MHC IIa and I were higher, particularly in L3. Fibre number in the plantaris muscle did not significantly differ between mini and normal muscles, although muscle mass was a significant positive correlate of fibre number. Small fibres were more abundant in mini than normal muscles in L3. Mitochondrial volume density was significantly higher in mini than normal muscle fibres in L3, but not in L6. Microscopy revealed a surprising attribute of the mini muscles: an abundance of small, minimally differentiated, myofibril-containing cells positioned in a disorderly fashion, particularly in the surface layer. We hypothesise that these unusual cells may be satellite cells or type IIb fibres that did not complete their differentiation. Together, these observations suggest that mice with the mini phenotype have reduced numbers of type IIb fibres in many of their hind-limb muscles, leading to a decrease in mass and an increase in mass-specific aerobic capacity in muscles that typically have a high proportion of type IIb fibres. Moreover, the several statistically significant interactions between muscle phenotype and line indicate that the effect of the underlying allele is altered by genetic background.

Constraining higher derivative supergravity with scattering amplitudes

DOE PAGES

Wang, Yifan; Yin, Xi

2015-08-31

We study supersymmetry constraints on higher derivative deformations of type IIB supergravity by consideration of superamplitudes. Thus, combining constraints of on-shell supervertices and basic results from string perturbation theory, we give a simple argument for the non-renormalization theorem of Green and Sethi, and some of its generalizations.

Integrin αIIbβ3

PubMed Central

Bledzka, Kamila; Smyth, Susan S.; Plow, Edward F.

2013-01-01

From the initial description of platelets in 1882, their propensity to aggregate and to contribute to thrombosis was apparent. Indeed, excessive platelet aggregation is associated with myocardial infarction and other thrombotic diseases whereas Glanzmann thrombasthenia, in which platelet aggregation is reduced, is a bleeding syndrome. Over the last half of the 20th century, many investigators have provided insights into the cellular and molecular basis for platelet aggregation. The major membrane protein on platelets, integrin αIIbβ3, mediates this response by rapidly transiting from its resting to an activated state in which it serves as a receptor for ligands that can bridge platelets together. Monoclonal antibodies, natural products, and small peptides were all shown to inhibit αIIbβ3 dependent platelet aggregation, and these inhibitors became the forerunners of antagonists that proceeded through preclinical testing and into large patient trials to treat acute coronary syndromes, particularly in the context of percutaneous coronary interventions. Three such αIIbβ3 antagonists, abciximab, eptifibatide, and tirofiban, received Food and Drug Administration approval. Over the past 15 years, millions of patients have been treated with these αIIbβ3 antagonists and many lives have been saved by their administration. With the side effect of increased bleeding and the development of new antithrombotic drugs, the use of αIIbβ3 antagonists is waning. Nevertheless, they are still widely used for the prevention of periprocedural thrombosis during percutaneous coronary interventions. This review focuses on the biology of αIIbβ3, the development of its antagonists, and some of the triumphs and shortcomings of αIIbβ3 antagonism. PMID:23580774

Integrin αIIbβ3 outside-in signaling

PubMed Central

2017-01-01

Integrin αIIbβ3 is a highly abundant heterodimeric platelet receptor that can transmit information bidirectionally across the plasma membrane, and plays a critical role in hemostasis and thrombosis. Upon platelet activation, inside-out signaling pathways increase the affinity of αIIbβ3 for fibrinogen and other ligands. Ligand binding and integrin clustering subsequently stimulate outside-in signaling, which initiates and amplifies a range of cellular events driving essential platelet processes such as spreading, thrombus consolidation, and clot retraction. Integrin αIIbβ3 has served as an excellent model for the study of integrin biology, and it has become clear that integrin outside-in signaling is highly complex and involves a vast array of enzymes, signaling adaptors, and cytoskeletal components. In this review, we provide a concise but comprehensive overview of αIIbβ3 outside-in signaling, focusing on the key players involved, and how they cooperate to orchestrate this critical aspect of platelet biology. We also discuss gaps in the current understanding of αIIbβ3 outside-in signaling and highlight avenues for future investigation. PMID:28794070

Soluble activin receptor type IIB decoy receptor differentially impacts murine osteogenesis imperfecta muscle function.

PubMed

Jeong, Youngjae; Daghlas, Salah A; Kahveci, Alp S; Salamango, Daniel; Gentry, Bettina A; Brown, Marybeth; Rector, R Scott; Pearsall, R Scott; Phillips, Charlotte L

2018-02-01

Osteogenesis imperfecta (OI) is characterized by skeletal fragility and muscle weakness. In this study we investigated the effects of soluble activin type IIB receptor (sActRIIB-mFc) on muscle mass and function in 2 distinct mouse models of OI: osteogenesis imperfecta murine (oim) and +/G610C. Wild-type (WT), +/G610C, and oim/oim mice were treated from 2 to 4 months of age with Tris-buffered saline (vehicle) or sActRIIB-mFc and their hindlimb muscles evaluated for mass, morphology, and contractile function. sActRIIB-mFc-treated WT, +/G610C, and oim/oim mice had increased hindlimb muscle weights and myofiber cross-sectional area compared with vehicle-treated counterparts. sActRIIB-mFc-treated oim/oim mice also exhibited increased contractile function relative to vehicle-treated counterparts. Blocking endogenous ActRIIB was effective at increasing muscle size in mouse models of OI, and increasing contractile function in oim/oim mice. ActRIIB inhibitors may provide a potential mutation-specific therapeutic option for compromised muscle function in OI. Muscle Nerve 57: 294-304, 2018. © 2017 Wiley Periodicals, Inc.

[Diabetes mellitus and breast cancer. A retrospective follow-up study].

PubMed

Unterburger, P; Sinop, A; Noder, W; Berger, M R; Fink, M; Edler, L; Schmähl, D; Ehrhart, H

1990-02-01

The influence of diabetes mellitus on the course of breast cancer was investigated retrospectively in 752 patients. Possible unfavourable prognostic factors like overweight, lipid disorders, age and menopausal status were considered as confounders in a Cochran-Mantel-Haensel analysis. There was no difference in primary tumor status and lymph node involvement between patients with diabetes mellitus and nondiabetic patients. Diabetic patients had more often overweight, lipid disorders and were older than nondiabetic patients. Metastatic disease was highly significant correlated with primary tumor status (p less than 10(-6)) lymph node involvement (p less than 10(-10)) and diabetes mellitus (p less than 10(-5)). Overweight, lipid disorders, age and menopausal status were not correlated with metastatic disease. A possible explanation of the correlation between diabetes mellitus and metastatic disease could be hyperinsulinism in type IIB diabetes. A type IIB diabetes in most of the patients included in this study is very plausible because of the correlation between overweight, lipid disorders, old age and diabetes mellitus. This type of diabetes is characterised by a relative resistence to insulin in the target tissues and a prolonged and exceeding insulin secretion. Experimental data demonstrate that insulin stimulates the growth of breast cancer cell in vivo and in vitro.

Evidence for complexation of P-450 IIC6 by an orphenadrine metabolite.

PubMed

Reidy, G F; Murray, M

1990-01-30

Removal of the orphenadrine metabolite from its complex with rat liver P-450 IIB1 is associated with a discrepancy in the reactivation of IIB1 activity. Two possible explanations are that either (1) NADPH-P-450-reductase is inaccessible to the restored IIB1, or (2) complexation of other P-450s may occur. Exogenous P-450 reductase increased all pathways of steroid hydroxylation (1.9 to 3.6-fold) but did not enhance reactivation of IIB1-dependent steroid 16 beta-hydroxylation. Instead, P-450 IIC6-dependent progesterone 21-hydroxylase activity was increased after dissociation to 122% of control. IIC6 activity was also inhibited in vitro in microsomes from phenobarbital-induced rats (ki = 151 microM). Thus, orphenadrine appears to complex P-450 IIC6 as well as IIB1 in rat liver.

Synergistic effect of signaling from receptors of soluble platelet agonists and outside-in signaling in formation of a stable fibrinogen-integrin αIIbβ3-actin cytoskeleton complex.

PubMed

Budnik, Ivan; Shenkman, Boris; Savion, Naphtali

2015-01-01

Thrombus formation in the injured vessel wall is a highly complex process involving various blood-born components that go through specific temporal and spatial changes as observed by intravital videomicroscopy. Platelets bind transiently to the developing thrombus and may either become stably incorporated into or disengage from the thrombus. The aim of the present study was to reveal the processes involved in the formation of a stable thrombus. Platelet-rich plasma and washed platelets were studied by the aggregometer. The aggregate stability was challenged by eptifibatide. Platelet Triton-insoluble fraction was prepared and the actin and αIIb content in the cytoskeleton was analyzed by western blot. Maximal actin polymerization is achieved 1min after platelet activation while maximal αIIbβ3-actin cytoskeleton association requires 5 to 10min of activation and fibrinogen-mediated platelet-to-platelet bridging. Thus, actin polymerization is dependent on platelet activation and requires neither αIIbβ3 integrin occupation nor platelet aggregation. Formation of a stable aggregate requires platelet activation for more than 1min, complete increase in actin cytoskeleton fraction and partial association of αIIbβ3 with the actin cytoskeleton. However, direct αIIbβ3 activation is not sufficient for cytoskeleton complex formation. Thus, stable αIIbβ3-fibrinogen interaction, representing stable aggregate, is achieved after more than 1min agonist activation, involving inside-out and outside-in signaling but not after direct integrin activation, involving only outside-in signaling. Formation of a stable fibrinogen-αIIbβ3-actin cytoskeleton complex is the result of the combined effect of platelet stimulation by soluble agonists, activation of αIIbβ3, fibrinogen binding and platelet-to-platelet bridging. Copyright © 2014 Elsevier Ltd. All rights reserved.

αIIbβ3 variants defined by next-generation sequencing: Predicting variants likely to cause Glanzmann thrombasthenia

PubMed Central

Buitrago, Lorena; Rendon, Augusto; Liang, Yupu; Simeoni, Ilenia; Negri, Ana; Filizola, Marta; Ouwehand, Willem H.; Coller, Barry S.; Alessi, Marie-Christine; Ballmaier, Matthias; Bariana, Tadbir; Bellissimo, Daniel; Bertoli, Marta; Bray, Paul; Bury, Loredana; Carrell, Robin; Cattaneo, Marco; Collins, Peter; French, Deborah; Favier, Remi; Freson, Kathleen; Furie, Bruce; Germeshausen, Manuela; Ghevaert, Cedric; Gomez, Keith; Goodeve, Anne; Gresele, Paolo; Guerrero, Jose; Hampshire, Dan J.; Hadinnapola, Charaka; Heemskerk, Johan; Henskens, Yvonne; Hill, Marian; Hogg, Nancy; Johnsen, Jill; Kahr, Walter; Kerr, Ron; Kunishima, Shinji; Laffan, Michael; Natwani, Amit; Neerman-Arbez, Marguerite; Nurden, Paquita; Nurden, Alan; Ormiston, Mark; Othman, Maha; Ouwehand, Willem; Perry, David; Vilk, Shoshana Ravel; Reitsma, Pieter; Rondina, Matthew; Simeoni, Ilenia; Smethurst, Peter; Stephens, Jonathan; Stevenson, William; Szkotak, Artur; Turro, Ernest; Van Geet, Christel; Vries, Minka; Ward, June; Waye, John; Westbury, Sarah; Whiteheart, Sidney; Wilcox, David; Zhang, Bi

2015-01-01

Next-generation sequencing is transforming our understanding of human genetic variation but assessing the functional impact of novel variants presents challenges. We analyzed missense variants in the integrin αIIbβ3 receptor subunit genes ITGA2B and ITGB3 identified by whole-exome or -genome sequencing in the ThromboGenomics project, comprising ∼32,000 alleles from 16,108 individuals. We analyzed the results in comparison with 111 missense variants in these genes previously reported as being associated with Glanzmann thrombasthenia (GT), 20 associated with alloimmune thrombocytopenia, and 5 associated with aniso/macrothrombocytopenia. We identified 114 novel missense variants in ITGA2B (affecting ∼11% of the amino acids) and 68 novel missense variants in ITGB3 (affecting ∼9% of the amino acids). Of the variants, 96% had minor allele frequencies (MAF) < 0.1%, indicating their rarity. Based on sequence conservation, MAF, and location on a complete model of αIIbβ3, we selected three novel variants that affect amino acids previously associated with GT for expression in HEK293 cells. αIIb P176H and β3 C547G severely reduced αIIbβ3 expression, whereas αIIb P943A partially reduced αIIbβ3 expression and had no effect on fibrinogen binding. We used receiver operating characteristic curves of combined annotation-dependent depletion, Polyphen 2-HDIV, and sorting intolerant from tolerant to estimate the percentage of novel variants likely to be deleterious. At optimal cut-off values, which had 69–98% sensitivity in detecting GT mutations, between 27% and 71% of the novel αIIb or β3 missense variants were predicted to be deleterious. Our data have implications for understanding the evolutionary pressure on αIIbβ3 and highlight the challenges in predicting the clinical significance of novel missense variants. PMID:25827233

Structure-guided design of a high-affinity platelet integrin αIIbβ3 receptor antagonist that disrupts Mg²⁺ binding to the MIDAS.

PubMed

Zhu, Jieqing; Choi, Won-Seok; McCoy, Joshua G; Negri, Ana; Zhu, Jianghai; Naini, Sarasija; Li, Jihong; Shen, Min; Huang, Wenwei; Bougie, Daniel; Rasmussen, Mark; Aster, Richard; Thomas, Craig J; Filizola, Marta; Springer, Timothy A; Coller, Barry S

2012-03-14

An integrin found on platelets, α(IIb)β(3) mediates platelet aggregation, and α(IIb)β(3) antagonists are effective antithrombotic agents in the clinic. Ligands bind to integrins in part by coordinating a magnesium ion (Mg(2+)) located in the β subunit metal ion-dependent adhesion site (MIDAS). Drugs patterned on the integrin ligand sequence Arg-Gly-Asp have a basic moiety that binds the α(IIb) subunit and a carboxyl group that coordinates the MIDAS Mg(2+) in the β(3) subunits. They induce conformational changes in the β(3) subunit that may have negative consequences such as exposing previously hidden epitopes and inducing the active conformation of the receptor. We recently reported an inhibitor of α(IIb)β(3) (RUC-1) that binds exclusively to the α(IIb) subunit; here, we report the structure-based design and synthesis of RUC-2, a RUC-1 derivative with a ~100-fold higher affinity. RUC-2 does not induce major conformational changes in β(3) as judged by monoclonal antibody binding, light scattering, gel chromatography, electron microscopy, and a receptor priming assay. X-ray crystallography of the RUC-2-α(IIb)β(3) headpiece complex in 1 mM calcium ion (Ca(2+))/5 mM Mg(2+) at 2.6 Å revealed that RUC-2 binds to α(IIb) the way RUC-1 does, but in addition, it binds to the β(3) MIDAS residue glutamic acid 220, thus displacing Mg(2+) from the MIDAS. When the Mg(2+) concentration was increased to 20 mM, however, Mg(2+) was identified in the MIDAS and RUC-2 was absent. RUC-2's ability to inhibit ligand binding and platelet aggregation was diminished by increasing the Mg(2+) concentration. Thus, RUC-2 inhibits ligand binding by a mechanism different from that of all other α(IIb)β(3) antagonists and may offer advantages as a therapeutic agent.

Effects of muscle fiber type on glycolytic potential and meat quality traits in different Tibetan pig muscles and their association with glycolysis-related gene expression.

PubMed

Shen, L Y; Luo, J; Lei, H G; Jiang, Y Z; Bai, L; Li, M Z; Tang, G Q; Li, X W; Zhang, S H; Zhu, L

2015-11-13

The myosin heavy chain (MyHC) composition, glycolytic potential, mitochondrial content, and gene expression related to energy metabolism were analyzed in eight muscles from Tibetan pigs, to study how meat quality develops in different muscle tissues. The muscles were classified into three clusters, based on MyHC composition: masseter, trapezius, and latissimus dorsi as 'slow-oxidative-type'; psoas major and semimembranosus as 'intermediate-type'; and longissimus dorsi, obliquus externus abdominis, and semitendinosus as 'fast-glycolytic-type'. The 'slow-oxidative-type' muscles had the highest MyHC I and MyHC IIA content (P < 0.01); 'intermediate-type' muscles, the highest MyHC IIx content (P < 0.01); and 'fast-glycolytic-type' muscles, the highest MyHC IIb content (P < 0.01). The pH values measured in 'slow-oxidative-type' muscles were higher than those in the other clusters were; however, the color of 'fast-glycolytic-type' muscles was palest (P < 0.01). Mitochondrial content increased in the order: fast-glycolytic-type < intermediate-type < slow-oxidative-type. In the 'slow-oxidative-type' muscles, the expression levels of genes related to ATP synthesis were higher, but were lower for those related to glycogen synthesis and glycolysis. Mitochondrial content was significantly positively correlated with MyHC I content, but negatively correlated with MyHC IIb content. MyHC I and mitochondrial content were both negatively correlated with glycolytic potential. Overall, muscles used frequently in exercise had a higher proportion of type I fibers. 'Slow-oxidative-type' muscles, rich in type I fibers with higher mitochondrial and lower glycogen and glucose contents, had a higher ATP synthesis efficiency and lower glycolytic capacity, which contributed to their superior meat quality.

Regulation of an antisense RNA with the transition of neonatal to IIb myosin heavy chain during postnatal development and hypothyroidism in rat skeletal muscle

PubMed Central

Jiang, Weihua; Qin, Anqi X.; Bodell, Paul W.; Baldwin, Kenneth M.; Haddad, Fadia

2012-01-01

Postnatal development of fast skeletal muscle is characterized by a transition in expression of myosin heavy chain (MHC) isoforms, from primarily neonatal MHC at birth to primarily IIb MHC in adults, in a tightly coordinated manner. These isoforms are encoded by distinct genes, which are separated by ∼17 kb on rat chromosome 10. The neonatal-to-IIb MHC transition is inhibited by a hypothyroid state. We examined RNA products [mRNA, pre-mRNA, and natural antisense transcript (NAT)] of developmental and adult-expressed MHC genes (embryonic, neonatal, I, IIa, IIx, and IIb) at 2, 10, 20, and 40 days after birth in normal and thyroid-deficient rat neonates treated with propylthiouracil. We found that a long noncoding antisense-oriented RNA transcript, termed bII NAT, is transcribed from a site within the IIb-Neo intergenic region and across most of the IIb MHC gene. NATs have previously been shown to mediate transcriptional repression of sense-oriented counterparts. The bII NAT is transcriptionally regulated during postnatal development and in response to hypothyroidism. Evidence for a regulatory mechanism is suggested by an inverse relationship between IIb MHC and bII NAT in normal and hypothyroid-treated muscle. Neonatal MHC transcription is coordinately expressed with bII NAT. A comparative phylogenetic analysis also suggests that bII NAT-mediated regulation has been a conserved trait of placental mammals for most of the eutherian evolutionary history. The evidence in support of the regulatory model implicates long noncoding antisense RNA as a mechanism to coordinate the transition between neonatal and IIb MHC during postnatal development. PMID:22262309

Regulation of an antisense RNA with the transition of neonatal to IIb myosin heavy chain during postnatal development and hypothyroidism in rat skeletal muscle.

PubMed

Pandorf, Clay E; Jiang, Weihua; Qin, Anqi X; Bodell, Paul W; Baldwin, Kenneth M; Haddad, Fadia

2012-04-01

Postnatal development of fast skeletal muscle is characterized by a transition in expression of myosin heavy chain (MHC) isoforms, from primarily neonatal MHC at birth to primarily IIb MHC in adults, in a tightly coordinated manner. These isoforms are encoded by distinct genes, which are separated by ∼17 kb on rat chromosome 10. The neonatal-to-IIb MHC transition is inhibited by a hypothyroid state. We examined RNA products [mRNA, pre-mRNA, and natural antisense transcript (NAT)] of developmental and adult-expressed MHC genes (embryonic, neonatal, I, IIa, IIx, and IIb) at 2, 10, 20, and 40 days after birth in normal and thyroid-deficient rat neonates treated with propylthiouracil. We found that a long noncoding antisense-oriented RNA transcript, termed bII NAT, is transcribed from a site within the IIb-Neo intergenic region and across most of the IIb MHC gene. NATs have previously been shown to mediate transcriptional repression of sense-oriented counterparts. The bII NAT is transcriptionally regulated during postnatal development and in response to hypothyroidism. Evidence for a regulatory mechanism is suggested by an inverse relationship between IIb MHC and bII NAT in normal and hypothyroid-treated muscle. Neonatal MHC transcription is coordinately expressed with bII NAT. A comparative phylogenetic analysis also suggests that bII NAT-mediated regulation has been a conserved trait of placental mammals for most of the eutherian evolutionary history. The evidence in support of the regulatory model implicates long noncoding antisense RNA as a mechanism to coordinate the transition between neonatal and IIb MHC during postnatal development.

Multi-Step Fibrinogen Binding to the Integrin αIIbβ3 Detected Using Force Spectroscopy

PubMed Central

Litvinov, Rustem I.; Bennett, Joel S.; Weisel, John W.; Shuman, Henry

2005-01-01

The regulated ability of integrin αIIbβ3 to bind fibrinogen plays a crucial role in platelet aggregation and hemostasis. We have developed a model system based on laser tweezers, enabling us to measure specific rupture forces needed to separate single receptor-ligand complexes. First of all, we performed a thorough and statistically representative analysis of nonspecific protein-protein binding versus specific αIIbβ3-fibrinogen interactions in combination with experimental evidence for single-molecule measurements. The rupture force distribution of purified αIIbβ3 and fibrinogen, covalently attached to underlying surfaces, ranged from ∼20 to 150 pN. This distribution could be fit with a sum of an exponential curve for weak to moderate (20–60 pN) forces, and a Gaussian curve for strong (>60 pN) rupture forces that peaked at 80–90 pN. The interactions corresponding to these rupture force regimes differed in their susceptibility to αIIbβ3 antagonists or Mn2+, an αIIbβ3 activator. Varying the surface density of fibrinogen changed the total binding probability linearly >3.5-fold but did not affect the shape of the rupture force distribution, indicating that the measurements represent single-molecule binding. The yield strength of αIIbβ3-fibrinogen interactions was independent of the loading rate (160–16,000 pN/s), whereas their binding probability markedly correlated with the duration of contact. The aggregate of data provides evidence for complex multi-step binding/unbinding pathways of αIIbβ3 and fibrinogen revealed at the single-molecule level. PMID:16040750

Relationship of angiotensin I-converting enzyme (ACE) and bradykinin B2 receptor (BDKRB2) polymorphism with diabetic nephropathy.

PubMed

Zou, Honghong; Wu, Guoqing; Lv, Jinlei; Xu, Gaosi

2017-06-01

To determine whether ACE 2 I/D and BDKRB2 3 +9/-9 polymorphism causatively affect diabetic nephropathy progression RESULTS: STZ-induced metabolic disorder, as well as inflammatory responses, was significantly aggravated in ACE II-B2R 4 +9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp diabetic mice but not ACE II-B2R-9bp, indicating the genetic susceptibility of ACE DD or B2R+9bp to diabetic nephropathy. Furthermore, ACE II-B2R+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp rather than ACE II-B2R-9bp, worsened renal performance and enhanced pathological alterations induced by STZ. Markedly elevated monocyte chemoattractant protein-1(MCP-1), podocin, osteopontin (OPN), transforming growth factor-β1 (TGF-β1), and reduced nephrin, podocin were also detected both in diabetic mice and podocytes under hyperglycemic conditions in response to ACE II-B2R+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp, versus ACE II-B2R-9bp. In addition, high glucose-induced mitochondrial oxidative stress and cell apoptosis were observably increased in response to ACE II-B2R+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp but not ACE II-B2R-9bp. We provide first evidence indicating the causation between ACE DD or B2R+9bp genotype and the increased risk for diabetic nephropathy, broadening our horizon about the role of genetic modulators in this disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Disease Burden of Invasive Listeriosis and Molecular Characterization of Clinical Isolates in Taiwan, 2000-2013

PubMed Central

Huang, Yu-Tsung; Ko, Wen-Chien; Chan, Yu-Jiun; Lu, Jang-Jih; Tsai, Hsih-Yeh; Liao, Chun-Hsing; Sheng, Wang-Huei; Teng, Lee-Jene; Hsueh, Po-Ren

2015-01-01

The information about disease burden and epidemiology of invasive listeriosis in Asia is scarce. From 2000 to 2013, a total of 338 patients with invasive listeriosis (bacteremia, meningitis, and peritonitis) were treated at four medical centers in Taiwan. The incidence (per 10,000 admissions) of invasive listeriosis increased significantly during the 14-year period among the four centers (0.15 in 2000 and >1.25 during 2010–2012) and at each of the four medical centers. Among these patients, 45.9% were elderly (>65 years old) and 3.3% were less than one year of age. More than one-third (36.7%) of the patients acquired invasive listeriosis in the spring (April to June). Among the 132 preserved Listeria monocytogenes isolates analyzed, the most frequently isolated PCR serogroup-sequence type (ST) was IIb-ST87 (23.5%), followed by IIa-ST378 (19.7%) and IIa-ST155 (12.1%). Isolation of PCR serogroups IIb and IVb increased significantly with year, with a predominance of IIb-ST87 isolates (23.5%) and IIb-ST 228 isolates emerging in 2013. A total of 12 different randomly amplified polymorphic DNA (RAPD) patterns (Patterns I to XII) were identified among the 112 L. monocytogenes isolates belonging to eight main PCR serogroup-STs. Identical RAPD patterns were found among the isolates exhibiting the same PCR serogroup-ST. In conclusion, our study revealed that during 2000–2013, listeriosis at four medical centers in Taiwan was caused by heterogeneous strains and that the upsurge in incidence beginning in 2005 was caused by at least two predominant clones. PMID:26555445

The He-rich stripped-envelope core-collapse supernova 2008ax

NASA Astrophysics Data System (ADS)

Taubenberger, S.; Navasardyan, H.; Maurer, J. I.; Zampieri, L.; Chugai, N. N.; Benetti, S.; Agnoletto, I.; Bufano, F.; Elias-Rosa, N.; Turatto, M.; Patat, F.; Cappellaro, E.; Mazzali, P. A.; Iijima, T.; Valenti, S.; Harutyunyan, A.; Claudi, R.; Dolci, M.

2011-05-01

Extensive optical and near-infrared (NIR) observations of the Type IIb supernova (SN IIb) 2008ax are presented, covering the first year after the explosion. The light curve is mostly similar in shape to that of the prototypical SN IIb 1993J, but shows a slightly faster decline rate at late phases and lacks the prominent narrow early-time peak of SN 1993J. From the bolometric light curve and ejecta expansion velocities, we estimate that about 0.07-0.15 M⊙ of 56Ni was produced during the explosion and that the total ejecta mass was between 2 and 5 M⊙, with a kinetic energy of at least 1051 erg. The spectral evolution of SN 2008ax is similar to that of SN Ib/IIb 2007Y, exhibiting high-velocity Ca II features at early phases and signs of ejecta-wind interaction from Hα observations at late times. NIR spectra show strong He I lines similar to SN Ib 1999ex and a large number of emission features at late times. Particularly interesting are the strong, double-peaked He I lines in late NIR spectra, which - together with the double-peaked [O I] emission in late optical spectra - provide clues for the asymmetry and large-scale Ni mixing in the ejecta. a Phase in days with respect to the explosion date (JD =245 4528.80 ± 0.15). B-band maximum light occurred on day 18.3. b Average seeing in arcsec over all filter bands. c CAFOS = Calar Alto 2.2m Telescope + CAFOS; DOLORES = 3.58m Telescopio Nazionale Galileo + DOLORES; AFOSC = Asiago 1.82m Copernico Telescope + AFOSC.

Effects of Calorie Restriction and Fiber Type on Glucose Uptake and Abundance of Electron Transport Chain and Oxidative Phosphorylation Proteins in Single Fibers from Old Rats.

PubMed

Wang, Haiyan; Arias, Edward B; Yu, Carmen S; Verkerke, Anthony R P; Cartee, Gregory D

2017-11-09

Calorie restriction (CR; reducing calorie intake by ~40% below ad libitum) can increase glucose uptake by insulin-stimulated muscle. Because skeletal muscle is comprised of multiple, heterogeneous fiber types, our primary aim was to determine the effects of CR (initiated at 14 weeks old) and fiber type on insulin-stimulated glucose uptake by single fibers of diverse fiber types in 23-26-month-old rats. Isolated epitrochlearis muscles from AL and CR rats were incubated with [3H]-2-deoxyglucose ± insulin. Glucose uptake and fiber type were determined for single fibers dissected from the muscles. We also determined CR-effects on abundance of several key metabolic proteins in single fibers. CR resulted in: (a) significantly (p < .05 to .001) greater glucose uptake by insulin-stimulated type I, IIA, IIB, IIBX, and IIX fibers; (b) significantly (p < .05 to .001) reduced abundance of several mitochondrial electron transport chain (ETC) and oxidative phosphorylation (OxPhos) proteins in type I, IIA, and IIBX but not IIB and IIX fibers; and (c) unaltered hexokinase II abundance in each fiber type. These results demonstrate that CR can enhance glucose uptake in each fiber type of rat skeletal muscle in the absence of upregulation of the abundance of hexokinase II or key mitochondrial ETC and OxPhos proteins. © The Author 2017. 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.

Endoscopic agger nasi type Draf IIb treatment for frontal sinus lesions.

PubMed

Shi, Linggai; Liu, Jun; Ma, Jiqing; Liu, Fei; Wang, Guangke

2016-09-01

Treatment of frontal sinus using surgery is complicated owing to the complex anatomical structure of the sinus region. The aim of the present study was to investigate the efficacy and safety of Draf IIb endoscopic frontal sinus surgery treatment for frontal sinus lesions using the agger nasi approach on 19 patients (28 left or and right nasal cavities). A 10-12 mm excision of the upper frontal maxilla was performed for endoscopic resection between the middle turbinate and lateral nasal wall. No serious complications in frontal sinus surgery treatment for the removal of the frontal sinus were observed. Patients were followed up after surgery for 6-36 months. Chronic sinusitis and nasal polyps were identified in 10 cases (19 left or and right nasal cavities; disease control, 15 left or and right nasal cavities; and disease partial control, 4 left or and right nasal cavities). Frontal sinus inverted papilloma was observed in 9 cases (9 left or and right nasal cavities). Frontal sinus inverted papilloma were successfully treated in 8 cases, and 1 case of recurrence was observed. In conclusion, the nasal endoscopic Draf IIb agger nasi approach is a minimally invasive treatment for frontal sinus lesions. This surgical procedure is safe and less complicated and may be applied in the clinic.

Arsenate transport by sodium/phosphate cotransporter type IIb

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

Villa-Bellosta, Ricardo, E-mail: rvilla@unizar.e; Sorribas, Victor, E-mail: sorribas@unizar.e

2010-08-15

Arsenic is a metalloid that causes the dysfunction of critical enzymes, oxidative stress, and malignancies. In recent years several transporters of As{sup III} have been identified, including aquaglyceroporins (AQP) and multidrug resistance proteins (MRP). As{sup V} transport, however, has not been sufficiently studied because it has been assumed that arsenate is taken up by mammalian cells through inorganic phosphate (Pi) transporters. In this paper we have analyzed the role of Pi transporters in the uptake of arsenate by directly using {sup 73}As{sup V} as a radiotracer in phosphate transporter-expressing Xenopus laevis oocytes. The affinities of Pi transporters for H{sub 3}AsO{submore » 4} were lower than the affinities for Pi. NaPiIIa, NaPiIIc, Pit1, and Pit2 showed a K{sub m} for arsenate that was > 1 mM (i.e., at least ten times lower than the affinities for Pi). The NaPiIIb isoform showed the highest affinity for As{sup V} in mouse (57 {mu}M), rat (51 {mu}M), and human (9.7 {mu}M), which are very similar to the affinities for Pi. Therefore, NaPiIIb can have a prominent role in the toxicokinetics of arsenic following oral exposure to freshwater or food contaminated with As{sup V}.« less

Chemical surface deposition of ultra-thin semiconductors

DOEpatents

McCandless, Brian E.; Shafarman, William N.

2003-03-25

A chemical surface deposition process for forming an ultra-thin semiconducting film of Group IIB-VIA compounds onto a substrate. This process eliminates particulates formed by homogeneous reactions in bath, dramatically increases the utilization of Group IIB species, and results in the formation of a dense, adherent film for thin film solar cells. The process involves applying a pre-mixed liquid coating composition containing Group IIB and Group VIA ionic species onto a preheated substrate. Heat from the substrate causes a heterogeneous reaction between the Group IIB and VIA ionic species of the liquid coating composition, thus forming a solid reaction product film on the substrate surface.

A critical role for topoisomerase IIb and DNA double strand breaks in transcription

PubMed Central

Calderwood, Stuart K.

2016-01-01

ABSTRACT Recent studies have indicated a novel role for topoisomerase IIb in transcription. Transcription of heat shock genes, serum-induced immediate early genes and nuclear receptor-activated genes, each required DNA double strands generated by topoisomerase IIb. Such strand breaks seemed both necessary and sufficient for transcriptional activation. In addition, such transcription was associated with initiation of the DNA damage response pathways, including the activation of the enzymes: ataxia-telangiectasia mutated (ATM), DNA-dependent protein kinase and poly (ADP ribose) polymerase 1. DNA damage response signaling was involved both in transcription and in repair of DNA breaks generated by topoisomerase IIb. PMID:27100743

A critical role for topoisomerase IIb and DNA double strand breaks in transcription.

PubMed

Calderwood, Stuart K

2016-05-26

Recent studies have indicated a novel role for topoisomerase IIb in transcription. Transcription of heat shock genes, serum-induced immediate early genes and nuclear receptor-activated genes, each required DNA double strands generated by topoisomerase IIb. Such strand breaks seemed both necessary and sufficient for transcriptional activation. In addition, such transcription was associated with initiation of the DNA damage response pathways, including the activation of the enzymes: ataxia-telangiectasia mutated (ATM), DNA-dependent protein kinase and poly (ADP ribose) polymerase 1. DNA damage response signaling was involved both in transcription and in repair of DNA breaks generated by topoisomerase IIb.

Elective neck dissection for primary oral cavity squamous cell carcinoma involving the tongue should include sublevel IIb.

PubMed

Maher, Nigel Gordon; Hoffman, Gary Russell

2014-11-01

The surgical clearance of sublevel IIb lymph nodes, facilitated by neck dissection, increases the risk of postoperative shoulder dysfunction. Our study purpose was to determine the value of including sublevel IIb in elective neck dissections for primary oral cavity squamous cell carcinoma (OCSCC). A retrospective cohort study based on a review of the pathology records accumulated by 1 head and neck surgeon was conducted for 71 patients with clinically node-negative, primary OCSCC treated from 2006 to June 2013. The predictor variables were the oral cavity subsite and tumor clinicopathologic characteristics (ie, perineural, perivascular, and perilymphatic invasion, tumor depth, and T stage). The primary outcome variable was the presence of sublevel IIb metastasis. The secondary outcome variables were the survival and tumor recurrence rates and metastases to any cervical level. Descriptive statistics were calculated for the categorical and continuous variables. A comparison of categorical variables was performed using Fisher's exact test; for continuous variables, t tests or the Mann-Whitney U test were used for 2 groups and analysis of variance or Kruskal-Wallis tests (with Bonferroni's correction) were used for more than 2 groups, depending on the distribution. Disease-specific survival (DSS) analyses were plotted for the predictor variables and patients with sublevel IIb metastasis. Competing risks models were created using the Fine and Gray method (SAS macro %PSHREG) to provide estimates of the crude and adjusted subhazard ratios for DSS for all variables. A total of 71 patients were included in the present study, of whom 69% were male. The greatest proportion of oral cavity subsites was from the tongue and floor of mouth. The overall frequency of sublevel IIb lymphatic metastases at neck dissection was 5.6% of the patient cohort. Sublevel IIb metastases occurred from the primary sites involving the tongue (n = 3) and retromolar trigone (n = 1). The incidence of perilymphatic and perivascular invasion was significantly associated with sublevel IIb lymphatic metastases (P < .02). Sublevel IIb is likely to be an important region to incorporate in elective neck dissections for primary OCSCC involving the tongue. More studies are needed, with greater numbers, to clarify the risk of metastasis to sublevel IIb from oral cavity subsites in primary OCSCC with clinically node-negative necks. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

76 FR 28265 - Solicitation of Comment To Assist in Study on Assigned Credit Ratings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-16

... Commission requests, in Section II.B, that interested parties address these matters through a series of... in rating structured finance products. For example, in what ways, if any, does the issuer... structured finance products? For example, do certain types of structured finance products account for a...

Power-law expansion of the Universe from the bosonic Lorentzian type IIB matrix model

NASA Astrophysics Data System (ADS)

Ito, Yuta; Nishimura, Jun; Tsuchiya, Asato

2015-11-01

Recent studies on the Lorentzian version of the type IIB matrix model show that (3+1)D expanding universe emerges dynamically from (9+1)D space-time predicted by superstring theory. Here we study a bosonic matrix model obtained by omitting the fermionic matrices. With the adopted simplification and the usage of a large-scale parallel computer, we are able to perform Monte Carlo calculations with matrix size up to N = 512, which is twenty times larger than that used previously for the studies of the original model. When the matrix size is larger than some critical value N c ≃ 110, we find that (3+1)D expanding universe emerges dynamically with a clear large- N scaling property. Furthermore, the observed increase of the spatial extent with time t at sufficiently late times is consistent with a power-law behavior t 1/2, which is reminiscent of the expanding behavior of the Friedmann-Robertson-Walker universe in the radiation dominated era. We discuss possible implications of this result on the original supersymmetric model including fermionic matrices.

Realizing three generations of the Standard Model fermions in the type IIB matrix model

NASA Astrophysics Data System (ADS)

Aoki, Hajime; Nishimura, Jun; Tsuchiya, Asato

2014-05-01

We discuss how the Standard Model particles appear from the type IIB matrix model, which is considered to be a nonperturbative formulation of superstring theory. In particular, we are concerned with a constructive definition of the theory, in which we start with finite- N matrices and take the large- N limit afterwards. In that case, it was pointed out recently that realizing chiral fermions in the model is more difficult than it had been thought from formal arguments at N = ∞ and that introduction of a matrix version of the warp factor is necessary. Based on this new insight, we show that two generations of the Standard Model fermions can be realized by considering a rather generic configuration of fuzzy S2 and fuzzy S2 × S2 in the extra dimensions. We also show that three generations can be obtained by squashing one of the S2's that appear in the configuration. Chiral fermions appear at the intersections of the fuzzy manifolds with nontrivial Yukawa couplings to the Higgs field, which can be calculated from the overlap of their wave functions.

Determination of lumbosacral transitional vertebrae in kidney urinary bladder x-ray films in the Saudi population

PubMed Central

Khashoggi, Khalid G.; Hafiz, Rawan M.; Bock, Yasmin M.; Kaki, Abdullah M.

2017-01-01

Objectives: To investigated the rate of occurrence of lumbosacral transitional vertebrae (LSTV), spinal variant, in kidney urinary bladder (KUB) plain radiographs in a Saudi population. Methods: Between January 2012 to January 2015, KUB plain films obtained from patients at King Abdulaziz University Hospital, Jeddah, Saudi Arabia, were reviewed, and the presence or absence of LSTV was documented and classified as incomplete or complete. Patients who had evidence of spinal surgery that would obscure the view were excluded. Results: A total of 2078 patients underwent KUB examinations during the study period; LSTV anomalies were detected in 158 of these. Sacralization was present in 153 (96.8%) of this cohort, while lumbarization was present in 5 (3.2%). A total of 136 (86.1%) of the sacralized segments were of the incomplete type, whereas 17 (10.7%) were complete. Of the lumbarized vertebrae, 3 (1.8%) were incomplete, and 2 (1.2%) were complete. The most frequent type in men was type Ib (28.5%) for sacralized segments, and type IIb for lumbarized segments (0.6%). In women, type Ia was the most common form of sacralized segments (11.3%) and type IIb was the most common form of lumbarized segments (2.8%). Conclusion: The prevalence of LSTV in Saudi patients is 7.6%, with a higher incidence of sacralization than lumbarization. Further studies with larger sample sizes and longer follow-up time are needed to demonstrate the clinical significance thereof. PMID:28762430

Head and neck cutaneous squamous cell carcinoma metastatic to cervical sublevel IIb lymph nodes occurred from primary sites involving the auricle and adjacent neck.

PubMed

Maher, Nigel Gordon; Hoffman, Gary Russell

2014-03-01

Neck dissections that include sublevel IIb increase the risk of postoperative shoulder dysfunction. The purpose of this investigation was to document the incidence of level IIb metastatic lymphatic spread in a group of patients undergoing neck dissection as part of the surgical management of cutaneous squamous cell carcinoma of the head and neck. A retrospective review of the pathology records taken from 1 surgeon from June 2006 through June 2013 was carried out. The predictor variable was the primary tumor site. The outcome variable was the metastatic nodal involvement according to neck level and sublevel. Secondary variables included T stage, pathologist, tumor depth, and the presence of perineural, perilymphatic, and perivascular invasion. Data analyses were by descriptive statistics. Thirty-six patients with a total of 40 neck dissections met the inclusion criteria. The average primary site tumor depth was 14.7 mm, and there were 16 cases of poorly differentiated squamous cell carcinoma. Sublevel IIb was involved in 7.5% of cases, all of which occurred from lateralized primary sites of the head and neck. Cutaneous squamous cell carcinoma arising from the auricle and neck sites adjacent to sublevel IIb may have increased risk of metastatic involvement of sublevel IIb nodes. Further studies with larger numbers are required to determine the risk of metastasis to sublevel IIb from midline sites of the face. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Studies of tricyclic piperazine/piperidine furnished molecules as novel integrin αvβ3/αIIbβ3 dual antagonists using 3D-QSAR and molecular docking.

PubMed

Yan, Yulian; Li, Yan; Zhang, Shuwei; Ai, Chunzhi

2011-02-01

The development of injectable integrin α(v)β(3)/α(IIb)β(3) dual antagonists attracts much attention of research for treating of acute ischemic diseases in recent years. In this work, based on a dataset composed of 102 tricyclic piperazine/piperidine furnished dual α(v)β(3) and α(IIb)β(3) antagonists, a variety of in silico modeling approaches including the comparative molecular field analysis (CoMFA), comparative similarity indices analysis (CoMSIA), and molecular docking were applied to reveal the requisite 3D structural features impacting the biological activities. Our statistical results show that the ligand-based 3D-QSAR models for both the α(v)β(3) and α(IIb)β(3) studies exhibited satisfactory internal and external predictability, i.e., for the CoMFA models, results of Q(2)=0.48, R(ncv)(2)=0.87, R(pred)(2)=0.71 for α(v)β(3) and Q(2)=0.50, R(ncv)(2)=0.85, R(pred)(2)=0.72 for α(IIb)β(3) analysis were obtained, and for the CoMSIA ones, the outcomes of Q(2)=0.55, R(ncv)(2)=0.90, R(pred)(2)=0.72 for α(v)β(3) and Q(2)=0.52, R(ncv)(2)=0.88, R(pred)(2)=0.74 for α(IIb)β(3) were achieved respectively. In addition, through a comparison between 3D-QSAR contour maps and docking results, it is revealed that that the most crucial interactions occurring between the tricyclic piperazine/piperidine derivatives and α(v)β(3)/α(IIb)β(3) receptor ligand binding pocket are H-bonding, and the key amino acids impacting the interactions are Arg214, Asn215, Ser123, and Lys253 for α(v)β(3), but Arg214, Asn215, Ser123 and Tyr190 for α(IIb)β(3) receptors, respectively. Halogen-containing groups at position 15 and 16, benzene sulfonamide substituent at position 23, and the replacement of piperazine with 4-aminopiperidine of ring B may increase the α(v)β(3)/α(IIb)β(3) antagonistic activity. The potencies for antagonists to inhibit isolated α(v)β(3) and α(IIb)β(3) are linear correlated, indicating that similar interaction mechanisms may exist for the series of molecules. To our best knowledge this is the first report on 3D-QSAR modeling of these dual α(v)β(3)/α(IIb)β(3) antagonists. The results obtained should provide information for better understanding of the mechanism of antagonism and thus be helpful in design of novel potent dual α(v)β(3)/α(IIb)β(3) antagonists. Copyright © 2011 Elsevier Inc. All rights reserved.

Fat content in individual muscle fibers of lean and obese subjects.

PubMed

Malenfant, P; Joanisse, D R; Thériault, R; Goodpaster, B H; Kelley, D E; Simoneau, J A

2001-09-01

To examine skeletal muscle intracellular triglyceride concentration in different fiber types in relation to obesity. Skeletal muscle fiber type distribution and intracellular lipid content were measured in vastus lateralis samples obtained by needle biopsy from lean and obese individuals. Seven lean controls (body mass index (BMI) 23.0+/-3.3 kg/m(2); mean+/-s.d.) and 14 obese (BMI 33.7+/-2.7 kg/m(2)) individuals; both groups included comparable proportions of men and women. Samples were histochemically stained for the identification of muscle fiber types (myosin ATPase) and intracellular lipid aggregates (oil red O dye). The number and size of fat aggregates as well as their concentration within type I, IIA and IIB muscle fiber types were measured. The cellular distribution of the lipid aggregates was also examined. The size of fat aggregates was not affected by obesity but the number of lipid droplets within muscle fibers was twice as abundant in obese compared to lean individuals. This was seen in type I (298+/-135 vs 129+/-75; obese vs lean, P<0.05), IIA (132+/-67 vs 79+/-29; P<0.05), and IIB (103+/-63 vs 51+/-13; P<0.05) muscle fibers. A more central distribution of lipid droplets was observed in muscle fibers of obese compared to lean subjects (27.2+/-5.7 vs 19.7+/-6.4%; P<0.05). The higher number of lipid aggregates and the disposition to a greater central distribution in all fiber types in obesity indicate important changes in lipid metabolism and/or storage that are fiber type-independent.

Structure and Activity Analyses of Escherichia coli K-12 NagD Provide Insight into the Evolution of Biochemical Function in the Haloakanoic Acid Dehlogenase Superfamily

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

Tremblay,L.; Dunaway-Mariano, D.; Allen, K.

2006-01-01

The HAD superfamily is a large superfamily of proteins which share a conserved core domain that provides those active site residues responsible for the chemistry common to all family members. The superfamily is further divided into the four subfamilies I, IIA, IIB, and III, based on the topology and insertion site of a cap domain that provides substrate specificity. This structural and functional division implies that members of a given HAD structural subclass may target substrates that have similar structural characteristics. To understand the structure/function relationships in all of the subfamilies, a type IIA subfamily member, NagD from Escherichia colimore » K-12, was selected (type I, IIB, and III members have been more extensively studied). The structure of the NagD protein was solved to 1.80 Angstroms with R{sub work} = 19.8% and R{sub free} = 21.8%. Substrate screening and kinetic analysis showed NagD to have high specificity for nucleotide monophosphates with kcat/Km = 3.12 x 10{sup 4} and 1.28 x 10{sup 4} {micro}M{sup -1} s{sup -1} for UMP and GMP, respectively. This specificity is consistent with the presence of analogues of NagD that exist as fusion proteins with a nucleotide pyrophosphatase from the Nudix family. Docking of the nucleoside substrate in the active site brings it in contact with conserved residues from the cap domain that can act as a substrate specificity loop (NagD residues 144-149) in the type IIA subfamily. NagD and other subfamily IIA and IIB members show the common trait that substrate specificity and catalytic efficiencies (k{sub cat}/K{sub m}) are low (1 x 10{sup 4} M{sup -1} s{sup -1}) and the boundaries defining physiological substrates are somewhat overlapping. The ability to catabolize other related secondary metabolites indicates that there is regulation at the genetic level.« less

Overexpression of caveolin-3-enhanced protein synthesis rather than proteolysis inhibition in C2C12 myoblasts: relationship with myostatin activity.

PubMed

Hadj Sassi, Abdessattar; Monteil, Julien; Sauvant, Patrick; Atgié, Claude

2012-12-01

Caveolin-3 (cav-3), which is involved in the regulation of signal transduction and vesicular trafficking, could interact with activin receptor IIB to inhibit myostatin (MSTN) activity and may therefore play a role in muscle development and hypertrophy. MSTN is a member of the transforming growth factor-β family, identified as a negative regulator of skeletal muscle mass. The expression of MSTN is fiber-type specific and the greatest amount of MSTN is present in fiber, which is composed of myosin heavy chain (MHC) type IIb. MSTN acts through the activin receptor IIB to activate smad2/3 which leads to an increase in gene transcription involved in muscle atrophy. Muscle hypertrophy is a consequence of two mechanisms: (1) the inhibition of proteolysis such as the calcium-dependent proteolytic system calpains and calpastatin and (2) an increase in protein synthesis through the Akt/mTOR/p70s6K pathway. In order to determine which of the two processes predominates in inhibition of MSTN activity in a cav-3 context, we transfected a C2C12 cell line with plasmids containing mstn or cav-3 wild genes. The results reported in this study demonstrate that inhibition of MSTN activity by overexpression of cav-3 induces an activation of protein synthesis rather than an inhibition of proteolysis through the calcium proteolytic system. The inhibition of phosphorylation of smad-3 due to overexpression of cav-3 causes an increase in the phosphorylation of the ribosomal protein S6, promoting the synthesis of MHC type II, probably through activation of Akt/mTOR/p70s6K. These data highlight the role of protein synthesis as the predominant mechanism in muscle hypertrophy observed when the expression of MSTN is altered and confirm the value of studying the physiological role of MSTN in the growing processes of skeletal muscle.

Reading off the nongeometric scalar potentials via the topological data of the compactifying Calabi-Yau manifolds

NASA Astrophysics Data System (ADS)

Shukla, Pramod

2016-10-01

In the context of studying the 4D-effective potentials of type IIB nongeometric flux compactifications, this article has a twofold goal. First, we present a modular invariant symplectic rearrangement of the tree level nongeometric scalar potential arising from a flux superpotential which includes the S-dual pairs of nongeometric fluxes (Q , P ), the standard NS-NS and RR three-form fluxes (F3 , H3 ), and the geometric flux (ω ). This "symplectic formulation" is valid for arbitrary numbers of Kähler moduli, and the complex structure moduli which are implicitly encoded in a set of symplectic matrices. In the second part, we further explicitly rewrite all the symplectic ingredients in terms of saxionic and axionic components of the complex structure moduli. The same leads to a compact form of the generic scalar potential being explicitly written out in terms of all the real moduli/axions. Moreover, the final form of the scalar potential needs only the knowledge of some topological data (such as Hodge numbers and the triple-intersection numbers) of the compactifying threefolds and their respective mirrors. Finally, we demonstrate how the same is equivalent to say that, for a given concrete example, various pieces of the scalar potential can be directly read off from our generic proposal, without the need of starting from the Kähler and superpotentials.

Hyperconifold transitions, mirror symmetry, and string theory

NASA Astrophysics Data System (ADS)

Davies, Rhys

2011-09-01

Multiply-connected Calabi-Yau threefolds are of particular interest for both string theorists and mathematicians. Recently it was pointed out that one of the generic degenerations of these spaces (occurring at codimension one in moduli space) is an isolated singularity which is a finite cyclic quotient of the conifold; these were called hyperconifolds. It was also shown that if the order of the quotient group is even, such singular varieties have projective crepant resolutions, which are therefore smooth Calabi-Yau manifolds. The resulting topological transitions were called hyperconifold transitions, and change the fundamental group as well as the Hodge numbers. Here Batyrev's construction of Calabi-Yau hypersurfaces in toric fourfolds is used to demonstrate that certain compact examples containing the remaining hyperconifolds — the Z and Z cases — also have Calabi-Yau resolutions. The mirrors of the resulting transitions are studied and it is found, surprisingly, that they are ordinary conifold transitions. These are the first examples of conifold transitions with mirrors which are more exotic extremal transitions. The new hyperconifold transitions are also used to construct a small number of new Calabi-Yau manifolds, with small Hodge numbers and fundamental group Z or Z. Finally, it is demonstrated that a hyperconifold is a physically sensible background in Type IIB string theory. In analogy to the conifold case, non-perturbative dynamics smooth the physical moduli space, such that hyperconifold transitions correspond to non-singular processes in the full theory.

Supernova 2010as: The Lowest-velocity Member of a Family of Flat-velocity Type IIb Supernovae

NASA Astrophysics Data System (ADS)

Folatelli, Gastón; Bersten, Melina C.; Kuncarayakti, Hanindyo; Olivares Estay, Felipe; Anderson, Joseph P.; Holmbo, Simon; Maeda, Keiichi; Morrell, Nidia; Nomoto, Ken'ichi; Pignata, Giuliano; Stritzinger, Maximilian; Contreras, Carlos; Förster, Francisco; Hamuy, Mario; Phillips, Mark M.; Prieto, José Luis; Valenti, Stefano; Afonso, Paulo; Altenmüller, Konrad; Elliott, Jonny; Greiner, Jochen; Updike, Adria; Haislip, Joshua B.; LaCluyze, Aaron P.; Moore, Justin P.; Reichart, Daniel E.

2014-09-01

We present extensive optical and near-infrared photometric and spectroscopic observations of the stripped-envelope supernova SN 2010as. Spectroscopic peculiarities such as initially weak helium features and low expansion velocities with a nearly flat evolution place this object in the small family of events previously identified as transitional Type Ib/c supernovae (SNe). There is ubiquitous evidence of hydrogen, albeit weak, in this family of SNe, indicating that they are in fact a peculiar kind of Type IIb SNe that we name "flat-velocity Type IIb. The flat-velocity evolution—which occurs at different levels between 6000 and 8000 km s-1 for different SNe—suggests the presence of a dense shell in the ejecta. Despite the spectroscopic similarities, these objects show surprisingly diverse luminosities. We discuss the possible physical or geometrical unification picture for such diversity. Using archival Hubble Space Telescope images, we associate SN 2010as with a massive cluster and derive a progenitor age of ≈6 Myr, assuming a single star-formation burst, which is compatible with a Wolf-Rayet progenitor. Our hydrodynamical modeling, on the contrary, indicates that the pre-explosion mass was relatively low, ≈4 M ⊙. The seeming contradiction between a young age and low pre-SN mass may be solved by a massive interacting binary progenitor. This paper includes data gathered with the following facilities in Chile: the 6.5 m Magellan Telescopes located at Las Campanas Observatory, the Gemini Observatory, Cerro Pachón (Gemini Program GS-2008B-Q-56), and the European Organisation for Astronomical Research in the Southern Hemisphere (ESO Programmes 076.A-0156, 078.D-0048, 080.A-0516, and 082.A-0526). We have also used data from the ESO Science Archive Facility under request number gfolatelli74580 and from the NASA/ESA Hubble Space Telescope, obtained from the Hubble Legacy Archive, which is a collaboration between the Space Telescope Science Institute (STScI/NASA), the Space Telescope European Coordinating Facility (ST-ECF/ESA), and the Canadian Astronomy Data Centre (CADC/NRC/CSA).

[Oncological outcomes of combined therapy in patients with cervical carcinoma FIGO stage IIB].

PubMed

Kornovski, Y; Ismail, E; Kaneva, M

2012-01-01

To establish the overall and disease-free survival and the role of surgery as well as in cervical cancer stage IIB (FIGO) patients submitted to combined radiotherapy and surgery. Between 2003-2011 86 patients with cervical cancer stage IIB had been operated on. Five patients were operated on after neoajuvant chemotherapy. Thirty one women (group 3) had primary pelvic surgery (radical hysterectomy class III and lymphonodulectomy) and adjuvant RT until 52 Gy and 50 women were operated on after preoperative RT (30 Gy) and were submitted to adjuvant RT until 52 Gy (group 4). After median follow of 45 months the acturial overall and disease-free survival (OS and DFS) were estimated as 75.6% and 77.9% respectively for all patients staged IIB (FIGO). In group 3 the incidence of local relapses and distant metastases was 9.7% and 12.9%, respectively and in group 4--local and distant recurrences were 6% and 14%, respectively. The acturial OS and DFS for group 3 were 80.6% and 77.5%, respectively and for group 4--76% and 80% (NS). Combinated treatment (RT and pelvic surgery) produce reliable local control of the disease (cervical cancer IIB stage) but is ineffective for metastases outside the small pelvis which is the cause of worse survival of patients with cervical cancer stage IIB (FIGO). Preoperative RT (group 4) doesn't change the OS and DFS significantly. The main indication for surgery in patients with cervical cancer stage IIB is the surgical staging (pelvic and paraaortic lymph node dissection) which enables the appropriate individual treatment planning.

Nonperturbative corrections to 4D string theory effective actions from SL(2,Z) duality and supersymmetry.

PubMed

Robles-Llana, Daniel; Rocek, Martin; Saueressig, Frank; Theis, Ulrich; Vandoren, Stefan

2007-05-25

We find the D(-1)- and D1-brane instanton contributions to the hypermultiplet moduli space of type IIB string compactifications on Calabi-Yau threefolds. These combine with known perturbative and world sheet instanton corrections into a single modular invariant function that determines the hypermultiplet low-energy effective action.

Small field axion inflation with sub-Planckian decay constant

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

Kadota, Kenji; Kobayashi, Tatsuo; Oikawa, Akane

2016-10-10

We study an axion inflation model recently proposed within the framework of type IIB superstring theory, where we pay a particular attention to a sub-Planckian axion decay constant. Our axion potential can lead to the small field inflation with a small tensor-to-scalar ratio, and a typical reheating temperature can be as low as GeV.

Validation of the prognostic grouping of the seventh edition of the tumor-nodes-metastasis classification using a large-scale prospective cohort study database of prostate cancer treated with primary androgen deprivation therapy.

PubMed

Kimura, Tomokazu; Onozawa, Mizuki; Miyazaki, Jun; Kawai, Koji; Nishiyama, Hiroyuki; Hinotsu, Shiro; Akaza, Hideyuki

2013-09-01

In the TNM seventh edition, a prognostic grouping for prostate cancer incorporating prostate-specific antigen and Gleason score was advocated. The present study was carried out to evaluate and validate prognostic grouping in prostate cancer patients. The 15 259 study patients treated with primary androgen deprivation therapy were enrolled in the Japan Study Group of Prostate Cancer. Overall survival was stratified by tumor-nodes-metastasis, Gleason score and prostate-specific antigen, and extensively analyzed. The accuracy of grouping systems was evaluated by the concordance index. The 5-year overall survival in prognostic grouping-I, IIA, IIB, III and IV was 90.0%, 88.3%, 84.8%, 80.6% and 57.1%, respectively. When considering subgroup stratification, the 5-year overall survival of subgroups prognostic grouping-IIA, IIB, III and IV was 80.9∼90.5%, 75.4∼91.8%, 75.7∼89.0% and 46.9∼86.2%, respectively. When prognostic grouping-IIB was subclassified into IIB1 (except IIB2) and IIB2 (T1-2b, prostate-specific antigen >20, Gleason score ≥8, and T2c, Gleason score ≥8), the 5-year overall survival of IIB2 was significantly lower than that of IIB1 (79.4% and 87.3%, P < 0.0001). Also, when prognostic grouping-IV was subclassified into IV1 (except IV2) and IV2 (M1, prostate-specific antigen >100 or Gleason score ≥8), the 5-year overall survival of prognostic grouping-IV1 was superior to that of IV2 (72.9% and 49.5%, P < 0.0001). Prognostic groupings were reclassified into modified prognostic groupings, divided into modified prognostic grouping-A (prognostic grouping-I, IIA, and IIB1), modified prognostic grouping-B (prognostic grouping-IIB2 and III), modified prognostic grouping-C (prognostic grouping-IV1) and modified prognostic grouping-D (prognostic grouping-IV2). The concordance index of prognostic grouping and modified prognostic grouping for overall survival was 0.670 and 0.685, respectively. Prognostic grouping could stratify the prognosis of prostate cancer patients. However, there is considerable variation among the prognostic grouping subgroups. Thus, the use of a modified prognostic grouping for patients treated with primary androgen deprivation therapy is advisable. © 2013 The Japanese Urological Association.

Is inflation from unwinding fluxes IIB?

NASA Astrophysics Data System (ADS)

Gautason, Fridrik Freyr; Schillo, Marjorie; Van Riet, Thomas

2017-03-01

In this paper we argue that the mechanism of unwinding inflation is naturally present in warped compactifications of type IIB string theory with local throats. The unwinding of flux is caused by its annihilation against branes. The resulting inflaton potential is linear with periodic modulations. We initiate an analysis of the inflationary dynamics and cosmological observables, which are highly constrained by moduli stabilization. For the simplified model of single-Kähler Calabi-Yau spaces we find that many, though not all of the consistency constraints can be satisfied. Particularly, in this simple model geometric constraints are in tension with obtaining the observed amplitude of the scalar power spectrum. However, we do find 60 efolds of inflation with a trans-Planckian field excursion which offers the hope that slightly more complicated models can lead to a fully consistent explicit construction of large field inflation of this kind.

Muscle Fiber Characteristics and Fatty Acid Compositions of the Four Major Muscles in Korean Native Black Goat.

PubMed

Hwang, Young-Hwa; Joo, Sung-Hyun; Bakhsh, Allah; Ismail, Ishamri; Joo, Seon-Tea

2017-01-01

The objective of this study was to investigate the relationship between muscle fiber characteristics and fatty acid composition of four major muscles in Korean native black goat (KNBG). Longissimus lumborum (LL), psoas major (PM), semimembranosus (SM), and gluteus medius (GM) were obtained from five male KNBGs of 36 mon of age and subjected to histochemical analysis and to determine fatty acid composition and meat quality traits. There were significant ( p <0.05) differences in fiber number percentage (FNP) and fiber area percentage (FAP) of fiber types among these four muscles. PM had the highest FNP of type I and the lowest FNP of type IIB, while SM had the highest FNP of type IIB. The highest fat content was observed in LL while SM had the lowest fat content. The proportions of SFA and MUFA were significantly ( p <0.05) different among four muscles due to differences in the majority of fatty acids such as oleic (C18:1) and palmitic (C16:0) acids. The PUFA/SFA ratio was significantly ( p <0.05) different among four muscles, and the highest PUFA/SFA ratio was observed in PM. Results suggested that LL and PM might be healthful because of higher desirable fatty acid value and PUFA/SFA ratio, respectively. Also, data showed that correlations between muscle fiber types and fatty acids proportion of goat muscles were reversed with those of cattle muscles.

30 CFR 57.22238 - Actions at 2.0 percent methane (I-B, II-B, V-B, and VI mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions at 2.0 percent methane (I-B, II-B, V-B... AND NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22238 Actions at 2.0 percent methane (I-B, II-B, V-B, and VI mines). If methane reaches 2.0 percent in the mine...

30 CFR 57.22235 - Actions at 1.0 percent methane (I-C, II-A, II-B, and IV mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions at 1.0 percent methane (I-C, II-A, II-B... AND NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22235 Actions at 1.0 percent methane (I-C, II-A, II-B, and IV mines). (a) If methane reaches 1.0 percent in the...

30 CFR 57.22231 - Actions at 0.25 percent methane (I-B, II-B, V-B, and VI mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions at 0.25 percent methane (I-B, II-B, V-B... AND NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22231 Actions at 0.25 percent methane (I-B, II-B, V-B, and VI mines). If methane reaches 0.25 percent in the...

Development of Medical Technology for Contingency Response to Marrow Toxic Agents

DTIC Science & Technology

2012-03-31

Development of Medical Technology for Contingency Response to Marrow Toxic Agents - Final Performance/Technical Report for March 01, 2010 to February 28...Development of Medical Technology for Contingency Response To Marrow Toxic Agents FINAL REPORT March 1, 2010 – March 31, 2012 National...Buccal Swabs 38 IIB.1.5 Enhancing HLA Data for Selected Donors 43 IIB.1.6 Maintain a Quality Control Program 46 IIB.2.1 Collection of Primary Data

Development of Medical Technology for Contingency Response to Marrow Toxic Agents

DTIC Science & Technology

2014-05-06

Development of Medical Technology for Contingency Response to Marrow Toxic Agents - Final Performance/Technical Report for January 01, 2011 to...Enhancing HLA Data for Selected Donors 44 IIB.1.6 Maintain a Quality Control Program 44 IIB.2.1 Collection of Primary Data 45 IIB.2.2 Validation of...Receptor Donor Selection KORI Korean LD Linkage Disequilibrium LTA Lymphotoxin Alpha MALDI-TOF Matrix-Assisted Laser Desorption/Ionization – Time Of

30 CFR 57.22238 - Actions at 2.0 percent methane (I-B, II-B, V-B, and VI mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Actions at 2.0 percent methane (I-B, II-B, V-B, and VI mines). 57.22238 Section 57.22238 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Actions at 2.0 percent methane (I-B, II-B, V-B, and VI mines). If methane reaches 2.0 percent in the mine...

30 CFR 57.22235 - Actions at 1.0 percent methane (I-C, II-A, II-B, and IV mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Actions at 1.0 percent methane (I-C, II-A, II-B, and IV mines). 57.22235 Section 57.22235 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Actions at 1.0 percent methane (I-C, II-A, II-B, and IV mines). (a) If methane reaches 1.0 percent in the...

30 CFR 57.22231 - Actions at 0.25 percent methane (I-B, II-B, V-B, and VI mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Actions at 0.25 percent methane (I-B, II-B, V-B, and VI mines). 57.22231 Section 57.22231 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Actions at 0.25 percent methane (I-B, II-B, V-B, and VI mines). If methane reaches 0.25 percent in the...

Family Caregiver Palliative Care Intervention in Supporting Caregivers of Patients With Stage II-IV Gastrointestinal, Gynecologic, Urologic and Lung Cancers

ClinicalTrials.gov

2018-02-12

Healthy Subject; Localized Transitional Cell Cancer of the Renal Pelvis and Ureter; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Psychosocial Effects of Cancer and Its Treatment; Recurrent Bladder Cancer; Recurrent Cervical Cancer; Recurrent Colon Cancer; Recurrent Gastric Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Renal Cell Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Recurrent Uterine Sarcoma; Regional Transitional Cell Cancer of the Renal Pelvis and Ureter; Stage II Bladder Cancer; Stage II Renal Cell Cancer; Stage II Urethral Cancer; Stage IIA Cervical Cancer; Stage IIA Colon Cancer; Stage IIA Gastric Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIA Pancreatic Cancer; Stage IIA Rectal Cancer; Stage IIA Uterine Sarcoma; Stage IIB Cervical Cancer; Stage IIB Colon Cancer; Stage IIB Gastric Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIB Pancreatic Cancer; Stage IIB Rectal Cancer; Stage IIB Uterine Sarcoma; Stage IIC Colon Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIC Rectal Cancer; Stage III Bladder Cancer; Stage III Pancreatic Cancer; Stage III Renal Cell Cancer; Stage III Urethral Cancer; Stage IIIA Cervical Cancer; Stage IIIA Colon Cancer; Stage IIIA Gastric Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Rectal Cancer; Stage IIIA Uterine Sarcoma; Stage IIIB Cervical Cancer; Stage IIIB Colon Cancer; Stage IIIB Gastric Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Rectal Cancer; Stage IIIB Uterine Sarcoma; Stage IIIC Colon Cancer; Stage IIIC Gastric Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Rectal Cancer; Stage IIIC Uterine Sarcoma; Stage IV Bladder Cancer; Stage IV Gastric Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer; Stage IV Renal Cell Cancer; Stage IV Urethral Cancer; Stage IVA Cervical Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVA Uterine Sarcoma; Stage IVB Cervical Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer; Stage IVB Uterine Sarcoma; Ureter Cancer; Stage IIA Lung Carcinoma; Stage IIB Lung Carcinoma; Stage IIIA Lung Carcinoma; Stage IIIB Lung Carcinoma

Alveolar hemorrhage: an underdiagnosed complication of treatment with glycoprotein IIb/IIIa inhibitors.

PubMed

Iskandar, Said B; Kasasbeh, Ehab S; Mechleb, Bassam K; Garcia, Israel; Jackson, Ann; Fahrig, Stephen; Albalbissi, Kaiss; Henry, Phillip D

2006-08-01

Alveolar hemorrhage (AH) is a rare complication of treatment with GP IIb/IIIa inhibitors. Hemoptysis, a constant sign, lacks in specificity, and may occur in confounding syndromes such as pulmonary edema, pulmonary infarction, and pneumonia. Nonspecific symptoms and signs often delay the diagnosis, thereby allowing serious or even fatal disease progression. Here, we performed a large-scale retrospective analysis to define the incidence and risk factors of AH in the setting of GP IIb/IIIa inhibitors therapy. Randomized controlled trials demonstrate that treatment with glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors may improve the outcome of acute myocardial infarction (AMI) and angioplastic procedures. However, this treatment may rarely lead to severe hemorrhagic complications, in particular AH. Unfortunately, the incidence and risk factors of AH remain poorly defined. We reviewed for the period extending from August 1998 to January 2005 consecutive histories of AMI patients receiving coronary arteriography and treatment with either eptifibatide or abciximab. Concomitantly admitted AMI patients not treated with GP IIb/IIIa inhibitors were reviewed and served as a control group. The diagnosis of AH required the demonstration of typical symptoms and signs including dyspnea, hemoptysis, arterial hypoxemia, pulmonary radiographic changes, and, when available, bronchoscopic signs for AH. Potential covariates including pulmonary disease, pulmonary hypertension, smoking, and use of other anticoagulant or antiplatelet agents were evaluated. Six of 1,810 patients (0.33%) receiving eptifibatide and five of 3,648 patients (0.14%) receiving abciximab exhibited typical symptoms and signs of AH. Contrarily, only one of 4,136 patients (0.025%) receiving no GP IIb/IIIa inhibitors presented with similar symptoms and signs. There was no fatal outcome, though two patients required blood transfusions. Statistically significant differences were found between control patients and patients receiving eptifibatide alone (P = 0.004). There was also a significant difference between untreated patients and those receiving eptifibatide and abciximab (P = 0.017). No differences were found between eptifibatide and abciximab-treated patients (P = 0.19) or between abciximab and untreated control patients (P = 0.105). AH is a rare complication of treatment with GP IIb/IIIa inhibitors. Its incidence ranged from 0.14% in patients treated with abciximab to 0.33% in those receiving eptifibatide. Compared to a control group, patients treated with GP IIb/IIIa inhibitors had a statistically increased risk for AH.

Coated platelets function in platelet-dependent fibrin formation via integrin αIIbβ3 and transglutaminase factor XIII

PubMed Central

Mattheij, Nadine J.A.; Swieringa, Frauke; Mastenbroek, Tom G.; Berny-Lang, Michelle A.; May, Frauke; Baaten, Constance C.F.M.J.; van der Meijden, Paola E.J.; Henskens, Yvonne M.C.; Beckers, Erik A.M.; Suylen, Dennis P.L.; Nolte, Marc W.; Hackeng, Tilman M.; McCarty, Owen J.T.; Heemskerk, Johan W.M.; Cosemans, Judith M.E.M.

2016-01-01

Coated platelets, formed by collagen and thrombin activation, have been characterized in different ways: i) by the formation of a protein coat of α-granular proteins; ii) by exposure of procoagulant phosphatidylserine; or iii) by high fibrinogen binding. Yet, their functional role has remained unclear. Here we used a novel transglutaminase probe, Rhod-A14, to identify a subpopulation of platelets with a cross-linked protein coat, and compared this with other platelet subpopulations using a panel of functional assays. Platelet stimulation with convulxin/thrombin resulted in initial integrin αIIbβ3 activation, the appearance of a platelet population with high fibrinogen binding, (independently of active integrins, but dependent on the presence of thrombin) followed by phosphatidylserine exposure and binding of coagulation factors Va and Xa. A subpopulation of phosphatidylserine-exposing platelets bound Rhod-A14 both in suspension and in thrombi generated on a collagen surface. In suspension, high fibrinogen and Rhod-A14 binding were antagonized by combined inhibition of transglutaminase activity and integrin αIIbβ3. Markedly, in thrombi from mice deficient in transglutaminase factor XIII, platelet-driven fibrin formation and Rhod-A14 binding were abolished by blockage of integrin αIIbβ3. Vice versa, star-like fibrin formation from platelets of a patient with deficiency in αIIbβ3 (Glanzmann thrombasthenia) was abolished upon blockage of transglutaminase activity. We conclude that coated platelets, with initial αIIbβ3 activation and high fibrinogen binding, form a subpopulation of phosphatidylserine-exposing platelets, and function in platelet-dependent star-like fibrin fiber formation via transglutaminase factor XIII and integrin αIIbβ3. PMID:26721892

Executive summary and recommendations from the WHO/UNAIDS/IAVI expert group consultation on 'Phase IIB-TOC trials as a novel strategy for evaluation of preventive HIV vaccines', 31 January-2 February 2006, IAVI, New York, USA.

PubMed

2007-02-19

This report summarizes the discussions and recommendations from a consultation held in New York City, USA (31 January-2 February 2006) organized by the joint World Health Organization-United Nations Programme on HIV/AIDS HIV Vaccine Initiative and the International AIDS Vaccine Initiative. The consultation discussed issues related to the design and implementation of phase IIB 'test of concept' trials (phase IIB-TOC), also referred to as 'proof of concept' trials, in evaluating candidate HIV vaccines and their implications for future approval and licensure. The results of a single phase IIB-TOC trial would not be expected to provide sufficient evidence of safety or efficacy required for licensure. In many instances, phase IIB-TOC trials may be undertaken relatively early in development, before manufacturing processes and capacity are developed sufficiently to distribute the vaccine on a large scale. However, experts at this meeting considered the pressure that could arise, particularly in regions hardest hit by AIDS, if a phase IIB-TOC trial showed high levels of efficacy. The group largely agreed that full-scale phase III trials would still be necessary to demonstrate that the vaccine candidate was safe and effective, but emphasized that governments and organizations conducting trials should consider these issues in advance. The recommendations from this meeting should be helpful for all organizations involved in HIV vaccine trials, in particular for the national regulatory authorities in assessing the utility of phase IIB-TOC trials in the overall HIV vaccine research and development process.

30 CFR 57.22232 - Actions at 0.5 percent methane (I-B, II-A, II-B, IV, V-B, and VI mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Actions at 0.5 percent methane (I-B, II-A, II-B, IV, V-B, and VI mines). 57.22232 Section 57.22232 Mineral Resources MINE SAFETY AND HEALTH....22232 Actions at 0.5 percent methane (I-B, II-A, II-B, IV, V-B, and VI mines). If methane reaches 0.5...

Nerve-sparing radical hysterectomy for stage IA2-IIB cervical cancer: 5-year survival of 501 consecutive cases.

PubMed

Papp, Z; Csapó, Zs; Hupuczi, P; Mayer, A

2006-01-01

The purpose of this study was to assess the 5-year survival and morbidity in cases with radical hysterectomy and pelvic lymphadenectomy with pre- and postoperative irradiation performed to treat Stage IA2-IIB cervical cancer. During a 10(1/2)-year period between July 1990 and December 2000, 501 consecutive radical hysterectomies with bilateral pelvic lymphadenectomy were performed by the same gynecological surgeon in Stage IA2, IB, IIA and IIB cervical cancer. The patients were treated by pre- and postoperative irradiation as well. Apart from recurrence, perioperative complications were minimal with no long-term morbidity. The absolute 5-year survival rates for the patients in Stage IA2, IB1, IB2, IIA and IIB were 94.4%, 90.7%, 84.1%, 71.1%, and 55.4%, respectively. The respective 5-year survival rates for patients without or with lymph node metastasis were 94.5% and 33.3% in Stage IB2, 81.7% and 48.7% in Stage IIA and 70.2% and 36.5% in Stage IIB, respectively. Nerve-sparing radical hysterectomy with pelvic lymph node dissection and pre- and postoperative irradiation remains the treatment of choice for most patients with early-stage and even Stage IIB cervical cancer. The radicalism and extent of lymph node dissection and parametrial resection should be individualized and tailored to tumor- and patient-related risk factors.

Spines vs. microspines: an overview of the sculpture exine in selected basal and derived Asteraceae with focus on Asteroideae.

PubMed

Tellería, María C

2017-11-01

This study presents a detailed examination of the echinate and microechinate sculpturing in relation to the size of pollen grains in 31 selected species of Asteraceae belonging to the subfamilies Barnadesioideae, Mutisioideae, Carduoideae and Asteroideae. The aims were to recognize sculpturing patterns, under LM and SEM, within large and small pollen of both basal and derived species and to explore the features that could have taxonomic value to apply in palynological disciplines. The detailed examination of the exine surface showed both the relevance and limits of sculptural patterns for taxonomy. Under LM, the microechinate sculpture gave little taxonomic information, whereas in the echinate sculpture, three exine types and two subtypes were recognized. Type I included microechinate exine, which is commonly present in large pollen grains of the basal lineages. Types II (subtypes IIa and IIb) and III included echinate and smaller pollen grains. In these types, spines were always regularly arranged and, were characterized by the length, shape, tip, perforations and distribution. Type IIa included more or less conical spines usually with a distended base, less than 4 µm in length, present in species of different tribes like Astereae, Eupatorieae, Helenieae, Gnaphalieae, Senecioideae and Heliantheae to a lesser extent. Type IIb includes slender spines with narrower bases, longer than 4 µm, present in species of Coreopsideae, Heliantheae, Tageteae and Eupatorieae to a lesser extent. Type III included spines with swollen base, blunt tip and perforations over their entire surface. This type was present in only one of the basal species-Carduus thoermeri-and in one species of the derived tribe Helenieae, Gaillardia megapotamica. Probably, this is due to evolutionary convergence.

Supersymmetric solutions of the cosmological, gauged, ℂ magic model

NASA Astrophysics Data System (ADS)

Chimento, Samuele; Ortín, Tomás; Ruipérez, Alejandro

2018-05-01

We construct supersymmetric solutions of theories of gauged N = 1 , d = 5 supergravity coupled to vector multiplets with a U(1)R Abelian (Fayet-Iliopoulos) gauging and an independent SU(2) gauging associated to an SU(2) isometry group of the Real Special scalar manifold. These theories provide minimal supersymmetrizations of 5-dimensional SU(2) Einstein-Yang-Mills theories with negative cosmological constant. We consider a minimal model with these gauge groups and the "magic model" based on the Jordan algebra J 3 ℂ with gauge group SU(3) × U(1)R, which is a consistent truncation of maximal SO(6)-gauged supergravity in d = 5 and whose solutions can be embedded in Type IIB Superstring Theory. We find several solutions containing selfdual SU(2) instantons, some of which asymptote to AdS5 and some of which are very small, supersymmetric, deformations of AdS5. We also show how some of those solutions can be embedded in Romans' SU(2) × U(1)-gauged half-maximal supergravity, which was obtained by Lu, Pope and Tran by compactification of the Type IIB Superstring effective action. This provides another way of uplifting those solutions to 10 dimensions.

30 CFR 57.22201 - Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). 57.22201 Section 57.22201 Mineral Resources MINE SAFETY AND HEALTH....22201 Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). All mines shall...

Overexpression and Initial Characterization of the Chromosomal Aminoglycoside 3′-O-Phosphotransferase APH(3′)-IIb from Pseudomonas aeruginosa▿†

PubMed Central

Hainrichson, Mariana; Yaniv, Orit; Cherniavsky, Marina; Nudelman, Igor; Shallom-Shezifi, Dalia; Yaron, Sima; Baasov, Timor

2007-01-01

The chromosomal gene aph(3′)-IIb, encoding an aminoglycoside 3′-phosphotransferase in Pseudomonas aeruginosa, was cloned and overexpressed in Escherichia coli. The APH(3′)-IIb enzyme was purified as a monomer in a two-step procedure and was shown to phosphorylate its substrates at the C-3′-OH position, with kcat/Km values of 0.4 × 104 to 36 × 104 M−1 s−1. PMID:17088479

26 CFR 1.6049-4 - Return of information as to interest paid and original issue discount includible in gross income...

Code of Federal Regulations, 2010 CFR

2010-04-01

... record date reporting under § 1.6049-1(a)(1)(ii)(b)(1) may be used, and if it is used, the original issue... aggregation rules of § 1.6049-1(a)(1)(ii)(b)(2) are being used, the aggregate amount or original issue... record date reporting under § 1.6049-1(a)(1)(ii)(b)(1) may be used, and if it is used, the original issue...

30 CFR 57.22501 - Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). 57.22501 Section 57.22501 Mineral Resources MINE SAFETY AND... Illumination § 57.22501 Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines...

30 CFR 57.22501 - Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). 57.22501 Section 57.22501 Mineral Resources MINE SAFETY AND... Illumination § 57.22501 Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines...

30 CFR 57.22227 - Approved testing devices (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Approved testing devices (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). 57.22227 Section 57.22227 Mineral Resources MINE SAFETY AND... Ventilation § 57.22227 Approved testing devices (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). (a...

30 CFR 57.22201 - Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). 57.22201 Section 57.22201 Mineral Resources MINE SAFETY AND HEALTH....22201 Mechanical ventilation (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). All mines shall...

Relationship between uterine biopsy score, endometrial infection and inflammation in the mare.

PubMed

Buczkowska, Justyna; Kozdrowski, Roland; Nowak, Marcin; Sikora, Monika

2016-06-16

Endometrial biopsy score is an accepted marker of uterine health and predicted fertility, and it has been suggested that endometrial alternations are correlated with susceptibility to persistent infectious endometritis. The objective of this study was to investigate associations of endometrial biopsy score with: 1) presence of polymorphonuclear cells (PMNs) in the epithelium and stratum compactum in histopathology; 2) presence of PMNs in cytology and 3) presence of infection in microbiology. The material for examination was collected from 69 mares suspected for subclinical endometritis (bred three or more times unsuccessfully in the same breeding season) and from 15 maiden mares. Samples were collected by endometrial biopsy and cytobrush technique. Endometrial alterations (biopsy score IIA, IIB, III) were found in 64 of 82 mares (78%). There was an increase in PMN occurrence for grades IIA, IIB and III. When comparing grades and PMNs infiltration, we observed statistically significant differences between grades I and IIA (p  = 0.222) and grades I and IIB (p = 0.042) in samples collected by endometrial biopsy. Statistically significant differences were found in microbiological examination (biopsy p = 0.036; cytobrush p = 0.189), cytological examination (biopsy p = 0.040; cytobrush p = 0.079) and PMN infiltration (p    =    0.042) between mares with biopsy scores I and IIB. Furthermore, the highest percentage of infected mares was in grade IIA and IIB, and we found statistically significant differences between grades I and IIA (p = 0.043), and grades I and IIB (p = 0.036) in biopsy samples. We observed a tendency to higher prevalence of endometrial infection in mares with biopsy score IIA, IIB and III than with biopsy score I in samples collected using cytobrush technique. However, there were no statistical significant differences. Degenerative endometrial changes can predispose to uterine infection and inflammation. Our study shows that mares with endometrial score I are less predisposed to infection than mares with category IIA, IIB and III. Endometrial biopsy is a reliable diagnostic tool.

Comparisons of different myosin heavy chain types, AMPK, and PGC-1α gene expression in the longissimus dorsi muscles in Bama Xiang and Landrace pigs.

PubMed

Huang, Y N; Ao, Q W; Jiang, Q Y; Guo, Y F; Lan, G Q; Jiang, H S

2016-07-14

Bama Xiang and Landrace pigs are the local fatty and lean breeds, respectively, in China. We compared differences in carcass traits, meat quality traits, and myosin heavy chain (MyHC) types in the longissimus dorsi muscles between Bama Xiang and Landrace pigs. This was done in pigs of the same age, using real-time PCR, to investigate the relationship between MyHC fiber types and carcass characteristics, meat quality traits, and the key factors regulating muscle fiber type. Bama Xiang pigs exhibited smaller size and slower growth than Landrace pigs (P < 0.01). We found that the superior meat quality, especially the high intramuscular fat (IMF) content in Bama Xiang pig, was related to elevated type I oxidative muscle fiber content (P < 0.01). In contrast, Landrace pig muscle had a higher glycolytic type IIb muscle fiber content (P < 0.01). MyHC I gene expression was significantly positively correlated with backfat thickness and IMF content (P < 0.01). MyHC IIb was significantly negatively correlated with IMF content (P < 0.05), and positively correlated with carcass yield (P < 0.05). AMP-activated protein kinase and peroxisome proliferator-activated receptor-g coactivator-1a are suggested to be the two key factors regulating muscle fiber type in pigs. Our results indicate that muscle fiber composition is one of the key differences leading to the differences of meat quality between Bama Xiang and Landrace pigs. These results may provide a theoretical basis for further studies of the molecular mechanism underlying the excellent meat quality of the Bama Xiang pig.

A Wolf-Rayet-Like Progenitor of SN 2013cu from Spectral Observations of a Stellar Wind

NASA Technical Reports Server (NTRS)

Gal-Yam, Avishay; Arcavi, I.; Ofek, E. O.; Ben-Ami, S.; Cenko, S. B.; Kasliwal, M. M.; Cao, Y.; Yaron, O.; Tal, D.; Silverman, J. M.;

Functional Interaction of CD154 Protein with α5β1 Integrin Is Totally Independent from Its Binding to αIIbβ3 Integrin and CD40 Molecules*

PubMed Central

El Fakhry, Youssef; Alturaihi, Haydar; Yacoub, Daniel; Liu, Lihui; Guo, Wenyan; Leveillé, Claire; Jung, Daniel; Khzam, Lara Bou; Merhi, Yahye; Wilkins, John A.; Li, Hongmin; Mourad, Walid

2012-01-01

In addition to its classical CD40 receptor, CD154 also binds to αIIbβ3, α5β1, and αMβ2 integrins. Binding of CD154 to these receptors seems to play a key role in the pathogenic processes of chronic inflammation. This investigation was aimed at analyzing the functional interaction of CD154 with CD40, αIIbβ3, and α5β1 receptors. We found that the binding affinity of CD154 for αIIbβ3 is ∼4-fold higher than for α5β1. We also describe the generation of sCD154 mutants that lost their ability to bind CD40 or αIIbβ3 and show that CD154 residues involved in its binding to CD40 or αIIbβ3 are distinct from those implicated in its interaction to α5β1, suggesting that sCD154 may bind simultaneously to different receptors. Indeed, sCD154 can bind simultaneously to CD40 and α5β1 and biologically activate human monocytic U937 cells expressing both receptors. The simultaneous engagement of CD40 and α5β1 activates the mitogen-activated protein kinases, p38, and extracellular signal-related kinases 1/2 and synergizes in the release of inflammatory mediators MMP-2 and -9, suggesting a cross-talk between these receptors. PMID:22461623

A new animal model for modulating myosin isoform expression by altered mechanical activity

NASA Technical Reports Server (NTRS)

Caiozzo, V. J.; Ma, E.; McCue, S. A.; Smith, E.; Herrick, R. E.; Baldwin, K. M.

1992-01-01

The purpose of this study was to develop a new rodent model that is capable of delineating the importance of mechanical loading on myosin heavy chain (MHC) isoform expression of the plantar and dorsi flexor muscles of the ankle. The essential components of this system include 1) stimulating electrodes that are chronically implanted into a muscle, allowing for the control of the activation pattern of the target muscle(s); 2) a training apparatus that translates the moment of the ankle into a linear force; and 3) a computer-controlled Cambridge 310 ergometer. The isovelocity profile of the ergometer ensured that the medial gastrocnemius (MG) produced forces that were > 90% of maximal isometric force (Po), and the eccentric contractions of the tibialis anterior (TA) were typically 120% of Po. Both the concentric and eccentric training programs produced statistically significant increases in the muscle mass of the MG (approximately 15%) and TA (approximately 7%) as well as a decrease in myofibrillar adenosinetriphosphatase activity. Both the white and red regions of the MG and TA exhibited significant increases in the relative content of the type IIa MHC and concomitant decreases in type IIb MHC expression. Although the red regions of the MG and red TA contained approximately 10% type I MHC, the training programs did not affect this isoform. It appears that when a fast-twitch muscle is stimulated at a high frequency (100 Hz) and required to contract either concentrically or eccentrically under high loading conditions, the expression of the type IIa MHC isoform will be upregulated, whereas that of the type IIb MHC will be concomitantly downregulated.

Myosin heavy chain expression in rodent skeletal muscle: effects of exposure to zero gravity

NASA Technical Reports Server (NTRS)

Haddad, F.; Herrick, R. E.; Adams, G. R.; Baldwin, K. M.

1993-01-01

This study ascertained the effects of 9 days of zero gravity on the relative (percentage of total) and calculated absolute (mg/muscle) content of isomyosin expressed in both antigravity and locomotor skeletal muscle of ground control (CON) and flight-exposed (FL) rats. Results showed that although there were no differences in body weight between FL and CON animals, a significant reduction in muscle mass occurred in the vastus intermedius (VI) (P < 0.05) but not in the vastus lateralis (VL) or the tibialis anterior. Both total muscle protein and myofibril protein content were not different between the muscle regions examined in the FL and CON groups. In the VI, there were trends for reductions in the relative content of type I and IIa myosin heavy chains (MHCs) that were offset by increases in the relative content of both type IIb and possibly type IIx MHC protein (P > 0.05). mRNA levels were consistent with this pattern (P < 0.05). The same pattern held true for the red region of the VL as examined at both the protein and mRNA level (P < 0.05). When the atrophy process was examined, there were net reductions in the absolute content of both type I and IIa MHCs that were offset by calculated increases in type IIb MHC in both VI and red VL. Collectively, these findings suggest that there are both absolute and relative changes occurring in MHC expression in the "red" regions of antigravity skeletal muscle during exposure to zero gravity that could affect muscle function.

Acarbose is an effective adjunct to dietary therapy in the treatment of hypertriglyceridaemias

PubMed Central

Malaguarnera, M; Giugno, I; Ruello, P; Rizzo, M; Motta, M; Mazzoleni, G

1999-01-01

Aims In diabetics, acarbose causes a reduction of blood glucose and triglyceride levels. The aim of this study was to assess the effect of this drug in non diabetic subjects with hypertriglyceridaemia. Methods Thirty non diabetic patients with hypertriglyceridaemia type IIb or IV (24 males, six females; mean age 51.1 ±10.2 years) were studied. They were stratified into two groups depending on their basal triglyceride concentration (group A: triglyceride values ≤4.5 mmol l−1; group B triglyceride values > 4.5 mmol l− 1). Treatment consisted of 4 week courses of diet plus acarbose (50 mg twice daily) alternating with 4 weeks of diet alone for a total period of 16 weeks. Results Mean triglyceride values decreased significantly during the first and third cycles of therapy, i.e. diet plus acarbose treatment cycles in both patient groups. Group A also had significant reductions in total cholesterol and HDL cholesterol concentrations after completion of the acarbose treatment. Reduction of triglyceride levels was observed after both acarbose courses in patients affected by hypertriglyceridaemia type IIb. A marked reduction of triglyceride concentrations was achieved by patients affected by hypertriglyceridaemia type IV after the second acarbose course only. Conclusions Diet alone did not reduce triglyceride concentrations to normal values in our patients. The data suggest that acarbose is a useful adjunct to dietary control in non-diabetic patients affected by severe hypertriglyceridaemia. PMID:10583032

Endothelial Fcγ Receptor IIB Activation Blunts Insulin Delivery to Skeletal Muscle to Cause Insulin Resistance in Mice

PubMed Central

Tanigaki, Keiji; Chambliss, Ken L.; Yuhanna, Ivan S.; Sacharidou, Anastasia; Ahmed, Mohamed; Atochin, Dmitriy N.; Huang, Paul L.

2016-01-01

Modest elevations in C-reactive protein (CRP) are associated with type 2 diabetes. We previously revealed in mice that increased CRP causes insulin resistance and mice globally deficient in the CRP receptor Fcγ receptor IIB (FcγRIIB) were protected from the disorder. FcγRIIB is expressed in numerous cell types including endothelium and B lymphocytes. Here we investigated how endothelial FcγRIIB influences glucose homeostasis, using mice with elevated CRP expressing or lacking endothelial FcγRIIB. Whereas increased CRP caused insulin resistance in mice expressing endothelial FcγRIIB, mice deficient in the endothelial receptor were protected. The insulin resistance with endothelial FcγRIIB activation was due to impaired skeletal muscle glucose uptake caused by attenuated insulin delivery, and it was associated with blunted endothelial nitric oxide synthase (eNOS) activation in skeletal muscle. In culture, CRP suppressed endothelial cell insulin transcytosis via FcγRIIB activation and eNOS antagonism. Furthermore, in knock-in mice harboring constitutively active eNOS, elevated CRP did not invoke insulin resistance. Collectively these findings reveal that by inhibiting eNOS, endothelial FcγRIIB activation by CRP blunts insulin delivery to skeletal muscle to cause insulin resistance. Thus, a series of mechanisms in endothelium that impairs insulin movement has been identified that may contribute to type 2 diabetes pathogenesis. PMID:27207525

A safety and feasibility report of combined direct thrombin and GP IIb/IIIa inhibition with bivalirudin and tirofiban in peripheral vascular disease intervention: treating critical limb ischemia like acute coronary syndrome.

PubMed

Allie, David E; Hebert, Chris J; Lirtzman, Mitchell D; Wyatt, Charles H; Keller, V Antoine; Khan, Mohamed H; Khan, Muhammad A; Fail, Peter S; Vivekananthan, Krishnamoorthy; Allie, Sonja E; Mitran, Elena V; Chaisson, Gary; Stagg, Samuel J; Allie, Adam A; McElderry, Michael W; Barker, Esmond A; Walker, Craig M

2005-08-01

The combination of glycoprotein (GP) IIb-IIIa inhibition and direct thrombin inhibition (DTI) with bivalirudin (Angiomax, The Medicines Company, Cambridge, Massachusetts) have shown ischemic and hemorrhagic outcomes benefit in coronary interventions and may have similar benefits in percutaneous peripheral interventions (PPI). The high incidence of diabetes, chronic renal disease, platelet dysfunction, hypercoagulability, inflammation and a thrombus-rich environment make a GP IIb-IIIa and DTI combination with tirofiban (Aggrastat Merck and Company, Inc., Whitehouse Station, New Jersey) an attractive anticoagulation strategy in the PPI treatment of critical limb ischemia (CLI). Between May 1, 2001 and January 31, 2003, a CLI treatment group of 149 patients received PPI with bivalirudin (0.75 mg per kg bolus with 1.75 mg per kg per hour periprocedural infusion) and tirofiban (10 mcg per kg per minute bolus with 12-hour 0.1 mcg per kg per minute infusion) as an anticoagulation and antiplatelet strategy, and were compared to a matched unfractionated heparin (UFH) control group without GP IIb-IIIa inhibitors. Clinical and hemostasis outcomes were analyzed, including distal embolization (DE). Procedural success was 95.9% and 97.3% in the UFH control group and DTI-GP IIb-IIIa group, respectively. Significant differences were observed in the sheath removal time < 2 hours (60.5% UFH group versus 19.4% DTI-GP IIb-IIIa group; p = < 0.0001). Vascular closure devices were used equally in both groups. No statistical significance was observed in major and minor complications, femoral access complications, acute (< 48 hours) or subacute (30 days) vessel thrombosis, and 6-month duplex ultrasound restenosis rate between the DTI-GP IIb-IIIa versus the UFH group. A trend towards statistical significance was observed in the 6-month secondary re-intervention and limb salvage rates (10.7% versus 18.8%; p = 0.0501 and 93.9% versus 88.5%; p = 0.053) in the DTI-GP IIb-IIIa versus the UFH group, respectively. Angiographically relevant DE occurred in 4 of 149 (1.3%) and 8 of 149 (5.4%) of the bivalirudin-tirofiban and UFH groups, respectively. The combination of DTI with bivalirudin and GP IIb-IIIa inhibition with tirofiban is a safe and feasible alternative anticoagulation and antiplatelet strategy in PPI, and may offer improved clinical and hemostasis outcomes in treating CLI. A larger, prospective randomized trial is warranted.

Method and making group IIB metal - telluride films and solar cells

DOEpatents

Basol, Bulent M.; Kapur, Vijay K.

1990-08-21

A technique is disclosed forming thin films (13) of group IIB metal-telluride, such as Cd.sub.x Zn.sub.1-x Te (0.ltoreq.x.ltoreq.1), on a substrate (10) which comprises depositing Te (18) and at least one of the elements (19) of Cd, Zn, and Hg onto a substrate and then heating the elements to form the telluride. A technique is also provided for doping this material by chemically forming a thin layer of a dopant on the surface of the unreacted elements and then heating the elements along with the layer of dopant. A method is disclosed of fabricating a thin film photovoltaic cell which comprises depositing Te and at least one of the elements of Cd, Zn, and Hg onto a substrate which contains on its surface a semiconductor film (12) and then heating the elements in the presence of a halide of the Group IIB metals, causing the formation of solar cell grade Group IIB metal-telluride film and also causing the formation of a rectifying junction, in situ, between the semiconductor film on the substrate and the Group IIB metal-telluride layer which has been formed.

Instantons in string theory

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

Ahlén, Olof, E-mail: olof.ahlen@aei.mpg.de

2015-12-17

These proceedings from the second Caesar Lattes meeting in Rio de Janeiro 2015 are a brief introduction to how automorphic forms appear in the low energy effective action of maximally supersymmetric string theory. The explicit example of the R{sup 4}-interaction of type IIB string theory in ten dimensions is discussed. Its Fourier expansion is interpreted in terms of perturbative and non-perturbative contributions to the four graviton amplitude.

National Marrow Donor Program. HLA Typing for Bone Marrow Transplantation

DTIC Science & Technology

2014-11-30

educate the transplant community about the critical importance of establishing a nationwide contingency response plan. 2. Rapid Identification of...Expand Network Communications 59 IIB 4.2 Central Contingency Management 59 IIC Immunogenetic Studies 63 IIC.1.1 Donor Recipient Pair Project 63 IIC...Amendment CMCR Centers for Medical Countermeasures Against Radiation CMDP China Marrow Donor Program CME Continuing Medical Education CMF Community

Glycoprotein IIb/IIIa inhibitors in patients with unstable angina/non-ST-segment elevation myocardial infarction: appropriate interpretation of the guidelines.

PubMed

Antman, Elliott M

2003-10-01

In 2002, the American College of Cardiology and the American Heart Association published an update to their guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction. These revised guidelines make specific recommendations regarding the use of glycoprotein IIb/IIIa inhibitors. This article briefly reviews the evidence supporting the use of glycoprotein IIb/IIIa inhibitors in unstable angina and non-ST-segment elevation myocardial infarction, before moving on to discuss interpretation of these new guidelines.

A TaqMan-Based Multiplex qPCR Assay and DNA Extraction Method for Phylotype IIB Sequevars 1&2 (Select Agent) Strains of Ralstonia solanacearum

PubMed Central

Stulberg, Michael J.; Huang, Qi

2015-01-01

Ralstonia solanacearum race 3 biovar 2 strains belonging to phylotype IIB, sequevars 1 and 2 (IIB-1&2) cause brown rot of potato in temperate climates, and are quarantined pathogens in Canada and Europe. Since these strains are not established in the U.S. and because of their potential risk to the potato industry, the U.S. government has listed them as select agents. Cultivated geraniums are also a host and have the potential to spread the pathogen through trade, and its extracts strongly inhibits DNA-based detection methods. We designed four primer and probe sets for an improved qPCR method that targets stable regions of DNA. RsSA1 and RsSA2 recognize IIB-1&2 strains, RsII recognizes the current phylotype II (the newly proposed R. solanacearum species) strains (and a non-plant associated R. mannitolilytica), and Cox1 recognizes eight plant species including major hosts of R. solanacearum such as potato, tomato and cultivated geranium as an internal plant control. We multiplexed the RsSA2 with the RsII and Cox1 sets to provide two layers of detection of a positive IIB-1&2 sample, and to validate plant extracts and qPCR reactions. The TaqMan-based uniplex and multiplex qPCR assays correctly identified 34 IIB-1&2 and 52 phylotype II strains out of 90 R. solanacearum species complex strains. Additionally, the multiplex qPCR assay was validated successfully using 169 artificially inoculated symptomatic and asymptomatic plant samples from multiple plant hosts including geranium. Furthermore, we developed an extraction buffer that allowed for a quick and easy DNA extraction from infected plants including geranium for detection of R. solanacearum by qPCR. Our multiplex qPCR assay, especially when coupled with the quick extraction buffer method, allows for quick, easy and reliable detection and differentiation of the IIB-1&2 strains of R. solanacearum. PMID:26426354

N6-Trimethyl-lysine metabolism. Structural identification of the metabolite 3-hydroxy-N6-trimethyl-lysine

PubMed Central

Novak, Raymond F.; Swift, Terrence J.; Hoppel, Charles L.

1980-01-01

1H and 13C nuclear-magnetic-resonance spectroscopy and functional-group analysis were used to determine the molecular structure of an isolated metabolite (IIb) of trimethyl-lysine as 3-hydroxy-N6-trimethyl-lysine, an important intermediate in the conversion of trimethyl-lysine into trimethylammoniobutyrate and carnitine [Hoppel, Cox & Novak (1980) Biochem. J. 188, 509–519]. Functional-group analysis revealed the presence of a primary amine and reaction of metabolite (IIb) with periodate yielded 4-N-trimethylammoniobutyrate as a product, showing 2,3-substitution on the molecule and suggesting that the 3-substitution on the molecule may be an alcohol ([unk]CH–OH), amine ([unk]CH[unk]–NH2) or carbonyl ([unk]C=O) functional group. 1H integration ratios, 1H and 13C chemical-shift data and 1H and 13C signal multiplicities from the sample (IIb) were used to complete the identification of metabolite (IIb) as 3-hydroxy-N6-trimethyl-lysine. For example, the proton multiplet at δ 4.2p.p.m. and doublet at δ 4.1p.p.m., positions representative of amine or alcohol substitution on methylene carbon atoms, integration ratios of 1:1:2:9:4 and a positive ninhydrin test suggest 3-hydroxy-N6-trimethyl-lysine as the molecular structure for metabolite (IIb). 13C chemical-shift data obtained from the sample (IIb) and compared with several model compounds (trimethylammoniohexanoate, trimethyl-lysine and 3-hydroxylysine) resulted in generation of the spectrum of the metabolite and allowed independent identification of metabolite (IIb) as 3-hydroxy-N6-trimethyl-lysine. The 1H spectrum of erythro- and threo-3-hydroxylysine are presented for comparison, and the 1H and 13C n.m.r. spectra of the erythro-isomer support this analysis. PMID:6772169

Capillarization in skeletal muscle of rats with cardiac hypertrophy.

PubMed

Degens, Hans; Anderson, Rebecca K; Alway, Stephen E

2002-02-01

Exercise intolerance during chronic heart failure (CHF) is localized mainly in skeletal muscle. A decreased capillarization may impair exchange of oxygen between capillaries and muscle tissue and in this way contribute to exercise intolerance. We assessed changes in capillary supply in plantaris and diaphragm muscles of a rat aorta-caval fistula (ACF) preparation, a volume overload model for CHF. An ACF was created under equithesin anesthesia. Plantaris and diaphragm muscles were removed 6 wk postsurgery and examined for myosin heavy chain (MyHC) content and capillary supply. Cardiac hypertrophy was 96% (P < 0.002) after ACF. The Type IIb MyHC content of the plantaris muscles increased (33.9 +/- 3.3 vs 49.8 +/- 3.8%; mean +/- SEM) at the expense of Type IIa MyHC (17.6 +/- 1.8 vs 11.2 +/- 1.7%) in ACF rats (P < 0.05). In the diaphragm, the number of Type I (32.1 +/- 2.3 vs 40.6 +/- 2.7%) and IIb fibers (40.6 +/- 1.9 vs 49.6 +/- 3.6%) increased at the expense of Type IIa fibers (26.8 +/- 2.5 vs 9.4 +/- 0.9%) (P < 0.05). The capillary number per fiber did not change, and this indicated that no capillary loss occurred with ACF. Also, the capillary density was maintained in the diaphragm and plantaris muscles of ACF rats. Furthermore, the coupling between fiber type, size, and metabolic type of surrounding fibers, with the capillary supply to a fiber, was maintained in rats with an ACF. The cardiac hypertrophy induced by volume overload seems adequate to prevent atrophy and changes in the microcirculation of limb and diaphragm muscles.

Modularity, quaternion-Kähler spaces, and mirror symmetry

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

Alexandrov, Sergei; Banerjee, Sibasish

2013-10-15

We provide an explicit twistorial construction of quaternion-Kähler manifolds obtained by deformation of c-map spaces and carrying an isometric action of the modular group SL(2,Z). The deformation is not assumed to preserve any continuous isometry and therefore this construction presents a general framework for describing NS5-brane instanton effects in string compactifications with N= 2 supersymmetry. In this context the modular invariant parametrization of twistor lines found in this work yields the complete non-perturbative mirror map between type IIA and type IIB physical fields.

Conservation of the Human Integrin-Type Beta-Propeller Domain in Bacteria

PubMed Central

Chouhan, Bhanupratap; Denesyuk, Alexander; Heino, Jyrki; Johnson, Mark S.; Denessiouk, Konstantin

2011-01-01

Integrins are heterodimeric cell-surface receptors with key functions in cell-cell and cell-matrix adhesion. Integrin α and β subunits are present throughout the metazoans, but it is unclear whether the subunits predate the origin of multicellular organisms. Several component domains have been detected in bacteria, one of which, a specific 7-bladed β-propeller domain, is a unique feature of the integrin α subunits. Here, we describe a structure-derived motif, which incorporates key features of each blade from the X-ray structures of human αIIbβ3 and αVβ3, includes elements of the FG-GAP/Cage and Ca2+-binding motifs, and is specific only for the metazoan integrin domains. Separately, we searched for the metazoan integrin type β-propeller domains among all available sequences from bacteria and unicellular eukaryotic organisms, which must incorporate seven repeats, corresponding to the seven blades of the β-propeller domain, and so that the newly found structure-derived motif would exist in every repeat. As the result, among 47 available genomes of unicellular eukaryotes we could not find a single instance of seven repeats with the motif. Several sequences contained three repeats, a predicted transmembrane segment, and a short cytoplasmic motif associated with some integrins, but otherwise differ from the metazoan integrin α subunits. Among the available bacterial sequences, we found five examples containing seven sequential metazoan integrin-specific motifs within the seven repeats. The motifs differ in having one Ca2+-binding site per repeat, whereas metazoan integrins have three or four sites. The bacterial sequences are more conserved in terms of motif conservation and loop length, suggesting that the structure is more regular and compact than those example structures from human integrins. Although the bacterial examples are not full-length integrins, the full-length metazoan-type 7-bladed β-propeller domains are present, and sometimes two tandem copies are found. PMID:22022374

A retrospective analysis and case series of glycoprotein IIb/IIIa inhibitor associated diffuse alveolar hemorrhage: two case reports

PubMed Central

Mikkilineni, Hima; Bruhl, Steven R; Pandya, Utpal

2009-01-01

Introduction Glycoprotein IIb/IIIa inhibitors have a key role in the treatment of patients with acute coronary syndromes undergoing percutaneous interventions. Although, an increased risk of bleeding complications is well recognized, its association with diffuse alveolar hemorrhage is much less recognized. Previous authors have suggested that the incidence of glycoprotein IIb/IIIa inhibitor associated diffuse alveolar hemorrhage has been significantly underestimated due to under reporting. Case presentations In order to help better determine the incidence of GP IIb/IIIa inhibitor associated DAH, a retrospective review of medical records was conducted over a 1 year period at a single high volume medical hospital. The medical records of all patients diagnosed with diffuse alveolar hemorrhage were evaluated for treatment with a GP IIb/IIIa inhibitor within 48 hours of its diagnosis. Each patient meeting the inclusion and exclusion criteria were included in the case series. This number was compared with the total number of patients receiving a GP IIb/IIIa inhibitor during the same time period and an incidence of the complication was calculated. 292 patients received either abciximab or eptifibatide during the one year review period and two patients were diagnosed with diffuse alveolar hemorrhage confirmed by serial bronchiolar lavage for an incidence of 0.68%. Of the total 292 patients receiving GP IIb/IIIa inhibitors, 172 patients received abciximab with one occurrence of diffuse alveolar hemorrhage for an incidence of 0.58% while 120 patients received eptifibatide with one occurrence for an incidence of 0.83%. Both patients developed significant morbidity as a result of the complication and 1 of the 2 patients died as a complication of the disease. Conclusions Our findings support the claim that the incidence of GP IIb/IIIa induced diffuse alveolar hemorrhage is substantially higher than initially suggested by drug manufacturer studies. Although these drugs have proven mortality benefits, its association with diffuse alveolar hemorrhage is likely under-recognized leading to significant under-reporting. The best way to more accurately determine the true incidence of this complication and decrease its morbidity and mortality is to increase awareness as well as include diffuse alveolar hemorrhage as a serious complication in product labeling. PMID:19830082

Hypofractionated Radiation Therapy in Treating Patients With Stage 0-IIB Breast Cancer

ClinicalTrials.gov

2018-05-11

Ductal Breast Carcinoma In Situ; Invasive Breast Carcinoma; Stage 0 Breast Cancer; Stage I Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer

Survivorship Care Planning in Patients With Colorectal or Non-Small Cell Lung Cancer

ClinicalTrials.gov

2013-12-16

Stage I Colon Cancer; Stage I Rectal Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Colon Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer

Modification of a Limbed Robot to Favor Climbing

NASA Technical Reports Server (NTRS)

Okon, Avi; Kennedy, Brett; Garrett, Michael; Magnone, Lee

2006-01-01

The figure shows the LEMUR IIb, which is a modified version of the LEMUR II the second generation of the Limbed Excursion Mechanical Utility Robot (LEMUR). Except as described below, the LEMUR IIb hardware is mostly the same as that of the LEMUR II. The IIb and II versions differ in their kinematic configurations and characteristics associated with their kinematic configurations. The differences are such that relative to the LEMUR II, the LEMUR IIb is simpler and is better suited to climbing on inclined surfaces. The first-generation LEMUR, now denoted the LEMUR I, was described in Six-Legged Experimental Robot (NPO-20897), NASA Tech Briefs, Vol. 25, No. 12 (December 2001), page 58. The LEMUR II was described in Second-Generation Six-Limbed Experimental Robot (NPO-35140) NASA Tech Briefs, Vol. 28, No. 11 (November 2004), page 55. To recapitulate: the LEMUR I and LEMUR II were six-legged or sixlimbed robots for demonstrating robotic capabilities for assembly, maintenance, and inspection. They were designed to be capable of walking autonomously along a truss structure toward a mechanical assembly at a prescribed location. They were equipped with stereoscopic video cameras and image-data-processing circuitry for navigation and mechanical operations. They were also equipped with wireless modems, through which they could be commanded remotely. Upon arrival at a mechanical assembly, the LEMUR I would perform simple mechanical operations by use of one or both of its front legs (or in the case of the LEMUR II, any of its limbs could be used to perform mechanical operations). Either LEMUR could also transmit images to a host computer. The differences between the LEMUR IIb and the LEMUR II are the following: Whereas the LEMUR II had six limbs, the LEMUR IIb has four limbs. This change has reduced both the complexity and mass of the legs and of the overall robot. Whereas each limb of the LEMUR II had four degrees of freedom (DOFs), each limb of the LEMUR IIb has three DOFs. This change has also reduced both complexity and mass. Notwithstanding the decrease in the number of DOFs, the three remaining DOFs are configured to provide greater dexterity for motion along a surface. To extend reach, the limbs of the LEMUR IIb are 25 percent longer than those of the LEMUR II. Additional benefits stemming from the modifications are that the robot body supported by the limbs is now less massive and its center of gravity is now closer to the surface along which the robot is to move. These benefits have been obtained without sacrificing load-carrying capacity. Hence, overall, the LEMUR IIb is a more adept climber.

Adaptation of rat jaw muscle fibers in postnatal development with a different food consistency: an immunohistochemical and electromyographic study.

PubMed

Kawai, Nobuhiko; Sano, Ryota; Korfage, Joannes A M; Nakamura, Saika; Kinouchi, Nao; Kawakami, Emi; Tanne, Kazuo; Langenbach, Geerling E J; Tanaka, Eiji

2010-06-01

The development of the craniofacial system occurs, among other reasons, as a response to functional needs. In particular, the deficiency of the proper masticatory stimulus affects the growth. The purpose of this study was to relate alterations of muscle activity during postnatal development to adaptational changes in the muscle fibers. Fourteen 21-day-old Wistar strain male rats were randomly divided into two groups and fed on either a solid (hard-diet group) or a powder (soft-diet group) diet for 63 days. A radio-telemetric device was implanted to record muscle activity continuously from the superficial masseter, anterior belly of digastric and anterior temporalis muscles. The degree of daily muscle use was quantified by the total duration of muscle activity per day (duty time), the total burst number and their average length exceeding specified levels of the peak activity (5, 20 and 50%). The fiber type composition of the muscles was examined by the myosin heavy chain content of fibers by means of immunohistochemical staining and their cross-sectional area was measured. All muscle fibers were identified as slow type I and fast type IIA, IIX or IIB (respectively, with increasing twitch contraction speed and fatigability). At lower activity levels (exceeding 5% of the peak activity), the duty time of the anterior belly of the digastric muscle was significantly higher in the soft-diet group than in the hard-diet group (P < 0.05). At higher activity levels (exceeding 20 and 50% of the peak activity), the duty time of the superficial masseter muscle in the soft-diet group was significantly lower than that in the hard-diet group (P < 0.05). There was no difference in the duty time of the anterior temporalis muscle at any muscle activity level. The percentage of type IIA fibers of the superficial masseter muscle in the soft-diet group was significantly lower than that in the hard-diet group (P < 0.01) and the opposite was true with regard to type IIB fibers (P < 0.05). The cross-sectional area of type IIX and type IIB fibers of the superficial masseter muscle was significantly smaller in the soft-diet group than in the hard-diet group (P < 0.05). There was no difference in the muscle fiber composition and the cross-sectional area of the anterior belly of the digastric and anterior temporalis muscles. In conclusion, for the jaw muscles of male rats reared on a soft diet, the slow-to-fast transition of muscle fiber was shown in only the superficial masseter muscle. Therefore, the reduction in the amount of powerful muscle contractions could be important for the slow-to-fast transition of the myosin heavy chain isoform in muscle fibers.

Higher derivative couplings in theories with sixteen supersymmetries

DOE PAGES

Lin, Ying -Hsuan; Shao, Shu -Heng; Yin, Xi; ...

2015-12-15

We give simple arguments for new non-renormalization theorems on higher derivative couplings of gauge theories to supergravity, with sixteen supersymmetries, by considerations of brane-bulk superamplitudes. This leads to some exact results on the effective coupling of D3-branes in type IIB string theory. As a result, we also derive exact results on higher dimensional operators in the torus compactification of the six dimensional (0, 2) superconformal theory.

Type IIB supergravity solution for the T-dual of the η-deformed AdS 5 × S 5 superstring

NASA Astrophysics Data System (ADS)

Hoare, B.; Tseytlin, A. A.

2015-10-01

We find an exact type IIB supergravity solution that represents a one-parameter deformation of the T-dual of the AdS 5 × S 5 background (with T-duality applied in all 6 abelian bosonic isometric directions). The non-trivial fields are the metric, dilaton and RR 5-form only. The latter has remarkably simple "undeformed" form when written in terms of a "deformation-rotated" vielbein basis. An unusual feature of this solution is that the dilaton contains a linear dependence on the isometric coordinates of the metric precluding a straightforward reversal of T-duality. If we still formally dualize back, we find exactly the metric, B-field and product of dilaton with RR field strengths as recently extracted from the η-deformed AdS 5 × S 5 superstring action in arXiv:1507.04239. We also discuss similar solutions for deformed AdS n × S n backgrounds with n = 2 , 3. In the η → i limit we demonstrate that all these backgrounds can be interpreted as special limits of gauged WZW models and are also related to (a limit of) the Pohlmeyer-reduced models of the AdS n × S n superstrings.

Organization of the BcgI restriction-modification protein for the cleavage of eight phosphodiester bonds in DNA

PubMed Central

Smith, Rachel M.; Marshall, Jacqueline J. T.; Jacklin, Alistair J.; Retter, Susan E.; Halford, Stephen E.; Sobott, Frank

2013-01-01

Type IIB restriction-modification systems, such as BcgI, feature a single protein with both endonuclease and methyltransferase activities. Type IIB nucleases require two recognition sites and cut both strands on both sides of their unmodified sites. BcgI cuts all eight target phosphodiester bonds before dissociation. The BcgI protein contains A and B polypeptides in a 2:1 ratio: A has one catalytic centre for each activity; B recognizes the DNA. We show here that BcgI is organized as A2B protomers, with B at its centre, but that these protomers self-associate to assemblies containing several A2B units. Moreover, like the well known FokI nuclease, BcgI bound to its site has to recruit additional protomers before it can cut DNA. DNA-bound BcgI can alternatively be activated by excess A subunits, much like the activation of FokI by its catalytic domain. Eight A subunits, each with one centre for nuclease activity, are presumably needed to cut the eight bonds cleaved by BcgI. Its nuclease reaction may thus involve two A2B units, each bound to a recognition site, with two more A2B units bridging the complexes by protein–protein interactions between the nuclease domains. PMID:23147005

Prevalence and Clinical Characteristics of Itch in Vitiligo and Its Clinical Significance.

PubMed

Vachiramon, Vasanop; Onprasert, Woranit; Harnchoowong, Sarawin; Chanprapaph, Kumutnart

2017-01-01

Vitiligo usually presented as asymptomatic depigmented macules and patches. Little is known regarding itch in vitiligo. This study aimed to evaluate the prevalence and characteristics of itch in vitiligo patients. A cross-sectional study was conducted on vitiligo patients. Itch character and intensity were determined through questionnaires. Evaluation was also made by dermatologists to define vitiligo subtype, body surface area, Koebner phenomenon (KP), and so on. Data were assessed by computer software. Results were considered statistically significant if p < 0.05. Among 402 patients, itch on vitiliginous lesion presented in 20.2%. Prevalence of itch was most common in focal vitiligo (29.4%), followed by segmental vitiligo (20.3%) and nonsegmental vitiligo (19.6%), respectively. Tingling sensation was the most common itch-related symptom (82.7%). The median itch intensity is 5 by 10-point visual analog scale. Daily activity and sleep disturbance were observed in 60.5% and 39.5% of patients who experience itch. Itch occurred approximately 3 days prior to the development of lesions in 48.1% of patients. Thirty-two patients (78.1%) with both itch and KP type IIb had active disease. Itch in vitiligo is not uncommon. The presence of itch with KP type IIb may warrant the active vitiligo.

Inhibition of Activin Receptor Type IIB Increases Strength and Lifespan in Myotubularin-Deficient Mice

PubMed Central

Lawlor, Michael W.; Read, Benjamin P.; Edelstein, Rachel; Yang, Nicole; Pierson, Christopher R.; Stein, Matthew J.; Wermer-Colan, Ariana; Buj-Bello, Anna; Lachey, Jennifer L.; Seehra, Jasbir S.; Beggs, Alan H.

2011-01-01

X-linked myotubular myopathy (XLMTM) is a congenital disorder caused by deficiency of the lipid phosphatase, myotubularin. Patients with XLMTM often have severe perinatal weakness that requires mechanical ventilation to prevent death from respiratory failure. Muscle biopsy specimens from patients with XLMTM exhibit small myofibers with central nuclei and central aggregations of organelles in many cells. It was postulated that therapeutically increasing muscle fiber size would cause symptomatic improvement in myotubularin deficiency. Recent studies have elucidated an important role for the activin-receptor type IIB (ActRIIB) in regulation of muscle growth and have demonstrated that ActRIIB inhibition results in significant muscle hypertrophy. To evaluate whether promoting muscle hypertrophy can attenuate symptoms resulting from myotubularin deficiency, the effect of ActRIIB-mFC treatment was determined in myotubularin-deficient (Mtm1δ4) mice. Compared with wild-type mice, untreated Mtm1δ4 mice have decreased body weight, skeletal muscle hypotrophy, and reduced survival. Treatment of Mtm1δ4 mice with ActRIIB-mFC produced a 17% extension of lifespan, with transient increases in weight, forelimb grip strength, and myofiber size. Pathologic analysis of Mtm1δ4 mice during treatment revealed that ActRIIB-mFC produced marked hypertrophy restricted to type 2b myofibers, which suggests that oxidative fibers in Mtm1δ4 animals are incapable of a hypertrophic response in this setting. These results support ActRIIB-mFC as an effective treatment for the weakness observed in myotubularin deficiency. PMID:21281811

Morphological and Biochemical Effects on the Skeletal Muscle of Ovariectomized Old Female Rats Submitted to the Intake of Diets with Vegetable or Animal Protein and Resistance Training

PubMed Central

Figueiredo Braggion, Glaucia; Ornelas, Elisabete; Carmona Sattin Cury, Jurema; Edviges Alves Lima, Natália; Aquino, Rita C.; Affonso Fonseca, Fernando Luiz; Maifrino, Laura Beatriz Mesiano

2016-01-01

Introduction. Sarcopenia is a process characterized by reduction in protein mass and muscle strength with increasing age, especially in the postmenopausal period, resulting in functional limitations and with great impact on the physical autonomy of the elderly. Objective. To evaluate the effects of diets with vegetable proteins (VP) or animal proteins (AP) associated with resistance training (RT) on the structural and biochemical parameters of the medial gastrocnemius muscle in Wistar rats with sarcopenia. Methods. An experimental model with ovariectomized rats was used to induce sarcopenia and resistance training. The histochemical technique was used for the typing of muscle fibers, the cross-sectional area of myocytes, and volume densities of myocytes and interstitium; the technique of Picrosirius stain was used to highlight the collagen fibers. Results. The VP diet was not able to minimize the effects of sarcopenia in the medial gastrocnemius of sedentary animals and when associated with RT, it promoted maintenance of the CSA, attenuating the atrophy of type IIB fibers in the medial gastrocnemius. The AP diet in sedentary animals protected the type I fibers. When combined with RT, the AP promoted muscle remodeling, with reduction in volume density of type I and IIA fibers, and increase of IIB fibers, together with an increase in collagen volume density. Conclusion. The data suggest a tendency to better results of hypertrophy in animal groups that consumed the AP diet, even the sedentary animals, although more evident in those trained. PMID:26885253

LOSS Revisited. II. The Relative Rates of Different Types of Supernovae Vary between Low- and High-mass Galaxies

NASA Astrophysics Data System (ADS)

Graur, Or; Bianco, Federica B.; Modjaz, Maryam; Shivvers, Isaac; Filippenko, Alexei V.; Li, Weidong; Smith, Nathan

2017-03-01

In Paper I of this series, we showed that the ratio between stripped-envelope (SE) supernova (SN) and Type II SN rates reveals a significant SE SN deficiency in galaxies with stellar masses ≲ {10}10 {M}⊙ . Here, we test this result by splitting the volume-limited subsample of the Lick Observatory Supernova Search (LOSS) SN sample into low- and high-mass galaxies and comparing the relative rates of various SN types found in them. The LOSS volume-limited sample contains 180 SNe and SN impostors and is complete for SNe Ia out to 80 Mpc and core-collapse SNe out to 60 Mpc. All of these transients were recently reclassified by us in Shivvers et al. We find that the relative rates of some types of SNe differ between low- and high-mass galaxies: SNe Ib and Ic are underrepresented by a factor of ˜3 in low-mass galaxies. These galaxies also contain the only examples of SN 1987A-like SNe in the sample and host about nine times as many SN impostors. Normal SNe Ia seem to be ˜30% more common in low-mass galaxies, making these galaxies better sources for homogeneous SN Ia cosmology samples. The relative rates of SNe IIb are consistent in both low- and high-mass galaxies. The same is true for broad-line SNe Ic, although our sample includes only two such objects. The results presented here are in tension with a similar analysis from the Palomar Transient Factory, especially as regards SNe IIb.

Supernovae from massive stars with extended tenuous envelopes

NASA Astrophysics Data System (ADS)

Dessart, Luc; Yoon, Sung-Chul; Livne, Eli; Waldman, Roni

2018-04-01

Massive stars with a core-halo structure are interesting objects for stellar physics and hydrodynamics. Using simulations for stellar evolution, radiation hydrodynamics, and radiative transfer, we study the explosion of stars with an extended and tenuous envelope (i.e. stars in which 95% of the mass is contained within 10% or less of the surface radius). We consider both H-rich supergiant and He-giant progenitors resulting from close-binary evolution and dying with a final mass of 2.8-5 M⊙. An extended envelope causes the supernova (SN) shock to brake and a reverse shock to form, sweeping core material into a dense shell. The shock-deposited energy, which suffers little degradation from expansion, is trapped in ejecta layers of moderate optical depth, thereby enhancing the SN luminosity at early times. With the delayed 56Ni heating, we find that the resulting optical and near-IR light curves all exhibit a double-peak morphology. We show how an extended progenitor can explain the blue and featureless optical spectra of some Type IIb and Ib SNe. The dense shell formed by the reverse shock leads to line profiles with a smaller and near-constant width. This ejecta property can explain the statistically narrower profiles of Type IIb compared to Type Ib SNe, as well as the peculiar Hα profile seen in SN 1993J. At early times, our He-giant star explosion model shows a high luminosity, a blue colour, and featureless spectra reminiscent of the Type Ib SN 2008D, suggesting a low-mass progenitor.

Gene Regions Responding to Skeletal Muscle Atrophy

NASA Technical Reports Server (NTRS)

Booth, Frank W.

1997-01-01

Our stated specific aims for this project were: 1) Identify the region(s) of the mouse IIb myosin heavy chain (MHC) promoter necessary for in vivo expression in mouse fast-twitch muscle, and 2) Identify the region(s) of the mouse IIb MHC promoter responsive to immobilization in mouse slow-twitch muscle in vivo. We sought to address these specific aims by introducing various MHC IIb promoter/reporter gene constructs directly into the tibialis anterior and gastrocnemius muscles of living mice. Although the method of somatic gene transfer into skeletal muscle by direct injection has been successfully used in our laboratory to study the regulation of the skeletal alpha actin gene in chicken skeletal muscle, we had many difficulties utilizing this procedure in the mouse. Because of the small size of the mouse soleus and the difficulty in obtaining consistent results, we elected not to study this muscle as first proposed. Rather, our MHC IIb promoter deletion experiments were performed in the gastrocnemius. Further, we decided to use hindlimb unloading via tail suspension to induce an upregulation of the MHC IIb gene, rather than immobilization of the hindlimbs via plaster casts. This change was made because tail suspension more closely mimics spaceflight, and this procedure in our lab results in a smaller loss of overall body mass than the mouse hindlimb immobilization procedure. This suggests that the stress level during tail suspension is less than during immobilization. This research has provided an important beginning point towards understanding the molecular regulation of the MHC lIb gene in response to unweighting of skeletal muscle Future work will focus on the regulation of MHC IIb mRNA stability in response to altered loading of skeletal muscle

Platelet gene therapy improves hemostatic function for integrin αIIbβ3-deficient dogs

PubMed Central

Fang, Juan; Jensen, Eric S.; Boudreaux, Mary K.; Du, Lily M.; Hawkins, Troy B.; Koukouritaki, Sevasti B.; Cornetta, Kenneth; Wilcox, David A.

2011-01-01

Activated blood platelets mediate the primary response to vascular injury. Although molecular abnormalities of platelet proteins occur infrequently, taken collectively, an inherited platelet defect accounts for a bleeding diathesis in ≈1:20,000 individuals. One rare example of a platelet disorder, Glanzmann thrombasthenia (GT), is characterized by life-long morbidity and mortality due to molecular abnormalities in a major platelet adhesion receptor, integrin αIIbβ3. Transfusion therapy is frequently inadequate because patients often generate antibodies to αIIbβ3, leading to immune-mediated destruction of healthy platelets. In the most severe cases allogeneic bone marrow transplantation has been used, yet because of the risk of the procedure it has been limited to few patients. Thus, hematopoietic stem cell gene transfer was explored as a strategy to improve platelet function within a canine model for GT. Bleeding complications necessitated the use of a mild pretransplant conditioning regimen; therefore, in vivo drug selection was used to improve engraftment of autologously transplanted cells. Approximately 5,000 αIIbβ3 receptors formed on 10% of platelets. These modest levels allowed platelets to adhere to αIIbβ3’s major ligand (fibrinogen), form aggregates, and mediate retraction of a fibrin clot. Remarkably, improved hemostatic function was evident, with ≤135-fold reduced blood loss, and improved buccal bleeding times decreased to 4 min for up to 5 y after transplant. One of four transplanted dogs developed a significant antibody response to αIIbβ3 that was attenuated effectively with transient immune suppression. These results indicate that gene therapy could become a practical approach for treating inherited platelet defects. PMID:21606353

A Prospective Study of Level IIB Nodal Metastasis (Supraretrospinal) in Clinically N0 Oral Squamous Cell Carcinoma in Indian Population.

PubMed

Chheda, Yogen P; Pillai, Sundaram K; Parikh, Devendra G; Dipayan, Nandy; Shah, Shakuntala V; Alaknanda, Gupta

2017-06-01

Oral cavity carcinoma is the most common cancer in Indian population. Metastatic nodal disease is the most important prognostic factor for oral cancers. In head and neck cancers with clinically N0 neck, standard selective neck dissection is performed by protecting the spinal accessory nerve to remove level IIA & IIB lymph nodes. The purpose of this study was to analyze the significance of level IIB dissection in patients of oral cavity cancer who underwent primary surgery with functional neck dissection. Two hundred ten patients with clinically N0 neck underwent neck dissection, where level IIB lymph nodes were dissected, labelled and processed separately. Among 210 patients of clinically N0 neck, 168 patients were pathologically N0 (80 %). Out of remaining 42 (20 %), 36 (17.14 %) were pN1 and 6 (2.86 %) were pN2. Among those with pN1 (36), level IB was involved in 24 patients (66.67 %) and level IIA was involved in 12 patients (33.33 %). Only 2 patients had involvement of level IIB lymph nodes. Among 6 patients of pN2 disease, 4 patients had simultaneous involvement of level IB and level IIA lymph nodes. Remaining 2 patients had isolated involvement of level III lymph nodes. Thus only 2 patients (< 1 %) out of 210 clinically N0 oral squamous cell carcinoma showed level IIB lymph node involvement. Thus we conclude that a frozen section of level 2a is advisable to decide the need for level 2b node dissection in clinically N0 neck as the sensitivity of clinical evaluation is extremely low.

Sporadic ganglioneuromatosis of esophagogastric junction in a patient with gastro-esophageal reflux disorder and intestinal metaplasia.

PubMed

Siderits, Richard; Hanna, Iman; Baig, Zahid; Godyn, Janusz-J

2006-12-28

A 58-year-old female with a recurrent history of upper abdominal pain and intermittent dysphagia underwent endoscopic evaluation that demonstrated an irregular and nodular esophago-gastric (EG) junction and grade I erosive esophagitis. Biopsies showed prominent intestinal metaplasia of Barrett's type without dysplasia, chronic inflammation and multiple aggregates of large cells within the mucosal lamina propria, some with spindle shaped nuclei. Immunohistochemistry stains for keratins AE-1/AE-3 were negative, while S-100 and NSE were positive. This, together with routine stains, was diagnostic for mucosal ganglioneuromatosis. The background of chronic inflammation with intestinal type metaplasia was consistent with long-term reflux esophagitis. No evidence of achalasia was seen. Biopsies of gastric antrum and fundus were unremarkable, without ganglioneural proliferation. Colonoscopy was unremarkable. No genetic syndromes were identified in the patient including familial adenomatous polyposis and multiple endocrine neoplasia type IIb (MEN IIb). Iansoprazole (Prevacid) was started by oral administration each day with partial relief of symptoms. Subsequent esophagogastroscopy repeated at 4 mo showed normal appearing EG junction. Esophageal manometry revealed a mild non-specific lower esophageal motility disorder. Mild motor dysfunction is seen with gastro-esophageal reflux disease (GERD) and we feel that the demonstration of localized ganglioneuromatosis was not likely related etiologically. In the absence of findings that might suggest neural hypertrophy, such as achalasia, the nodular mucosal irregularity seen with this instance of ganglioneuromatosis may, however, have exacerbated the patient's reflux.

A TaqMan-based multiplex qPCR assay and DNA extraction method for phylotype IIB sequevars 1&2 (select agent) strains of Ralstonia solanacearum

DOE PAGES

Stulberg, Michael J.; Huang, Qi

2015-10-01

Ralstonia solanacearum race 3 biovar 2 strains belonging to phylotype IIB, sequevars 1 and 2 (IIB-1&2) cause brown rot of potato in temperate climates, and are quarantined pathogens in Canada and Europe. Since these strains are not established in the U.S. and because of their potential risk to the potato industry, the U.S. government has listed them as select agents. Cultivated geraniums are also a host and have the potential to spread the pathogen through trade, and its extracts strongly inhibits DNA-based detection methods. We designed four primer and probe sets for an improved qPCR method that targets stable regionsmore » of DNA. RsSA1 and RsSA2 recognize IIB-1&2 strains, RsII recognizes the current phylotype II (the newly proposed R. solanacearum species) strains (and a non-plant associated R. mannitolilytica), and Cox1 recognizes eight plant species including major hosts of R. solanacearum such as potato, tomato and cultivated geranium as an internal plant control. We multiplexed the RsSA2 with the RsII and Cox1 sets to provide two layers of detection of a positive IIB-1&2 sample, and to validate plant extracts and qPCR reactions. The TaqMan-based uniplex and multiplex qPCR assays correctly identified 34 IIB-1&2 and 52 phylotype II strains out of 90 R. solanacearum species complex strains. Additionally, the multiplex qPCR assay was validated successfully using 169 artificially inoculated symptomatic and asymptomatic plant samples from multiple plant hosts including geranium. Moreover, we developed an extraction buffer that allowed for a quick and easy DNA extraction from infected plants including geranium for detection of R. solanacearum by qPCR. Our multiplex qPCR assay, especially when coupled with the quick extraction buffer method, allows for quick, easy and reliable detection and differentiation of the IIB-1&2 strains of R. solanacearum.« less

The concentration of manganese, iron and strontium in bone of red fox Vulpes vulpes (L. 1758).

PubMed

Budis, Halina; Kalisinska, Elzbieta; Lanocha, Natalia; Kosik-Bogacka, Danuta I

2013-12-01

The aims of the study were to determine manganese (Mn), iron (Fe) and strontium (Sr) concentrations in fox bone samples from north-western Poland and to examine the relationships between the bone Mn, Fe and Sr concentrations and the sex and age of the foxes. In the studied samples of fox cartilage, cartilage with adjacent compact bone, compact bone and spongy bone, the concentrations of the analysed metals had the following descending order: Fe > Sr > Mn. The only exception was in compact bone, in which the concentrations were arranged in the order Sr > Fe > Mn. Manganese concentrations were significantly higher in cartilage, compact bone and cartilage with compact bone than in spongy bone. Iron concentrations were higher in cartilage and spongy bone compared with compact bone. Strontium concentrations were greater in compact bone than in cartilage and spongy bone. The manganese, iron and strontium concentrations in the same type of bone material in many cases correlated with each other, with the strongest correlation (r > 0.70) between Mn and Fe in almost all types of samples. In addition, concentrations of the same metals in different bone materials were closely correlated for Mn and Fe in cartilage and cartilage with adjacent compact bone, and for Sr in compact bone and cartilage with compact bone. In the fox from NW Poland, there were no statistically significant differences in Mn, Fe and Sr in any of the types of bone material between the sexes and immature and adult foxes.

Myofiber metabolic type determination by mass spectrometry imaging.

PubMed

Centeno, Delphine; Vénien, Annie; Pujos-Guillot, Estelle; Astruc, Thierry; Chambon, Christophe; Théron, Laëtitia

2017-08-01

Matrix assisted laser desorption/ionization (MALDI) mass spectrometry imaging is a powerful tool that opens new research opportunities in the field of biology. In this work, predictive model was developed to discriminate metabolic myofiber types using the MALDI spectral data. Rat skeletal muscles are constituted of type I and type IIA fiber, which have an oxidative metabolism for glycogen degradation, and type IIX and type IIB fiber which have a glycolytic metabolism, present in different proportions according to the muscle function and physiological state. So far, myofiber type is determined by histological methods that are time consuming. Thanks to the predictive model, we were able to predict not only the metabolic fiber type but also their location, on the same muscle section that was used for MALDI imaging. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Dissimilar distribution of Trypanosoma cruzi clones in humans after chemotherapy with allopurinol and itraconazole.

PubMed

Coronado, Ximena; Zulantay, Inés; Rozas, Marlene; Apt, Werner; Sánchez, Gittith; Rodríguez, Jorge; Ortiz, Sylvia; Solari, Aldo

2006-07-01

The aim of this work was to study the distribution of Trypanosoma cruzi clones after treatment failure with itraconazole or allopurinol in infected humans. Blood samples from treated and untreated individuals were used to detect T. cruzi by PCR assays and were confirmed by hybridization tests using total kinetoplast DNA as a universal probe. Also, xenodiagnosis (XD) tests were performed with Triatoma infestans fed from the same group of patients. We performed Southern-blot analyses of PCR products from blood or XD samples using a panel of four genotype-specific probes: corresponding to T. cruzi clones TcI, TcIIb, TcIId and TcIIe. The membranes were hybridized with radiolabelled probes and exposed in a Personal Molecular Imager. When comparing the presence of T. cruzi clones in the allopurinol-treated group with the non-treated group significant differences were only observed for XD samples. Clone TcI was present in 9/13 (69.2%) of the XD samples of the treated group, but only in 8/27 (29.6%) in the non-treated group (P = 0.0178). When the itraconazole-treated group and the control group were compared, significant differences were found in both the blood and XD samples. In blood, the clone TcIIb was detected in 6/17 (35.5%) of the treated group and in 18/27 (66.7%) of the non-treated group (P = 0.0207). When XD samples were analysed, the clone TcI was observed in 14/17 (82.3%) of the itraconazole-treated group but only in 8/27 (29.6%) of the control group (P = 0.0006), which suggests resistance of this clone to itraconazole. We detected a dissimilar distribution of T. cruzi clones in treated and untreated groups of patients. The presence of TcI increased in patients treated with allopurinol and itraconazole, whereas the presence of TcIIb decreased in itraconazole-treated patients. The type of T. cruzi clone that prevails suggests that TcI is resistant to both drugs and that TcIIb is susceptible to itraconazole.

Effect of early dietary energy restriction and phosphorus level on subsequent growth performance, intestinal phosphate transport, and AMPK activity in young broilers

PubMed Central

Miao, Zhiqiang; Zhang, Guixian; Zhang, Junzhen; Yang, Yu

2017-01-01

We aimed to determine the effect of low dietary energy on intestinal phosphate transport and the possible underlying mechanism to explain the long-term effects of early dietary energy restriction and non-phytate phosphorus (NPP). A 2 × 3 factorial experiment, consisting of 2 energy levels and 3 NPP levels, was conducted. Broiler growth performance, intestinal morphology in 0–21 days and 22–35 days, type IIb sodium-phosphate co-transporter (NaPi-IIb) mRNA expression, adenylate purine concentrations in the duodenum, and phosphorylated adenosine monophosphate-activated protein kinase (AMPK-α) activity in 0–21 days were determined. The following results were obtained. (1) Low dietary energy (LE) induced a high feed conversion ratio (FCR) and significantly decreased body weight gain in young broilers, but LE induced significantly higher compensatory growth in low NPP (LP) groups than in the high or medium NPP groups (HP and MP). (2) LE decreased the villus height (VH) in the intestine, and LE-HP resulted in the lowest crypt depth (CD) and the highest VH:CD ratio in the initial phase. However, in the later period, the LE-LP group showed an increased VH:CD ratio and decreased CD in the intestine. (3) LE increased ATP synthesis and decreased AMP:ATP ratio in the duodenal mucosa of chickens in 0–21 days, and LP diet increased ATP synthesis and adenylate energy charges but decreased AMP production and AMP:ATP ratio. (4) LE led to weaker AMPK phosphorylation, higher mTOR phosphorylation, and higher NaPi-IIb mRNA expression. Thus, LE and LP in the early growth phase had significant compensatory and interactive effect on later growth and intestinal development in broilers. The effect might be relevant to energy status that LE leads to weaker AMPK phosphorylation, causing a lower inhibitory action toward mTOR phosphorylation. This series of events stimulates NaPi-IIb mRNA expression. Our findings provide a theoretical basis and a new perspective on intestinal phosphate transport regulation, with potential applications in broiler production. PMID:29240752

[The survivability of patients with cervical cancer of IIB stage].

PubMed

Kryzhanivs'ka, A Ie; Diakiv, I B

2014-01-01

To the present tense finally mine-out not tactic of treatment of patients with the cervical cancer (CC) of IIB stage, but in the standards of diagnostics and treatment there are different variants of treatment of this pathology, and choice, most optimum, as a rule, depends on subjective opinion of doctor. Consequently, purpose of our work--to promote efficiency of treatment of patients on CC IIB the stage, by application of neoadjuvant chemotherapy in the combined treatment. The results of treatment are analysed 291 patients on CC IIB stages which got radical treatment in Ivano-Frankivsk OKOD from 1998 to 2013 years. At the use of neoadjuvant chemotherapy index of general 5-years-survival and nonrecurrence survivability made 74.4% and 70.8%, and to preoperative chemotherapy--70.8% and 68.3% accordingly. At application of independent chemoradial therapy, to the index of general 5-years-survival and nonrecurrence survivability was 51.1% and 49.3%, accordingly. It is not exposed reliable difference (P < 0.05) at comparison of indexes of 5-years-survivability of patients which have got the combined methods of treatment, but a reliable difference is exposed when compared to patients which have got independent chemoradial therapy (P > 0.05). Consequently, application of the combined methods of treatment of patients of CC IIB stages were improved by indexes general 5-years and to nonrecurrence survivability by comparison to independent cheradial therapy. .

Boosting the down-shifting luminescence of rare-earth nanocrystals for biological imaging beyond 1500 nm.

PubMed

Zhong, Yeteng; Ma, Zhuoran; Zhu, Shoujun; Yue, Jingying; Zhang, Mingxi; Antaris, Alexander L; Yuan, Jie; Cui, Ran; Wan, Hao; Zhou, Ying; Wang, Weizhi; Huang, Ngan F; Luo, Jian; Hu, Zhiyuan; Dai, Hongjie

2017-09-29

In vivo fluorescence imaging in the near-infrared region between 1500-1700 nm (NIR-IIb window) affords high spatial resolution, deep-tissue penetration, and diminished auto-fluorescence due to the suppressed scattering of long-wavelength photons and large fluorophore Stokes shifts. However, very few NIR-IIb fluorescent probes exist currently. Here, we report the synthesis of a down-conversion luminescent rare-earth nanocrystal with cerium doping (Er/Ce co-doped NaYbF 4 nanocrystal core with an inert NaYF 4 shell). Ce doping is found to suppress the up-conversion pathway while boosting down-conversion by ~9-fold to produce bright 1550 nm luminescence under 980 nm excitation. Optimization of the inert shell coating surrounding the core and hydrophilic surface functionalization minimize the luminescence quenching effect by water. The resulting biocompatible, bright 1550 nm emitting nanoparticles enable fast in vivo imaging of blood vasculature in the mouse brain and hindlimb in the NIR-IIb window with short exposure time of 20 ms for rare-earth based probes.Fluorescence imaging in the near-infrared window between 1500-1700 nm (NIR-IIb window) offers superior spatial resolution and tissue penetration depth, but few NIR-IIb probes exist. Here, the authors synthesize rare earth down-converting nanocrystals as promising fluorescent probes for in vivo imaging in this spectral region.

Antibodies causing thrombocytopenia in patients treated with RGD-mimetic platelet inhibitors recognize ligand-specific conformers of αIIb/β3 integrin

PubMed Central

Rasmussen, Mark; Zhu, Jieqing; Aster, Richard H.

2012-01-01

Arginine-glycine-aspartic acid (RGD)–mimetic platelet inhibitors act by occupying the RGD recognition site of αIIb/β3 integrin (GPIIb/IIIa), thereby preventing the activated integrin from reacting with fibrinogen. Thrombocytopenia is a well-known side effect of treatment with this class of drugs and is caused by Abs, often naturally occurring, that recognize αIIb/β3 in a complex with the drug being administered. RGD peptide and RGD-mimetic drugs are known to induce epitopes (ligand-induced binding sites [LIBS]) in αIIb/β3 that are recognized by certain mAbs. It has been speculated, but not shown experimentally, that Abs from patients who develop thrombocytopenia when treated with an RGD-mimetic inhibitor similarly recognize LIBS determinants. We addressed this question by comparing the reactions of patient Abs and LIBS-specific mAbs against αIIb/β3 in a complex with RGD and RGD-mimetic drugs, and by examining the ability of selected non-LIBS mAbs to block binding of patient Abs to the liganded integrin. Findings made provide evidence that the patient Abs recognize subtle, drug-induced structural changes in the integrin head region that are clustered about the RGD recognition site. The target epitopes differ from classic LIBS determinants, however, both in their location and by virtue of being largely drug-specific. PMID:22490676

Combining universal and odd RR axions for aligned natural inflation

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

Gao, Xin; Li, Tianjun; Shukla, Pramod, E-mail: xingao@vt.edu, E-mail: tli@itp.ac.cn, E-mail: pkshukla@to.infn.it

2014-10-01

We successfully embed the Kim-Nilles-Peloso (KNP) alignment mechanism for enhancing the axion decay constant in the context of large volume type IIB orientifolds. The flat direction is generated in the plane of (C{sub 0}-C{sub 2}) axions corresponding to the involutively even universal axion C{sub 0} and odd axion C{sub 2}, respectively. The moduli stabilization with large volume scheme has been established as well.

Restoration of pharyngeal dilator muscle force in dystrophin-deficient (mdx) mice following co-treatment with neutralizing interleukin-6 receptor antibodies and urocortin 2.

PubMed

Burns, David P; Rowland, Jane; Canavan, Leonie; Murphy, Kevin H; Brannock, Molly; O'Malley, Dervla; O'Halloran, Ken D; Edge, Deirdre

2017-09-01

What is the central question of this study? We previously reported impaired upper airway dilator muscle function in the mdx mouse model of Duchenne muscular dystrophy (DMD). Our aim was to assess the effect of blocking interleukin-6 receptor signalling and stimulating corticotrophin-releasing factor receptor 2 signalling on mdx sternohyoid muscle structure and function. What is the main finding and its importance? The interventional treatment had a positive inotropic effect on sternohyoid muscle force, restoring mechanical work and power to wild-type values, reduced myofibre central nucleation and preserved the myosin heavy chain type IIb fibre complement of mdx sternohyoid muscle. These data might have implications for development of pharmacotherapies for DMD with relevance to respiratory muscle performance. The mdx mouse model of Duchenne muscular dystrophy shows evidence of impaired pharyngeal dilator muscle function. We hypothesized that inflammatory and stress-related factors are implicated in airway dilator muscle dysfunction. Six-week-old mdx (n = 26) and wild-type (WT; n = 26) mice received either saline (0.9% w/v) or a co-administration of neutralizing interleukin-6 receptor antibodies (0.2 mg kg -1 ) and corticotrophin-releasing factor receptor 2 agonist (urocortin 2; 30 μg kg -1 ) over 2 weeks. Sternohyoid muscle isometric and isotonic contractile function was examined ex vivo. Muscle fibre centronucleation and muscle cellular infiltration, collagen content, fibre-type distribution and fibre cross-sectional area were determined by histology and immunofluorescence. Muscle chemokine content was examined by use of a multiplex assay. Sternohyoid peak specific force at 100 Hz was significantly reduced in mdx compared with WT. Drug treatment completely restored force in mdx sternohyoid to WT levels. The percentage of centrally nucleated muscle fibres was significantly increased in mdx, and this was partly ameliorated after drug treatment. The areal density of infiltrates and collagen content were significantly increased in mdx sternohyoid; both indices were unaffected by drug treatment. The abundance of myosin heavy chain type IIb fibres was significantly decreased in mdx sternohyoid; drug treatment preserved myosin heavy chain type IIb complement in mdx muscle. The chemokines macrophage inflammatory protein 2, interferon-γ-induced protein 10 and macrophage inflammatory protein 3α were significantly increased in mdx sternohyoid compared with WT. Drug treatment significantly increased chemokine expression in mdx but not WT sternohyoid. Recovery of contractile function was impressive in our study, with implications for Duchenne muscular dystrophy. The precise molecular mechanisms by which the drug treatment exerts an inotropic effect on mdx sternohyoid muscle remain to be elucidated. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

Searching for Compact Radio Sources Associated with UCH ii Regions

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

Masqué, Josep M.; Trinidad, Miguel A.; Rodríguez-Rico, Carlos A.

Ultra-compact (UC)H ii regions represent a very early stage of massive star formation. The structure and evolution of these regions are not yet fully understood. Interferometric observations showed in recent years that compact sources of uncertain nature are associated with some UCH ii regions. To examine this, we carried out VLA 1.3 cm observations in the A configuration of selected UCH ii regions in order to report additional cases of compact sources embedded in UCH ii regions. With these observations, we find 13 compact sources that are associated with 9 UCH ii regions. Although we cannot establish an unambiguous naturemore » for the newly detected sources, we assess some of their observational properties. According to the results, we can distinguish between two types of compact sources. One type corresponds to sources that are probably deeply embedded in the dense ionized gas of the UCH ii region. These sources are photoevaporated by the exciting star of the region and will last for 10{sup 4}–10{sup 5} years. They may play a crucial role in the evolution of the UCH ii region as the photoevaporated material could replenish the expanding plasma and might provide a solution to the so-called lifetime problem of these regions. The second type of compact sources is not associated with the densest ionized gas of the region. A few of these sources appear resolved and may be photoevaporating objects such as those of the first type, but with significantly lower mass depletion rates. The remaining sources of this second type appear unresolved, and their properties are varied. We speculate on the similarity between the sources of the second type and those of the Orion population of radio sources.« less

Brentuximab Vedotin and Combination Chemotherapy in Treating Children and Young Adults With Stage IIB or Stage IIIB-IVB Hodgkin Lymphoma

ClinicalTrials.gov

2018-06-25

Ann Arbor Stage IIB Hodgkin Lymphoma; Ann Arbor Stage IIIB Hodgkin Lymphoma; Ann Arbor Stage IV Hodgkin Lymphoma; Ann Arbor Stage IVA Hodgkin Lymphoma; Ann Arbor Stage IVB Hodgkin Lymphoma; Childhood Hodgkin Lymphoma; Classic Hodgkin Lymphoma

The GLAS editing procedures for the FGGE level II-B data collected during SOP-1 and 2

NASA Technical Reports Server (NTRS)

Baker, W.; Edelmann, D.; Carus, H.

1981-01-01

The modifications made to the FGGE Level II-b data are discussed and the FORTRAN program developed to perform the modifications is described. It is suggested that the edited database is the most accurate one available for FGGE SOP-1 and 2.

Association of vitamin D and vitamin D receptor gene polymorphisms with chronic inflammation, insulin resistance and metabolic syndrome components in type 2 diabetic Egyptian patients.

PubMed

Mackawy, Amal M H; Badawi, Mohammed E H

2014-12-01

To date the published data concerning the possible interplay between vitamin D (VitD) and Vit D receptor (VDR) gene polymorphism with the immune/inflammatory mediators in type 2 diabetes mellitus (DM) is insufficient. Some of the immune non-classical actions of vitamin D may point to its role in the pathogenesis of type 2 DM through down-regulation of cytokines (IL-6). Although there is evidence to support a relationship among vitamin D status, chronic inflammation and insulin resistance, the underlying mechanism requires further exploration. We aimed to investigate the role of vitamin D in chronic inflammation and insulin resistance in type 2 DM. Moreover, to examine the association of VDR gene polymorphisms [VDR 2228570 C > T (FokI); VDR 1544410 A > G (BsmI)] with the components of metabolic syndrome (MetSyn) in type 2 diabetic Egyptian patients . A total of 190 subjects were enrolled in this study, 60 controls and 130 type 2 diabetic patients (Group II). Group II was subdivided into 63 patients without MetSyn (subgroup IIa) and 67 patients with MetSyn (subgroup IIb). Genetic analysis for VDR gene polymorphisms was done in all subjects. VitD and IL-6 plasma levels were estimated. The TT genotype for the VDR FokI was significantly more frequent in subgroup IIb than in subgroup IIa and controls (X (2) = 6.83, P = 0.03 and X (2) = 16.592, P = 0.000) respectively. The T allele was more frequent in the MetSyn group as compared to diabetics without MetSyn (p = 0.001), odds ratio (OR) and 95% CI for the T allele of C > T (FokI) = 2.30 (1.37-3.86). We did not detect any significant difference in VDR BsmI genotypes between patients and control groups (P = 0.947). FokI VDR was significantly associated with the lipid profile parameters, VitD and IL-6 plasma levels in subgroup IIa and associated with HOMA-IR, insulin, VitD, IL-6 levels, waist circumference (WC) and body mass index (BMI) in subgroup IIb while BsmI VDR variant was associated only with VitD values in both subgroups. The present study suggests an interaction between VDR polymorphisms and important components of MetSyn, VitD and pro-inflammatory cytokines (IL-6). FokI VDR polymorphisms may be linked to mild inflammation and insulin resistance and might represent a genetic determinant for developing MetSyn in type 2 diabetic Egyptian patients. The challenge is determining the mechanisms of VitD action for recommendation of VitD supplementation that reduces the risks of MetSyn, insulin resistance and progression to type 2 diabetes.

Association of vitamin D and vitamin D receptor gene polymorphisms with chronic inflammation, insulin resistance and metabolic syndrome components in type 2 diabetic Egyptian patients

PubMed Central

Mackawy, Amal M.H.; Badawi, Mohammed E.H.

2014-01-01

Background To date the published data concerning the possible interplay between vitamin D (VitD) and Vit D receptor (VDR) gene polymorphism with the immune/inflammatory mediators in type 2 diabetes mellitus (DM) is insufficient. Some of the immune non-classical actions of vitamin D may point to its role in the pathogenesis of type 2 DM through down-regulation of cytokines (IL-6). Although there is evidence to support a relationship among vitamin D status, chronic inflammation and insulin resistance, the underlying mechanism requires further exploration. We aimed to investigate the role of vitamin D in chronic inflammation and insulin resistance in type 2 DM. Moreover, to examine the association of VDR gene polymorphisms [VDR 2228570 C > T (FokI); VDR 1544410 A > G (BsmI)] with the components of metabolic syndrome (MetSyn) in type 2 diabetic Egyptian patients . Subjects and methods A total of 190 subjects were enrolled in this study, 60 controls and 130 type 2 diabetic patients (Group II). Group II was subdivided into 63 patients without MetSyn (subgroup IIa) and 67 patients with MetSyn (subgroup IIb). Genetic analysis for VDR gene polymorphisms was done in all subjects. VitD and IL-6 plasma levels were estimated. Results The TT genotype for the VDR FokI was significantly more frequent in subgroup IIb than in subgroup IIa and controls (X2 = 6.83, P = 0.03 and X2 = 16.592, P = 0.000) respectively. The T allele was more frequent in the MetSyn group as compared to diabetics without MetSyn (p = 0.001), odds ratio (OR) and 95% CI for the T allele of C > T (FokI) = 2.30 (1.37–3.86). We did not detect any significant difference in VDR BsmI genotypes between patients and control groups (P = 0.947). FokI VDR was significantly associated with the lipid profile parameters, VitD and IL-6 plasma levels in subgroup IIa and associated with HOMA-IR, insulin, VitD, IL-6 levels, waist circumference (WC) and body mass index (BMI) in subgroup IIb while BsmI VDR variant was associated only with VitD values in both subgroups. Conclusion The present study suggests an interaction between VDR polymorphisms and important components of MetSyn, VitD and pro-inflammatory cytokines (IL-6). FokI VDR polymorphisms may be linked to mild inflammation and insulin resistance and might represent a genetic determinant for developing MetSyn in type 2 diabetic Egyptian patients. The challenge is determining the mechanisms of VitD action for recommendation of VitD supplementation that reduces the risks of MetSyn, insulin resistance and progression to type 2 diabetes. PMID:25606437

A new stylolite classification scheme to estimate compaction and local permeability variations

NASA Astrophysics Data System (ADS)

Koehn, D.; Rood, M. P.; Beaudoin, N.; Chung, P.; Bons, P. D.; Gomez-Rivas, E.

2016-12-01

We modeled the geometrical roughening of bedding-parallel, mainly layer-dominated stylolites in order to understand their structural evolution, to present an advanced classification of stylolite shapes and to relate this classification to chemical compaction and permeability variations at stylolites. Stylolites are rough dissolution seams that develop in sedimentary basins during chemical compaction. In the Zechstein 2 carbonate units, an important lean gas reservoir in the southern Permian Zechstein basin in Germany, stylolites influence local fluid flow, mineral replacement reactions and hence the permeability of the reservoir. Our simulations demonstrate that layer-dominated stylolites can grow in three distinct stages: an initial slow nucleation phase, a fast layer-pinning phase and a final freezing phase if the layer is completely dissolved during growth. Dissolution of the pinning layer and thus destruction of the stylolite's compaction tracking capabilities is a function of the background noise in the rock and the dissolution rate of the layer itself. Low background noise needs a slower dissolving layer for pinning to be successful but produces flatter teeth than higher background noise. We present an advanced classification based on our simulations and separate stylolites into four classes: (1) rectangular layer type, (2) seismogram pinning type, (3) suture/sharp peak type and (4) simple wave-like type. Rectangular layer type stylolites are the most appropriate for chemical compaction estimates because they grow linearly and record most of the actual compaction (up to 40 mm in the Zechstein example). Seismogram pinning type stylolites also provide good tracking capabilities, with the largest teeth tracking most of the compaction. Suture/sharp peak type stylolites grow in a non-linear fashion and thus do not record most of the actual compaction. However, when a non-linear growth law is used, the compaction estimates are similar to those making use of the rectangular layer type stylolites. Simple wave-like stylolites are not useful for compaction estimates, since their growth is highly non-linear with a very low growth exponent. In the case where sealing material is collected at the tooth during dissolution, stylolites can act as barriers for local fluid flow as they intensify sealing capabilities of pinning layers. However, the development of teeth and spikes offsets and thus destroys continuous stylolite seams so that the permeability across the stylolite becomes very heterogeneous and they are no continuous barriers. This behavior is best shown in rectangular layer and seismogram pinning type stylolites that develop efficient fluid barriers at teeth tips but destroy sealing capabilities of layers by offsetting them at the flank, leading to a permeability anisotropy along 2-D stylolite planes. Suture/sharp peak stylolites can create fluid barriers if they collect enough sealing material. However, if the collecting material does not seal or if spikes offset the sealing material the stylolite leaks. We propose that our classification can be used to realistically estimate chemical compaction in reservoirs and gives an indication on how heterogeneous the permeability of stylolites can be.

Efficacy and safety of coadministration of fenofibrate and ezetimibe compared with each as monotherapy in patients with type IIb dyslipidemia and features of the metabolic syndrome: a prospective, randomized, double-blind, three-parallel arm, multicenter, comparative study.

PubMed

Ansquer, Jean-Claude; Bekaert, Ivan; Guy, Martine; Hanefeld, Markolf; Simon, Alain

2009-01-01

Patients with type IIb, or mixed, dyslipidemia have high levels of low-density lipoprotein cholesterol (LDL-C) with predominance of small dense LDL particles, high levels of triglycerides (TG), and low levels of high-density lipoprotein cholesterol (HDL-C). Fenofibrate significantly reduces TG and, more moderately, LDL-C, increases HDL-C and produces a shift from small to large LDL particle size; the main effect of ezetimibe is a reduction in LDL-C levels. Combined treatment with fenofibrate and ezetimibe may correct all the abnormalities of type IIb dyslipidemia. To assess the efficacy and safety of coadministration of fenofibrate (NanoCrystal(R)) and ezetimibe in patients with type IIb dyslipidemia and the metabolic syndrome compared with administration of fenofibrate and ezetimibe alone (ClinicalTrials.gov Identifier: NCT00349284; Study ID: CLF178P 04 01). This was a prospective, randomized, double-blind, three-parallel arm, multicenter, comparative study. Sixty ambulatory patients (mean age 56 years; 50% women, 50% men) were treated in each group. For inclusion in the study, patients were required to have LDL-C >or=4.13 mmol/L (>or=160 mg/dL), TG >or=1.71 mmol/L and or=150 mg/dL and

Unifying Type-II Strings by Exceptional Groups

NASA Astrophysics Data System (ADS)

Arvanitakis, Alex S.; Blair, Chris D. A.

2018-05-01

We construct the exceptional sigma model: a two-dimensional sigma model coupled to a supergravity background in a manifestly (formally) ED (D )-covariant manner. This formulation of the background is provided by exceptional field theory (EFT), which unites the metric and form fields of supergravity in ED (D ) multiplets before compactification. The realization of the symmetries of EFT on the world sheet uniquely fixes the Weyl-invariant Lagrangian and allows us to relate our action to the usual type-IIA fundamental string action and a form of the type-IIB (m , n ) action. This uniqueness "predicts" the correct form of the couplings to gauge fields in both Neveu-Schwarz and Ramond sectors, without invoking supersymmetry.

Spontaneous closure of intracranial dural arteriovenous fistulas: a report of 3 cases.

PubMed

Clarençon, Frédéric; Biondi, Alessandra; Sourour, Nader-Antoine; Di Maria, Federico; Iosif, Christina; Nouet, Aurélien; Navarro, Soledad; Le Jean, Lise; Chiras, Jacques

2013-07-01

Spontaneous closures of dural arteriovenous fistulas (dAVFs) are rare. We present spontaneous occlusion of dAVFs in 3 cases (one type IIa dAVF, one type IIb and one type III). Patients were 3 males with a mean age of 55 years (range 45-61). For two patients, the dAVF was revealed by hemorrhage. No head trauma was recorded at the interrogatory. Mean delay for spontaneous closure was 4 months (3-5 months). Review of the literature about this rare occurrence is presented and the factors that may lead to spontaneous occlusion of dAVFs are discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

R 4 couplings in M- and type II theories on Calabi-Yau spaces

NASA Astrophysics Data System (ADS)

Antoniadis, I.; Feffara, S.; Minasian, R.; Narain, K. S.

1997-02-01

We discuss several implications of R 4 couplings in M-theory when compactified on Calabi-Yau (CY) manifolds. In particular, these couplings can be predicted by supersymmetry from the mixed gauge-gravitational Chem-Simons couplings in five dimensions and are related to the one-loop holomorphic anomaly in four-dimensional N = 2 theories. We find a new contribution to the Einstein term in five dimensions proportional to the Euler number of the internal CY threefold, which corresponds to a one-loop correction of the hypermultiplet geometry. This correction is reproduced by a direct computation in type 11 string theories. Finally, we discuss a universal non-perturbative correction to the type IIB hyper-metric.

30 CFR 57.22604 - Blasting from the surface (II-B mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... MINES Safety Standards for Methane in Metal and Nonmetal Mines Explosives § 57.22604 Blasting from the surface (II-B mines). All development, production, and bench rounds shall be initiated from the surface... methane tests shall not enter the mine until all blast areas have been tested for methane. ...

30 CFR 57.22604 - Blasting from the surface (II-B mines).

Code of Federal Regulations, 2013 CFR

2013-07-01

... MINES Safety Standards for Methane in Metal and Nonmetal Mines Explosives § 57.22604 Blasting from the surface (II-B mines). All development, production, and bench rounds shall be initiated from the surface... methane tests shall not enter the mine until all blast areas have been tested for methane. ...

30 CFR 57.22604 - Blasting from the surface (II-B mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... MINES Safety Standards for Methane in Metal and Nonmetal Mines Explosives § 57.22604 Blasting from the surface (II-B mines). All development, production, and bench rounds shall be initiated from the surface... methane tests shall not enter the mine until all blast areas have been tested for methane. ...

30 CFR 57.22604 - Blasting from the surface (II-B mines).

Code of Federal Regulations, 2014 CFR

2014-07-01

... MINES Safety Standards for Methane in Metal and Nonmetal Mines Explosives § 57.22604 Blasting from the surface (II-B mines). All development, production, and bench rounds shall be initiated from the surface... methane tests shall not enter the mine until all blast areas have been tested for methane. ...

30 CFR 57.22604 - Blasting from the surface (II-B mines).

Code of Federal Regulations, 2012 CFR

2012-07-01

... MINES Safety Standards for Methane in Metal and Nonmetal Mines Explosives § 57.22604 Blasting from the surface (II-B mines). All development, production, and bench rounds shall be initiated from the surface... methane tests shall not enter the mine until all blast areas have been tested for methane. ...

Myosin IIb-dependent Regulation of Actin Dynamics Is Required for N-Methyl-D-aspartate Receptor Trafficking during Synaptic Plasticity.

PubMed

Bu, Yunfei; Wang, Ning; Wang, Shaoli; Sheng, Tao; Tian, Tian; Chen, Linlin; Pan, Weiwei; Zhu, Minsheng; Luo, Jianhong; Lu, Wei

2015-10-16

N-Methyl-d-aspartate receptor (NMDAR) synaptic incorporation changes the number of NMDARs at synapses and is thus critical to various NMDAR-dependent brain functions. To date, the molecules involved in NMDAR trafficking and the underlying mechanisms are poorly understood. Here, we report that myosin IIb is an essential molecule in NMDAR synaptic incorporation during PKC- or θ burst stimulation-induced synaptic plasticity. Moreover, we demonstrate that myosin light chain kinase (MLCK)-dependent actin reorganization contributes to NMDAR trafficking. The findings from additional mutual occlusion experiments demonstrate that PKC and MLCK share a common signaling pathway in NMDAR-mediated synaptic regulation. Because myosin IIb is the primary substrate of MLCK and can regulate actin dynamics during synaptic plasticity, we propose that the MLCK- and myosin IIb-dependent regulation of actin dynamics is required for NMDAR trafficking during synaptic plasticity. This study provides important insights into a mechanical framework for understanding NMDAR trafficking associated with synaptic plasticity. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Data on the influence of cold isostatic pre-compaction on mechanical properties of polycrystalline nickel sintered using Spark Plasma Sintering.

PubMed

Dutel, Guy-Daniel; Langlois, Patrick; Tingaud, David; Vrel, Dominique; Dirras, Guy

2017-04-01

Data regarding bulk polycrystalline nickel samples obtained by powder metallurgy using Spark Plasma Sintering (SPS) are presented, with a special emphasis on the influence of a cold isostatic pre-compaction on the resulting morphologies and subsequent mechanical properties. Three types of initial powders are used, nanometric powders, micrometric powders and a mixture of the formers. For each type of powder, the SPS cycle has been optimized for the powders without pre-compaction and the same cycle has been used to also sinter pre-compacted powders.

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

Chang, C.; Coggill, P.; Bateman, A.

Many Gram-positive lactic acid bacteria (LAB) produce anti-bacterial peptides and small proteins called bacteriocins, which enable them to compete against other bacteria in the environment. These peptides fall structurally into three different classes, I, II, III, with class IIa being pediocin-like single entities and class IIb being two-peptide bacteriocins. Self-protective cognate immunity proteins are usually co-transcribed with these toxins. Several examples of cognates for IIa have already been solved structurally. Streptococcus pyogenes, closely related to LAB, is one of the most common human pathogens, so knowledge of how it competes against other LAB species is likely to prove invaluable. Wemore » have solved the crystal structure of the gene-product of locus Spy-2152 from S. pyogenes, (PDB: 2fu2), and found it to comprise an anti-parallel four-helix bundle that is structurally similar to other bacteriocin immunity proteins. Sequence analyses indicate this protein to be a possible immunity protein protective against class IIa or IIb bacteriocins. However, given that S. pyogenes appears to lack any IIa pediocin-like proteins but does possess class IIb bacteriocins, we suggest this protein confers immunity to IIb-like peptides. Combined structural, genomic and proteomic analyses have allowed the identification and in silico characterization of a new putative immunity protein from S. pyogenes, possibly the first structure of an immunity protein protective against potential class IIb two-peptide bacteriocins. We have named the two pairs of putative bacteriocins found in S. pyogenes pyogenecin 1, 2, 3 and 4.« less

Vaccine Therapy With or Without Sirolimus in Treating Patients With NY-ESO-1 Expressing Solid Tumors

ClinicalTrials.gov

2016-10-03

Anaplastic Astrocytoma; Anaplastic Oligoastrocytoma; Anaplastic Oligodendroglioma; Estrogen Receptor Negative; Estrogen Receptor Positive; Glioblastoma; Hormone-Resistant Prostate Cancer; Metastatic Prostate Carcinoma; Metastatic Renal Cell Cancer; Recurrent Adult Brain Neoplasm; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Colorectal Carcinoma; Recurrent Esophageal Carcinoma; Recurrent Gastric Carcinoma; Recurrent Hepatocellular Carcinoma; Recurrent Lung Carcinoma; Recurrent Melanoma; Recurrent Ovarian Carcinoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Uterine Corpus Carcinoma; Resectable Hepatocellular Carcinoma; Sarcoma; Stage IA Breast Cancer; Stage IA Ovarian Cancer; Stage IA Uterine Corpus Cancer; Stage IB Breast Cancer; Stage IB Ovarian Cancer; Stage IB Uterine Corpus Cancer; Stage IC Ovarian Cancer; Stage II Uterine Corpus Cancer; Stage IIA Breast Cancer; Stage IIA Lung Carcinoma; Stage IIA Ovarian Cancer; Stage IIB Breast Cancer; Stage IIB Esophageal Cancer; Stage IIB Lung Carcinoma; Stage IIB Ovarian Cancer; Stage IIB Skin Melanoma; Stage IIC Ovarian Cancer; Stage IIC Skin Melanoma; Stage IIIA Breast Cancer; Stage IIIA Esophageal Cancer; Stage IIIA Lung Carcinoma; Stage IIIA Ovarian Cancer; Stage IIIA Skin Melanoma; Stage IIIA Uterine Corpus Cancer; Stage IIIB Breast Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Skin Melanoma; Stage IIIB Uterine Corpus Cancer; Stage IIIC Breast Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Skin Melanoma; Stage IIIC Uterine Corpus Cancer; Stage IV Bladder Urothelial Carcinoma; Stage IV Esophageal Cancer; Stage IV Ovarian Cancer; Stage IV Prostate Cancer; Stage IV Skin Melanoma; Stage IVA Uterine Corpus Cancer; Stage IVB Uterine Corpus Cancer

Non-Muscle Myosin II Isoforms Have Different Functions in Matrix Rearrangement by MDA-MB-231 Cells

PubMed Central

Hindman, Bridget; Goeckeler, Zoe; Sierros, Kostas; Wysolmerski, Robert

2015-01-01

The role of a stiffening extra-cellular matrix (ECM) in cancer progression is documented but poorly understood. Here we use a conditioning protocol to test the role of nonmuscle myosin II isoforms in cell mediated ECM arrangement using collagen constructs seeded with breast cancer cells expressing shRNA targeted to either the IIA or IIB heavy chain isoform. While there are several methods available to measure changes in the biophysical characteristics of the ECM, we wanted to use a method which allows for the measurement of global stiffness changes as well as a dynamic response from the sample over time. The conditioning protocol used allows the direct measurement of ECM stiffness. Using various treatments, it is possible to determine the contribution of various construct and cellular components to the overall construct stiffness. Using this assay, we show that both the IIA and IIB isoforms are necessary for efficient matrix remodeling by MDA-MB-231 breast cancer cells, as loss of either isoform changes the stiffness of the collagen constructs as measured using our conditioning protocol. Constructs containing only collagen had an elastic modulus of 0.40 Pascals (Pa), parental MDA-MB-231 constructs had an elastic modulus of 9.22 Pa, while IIA and IIB KD constructs had moduli of 3.42 and 7.20 Pa, respectively. We also calculated the cell and matrix contributions to the overall sample elastic modulus. Loss of either myosin isoform resulted in decreased cell stiffness, as well as a decrease in the stiffness of the cell-altered collagen matrices. While the total construct modulus for the IIB KD cells was lower than that of the parental cells, the IIB KD cell-altered matrices actually had a higher elastic modulus than the parental cell-altered matrices (4.73 versus 4.38 Pa). These results indicate that the IIA and IIB heavy chains play distinct and non-redundant roles in matrix remodeling. PMID:26136073

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

Stulberg, Michael J.; Huang, Qi

Ralstonia solanacearum race 3 biovar 2 strains belonging to phylotype IIB, sequevars 1 and 2 (IIB-1&2) cause brown rot of potato in temperate climates, and are quarantined pathogens in Canada and Europe. Since these strains are not established in the U.S. and because of their potential risk to the potato industry, the U.S. government has listed them as select agents. Cultivated geraniums are also a host and have the potential to spread the pathogen through trade, and its extracts strongly inhibits DNA-based detection methods. We designed four primer and probe sets for an improved qPCR method that targets stable regionsmore » of DNA. RsSA1 and RsSA2 recognize IIB-1&2 strains, RsII recognizes the current phylotype II (the newly proposed R. solanacearum species) strains (and a non-plant associated R. mannitolilytica), and Cox1 recognizes eight plant species including major hosts of R. solanacearum such as potato, tomato and cultivated geranium as an internal plant control. We multiplexed the RsSA2 with the RsII and Cox1 sets to provide two layers of detection of a positive IIB-1&2 sample, and to validate plant extracts and qPCR reactions. The TaqMan-based uniplex and multiplex qPCR assays correctly identified 34 IIB-1&2 and 52 phylotype II strains out of 90 R. solanacearum species complex strains. Additionally, the multiplex qPCR assay was validated successfully using 169 artificially inoculated symptomatic and asymptomatic plant samples from multiple plant hosts including geranium. Moreover, we developed an extraction buffer that allowed for a quick and easy DNA extraction from infected plants including geranium for detection of R. solanacearum by qPCR. Our multiplex qPCR assay, especially when coupled with the quick extraction buffer method, allows for quick, easy and reliable detection and differentiation of the IIB-1&2 strains of R. solanacearum.« less

Ability of anti-glycoprotein IIb/IIIa agents to dissolve platelet thrombi formed on a collagen surface under blood flow conditions.

PubMed

Goto, Shinya; Tamura, Noriko; Ishida, Hideyuki

2004-07-21

We examined the lytic effects of anti-glycoprotein (GP) IIb/IIIa agents on platelet thrombi formed on the collagen surface under blood flow conditions. Anti-GP IIb/IIIa agents may influence platelet thrombi already formed. Blood samples were anticoagulated either by the specific antithrombin Argatroban (100 microM) or by unfractionated heparin (0.1 U/ml). After platelet thrombi were formed on a collagen surface following 6-min perfusion of whole blood obtained from eight adult donors containing fluorescinated platelets at a wall shear rate of 1,500 s(-1), additional blood samples from the same donors either containing or not containing anti-GP IIb/IIIa agents (abciximab, eptifibatide, or tirofiban) were perfused on these thrombi. The three-dimensional structures of the platelet thrombi were continuously observed by laser confocal microscopy equipped with a piezo-electric motor control unit and recorded. The platelet thrombi started to dissolve after perfusion of blood containing the anti-GP IIb/IIIa agents, whereas their growth resumed after subsequent perfusion of control blood. Only a single layer of platelets having heights of 3 +/- 1 microm, 3 +/- 2 microm, and 3 +/- 1 microm, respectively, could be seen after 6-min perfusion of blood containing abciximab, eptifibatide, and tirofiban, whereas the initial height of the platelet thrombi of 8 +/- 2 microm increased to 11 +/- 4 microm after subsequent perfusion of control blood (n = 8). The volume of the platelet thrombi, which was 3,352 +/- 1,045 microm(3) before starting the second perfusion, was reduced to 778 +/- 102 microm(3), 812 +/- 122 microm(3), and 856 +/- 144 microm(3) after 6-min perfusion of blood containing abciximab, eptifibatide, and tirofiban, respectively. We have shown in this study that anti-GP IIb/IIIa agents possess the ability to dissolve platelet thrombi.

Regulation of pathogenicity in hop stunt viroid-related group II citrus viroids.

PubMed

Reanwarakorn, K; Semancik, J S

1998-12-01

Nucleotide sequences were determined for two hop stunt viroid-related Group II citrus viroids characterized as either a cachexia disease non-pathogenic variant (CVd-IIa) or a pathogenic variant (CVd-IIb). Sequence identity between the two variants of 95.6% indicated a conserved genome with the principal region of nucleotide difference clustered in the variable (V) domain. Full-length viroid RT-PCR cDNA products were cloned into plasmid SP72. Viroid cDNA clones as well as derived RNA transcripts were transmissible to citron (Citrus medica L.) and Luffa aegyptiaca Mill. To determine the locus of cachexia pathogenicity as well as symptom expression in Luffa, chimeric viroid cDNA clones were constructed from segments of either the left terminal, pathogenic and conserved (T1-P-C) domains or the conserved, variable and right terminal (C-V-T2) domains of CVd-IIa or CVd-IIb in reciprocal exchanges. Symptoms induced by the various chimeric constructs on the two bioassay hosts reflected the differential response observed with CVd-IIa and -IIb. Constructs with the C-V-T2 domains region from clone-IIa induced severe symptoms on Luffa typical of CVd-IIa, but were non-symptomatic on mandarin as a bioassay host for the cachexia disease. Constructs with the same region (C-V-T2) from the clone-IIb genome induced only mild symptoms on Luffa, but produced a severe reaction on mandarin, as observed for CVd-IIb. Specific site-directed mutations were introduced into the V domain of the CVd-IIa clone to construct viroid cDNA clones with either partial or complete conversions to the CVd-IIb sequence. With the introduction of six site-specific changes into the V domain of the clone-IIa genome, cachexia pathogenicity was acquired as well as a moderation of severe symptoms on Luffa.

Solution structure of the IIAChitobiose-IIBChitobiose complex of the N,N'-diacetylchitobiose branch of the Escherichia coli phosphotransferase system.

PubMed

Jung, Young-Sang; Cai, Mengli; Clore, G Marius

2010-02-05

The solution structure of the IIA-IIB complex of the N,N'-diacetylchitobiose (Chb) transporter of the Escherichia coli phosphotransferase system has been solved by NMR. The active site His-89 of IIA(Chb) was mutated to Glu to mimic the phosphorylated state and the active site Cys-10 of IIB(Chb) was substituted by serine to prevent intermolecular disulfide bond formation. Binding is weak with a K(D) of approximately 1.3 mm. The two complementary interaction surfaces are largely hydrophobic, with the protruding active site loop (residues 9-16) of IIB(Chb) buried deep within the active site cleft formed at the interface of two adjacent subunits of the IIA(Chb) trimer. The central hydrophobic portion of the interface is surrounded by a ring of polar and charged residues that provide a relatively small number of electrostatic intermolecular interactions that serve to correctly align the two proteins. The conformation of the active site loop in unphosphorylated IIB(Chb) is inconsistent with the formation of a phosphoryl transition state intermediate because of steric hindrance, especially from the methyl group of Ala-12 of IIB(Chb). Phosphorylation of IIB(Chb) is accompanied by a conformational change within the active site loop such that its path from residues 11-13 follows a mirror-like image relative to that in the unphosphorylated state. This involves a transition of the phi/psi angles of Gly-13 from the right to left alpha-helical region, as well as smaller changes in the backbone torsion angles of Ala-12 and Met-14. The resulting active site conformation is fully compatible with the formation of the His-89-P-Cys-10 phosphoryl transition state without necessitating any change in relative translation or orientation of the two proteins within the complex.

Immunological characterization of eristostatin and echistatin binding sites on alpha IIb beta 3 and alpha V beta 3 integrins.

PubMed Central

Marcinkiewicz, C; Rosenthal, L A; Mosser, D M; Kunicki, T J; Niewiarowski, S

1996-01-01

Two disintegrins with a high degree of amino acid sequence similarity, echistatin and eristostatin, showed a low level of interaction with Chinese hamster ovary (CHO) cells, but they bound to CHO cells transfected with alpha IIb beta 3 genes (A5 cells) and to CHO cells transfected with alpha v beta 3 genes (VNRC3 cells) in a reversible and saturable manner. Scatchard analysis revealed that eristostatin bound to 816000 sites per A5 cell (Kd 28 nM) and to 200000 sites (Kd 14 nM) per VNRC3 cell respectively. However, VNRC3 cells did not bind to immobilized eristostatin. Echistatin bound to 495000 sites (Kd 53 nM) per A5 cell and to 443000 sites (Kd 20 nM) per VNRC3 cell. As determined by flow cytometry, radiobinding assay and adhesion studies, binding of both disintegrins to A5 cells and resting platelets and binding of echistatin to VNRC3 cells resulted in the expression of ligand-induced binding sites (LIBS) on the beta 3 subunit. Eristostatin inhibited, more strongly than echistatin, the binding of three monoclonal antibodies: OPG2 (RGD motif dependent), A2A9 (alpha IIb beta 3 complex dependent) and 7E3 (alpha IIb beta 3 and alpha v beta 3 complex dependent) to A5 cells, to resting and to activated platelets and to purified alpha IIb beta 3. Experiments in which echistatin and eristostatin were used alone or in combination to inhibit the binding of 7E3 and OPG2 antibodies to resting platelets suggested that these two disintegrins bind to different but overlapping sites on alpha IIb beta 3 integrin. Monoclonal antibody LM 609 and echistatin seemed to bind to different sites on alpha v beta 3 integrin. However, echistatin inhibited binding of 7E3 antibody to VNRC3 cells and to purified alpha v beta 3 suggesting that alpha v beta 3 and alpha IIb beta 3 might share the same epitope to which both echistatin and 7E3 bind. Eristostatin had no effect in these systems, providing further evidence that it binds to a different epitope on alpha v beta 3. PMID:8760368

How do roll compaction/dry granulation affect the tableting behaviour of inorganic materials? Microhardness of ribbons and mercury porosimetry measurements of tablets.

PubMed

Freitag, Franziska; Reincke, Katrin; Runge, Jürgen; Grellmann, Wolfgang; Kleinebudde, Peter

2004-07-01

The effect of roll compaction/dry granulation on the ribbon and tablet properties produced using different magnesium carbonates was evaluated. The ribbon microhardness and the pore size distribution of tablets were used as evaluation factors. Increasing the specific compaction force resulted in higher microhardness for ribbons prepared with all four magnesium carbonates accompanied with decreased part of fine. Consequently, the corresponding produced tablets displayed a lower tensile strength. A possible correlation between the particle shape, surface area and the resulting pore structure of tablets produced with the four different types of magnesium carbonate was observed. The tensile strength of tablets prepared using granules was lower than tensile strength of tablets produced using starting materials. The partial loss of compactibility resulted in a demand of low loads during roll compaction. However, the impact of changes in the material properties during the roll compaction depended greatly on the type of magnesium carbonate, the specific compaction force and the tableting pressure applied.

Use of plate fixation without coracoclavicular ligament augmentation for unstable distal clavicle fractures.

PubMed

Shin, Sang-Jin; Ko, Young-Won; Lee, Juyeob; Park, Min-Gyue

2016-06-01

The purpose of this study was to evaluate the clinical and radiologic outcomes of unstable distal clavicle fractures treated with anatomic plate fixation without coracoclavicular ligament augmentation and to compare the outcome of Neer type IIA with that of type IIB. Twenty-five patients with unstable distal clavicle fractures who underwent anatomic plate fixation without coracoclavicular ligament augmentation were enrolled prospectively, including 9 patients of Neer type IIA and 16 patients of Neer type IIB. Clinical outcomes were evaluated using Constant and University of California-Los Angeles (UCLA) scores. Coracoclavicular distance was measured on plain radiographs. Bone union was achieved in all patients. Satisfactory clinical and radiologic outcomes were obtained regardless of fracture type. After operation, the mean coracoclavicular distance on the injured side was increased by 10% compared with the uninjured side. However, between the patients who showed an increased coracoclavicular distance >10% (Constant score, 89.4 ± 3.7; UCLA score, 32.6 ± 3) and the patients with increased coracoclavicular distance <10% of the uninjured side (Constant score, 88.7 ± 3.6; UCLA score, 31.9 ± 3), there was no statistically significant difference in clinical outcomes of Constant score (P = .934) and UCLA score (P = .598). In unstable distal clavicle fractures, precontoured anatomic plate fixation without coracoclavicular ligament augmentation showed satisfactory clinical outcomes and high union rates even with a small lateral fragment. Patients who had increased coracoclavicular distance also demonstrated satisfactory shoulder functional outcomes regardless of the fracture type. Therefore, anatomic plate fixation without additional coracoclavicular ligament augmentation can be considered one of the treatment options for unstable distal clavicle fracture. Level IV; Case Series; Treatment Study. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Treatment with soluble activin type IIB-receptor improves bone mass and strength in a mouse model of Duchenne muscular dystrophy.

PubMed

Puolakkainen, Tero; Ma, Hongqian; Kainulainen, Heikki; Pasternack, Arja; Rantalainen, Timo; Ritvos, Olli; Heikinheimo, Kristiina; Hulmi, Juha J; Kiviranta, Riku

2017-01-19

Inhibition of activin/myostatin pathway has emerged as a novel approach to increase muscle mass and bone strength. Duchenne muscular dystrophy (DMD) is a neuromuscular disorder that leads to progressive muscle degeneration and also high incidence of fractures. The aim of our study was to test whether inhibition of activin receptor IIB ligands with or without exercise could improve bone strength in the mdx mouse model for DMD. Thirty-two mdx mice were divided to running and non-running groups and to receive either PBS control or soluble activin type IIB-receptor (ActRIIB-Fc) once weekly for 7 weeks. Treatment of mdx mice with ActRIIB-Fc resulted in significantly increased body and muscle weights in both sedentary and exercising mice. Femoral μCT analysis showed increased bone volume and trabecular number (BV/TV +80%, Tb.N +70%, P < 0.05) in both ActRIIB-Fc treated groups. Running also resulted in increased bone volume and trabecular number in PBS-treated mice. However, there was no significant difference in trabecular bone structure or volumetric bone mineral density between the ActRIIB-Fc and ActRIIB-Fc-R indicating that running did not further improve bone structure in ActRIIB-Fc-treated mice. ActRIIB-Fc increased bone mass also in vertebrae (BV/TV +20%, Tb.N +30%, P < 0.05) but the effects were more modest. The number of osteoclasts was decreased in histological analysis and the expression of several osteoblast marker genes was increased in ActRIIB-Fc treated mice suggesting decreased bone resorption and increased bone formation in these mice. Increased bone mass in femurs translated into enhanced bone strength in biomechanical testing as the maximum force and stiffness were significantly elevated in ActRIIB-Fc-treated mice. Our results indicate that treatment of mdx mice with the soluble ActRIIB-Fc results in a robust increase in bone mass, without any additive effect by voluntary running. Thus ActRIIB-Fc could be an attractive option in the treatment of musculoskeletal disorders.

Comparative analysis of locking plate versus hook plate osteosynthesis of Neer type IIB lateral clavicle fractures.

PubMed

Erdle, Benjamin; Izadpanah, Kaywan; Jaeger, Martin; Jensen, Patrizia; Konstantinidis, Lukas; Zwingmann, Jörn; Südkamp, Norbert P; Maier, Dirk

2017-05-01

Controversy exists on optimal operative treatment of vertically unstable Neer IIB lateral clavicle fractures. Aim of this study was to analyse and compare clinical and radiological results and complications of locking plate osteosynthesis (LPO) versus hook plate osteosynthesis (HPO) with acromioclavicular joint (ACJ) stabilization. The hypothesis was, that HPO would recreate coracoclavicular stability more effectively and potentially lead to a superior outcome. This retrospective, observational cohort study included 32 patients (19 HPO, 13 LPO) with a mean age of 44.1 ± 14.2 years at surgery. The mean follow-up period was 54.2 months (range 25.2-111.4 months). Besides standard radiography, bilateral coracoclavicular distances were assessed by means of preoperative and follow-up stress radiographs after implant removal. Clinical outcome measures included the Constant score (CS), the Oxford shoulder score (OSS), the subjective shoulder value (SSV) and the Taft score (TS). Bone union occurred in all but one patient and proved to occur delayed in five patients (15.6%). Radiographical healing required a mean of 4.2 ± 4.0 months irrespective of the type of osteosynthesis. At follow-up, mean coracoclavicular distance was increased by 34% (±36) without significant differences between both groups. HPO patients obtained a significantly lower TS (HPO: 9.5 ± 1.5 points, LPO: 11.1 ± 1.3 points; p = 0.005). Other mean score values did not differ (CS: 90.1 ± 7.4 points, OSS: 43.2 ± 9.2 points, SSV: 91.1 ± 14.7%). Sixteen patients (50.0%) experienced complications. Overall prevalence of complications was significantly higher in the HPO group (p = 0.014). Both HPO and LPO were equally effective in relation to restoration of vertical stability, overall functional outcome and fracture consolidation in treatment of Neer IIB fractures. Contrary to our hypothesis, HPO was not associated with superior recreation of the coracoclavicular distance. Considerable drawbacks of HPO were an inferior ACJ-specific outcome (Taft-Score) and a higher overall complication rate. Level of evidence IV.

Biased ligand of the angiotensin II type 1 receptor in patients with acute heart failure: a randomized, double-blind, placebo-controlled, phase IIB, dose ranging trial (BLAST-AHF).

PubMed

Pang, Peter S; Butler, Javed; Collins, Sean P; Cotter, Gad; Davison, Beth A; Ezekowitz, Justin A; Filippatos, Gerasimos; Levy, Phillip D; Metra, Marco; Ponikowski, Piotr; Teerlink, John R; Voors, Adriaan A; Bharucha, David; Goin, Kathleen; Soergel, David G; Felker, G Michael

2017-08-07

Currently, no acute heart failure (AHF) therapy definitively improves outcomes. Reducing morbidity and mortality from acute heart failure (AHF) remains an unmet need. TRV027 is a novel 'biased' ligand of the angiotensin II type 1 receptor (AT1R), selectively antagonizing the negative effects of angiotensin II, while preserving the potential pro-contractility effects of AT1R stimulation. BLAST-AHF was designed to determine the safety, efficacy, and optimal dose of TRV027 to advance into future studies. BLAST-AHF was a multi-centre, international, randomized, double-blind, placebo-controlled, parallel group, phase IIb dose-ranging study, enrolling patients with AHF into 4 groups: placebo, 1, 5, or 25 mg/h of TRV027. Treatment was by IV infusion for 48-96 h. The primary composite endpoint was comprised of the following: (i) time from baseline to death through day 30, (ii) time from baseline to heart failure re-hospitalization through day 30, (iii) the first assessment time point following worsening heart failure through day 5, (iv) change in dyspnea visual analogue scale (VAS) score calculated as the area under the curve (AUC) representing the change from baseline over time from baseline through day 5, and (v) length of initial hospital stay (in days) from baseline. Analyses were by modified intention-to-treat. Overall, 621 patients were enrolled. After 254 patients, a pre-specified interim analysis resulted in several protocol changes, including a lower blood pressure inclusion criterion as well as a new allocation scheme of 2:1:2:1, overweighting both placebo, and the 5 mg/h dose. TRV027 did not confer any benefit over placebo at any dose with regards to the primary composite endpoint or any of the individual components. There were no significant safety issues with TRV027. In this phase IIb dose-ranging AHF study, TRV027 did not improve clinical status through 30-day follow-up compared with placebo. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Extended Cancer Education for Longer-Term Survivors in Primary Care for Patients With Stage I-II Breast or Prostate Cancer or Stage I-III Colorectal Cancer

ClinicalTrials.gov

2017-11-15

Stage I Breast Cancer; Stage I Colorectal Cancer AJCC v6 and v7; Stage I Prostate Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage II Breast Cancer; Stage II Colorectal Cancer AJCC v7; Stage II Prostate Cancer; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer AJCC v7; Stage IIA Prostate Cancer; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer AJCC v7; Stage IIB Prostate Cancer; Stage IIC Colorectal Cancer AJCC v7; Stage III Colorectal Cancer AJCC v7; Stage IIIA Colorectal Cancer AJCC v7; Stage IIIB Colorectal Cancer AJCC v7; Stage IIIC Colorectal Cancer AJCC v7

Chemotaxonomy of heterocystous cyanobacteria using FAME profiling as species markers.

PubMed

Shukla, Ekta; Singh, Satya Shila; Singh, Prashant; Mishra, Arun Kumar

2012-07-01

The fatty acid methyl ester (FAME) analysis of the 12 heterocystous cyanobacterial strains showed different fatty acid profiling based on the presence/absence and the percentage of 13 different types of fatty acids. The major fatty acids viz. palmitic acid (16:0), hexadecadienoic acid (16:2), stearic acid (18:0), oleic acid (18:1), linoleic (18:2), and linolenic acid (18:3) were present among all the strains except Cylindrospermum musicola where oleic acid (18:1) was absent. All the strains showed high levels of polyunsaturated fatty acid (PUFAs; 41-68.35%) followed by saturated fatty acid (SAFAs; 1.82-40.66%) and monounsaturated fatty acid (0.85-24.98%). Highest percentage of PUFAs and essential fatty acid (linolenic acid; 18:3) was reported in Scytonema bohnerii which can be used as fatty acid supplement in medical and biotechnological purpose. The cluster analysis based on FAME profiling suggests the presence of two distinct clusters with Euclidean distance ranging from 0 to 25. S. bohnerii of cluster I was distantly related to the other strains of cluster II. The genotypes of cluster II were further divided into two subclusters, i.e., IIa with C. musicola showing great divergence with the other genotypes of IIb which was further subdivided into two groups. Subsubcluster IIb(1) was represented by a genotype, Anabaena sp. whereas subsubcluster IIb(2) was distinguished by two groups, i.e., one group having significant similarity among their three genotypes showed distant relation with the other group having closely related six genotypes. To test the validity of the fatty acid profiles as a marker, cluster analysis has also been generated on the basis of morphological attributes. Our results suggest that FAME profiling might be used as species markers in the study of polyphasic approach based taxonomy and phylogenetic relationship.

Effects of age on intestinal phosphate transport and biochemical values of broiler chickens

PubMed Central

Li, Jianhui; Yuan, Jianmin; Miao, Zhiqiang; Guo, Yuming

2017-01-01

Objective The objective of this experiment was to characterize the mRNA expression profile of type IIb sodium-inorganic phosphate cotransporter (NaPi-IIb) and the biochemical values of serum alkaline phosphatase (AKP), calcium, inorganic phosphorus, tibial ash and minerals of broiler chickens with aging. Methods A total of 56 one-day-old Arbor Acres male broiler chickens were used. Broiler chickens were weighed and samples were collected weekly from day 1. Results The result showed that before the growth inflection point, ash, calcium, and phosphorus content in the tibia of broiler chickens increased with growth (before 3 weeks of age), although there were no significant differences in chicks at different ages in the later period of the experiment and weight gain rate was relatively slow at this stage (4 to 6 weeks). NaPi-IIb gene expression in the small intestine in the early growth stage was higher than that in the later growth stage. Expression of calbindin and the vitamin D receptor protein in the intestinal mucosa increased with age in the duodenum and jejunum. Serum AKP activity first increased and subsequently decreased after peaking at 1 week of age, but there was no significant difference after 3 weeks of age. Conclusion These results show that compared with the early growth stage, the weight-gain rate of broiler chickens in the late growth stage gradually decreased with gradual tibia maturation, along with weaker positive transport of phosphorus in the intestine and reinforced re-absorption of phosphorus in the kidney, which might be the reason that phosphorus requirement in the late growth stage was decreased. PMID:27703131

β3 Integrin Haplotype Influences Gene Regulation and Plasma von Willebrand Factor Activity

PubMed Central

Payne, Katie E; Bray, Paul F; Grant, Peter J; Carter, Angela M

2008-01-01

The Leu33Pro polymorphism of the gene encoding β3 integrin (ITGB3) is associated with acute coronary syndromes and influences platelet aggregation. Three common promoter polymorphisms have also been identified. The aims of this study were to (1) investigate the influence of the ITGB3 −400C/A, −425A/C and −468G/A promoter polymorphisms on reporter gene expression and nuclear protein binding and (2) determine genotype and haplotype associations with platelet αIIbβ3 receptor density. Promoter haplotypes were introduced into an ITGB3 promoter-pGL3 construct by site directed mutagenesis and luciferase reporter gene expression analysed in HEL and HMEC-1 cells. Binding of nuclear proteins was assessed by electrophoretic mobility shift assay. The association of ITGB3 haplotype with platelet αIIbβ3 receptor density was determined in 223 subjects. Species conserved motifs were identified in the ITGB3 promoter in the vicinity of the 3 polymorphisms. The GAA, GCC, AAC, AAA and ACC constructs induced ~50% increased luciferase expression relative to the GAC construct in both cell types. Haplotype analysis including Leu33Pro indicated 5 common haplotypes; no associations between ITGB3 haplotypes and receptor density were found. However, the GCC-Pro33 haplotype was associated with significantly higher vWF activity (128.6 [112.1–145.1]%) compared with all other haplotypes (107.1 [101.2–113.0]%, p=0.02). In conclusion, the GCC-Pro33 haplotype was associated with increased vWF activity but not with platelet αIIbβ3 receptor density, which may indicate ITGB3 haplotype influences endothelial function. PMID:18045606

Topological vertex formalism with O5-plane

NASA Astrophysics Data System (ADS)

Kim, Sung-Soo; Yagi, Futoshi

2018-01-01

We propose a new topological vertex formalism for a type IIB (p ,q ) 5-brane web with an O5-plane. We apply our proposal to five-dimensional N =1 Sp(1) gauge theory with Nf=0 , 1, 8 flavors to compute the topological string partition functions and check the agreement with the known results. Especially for the Nf=8 case, which corresponds to E-string theory on a circle, we obtain a new, yet simple, expression of the partition function with a two Young diagram sum.

Analysis of Title IIB Mathematics and Science Partnerships in the Northwest Region. Issues & Answers. REL 2007-No. 008

ERIC Educational Resources Information Center

Gummer, Edith; Stepanek, Jennifer

2007-01-01

This report describes the first year of the funded professional development activities in the Title IIB Math and Science Partnership (MSP) projects in the Northwest Region and the evaluation models. The analysis is structured around the factors of professional development associated with changes in teacher knowledge and practice. This study is…

Alloimmunization in Congenital Deficiencies of Platelet Surface Glycoproteins: Focus on Glanzmann's Thrombasthenia and Bernard-Soulier's Syndrome.

PubMed

Poon, Man-Chiu; d'Oiron, Roseline

2018-06-07

Glanzmann's thrombasthenia (GT) and Bernard-Soulier's syndrome (BSS) are well-understood congenital bleeding disorders, showing defect/deficiency of platelet glycoprotein (GP) IIb/IIIa (integrin αIIbβ3) and GPIb-IX-V complexes respectively, with relevant clinical, laboratory, biochemical, and genetic features. Following platelet transfusion, affected patients may develop antiplatelet antibodies (to human leukocyte antigen [HLA], and/or αIIbβ3 in GT or GPIb-IX in BSS), which may render future platelet transfusion ineffective. Anti-αIIbβ3 and anti-GPIb-IX may also cross the placenta during pregnancy to cause thrombocytopenia and bleeding in the fetus/neonate. This review will focus particularly on the better studied GT to illustrate the natural history and complications of platelet alloimmunization. BSS will be more briefly discussed. Platelet transfusion, if unavoidable, should be given judiciously with good indications. Patients following platelet transfusion, and women during and after pregnancy, should be monitored for the development of platelet antibodies. There is now a collection of data suggesting the safety and effectiveness of recombinant activated factor VII in the management of affected patients with platelet antibodies. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Low heat transfer oxidizer heat exchanger design and analysis

NASA Technical Reports Server (NTRS)

Kanic, P. G.; Kmiec, T. D.; Peckham, R. J.

1987-01-01

The RL10-IIB engine, a derivative of the RLIO, is capable of multi-mode thrust operation. This engine operates at two low thrust levels: tank head idle (THI), which is approximately 1 to 2 percent of full thrust, and pumped idle (PI), which is 10 percent of full thrust. Operation at THI provides vehicle propellant settling thrust and efficient engine thermal conditioning; PI operation provides vehicle tank pre-pressurization and maneuver thrust for log-g deployment. Stable combustion of the RL10-IIB engine at THI and PI thrust levels can be accomplished by providing gaseous oxygen at the propellant injector. Using gaseous hydrogen from the thrust chamber jacket as an energy source, a heat exchanger can be used to vaporize liquid oxygen without creating flow instability. This report summarizes the design and analysis of a United Aircraft Products (UAP) low-rate heat transfer heat exchanger concept for the RL10-IIB rocket engine. The design represents a second iteration of the RL10-IIB heat exchanger investigation program. The design and analysis of the first heat exchanger effort is presented in more detail in NASA CR-174857. Testing of the previous design is detailed in NASA CR-179487.

How to Make Eccentricity Cycles in Stratigraphy: the Role of Compaction

NASA Astrophysics Data System (ADS)

Liu, W.; Hinnov, L.; Wu, H.; Pas, D.

2017-12-01

Milankovitch cycles from astronomically driven climate variations have been demonstrated as preserved in cyclostratigraphy throughout geologic time. These stratigraphic cycles have been identified in many types of proxies, e.g., gamma ray, magnetic susceptibility, oxygen isotopes, carbonate content, grayscale, etc. However, the commonly prominent spectral power of orbital eccentricity cycles in stratigraphy is paradoxical to insolation, which is dominated by precession index power. How is the spectral power transferred from precession to eccentricity in stratigraphy? Nonlinear sedimentation and bioturbation have long been identified as players in this transference. Here, we propose that in the absence of bioturbation differential compaction can generate the transference. Using insolation time series, we trace the steps by which insolation is transformed into stratigraphy, and how differential compaction of lithology acts to transfer spectral power from precession to eccentricity. Differential compaction is applied to unique values of insolation, which is assumed to control the type of deposited sediment. High compaction is applied to muds, and progressively lower compaction is applied to silts and sands, or carbonate. Linear differential compaction promotes eccentricity spectral power, but nonlinear differential compaction elevates eccentricity spectral power to dominance and precession spectral power to near collapse as is often observed in real stratigraphy. Keywords: differential compaction, cyclostratigraphy, insolation, eccentricity

Carbon dioxide exchange in compact and semi-open sorghum inflorescences

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

Eastin, J.D.; Sullivan, C.Y.

Carbon dioxide exchange rates were monitored in light and dark in compact and semi-open heads of sorghum (Sorghum bicolor (L.) Moench). Developmental stages ranged from bottom to hard dough in the grain. Highest CO/sub 2/ uptake in both head types occurred at the bloom stage when net uptake rates for semi-open and compact type heads were 3.9 and 1.2 mg CO/sub 2/ g dry wt/sup -1/ hr/sup -1/, respectively. Beginning at the milk stage, a net CO/sub 2/ evolution on the order of 1 to 1.4 mg g dry wt/sup -1/ hr/sup -1/ occurred in compact heads in the light.more » The semi-open head type continued a small net CO/sub 2/ uptake in the light through the milk and soft dough stages. Both head types evolved CO/sub 2/ at hard dough stage. Dark respiration was similar in both head types and decreased from about 4 to 1 mg CO/sub 2/ g dry wt/sup -1/ hr/sup -1/ from bloom to hard dough. 16 references, 1 figure.« less

Vaccine Therapy and Cyclophosphamide in Treating Patients With Stage II-III Breast or Stage II-IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

ClinicalTrials.gov

2017-08-28

Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IIA Breast Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Breast Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Breast Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Breast Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Breast Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

Morphological and biochemical alterations of skeletal muscles from the genetically obese (ob/ob) mouse.

PubMed

Kemp, J G; Blazev, R; Stephenson, D G; Stephenson, G M M

2009-08-01

Knowledge of the morphological and biochemical alterations occurring in skeletal muscles of obese animals is relatively limited, particularly with respect to non-limb muscles and relationship to fibre type. Sternomastoid (SM; fast-twitch), extensor digitorum longus (EDL; fast-twitch), and soleus (SOL; mixed) muscles of ob/ob mouse (18-22 weeks) were examined with respect to size (mass, muscle mass-to-body mass ratio, cross-sectional area (CSA)), fibre CSA, protein content, myosin heavy chain (MHC) content, MHC isoform (MHC(i)) composition, MHC(i)-based fibre type composition, and lactate dehydrogenase isoenzyme (LDH(iso)) composition. Compared with (control) muscles from lean mice, all the three muscles from ob/ob mice were smaller in size (by 13-30%), with SM and EDL being the most affected. The CSA of IIB and IIB+IID fibres (the predominant fibre types in SM and EDL muscles) was markedly smaller (by approximately 30%) in ob/ob mice, consistent with differences in muscle size. Total protein content (normalised to muscle mass) was significantly lower in EDL (-9.7%) and SOL (-14.1%) muscles of ob/ob mice, but there were no differences between SM, EDL, and SOL muscles from the two animal groups with respect to MHC content (also normalised to muscle mass). Electrophoretic analyses of MHC(i) composition in whole muscle homogenates and single muscle fibres showed a shift towards slower MHC(i) content, slower MHC(i) containing fibres, and a greater proportion of hybrid fibres in all the three muscles of ob/ob mice, with a shift towards a more aerobic-oxidative phenotype also observed with respect to LDH(iso) composition. This study showed that SM, EDL, and SOL muscles of ob/ob mice display size reductions to an extent that seems to be largely related to fibre type composition, and a shift in fibre type composition that may result from a process of structural remodelling, as suggested by the increased proportion of hybrid fibres in muscles of ob/ob mice.

Alterations in muscle mass and contractile phenotype in response to unloading models: role of transcriptional/pretranslational mechanisms

PubMed Central

Baldwin, Kenneth M.; Haddad, Fadia; Pandorf, Clay E.; Roy, Roland R.; Edgerton, V. Reggie

2013-01-01

Skeletal muscle is the largest organ system in mammalian organisms providing postural control and movement patterns of varying intensity. Through evolution, skeletal muscle fibers have evolved into three phenotype clusters defined as a motor unit which consists of all muscle fibers innervated by a single motoneuron linking varying numbers of fibers of similar phenotype. This fundamental organization of the motor unit reflects the fact that there is a remarkable interdependence of gene regulation between the motoneurons and the muscle mainly via activity-dependent mechanisms. These fiber types can be classified via the primary type of myosin heavy chain (MHC) gene expressed in the motor unit. Four MHC gene encoded proteins have been identified in striated muscle: slow type I MHC and three fast MHC types, IIa, IIx, and IIb. These MHCs dictate the intrinsic contraction speed of the myofiber with the type I generating the slowest and IIb the fastest contractile speed. Over the last ~35 years, a large body of knowledge suggests that altered loading state cause both fiber atrophy/wasting and a slow to fast shift in the contractile phenotype in the target muscle(s). Hence, this review will examine findings from three different animal models of unloading: (1) space flight (SF), i.e., microgravity; (2) hindlimb suspension (HS), a procedure that chronically eliminates weight bearing of the lower limbs; and (3) spinal cord isolation (SI), a surgical procedure that eliminates neural activation of the motoneurons and associated muscles while maintaining neurotrophic motoneuron-muscle connectivity. The collective findings demonstrate: (1) all three models show a similar pattern of fiber atrophy with differences mainly in the magnitude and kinetics of alteration; (2) transcriptional/pretranslational processes play a major role in both the atrophy process and phenotype shifts; and (3) signaling pathways impacting these alterations appear to be similar in each of the models investigated. PMID:24130531

Intraoperative validation of CT-based lymph nodal levels, sublevels IIa and IIb: Is it of clinical relevance in selective radiation therapy?

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

Levendag, Peter; Gregoire, Vincent; Hamoir, Marc

2005-07-01

Purpose: The objectives of this study are to discuss the intraoperative validation of CT-based boundaries of lymph nodal levels in the neck, and in particular the clinical relevance of the delineation of sublevels IIa and IIb in case of selective radiation therapy (RT). Methods and Materials: To validate the radiologically defined level contours, clips were positioned intraoperatively at the level boundaries defined by surgical anatomy. In 10 consecutive patients, clips were placed, at the time of a neck dissection being performed, at the most cranial border of the neck. Anterior-posterior and lateral X-ray films were obtained intraoperatively. Next, in 3more » patients, neck levels were contoured on preoperative contrast-enhanced CT scans according to the international consensus guidelines. From each of these 3 patients, an intraoperative CT scan was also obtained, with clips placed at the surgical-anatomy-based level boundaries. The preoperative (CT-based) and intraoperative (surgery-defined) CT scans were matched. Results: Clips placed at the most cranial part of the neck lined up at the caudal part of the transverse process of the cervical vertebra C-I. The posterior border of surgical level IIa (spinal accessory nerve [SAN]) did not match with the posterior border of CT-based level IIa (internal jugular vein [IJV]). Other surgical boundaries and CT-based contours were in good agreement. Conclusions: The cranial border of the neck, i.e., the cranial border of level IIa/IIb, corresponds to the caudal edge of the lateral process of C-I. Except for the posterior border between level IIa and level IIb, a perfect match was observed between the other surgical-clip-identified levels II-V boundaries (surgical-anatomy) and the CT-based delineation contours. It is argued that (1) because of the parotid gland overlapping part of level II, and (2) the frequent infestation of occult metastatic cells in the lymph channels around the IJV, the division of level II into radiologic sublevels IIa and IIb may not be relevant. Sparing of, for example, the ipsilateral parotid gland in selective RT can even be a treacherous undertaking with respect to regional tumor control. In contrast, the surgeon's reasoning for preserving the surgical sublevel IIb is that the morbidity associated with dissection of the supraspinal accessory nerve compartment of level II is reduced, whereas there is evidence from the surgical literature that no extra risk for regional tumor control is observed. Therefore, in selective neck dissections, the division into surgical sublevels IIa/IIb makes sense.« less

Myostatin propeptide mutation of the hypermuscular Compact mice decreases the formation of myostatin and improves insulin sensitivity.

PubMed

Kocsis, Tamas; Trencsenyi, Gyorgy; Szabo, Kitti; Baan, Julia Aliz; Muller, Geza; Mendler, Luca; Garai, Ildiko; Reinauer, Hans; Deak, Ferenc; Dux, Laszlo; Keller-Pinter, Aniko

2017-03-01

The TGFβ family member myostatin (growth/differentiation factor-8) is a negative regulator of skeletal muscle growth. The hypermuscular Compact mice carry the 12-bp Mstn(Cmpt-dl1Abc) deletion in the sequence encoding the propeptide region of the precursor promyostatin, and additional modifier genes of the Compact genetic background contribute to determine the full expression of the phenotype. In this study, by using mice strains carrying mutant or wild-type myostatin alleles with the Compact genetic background and nonmutant myostatin with the wild-type background, we studied separately the effect of the Mstn(Cmpt-dl1Abc) mutation or the Compact genetic background on morphology, metabolism, and signaling. We show that both the Compact myostatin mutation and Compact genetic background account for determination of skeletal muscle size. Despite the increased musculature of Compact s, the absolute size of heart and kidney is not influenced by myostatin mutation; however, the Compact genetic background increases them. Both Compact myostatin and genetic background exhibit systemic metabolic effects. The Compact mutation decreases adiposity and improves whole body glucose uptake, insulin sensitivity, and 18 FDG uptake of skeletal muscle and white adipose tissue, whereas the Compact genetic background has the opposite effect. Importantly, the mutation does not prevent the formation of mature myostatin; however, a decrease in myostatin level was observed, leading to altered activation of Smad2, Smad1/5/8, and Akt, and an increased level of p-AS160, a Rab-GTPase-activating protein responsible for GLUT4 translocation. Based on our analysis, the Compact genetic background strengthens the effect of myostatin mutation on muscle mass, but those can compensate for each other when systemic metabolic effects are compared. Copyright © 2017 the American Physiological Society.

UNITED PRESBYTERIAN NATIONAL EDUCATION SURVEY, AN INTERDISCIPLINARY RESEARCH PROJECT. VOLUMES IIA AND IIB, COMMUNICATIONS VARIABLES IN THE CHURCH.

ERIC Educational Resources Information Center

WHITMAN, LAURIS B.; AND OTHERS

THE DEPARTMENT OF RESEARCH OF THE NATIONAL COUNCIL OF CHURCHES CONDUCTED A SURVEY FOR THE UNITED PRESBYTERIAN CHURCH OF ITS MEMBERSHIP AND RELIGIOUS BELIEFS. THE AIM WAS TO COMPARE VARIOUS POPULATIONS (CLERGY, COMMUNICANTS, CHURCH SCHOOL TEACHERS, AND YOUTH), CONCERNING THE EXTENT OF THEIR ORTHODOXY. VOLUMES IIA AND IIB OF THE REPORT RELATE TO THE…

Survivorship Care Plan in Promoting Physical Activity in Breast or Colorectal Cancer Survivors in Wisconsin

ClinicalTrials.gov

2018-01-29

Cancer Survivor; Healthy Subject; Stage I Colorectal Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer; Stage IIC Colorectal Cancer; Stage IIIA Breast Cancer; Stage IIIA Colorectal Cancer; Stage IIIB Breast Cancer; Stage IIIB Colorectal Cancer; Stage IIIC Breast Cancer; Stage IIIC Colorectal Cancer

[Evaluation of Livestock Carcasses and Performance.] Student Materials. V.A. III. [II-B-1 through II-B-2; II-D-1].

ERIC Educational Resources Information Center

Texas A and M Univ., College Station. Vocational Instructional Services.

Part of a series of eight student learning modules in vocational agriculture, this booklet deals with evaluation of livestock. It contains sections on carcass evaluation, the evaluation of performance and production, and the design of livestock production facilities. Each of the first two sections has a glossary, and all three conclude with a…

Patterns of evolution of MHC class II genes of crows (Corvus) suggest trans-species polymorphism

PubMed Central

Townsend, Andrea K.; Sepil, Irem; Nishiumi, Isao; Satta, Yoko

2015-01-01

A distinguishing characteristic of genes that code for the major histocompatibility complex (MHC) is that alleles often share more similarity between, rather than within species. There are two likely mechanisms that can explain this pattern: convergent evolution and trans-species polymorphism (TSP), in which ancient allelic lineages are maintained by balancing selection and retained by descendant species. Distinguishing between these two mechanisms has major implications in how we view adaptation of immune genes. In this study we analyzed exon 2 of the MHC class IIB in three passerine bird species in the genus Corvus: jungle crows (Corvus macrorhynchos japonensis) American crows (C. brachyrhynchos) and carrion crows (C. corone orientalis). Carrion crows and American crows are recently diverged, but allopatric, sister species, whereas carrion crows and jungle crows are more distantly related but sympatric species, and possibly share pathogens linked to MHC IIB polymorphisms. These patterns of evolutionary divergence and current geographic ranges enabled us to test for trans-species polymorphism and convergent evolution of the MHC IIB in crows. Phylogenetic reconstructions of MHC IIB sequences revealed several well supported interspecific clusters containing all three species, and there was no biased clustering of variants among the sympatric carrion crows and jungle crows. The topologies of phylogenetic trees constructed from putatively selected sites were remarkably different than those constructed from putatively neutral sites. In addition, trees constructed using non-synonymous substitutions from a continuous fragment of exon 2 had more, and generally more inclusive, supported interspecific MHC IIB variant clusters than those constructed from the same fragment using synonymous substitutions. These phylogenetic patterns suggest that recombination, especially gene conversion, has partially erased the signal of allelic ancestry in these species. While clustering of positively selected amino acids by supertyping revealed a single supertype shared by only jungle and carrion crows, a pattern consistent with convergence, the overall phylogenetic patterns we observed suggest that TSP, rather than convergence, explains the interspecific allelic similarity of MHC IIB genes in these species of crows. PMID:25802816

Locking plate and fibular strut-graft augmentation in the reconstruction of unicameral bone cyst of proximal femur in the paediatric population.

PubMed

Jamshidi, Khodamorad; Mirkazemi, Masoud; Izanloo, Azra; Mirzaei, Alireza

2018-01-01

Several therapeutic strategies have been used for managing unicameral bone cyst (UBC) of the proximal femur. However, there is insufficient evidence to support one treatment over another, and the optimal treatment is controversial. This study aims at describing our experience with surgical reconstruction of paediatric UBCs of the proximal femur using a proximal locking plate and fibular strut allograft. In total, 14 consecutive paediatric patients with Dormans types IB (four cases) and IIB (10 cases) UBC were assessed. Mean patient age was 8.6 ± 2.3 years, and mean follow-up period was 41.7 ± 29.8 months. Six patients (42.8%) were referred with a pathologic fracture. Clinical/radiological outcome and complication rates were evaluated at the final follow-up session. No cysts were Capanna's class III (recurrence) or IV (no response). Complete healing (Capanna's class I) was seen in ten cysts, while four other cysts healed with residual radiolucent areas (Capanna's class II). Mean healing period was 14.1 ± 5.1 (9-24 months). One patient had superficial infection, one heterotopic ossification, and one mild coxa vara, and mean Musculoskeletal Tumor Society (MSTS) score was 99.5%. According to our results, locking plate and fibular strut graft in Dormans classification types IB and IIB results in a favorable outcome in managing UBC of the proximal femur in the paediatric population.

Time course of myosin heavy chain transitions in neonatal rats: importance of innervation and thyroid state

NASA Technical Reports Server (NTRS)

Adams, G. R.; McCue, S. A.; Zeng, M.; Baldwin, K. M.

1999-01-01

During the postnatal period, rat limb muscles adapt to weight bearing via the replacement of embryonic (Emb) and neonatal (Neo) myosin heavy chains (MHCs) by the adult isoforms. Our aim was to characterize this transition in terms of the six MHC isoforms expressed in skeletal muscle and to determine the importance of innervation and thyroid hormone status on the attainment of the adult MHC phenotype. Neonatal rats were made hypothyroid via propylthiouracil (PTU) injection. In normal and PTU subgroups, leg muscles were unilaterally denervated at 15 days of age. The MHC profiles of plantaris (PLN) and soleus (Sol) muscles were determined at 7, 14, 23, and 30 days postpartum. At day 7, the Sol MHC profile was 55% type I, 30% Emb, and 10% Neo; in the PLN, the pattern was 60% Neo and 25% Emb. By day 30 the Sol and PLN had essentially attained an adult MHC profile in the controls. PTU augmented slow MHC expression in the Sol, whereas in the PLN it markedly repressed IIb MHC by retaining neonatal MHC expression. Denervation blunted the upregulation of IIb in the PLN and of Type I in the Sol and shifted the pattern to greater expression of IIa and IIx MHCs in both muscles. In contrast to previous observations, these findings collectively suggest that both an intact thyroid and innervation state are obligatory for the attainment of the adult MHC phenotype, particularly in fast-twitch muscles.

Uncovering the Putative B-Star Binary Companion of the SN 1993J Progenitor

NASA Technical Reports Server (NTRS)

Fox, Ori D.; Bostroem, K. Azalee; Van Dyk, Schuyler D.; Filippenko, Alexei V.; Fransson, Claes; Matheson, Thomas; Cenko, S. Bradley; Chandra, Poonam; Dwarkadas, Vikram; Li, Weidong;

Comparison of platelet function and viscoelastic test results between healthy dogs and dogs with naturally occurring chronic kidney disease.

PubMed

Dudley, Alicia; Byron, Julie K; Burkhard, Mary Jo; Warry, Emma; Guillaumin, Julien

2017-05-01

OBJECTIVE To compare platelet function and viscoelastic test results between healthy dogs and dogs with chronic kidney disease (CKD) to assess whether dogs with CKD have platelet dysfunction and altered blood coagulation. ANIMALS 10 healthy control dogs and 11 dogs with naturally occurring CKD. PROCEDURES Blood and urine were collected once from each dog for a CBC, serum biochemical analysis, urinalysis, and determination of the urine protein-to-creatinine ratio, prothrombin time, activated partial thromboplastin time, plasma fibrinogen concentration, and antithrombin activity. Closure time was determined by use of a platelet function analyzer and a collagen-ADP platelet agonist. Thromboelastography (TEG) variables (reaction time, clotting time, α angle, maximum amplitude, and global clot strength [G value]) were determined by use of recalcified nonactivated TEG. Platelet expression of glycoprotein Ib (GPIb; receptor for von Willebrand factor), integrin αIIbβ3 (αIIbβ3; receptor for fibrinogen), and P-selectin (marker for platelet activation) was assessed by flow cytometry. RESULTS Compared with healthy control dogs, the median closure time was prolonged, the median maximum amplitude and G value were increased, and the median clotting time was decreased for dogs with CKD. Platelet expression of both αIIbβ3 and P-selectin was also significantly increased for dogs with CKD, compared with that for control dogs. Platelet expression of GPIb, αIIbβ3, and P-selectin was not correlated with closure time or any TEG variable. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that dogs with CKD frequently had evidence of platelet dysfunction and hypercoagulability that were not totally attributable to alterations in platelet surface expression of GPIb, αIIbβ3, and P-selectin.

Value of Magnetic Resonance Imaging Without or With Applicator in Place for Target Definition in Cervix Cancer Brachytherapy.

PubMed

Pötter, Richard; Federico, Mario; Sturdza, Alina; Fotina, Irina; Hegazy, Neamat; Schmid, Maximilian; Kirisits, Christian; Nesvacil, Nicole

2016-03-01

To define, in the setting of cervical cancer, to what extent information from additional pretreatment magnetic resonance imaging (MRI) without the brachytherapy applicator improves conformity of CT-based high-risk clinical target volume (CTVHR) contours, compared with the MRI for various tumor stages (International Federation of Gynecology and Obstetrics [FIGO] stages I-IVA). The CTVHR was contoured in 39 patients with cervical cancer (FIGO stages I-IVA) (1) on CT images based on clinical information (CTVHR-CTClinical) alone; and (2) using an additional MRI before brachytherapy, without the applicator (CTVHR-CTpre-BT MRI). The CT contours were compared with reference contours on MRI with the applicator in place (CTVHR-MRIref). Width, height, thickness, volumes, and topography were analyzed. The CT-MRIref differences hardly varied in stage I tumors (n=8). In limited-volume stage IIB and IIIB tumors (n=19), CTVHR-CTpre-BT MRI-MRIref volume differences (2.6 cm(3) [IIB], 7.3 cm(3) [IIIB]) were superior to CTVHR-CTClinical-MRIref (11.8 cm(3) [IIB], 22.9 cm(3) [IIIB]), owing to significant improvement of height and width (P<.05). In advanced disease (n=12), improved agreement with MR volume, width, and height was achieved for CTVHR-CTpre-BT MRI. In 5 of 12 cases, MRIref contours were partly missed on CT. Pre-BT MRI helps to define CTVHR before BT implantation appropriately, if only CT images with the applicator in place are available for BT planning. Significant improvement is achievable in limited-volume stage IIB and IIIB tumors. In more advanced disease (extensive IIB to IVA), improvement of conformity is possible but may be associated with geographic misses. Limited impact on precision of CTVHR-CT is expected in stage IB tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

Psychosexual Intervention in Patients With Stage I-III Gynecologic or Breast Cancer

ClinicalTrials.gov

2018-05-25

Ovarian Sarcoma; Ovarian Stromal Cancer; Stage I Uterine Sarcoma; Stage I Vaginal Cancer; Stage I Vulvar Cancer; Stage IA Cervical Cancer; Stage IA Endometrial Carcinoma; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Epithelial Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IA Primary Peritoneal Cavity Cancer; Stage IB Cervical Cancer; Stage IB Endometrial Carcinoma; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Epithelial Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IB Primary Peritoneal Cavity Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Epithelial Cancer; Stage IC Ovarian Germ Cell Tumor; Stage IC Primary Peritoneal Cavity Cancer; Stage II Endometrial Carcinoma; Stage II Gestational Trophoblastic Tumor; Stage II Uterine Sarcoma; Stage II Vaginal Cancer; Stage II Vulvar Cancer; Stage IIA Cervical Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIA Primary Peritoneal Cavity Cancer; Stage IIB Cervical Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIB Primary Peritoneal Cavity Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIC Primary Peritoneal Cavity Cancer; Stage III Gestational Trophoblastic Tumor; Stage III Uterine Sarcoma; Stage III Vaginal Cancer; Stage III Vulvar Cancer; Stage IIIA Cervical Cancer; Stage IIIA Endometrial Carcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Cervical Cancer; Stage IIIB Endometrial Carcinoma; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Endometrial Carcinoma; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cavity Cancer; Breast Cancer

Platelet gene therapy improves hemostatic function for integrin alphaIIbbeta3-deficient dogs.

PubMed

Fang, Juan; Jensen, Eric S; Boudreaux, Mary K; Du, Lily M; Hawkins, Troy B; Koukouritaki, Sevasti B; Cornetta, Kenneth; Wilcox, David A

2011-06-07

Activated blood platelets mediate the primary response to vascular injury. Although molecular abnormalities of platelet proteins occur infrequently, taken collectively, an inherited platelet defect accounts for a bleeding diathesis in ≈1:20,000 individuals. One rare example of a platelet disorder, Glanzmann thrombasthenia (GT), is characterized by life-long morbidity and mortality due to molecular abnormalities in a major platelet adhesion receptor, integrin αIIbβ3. Transfusion therapy is frequently inadequate because patients often generate antibodies to αIIbβ3, leading to immune-mediated destruction of healthy platelets. In the most severe cases allogeneic bone marrow transplantation has been used, yet because of the risk of the procedure it has been limited to few patients. Thus, hematopoietic stem cell gene transfer was explored as a strategy to improve platelet function within a canine model for GT. Bleeding complications necessitated the use of a mild pretransplant conditioning regimen; therefore, in vivo drug selection was used to improve engraftment of autologously transplanted cells. Approximately 5,000 αIIbβ3 receptors formed on 10% of platelets. These modest levels allowed platelets to adhere to αIIbβ3's major ligand (fibrinogen), form aggregates, and mediate retraction of a fibrin clot. Remarkably, improved hemostatic function was evident, with ≤135-fold reduced blood loss, and improved buccal bleeding times decreased to 4 min for up to 5 y after transplant. One of four transplanted dogs developed a significant antibody response to αIIbβ3 that was attenuated effectively with transient immune suppression. These results indicate that gene therapy could become a practical approach for treating inherited platelet defects.

Prognostic stratification of patients with T3N1M0 non-small cell lung cancer: which phase should it be?

PubMed

Kilicgun, Ali; Tanriverdi, Ozgur; Turna, Akif; Metin, Muzaffer; Sayar, Adnan; Solak, Okan; Urer, Nur; Gurses, Atilla

2012-06-01

In the 1997 revision of the TNM staging system for lung cancer, patients with T3N0M0 disease were moved from stage IIIA to stage IIB since these patients have a better prognosis. Despite this modification, the local lymph node metastasis remained the most important prognostic factor in patients with lung cancer. The present study aimed to evaluate the prognosis of patients with T3N1 disease as compared with that of patients with stages IIIA and IIB disease. During 7-year period, 313 patients with non-small cell lung cancer (297 men, 16 women) who had resection were enrolled. The patients were staged according the 2007 revision of Lung Cancer Staging by American Joint Committee on Cancer. The Kaplan-Meier statistics was used for survival analysis, and comparisons were made using Cox proportional hazard method. The 5-year survival of patients with stage IIIA disease excluding T3N1 patients was 40%, whereas the survival of the patients with stage IIB disease was 66% at 5 years. The 5-year survival rates of stage III T3N1 patients (single-station N1) was found to be higher than those of patients with stage IIIA disease (excluding pT3N1 patients, P = 0.04), while those were found to be similar with those of patients with stage IIB disease (P = 0.4). Survival of the present cohort of patients with T3N1M0 disease represented the survival of IIB disease rather than IIIA non-small cell lung cancer. Further studies are needed to suggest further revisions in the recent staging system regarding T3N1MO disease.

Intracellular Bacteria in the Pathogenesis of Escherichia coli Urinary Tract Infection in Children

PubMed Central

Robino, Luciana; Scavone, Paola; Araujo, Lucia; Algorta, Gabriela; Zunino, Pablo; Pírez, María Catalina; Vignoli, Rafael

2014-01-01

Background. Uropathogenic Escherichia coli (UPEC) is the most common agent of urinary tract infection (UTI). The classic model of pathogenesis proposes the ascent of UPEC by the urethra and external adherence to the urothelium. Recently, the ability of UPEC to invade urothelial cells and to form intracellular bacterial communities (IBCs) has been described. Methods. The objective of the present study was to determine the presence of intracellular bacteria (IB) in children with UTI caused by E. coli and to characterize its virulence attributes and its relation with clinical outcomes. One hundred thirty-three children with E. coli UTI who attended a reference children's hospital between June and November 2012 were included. Urine samples were analyzed by optical and confocal microscopy looking for exfoliated urothelial cells with IB. Phylogenetic group and 24 virulence factors of UPEC were determined using multiplex polymerase chain reaction. Medical records were analyzed. Results. The presence of IB was detected in 49 of 133 (36.8%) samples by confocal microscopy, in 30 cases as IBC, and in 19 as isolated intracellular bacteria (IIB). Only 50% of these cases could be detected by light microscopy. Seventy-four medical records were analyzed, 34 with IBC/IIB, 40 without IB. Any virulence gene was associated with IBC/IIB. The presence of IBC/IIB was associated with recurrent UTI (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.3–9; P = .017), especially in children without urinary tract functional or morphological abnormalities (OR, 8.0; 95% CI, 2.3–27.4; P = .000). IBCs were associated with lower urinary tract syndrome (OR, 3.6; 95% CI, 1.1–11.8; P = .05) and absence of fever (P = .009). Conclusions. IBCs/IIB could explain a high proportion of children with recurrent UTI. PMID:25091303

A National-Level Validation of the New American Joint Committee on Cancer 8th Edition Subclassification of Stage IIA and B Anal Squamous Cell Cancer.

PubMed

Goffredo, Paolo; Garancini, Mattia; Robinson, Timothy J; Frakes, Jessica; Hoshi, Hisakazu; Hassan, Imran

2018-06-01

The 8th edition of the American Joint Committee on Cancer (AJCC) updated the staging system of anal squamous cell cancer (ASCC) by subdividing stage II into A (T2N0M0) and B (T3N0M0) based on a secondary analysis of the RTOG 98-11 trial. We aimed to validate this new subclassification utilizing two nationally representative databases. The National Cancer Database (NCDB) [2004-2014] and the Surveillance, Epidemiology, and End Results (SEER) database [1988-2013] were queried to identify patients with stage II ASCC. A total of 6651 and 2579 stage IIA (2-5 cm) and 1777 and 641 stage IIB (> 5 cm) patients were identified in the NCDB and SEER databases, respectively. Compared with stage IIB patients, stage IIA patients within the NCDB were more often females with fewer comorbidities. No significant differences were observed between age, race, receipt of chemotherapy and radiation, and mean radiation dose. Demographic, clinical, and pathologic characteristics were comparable between patients in both datasets. The 5-year OS was 72% and 69% for stage IIA versus 57% and 50% for stage IIB in the NCDB and SEER databases, respectively (p < 0.001). After adjustment for available demographic and clinical confounders, stage IIB was significantly associated with worse survival in both cohorts (hazard ratio 1.58 and 2.01, both p < 0.001). This study validates the new AJCC subclassification of stage II anal cancer into A and B based on size (2-5 cm vs. > 5 cm) in the general ASCC population. AJCC stage IIB patients represent a higher risk category that should be targeted with more aggressive/novel therapies.

Integrin alphaIIb-subunit cytoplasmic domain mutations demonstrate a requirement for tyrosine phosphorylation of beta3-subunits in actin cytoskeletal organization.

PubMed

Yamodo, Innocent H; Blystone, Scott D

2004-01-01

Using truncated or mutated alphaIIb integrin cytoplasmic domains fused to the alphaV extracellular domain and expressed with the beta3 integrin subunit, we demonstrate that the double mutation of proline residues 998 and 999 to alanine (PP998/999AA), previously shown to disturb the C-terminal conformation of the alphaIIb integrin cytoplasmic domain, prevents tyrosine phosphorylation of beta3 integrin induced by Arg-Gly-Asp peptide ligation. This mutation also inhibits integrin mediated actin assembly and cell adhesion to vitronectin. In contrast, progressive truncation of the alphaIIb-subunit cytoplasmic domain did not reproduce these effects. Interestingly, the PP998/999AA mutations of alphaIIb did not affect beta3 tyrosine phosphorylation, cell adhesion, or actin polymerization induced by manganese. Exogenous addition of manganese was sufficient to rescue beta3 phosphorylation, cell adhesion, and actin assembly in cells expressing the PP998/999AA mutation when presented with a vitronectin substrate. Further, induction of the high affinity conformation of this mutant beta3 integrin by incubation with either Arg-Gly-Asp peptide or exogenous manganese was equivalent. These results suggest that the extracellular structure of beta3 integrins in the high affinity conformation is not directly related to the structure of the cytoplasmic face of the integrin. Moreover, the requirement for beta3 phosphorylation is demonstrated without mutation of the beta3 subunit. In support of our previous hypothesis of a role for beta3 phosphorylation in adhesion, these studies demonstrate a strong correlation between beta3 tyrosine phosphorylation and assembly of a cytoskeleton competent to support firm cell adhesion.

Associations of serum adiponectin with skeletal muscle morphology and insulin sensitivity.

PubMed

Ingelsson, Erik; Arnlöv, Johan; Zethelius, Björn; Vasan, Ramachandran S; Flyvbjerg, Allan; Frystyk, Jan; Berne, Christian; Hänni, Arvo; Lind, Lars; Sundström, Johan

2009-03-01

Skeletal muscle morphology and function are strongly associated with insulin sensitivity. The objective of the study was to test the hypothesis that circulating adiponectin is associated with skeletal muscle morphology and that adiponectin mediates the relation of muscle morphology to insulin sensitivity. This was a cross-sectional investigation of 461 men aged 71 yr, participants of the community-based Uppsala Longitudinal Study of Adult Men study. Measures included serum adiponectin, insulin sensitivity measured with euglycemic insulin clamp technique, and capillary density and muscle fiber composition determined from vastus lateralis muscle biopsies. In multivariable linear regression models (adjusting for age, physical activity, fasting glucose, and pharmacological treatment for diabetes), serum adiponectin levels rose with increasing capillary density (beta, 0.30 per 50 capillaries per square millimeter increase; P = 0.041) and higher proportion of type I muscle fibers (beta, 0.27 per 10% increase; P = 0.036) but declined with a higher proportion of type IIb fibers (beta, -0.39 per 10% increase; P = 0.014). Using bootstrap methods to examine the potential role of adiponectin in associations between muscle morphology and insulin sensitivity and the associations of capillary density (beta difference, 0.041; 95% confidence interval 0.001, 0.085) and proportion of type IIb muscle fibers (beta difference, -0.053; 95% confidence interval -0.107, -0.002) with insulin sensitivity were significantly attenuated when adiponectin was included in the models. Circulating adiponectin concentrations were higher with increasing skeletal muscle capillary density and in individuals with higher proportion of slow oxidative muscle fibers. Furthermore, our results indicate that adiponectin could be a partial mediator of the relations between skeletal muscle morphology and insulin sensitivity.

Searching for the Expelled Hydrogen Envelope in Type I Supernovae via Late-Time H α Emission

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

Vinko, J.; Silverman, J. M.; Wheeler, J. C.

2017-03-01

We report the first results from our long-term observational survey aimed at discovering late-time interaction between the ejecta of hydrogen-poor Type I supernovae (SNe I) and the hydrogen-rich envelope expelled from the progenitor star several decades/centuries before explosion. The expelled envelope, moving with a velocity of ∼10–100 km s{sup −1}, is expected to be caught up by the fast-moving SN ejecta several years/decades after explosion, depending on the history of the mass-loss process acting in the progenitor star prior to explosion. The collision between the SN ejecta and the circumstellar envelope results in net emission in the Balmer lines, especiallymore » H α . We look for signs of late-time H α emission in older SNe Ia/Ibc/IIb with hydrogen-poor ejecta via narrowband imaging. Continuum-subtracted H α emission has been detected for 13 point sources: 9 SN Ibc, 1 SN IIb, and 3 SN Ia events. Thirty-eight SN sites were observed on at least two epochs, from which three objects (SN 1985F, SN 2005kl, and SN 2012fh) showed significant temporal variation in the strength of their H α emission in our Direct Imaging Auxiliary Functions Instrument (DIAFI) data. This suggests that the variable emission is probably not due to nearby H ii regions unassociated with the SN and hence is an important additional hint that ejecta–circumstellar medium interaction may take place in these systems. Moreover, we successfully detected the late-time H α emission from the Type Ib SN 2014C, which was recently discovered as a strongly interacting SN in various (radio, infrared, optical, and X-ray) bands.« less

High-intensity interval and endurance training are associated with divergent skeletal muscle adaptations in a rodent model of hypertension.

PubMed

Holloway, Tanya M; Bloemberg, Darin; da Silva, Mayne L; Quadrilatero, Joe; Spriet, Lawrence L

2015-06-01

Skeletal muscle is extremely adaptable to a variety of metabolic challenges, as both traditional moderate-intensity endurance (ET) and high-intensity interval training (HIIT) increases oxidative potential in a coordinated manner. Although these responses have been clearly demonstrated in healthy individuals, it remains to be determined whether both produce similar responses in the context of hypertension, one of the most prevalent and costly diseases worldwide. Therefore, in the current study, we used the Dahl sodium-sensitive rat, a model of hypertension, to determine the molecular responses to 4 wk of either ET or HIIT in the red (RG) and white gastrocnemius (WG) muscles. In the RG, both ET and HIIT increased the content of electron transport chain proteins and increased succinate dehydrogenase (SDH) content in type I fibers. Although both intensities of exercise shifted fiber type in RG (increased IIA, decreased IIX), only HIIT was associated with a reduction in endothelial nitric oxide synthase and an increase in HIF-1α proteins. In the WG, both ET and HIIT increased markers of the electron transport chain; however, HIIT decreased SDH content in a fiber-specific manner. ET increased type IIA, decreased IIB fibers, and increased capillarization, while, in contrast, HIIT increased the percentage of IIB fibers, decreased capillary-to-fiber ratios, decreased endothelial nitric oxide synthase, and increased hypoxia inducible factor-1α (HIF-1α) protein. Altogether, these data show that unlike in healthy animals, ET and HIIT have divergent effects in the skeletal muscle of hypertensive rats. This suggests ET may be optimal at improving the oxidative capacity of skeletal muscle in animals with hypertension. Copyright © 2015 the American Physiological Society.

Maternal Creatine Supplementation during Pregnancy Prevents Long-Term Changes in Diaphragm Muscle Structure and Function after Birth Asphyxia

PubMed Central

LaRosa, Domenic A.; Ellery, Stacey J.; Parkington, Helena C.; Snow, Rod J.

2016-01-01

Using a model of birth asphyxia, we previously reported significant structural and functional deficits in the diaphragm muscle in spiny mice, deficits that are prevented by supplementing the maternal diet with 5% creatine from mid-pregnancy. The long-term effects of this exposure are unknown. Pregnant spiny mice were fed control or 5% creatine-supplemented diet for the second half of pregnancy, and fetuses were delivered by caesarean section with or without 7.5 min of in-utero asphyxia. Surviving pups were raised by a cross-foster dam until 33±2 days of age when they were euthanized to obtain the diaphragm muscle for ex-vivo study of twitch tension and muscle fatigue, and for structural and enzymatic analyses. Functional analysis of the diaphragm revealed no differences in single twitch contractile parameters between any groups. However, muscle fatigue, induced by stimulation of diaphragm strips with a train of pulses (330ms train/sec, 40Hz) for 300sec, was significantly greater for asphyxia pups compared with controls (p<0.05), and this did not occur in diaphragms of creatine + asphyxia pups. Birth asphyxia resulted in a significant increase in the proportion of glycolytic, fast-twitch fibres and a reduction in oxidative capacity of Type I and IIb fibres in male offspring, as well as reduced cross-sectional area of all muscle fibre types (Type I, IIa, IIb/d) in both males and females at 33 days of age. None of these changes were observed in creatine + asphyxia animals. Thus, the changes in diaphragm fatigue and structure induced by birth asphyxia persist long-term but are prevented by maternal creatine supplementation. PMID:26930669

Narrowband Hα Imaging of Old Hydrogen-deficient Supernovae

NASA Astrophysics Data System (ADS)

Pooley, David A.; Vinko, Jozsef; Silverman, Jeffrey M.; Wheeler, J. Craig Craig; Szalai, Tamas; MacQueen, Phillip; Marion, Howie H.; Sárneczky, Krisztián

2017-06-01

We report results from our long-term observational survey aimed at discovering late-time interaction between the ejecta of hydrogen-deficient Type I supernovae and the hydrogen-rich envelope expelled from the progenitor star several decades to centuries before explosion. The expelled envelope, moving with a velocity of ˜10-100 km/s, is expected to be caught up by the fast-moving SN ejecta several years to decades after explosion depending on the history of the mass-loss process acting in the progenitor star prior to explosion. The collision between the SN ejecta and the circumstellar envelope results in net emission in the Balmer-lines, especially in Hα. For the past three years, we have been using the Direct Imaging Auxiliary Functions Instrument (DIAFI) on the 2.7m Harlan J. Smith Telescope at McDonald Observatory to look for signs of late-time Hα emission in older Type Ia/Ibc/IIb SNe having hydrogen-poor ejecta, via narrow-band imaging. Continuum-subtracted Hα emission has been detected for 13 point sources: 9 SN Ibc, 1 SN IIb and 3 SN Ia events. Thirty-eight SN sites were observed on at least two epochs, from which three objects (SN 1985F, SN 2005kl, SN 2012fh) showed significant temporal variation in the strength of their Hα emission in our DIAFI data. This suggests that the variable emission is probably not due to nearby HII regions, and hence is an important additional hint that ejecta-CSM interaction may take place in these systems. Moreover, we successfully detected the late-time Hα emission from the Type Ib SN 2014C, which was recently discovered as a strongly interacting SN in other wavebands.

Soil compaction vulnerability at Organ Pipe Cactus National Monument, Arizona

USGS Publications Warehouse

Webb, Robert H.; Nussear, Kenneth E.; Carmichael, Shinji; Esque, Todd C.

2014-01-01

Compaction vulnerability of different types of soils by hikers and vehicles is poorly known, particularly for soils of arid and semiarid regions. Engineering analyses have long shown that poorly sorted soils (for example, sandy loams) compact to high densities, whereas well-sorted soils (for example, eolian sand) do not compact, and high gravel content may reduce compaction. Organ Pipe Cactus National Monument (ORPI) in southwestern Arizona, is affected greatly by illicit activities associated with the United States–Mexico border, and has many soils that resource managers consider to be highly vulnerable to compaction. Using geospatial soils data for ORPI, compaction vulnerability was estimated qualitatively based on the amount of gravel and the degree of sorting of sand and finer particles. To test this qualitative assessment, soil samples were collected from 48 sites across all soil map units, and undisturbed bulk densities were measured. A scoring system was used to create a vulnerability index for soils on the basis of particle-size sorting, soil properties derived from Proctor compaction analyses, and the field undisturbed bulk densities. The results of the laboratory analyses indicated that the qualitative assessments of soil compaction vulnerability underestimated the area of high vulnerability soils by 73 percent. The results showed that compaction vulnerability of desert soils, such as those at ORPI, can be quantified using laboratory tests and evaluated using geographic information system analyses, providing a management tool that managers potentially could use to inform decisions about activities that reduce this type of soil disruption in protected areas.

Sirolimus and Vaccine Therapy in Treating Patients With Stage II-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Cancer

ClinicalTrials.gov

2018-03-28

Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Primary Peritoneal Cavity Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Primary Peritoneal Cavity Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer

Adherence to Survivorship Care Guidelines in Health Care Providers for Non-Small Cell Lung Cancer and Colorectal Cancer Survivor Care

ClinicalTrials.gov

2017-04-05

Adenocarcinoma of the Lung; Mucinous Adenocarcinoma of the Colon; Mucinous Adenocarcinoma of the Rectum; Signet Ring Adenocarcinoma of the Colon; Signet Ring Adenocarcinoma of the Rectum; Squamous Cell Lung Cancer; Stage I Colon Cancer; Stage I Rectal Cancer; Stage IA Non-small Cell Lung Cancer; Stage IB Non-small Cell Lung Cancer; Stage IIA Colon Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Non-small Cell Lung Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer

S1415CD, Trial Assessing CSF Prescribing Effectiveness and Risk (TrACER)

ClinicalTrials.gov

2018-03-20

Febrile Neutropenia; Stage 0 Breast Cancer; Stage 0 Colorectal Cancer; Stage 0 Non-Small Cell Lung Cancer; Stage I Colorectal Cancer; Stage IA Breast Cancer; Stage IA Non-Small Cell Lung Carcinoma; Stage IB Breast Cancer; Stage IB Non-Small Cell Lung Carcinoma; Stage IIA Breast Cancer; Stage IIA Colorectal Cancer; Stage IIA Non-Small Cell Lung Carcinoma; Stage IIB Breast Cancer; Stage IIB Colorectal Cancer; Stage IIB Non-Small Cell Lung Carcinoma; Stage IIC Colorectal Cancer; Stage IIIA Breast Cancer; Stage IIIA Colorectal Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Breast Cancer; Stage IIIB Colorectal Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIC Breast Cancer; Stage IIIC Colorectal Cancer; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IVA Colorectal Cancer; Stage IVB Colorectal Cancer

Electronic Monitoring Device of Patient-Reported Outcomes and Function in Improving Patient-Centered Care in Patients With Gastrointestinal Cancer Undergoing Surgery

ClinicalTrials.gov

2018-06-06

Stage I Adult Liver Cancer; Stage I Colorectal Cancer; Stage IA Gastric Cancer; Stage IA Pancreatic Cancer; Stage IB Gastric Cancer; Stage IB Pancreatic Cancer; Stage II Adult Liver Cancer; Stage IIA Colorectal Cancer; Stage IIA Gastric Cancer; Stage IIA Pancreatic Cancer; Stage IIB Colorectal Cancer; Stage IIB Gastric Cancer; Stage IIB Pancreatic Cancer; Stage IIC Colorectal Cancer; Stage III Pancreatic Cancer; Stage IIIA Adult Liver Cancer; Stage IIIA Colorectal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Adult Liver Cancer; Stage IIIB Colorectal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Adult Liver Cancer; Stage IIIC Colorectal Cancer; Stage IIIC Gastric Cancer; Stage IV Gastric Cancer; Stage IVA Colorectal Cancer; Stage IVA Liver Cancer; Stage IVA Pancreatic Cancer; Stage IVB Colorectal Cancer; Stage IVB Liver Cancer; Stage IVB Pancreatic Cancer

Radiative Kähler moduli stabilization

NASA Astrophysics Data System (ADS)

Kobayashi, Tatsuo; Omoto, Naoya; Otsuka, Hajime; Tatsuishi, Takuya H.

2018-05-01

We propose a new type of Kähler moduli stabilization mechanisms in type IIB superstring theory on Calabi-Yau manifolds with the positive Euler number. The overall Kähler modulus can be perturbatively stabilized by radiative corrections due to sparticles. Its minimum is the anti-de Sitter vacuum, where supersymmetry is broken. We can uplift it to the de Sitter vacuum by introducing anti-D-branes, keeping the modulus stabilized. Although our numerical results depend on the choice of the cutoff scale and degeneracies of sparticles, at any rate there exist the parameter spaces where the masses of Kaluza-Klein and stringy modes are larger than the cutoff scale. Furthermore, this stabilization scenario predicts an ultralight axion.

Erlotinib Hydrochloride in Treating Patients With Stage I-III Colorectal Cancer or Adenoma

ClinicalTrials.gov

2014-12-22

Adenomatous Polyp; Recurrent Colon Cancer; Recurrent Rectal Cancer; Stage I Colon Cancer; Stage I Rectal Cancer; Stage IIA Colon Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer

Stable expression of rat cytochrome P-450IIB1 cDNA in Chinese hamster cells (V79) and metabolic activation of aflatoxin B1.

PubMed Central

Doehmer, J; Dogra, S; Friedberg, T; Monier, S; Adesnik, M; Glatt, H; Oesch, F

1988-01-01

V79 Chinese hamster fibroblasts are widely used for mutagenicity testing but have the serious limitation that they do not express cytochromes P-450, which are needed for the activation of many promutagens to mutagenic metabolites. A full-length cDNA clone encoding the monooxygenase cytochrome P-450IIB1 under control of the simian virus 40 early promoter was constructed and cointroduced with the selection marker neomycin phosphotransferase (conferring resistance to G418) into V79 Chinese hamster cells. G418-resistant cells were selected, established as cell lines, and tested for cytochrome P-450IIB1 expression and enzymatic activity. Two cell lines (SD1 and SD3) were found that stably produce cytochrome P-450IIB1. Although purified cytochromes P-450 possess monooxygenase activity only after reconstitution with cytochrome P-450 reductase and phospholipid, the gene product of the construct exhibited this activity. This implies that the gene product is intracellularly localized in a way that allows access to the required components. If compared with V79 cells, the mutation rate for the hypoxanthine phosphoribosyltransferase (HPRT) locus in SD1 cells is markedly increased when exposed to aflatoxin B1, which is activated by this enzyme. Images PMID:3137560

Compact, Lightweight Servo-Controllable Brakes

NASA Technical Reports Server (NTRS)

Lovchik, Christopher S.; Townsend, William; Guertin, Jeffrey; Matsuoka, Yoky

2010-01-01

Compact, lightweight servo-controllable brakes capable of high torques are being developed for incorporation into robot joints. A brake of this type is based partly on the capstan effect of tension elements. In a brake of the type under development, a controllable intermediate state of torque is reached through on/off switching at a high frequency.

Platelet GP IIb-IIIa Receptor Antagonists in Primary Angioplasty: Back to the Future.

PubMed

De Luca, Giuseppe; Savonitto, Stefano; van't Hof, Arnoud W J; Suryapranata, Harry

2015-07-01

Coronary artery disease and acute myocardial infarction still represent the leading cause of mortality in developed countries. Therefore, great efforts have been made in the last decades to improve reperfusion strategies and adjunctive antithrombotic therapies. In fact, despite optimal epicardial recanalisation, a large proportion of patients still experience impaired reperfusion and in-stent thrombosis. The adjunctive use of glycoprotein (GP) IIb-IIIa inhibitors may certainly contribute in the reduction of such complications, especially when administered in the early phase of infarction. In fact, in this phase a larger platelet composition of the thrombus and the presence of a larger amount of viable myocardium, as compared to a delayed phase, may increase the benefits from this therapy and counterbalance the potential higher risk of bleeding. A large body of evidence has been accumulated on the benefits from GP IIb-IIIa inhibitors in terms of prevention of stent thrombosis, and benefits in mortality, especially among high-risk patients and as upstream strategy. Therefore, based on current available data, GP IIb-IIIa inhibitors can be recommended as early as possible (upstream strategy) among high-risk patients, such as those with advanced Killip class or anterior myocardial infarction (MI), and those presenting within the first three hours. Even though it is not universally accepted, in our opinion this strategy should be implemented in a pre-hospital setting (in ambulance) or at first hospital admission (Emergency Room or Coronary Care Unit, irrespective of whether they are in the spoke or hub hospitals). Peri-procedural intracoronary administration of GP IIb-IIIa inhibitors has not provided additional benefits as compared to intravenous administration and therefore cannot be recommended. Even though the vast majority of trials have been conducted with abciximab, several meta-analyses comparing small molecules (mainly high-dose tirofiban rather than eptifibatide) versus abciximab showed similar angiographic and clinical results between the molecules. Several recent investigations and meta-analyses have documented the higher risk of stent thrombosis associated with bivalirudin as compared to unfractionated heparin (UFH). Being that these results are independent from the use of GP IIb-IIIa inhibitors, UFH should still remain the anticoagulation therapy of choice in ST-segment elevation myocardial infarction (STEMI) patients. Minimisation of bleeding complications by extensive use of the radial approach, in the setting of STEMI, may further contribute to the adoption of a more aggressive antithrombotic and antiplatelet therapy incorporating the use of GP IIb-IIIa inhibitors. The establishment of dedicated networks for STEMI, and the large STEMI campaign, will certainly contribute to increase the proportion of patients presenting at first medical contact within the early phase (3 h) of infarction and therefore highly suitable for a more aggressive pharmacoinvasive approach with upstream administration of GP IIb-IIIa inhibitors. In fact, although the current therapeutic targets of increased rates of timely reperfusion, mainly by primary percutaneous coronary intervention (PCI), has been achieved, a deep look into the future in the fight against MI will certainly put aborting infarction as the major desirable target to be achieved.

Disappearance of the Supergiant Progenitor of SN 2011dh in M51

NASA Astrophysics Data System (ADS)

Van Dyk, Schuyler D.; Filippenko, Alexei V.; Fox, Ori; Kelly, Patrick; Smith, Nathan

2013-03-01

We report that in Hubble Space Telescope (HST) Wide Field Camera 3 (WFC3) observations at F555W and F814W with the UVIS channel, conducted on 2013 March 2 UT as part of our Cycle 20 Snapshot program GO-13029 (PI: A. Filippenko), we have discovered that the yellow supergiant star, identified by Van Dyk et al. (2011, ApJ, 741, L28) and Maund et al. (2011, MNRAS, 739, L37) at the position of the Type IIb SN 2011dh in M51, has vanished.

Accidental Kähler moduli inflation

NASA Astrophysics Data System (ADS)

Maharana, Anshuman; Rummel, Markus; Sumitomo, Yoske

2015-09-01

We study a model of accidental inflation in type IIB string theory where inflation occurs near the inflection point of a small Kähler modulus. A racetrack structure helps to alleviate the known concern that string-loop corrections may spoil Kähler Moduli Inflation unless having a significant suppression via the string coupling or a special brane setup. Also, the hierarchy of gauge group ranks required for the separation between moduli stabilization and inflationary dynamics is relaxed. The relaxation becomes more significant when we use the recently proposed D-term generated racetrack model.

Performance of compact fast pyrolysis reactor with Auger-type modules for the continuous liquid biofuel production

NASA Astrophysics Data System (ADS)

Nishimura, Shun; Ebitani, Kohki

2018-01-01

Development of a compact fast pyrolysis reactor constructed using Auger-type technology to afford liquid biofuel with high yield has been an interesting concept in support of local production for local consumption. To establish a widely useable module package, details of the performance of the developing compact module reactor were investigated. This study surveyed the properties of as-produced pyrolysis oil as a function of operation time, and clarified the recent performance of the developing compact fast pyrolysis reactor. Results show that after condensation in the scrubber collector, e.g. approx. 10 h for a 25 kg/h feedstock rate, static performance of pyrolysis oil with approximately 20 MJ/kg (4.8 kcal/g) calorific values were constantly obtained after an additional 14 h. The feeding speed of cedar chips strongly influenced the time for oil condensation process: i.e. 1.6 times higher feeding speed decreased the condensation period by half (approx. 5 h in the case of 40 kg/h). Increasing the reactor throughput capacity is an important goal for the next stage in the development of a compact fast pyrolysis reactor with Auger-type modules.

New Proximal Femoral Compaction Blade Provides Strong Antirotation Stability of the Femoral Head.

PubMed

Hayashi, Shinya; Hirata, Yukiaki; Okamoto, Daiki; Kakunai, Satoshi; Hashimoto, Shingo; Takayama, Koji; Matsumoto, Tomoyuki; Niikura, Takahiro; Fujishiro, Takaaki; Hiranaka, Takafumi; Nishida, Kotaro; Kuroda, Ryosuke

2017-05-01

This study investigated the mechanical properties of a new rectangular compaction blade and compared this blade with other types of nail. Three types of nail were tested: the Magnum lag screw (Robert Reid Inc, Tokyo, Japan), proximal femoral nail, and Magnum Fid blade (Robert Reid Inc). The nails were inserted into solid rigid polyurethane foam, and the torsional moments were loaded with an Instron testing machine (Instron, Kanagawa, Japan). The force curve was recorded, and the average maximum torque was calculated from this curve. A simulation study was performed with finite element models to determine the mechanism underlying differences in rotational stability. Mechanical testing showed that the new compaction blade had stronger resistance against rotational force than the helical blade and lag screw implants. Finite element analysis also showed that the new compaction blade had stronger resistance to migration of the polyurethane foam cylinder than the other implant types. In addition, the new compaction blade had strong rotational stability. This implant should be useful for the treatment of unstable trochanteric fracture in patients with osteoporosis. [Orthopedics. 2017; 40(3):e491-e494.]. Copyright 2017, SLACK Incorporated.

PTF12os and iPTF13bvn: Two stripped-envelope supernovae from low-mass progenitors in NGC 5806

DOE PAGES

Fremling, C.; Sollerman, J.; Taddia, F.; ...

2016-09-22

Context. In this paper, we investigate two stripped-envelope supernovae (SNe) discovered in the nearby galaxy NGC 5806 by the (intermediate) Palomar Transient Factory [(i)PTF]. These SNe, designated PTF12os/SN 2012P and iPTF13bvn, exploded within ~520 days of one another at a similar distance from the host-galaxy center. We classify PTF12os as a Type IIb SN based on our spectral sequence; iPTF13bvn has previously been classified as Type Ib having a likely progenitor with zero age main sequence (ZAMS) mass below ~17 M ⊙. Because of the shared and nearby host, we are presented with a unique opportunity to compare these twomore » SNe. Aims. Our main objective is to constrain the explosion parameters of iPTF12os and iPTF13bvn, and to put constraints on the SN progenitors. We also aim to spatially map the metallicity in the host galaxy, and to investigate the presence of hydrogen in early-time spectra of both SNe. Methods. We present comprehensive datasets collected on PTF12os and iPTF13bvn, and introduce a new automatic reference-subtraction photometry pipeline (FPipe) currently in use by the iPTF. We perform a detailed study of the light curves (LCs) and spectral evolution of the SNe. The bolometric LCs are modeled using the hydrodynamical code hyde. We analyze early spectra of both SNe to investigate the presence of hydrogen; for iPTF13bvn we also investigate the regions of the Paschen lines in infrared spectra. We perform spectral line analysis of helium and iron lines to map the ejecta structure of both SNe. We use nebular models and late-time spectroscopy to constrain the ZAMS mass of the progenitors. We also perform image registration of ground-based images of PTF12os to archival HST images of NGC 5806 to identify a potential progenitor candidate. Results. We find that our nebular spectroscopy of iPTF13bvn remains consistent with a low-mass progenitor, likely having a ZAMS mass of ~12M ⊙. Our late-time spectroscopy of PTF12os is consistent with a ZAMS mass of ~15M ⊙. We successfully identify a source in pre-explosion HST images coincident with PTF12os. The colors and absolute magnitude of this object are consistent between pre-explosion and late-time HST images, implying it is a cluster of massive stars. Our hydrodynamical modeling suggests that the progenitor of PTF12os had a compact He core with a mass of 3.25 + 0.77 -0.56M ⊙ at the time of the explosion, which had a total kinetic energy of 0.54 + 0.41 -0.25 × 10 51 erg and synthesized 0.063 + 0.020 -0.011M ⊙ of strongly mixed 56Ni. Spectral comparisons to the Type IIb SN 2011dh indicate that the progenitor of PTF12os was surrounded by a thin hydrogen envelope with a mass lower than 0.02M ⊙. We also find tentative evidence that the progenitor of iPTF13bvn could have been surrounded by a small amount of hydrogen prior to the explosion. Finally, this result is supported by possible weak signals of hydrogen in both optical and infrared spectra.« less

A family with autosomal dominant mutilating neuropathy not linked to either Charcot-Marie-Tooth disease type 2B (CMT2B) or hereditary sensory neuropathy type I (HSN I) loci.

PubMed

Bellone, Emilia; Rodolico, Carmelo; Toscano, Antonio; Di Maria, Emilio; Cassandrini, Denise; Pizzuti, Antonio; Pigullo, Simona; Mazzeo, Anna; Macaione, Vincenzo; Girlanda, Paolo; Vita, Giuseppe; Ajmar, Franco; Mandich, Paola

2002-03-01

Sensory loss and ulcero-mutilating features have been observed in hereditary sensory neuropathy type I and in hereditary motor and sensory neuropathy type IIB, also referred as Charcot-Marie-Tooth disease type 2B. To date two loci associated with ulcero-mutilating neuropathy have been described: CMT2B at 3q13-q22 and HSN I at 9q22.1-q22.3. We performed linkage analysis with chromosomal markers representing the hereditary sensory neuropathy type I and Charcot-Marie-Tooth disease type 2B loci on an Italian family with a severe distal sensory loss leading to an ulcero-mutilating peripheral neuropathy. Negative likelihood-of-odds scores excluded any evidence of linkage to both chromosome 3q13 and chromosome 9q22 markers, confirming the genetic heterogeneity of this clinical entity and the presence of a third locus responsible for ulcero-mutilating neuropathies.

Programs to Support You During Chemotherapy (Pro-You)

ClinicalTrials.gov

2015-06-19

Depressive Symptoms; Fatigue; Psychosocial Effects of Cancer and Its Treatment; Stage IIA Colon Cancer; Stage IIA Rectal Cancer; Stage IIB Colon Cancer; Stage IIB Rectal Cancer; Stage IIC Colon Cancer; Stage IIC Rectal Cancer; Stage IIIA Colon Cancer; Stage IIIA Rectal Cancer; Stage IIIB Colon Cancer; Stage IIIB Rectal Cancer; Stage IIIC Colon Cancer; Stage IIIC Rectal Cancer; Stage IVA Colon Cancer; Stage IVA Rectal Cancer; Stage IVB Colon Cancer; Stage IVB Rectal Cancer

IIB supergravity and the E 6(6) covariant vector-tensor hierarchy

DOE PAGES

Ciceri, Franz; de Wit, Bernard; Varela, Oscar

2015-04-20

IIB supergravity is reformulated with a manifest local USp(8) invariance that makes the embedding of five-dimensional maximal supergravities transparent. In this formulation the ten-dimensional theory exhibits all the 27 one-form fields and 22 of the 27 two-form fields that are required by the vector-tensor hierarchy of the five-dimensional theory. The missing 5 two-form fields must transform in the same representation as a descendant of the ten-dimensional ‘dual graviton’. The invariant E 6(6) symmetric tensor that appears in the vector-tensor hierarchy is reproduced. Generalized vielbeine are derived from the supersymmetry transformations of the vector fields, as well as consistent expressions formore » the USp(8) covariant fermion fields. Implications are further discussed for the consistency of the truncation of IIB supergravity compactified on the five-sphere to maximal gauged supergravity in five space-time dimensions with an SO(6) gauge group.« less

Rhenium-osmium concentration and isotope systematics in group IIAB iron meteorites

USGS Publications Warehouse

Morgan, J.W.; Horan, M.F.; Walker, R.J.; Grossman, J.N.

1995-01-01

Rhenium and osmium abundances, and osmium isotopic compositions were measured by negative thermal ionization mass spectrometry in thirty samples, including replicates, of five IIA and eight IIB iron meteorites. Log plots of Os vs. Re abundances for IIA and IIB irons describe straight lines that approximately converge on Lombard, which has the lowest Re and Os abundances and highest 187Re/188Os measured in a IIA iron to date. The linear IIA trend may be exactly reproduced by fractional crystallization, but is not well fitted using variable partition coefficients. The IIB iron trend, however, cannot be entirely explained by simple fractional crystallization. One explanation is that small amounts of Re and Os were added to the asteroid core during the final stages of crystallization. Another possibility is that diffusional enrichment of Os may have occurred in samples most depleted in Re and Os. -from Authors

Bivalirudin: a pharmacoeconomic profile of its use in patients with acute coronary syndromes.

PubMed

Lyseng-Williamson, Katherine A

2011-04-01

Bivalirudin (Angiox®; Angiomax®), a direct thrombin inhibitor, is an intravenous anticoagulant. The efficacy of bivalirudin in the management of patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) or ST-segment elevation myocardial infarction (STEMI) planned for invasive interventions has been shown in large, pivotal, open-label trials. Bivalirudin provided similar ischaemic protection to heparin plus a glycoprotein (GP) IIb/IIIa inhibitor, but with a significant reduction in bleeding events, in patients with NSTE-ACS planned for urgent or early intervention and those with STEMI planned for primary percutaneous coronary intervention (PCI). Mortality rates were also significantly lower in patients with STEMI receiving bivalirudin than in those receiving heparin plus a GP IIb/IIIa inhibitor in the key trial of patients with STEMI. Based on this clinical data, modelled cost-utility analyses from the perspective of various UK NHS providers have predicted that bivalirudin would be highly likely to be cost effective with regard to the cost per QALY gained relative to a heparin plus GP IIb/IIIa inhibitor-based strategy over a lifetime horizon in these patient populations. In patients with NSTE-ACS planned for urgent or early invasive intervention, a bivalirudin-based strategy was considered to be cost effective in the UK, Scotland and Wales. In patients with STEMI planned for primary PCI, a bivalirudin-based strategy was dominant in the UK and Scotland. Parallel and sensitivity analyses demonstrated that base-case conclusions were robust over a range of plausible changes in parameter estimates and assumptions, including changes made to more closely reflect current local clinical practice. In addition, budgetary impact analyses in several countries suggested that the implementation of a bivalirudin-based strategy, instead of a heparin plus GP IIb/IIIa inhibitor-based strategy, would be cost saving from a hospital perspective in patients with NSTE-ACS undergoing urgent or early PCI, as well as in patients with STEMI undergoing primary PCI. Likewise, prospective and retrospective treatment cost studies in the US indicated that treatment with bivalirudin was less costly than treatment with heparin plus a GP IIb/IIIa inhibitor in these indications. In conclusion, available pharmacoeconomic data from several countries, despite some inherent limitations, support the use of strategies based on bivalirudin over those based on heparin plus a GP IIb/IIIa inhibitor in patients with NSTE-ACS planned for urgent or early invasive intervention or STEMI planned for primary PCI. These pharmacoeconomic advantages primarily reflect that, relative to heparin plus a GP IIb/IIIa inhibitor, bivalirudin is associated with lower rates of bleeding over the short term, and is associated with lower rates of early mortality that are subsequently maintained over the longer term in patients with STEMI.

SGC Tests for Influence of Material Composition on Compaction Characteristic of Asphalt Mixtures

PubMed Central

Chen, Qun

2013-01-01

Compaction characteristic of the surface layer asphalt mixture (13-type gradation mixture) was studied using Superpave gyratory compactor (SGC) simulative compaction tests. Based on analysis of densification curve of gyratory compaction, influence rules of the contents of mineral aggregates of all sizes and asphalt on compaction characteristic of asphalt mixtures were obtained. SGC Tests show that, for the mixture with a bigger content of asphalt, its density increases faster, that there is an optimal amount of fine aggregates for optimal compaction and that an appropriate amount of mineral powder will improve workability of mixtures, but overmuch mineral powder will make mixtures dry and hard. Conclusions based on SGC tests can provide basis for how to adjust material composition for improving compaction performance of asphalt mixtures, and for the designed asphalt mixture, its compaction performance can be predicted through these conclusions, which also contributes to the choice of compaction schemes. PMID:23818830

SGC tests for influence of material composition on compaction characteristic of asphalt mixtures.

PubMed

Chen, Qun; Li, Yuzhi

2013-01-01

Compaction characteristic of the surface layer asphalt mixture (13-type gradation mixture) was studied using Superpave gyratory compactor (SGC) simulative compaction tests. Based on analysis of densification curve of gyratory compaction, influence rules of the contents of mineral aggregates of all sizes and asphalt on compaction characteristic of asphalt mixtures were obtained. SGC Tests show that, for the mixture with a bigger content of asphalt, its density increases faster, that there is an optimal amount of fine aggregates for optimal compaction and that an appropriate amount of mineral powder will improve workability of mixtures, but overmuch mineral powder will make mixtures dry and hard. Conclusions based on SGC tests can provide basis for how to adjust material composition for improving compaction performance of asphalt mixtures, and for the designed asphalt mixture, its compaction performance can be predicted through these conclusions, which also contributes to the choice of compaction schemes.

Influence of nano-material on the expansive and shrinkage soil behavior

NASA Astrophysics Data System (ADS)

Taha, Mohd Raihan; Taha, Omer Muhie Eldeen

2012-10-01

This paper presents an experimental study performed on four types of soils mixed with three types of nano-material of different percentages. The expansion and shrinkage tests were conducted to investigate the effect of three type of nano-materials (nano-clay, nano-alumina, and nano-copper) additive on repressing strains in compacted residual soil mixed with different ratios of bentonite (S1 = 0 % bentonite, S2 = 5 % bentonite, S3 = 10 % bentonite, and S4 = 20 % bentonite). The soil specimens were compacted under the condition of maximum dry unit weight and optimum water content ( w opt) using standard compaction test. The physical and mechanical results of the treated samples were determined. The untreated soil values were used as control points for comparison purposes. It was found that with the addition of optimum percentage of nano-material, both the swell strain and shrinkage strain reduced. The results show that nano-material decreases the development of desiccation cracks on the surface of compacted samples without decrease in the hydraulic conductivity.

Compact piezoelectric tripod manipulator based on a reverse bridge-type amplification mechanism

NASA Astrophysics Data System (ADS)

Na, Tae-Won; Choi, Jun-Ho; Jung, Jin-Young; Kim, Hyeong-Geon; Han, Jae-Hung; Park, Kwang-Chun; Oh, Il-Kwon

2016-09-01

We report a hierarchical piezoelectric tripod manipulator based on a reverse bridge-type displacement amplifier. The reverse bridge-type amplification mechanism is pre-strained by each piezo-stack actuator up to 60 μm and is cross-stacked in a series arrangement to make a compact and high-stroke manipulator having load-bearing characteristics. The designed manipulator with three degrees of freedom is compact with a height of 56.0 mm, a diameter of 48.6 mm and total weight of 115 g. It achieves a translational stroke of up to 880 μm in heaving motion and a tilting angle of up to 2.0° in rotational motion within the operating voltage and power range of the piezoelectric stack actuator. A key feature of the present design is built-in and pre-strained displacement amplification mechanisms integrated with piezoelectric stacked actuators, resulting in a compact tripod manipulator having exceptionally high stroke and load-bearing capacity.

Compact Neutral Hydrogen Clouds: Searching for Undiscovered Dwarf Galaxies and Gas Associated with an Algol-type Variable Star

NASA Astrophysics Data System (ADS)

Grcevich, Jana; Berger, Sabrina; Putman, Mary E.; Eli Goldston Peek, Joshua

2016-01-01

Several interesting compact neutral hydrogen clouds were found in the GALFA-HI (Galactic Arecibo L-Band Feed Array HI) survey which may represent undiscovered dwarf galaxy candidates. The continuation of this search is motivated by successful discoveries of Local Volume dwarfs in the GALFA-HI DR1. We identify additional potential dwarf galaxies from the GALFA-HI DR1 Compact Cloud Catalog which are indentified as having unexpected velocities given their other characteristics via the bayesian analysis software BayesDB. We also present preliminary results of a by-eye search for dwarf galaxies in the GALFA-HI DR2, which provides additional sky coverage. Interestingly, one particularly compact cloud discovered during our dwarf galaxy search is spatially coincident with an Algol-type variable star. Although the association is tentative, Algol-type variables are thought to have undergone significant gas loss and it is possible this gas may be observable in HI.

Ling classification describes endoscopic progressive process of achalasia and successful peroral endoscopy myotomy prevents endoscopic progression of achalasia.

PubMed

Zhang, Wen-Gang; Linghu, En-Qiang; Chai, Ning-Li; Li, Hui-Kai

2017-05-14

To verify the hypothesis that the Ling classification describes the endoscopic progressive process of achalasia and determine the ability of successful peroral endoscopic myotomy (POEM) to prevent endoscopic progression of achalasia. We retrospectively reviewed the endoscopic findings, symptom duration, and manometric data in patients with achalasia. A total of 359 patients (197 women, 162 men) with a mean age of 42.1 years (range, 12-75 years) were evaluated. Symptom duration ranged from 2 to 360 mo, with a median of 36 mo. Patients were classified with Ling type I ( n = 119), IIa ( n = 106), IIb ( n = 60), IIc ( n = 60), or III ( n = 14), according to the Ling classification. Of the 359 patients, 349 underwent POEM, among whom 21 had an endoscopic follow-up for more than 2 years. Pre-treatment and post-treatment Ling classifications of these 21 patients were compared. Symptom duration increased significantly with increasing Ling classification (from I to III) ( P < 0.05), whereas lower esophageal sphincter pressure decreased with increasing Ling type (from I to III) ( P < 0.05). There was no difference in sex ratio or onset age among the Ling types, although the age at time of diagnosis was higher in Ling types IIc and III than in Ling types I, IIa, and IIb. Of the 21 patients, 19 underwent high-resolution manometry both before and after treatment. The mean preoperative and postoperative lower esophageal sphincter pressure were 34.6 mmHg (range, 15.3-59.4 mmHg) and 15.0 mmHg (range, 2.1-21.6 mmHg), respectively, indicating a statistically significant decrease after POEM. All of the 21 patients were treated successfully by POEM (postoperative Eckardt score ≤ 3) and still had the same Ling type during a mean follow-up period of 37.8 mo (range, 24-51 mo). The Ling classification represents the endoscopic progressive process of achalasia and may be able to serve as an endoscopic assessment criterion for achalasia. Successful POEM (Eckardt score ≤ 3) seems to have the ability to prevent endoscopic evolvement of achalasia. However, studies with larger populations are warranted to confirm our findings.

Spherical torus fusion reactor

DOEpatents

Martin Peng, Y.K.M.

1985-10-03

The object of this invention is to provide a compact torus fusion reactor with dramatic simplification of plasma confinement design. Another object of this invention is to provide a compact torus fusion reactor with low magnetic field and small aspect ratio stable plasma confinement. In accordance with the principles of this invention there is provided a compact toroidal-type plasma confinement fusion reactor in which only the indispensable components inboard of a tokamak type of plasma confinement region, mainly a current conducting medium which carries electrical current for producing a toroidal magnet confinement field about the toroidal plasma region, are retained.

A compact finite element method for elastic bodies

NASA Technical Reports Server (NTRS)

Rose, M. E.

1984-01-01

A nonconforming finite method is described for treating linear equilibrium problems, and a convergence proof showing second order accuracy is given. The close relationship to a related compact finite difference scheme due to Phillips and Rose is examined. A condensation technique is shown to preserve the compactness property and suggests an approach to a certain type of homogenization.

Ultra-compact Marx-type high-voltage generator

DOEpatents

Goerz, David A.; Wilson, Michael J.

2000-01-01

An ultra-compact Marx-type high-voltage generator includes individual high-performance components that are closely coupled and integrated into an extremely compact assembly. In one embodiment, a repetitively-switched, ultra-compact Marx generator includes low-profile, annular-shaped, high-voltage, ceramic capacitors with contoured edges and coplanar extended electrodes used for primary energy storage; low-profile, low-inductance, high-voltage, pressurized gas switches with compact gas envelopes suitably designed to be integrated with the annular capacitors; feed-forward, high-voltage, ceramic capacitors attached across successive switch-capacitor-switch stages to couple the necessary energy forward to sufficiently overvoltage the spark gap of the next in-line switch; optimally shaped electrodes and insulator surfaces to reduce electric field stresses in the weakest regions where dissimilar materials meet, and to spread the fields more evenly throughout the dielectric materials, allowing them to operate closer to their intrinsic breakdown levels; and uses manufacturing and assembly methods to integrate the capacitors and switches into stages that can be arranged into a low-profile Marx generator.

Explicit and implicit compact high-resolution shock-capturing methods for multidimensional Euler equations 1: Formulation

NASA Technical Reports Server (NTRS)

Yee, H. C.

1995-01-01

Two classes of explicit compact high-resolution shock-capturing methods for the multidimensional compressible Euler equations for fluid dynamics are constructed. Some of these schemes can be fourth-order accurate away from discontinuities. For the semi-discrete case their shock-capturing properties are of the total variation diminishing (TVD), total variation bounded (TVB), total variation diminishing in the mean (TVDM), essentially nonoscillatory (ENO), or positive type of scheme for 1-D scalar hyperbolic conservation laws and are positive schemes in more than one dimension. These fourth-order schemes require the same grid stencil as their second-order non-compact cousins. One class does not require the standard matrix inversion or a special numerical boundary condition treatment associated with typical compact schemes. Due to the construction, these schemes can be viewed as approximations to genuinely multidimensional schemes in the sense that they might produce less distortion in spherical type shocks and are more accurate in vortex type flows than schemes based purely on one-dimensional extensions. However, one class has a more desirable high-resolution shock-capturing property and a smaller operation count in 3-D than the other class. The extension of these schemes to coupled nonlinear systems can be accomplished using the Roe approximate Riemann solver, the generalized Steger and Warming flux-vector splitting or the van Leer type flux-vector splitting. Modification to existing high-resolution second- or third-order non-compact shock-capturing computer codes is minimal. High-resolution shock-capturing properties can also be achieved via a variant of the second-order Lax-Friedrichs numerical flux without the use of Riemann solvers for coupled nonlinear systems with comparable operations count to their classical shock-capturing counterparts. The simplest extension to viscous flows can be achieved by using the standard fourth-order compact or non-compact formula for the viscous terms.

30 CFR 57.22232 - Actions at 0.5 percent methane (I-B, II-A, II-B, IV, V-B, and VI mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions at 0.5 percent methane (I-B, II-A, II-B...-UNDERGROUND METAL AND NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22232 Actions at 0.5 percent methane (I-B, II-A, II-B, IV, V-B, and VI mines). If methane reaches 0.5...

Two CRM protein subfamilies cooperate in the splicing of group IIB introns in chloroplasts.

PubMed

Asakura, Yukari; Bayraktar, Omer Ali; Barkan, Alice

2008-11-01

Chloroplast genomes in angiosperms encode approximately 20 group II introns, approximately half of which are classified as subgroup IIB. The splicing of all but one of the subgroup IIB introns requires a heterodimer containing the peptidyl-tRNA hydrolase homolog CRS2 and one of two closely related proteins, CAF1 or CAF2, that harbor a recently recognized RNA binding domain called the CRM domain. Two CRS2/CAF-dependent introns require, in addition, a CRM domain protein called CFM2 that is only distantly related to CAF1 and CAF2. Here, we show that CFM3, a close relative of CFM2, associates in vivo with those CRS2/CAF-dependent introns that are not CFM2 ligands. Mutant phenotypes in rice and Arabidopsis support a role for CFM3 in the splicing of most of the introns with which it associates. These results show that either CAF1 or CAF2 and either CFM2 or CFM3 simultaneously bind most chloroplast subgroup IIB introns in vivo, and that the CAF and CFM subunits play nonredundant roles in splicing. These results suggest that the expansion of the CRM protein family in plants resulted in two subfamilies that play different roles in group II intron splicing, with further diversification within a subfamily to accommodate multiple intron ligands.

Non-muscle myosin IIB (Myh10) is required for epicardial function and coronary vessel formation during mammalian development

PubMed Central

Mitchell, Karen; Al-Anbaki, Ali; Shaikh Qureshi, Wasay Mohiuddin; Tenin, Gennadiy; Lu, Yinhui; Clowes, Christopher; Robertson, Abigail; Barnes, Emma; Wright, Jayne A.; Keavney, Bernard; Lovell, Simon C.

2017-01-01

The coronary vasculature is an essential vessel network providing the blood supply to the heart. Disruptions in coronary blood flow contribute to cardiac disease, a major cause of premature death worldwide. The generation of treatments for cardiovascular disease will be aided by a deeper understanding of the developmental processes that underpin coronary vessel formation. From an ENU mutagenesis screen, we have isolated a mouse mutant displaying embryonic hydrocephalus and cardiac defects (EHC). Positional cloning and candidate gene analysis revealed that the EHC phenotype results from a point mutation in a splice donor site of the Myh10 gene, which encodes NMHC IIB. Complementation testing confirmed that the Myh10 mutation causes the EHC phenotype. Characterisation of the EHC cardiac defects revealed abnormalities in myocardial development, consistent with observations from previously generated NMHC IIB null mouse lines. Analysis of the EHC mutant hearts also identified defects in the formation of the coronary vasculature. We attribute the coronary vessel abnormalities to defective epicardial cell function, as the EHC epicardium displays an abnormal cell morphology, reduced capacity to undergo epithelial-mesenchymal transition (EMT), and impaired migration of epicardial-derived cells (EPDCs) into the myocardium. Our studies on the EHC mutant demonstrate a requirement for NMHC IIB in epicardial function and coronary vessel formation, highlighting the importance of this protein in cardiac development and ultimately, embryonic survival. PMID:29084269

Species-Specific Involvement of Integrin αIIbβ3 in a Monoclonal Antibody CH12 Triggers Off-Target Thrombocytopenia in Cynomolgus Monkeys.

PubMed

Zhang, Yiting; Sun, Jianhua; Tan, Minjia; Liu, Yongzhen; Li, Qian; Jiang, Hua; Wang, Huamao; Li, Zonghai; Wan, Wei; Jiang, Hualiang; Lu, Henglei; Wang, Bingshun; Ren, Jin; Gong, Likun

2018-04-07

CH12 is a novel humanized monoclonal antibody against epidermal growth factor receptor variant III (EGFRvIII) for cancer treatment. Unfortunately, in pre-clinical safety evaluation studies, acute thrombocytopenia was observed after administration of CH12 in cynomolgus monkeys, but not rats. More importantly, in vitro experiments found that CH12 can bind and activate platelets in cynomolgus monkey, but not human peripheral blood samples. Cynomolgus monkey-specific thrombocytopenia has been reported previously; however, the underlying mechanism remains unclear. Here, we first showed that CH12 induced thrombocytopenia in cynomolgus monkeys through off-target platelet binding and activation, resulting in platelet destruction. We subsequently found that integrin αIIbβ3 (which is expressed on platelets) contributed to this off-target toxicity. Furthermore, three-dimensional structural modeling of the αIIbβ3 molecules in cynomolgus monkeys, humans, and rats suggested that an additional unique loop exists in the ligand-binding pocket of the αIIb subunit in cynomolgus monkeys, which may explain why CH12 binds to platelets only in cynomolgus monkeys. Moreover, this study supported the hypothesis that the minor differences between cynomolgus monkeys and humans can confuse human risk assessments and suggests that species differences can help the prediction of human risks and avoid losses in drug development. Copyright © 2018. Published by Elsevier Inc.

Hyperreactivity of junctional adhesion molecule A-deficient platelets accelerates atherosclerosis in hyperlipidemic mice.

PubMed

Karshovska, Ela; Zhao, Zhen; Blanchet, Xavier; Schmitt, Martin M N; Bidzhekov, Kiril; Soehnlein, Oliver; von Hundelshausen, Philipp; Mattheij, Nadine J; Cosemans, Judith M E M; Megens, Remco T A; Koeppel, Thomas A; Schober, Andreas; Hackeng, Tilman M; Weber, Christian; Koenen, Rory R

2015-02-13

Besides their essential role in hemostasis, platelets also have functions in inflammation. In platelets, junctional adhesion molecule (JAM)-A was previously identified as an inhibitor of integrin αIIbβ3-mediated outside-in signaling and its genetic knockdown resulted in hyperreactivity. This gain-of-function was specifically exploited to investigate the role of platelet hyperreactivity in plaque development. JAM-A-deficient platelets showed increased aggregation and cellular and sarcoma tyrosine-protein kinase activation. On αIIbβ3 ligation, JAM-A was shown to be dephosphorylated, which could be prevented by protein tyrosine phosphatase nonreceptor type 1 inhibition. Mice with or without platelet-specific (tr)JAM-A-deficiency in an apolipoprotein e (apoe(-/-)) background were fed a high-fat diet. After ≤12 weeks of diet, trJAM-A(-/-)apoe-/- mice showed increased aortic plaque formation when compared with trJAM-A(+/+) apoe(-/-) controls, and these differences were most evident at early time points. At 2 weeks, the plaques of the trJAM-A(-/-) apoe(-/-) animals revealed increased macrophage, T cell, and smooth muscle cell content. Interestingly, plasma levels of chemokines CC chemokine ligand 5 and CXC-chemokine ligand 4 were increased in the trJAM-A(-/-) apoe(-/-)mice, and JAM-A-deficient platelets showed increased binding to monocytes and neutrophils. Whole-blood perfusion experiments and intravital microscopy revealed increased recruitment of platelets and monocytes to the inflamed endothelium in blood of trJAM-A(-/-) apoe(-/-)mice. Notably, these proinflammatory effects of JAM-A-deficient platelets could be abolished by the inhibition of αIIbβ3 signaling in vitro. Deletion of JAM-A causes a gain-of-function in platelets, with lower activation thresholds and increased inflammatory activities. This leads to an increase of plaque formation, particularly in early stages of the disease. © 2014 American Heart Association, Inc.

Acoustic emission studies for characterization of fatigue crack growth behavior in HSLA steel

NASA Astrophysics Data System (ADS)

Kumar, Jalaj; Ahmad, S.; Mukhopadhyay, C. K.; Jayakumar, T.; Kumar, Vikas

2016-01-01

High strength low alloy (HSLA) steels are a group of low carbon steels and used in oil and gas pipelines, automotive components, offshore structures and shipbuilding. Fatigue crack growth (FCG) characteristics of a HSLA steel have been studied at two different stress ratios (R = 0.3 and 0.5). Acoustic emission (AE) signals generated during the FCG tests have been used to understand the FCG processes. The AE signals were captured by mounting two piezoelectric sensors on compact tension specimens in liner location configuration. The AE generated in stage II of the linear Paris region of FCG has been attributed to the presence of two sub-stages with two different slopes. The AE generated at higher values of stress intensity factor is found to be useful to identify the transition from stage II to stage III of the FCG. AE location analysis has provided support for increased damage at the crack tip for higher stress ratio. The peak stress intensity (Kmax) values at the crack tip have shown good correlation with the transitions from stage IIa to stage IIb and stage II to stage III of the FCG for the two stress ratios.

Asphaltic mixture compaction and density validation : research brief.

DOT National Transportation Integrated Search

2017-02-01

Research Objectives: : Evaluate HMA longitudinal joint type, method and compaction data to produce specification recommendations to ensure the highest density at longitudinal joints : Evaluate thin lift overlay HMA and provide recommendations...

Type IIB thyroplasty for phonic tics in a pediatric patient with autism spectrum disorder: a case report.

PubMed

Ahmed, Mostafa M; Heckman, W Wesley; Dailey, Seth H

2013-03-01

Autism spectrum disorders (ASDs) are commonly associated with Tourette syndrome (TS). TS is classically associated with tic production. A tic is defined as sudden, brief, involuntary production of movement (motor tics) or sound (phonic tics). Case report. We present a case report of a 14-year-old boy with ASD and vocal tics. Vocal tic frequency was nearly 2000 per day and 90 dB in volume. He presented to our laryngology clinic after multiple failed attempts of pharmacologic management of vocal fold botulinum toxin injection. After evaluation in our clinic, we recommended a lateralization (type IIB) thyroplasty. An autologous cartilage graft from the superior thyroid ala was used and held in place with a bioresorbable mesh. Using 4-0 prolene sutures, the mesh was secured in place. The operation was well tolerated with minimal signs of aspiration, and he was discharged to his home within 48 hours. Six months postoperatively, there was 90% reduction in tic frequency and 50% reduction in intensity. Additionally, he has shown improved ability to converse with his peers, participate in school activities, and even has improved nutritional status. Alteration of laryngeal geometry could serve as an effective site of intervention for intractable phonic tics. Reduction of phonic tic frequency and intensity may also stimulate language development in patients ASD. We also demonstrate additional use of bioresorbable plates in pediatric laryngeal framework surgery. Additional neurophysiologic studies are needed to explore the mechanism by which midline lateralization thyroplasty influences phonic tic generation. Copyright © 2013 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

Extremal Correlators in the Ads/cft Correspondence

NASA Astrophysics Data System (ADS)

D'Hoker, Eric; Freedman, Daniel Z.; Mathur, Samir D.; Matusis, Alec; Rastelli, Leonardo

The non-renormalization of the 3-point functions

P-selectin ligation induces platelet activation and enhances microaggregate and thrombus formation.

PubMed

Théorêt, Jean-François; Yacoub, Daniel; Hachem, Ahmed; Gillis, Marc-Antoine; Merhi, Yahye

2011-09-01

Platelet P-selectin is a thrombo-inflammatory molecule involved in platelet activation and aggregation. This may occur via the adhesive function of P-selectin and its potential capacity to trigger intracellular signaling. However, its impact on platelet function remains elusive. This study was therefore designed to investigate the relationship between the signaling potential of platelet P-selectin and its function in platelet physiology. Human and mouse platelets were freshly isolated from whole blood. Platelet activation was assessed using flow cytometry and western blot analysis, while platelet physiological responses were evaluated through aggregation, microaggregate formation and in a thrombosis model in wild-type and P-selectin-deficient (CD62P(-/-)) mice. Interaction of P-selectin with its high-affinity ligand, a recombinant soluble form of P-Selectin Glycoprotein Ligand-1 (rPSGL-1), enhances platelet activation, adhesion and microaggregate formation. This augmented platelet microaggregates requires an intact cytoskeleton, but occurs independently of platelet α(IIb)β(3). Thrombus formation and microaggregate were both enhanced by rPSGL-1 in wild-type, but not in CD62P(-/-) mice. In addition, CD62P(-/-) mice exhibited thrombosis abnormalities without an α(IIb)β(3) activation defect. This study demonstrates that the role of platelet P-selectin is not solely adhesive; its binding to PSGL-1 induces platelet activation that enhances platelet aggregation and thrombus formation. Therefore, targeting platelet P-selectin or its ligand PSGL-1 could provide a potential therapeutic approach in the management of thrombotic disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

Reflection states in Ding-Iohara-Miki algebra and brane-web for D-type quiver

NASA Astrophysics Data System (ADS)

Bourgine, J.-E.; Fukuda, M.; Matsuo, Y.; Zhu, R.-D.

2017-12-01

Reflection states are introduced in the vertical and horizontal modules of the Ding-Iohara-Miki (DIM) algebra (quantum toroidal gl_1 ). Webs of DIM representations are in correspondence with ( p, q)-web diagrams of type IIB string theory, under the identification of the algebraic intertwiner of Awata, Feigin and Shiraishi with the refined topological vertex. Extending the correspondence to the vertical reflection states, it is possible to engineer the N=1 quiver gauge theory of D-type (with unitary gauge groups). In this way, the Nekrasov instanton partition function is reproduced from the evaluation of expectation values of intertwiners. This computation leads to the identification of the vertical reflection state with the orientifold plane of string theory. We also provide a translation of this construction in the Iqbal-Kozcaz-Vafa refined topological vertex formalism.

T-duality of singular spacetime compactifications in an H-flux

NASA Astrophysics Data System (ADS)

Linshaw, Andrew; Mathai, Varghese

2018-07-01

We begin by presenting a symmetric version of the circle equivariant T-duality result in a joint work of the second author with Siye Wu, thereby generalizing the results there. We then initiate the study of twisted equivariant Courant algebroids and equivariant generalized geometry and apply it to our context. As before, T-duality exchanges type IIA and type IIB string theories. In our theory, both spacetime and the T-dual spacetime can be singular spaces when the fixed point set is non-empty; the singularities correspond to Kaluza-Klein monopoles. We propose that the Ramond-Ramond charges of type II string theories on the singular spaces are classified by twisted equivariant cohomology groups, consistent with the previous work of Mathai and Wu, and prove that they are naturally isomorphic. We also establish the corresponding isomorphism of twisted equivariant Courant algebroids.

In vivo emergence of vicriviroc resistance in a human immunodeficiency virus type 1 subtype C-infected subject.

PubMed

Tsibris, Athe M N; Sagar, Manish; Gulick, Roy M; Su, Zhaohui; Hughes, Michael; Greaves, Wayne; Subramanian, Mani; Flexner, Charles; Giguel, Françoise; Leopold, Kay E; Coakley, Eoin; Kuritzkes, Daniel R

2008-08-01

Little is known about the in vivo development of resistance to human immunodeficiency virus type 1 (HIV-1) CCR5 antagonists. We studied 29 subjects with virologic failure from a phase IIb study of the CCR5 antagonist vicriviroc (VCV) and identified one individual with HIV-1 subtype C who developed VCV resistance. Studies with chimeric envelopes demonstrated that changes within the V3 loop were sufficient to confer VCV resistance. Resistant virus showed VCV-enhanced replication, cross-resistance to another CCR5 antagonist, TAK779, and increased sensitivity to aminooxypentane-RANTES and the CCR5 monoclonal antibody HGS004. Pretreatment V3 loop sequences reemerged following VCV discontinuation, implying that VCV resistance has associated fitness costs.

Sun shield

NASA Technical Reports Server (NTRS)

Frank, Arthur M. (Inventor); Derespinis, Silvio F. (Inventor); Mockovciak, John, Jr. (Inventor)

1987-01-01

A shading device which is capable of compactly storing a flexible shade on a biased, window shade type spring roller is disclosed. It is controlled to deliver the shade selectively to either its operative shading or compact storage orientation.

Specificity of RSG-1.2 Peptide Binding to RRE-IIB RNA Element of HIV-1 over Rev Peptide Is Mainly Enthalpic in Origin

PubMed Central

Kumar, Santosh; Bose, Debojit; Suryawanshi, Hemant; Sabharwal, Harshana; Mapa, Koyeli; Maiti, Souvik

2011-01-01

Rev is an essential HIV-1 regulatory protein which binds to the Rev responsive element (RRE) present within the env gene of HIV-1 RNA genome. This binding facilitates the transport of the RNA to the cytoplasm, which in turn triggers the switch between viral latency and active viral replication. Essential components of this complex have been localized to a minimal arginine rich Rev peptide and stem IIB region of RRE. A synthetic peptide known as RSG-1.2 binds with high binding affinity and specificity to the RRE-IIB than the Rev peptide, however the thermodynamic basis of this specificity has not yet been addressed. The present study aims to probe the thermodynamic origin of this specificity of RSG-1.2 over Rev Peptide for RRE-IIB. The temperature dependent melting studies show that RSG-1.2 binding stabilizes the RRE structure significantly (ΔT m = 4.3°C), in contrast to Rev binding. Interestingly the thermodynamic signatures of the binding have also been found to be different for both the peptides. At pH 7.5, RSG-1.2 binds RRE-IIB with a Ka = 16.2±0.6×107 M−1 where enthalpic change ΔH = −13.9±0.1 kcal/mol is the main driving force with limited unfavorable contribution from entropic change TΔS = −2.8±0.1 kcal/mol. A large part of ΔH may be due to specific stacking between U72 and Arg15. In contrast binding of Rev (Ka = 3.1±0.4×107 M−1) is driven mainly by entropy (ΔH = 0 kcal/mol and TΔS = 10.2±0.2 kcal/mol) which arises from major conformational changes in the RNA upon binding. PMID:21853108

Specificity of RSG-1.2 peptide binding to RRE-IIB RNA element of HIV-1 over Rev peptide is mainly enthalpic in origin.

PubMed

Kumar, Santosh; Bose, Debojit; Suryawanshi, Hemant; Sabharwal, Harshana; Mapa, Koyeli; Maiti, Souvik

2011-01-01

Rev is an essential HIV-1 regulatory protein which binds to the Rev responsive element (RRE) present within the env gene of HIV-1 RNA genome. This binding facilitates the transport of the RNA to the cytoplasm, which in turn triggers the switch between viral latency and active viral replication. Essential components of this complex have been localized to a minimal arginine rich Rev peptide and stem IIB region of RRE. A synthetic peptide known as RSG-1.2 binds with high binding affinity and specificity to the RRE-IIB than the Rev peptide, however the thermodynamic basis of this specificity has not yet been addressed. The present study aims to probe the thermodynamic origin of this specificity of RSG-1.2 over Rev Peptide for RRE-IIB. The temperature dependent melting studies show that RSG-1.2 binding stabilizes the RRE structure significantly (ΔT(m) = 4.3°C), in contrast to Rev binding. Interestingly the thermodynamic signatures of the binding have also been found to be different for both the peptides. At pH 7.5, RSG-1.2 binds RRE-IIB with a K(a) = 16.2±0.6×10(7) M(-1) where enthalpic change ΔH = -13.9±0.1 kcal/mol is the main driving force with limited unfavorable contribution from entropic change TΔS = -2.8±0.1 kcal/mol. A large part of ΔH may be due to specific stacking between U72 and Arg15. In contrast binding of Rev (K(a) = 3.1±0.4×10(7) M(-1)) is driven mainly by entropy (ΔH = 0 kcal/mol and TΔS = 10.2±0.2 kcal/mol) which arises from major conformational changes in the RNA upon binding.

Genomic Porosity between Invasive Chondrostoma nasus and Endangered Endemic Parachondrostoma toxostoma (Cyprinidae): The Evolution of MHC IIB Genes

PubMed Central

Šimková, Andrea; Civáňová, Kristína; Gettová, Lenka; Gilles, André

2013-01-01

Two cyprinid species, Parachondrostoma toxostoma, an endemic threatened species, and Chondrostoma nasus, an invasive species, live in sympatry in southern France and form two sympatric zones where the presence of intergeneric hybrids is reported. To estimate the potential threat to endemic species linked to the introduction of invasive species, we focused on the DAB genes (functional MHC IIB genes) because of their adaptive significance and role in parasite resistance. More specifically, we investigated (1) the variability of MHC IIB genes, (2) the selection pattern shaping MHC polymorphism, and (3) the extent to which trans-species evolution and intergeneric hybridization affect MHC polymorphism. In sympatric areas, the native species has more diversified MHC IIB genes when compared to the invasive species, probably resulting from the different origins and dispersal of both species. A similar level of MHC polymorphism was found at population level in both species, suggesting similar mechanisms generating MHC diversity. In contrast, a higher number of DAB-like alleles per specimen were found in invasive species. Invasive species tended to express the alleles of two DAB lineages, whilst native species tended to express the alleles of only the DAB3 lineage. Hybrids have a pattern of MHC expression intermediate between both species. Whilst positive selection acting on peptide binding sites (PBS) was demonstrated in both species, a slightly higher number of positively selected sites were identified in C. nasus, which could result from parasite-mediated selection. Bayesian clustering analysis revealed a similar pattern of structuring for the genetic variation when using microsatellites or the MHC approach. We confirmed the importance of trans-species evolution for MHC polymorphism. In addition, we demonstrated bidirectional gene flow for MHC IIB genes in sympatric areas. The positive significant correlation between MHC and microsatellites suggests that demographic factors may contribute to MHC variation on a short time scale. PMID:23824831

Intracellular bacteria in the pathogenesis of Escherichia coli urinary tract infection in children.

PubMed

Robino, Luciana; Scavone, Paola; Araujo, Lucia; Algorta, Gabriela; Zunino, Pablo; Pírez, María Catalina; Vignoli, Rafael

2014-12-01

Uropathogenic Escherichia coli (UPEC) is the most common agent of urinary tract infection (UTI). The classic model of pathogenesis proposes the ascent of UPEC by the urethra and external adherence to the urothelium. Recently, the ability of UPEC to invade urothelial cells and to form intracellular bacterial communities (IBCs) has been described. The objective of the present study was to determine the presence of intracellular bacteria (IB) in children with UTI caused by E. coli and to characterize its virulence attributes and its relation with clinical outcomes. One hundred thirty-three children with E. coli UTI who attended a reference children's hospital between June and November 2012 were included. Urine samples were analyzed by optical and confocal microscopy looking for exfoliated urothelial cells with IB. Phylogenetic group and 24 virulence factors of UPEC were determined using multiplex polymerase chain reaction. Medical records were analyzed. The presence of IB was detected in 49 of 133 (36.8%) samples by confocal microscopy, in 30 cases as IBC, and in 19 as isolated intracellular bacteria (IIB). Only 50% of these cases could be detected by light microscopy. Seventy-four medical records were analyzed, 34 with IBC/IIB, 40 without IB. Any virulence gene was associated with IBC/IIB. The presence of IBC/IIB was associated with recurrent UTI (odds ratio [OR], 3.3; 95% confidence interval [CI], 1.3-9; P = .017), especially in children without urinary tract functional or morphological abnormalities (OR, 8.0; 95% CI, 2.3-27.4; P = .000). IBCs were associated with lower urinary tract syndrome (OR, 3.6; 95% CI, 1.1-11.8; P = .05) and absence of fever (P = .009). IBCs/IIB could explain a high proportion of children with recurrent UTI. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Molecular Mechanisms Regulating Muscle Fiber Composition Under Microgravity

NASA Technical Reports Server (NTRS)

Rosenthal, Nadia A.

1999-01-01

The overall goal of this project is to reveal the molecular mechanisms underlying the selective and debilitating atrophy of specific skeletal muscle fiber types that accompanies sustained conditions of microgravity. Since little is currently known about the regulation of fiber-specific gene expression programs in mammalian muscle, elucidation of the basic mechanisms of fiber diversification is a necessary prerequisite to the generation of therapeutic strategies for attenuation of muscle atrophy on earth or in space. Vertebrate skeletal muscle development involves the fusion of undifferentiated mononucleated myoblasts to form multinucleated myofibers, with a concomitant activation of muscle-specific genes encoding proteins that form the force-generating contractile apparatus. The regulatory circuitry controlling skeletal muscle gene expression has been well studied in a number of vertebrate animal systems. The goal of this project has been to achieve a similar level of understanding of the mechanisms underlying the further specification of muscles into different fiber types, and the role played by innervation and physical activity in the maintenance and adaptation of different fiber phenotypes into adulthood. Our recent research on the genetic basis of fiber specificity has focused on the emergence of mature fiber types and have implicated a group of transcriptional regulatory proteins, known as E proteins, in the control of fiber specificity. The restriction of E proteins to selected muscle fiber types is an attractive hypothetical mechanism for the generation of muscle fiber-specific patterns of gene expression. To date our results support a model wherein different E proteins are selectively expressed in muscle cells to determine fiber-restricted gene expression. These studies are a first step to define the molecular mechanisms responsible for the shifts in fiber type under conditions of microgravity, and to determine the potential importance of E proteins as upstream targets for the effects of weightlessness. In the past year we have determined that the expression of E Proteins is restricted to specific fiber types by post-transcriptional mechanisms. By far, the most prevalent mechanism of cellular control for achieving post-transcriptional regulation of gene expression is selective proteolysis -through the ubiquitin -proteasome pathway. Steady-state levels of HEB message are similar in all fast and slow skeletal muscle fiber types, yet the protein is restricted to Type IIX fibers. HEB appears to be a nodal point for regulating fiber-specific transcription, as expression of the transcription factor is regulated at the post-transcriptional level. It is not clear at present whether the regulation is at the level of protein synthesis or degradation. We are now poised to evaluate the biological role of ubiquitination in fiber specific-gene expression by controlling the post-transcriptional expression of E Proteins. The use of metabolic labelling and pharmacological inhibitors of the ubiquitin pathway will be used to identify the mode of regulation of the Type IIX expression pattern. The potential role of specific kinases in effecting the restriction of HEB expression will be examined by using both inhibitors and activators. The results of these studies will provide the necessary information to evaluate the biological role of E proteins in controlling fiber type transitions, and in potentially attenuating the atrophic effects of microgravity conditions. We have also recently shown that ectopic expression of the HEB protein transactivates the Type IIX-specific skeletal a-actin reporter. The 218 bp skeletal a-actin promoter drives transgene expression solely in mature Type IIX fibers. A mouse also carrying the transgene MLCI/HEB (which ectopically expresses the E Protein HEB in Type IIB fibers) forces expression of the skeletal a-actin reporter gene in Type IIB fibers. We can now dissect the composition of this fiber-specific cis-element. The skeletal a-actin promoter is quite compact and has been extensively characterized in vitro for activity and binding factors. The single E box may act as a binding target of myogenic factor/HEB heterodimer to allow for IIX expression. The HEB transcription factor may recognize either the precise flanking sequences of the E Box, or perhaps interacting with other proteins bound nearby, and activating expression in Type IIX fibers. This E box will be both ablated, and alternatively, as ablation may well destroy any muscle-specific transcriptional activity, flanking sequences substituted with those surrounding the E box (El) of the myogenin promoter. Modification of fiber-specific transgene expression will be tested in transgenic mice. The results of these studies will provide basic information on the regulatory circuitry underlying fiber specificity, and will form the basis for building appropriate transgenic regulatory cassettes to effect fiber transitions in subsequent experimental manipulations on unweighted muscles.

Platelet glycoprotein IIb/IIIa inhibitors in acute ischemic stroke.

PubMed

Kumar, Sudhir; Rajshekher, G; Prabhakar, Subhashini

2008-01-01

Acute ischemic stroke (AIS) is a common cause of morbidity and mortality worldwide. Thrombolytic therapy with tissue plasminogen activator, the only approved treatment for AIS, is received by less than 2% of patients. Moreover, there is a slight increase in hemorrhagic complications with thrombolysis. Therefore, there is a need for newer therapeutic modalities in AIS, which could be used in window periods beyond 3-6 h after stroke onset with fewer hemorrhagic complications. Glycoprotein IIb/IIIa inhibitors (GPI), after their initial success in patients with acute coronary syndromes, promised much in patients with AIS over the past decade or so. However, their exact role in patients with AIS, including the window periods and type of strokes, and the risk of symptomatic or asymptomatic hemorrhage are unclear at the moment. The current review focuses on the literature concerning the use of GPI in AIS and looks at the available evidence regarding their use. Abciximab thought to be safe and effective in initial case series and early trials, has not been shown to improve outcomes in AIS, and is associated with higher rates of hemorrhage. Tirofiban appears to be safe and effective in initial trials and there is a need to conduct further trials to establish its role in AIS.

Differential Dynamics of Platelet Contact and Spreading

PubMed Central

Lee, Dooyoung; Fong, Karen P.; King, Michael R.; Brass, Lawrence F.; Hammer, Daniel A.

2012-01-01

Platelet spreading is critical for hemostatic plug formation and thrombosis. However, the detailed dynamics of platelet spreading as a function of receptor-ligand adhesive interactions has not been thoroughly investigated. Using reflection interference contrast microscopy, we found that both adhesive interactions and PAR4 activation affect the dynamics of platelet membrane contact formation during spreading. The initial growth of close contact area during spreading was controlled by the combination of different immobilized ligands or PAR4 activation on fibrinogen, whereas the growth of the total area of spreading was independent of adhesion type and PAR4 signaling. We found that filopodia extend to their maximal length and then contract over time; and that filopodial protrusion and expansion were affected by PAR4 signaling. Upon PAR4 activation, the integrin αIIbβ3 mediated close contact to fibrinogen substrata and led to the formation of ringlike patterns in the platelet contact zone. A systematic study of platelet spreading of GPVI-, α2-, or β3-deficient platelets on collagen or fibrinogen suggests the integrin α2 is indispensable for spreading on collagen. The platelet collagen receptors GPVI and α2 regulate integrin αIIbβ3-mediated platelet spreading on fibrinogen. This work elucidates quantitatively how receptor-ligand adhesion and biochemical signals synergistically control platelet spreading. PMID:22325269

A Medical Center Network for Optimized Lung Cancer Biospecimen Banking

DTIC Science & Technology

2013-10-01

Carcinoma Stage IIB N N .149 1 8 .132 1 8 .092 1 No - Quit Smoking 50 AR Agent Orange , Nuclear weapons, Second-hand smoke Agent Orange , Nuclear weapons...Smoking 30 None Agent Orange , Asbestos, Second-hand smoke Agent Orange , Asbestos, Second-hand smoke S0159 Squamous Cell Carcinoma Stage IIB Y N...2.560 100 80 25 6 7 0.670 4 4 0.370 1 No - Quit Smoking 30 NV Agent Orange , Asbestos, Nuclear weapons, Second- hand smoke Agent Orange , Asbestos

30 CFR 57.22501 - Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Personal electric lamps (I-A, I-B, I-C, II-A... Illumination § 57.22501 Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). Electric lamps used for personal illumination shall be approved by MSHA under the requirements of 30 CFR...

30 CFR 57.22501 - Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Personal electric lamps (I-A, I-B, I-C, II-A... Illumination § 57.22501 Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). Electric lamps used for personal illumination shall be approved by MSHA under the requirements of 30 CFR...

30 CFR 57.22501 - Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines).

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Personal electric lamps (I-A, I-B, I-C, II-A... Illumination § 57.22501 Personal electric lamps (I-A, I-B, I-C, II-A, II-B, III, IV, V-A, and V-B mines). Electric lamps used for personal illumination shall be approved by MSHA under the requirements of 30 CFR...

Chemoradiation Therapy and Ipilimumab in Treating Patients With Stages IB2-IIB or IIIB-IVA Cervical Cancer

ClinicalTrials.gov

2018-05-24

Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Positive Para-Aortic Lymph Node; Positive Pelvic Lymph Node; Stage IB2 Cervical Cancer AJCC v6 and v7; Stage II Cervical Cancer AJCC v7; Stage IIA Cervical Cancer AJCC v7; Stage IIB Cervical Cancer AJCC v6 and v7; Stage IIIB Cervical Cancer AJCC v6 and v7; Stage IVA Cervical Cancer AJCC v6 and v7

CDX-1401 and Poly-ICLC Vaccine Therapy With or Without CDX-301 in Treating Patients With Stage IIB-IV Melanoma

ClinicalTrials.gov

2018-03-12

Cutaneous Melanoma; Mucosal Melanoma; NY-ESO-1 Positive Tumor Cells Present; Ocular Melanoma; Stage IIB Cutaneous Melanoma AJCC v6 and v7; Stage IIC Cutaneous Melanoma AJCC v6 and v7; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7

Deep Compaction Control of Sandy Soils

NASA Astrophysics Data System (ADS)

Bałachowski, Lech; Kurek, Norbert

2015-02-01

Vibroflotation, vibratory compaction, micro-blasting or heavy tamping are typical improvement methods for the cohesionless deposits of high thickness. The complex mechanism of deep soil compaction is related to void ratio decrease with grain rearrangements, lateral stress increase, prestressing effect of certain number of load cycles, water pressure dissipation, aging and other effects. Calibration chamber based interpretation of CPTU/DMT can be used to take into account vertical and horizontal stress and void ratio effects. Some examples of interpretation of soundings in pre-treated and compacted sands are given. Some acceptance criteria for compaction control are discussed. The improvement factors are analysed including the normalised approach based on the soil behaviour type index.

Agonist muscle adaptation accompanied by antagonist muscle atrophy in the hindlimb of mice following stretch-shortening contraction training.

PubMed

Rader, Erik P; Naimo, Marshall A; Ensey, James; Baker, Brent A

2017-02-02

The vast majority of dynamometer-based animal models for investigation of the response to chronic muscle contraction exposure has been limited to analysis of isometric, lengthening, or shortening contractions in isolation. An exception to this has been the utilization of a rat model to study stretch-shortening contractions (SSCs), a sequence of consecutive isometric, lengthening, and shortening contractions common during daily activity and resistance-type exercise. However, the availability of diverse genetic strains of rats is limited. Therefore, the purpose of the present study was to develop a dynamometer-based SSC training protocol to induce increased muscle mass and performance in plantarflexor muscles of mice. Young (3 months old) C57BL/6 mice were subjected to 1 month of plantarflexion SSC training. Hindlimb muscles were analyzed for muscle mass, quantitative morphology, myogenesis/myopathy relevant gene expression, and fiber type distribution. The main aim of the research was achieved when training induced a 2-fold increase in plantarflexion peak torque output and a 19% increase in muscle mass for the agonist plantaris (PLT) muscle. In establishing this model, several outcomes emerged which raised the value of the model past that of being a mere recapitulation of the rat model. An increase in the number of muscle fibers per transverse muscle section accounted for the PLT muscle mass gain while the antagonist tibialis anterior (TA) muscle atrophied by 30% with preferential atrophy of type IIb and IIx fibers. These alterations were accompanied by distinct gene expression profiles. The findings confirm the development of a stretch-shortening contraction training model for the PLT muscle of mice and demonstrate that increased cross-sectional fiber number can occur following high-intensity SSC training. Furthermore, the TA muscle atrophy provides direct evidence for the concept of muscle imbalance in phasic non-weight bearing muscles, a concept largely characterized based on clinical observation of patients. The susceptibility to this imbalance is demonstrated to be selective for the type IIb and IIx muscle fiber types. Overall, the study highlights the importance of considering muscle fiber number modulation and the effect of training on surrounding muscles in exercise comprised of SSCs.

Effects of compaction pressure and particle shape on the porosity and compression mechanical properties of sintered Ti6Al4V powder compacts for hard tissue implantation.

PubMed

Güden, Mustafa; Celik, Emrah; Hizal, Alpay; Altindiş, Mustafa; Cetiner, Sinan

2008-05-01

Sintered Ti6Al4V powder compacts potentially to be used in implant applications were prepared using commercially available spherical and angular powders (100-200 mum) within the porosity range of 34-54%. Cylindrical green powder compacts were cold compacted at various pressures and then sintered at 1200 degrees C for 2 h. The final percent porosity and mean pore sizes were determined as functions of the applied compaction pressure and powder type. The mechanical properties were investigated through compression testing. Results have shown that yield strength of the powder compacts of 40-42% porosity was comparable with that of human cortical bone. As compared with previously investigated Ti powder compacts, Ti6Al4V powder compacts showed higher strength at similar porosity range. Microscopic observations on the failed compact samples revealed that failure occurred primarily by the separation of interparticle bond regions in the planes 45 degrees to the loading axis. Copyright 2007 Wiley Periodicals, Inc.

Dry minor mergers and size evolution of high-z compact massive early-type galaxies

NASA Astrophysics Data System (ADS)

Oogi, Taira; Habe, Asao

2012-09-01

Recent observations show evidence that high-z (z ~ 2 - 3) early-type galaxies (ETGs) are quite compact than that with comparable mass at z ~ 0. Dry merger scenario is one of the most probable one that can explain such size evolution. However, previous studies based on this scenario do not succeed to explain both properties of high-z compact massive ETGs and local ETGs, consistently. We investigate effects of sequential, multiple dry minor (stellar mass ratio M2/M1<1/4) mergers on the size evolution of compact massive ETGs. We perform N-body simulations of the sequential minor mergers with parabolic and head-on orbits, including a dark matter component and a stellar component. We show that the sequential minor mergers of compact satellite galaxies are the most efficient in the size growth and in decrease of the velocity dispersion of the compact massive ETGs. The change of stellar size and density of the merger remnant is consistent with the recent observations. Furthermore, we construct the merger histories of candidates of high-z compact massive ETGs using the Millennium Simulation Database, and estimate the size growth of the galaxies by dry minor mergers. We can reproduce the mean size growth factor between z = 2 and z = 0, assuming the most efficient size growth obtained in the case of the sequential minor mergers in our simulations.

Compression force sensing regulates integrin αIIbβ3 adhesive function on diabetic platelets.

PubMed

Ju, Lining; McFadyen, James D; Al-Daher, Saheb; Alwis, Imala; Chen, Yunfeng; Tønnesen, Lotte L; Maiocchi, Sophie; Coulter, Brianna; Calkin, Anna C; Felner, Eric I; Cohen, Neale; Yuan, Yuping; Schoenwaelder, Simone M; Cooper, Mark E; Zhu, Cheng; Jackson, Shaun P

2018-03-14

Diabetes is associated with an exaggerated platelet thrombotic response at sites of vascular injury. Biomechanical forces regulate platelet activation, although the impact of diabetes on this process remains ill-defined. Using a biomembrane force probe (BFP), we demonstrate that compressive force activates integrin α IIb β 3 on discoid diabetic platelets, increasing its association rate with immobilized fibrinogen. This compressive force-induced integrin activation is calcium and PI 3-kinase dependent, resulting in enhanced integrin affinity maturation and exaggerated shear-dependent platelet adhesion. Analysis of discoid platelet aggregation in the mesenteric circulation of mice confirmed that diabetes leads to a marked enhancement in the formation and stability of discoid platelet aggregates, via a mechanism that is not inhibited by therapeutic doses of aspirin and clopidogrel, but is eliminated by PI 3-kinase inhibition. These studies demonstrate the existence of a compression force sensing mechanism linked to α IIb β 3 adhesive function that leads to a distinct prothrombotic phenotype in diabetes.

Fluorescence Imaging In Vivo at Wavelengths beyond 1500 nm.

PubMed

Diao, Shuo; Blackburn, Jeffrey L; Hong, Guosong; Antaris, Alexander L; Chang, Junlei; Wu, Justin Z; Zhang, Bo; Cheng, Kai; Kuo, Calvin J; Dai, Hongjie

2015-12-01

Compared to imaging in the visible and near-infrared regions below 900 nm, imaging in the second near-infrared window (NIR-II, 1000-1700 nm) is a promising method for deep-tissue high-resolution optical imaging in vivo mainly owing to the reduced scattering of photons traversing through biological tissues. Herein, semiconducting single-walled carbon nanotubes with large diameters were used for in vivo fluorescence imaging in the long-wavelength NIR region (1500-1700 nm, NIR-IIb). With this imaging agent, 3-4 μm wide capillary blood vessels at a depth of about 3 mm could be resolved. Meanwhile, the blood-flow speeds in multiple individual vessels could be mapped simultaneously. Furthermore, NIR-IIb tumor imaging of a live mouse was explored. NIR-IIb imaging can be generalized to a wide range of fluorophores emitting at up to 1700 nm for high-performance in vivo optical imaging. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structure-activity relationships of an antimicrobial peptide plantaricin s from two-peptide class IIb bacteriocins.

PubMed

Soliman, Wael; Wang, Liru; Bhattacharjee, Subir; Kaur, Kamaljit

2011-04-14

Class IIb bacteriocins are ribosomally synthesized antimicrobial peptides comprising two different peptides synergistically acting in equal amounts for optimal potency. In this study, we demonstrate for the first time potent (nanomolar) antimicrobial activity of a representative class IIb bacteriocin, plantaricin S (Pls), against four pathogenic gram-positive bacteria, including Listeria monocytogenes. The structure-activity relationships for Pls were studied using activity assays, circular dichroism (CD), and molecular dynamics (MD) simulations. The two Pls peptides and five Pls derived fragments were synthesized. The CD spectra of the Pls and selected fragments revealed helical conformations in aqueous 2,2,2-trifluoroethanol. The MD simulations showed that when the two Pls peptides are in antiparallel orientation, the helical regions interact and align, mediated by strong attraction between conserved GxxxG/AxxxA motifs. The results strongly correlate with the antimicrobial activity suggesting that helix-helix alignment of the two Pls peptides and interaction between the conserved motifs are crucial for interaction with the target cell membrane.

Carevive Survivor Care Planning System in Improving Quality of Life in Breast Cancer Survivors

ClinicalTrials.gov

2018-02-20

Stage I Breast Cancer; Stage I Cervical Cancer; Stage I Ovarian Cancer; Stage I Uterine Corpus Cancer; Stage IA Breast Cancer; Stage IA Cervical Cancer; Stage IA Ovarian Cancer; Stage IA Uterine Corpus Cancer; Stage IB Breast Cancer; Stage IB Cervical Cancer; Stage IB Ovarian Cancer; Stage IB Uterine Corpus Cancer; Stage IC Ovarian Cancer; Stage II Breast Cancer; Stage II Cervical Cancer; Stage II Ovarian Cancer; Stage II Uterine Corpus Cancer; Stage IIA Breast Cancer; Stage IIA Cervical Cancer; Stage IIA Ovarian Cancer; Stage IIB Breast Cancer; Stage IIB Cervical Cancer; Stage IIB Ovarian Cancer; Stage IIC Ovarian Cancer; Stage III Breast Cancer; Stage III Cervical Cancer; Stage III Ovarian Cancer; Stage III Uterine Corpus Cancer; Stage IIIA Breast Cancer; Stage IIIA Cervical Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Uterine Corpus Cancer; Stage IIIB Breast Cancer; Stage IIIB Cervical Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Uterine Corpus Cancer; Stage IIIC Breast Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Uterine Corpus Cancer

Weak coupling limit of F-theory models with MSSM spectrum and massless U(1)'s

NASA Astrophysics Data System (ADS)

Mayorga Peña, Damián Kaloni; Valandro, Roberto

2018-03-01

We consider the Sen limit of several global F-theory compactifications, some of which exhibit an MSSM-like spectrum. We show that these indeed have a consistent limit where they can be viewed as resulting from an intersecting brane configuration in type IIB. We discuss the match of the fluxes and the chiral spectrum in detail. We find that some D5-tadpole canceling gauge fluxes do not lift to harmonic vertical four-form fluxes in the resolved F-theory manifold. We discuss the connection between splitting of curves at weak coupling and remnant discrete symmetries.

A fluid inclusion study of blueschist-facies lithologies from the Indus suture zone, Ladakh (India): Implications for the exhumation of the subduction related Sapi-Shergol ophiolitic mélange

NASA Astrophysics Data System (ADS)

Sachan, Himanshu Kumar; Kharya, Aditya; Singh, P. Chandra; Rolfo, Franco; Groppo, Chiara; Tiwari, Sameer K.

2017-09-01

The best occurrence of blueschist-facies lithologies in Himalaya is that of the Shergol Ophiolitic Mélange along the Indus suture zone in Ladakh region of north-western India. These lithologies are characterized by well preserved lawsonite-glaucophane-garnet-quartz assemblages. This paper presents for the first time the results of a detailed fluid inclusion study on these lithologies, in order to understand the fluid P-T evolution and its tectonic implications. The blueschist rocks from Shergol Ophiolitic Mélange record metamorphic peak conditions at ∼19 kbar, 470 °C. Several types of fluid inclusions are trapped in quartz and garnet, most of them being two-phase at room temperature. Three types of fluid inclusions have been recognised, basing on microtextures and fluid composition: Type-I are primary two-phase carbonic-aqueous fluid inclusions (VCO2 - LH2O); Type-II are two-phase (LH2O - VH2O) aqueous fluid inclusions, either primary (Type-IIa) or secondary (Type-IIb); Type-III are re-equilibrated fluid inclusions. In the Type-I primary carbonic-aqueous inclusions, H2O is strongly predominant with respect to CO2; the homogenization temperature of CO2 range from -7 to -2 °C. The clathrate melting temperature in such inclusions varies in between +7.1 and +8.6 °C. Type-II two-phase aqueous fluid inclusions show a wide range of salinity, from 7.8-14 wt.% NaCleq (Type-IIa) to 1.65-6.37 wt.% NaCleq (Type-IIb) with accuracy ±0.4 wt.% NaCleq. Type-I and Type-IIa primary fluid inclusions are hosted in peak minerals (garnet and quartz included in garnet), therefore they were likely entrapped at, or near to, peak P-T conditions. The dominantly aqueous fluid of both Type-I and Type-IIa inclusions was most likely produced through metamorphic devolatilization reactions occurring in the subducting slab. Despite their primary nature, the isochores of Type-I and Type-IIa inclusions do not intersect the peak metamorphic conditions of the blueschist mineral assemblage, suggesting that these inclusions stretched or re-equilibrated during nearly isothermal decompression from 19 kbar to 3 kbar or less, at T = 290 °C. This conclusion is further supported by their large variability in shapes and sizes which range from irregular inclusions ('C'/arc shaped, hook shape and satellite type). This decompression stage was followed by nearly isobaric cooling, testified by the occurrence of dendritic networks of decrepitated and 'imploded' fluid inclusions.

Posttransfusion purpura associated with an autoantibody directed against a previously undefined platelet antigen.

PubMed

Stricker, R B; Lewis, B H; Corash, L; Shuman, M A

1987-05-01

Although alloantibody against the PLA1 platelet antigen is usually found in patients with posttransfusion purpura (PTP), the mechanism of destruction of the patient's own PLA1-negative platelets is unexplained. We used a sensitive immunoblot technique to detect antiplatelet antibodies in a patient with classic PTP. The patient's acute-phase serum contained antibodies against three proteins present in control (PLA1-positive) platelets: an antibody that bound to a previously unrecognized platelet protein of mol wt 120,000 [glycoprotein (GP) 120], antibodies that bound to PLA1 (mol wt 90,000), and an epitope of GP IIb (mol wt 140,000). The antibodies against PLA1 and GP IIb did not react with the patient's own PLA1-negative platelets, control PLA1-negative platelets, or thrombasthenic platelets. In contrast, the antibody against GP 120 recognized this protein in all three platelet preparations, but not in Bernard-Soulier or Leka (Baka)-negative platelets. Antibody against GP 120 was not detected in the patient's recovery serum, although the antibodies against PLA1 and GP IIb persisted. F(ab)2 prepared from the patient's acute-phase serum also bound to GP 120. These results suggest that in PTP, transient autoantibody production may be responsible for autologous (PLA1-negative) platelet destruction. In addition, alloantibodies against more than one platelet alloantigen may be found in this disease. The nature of the GP 120 autoantigen and the GP IIb-related alloantigen defined by our patient's serum remains to be determined.

Genetically different isolates of Trypanosoma cruzi elicit different infection dynamics in raccoons (Procyon lotor) and Virginia opossums (Didelphis virginiana)

PubMed Central

Roellig, Dawn M.; Ellis, Angela E.; Yabsley, Michael J.

2009-01-01

Trypanosoma cruzi is a genetically and biologically diverse species. In the current study we determined T. cruzi infection dynamics in two common North American reservoirs, Virginia opossums (Didelphis virginiana) and raccoons (Procyon lotor). Based on previous molecular and culture data from naturally-exposed animals, we hypothesized that raccoons would have a longer patent period than opossums, and raccoons would be competent reservoirs for both genotypes T. cruzi I (TcI) and TcIIa, while opossums would only serve as hosts for TcI. Individuals (n = 2 or 3) of each species were inoculated with 1 × 106 culture-derived T. cruzi trypomastigotes of TcIIa (North American (NA) - raccoon), TcI (NA - opossum), TcIIb (South American - human), or both TcI and TcIIa. Parasitemias in opossums gradually increased and declined rapidly, whereas parasitemias peaked sooner in raccoons and they maintained relatively high parasitemia for 5 weeks. Raccoons became infected with all three T. cruzi strains, while opossums only became infected with TcI and TcIIb. Although opossums were susceptible to TcIIb, infection dynamics were dramatically different compared with TcI. Opossums inoculated with TcIIb seroconverted, but parasitemia duration was short and only detectable by PCR. In addition, raccoons seroconverted sooner (3–7 days post inoculation) than opossums (10 days post inoculation). These data suggest that infection dynamics of various T. cruzi strains can differ considerably in different wildlife hosts. PMID:19607833

Functional pools of oxidative and glycolytic fibers in human muscle observed by 31P magnetic resonance spectroscopy during exercise.

PubMed Central

Park, J H; Brown, R L; Park, C R; McCully, K; Cohn, M; Haselgrove, J; Chance, B

1987-01-01

Quantitative probing of heterogeneous regions in muscle is feasible with phosphorus-31 magnetic resonance spectroscopy because of the differentiation of metabolic patterns of glycolytic and oxidative fibers. A differential recruitment of oxidative and glycolytic fibers during exercise was demonstrated in 4 of 10 untrained young men by following changes in phosphate metabolites. Concentrations of inorganic phosphate (Pi), phosphocreatine, and ATP were estimated in the wrist flexor muscles of the forearm at rest, during two cycles of three grades of exercise, and in recovery. At high work levels (40% of maximum strength), two distinct Pi peaks were observed and identified with Pi pools at pH 6.9 and pH 5.9-6.4, respectively. These could be accounted for as follows. At the lowest level of work (using 20% of maximum strength), early recruitment primarily of oxidative (type I) and possibly some intermediate (type IIA) muscle fibers occurs with relatively little net lactate production and consequently little decrease in pH. At higher work loads, however, primarily glycolytic (type IIB) muscle fibers are recruited, which have relatively high net lactate production and therefore generate a second pool of Pi at low pH. ATP depletion (35-54%) and Pi losses accompanied the reduction in ability to perform during the first exercise cycle. When the cycle of graded exercise was repeated immediately, the total Pi remained high but gave rise to only one peak at pH 6.8-7.0. These observations indicated exhaustion of glycolytic type IIB fibers, removal of lactate by high local blood flow, and sustained contractions largely by oxidative type I and IIA fibers. A functional differentiation of fiber types could also be demonstrated during recovery if exercise was stopped while two pools of Pi were still apparent. In the first 3 min of recovery, the Pi peak at pH 6.8-6.9 disappeared almost entirely, whereas the Pi peak at pH 6.0 remained unaltered, reflecting the faster recovery of oxidative type I fibers. The potential of magnetic resonance spectroscopy to characterize oxidative and glycolytic fibers, predict capacity for aerobic performance, and signal the presence of muscle pathology is discussed. PMID:3480522

Geometric engineering on flops of length two

NASA Astrophysics Data System (ADS)

Collinucci, Andrés; Fazzi, Marco; Valandro, Roberto

2018-04-01

Type IIA on the conifold is a prototype example for engineering QED with one charged hypermultiplet. The geometry admits a flop of length one. In this paper, we study the next generation of geometric engineering on singular geometries, namely flops of length two such as Laufer's example, which we affectionately think of as the conifold 2.0. Type IIA on the latter geometry gives QED with higher-charge states. In type IIB, even a single D3-probe gives rise to a nonabelian quiver gauge theory. We study this class of geometries explicitly by leveraging their quiver description, showing how to parametrize the exceptional curve, how to see the flop transition, and how to find the noncompact divisors intersecting the curve. With a view towards F-theory applications, we show how these divisors contribute to the enhancement of the Mordell-Weil group of the local elliptic fibration defined by Laufer's example.

Soil compaction associated with cut-to-length and whole-tree harvesting of a coniferous forest

Treesearch

Sang-Kyun Han; Han Han-Sup; Deborah Page-Dumroese; Leonard R. Johnson

2009-01-01

The degree and extent of soil compaction, which may reduce productivity of forest soils, is believed to vary by the type of harvesting system, and a field-based study was conducted to compare soil compaction from cut-to-length (CTL) and whole-tree (WT) harvesting operations. The CTL harvesting system used less area to transport logs to the landings than did the WT...

Little string origin of surface defects

NASA Astrophysics Data System (ADS)

Haouzi, Nathan; Schmid, Christian

2017-05-01

We derive a large class of codimension-two defects of 4d \\mathcal{N}=4 Super Yang-Mills (SYM) theory from the (2, 0) little string. The origin of the little string is type IIB theory compactified on an ADE singularity. The defects are D-branes wrapping the 2-cycles of the singularity. We use this construction to make contact with the description of SYM defects due to Gukov and Witten [1]. Furthermore, we provide a geometric perspective on the nilpotent orbit classification of codimension-two defects, and the connection to ADE-type Toda CFT. The only data needed to specify the defects is a set of weights of the algebra obeying certain constraints, which we give explicitly. We highlight the differences between the defect classification in the little string theory and its (2 , 0) CFT limit.

Bevacizumab and Combination Chemotherapy Before Surgery in Treating Patients With Locally Advanced Esophageal or Stomach Cancer

ClinicalTrials.gov

2018-02-23

Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Mixed Adenocarcinoma of the Stomach; Squamous Cell Carcinoma of the Esophagus; Stage IA Esophageal Cancer; Stage IA Gastric Cancer; Stage IB Esophageal Cancer; Stage IB Gastric Cancer; Stage IIA Esophageal Cancer; Stage IIA Gastric Cancer; Stage IIB Esophageal Cancer; Stage IIB Gastric Cancer; Stage IIIA Esophageal Cancer; Stage IIIA Gastric Cancer; Stage IIIB Esophageal Cancer; Stage IIIB Gastric Cancer; Stage IIIC Esophageal Cancer; Stage IIIC Gastric Cancer

WisDOT asphaltic mixture new specifications implementation : field compaction and density.

DOT National Transportation Integrated Search

2016-06-01

The main research objectives of this study were to evaluate HMA Longitudinal Joint type, method and compaction data to produce specification recommendations that will ensure the highest density longitudinal joint, as well as evaluate and produce a sp...

How do roll compaction/dry granulation affect the tableting behaviour of inorganic materials? Comparison of four magnesium carbonates.

PubMed

Freitag, Franziska; Kleinebudde, Peter

2003-07-01

The effect of roll compaction/dry granulation on the particle and bulk material characteristics of different magnesium carbonates was evaluated. The flowability of all materials could be improved, even by the application of low specific compaction forces. The tablet properties made of powder and dry granulated magnesium carbonate were compared. Roll compaction/dry granulation resulted in a modified compactibility of the material and, consequently, tablets with reduced tensile strength. The higher relative tap density of the compacted material does not allow a densification to the same extent as the uncompacted powder. The degree of densification during tableting can be expressed as the ratio of the relative tablet density to the relative tap density of the feed material. Increasing the specific compaction forces resulted in higher apparent mean yield pressure, gained from Heckel plots, of all materials analysed. The partial loss of compactibility leads to the demand of low loads during roll compaction. Comparing the tablet properties of different magnesium carbonates reveals an obvious capping disposition. However, it depends on the type of magnesium carbonate, the specific compaction force and also on the tableting force applied.

Compact fast analyzer of rotary cuvette type

DOEpatents

Thacker, Louis H.

1976-01-01

A compact fast analyzer of the rotary cuvette type is provided for simultaneously determining concentrations in a multiplicity of discrete samples using either absorbance or fluorescence measurement techniques. A rigid, generally rectangular frame defines optical passageways for the absorbance and fluorescence measurement systems. The frame also serves as a mounting structure for various optical components as well as for the cuvette rotor mount and drive system. A single light source and photodetector are used in making both absorbance and fluorescence measurements. Rotor removal and insertion are facilitated by a swing-out drive motor and rotor mount. BACKGROUND OF THE INVENTION The invention relates generally to concentration measuring instruments and more specifically to a compact fast analyzer of the rotary cuvette type which is suitable for making either absorbance or fluorescence measurements. It was made in the course of, or under, a contract with the U.S. Atomic Energy Commission.

α-[¹¹C]-methyl-L-tryptophan PET for tracer localization of epileptogenic brain regions: clinical studies.

PubMed

Kumar, Ajay; Asano, Eishi; Chugani, Harry T

2011-10-01

Of several molecular probes used in PET, only α-[(11)C]-methyl-L-tryptophan (AMT) is able to pinpoint the epileptic focus itself in the interictal state, by revealing a focus of increased AMT uptake, even when an MRI or glucose metabolism PET demonstrates normal findings. AMT PET appears to be particularly useful in patients with tuberous sclerosis complex and in patients with cortical developmental malformations. Although the sensitivity of AMT PET in finding the epileptic focus is about 70%, its specificity is almost 100%, indicating that if AMT PET identifies an area of increased uptake, it likely represents the epileptic focus which needs to be resected for better surgical outcome. In nontuberous sclerosis complex patients with cortical dysplasia, increased AMT uptake is usually associated with cortical dysplasia type IIB and a very good surgical outcome. Previously, no imaging modality has been able to predict the exact pathology subtype or differentiate between epileptogenic and nonepileptogenic lesions interictally. The neuropathological similarities between tubers and type IIB cortical dysplasia suggest a common mechanism of epilepsy, for which AMT PET is a biomarker. Due to the limited access to AMT PET, as presently it is labeled with (11)C, which has a half-life of only 20 min and therefore has to be synthesized on site using a cyclotron, most of the AMT experience has originated primarily from only two centers. Therefore, there is a need for more clinical studies from other centers and this can be greatly facilitated if AMT can be labeled with (18)F, a PET radionuclide widely available with a half-life of 110 min.

Treatment of distal-third clavicular fractures (Neer type ii-b) with a triple button device.

PubMed

Cano-Martínez, J A; Nicolás-Serrano, G; Andrés-Grau, J; Bento-Gerard, J

The purpose of this study is to describe the outcomes of using a triple button device for the treatment of displaced distal-third clavicle fractures (Neer, type ii-b). A retrospective review was conducted on a series of patients between November 2011 and December 2014. Fourteen patients initially met the inclusion criteria, but 2 were excluded, leaving 12 patients (83.3% male; mean age 32.2 years) for the final analysis at a mean follow-up of 26±11.24 months (range, 12-48). Post-operative follow-up was performed at 2 weeks (two first months), and monthly thereafter, until was achieving clinically and radiological healing. The functional outcome was evaluated using the Constant score, and DASH score in the last follow-up. The mean Constant Score was 95.5±5.2 points (range, 85-100), with a mean DASH score of 3.3±4.4 points (range, 0-12.5). The mean time to clinical healing was10.3±3.1 weeks (range, 8-16), and the mean time to radiological healing was 13.6±2.6 weeks (range, 12-20). There were no major complications. There were 5 minor complications without clinical impact: 2 coracoclavicular calcifications, 1 hypertrophic scar, 1 patient with discomfort due to the device, and 1 superficial wound infection. All patients returned their previous activity. Good clinical results can be achieved with the triple button device in unstable distal fractures of the clavicle, without the need to remove the hardware. Copyright © 2016 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.

Transcriptional expression analysis of genes involved in regulation of calcium translocation and storage in finger millet (Eleusine coracana L. Gartn.).

PubMed

Mirza, Neelofar; Taj, Gohar; Arora, Sandeep; Kumar, Anil

2014-10-25

Finger millet (Eleusine coracana) variably accumulates calcium in different tissues, due to differential expression of genes involved in uptake, translocation and accumulation of calcium. Ca(2+)/H(+) antiporter (CAX1), two pore channel (TPC1), CaM-stimulated type IIB Ca(2+) ATPase and two CaM dependent protein kinase (CaMK1 and 2) homologs were studied in finger millet. Two genotypes GP-45 and GP-1 (high and low calcium accumulating, respectively) were used to understand the role of these genes in differential calcium accumulation. For most of the genes higher expression was found in the high calcium accumulating genotype. CAX1 was strongly expressed in the late stages of spike development and could be responsible for accumulating high concentrations of calcium in seeds. TPC1 and Ca(2+) ATPase homologs recorded strong expression in the root, stem and developing spike and signify their role in calcium uptake and translocation, respectively. Calmodulin showed strong expression and a similar expression pattern to the type IIB ATPase in the developing spike only and indicating developing spike or even seed specific isoform of CaM affecting the activity of downstream target of calcium transportation. Interestingly, CaMK1 and CaMK2 had expression patterns similar to ATPase and TPC1 in various tissues raising a possibility of their respective regulation via CaM kinase. Expression pattern of 14-3-3 gene was observed to be similar to CAX1 gene in leaf and developing spike inferring a surprising possibility of CAX1 regulation through 14-3-3 protein. Our results provide a molecular insight for explaining the mechanism of calcium accumulation in finger millet. Copyright © 2014 Elsevier B.V. All rights reserved.

Wavelet Imaging on Multiple Scales (WIMS) reveals focal adhesion distributions, dynamics and coupling between actomyosin bundle stability

PubMed Central

Toplak, Tim; Palmieri, Benoit; Juanes-García, Alba; Vicente-Manzanares, Miguel; Grant, Martin; Wiseman, Paul W.

2017-01-01

We introduce and use Wavelet Imaging on Multiple Scales (WIMS) as an improvement to fluorescence correlation spectroscopy to measure physical processes and features that occur across multiple length scales. In this study, wavelet transforms of cell images are used to characterize molecular dynamics at the cellular and subcellular levels (i.e. focal adhesions). We show the usefulness of the technique by applying WIMS to an image time series of a migrating osteosarcoma cell expressing fluorescently labelled adhesion proteins, which allows us to characterize different components of the cell ranging from optical resolution scale through to focal adhesion and whole cell size scales. Using WIMS we measured focal adhesion numbers, orientation and cell boundary velocities for retraction and protrusion. We also determine the internal dynamics of individual focal adhesions undergoing assembly, disassembly or elongation. Thus confirming as previously shown, WIMS reveals that the number of adhesions and the area of the protruding region of the cell are strongly correlated, establishing a correlation between protrusion size and adhesion dynamics. We also apply this technique to characterize the behavior of adhesions, actin and myosin in Chinese hamster ovary cells expressing a mutant form of myosin IIB (1935D) that displays decreased filament stability and impairs front-back cell polarity. We find separate populations of actin and myosin at each adhesion pole for both the mutant and wild type form. However, we find these populations move rapidly inwards toward one another in the mutant case in contrast to the cells that express wild type myosin IIB where those populations remain stationary. Results obtained with these two systems demonstrate how WIMS has the potential to reveal novel correlations between chosen parameters that belong to different scales. PMID:29049414

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

Jencson, Jacob E.; Kasliwal, Mansi M.; Cao, Yi

SPitzer InfraRed Intensive Transients Survey—SPIRITS—is an ongoing survey of nearby galaxies searching for infrared (IR) transients with Spitzer /IRAC. We present the discovery and follow-up observations of one of our most luminous ( M {sub [4.5]} = −17.1 ± 0.4 mag, Vega) and reddest ([3.6] − [4.5] = 3.0 ± 0.2 mag) transients, SPIRITS 15c. The transient was detected in a dusty spiral arm of IC 2163 ( D ≈ 35.5 Mpc). Pre-discovery ground-based imaging revealed an associated, shorter-duration transient in the optical and near-IR (NIR). NIR spectroscopy showed a broad (≈8400 km s{sup −1}), double-peaked emission line of Hemore » i at 1.083 μ m, indicating an explosive origin. The NIR spectrum of SPIRITS 15c is similar to that of the Type IIb SN 2011dh at a phase of ≈200 days. Assuming an A {sub V} = 2.2 mag of extinction in SPIRITS 15c provides a good match between their optical light curves. The NIR light curves, however, show some minor discrepancies when compared with SN 2011dh, and the extreme [3.6]–[4.5] color has not been previously observed for any SN IIb. Another luminous ( M {sub 4.5} = −16.1 ± 0.4 mag) event, SPIRITS 14buu, was serendipitously discovered in the same galaxy. The source displays an optical plateau lasting ≳80 days, and we suggest a scenario similar to the low-luminosity Type IIP SN 2005cs obscured by A{sub V} ≈ 1.5 mag. Other classes of IR-luminous transients can likely be ruled out in both cases. If both events are indeed SNe, this may suggest that ≳18% of nearby core-collapse SNe are missed by currently operating optical surveys.« less

A rare case of unprovoked venous thromboembolism manifestation in a young patient with antithrombin Type IIB deficiency combined with inferior vena cava anomaly from Lithuania.

PubMed

Saulytė-Trakymienė, Sonata; Adomaitienė, Irina; Unkrig, Susanne; Oldenburg, Johannes; Ivaškevičius, Vytautas

2017-01-01

Hereditary antithrombin (AT) deficiency is an autosomal-dominant disorder predisposing to venous and arterial thrombosis. Homozygosity resulting in severe AT deficiency is not compatible with life, apart from homozygous mutations affecting the heparin-binding site representing the most severe thrombophilia. A 12-year-old previously healthy boy of Romani origin presented with a swollen, painful left leg and fever. Imaging revealed signs of inferior vena cava (IVC) thrombosis, the presence of interrupted intrahepatic IVC with azygos continuation and bilateral iliofemoral thrombosis with enlargement of the azygous and hemiazygos venous system. In addition, right pleural effusion and signs of bilateral renal pericortical cysts, possibly caused by retroperitoneal lymphangiectasia, were disclosed. Thrombophilia screening involving protein C, Protein S, Antithrombin (chromogenic assays based on the inhibition of FIIa and FXa, antigen concentration), APC resistance, prothrombin mutation and Lupus anticoagulants was performed using standard laboratory methods. Genetic analysis of the SERPINC1 gene was done by direct sequencing. Thrombophilia screening showed isolated decreased AT activity at 21% (RR 80-120%). AT levels were retested and remained decreased (33-36%) on two consecutive occasions. SERPINC1 gene analysis revealed a previously described homozygous mutation (Budapest III) causing type IIB deficiency (c.391C>T; p.Leu131Phe). A family study confirmed the same mutation in both parents and three siblings. The patient improved significantly following warfarin therapy and over the past 2.5 years did not experience new thromboembolism. This case represents a rare combination of two risk factors provoking manifestation of spontaneous venous thromboembolism at a young age requiring permanent anticoagulant therapy. Schattauer GmbH.

Heat-labile Enterotoxins as Adjuvants or Anti-Inflammatory Agents

PubMed Central

Liang, Shuang; Hajishengallis, George

2010-01-01

Escherichia coli and Vibrio cholerae produce structurally related AB5-type heat-labile enterotoxins which are classified into two major types. The Type I subfamily includes cholera toxin and E. coli LT-I, whereas the Type II subfamily comprises LT-IIa and LT-IIb. In addition to their roles in microbial pathogenesis, the enterotoxins are widely and intensively studied for their exceptionally strong adjuvant and immunomodulatory activities, which are not necessarily dependent upon their abilities to elevate intracellular cAMP levels. Despite general structural similarities, these molecules, in intact or derivative form, display notable differences in their interactions with gangliosides or Toll-like receptors. This divergence results in differential immune response outcomes, the underlying mechanisms of which remain largely uncharacterized. Whereas the study of these molecules has been pivotal in understanding basic mechanisms of immune regulation, a formidable challenge is to dissociate toxicity from useful properties that can be exploited in vaccine development or for the treatment of autoimmune inflammatory diseases. PMID:20461887

Heat-labile enterotoxins as adjuvants or anti-inflammatory agents.

PubMed

Liang, Shuang; Hajishengallis, George

2010-01-01

Escherichia coli and Vibrio cholerae produce structurally related AB5-type heat-labile enterotoxins, which are classified into two major types. The Type I subfamily includes cholera toxin and E. coli LT-I, whereas the Type II subfamily comprises LT-IIa and LT-IIb. In addition to their roles in microbial pathogenesis, the enterotoxins are widely and intensively studied for their exceptionally strong adjuvant and immunomodulatory activities, which are not necessarily dependent upon their abilities to elevate intracellular cAMP levels. Despite general structural similarities, these molecules, in intact or derivative form, display notable differences in their interactions with gangliosides or Toll-like receptors. This divergence results in differential immune response outcomes, the underlying mechanisms of which remain largely uncharacterized. Whereas the study of these molecules has been pivotal in understanding basic mechanisms of immune regulation, a formidable challenge is to dissociate toxicity from useful properties that can be exploited in vaccine development or for the treatment of autoimmune inflammatory diseases.

Loss of function of 1-FEH IIb has more impact on post-harvest inulin degradation in Cichorium intybus than copy number variation of its close paralog 1-FEH IIa

PubMed Central

Dauchot, Nicolas; Raulier, Pierre; Maudoux, Olivier; Notté, Christine; Draye, Xavier; Van Cutsem, Pierre

2015-01-01

Key Message: The loss of mini-exon 2 in the 1-FEH IIb glycosyl-hydrolase results in a putative non-functional allele. This loss of function has a strong impact on the susceptibility to post-harvest inulin depolymerization. Significant variation of copy number was identified in its close paralog 1-FEH IIa, but no quantitative effect of copy number on carbohydrates-related phenotypes was detected. Inulin polyfructan is the second most abundant storage carbohydrate in flowering plants. After harvest, it is depolymerized by fructan exohydrolases (FEHs) as an adaptive response to end-season cold temperatures. In chicory, the intensity of this depolymerization differs between cultivars but also between individuals within a cultivar. Regarding this phenotypic variability, we recently identified statistically significant associations between inulin degradation and genetic polymorphisms located in three FEHs. We present here new results of a systematic analysis of copy number variation (CNV) in five key members of the chicory (Cichorium intybus) GH32 multigenic family, including three FEH genes and the two inulin biosynthesis genes: 1-SST and 1-FFT. qPCR analysis identified a significant variability of relative copy number only in the 1-FEH IIa gene. However, this CNV had no quantitative effect. Instead, cloning of the full length gDNA of a close paralogous sequence (1-FEH IIb) identified a 1028 bp deletion in lines less susceptible to post-harvest inulin depolymerization. This region comprises a 9 bp mini-exon containing one of the three conserved residues of the active site. This results in a putative non-functional 1-FEH IIb allele and an observed lower inulin depolymerization. Extensive genotyping confirmed that the loss of mini-exon 2 in 1-FEH IIb and the previously identified 47 bp duplication located in the 3′UTR of 1-FEH IIa belong to a single haplotype, both being statistically associated with reduced susceptibility to post-harvest inulin depolymerization. Emergence of these haplotypes is discussed. PMID:26157446

Selective inhibition of class I but not class IIb histone deacetylases exerts cardiac protection from ischemia reperfusion

PubMed Central

Aune, Sverre E.; Herr, Daniel J.; Mani, Santhosh K.; Menick, Donald R.

2014-01-01

While inhibition of class I/IIb histone deacetylases (HDACs) protects the mammalian heart from ischemia reperfusion (IR) injury, class selective effects remain unexamined. We hypothesized that selective inhibition of class I HDACs would preserve left ventricular contractile function following IR in isolated hearts. Male Sprague Dawley rats (n=6 per group) were injected with vehicle (dimethylsulfoxide, 0.63 mg/kg), the class I/IIb HDAC inhibitor trichostatin A (1 mg/kg), the class I HDAC inhibitor entinostat (MS-275, 10 mg/kg), or the HDAC6 (class IIb) inhibitor tubastatin A (10 mg/kg). After 24 h, hearts were isolated and perfused in Langendorff mode for 30 min (Sham) or subjected to 30 min global ischemia and 120 min global reperfusion (IR). A saline filled balloon attached to a pressure transducer was placed in the LV to monitor contractile function. After perfusion, LV tissue was collected for measurements of antioxidant protein levels and infarct area. At the conclusion of IR, MS-275 pretreatment was associated with significant preservation of developed pressure, rate of pressure generation, rate of pressure relaxation and rate pressure product, as compared to vehicle treated hearts. There was significant reduction of infarct area with MS-275 pretreatment. Contractile function was not significantly restored in hearts treated with trichostatin A or tubastatin A. Mitochondrial superoxide dismutase (SOD2) and catalase protein and mRNA in hearts from animals pretreated with MS-275 were increased following IR, as compared to Sham. This was associated with a dramatic enrichment of nuclear FOXO3a transcription factor, which mediates the expression of SOD2 and catalase. Tubastatin A treatment was associated with significantly decreased catalase levels after IR. Class I HDAC inhibition elicits protection of contractile function following IR, which is associated with increased expression of endogenous antioxidant enzymes. Class I/IIb HDAC inhibition with trichostatin A or selective inhibition of HDAC6 with tubastatin A was not protective. This study highlights the need for the development of new strategies that target specific HDAC isoforms in cardiac ischemia reperfusion. PMID:24632412

Radiolabeled Cyclic RGD Peptides as Radiotracers for Imaging Tumors and Thrombosis by SPECT

PubMed Central

Zhou, Yang; Chakraborty, Sudipta; Liu, Shuang

2011-01-01

The integrin family is a group of transmembrane glycoprotein comprised of 19 α- and 8 β-subunits that are expressed in 25 different α/β heterodimeric combinations on the cell surface. Integrins play critical roles in many physiological processes, including cell attachment, proliferation, bone remodeling, and wound healing. Integrins also contribute to pathological events such as thrombosis, atherosclerosis, tumor invasion, angiogenesis and metastasis, infection by pathogenic microorganisms, and immune dysfunction. Among 25 members of the integrin family, the αvβ3 is studied most extensively for its role of tumor growth, progression and angiogenesis. In contrast, the αIIbβ3 is expressed exclusively on platelets, facilitates the intercellular bidirectional signaling (“inside-out” and “outside-in”) and allows the aggregation of platelets during vascular injury. The αIIbβ3 plays an important role in thrombosis by its activation and binding to fibrinogen especially in arterial thrombosis due to the high blood flow rate. In the resting state, the αIIbβ3 on platelets does not bind to fibrinogen; on activation, the conformation of platelet is altered and the binding sites of αIIbβ3 are exposed for fibrinogen to crosslink platelets. Over the last two decades, integrins have been proposed as the molecular targets for diagnosis and therapy of cancer, thrombosis and other diseases. Several excellent review articles have appeared recently to cover a broad range of topics related to the integrin-targeted radiotracers and their nuclear medicine applications in tumor imaging by single photon emission computed tomography (SPECT) or a positron-emitting radionuclide for positron emission tomography (PET). This review will focus on recent developments of αvβ3-targeted radiotracers for imaging tumors and the use of αIIbβ3-targeted radiotracers for thrombosis imaging, and discuss different approaches to maximize the targeting capability of cyclic RGD peptides and improve the radiotracer excretion kinetics from non-cancerous organs. Improvement of target uptake and target-to-background ratios is critically important for target-specific radiotracers. PMID:21547153

The impact of traumatic subarachnoid hemorrhage on outcome: a study with grouping of traumatic subarachnoid hemorrhage and transcranial Doppler sonography.

PubMed

Lin, Tzu-Kang; Tsai, Hong-Chieh; Hsieh, Tsung-Che

2012-07-01

To clarify the clinical role of traumatic subarachnoid hemorrhage (tSAH), stratified analysis with grouping of tSAH was performed. Their blood flow changes and correlations with outcome were assayed. One hundred seventeen tSAH patients were classified into several groups according to their initial computerized tomography scans. Group I included patients with tSAH only in the posterior interhemispheric fissure, whereas Group II contained patients with tSAH located elsewhere. Group II was further subdivided into IIa, little SAH; IIb, extensive SAH; IIc, little SAH with intraventricular hemorrhage (IVH); and IId, extensive SAH with IVH. The cerebral blood flow velocity was monitored using transcranial Doppler sonography (TCD). Both age and initial coma scale were independent predictors of poor outcome. The poor outcome rates in various subgroups of tSAH increased stepwise from group I to group IId (I, 7.4%; IIa, 18.4%; IIb, 33.3%; IIc, 62.5%; and IId, 90.9%) (p = 0.0010). Stratified analyses revealed that patients with extensive tSAH (group IIb + IId) were more likely to have unfavorable outcomes (47.7%) than patients with little tSAH (group IIa + IIc) (26.1%) (p = 0.0185); patients with IVH (group IIc + IId) also displayed a higher incidence (78.9%) of poor outcomes than patients without IVH (group IIa + IIb) (25.4%) (p = 0.0030). TCD study demonstrated that patients with extensive tSAH (group IIb + IId) were more likely to have the vasospasm based on TCD criteria than did patients in group I and group IIa + IIc (37.5% vs. 5.9% and 7.7%, p = 0.0105). Notably, there was a tendency of worse outcome in patients with vasospasm on the basis of TCD-derived criteria than those without, with the unfavorable outcome rates being 47.4% and 24.7% (p = 0.0799). Age, initial coma scale, extensive tSAH, and IVH are independent predictors of poor outcome in the cohort of tSAH patients. Statistically, patients with extensive tSAH are significantly more likely to have vasospasm.

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

Pötter, Richard; Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Vienna; Federico, Mario

Purpose: To define, in the setting of cervical cancer, to what extent information from additional pretreatment magnetic resonance imaging (MRI) without the brachytherapy applicator improves conformity of CT-based high-risk clinical target volume (CTV{sub HR}) contours, compared with the MRI for various tumor stages (International Federation of Gynecology and Obstetrics [FIGO] stages I-IVA). Methods and Materials: The CTV{sub HR} was contoured in 39 patients with cervical cancer (FIGO stages I-IVA) (1) on CT images based on clinical information (CTV{sub HR}-CT{sub Clinical}) alone; and (2) using an additional MRI before brachytherapy, without the applicator (CTV{sub HR}-CT{sub pre-BT} {sub MRI}). The CT contours were compared withmore » reference contours on MRI with the applicator in place (CTV{sub HR}-MRI{sub ref}). Width, height, thickness, volumes, and topography were analyzed. Results: The CT-MRI{sub ref} differences hardly varied in stage I tumors (n=8). In limited-volume stage IIB and IIIB tumors (n=19), CTV{sub HR}-CT{sub pre-BT} {sub MRI}–MRI{sub ref} volume differences (2.6 cm{sup 3} [IIB], 7.3 cm{sup 3} [IIIB]) were superior to CTV{sub HR}-CT{sub Clinical}–MRI{sub ref} (11.8 cm{sup 3} [IIB], 22.9 cm{sup 3} [IIIB]), owing to significant improvement of height and width (P<.05). In advanced disease (n=12), improved agreement with MR volume, width, and height was achieved for CTV{sub HR}-CT{sub pre-BT} {sub MRI}. In 5 of 12 cases, MRI{sub ref} contours were partly missed on CT. Conclusions: Pre-BT MRI helps to define CTV{sub HR} before BT implantation appropriately, if only CT images with the applicator in place are available for BT planning. Significant improvement is achievable in limited-volume stage IIB and IIIB tumors. In more advanced disease (extensive IIB to IVA), improvement of conformity is possible but may be associated with geographic misses. Limited impact on precision of CTV{sub HR}-CT is expected in stage IB tumors.« less

An uncertainty principle for unimodular quantum groups

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

Crann, Jason; Université Lille 1 - Sciences et Technologies, UFR de Mathématiques, Laboratoire de Mathématiques Paul Painlevé - UMR CNRS 8524, 59655 Villeneuve d'Ascq Cédex; Kalantar, Mehrdad, E-mail: jason-crann@carleton.ca, E-mail: mkalanta@math.carleton.ca

2014-08-15

We present a generalization of Hirschman's entropic uncertainty principle for locally compact Abelian groups to unimodular locally compact quantum groups. As a corollary, we strengthen a well-known uncertainty principle for compact groups, and generalize the relation to compact quantum groups of Kac type. We also establish the complementarity of finite-dimensional quantum group algebras. In the non-unimodular setting, we obtain an uncertainty relation for arbitrary locally compact groups using the relative entropy with respect to the Haar weight as the measure of uncertainty. We also show that when restricted to q-traces of discrete quantum groups, the relative entropy with respect tomore » the Haar weight reduces to the canonical entropy of the random walk generated by the state.« less

[Physical work capacity of ischemic heart disease patients with various types of hyperlipoproteinemias].

PubMed

Zadionchenko, V S; Kopalova, S M

1980-08-01

The results of ergometric examination of 316 patients with chronic coronary insufficiency and various types of hyperlipoproteinemia have shown a clear diminution of physical working capacity in patients with hyperlipidemia as compared to patients with hyperlipidemia as compared to patients in whom the lipid content is within normal values. Working capacity was most diminished in IIa and particularly IIb types of hyperlipoproteinemia; in type IV physical working capacity was not reduced. The effect of hyperlipoproteinemia is most significant in the mildest degree of coronary insufficiency, but reduces or vanishes completely with increasing severity of the disease. An inverse relationship has been established between the value of physical working capacity and the level of cholesterol and beta-lipoproteins and a direct relationship in regard to NEFA concentration. Ergometry in patients with type II hyperlipoproteinemia showed that as compared to patients with normolipemia and type IV hyperlipoproteinemia an equal degree in the severity of the disease, the frequency and marked character of changes on the ECG increase; this evidences a more marked transitory myocardial ischemia.

Blood plasma apolipoproteins A-I and B in different types of hyperlipoproteinaemia: comparative analysis of population groups in Moscow and Prague.

PubMed

Metel'skaya, V A; Ceska, R; Perova, N V; Sobra, J

1988-01-01

The level of blood plasma apolipoproteins A-I and B was studied in Moscow and Prague residents with different types of hyperlipoproteinaemia (HLP). The analysis proceeded in two directions. On the one hand, lipoprotein (LP) spectra in residents of both cities with the same type of LP disturbance (HLP type IIa, IIb or IV) were compared; in Prague lipid and apolipoprotein content was compared in inhabitants with a normal lipid level and those with HLP types I, III and V. The analysis showed that inhabitants of Prague with types II and IV HLP have a higher concentrations of high density LP cholesterol. At the same time, it was found that the apolipoprotein profile of blood plasma LP in HLP patients was similar to that in patients living elsewhere. The authors regard comparative study of LP system disturbances in residents of different cities and countries differing in their geographical, ethnic and ecological conditions as a promising approach to understanding the mechanisms responsible for the development of HLP.

What is the role of endoscopic retrograde cholangiopancreatography in assessing traumatic rupture of the pancreatic in children?

PubMed

Keil, Radan; Drabek, Jiri; Lochmannova, Jindra; Stovicek, Jan; Rygl, Michal; Snajdauf, Jiri; Hlava, Stepan

2016-01-01

Trauma is one of the most common causes of morbidity and mortality in the pediatric population. The diagnosis of pancreatic injury is based on clinical presentation, laboratory and imaging findings, and endoscopic methods. CT scanning is considered the gold standard for diagnosing pancreatic trauma in children. This retrospective study evaluates data from 25 pediatric patients admitted to the University Hospital Motol, Prague, with blunt pancreatic trauma between January 1999 and June 2013. The exact grade of injury was determined by CT scans in 11 patients (47.8%). All 25 children underwent endoscopic retrograde cholangiopancreatography (ERCP). Distal pancreatic duct injury (grade III) was found in 13 patients (52%). Proximal pancreatic duct injury (grade IV) was found in four patients (16 %). Major contusion without duct injury (grade IIB) was found in six patients (24%). One patient experienced duodeno-gastric abruption not diagnosed on the CT scan. The diagnosis was made endoscopically during ERCP. Grade IIB pancreatic injury was found in this patient. One patient (4%) with pancreatic pseudocyst had a major contusion of pancreas without duct injury (grade IIA). Four patients (16%) with grade IIB, III and IV pancreatic injury were treated exclusively and nonoperatively with a pancreatic stent insertion and somatostatine. Two patients (8%) with a grade IIB injury were treated conservatively only with somatostatine without drainage. Eighteen (72 %) children underwent surgical intervention within 24 h after ERCP. ERCP is helpful when there is suspicion of pancreatic duct injury in order to exclude ductal leakage and the possibility of therapeutic intervention. ERCP can speed up diagnosis of higher grade of pancreatic injuries.

Vibrated and self-compacting fibre reinforced concrete: experimental investigation on the fibre orientation

NASA Astrophysics Data System (ADS)

Conforti, A.; Plizzari, G. A.; Zerbino, R.

2017-09-01

In addition to the fibre type and content, the residual properties of fibre reinforced concrete are influenced by fibre orientation. Consequently, the performance fibre reinforced concrete can be affected by its fresh properties (workability, flowing capacity) and by casting and compaction processes adopted. This paper focuses on the study of the orientation of steel or macro-synthetic fibres in two materials characterized by very different fresh properties: vibrated and self-compacting concrete. Four rectangular slabs 1800 mm long, 925 mm wide and 100 mm high were produced changing concrete and fibre type. From each slab, eighteen small prisms (550 mm long) were firstly cut either orthogonal or parallel to casting direction and, secondly, notched and tested in bending according to EN 14651. Experimental results showed that the toughness properties of a thin slab significantly varies both in vibrated and self-compacting concrete, even if in case of self-compacting concrete this variation resulted higher. Steel fibres led to greater variability of results compared to polymer one, underlining a different fibre orientation. A discussion on the relative residual capacity measured on the prisms sawn from the slabs and the parameters obtained from standard specimens is performed.

Meta-analyses and adaptive group sequential designs in the clinical development process.

PubMed

Jennison, Christopher; Turnbull, Bruce W

2005-01-01

The clinical development process can be viewed as a succession of trials, possibly overlapping in calendar time. The design of each trial may be influenced by results from previous studies and other currently proceeding trials, as well as by external information. Results from all of these trials must be considered together in order to assess the efficacy and safety of the proposed new treatment. Meta-analysis techniques provide a formal way of combining the information. We examine how such methods can be used in combining results from: (1) a collection of separate studies, (2) a sequence of studies in an organized development program, and (3) stages within a single study using a (possibly adaptive) group sequential design. We present two examples. The first example concerns the combining of results from a Phase IIb trial using several dose levels or treatment arms with those of the Phase III trial comparing the treatment selected in Phase IIb against a control This enables a "seamless transition" from Phase IIb to Phase III. The second example examines the use of combination tests to analyze data from an adaptive group sequential trial.

Vaccine Therapy and IDO1 Inhibitor INCB024360 in Treating Patients With Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Are in Remission

ClinicalTrials.gov

2013-12-17

Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Epithelial Cancer; Stage IA Primary Peritoneal Cavity Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Epithelial Cancer; Stage IB Primary Peritoneal Cavity Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Epithelial Cancer; Stage IC Primary Peritoneal Cavity Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Primary Peritoneal Cavity Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Primary Peritoneal Cavity Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer

Essential role of protein kinase C delta in platelet signaling, alpha IIb beta 3 activation, and thromboxane A2 release.

PubMed

Yacoub, Daniel; Théorêt, Jean-François; Villeneuve, Louis; Abou-Saleh, Haissam; Mourad, Walid; Allen, Bruce G; Merhi, Yahye

2006-10-06

The protein kinase C (PKC) family is an essential signaling mediator in platelet activation and aggregation. However, the relative importance of the major platelet PKC isoforms and their downstream effectors in platelet signaling and function remain unclear. Using isolated human platelets, we report that PKCdelta, but not PKCalpha or PKCbeta, is required for collagen-induced phospholipase C-dependent signaling, activation of alpha(IIb)beta(3), and platelet aggregation. Analysis of PKCdelta phosphorylation and translocation to the membrane following activation by both collagen and thrombin indicates that it is positively regulated by alpha(IIb)beta(3) outside-in signaling. Moreover, PKCdelta triggers activation of the mitogen-activated protein kinase-kinase (MEK)/extracellular-signal regulated kinase (ERK) and the p38 MAPK signaling. This leads to the subsequent release of thromboxane A(2), which is essential for collagen-induced but not thrombin-induced platelet activation and aggregation. This study adds new insight to the role of PKCs in platelet function, where PKCdelta signaling, via the MEK/ERK and p38 MAPK pathways, is required for the secretion of thromboxane A(2).

Low molecular weight squash trypsin inhibitors from Sechium edule seeds.

PubMed

Laure, Hélen J; Faça, Vítor M; Izumi, Clarice; Padovan, Júlio C; Greene, Lewis J

2006-02-01

Nine chromatographic components containing trypsin inhibitor activity were isolated from Sechium edule seeds by acetone fractionation, gel filtration, affinity chromatography and RP-HPLC in an overall yield of 46% of activity and 0.05% of protein. The components obtained with highest yield of total activity and highest specific activity were sequenced by Edman degradation and their molecular masses determined by mass spectrometry. The inhibitors contained 31, 32 and 27 residues per molecule and their sequences were: SETI-IIa, EDRKCPKILMRCKRDSDCLAKCTCQESGYCG; SETI-IIb, EEDRKCPKILMRCKRDSDCLAKCTCQESGYCG and SETI-V, CPRILMKCKLDTDCFPTCTCRPSGFCG. SETI-IIa and SETI-IIb, which differed by an amino-terminal E in the IIb form, were not separable under the conditions employed. The sequences are consistent with consensus sequences obtained from 37 other inhibitors: CPriI1meCk_DSDCla_C_C_G_CG, where capital letters are invariant amino acid residues and lower case letters are the most preserved in this position. SETI-II and SETI-V form complexes with trypsin with a 1:1 stoichiometry and have dissociation constants of 5.4x10(-11)M and 1.1x10(-9)M, respectively.

Trapping of Neutrinos in Extremely Compact Stars and the Influence of Brane Tension on This Process

NASA Astrophysics Data System (ADS)

Stuchlík, Zdenäěk; Hladík, Jan; Urbanec, Martin

We present estimates on the efficiency of neutrino trapping in brany extremely compact stars, using the simplest model with uniform distribution of energy density, assuming massless neutrinos and uniform distribution of neutrino emissivity. Computation have been done for two different uniform-density stellar solution in the Randall-Sundrum II type braneworld, namely with the Reissner-Nordström-type of geometry and the second one, derived by Germani and Maartens.1

Protein A Sepharose immunoadsorption can restore the efficacy of platelet concentrates in patients with Glanzmann's thrombasthenia and anti-glycoprotein IIb-IIIa antibodies.

PubMed

Martin, Isabelle; Kriaa, Fayçal; Proulle, Valérie; Guillet, Benoît; Kaplan, Cécile; D'Oiron, Roseline; Debré, Marianne; Fressinaud, Edith; Laurian, Yyes; Tchernia, Gil; Charpentier, Bernard; Lambert, Thierry; Dreyfus, Marie

2002-12-01

Type I Glanzmann's thrombasthenia is a rare congenital platelet function disorder, characterized by undetectable platelet membrane glycoprotein IIb-IIIa (GPIIb-IIIa). Severe bleeding is controlled by transfusion of normal platelets, leading in some cases to the occurrence of anti-GPIIb-IIIa isoantibodies, which induces a loss of transfused platelet efficacy. We used immunoadsorption on protein A Sepharose (IA-PA), which has been shown to be efficient in decreasing the titre of antibodies in several immune diseases, in three patients with Glanzmann's thrombasthenia and anti-GPIIb-IIIa isoantibodies on five different occasions. IA-PA was well tolerated with no deleterious side-effects reported. It induced a dramatic decrease of total immunoglobulin (Ig)G, including anti-GPIIb-IIIa isoantibody levels, as assessed by the monoclonal antibody-specific immobilization of platelet antigens test and the ex vivo inhibition of normal platelet aggregation induced by the patient's platelet-rich or platelet-poor plasma. Elimination of the antibody was associated with a correction of the bleeding time following platelet transfusion. IA-PA combined with platelet transfusion made it possible to control two life-threatening haemorrhages, and allowed two surgical procedures and one bone marrow transplantation to be performed safely. Our experience suggests that IA-PA, which restores the haemostatic efficacy of platelet transfusion, is a valuable therapeutic strategy in patients with Glanzmann's thrombasthenia and anti-GPIIb-IIIa isoantibodies.

Environmental impacts of lighting technologies - Life cycle assessment and sensitivity analysis

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

Welz, Tobias; Hischier, Roland, E-mail: Roland.Hischier@empa.ch; Hilty, Lorenz M.

2011-04-15

With two regulations, 244/2009 and 245/2009, the European Commission recently put into practice the EuP Directive in the area of lighting devices, aiming to improve energy efficiency in the domestic lighting sector. This article presents a comprehensive life cycle assessment comparison of four different lighting technologies: the tungsten lamp, the halogen lamp, the conventional fluorescent lamp and the compact fluorescent lamp. Taking advantage of the most up-to-date life cycle inventory database available (ecoinvent data version 2.01), all life cycle phases were assessed and the sensitivity of the results for varying assumptions analysed: different qualities of compact fluorescent lamps (production phase),more » different electricity mixes (use phase), and end-of-life scenarios for WEEE recycling versus municipal solid waste incineration (disposal phase). A functional unit of 'one hour of lighting' was defined and the environmental burdens for the whole life cycle for all four lamp types were calculated, showing a clearly lower impact for the two gas-discharge lamps, i.e. the fluorescent and the compact fluorescent lamp. Differences in the product quality of the compact fluorescent lamps reveal to have only a very small effect on the overall environmental performance of this lamp type; a decline of the actual life time of this lamp type doesn't result in a change of the rank order of the results of the here examined four lamp types. It was also shown that the environmental break-even point of the gas-discharge lamps is reached long before the end of their expected life-span. All in all, it can be concluded that a change from today's tungsten lamp technology to a low-energy-consuming technology such as the compact fluorescent lamp results in a substantial environmental benefit.« less

Towards an explicit model of large field inflation

NASA Astrophysics Data System (ADS)

Dorronsoro, Juan Diaz; Schillo, Marjorie

2018-05-01

The unwinding inflation mechanism is studied in a type IIB flux compactification where all moduli are stabilized using flux, non-perturbative effects, and the leading α' corrections of the large volume scenario. We consider the backreaction on the geometry due to the presence of anti-D3 branes as well as the backreaction of inflation on the Kähler moduli, and compute the resulting corrections to the slow-roll potential. By taking large flux numbers, we are able to find inflationary epochs where backreaction effects are under control, the inflaton traverses a super-Planckian field range, and the resulting amplitude of scalar perturbations is consistent with observation.

EXACT S-MATRICES FOR AdS3/CFT2

NASA Astrophysics Data System (ADS)

Ahn, Changrim; Bombardelli, Diego

2013-12-01

We propose exact S-matrices for the AdS3/CFT2 duality between type IIB strings on AdS3×S3×M4 with M4 = S3×S1 or T4 and the corresponding two-dimensional conformal field theories. We fix the two-particle S-matrices on the basis of the symmetries su(1|1) and su(1|1)×su(1|1). A crucial justification comes from the derivation of the all-loop Bethe ansatz matching exactly the recent conjecture proposed by Babichenko et al. [J. High Energy Phys.1003, 058 (2010), arXiv:0912.1723 [hep-th

Holographic cosmology and phase transitions of SYM theory

NASA Astrophysics Data System (ADS)

Ghoroku, Kazuo; Meyer, René; Toyoda, Fumihiko

2017-10-01

We study the time development of strongly coupled N =4 supersymmetric Yang Mills (SYM) theory on cosmological Friedmann-Robertson-Walker (FRW) backgrounds via the AdS/CFT correspondence. We implement the cosmological background as a boundary metric fulfilling the Friedmann equation with a four-dimensional cosmological constant and a dark radiation term. We analyze the dual bulk solution of the type IIB supergravity and find that the time dependence of the FRW background strongly influences the dynamical properties of the SYM theory. We in particular find a phase transition between a confined and a deconfined phase. We also argue that some cosmological solutions could be related to the inflationary scenario.

Romidepsin and Lenalidomide in Treating Patients With Previously Untreated Peripheral T-Cell Lymphoma

ClinicalTrials.gov

2018-01-05

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Peripheral T-cell Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIA Mycosis Fungoides/Sezary Syndrome; Stage IIB Mycosis Fungoides/Sezary Syndrome; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIIA Mycosis Fungoides/Sezary Syndrome; Stage IIIB Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IVA Mycosis Fungoides/Sezary Syndrome; Stage IVB Mycosis Fungoides/Sezary Syndrome

Grout compactness monitoring of concrete-filled fiber-reinforced polymer tube using electromechanical impedance

NASA Astrophysics Data System (ADS)

Shi, Yaokun; Luo, Mingzhang; Li, Weijie; Song, Gangbing

2018-05-01

The concrete-filled fiber-reinforced polymer tube (CFFT) is a type of structural element widely used in corrosive environments. Poor grout compactness results in incomplete contact or even no contact between the fiber-reinforced polymer (FRP) tube and the concrete grout, which reduces the load bearing capacity of a CFFT. The monitoring of grout compactness for CFFTs is important. The piezoceramic-based electromechanical impedance (EMI) method has emerged as an efficient and low-cost structural health monitoring technique. This paper presents a feasibility study using the EMI method to monitor grout compactness of CFFTs. In this research, CFFT specimens with different levels of compactness (empty, 1/5, 1/3, 1/2, 2/3, and full compactness) were prepared and subjected to EMI measurement by using four piezoceramic patches that were bonded circumferentially along the outer surface of the CFFT. To analyze the correlation between grout compactness and EMI signatures, a compactness index (CI) was proposed based on the root-mean-square deviation (RMSD). The experimental results show that the changes in admittance signatures are able to determine the grout compactness qualitatively. The proposed CI is able to effectively identify the compactness of the CFFT, and provides location information of the incomplete concrete infill.

[Complications of surgical stage of treatment in patients with cancer of cervix uteri stage IIB].

PubMed

Kryzhanivs'ka, A Ie

2013-11-01

The results of treatment of 127 patients, suffering cervix uteri cancer stage IIB in period of 1998 - 2012 yrs, were analyzed. Complications of surgical stage of the combined treatment have had occurred in 40.9% patients, including 40.5% patients, to whom neoadjuvant chemotherapy was conducted and in 41.5%--radiation therapy (RTH). The main postoperative complications--retroperitoneal lymphatic cysts--were revealed in 35.4% patients. The factors, raising the risk of postoperative complications occurrence, are following: the primary tumor spreading, metastatic affection of lymphatic nodes of pelvic cavity, preoperative conduction of RTH or chemotherapy.

The evolution of WRKY transcription factors.

PubMed

Rinerson, Charles I; Rabara, Roel C; Tripathi, Prateek; Shen, Qingxi J; Rushton, Paul J

2015-02-27

The availability of increasing numbers of sequenced genomes has necessitated a re-evaluation of the evolution of the WRKY transcription factor family. Modern day plants descended from a charophyte green alga that colonized the land between 430 and 470 million years ago. The first charophyte genome sequence from Klebsormidium flaccidum filled a gap in the available genome sequences in the plant kingdom between unicellular green algae that typically have 1-3 WRKY genes and mosses that contain 30-40. WRKY genes have been previously found in non-plant species but their occurrence has been difficult to explain. Only two WRKY genes are present in the Klebsormidium flaccidum genome and the presence of a Group IIb gene was unexpected because it had previously been thought that Group IIb WRKY genes first appeared in mosses. We found WRKY transcription factor genes outside of the plant lineage in some diplomonads, social amoebae, fungi incertae sedis, and amoebozoa. This patchy distribution suggests that lateral gene transfer is responsible. These lateral gene transfer events appear to pre-date the formation of the WRKY groups in flowering plants. Flowering plants contain proteins with domains typical for both resistance (R) proteins and WRKY transcription factors. R protein-WRKY genes have evolved numerous times in flowering plants, each type being restricted to specific flowering plant lineages. These chimeric proteins contain not only novel combinations of protein domains but also novel combinations and numbers of WRKY domains. Once formed, R protein WRKY genes may combine different components of signalling pathways that may either create new diversity in signalling or accelerate signalling by short circuiting signalling pathways. We propose that the evolution of WRKY transcription factors includes early lateral gene transfers to non-plant organisms and the occurrence of algal WRKY genes that have no counterparts in flowering plants. We propose two alternative hypotheses of WRKY gene evolution: The "Group I Hypothesis" sees all WRKY genes evolving from Group I C-terminal WRKY domains. The alternative "IIa + b Separate Hypothesis" sees Groups IIa and IIb evolving directly from a single domain algal gene separate from the Group I-derived lineage.

Assessment of Parametrial Response by Growth Pattern in Patients With International Federation of Gynecology and Obstetrics Stage IIB and IIIB Cervical Cancer: Analysis of Patients From a Prospective, Multicenter Trial (EMBRACE)

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

Yoshida, Kenji; Kobe University Graduate School of Medicine, Kobe; Jastaniyah, Noha

Purpose: To assess disease response along the parametrial space according to tumor morphology in patients with International Federation of Gynecology and Obstetrics (FIGO) stage IIB and IIIB cervical cancer at the time of image-guided adaptive brachytherapy. Methods and Materials: Patients with FIGO stage IIB and IIIB cervical cancer registered as of November 2013 in the EMBRACE study were evaluated. Tumors were stratified according to morphologic subtype on magnetic resonance imaging (expansive and infiltrative), and the characteristics of those subtypes were analyzed. Parametrial involvement at diagnosis and at brachytherapy was evaluated, and the response to chemo-radiotherapy was classified as good, moderate,more » or poor. The response grade was compared between the 2 groups and analyzed with regard to tumor volumes, and dosimetric parameters. Results: A total of 452 patients were evaluated, of whom 186 had expansive growth type and 266 had infiltrative morphology. Patients with infiltrative tumors had more extensive disease, as indicated by a higher rate of FIGO stage IIIB disease, as well as radiologic evidence of extension into the distal parametrial space and to the pelvic side wall on magnetic resonance imaging. Cervical necrosis was more common in the infiltrative group. Good response was more common in the expansive group (34% vs 24%; P=.02), and poor response was more common in the infiltrative group (11% and 19%; P=.02). Mean gross tumor volume at diagnosis was equal in both groups (51.7 cm{sup 3}). The high-risk clinical target volume was larger in infiltrative tumors (37.9 cm{sup 3} vs 33.3 cm{sup 3}, P=.005). The mean high-risk clinical target volume D{sub 90} was slightly higher in expansive tumors (92.7 Gy and 89.4 Gy, P<.001). Conclusion: Infiltrative tumors are more advanced at presentation and respond less favorably to chemo-radiotherapy when compared with expansive tumors that are more or less equivalent in size. The use of image-guided adaptive brachytherapy allows achieving reasonably high doses in both groups.« less

A macromolecular crowding study of RNA folding and activity: polymer pore size matters! (Conference Presentation)

NASA Astrophysics Data System (ADS)

Börner, Richard; Fiorini, Erica; Paudel, Bishnu; Rueda, David; Sigel, Roland K. O.

2016-03-01

Catalytic RNAs, like the group IIB intron ribozyme of S. cerevesiae, require a high magnesium(II) concentration to show folding and function in vitro [1]. In contrast, in vivo conditions are characterized by a highly crowded cellular environment and much lower ion concentration. Molecular crowding agents are a widespread tool to mimic cellular crowding [2]. However, particular physical/chemical properties explaining the crowders influence are mostly not understood. In this study, we gain new insights on how polymer properties like viscosity, pore size etc. influence the activity and folding of a large RNA. We combined bulk activity assays and single-molecule Förster Resonance Energy Transfer experiments, screening the PEG volume fraction (%) and molecular weight (MW). Our results revealed that upon the influence of crowding agents, a compaction of the underlying structure depends on the PEG % and the presence of different PEG MW and % unveiled an optimal pore size in terms of catalytic activity. In summary, an increasing density of the crowding environment shifts the RNA towards the most compact state, but the ribozyme is only active if the crowders network matches its size [4]. We interpret the most compact state as necessary, but not sufficient, to keep the ribozyme active. Financial support from the European Research Council (MIRNA N° 259092, to RKOS), the Swiss National Fund (SNF), and the Forschungskredit Grant of the University of Zürich (FK-14-096 and 15-092 to RB) are gratefully acknowledged. [1] Swisher J.F., Su L.J., Brenowitz M., Anderson V.E., Pyle A.M., J. Mol. Bio., 315, 297-310 (2002). [2] Kilburn D., Roh J.H., Guo L., Briber R.M., Woodson S.A., JACS, 132, 8690-6 (2010). [3] Steiner M., Karunatilaka K.S., Sigel R.K.O., Rueda D., Proc. Natl. Acad. Sci. U.S.A.,105, 13853-8 (2008). [4] aBörner R, Fiorini E, Sigel R.K.O., Chimia, 69, 207-212 (2015).; bFiorini E., Paudel B., Börner R., Rueda D., Sigel R.K.O., submitted. [5] König S.L.B., Hadzic M., Fiorini E., Börner R., Kowerko D., Blanckenhorn W.U., Sigel R.K.O., PLoS ONE, 8, e84157 (2013).

Partial transformation from fast to slow muscle fibers induced by deafferentation of capsaicin-sensitive muscle afferents.

PubMed

Brunetti, O; Barazzoni, A M; Della Torre, G; Clavenzani, P; Pettorossi, V E; Bortolami, R

1997-11-01

Mechanical and histochemical characteristics of the lateral gastrocnemius (LG) muscle of the rat were examined 21 days after capsaicin injection into the LG muscle. The capsaicin caused a decrease in generation rate of twitch and tetanic tension and an increase in fatigue resistance of LG muscle. The histochemical muscle fiber profile evaluated by myosin adenosine triphosphatase and reduced nicotinamide adenine dinucleotide tetrazolium reductase methods showed an increase of type I and IIC fibers and a decrease of the type IIB in whole muscle, and a decrease of the IIA, IIX fibers in the red part accompanied by their increase in the white part. Therefore the capsaicin treatment, which selectively eliminated fibers belonging to the III and IV groups of muscle afferents, induced muscle fiber transformation from fast contracting fatiguing fibers to slowly contracting nonfatiguing ones.

[Types of dislipidemia in children with metabolic syndrome].

PubMed

Hromnats'ka, N M

2014-01-01

To study dyslipidemia types in children with metabolic syndrome. From 1520 children of total population 155 children aged from 9 to 18 years were selected, who formed 2 groups: 1 group--85 children with metabolic syndrome, 2 group--54 children with normal body mass. Anthropometry, blood pressure measurement, estimation of total cholesterol, low density cholesterol, very low density cholesterol, high density cholesterol, tryglicerides in blood were done. The total cholesterol level was 1,1 times higher (p = 0.001), low density cholesterol 1,4 times higher (p = 0.001), very low density cholesterol 1,1 times higher (p= 0.015), tryglicerides 1,1 times higher (p = 0.020) in children with metabolic syndrome than in children of control group. In children with metabolic syndrome sensitively more often IIa, IV dislipidemia types and isolated hypercholesterolemia and less often IIb, III dislipidemia types and high density cholesterol isolated decrease were diagnosed. So children with metabolic syndrome were characterized by atherogenic types of dislipidemias which determine early atherosclerosis development. Children with metabolic syndrome must be examined on the lipid metabolism violation with the aim of its prevention and correction.

Qubit and fermionic Fock spaces from type II superstring black holes

NASA Astrophysics Data System (ADS)

Belhaj, A.; Bensed, M.; Benslimane, Z.; Sedra, M. B.; Segui, A.

Using Hodge diagram combinatorial data, we study qubit and fermionic Fock spaces from the point of view of type II superstring black holes based on complex compactifications. Concretely, we establish a one-to-one correspondence between qubits, fermionic spaces and extremal black holes in maximally supersymmetric supergravity obtained from type II superstring on complex toroidal and Calabi-Yau compactifications. We interpret the differential forms of the n-dimensional complex toroidal compactification as states of n-qubits encoding information on extremal black hole charges. We show that there are 2n copies of n qubit systems which can be split as 2n = 2n-1 + 2n-1. More precisely, 2n-1 copies are associated with even D-brane charges in type IIA superstring and the other 2n-1 ones correspond to odd D-brane charges in IIB superstring. This correspondence is generalized to a class of Calabi-Yau manifolds. In connection with black hole charges in type IIA superstring, an n-qubit system has been obtained from a canonical line bundle of n factors of one-dimensional projective space ℂℙ1.

Partial Diversity Generates Effector Immunity Specificity of the Bac41-Like Bacteriocins of Enterococcus faecalis Clinical Strains.

PubMed

Kurushima, Jun; Ike, Yasuyoshi; Tomita, Haruyoshi

2016-09-01

Bacteriocin 41 (Bac41) is the plasmid-encoded bacteriocin produced by the opportunistic pathogen Enterococcus faecalis Its genetic determinant consists of bacL1 (effector), bacL2 (regulator), bacA (effector), and bacI (immunity). The secreted effectors BacL1 and BacA coordinate to induce the lytic cell death of E. faecalis Meanwhile, the immunity factor BacI provides self-resistance to the Bac41 producer, E. faecalis, against the action of BacL1 and BacA. In this study, we demonstrated that more than half of the 327 clinical strains of E. faecalis screened had functional Bac41 genes. Analysis of the genetic structure of the Bac41 genes in the DNA sequences of the E. faecalis strains revealed that the Bac41-like genes consist of a relatively conserved region and a variable region located downstream from bacA Based on similarities in the variable region, the Bac41-like genes could be classified into type I, type IIa, and type IIb. Interestingly, the distinct Bac41 types had specific immunity factors for self-resistance, BacI1 or BacI2, and did not show cross-immunity to the other type of effector. We also demonstrated experimentally that the specificity of the immunity was determined by the combination of the C-terminal region of BacA and the presence of the unique BacI1 or BacI2 factor. These observations suggested that Bac41-like bacteriocin genes are extensively disseminated among E. faecalis strains in the clinical environment and can be grouped into at least three types. It was also indicated that the partial diversity results in specificity of self-resistance which may offer these strains a competitive advantage. Bacteriocins are antibacterial effectors produced by bacteria. In general, a bacteriocin-coding gene is accompanied by a cognate immunity gene that confers self-resistance on the bacteriocin-producing bacterium itself. We demonstrated that one of the bacteriocins, Bac41, is disseminated among E. faecalis clinical strains and the Bac41 subtypes with partial diversity. The Bac41-like bacteriocins were found to be classified into type I, type IIa, and type IIb by variation of the cognate immunity factors. The antibacterial activity of the respective effectors was specifically inhibited by the immunity factor from the same type of Bac41 but not the other types. This specificity of effector-immunity pairs suggests that bacteriocin genes might have evolved to change the immunity specificity to acquire an advantage in interbacterial competition. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Abelian gauge symmetries in F-theory and dual theories

NASA Astrophysics Data System (ADS)

Song, Peng

In this dissertation, we focus on important physical and mathematical aspects, especially abelian gauge symmetries, of F-theory compactifications and its dual formulations within type IIB and heterotic string theory. F-theory is a non-perturbative formulation of type IIB string theory which enjoys important dualities with other string theories such as M-theory and E8 x E8 heterotic string theory. One of the main strengths of F-theory is its geometrization of many physical problems in the dual string theories. In particular, its study requires a lot of mathematical tools such as advanced techniques in algebraic geometry. Thus, it has also received a lot of interests among mathematicians, and is a vivid area of research within both the physics and the mathematics community. Although F-theory has been a long-standing theory, abelian gauge symmetry in Ftheory has been rarely studied, until recently. Within the mathematics community, in 2009, Grassi and Perduca first discovered the possibility of constructing elliptically fibered varieties with non-trivial toric Mordell-Weil group. In the physics community, in 2012, Morrison and Park first made a major advancement by constructing general F-theory compactifications with U(1) abelian gauge symmetry. They found that in such cases, the elliptically-fibered Calabi-Yau manifold that F-theory needs to be compactified on has its fiber being a generic elliptic curve in the blow-up of the weighted projective space P(1;1;2) at one point. Subsequent developments have been made by Cvetic, Klevers and Piragua extended the works of Morrison and Park and constructed general F-theory compactifications with U(1) x U(1) abelian gauge symmetry. They found that in the U(1) x U(1) abelian gauge symmetry case, the elliptically-fibered Calabi-Yau manifold that F-theory needs to be compactified on has its fiber being a generic elliptic curve in the del Pezzo surface dP2. In chapter 2 of this dissertation, I bring this a step further by constructing general F-theory compactifications with U(1) x U(1) x U(1) abelian gauge symmetry. In chapter 1 of this dissertation, I proved finiteness of a region of the string landscape in Type IIB compactifications. String compactifications give rise to a collection of effective low energy theories, known as the string landscape. In chapter 3 of this dissertation, I study abelian gauge symmetries in the duality between F-theory and E8 x E8 heterotic string theory. However, how abelian gauge symmetries can arise in the dual heterotic string theory has never been studied. The main goal of this chapter is to study exactly this. We start with F-theory compactifications with abelian gauge symmetry. With the help of a mathematical lemma as well as a computer code that I came up with, I was able to construct a rich list of specialized examples with specific abelian and nonabelian gauge groups on the F-theory side. (Abstract shortened by ProQuest.).

Active Galactic Nuclei and X-ray Ovservations

NASA Astrophysics Data System (ADS)

Vasylenko, A. A.; Zhdanov, V. I.; Fedorova, E. V.

2016-11-01

Active galactic nuclei (AGN) are the brightest objects in the Universe and their brightness is mainly caused by accretion of m atter onto supermassive black holes (SMBH). This is the common reason of the AGN activity. However, every AGN has differences and fine features, which are the subject of an intensive investigation. The occurrence of such highly-relativistic objects as SMBH residing at the AGN core makes them an excellent laboratory for testing the fundamental physical theories. The X-rays and gamma-rays generated in a corona of an accretion disc around SMBH yield valuable information for these tests, the radiation in the range of 1-100 keV being at present the most informative source. However, there are a number of obstacles for such a study due to different physical processes that complicate the interpretation of observations in different bands of the electromagnetic radiation. In this paper, we review the current concepts concerning the structure of AGNs with a focus on the central part of these objects th at require relativistic theories for their understanding. The basic notions of the unified AGN schemes are considered; some modifications are reviewed. The paper contains the following sections. I. Introduction; II. Observational manifestations and classification of galaxies with active nuclei (II.A. Optical observations; II.B. Radio observations; II.C. X-ray data; II.D Infrared data; II.E. AGN anatomy with multywave data); III. AGN "central machine"; III.A. Black holes; III.B. Accretion disc types; III.C. Corona; III.D. AGN unified scheme); IV. Simulation X-ray AGN spectra (IV.A. The power-law contimuum and the exponential cut-off; IV.B. The absorption of X-rays; IV.C. Reflection; IV.D. Fe K a line; IV.E. Spin paradigm); V. AGN as a laboratory to test the fundamental interactions (V.A. Strong gravitational fields; V.B. Dynamic dark energy near compact astrophysical objects

Kinetic Characterization of Nonmuscle Myosin IIB at the Single Molecule Level*

PubMed Central

Nagy, Attila; Takagi, Yasuharu; Billington, Neil; Sun, Sara A.; Hong, Davin K. T.; Homsher, Earl; Wang, Aibing; Sellers, James R.

2013-01-01

Nonmuscle myosin IIB (NMIIB) is a cytoplasmic myosin, which plays an important role in cell motility by maintaining cortical tension. It forms bipolar thick filaments with ∼14 myosin molecule dimers on each side of the bare zone. Our previous studies showed that the NMIIB is a moderately high duty ratio (∼20–25%) motor. The ADP release step (∼0.35 s−1) of NMIIB is only ∼3 times faster than the rate-limiting phosphate release (0.13 ± 0.01 s−1). The aim of this study was to relate the known in vitro kinetic parameters to the results of single molecule experiments and to compare the kinetic and mechanical properties of single- and double-headed myosin fragments and nonmuscle IIB thick filaments. Examination of the kinetics of NMIIB interaction with actin at the single molecule level was accomplished using total internal reflection fluorescence (TIRF) with fluorescence imaging with 1-nm accuracy (FIONA) and dual-beam optical trapping. At a physiological ATP concentration (1 mm), the rate of detachment of the single-headed and double-headed molecules was similar (∼0.4 s−1). Using optical tweezers we found that the power stroke sizes of single- and double-headed heavy meromyosin (HMM) were each ∼6 nm. No signs of processive stepping at the single molecule level were observed in the case of NMIIB-HMM in optical tweezers or TIRF/in vitro motility experiments. In contrast, robust motility of individual fluorescently labeled thick filaments of full-length NMIIB was observed on actin filaments. Our results are in good agreement with the previous steady-state and transient kinetic studies and show that the individual nonprocessive nonmuscle myosin IIB molecules form a highly processive unit when polymerized into filaments. PMID:23148220

Action of thrombopoietin at the megakaryocyte progenitor level is critical for the subsequent proplatelet production.

PubMed

Horie, K; Miyazaki, H; Hagiwara, T; Tahara, E; Matsumoto, A; Kadoya, T; Ogami, K; Kato, T

1997-02-01

Formation of proplatelets from megakaryocytes is believed to be the first step of platelet production in vitro. In this study, we evaluated the effects of recombinant human thrombopoietin (hTPO) on the development of proplatelets from a GpIIb/IIIa+ population of rat bone marrow cells highly enriched for late megakaryocyte progenitors (GpIIb/IIIa+ CFU-MK) that we recently found to be a primary target population of TPO. Quantitative measurement of hTPO-induced proplatelet formation was performed in liquid cultures. Proplatelet formation from megakaryocytes derived from GpIIb/IIIa+ CFU-MK in the presence of hTPO began on day 4 of culture and peaked the following day. On day 5 of culture, lower concentrations of hTPO expanded the number of megakaryocytes, increased the number of proplatelets and the percentage of proplatelet-developing megakaryocytes. Increasing hTPO concentrations resulted in a modest decrease in proplatelet development. We next used hTPO to derive immature or mature megakaryocytes from GpIIb/IIIa+ CFU-MK. These populations of cultured megakaryocytes spontaneously formed proplatelets when recultured in the absence of exogenous hTPO. The addition of hTPO at higher concentrations modestly augmented proplatelet production from immature megakaryocytes derived from 2-day liquid cultures. However, either murine interleukin-6 (IL-6) or human IL-11, but not rat IL-3, was more potent than hTPO in augmenting proplatelet formation from immature megakaryocytes. Each of these four cytokines had an inhibitory effect on proplatelet formation from more differentiated megakaryocytes derived from 3-day liquid cultures. These results indicate that TPO enhances proplatelet production primarily by stimulating CFU-MK to increase the number of proplatelet-forming megakaryocytes and that its action is clearly different from those of other cytokines that also stimulate megakaryocytopoiesis.

Arf6 controls platelet spreading and clot retraction via integrin αIIbβ3 trafficking

PubMed Central

Huang, Yunjie; Joshi, Smita; Xiang, Binggang; Kanaho, Yasunori; Li, Zhenyu; Bouchard, Beth A.; Moncman, Carole L.

2016-01-01

Platelet and megakaryocyte endocytosis is important for loading certain granule cargo (ie, fibrinogen [Fg] and vascular endothelial growth factor); however, the mechanisms of platelet endocytosis and its functional acute effects are understudied. Adenosine 5'-diphosphate–ribosylation factor 6 (Arf6) is a small guanosine triphosphate–binding protein that regulates endocytic trafficking, especially of integrins. To study platelet endocytosis, we generated platelet-specific Arf6 knockout (KO) mice. Arf6 KO platelets had less associated Fg suggesting that Arf6 affects αIIbβ3-mediated Fg uptake and/or storage. Other cargo was unaffected. To measure Fg uptake, mice were injected with biotinylated- or fluorescein isothiocyanate (FITC)–labeled Fg. Platelets from the injected Arf6 KO mice showed lower accumulation of tagged Fg, suggesting an uptake defect. Ex vivo, Arf6 KO platelets were also defective in FITC-Fg uptake and storage. Immunofluorescence analysis showed initial trafficking of FITC-Fg to a Rab4-positive compartment followed by colocalization with Rab11-positive structures, suggesting that platelets contain and use both early and recycling endosomes. Resting and activated αIIbβ3 levels, as measured by flow cytometry, were unchanged; yet, Arf6 KO platelets exhibited enhanced spreading on Fg and faster clot retraction. This was not the result of alterations in αIIbβ3 signaling, because myosin light-chain phosphorylation and Rac1/RhoA activation were unaffected. Consistent with the enhanced clot retraction and spreading, Arf6 KO mice showed no deficits in tail bleeding or FeCl3-induced carotid injury assays. Our studies present the first mouse model for defining the functions of platelet endocytosis and suggest that altered integrin trafficking may affect the efficacy of platelet function. PMID:26738539

Arf6 controls platelet spreading and clot retraction via integrin αIIbβ3 trafficking.

PubMed

Huang, Yunjie; Joshi, Smita; Xiang, Binggang; Kanaho, Yasunori; Li, Zhenyu; Bouchard, Beth A; Moncman, Carole L; Whiteheart, Sidney W

2016-03-17

Platelet and megakaryocyte endocytosis is important for loading certain granule cargo (ie, fibrinogen [Fg] and vascular endothelial growth factor); however, the mechanisms of platelet endocytosis and its functional acute effects are understudied. Adenosine 5'-diphosphate-ribosylation factor 6 (Arf6) is a small guanosine triphosphate-binding protein that regulates endocytic trafficking, especially of integrins. To study platelet endocytosis, we generated platelet-specific Arf6 knockout (KO) mice. Arf6 KO platelets had less associated Fg suggesting that Arf6 affects αIIbβ3-mediated Fg uptake and/or storage. Other cargo was unaffected. To measure Fg uptake, mice were injected with biotinylated- or fluorescein isothiocyanate (FITC)-labeled Fg. Platelets from the injected Arf6 KO mice showed lower accumulation of tagged Fg, suggesting an uptake defect. Ex vivo, Arf6 KO platelets were also defective in FITC-Fg uptake and storage. Immunofluorescence analysis showed initial trafficking of FITC-Fg to a Rab4-positive compartment followed by colocalization with Rab11-positive structures, suggesting that platelets contain and use both early and recycling endosomes. Resting and activated αIIbβ3 levels, as measured by flow cytometry, were unchanged; yet, Arf6 KO platelets exhibited enhanced spreading on Fg and faster clot retraction. This was not the result of alterations in αIIbβ3 signaling, because myosin light-chain phosphorylation and Rac1/RhoA activation were unaffected. Consistent with the enhanced clot retraction and spreading, Arf6 KO mice showed no deficits in tail bleeding or FeCl3-induced carotid injury assays. Our studies present the first mouse model for defining the functions of platelet endocytosis and suggest that altered integrin trafficking may affect the efficacy of platelet function. © 2016 by The American Society of Hematology.

Genetic Analysis of the Role of Protein Kinase Cθ in Platelet Function and Thrombus Formation

PubMed Central

Hall, Kellie J.; Harper, Matthew T.; Gilio, Karen; Cosemans, Judith M.; Heemskerk, Johan W. M.; Poole, Alastair W.

2008-01-01

Background PKCθ is a novel protein kinase C isozyme, predominately expressed in T cells and platelets. PKCθ−/− T cells exhibit reduced activation and PKCθ−/− mice are resistant to autoimmune disease, making PKCθ an attractive therapeutic target for immune modulation. Collagen is a major agonist for platelets, operating through an immunoreceptor-like signalling pathway from its receptor GPVI. Although it has recently been shown that PKCθ positively regulates outside-in signalling through integrin αIIbβ3 in platelets, the role of PKCθ in GPVI-dependent signalling and functional activation of platelets has not been assessed. Methodology/Principal Findings In the present study we assessed static adhesion, cell spreading, granule secretion, integrin αIIbβ3 activation and platelet aggregation in washed mouse platelets lacking PKCθ. Thrombus formation on a collagen-coated surface was assessed in vitro under flow. PKCθ−/− platelets exhibited reduced static adhesion and filopodia generation on fibrinogen, suggesting that PKCθ positively regulates outside-in signalling, in agreement with a previous report. In contrast, PKCθ−/− platelets also exhibited markedly enhanced GPVI-dependent α-granule secretion, although dense granule secretion was unaffected, suggesting that PKCθ differentially regulates these two granules. Inside-out regulation of αIIbβ3 activation was also enhanced downstream of GPVI stimulation. Although this did not result in increased aggregation, importantly thrombus formation on collagen under high shear (1000 s−1) was enhanced. Conclusions/Significance These data suggest that PKCθ is an important negative regulator of thrombus formation on collagen, potentially mediated by α-granule secretion and αIIbβ3 activation. PKCθ therefore may act to restrict thrombus growth, a finding that has important implications for the development and safe clinical use of PKCθ inhibitors. PMID:18815612

Multicenter phase II study of apatinib, a novel VEGFR inhibitor in heavily pretreated patients with metastatic triple-negative breast cancer.

PubMed

Hu, Xichun; Zhang, Jian; Xu, Binghe; Jiang, Zefei; Ragaz, Joseph; Tong, Zhongsheng; Zhang, Qingyuan; Wang, Xiaojia; Feng, Jifeng; Pang, Danmei; Fan, Minhao; Li, Jin; Wang, Biyun; Wang, Zhonghua; Zhang, Qunling; Sun, Si; Liao, Chunmei

2014-10-15

Apatinib is an oral, highly potent tyrosine-kinase inhibitor targeting VEGFR2. Phase I study showed the recommended dose of 750 mg/day with substantial antitumor activity. This phase II study aims to evaluate the optimum dose level for the efficacy and safety of apatinib monotherapy in heavily pretreated patients with metastatic triple negative breast cancer (mTNBC) in China. Phase IIa was first performed among 25 patients previously treated with anthracycline and/or taxane. All patients received apatinib 750 mg/day p.o. in a 4-week cycle. Subsequently, a phase IIb study of 59 patients was activated, with the endpoint progression-free survival (PFS). The dosage of drug for the Phase IIb was determined according to safety, tolerability and efficacy from the phase IIa study. As a result of toxicity associated with the 750 mg dose in phase IIa, the recommended initial dose of apatinib in the phase IIb was 500 mg/day. In phase IIb, grade 3/4 hematologic toxicities were thrombocytopenia (13.6%), leukopenia (6.8%), neutropenia (3.4%) and anemia (1.7%). The most frequent grade 3/4 nonhematologic toxicities were hand-foot syndrome, proteinuria, hypertension, and increased ALT. In the 56 evaluable patients, overall response rate and clinical benefit rate (CBR) were 10.7 and 25.0%, respectively. Median PFS and overall survival were 3.3 (95% CI 1.7-5.0) and 10.6 (95% CI 5.6-15.7) months, respectively. Our results indicate that apatinib dose of 500 mg rather than 750 mg is the recommended starting dose for the heavily pretreated mTNBC patients with measurable rate of partial response and PFS. © 2014 UICC.

Radiotherapy Treatment Planning for Testicular Seminoma

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

Wilder, Richard B., E-mail: richardbwilder@yahoo.com; Buyyounouski, Mark K.; Efstathiou, Jason A.

2012-07-15

Virtually all patients with Stage I testicular seminoma are cured regardless of postorchiectomy management. For patients treated with adjuvant radiotherapy, late toxicity is a major concern. However, toxicity may be limited by radiotherapy techniques that minimize radiation exposure of healthy normal tissues. This article is an evidence-based review that provides radiotherapy treatment planning recommendations for testicular seminoma. The minority of Stage I patients who choose adjuvant treatment over surveillance may be considered for (1) para-aortic irradiation to 20 Gy in 10 fractions, or (2) carboplatin chemotherapy consisting of area under the curve, AUC = 7 Multiplication-Sign 1-2 cycles. Two-dimensional radiotherapymore » based on bony anatomy is a simple and effective treatment for Stage IIA or IIB testicular seminoma. Centers with expertise in vascular and nodal anatomy may consider use of anteroposterior-posteroanterior fields based on three-dimensional conformal radiotherapy instead. For modified dog-leg fields delivering 20 Gy in 10 fractions, clinical studies support placement of the inferior border at the top of the acetabulum. Clinical and nodal mapping studies support placement of the superior border of all radiotherapy fields at the top of the T12 vertebral body. For Stage IIA and IIB patients, an anteroposterior-posteroanterior boost is then delivered to the adenopathy with a 2-cm margin to the block edge. The boost dose consists of 10 Gy in 5 fractions for Stage IIA and 16 Gy in 8 fractions for Stage IIB. Alternatively, bleomycin, etoposide, and cisplatin chemotherapy for 3 cycles or etoposide and cisplatin chemotherapy for 4 cycles may be delivered to Stage IIA or IIB patients (e.g., if they have a horseshoe kidney, inflammatory bowel disease, or a history of radiotherapy).« less

Design and analysis report for the flight weight 20-inch Columbium secondary nozzle for the RL10 engine

NASA Technical Reports Server (NTRS)

Castro, J. H.

1989-01-01

Pratt & Whitney (P and W) is currently under contract to NASA-LeRC for a multi-year program to evaluate the feasibility of the RL10-IIB/IIC engine models and the various improvements which broaden the engine capabilities and range of applications. The features being evaluated include the operation of the RL10 engine at low thrust levels and/or high mixture ratio levels and the addition of a high area ratio (250:1) translating nozzle to the engine to increase its specific impulse while shortening the installed engine length. The translating nozzle for the RL10-IIB/IIC engine is approximately 55 inches long with an exit plane diameter of 71 inches and an inlet plane diameter of 40 inches. This report documents the design and analysis work done investigating a small subscale Columbium nozzle which could be built and tested to provide findings which then could be incorporated into the high area ratio nozzle final design for the RL10-IIB/IIC engine. This report documents the design and analysis work done investigating a small subscale Columbium nozzle which could be built and tested to provide findings which then could be incorporated into the high area ratio nozzle final design for the RL10-IIB/IIC engine. The length of the subscale nozzle is 20 in.; its exit diameter is 46 in. With the nozzle in the stowed position, an RL10A-3-3A engine system is 70 inches long (Area Ratio = 61:1); with the nozzle deployed the engine length and area ratio are increased to 90 inches and 83:1 respectively. The increase in area ratio provides a calculated increase of 7 + or - 1 second of specific impulse.

Concurrent Chemoradiotherapy With Paclitaxel and Nedaplatin Followed by Consolidation Chemotherapy in Locally Advanced Squamous Cell Carcinoma of the Uterine Cervix: Preliminary Results of a Phase II Study

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

Zhang Meiqin, E-mail: pianozmq@hotmail.co; Liu Suping; Wang, Xiang-E.

Purpose: To evaluate the efficacy and toxicities of concurrent chemoradiotherapy (CCRT) and consolidation chemotherapy in patients with locally advanced squamous cell cervical carcinoma. Methods and Materials: Patients with LASCC (FIGO Stage IIB-IIIB) were treated with pelvic external beam radiotherapy (45 Gy for Stage IIB and 50 Gy for Stage III) and high-dose-rate intracavitary brachytherapy (50 Gy for Stage IIB and 35 Gy for Stage III). The cumulative dose at point A was 50 Gy for Stage IIB and 65 Gy for Stage III. Concurrent chemotherapy with paclitaxel (35 mg/m{sup 2}) and nedaplatin (20 mg/m{sup 2}) was given every week formore » 6 weeks. Consolidation chemotherapy with paclitaxel (135 mg/m{sup 2}) and nedaplatin (60 mg/m{sup 2}) was administered every 3 weeks for 4 cycles. Results: All patients completed CCRT, and 28 of 34 patients completed consolidation chemotherapy. The complete response rate was 88% (95% CI, 73-96%). The most common Grade 3 or higher toxicities were leukopenia/neutropenia (10.9% of the cycles). During a median follow up of 23 months (range, 14-30 months), 5 patients had locoregional failure and 1 patient had distant metastasis. The estimated 2-year progression-free survival and overall survival were 82% (95% CI, 68-95%) and 93% (95% CI, 83-100%), respectively. Grade 3 late complications occurred in 3 patients (9%). Conclusions: CCRT with paclitaxel and nedaplatin followed by consolidation chemotherapy is well tolerated and effective in patients with locally advanced squamous cell cervical carcinoma. Further randomized trials of comparing this regimen with the standard treatment are worth while.« less

Adaptive functional specialisation of architectural design and fibre type characteristics in agonist shoulder flexor muscles of the llama, Lama glama.

PubMed

Graziotti, Guillermo H; Chamizo, Verónica E; Ríos, Clara; Acevedo, Luz M; Rodríguez-Menéndez, J M; Victorica, C; Rivero, José-Luis L

2012-08-01

Like other camelids, llamas (Lama glama) have the natural ability to pace (moving ipsilateral limbs in near synchronicity). But unlike the Old World camelids (bactrian and dromedary camels), they are well adapted for pacing at slower or moderate speeds in high-altitude habitats, having been described as good climbers and used as pack animals for centuries. In order to gain insight into skeletal muscle design and to ascertain its relationship with the llama's characteristic locomotor behaviour, this study examined the correspondence between architecture and fibre types in two agonist muscles involved in shoulder flexion (M. teres major - TM and M. deltoideus, pars scapularis - DS and pars acromialis - DA). Architectural properties were found to be correlated with fibre-type characteristics both in DS (long fibres, low pinnation angle, fast-glycolytic fibre phenotype with abundant IIB fibres, small fibre size, reduced number of capillaries per fibre and low oxidative capacity) and in DA (short fibres, high pinnation angle, slow-oxidative fibre phenotype with numerous type I fibres, very sparse IIB fibres, and larger fibre size, abundant capillaries and high oxidative capacity). This correlation suggests a clear division of labour within the M. deltoideus of the llama, DS being involved in rapid flexion of the shoulder joint during the swing phase of the gait, and DA in joint stabilisation during the stance phase. However, the architectural design of the TM muscle (longer fibres and lower fibre pinnation angle) was not strictly matched with its fibre-type characteristics (very similar to those of the postural DA muscle). This unusual design suggests a dual function of the TM muscle both in active flexion of the shoulder and in passive support of the limb during the stance phase, pulling the forelimb to the trunk. This functional specialisation seems to be well suited to a quadruped species that needs to increase ipsilateral stability of the limb during the support phase of the pacing gait. Compared with other species, llama skeletal muscles are well suited for greater force generation combined with higher fatigue resistance during exercise. These characteristics are interpreted as being of high adaptive value, given the llama's habitat and its use as a pack animal. © 2012 The Authors. Journal of Anatomy © 2012 Anatomical Society.

Adaptive functional specialisation of architectural design and fibre type characteristics in agonist shoulder flexor muscles of the llama, Lama glama

PubMed Central

Graziotti, Guillermo H; Chamizo, Verónica E; Ríos, Clara; Acevedo, Luz M; Rodríguez-Menéndez, J M; Victorica, C; Rivero, José-Luis L

2012-01-01

Like other camelids, llamas (Lama glama) have the natural ability to pace (moving ipsilateral limbs in near synchronicity). But unlike the Old World camelids (bactrian and dromedary camels), they are well adapted for pacing at slower or moderate speeds in high-altitude habitats, having been described as good climbers and used as pack animals for centuries. In order to gain insight into skeletal muscle design and to ascertain its relationship with the llama’s characteristic locomotor behaviour, this study examined the correspondence between architecture and fibre types in two agonist muscles involved in shoulder flexion (M. teres major – TM and M. deltoideus, pars scapularis – DS and pars acromialis – DA). Architectural properties were found to be correlated with fibre-type characteristics both in DS (long fibres, low pinnation angle, fast-glycolytic fibre phenotype with abundant IIB fibres, small fibre size, reduced number of capillaries per fibre and low oxidative capacity) and in DA (short fibres, high pinnation angle, slow-oxidative fibre phenotype with numerous type I fibres, very sparse IIB fibres, and larger fibre size, abundant capillaries and high oxidative capacity). This correlation suggests a clear division of labour within the M. deltoideus of the llama, DS being involved in rapid flexion of the shoulder joint during the swing phase of the gait, and DA in joint stabilisation during the stance phase. However, the architectural design of the TM muscle (longer fibres and lower fibre pinnation angle) was not strictly matched with its fibre-type characteristics (very similar to those of the postural DA muscle). This unusual design suggests a dual function of the TM muscle both in active flexion of the shoulder and in passive support of the limb during the stance phase, pulling the forelimb to the trunk. This functional specialisation seems to be well suited to a quadruped species that needs to increase ipsilateral stability of the limb during the support phase of the pacing gait. Compared with other species, llama skeletal muscles are well suited for greater force generation combined with higher fatigue resistance during exercise. These characteristics are interpreted as being of high adaptive value, given the llama’s habitat and its use as a pack animal. PMID:22625659

Interaction between the compact tori and coated stainless-steel samples

NASA Astrophysics Data System (ADS)

Rohollahi, A.; Khatir, S.; Xiao, C.; Hirose, A.

2017-02-01

The surface damages due to the transient heat load and particle fluxes on the surface of the coated stainless-steel (SS) samples have been investigated. University of Saskatchewan compact torus injector has been used to inject the high heat load and the particle flux on the surface of stainless samples with three different types of coatings. The type 1 samples were made from a SS plate coated by tungsten. The other two samples had additional films of either nickel (type 2) or chromium (type 3) on the type 1 samples. The vacuum plasma spray technique has been applied for the coating of the samples. Surface cracking and melting have been observed on the surface after the samples were impacted by many high-speed and dense plasmoids.

Immunogenicity and safety evaluation of bivalent types 1 and 3 oral poliovirus vaccine by comparing different poliomyelitis vaccination schedules in China: A randomized controlled non-inferiority clinical trial.

PubMed

Qiu, Jingjun; Yang, Yunkai; Huang, Lirong; Wang, Ling; Jiang, Zhiwei; Gong, Jian; Wang, Wei; Wang, Hongyan; Guo, Shaohong; Li, Chanjuan; Wei, Shuyuan; Mo, Zhaojun; Xia, Jielai

2017-06-03

The type 2 component of the oral poliovirus vaccine is targeted for global withdrawal through a switch from the trivalent oral poliovirus vaccine (tOPV) to a bivalent oral poliovirus vaccine (bOPV). The switch is intended to prevent paralytic polio caused by circulating vaccine-derived poliovirus type 2. We aimed to assess the immunogenicity and safety profile of 6 vaccination schedules with different sequential doses of inactivated poliovirus vaccine (IPV), tOPV, or bOPV. A randomized controlled trial was conducted in China in 2015. Healthy newborn babies randomly received one of the following 6 vaccination schedules: cIPV-bOPV-bOPV(I-B-B), cIPV-tOPV-tOPV(I-T-T), cIPV-cIPV-bOPV(I-I-B), cIPV-cIPV-tOPV(I-I-T), cIPV-cIPV-cIPV(I-I-I), or tOPV-tOPV-tOPV(T-T-T). Doses were administered sequentially at 4-6 week intervals after collecting baseline blood samples. Patients were proactively followed up for observation of adverse events after the first dose and 30 days after all doses. The primary study objective was to investigate the immunogenicity and safety profile of different vaccine schedules, evaluated by seroconversion, seroprotection and antibody titer against poliovirus types 1, 2, and 3 in the per-protocol population. Of 600 newborn babies enrolled, 504 (84.0%) were included in the per-protocol population. For type 1 poliovirus, the differences in the seroconversion were 1.17% (95% CI = -2.74%, 5.08%) between I-B-B and I-T-T and 0.00% (95% CI: -6.99%, 6.99%) between I-I-B and I-I-T; for type 3 poliovirus, differences in the seroconversion were 3.49% (95% CI: -1.50%, 8.48%) between I-B-B and I-T-T and -2.32% (95% CI: -5.51%, 0.86%) between I-I-B and I-I-T. The non-inferiority conclusion was achieved in both poliovirus type 1 and 3 with the margin of -10%. Of 24 serious adverse events reported, no one was vaccine-related. The vaccination schedules with bOPV followed by one or 2 doses of IPV were recommended to substitute for vaccinations involving tOPV without compromising the immunogenicity and safety in the Chinese population. The findings will be essential for policy formulation by national and global authorities to facilitate polio elimination.

A study of the properties of tablets made of directly compressible maltose.

PubMed

Muzíková, J; Balhárková, J

2008-01-01

The paper deals with the study of the strength and disintegration time of tablets made of directly compressible maltose Advantose 100. It studies the differences of the effects of two types of lubricants, magnesium stearate and sodium stearylfumarate, on the above-mentioned properties, and it also tests the mixtures of the substance with microcrystalline cellulose Vivapur 102 in a ratio of 1:1 and with ascorbic and acetylsalicylic acids. The compacts are obtained by using three compression forces, excepting mixtures with active ingredients, where one compression force is used. In the compression forces of 6 and 8 kN, no statistically significant difference was found in the intervention of the lubricants into the strength of the compacts made of Advantose 100, only in the compression force of 10 kN Pruv decreased the strength more than stearate. The mixture of Advantose 100 and Vivapur 102 yielded the strongest tablets, an addition of Pruv to it decreased the strength of compacts more than stearate. The periods of disintegration time of Advantose compacts as well as those of the mixture of dry binders were longer with an addition of Pruv. The compacts with acetylsalicylic acid possessed higher strength and a longer period of disintegration than those with ascorbic acid. There was no statistically significant difference within the type of the lubricant employed, both in the case of Advantose 100 and its mixture with Vivapur 102, between the values of strength of the compacts with acetylsalicylic acid.

Compaction Behavior of Granular Materials

NASA Astrophysics Data System (ADS)

Endicott, Mark R.; Kenkre, V. M.; Glass, S. Jill; Hurd, Alan J.

1996-03-01

We report the results of our recent study of compaction of granular materials. A theoretical model is developed for the description of the compaction of granular materials exemplified by granulated ceramic powders. Its predictions are compared to observations of uniaxial compaction tests of ceramic granules of PMN-PT, spray dried alumina and rutile. The theoretical model employs a volume-based statistical mechanics treatment and an activation analogy. Results of a computer simulation of random packing of discs in two dimensions are also reported. The effect of type of particle size distribution and other parameters of that distribution on the calculated quantities are discussed. We examine the implications of the results of the simulation for the theoretical model.

Compaction of quasi-one-dimensional elastoplastic materials.

PubMed

Shaebani, M Reza; Najafi, Javad; Farnudi, Ali; Bonn, Daniel; Habibi, Mehdi

2017-06-06

Insight into crumpling or compaction of one-dimensional objects is important for understanding biopolymer packaging and designing innovative technological devices. By compacting various types of wires in rigid confinements and characterizing the morphology of the resulting crumpled structures, here, we report how friction, plasticity and torsion enhance disorder, leading to a transition from coiled to folded morphologies. In the latter case, where folding dominates the crumpling process, we find that reducing the relative wire thickness counter-intuitively causes the maximum packing density to decrease. The segment size distribution gradually becomes more asymmetric during compaction, reflecting an increase of spatial correlations. We introduce a self-avoiding random walk model and verify that the cumulative injected wire length follows a universal dependence on segment size, allowing for the prediction of the efficiency of compaction as a function of material properties, container size and injection force.

Influence of implant collar design on stress and strain distribution in the crestal compact bone: a three-dimensional finite element analysis.

PubMed

Shen, Wan-Ling; Chen, Chen-Sheng; Hsu, Ming-Lun

2010-01-01

To evaluate the influence of implant collar geometry on the distribution of stress and strain in the crestal compact bone contiguous to an implant collar for four types of bone under axial and oblique loads. Finite element models of threaded implants with three kinds of implant collar designs (divergent, straight, and convergent) with their corresponding suprastructures embedded in the posterior mandible were created with ANSYS software. Eight different test conditions incorporating four types of bone (orthotropic and effectively isotropic in part 1 and high and low densities in part 2) under separate 100-N axial and 35.6-degree oblique forces were created to investigate the stress and strain distributions in the crestal compact bone around the implant collars. In all eight conditions, the divergent collar demonstrated the lowest maximum von Mises and principal stresses and strains in the crestal compact bone contiguous to the implant collar, followed by the straight and convergent collars. The oblique load induced higher peak values than the axial load. The orthotropic design amplified and increased the pathologic microstrains and tensile stresses in the crestal compact bone compared to the effectively isotropic design, especially in models with a convergent collar design. In part 2 of the study, the maximum von Mises stresses and strains increased with a decrease in the cancellous bone density. Under oblique loading, the convergent and straight collars showed pathologic microstrain values as well as excessive ultimate tensile stresses in the orthotropic bone model with low-density cancellous bone. Within the limitations, it was concluded that stress and strain distributions in the adjacent compact bone are influenced by the implant collar design. The divergent implant collar design was associated with the lowest stress and strain concentrations in the crestal compact bone.

Sirolimus and Vaccine Therapy in Treating Patients With Stage II-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

ClinicalTrials.gov

2018-04-27

Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

Bevacizumab and Intravenous or Intraperitoneal Chemotherapy in Treating Patients With Stage II-III Ovarian Epithelial Cancer, Fallopian Tube Cancer, or Primary Peritoneal Cancer

ClinicalTrials.gov

2018-05-25

Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Serous Cystadenocarcinoma; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

Coronary intervention in thrombus-rich lesions: beyond stents and glycoprotein IIb/IIIa inhibitors.

PubMed

Halkin, Amir; Keren, Gad; Stone, Gregg W; Holmes, David R; Rosenschein, Uri

2003-11-01

Despite widespread use of stents and GP IIb/IIIa antagonists, complications following percutaneous treatment of thrombus-rich lesions continue to plague patients with ACS. In these patients the angiographically evident coronary thrombosis may represent a high degree of thrombus burden, which leads to a higher level of microembolization and its clinical sequelae. New catheter-based thrombus burden reduction systems and distal protection devices show promise for improving the prognosis of these high risk patients by decreasing distal microembolization, and thereby preventing myonecrosis. Careful procedural timing and patient selection are also likely to improve outcomes and resource utilization in the management of ACS patients.

Replacement of chemical rocket launchers by beamed energy propulsion.

PubMed

Fukunari, Masafumi; Arnault, Anthony; Yamaguchi, Toshikazu; Komurasaki, Kimiya

2014-11-01

Microwave Rocket is a beamed energy propulsion system that is expected to reach space at drastically lower cost. This cost reduction is estimated by replacing the first-stage engine and solid rocket boosters of the Japanese H-IIB rocket with Microwave Rocket, using a recently developed thrust model in which thrust is generated through repetitively pulsed microwave detonation with a reed-valve air-breathing system. Results show that Microwave Rocket trajectory, in terms of velocity versus altitude, can be designed similarly to the current H-IIB first stage trajectory. Moreover, the payload ratio can be increased by 450%, resulting in launch-cost reduction of 74%.

Isolation and characterization of major histocompatibility complex class IIB genes from the nurse shark.

PubMed

Bartl, S; Weissman, I L

1994-01-04

The major histocompatibility complex (MHC) contains a set of linked genes which encode cell surface proteins involved in the binding of small peptide antigens for their subsequent recognition by T lymphocytes. MHC proteins share structural features and the presence and location of polymorphic residues which play a role in the binding of antigens. In order to compare the structure of these molecules and gain insights into their evolution, we have isolated two MHC class IIB genes from the nurse shark, Ginglymostoma cirratum. Two clones, most probably alleles, encode proteins which differ by 13 amino acids located in the putative antigen-binding cleft. The protein structure and the location of polymorphic residues are similar to their mammalian counterparts. Although these genes appear to encode a typical MHC protein, no T-cell-mediated responses have been demonstrated in cartilaginous fish. The nurse shark represents the most phylogenetically primitive organism in which both class IIA [Kasahara, M., Vazquez, M., Sato, K., McKinney, E.C. & Flajnik, M.F. (1992) Proc. Natl. Acad. Sci USA 89, 6688-6692] and class IIB genes, presumably encoding the alpha/beta heterodimer, have been isolated.

Antiplatelet activity of L-sulforaphane by regulation of platelet activation factors, glycoprotein IIb/IIIa and thromboxane A2.

PubMed

Oh, Chung-Hun; Shin, Jang-In; Mo, Sang Joon; Yun, Sung-Jo; Kim, Sung-Hoon; Rhee, Yun-Hee

2013-07-01

L-sulforaphane was identified as an anticarcinogen that could produce quinine reductase and a phase II detoxification enzyme. In recent decades, multi-effects of L-sulforaphane may have been investigated, but, to the authors' knowledge, the antiplatelet activation of L-sulforaphane has not been studied yet.In this study, 2 μg/ml of collagen, 50 μg/ml of ADP and 5 μg/ml of thrombin were used for platelet aggregations with or without L-sulforaphane. L-sulforaphane inhibited the platelet aggregation dose-dependently. Among these platelet activators, collagen was most inhibited by L-sulforaphane, which markedly decreased collagen-induced glycoprotein IIb/IIIa activation and thromboxane A2 (TxA2) formation in vitro. L-sulforaphane also reduced the collagen and epinephrine-induced pulmonary embolism, but did not affect prothrombin time (PT) in vivo. This finding demonstrated that L-sulforaphane inhibited the platelet activation through an intrinsic pathway.L-sulforaphane had a beneficial effect on various pathophysiological pathways of the collagen-induced platelet aggregation and thrombus formation as a selective inhibition of cyclooxygenase and glycoprotein IIb/IIIa antagonist. Thus, we recommend L-sulforaphane as a potential antithrombotic drug.

The fibronectin synergy site re-enforces cell adhesion and mediates a crosstalk between integrin classes

PubMed Central

Benito-Jardón, Maria; Klapproth, Sarah; Gimeno-LLuch, Irene; Petzold, Tobias; Bharadwaj, Mitasha; Müller, Daniel J; Zuchtriegel, Gabriele; Reichel, Christoph A; Costell, Mercedes

2017-01-01

Fibronectin (FN), a major extracellular matrix component, enables integrin-mediated cell adhesion via binding of α5β1, αIIbβ3 and αv-class integrins to an RGD-motif. An additional linkage for α5 and αIIb is the synergy site located in close proximity to the RGD motif. We report that mice with a dysfunctional FN-synergy motif (Fn1syn/syn) suffer from surprisingly mild platelet adhesion and bleeding defects due to delayed thrombus formation after vessel injury. Additional loss of β3 integrins dramatically aggravates the bleedings and severely compromises smooth muscle cell coverage of the vasculature leading to embryonic lethality. Cell-based studies revealed that the synergy site is dispensable for the initial contact of α5β1 with the RGD, but essential to re-enforce the binding of α5β1/αIIbβ3 to FN. Our findings demonstrate a critical role for the FN synergy site when external forces exceed a certain threshold or when αvβ3 integrin levels decrease below a critical level. DOI: http://dx.doi.org/10.7554/eLife.22264.001 PMID:28092265

Compaction of fibrin clots reveals the antifibrinolytic effect of factor XIII.

PubMed

Rijken, D C; Abdul, S; Malfliet, J J M C; Leebeek, F W G; Uitte de Willige, S

2016-07-01

Essentials Factor XIIIa inhibits fibrinolysis by forming fibrin-fibrin and fibrin-inhibitor cross-links. Conflicting studies about magnitude and mechanisms of inhibition have been reported. Factor XIIIa most strongly inhibits lysis of mechanically compacted or retracted plasma clots. Cross-links of α2-antiplasmin to fibrin prevent the inhibitor from being expelled from the clot. Background Although insights into the underlying mechanisms of the effect of factor XIII on fibrinolysis have improved considerably in the last few decades, in particular with the discovery that activated FXIII (FXIIIa) cross-links α2 -antiplasmin to fibrin, the topic remains a matter of debate. Objective To elucidate the mechanisms of the antifibrinolytic effect of FXIII. Methods and Results Platelet-poor plasma clot lysis, induced by the addition of tissue-type plasminogen activator, was measured in the presence or absence of a specific FXIIIa inhibitor. Both in a turbidity assay and in a fluorescence assay, the FXIIIa inhibitor had only a small inhibitory effect: 1.6-fold less tissue-type plasminogen activator was required for 50% clot lysis in the presence of the FXIIIa inhibitor. However, when the plasma clot was compacted by centrifugation, the FXIIIa inhibitor had a strong inhibitory effect, with 7.7-fold less tissue-type plasminogen activator being required for 50% clot lysis in the presence of the FXIIIa inhibitor. In both experiments, the effects of the FXIIIa inhibitor were entirely dependent on the cross-linking of α2 -antiplasmin to fibrin. The FXIIIa inhibitor reduced the amount of α2 -antiplasmin present in the compacted clots from approximately 30% to < 4%. The results were confirmed with experiments in which compaction was achieved by platelet-mediated clot retraction. Conclusions Compaction or retraction of fibrin clots reveals the strong antifibrinolytic effect of FXIII. This is explained by the cross-linking of α2 -antiplasmin to fibrin by FXIIIa, which prevents the plasmin inhibitor from being fully expelled from the clot during compaction/retraction. © 2016 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Holographic Compact Disk Read-Only Memories

NASA Technical Reports Server (NTRS)

Liu, Tsuen-Hsi

1996-01-01

Compact disk read-only memories (CD-ROMs) of proposed type store digital data in volume holograms instead of in surface differentially reflective elements. Holographic CD-ROM consist largely of parts similar to those used in conventional CD-ROMs. However, achieves 10 or more times data-storage capacity and throughput by use of wavelength-multiplexing/volume-hologram scheme.

Soil properties and aspen development five years after compaction and forest floor removal

Treesearch

Douglas M. Stone; John D. Elioff

1998-01-01

Forest management activities that decrease soil porosity and remove organic matter have been associated with declines in site productivity. In the northern Lake States region, research is in progress in the aspen (Populus tremuloides Michx. and P. grandidentata Michx.) forest type to determine effects of soil compaction and organic...

ROSAT observations of compact groups of galaxies

NASA Technical Reports Server (NTRS)

Pildis, Rachel A.; Bregman, Joel N.; Evrard, August E.

1995-01-01

We have systematically analyzed a sample of 13 new and archival ROSAT Position Sensitive Proportional Counter (PSPC) observations of compact groups of galaxies: 12 Hickson compact groups plus the NCG 2300 group. We find that approximately two-thirds of the groups have extended X-ray emission and, in four of these, the emission is resolved into diffuse emission from gas at a temperature of kT approximately 1 keV in the group potential. All but one of the groups with extended emission have a spiral fraction of less than 50%. The baryon fraction of groups with diffuse emission is 5%-19%, similar to the values in clusters of galaxies. However, with a single exception (HCG 62), the gas-to-stellar mass ratio in our groups has a median value near 5%, somewhat greater than the values for individual early-type galaxies and two orders of magnitude than in clusters of galaxies. The X-ray luminosities of individual group galaxies are comparable to those of similar field galaxies, although the L(sub X)-L(sub B) relation for early-type galaxies may be flatter in compact groups than in the field.

Everything you ever wanted to know about the ultraviolet spectra of star-forming galaxies but were afraid to ask

NASA Technical Reports Server (NTRS)

Kinney, A. L.; Bohlin, R.; Calzetti, D.; Panagia, N.; Wyse, R.

1993-01-01

We present ultraviolet spectra of 143 star-forming galaxies of different morphological types and activity classes including S0, Sa, Sb, Sc, Sd, irregular, starburst, blue compact, blue compact dwarf, Liner, and Seyfert 2 galaxies. These IUE spectra cover the wavelength range from 1200 to 3200 A and are taken in a large aperture (10 x 20 inch). The ultraviolet spectral energy distributions are shown for a subset of the galaxies, ordered by spectral index, and separated by type for normal galaxies, Liners, starburst galaxies, blue compact (BCG) and blue compact dwarf (BCDG) galaxies, and Seyfert 2 galaxies. The ultraviolet spectra of Liners are, for the most part, indistinguishable from the spectra of normal galaxies. Starburst galaxies have a large range of ultraviolet slope, from blue to red. The star-forming galaxies which are the bluest in the optical (BCG and BCDG), also have the 'bluest' average ultraviolet slope of beta = -1.75 +/- 0.63. Seyfert 2 galaxies are the only galaxies in the sample that consistently have detectable UV emission lines.

Effect of target-fixture geometry on shock-wave compacted copper powders

NASA Astrophysics Data System (ADS)

Kim, Wooyeol; Ahn, Dong-Hyun; Yoon, Jae Ik; Park, Lee Ju; Kim, Hyoung Seop

2018-01-01

In shock compaction with a single gas gun system, a target fixture is used to safely recover a powder compact processed by shock-wave dynamic impact. However, no standard fixture geometry exists, and its effect on the processed compact is not well studied. In this study, two types of fixture are used for the dynamic compaction of hydrogen-reduced copper powders, and the mechanical properties and microstructures are investigated using the Vickers microhardness test and electron backscatter diffraction, respectively. With the assistance of finite element method simulations, we analyze several shock parameters that are experimentally hard to control. The results of the simulations indicate that the target geometry clearly affects the characteristics of incident and reflected shock waves. The hardness distribution and the microstructure of the compacts also show their dependence on the geometry. With the results of the simulations and the experiment, it is concluded that the target geometry affects the shock wave propagation and wave interaction in the specimen.

Study on Effects of Different Replacement Rate on Bending Behavior of Big Recycled Aggregate Self Compacting Concrete

NASA Astrophysics Data System (ADS)

Li, Jing; Guo, Tiantian; Gao, Shuai; Jiang, Lin; Zhao, Zhijun; Wang, Yalin

2018-03-01

Big recycled aggregate self compacting concrete is a new type of recycled concrete, which has the advantages of low hydration heat and green environmental protection, but its bending behavior can be affected by different replacement rate. Therefor, in this paper, the research status of big Recycled aggregate self compacting concrete was systematically introduced, and the effect of different replacement rate of big recycled aggregate on failure mode, crack distribution and bending strength of the beam were studied through the bending behavior test of 4 big recycled aggregate self compacting concrete beams. The results show that: The crack distribution of the beam can be affected by the replacement rate; The failure modes of big recycled aggregate beams are the same as those of ordinary concrete; The plane section assumption is applicable to the big recycled aggregate self compacting concrete beam; The higher the replacement rate, the lower the bending strength of big recycled aggregate self compacting concrete beams.

Targeted activation of diverse CRISPR-Cas systems for mammalian genome editing via proximal CRISPR targeting.

PubMed

Chen, Fuqiang; Ding, Xiao; Feng, Yongmei; Seebeck, Timothy; Jiang, Yanfang; Davis, Gregory D

2017-04-07

Bacterial CRISPR-Cas systems comprise diverse effector endonucleases with different targeting ranges, specificities and enzymatic properties, but many of them are inactive in mammalian cells and are thus precluded from genome-editing applications. Here we show that the type II-B FnCas9 from Francisella novicida possesses novel properties, but its nuclease function is frequently inhibited at many genomic loci in living human cells. Moreover, we develop a proximal CRISPR (termed proxy-CRISPR) targeting method that restores FnCas9 nuclease activity in a target-specific manner. We further demonstrate that this proxy-CRISPR strategy is applicable to diverse CRISPR-Cas systems, including type II-C Cas9 and type V Cpf1 systems, and can facilitate precise gene editing even between identical genomic sites within the same genome. Our findings provide a novel strategy to enable use of diverse otherwise inactive CRISPR-Cas systems for genome-editing applications and a potential path to modulate the impact of chromatin microenvironments on genome modification.

Targeted activation of diverse CRISPR-Cas systems for mammalian genome editing via proximal CRISPR targeting

PubMed Central

Chen, Fuqiang; Ding, Xiao; Feng, Yongmei; Seebeck, Timothy; Jiang, Yanfang; Davis, Gregory D.

2017-01-01

Bacterial CRISPR–Cas systems comprise diverse effector endonucleases with different targeting ranges, specificities and enzymatic properties, but many of them are inactive in mammalian cells and are thus precluded from genome-editing applications. Here we show that the type II-B FnCas9 from Francisella novicida possesses novel properties, but its nuclease function is frequently inhibited at many genomic loci in living human cells. Moreover, we develop a proximal CRISPR (termed proxy-CRISPR) targeting method that restores FnCas9 nuclease activity in a target-specific manner. We further demonstrate that this proxy-CRISPR strategy is applicable to diverse CRISPR–Cas systems, including type II-C Cas9 and type V Cpf1 systems, and can facilitate precise gene editing even between identical genomic sites within the same genome. Our findings provide a novel strategy to enable use of diverse otherwise inactive CRISPR–Cas systems for genome-editing applications and a potential path to modulate the impact of chromatin microenvironments on genome modification. PMID:28387220

InP-based compact transversal filter for monolithically integrated light source array.

PubMed

Ueda, Yuta; Fujisawa, Takeshi; Takahata, Kiyoto; Kohtoku, Masaki; Ishii, Hiroyuki

2014-04-07

We developed an InP-based 4x1 transversal filter (TF) with multi-mode interference couplers (MMIs) as a compact wavelength multiplexer (MUX) 1700 μm x 400 μm in size. Furthermore, we converted the MMI-based TF to a reflection type to obtain an ultra-compact MUX of only 900 μm x 50 μm. These MUXs are made with a simple fabrication process and show a satisfactory wavelength filtering operation as MUXs of monolithically integrated light source arrays, for example, for 100G bit Ethernet.

Classifying and Finding Nearby Compact Stellar Systems

NASA Astrophysics Data System (ADS)

Colebaugh, Alexander; Cunningham, Devin; Dixon, Christopher; Romanowsky, Aaron; Striegel, Stephanie

2018-01-01

Compact stellar systems (CSSs) such as compact ellipticals (cEs) and ultracompact dwarfs (UCDs) are relatively rare and poorly understood types of galaxies. To build a more complete picture of these objects, we create search queries using the Sloan Digital Sky Survey, to inventory CSSs in the nearby universe and to explore their properties. We develop an objective set of criteria for classifying cEs, and use these to construct a large, novel catalog of cEs both during and after formation. We also investigate the numbers of cEs and UCDs around nearby giant galaxies.

BIOCHEMISTRY OF THE ANTERIOR, MEDIAL, AND POSTERIOR GENIOGLOSSUS IN THE AGED RAT

PubMed Central

Schaser, Allison J.; Wang, Hao; Volz, Lana M.; Connor, Nadine P.

2010-01-01

Age-related tongue weakness may contribute to swallowing deficits in the elderly. One contributing factor may be an alteration in muscle fiber type properties with aging. However, it is not clear how muscle fiber types within the aged tongue may vary from those found in young adults, or how fiber types may vary across the anteroposterior axis of the extrinsic tongue muscles. We examined myosin heavy chain (MHC) composition of anterior, medial, and posterior sections of the genioglossus muscle (GG) in 10 old male Fischer 344/Brown Norway rats and compared findings to previously reported data from young adult male rats. Significant differences (p< .01) between young adult and old rats were found in the distribution of MHC isoforms along the anteroposterior axis of the muscle. In the anterior, medial, and posterior regions, there was a significantly smaller proportion of type IIb MHC in the old rat GG muscles, while the proportion of type IIx MHC was significantly greater. In the medial region, the proportion of type I MHC was found to be significantly greater in the old rats. Thus, we found a shift to more slowly contracting muscle fibers in the aged rat tongue. PMID:20809174

Early and late lithification of aragonitic bivalve beds in the Purbeck Formation (upper jurassic-lower cretaceous) of Southern England

NASA Astrophysics Data System (ADS)

El-Shahat, Adam; West, Ian

1983-05-01

Beds of euryhaline bivalves alternating with shales constitute much of the middle Purbeck Formation. They originated on "tidal" flats at the western margin of an extensive brackish lagoon. When these shell beds are thin and enclosed in shale they are often still preserved as aragonite and are associated with "beef", fibrous calcite formed during compaction. In most cases, however, the shell debris has been converted by diagenesis into calcitic biosparrudite limestones. A compacted type has been lithified at a late stage, after deep burial. In this, pyrite is abundant and most of the shell aragonite has been replaced neomorphically by ferroan pseudopleochroic calcite. A contrasting uncompacted type of biosparrudite is characterised by bivalve fragments with micrite envelopes. Shells and former pores are occupied by non-ferroan sparry calcite cement, and there is little pyrite. These limestones frequently contain dinosaur footprints and originated in "supratidal" environments where they were cemented early, mainly in meteoric water. Once lithified they were unaffected by compaction. This uncompacted type indicates phases of mild uplift or halts in subsidence. These shell-bed lithologies, and also intermediate types described here, will probably be recognised in other lagoonal formations.

Fine Structure in the Secondary Electron Emission Peak for Diamond Crystal with (100) Negative Electron Affinity Surface

NASA Technical Reports Server (NTRS)

Asnin, V. M.; Krainsky, I. L.

1998-01-01

A fine structure was discovered in the low-energy peak of the secondary electron emission spectra of the diamond surface with negative electron affinity. We studied this structure for the (100) surface of the natural type-IIb diamond crystal. We have found that the low-energy peak consists of a total of four maxima. The relative energy positions of three of them could be related to the electron energy minima near the bottom of the conduction band. The fourth peak, having the lowest energy, was attributed to the breakup of the bulk exciton at the surface during the process of secondary electron emission.

Equivalence of several descriptions for 6d SCFT

NASA Astrophysics Data System (ADS)

Hayashi, Hirotaka; Kim, Sung-Soo; Lee, Kimyeong; Yagi, Futoshi

2017-01-01

We show that the three different looking BPS partition functions, namely the elliptic genus of the 6d N=(1, 0) Sp(1) gauge theory with 10 flavors and a tensor multiplet, the Nekrasov partition function of the 5d N=1 Sp(2) gauge theory with 10 flavors, and the Nekrasov partition function of the 5d N=1 SU(3) gauge theory with 10 flavors, are all equal to each other under specific maps among gauge theory parameters. This result strongly suggests that the three gauge theories have an identical UV fixed point. Type IIB 5-brane web diagrams play an essential role to compute the SU(3) Nekrasov partition function as well as establishing the maps.

Transmogrifying fuzzy vortices

NASA Astrophysics Data System (ADS)

Murugan, Jeff; Millner, Antony

2004-04-01

We show that the construction of vortex solitons of the noncommutative abelian-Higgs model can be extended to a critically coupled gauged linear sigma model with Fayet-Illiopolous D-terms. Like its commutative counterpart, this fuzzy linear sigma model has a rich spectrum of BPS solutions. We offer an explicit construction of the degree-k static semilocal vortex and study in some detail the infinite coupling limit in which it descends to a degree-k Bbb CBbb PkN instanton. This relation between the fuzzy vortex and noncommutative lump is used to suggest an interpretation of the noncommutative sigma model soliton as tilted D-strings stretched between an NS5-brane and a stack of D3-branes in type-IIB superstring theory.

Tensor modes on the string theory landscape

NASA Astrophysics Data System (ADS)

Westphal, Alexander

2013-04-01

We attempt an estimate for the distribution of the tensor mode fraction r over the landscape of vacua in string theory. The dynamics of eternal inflation and quantum tunneling lead to a kind of democracy on the landscape, providing no bias towards large-field or small-field inflation regardless of the class of measure. The tensor mode fraction then follows the number frequency distributions of inflationary mechanisms of string theory over the landscape. We show that an estimate of the relative number frequencies for small-field vs large-field inflation, while unattainable on the whole landscape, may be within reach as a regional answer for warped Calabi-Yau flux compactifications of type IIB string theory.

Structure and Mode-of-Action of the Two-Peptide (Class-IIb) Bacteriocins.

PubMed

Nissen-Meyer, Jon; Oppegård, Camilla; Rogne, Per; Haugen, Helen Sophie; Kristiansen, Per Eugen

2010-03-01

This review focuses on the structure and mode-of-action of the two-peptide (class-IIb) bacteriocins that consist of two different peptides whose genes are next to each other in the same operon. Optimal antibacterial activity requires the presence of both peptides in about equal amounts. The two peptides are synthesized as preforms that contain a 15-30 residue double-glycine-type N-terminal leader sequence that is cleaved off at the C-terminal side of two glycine residues by a dedicated ABC-transporter that concomitantly transfers the bacteriocin peptides across cell membranes. Two-peptide bacteriocins render the membrane of sensitive bacteria permeable to a selected group of ions, indicating that the bacteriocins form or induce the formation of pores that display specificity with respect to the transport of molecules. Based on structure-function studies, it has been proposed that the two peptides of two-peptide bacteriocins form a membrane-penetrating helix-helix structure involving helix-helix-interacting GxxxG-motifs that are present in all characterized two-peptide bacteriocins. It has also been suggested that the membrane-penetrating helix-helix structure interacts with an integrated membrane protein, thereby triggering a conformational alteration in the protein, which in turn causes membrane-leakage. This proposed mode-of-action is similar to the mode-of-action of the pediocin-like (class-IIa) bacteriocins and lactococcin A (a class-IId bacteriocin), which bind to a membrane-embedded part of the mannose phosphotransferase permease in a manner that causes membrane-leakage and cell death.

Surgical Management of Ipsilateral Fracture of the Femur and Tibia in Adults (the Floating Knee): Postoperative Clinical, Radiological, and Functional Outcomes

PubMed Central

2011-01-01

Background This study evaluated the outcomes of surgical management of ipsilateral femoral and tibial fractures in adults. Methods Fifteen patients (13 men, 2 women; mean age, 34.8 years; range, 18 to 65 years) were enrolled in this study. The fractures types were classified according to the classification by Fraser et al. as follows: type I (5), type IIa (3), IIb (4), IIc (3). Femur fractures were treated using locked intramedullary nails, plate-screws, or dynamic condylar screws, and tibia fractures were treated with an external fixator (in open fractures), or plate-screws, and locked intramedullary nailing. The mean follow-up duration was 2.2 years (range, 1.3 to 4 years). Results The extent of bony union according to the Karlstrom criteria was as follows: excellent, 8; good, 4; acceptable, 2; poor, 1. Conclusions The associated injuries and type of fracture (open, intra-articular, comminution) are prognostic factors in a floating knee. The best management of the associated injuries for good final outcome involves intramedullary nailing of both the fractures and postoperative rehabilitation. PMID:21629474

Large field inflation from axion mixing

NASA Astrophysics Data System (ADS)

Shiu, Gary; Staessens, Wieland; Ye, Fang

2015-06-01

We study the general multi-axion systems, focusing on the possibility of large field inflation driven by axions. We find that through axion mixing from a non-diagonal metric on the moduli space and/or from Stückelberg coupling to a U(1) gauge field, an effectively super-Planckian decay constant can be generated without the need of "alignment" in the axion decay constants. We also investigate the consistency conditions related to the gauge symmetries in the multi-axion systems, such as vanishing gauge anomalies and the potential presence of generalized Chern-Simons terms. Our scenario applies generally to field theory models whose axion periodicities are intrinsically sub-Planckian, but it is most naturally realized in string theory. The types of axion mixings invoked in our scenario appear quite commonly in D-brane models, and we present its implementation in type II superstring theory. Explicit stringy models exhibiting all the characteristics of our ideas are constructed within the frameworks of Type IIA intersecting D6-brane models on and Type IIB intersecting D7-brane models on Swiss-Cheese Calabi-Yau orientifolds.