Optimization Testbed Cometboards Extended into Stochastic Domain

NASA Technical Reports Server (NTRS)

Patnaik, Surya N.; Pai, Shantaram S.; Coroneos, Rula M.; Patnaik, Surya N.

2010-01-01

COMparative Evaluation Testbed of Optimization and Analysis Routines for the Design of Structures (CometBoards) is a multidisciplinary design optimization software. It was originally developed for deterministic calculation. It has now been extended into the stochastic domain for structural design problems. For deterministic problems, CometBoards is introduced through its subproblem solution strategy as well as the approximation concept in optimization. In the stochastic domain, a design is formulated as a function of the risk or reliability. Optimum solution including the weight of a structure, is also obtained as a function of reliability. Weight versus reliability traced out an inverted-S-shaped graph. The center of the graph corresponded to 50 percent probability of success, or one failure in two samples. A heavy design with weight approaching infinity could be produced for a near-zero rate of failure that corresponded to unity for reliability. Weight can be reduced to a small value for the most failure-prone design with a compromised reliability approaching zero. The stochastic design optimization (SDO) capability for an industrial problem was obtained by combining three codes: MSC/Nastran code was the deterministic analysis tool, fast probabilistic integrator, or the FPI module of the NESSUS software, was the probabilistic calculator, and CometBoards became the optimizer. The SDO capability requires a finite element structural model, a material model, a load model, and a design model. The stochastic optimization concept is illustrated considering an academic example and a real-life airframe component made of metallic and composite materials.

A fictitious domain approach for the Stokes problem based on the extended finite element method

NASA Astrophysics Data System (ADS)

Court, Sébastien; Fournié, Michel; Lozinski, Alexei

2014-01-01

In the present work, we propose to extend to the Stokes problem a fictitious domain approach inspired by eXtended Finite Element Method and studied for Poisson problem in [Renard]. The method allows computations in domains whose boundaries do not match. A mixed finite element method is used for fluid flow. The interface between the fluid and the structure is localized by a level-set function. Dirichlet boundary conditions are taken into account using Lagrange multiplier. A stabilization term is introduced to improve the approximation of the normal trace of the Cauchy stress tensor at the interface and avoid the inf-sup condition between the spaces for velocity and the Lagrange multiplier. Convergence analysis is given and several numerical tests are performed to illustrate the capabilities of the method.

Studies to enhance the hyperpolarization level in PHIP-SAH-produced C13-pyruvate

NASA Astrophysics Data System (ADS)

Cavallari, Eleonora; Carrera, Carla; Aime, Silvio; Reineri, Francesca

2018-04-01

The use of [1-13C]pyruvate, hyperpolarized by dissolution-Dynamic Nuclear Polarization (d-DNP), in in vivo metabolic studies has developed quickly, thanks to the imaging probe's diagnostic relevance. Nevertheless, the cost of a d-DNP polarizer is quite high and the speed of hyperpolarization process is relatively slow, meaning that its use is limited to few research laboratories. ParaHydrogen Induced Polarization Side Arm Hydrogenation (PHIP-SAH) (Reineri et al., 2015) is a cost effective and easy-to-handle method that produces 13C-MR hyperpolarization in [1-13C]pyruvate and other metabolites. This work aims to identify the main determinants of the hyperpolarization levels observed in C13-pyruvate using this method. By dissecting the various steps of the PHIP-SAH procedure, it has been possible to assess the role of several experimental parameters whose optimization must be pursued if this method is to be made suitable for future translational steps. The search for possible solutions has led to improvements in the polarization of sodium [1-13C]pyruvate from 2% to 5%. Moreover, these results suggest that observed polarization levels could be increased considerably by an automatized procedure which would reduce the time required for the work-up passages that are currently carried out manually. The results reported herein mean that the attainment of polarization levels suitable for the metabolic imaging applications of these hyperpolarized substrates show significant promise.

Non-invasive assessment of vasospasm following aneurysmal SAH using C-arm FDCT parenchymal blood volume measurement in the neuro-interventional suite: Technical feasibility

PubMed Central

Downer, Jonathan; Corkill, Rufus; Byrne, James V

2015-01-01

Introduction Cerebral vasospasm is the leading cause of morbidity and mortality in patients with aneurysmal subarachnoid haemorrhage (SAH) surviving the initial ictus. Commonly used techniques for vasospasm assessment are digital subtraction angiography and transcranial Doppler sonography. These techniques can reliably identify only the major vessel spasm and fail to estimate its haemodynamic significance. To overcome these issues and to enable comprehensive non-invasive assessment of vasospasm inside the interventional suite, a novel protocol involving measurement of parenchymal blood volume (PBV) using C-arm flat detector computed tomography (FDCT) was implemented. Materials and methods Patients from the neuro-intensive treatment unit (ITU) with suspected vasospasm following aneurysmal SAH were scanned with a biplane C-arm angiography system using an intravenous contrast injection protocol. The PBV maps were generated using prototype software. Contemporaneous clinically indicated MR scan including the diffusion- and perfusion-weighted sequences was performed. C-arm PBV maps were compared against the MR perfusion maps. Results Distribution of haemodynamic impairment on C-arm PBV maps closely matched the pattern of abnormality on MR perfusion maps. On visual comparison between the two techniques, the extent of abnormality indicated PBV to be both cerebral blood flow and cerebral blood volume weighted. Conclusion C-arm FDCT PBV measurements allow an objective assessment of the severity and localisation of cerebral hypoperfusion resulting from vasospasm. The technique has proved feasible and useful in very sick patients after aneurysmal SAH. The promise shown in this early study indicates that it deserves further evaluation both for post-SAH vasospasm and in other relevant clinical settings. PMID:26017197

Non-invasive assessment of vasospasm following aneurysmal SAH using C-arm FDCT parenchymal blood volume measurement in the neuro-interventional suite: Technical feasibility.

PubMed

Kamran, Mudassar; Downer, Jonathan; Corkill, Rufus; Byrne, James V

2015-08-01

Cerebral vasospasm is the leading cause of morbidity and mortality in patients with aneurysmal subarachnoid haemorrhage (SAH) surviving the initial ictus. Commonly used techniques for vasospasm assessment are digital subtraction angiography and transcranial Doppler sonography. These techniques can reliably identify only the major vessel spasm and fail to estimate its haemodynamic significance. To overcome these issues and to enable comprehensive non-invasive assessment of vasospasm inside the interventional suite, a novel protocol involving measurement of parenchymal blood volume (PBV) using C-arm flat detector computed tomography (FDCT) was implemented. Patients from the neuro-intensive treatment unit (ITU) with suspected vasospasm following aneurysmal SAH were scanned with a biplane C-arm angiography system using an intravenous contrast injection protocol. The PBV maps were generated using prototype software. Contemporaneous clinically indicated MR scan including the diffusion- and perfusion-weighted sequences was performed. C-arm PBV maps were compared against the MR perfusion maps. Distribution of haemodynamic impairment on C-arm PBV maps closely matched the pattern of abnormality on MR perfusion maps. On visual comparison between the two techniques, the extent of abnormality indicated PBV to be both cerebral blood flow and cerebral blood volume weighted. C-arm FDCT PBV measurements allow an objective assessment of the severity and localisation of cerebral hypoperfusion resulting from vasospasm. The technique has proved feasible and useful in very sick patients after aneurysmal SAH. The promise shown in this early study indicates that it deserves further evaluation both for post-SAH vasospasm and in other relevant clinical settings. © The Author(s) 2015.

Extended depth of focus adaptive optics spectral domain optical coherence tomography

PubMed Central

Sasaki, Kazuhiro; Kurokawa, Kazuhiro; Makita, Shuichi; Yasuno, Yoshiaki

2012-01-01

We present an adaptive optics spectral domain optical coherence tomography (AO-SDOCT) with a long focal range by active phase modulation of the pupil. A long focal range is achieved by introducing AO-controlled third-order spherical aberration (SA). The property of SA and its effects on focal range are investigated in detail using the Huygens-Fresnel principle, beam profile measurement and OCT imaging of a phantom. The results indicate that the focal range is extended by applying SA, and the direction of extension can be controlled by the sign of applied SA. Finally, we demonstrated in vivo human retinal imaging by altering the applied SA. PMID:23082278

Extended depth of focus adaptive optics spectral domain optical coherence tomography.

PubMed

Sasaki, Kazuhiro; Kurokawa, Kazuhiro; Makita, Shuichi; Yasuno, Yoshiaki

2012-10-01

We present an adaptive optics spectral domain optical coherence tomography (AO-SDOCT) with a long focal range by active phase modulation of the pupil. A long focal range is achieved by introducing AO-controlled third-order spherical aberration (SA). The property of SA and its effects on focal range are investigated in detail using the Huygens-Fresnel principle, beam profile measurement and OCT imaging of a phantom. The results indicate that the focal range is extended by applying SA, and the direction of extension can be controlled by the sign of applied SA. Finally, we demonstrated in vivo human retinal imaging by altering the applied SA.

The Development of SAH Reading Passage Compendium: A Tool for the Assessment of Reading Performance Related to Visual Function

ERIC Educational Resources Information Center

Chen, Ai-Hong; Buari, Noor Halilah; Jufri, Shauqiah

2017-01-01

Passages with continuous sentences are commonly used for the assessment of reading performance related to visual function, and rehabilitation in optometric practices. Passages created in native languages are crucial for a reliable interpretation in a real scenario. This study aimed to report the development of SAH Reading Passage Compendium…

Brain iron metabolism and brain injury following subarachnoid hemorrhage: iCeFISH-pilot (CSF iron in SAH).

PubMed

Gomes, Joao A; Selim, Magdy; Cotleur, Anne; Hussain, M Shazam; Toth, Gabor; Koffman, Lauren; Asi, Khaled; Provencio, J Javier

2014-10-01

Iron-mediated oxidative damage has been implicated in the genesis of cerebral vasospasm in animal models of SAH. We sought to explore the relationship between levels of non-protein bound iron in cerebrospinal fluid and the development of brain injury in patients with aneurysmal SAH. Patients admitted with aneurysmal subarachnoid hemorrhage to a Neurointensive care unit of an academic, tertiary medical center, with Hunt and Hess grades 2-4 requiring ventriculostomy insertion as part of their clinical management were included in this pilot study. Samples of cerebrospinal fluid (CSF) were obtained on days 1, 3, and 5. A fluorometric assay that relies on an oxidation sensitive probe was used to measure unbound iron, and levels of iron-handling proteins were measured by means of enzyme-linked immunosorbent assays. We prospectively collected and recorded demographic, clinical, and radiological data. A total of 12 patients were included in this analysis. Median Hunt and Hess score on admission was 3.5 (IQR: 1) and median modified Fisher scale score was 4 (IQR: 1). Seven of 12 patients (58 %) developed delayed cerebral ischemia (DCI). Day 5 non-transferrin bound iron (NTBI) (7.88 ± 1 vs. 3.58 ± 0.8, p = 0.02) and mean NTBI (7.39 ± 0.4 vs. 3.34 + 0.4 p = 0.03) were significantly higher in patients who developed DCI. Mean redox-active iron, as well as day 3 levels of redox-active iron correlated with development of angiographic vasospasm in logistic regression analysis (p = 0.02); while mean redox-active iron and lower levels of ceruloplasmin on days 3, 5, and peak concentration were correlated with development of deep cerebral infarcts. Our preliminary data indicate a causal relationship between unbound iron and brain injury following SAH and suggest a possible protective role for ceruloplasmin in this setting, particularly in the prevention of cerebral ischemia. Further studies are needed to validate these findings and to probe their clinical significance.

Performance analysis of FET microwave devices by use of extended spectral-element time-domain method

NASA Astrophysics Data System (ADS)

Sheng, Yijun; Xu, Kan; Wang, Daoxiang; Chen, Rushan

2013-05-01

The extended spectral-element time-domain (SETD) method is employed to analyse field effect transistor (FET) microwave devices. In order to impose the contribution of the FET microwave devices into the electromagnetic simulation, the SETD method is extended by introducing a lumped current term into the vector Helmholtz equation. The change of currents on each lumped component can be expressed by the change of voltage via corresponding models of equivalent circuit. The electric fields around the lumped component must be influenced by the change of voltage on each lumped component, and vice versa. So a global coupling about the EM-circuit can be built directly. The fully explicit solving scheme is maintained in this extended SETD method and the CPU time can be saved spontaneously. Three practical FET microwave devices are analysed in this article. The numerical results demonstrate the ability and accuracy of this method.

A molecular dynamics simulation study decodes the Zika virus NS5 methyltransferase bound to SAH and RNA analogue.

PubMed

Chuang, Chih-Hung; Chiou, Shean-Jaw; Cheng, Tian-Lu; Wang, Yeng-Tseng

2018-04-20

Since 2015, widespread Zika virus outbreaks in Central and South America have caused increases in microcephaly cases, and this acute problem requires urgent attention. We employed molecular dynamics and Gaussian accelerated molecular dynamics techniques to investigate the structure of Zika NS5 protein with S-adenosyl-L-homocysteine (SAH) and an RNA analogue, namely 7-methylguanosine 5'-triphosphate (m7GTP). For the binding motif of Zika virus NS5 protein and SAH, we suggest that the four Zika NS5 substructures (residue orders: 101-112, 54-86, 127-136 and 146-161) and the residues (Ser56, Gly81, Arg84, Trp87, Thr104, Gly106, Gly107, His110, Asp146, Ile147, and Gly148) might be responsible for the selectivity of the new Zika virus drugs. For the binding motif of Zika NS5 protein and m7GTP, we suggest that the three Zika NS5 substructures (residue orders: 11-31, 146-161 and 207-218) and the residues (Asn17, Phe24, Lys28, Lys29, Ser150, Arg213, and Ser215) might be responsible for the selectivity of the new Zika virus drugs.

High-speed extended-term time-domain simulation for online cascading analysis of power system

NASA Astrophysics Data System (ADS)

Fu, Chuan

A high-speed extended-term (HSET) time domain simulator (TDS), intended to become a part of an energy management system (EMS), has been newly developed for use in online extended-term dynamic cascading analysis of power systems. HSET-TDS includes the following attributes for providing situational awareness of high-consequence events: (i) online analysis, including n-1 and n-k events, (ii) ability to simulate both fast and slow dynamics for 1-3 hours in advance, (iii) inclusion of rigorous protection-system modeling, (iv) intelligence for corrective action ID, storage, and fast retrieval, and (v) high-speed execution. Very fast on-line computational capability is the most desired attribute of this simulator. Based on the process of solving algebraic differential equations describing the dynamics of power system, HSET-TDS seeks to develop computational efficiency at each of the following hierarchical levels, (i) hardware, (ii) strategies, (iii) integration methods, (iv) nonlinear solvers, and (v) linear solver libraries. This thesis first describes the Hammer-Hollingsworth 4 (HH4) implicit integration method. Like the trapezoidal rule, HH4 is symmetrically A-Stable but it possesses greater high-order precision (h4 ) than the trapezoidal rule. Such precision enables larger integration steps and therefore improves simulation efficiency for variable step size implementations. This thesis provides the underlying theory on which we advocate use of HH4 over other numerical integration methods for power system time-domain simulation. Second, motivated by the need to perform high speed extended-term time domain simulation (HSET-TDS) for on-line purposes, this thesis presents principles for designing numerical solvers of differential algebraic systems associated with power system time-domain simulation, including DAE construction strategies (Direct Solution Method), integration methods(HH4), nonlinear solvers(Very Dishonest Newton), and linear solvers(SuperLU). We have

Skierarchy: Extending the Power of Crowdsourcing Using a Hierarchy of Domain Experts, Crowd and Machine Learning

DTIC Science & Technology

2012-11-01

college background and good reading comprehension skills in English, and bring to them to the office space to work for us full-time on micro-tasks. This...reasonable reading comprehension skills in English. The expert spent only 1/3rd the time as each member of the crowd in the entire annotation process...3. DATES COVERED 00-00-2012 to 00-00-2012 4. TITLE AND SUBTITLE Skierarchy: Extending the Power of Crowdsourcing Using a Hierarchy of Domain

Ca2+-Induced Rigidity Change of the Myosin VIIa IQ Motif-Single α Helix Lever Arm Extension.

PubMed

Li, Jianchao; Chen, Yiyun; Deng, Yisong; Unarta, Ilona Christy; Lu, Qing; Huang, Xuhui; Zhang, Mingjie

2017-04-04

Several unconventional myosins contain a highly charged single α helix (SAH) immediately following the calmodulin (CaM) binding IQ motifs, functioning to extend lever arms of these myosins. How such SAH is connected to the IQ motifs and whether the conformation of the IQ motifs-SAH segments are regulated by Ca 2+ fluctuations are not known. Here, we demonstrate by solving its crystal structure that the predicted SAH of myosin VIIa (Myo7a) forms a stable SAH. The structure of Myo7a IQ5-SAH segment in complex with apo-CaM reveals that the SAH sequence can extend the length of the Myo7a lever arm. Although Ca 2+ -CaM remains bound to IQ5-SAH, the Ca 2+ -induced CaM binding mode change softens the conformation of the IQ5-SAH junction, revealing a Ca 2+ -induced lever arm flexibility change for Myo7a. We further demonstrate that the last IQ motif of several other myosins also binds to both apo- and Ca 2+ -CaM, suggesting a common Ca 2+ -induced conformational regulation mechanism. Copyright © 2017 Elsevier Ltd. All rights reserved.

Extending the limits of complex learning in organic amnesia: computer training in a vocational domain.

PubMed

Glisky, E L; Schacter, D L

1989-01-01

This study explored the limits of learning that could be achieved by an amnesic patient in a complex real-world domain. Using a cuing procedure known as the method of vanishing cues, a severely amnesic encephalitic patient was taught over 250 discrete pieces of new information concerning the rules and procedures for performing a task involving data entry into a computer. Subsequently, she was able to use this acquired knowledge to perform the task accurately and efficiently in the workplace. These results suggest that amnesic patients' preserved learning abilities can be extended well beyond what has been reported previously.

The extended Fourier pseudospectral time-domain method for atmospheric sound propagation.

PubMed

Hornikx, Maarten; Waxler, Roger; Forssén, Jens

2010-10-01

An extended Fourier pseudospectral time-domain (PSTD) method is presented to model atmospheric sound propagation by solving the linearized Euler equations. In this method, evaluation of spatial derivatives is based on an eigenfunction expansion. Evaluation on a spatial grid requires only two spatial points per wavelength. Time iteration is done using a low-storage optimized six-stage Runge-Kutta method. This method is applied to two-dimensional non-moving media models, one with screens and one for an urban canyon, with generally high accuracy in both amplitude and phase. For a moving atmosphere, accurate results have been obtained in models with both a uniform and a logarithmic wind velocity profile over a rigid ground surface and in the presence of a screen. The method has also been validated for three-dimensional sound propagation over a screen. For that application, the developed method is in the order of 100 times faster than the second-order-accurate FDTD solution to the linearized Euler equations. The method is found to be well suited for atmospheric sound propagation simulations where effects of complex meteorology and straight rigid boundary surfaces are to be investigated.

Heterologous Expression of sahH Reveals That Biofilm Formation Is Autoinducer-2-independent in Streptococcus sanguinis but Is Associated with an Intact Activated Methionine Cycle*

PubMed Central

Redanz, Sylvio; Standar, Kerstin; Podbielski, Andreas; Kreikemeyer, Bernd

2012-01-01

Numerous studies have claimed deleterious effects of LuxS mutation on many bacterial phenotypes, including bacterial biofilm formation. Genetic complementation mostly restored the observed mutant phenotypes to WT levels, leading to the postulation that quorum sensing via a family of molecules generically termed autoinducer-2 (AI-2) is essential for many phenotypes. Because LuxS mutation has dual effects, this hypothesis needs to be investigated into the details for each bacterial species. In this study we used S. sanguinis SK36 as a model biofilm bacterium and employed physiological characterization and transcriptome approaches on WT and luxS-deficient strains, in combination with chemical, luxS, and sahH complementation experiments. SahH enables a direct conversion of SAH to homocysteine and thereby restores the activated methionine cycle in a luxS-negative background without formation of the AI-2 precursor 4,5-dihydroxy-2,3-pentanedione. With this strategy we were able to dissect the individual contribution of LuxS and AI-2 activity in detail. Our data revealed that S. sanguinis biofilm formation is independent from AI-2 substance pools and is rather supported by an intact activated methyl cycle. Of 216 differentially transcribed genes in the luxS mutant, 209 were restored by complementation with a gene encoding the S-adenosylhomocysteine hydrolase. Only nine genes, mainly involved in natural competence, were directly affected by the AI-2 quorum-sensing substance pool. Cumulatively, this suggested that biofilm formation in S. sanguinis is not under control of AI-2. Our study suggests that previously evaluated LuxS mutants in other species need to be revisited to resolve the precise contribution of AI-2 substance pools and the methionine pathways. PMID:22942290

Clinical and diagnostic approach to patients with hypopituitarism due to traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), and ischemic stroke (IS).

PubMed

Karamouzis, Ioannis; Pagano, Loredana; Prodam, Flavia; Mele, Chiara; Zavattaro, Marco; Busti, Arianna; Marzullo, Paolo; Aimaretti, Gianluca

2016-06-01

The hypothalamic-pituitary dysfunction attributable to traumatic brain injury (TBI), aneurysmal subarachnoid hemorrhage (SAH), and ischemic stroke (IS) has been lately highlighted. The diagnosis of TBI-induced-hypopituitarism, defined as a deficient secretion of one or more pituitary hormones, is made similarly to the diagnosis of classical hypopituitarism because of hypothalamic/pituitary diseases. Hypopituitarism is believed to contribute to TBI-associated morbidity and to functional and cognitive final outcome, and quality-of-life impairment. Each pituitary hormone must be tested separately, since there is a variable pattern of hormone deficiency among patients with TBI-induced-hypopituitarism. Similarly, the SAH and IS may lead to pituitary dysfunction although the literature in this field is limited. The drive to diagnose hypopituitarism is the suspect that the secretion of one/more pituitary hormone may be subnormal. This suspicion can be based upon the knowledge that the patient has an appropriate clinical context in which hypopituitarism can be present, or a symptom known as caused by hypopituitarism. Hypopituitarism should be diagnosed as a combination of low peripheral and inappropriately normal/low pituitary hormones although their basal evaluation may be not distinctive due to pulsatile, circadian, or situational secretion of some hormones. Evaluation of the somatotroph and corticotroph axes require dynamic stimulation test (ITT for both axes, GHRH + arginine test for somatotroph axis) in order to clearly separate normal from deficient responses.

Extended-range high-resolution dynamical downscaling over a continental-scale spatial domain with atmospheric and surface nudging

NASA Astrophysics Data System (ADS)

Husain, S. Z.; Separovic, L.; Yu, W.; Fernig, D.

2014-12-01

Extended-range high-resolution mesoscale simulations with limited-area atmospheric models when applied to downscale regional analysis fields over large spatial domains can provide valuable information for many applications including the weather-dependent renewable energy industry. Long-term simulations over a continental-scale spatial domain, however, require mechanisms to control the large-scale deviations in the high-resolution simulated fields from the coarse-resolution driving fields. As enforcement of the lateral boundary conditions is insufficient to restrict such deviations, large scales in the simulated high-resolution meteorological fields are therefore spectrally nudged toward the driving fields. Different spectral nudging approaches, including the appropriate nudging length scales as well as the vertical profiles and temporal relaxations for nudging, have been investigated to propose an optimal nudging strategy. Impacts of time-varying nudging and generation of hourly analysis estimates are explored to circumvent problems arising from the coarse temporal resolution of the regional analysis fields. Although controlling the evolution of the atmospheric large scales generally improves the outputs of high-resolution mesoscale simulations within the surface layer, the prognostically evolving surface fields can nevertheless deviate from their expected values leading to significant inaccuracies in the predicted surface layer meteorology. A forcing strategy based on grid nudging of the different surface fields, including surface temperature, soil moisture, and snow conditions, toward their expected values obtained from a high-resolution offline surface scheme is therefore proposed to limit any considerable deviation. Finally, wind speed and temperature at wind turbine hub height predicted by different spectrally nudged extended-range simulations are compared against observations to demonstrate possible improvements achievable using higher spatiotemporal

A Twelve-Week Moderate Exercise Programme Improved Symptoms of Depression, Insomnia, and Verbal Learning in Post-Aneurysmal Subarachnoid Haemorrhage Patients: A Comparison with Meningioma Patients and Healthy Controls.

PubMed

Colledge, Flora; Brand, Serge; Pühse, Uwe; Holsboer-Trachsler, Edith; Zimmerer, Stefan; Schleith, Ramona; Gerber, Markus

2018-04-25

Deficits in psychological functioning, cognitive functioning, and sleep are frequently experienced by individuals who have survived aneurysmal subarachnoid haemorrhage (aSAH). Exercise has been shown to improve these domains; to date, it has never been explored in patients following aSAH. The aim of this exploratory study is to compare the effects of an exercise programme in this population with another patient group, and a group of healthy controls. The present study explored the effects of 12 weeks of moderate aerobic exercise training on 15 aSAH patients, 16 meningioma patients, and 17 healthy controls. Data on symptoms of depression, hypochondria, perceived stress, satisfaction with life, verbal learning and memory, and subjective and objective sleep, were gathered at baseline, following intervention, and at 6-month follow-up. aSAH patients and meningioma patients had decreased symptoms of depression and insomnia at follow-up. While perceived stress decreased in the meningioma group, in aSAH patients it increased. Total learning performance increased in all three groups. An exercise programme had a positive effect on symptoms of depression, insomnia, and verbal learning in patients following aSAH. No positive changes in other domains were observed. This may be due to the cautious approach taken with regard to exercise intensity. © 2018 S. Karger AG, Basel.

The Degrees of Freedom Concept--Extending the Domain

ERIC Educational Resources Information Center

Biernacki, J. J.

2016-01-01

The degrees of freedom (DOF) concept is a powerful tool that has been taught since at least the '70s in undergraduate curriculum, typically introduced in the context of a first course on material and energy balances. The concept, however, has not been widely applied beyond the material balance domain and in general is not taught as a unified…

Extended reactance domain algorithms for DoA estimation onto an ESPAR antennas

NASA Astrophysics Data System (ADS)

Harabi, F.; Akkar, S.; Gharsallah, A.

2016-07-01

Based on an extended reactance domain (RD) covariance matrix, this article proposes new alternatives for directions of arrival (DoAs) estimation of narrowband sources through an electronically steerable parasitic array radiator (ESPAR) antennas. Because of the centro symmetry of the classic ESPAR antennas, an unitary transformation is applied to the collected data that allow an important reduction in both computational cost and processing time and, also, an enhancement of the resolution capabilities of the proposed algorithms. Moreover, this article proposes a new approach for eigenvalues estimation through only some linear operations. The developed DoAs estimation algorithms based on this new approach has illustrated a good behaviour with less calculation cost and processing time as compared to other schemes based on the classic eigenvalues approach. The conducted simulations demonstrate that high-precision and high-resolution DoAs estimation can be reached especially in very closely sources situation and low sources power as compared to the RD-MUSIC algorithm and the RD-PM algorithm. The asymptotic behaviours of the proposed DoAs estimators are analysed in various scenarios and compared with the Cramer-Rao bound (CRB). The conducted simulations testify the high-resolution of the developed algorithms and prove the efficiently of the proposed approach.

Crystal structure of Rv2258c from Mycobacterium tuberculosis H37Rv, an S-adenosyl-l-methionine-dependent methyltransferase.

PubMed

Im, Ha Na; Kim, Hyoun Sook; An, Doo Ri; Jang, Jun Young; Kim, Jieun; Yoon, Hye-Jin; Yang, Jin Kuk; Suh, Se Won

2016-03-01

The Mycobacterium tuberculosis Rv2258c protein is an S-adenosyl-L-methionine (SAM)-dependent methyltransferase (MTase). Here, we have determined its crystal structure in three forms: a ligand-unbound form, a binary complex with sinefungin (SFG), and a binary complex with S-adenosyl-L-homocysteine (SAH). The monomer structure of Rv2258c consists of two domains which are linked by a long α-helix. The N-terminal domain is essential for dimerization and the C-terminal domain has the Class I MTase fold. Rv2258c forms a homodimer in the crystal, with the N-terminal domains facing each other. It also exists as a homodimer in solution. A DALI structural similarity search with Rv2258c reveals that the overall structure of Rv2258c is very similar to small-molecule SAM-dependent MTases. Rv2258c interacts with the bound SFG (or SAH) in an extended conformation maintained by a network of hydrogen bonds and stacking interactions. Rv2258c has a relatively large hydrophobic cavity for binding of the methyl-accepting substrate, suggesting that bulky nonpolar molecules with aromatic rings might be targeted for methylation by Rv2258c in M. tuberculosis. However, the ligand-binding specificity and the biological role of Rv2258c remain to be elucidated due to high variability of the amino acid residues defining the substrate-binding site. Copyright © 2016 Elsevier Inc. All rights reserved.

Spectral domain optical coherence tomography with extended depth-of-focus by aperture synthesis

NASA Astrophysics Data System (ADS)

Bo, En; Liu, Linbo

2016-10-01

We developed a spectral domain optical coherence tomography (SD-OCT) with an extended depth-of-focus (DOF) by synthetizing aperture. For a designated Gaussian-shape light source, the lateral resolution was determined by the numerical aperture (NA) of the objective lens and can be approximately maintained over the confocal parameter, which was defined as twice the Rayleigh range. However, the DOF was proportional to the square of the lateral resolution. Consequently, a trade-off existed between the DOF and lateral resolution, and researchers had to weigh and judge which was more important for their research reasonably. In this study, three distinct optical apertures were obtained by imbedding a circular phase spacer in the sample arm. Due to the optical path difference between three distinct apertures caused by the phase spacer, three images were aligned with equal spacing along z-axis vertically. By correcting the optical path difference (OPD) and defocus-induced wavefront curvature, three images with distinct depths were coherently summed together. This system digitally refocused the sample tissue and obtained a brand new image with higher lateral resolution over the confocal parameter when imaging the polystyrene calibration beads.

AIDA: ab initio domain assembly for automated multi-domain protein structure prediction and domain–domain interaction prediction

PubMed Central

Xu, Dong; Jaroszewski, Lukasz; Li, Zhanwen; Godzik, Adam

2015-01-01

Motivation: Most proteins consist of multiple domains, independent structural and evolutionary units that are often reshuffled in genomic rearrangements to form new protein architectures. Template-based modeling methods can often detect homologous templates for individual domains, but templates that could be used to model the entire query protein are often not available. Results: We have developed a fast docking algorithm ab initio domain assembly (AIDA) for assembling multi-domain protein structures, guided by the ab initio folding potential. This approach can be extended to discontinuous domains (i.e. domains with ‘inserted’ domains). When tested on experimentally solved structures of multi-domain proteins, the relative domain positions were accurately found among top 5000 models in 86% of cases. AIDA server can use domain assignments provided by the user or predict them from the provided sequence. The latter approach is particularly useful for automated protein structure prediction servers. The blind test consisting of 95 CASP10 targets shows that domain boundaries could be successfully determined for 97% of targets. Availability and implementation: The AIDA package as well as the benchmark sets used here are available for download at http://ffas.burnham.org/AIDA/. Contact: adam@sanfordburnham.org Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25701568

Extended HSR/CARD domain mediates AIRE binding to DNA

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

Maslovskaja, Julia, E-mail: julia.maslovskaja@ut.ee; Saare, Mario; Liiv, Ingrid

Autoimmune regulator (AIRE) activates the transcription of many genes in an unusual promiscuous and stochastic manner. The mechanism by which AIRE binds to the chromatin and DNA is not fully understood, and the regulatory elements that AIRE target genes possess are not delineated. In the current study, we demonstrate that AIRE activates the expression of transiently transfected luciferase reporters that lack defined promoter regions, as well as intron and poly(A) signal sequences. Our protein-DNA interaction experiments with mutated AIRE reveal that the intact homogeneously staining region/caspase recruitment domain (HSR/CARD) and amino acids R113 and K114 are key elements involved inmore » AIRE binding to DNA. - Highlights: • Promoter and mRNA processing elements are not important for AIRE to activate gene expression from reporter plasmids. • AIRE protein fragment aa 1–138 mediates direct binding to DNA. • Integrity of the HSR/CARD domain is needed for AIRE binding to DNA.« less

Domain structure of human complement C4b extends with increasing NaCl concentration: implications for its regulatory mechanism.

PubMed

Fung, Ka Wai; Wright, David W; Gor, Jayesh; Swann, Marcus J; Perkins, Stephen J

2016-12-01

During the activation of complement C4 to C4b, the exposure of its thioester domain (TED) is crucial for the attachment of C4b to activator surfaces. In the C4b crystal structure, TED forms an Arg 104 -Glu 1032 salt bridge to tether its neighbouring macroglobulin (MG1) domain. Here, we examined the C4b domain structure to test whether this salt bridge affects its conformation. Dual polarisation interferometry of C4b immobilised at a sensor surface showed that the maximum thickness of C4b increased by 0.46 nm with an increase in NaCl concentration from 50 to 175 mM NaCl. Analytical ultracentrifugation showed that the sedimentation coefficient s 20,w of monomeric C4b of 8.41 S in 50 mM NaCl buffer decreased to 7.98 S in 137 mM NaCl buffer, indicating that C4b became more extended. Small angle X-ray scattering reported similar R G values of 4.89-4.90 nm for C4b in 137-250 mM NaCl. Atomistic scattering modelling of the C4b conformation showed that TED and the MG1 domain were separated by 4.7 nm in 137-250 mM NaCl and this is greater than that of 4.0 nm in the C4b crystal structure. Our data reveal that in low NaCl concentrations, both at surfaces and in solution, C4b forms compact TED-MG1 structures. In solution, physiologically relevant NaCl concentrations lead to the separation of the TED and MG1 domain, making C4b less capable of binding to its complement regulators. These conformational changes are similar to those seen previously for complement C3b, confirming the importance of this salt bridge for regulating both C4b and C3b. © 2016 The Author(s).

Optical-domain subsampling for data efficient depth ranging in Fourier-domain optical coherence tomography

PubMed Central

Siddiqui, Meena; Vakoc, Benjamin J.

2012-01-01

Recent advances in optical coherence tomography (OCT) have led to higher-speed sources that support imaging over longer depth ranges. Limitations in the bandwidth of state-of-the-art acquisition electronics, however, prevent adoption of these advances into the clinical applications. Here, we introduce optical-domain subsampling as a method for imaging at high-speeds and over extended depth ranges but with a lower acquisition bandwidth than that required using conventional approaches. Optically subsampled laser sources utilize a discrete set of wavelengths to alias fringe signals along an extended depth range into a bandwidth limited frequency window. By detecting the complex fringe signals and under the assumption of a depth-constrained signal, optical-domain subsampling enables recovery of the depth-resolved scattering signal without overlapping artifacts from this bandwidth-limited window. We highlight key principles behind optical-domain subsampled imaging, and demonstrate this principle experimentally using a polygon-filter based swept-source laser that includes an intra-cavity Fabry-Perot (FP) etalon. PMID:23038343

Quality of Life after Brain Injury (QOLIBRI) Overall Scale for patients after aneurysmal subarachnoid hemorrhage.

PubMed

Wong, George Kwok Chu; Lam, Sandy Wai; Ngai, Karine; Wong, Adrian; Mok, Vincent; Poon, Wai Sang

2014-06-01

The Quality of Life after Brain Injury Overall Scale (QOLIBRI-OS) is a recently developed instrument that provides a brief summary measure of health-related quality of life (HRQoL) in domains typically affected by brain injury. This study examined the application of the six item QOLIBRI-OS in patients after aneurysmal subarachnoid hemorrhage (aSAH). Hong Kong Chinese aSAH patients were evaluated prospectively within the chronic phase of 1 year after aSAH in this multi-center observational study. Cronbach's α was 0.88, and correlations were satisfactory for all six items. QOLIBRI-OS demonstrated good criterion validity with other 1 year outcome assessments. In conclusion, QOLIBRI-OS can be used as a brief index for disease-specific HRQoL assessment after aSAH. Further validation in another population of aSAH patients is recommended. Copyright © 2013 Elsevier Ltd. All rights reserved.

Human immunoglobulin E flexes between acutely bent and extended conformations

PubMed Central

Keeble, Anthony H; Wright, Michael; Cain, Katharine; Hailu, Hanna; Oxbrow, Amanda; Delgado, Jean; Shuttleworth, Lindsay K; Kao, Michael W-P; McDonnell, James M; Beavil, Andrew J; Henry, Alistair J; Sutton, Brian J

2014-01-01

Crystallographic and solution studies have shown that IgE molecules are acutely bent in their Fc region. Crystal structures reveal the Cε2 domain pair folded back onto the Cε3-Cε4 domains, but is the molecule exclusively bent or can the Cε2 domains adopt extended conformations and even “flip” from one side of the molecule to the other? We report the crystal structure of IgE-Fc captured in a fully extended, symmetrical conformation and show by molecular dynamics, calorimetry, stopped-flow kinetic, SPR and FRET analyses, that the antibody can indeed adopt such extended conformations in solution. This diversity of conformational states available to IgE-Fc offers a new perspective on IgE function in allergen recognition, as part of the B cell receptor and as a therapeutic target in allergic disease. PMID:24632569

Extending the DIDEO ontology to include entities from the natural product drug interaction domain of discourse.

PubMed

Judkins, John; Tay-Sontheimer, Jessica; Boyce, Richard D; Brochhausen, Mathias

2018-05-09

Prompted by the frequency of concomitant use of prescription drugs with natural products, and the lack of knowledge regarding the impact of pharmacokinetic-based natural product-drug interactions (PK-NPDIs), the United States National Center for Complementary and Integrative Health has established a center of excellence for PK-NPDI. The Center is creating a public database to help researchers (primarly pharmacologists and medicinal chemists) to share and access data, results, and methods from PK-NPDI studies. In order to represent the semantics of the data and foster interoperability, we are extending the Drug-Drug Interaction and Evidence Ontology (DIDEO) to include definitions for terms used by the data repository. This is feasible due to a number of similarities between pharmacokinetic drug-drug interactions and PK-NPDIs. To achieve this, we set up an iterative domain analysis in the following steps. In Step 1 PK-NPDI domain experts produce a list of terms and definitions based on data from PK-NPDI studies, in Step 2 an ontology expert creates ontologically appropriate classes and definitions from the list along with class axioms, in Step 3 there is an iterative editing process during which the domain experts and the ontology experts review, assess, and amend class labels and definitions and in Step 4 the ontology expert implements the new classes in the DIDEO development branch. This workflow often results in different labels and definitions for the new classes in DIDEO than the domain experts initially provided; the latter are preserved in DIDEO as separate annotations. Step 1 resulted in a list of 344 terms. During Step 2 we found that 9 of these terms already existed in DIDEO, and 6 existed in other OBO Foundry ontologies. These 6 were imported into DIDEO; additional terms from multiple OBO Foundry ontologies were also imported, either to serve as superclasses for new terms in the initial list or to build axioms for these terms. At the time of writing, 7

Mental versus physical fatigue after subarachnoid hemorrhage: differential associations with outcome.

PubMed

Buunk, Anne M; Groen, Rob J M; Wijbenga, Rianne A; Ziengs, Aaltje L; Metzemaekers, Jan D M; van Dijk, J Marc C; Spikman, Jacoba M

2018-06-20

Fatigue is a major consequence of subarachnoid hemorrhage (SAH), but the specific characteristics are unclear. Our objective was to investigate the nature of post-SAH fatigue (mental or physical) and to determine the relationship with functional outcome in the chronic stage. Also, the possible influence of mood disorders and acute SAH-related factors (SAH type and external cerebrospinal fluid (CSF) drainage) on the presence of fatigue was investigated. Patients with an aneurysmal SAH (aSAH) or angiographically negative SAH (anSAH) were assessed 3 to 10 years post-SAH (N = 221). Questionnaires were used to investigate mental and physical fatigue and mood. Functional outcome was examined with the Glasgow Outcome Scale Extended (GOSE). Between-group comparisons and binary logistic regression analysis were performed. Frequencies of mental and physical fatigue were 48.4% and 38.5% respectively, with prevalence of mental fatigue being significantly higher. A two-way ANOVA with SAH type and external CSF drainage as independent variables and mental fatigue as dependent variable, showed a significant main effect of CSF drainage only (p < 0.001). Only mental fatigue explained a significant part of the variance in long-term functional outcome (Model χ 2 = 52.99, p < 0.001; Nagelkerke R² = 0.32). Mental fatigue after SAH is a serious burden to the patient and is associated with impaired long-term functional outcome. Distinguishing different aspects of fatigue is relevant as mental post-SAH fatigue might be a target for treatment aimed to improve long-term outcome. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Socially Extended Cognition and Shared Intentionality

PubMed Central

Lyre, Holger

2018-01-01

The paper looks at the intersection of extended cognition and social cognition. The central claim is that the mechanisms of shared intentionality can equally be considered as coupling mechanisms of cognitive extension into the social domain. This claim will be demonstrated by investigating a detailed example of cooperative action, and it will be argued that such cases imply that socially extended cognition is not only about cognitive vehicles, but that content must additionally be taken into account. It is finally outlined how social content externalism can in principle be grounded in socially extended cognition. PMID:29892254

Extending the Serum Half-Life of G-CSF via Fusion with the Domain III of Human Serum Albumin

PubMed Central

Zhao, Shuqiang; Zhang, Yu; Tian, Hong; Chen, Xiaofei; Cai, Di; Yao, Wenbing; Gao, Xiangdong

2013-01-01

Protein fusion technology is one of the most commonly used methods to extend the half-life of therapeutic proteins. In this study, in order to prolong the half-life of Granulocyte colony stimulating factor (G-CSF), the domain III of human serum albumin (3DHSA) was genetically fused to the N-terminal of G-CSF. The 3DHSA-G-CSF fusion gene was cloned into pPICZαA along with the open reading frame of the α-factor signal under the control of the AOX1 promoter. The recombinant expression vector was transformed into Pichia pastoris GS115, and the recombinant strains were screened by SDS-PAGE. As expected, the 3DHSA-G-CSF showed high binding affinity with HSA antibody and G-CSF antibody, and the natural N-terminal of 3DHSA was detected by N-terminal sequencing. The bioactivity and pharmacokinetic studies of 3DHSA-G-CSF were respectively determined using neutropenia model mice and human G-CSF ELISA kit. The results demonstrated that 3DHSA-G-CSF has the ability to increase the peripheral white blood cell (WBC) counts of neutropenia model mice, and the half-life of 3DHSA-G-CSF is longer than that of native G-CSF. In conclusion, 3DHSA can be used to extend the half-life of G-CSF. PMID:24151579

Alcohol-induced S-adenosylhomocysteine accumulation in the liver sensitizes to TNF hepatotoxicity: possible involvement of mitochondrial S-adenosylmethionine transport.

PubMed

Song, Zhenyuan; Zhou, Zhanxiang; Song, Ming; Uriarte, Silvia; Chen, Theresa; Deaciuc, Ion; McClain, Craig J

2007-08-01

Hepatocytes are resistant to tumor necrosis factor-alpha- (TNF) induced killing/apoptosis under normal circumstances, but primary hepatocytes from rats chronically fed alcohol have increased TNF cytotoxicity. Therefore, there must be mechanism(s) by which alcohol exposure "sensitizes" to TNF hepatotoxicity. Abnormal metabolism of methionine and S-adenosylmethionine (SAM) are well-documented acquired metabolic abnormalities in ALD. S-adenosylhomocysteine (SAH) is the product of SAM in hepatic transmethylation reactions, and SAH hydrolase (SAHH) is the only enzyme to metabolize SAH to homocysteine and adenosine. Our previous studies demonstrated that chronic intracellular accumulation of SAH sensitized hepatocytes to TNF cytotoxicity in vitro. In the current study, we extended our previous observations by further characterizing the effects of chronic alcohol intake on mitochondrial SAM levels in liver and examining its possible involvement in SAH sensitization to TNF hepatotoxicity. Chronic alcohol consumption in mice not only increased cytosolic SAH levels, but also decreased mitochondrial SAM concentration, leading to decreased mitochondrial SAM to SAH ratio. Moreover, accumulation of hepatic SAH induced by administration of 3-deaza-adenosine (DZA-a potent inhibitor of SAHH) enhanced lipopolysaccharide (LPS)/TNF hepatotoxicity in mice in vivo. Inhibition of SAHH by DZA resulted not only in accumulation of cytoplasmic SAH, but also in depletion of the mitochondrial SAM pool. Further studies using mitochondrial SAM transporter inhibitors showed that inhibition of SAM transport into mitochondria sensitized HepG2 cells to TNF cytotoxicity. In conclusion, our results demonstrate that depletion of the mitochondrial SAM pool by SAH, which is elevated during chronic alcohol consumption, plays a critical role in SAH induced sensitization to TNF hepatotoxicity.

Frequency domain FIR and IIR adaptive filters

NASA Technical Reports Server (NTRS)

Lynn, D. W.

1990-01-01

A discussion of the LMS adaptive filter relating to its convergence characteristics and the problems associated with disparate eigenvalues is presented. This is used to introduce the concept of proportional convergence. An approach is used to analyze the convergence characteristics of block frequency-domain adaptive filters. This leads to a development showing how the frequency-domain FIR adaptive filter is easily modified to provide proportional convergence. These ideas are extended to a block frequency-domain IIR adaptive filter and the idea of proportional convergence is applied. Experimental results illustrating proportional convergence in both FIR and IIR frequency-domain block adaptive filters is presented.

Time-Domain Stability Margin Assessment

NASA Technical Reports Server (NTRS)

Clements, Keith

2016-01-01

The baseline stability margins for NASA's Space Launch System (SLS) launch vehicle were generated via the classical approach of linearizing the system equations of motion and determining the gain and phase margins from the resulting frequency domain model. To improve the fidelity of the classical methods, the linear frequency domain approach can be extended by replacing static, memoryless nonlinearities with describing functions. This technique, however, does not address the time varying nature of the dynamics of a launch vehicle in flight. An alternative technique for the evaluation of the stability of the nonlinear launch vehicle dynamics along its trajectory is to incrementally adjust the gain and/or time delay in the time domain simulation until the system exhibits unstable behavior. This technique has the added benefit of providing a direct comparison between the time domain and frequency domain tools in support of simulation validation.

Extended mind and after: socially extended mind and actor-network.

PubMed

Kono, Tetsuya

2014-03-01

The concept of extended mind has been impressively developed over the last 10 years by many philosophers and cognitive scientists. The extended mind thesis (EM) affirms that the mind is not simply ensconced inside the head, but extends to the whole system of brain-body-environment. Recently, some philosophers and psychologists try to adapt the idea of EM to the domain of social cognition research. Mind is socially extended (SEM). However, EM/SEM theory has problems to analyze the interactions among a subject and its surroundings with opposition, antagonism, or conflict; it also tends to think that the environment surrounding the subject is passive or static, and to neglect the power of non-human actants to direct and regulate the human subject. In these points, actor-network theory (ANT) proposed by Latour and Callon is more persuasive, while sharing some important ideas with EM/SEM theory. Actor-network is a hybrid community which is composed of a series of heterogeneous elements, animate and inanimate for a certain period of time. I shall conclude that EM/SEM could be best analyzed as a special case of actor-network. EM/SEM is a system which can be controlled by a human agent alone. In order to understand collective behavior, philosophy and psychology have to study the actor-network in which human individuals are situated.

Structure of the kinase domain of Gilgamesh from Drosophila melanogaster

PubMed Central

Han, Ni; Chen, CuiCui; Shi, Zhubing; Cheng, Dianlin

2014-01-01

The CK1 family kinases regulate multiple cellular aspects and play important roles in Wnt/Wingless and Hedgehog signalling. The kinase domain of Drosophila Gilgamesh isoform I (Gilgamesh-I), a homologue of human CK1-γ, was purified and crystallized. Crystals of methylated Gilgamesh-I kinase domain with a D210A mutation diffracted to 2.85 Å resolution and belonged to space group P43212, with unit-cell parameters a = b = 52.025, c = 291.727 Å. The structure of Gilgamesh-I kinase domain, which was determined by molecular replacement, has conserved catalytic elements and an active conformation. Structural comparison indicates that an extended loop between the α1 helix and the β4 strand exists in the Gilgamesh-I kinase domain. This extended loop may regulate the activity and function of Gilgamesh-I. PMID:24699734

Time-domain wavefield reconstruction inversion

NASA Astrophysics Data System (ADS)

Li, Zhen-Chun; Lin, Yu-Zhao; Zhang, Kai; Li, Yuan-Yuan; Yu, Zhen-Nan

2017-12-01

Wavefield reconstruction inversion (WRI) is an improved full waveform inversion theory that has been proposed in recent years. WRI method expands the searching space by introducing the wave equation into the objective function and reconstructing the wavefield to update model parameters, thereby improving the computing efficiency and mitigating the influence of the local minimum. However, frequency-domain WRI is difficult to apply to real seismic data because of the high computational memory demand and requirement of time-frequency transformation with additional computational costs. In this paper, wavefield reconstruction inversion theory is extended into the time domain, the augmented wave equation of WRI is derived in the time domain, and the model gradient is modified according to the numerical test with anomalies. The examples of synthetic data illustrate the accuracy of time-domain WRI and the low dependency of WRI on low-frequency information.

Effective description of domain wall strings

NASA Astrophysics Data System (ADS)

Rodrigues, Davi R.; Abanov, Ar.; Sinova, J.; Everschor-Sitte, K.

2018-04-01

The analysis of domain wall dynamics is often simplified to one-dimensional physics. For domain walls in thin films, more realistic approaches require the description as two-dimensional objects. This includes the study of vortices and curvatures along the domain walls as well as the influence of boundary effects. Here we provide a theory in terms of soft modes that allows us to analytically study the physics of extended domain walls and their stability. By considering irregularly shaped skyrmions as closed domain walls, we analyze their plasticity and compare their dynamics with those of circular skyrmions. Our theory directly provides an analytical description of the excitation modes of magnetic skyrmions, previously accessible only through sophisticated micromagnetic numerical calculations and spectral analysis. These analytical expressions provide the scaling behavior of the different physics on parameters that experiments can test.

Extended Malus Law with metallic linear polarizers in terahertz and microwave domains

NASA Astrophysics Data System (ADS)

Romain, Xavier; Baida, Fadi; Boyer, Philippe

2016-04-01

An extended Malus' Law for the well-known Polarizer-Analyzer Mounting (PAM) is analytically obtained and investigated. The PAM is composed of two perfectly parallel Metallic Linear Polarizers (MLP), with subwavelength periodic pattern composed of rectangular holes. Our analytical theory especially highlights the influence of multiple reflections between the two MLPs which leads to an extended and tunable Malus Law. We demonstrate that the classical Malus Law (obtained for dichroic polarizers) is modulated by a factor which also depends on the angular difference between both MLP axes. In our analysis, the Malus' law is studied at the resonance wavelengths. Due to the interactions between the two MLP, the modulation factor is tuned by the optical distance between them which makes substantial variations of the Malus Law. We mention that, for each reflections, the light is re-polarized according to the orientation of the MLP. This tunable Malus' Law provides an original tool for ultrasensitive detection in the terahertz or microwave regime. For example, one can use an ultra-narrow angle Malus' Law as a hyper-sensitive device to analyze with a high accuracy the electro-optical response of a material sandwiched between polarizer and analyzer. We theoretically propose one PAM designed to detect a refractive index variation as small as 10-5. Finally, we extend the theory, which takes the form of an extended Jones formalism, to a large number of stacked MLP. It is applied to achieve many polarization manipulation processes as total polarization conversion with tunable spectral bandwidth, for instance.

Traumatic midline subarachnoid hemorrhage on initial computed tomography as a marker of severe diffuse axonal injury.

PubMed

Mata-Mbemba, Daddy; Mugikura, Shunji; Nakagawa, Atsuhiro; Murata, Takaki; Ishii, Kiyoshi; Kushimoto, Shigeki; Tominaga, Teiji; Takahashi, Shoki; Takase, Kei

2018-01-05

OBJECTIVE The objective of this study was to test the hypothesis that midline (interhemispheric or perimesencephalic) traumatic subarachnoid hemorrhage (tSAH) on initial CT may implicate the same shearing mechanism that underlies severe diffuse axonal injury (DAI). METHODS The authors enrolled 270 consecutive patients (mean age [± SD] 43 ± 23.3 years) with a history of head trauma who had undergone initial CT within 24 hours and brain MRI within 30 days. Six initial CT findings, including intraventricular hemorrhage (IVH) and tSAH, were used as candidate predictors of DAI. The presence of tSAH was determined at the cerebral convexities, sylvian fissures, sylvian vallecula, cerebellar folia, interhemispheric fissure, and perimesencephalic cisterns. Following MRI, patients were divided into negative and positive DAI groups, and were assigned to a DAI stage: 1) stage 0, negative DAI; 2) stage 1, DAI in lobar white matter or cerebellum; 3) stage 2, DAI involving the corpus callosum; and 4) stage 3, DAI involving the brainstem. Glasgow Outcome Scale-Extended (GOSE) scores were obtained in 232 patients. RESULTS Of 270 patients, 77 (28.5%) had DAI; tSAH and IVH were independently associated with DAI (p < 0.05). Of tSAH locations, midline tSAH was independently associated with both overall DAI and DAI stage 2 or 3 (severe DAI; p < 0.05). The midline tSAH on initial CT had sensitivity of 60.8%, specificity of 81.7%, and positive and negative predictive values of 43.7% and 89.9%, respectively, for severe DAI. When adjusted for admission Glasgow Coma Score, the midline tSAH independently predicted poor GOSE score at both hospital discharge and after 6 months. CONCLUSIONS Midline tSAH could implicate the same shearing mechanism that underlies severe DAI, for which midline tSAH on initial CT is a probable surrogate.

An Extended Structure of the APOBEC3G Catalytic Domain Suggests a Unique Holoenzyme Model

PubMed Central

Harjes, Elena; Gross, Phillip J.; Chen, Kuan-Ming; Lu, Yongjian; Shindo, Keisuke; Nowarski, Roni; Gross, John D.; Kotler, Moshe; Harris, Reuben S.; Matsuo, Hiroshi

2009-01-01

Summary Human APOBEC3G (A3G) belongs to a family of polynucleotide cytidine deaminases. This family includes APOBEC1 and AID, which edit APOB mRNA and antibody gene DNA, respectively. A3G deaminates cytidines to uridines in single-strand DNA and inhibits the replication of HIV-1, other retroviruses and retrotransposons. Although the mechanism of A3G-catalyzed DNA deamination has been investigated genetically and biochemically, atomic details are just starting to emerge. Here, we compare the DNA cytidine deaminase activities and NMR structures of two A3G catalytic domain constructs. The longer A3G191-384 protein is considerably more active than the shorter A3G198-384 variant. The longer structure has an α1 helix (residues 201–206) that was not apparent in the shorter protein and it contributes to catalytic activity through interactions with hydrophobic core structures (β1, β3, α5 and α6). Both A3G catalytic domain solution structures have a discontinuous β2 region that is clearly different than the continuous β2 strand of another family member APOBEC2. In addition, the longer A3G191-384 structure revealed part of the N-terminal pseudo-catalytic domain including the inter-domain linker and some of the last α-helix. These structured residues (191–196) enabled a novel full-length A3G model by providing physical overlap between the N-terminal pseudo-catalytic domain and the new C-terminal catalytic domain structure. Contrary to predictions, this structurally constrained model suggested that the two domains are tethered by structured residues and that the N- and C-terminal β2 regions are too distant from one another to participate in this interaction. PMID:19389408

Direct observation of interlocked domain walls and topological four-state vortex-like domain patterns in multiferroic YMnO{sub 3} single crystal

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

Tian, Lei; School of Materials Science and Engineering, Dalian Jiaotong University, Dalian, Liaoning 116028; Wang, Yumei, E-mail: wangym@iphy.ac.cn

2015-03-16

Using the advanced spherical aberration-corrected high angle annular dark field scanning transmission electron microscope imaging techniques, we investigated atomic-scale structural features of domain walls and domain patterns in YMnO{sub 3} single crystal. Three different types of interlocked ferroelectric-antiphase domain walls and two abnormal topological four-state vortex-like domain patterns are identified. Each ferroelectric domain wall is accompanied by a translation vector, i.e., 1/6[210] or −1/6[210], demonstrating its interlocked nature. Different from the four-state vortex domain patterns caused by a partial edge dislocation, two four-state vortex-like domain configurations have been obtained at atomic level. These observed phenomena can further extend our understandingmore » of the fascinating vortex domain patterns in multiferroic hexagonal rare-earth manganites.« less

Time Domain Stability Margin Assessment Method

NASA Technical Reports Server (NTRS)

Clements, Keith

2017-01-01

The baseline stability margins for NASA's Space Launch System (SLS) launch vehicle were generated via the classical approach of linearizing the system equations of motion and determining the gain and phase margins from the resulting frequency domain model. To improve the fidelity of the classical methods, the linear frequency domain approach can be extended by replacing static, memoryless nonlinearities with describing functions. This technique, however, does not address the time varying nature of the dynamics of a launch vehicle in flight. An alternative technique for the evaluation of the stability of the nonlinear launch vehicle dynamics along its trajectory is to incrementally adjust the gain and/or time delay in the time domain simulation until the system exhibits unstable behavior. This technique has the added benefit of providing a direct comparison between the time domain and frequency domain tools in support of simulation validation.

Kinematics of reflections in subsurface offset and angle-domain image gathers

NASA Astrophysics Data System (ADS)

Dafni, Raanan; Symes, William W.

2018-05-01

Seismic migration in the angle-domain generates multiple images of the earth's interior in which reflection takes place at different scattering-angles. Mechanically, the angle-dependent reflection is restricted to happen instantaneously and at a fixed point in space: Incident wave hits a discontinuity in the subsurface media and instantly generates a scattered wave at the same common point of interaction. Alternatively, the angle-domain image may be associated with space-shift (regarded as subsurface offset) extended migration that artificially splits the reflection geometry. Meaning that, incident and scattered waves interact at some offset distance. The geometric differences between the two approaches amount to a contradictory angle-domain behaviour, and unlike kinematic description. We present a phase space depiction of migration methods extended by the peculiar subsurface offset split and stress its profound dissimilarity. In spite of being in radical contradiction with the general physics, the subsurface offset reveals a link to some valuable angle-domain quantities, via post-migration transformations. The angle quantities are indicated by the direction normal to the subsurface offset extended image. They specifically define the local dip and scattering angles if the velocity at the split reflection coordinates is the same for incident and scattered wave pairs. Otherwise, the reflector normal is not a bisector of the opening angle, but of the corresponding slowness vectors. This evidence, together with the distinguished geometry configuration, fundamentally differentiates the angle-domain decomposition based on the subsurface offset split from the conventional decomposition at a common reflection point. An asymptotic simulation of angle-domain moveout curves in layered media exposes the notion of split versus common reflection point geometry. Traveltime inversion methods that involve the subsurface offset extended migration must accommodate the split geometry

The Hcp proteins fused with diverse extended-toxin domains represent a novel pattern of antibacterial effectors in type VI secretion systems

PubMed Central

Ma, Jiale; Pan, Zihao; Huang, Jinhu; Sun, Min; Lu, Chengping; Yao, Huochun

2017-01-01

ABSTRACT The type VI secretion system (T6SS) is a widespread molecular weapon deployed by many bacterial species to target eukaryotic host cells or rival bacteria. Using a dynamic injection mechanism, diverse effectors can be delivered by T6SS directly into recipient cells. Here, we report a new family of T6SS effectors encoded by extended Hcps carrying diverse toxin domains. Bioinformatic analyses revealed that these Hcps with C-terminal extension toxins, designated as Hcp-ET, exist widely in the Enterobacteriaceae. To verify our findings, Hcp-ET1 was tested for its antibacterial effect, and showed effective inhibition of target cell growth via the predicted HNH-DNase activity by T6SS-dependent delivery. Further studies showed that Hcp-ET2 mediated interbacterial antagonism via a Tle1 phospholipase (encoded by DUF2235 domain) activity. Notably, comprehensive analyses of protein homology and genomic neighborhoods revealed that Hcp-ET3–4 is fused with 2 toxin domains (Pyocin S3 and Colicin-DNase) C-terminally, and its encoding gene is followed 3 duplications of the cognate immunity genes. However, some bacteria encode a separated hcp-et3 and an orphan et4 (et4O1) genes caused by a termination-codon mutation in the fusion region between Pyocin S3 and Colicin-DNase encoding fragments. Our results demonstrated that both of these toxins had antibacterial effects. Further, all duplications of the cognate immunity protein contributed to neutralize the DNase toxicity of Pyocin S3 and Colicin, which has not been reported previously. In conclusion, we propose that Hcp-ET proteins are polymorphic T6SS effectors, and thus present a novel encoding pattern of T6SS effectors. PMID:28060574

Domain adaptation via transfer component analysis.

PubMed

Pan, Sinno Jialin; Tsang, Ivor W; Kwok, James T; Yang, Qiang

2011-02-01

Domain adaptation allows knowledge from a source domain to be transferred to a different but related target domain. Intuitively, discovering a good feature representation across domains is crucial. In this paper, we first propose to find such a representation through a new learning method, transfer component analysis (TCA), for domain adaptation. TCA tries to learn some transfer components across domains in a reproducing kernel Hilbert space using maximum mean miscrepancy. In the subspace spanned by these transfer components, data properties are preserved and data distributions in different domains are close to each other. As a result, with the new representations in this subspace, we can apply standard machine learning methods to train classifiers or regression models in the source domain for use in the target domain. Furthermore, in order to uncover the knowledge hidden in the relations between the data labels from the source and target domains, we extend TCA in a semisupervised learning setting, which encodes label information into transfer components learning. We call this extension semisupervised TCA. The main contribution of our work is that we propose a novel dimensionality reduction framework for reducing the distance between domains in a latent space for domain adaptation. We propose both unsupervised and semisupervised feature extraction approaches, which can dramatically reduce the distance between domain distributions by projecting data onto the learned transfer components. Finally, our approach can handle large datasets and naturally lead to out-of-sample generalization. The effectiveness and efficiency of our approach are verified by experiments on five toy datasets and two real-world applications: cross-domain indoor WiFi localization and cross-domain text classification.

Restrictions and satisfaction with participation in patients who are ADL-independent after an aneurysmal subarachnoid hemorrhage.

PubMed

Huenges Wajer, Irene M C; Visser-Meily, Johanna M A; Greebe, Paut; Post, Marcel W M; Rinkel, Gabriel J E; van Zandvoort, Martine J E

2017-03-01

Most survivors of an aneurysmal subarachnoid hemorrhage (aSAH) are ADL-independent, but they often experience restrictions in (social) activities and, therefore, cannot regain their pre-morbid level of participation. In this study, participation restrictions and participation satisfaction experienced after aSAH were assessed. Moreover, possible predictors of participation after aSAH were examined to identify goals for rehabilitation. Participation restrictions experienced by a series of 67 patients visiting our SAH outpatient clinic were assessed as part of standard clinical care using the Participation Restrictions and Satisfaction sections of the Utrecht Scale for Evaluation of Rehabilitation Participation (USER-Participation) 6 months after aSAH. Cognitive impairments, cognitive and emotional complaints, and symptoms of depression and anxiety, assessed 10 weeks after aSAH, were examined as possible predictors of participation by means of linear regression analysis. Although patients were ADL-independent, 64% reported one or more participation restrictions and 60% were dissatisfied in one or more participation domains. Most commonly experienced restrictions concerned housekeeping, chores in and around the house, and physical exercise. Dissatisfaction was most often reported about outdoor activities, mobility, and work/housekeeping. The main predictors of participation restrictions as well as satisfaction with participation were cognitive complaints (subjective) (β = -.30, p = .03 and β = -.40, p = .002, respectively) and anxiety (β = .32, p = .02 and β = -.34, p = .007, respectively). Almost two-thirds of the ADL-independent patients experienced problems of participation 6 months after aSAH. Cognitive complaints (subjective) and anxiety symptoms showed the strongest association with participation restrictions and satisfaction. Cognitive rehabilitation and anxiety-reducing interventions may help to optimize rehabilitation and increase

Domain-Invariant Partial-Least-Squares Regression.

PubMed

Nikzad-Langerodi, Ramin; Zellinger, Werner; Lughofer, Edwin; Saminger-Platz, Susanne

2018-05-11

Multivariate calibration models often fail to extrapolate beyond the calibration samples because of changes associated with the instrumental response, environmental condition, or sample matrix. Most of the current methods used to adapt a source calibration model to a target domain exclusively apply to calibration transfer between similar analytical devices, while generic methods for calibration-model adaptation are largely missing. To fill this gap, we here introduce domain-invariant partial-least-squares (di-PLS) regression, which extends ordinary PLS by a domain regularizer in order to align the source and target distributions in the latent-variable space. We show that a domain-invariant weight vector can be derived in closed form, which allows the integration of (partially) labeled data from the source and target domains as well as entirely unlabeled data from the latter. We test our approach on a simulated data set where the aim is to desensitize a source calibration model to an unknown interfering agent in the target domain (i.e., unsupervised model adaptation). In addition, we demonstrate unsupervised, semisupervised, and supervised model adaptation by di-PLS on two real-world near-infrared (NIR) spectroscopic data sets.

Polar Domain Discovery with Sparkler

NASA Astrophysics Data System (ADS)

Duerr, R.; Khalsa, S. J. S.; Mattmann, C. A.; Ottilingam, N. K.; Singh, K.; Lopez, L. A.

2017-12-01

The scientific web is vast and ever growing. It encompasses millions of textual, scientific and multimedia documents describing research in a multitude of scientific streams. Most of these documents are hidden behind forms which require user action to retrieve and thus can't be directly accessed by content crawlers. These documents are hosted on web servers across the world, most often on outdated hardware and network infrastructure. Hence it is difficult and time-consuming to aggregate documents from the scientific web, especially those relevant to a specific domain. Thus generating meaningful domain-specific insights is currently difficult. We present an automated discovery system (Figure 1) using Sparkler, an open-source, extensible, horizontally scalable crawler which facilitates high throughput and focused crawling of documents pertinent to a particular domain such as information about polar regions. With this set of highly domain relevant documents, we show that it is possible to answer analytical questions about that domain. Our domain discovery algorithm leverages prior domain knowledge to reach out to commercial/scientific search engines to generate seed URLs. Subject matter experts then annotate these seed URLs manually on a scale from highly relevant to irrelevant. We leverage this annotated dataset to train a machine learning model which predicts the `domain relevance' of a given document. We extend Sparkler with this model to focus crawling on documents relevant to that domain. Sparkler avoids disruption of service by 1) partitioning URLs by hostname such that every node gets a different host to crawl and by 2) inserting delays between subsequent requests. With an NSF-funded supercomputer Wrangler, we scaled our domain discovery pipeline to crawl about 200k polar specific documents from the scientific web, within a day.

Pair correlation functions for identifying spatial correlation in discrete domains

NASA Astrophysics Data System (ADS)

Gavagnin, Enrico; Owen, Jennifer P.; Yates, Christian A.

2018-06-01

Identifying and quantifying spatial correlation are important aspects of studying the collective behavior of multiagent systems. Pair correlation functions (PCFs) are powerful statistical tools that can provide qualitative and quantitative information about correlation between pairs of agents. Despite the numerous PCFs defined for off-lattice domains, only a few recent studies have considered a PCF for discrete domains. Our work extends the study of spatial correlation in discrete domains by defining a new set of PCFs using two natural and intuitive definitions of distance for a square lattice: the taxicab and uniform metric. We show how these PCFs improve upon previous attempts and compare between the quantitative data acquired. We also extend our definitions of the PCF to other types of regular tessellation that have not been studied before, including hexagonal, triangular, and cuboidal. Finally, we provide a comprehensive PCF for any tessellation and metric, allowing investigation of spatial correlation in irregular lattices for which recognizing correlation is less intuitive.

Protein unfolding under isometric tension-what force can integrins generate, and can it unfold FNIII domains?

PubMed

Erickson, Harold P

2017-02-01

Extracellular matrix fibrils of fibronectin (FN) are highly elastic, and are typically stretched three to four times their relaxed length. The mechanism of stretching has been controversial, in particular whether it involves tension-induced unfolding of FNIII domains. Recent studies have found that ∼5pN is the threshold isometric force for unfolding various protein domains. FNIII domains should therefore not be unfolded until the tension approaches 5pN. Integrins have been reported to generate forces ranging from 1 to >50pN, but I argue that studies reporting 1-2pN are the most convincing. This is not enough to unfold FNIII domains. Even if domains were unfolded, 2pN would only extend the worm-like-chain to about twice the length of the folded domain. Overall I conclude that stretching FN matrix fibrils involves primarily the compact to extended conformational change of FN dimers, with minimal contribution from unfolding FNIII domains. Copyright © 2016 Elsevier Ltd. All rights reserved.

Time multiplexing based extended depth of focus imaging.

PubMed

Ilovitsh, Asaf; Zalevsky, Zeev

2016-01-01

We propose to utilize the time multiplexing super resolution method to extend the depth of focus of an imaging system. In standard time multiplexing, the super resolution is achieved by generating duplication of the optical transfer function in the spectrum domain, by the use of moving gratings. While this improves the spatial resolution, it does not increase the depth of focus. By changing the gratings frequency and, by that changing the duplication positions, it is possible to obtain an extended depth of focus. The proposed method is presented analytically, demonstrated via numerical simulations and validated by a laboratory experiment.

DC-SIGN neck domain is a pH-sensor controlling oligomerization: SAXS and hydrodynamic studies of extracellular domain.

PubMed

Tabarani, Georges; Thépaut, Michel; Stroebel, David; Ebel, Christine; Vivès, Corinne; Vachette, Patrice; Durand, Dominique; Fieschi, Franck

2009-08-07

DC-SIGN is a C-type lectin receptor of dendritic cells and is involved in the early stages of numerous infectious diseases. DC-SIGN is organized into a tetramer enabling multivalent interaction with pathogens. Once formed, the DC-SIGN-pathogen complex can be internalized into compartments of increasing acidity. We have studied the pH dependence of the oligomerization state and conformation of the entire extracellular domain and neck region. We present evidence for equilibrium between the monomeric and tetrameric states of the extracellular domain, which exhibits a marked dependence with respect to both pH and ionic strength. Using solution x-ray scattering we have obtained a molecular envelope of the extracellular domain in which a model has been built. Our results highlight the central role of the neck domain in the pH-sensitive control of the oligomerization state, in the extended conformation of the protein, and in carbohydrate recognition domain organization and presentation. This work opens new insight into the molecular mechanism of ligand release and points to new avenues to block the first step of this important infection pathway.

[Angiopoietins predict long-term outcomes after aneurysmal subarachnoid hemorrhage during an early period].

PubMed

Wang, Yi; Wang, Dong; Wei, Huijie; Tian, Ye; Jiang, Rongcai; Yue, Shuyuan; Zhang, Jianning

2015-05-19

To evaluate the association between serum levels of angiopoietins (Ang) during an early period (within 72 h) and clinical outcomes after aneurysmal subarachnoid haemorrhage (aSAH). This prospective study was conducted at Department of Neurosurgery, Tianjin Medical University General Hospital. Blood samples from 37 aSAH patients were collected at 8 h (or < 8 h), 24 h, 72 h after an onset of SAH. The serum levels of Ang-1, Ang-2 and Tie-2 were measured by enzyme-linked immunosorbent assay (ELISA). They were followed up for 3 months by Glasgow outcome score extended (GOSE). Those with GOSE > 5 were counted as a good outcome while those with GOSE ≤ 5 had a poor outcome. A total of 37 patients with aSAH and 39 healthy controls (HC) were enrolled. The aSAH patients showed a significant rise of Ang-1 within 8 h as compared with HC. The outcomes were good (n = 15) and poor (n = 22). Serum Ang-1 at 8 h (or < 8 h), 24 h and 72 h in good outcomers showed significantly higher than that in poor outcomers [(52 ± 24) vs (37 ± 17) mg/L, (62 ± 26) vs (45 ± 17) mg/L, (107 ± 27) vs (72 ± 18) mg/L]. The serum level of Ang-1 at 8 h and 24 h was one of independent risk factors for aSAH patients by multiariable Logistic regression analysis [adjected OR (95% CI) 1.095 (1.015-1.181) and 1.109 (1.016-1.211)] (P < 0.05). High serum level of Ang-1 during an early period (within 72 h) was associated with good outcomers (r = 0.627, P < 0.001). The serum levels of angiopoietins are significantly altered in aSAH patients, especially higher in good outcomers. And abnormal levels of angiopoietins may affect early brain injury (EBI) after SAH, structural integrity and recovery of blood-brain barrier (BBB) and long-term outcomes in aSAH patients.

Using neighborhood cohesiveness to infer interactions between protein domains.

PubMed

Segura, Joan; Sorzano, C O S; Cuenca-Alba, Jesus; Aloy, Patrick; Carazo, J M

2015-08-01

In recent years, large-scale studies have been undertaken to describe, at least partially, protein-protein interaction maps, or interactomes, for a number of relevant organisms, including human. However, current interactomes provide a somehow limited picture of the molecular details involving protein interactions, mostly because essential experimental information, especially structural data, is lacking. Indeed, the gap between structural and interactomics information is enlarging and thus, for most interactions, key experimental information is missing. We elaborate on the observation that many interactions between proteins involve a pair of their constituent domains and, thus, the knowledge of how protein domains interact adds very significant information to any interactomic analysis. In this work, we describe a novel use of the neighborhood cohesiveness property to infer interactions between protein domains given a protein interaction network. We have shown that some clustering coefficients can be extended to measure a degree of cohesiveness between two sets of nodes within a network. Specifically, we used the meet/min coefficient to measure the proportion of interacting nodes between two sets of nodes and the fraction of common neighbors. This approach extends previous works where homolog coefficients were first defined around network nodes and later around edges. The proposed approach substantially increases both the number of predicted domain-domain interactions as well as its accuracy as compared with current methods. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Different functional modes of BAR domain proteins in formation and plasticity of mammalian postsynapses.

PubMed

Kessels, Michael M; Qualmann, Britta

2015-09-01

A plethora of cell biological processes involve modulations of cellular membranes. By using extended lipid-binding interfaces, some proteins have the power to shape membranes by attaching to them. Among such membrane shapers, the superfamily of Bin-Amphiphysin-Rvs (BAR) domain proteins has recently taken center stage. Extensive structural work on BAR domains has revealed a common curved fold that can serve as an extended membrane-binding interface to modulate membrane topologies and has allowed the grouping of the BAR domain superfamily into subfamilies with structurally slightly distinct BAR domain subtypes (N-BAR, BAR, F-BAR and I-BAR). Most BAR superfamily members are expressed in the mammalian nervous system. Neurons are elaborately shaped and highly compartmentalized cells. Therefore, analyses of synapse formation and of postsynaptic reorganization processes (synaptic plasticity) - a basis for learning and memory formation - has unveiled important physiological functions of BAR domain superfamily members. These recent advances, furthermore, have revealed that the functions of BAR domain proteins include different aspects. These functions are influenced by the often complex domain organization of BAR domain proteins. In this Commentary, we review these recent insights and propose to classify BAR domain protein functions into (1) membrane shaping, (2) physical integration, (3) action through signaling components, and (4) suppression of other BAR domain functions. © 2015. Published by The Company of Biologists Ltd.

The organization of domains in proteins obeys Menzerath-Altmann's law of language.

PubMed

Shahzad, Khuram; Mittenthal, Jay E; Caetano-Anollés, Gustavo

2015-08-11

The combination of domains in multidomain proteins enhances their function and structure but lengthens the molecules and increases their cost at cellular level. The dependence of domain length on the number of domains a protein holds was surveyed for a set of 60 proteomes representing free-living organisms from all kingdoms of life. Distributions were fitted using non-linear functions and fitted parameters interpreted with a formulation of decreasing returns. We find that domain length decreases with increasing number of domains in proteins, following the Menzerath-Altmann (MA) law of language. Highly significant negative correlations exist for the set of proteomes examined. Mathematically, the MA law expresses as a power law relationship that unfolds when molecular persistence P is a function of domain accretion. P holds two terms, one reflecting the matter-energy cost of adding domains and extending their length, the other reflecting how domain length and number impinges on information and biophysics. The pattern of diminishing returns can therefore be explained as a frustrated interplay between the strategies of economy, flexibility and robustness, matching previously observed trade-offs in the domain makeup of proteomes. Proteomes of Archaea, Fungi and to a lesser degree Plants show the largest push towards molecular economy, each at their own economic stratum. Fungi increase domain size in single domain proteins while reinforcing the pattern of diminishing returns. In contrast, Metazoa, and to lesser degrees Protista and Bacteria, relax economy. Metazoa achieves maximum flexibility and robustness by harboring compact molecules and complex domain organization, offering a new functional vocabulary for molecular biology. The tendency of parts to decrease their size when systems enlarge is universal for language and music, and now for parts of macromolecules, extending the MA law to natural systems.

Learning from Experts: Fostering Extended Thinking in the Early Phases of the Design Process

ERIC Educational Resources Information Center

Haupt, Grietjie

2015-01-01

Empirical evidence on the way in which expert designers from different domains cognitively connect their internal processes with external resources is presented in the context of an extended cognition model. The article focuses briefly on the main trends in the extended design cognition theory and in particular on recent trends in information…

From sequencing to annotating: extending the metaphor of the book of life from genetics to genomics.

PubMed

Hellsten, Iina

2005-12-01

The article discusses how the metaphor of the Book of Life was extended over time to cover the life cycle of the Human Genome Project from genetics to genomics. In particular, the focus is on the role of extendable metaphors in the debate on the Human Genome Project in three European newspapers, popular scientific journals and scientific and scholarly articles from 1990 to 2002. In these different domains of use, various parts of the metaphor were highlighted. The metaphor of Book of Life was mainly used to justify the continuation of the gene research from gene sequencing to comparative genomics. Readily extendable metaphors, such as the Book of Life, function as useful communicative tools both over time and across domains of use.

The Application of Deterministic Spectral Domain Method to the Analysis of Planar Circuit Discontinuities on Open Substrates

DTIC Science & Technology

1990-08-01

the spectral domain is extended to include the effects of two-dimensional, two-component current flow in planar transmission line discontinuities 6n...PROFESSOR: Tatsuo Itoh A deterministic formulation of the method of moments carried out in the spectral domain is extended to include the effects of...two-dimensional, two- component current flow in planar transmission line discontinuities on open substrates. The method includes the effects of space

Large exchange-dominated domain wall velocities in antiferromagnetically coupled nanowires

NASA Astrophysics Data System (ADS)

Kuteifan, Majd; Lubarda, M. V.; Fu, S.; Chang, R.; Escobar, M. A.; Mangin, S.; Fullerton, E. E.; Lomakin, V.

2016-04-01

Magnetic nanowires supporting field- and current-driven domain wall motion are envisioned for methods of information storage and processing. A major obstacle for their practical use is the domain-wall velocity, which is traditionally limited for low fields and currents due to the Walker breakdown occurring when the driving component reaches a critical threshold value. We show through numerical and analytical modeling that the Walker breakdown limit can be extended or completely eliminated in antiferromagnetically coupled magnetic nanowires. These coupled nanowires allow for large domain-wall velocities driven by field and/or current as compared to conventional nanowires.

Cell Adhesion Molecule L1 in Folded (Horseshoe) and Extended Conformations

PubMed Central

Schürmann, Gregor; Haspel, Jeffrey; Grumet, Martin; Erickson, Harold P.

2001-01-01

We have investigated the structure of the cell adhesion molecule L1 by electron microscopy. We were particularly interested in the conformation of the four N-terminal immunoglobulin domains, because x-ray diffraction showed that these domains are bent into a horseshoe shape in the related molecules hemolin and axonin-1. Surprisingly, rotary-shadowed specimens showed the molecules to be elongated, with no indication of the horseshoe shape. However, sedimentation data suggested that these domains of L1 were folded into a compact shape in solution; therefore, this prompted us to look at the molecules by an alternative technique, negative stain. The negative stain images showed a compact shape consistent with the expected horseshoe conformation. We speculate that in rotary shadowing the contact with the mica caused a distortion of the protein, weakening the bonds forming the horseshoe and permitting the molecule to extend. We have thus confirmed that the L1 molecule is primarily in the horseshoe conformation in solution, and we have visualized for the first time its opening into an extended conformation. Our study resolves conflicting interpretations from previous electron microscopy studies of L1. PMID:11408583

Revisiting and Extending Interface Penalties for Multi-Domain Summation-by-Parts Operators

NASA Technical Reports Server (NTRS)

Carpenter, Mark H.; Nordstrom, Jan; Gottlieb, David

2007-01-01

General interface coupling conditions are presented for multi-domain collocation methods, which satisfy the summation-by-parts (SBP) spatial discretization convention. The combined interior/interface operators are proven to be L2 stable, pointwise stable, and conservative, while maintaining the underlying accuracy of the interior SBP operator. The new interface conditions resemble (and were motivated by) those used in the discontinuous Galerkin finite element community, and maintain many of the same properties. Extensive validation studies are presented using two classes of high-order SBP operators: 1) central finite difference, and 2) Legendre spectral collocation.

Rating knowledge sharing in cross-domain collaborative filtering.

PubMed

Li, Bin; Zhu, Xingquan; Li, Ruijiang; Zhang, Chengqi

2015-05-01

Cross-domain collaborative filtering (CF) aims to share common rating knowledge across multiple related CF domains to boost the CF performance. In this paper, we view CF domains as a 2-D site-time coordinate system, on which multiple related domains, such as similar recommender sites or successive time-slices, can share group-level rating patterns. We propose a unified framework for cross-domain CF over the site-time coordinate system by sharing group-level rating patterns and imposing user/item dependence across domains. A generative model, say ratings over site-time (ROST), which can generate and predict ratings for multiple related CF domains, is developed as the basic model for the framework. We further introduce cross-domain user/item dependence into ROST and extend it to two real-world cross-domain CF scenarios: 1) ROST (sites) for alleviating rating sparsity in the target domain, where multiple similar sites are viewed as related CF domains and some items in the target domain depend on their correspondences in the related ones; and 2) ROST (time) for modeling user-interest drift over time, where a series of time-slices are viewed as related CF domains and a user at current time-slice depends on herself in the previous time-slice. All these ROST models are instances of the proposed unified framework. The experimental results show that ROST (sites) can effectively alleviate the sparsity problem to improve rating prediction performance and ROST (time) can clearly track and visualize user-interest drift over time.

Structure of a two-CAP-domain protein from the human hookworm parasite Necator americanus

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

Asojo, Oluwatoyin A., E-mail: oasojo@unmc.edu

2011-05-01

The first structure of a two-CAP-domain protein, Na-ASP-1, from the major human hookworm parasite N. americanus refined to a resolution limit of 2.2 Å is presented. Major proteins secreted by the infective larval stage hookworms upon host entry include Ancylostoma secreted proteins (ASPs), which are characterized by one or two CAP (cysteine-rich secretory protein/antigen 5/pathogenesis related-1) domains. The CAP domain has been reported in diverse phylogenetically unrelated proteins, but has no confirmed function. The first structure of a two-CAP-domain protein, Na-ASP-1, from the major human hookworm parasite Necator americanus was refined to a resolution limit of 2.2 Å. The structuremore » was solved by molecular replacement (MR) using Na-ASP-2, a one-CAP-domain ASP, as the search model. The correct MR solution could only be obtained by truncating the polyalanine model of Na-ASP-2 and removing several loops. The structure reveals two CAP domains linked by an extended loop. Overall, the carboxyl-terminal CAP domain is more similar to Na-ASP-2 than to the amino-terminal CAP domain. A large central cavity extends from the amino-terminal CAP domain to the carboxyl-terminal CAP domain, encompassing the putative CAP-binding cavity. The putative CAP-binding cavity is a characteristic cavity in the carboxyl-terminal CAP domain that contains a His and Glu pair. These residues are conserved in all single-CAP-domain proteins, but are absent in the amino-terminal CAP domain. The conserved His residues are oriented such that they appear to be capable of directly coordinating a zinc ion as observed for CAP proteins from reptile venoms. This first structure of a two-CAP-domain ASP can serve as a template for homology modeling of other two-CAP-domain proteins.« less

Multiple hypothesis tracking for the cyber domain

NASA Astrophysics Data System (ADS)

Schwoegler, Stefan; Blackman, Sam; Holsopple, Jared; Hirsch, Michael J.

2011-09-01

This paper discusses how methods used for conventional multiple hypothesis tracking (MHT) can be extended to domain-agnostic tracking of entities from non-kinematic constraints such as those imposed by cyber attacks in a potentially dense false alarm background. MHT is widely recognized as the premier method to avoid corrupting tracks with spurious data in the kinematic domain but it has not been extensively applied to other problem domains. The traditional approach is to tightly couple track maintenance (prediction, gating, filtering, probabilistic pruning, and target confirmation) with hypothesis management (clustering, incompatibility maintenance, hypothesis formation, and Nassociation pruning). However, by separating the domain specific track maintenance portion from the domain agnostic hypothesis management piece, we can begin to apply the wealth of knowledge gained from ground and air tracking solutions to the cyber (and other) domains. These realizations led to the creation of Raytheon's Multiple Hypothesis Extensible Tracking Architecture (MHETA). In this paper, we showcase MHETA for the cyber domain, plugging in a well established method, CUBRC's INFormation Engine for Real-time Decision making, (INFERD), for the association portion of the MHT. The result is a CyberMHT. We demonstrate the power of MHETA-INFERD using simulated data. Using metrics from both the tracking and cyber domains, we show that while no tracker is perfect, by applying MHETA-INFERD, advanced nonkinematic tracks can be captured in an automated way, perform better than non-MHT approaches, and decrease analyst response time to cyber threats.

Pan-Cancer Analysis of Mutation Hotspots in Protein Domains.

PubMed

Miller, Martin L; Reznik, Ed; Gauthier, Nicholas P; Aksoy, Bülent Arman; Korkut, Anil; Gao, Jianjiong; Ciriello, Giovanni; Schultz, Nikolaus; Sander, Chris

2015-09-23

In cancer genomics, recurrence of mutations in independent tumor samples is a strong indicator of functional impact. However, rare functional mutations can escape detection by recurrence analysis owing to lack of statistical power. We enhance statistical power by extending the notion of recurrence of mutations from single genes to gene families that share homologous protein domains. Domain mutation analysis also sharpens the functional interpretation of the impact of mutations, as domains more succinctly embody function than entire genes. By mapping mutations in 22 different tumor types to equivalent positions in multiple sequence alignments of domains, we confirm well-known functional mutation hotspots, identify uncharacterized rare variants in one gene that are equivalent to well-characterized mutations in another gene, detect previously unknown mutation hotspots, and provide hypotheses about molecular mechanisms and downstream effects of domain mutations. With the rapid expansion of cancer genomics projects, protein domain hotspot analysis will likely provide many more leads linking mutations in proteins to the cancer phenotype. Copyright © 2015 Elsevier Inc. All rights reserved.

Beta oscillations define discrete perceptual cycles in the somatosensory domain.

PubMed

Baumgarten, Thomas J; Schnitzler, Alfons; Lange, Joachim

2015-09-29

Whether seeing a movie, listening to a song, or feeling a breeze on the skin, we coherently experience these stimuli as continuous, seamless percepts. However, there are rare perceptual phenomena that argue against continuous perception but, instead, suggest discrete processing of sensory input. Empirical evidence supporting such a discrete mechanism, however, remains scarce and comes entirely from the visual domain. Here, we demonstrate compelling evidence for discrete perceptual sampling in the somatosensory domain. Using magnetoencephalography (MEG) and a tactile temporal discrimination task in humans, we find that oscillatory alpha- and low beta-band (8-20 Hz) cycles in primary somatosensory cortex represent neurophysiological correlates of discrete perceptual cycles. Our results agree with several theoretical concepts of discrete perceptual sampling and empirical evidence of perceptual cycles in the visual domain. Critically, these results show that discrete perceptual cycles are not domain-specific, and thus restricted to the visual domain, but extend to the somatosensory domain.

Discrimination between Closely Related Cellular Metabolites by the SAM-I Riboswitch

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

Montange, R.; Mondragon, E; van Tyne, D

2010-01-01

The SAM-I riboswitch is a cis-acting element of genetic control found in bacterial mRNAs that specifically binds S-adenosylmethionine (SAM). We previously determined the 2.9-{angstrom} X-ray crystal structure of the effector-binding domain of this RNA element, revealing details of RNA-ligand recognition. To improve this structure, variations were made to the RNA sequence to alter lattice contacts, resulting in a 0.5-{angstrom} improvement in crystallographic resolution and allowing for a more accurate refinement of the crystallographic model. The basis for SAM specificity was addressed by a structural analysis of the RNA complexed to S-adenosylhomocysteine (SAH) and sinefungin and by measuring the affinity ofmore » SAM and SAH for a series of mutants using isothermal titration calorimetry. These data illustrate the importance of two universally conserved base pairs in the RNA that form electrostatic interactions with the positively charged sulfonium group of SAM, thereby providing a basis for discrimination between SAM and SAH.« less

A test of the domain-specific acculturation strategy hypothesis.

PubMed

Miller, Matthew J; Yang, Minji; Lim, Robert H; Hui, Kayi; Choi, Na-Yeun; Fan, Xiaoyan; Lin, Li-Ling; Grome, Rebekah E; Farrell, Jerome A; Blackmon, Sha'kema

2013-01-01

Acculturation literature has evolved over the past several decades and has highlighted the dynamic ways in which individuals negotiate experiences in multiple cultural contexts. The present study extends this literature by testing M. J. Miller and R. H. Lim's (2010) domain-specific acculturation strategy hypothesis-that individuals might use different acculturation strategies (i.e., assimilated, bicultural, separated, and marginalized strategies; J. W. Berry, 2003) across behavioral and values domains-in 3 independent cluster analyses with Asian American participants. Present findings supported the domain-specific acculturation strategy hypothesis as 67% to 72% of participants from 3 independent samples using different strategies across behavioral and values domains. Consistent with theory, a number of acculturation strategy cluster group differences emerged across generational status, acculturative stress, mental health symptoms, and attitudes toward seeking professional psychological help. Study limitations and future directions for research are discussed.

Coupling complement regulators to immunoglobulin domains generates effective anti-complement reagents with extended half-life in vivo

PubMed Central

HARRIS, C L; WILLIAMS, A S; LINTON, S M; MORGAN, B P

2002-01-01

Complement activation and subsequent generation of inflammatory molecules and membrane attack complex contributes to the pathology of a number of inflammatory and degenerative diseases, including arthritis, glomerulonephritis and demyelination. Agents that specifically inhibit complement activation might prove beneficial in the treatment of these diseases. Soluble recombinant forms of the naturally occurring membrane complement regulatory proteins (CRP) have been exploited for this purpose. We have undertaken to design better therapeutics based on CRP. Here we describe the generation of soluble, recombinant CRP comprising rat decay accelerating factor (DAF) or rat CD59 expressed as Fc fusion proteins, antibody-like molecules comprising two CRP moieties in place of the antibody Fab arms (CRP-Ig). Reagents bearing DAF on each arm (DAF-Ig), CD59 on each arm (CD59-Ig) and a hybrid reagent containing both DAF and CD59 were generated. All three reagents inhibited C activation in vitro. Compared with soluble CRP lacking Fc domains, activity was reduced, but was fully restored by enzymatic release of the regulator from the Ig moiety, implicating steric constraints in reducing functional activity. In vivo studies showed that DAF-Ig, when compared to soluble DAF, had a much extended half-life in the circulation in rats and concomitantly caused a sustained reduction in plasma complement activity. When given intra-articularly to rats in a model of arthritis, DAF-Ig significantly reduced severity of disease. The data demonstrate the potential of CRP-Ig as reagents for sustained therapy of inflammatory disorders, including arthritis, but emphasize the need for careful design of fusion proteins to retain function. PMID:12165074

First experience with the new .cern Top Level Domain

NASA Astrophysics Data System (ADS)

Alvarez, E.; Malo de Molina, M.; Salwerowicz, M.; Silva De Sousa, B.; Smith, T.; Wagner, A.

2017-10-01

In October 2015, CERN’s core website has been moved to a new address, http://home.cern, marking the launch of the brand new top-level domain .cern. In combination with a formal governance and registration policy, the IT infrastructure needed to be extended to accommodate the hosting of Web sites in this new top level domain. We will present the technical implementation in the framework of the CERN Web Services that allows to provide virtual hosting, a reverse proxy solution and that also includes the provisioning of SSL server certificates for secure communications.

Crystal structure of the motor domain of a class-I myosin

PubMed Central

Kollmar, Martin; Dürrwang, Ulrike; Kliche, Werner; Manstein, Dietmar J.; Kull, F.Jon

2002-01-01

The crystal structure of the motor domain of Dictyostelium discoideum myosin-IE, a monomeric unconventional myosin, was determined. The crystallographic asymmetric unit contains four independently resolved molecules, highlighting regions that undergo large conformational changes. Differences are particularly pronounced in the actin binding region and the converter domain. The changes in position of the converter domain reflect movements both parallel to and perpendicular to the actin axis. The orientation of the converter domain is ∼30° further up than in other myosin structures, indicating that MyoE can produce a larger power stroke by rotating its lever arm through a larger angle. The role of extended loops near the actin-binding site is discussed in the context of cellular localization. The core regions of the motor domain are similar, and the structure reveals how that core is stabilized in the absence of an N-terminal SH3-like domain. PMID:12032065

XML Based Markup Languages for Specific Domains

NASA Astrophysics Data System (ADS)

Varde, Aparna; Rundensteiner, Elke; Fahrenholz, Sally

A challenging area in web based support systems is the study of human activities in connection with the web, especially with reference to certain domains. This includes capturing human reasoning in information retrieval, facilitating the exchange of domain-specific knowledge through a common platform and developing tools for the analysis of data on the web from a domain expert's angle. Among the techniques and standards related to such work, we have XML, the eXtensible Markup Language. This serves as a medium of communication for storing and publishing textual, numeric and other forms of data seamlessly. XML tag sets are such that they preserve semantics and simplify the understanding of stored information by users. Often domain-specific markup languages are designed using XML, with a user-centric perspective. Standardization bodies and research communities may extend these to include additional semantics of areas within and related to the domain. This chapter outlines the issues to be considered in developing domain-specific markup languages: the motivation for development, the semantic considerations, the syntactic constraints and other relevant aspects, especially taking into account human factors. Illustrating examples are provided from domains such as Medicine, Finance and Materials Science. Particular emphasis in these examples is on the Materials Markup Language MatML and the semantics of one of its areas, namely, the Heat Treating of Materials. The focus of this chapter, however, is not the design of one particular language but rather the generic issues concerning the development of domain-specific markup languages.

Entropy gives rise to topologically associating domains

PubMed Central

Vasquez, Paula A.; Hult, Caitlin; Adalsteinsson, David; Lawrimore, Josh; Forest, Mark G.; Bloom, Kerry

2016-01-01

We investigate chromosome organization within the nucleus using polymer models whose formulation is closely guided by experiments in live yeast cells. We employ bead-spring chromosome models together with loop formation within the chains and the presence of nuclear bodies to quantify the extent to which these mechanisms shape the topological landscape in the interphase nucleus. By investigating the genome as a dynamical system, we show that domains of high chromosomal interactions can arise solely from the polymeric nature of the chromosome arms due to entropic interactions and nuclear confinement. In this view, the role of bio-chemical related processes is to modulate and extend the duration of the interacting domains. PMID:27257057

A structural portrait of the PDZ domain family.

PubMed

Ernst, Andreas; Appleton, Brent A; Ivarsson, Ylva; Zhang, Yingnan; Gfeller, David; Wiesmann, Christian; Sidhu, Sachdev S

2014-10-23

PDZ (PSD-95/Discs-large/ZO1) domains are interaction modules that typically bind to specific C-terminal sequences of partner proteins and assemble signaling complexes in multicellular organisms. We have analyzed the existing database of PDZ domain structures in the context of a specificity tree based on binding specificities defined by peptide-phage binding selections. We have identified 16 structures of PDZ domains in complex with high-affinity ligands and have elucidated four additional structures to assemble a structural database that covers most of the branches of the PDZ specificity tree. A detailed comparison of the structures reveals features that are responsible for the diverse specificities across the PDZ domain family. Specificity differences can be explained by differences in PDZ residues that are in contact with the peptide ligands, but these contacts involve both side-chain and main-chain interactions. Most PDZ domains bind peptides in a canonical conformation in which the ligand main chain adopts an extended β-strand conformation by interacting in an antiparallel fashion with a PDZ β-strand. However, a subset of PDZ domains bind peptides with a bent main-chain conformation and the specificities of these non-canonical domains could not be explained based on canonical structures. Our analysis provides a structural portrait of the PDZ domain family, which serves as a guide in understanding the structural basis for the diverse specificities across the family. Copyright © 2014 Elsevier Ltd. All rights reserved.

SIRT1 activation by resveratrol reduces brain edema and neuronal apoptosis in an experimental rat subarachnoid hemorrhage model.

PubMed

Qian, Cong; Jin, Jianxiang; Chen, Jingyin; Li, Jianru; Yu, Xiaobo; Mo, Hangbo; Chen, Gao

2017-12-01

Early brain injury is considered to be a major risk that is related to the prognosis of subarachnoid hemorrhage (SAH). In SAH model rats, brain edema and apoptosis have been closely related with death rate and neurological function. Sirtuin 1 (SIRT1) was reported to be involved in apoptosis in cerebral ischemia and brain tumor formation through p53 deacetylation. The present study aimed to evaluate the role of SIRT1 in a rat endovascular perforation model of SAH. The SIRT1 activator resveratrol (RES) was administered 48 h prior to SAH induction and the SIRT1 inhibitor Sirtinol (SIR) was used to reverse the effects of RES on SIRT1 expression. Mortality rate, neurological function and brain water content were measured 24 h post‑SAH induction. Proteins associated with the blood brain barrier (BBB), apoptosis and SIRT1 in the cortex, such as zona occludens 1 (ZO‑1), occludin, claudin‑5, SIRT1, p53 and cleaved caspase3 were investigated. mRNA expression of the p53 downstream molecules including Bcl‑associated X protein, P53 upregulated modulator of apoptosis, Noxa and BH3 interacting‑domain death agonist were also investigated. Neuronal apoptosis was also investigated by immunofluorescence. RES pretreatment reduced the mortality rate and improved neurological function, which was consistent with reduced brain water content and neuronal apoptosis; these effects were partially reversed by co‑treatment with SIR. SIRT1 may reduce the brain water content by improvement of dysfunctional BBB permeability, and protein analysis revealed that both ZO‑1, occludin and claudin‑5 may be involved, and these effects were reversed by SIRT1 inhibition. SIRT1 may also affect apoptosis post‑SAH through p53 deacetylation, and the analysis of p53 related downstream pro‑apoptotic molecules supported this hypothesis. Localization of neuron specific apoptosis revealed that SIRT1 may regulate neuronal apoptosis following SAH. SIRT1 may also ease brain edema and neuronal

Pushing the P300-based brain-computer interface beyond 100 bpm: extending performance guided constraints into the temporal domain.

PubMed

Townsend, G; Platsko, V

2016-04-01

A new presentation paradigm for the P300-based brain-computer interface (BCI) referred to as the 'asynchronous paradigm' (ASP) is introduced and studied. It is based on the principle of performance guided constraints (Townsend et al 2012 Neurosci. Lett. 531 63-8) extended from the spatial domain into the temporal domain. The traditional constraint of flashing targets in predefined constant epochs of time is eliminated and targets flash asynchronously with timing based instead on constraints intended to improve performance. We propose appropriate temporal constraints to derive the ASP and compare its performance to that of the 'checkerboard paradigm' (CBP), which has previously been shown to be superior to the standard 'row/column paradigm' introduced by Farwell and Donchin (1988 Electroencephalogr. Clin. Neurophysiol. 70 510-23). Ten participants were tested in the ASP and CBP conditions both with traditional flashing items and with flashing faces in place of the targets (see Zhang et al 2012 J. Neural Eng. 9 026018; Kaufmann and Kübler 2014 J. Neural Eng. 11 ; Chen et al 2015 J. Neurosci. Methods 239 18-27). Eleven minutes of calibration data were used as input to a stepwise linear discriminant analysis to derive classification coefficients used for online classification. Accuracy was consistently high for both paradigms (87% and 93%) while information transfer rate was 45% higher for the ASP than the CBP. In a free spelling task, one subject spelled a 66 character sentence (from a 72 item matrix) with 100% accuracy in 3 min and 24 s demonstrating a practical throughput of 120 bits per minute (bpm) with a theoretical upper bound of 258 bpm. The subject repeated the task three times in a row without error. This work represents an advance in P300 speller technology and raises the ceiling that was being reached on P300-based BCIs. Most importantly, the research presented here is a novel and effective general strategy for organising timing for flashing items. The ASP

Novel Exenatide Analogs with Peptidic Albumin Binding Domains: Potent Anti-Diabetic Agents with Extended Duration of Action

PubMed Central

Levy, Odile E.; Jodka, Carolyn M.; Ren, Shijun Steven; Mamedova, Lala; Sharma, Abhinandini; Samant, Manoj; D’Souza, Lawrence J.; Soares, Christopher J.; Yuskin, Diane R.; Jin, Li Jenny; Parkes, David G.; Tatarkiewicz, Krystyna; Ghosh, Soumitra S.

2014-01-01

The design, synthesis and pharmacology of novel long-acting exenatide analogs for the treatment of metabolic diseases are described. These molecules display enhanced pharmacokinetic profile and potent glucoregulatory and weight lowering actions compared to native exenatide. [Leu14]exenatide-ABD is an 88 residue peptide amide incorporating an Albumin Binding Domain (ABD) scaffold. [Leu14]exenatide-ABP is a 53 residue peptide incorporating a short Albumin Binding Peptide (ABP). [Leu14]exenatide-ABD and [Leu14]exenatide-ABP exhibited nanomolar functional GLP-1 receptor potency and were metabolically stable in vitro in human plasma and in a pancreatic digestive enzyme mixture. Both molecules displayed picomolar and nanomolar binding association with albumin across multiple species and circulating half lives of 16 and 11 hours, respectively, post a single IV dose in rats. Unlike exenatide, both molecules elicited robust glucose lowering when injected 1 day prior to an oral glucose tolerance test, indicative of their extended duration of action. [Leu14]exenatide-ABD was compared to exenatide in a Lep ob/ob mouse model of diabetes. Twice-weekly subcutaneously dosed [Leu14]exenatide-ABD displayed superior glucose lowering and weight loss in diabetic mice when compared to continuously infused exenatide at the same total weekly dose. A single oral administration of each molecule via an enteric coated capsule to cynomolgus monkeys showed superior pharmacokinetics for [Leu14]exenatide-ABD as compared to [Leu14]exenatide-ABP with detectable exposure longer than 14 days. These studies support the potential use of these novel long acting exenatide analogs with different routes of administration for the treatment of type 2 diabetes. PMID:24503632

Pivotal role of extended linker 2 in the activation of Gα by G protein-coupled receptor.

PubMed

Huang, Jianyun; Sun, Yutong; Zhang, J Jillian; Huang, Xin-Yun

2015-01-02

G protein-coupled receptors (GPCRs) relay extracellular signals mainly to heterotrimeric G-proteins (Gαβγ) and they are the most successful drug targets. The mechanisms of G-protein activation by GPCRs are not well understood. Previous studies have revealed a signal relay route from a GPCR via the C-terminal α5-helix of Gα to the guanine nucleotide-binding pocket. Recent structural and biophysical studies uncover a role for the opening or rotating of the α-helical domain of Gα during the activation of Gα by a GPCR. Here we show that β-adrenergic receptors activate eight Gαs mutant proteins (from a screen of 66 Gαs mutants) that are unable to bind Gβγ subunits in cells. Five of these eight mutants are in the αF/Linker 2/β2 hinge region (extended Linker 2) that connects the Ras-like GTPase domain and the α-helical domain of Gαs. This extended Linker 2 is the target site of a natural product inhibitor of Gq. Our data show that the extended Linker 2 is critical for Gα activation by GPCRs. We propose that a GPCR via its intracellular loop 2 directly interacts with the β2/β3 loop of Gα to communicate to Linker 2, resulting in the opening and closing of the α-helical domain and the release of GDP during G-protein activation. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Cognitive reserve is not associated with improved performance in all cognitive domains.

PubMed

Lavrencic, Louise M; Churches, Owen F; Keage, Hannah A D

2017-06-08

Cognitive reserve beneficially affects cognitive performance, even into advanced age. However, the benefits afforded by high cognitive reserve may not extend to all cognitive domains. This study investigated whether cognitive reserve differentially affects performance on cognitive tasks, in 521 cognitively healthy individuals aged 60 to 98 years (Mage = 68, SD = 6.22, 287 female); years of education was used to index cognitive reserve. Cognitive performance variables assessed attention, executive functions, verbal memory, motor performance, orientation, perception of emotion, processing speed, and working memory. Bootstrapped regression analyses revealed that cognitive reserve was associated with attention, executive functions, verbal and working memory, and orientation; and not significantly related to emotion perception, processing speed, or motor performance. Cognitive reserve appears to differentially affect individual cognitive domains, which extends current theory that purports benefits for all domains. This finding highlights the possibility of using tests not (or minimally) associated with cognitive reserve, to screen for cognitive impairment and dementia in late life; these tests will likely best track brain health, free of compensatory neural mechanisms.

Decoding rule search domain in the left inferior frontal gyrus

PubMed Central

Babcock, Laura; Vallesi, Antonino

2018-01-01

Traditionally, the left hemisphere has been thought to extract mainly verbal patterns of information, but recent evidence has shown that the left Inferior Frontal Gyrus (IFG) is active during inductive reasoning in both the verbal and spatial domains. We aimed to understand whether the left IFG supports inductive reasoning in a domain-specific or domain-general fashion. To do this we used Multi-Voxel Pattern Analysis to decode the representation of domain during a rule search task. Thirteen participants were asked to extract the rule underlying streams of letters presented in different spatial locations. Each rule was either verbal (letters forming words) or spatial (positions forming geometric figures). Our results show that domain was decodable in the left prefrontal cortex, suggesting that this region represents domain-specific information, rather than processes common to the two domains. A replication study with the same participants tested two years later confirmed these findings, though the individual representations changed, providing evidence for the flexible nature of representations. This study extends our knowledge on the neural basis of goal-directed behaviors and on how information relevant for rule extraction is flexibly mapped in the prefrontal cortex. PMID:29547623

Domain wall assisted GMR head with spin-Hall effect

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

Arun, R., E-mail: arunbdu@gmail.com; Sabareesan, P., E-mail: sendtosabari@gmail.com; Daniel, M., E-mail: danielcnld@gmail.com

2016-05-06

We theoretically study the dynamics of a field induced domain wall in the Py/Pt bi-layer structure in the presence of spin-Hall effect (SHE) by solving the Landau-Lifshitz-Gilbert (LLG) equation along with the adiabatic, nonadiabatic and SHE spin-transfer torques (STTs). It is observed that a weak magnetic field moves the domain wall with high velocity in the presence of SHE and the direction of the velocity is changed by changing the direction of the weak field. The numerical results show that the magnetization of the ferromagnetic layer can be reversed quickly through domain wall motion by changing the direction of amore » weak external field in the presence of SHE while the direction of current is fixed. The SHE reduces the magnetization reversal time of 1000 nm length strip by 14.7 ns. This study is extended to model a domain wall based GMR (Giant Magnetoresistance) read head with SHE.« less

Domain decomposition for aerodynamic and aeroacoustic analyses, and optimization

NASA Technical Reports Server (NTRS)

Baysal, Oktay

1995-01-01

The overarching theme was the domain decomposition, which intended to improve the numerical solution technique for the partial differential equations at hand; in the present study, those that governed either the fluid flow, or the aeroacoustic wave propagation, or the sensitivity analysis for a gradient-based optimization. The role of the domain decomposition extended beyond the original impetus of discretizing geometrical complex regions or writing modular software for distributed-hardware computers. It induced function-space decompositions and operator decompositions that offered the valuable property of near independence of operator evaluation tasks. The objectives have gravitated about the extensions and implementations of either the previously developed or concurrently being developed methodologies: (1) aerodynamic sensitivity analysis with domain decomposition (SADD); (2) computational aeroacoustics of cavities; and (3) dynamic, multibody computational fluid dynamics using unstructured meshes.

Mapping the Shh long-range regulatory domain

PubMed Central

Anderson, Eve; Devenney, Paul S.; Hill, Robert E.; Lettice, Laura A.

2014-01-01

Coordinated gene expression controlled by long-distance enhancers is orchestrated by DNA regulatory sequences involving transcription factors and layers of control mechanisms. The Shh gene and well-established regulators are an example of genomic composition in which enhancers reside in a large desert extending into neighbouring genes to control the spatiotemporal pattern of expression. Exploiting the local hopping activity of the Sleeping Beauty transposon, the lacZ reporter gene was dispersed throughout the Shh region to systematically map the genomic features responsible for expression activity. We found that enhancer activities are retained inside a genomic region that corresponds to the topological associated domain (TAD) defined by Hi-C. This domain of approximately 900 kb is in an open conformation over its length and is generally susceptible to all Shh enhancers. Similar to the distal enhancers, an enhancer residing within the Shh second intron activates the reporter gene located at distances of hundreds of kilobases away, suggesting that both proximal and distal enhancers have the capacity to survey the Shh topological domain to recognise potential promoters. The widely expressed Rnf32 gene lying within the Shh domain evades enhancer activities by a process that may be common among other housekeeping genes that reside in large regulatory domains. Finally, the boundaries of the Shh TAD do not represent the absolute expression limits of enhancer activity, as expression activity is lost stepwise at a number of genomic positions at the verges of these domains. PMID:25252942

Going from microscopic to macroscopic on nonuniform growing domains.

PubMed

Yates, Christian A; Baker, Ruth E; Erban, Radek; Maini, Philip K

2012-08-01

Throughout development, chemical cues are employed to guide the functional specification of underlying tissues while the spatiotemporal distributions of such chemicals can be influenced by the growth of the tissue itself. These chemicals, termed morphogens, are often modeled using partial differential equations (PDEs). The connection between discrete stochastic and deterministic continuum models of particle migration on growing domains was elucidated by Baker, Yates, and Erban [Bull. Math. Biol. 72, 719 (2010)] in which the migration of individual particles was modeled as an on-lattice position-jump process. We build on this work by incorporating a more physically reasonable description of domain growth. Instead of allowing underlying lattice elements to instantaneously double in size and divide, we allow incremental element growth and splitting upon reaching a predefined threshold size. Such a description of domain growth necessitates a nonuniform partition of the domain. We first demonstrate that an individual-based stochastic model for particle diffusion on such a nonuniform domain partition is equivalent to a PDE model of the same phenomenon on a nongrowing domain, providing the transition rates (which we derive) are chosen correctly and we partition the domain in the correct manner. We extend this analysis to the case where the domain is allowed to change in size, altering the transition rates as necessary. Through application of the master equation formalism we derive a PDE for particle density on this growing domain and corroborate our findings with numerical simulations.

Low resolution solution structure of HAMLET and the importance of its alpha-domains in tumoricidal activity.

PubMed

Ho, C S James; Rydstrom, Anna; Manimekalai, Malathy Sony Subramanian; Svanborg, Catharina; Grüber, Gerhard

2012-01-01

HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is the first member in a new family of protein-lipid complexes with broad tumoricidal activity. Elucidating the molecular structure and the domains crucial for HAMLET formation is fundamental for understanding its tumoricidal function. Here we present the low-resolution solution structure of the complex of oleic acid bound HAMLET, derived from small angle X-ray scattering data. HAMLET shows a two-domain conformation with a large globular domain and an extended part of about 2.22 nm in length and 1.29 nm width. The structure has been superimposed into the related crystallographic structure of human α-lactalbumin, revealing that the major part of α-lactalbumin accommodates well in the shape of HAMLET. However, the C-terminal residues from L105 to L123 of the crystal structure of the human α-lactalbumin do not fit well into the HAMLET structure, resulting in an extended conformation in HAMLET, proposed to be required to form the tumoricidal active HAMLET complex with oleic acid. Consistent with this low resolution structure, we identified biologically active peptide epitopes in the globular as well as the extended domains of HAMLET. Peptides covering the alpha1 and alpha2 domains of the protein triggered rapid ion fluxes in the presence of sodium oleate and were internalized by tumor cells, causing rapid and sustained changes in cell morphology. The alpha peptide-oleate bound forms also triggered tumor cell death with comparable efficiency as HAMLET. In addition, shorter peptides corresponding to those domains are biologically active. These findings provide novel insights into the structural prerequisites for the dramatic effects of HAMLET on tumor cells.

Low Resolution Solution Structure of HAMLET and the Importance of Its Alpha-Domains in Tumoricidal Activity

PubMed Central

Ho CS, James; Rydstrom, Anna; Manimekalai, Malathy Sony Subramanian; Svanborg, Catharina; Grüber, Gerhard

2012-01-01

HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is the first member in a new family of protein-lipid complexes with broad tumoricidal activity. Elucidating the molecular structure and the domains crucial for HAMLET formation is fundamental for understanding its tumoricidal function. Here we present the low-resolution solution structure of the complex of oleic acid bound HAMLET, derived from small angle X-ray scattering data. HAMLET shows a two-domain conformation with a large globular domain and an extended part of about 2.22 nm in length and 1.29 nm width. The structure has been superimposed into the related crystallographic structure of human α-lactalbumin, revealing that the major part of α-lactalbumin accommodates well in the shape of HAMLET. However, the C-terminal residues from L105 to L123 of the crystal structure of the human α-lactalbumin do not fit well into the HAMLET structure, resulting in an extended conformation in HAMLET, proposed to be required to form the tumoricidal active HAMLET complex with oleic acid. Consistent with this low resolution structure, we identified biologically active peptide epitopes in the globular as well as the extended domains of HAMLET. Peptides covering the alpha1 and alpha2 domains of the protein triggered rapid ion fluxes in the presence of sodium oleate and were internalized by tumor cells, causing rapid and sustained changes in cell morphology. The alpha peptide-oleate bound forms also triggered tumor cell death with comparable efficiency as HAMLET. In addition, shorter peptides corresponding to those domains are biologically active. These findings provide novel insights into the structural prerequisites for the dramatic effects of HAMLET on tumor cells. PMID:23300861

Sigma 1 protein of mammalian reoviruses extends from the surfaces of viral particles

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

Furlong, D.B.; Nibert, M.L.; Fields, B.N.

1988-01-01

Electron microscopy revealed structures consisting of long fibers topped with knobs extending from the surfaces of virions of mammalian reoviruses. The morphology of these structures was reminiscent of the fiber protein of adenovirus. Fibers were also seen extending from the reovirus top component and intermediate subviral particles but not from cores, suggesting that the fibers consist of either the ..mu..1C or sigma1 outer capsid protein. Amino acid sequence analysis predicts that the reovirus cell attachment protein sigma1 contains an extended fiber domain. When sigma1 protein was released from viral particles with mild heat and subsequently obtained in isolation, it wasmore » found to have a morphology identical to that of the fiber structures seen extending from the viral particles. The identification of an extended form of sigma1 has important implications for its function in cell attachment. Other evidence suggest that sigma1 protein may occur in virions in both an extended and an unextended state.« less

Time-Extended Policies in Mult-Agent Reinforcement Learning

NASA Technical Reports Server (NTRS)

Tumer, Kagan; Agogino, Adrian K.

2004-01-01

Reinforcement learning methods perform well in many domains where a single agent needs to take a sequence of actions to perform a task. These methods use sequences of single-time-step rewards to create a policy that tries to maximize a time-extended utility, which is a (possibly discounted) sum of these rewards. In this paper we build on our previous work showing how these methods can be extended to a multi-agent environment where each agent creates its own policy that works towards maximizing a time-extended global utility over all agents actions. We show improved methods for creating time-extended utilities for the agents that are both "aligned" with the global utility and "learnable." We then show how to crate single-time-step rewards while avoiding the pi fall of having rewards aligned with the global reward leading to utilities not aligned with the global utility. Finally, we apply these reward functions to the multi-agent Gridworld problem. We explicitly quantify a utility's learnability and alignment, and show that reinforcement learning agents using the prescribed reward functions successfully tradeoff learnability and alignment. As a result they outperform both global (e.g., team games ) and local (e.g., "perfectly learnable" ) reinforcement learning solutions by as much as an order of magnitude.

Extended Cost-Effectiveness Analysis for Health Policy Assessment: A Tutorial.

PubMed

Verguet, Stéphane; Kim, Jane J; Jamison, Dean T

2016-09-01

Health policy instruments such as the public financing of health technologies (e.g., new drugs, vaccines) entail consequences in multiple domains. Fundamentally, public health policies aim at increasing the uptake of effective and efficient interventions and at subsequently leading to better health benefits (e.g., premature mortality and morbidity averted). In addition, public health policies can provide non-health benefits in addition to the sole well-being of populations and beyond the health sector. For instance, public policies such as social and health insurance programs can prevent illness-related impoverishment and procure financial risk protection. Furthermore, public policies can improve the distribution of health in the population and promote the equalization of health among individuals. Extended cost-effectiveness analysis was developed to address health policy assessment, specifically to evaluate the health and financial consequences of public policies in four domains: (1) the health gains; (2) the financial risk protection benefits; (3) the total costs to the policy makers; and (4) the distributional benefits. Here, we present a tutorial that describes both the intent of extended cost-effectiveness analysis and its keys to allow easy implementation for health policy assessment.

Domain walls in the extensions of the Standard Model

NASA Astrophysics Data System (ADS)

Krajewski, Tomasz; Lalak, Zygmunt; Lewicki, Marek; Olszewski, Paweł

2018-05-01

Our main interest is the evolution of domain walls of the Higgs field in the early Universe. The aim of this paper is to understand how dynamics of Higgs domain walls could be influenced by yet unknown interactions from beyond the Standard Model. We assume that the Standard Model is valid up to certain, high, energy scale Λ and use the framework of the effective field theory to describe physics below that scale. Performing numerical simulations with different values of the scale Λ we are able to extend our previous analysis [1]. Our recent numerical simulations show that evolution of Higgs domain walls is rather insensitive to interactions beyond the Standard Model as long as masses of new particles are grater than 1012 GeV. For lower values of Λ the RG improved effective potential is strongly modified at field strengths crucial to the evolution of domain walls. However, we find that even for low values of Λ, Higgs domain walls decayed shortly after their formation for generic initial conditions. On the other hand, in simulations with specifically chosen initial conditions Higgs domain walls can live longer and enter the scaling regime. We also determine the energy spectrum of gravitational waves produced by decaying domain walls of the Higgs field. For generic initial field configurations the amplitude of the signal is too small to be observed in planned detectors.

Structural Basis for Endosomal Targeting by the Bro1 Domain

PubMed Central

Kim, Jaewon; Sitaraman, Sujatha; Hierro, Aitor; Beach, Bridgette M.; Odorizzi, Greg; Hurley, James H.

2010-01-01

Summary Proteins delivered to the lysosome or the yeast vacuole via late endosomes are sorted by the ESCRT complexes and by associated proteins, including Alix and its yeast homolog Bro1. Alix, Bro1, and several other late endosomal proteins share a conserved 160 residue Bro1 domain whose boundaries, structure, and function have not been characterized. The crystal structure of the Bro1 domain of Bro1 reveals a folded core of 367 residues. The extended Bro1 domain is necessary and sufficient for binding to the ESCRT-III subunit Snf7 and for the recruitment of Bro1 to late endosomes. The structure resembles a boomerang with its concave face filled in and contains a triple tetratricopeptide repeat domain as a substructure. Snf7 binds to a conserved hydrophobic patch on Bro1 that is required for protein complex formation and for the protein-sorting function of Bro1. These results define a conserved mechanism whereby Bro1 domain-containing proteins are targeted to endosomes by Snf7 and its orthologs. PMID:15935782

Risk factors for catheter-associated urinary tract infections in critically ill patients with subarachnoid hemorrhage.

PubMed

Hagerty, Thomas; Kertesz, Louise; Schmidt, J Michael; Agarwal, Sachin; Claassen, Jan; Mayer, Stephan A; Larson, Elaine L; Shang, Jingjing

2015-02-01

Catheter-associated urinary tract infections (CAUTIs) are preventable adverse outcomes that cause increased morbidity, mortality, and financial burdens to hospitals. These are particularly prevalent in intensive care units (ICUs). Patients with subarachnoid hemorrhage (SAH) in neurological ICUs have extended lengths of stay and may be at higher risk for CAUTIs. The purpose of this study was to assess the prevalence of and risk factors for CAUTIs among patients with SAH in the neurological ICU of a large urban teaching hospital in the eastern United States. This is a retrospective analysis using the Columbia University SAH Outcomes Project data set collected between 2005 and 2012. Logistic regression is used to identify predictors of CAUTI. Catheterized adult patients (n = 242) with SAH over the 8-year period were included. The rate of CAUTIs was 20.7 per 1,000 catheter days, six times higher than the reported national average. Variables significantly associated with CAUTI were older age (odds ratio [OR] = 1.06, 95% confidence interval [CI] [1.01, 1.11]), blood sugar > 200 mg/dl (OR = 13.0, 95% CI [1.28, 107.4]), and anemia requiring transfusion (OR = 3.78, 95% CI [0.977, 14.67]). Higher CAUTI rates in this study were likely associated with prolonged catheterization. On the basis of these findings, careful assessment of the need for catheterization and increased vigilance regarding urinary catheter care in patients with SAH is indicated, particularly among those who are older, with anemia requiring transfusion and elevated blood glucose levels.

Finite difference time domain calculation of transients in antennas with nonlinear loads

NASA Technical Reports Server (NTRS)

Luebbers, Raymond J.; Beggs, John H.; Kunz, Karl S.; Chamberlin, Kent

1991-01-01

Determining transient electromagnetic fields in antennas with nonlinear loads is a challenging problem. Typical methods used involve calculating frequency domain parameters at a large number of different frequencies, then applying Fourier transform methods plus nonlinear equation solution techniques. If the antenna is simple enough so that the open circuit time domain voltage can be determined independently of the effects of the nonlinear load on the antennas current, time stepping methods can be applied in a straightforward way. Here, transient fields for antennas with more general geometries are calculated directly using Finite Difference Time Domain (FDTD) methods. In each FDTD cell which contains a nonlinear load, a nonlinear equation is solved at each time step. As a test case, the transient current in a long dipole antenna with a nonlinear load excited by a pulsed plane wave is computed using this approach. The results agree well with both calculated and measured results previously published. The approach given here extends the applicability of the FDTD method to problems involving scattering from targets, including nonlinear loads and materials, and to coupling between antennas containing nonlinear loads. It may also be extended to propagation through nonlinear materials.

Frequency-domain-independent vector analysis for mode-division multiplexed transmission

NASA Astrophysics Data System (ADS)

Liu, Yunhe; Hu, Guijun; Li, Jiao

2018-04-01

In this paper, we propose a demultiplexing method based on frequency-domain independent vector analysis (FD-IVA) algorithm for mode-division multiplexing (MDM) system. FD-IVA extends frequency-domain independent component analysis (FD-ICA) from unitary variable to multivariate variables, and provides an efficient method to eliminate the permutation ambiguity. In order to verify the performance of FD-IVA algorithm, a 6 ×6 MDM system is simulated. The simulation results show that the FD-IVA algorithm has basically the same bit-error-rate(BER) performance with the FD-ICA algorithm and frequency-domain least mean squares (FD-LMS) algorithm. Meanwhile, the convergence speed of FD-IVA algorithm is the same as that of FD-ICA. However, compared with the FD-ICA and the FD-LMS, the FD-IVA has an obviously lower computational complexity.

Crystal Structure of the Bovine lactadherin C2 Domain, a Membrane Binding Motif, Shows Similarity of the C2 Domains of Factor V and Factor VIII

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

Lin,L.; Huai, Q.; Huang, M.

2007-01-01

Lactadherin, a glycoprotein secreted by a variety of cell types, contains two EGF domains and two C domains with sequence homology to the C domains of blood coagulation proteins factor V and factor VIII. Like these proteins, lactadherin binds to phosphatidylserine (PS)-containing membranes with high affinity. We determined the crystal structure of the bovine lactadherin C2 domain (residues 1 to 158) at 2.4 Angstroms. The lactadherin C2 structure is similar to the C2 domains of factors V and VIII (rmsd of C? atoms of 0.9 Angstroms and 1.2 Angstroms, and sequence identities of 43% and 38%, respectively). The lactadherin C2more » domain has a discoidin-like fold containing two ?-sheets of five and three antiparallel ?-strands packed against one another. The N and C termini are linked by a disulfide bridge between Cys1 and Cys158. One ?-turn and two loops containing solvent-exposed hydrophobic residues extend from the C2 domain ?-sandwich core. In analogy with the C2 domains of factors V and VIII, some or all of these solvent-exposed hydrophobic residues, Trp26, Leu28, Phe31, and Phe81, likely participate in membrane binding. The C2 domain of lactadherin may serve as a marker of cell surface phosphatidylserine exposure and may have potential as a unique anti-thrombotic agent.« less

Crystal Structure of the Passenger Domain of the Escherichia coli Autotransporter EspP

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

Khan, Shekeb; Mian, Hira S.; Sandercock, Linda E.

2013-03-07

Autotransporters represent a large superfamily of known and putative virulence factors produced by Gram-negative bacteria. They consist of an N-terminal 'passenger domain' responsible for the specific effector functions of the molecule and a C-terminal '{beta}-domain' responsible for translocation of the passenger across the bacterial outer membrane. Here, we present the 2.5-{angstrom} crystal structure of the passenger domain of the extracellular serine protease EspP, produced by the pathogen Escherichia coli O157:H7 and a member of the serine protease autotransporters of Enterobacteriaceae (SPATEs). Like the previously structurally characterized SPATE passenger domains, the EspP passenger domain contains an extended right-handed parallel {beta}-helix precededmore » by an N-terminal globular domain housing the catalytic function of the protease. Of note, however, is the absence of a second globular domain protruding from this {beta}-helix. We describe the structure of the EspP passenger domain in the context of previous results and provide an alternative hypothesis for the function of the {beta}-helix within SPATEs.« less

Reconstruction of transient vibration and sound radiation of an impacted plate using time domain plane wave superposition method

NASA Astrophysics Data System (ADS)

Geng, Lin; Zhang, Xiao-Zheng; Bi, Chuan-Xing

2015-05-01

Time domain plane wave superposition method is extended to reconstruct the transient pressure field radiated by an impacted plate and the normal acceleration of the plate. In the extended method, the pressure measured on the hologram plane is expressed as a superposition of time convolutions between the time-wavenumber normal acceleration spectrum on a virtual source plane and the time domain propagation kernel relating the pressure on the hologram plane to the normal acceleration spectrum on the virtual source plane. By performing an inverse operation, the normal acceleration spectrum on the virtual source plane can be obtained by an iterative solving process, and then taken as the input to reconstruct the whole pressure field and the normal acceleration of the plate. An experiment of a clamped rectangular steel plate impacted by a steel ball is presented. The experimental results demonstrate that the extended method is effective in visualizing the transient vibration and sound radiation of an impacted plate in both time and space domains, thus providing the important information for overall understanding the vibration and sound radiation of the plate.

Scalable domain decomposition solvers for stochastic PDEs in high performance computing

DOE PAGES

Desai, Ajit; Khalil, Mohammad; Pettit, Chris; ...

2017-09-21

Stochastic spectral finite element models of practical engineering systems may involve solutions of linear systems or linearized systems for non-linear problems with billions of unknowns. For stochastic modeling, it is therefore essential to design robust, parallel and scalable algorithms that can efficiently utilize high-performance computing to tackle such large-scale systems. Domain decomposition based iterative solvers can handle such systems. And though these algorithms exhibit excellent scalabilities, significant algorithmic and implementational challenges exist to extend them to solve extreme-scale stochastic systems using emerging computing platforms. Intrusive polynomial chaos expansion based domain decomposition algorithms are extended here to concurrently handle high resolutionmore » in both spatial and stochastic domains using an in-house implementation. Sparse iterative solvers with efficient preconditioners are employed to solve the resulting global and subdomain level local systems through multi-level iterative solvers. We also use parallel sparse matrix–vector operations to reduce the floating-point operations and memory requirements. Numerical and parallel scalabilities of these algorithms are presented for the diffusion equation having spatially varying diffusion coefficient modeled by a non-Gaussian stochastic process. Scalability of the solvers with respect to the number of random variables is also investigated.« less

Scalable domain decomposition solvers for stochastic PDEs in high performance computing

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

Desai, Ajit; Khalil, Mohammad; Pettit, Chris

Stochastic spectral finite element models of practical engineering systems may involve solutions of linear systems or linearized systems for non-linear problems with billions of unknowns. For stochastic modeling, it is therefore essential to design robust, parallel and scalable algorithms that can efficiently utilize high-performance computing to tackle such large-scale systems. Domain decomposition based iterative solvers can handle such systems. And though these algorithms exhibit excellent scalabilities, significant algorithmic and implementational challenges exist to extend them to solve extreme-scale stochastic systems using emerging computing platforms. Intrusive polynomial chaos expansion based domain decomposition algorithms are extended here to concurrently handle high resolutionmore » in both spatial and stochastic domains using an in-house implementation. Sparse iterative solvers with efficient preconditioners are employed to solve the resulting global and subdomain level local systems through multi-level iterative solvers. We also use parallel sparse matrix–vector operations to reduce the floating-point operations and memory requirements. Numerical and parallel scalabilities of these algorithms are presented for the diffusion equation having spatially varying diffusion coefficient modeled by a non-Gaussian stochastic process. Scalability of the solvers with respect to the number of random variables is also investigated.« less

An extended model of the Barkhausen effect based on the ABBM model

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

Clatterbuck, D. M.; Garcia, V. J.; Johnson, M. J.

2000-05-01

The Barkhausen model of Alessandro et al. [J. Appl. Phys. 68, 2901 (1990)] has been extended to nonstationary domain wall dynamics. The assumptions of the original model limit, its use to situations where the differential permeability, and time derivative of applied field are constant. The later model of Jiles et al. assumes that the Barkhausen activity in a given time interval is proportional to the rate of change of irreversible magnetization which can be calculated from hysteresis models. The extended model presented here incorporates ideas from both of these. It assumes that the pinning field and domain wall velocity behavemore » according to the Alessandro model, but allows the rate of change of the magnetic flux to vary around a moving average which is determined by the shape of the hysteresis curve and the applied magnetic field wave form. As a result, the new model allows for changes in permeability with applied field and can also reproduce the frequency response of experimental Barkhausen signals. (c) 2000 American Institute of Physics.« less

Domain decomposition: A bridge between nature and parallel computers

NASA Technical Reports Server (NTRS)

Keyes, David E.

1992-01-01

Domain decomposition is an intuitive organizing principle for a partial differential equation (PDE) computation, both physically and architecturally. However, its significance extends beyond the readily apparent issues of geometry and discretization, on one hand, and of modular software and distributed hardware, on the other. Engineering and computer science aspects are bridged by an old but recently enriched mathematical theory that offers the subject not only unity, but also tools for analysis and generalization. Domain decomposition induces function-space and operator decompositions with valuable properties. Function-space bases and operator splittings that are not derived from domain decompositions generally lack one or more of these properties. The evolution of domain decomposition methods for elliptically dominated problems has linked two major algorithmic developments of the last 15 years: multilevel and Krylov methods. Domain decomposition methods may be considered descendants of both classes with an inheritance from each: they are nearly optimal and at the same time efficiently parallelizable. Many computationally driven application areas are ripe for these developments. A progression is made from a mathematically informal motivation for domain decomposition methods to a specific focus on fluid dynamics applications. To be introductory rather than comprehensive, simple examples are provided while convergence proofs and algorithmic details are left to the original references; however, an attempt is made to convey their most salient features, especially where this leads to algorithmic insight.

Prediction of cancer proteins by integrating protein interaction, domain frequency, and domain interaction data using machine learning algorithms.

PubMed

Huang, Chien-Hung; Peng, Huai-Shun; Ng, Ka-Lok

2015-01-01

Many proteins are known to be associated with cancer diseases. It is quite often that their precise functional role in disease pathogenesis remains unclear. A strategy to gain a better understanding of the function of these proteins is to make use of a combination of different aspects of proteomics data types. In this study, we extended Aragues's method by employing the protein-protein interaction (PPI) data, domain-domain interaction (DDI) data, weighted domain frequency score (DFS), and cancer linker degree (CLD) data to predict cancer proteins. Performances were benchmarked based on three kinds of experiments as follows: (I) using individual algorithm, (II) combining algorithms, and (III) combining the same classification types of algorithms. When compared with Aragues's method, our proposed methods, that is, machine learning algorithm and voting with the majority, are significantly superior in all seven performance measures. We demonstrated the accuracy of the proposed method on two independent datasets. The best algorithm can achieve a hit ratio of 89.4% and 72.8% for lung cancer dataset and lung cancer microarray study, respectively. It is anticipated that the current research could help understand disease mechanisms and diagnosis.

Prediction of Cancer Proteins by Integrating Protein Interaction, Domain Frequency, and Domain Interaction Data Using Machine Learning Algorithms

PubMed Central

2015-01-01

Many proteins are known to be associated with cancer diseases. It is quite often that their precise functional role in disease pathogenesis remains unclear. A strategy to gain a better understanding of the function of these proteins is to make use of a combination of different aspects of proteomics data types. In this study, we extended Aragues's method by employing the protein-protein interaction (PPI) data, domain-domain interaction (DDI) data, weighted domain frequency score (DFS), and cancer linker degree (CLD) data to predict cancer proteins. Performances were benchmarked based on three kinds of experiments as follows: (I) using individual algorithm, (II) combining algorithms, and (III) combining the same classification types of algorithms. When compared with Aragues's method, our proposed methods, that is, machine learning algorithm and voting with the majority, are significantly superior in all seven performance measures. We demonstrated the accuracy of the proposed method on two independent datasets. The best algorithm can achieve a hit ratio of 89.4% and 72.8% for lung cancer dataset and lung cancer microarray study, respectively. It is anticipated that the current research could help understand disease mechanisms and diagnosis. PMID:25866773

Optimising predictor domains for spatially coherent precipitation downscaling

NASA Astrophysics Data System (ADS)

Radanovics, S.; Vidal, J.-P.; Sauquet, E.; Ben Daoud, A.; Bontron, G.

2013-10-01

Statistical downscaling is widely used to overcome the scale gap between predictors from numerical weather prediction models or global circulation models and predictands like local precipitation, required for example for medium-term operational forecasts or climate change impact studies. The predictors are considered over a given spatial domain which is rarely optimised with respect to the target predictand location. In this study, an extended version of the growing rectangular domain algorithm is proposed to provide an ensemble of near-optimum predictor domains for a statistical downscaling method. This algorithm is applied to find five-member ensembles of near-optimum geopotential predictor domains for an analogue downscaling method for 608 individual target zones covering France. Results first show that very similar downscaling performances based on the continuous ranked probability score (CRPS) can be achieved by different predictor domains for any specific target zone, demonstrating the need for considering alternative domains in this context of high equifinality. A second result is the large diversity of optimised predictor domains over the country that questions the commonly made hypothesis of a common predictor domain for large areas. The domain centres are mainly distributed following the geographical location of the target location, but there are apparent differences between the windward and the lee side of mountain ridges. Moreover, domains for target zones located in southeastern France are centred more east and south than the ones for target locations on the same longitude. The size of the optimised domains tends to be larger in the southeastern part of the country, while domains with a very small meridional extent can be found in an east-west band around 47° N. Sensitivity experiments finally show that results are rather insensitive to the starting point of the optimisation algorithm except for zones located in the transition area north of this east

Evidence of benzenoid domains in nanographenes.

PubMed

Baldoni, Matteo; Mercuri, Francesco

2015-01-21

Calculations based on density functional theory demonstrate the occurrence of local deformations of the perfect honeycomb lattice in nanographenes to form arrangements, with triangular symmetry, composed of six-membered ring patterns. The formation of these locally regular superstructures, which can be considered as benzenoid-like domains on the 2D graphene lattice, is ascribed to the gain in resonance energy deriving from aromaticity. The relationship between the atomic morphology of nanographenes and details of the relaxed structure is rationalized in terms of Clar's theory of the aromatic sextet and by extending concepts borrowed from valence bond theory to 2D carbon nanostructures. Namely, two regular arrangements can be evidenced, defined as Clar (fully benzenoid) and Kekulé domains, which correspond to two different regular bond patterns in sets of adjacent six-membered rings. Our findings are compatible with recent experiments and have potentially relevant consequences in the development of novel electronic devices based on graphene materials.

Proposal of an Extended Taxonomy of Serious Games for Health Rehabilitation.

PubMed

Rego, Paula Alexandra; Moreira, Pedro Miguel; Reis, Luís Paulo

2018-06-29

Serious Games is a field of research that has evolved substantially with valuable contributions to many application domains and areas. Patients often consider traditional rehabilitation approaches to be repetitive and boring, making it difficult for them to maintain their ongoing interest and assure the completion of the treatment program. Since the publication of our first taxonomy of Serious Games for Health Rehabilitation (SGHR), many studies have been published with game prototypes in this area. Based on literature review, our goal is to propose an updated taxonomy taking into account the works, updates, and innovations in game criteria that have been researched since our first publication in 2010. In addition, we aim to present the validation mechanism used for the proposed extended taxonomy. Based on a literature review in the area and on the analysis of the contributions made by other researchers, we propose an extended taxonomy for SGHR. For validating the taxonomy proposal, a questionnaire was designed to use on a survey among experts in the area. An extended taxonomy for SGHR was proposed. As we have identified that, in general, and besides the mechanisms associated with the adoption of a given taxonomy, there were no reported validation mechanisms for the proposals, we designed a mechanism to validate our proposal. The mechanism uses a questionnaire addressed to a sample of researchers and professionals with experience and expertise in domains of knowledge interrelated with SGHR, such as Computer Graphics, Game Design, Interaction Design, Computer Programming, and Health Rehabilitation. The extended taxonomy proposal for health rehabilitation serious games provides the research community with a tool to fully characterize serious games. The mechanism designed for validating the taxonomy proposal is another contribution of this work.

Crystal Structure of the Bovine lactadherin C2 Domain, a Membrane Binding Motif, Shows Similarity to the C2 Domains of Factor V and Factor VIII

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

Lin,L.

2007-01-01

Lactadherin, a glycoprotein secreted by a variety of cell types, contains two EGF domains and two C domains with sequence homology to the C domains of blood coagulation proteins factor V and factor VIII. Like these proteins, lactadherin binds to phosphatidylserine (PS)-containing membranes with high affinity. We determined the crystal structure of the bovine lactadherin C2 domain (residues 1 to 158) at 2.4 {angstrom}. The lactadherin C2 structure is similar to the C2 domains of factors V and VIII (rmsd of C{sub {alpha}} atoms of 0.9 {angstrom} and 1.2 {angstrom}, and sequence identities of 43% and 38%, respectively). The lactadherinmore » C2 domain has a discoidin-like fold containing two {beta}-sheets of five and three antiparallel {beta}-strands packed against one another. The N and C termini are linked by a disulfide bridge between Cys1 and Cys158. One {beta}-turn and two loops containing solvent-exposed hydrophobic residues extend from the C2 domain {beta}-sandwich core. In analogy with the C2 domains of factors V and VIII, some or all of these solvent-exposed hydrophobic residues, Trp26, Leu28, Phe31, and Phe81, likely participate in membrane binding. The C2 domain of lactadherin may serve as a marker of cell surface phosphatidylserine exposure and may have potential as a unique anti-thrombotic agent.« less

Mechanistic insights into phosphoprotein-binding FHA domains.

PubMed

Liang, Xiangyang; Van Doren, Steven R

2008-08-01

[Structure: see text]. FHA domains are protein modules that switch signals in diverse biological pathways by monitoring the phosphorylation of threonine residues of target proteins. As part of the effort to gain insight into cellular avoidance of cancer, FHA domains involved in the cellular response to DNA damage have been especially well-characterized. The complete protein where the FHA domain resides and the interaction partners determine the nature of the signaling. Thus, a key biochemical question is how do FHA domains pick out their partners from among thousands of alternatives in the cell? This Account discusses the structure, affinity, and specificity of FHA domains and the formation of their functional structure. Although FHA domains share sequence identity at only five loop residues, they all fold into a beta-sandwich of two beta-sheets. The conserved arginine and serine of the recognition loops recognize the phosphorylation of the threonine targeted. Side chains emanating from loops that join beta-strand 4 with 5, 6 with 7, or 10 with 11 make specific contacts with amino acids of the ligand that tailor sequence preferences. Many FHA domains choose a partner in extended conformation, somewhat according to the residue three after the phosphothreonine in sequence (pT + 3 position). One group of FHA domains chooses a short carboxylate-containing side chain at pT + 3. Another group chooses a long, branched aliphatic side chain. A third group prefers other hydrophobic or uncharged polar side chains at pT + 3. However, another FHA domain instead chooses on the basis of pT - 2, pT - 3, and pT + 1 positions. An FHA domain from a marker of human cancer instead chooses a much longer protein fragment that adds a beta-strand to its beta-sheet and that presents hydrophobic residues from a novel helix to the usual recognition surface. This novel recognition site and more remote sites for the binding of other types of protein partners were predicted for the entire family

Generating Dynamic Persistence in the Time Domain

NASA Astrophysics Data System (ADS)

Guerrero, A.; Smith, L. A.; Smith, L. A.; Kaplan, D. T.

2001-12-01

Many dynamical systems present long-range correlations. Physically, these systems vary from biological to economical, including geological or urban systems. Important geophysical candidates for this type of behaviour include weather (or climate) and earthquake sequences. Persistence is characterised by slowly decaying correlation function; that, in theory, never dies out. The Persistence exponent reflects the degree of memory in the system and much effort has been expended creating and analysing methods that successfully estimate this parameter and model data that exhibits persistence. The most widely used methods for generating long correlated time series are not dynamical systems in the time domain, but instead are derived from a given spectral density. Little attention has been drawn to modelling persistence in the time domain. The time domain approach has the advantage that an observation at certain time can be calculated using previous observations which is particularly suitable when investigating the predictability of a long memory process. We will describe two of these methods in the time domain. One is a traditional approach using fractional ARIMA (autoregressive and moving average) models; the second uses a novel approach to extending a given series using random Fourier basis functions. The statistical quality of the two methods is compared, and they are contrasted with weather data which shows, reportedly, persistence. The suitability of this approach both for estimating predictability and for making predictions is discussed.

Dynamics of the Tec‐family tyrosine kinase SH3 domains

PubMed Central

Roberts, Justin M.; Tarafdar, Sreya; Joseph, Raji E.; Andreotti, Amy H.; Smithgall, Thomas E.; Engen, John R.

2016-01-01

Abstract The Src Homology 3 (SH3) domain is an important regulatory domain found in many signaling proteins. X‐ray crystallography and NMR structures of SH3 domains are generally conserved but other studies indicate that protein flexibility and dynamics are not. We previously reported that based on hydrogen exchange mass spectrometry (HX MS) studies, there is variable flexibility and dynamics among the SH3 domains of the Src‐family tyrosine kinases and related proteins. Here we have extended our studies to the SH3 domains of the Tec family tyrosine kinases (Itk, Btk, Tec, Txk, Bmx). The SH3 domains of members of this family augment the variety in dynamics observed in previous SH3 domains. Txk and Bmx SH3 were found to be highly dynamic in solution by HX MS and Bmx was unstructured by NMR. Itk and Btk SH3 underwent a clear EX1 cooperative unfolding event, which was localized using pepsin digestion and mass spectrometry after hydrogen exchange labeling. The unfolding was localized to peptide regions that had been previously identified in the Src‐family and related protein SH3 domains, yet the kinetics of unfolding were not. Sequence alignment does not provide an easy explanation for the observed dynamics behavior, yet the similarity of location of EX1 unfolding suggests that higher‐order structural properties may play a role. While the exact reason for such dynamics is not clear, such motions can be exploited in intra‐ and intermolecular binding assays of proteins containing the domains. PMID:26808198

Time domain passivity controller for 4-channel time-delay bilateral teleoperation.

PubMed

Rebelo, Joao; Schiele, Andre

2015-01-01

This paper presents an extension of the time-domain passivity control approach to a four-channel bilateral controller under the effects of time delays. Time-domain passivity control has been used successfully to stabilize teleoperation systems with position-force and position-position controllers; however, the performance with such control architectures is sub-optimal both with and without time delays. This work extends the network representation of the time-domain passivity controller to the four-channel architecture, which provides perfect transparency to the user without time delay. The proposed architecture is based on modelling the controllers as dependent voltage sources and using only series passivity controllers. The obtained results are shown on a one degree-of-freedom setup and illustrate the stabilization behaviour of the proposed controller when time delay is present in the communication channel.

Titin domains progressively unfolded by force are homogenously distributed along the molecule.

PubMed

Bianco, Pasquale; Mártonfalvi, Zsolt; Naftz, Katalin; Kőszegi, Dorina; Kellermayer, Miklós

2015-07-21

Titin is a giant filamentous protein of the muscle sarcomere in which stretch induces the unfolding of its globular domains. However, the mechanisms of how domains are progressively selected for unfolding and which domains eventually unfold have for long been elusive. Based on force-clamp optical tweezers experiments we report here that, in a paradoxical violation of mechanically driven activation kinetics, neither the global domain unfolding rate, nor the folded-state lifetime distributions of full-length titin are sensitive to force. This paradox is reconciled by a gradient of mechanical stability so that domains are gradually selected for unfolding as the magnitude of the force field increases. Atomic force microscopic screening of extended titin molecules revealed that the unfolded domains are distributed homogenously along the entire length of titin, and this homogeneity is maintained with increasing overstretch. Although the unfolding of domains with progressively increasing mechanical stability makes titin a variable viscosity damper, the spatially randomized variation of domain stability ensures that the induced structural changes are not localized but are distributed along the molecule's length. Titin may thereby provide complex safety mechanims for protecting the sarcomere against structural disintegration under excessive mechanical conditions. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Combinatorial administration of insulin and vitamin C alleviates the cerebral vasospasm after experimental subarachnoid hemorrhage in rabbit

PubMed Central

2011-01-01

Background Cerebral vasospasm (CVS) is a common serious complication after the spontaneous subarachnoid hemorrhage (SAH). Despite recent advances in medical and surgical treatments, the 30-day mortality rate of SAH remains high, and there is lack of especially effective clinical treatment to alleviate and improve CVS. The present study has investigated the therapeutic effect of insulin and vitamin C on CVS after SAH. Results Five days after SAH, there is obvious basilar artery spasm in SAH group, whose average vascular cross-sectional area (233,099 ± 16,750 μm2) is significantly smaller than that in control group (462,128 ± 74,756 μm2), which is also significantly different from those in SAH + insulin group (221,114 ± 43,457 μm2) and SAH + vitamin C group (237,820 ± 21,703 μm2). SAH + insulin + vitamin C group shows no evident vasospasm and maintains a vascular cross-sectional area of 425,530 ± 45,503 μm2, which is significantly different from that in SAH group. Insulin receptor α (InRα) expression is significantly downregulated in the vascular endothelial cells of SAH, SAH + insulin, and SAH + vitamin C groups (P < 0.01) but remains unchanged in vascular endothelial cells of SAH + insulin + vitamin C group (P > 0.05). Five days after SAH, serum and cerebrospinal fluid NO levels in SAH, SAH + insulin, and SAH + vitamin C groups decrease significantly (P < 0.01) compared to that in control group, whereas the reduction is not evident in SAH + insulin + vitamin C group (P > 0.05). Conclusion Combinatorial treatment with insulin and vitamin C has effectively relieved the CVS after SAH in rabbit, possibly through increasing the InRα expression and NO level, whereas treatment with insulin or vitamin C alone fails to do so. PMID:21801458

Interdependence of the rad50 hook and globular domain functions.

PubMed

Hohl, Marcel; Kochańczyk, Tomasz; Tous, Cristina; Aguilera, Andrés; Krężel, Artur; Petrini, John H J

2015-02-05

Rad50 contains a conserved Zn(2+) coordination domain (the Rad50 hook) that functions as a homodimerization interface. Hook ablation phenocopies Rad50 deficiency in all respects. Here, we focused on rad50 mutations flanking the Zn(2+)-coordinating hook cysteines. These mutants impaired hook-mediated dimerization, but recombination between sister chromatids was largely unaffected. This may reflect that cohesin-mediated sister chromatid interactions are sufficient for double-strand break repair. However, Mre11 complex functions specified by the globular domain, including Tel1 (ATM) activation, nonhomologous end joining, and DNA double-strand break end resection were affected, suggesting that dimerization exerts a broad influence on Mre11 complex function. These phenotypes were suppressed by mutations within the coiled-coil and globular ATPase domains, suggesting a model in which conformational changes in the hook and globular domains are transmitted via the extended coils of Rad50. We propose that transmission of spatial information in this manner underlies the regulation of Mre11 complex functions. Copyright © 2015 Elsevier Inc. All rights reserved.

Supra-domains: evolutionary units larger than single protein domains.

PubMed

Vogel, Christine; Berzuini, Carlo; Bashton, Matthew; Gough, Julian; Teichmann, Sarah A

2004-02-20

Domains are the evolutionary units that comprise proteins, and most proteins are built from more than one domain. Domains can be shuffled by recombination to create proteins with new arrangements of domains. Using structural domain assignments, we examined the combinations of domains in the proteins of 131 completely sequenced organisms. We found two-domain and three-domain combinations that recur in different protein contexts with different partner domains. The domains within these combinations have a particular functional and spatial relationship. These units are larger than individual domains and we term them "supra-domains". Amongst the supra-domains, we identified some 1400 (1203 two-domain and 166 three-domain) combinations that are statistically significantly over-represented relative to the occurrence and versatility of the individual component domains. Over one-third of all structurally assigned multi-domain proteins contain these over-represented supra-domains. This means that investigation of the structural and functional relationships of the domains forming these popular combinations would be particularly useful for an understanding of multi-domain protein function and evolution as well as for genome annotation. These and other supra-domains were analysed for their versatility, duplication, their distribution across the three kingdoms of life and their functional classes. By examining the three-dimensional structures of several examples of supra-domains in different biological processes, we identify two basic types of spatial relationships between the component domains: the combined function of the two domains is such that either the geometry of the two domains is crucial and there is a tight constraint on the interface, or the precise orientation of the domains is less important and they are spatially separate. Frequently, the role of the supra-domain becomes clear only once the three-dimensional structure is known. Since this is the case for only a

Does magnetic resonance imaging produce further benefit for detecting a bleeding source in subarachnoid hemorrhage of unknown origin?

PubMed

Maslehaty, Homajoun; Petridis, Athanassios K; Barth, Harald; Doukas, Alexandros; Mehdorn, Hubertus Maximilian

2011-01-01

Spontaneous subarachnoid hemorrhage (SAH) without evidence of a bleeding source on the first digital subtraction angiogram (DSA) - also called SAH of unknown origin - is observed in up to 27% of all cases. Depending on the bleeding pattern on CT scanning, SAH can be differentiated into perimesencephalic (PM-SAH) and non-perimesencephalic SAH (NON-PM-SAH). The aim of our study was to investigate the effectiveness of magnetic resonance imaging (MRI) for detecting a bleeding source in SAH of unknown origin. We retrospectively reviewed 1,226 patients with spontaneous SAH between January 1991 and December 2008 in our department. DSA was performed in 1,068 patients, with negative results in 179 patients. Forty-seven patients were categorized as having PM-SAH and 132 patients as having NON-PM-SAH. MRI of the brain and the craniocervical region was performed within 72 h after diagnosis of SAH and demonstrated no bleeding sources in any of the PM-SAH and NON-PM-SAH patients (100% negative). In our experience MRI did not produce any additional benefit for detecting a bleeding source after SAH with a negative angiogram. The costs of this examination exceeded the clinical value. Despite our results MRI should be discussed on a case-by-case basis because rare bleeding sources are periodically diagnosed in cases of NON-PM-SAH.

The role of internal duplication in the evolution of multi-domain proteins.

PubMed

Nacher, J C; Hayashida, M; Akutsu, T

2010-08-01

Many proteins consist of several structural domains. These multi-domain proteins have likely been generated by selective genome growth dynamics during evolution to perform new functions as well as to create structures that fold on a biologically feasible time scale. Domain units frequently evolved through a variety of genetic shuffling mechanisms. Here we examine the protein domain statistics of more than 1000 organisms including eukaryotic, archaeal and bacterial species. The analysis extends earlier findings on asymmetric statistical laws for proteome to a wider variety of species. While proteins are composed of a wide range of domains, displaying a power-law decay, the computation of domain families for each protein reveals an exponential distribution, characterizing a protein universe composed of a thin number of unique families. Structural studies in proteomics have shown that domain repeats, or internal duplicated domains, represent a small but significant fraction of genome. In spite of its importance, this observation has been largely overlooked until recently. We model the evolutionary dynamics of proteome and demonstrate that these distinct distributions are in fact rooted in an internal duplication mechanism. This process generates the contemporary protein structural domain universe, determines its reduced thickness, and tames its growth. These findings have important implications, ranging from protein interaction network modeling to evolutionary studies based on fundamental mechanisms governing genome expansion.

Effects of blockade of cerebral lymphatic drainage on regional cerebral blood flow and brain edema after subarachnoid hemorrhage.

PubMed

Sun, Bao-Liang; Xia, Zuo-Li; Wang, Jing-Ru; Yuan, Hui; Li, Wen-Xia; Chen, Yu-She; Yang, Ming-Feng; Zhang, Su-Ming

2006-01-01

The study was designed to observe the influence of blockade of cerebral lymphatic drainage on the regional cerebral blood flow (rCBF) and brain edema after experimental subarachnoid hemorrhage (SAH). Wistar rats were divided into non-SAH, SAH, and SAH plus cervical lymphatic blockade (SAH + CLB) groups. Autologous arterial hemolysate was injected into rat's cisterna magna to induce SAH. The rCBF was recorded continuously by a laser Doppler flowmeter. Intracranial pressure (ICP) was also monitored. After 24 hours and 72 hours of SAH, the rats were sacrificed and the brain was harvested for water content detection. It was found that there was no obvious change of rCBF and brain water content during the experiment in non-SAH group. An immediate and persistent drop in rCBF was found in SAH group. The drop in rCBF was more obvious in SAH + CLB group. CLB also worsened the SAH-induced increase in ICP. The brain water content 24 hours and 72 hours after induction of SAH in SAH group increased significantly. CLB led to a further increase of brain water content. In conclusion, blockade of cerebral lymphatic drainage pathway deteriorates the secondary cerebral ischemia and brain edema after SAH.

Small Molecule Inhibitors That Selectively Block Dengue Virus Methyltransferase*

PubMed Central

Lim, Siew Pheng; Sonntag, Louis Sebastian; Noble, Christian; Nilar, Shahul H.; Ng, Ru Hui; Zou, Gang; Monaghan, Paul; Chung, Ka Yan; Dong, Hongping; Liu, Boping; Bodenreider, Christophe; Lee, Gladys; Ding, Mei; Chan, Wai Ling; Wang, Gang; Jian, Yap Li; Chao, Alexander Theodore; Lescar, Julien; Yin, Zheng; Vedananda, T. R.; Keller, Thomas H.; Shi, Pei-Yong

2011-01-01

Crystal structure analysis of Flavivirus methyltransferases uncovered a flavivirus-conserved cavity located next to the binding site for its cofactor, S-adenosyl-methionine (SAM). Chemical derivatization of S-adenosyl-homocysteine (SAH), the product inhibitor of the methylation reaction, with substituents that extend into the identified cavity, generated inhibitors that showed improved and selective activity against dengue virus methyltransferase (MTase), but not related human enzymes. Crystal structure of dengue virus MTase with a bound SAH derivative revealed that its N6-substituent bound in this cavity and induced conformation changes in residues lining the pocket. These findings demonstrate that one of the major hurdles for the development of methyltransferase-based therapeutics, namely selectivity for disease-related methyltransferases, can be overcome. PMID:21147775

Enhancing protein stability with extended disulfide bonds

DOE PAGES

Liu, Tao; Wang, Yan; Luo, Xiaozhou; ...

2016-05-09

Disulfide bonds play an important role in protein folding and stability. However, the cross-linking of sites within proteins by cysteine disulfides has significant distance and dihedral angle constraints. In this paper, we report the genetic encoding of noncanonical amino acids containing long side-chain thiols that are readily incorporated into both bacterial and mammalian proteins in good yields and with excellent fidelity. These amino acids can pair with cysteines to afford extended disulfide bonds and allow cross-linking of more distant sites and distinct domains of proteins. To demonstrate this notion, we preformed growth-based selection experiments at nonpermissive temperatures using a librarymore » of random β-lactamase mutants containing these noncanonical amino acids. A mutant enzyme that is cross-linked by one such extended disulfide bond and is stabilized by ~9 °C was identified. Finally, this result indicates that an expanded set of building blocks beyond the canonical 20 amino acids can lead to proteins with improved properties by unique mechanisms, distinct from those possible through conventional mutagenesis schemes.« less

Optical, analog and digital domain architectural considerations for visual communications

NASA Astrophysics Data System (ADS)

Metz, W. A.

2008-01-01

The end of the performance entitlement historically achieved by classic scaling of CMOS devices is within sight, driven ultimately by fundamental limits. Performance entitlements predicted by classic CMOS scaling have progressively failed to be realized in recent process generations due to excessive leakage, increasing interconnect delays and scaling of gate dielectrics. Prior to reaching fundamental limits, trends in technology, architecture and economics will pressure the industry to adopt new paradigms. A likely response is to repartition system functions away from digital implementations and into new architectures. Future architectures for visual communications will require extending the implementation into the optical and analog processing domains. The fundamental properties of these domains will in turn give rise to new architectural concepts. The limits of CMOS scaling and impact on architectures will be briefly reviewed. Alternative approaches in the optical, electronic and analog domains will then be examined for advantages, architectural impact and drawbacks.

Space and power: young mothers' management of smoking in extended families in China.

PubMed

Mao, Aimei

2013-05-01

Multigenerational co-residence is a widespread phenomenon in China but there is little knowledge about the impact of power dynamics on smoking behaviors among extended family residents. Using a gender lens, this ethnographic study explored how young mothers in extended families in mainland China managed the smoking of their husbands and other family members. Analysis of data resulted in a model of 'two units-three domains' to reflect gendered relationships between young mothers and other family members, and young mothers' participation in family management. Exploration of the mothers' efforts to deal with household smoking using the model provided an explanation for why the young mothers had limited control over household space and could only impose partial restrictions on home smoking in the extended family. Copyright © 2013 Elsevier Ltd. All rights reserved.

Inequalities of extended beta and extended hypergeometric functions.

PubMed

Mondal, Saiful R

2017-01-01

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

Prioritisation of associations between protein domains and complex diseases using domain-domain interaction networks.

PubMed

Wang, W; Zhang, W; Jiang, R; Luan, Y

2010-05-01

It is of vital importance to find genetic variants that underlie human complex diseases and locate genes that are responsible for these diseases. Since proteins are typically composed of several structural domains, it is reasonable to assume that harmful genetic variants may alter structures of protein domains, affect functions of proteins and eventually cause disorders. With this understanding, the authors explore the possibility of recovering associations between protein domains and complex diseases. The authors define associations between protein domains and disease families on the basis of associations between non-synonymous single nucleotide polymorphisms (nsSNPs) and complex diseases, similarities between diseases, and relations between proteins and domains. Based on a domain-domain interaction network, the authors propose a 'guilt-by-proximity' principle to rank candidate domains according to their average distance to a set of seed domains in the domain-domain interaction network. The authors validate the method through large-scale cross-validation experiments on simulated linkage intervals, random controls and the whole genome. Results show that areas under receiver operating characteristic curves (AUC scores) can be as high as 77.90%, and the mean rank ratios can be as low as 21.82%. The authors further offer a freely accessible web interface for a genome-wide landscape of associations between domains and disease families.

SMP-domain proteins at membrane contact sites: Structure and function.

PubMed

Reinisch, Karin M; De Camilli, Pietro

2016-08-01

SMP-domains are found in proteins that localize to membrane contact sites. Elucidation of the properties of these proteins gives clues as to the molecular bases underlying processes that occur at such sites. Described here are recent discoveries concerning the structure, function, and regulation of the Extended-Synaptotagmin proteins and ERMES complex subunits, SMP-domain proteins at endoplasmic reticulum (ER)-plasma membrane and ER-mitochondrial contacts, respectively. They act as tethers contributing to the architecture of these sites and as lipid transporters that convey glycerolipids between apposed membranes. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. Copyright © 2016. Published by Elsevier B.V.

Comparison of Current and Field Driven Domain Wall Motion in Beaded Permalloy Nanowires

NASA Astrophysics Data System (ADS)

Lage, Enno; Dutta, Sumit; Ross, Caroline A.

2015-03-01

Domain wall based devices are promising candidates for non-volatile memory devices with no static power consumption. A common approach is the use of (field assisted) current driven domain wall motion in magnetic nanowires. In such systems local variations in linewidth act as obstacles for propagating domain walls. In this study we compare simulated field driven and current driven domain wall motion in permalloy nanowires with anti-notches. The simulations were obtained using the Object Oriented MicroMagnetics Framework (OOMMF). The wires with a constant thickness of 8 nm exhibit linewidths ranging from 40 nm to 300 nm. Circular shaped anti-notches extend the linewidth locally by 10% to 30% and raise information about the domain wall propagation in such beaded nanowires. The results are interpreted in terms of the observed propagation behavior and summarized in maps indicating ranges of different ability to overcome the pinning caused by anti-notches of different sizes. Furthermore, regimes of favored domain wall type (transverse walls or vortex walls) and complex propagation effects like walker breakdown behavior or dynamic change between domain wall structures are identified The authors thank the German Academic Exchange Service (DAAD) for funding.

Molecular Mechanics of the α-Actinin Rod Domain: Bending, Torsional, and Extensional Behavior

PubMed Central

Golji, Javad; Collins, Robert; Mofrad, Mohammad R. K.

2009-01-01

α-Actinin is an actin crosslinking molecule that can serve as a scaffold and maintain dynamic actin filament networks. As a crosslinker in the stressed cytoskeleton, α-actinin can retain conformation, function, and strength. α-Actinin has an actin binding domain and a calmodulin homology domain separated by a long rod domain. Using molecular dynamics and normal mode analysis, we suggest that the α-actinin rod domain has flexible terminal regions which can twist and extend under mechanical stress, yet has a highly rigid interior region stabilized by aromatic packing within each spectrin repeat, by electrostatic interactions between the spectrin repeats, and by strong salt bridges between its two anti-parallel monomers. By exploring the natural vibrations of the α-actinin rod domain and by conducting bending molecular dynamics simulations we also predict that bending of the rod domain is possible with minimal force. We introduce computational methods for analyzing the torsional strain of molecules using rotating constraints. Molecular dynamics extension of the α-actinin rod is also performed, demonstrating transduction of the unfolding forces across salt bridges to the associated monomer of the α-actinin rod domain. PMID:19436721

Vibration sensing in flexible structures using a distributed-effect modal domain optical fiber sensor

NASA Technical Reports Server (NTRS)

Reichard, Karl M.; Lindner, Douglas K.; Claus, Richard O.

1991-01-01

Modal domain optical fiber sensors have recently been employed in the implementation of system identification algorithms and the closed-loop control of vibrations in flexible structures. The mathematical model of the modal domain optical fiber sensor used in these applications, however, only accounted for the effects of strain in the direction of the fiber's longitudinal axis. In this paper, we extend this model to include the effects of arbitrary stress. Using this sensor model, we characterize the sensor's sensitivity and dynamic range.

Minimum-domain impulse theory for unsteady aerodynamic force

NASA Astrophysics Data System (ADS)

Kang, L. L.; Liu, L. Q.; Su, W. D.; Wu, J. Z.

2018-01-01

We extend the impulse theory for unsteady aerodynamics from its classic global form to finite-domain formulation then to minimum-domain form and from incompressible to compressible flows. For incompressible flow, the minimum-domain impulse theory raises the finding of Li and Lu ["Force and power of flapping plates in a fluid," J. Fluid Mech. 712, 598-613 (2012)] to a theorem: The entire force with discrete wake is completely determined by only the time rate of impulse of those vortical structures still connecting to the body, along with the Lamb-vector integral thereof that captures the contribution of all the rest disconnected vortical structures. For compressible flows, we find that the global form in terms of the curl of momentum ∇ × (ρu), obtained by Huang [Unsteady Vortical Aerodynamics (Shanghai Jiaotong University Press, 1994)], can be generalized to having an arbitrary finite domain, but the formula is cumbersome and in general ∇ × (ρu) no longer has discrete structures and hence no minimum-domain theory exists. Nevertheless, as the measure of transverse process only, the unsteady field of vorticity ω or ρω may still have a discrete wake. This leads to a minimum-domain compressible vorticity-moment theory in terms of ρω (but it is beyond the classic concept of impulse). These new findings and applications have been confirmed by our numerical experiments. The results not only open an avenue to combine the theory with computation-experiment in wide applications but also reveal a physical truth that it is no longer necessary to account for all wake vortical structures in computing the force and moment.

Long-term reintegration and quality of life in patients with subarachnoid hemorrhage and a good neurological outcome: findings after more than 20 years.

PubMed

Sonesson, Bengt; Kronvall, Erik; Säveland, Hans; Brandt, Lennart; Nilsson, Ola G

2018-03-01

OBJECTIVE The goal of this study was to examine long-term quality of life (QOL) and reintegration in patients with good neurological recovery after aneurysmal subarachnoid hemorrhage (aSAH) and SAH of unknown cause (SAH NUD). METHODS A long-term follow-up was performed in an original cohort of 113 individuals who had suffered SAH (93 with aSAH and 20 with SAH NUD) between 1977 and 1984. Self-reporting assessments, performed > 20 years after the bleeding episode, included the Quality of Life Scale (QOLS), Psychological General Well-Being (PGWB) index, and Reintegration to Normal Living (RNL) index, along with information on sleep disturbances and work status. RESULTS Seventy-one survivors were identified. Questionnaires were returned by 67 individuals who had suffered SAH 20-28 years previously. The QOL was rated in the normal range for both the QOLS score (aSAH 90.3 vs SAH NUD 88.6) and the PGWB index (aSAH 105.9 vs SAH NUD 102.8). Ninety percent of patients had returned to their previous employment. Complete RNL was reported by 40% of patients with aSAH and by 46% of patients with SAH NUD; mild to moderate readjustment difficulties by 55% and 38%, respectively; and severe difficulties by 5% of patients with aSAH and 15% of patients with SAH NUD. Self-rated aspects of cognition, mood, and energy resources in addition resulted in a substantial drop in overall reintegration. Sleep disturbances were reported by 26%. CONCLUSIONS More than half of patients with SAH who had early good neurological recovery experienced reintegration difficulties after > 20 years. However, the general QOL was not adversely affected by this impairment. Inability to return to work after SAH was associated with lower QOLS scores. Sleep disturbances were associated with lower PGWB scores.

Distinct Ubiquitin Binding Modes Exhibited by SH3 Domains: Molecular Determinants and Functional Implications

PubMed Central

Ortega Roldan, Jose L.; Casares, Salvador; Ringkjøbing Jensen, Malene; Cárdenes, Nayra; Bravo, Jerónimo; Blackledge, Martin; Azuaga, Ana I.; van Nuland, Nico A. J.

2013-01-01

SH3 domains constitute a new type of ubiquitin-binding domains. We previously showed that the third SH3 domain (SH3-C) of CD2AP binds ubiquitin in an alternative orientation. We have determined the structure of the complex between first CD2AP SH3 domain and ubiquitin and performed a structural and mutational analysis to decipher the determinants of the SH3-C binding mode to ubiquitin. We found that the Phe-to-Tyr mutation in CD2AP and in the homologous CIN85 SH3-C domain does not abrogate ubiquitin binding, in contrast to previous hypothesis and our findings for the first two CD2AP SH3 domains. The similar alternative binding mode of the SH3-C domains of these related adaptor proteins is characterised by a higher affinity to C-terminal extended ubiquitin molecules. We conclude that CD2AP/CIN85 SH3-C domain interaction with ubiquitin constitutes a new ubiquitin-binding mode involved in a different cellular function and thus changes the previously established mechanism of EGF-dependent CD2AP/CIN85 mono-ubiquitination. PMID:24039852

Negative tail fusions can improve ruggedness of single domain antibodies.

PubMed

Goldman, Ellen R; Brozozog-Lee, P Audrey; Zabetakis, Dan; Turner, Kendrick B; Walper, Scott A; Liu, Jinny L; Anderson, George P

2014-03-01

Single-domain antibodies (sdAbs), the recombinantly expressed binding domains derived from the heavy-chain-only antibodies found in camelids and sharks, are valued for their ability to refold after heat denaturation. However, some sdAbs are prone to aggregation on extended heating at high concentration. Additionally, sdAbs prepared cytoplasmically often lack the conserved disulfide bond found in variable heavy domains, which both decreases their melting point and can decrease their ability to refold. Genetic fusions of sdAbs with the acid tail of α-synuclein (ATS) resulted in constructs that had enhanced ability to resist aggregation. In addition, almost complete refolding was observed even in the absence of the disulfide bond. These sdAb-ATS fusions expand the utility of sdAbs. They provide sdAbs that are resistant to aggregation, and enable the production of re-foldable sdAbs in the reducing environment of the cytoplasm. Published by Elsevier Inc.

Extended hours hemodialysis and survival: extended hours, extended evidence?

PubMed

Wald, Ron; Perl, Jeffrey

2016-12-01

Extended-hours hemodialysis presents another approach to the intensification of therapy for maintenance hemodialysis recipients. Smaller studies have demonstrated several potential benefits with this modality, but the impact on patient-centered outcomes has been unclear. We review the largest published study to compare survival among patients who received extended-hours hemodialysis with those who received conventional hemodialysis. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Ring-like oligomers of Synaptotagmins and related C2 domain proteins

PubMed Central

Zanetti, Maria N; Bello, Oscar D; Wang, Jing; Coleman, Jeff; Cai, Yiying; Sindelar, Charles V; Rothman, James E; Krishnakumar, Shyam S

2016-01-01

We recently reported that the C2AB portion of Synaptotagmin 1 (Syt1) could self-assemble into Ca2+-sensitive ring-like oligomers on membranes, which could potentially regulate neurotransmitter release. Here we report that analogous ring-like oligomers assemble from the C2AB domains of other Syt isoforms (Syt2, Syt7, Syt9) as well as related C2 domain containing protein, Doc2B and extended Synaptotagmins (E-Syts). Evidently, circular oligomerization is a general and conserved structural aspect of many C2 domain proteins, including Synaptotagmins. Further, using electron microscopy combined with targeted mutations, we show that under physiologically relevant conditions, both the Syt1 ring assembly and its rapid disruption by Ca2+ involve the well-established functional surfaces on the C2B domain that are important for synaptic transmission. Our data suggests that ring formation may be triggered at an early step in synaptic vesicle docking and positions Syt1 to synchronize neurotransmitter release to Ca2+ influx. DOI: http://dx.doi.org/10.7554/eLife.17262.001 PMID:27434670

Distribution of PASTA domains in penicillin-binding proteins and serine/threonine kinases of Actinobacteria.

PubMed

Ogawara, Hiroshi

2016-09-01

PASTA domains (penicillin-binding protein and serine/threonine kinase-associated domains) have been identified in penicillin-binding proteins and serine/threonine kinases of Gram-positive Firmicutes and Actinobacteria. They are believed to bind β-lactam antibiotics, and be involved in peptidoglycan metabolism, although their biological function is not definitively clarified. Actinobacteria, especially Streptomyces species, are distinct in that they undergo complex cellular differentiation and produce various antibiotics including β-lactams. This review focuses on the distribution of PASTA domains in penicillin-binding proteins and serine/threonine kinases in Actinobacteria. In Actinobacteria, PASTA domains are detectable exclusively in class A but not in class B penicillin-binding proteins, in sharp contrast to the cases in other bacteria. In penicillin-binding proteins, PASTA domains distribute independently from taxonomy with some distribution bias. Particularly interesting thing is that no Streptomyces species have penicillin-binding protein with PASTA domains. Protein kinases in Actinobacteria possess 0 to 5 PASTA domains in their molecules. Protein kinases in Streptomyces can be classified into three groups: no PASTA domain, 1 PASTA domain and 4 PASTA domain-containing groups. The 4 PASTA domain-containing groups can be further divided into two subgroups. The serine/threonine kinases in different groups may perform different functions. The pocket region in one of these subgroup is more dense and extended, thus it may be involved in binding of ligands like β-lactams more efficiently.

Genoarchitecture of the extended amygdala in zebra finch, and expression of FoxP2 in cell corridors of different genetic profile.

PubMed

Vicario, Alba; Mendoza, Ezequiel; Abellán, Antonio; Scharff, Constance; Medina, Loreta

2017-01-01

We used a battery of genes encoding transcription factors (Pax6, Islet1, Nkx2.1, Lhx6, Lhx5, Lhx9, FoxP2) and neuropeptides to study the extended amygdala in developing zebra finches. We identified different components of the central extended amygdala comparable to those found in mice and chickens, including the intercalated amygdalar cells, the central amygdala, and the lateral bed nucleus of the stria terminalis. Many cells likely originate in the dorsal striatal domain, ventral striatal domain, or the pallidal domain, as is the case in mice and chickens. Moreover, a cell subpopulation of the central extended amygdala appears to originate in the prethalamic eminence. As a general principle, these different cells with specific genetic profiles and embryonic origin form separate or partially intermingled cell corridors along the extended amygdala, which may be involved in different functional pathways. In addition, we identified the medial amygdala of the zebra finch. Like in the chickens and mice, it is located in the subpallium and is rich in cells of pallido-preoptic origin, containing minor subpopulations of immigrant cells from the ventral pallium, alar hypothalamus and prethalamic eminence. We also proposed that the medial bed nucleus of the stria terminalis is composed of several parallel cell corridors with different genetic profile and embryonic origin: preoptic, pallidal, hypothalamic, and prethalamic. Several of these cell corridors with distinct origin express FoxP2, a transcription factor implicated in synaptic plasticity. Our results pave the way for studies using zebra finches to understand the neural basis of social behavior, in which the extended amygdala is involved.

Autopoiesis + extended cognition + nature = can buildings think?

PubMed Central

Dollens, Dennis

2015-01-01

To incorporate metabolic, bioremedial functions into the performance of buildings and to balance generative architecture's dominant focus on computational programming and digital fabrication, this text first discusses hybridizing Maturana and Varela's biological theory of autopoiesis with Andy Clark's hypothesis of extended cognition. Doing so establishes a procedural protocol to research biological domains from which design could source data/insight from biosemiotics, sensory plants, and biocomputation. I trace computation and botanic simulations back to Alan Turing's little-known 1950s Morphogenetic drawings, reaction-diffusion algorithms, and pioneering artificial intelligence (AI) in order to establish bioarchitecture's generative point of origin. I ask provocatively, Can buildings think? as a question echoing Turing's own, "Can machines think?" PMID:26478784

Proving refinement transformations using extended denotational semantics

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

Winter, V.L.; Boyle, J.M.

1996-04-01

TAMPR is a fully automatic transformation system based on syntactic rewrites. Our approach in a correctness proof is to map the transformation into an axiomatized mathematical domain where formal (and automated) reasoning can be performed. This mapping is accomplished via an extended denotational semantic paradigm. In this approach, the abstract notion of a program state is distributed between an environment function and a store function. Such a distribution introduces properties that go beyond the abstract state that is being modeled. The reasoning framework needs to be aware of these properties in order to successfully complete a correctness proof. This papermore » discusses some of our experiences in proving the correctness of TAMPR transformations.« less

Incidence and outcome of subarachnoid haemorrhage in the general and emergency department populations in Queensland from 2010 to 2014.

PubMed

Chu, Kevin H; Mahmoud, Ibrahim; Hou, Xiang-Yu; Winter, Craig D; Jeffree, Rosalind L; Brown, Nathan J; Brown, Anthony Ft

2018-02-05

To determine: (i) incidence and outcome of subarachnoid haemorrhage (SAH) in the general population; and (ii) proportions of SAH in both the general ED population and in ED patients presenting with headache. A population-based study in Queensland from January 2010 to December 2014 was conducted. Data were sourced from the Australian Bureau of Statistics, Queensland Hospital Admitted Patient Data Collection linked to the Queensland death registry and ED Information System. Admitted patients with SAH were identified from ICD-10-AM codes. Inter-hospital transfers and repeat admissions for previously diagnosed SAH were excluded. Pre-hospital deaths from SAH were included. ED patients with headache were identified from ICD-10-AM codes and finding 'headache' in the triage free-text entry. The incidence of SAH, in-hospital mortality, proportions of SAH in the general ED population and ED patients with headache were calculated. There were 1975 incident cases of SAH in admitted patients and 294 pre-hospital deaths from SAH. The incidence of SAH was 9.9 (95% confidence interval [CI] 9.5-10.4) per 100 000 person-years. The incidence standardised to the 'World Standard Population' was 7.0 per 100 000 person-years. The in-hospital mortality was 23.8% (95% CI 22.0-25.8%). SAH was found in 1407 (1.9%, 95% CI 1.8-2.0) of ED patients with headache. Overall, there were 2.4 (95% CI 2.3-2.5) SAH per 10 000 of all ED attendances. The incidence of SAH was similar to that previously reported for Australia. One in 50 ED patients with headache had SAH. Ten in 50 000 ED attendances had a SAH. These estimates can assist in the risk assessment for SAH. © 2018 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

On the use of transition matrix methods with extended ensembles.

PubMed

Escobedo, Fernando A; Abreu, Charlles R A

2006-03-14

Different extended ensemble schemes for non-Boltzmann sampling (NBS) of a selected reaction coordinate lambda were formulated so that they employ (i) "variable" sampling window schemes (that include the "successive umbrella sampling" method) to comprehensibly explore the lambda domain and (ii) transition matrix methods to iteratively obtain the underlying free-energy eta landscape (or "importance" weights) associated with lambda. The connection between "acceptance ratio" and transition matrix methods was first established to form the basis of the approach for estimating eta(lambda). The validity and performance of the different NBS schemes were then assessed using as lambda coordinate the configurational energy of the Lennard-Jones fluid. For the cases studied, it was found that the convergence rate in the estimation of eta is little affected by the use of data from high-order transitions, while it is noticeably improved by the use of a broader window of sampling in the variable window methods. Finally, it is shown how an "elastic" window of sampling can be used to effectively enact (nonuniform) preferential sampling over the lambda domain, and how to stitch the weights from separate one-dimensional NBS runs to produce a eta surface over a two-dimensional domain.

Thermoplastic Polyurethanes with Isosorbide Chain Extender

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

Javni, Ivan; Bilic, Olivera; Bilic, Nikola

2015-12-15

Isosorbide, a renewable diol derived from starch, was used alone or in combination with butane diol (BD) as the chain extender in two series of thermoplastic polyurethanes (TPU) with 50 and 70% polytetramethylene ether glycol (PTMEG) soft segment concentration (SSC), respectively. In the synthesized TPUs, the hard segment composition was systematically varied in both series following BD/isosorbide molar ratios of 100 : 0; 75 : 25; 50 : 50; 25 : 75, and 0 : 100 to examine in detail the effect of chain extenders on properties of segmented polyurethane elastomers with different morphologies. We found that polyurethanes with 50%more » SSC were hard elastomers with Shore D hardness of around 50, which is consistent with assumed co-continuous morphology. Polymers with 70% SSC displayed lower Shore A hardness of 74–79 (Shore D around 25) as a result of globular hard domains dispersed in the soft matrix. Insertion of isosorbide increased rigidity, melting point and glass transition temperature of hard segments and tensile strength of elastomers with 50% SSC. These effects were weaker or non-existent in 70% SSC series due to the short hard segments and low content of isosorbide. We also found that the thermal stability was lowered by increasing isosorbide content in both series.« less

Phase I study of BAY 94-9027, a PEGylated B-domain-deleted recombinant factor VIII with an extended half-life, in subjects with hemophilia A.

PubMed

Coyle, T E; Reding, M T; Lin, J C; Michaels, L A; Shah, A; Powell, J

2014-04-01

BAY 94-9027 is a B-domain-deleted recombinant factor VIII (rFVIII) with site-specific attachment of poly(ethylene glycol) that has shown an extended half-life in animal models of hemophilia. To assess the pharmacokinetics and safety of BAY 94-9027 after single and repeated administration in subjects with severe hemophilia A. This 8-week, prospective, multicenter, open-label, phase I trial was conducted in 14 subjects aged 21–58 years with FVIII of < 1%, ≥ 150 days of exposure to FVIII, and no history of FVIII inhibitors. After a ≥ 3-day washout, subjects received a single dose of sucrose-formulated rFVIII (rFVIII-FS) (cohort 1 [n = 7], 25 IU kg−1; cohort 2 [n = 7], 50 IU kg−1) for a 48-h pharmacokinetic (PK) study. After another ≥ 3-day washout, cohort 1 received twice-weekly BAY 94-9027 at 25 IU kg−1 (16 doses), and cohort 2 received once-weekly BAY 94-9027 at 60 IU kg−1 (nine doses). A 168-h PK study was performed after the first and last BAY 94-9027 doses. BAY 94-9027 showed equivalent recovery and an improved PK profile vs. rFVIII-FS, with a half-life of ~ 19 h (vs. ~ 13.0 h for rFVIII-FS). BAY 94-9027 was well tolerated, and no immunogenicity was observed. This phase I study demonstrates that BAY 94-9027 has an extended half-life in subjects with hemophilia A and, after multiple dosing, was well tolerated with no immunogenicity during the 8-week trial. A phase III study in a larger number of subjects is underway to fully characterize how this prolonged half-life will permit less frequent prophylaxis dosing for patients with hemophilia.

Acousto-Optic–Based Wavelength-Comb-Swept Laser for Extended Displacement Measurements

PubMed Central

Park, Nam Su; Chun, Soo Kyung; Han, Ga-Hee; Kim, Chang-Seok

2017-01-01

We demonstrate a novel wavelength-comb-swept laser based on two intra-cavity filters: an acousto-optic tunable filter (AOTF) and a Fabry-Pérot etalon filter. The AOTF is used for the tunable selection of the output wavelength with time and the etalon filter for the narrowing of the spectral linewidth to extend the coherence length. Compared to the conventional wavelength-swept laser, the acousto-optic–based wavelength-comb-swept laser (WCSL) can extend the measureable range of displacement measurements by decreasing the sensitivity roll-off of the point spread function. Because the AOTF contains no mechanical moving parts to select the output wavelength acousto-optically, the WCSL source has a high wavenumber (k) linearity of R2 = 0.9999 to ensure equally spaced wavelength combs in the wavenumber domain. PMID:28362318

MutationAligner: a resource of recurrent mutation hotspots in protein domains in cancer

PubMed Central

Gauthier, Nicholas Paul; Reznik, Ed; Gao, Jianjiong; Sumer, Selcuk Onur; Schultz, Nikolaus; Sander, Chris; Miller, Martin L.

2016-01-01

The MutationAligner web resource, available at http://www.mutationaligner.org, enables discovery and exploration of somatic mutation hotspots identified in protein domains in currently (mid-2015) more than 5000 cancer patient samples across 22 different tumor types. Using multiple sequence alignments of protein domains in the human genome, we extend the principle of recurrence analysis by aggregating mutations in homologous positions across sets of paralogous genes. Protein domain analysis enhances the statistical power to detect cancer-relevant mutations and links mutations to the specific biological functions encoded in domains. We illustrate how the MutationAligner database and interactive web tool can be used to explore, visualize and analyze mutation hotspots in protein domains across genes and tumor types. We believe that MutationAligner will be an important resource for the cancer research community by providing detailed clues for the functional importance of particular mutations, as well as for the design of functional genomics experiments and for decision support in precision medicine. MutationAligner is slated to be periodically updated to incorporate additional analyses and new data from cancer genomics projects. PMID:26590264

Oracle, a novel PDZ-LIM domain protein expressed in heart and skeletal muscle.

PubMed

Passier, R; Richardson, J A; Olson, E N

2000-04-01

In order to identify novel genes enriched in adult heart, we performed a subtractive hybridization for genes expressed in mouse heart but not in skeletal muscle. We identified two alternative splicing variants of a novel PDZ-LIM domain protein, which we named Oracle. Both variants contain a PDZ domain at the amino-terminus and three LIM domains at the carboxy-terminus. Highest homology of Oracle was found with the human and rat enigma proteins in the PDZ domain (62 and 61%, respectively) and in the LIM domains (60 and 69%, respectively). By Northern hybridization analysis, we showed that expression is highest in adult mouse heart, low in skeletal muscle and undetectable in other adult mouse tissues. In situ hybridization in mouse embryos confirmed and extended these data by showing high expression of Oracle mRNA in atrial and ventricular myocardial cells from E8.5. From E9.5 low expression of Oracle mRNA was detectable in myotomes. These data suggest a role for Oracle in the early development and function of heart and skeletal muscle.

Thermal runaway and microwave heating in thin cylindrical domains

NASA Astrophysics Data System (ADS)

Ward, Michael J.

2002-04-01

The behaviour of the solution to two nonlinear heating problems in a thin cylinder of revolution of variable cross-sectional area is analysed using asymptotic and numerical methods. The first problem is to calculate the fold point, corresponding to the onset of thermal runaway, for a steady-state nonlinear elliptic equation that arises in combustion theory. In the limit of thin cylindrical domains, it is shown that the onset of thermal runaway can be delayed when a circular cylindrical domain is perturbed into a dumbell shape. Numerical values for the fold point for different domain shapes are obtained asymptotically and numerically. The second problem that is analysed is a nonlinear parabolic equation modelling the microwave heating of a ceramic cylinder by a known electric field. The basic model in a thin circular cylindrical domain was analysed in Booty & Kriegsmann (Meth. Appl. Anal. 4 (1994) p. 403). Their analysis is extended to treat thin cylindrical domains of variable cross-section. It is shown that the steady-state and dynamic behaviours of localized regions of high temperature, called hot-spots, depend on a competition between the maxima of the electric field and the maximum deformation of the circular cylinder. For a dumbell-shaped region it is shown that two disconnected hot-spot regions can occur. Depending on the parameters in the model, these regions, ultimately, either merge as time increases or else remain as disconnected regions for all time.

Simultaneous Binding of Two Peptidyl Ligands by a Src Homology 2 Domain

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

Zhang, Yanyan; Zhang, Jinjin; Yuan, Chunhua

Src homology 2 (SH2) domains mediate protein-protein interactions by recognizing phosphotyrosine (pY)-containing sequences of target proteins. In all of the SH2 domain-pY peptide interactions described to date, the SH2 domain binds to a single pY peptide. Here, determination of the cocrystal structure of the N-terminal SH2 domain of phosphatase SHP-2 bound to a class IV peptide (VIpYFVP) revealed a noncanonical 1:2 (protein-peptide) complex. The first peptide binds in a canonical manner with its pY side chain inserted in the usual binding pocket, while the second pairs up with the first to form two antiparallel {beta}-strands that extend the central {beta}-sheetmore » of the SH2 domain. This unprecedented binding mode was confirmed in the solution phase by NMR experiments and shown to be adopted by pY peptides derived from cellular proteins. Site-directed mutagenesis and surface plasmon resonance studies revealed that the binding of the first peptide is pY-dependent, but phosphorylation is not required for the second peptide. Our findings suggest a potential new function for the SH2 domain as a molecular clamp to promote dimerization of signaling proteins.« less

Crystal structure of secretory abundant heat soluble protein 4 from one of the toughest “water bears” micro‐animals Ramazzottius Varieornatus

PubMed Central

Fukuda, Yohta

2018-01-01

Abstract Though anhydrobiotic tardigrades (micro‐animals also known as water bears) possess many genes of secretory abundant heat soluble (SAHS) proteins unique to Tardigrada, their functions are unknown. A previous crystallographic study revealed that a SAHS protein (RvSAHS1) from one of the toughest tardigrades, Ramazzottius varieornatus, has a β‐barrel architecture similar to fatty acid binding proteins (FABPs) and two putative ligand binding sites (LBS1 and LBS2) where fatty acids can bind. However, some SAHS proteins such as RvSAHS4 have different sets of amino acid residues at LBS1 and LBS2, implying that they prefer other ligands and have different functions. Here RvSAHS4 was crystallized and analyzed under a condition similar to that for RvSAHS1. There was no electron density corresponding to a fatty acid at LBS1 of RvSAHS4, where a putative fatty acid was observed in RvSAHS1. Instead, LBS2 of RvSAHS4, which was composed of uncharged residues, captured a putative polyethylene glycol molecule. These results suggest that RvSAHS4 mainly uses LBS2 for the binding of uncharged molecules. PMID:29493034

Time domain analysis of thin-wire antennas over lossy ground using the reflection-coefficient approximation

NASA Astrophysics Data System (ADS)

FernáNdez Pantoja, M.; Yarovoy, A. G.; Rubio Bretones, A.; GonzáLez GarcíA, S.

2009-12-01

This paper presents a procedure to extend the methods of moments in time domain for the transient analysis of thin-wire antennas to include those cases where the antennas are located over a lossy half-space. This extended technique is based on the reflection coefficient (RC) approach, which approximates the fields incident on the ground interface as plane waves and calculates the time domain RC using the inverse Fourier transform of Fresnel equations. The implementation presented in this paper uses general expressions for the RC which extend its range of applicability to lossy grounds, and is proven to be accurate and fast for antennas located not too near to the ground. The resulting general purpose procedure, able to treat arbitrarily oriented thin-wire antennas, is appropriate for all kind of half-spaces, including lossy cases, and it has turned out to be as computationally fast solving the problem of an arbitrary ground as dealing with a perfect electric conductor ground plane. Results show a numerical validation of the method for different half-spaces, paying special attention to the influence of the antenna to ground distance in the accuracy of the results.

Effect of dipolar moments in domain sizes of lipid bilayers and monolayers

NASA Astrophysics Data System (ADS)

Travesset, A.

2006-08-01

Lipid domains are found in systems such as multicomponent bilayer membranes and single component monolayers at the air-water interface. It was shown by Keller et al. [J. Phys. Chem. 91, 6417 (1987)] that in monolayers, the size of the domains results from balancing the line tension, which favors the formation of a large single circular domain, against the electrostatic cost of assembling the dipolar moments of the lipids. In this paper, we present an exact analytical expression for the electric potential, ion distribution, and electrostatic free energy for different problems consisting of three different slabs with different dielectric constants and Debye lengths, with a circular homogeneous dipolar density in the middle slab. From these solutions, we extend the calculation of domain sizes for monolayers to include the effects of finite ionic strength, dielectric discontinuities (or image charges), and the polarizability of the dipoles and further generalize the calculations to account for domains in lipid bilayers. In monolayers, the size of the domains is dependent on the different dielectric constants but independent of ionic strength. In asymmetric bilayers, where the inner and outer leaflets have different dipolar densities, domains show a strong size dependence with ionic strength, with molecular-sized domains that grow to macroscopic phase separation with increasing ionic strength. We discuss the implications of the results for experiments and briefly consider their relation to other two dimensional systems such as Wigner crystals or heteroepitaxial growth.

Tendencies in cerebral aneurism treatment: Analysis of a hospital series.

PubMed

Lago, A; López-Cuevas, R; Tembl, J I; Fortea, G; Górriz, D; Aparici, F; Parkhutik, V

To discover if there have been changes in the treatment time for SAH in our hospital environment. Comparative analysis of 571 patients treated at Hospital Universitari la Fe during 2 different time periods. The SAH-OLD group consisted of 462 patients attended consecutively between April 1997 and March 2005, while SAH-NEW comprised 109 patients attended consecutively between March 2007 and April 2010. We analysed demographic factors, risk factors, severity at time of admission, time to arteriography, diagnosis of aneurysm, use of surgical or endovascular treatment and time to treatment, frequency of neurological complications, in-hospital deaths, and modified Rankin Scale (mRS) at discharge. Mean time to arteriography was 2.18 ± 2.5 days for the SAH-OLD group and 2.37 ± 2.23 days, for the SAH-NEW group (P=.49). Mortality rates for SAH-OLD patients were calculated at 30%, compared to 18.3% in SAH-NEW patients (P=.01). Among patients surviving the hospital stay in the SAH-OLD group, 13.3% had an mRS > 3, compared to 21.3% of survivors in the SAH-NEW group (P=.06). Two hundred forty-five patients in the SAH-OLD group had cerebral aneurysms and 208 were treated (45% of the patient total). Sixty-five of the SAH-NEW patients received treatment (60% of the patient total, P=.007). In the SAH-OLD group, 62.9% of the patients underwent embolisation vs 74.6% in the SAH-NEW group (P=.08). Time to embolisation was 4.7 ± 8.2 days for SAH-OLD patients and 2.12 ± 2.2 days for SAH-NEW patients (P=.01). Twenty-two percent of SAH-OLD patients underwent surgery, compared to 25.4% in the SAH-NEW group (P=.62). Care for SAH patients has improved in this hospital: results include fewer mortalities, a higher number of treatments with a smaller proportion of endovascular treatments, and shorter times to treatment. Elapsed time to arteriography remains stable. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

The transmembrane collagen COL-99 guides longitudinally extending axons in C. elegans.

PubMed

Taylor, Jesse; Unsoeld, Thomas; Hutter, Harald

2018-06-01

We have identified the transmembrane collagen, COL-99, in a genetic screen for novel genes involved in axon guidance in the nematode C. elegans. COL-99 is similar to transmembrane collagens type XIII, XXIII and XXV in vertebrates. col-99 mutants exhibit guidance defects in axons extending along the major longitudinal axon tracts, most prominently the left ventral nerve cord (VNC). COL-99 is expressed in the hypodermis during the time of axon outgrowth. We provide evidence that a furin cleavage site in COL-99 is essential for function, suggesting that COL-99 is released from the cells producing it. Vertebrate homologs of COL-99 have been shown to be expressed in mammalian nervous systems and linked to various neurological disease but have not been associated with guidance of extending neurons. col-99 acts genetically with the discoidin domain receptors ddr-1 and ddr-2, which are expressed by neurons affected in col-99 mutants. Discoidin domain receptors are activated by collagens in vertebrates. DDR-1 and DDR-2 may function as receptors for COL-99. Our results establish a novel role for a transmembrane collagen in axonal guidance and asymmetry establishment of the VNC. Copyright © 2018 Elsevier Inc. All rights reserved.

Protein sorting by lipid phase-like domains supports emergent signaling function in B lymphocyte plasma membranes.

PubMed

Stone, Matthew B; Shelby, Sarah A; Núñez, Marcos F; Wisser, Kathleen; Veatch, Sarah L

2017-02-01

Diverse cellular signaling events, including B cell receptor (BCR) activation, are hypothesized to be facilitated by domains enriched in specific plasma membrane lipids and proteins that resemble liquid-ordered phase-separated domains in model membranes. This concept remains controversial and lacks direct experimental support in intact cells. Here, we visualize ordered and disordered domains in mouse B lymphoma cell membranes using super-resolution fluorescence localization microscopy, demonstrate that clustered BCR resides within ordered phase-like domains capable of sorting key regulators of BCR activation, and present a minimal, predictive model where clustering receptors leads to their collective activation by stabilizing an extended ordered domain. These results provide evidence for the role of membrane domains in BCR signaling and a plausible mechanism of BCR activation via receptor clustering that could be generalized to other signaling pathways. Overall, these studies demonstrate that lipid mediated forces can bias biochemical networks in ways that broadly impact signal transduction.

Kernel Manifold Alignment for Domain Adaptation.

PubMed

Tuia, Devis; Camps-Valls, Gustau

2016-01-01

The wealth of sensory data coming from different modalities has opened numerous opportunities for data analysis. The data are of increasing volume, complexity and dimensionality, thus calling for new methodological innovations towards multimodal data processing. However, multimodal architectures must rely on models able to adapt to changes in the data distribution. Differences in the density functions can be due to changes in acquisition conditions (pose, illumination), sensors characteristics (number of channels, resolution) or different views (e.g. street level vs. aerial views of a same building). We call these different acquisition modes domains, and refer to the adaptation problem as domain adaptation. In this paper, instead of adapting the trained models themselves, we alternatively focus on finding mappings of the data sources into a common, semantically meaningful, representation domain. This field of manifold alignment extends traditional techniques in statistics such as canonical correlation analysis (CCA) to deal with nonlinear adaptation and possibly non-corresponding data pairs between the domains. We introduce a kernel method for manifold alignment (KEMA) that can match an arbitrary number of data sources without needing corresponding pairs, just few labeled examples in all domains. KEMA has interesting properties: 1) it generalizes other manifold alignment methods, 2) it can align manifolds of very different complexities, performing a discriminative alignment preserving each manifold inner structure, 3) it can define a domain-specific metric to cope with multimodal specificities, 4) it can align data spaces of different dimensionality, 5) it is robust to strong nonlinear feature deformations, and 6) it is closed-form invertible, which allows transfer across-domains and data synthesis. To authors' knowledge this is the first method addressing all these important issues at once. We also present a reduced-rank version of KEMA for computational

Structural Landscape of the Proline-Rich Domain of Sos1 Nucleotide Exchange Factor

PubMed Central

McDonald, Caleb B.; Bhat, Vikas; Kurouski, Dmitry; Mikles, David C.; Deegan, Brian J.; Seldeen, Kenneth L.; Lednev, Igor K.; Farooq, Amjad

2013-01-01

Despite its key role in mediating a plethora of cellular signaling cascades pertinent to health and disease, little is known about the structural landscape of the proline-rich (PR) domain of Sos1 guanine nucleotide exchange factor. Herein, using a battery of biophysical tools, we provide evidence that the PR domain of Sos1 is structurally disordered and adopts an extended random coil-like conformation in solution. Of particular interest is the observation that while chemical denaturation of PR domain results in the formation of a significant amount of polyproline II (PPII) helices, it has little or negligible effect on its overall size as measured by its hydrodynamic radius. Our data also show that the PR domain displays a highly dynamic conformational basin in agreement with the knowledge that the intrinsically unstructured proteins rapidly interconvert between an ensemble of conformations. Collectively, our study provides new insights into the conformational equilibrium of a key signaling molecule with important consequences on its physiological function. PMID:23528987

Crystal Structure of the Central Coiled-Coil Domain from Human Liprin-[beta]2

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

Stafford, Ryan L.; Tang, Ming-Yun; Sawaya, Michael R.

2012-02-07

Liprins are a conserved family of scaffolding proteins important for the proper regulation and development of neuronal synapses. Humans have four liprin-{alpha}s and two liprin-{beta}s which all contain long coiled-coil domains followed by three tandem SAM domains. Complex interactions between the coiled-coil and SAM domains are thought to create liprin scaffolds, but the structural and biochemical properties of these domains remain largely uncharacterized. In this study we find that the human liprin-{beta}2 coiled-coil forms an extended dimer. Several protease-resistant subdomains within the liprin-{beta}1 and liprin-{beta}2 coiled-coils were also identified. A 2.0 {angstrom} crystal structure of the central, protease-resistant core ofmore » the liprin-{beta}2 coiled-coil reveals a parallel helix orientation. These studies represent an initial step toward determining the overall architecture of liprin scaffolds and understanding the molecular basis for their synaptic functions.« less

SOME NEW FINITE DIFFERENCE METHODS FOR HELMHOLTZ EQUATIONS ON IRREGULAR DOMAINS OR WITH INTERFACES

PubMed Central

Wan, Xiaohai; Li, Zhilin

2012-01-01

Solving a Helmholtz equation Δu + λu = f efficiently is a challenge for many applications. For example, the core part of many efficient solvers for the incompressible Navier-Stokes equations is to solve one or several Helmholtz equations. In this paper, two new finite difference methods are proposed for solving Helmholtz equations on irregular domains, or with interfaces. For Helmholtz equations on irregular domains, the accuracy of the numerical solution obtained using the existing augmented immersed interface method (AIIM) may deteriorate when the magnitude of λ is large. In our new method, we use a level set function to extend the source term and the PDE to a larger domain before we apply the AIIM. For Helmholtz equations with interfaces, a new maximum principle preserving finite difference method is developed. The new method still uses the standard five-point stencil with modifications of the finite difference scheme at irregular grid points. The resulting coefficient matrix of the linear system of finite difference equations satisfies the sign property of the discrete maximum principle and can be solved efficiently using a multigrid solver. The finite difference method is also extended to handle temporal discretized equations where the solution coefficient λ is inversely proportional to the mesh size. PMID:22701346

SOME NEW FINITE DIFFERENCE METHODS FOR HELMHOLTZ EQUATIONS ON IRREGULAR DOMAINS OR WITH INTERFACES.

PubMed

Wan, Xiaohai; Li, Zhilin

2012-06-01

Solving a Helmholtz equation Δu + λu = f efficiently is a challenge for many applications. For example, the core part of many efficient solvers for the incompressible Navier-Stokes equations is to solve one or several Helmholtz equations. In this paper, two new finite difference methods are proposed for solving Helmholtz equations on irregular domains, or with interfaces. For Helmholtz equations on irregular domains, the accuracy of the numerical solution obtained using the existing augmented immersed interface method (AIIM) may deteriorate when the magnitude of λ is large. In our new method, we use a level set function to extend the source term and the PDE to a larger domain before we apply the AIIM. For Helmholtz equations with interfaces, a new maximum principle preserving finite difference method is developed. The new method still uses the standard five-point stencil with modifications of the finite difference scheme at irregular grid points. The resulting coefficient matrix of the linear system of finite difference equations satisfies the sign property of the discrete maximum principle and can be solved efficiently using a multigrid solver. The finite difference method is also extended to handle temporal discretized equations where the solution coefficient λ is inversely proportional to the mesh size.

Persistence of evolutionary memory: primordial six-transmembrane helical domain mu opiate receptors selectively linked to endogenous morphine signaling.

PubMed

Kream, Richard M; Sheehan, Melinda; Cadet, Patrick; Mantione, Kirk J; Zhu, Wei; Casares, Federico; Stefano, George B

2007-12-01

Biochemical, molecular and pharmacological evidence for two unique six-transmembrane helical (TMH) domain opiate receptors expressed from the micro opioid receptor (MOR) gene have been shown. Designated micro3 and micro4 receptors, both protein species are Class A rhodopsin-like members of the superfamily of G-protein coupled receptors but are selectively tailored to mediate the cellular regulatory effects of endogenous morphine and related morphinan alkaloids via stimulation of nitric oxide (NO) production and release. Both micro3 and micro4 receptors lack an amino acid sequence of approximately 90 amino acids that constitute the extracellular N-terminal and TMH1 domains and part of the first intracellular loop of the micro1 receptor, but retain the empirically defined ligand binding pocket distributed across conserved TMH2, TMH3, and TMH7 domains of the micro1 sequence. Additionally, the receptor proteins are terminated by unique intracellular C-terminal amino acid sequences that serve as putative coupling or docking domains required for constitutive NO synthase activation. Because the recognition profile of micro3 and micro4 receptors is restricted to rigid benzylisoquinoline alkaloids typified by morphine and its extended family of chemical congeners, it is hypothesized that conformational stabilization provided by interaction of extended extracellular N-terminal protein domains and the extracellular loops is required for binding of endogenous opioid peptides as well as synthetic flexible opiate alkaloids.

On the maximum principle for complete second-order elliptic operators in general domains

NASA Astrophysics Data System (ADS)

Vitolo, Antonio

This paper is concerned with the maximum principle for second-order linear elliptic equations in a wide generality. By means of a geometric condition previously stressed by Berestycki-Nirenberg-Varadhan, Cabré was very able to improve the classical ABP estimate obtaining the maximum principle also in unbounded domains, such as infinite strips and open connected cones with closure different from the whole space. Now we introduce a new geometric condition that extends the result to a more general class of domains including the complements of hypersurfaces, as for instance the cut plane. The methods developed here allow us to deal with complete second-order equations, where the admissible first-order term, forced to be zero in a preceding result with Cafagna, depends on the geometry of the domain.

Domain atrophy creates rare cases of functional partial protein domains.

PubMed

Prakash, Ananth; Bateman, Alex

2015-04-30

Protein domains display a range of structural diversity, with numerous additions and deletions of secondary structural elements between related domains. We have observed a small number of cases of surprising large-scale deletions of core elements of structural domains. We propose a new concept called domain atrophy, where protein domains lose a significant number of core structural elements. Here, we implement a new pipeline to systematically identify new cases of domain atrophy across all known protein sequences. The output of this pipeline was carefully checked by hand, which filtered out partial domain instances that were unlikely to represent true domain atrophy due to misannotations or un-annotated sequence fragments. We identify 75 cases of domain atrophy, of which eight cases are found in a three-dimensional protein structure and 67 cases have been inferred based on mapping to a known homologous structure. Domains with structural variations include ancient folds such as the TIM-barrel and Rossmann folds. Most of these domains are observed to show structural loss that does not affect their functional sites. Our analysis has significantly increased the known cases of domain atrophy. We discuss specific instances of domain atrophy and see that there has often been a compensatory mechanism that helps to maintain the stability of the partial domain. Our study indicates that although domain atrophy is an extremely rare phenomenon, protein domains under certain circumstances can tolerate extreme mutations giving rise to partial, but functional, domains.

CCR+: Metadata Based Extended Personal Health Record Data Model Interoperable with the ASTM CCR Standard.

PubMed

Park, Yu Rang; Yoon, Young Jo; Jang, Tae Hun; Seo, Hwa Jeong; Kim, Ju Han

2014-01-01

Extension of the standard model while retaining compliance with it is a challenging issue because there is currently no method for semantically or syntactically verifying an extended data model. A metadata-based extended model, named CCR+, was designed and implemented to achieve interoperability between standard and extended models. Furthermore, a multilayered validation method was devised to validate the standard and extended models. The American Society for Testing and Materials (ASTM) Community Care Record (CCR) standard was selected to evaluate the CCR+ model; two CCR and one CCR+ XML files were evaluated. In total, 188 metadata were extracted from the ASTM CCR standard; these metadata are semantically interconnected and registered in the metadata registry. An extended-data-model-specific validation file was generated from these metadata. This file can be used in a smartphone application (Health Avatar CCR+) as a part of a multilayered validation. The new CCR+ model was successfully evaluated via a patient-centric exchange scenario involving multiple hospitals, with the results supporting both syntactic and semantic interoperability between the standard CCR and extended, CCR+, model. A feasible method for delivering an extended model that complies with the standard model is presented herein. There is a great need to extend static standard models such as the ASTM CCR in various domains: the methods presented here represent an important reference for achieving interoperability between standard and extended models.

Morphological characterization of rat entorhinal neurons in vivo: soma-dendritic structure and axonal domains.

PubMed

Lingenhöhl, K; Finch, D M

1991-01-01

We used in vivo intracellular labeling with horseradish peroxidase in order to study the soma-dendritic morphology and axonal projections of rat entorhinal neurons. The cells responded to hippocampal stimulation with inhibitory postsynaptic potentials, and thus likely received direct or indirect hippocampal input. All cells (n = 24) showed extensive dendritic domains that extended in some cases for more than 1 mm. The dendrites of layer II neurons were largely restricted to layers I and II or layers I-III, while the dendrites of deeper cells could extend through all cortical layers. Computed 3D rotations showed that the basilar dendrites of deep pyramids extended roughly parallel to the cortical layering, and that they were mostly confined to the layer containing the soma and layers immediately adjacent. Total dendritic lengths averaged 9.8 mm +/- 3.8 (SD), and ranged from 5 mm to more than 18 mm. Axonal processes could be visualized in 21 cells. Most of these showed axonal branching within the entorhinal cortex, sometimes extensive. Efferent axonal domains were reconstructed in detail in 3 layer II stellate cells. All 3 projected axons across the subicular complex to the dentate gyrus. One of these cells showed an extensive net-like axonal domain that also projected to several other structures, including the hippocampus proper, subicular complex, and the amygdalo-piriform transition area. The axons of layer III and IV cells projected to the angular bundle, where they continued in a rostral direction. In contrast to the layer II, III and IV cells, no efferent axonal branches leaving the entorhinal cortex could be visualized in 5 layer V neurons. The data indicate that entorhinal neurons can integrate input from a considerable volume of entorhinal cortex by virtue of their extensive dendritic domains, and provide a further basis for specifying the layers in which cells receive synaptic input. The extensive axonal branching pattern seen in most of the cells would

Extended Impact of Pin1 Catalytic Loop Phosphorylation Revealed by S71E Phosphomimetic.

PubMed

Mahoney, Brendan J; Zhang, Meiling; Zintsmaster, John S; Peng, Jeffrey W

2018-03-02

Pin1 is a two-domain human protein that catalyzes the cis-trans isomerization of phospho-Ser/Thr-Pro (pS/T-P) motifs in numerous cell-cycle regulatory proteins. These pS/T-P motifs bind to Pin1's peptidyl-prolyl isomerase (PPIase) domain in a catalytic pocket, between an extended catalytic loop and the PPIase domain core. Previous studies showed that post-translational phosphorylation of S71 in the catalytic loop decreases substrate binding affinity and isomerase activity. To define the origins for these effects, we investigated a phosphomimetic Pin1 mutant, S71E-Pin1, using solution NMR. We find that S71E perturbs not only its host loop but also the nearby PPIase core. The perturbations identify a local network of hydrogen bonds and salt bridges that is more extended than previously thought, and includes interactions between the catalytic loop and the α2/α3 turn in the PPIase core. Explicit-solvent molecular dynamics simulations and phylogenetic analysis suggest that these interactions act as conserved "latches" between the loop and PPIase core that enhance binding of phosphorylated substrates, as they are absent in PPIases lacking pS/T-P specificity. Our results suggest that S71 is a hub residue within an electrostatic network primed for phosphorylation, and may illustrate a common mechanism of phosphorylation-mediated allostery. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

6-Mercaptopurine attenuates adhesive molecules in experimental vasospasm.

PubMed

Chang, Chih-Zen; Lin, Chih-Lung; Kassel, Neal F; Kwan, Aij-Lie; Howng, Shen-Long

2010-05-01

Adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin, are important inflammatory mediators which are elevated in the serum of patients following aneurysmal subarachnoid hemorrhage (SAH). The authors previously found that 6-mercaptopurine (6-mp) was effective in preventing and reversing arterial narrowing in a rodent SAH model. The present study was to examine whether levels of adhesion molecules were altered after treatment with 6-mp in this animal model. Animals were each injected with autologous blood into the cisterna magna, and intraperitoneal treatment with 6-mp (2 mg/kg) was initiated 1 h before (prevention) or later (treatment). The compound was subsequently administered at 24 and 48 h post-SAH. Blood samples were collected at 72 h post-SAH to measure ICAM-1, VCAM-1, and E-selectin levels. The basilar arteries were harvested and sliced, and their cross-sectional areas were measured. Morphologically, convolution of the internal elastic lamina, distorted endothelial wall, and myonecrosis of the smooth muscle were prominently observed in the SAH only and vehicle-treated SAH groups, but not in the 6-mp-treated SAH group or in healthy controls. No significant differences were found in the levels of VCAM-1 among all groups. However, the levels of E-selectin were increased in all animals subjected to SAH (SAH only and SAH plus vehicle groups) compared with healthy controls (no SAH), but not in the 6-mp group (SAH plus 6-mp treatment and preventive treatment with 6-mp).Likewise, the levels of ICAM-1 in the SAH only and SAH plus vehicle groups were significantly elevated (p < 0.001), and pretreatment and treatment with 6-mp reduced ICAM-1 to control levels. These results show that ICAM-1 and E-selectin may play a role in mediating SAH-induced vasospasm and that a reduction of both adhesive molecules after SAH may partly contribute to the antispastic effect of 6-mp.

Magnetic switching, relaxation, and domain structure of a Co/Si(111) film

NASA Astrophysics Data System (ADS)

Baird, M. J.; Bland, J. A. C.; Gu, E.; Ives, A. J. R.; Schumann, F. O.; Hughes, H. P.

1993-11-01

We have used scanning magneto-optic Kerr effect (MOKE) microscopy to investigate the magnetic relaxation of a polycrystalline hcp 125 Å Co/Si(111) film with planar uniaxial anisotropy, on time scales between 10 and 2400 s and with a spatial resolution of 15 μm. In a static magnetic field slightly less than the coercive field and applied along the easy axis direction, domains develop and the magnetization reversal proceeds via displacements of 180° domain walls. Microscopic images of this metastable state allow the 180° domains to be identified by calibration of the MOKE signal with respect to that for the saturated magnetization states. The 180° reversed domains are observed to grow in the direction of the field in the form of narrow fingers, extending via short Barkhausen jumps, randomly spaced in time over the entire time-scale range investigated, with typical distances between pinning sites of the order of microns. This reversal behavior is qualitatively similar to that reported for Au/Co perpendicular anisotropy films a few monolayers thick.

Homeopathic potentization based on nanoscale domains.

PubMed

Czerlinski, George; Ypma, Tjalling

2011-12-01

The objectives of this study were to present a simple descriptive and quantitative model of how high potencies in homeopathy arise. The model begins with the mechanochemical production of hydrogen and hydroxyl radicals from water and the electronic stabilization of the resulting nanodomains of water molecules. The life of these domains is initially limited to a few days, but may extend to years when the electromagnetic characteristic of a homeopathic agent is copied onto the domains. This information is transferred between the original agent and the nanodomains, and also between previously imprinted nanodomains and new ones. The differential equations previously used to describe these processes are replaced here by exponential expressions, corresponding to simplified model mechanisms. Magnetic stabilization is also involved, since these long-lived domains apparently require the presence of the geomagnetic field. Our model incorporates this factor in the formation of the long-lived compound. Numerical simulation and graphs show that the potentization mechanism can be described quantitatively by a very simplified mechanism. The omitted factors affect only the fine structure of the kinetics. Measurements of pH changes upon absorption of different electromagnetic frequencies indicate that about 400 nanodomains polymerize to form one cooperating unit. Singlet excited states of some compounds lead to dramatic changes in their hydrogen ion dissociation constant, explaining this pH effect and suggesting that homeopathic information is imprinted as higher singlet excited states. A simple description is provided of the process of potentization in homeopathic dilutions. With the exception of minor details, this simple model replicates the results previously obtained from a more complex model. While excited states are short lived in isolated molecules, they become long lived in nanodomains that form coherent cooperative aggregates controlled by the geomagnetic field. These

Signaling Pathway in Early Brain Injury after Subarachnoid Hemorrhage: News Update.

PubMed

Ji, Chengyuan; Chen, Gang

2016-01-01

The annual incidence of subarachnoid hemorrhage (SAH) caused by intracranial aneurysm rupture is approximately 10.5/10 million people in China, making SAH the third most frequently occurring hemorrhage of the intracranial type after cerebral embolism and hypertensive intracerebral hemorrhage. SAH caused by ruptured aneurysm leads to a mortality rate as high as 67 %, and, because of the sudden onset of this disease, approximately 12-15 % of patients die before they can receive effective treatment. Early brain injury (EBI) is the brain damage occurring within the first 72 h after SAH. Two-thirds of mortality caused by SAH occurs within 48 h, mainly as a result of EBI. With the development of molecular biology and medicine microscopy techniques, various signaling pathways involved in EBI after SAH have been revealed. Understanding these signaling pathways may help clinicians treat EBI after SAH and improve long-term prognosis of SAH patients. This chapter summarizes several important signaling pathways implicated in EBI caused by SAH.

Exploring the Roles of Proline in Three-Dimensional Domain Swapping from Structure Analysis and Molecular Dynamics Simulations.

PubMed

Huang, Yongqi; Gao, Meng; Su, Zhengding

2018-02-01

Three-dimensional (3D) domain swapping is a mechanism to form protein oligomers. It has been proposed that several factors, including proline residues in the hinge region, may affect the occurrence of 3D domain swapping. Although introducing prolines into the hinge region has been found to promote domain swapping for some proteins, the opposite effect has also been observed in several studies. So far, how proline affects 3D domain swapping remains elusive. In this work, based on a large set of 3D domain-swapped structures, we performed a systematic analysis to explore the correlation between the presence of proline in the hinge region and the occurrence of 3D domain swapping. We further analyzed the conformations of proline and pre-proline residues to investigate the roles of proline in 3D domain swapping. We found that more than 40% of the domain-swapped structures contained proline residues in the hinge region. Unexpectedly, conformational transitions of proline residues were rarely observed upon domain swapping. Our analyses showed that hinge regions containing proline residues preferred more extended conformations, which may be beneficial for the occurrence of domain swapping by facilitating opening of the exchanged segments.

Successful application of frequency-domain airborne electromagnetic system with a grounded electric source

NASA Astrophysics Data System (ADS)

Kang, L.; Lin, J.; Liu, C.; Zhou, H.; Ren, T.; Yao, Y.

2017-12-01

A new frequency-domain AEM system with a grounded electric source, which was called ground-airborne frequency-domain electromagnetic (GAFEM) system, was proposed to extend penetration depth without compromising the resolution and detection efficiency. In GAFEM system, an electric source was placed on the ground to enlarge the strength of response signals. UVA was chosen as aircraft to reduce interaction noise and improve its ability to adapt to complex terrain. Multi-source and multi-frequency emission method has been researched and applied to improve the efficiency of GAFEM system. 2n pseudorandom sequence was introduced as transmitting waveform, to ensure resolution and detection efficiency. Inversion-procedure based on full-space apparent resistivity formula was built to realize GAFEM method and extend the survey area to non-far field. Based on GAFEM system, two application was conducted in Changchun, China, to map the deep conductive structure. As shown in the results of this exploration, GAFEM system shows its effectiveness to conductive structure, obtaining a depth of about 1km with a source-receiver distance of over 6km. And it shows the same level of resolution with CSAMT method with an over 10 times of efficiency. This extended a range of important applications where the terrain is too complex to be accessed or large penetration depth is required in a large survey area.

Properties of branching exponential flights in bounded domains

NASA Astrophysics Data System (ADS)

Zoia, A.; Dumonteil, E.; Mazzolo, A.

2012-11-01

In a series of recent works, important results have been reported concerning the statistical properties of exponential flights evolving in bounded domains, a widely adopted model for finite-speed transport phenomena (Blanco S. and Fournier R., Europhys. Lett., 61 (2003) 168; Mazzolo A., Europhys. Lett., 68 (2004) 350; Bénichou O. et al., Europhys. Lett., 70 (2005) 42). Motivated by physical and biological systems where random spatial displacements are coupled with Galton-Watson birth-death mechanisms, such as neutron multiplication, diffusion of reproducing bacteria or spread of epidemics, in this letter we extend those results in two directions, via a Feynman-Kac formalism. First, we characterize the occupation statistics of exponential flights in the presence of absorption and branching, and give explicit moment formulas for the total length travelled by the walker and the number of performed collisions in a given domain. Then, we show that the survival and escape probability can be derived as well by resorting to a similar approach.

Extended Kalman filtering for the detection of damage in linear mechanical structures

NASA Astrophysics Data System (ADS)

Liu, X.; Escamilla-Ambrosio, P. J.; Lieven, N. A. J.

2009-09-01

This paper addresses the problem of assessing the location and extent of damage in a vibrating structure by means of vibration measurements. Frequency domain identification methods (e.g. finite element model updating) have been widely used in this area while time domain methods such as the extended Kalman filter (EKF) method, are more sparsely represented. The difficulty of applying EKF in mechanical system damage identification and localisation lies in: the high computational cost, the dependence of estimation results on the initial estimation error covariance matrix P(0), the initial value of parameters to be estimated, and on the statistics of measurement noise R and process noise Q. To resolve these problems in the EKF, a multiple model adaptive estimator consisting of a bank of EKF in modal domain was designed, each filter in the bank is based on different P(0). The algorithm was iterated by using the weighted global iteration method. A fuzzy logic model was incorporated in each filter to estimate the variance of the measurement noise R. The application of the method is illustrated by simulated and real examples.

Extending a CAD-Based Cartesian Mesh Generator for the Lattice Boltzmann Method

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

Cantrell, J Nathan; Inclan, Eric J; Joshi, Abhijit S

2012-01-01

This paper describes the development of a custom preprocessor for the PaRAllel Thermal Hydraulics simulations using Advanced Mesoscopic methods (PRATHAM) code based on an open-source mesh generator, CartGen [1]. PRATHAM is a three-dimensional (3D) lattice Boltzmann method (LBM) based parallel flow simulation software currently under development at the Oak Ridge National Laboratory. The LBM algorithm in PRATHAM requires a uniform, coordinate system-aligned, non-body-fitted structured mesh for its computational domain. CartGen [1], which is a GNU-licensed open source code, already comes with some of the above needed functionalities. However, it needs to be further extended to fully support the LBM specificmore » preprocessing requirements. Therefore, CartGen is being modified to (i) be compiler independent while converting a neutral-format STL (Stereolithography) CAD geometry to a uniform structured Cartesian mesh, (ii) provide a mechanism for PRATHAM to import the mesh and identify the fluid/solid domains, and (iii) provide a mechanism to visually identify and tag the domain boundaries on which to apply different boundary conditions.« less

TOPDOM: database of conservatively located domains and motifs in proteins.

PubMed

Varga, Julia; Dobson, László; Tusnády, Gábor E

2016-09-01

The TOPDOM database-originally created as a collection of domains and motifs located consistently on the same side of the membranes in α-helical transmembrane proteins-has been updated and extended by taking into consideration consistently localized domains and motifs in globular proteins, too. By taking advantage of the recently developed CCTOP algorithm to determine the type of a protein and predict topology in case of transmembrane proteins, and by applying a thorough search for domains and motifs as well as utilizing the most up-to-date version of all source databases, we managed to reach a 6-fold increase in the size of the whole database and a 2-fold increase in the number of transmembrane proteins. TOPDOM database is available at http://topdom.enzim.hu The webpage utilizes the common Apache, PHP5 and MySQL software to provide the user interface for accessing and searching the database. The database itself is generated on a high performance computer. tusnady.gabor@ttk.mta.hu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Scalable Parallel Computation for Extended MHD Modeling of Fusion Plasmas

NASA Astrophysics Data System (ADS)

Glasser, Alan H.

2008-11-01

Parallel solution of a linear system is scalable if simultaneously doubling the number of dependent variables and the number of processors results in little or no increase in the computation time to solution. Two approaches have this property for parabolic systems: multigrid and domain decomposition. Since extended MHD is primarily a hyperbolic rather than a parabolic system, additional steps must be taken to parabolize the linear system to be solved by such a method. Such physics-based preconditioning (PBP) methods have been pioneered by Chac'on, using finite volumes for spatial discretization, multigrid for solution of the preconditioning equations, and matrix-free Newton-Krylov methods for the accurate solution of the full nonlinear preconditioned equations. The work described here is an extension of these methods using high-order spectral element methods and FETI-DP domain decomposition. Application of PBP to a flux-source representation of the physics equations is discussed. The resulting scalability will be demonstrated for simple wave and for ideal and Hall MHD waves.

A Third-Order Item Response Theory Model for Modeling the Effects of Domains and Subdomains in Large-Scale Educational Assessment Surveys

ERIC Educational Resources Information Center

Rijmen, Frank; Jeon, Minjeong; von Davier, Matthias; Rabe-Hesketh, Sophia

2014-01-01

Second-order item response theory models have been used for assessments consisting of several domains, such as content areas. We extend the second-order model to a third-order model for assessments that include subdomains nested in domains. Using a graphical model framework, it is shown how the model does not suffer from the curse of…

Conformational Rearrangement Within the Soluble Domains of the CD4 Receptor is Ligand-Specific

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

Ashish,F.; Juncadella, I.; Garg, R.

2008-01-01

Ligand binding induces shape changes within the four modular ectodomains (D1-D4) of the CD4 receptor, an important receptor in immune signaling. Small angle x-ray scattering (SAXS) on both a two-domain and a four-domain construct of the soluble CD4 (sCD4) is consistent with known crystal structures demonstrating a bilobal and a semi-extended tetralobal Z conformation in solution, respectively. Detection of conformational changes within sCD4 as a result of ligand binding was followed by SAXS on sCD4 bound to two different glycoprotein ligands: the tick saliva immunosuppressor Salp15 and the HIV-1 envelope protein gp120. Ab initio modeling of these data showed thatmore » both Salp15 and gp120 bind to the D1 domain of sCD4 and yet induce drastically different structural rearrangements. Upon binding, Salp15 primarily distorts the characteristic lobal architecture of the sCD4 without significantly altering the semi-extended shape of the sCD4 receptor. In sharp contrast, the interaction of gp120 with sCD4 induces a shape change within sCD4 that can be described as a Z-to-U bi-fold closure of the four domains across its flexible D2-D3 linker. Placement of known crystal structures within the boundaries of the SAXS-derived models suggests that the ligand-induced shape changes could be a result of conformational changes within this D2-D3 linker. Functionally, the observed shape changes in CD4 receptor causes dissociation of lymphocyte kinase from the cytoplasmic domain of Salp15-bound CD4 and facilitates an interaction between the exposed V3 loops of CD4-bound gp120 molecule to the extracellular loops of its co-receptor, a step essential for HIV-1 viral entry.« less

Magnetic domain formation in monolayer nanoparticle films

NASA Astrophysics Data System (ADS)

Maranville, Brian; Krycka, Kathryn; Borchers, Julie; Hogg, Charles; Majetich, Sara; Ijiri, Yumi

2009-03-01

Self-assembled magnetic nanoparticle films offer promise as data storage media, but an understanding of the interactions is missing. Modified Langmuir-Blodgett methods were used to prepare monolayer films of 7 and 11 nm diameter Fe3O4 nanoparticles with large structural domains. Small-angle neutron scattering (SANS) shows a peak at a wavevector Q corresponding to the particle size and spacing, and scattering at intermediate Q indicating possible long-range correlations. We extend to lower Q with off-specular neutron reflectivity, achieving high intensity by sacrificing resolution along one in-plane direction y while retaining high resolution in the other in-plane direction x and the normal direction z. We measure in saturation and zero field to extract magnetic scattering. In high fields, the specular scattering (Qx=0) is increased, consistent with aligned moments. Preliminary results show weak magnetic scattering for nonzero Qx . Since the maximal Qx roughly corresponds to the lowest Q in SANS, the combination of these techniques allows us to quantify field-dependent magnetic domain size.

Crystal Structure of a Complex of the Intracellular Domain of Interferon λ Receptor 1 (IFNLR1) and the FERM/SH2 Domains of Human JAK1.

PubMed

Zhang, Di; Wlodawer, Alexander; Lubkowski, Jacek

2016-11-20

The crystal structure of a construct consisting of the FERM and SH2-like domains of the human Janus kinase 1 (JAK1) bound to a fragment of the intracellular domain of the interferon-λ receptor 1 (IFNLR1) has been determined at the nominal resolution of 2.1Å. In this structure, the receptor peptide forms an 85-Å-long extended chain, in which both the previously identified box1 and box2 regions bind simultaneously to the FERM and SH2-like domains of JAK1. Both domains of JAK1 are generally well ordered, with regions not seen in the crystal structure limited to loops located away from the receptor-binding regions. The structure provides a much more complete and accurate picture of the interactions between JAK1 and IFNLR1 than those given in earlier reports, illuminating the molecular basis of the JAK-cytokine receptor association. A glutamate residue adjacent to the box2 region in IFNLR1 mimics the mode of binding of a phosphotyrosine in classical SH2 domains. It was shown here that a deletion of residues within the box1 region of the receptor abolishes stable interactions with JAK1, although it was previously shown that box2 alone is sufficient to stabilize a similar complex of the interferon-α receptor and TYK2. Published by Elsevier Ltd.

Cognitive ability, academic achievement and academic self-concept: extending the internal/external frame of reference model.

PubMed

Chen, Ssu-Kuang; Hwang, Fang-Ming; Yeh, Yu-Chen; Lin, Sunny S J

2012-06-01

Marsh's internal/external (I/E) frame of reference model depicts the relationship between achievement and self-concept in specific academic domains. Few efforts have been made to examine concurrent relationships among cognitive ability, achievement, and academic self-concept (ASC) within an I/E model framework. To simultaneously examine the influences of domain-specific cognitive ability and grades on domain self-concept in an extended I/E model, including the indirect effect of domain-specific cognitive ability on domain self-concept via grades. Tenth grade respondents (628 male, 452 female) to a national adolescent survey conducted in Taiwan. Respondents completed surveys designed to measure maths and verbal aptitudes. Data on Maths and Chinese class grades and self-concepts were also collected. Statistically significant and positive path coefficients were found between cognitive ability and self-concept in the same domain (direct effect) and between these two constructs via grades (indirect effect). The cross-domain effects of either ability or grades on ASC were negatively significant. Taiwanese 10th graders tend to evaluate their ASCs based on a mix of ability and achievement, with achievement as a mediator exceeding ability as a predictor. In addition, the cross-domain effects suggest that Taiwanese students are likely to view Maths and verbal abilities and achievements as distinctly different. ©2011 The British Psychological Society.

Fourier phase in Fourier-domain optical coherence tomography.

PubMed

Uttam, Shikhar; Liu, Yang

2015-12-01

Phase of an electromagnetic wave propagating through a sample-of-interest is well understood in the context of quantitative phase imaging in transmission-mode microscopy. In the past decade, Fourier-domain optical coherence tomography has been used to extend quantitative phase imaging to the reflection-mode. Unlike transmission-mode electromagnetic phase, however, the origin and characteristics of reflection-mode Fourier phase are poorly understood, especially in samples with a slowly varying refractive index. In this paper, the general theory of Fourier phase from first principles is presented, and it is shown that Fourier phase is a joint estimate of subresolution offset and mean spatial frequency of the coherence-gated sample refractive index. It is also shown that both spectral-domain phase microscopy and depth-resolved spatial-domain low-coherence quantitative phase microscopy are special cases of this general theory. Analytical expressions are provided for both, and simulations are presented to explain and support the theoretical results. These results are further used to show how Fourier phase allows the estimation of an axial mean spatial frequency profile of the sample, along with depth-resolved characterization of localized optical density change and sample heterogeneity. Finally, a Fourier phase-based explanation of Doppler optical coherence tomography is also provided.

Fourier phase in Fourier-domain optical coherence tomography

PubMed Central

Uttam, Shikhar; Liu, Yang

2015-01-01

Phase of an electromagnetic wave propagating through a sample-of-interest is well understood in the context of quantitative phase imaging in transmission-mode microscopy. In the past decade, Fourier-domain optical coherence tomography has been used to extend quantitative phase imaging to the reflection-mode. Unlike transmission-mode electromagnetic phase, however, the origin and characteristics of reflection-mode Fourier phase are poorly understood, especially in samples with a slowly varying refractive index. In this paper, the general theory of Fourier phase from first principles is presented, and it is shown that Fourier phase is a joint estimate of subresolution offset and mean spatial frequency of the coherence-gated sample refractive index. It is also shown that both spectral-domain phase microscopy and depth-resolved spatial-domain low-coherence quantitative phase microscopy are special cases of this general theory. Analytical expressions are provided for both, and simulations are presented to explain and support the theoretical results. These results are further used to show how Fourier phase allows the estimation of an axial mean spatial frequency profile of the sample, along with depth-resolved characterization of localized optical density change and sample heterogeneity. Finally, a Fourier phase-based explanation of Doppler optical coherence tomography is also provided. PMID:26831383

Study of human phonation in a full-body domain

NASA Astrophysics Data System (ADS)

Saurabh, Shakti; Bodony, Daniel

2015-11-01

The generation and propagation of the human voice is studied in two-dimensions using a full-body domain, using direct numerical simulation. The fluid/air in the vocal tract is modeled as a compressible and viscous fluid interacting with the non-linear, viscoelastic vocal folds (VF). The VF tissue material properties are multi-layered, with varying stiffness, and a finite-strain model is utilized and implemented in a quadratic finite element code. The fluid-solid domains are coupled through a boundary-fitted interface and utilize a Poisson equation-based mesh deformation method. The full-body domain includes the near VF region, the vocal tract, a simplified model of the soft palate and mouth, and extends out into the acoustic far-field. A new kind of inflow boundary condition based upon a quasi-one-dimensional formulation with constant sub-glottal volume velocity, which is linked to the VF movement, has been adopted. The sound pressure levels (SPL) measured are realistic and we analyze their connection to the VF dynamics and glottal and vocal tract geometries. Supported by the National Science Foundation (CAREER award number 1150439).

Dimers in Piecewise Temperleyan Domains

NASA Astrophysics Data System (ADS)

Russkikh, Marianna

2018-03-01

We study the large-scale behavior of the height function in the dimer model on the square lattice. Richard Kenyon has shown that the fluctuations of the height function on Temperleyan discretizations of a planar domain converge in the scaling limit (as the mesh size tends to zero) to the Gaussian Free Field with Dirichlet boundary conditions. We extend Kenyon's result to a more general class of discretizations. Moreover, we introduce a new factorization of the coupling function of the double-dimer model into two discrete holomorphic functions, which are similar to discrete fermions defined in Smirnov (Proceedings of the international congress of mathematicians (ICM), Madrid, Spain, 2006; Ann Math (2) 172:1435-1467, 2010). For Temperleyan discretizations with appropriate boundary modifications, the results of Kenyon imply that the expectation of the double-dimer height function converges to a harmonic function in the scaling limit. We use the above factorization to extend this result to the class of all polygonal discretizations, that are not necessarily Temperleyan. Furthermore, we show that, quite surprisingly, the expectation of the double-dimer height function in the Temperleyan case is exactly discrete harmonic (for an appropriate choice of Laplacian) even before taking the scaling limit.

Controversies and Evolving New Mechanisms in Subarachnoid Hemorrhage

PubMed Central

Chen, Sheng; Feng, Hua; Sherchan, Prativa; Klebe, Damon; Zhao, Gang; Sun, Xiaochuan; Zhang, Jianmin; Tang, Jiping; Zhang, John H.

2013-01-01

Despite decades of study, subarachnoid hemorrhage (SAH) continues to be a serious and significant health problem in the United States and worldwide. The mechanisms contributing to brain injury after SAH remain unclear. Traditionally, most in vivo research has heavily emphasized the basic mechanisms of SAH over the pathophysiological or morphological changes of delayed cerebral vasospasm after SAH. Unfortunately, the results of clinical trials based on this premise have mostly been disappointing, implicating some other pathophysiological factors, independent of vasospasm, as contributors to poor clinical outcomes. Delayed cerebral vasospasm is no longer the only culprit. In this review, we summarize recent data from both experimental and clinical studies of SAH and discuss the vast array of physiological dysfunctions following SAH that ultimately lead to cell death. Based on the progress in neurobiological understanding of SAH, the terms “early brain injury” and “delayed brain injury” are used according to the temporal progression of SAH-induced brain injury. Additionally, a new concept of the vasculo-neuronal-glia triad model for SAH study is highlighted and presents the challenges and opportunities of this model for future SAH applications. PMID:24076160

Structural and functional analysis of the YAP-binding domain of human TEAD2

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

Tian, Wei; Yu, Jianzhong; Tomchick, Diana R.

2010-06-15

The Hippo pathway controls organ size and suppresses tumorigenesis in metazoans by blocking cell proliferation and promoting apoptosis. The TEAD1-4 proteins (which contain a DNA-binding domain but lack an activation domain) interact with YAP (which lacks a DNA-binding domain but contains an activation domain) to form functional heterodimeric transcription factors that activate proliferative and prosurvival gene expression programs. The Hippo pathway inhibits the YAP-TEAD hybrid transcription factors by phosphorylating and promoting cytoplasmic retention of YAP. Here we report the crystal structure of the YAP-binding domain (YBD) of human TEAD2. TEAD2 YBD adopts an immunoglobulin-like {beta}-sandwich fold with two extra helix-turn-helixmore » inserts. NMR studies reveal that the TEAD-binding domain of YAP is natively unfolded and that TEAD binding causes localized conformational changes in YAP. In vitro binding and in vivo functional assays define an extensive conserved surface of TEAD2 YBD as the YAP-binding site. Therefore, our studies suggest that a short segment of YAP adopts an extended conformation and forms extensive contacts with a rigid surface of TEAD. Targeting a surface-exposed pocket of TEAD might be an effective strategy to disrupt the YAP-TEAD interaction and to reduce the oncogenic potential of YAP.« less

Extended causal modeling to assess Partial Directed Coherence in multiple time series with significant instantaneous interactions.

PubMed

Faes, Luca; Nollo, Giandomenico

2010-11-01

The Partial Directed Coherence (PDC) and its generalized formulation (gPDC) are popular tools for investigating, in the frequency domain, the concept of Granger causality among multivariate (MV) time series. PDC and gPDC are formalized in terms of the coefficients of an MV autoregressive (MVAR) model which describes only the lagged effects among the time series and forsakes instantaneous effects. However, instantaneous effects are known to affect linear parametric modeling, and are likely to occur in experimental time series. In this study, we investigate the impact on the assessment of frequency domain causality of excluding instantaneous effects from the model underlying PDC evaluation. Moreover, we propose the utilization of an extended MVAR model including both instantaneous and lagged effects. This model is used to assess PDC either in accordance with the definition of Granger causality when considering only lagged effects (iPDC), or with an extended form of causality, when we consider both instantaneous and lagged effects (ePDC). The approach is first evaluated on three theoretical examples of MVAR processes, which show that the presence of instantaneous correlations may produce misleading profiles of PDC and gPDC, while ePDC and iPDC derived from the extended model provide here a correct interpretation of extended and lagged causality. It is then applied to representative examples of cardiorespiratory and EEG MV time series. They suggest that ePDC and iPDC are better interpretable than PDC and gPDC in terms of the known cardiovascular and neural physiologies.

HangOut: generating clean PSI-BLAST profiles for domains with long insertions.

PubMed

Kim, Bong-Hyun; Cong, Qian; Grishin, Nick V

2010-06-15

Profile-based similarity search is an essential step in structure-function studies of proteins. However, inclusion of non-homologous sequence segments into a profile causes its corruption and results in false positives. Profile corruption is common in multidomain proteins, and single domains with long insertions are a significant source of errors. We developed a procedure (HangOut) that, for a single domain with specified insertion position, cleans erroneously extended PSI-BLAST alignments to generate better profiles. HangOut is implemented in Python 2.3 and runs on all Unix-compatible platforms. The source code is available under the GNU GPL license at http://prodata.swmed.edu/HangOut/. Supplementary data are available at Bioinformatics online.

MutationAligner: a resource of recurrent mutation hotspots in protein domains in cancer.

PubMed

Gauthier, Nicholas Paul; Reznik, Ed; Gao, Jianjiong; Sumer, Selcuk Onur; Schultz, Nikolaus; Sander, Chris; Miller, Martin L

2016-01-04

The MutationAligner web resource, available at http://www.mutationaligner.org, enables discovery and exploration of somatic mutation hotspots identified in protein domains in currently (mid-2015) more than 5000 cancer patient samples across 22 different tumor types. Using multiple sequence alignments of protein domains in the human genome, we extend the principle of recurrence analysis by aggregating mutations in homologous positions across sets of paralogous genes. Protein domain analysis enhances the statistical power to detect cancer-relevant mutations and links mutations to the specific biological functions encoded in domains. We illustrate how the MutationAligner database and interactive web tool can be used to explore, visualize and analyze mutation hotspots in protein domains across genes and tumor types. We believe that MutationAligner will be an important resource for the cancer research community by providing detailed clues for the functional importance of particular mutations, as well as for the design of functional genomics experiments and for decision support in precision medicine. MutationAligner is slated to be periodically updated to incorporate additional analyses and new data from cancer genomics projects. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

A new method for solving reachable domain of spacecraft with a single impulse

NASA Astrophysics Data System (ADS)

Chen, Qi; Qiao, Dong; Shang, Haibin; Liu, Xinfu

2018-04-01

This paper develops a new approach to solve the reachable domain of a spacecraft with a single maximum available impulse. First, the distance in a chosen direction, started from a given position on the initial orbit, is formulated. Then, its extreme value is solved to obtain the maximum reachable distance in this direction. The envelop of the reachable domain in three-dimensional space is determined by solving the maximum reachable distance in all directions. Four scenarios are analyzed, including three typical scenarios (either the maneuver position or impulse direction is fixed, or both are arbitrary) and a new extended scenario (the maneuver position is restricted to an interval and the impulse direction is arbitrary). Moreover, the symmetry and the boundedness of the reachable domain are discussed in detail. The former is helpful to reduce the numerical computation, while the latter decides the maximum eccentricity of the initial orbit for a maximum available impulse. The numerical simulations verify the effectiveness of the proposed method for solving the reachable domain in all four scenarios. Especially, the reachable domain with a highly elliptical initial orbit can be determined successfully, which remains unsolved in the existing papers.

Cognitive deficits after aneurysmal and angiographically negative subarachnoid hemorrhage: Memory, attention, executive functioning, and emotion recognition.

PubMed

Buunk, Anne M; Groen, Rob J M; Veenstra, Wencke S; Metzemaekers, Jan D M; van der Hoeven, Johannes H; van Dijk, J Marc C; Spikman, Jacoba M

2016-11-01

The authors' aim was to investigate cognitive outcome in patients with aneurysmal and angiographically negative subarachnoid hemorrhage (aSAH and anSAH), by comparing them to healthy controls and to each other. Besides investigating cognitive functions as memory and attention, they focused on higher-order prefrontal functions, namely executive functioning (EF) and emotion recognition. Patients and healthy controls were assessed with tests measuring memory (15 Words Test, Digit Span), attention and processing speed (Trail Making Test A and B), EF (Zoo Map, Letter Fluency, Dysexecutive Questionnaire), and emotion recognition (Facial Expressions of Emotion Stimuli and Tests). Between-groups comparisons of test performances were made. Patients with aSAH scored significantly lower than healthy controls on measures of memory, processing speed, and attention, but anSAH patients did not. In the higher-order prefrontal functions (EF and emotion recognition), aSAH patients were clearly impaired when compared to healthy controls. However, anSAH patients did not perform significantly better than aSAH patients on the majority of the tests. In the subacute phase after SAH, cognitive functions, including the higher-order prefrontal functions EF and emotion recognition, were clearly impaired in aSAH patients. Patients with anSAH did not perform better than aSAH patients, which indicates that these functions may also be affected to some extent in anSAH patients. Considering the importance of these higher-order prefrontal functions for daily life functioning, and following the results of the present study, tests that measure emotion recognition and EF should be part of the standard neuropsychological assessment after SAH. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

CCR+: Metadata Based Extended Personal Health Record Data Model Interoperable with the ASTM CCR Standard

PubMed Central

Park, Yu Rang; Yoon, Young Jo; Jang, Tae Hun; Seo, Hwa Jeong

2014-01-01

Objectives Extension of the standard model while retaining compliance with it is a challenging issue because there is currently no method for semantically or syntactically verifying an extended data model. A metadata-based extended model, named CCR+, was designed and implemented to achieve interoperability between standard and extended models. Methods Furthermore, a multilayered validation method was devised to validate the standard and extended models. The American Society for Testing and Materials (ASTM) Community Care Record (CCR) standard was selected to evaluate the CCR+ model; two CCR and one CCR+ XML files were evaluated. Results In total, 188 metadata were extracted from the ASTM CCR standard; these metadata are semantically interconnected and registered in the metadata registry. An extended-data-model-specific validation file was generated from these metadata. This file can be used in a smartphone application (Health Avatar CCR+) as a part of a multilayered validation. The new CCR+ model was successfully evaluated via a patient-centric exchange scenario involving multiple hospitals, with the results supporting both syntactic and semantic interoperability between the standard CCR and extended, CCR+, model. Conclusions A feasible method for delivering an extended model that complies with the standard model is presented herein. There is a great need to extend static standard models such as the ASTM CCR in various domains: the methods presented here represent an important reference for achieving interoperability between standard and extended models. PMID:24627817

Toward domain-specific design environments: Some representation ideas from the telecommunications domain

NASA Technical Reports Server (NTRS)

Greenspan, Sol; Feblowitz, Mark

1992-01-01

ACME is an experimental environment for investigating new approaches to modeling and analysis of system requirements and designs. ACME is built on and extends object-oriented conceptual modeling techniques and knowledge representation and reasoning (KRR) tools. The most immediate intended use for ACME is to help represent, understand, and communicate system designs during the early stages of system planning and requirements engineering. While our research is ostensibly aimed at software systems in general, we are particularly motivated to make an impact in the telecommunications domain, especially in the area referred to as Intelligent Networks (IN's). IN systems contain the software to provide services to users of a telecommunications network (e.g., call processing services, information services, etc.) as well as the software that provides the internal infrastructure for providing the services (e.g., resource management, billing, etc.). The software includes not only systems developed by the network proprietors but also by a growing group of independent service software providers.

Extended FDD-WT method based on correcting the errors due to non-synchronous sensing of sensors

NASA Astrophysics Data System (ADS)

Tarinejad, Reza; Damadipour, Majid

2016-05-01

In this research, a combinational non-parametric method called frequency domain decomposition-wavelet transform (FDD-WT) that was recently presented by the authors, is extended for correction of the errors resulting from asynchronous sensing of sensors, in order to extend the application of the algorithm for different kinds of structures, especially for huge structures. Therefore, the analysis process is based on time-frequency domain decomposition and is performed with emphasis on correcting time delays between sensors. Time delay estimation (TDE) methods are investigated for their efficiency and accuracy for noisy environmental records and the Phase Transform - β (PHAT-β) technique was selected as an appropriate method to modify the operation of traditional FDD-WT in order to achieve the exact results. In this paper, a theoretical example (3DOF system) has been provided in order to indicate the non-synchronous sensing effects of the sensors on the modal parameters; moreover, the Pacoima dam subjected to 13 Jan 2001 earthquake excitation was selected as a case study. The modal parameters of the dam obtained from the extended FDD-WT method were compared with the output of the classical signal processing method, which is referred to as 4-Spectral method, as well as other literatures relating to the dynamic characteristics of Pacoima dam. The results comparison indicates that values are correct and reliable.

Inferring Domain-Domain Interactions from Protein-Protein Interactions with Formal Concept Analysis

PubMed Central

Khor, Susan

2014-01-01

Identifying reliable domain-domain interactions will increase our ability to predict novel protein-protein interactions, to unravel interactions in protein complexes, and thus gain more information about the function and behavior of genes. One of the challenges of identifying reliable domain-domain interactions is domain promiscuity. Promiscuous domains are domains that can occur in many domain architectures and are therefore found in many proteins. This becomes a problem for a method where the score of a domain-pair is the ratio between observed and expected frequencies because the protein-protein interaction network is sparse. As such, many protein-pairs will be non-interacting and domain-pairs with promiscuous domains will be penalized. This domain promiscuity challenge to the problem of inferring reliable domain-domain interactions from protein-protein interactions has been recognized, and a number of work-arounds have been proposed. This paper reports on an application of Formal Concept Analysis to this problem. It is found that the relationship between formal concepts provides a natural way for rare domains to elevate the rank of promiscuous domain-pairs and enrich highly ranked domain-pairs with reliable domain-domain interactions. This piggybacking of promiscuous domain-pairs onto less promiscuous domain-pairs is possible only with concept lattices whose attribute-labels are not reduced and is enhanced by the presence of proteins that comprise both promiscuous and rare domains. PMID:24586450

Atmospheric Pressure Variation is a Delayed Trigger for Aneurysmal Subarachnoid Hemorrhage.

PubMed

van Donkelaar, Carlina E; Potgieser, Adriaan R E; Groen, Henk; Foumani, Mahrouz; Abdulrahman, Herrer; Sluijter, Rob; van Dijk, J Marc C; Groen, Rob J M

2018-04-01

There is an ongoing search for conditions that induce spontaneous subarachnoid hemorrhage (SAH). The seasonal pattern of SAH is shown in a large meta-analysis of the literature, but its explanation remains undecided. There is a clear need for sound meteorologic data to further elucidate the seasonal influence on SAH. Because of the stable and densely monitored atmospheric situation in the north of the Netherlands, we reviewed our unique cohort on the seasonal incidence of SAH and the association between SAH and local atmospheric changes. Our observational cohort study included 1535 patients with spontaneous SAH admitted to our neurovascular center in the north of the Netherlands between 2000 and 2015. Meteorologic data could be linked to the day of the ictus. To compare SAH incidences over the year and to test the association with meteorologic conditions, incidence rate ratios (IRRs) with corresponding 95% confidence intervals (CIs) were used, calculated by Poisson regression analyses. Atmospheric pressure variations were significantly associated with aneurysmal SAH. In particular, the pressure change on the second and third day before the ictus was independently correlated to a higher incidence of aneurysmal SAH (IRR, 1.11; 95% CI, 1.00-1.23). The IRR for aneurysmal SAH in July was calculated 0.67 (95% CI, 0.49-0.92) after adjustment for temperature and atmospheric pressure changes. Atmospheric pressure variations are a delayed trigger for aneurysmal SAH. Also, a significantly decreased incidence of aneurysmal SAH was noted in July. Copyright © 2018 Elsevier Inc. All rights reserved.

Finite difference time domain calculation of transients in antennas with nonlinear loads

NASA Technical Reports Server (NTRS)

Luebbers, Raymond J.; Beggs, John H.; Kunz, Karl S.; Chamberlin, Kent

1991-01-01

In this paper transient fields for antennas with more general geometries are calculated directly using Finite Difference Time Domain methods. In each FDTD cell which contains a nonlinear load, a nonlinear equation is solved at each time step. As a test case the transient current in a long dipole antenna with a nonlinear load excited by a pulsed plane wave is computed using this approach. The results agree well with both calculated and measured results previously published. The approach given here extends the applicability of the FDTD method to problems involving scattering from targets including nonlinear loads and materials, and to coupling between antennas containing nonlinear loads. It may also be extended to propagation through nonlinear materials.

Structural plasticity of the TDRD3 Tudor domain probed by a fragment screening hit.

PubMed

Liu, Jiuyang; Zhang, Shuya; Liu, Mingqing; Liu, Yaqian; Nshogoza, Gilbert; Gao, Jia; Ma, Rongsheng; Yang, Yang; Wu, Jihui; Zhang, Jiahai; Li, Fudong; Ruan, Ke

2018-04-12

As a reader of di-methylated arginine on various proteins, such as histone, RNA polymerase II, PIWI and Fragile X mental retardation protein, the Tudor domain of Tudor domain-containing protein 3 (TDRD3) mediates transcriptional activation in nucleus and formation of stress granules in the cytoplasm. Despite the TDRD3 implication in cancer cell proliferation and invasion, warheads to block the di-methylated arginine recognition pocket of the TDRD3 Tudor domain have not yet been uncovered. Here we identified 14 small molecule hits against the TDRD3 Tudor domain through NMR fragment-based screening. These hits were further cross-validated by using competitive fluorescence polarization and isothermal titration calorimetry experiments. The crystal structure of the TDRD3 Tudor domain in complex with hit 1 reveals a distinct binding mode from the nature substrate. Hit 1 protrudes into the aromatic cage of the TDRD3 Tudor domain, where the aromatic residues are tilted to accommodate a sandwich-like π-π interaction. The side chain of the conserved residue N596 swings away 3.1 Å to form a direct hydrogen bond with hit 1. Moreover, this compound shows a decreased affinity against the single Tudor domain of survival motor neuron protein, but no detectable binding to neither the tandem Tudor domain of TP53-binding protein 1 nor the extended Tudor domain of staphylococcal nuclease domain-containing protein 1. Our work depicts the structural plasticity of the TDRD3 Tudor domain and paves the way for the subsequent structure-guided discovery of selective inhibitors targeting Tudor domains. Structural data are available in the PDB under the accession number 5YJ8. © 2018 Federation of European Biochemical Societies.

Structural landscape of the proline-rich domain of Sos1 nucleotide exchange factor.

PubMed

McDonald, Caleb B; Bhat, Vikas; Kurouski, Dmitry; Mikles, David C; Deegan, Brian J; Seldeen, Kenneth L; Lednev, Igor K; Farooq, Amjad

2013-01-01

Despite its key role in mediating a plethora of cellular signaling cascades pertinent to health and disease, little is known about the structural landscape of the proline-rich (PR) domain of Sos1 guanine nucleotide exchange factor. Herein, using a battery of biophysical tools, we provide evidence that the PR domain of Sos1 is structurally disordered and adopts an extended random coil-like conformation in solution. Of particular interest is the observation that while chemical denaturation of PR domain results in the formation of a significant amount of polyproline II (PPII) helices, it has little or negligible effect on its overall size as measured by its hydrodynamic radius. Our data also show that the PR domain displays a highly dynamic conformational basin in agreement with the knowledge that the intrinsically unstructured proteins rapidly interconvert between an ensemble of conformations. Collectively, our study provides new insights into the conformational equilibrium of a key signaling molecule with important consequences on its physiological function. Copyright © 2013 Elsevier B.V. All rights reserved.

Triggers of subarachnoid hemorrhage: role of physical exertion, smoking, and alcohol in the Australasian Cooperative Research on Subarachnoid Hemorrhage Study (ACROSS).

PubMed

Anderson, Craig; Ni Mhurchu, Cliona; Scott, David; Bennett, Derrick; Jamrozik, Konrad; Hankey, Graeme

2003-07-01

Unaccustomed strenuous physical exertion can trigger myocardial infarction, but little is known about the mechanisms precipitating subarachnoid hemorrhage (SAH). We identified all cases of first-ever SAH among the combined populations (2.8 million) of 4 urban centers in Australia and New Zealand. Information on the type, time, and intensity of exposures in the 26 hours before the onset of SAH was ascertained by structured interviews. We used the case-crossover technique to assess the risk of SAH associated with transient exposures of moderate to extreme physical exertion, heavy cigarette smoking, and binge alcohol consumption. We registered 432 first-ever cases of SAH (62% women; mean age, 56.5 years). A definite time of onset of SAH was established for 393 patients (91%), and information on the levels of physical activity in the preceding 26 hours was obtained in 338 (78%). Of these patients, 19% engaged in moderate to extreme exertion (>or=5 metabolic equivalents) in the 2 hours before SAH, which was associated with a tripling in the risk of SAH (odds ratio [OR], 2.7; 95% CI, 1.6 to 4.6). There was no evidence of any association between heavy cigarette smoking or binge drinking and risk of SAH in the subsequent 2 hours (OR, 1.1; 95% CI, 0.4 to 3.7; and OR, 0.41; 95% CI, - infinity to 5.3). Habitual exercise did not appear to alter the risk of SAH associated with moderate to extreme exertion. Moderate to extreme physical exertion tripled the risk of SAH, but there was no association between transient heavy smoking or binge drinking and risk of SAH. These data suggest that heavy physical activity may trigger SAH.

Reconstruction of instantaneous surface normal velocity of a vibrating structure using interpolated time-domain equivalent source method

NASA Astrophysics Data System (ADS)

Geng, Lin; Bi, Chuan-Xing; Xie, Feng; Zhang, Xiao-Zheng

2018-07-01

Interpolated time-domain equivalent source method is extended to reconstruct the instantaneous surface normal velocity of a vibrating structure by using the time-evolving particle velocity as the input, which provides a non-contact way to overall understand the instantaneous vibration behavior of the structure. In this method, the time-evolving particle velocity in the near field is first modeled by a set of equivalent sources positioned inside the vibrating structure, and then the integrals of equivalent source strengths are solved by an iterative solving process and are further used to calculate the instantaneous surface normal velocity. An experiment of a semi-cylindrical steel plate impacted by a steel ball is investigated to examine the ability of the extended method, where the time-evolving normal particle velocity and pressure on the hologram surface measured by a Microflown pressure-velocity probe are used as the inputs of the extended method and the method based on pressure measurements, respectively, and the instantaneous surface normal velocity of the plate measured by a laser Doppler vibrometry is used as the reference for comparison. The experimental results demonstrate that the extended method is a powerful tool to visualize the instantaneous surface normal velocity of a vibrating structure in both time and space domains and can obtain more accurate results than that of the method based on pressure measurements.

Characterizing Functional Domains for TIM-Mediated Enveloped Virus Entry

PubMed Central

Moller-Tank, Sven; Albritton, Lorraine M.; Rennert, Paul D.

2014-01-01

ABSTRACT T-cell immunoglobulin and mucin domain 1 (TIM-1) and other TIM family members were recently identified as phosphatidylserine (PtdSer)-mediated virus entry-enhancing receptors (PVEERs). These proteins enhance entry of Ebola virus (EBOV) and other viruses by binding PtdSer on the viral envelope, concentrating virus on the cell surface, and promoting subsequent internalization. The PtdSer-binding activity of the immunoglobulin-like variable (IgV) domain is essential for both virus binding and internalization by TIM-1. However, TIM-3, whose IgV domain also binds PtdSer, does not effectively enhance virus entry, indicating that other domains of TIM proteins are functionally important. Here, we investigate the domains supporting enhancement of enveloped virus entry, thereby defining the features necessary for a functional PVEER. Using a variety of chimeras and deletion mutants, we found that in addition to a functional PtdSer-binding domain PVEERs require a stalk domain of sufficient length, containing sequences that promote an extended structure. Neither the cytoplasmic nor the transmembrane domain of TIM-1 is essential for enhancing virus entry, provided the protein is still plasma membrane bound. Based on these defined characteristics, we generated a mimic lacking TIM sequences and composed of annexin V, the mucin-like domain of α-dystroglycan, and a glycophosphatidylinositol anchor that functioned as a PVEER to enhance transduction of virions displaying Ebola, Chikungunya, Ross River, or Sindbis virus glycoproteins. This identification of the key features necessary for PtdSer-mediated enhancement of virus entry provides a basis for more effective recognition of unknown PVEERs. IMPORTANCE T-cell immunoglobulin and mucin domain 1 (TIM-1) and other TIM family members are recently identified phosphatidylserine (PtdSer)-mediated virus entry-enhancing receptors (PVEERs). These proteins enhance virus entry by binding the phospholipid, PtdSer, present on the viral

Predicting domain-domain interaction based on domain profiles with feature selection and support vector machines

PubMed Central

2010-01-01

Background Protein-protein interaction (PPI) plays essential roles in cellular functions. The cost, time and other limitations associated with the current experimental methods have motivated the development of computational methods for predicting PPIs. As protein interactions generally occur via domains instead of the whole molecules, predicting domain-domain interaction (DDI) is an important step toward PPI prediction. Computational methods developed so far have utilized information from various sources at different levels, from primary sequences, to molecular structures, to evolutionary profiles. Results In this paper, we propose a computational method to predict DDI using support vector machines (SVMs), based on domains represented as interaction profile hidden Markov models (ipHMM) where interacting residues in domains are explicitly modeled according to the three dimensional structural information available at the Protein Data Bank (PDB). Features about the domains are extracted first as the Fisher scores derived from the ipHMM and then selected using singular value decomposition (SVD). Domain pairs are represented by concatenating their selected feature vectors, and classified by a support vector machine trained on these feature vectors. The method is tested by leave-one-out cross validation experiments with a set of interacting protein pairs adopted from the 3DID database. The prediction accuracy has shown significant improvement as compared to InterPreTS (Interaction Prediction through Tertiary Structure), an existing method for PPI prediction that also uses the sequences and complexes of known 3D structure. Conclusions We show that domain-domain interaction prediction can be significantly enhanced by exploiting information inherent in the domain profiles via feature selection based on Fisher scores, singular value decomposition and supervised learning based on support vector machines. Datasets and source code are freely available on the web at http

Frequency domain, waveform inversion of laboratory crosswell radar data

USGS Publications Warehouse

Ellefsen, Karl J.; Mazzella, Aldo T.; Horton, Robert J.; McKenna, Jason R.

2010-01-01

A new waveform inversion for crosswell radar is formulated in the frequency-domain for a 2.5D model. The inversion simulates radar waves using the vector Helmholtz equation for electromagnetic waves. The objective function is minimized using a backpropagation method suitable for a 2.5D model. The inversion is tested by processing crosswell radar data collected in a laboratory tank. The estimated model is consistent with the known electromagnetic properties of the tank. The formulation for the 2.5D model can be extended to inversions of acoustic and elastic data.

Effects of deferoxamine on blood-brain barrier disruption after subarachnoid hemorrhage.

PubMed

Li, Yanjiang; Yang, Heng; Ni, Wei; Gu, Yuxiang

2017-01-01

Blood brain barrier (BBB) disruption is a key mechanism of subarachnoid hemorrhage (SAH)-induced brain injury. This study examined the mechanism of iron-induced BBB disruption after SAH and investigated the potential therapeutic effect of iron chelation on SAH. Male adult Sprague-Dawley rats had an endovascular perforation of left internal carotid artery bifurcation or sham operation. The rats were treated with deferoxamine (DFX) or vehicle (100mg/kg) for a maximum of 7 days. Brain edema, BBB leakage, behavioral and cognitive impairment were examined. In SAH rat, the peak time of brain edema and BBB impairment in the cortex was at day 3 after SAH. SAH resulted in a significant increase in ferritin expression in the cortex. The ferritin positive cells were colocalized with endothelial cells, pericytes, astrocytes, microglia and neurons. Compared with vehicle, DFX caused less ferritin upregulation, brain water content, BBB impairment, behavioral and cognitive deficits in SAH rats. The results suggest iron overload could be a therapeutic target for SAH induced BBB damage.

Naringin alleviates early brain injury after experimental subarachnoid hemorrhage by reducing oxidative stress and inhibiting apoptosis.

PubMed

Han, Yuwei; Su, Jingyuan; Liu, Xiujuan; Zhao, Yuan; Wang, Chenchen; Li, Xiaoming

2017-07-01

This study aims to clarify the neuroprotective effect of naringin on early brain injury (EBI) following subarachnoid hemorrhage (SAH) and the possible mechanisms of naringin in the treatment of SAH. The endovascular puncture model was performed to induce SAH model in rats and the efficacy of 40mg/kg and 80mg/kg naringin were tested by intraperitoneally administration. SAH grade, neurological score, brain edema, blood-brain barrier permeability, the changes of oxidative stress related factors, apoptosis-related proteins, mitogen-activated protein kinase (MAPK) signaling pathway and neuronal morphology were detected to analyze the potential effect of naringin against SAH. The results demonstrated that naringin significantly ameliorated EBI, including SAH severity, neurologic deficits, brain edema and blood-brain barrier integrity by attenuating SAH-induced oxidative stress and apoptosis, and reduced the oxidant damage and apoptosis by inhibiting the activation of MAPK signaling pathway, which suggested a therapeutic potential of naringin in providing neuroprotection after SAH. Copyright © 2016 Elsevier Inc. All rights reserved.

Incidence of aneurysmal subarachnoid hemorrhage in Shimokita, Japan, from 1989 to 1998.

PubMed

Ohkuma, Hiroki; Fujita, Seiichiroh; Suzuki, Shigeharu

2002-01-01

The incidence of subarachnoid hemorrhage (SAH) has been investigated in many studies. A recent study in Izumo, Japan, indicates that the incidence of SAH is as high as that in Finland. The purpose of this study was to confirm the high incidence of SAH in Japan. The incidence rate of SAH was investigated from 1989 through 1998 in the Shimokita peninsula, which is a clearly defined closed-boundary area in northern Japan with a population of 89 991. The registration was based on the complete referral system of SAH patients. All cases suspected of SAH underwent CT scan, and the images were referred to stroke specialists. The moribund cases and dead-on-arrival cases suspected of SAH also underwent CT scan. From 1989 through 1998, 198 cases were diagnosed as having aneurysmal SAH. Out of these, 26 cases were moribund or dead when the initial CT scan was performed. The age-adjusted annual incidence of SAH was 21 per 100 000 person-years. The age and sex distribution of the cases indicated that the incidence plateaued after age 45 in men and the incidence increased after age 45 and reached the peak after 75 years in women. The high incidence of SAH in Japan is confirmed. The incidence of SAH obtained in this study is near to that of the Izumo study, of which the size of the geographic region and denominator and diagnostic criteria were similar to this study.

Electrophysiological Evidence for Domain-General Processes in Task-Switching

PubMed Central

Capizzi, Mariagrazia; Ambrosini, Ettore; Arbula, Sandra; Mazzonetto, Ilaria; Vallesi, Antonino

2016-01-01

The ability to flexibly switch between tasks is a hallmark of cognitive control. Despite previous studies that have investigated whether different task-switching types would be mediated by distinct or overlapping neural mechanisms, no definitive consensus has been reached on this question yet. Here, we aimed at directly addressing this issue by recording the event-related potentials (ERPs) elicited by two types of task-switching occurring in the context of spatial and verbal cognitive domains. Source analysis was also applied to the ERP data in order to track the spatial dynamics of brain activity underlying task-switching abilities. In separate blocks of trials, participants had to perform either spatial or verbal switching tasks both of which employed the same type of stimuli. The ERP analysis, which was carried out through a channel- and time-uninformed mass univariate approach, showed no significant differences between the spatial and verbal domains in the modulation of switch and repeat trials. Specifically, relative to repeat trials, switch trials in both domains were associated with a first larger positivity developing over left parieto-occipital electrodes and with a subsequent larger negativity distributed over mid-left fronto-central sites. The source analysis reconstruction for the two ERP components complemented these findings by highlighting the involvement of left-lateralized prefrontal areas in task-switching. Overall, our results join and extend recent research confirming the existence of left-lateralized domain-general task-switching processes. PMID:27047366

Structural insights into a secretory abundant heat-soluble protein from an anhydrobiotic tardigrade, Ramazzottius varieornatus.

PubMed

Fukuda, Yohta; Miura, Yoshimasa; Mizohata, Eiichi; Inoue, Tsuyoshi

2017-08-01

Upon stopping metabolic processes, some tardigrades can undergo anhydrobiosis. Secretory abundant heat-soluble (SAHS) proteins have been reported as candidates for anhydrobiosis-related proteins in tardigrades, which seem to protect extracellular components and/or secretory organelles. We determined structures of a SAHS protein from Ramazzottius varieornatus (RvSAHS1), which is one of the toughest tardigrades. RvSAHS1 shows a β-barrel structure similar to fatty acid-binding proteins (FABPs), in which hydrophilic residues form peculiar hydrogen bond networks, which would provide RvSAHS1 with better tolerance against dehydration. We identified two putative ligand-binding sites: one that superimposes on those of some FABPs and the other, unique to and conserved in SAHS proteins. These results indicate that SAHS proteins constitute a new FABP family. © 2017 Federation of European Biochemical Societies.

Nonaneurysmal "Pseudo-Subarachnoid Hemorrhage" Computed Tomography Patterns: Challenges in an Acute Decision-Making Heuristics.

PubMed

Hasan, Tasneem F; Duarte, Walter; Akinduro, Oluwaseun O; Goldstein, Eric D; Hurst, Rebecca; Haranhalli, Neil; Miller, David A; Wharen, Robert E; Tawk, Rabih G; Freeman, William D

2018-06-05

Acute aneurysmal subarachnoid hemorrhage (SAH) is a medical and neurosurgical emergency from ruptured brain aneurysm. Aneurysmal SAH is identified on brain computed tomography (CT) as increased density of basal cisterns and subarachnoid spaces from acute blood products. Aneurysmal SAH-like pattern on CT appears as an optical illusion effect of hypodense brain parenchyma and/or hyperdense surrounding cerebral cisterns and blood vessels termed as "pseudo-subarachnoid hemorrhage" (pseudo-SAH). We reviewed clinical, laboratory, and radiographic data of all SAH diagnoses between January 2013 and January 2018, and found subsets of nonaneurysmal SAH, originally suspected to be aneurysmal in origin. We performed a National Library of Medicine search methodology using terms "subarachnoid hemorrhage," "pseudo," and "non-aneurysmal subarachnoid hemorrhage" singly and in combination to understand the sensitivity, specificity, and precision of pseudo-SAH. Over 5 years, 230 SAH cases were referred to our tertiary academic center and only 7 (3%) met the definition of pseudo-SAH. Searching the National Library of Medicine using subarachnoid hemorrhage yielded 27,402 results. When subarachnoid hemorrhage and pseudo were combined, this yielded 70 results and sensitivity was 50% (n = 35). Similarly, search precision was relatively low (26%) as only 18 results fit the clinical description similar to the 7 cases discussed in our series. Aneurysmal SAH pattern on CT is distinct from nonaneurysmal and pseudo-SAH patterns. The origin of pseudo-SAH terminology appears mostly tied to comatose cardiac arrest patients with diffuse dark brain Hounsfield units and cerebral edema, and is a potential imaging pitfall in acute medical decision-making. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Four Amino Acids within a Tandem QxVx Repeat in a Predicted Extended α-Helix of the Smad-Binding Domain of Sip1 Are Necessary for Binding to Activated Smad Proteins

PubMed Central

Conidi, Andrea; van den Berghe, Veronique; Leslie, Kris; Stryjewska, Agata; Xue, Hua; Chen, Ye-Guang; Seuntjens, Eve; Huylebroeck, Danny

2013-01-01

The zinc finger transcription factor Smad-interacting protein-1 (Sip1; Zeb2, Zfhx1b) plays an important role during vertebrate embryogenesis in various tissues and differentiating cell types, and during tumorigenesis. Previous biochemical analysis suggests that interactions with several partner proteins, including TGFβ family receptor-activated Smads, regulate the activities of Sip1 in the nucleus both as a DNA-binding transcriptional repressor and activator. Using a peptide aptamer approach we mapped in Sip1 its Smad-binding domain (SBD), initially defined as a segment of 51 amino acids, to a shorter stretch of 14 amino acids within this SBD. Modelling suggests that this short SBD stretch is part of an extended α-helix that may fit the binding to a hydrophobic corridor within the MH2 domain of activated Smads. Four amino acids (two polar Q residues and two non-polar V residues) that form the tandem repeat (QxVx)2 in this 14-residue stretch were found to be crucial for binding to both TGFβ/Nodal/Activin-Smads and BMP-Smads. A full-length Sip1 with collective mutation of these Q and V residues (to A) no longer binds to Smads, while it retains its binding activity to its cognate bipartite target DNA sequence. This missense mutant Sip1(AxAx)2 provides a new molecular tool to identify SBD (in)dependent target genes in Sip1-controlled TGFβ and/or BMP (de)regulated cellular, developmental and pathological processes. PMID:24146916

Phosphorylation of Akt by SC79 Prevents Iron Accumulation and Ameliorates Early Brain Injury in a Model of Experimental Subarachnoid Hemorrhage.

PubMed

Hao, Shuangying; Song, Chuanhui; Shang, Longcheng; Yu, Jiang; Qiao, Tong; Li, Kuanyu

2016-03-10

Previous studies have demonstrated that activation of Akt may alleviate early brain injury (EBI) following subarachnoid hemorrhage (SAH). This study is undertaken to determine whether iron metabolism is involved in the beneficial effect of Akt activation after SAH. Therefore, we used a novel molecule, SC79, to activate Akt in an experimental Sprague-Dawley rat model of SAH. Rats were randomly divided into four groups as follows: sham, SAH, SAH + vehicle, SAH + SC79. The results confirmed that SC79 effectively enhanced the defense against oxidative stress and alleviated EBI in the temporal lobe after SAH. Interestingly, we found that phosphorylation of Akt by SC79 reduced cell surface transferrin receptor-mediated iron uptake and promoted ferroportin-mediated iron transport after SAH. As a result, SC79 administration diminished the iron content in the brain tissue. Moreover, the impaired Fe-S cluster biogenesis was recovered and loss of the activities of the Fe-S cluster-containing enzymes were regained, indicating that injured mitochondrial functions are restored to healthy levels. These findings suggest that disrupted iron homeostasis could contribute to EBI and Akt activation may regulate iron metabolism to relieve iron toxicity, further protecting neurons from EBI after SAH.

Nonlinear dielectric response and transient current: An effective potential for ferroelectric domain wall displacement

NASA Astrophysics Data System (ADS)

Placeres Jiménez, Rolando; Pedro Rino, José; Marino Gonçalves, André; Antonio Eiras, José

2013-09-01

Ferroelectric domain walls are modeled as rigid bodies moving under the action of a potential field in a dissipative medium. Assuming that the dielectric permittivity follows the dependence ɛ '∝1/(α+βE2), it obtained the exact expression for the effective potential. Simulations of polarization current correctly predict a power law. Such results could be valuable in the study of domain wall kinetic and ultrafast polarization processes. The model is extended to poled samples allowing the study of nonlinear dielectric permittivity under subswitching electric fields. Experimental nonlinear data from PZT 20/80 thin films and Fe+3 doped PZT 40/60 ceramic are reproduced.

Errors due to the truncation of the computational domain in static three-dimensional electrical impedance tomography.

PubMed

Vauhkonen, P J; Vauhkonen, M; Kaipio, J P

2000-02-01

In electrical impedance tomography (EIT), an approximation for the internal resistivity distribution is computed based on the knowledge of the injected currents and measured voltages on the surface of the body. The currents spread out in three dimensions and therefore off-plane structures have a significant effect on the reconstructed images. A question arises: how far from the current carrying electrodes should the discretized model of the object be extended? If the model is truncated too near the electrodes, errors are produced in the reconstructed images. On the other hand if the model is extended very far from the electrodes the computational time may become too long in practice. In this paper the model truncation problem is studied with the extended finite element method. Forward solutions obtained using so-called infinite elements, long finite elements and separable long finite elements are compared to the correct solution. The effects of the truncation of the computational domain on the reconstructed images are also discussed and results from the three-dimensional (3D) sensitivity analysis are given. We show that if the finite element method with ordinary elements is used in static 3D EIT, the dimension of the problem can become fairly large if the errors associated with the domain truncation are to be avoided.

Time Domain Stability Margin Assessment of the NASA Space Launch System GN&C Design for Exploration Mission One

NASA Technical Reports Server (NTRS)

Clements, Keith; Wall, John

2017-01-01

The baseline stability margins for NASA's Space Launch System (SLS) launch vehicle were generated via the classical approach of linearizing the system equations of motion and determining the gain and phase margins from the resulting frequency domain model. To improve the fidelity of the classical methods, the linear frequency domain approach can be extended by replacing static, memoryless nonlinearities with describing functions. This technique, however, does not address the time varying nature of the dynamics of a launch vehicle in flight. An alternative technique for the evaluation of the stability of the nonlinear launch vehicle dynamics along its trajectory is to incrementally adjust the gain and/or time delay in the time domain simulation until the system exhibits unstable behavior. This technique has the added benefit of providing a direct comparison between the time domain and frequency domain tools in support of simulation validation.

Time Domain Stability Margin Assessment of the NS Space Launch System GN&C Design for Exploration Mission One

NASA Technical Reports Server (NTRS)

Clements, Keith; Wall, John

2017-01-01

The baseline stability margins for NASA's Space Launch System (SLS) launch vehicle were generated via the classical approach of linearizing the system equations of motion and determining the gain and phase margins from the resulting frequency domain model. To improve the fidelity of the classical methods, the linear frequency domain approach can be extended by replacing static, memoryless nonlinearities with describing functions. This technique, however, does not address the time varying nature of the dynamics of a launch vehicle in flight. An alternative technique for the evaluation of the stability of the nonlinear launch vehicle dynamics along its trajectory is to incrementally adjust the gain and/or time delay in the time domain simulation until the system exhibits unstable behavior. This technique has the added benefit of providing a direct comparison between the time domain and frequency domain tools in support of simulation validation.

Novel functions of CCM1 delimit the relationship of PTB/PH domains.

PubMed

Zhang, Jun; Dubey, Pallavi; Padarti, Akhil; Zhang, Aileen; Patel, Rinkal; Patel, Vipulkumar; Cistola, David; Badr, Ahmed

2017-10-01

relationship of PTB, PH and FERM domains has been proposed, which extends the importance of the NPXY-PTB/PH interaction on the CSC signaling and/or other cell receptors with great potential pointing to new therapeutic strategies. The study provides new insight into the structural characteristics of PTB/PH domains, essential structural elements of PTB/PH domain required for NPXY motif-binding, and function and relationship among PTB, PH and FERM domains. Copyright © 2017 Elsevier B.V. All rights reserved.

The Utility of the Extended Images in Ambient Seismic Wavefield Migration

NASA Astrophysics Data System (ADS)

Girard, A. J.; Shragge, J. C.

2015-12-01

Active-source 3D seismic migration and migration velocity analysis (MVA) are robust and highly used methods for imaging Earth structure. One class of migration methods uses extended images constructed by incorporating spatial and/or temporal wavefield correlation lags to the imaging conditions. These extended images allow users to directly assess whether images focus better with different parameters, which leads to MVA techniques that are based on the tenets of adjoint-state theory. Under certain conditions (e.g., geographical, cultural or financial), however, active-source methods can prove impractical. Utilizing ambient seismic energy that naturally propagates through the Earth is an alternate method currently used in the scientific community. Thus, an open question is whether extended images are similarly useful for ambient seismic migration processing and verifying subsurface velocity models, and whether one can similarly apply adjoint-state methods to perform ambient migration velocity analysis (AMVA). Herein, we conduct a number of numerical experiments that construct extended images from ambient seismic recordings. We demonstrate that, similar to active-source methods, there is a sensitivity to velocity in ambient seismic recordings in the migrated extended image domain. In synthetic ambient imaging tests with varying degrees of error introduced to the velocity model, the extended images are sensitive to velocity model errors. To determine the extent of this sensitivity, we utilize acoustic wave-equation propagation and cross-correlation-based migration methods to image weak body-wave signals present in the recordings. Importantly, we have also observed scenarios where non-zero correlation lags show signal while zero-lags show none. This may be a valuable missing piece for ambient migration techniques that have yielded largely inconclusive results, and might be an important piece of information for performing AMVA from ambient seismic recordings.

Applicability domain: towards a more formal definition.

PubMed

Hanser, T; Barber, C; Marchaland, J F; Werner, S

2016-11-01

In recent years the applicability domain (AD) of a prediction system has become an important concern in (Q)SAR modelling, especially in the context of human safety assessment. Today AD is an active research topic, and many methods have been designed to estimate the adequacy of a model and the confidence in its outcome for a given prediction task. Unfortunately, the wide spectrum of techniques developed for this purpose is based on various definitions of the concept of AD, often taking into account different types of information. This variety of methodologies confuses the end users and makes the comparison of the AD for different models almost impossible. In this article, we demonstrate that AD is not a monolithic concept and can be broken down into three well-defined sub-domains assessing confidence at the model, prediction and decision levels, respectively. By leveraging this separation of concerns we have an opportunity to clarify, formalize and extend the definition of AD. We propose a framework that captures this new vision with the aim to initiate a global effort to converge towards a common AD definition within the (Q)SAR community.

An Exemplar-Based Multi-View Domain Generalization Framework for Visual Recognition.

PubMed

Niu, Li; Li, Wen; Xu, Dong; Cai, Jianfei

2018-02-01

In this paper, we propose a new exemplar-based multi-view domain generalization (EMVDG) framework for visual recognition by learning robust classifier that are able to generalize well to arbitrary target domain based on the training samples with multiple types of features (i.e., multi-view features). In this framework, we aim to address two issues simultaneously. First, the distribution of training samples (i.e., the source domain) is often considerably different from that of testing samples (i.e., the target domain), so the performance of the classifiers learnt on the source domain may drop significantly on the target domain. Moreover, the testing data are often unseen during the training procedure. Second, when the training data are associated with multi-view features, the recognition performance can be further improved by exploiting the relation among multiple types of features. To address the first issue, considering that it has been shown that fusing multiple SVM classifiers can enhance the domain generalization ability, we build our EMVDG framework upon exemplar SVMs (ESVMs), in which a set of ESVM classifiers are learnt with each one trained based on one positive training sample and all the negative training samples. When the source domain contains multiple latent domains, the learnt ESVM classifiers are expected to be grouped into multiple clusters. To address the second issue, we propose two approaches under the EMVDG framework based on the consensus principle and the complementary principle, respectively. Specifically, we propose an EMVDG_CO method by adding a co-regularizer to enforce the cluster structures of ESVM classifiers on different views to be consistent based on the consensus principle. Inspired by multiple kernel learning, we also propose another EMVDG_MK method by fusing the ESVM classifiers from different views based on the complementary principle. In addition, we further extend our EMVDG framework to exemplar-based multi-view domain

Same but not alike: Structure, flexibility and energetics of domains in multi-domain proteins are influenced by the presence of other domains

PubMed Central

Vishwanath, Sneha

2018-01-01

The majority of the proteins encoded in the genomes of eukaryotes contain more than one domain. Reasons for high prevalence of multi-domain proteins in various organisms have been attributed to higher stability and functional and folding advantages over single-domain proteins. Despite these advantages, many proteins are composed of only one domain while their homologous domains are part of multi-domain proteins. In the study presented here, differences in the properties of protein domains in single-domain and multi-domain systems and their influence on functions are discussed. We studied 20 pairs of identical protein domains, which were crystallized in two forms (a) tethered to other proteins domains and (b) tethered to fewer protein domains than (a) or not tethered to any protein domain. Results suggest that tethering of domains in multi-domain proteins influences the structural, dynamic and energetic properties of the constituent protein domains. 50% of the protein domain pairs show significant structural deviations while 90% of the protein domain pairs show differences in dynamics and 12% of the residues show differences in the energetics. To gain further insights on the influence of tethering on the function of the domains, 4 pairs of homologous protein domains, where one of them is a full-length single-domain protein and the other protein domain is a part of a multi-domain protein, were studied. Analyses showed that identical and structurally equivalent functional residues show differential dynamics in homologous protein domains; though comparable dynamics between in-silico generated chimera protein and multi-domain proteins were observed. From these observations, the differences observed in the functions of homologous proteins could be attributed to the presence of tethered domain. Overall, we conclude that tethered domains in multi-domain proteins not only provide stability or folding advantages but also influence pathways resulting in differences in

Same but not alike: Structure, flexibility and energetics of domains in multi-domain proteins are influenced by the presence of other domains.

PubMed

Vishwanath, Sneha; de Brevern, Alexandre G; Srinivasan, Narayanaswamy

2018-02-01

The majority of the proteins encoded in the genomes of eukaryotes contain more than one domain. Reasons for high prevalence of multi-domain proteins in various organisms have been attributed to higher stability and functional and folding advantages over single-domain proteins. Despite these advantages, many proteins are composed of only one domain while their homologous domains are part of multi-domain proteins. In the study presented here, differences in the properties of protein domains in single-domain and multi-domain systems and their influence on functions are discussed. We studied 20 pairs of identical protein domains, which were crystallized in two forms (a) tethered to other proteins domains and (b) tethered to fewer protein domains than (a) or not tethered to any protein domain. Results suggest that tethering of domains in multi-domain proteins influences the structural, dynamic and energetic properties of the constituent protein domains. 50% of the protein domain pairs show significant structural deviations while 90% of the protein domain pairs show differences in dynamics and 12% of the residues show differences in the energetics. To gain further insights on the influence of tethering on the function of the domains, 4 pairs of homologous protein domains, where one of them is a full-length single-domain protein and the other protein domain is a part of a multi-domain protein, were studied. Analyses showed that identical and structurally equivalent functional residues show differential dynamics in homologous protein domains; though comparable dynamics between in-silico generated chimera protein and multi-domain proteins were observed. From these observations, the differences observed in the functions of homologous proteins could be attributed to the presence of tethered domain. Overall, we conclude that tethered domains in multi-domain proteins not only provide stability or folding advantages but also influence pathways resulting in differences in

Neuroprotective effect of curcumin in an experimental rat model of subarachnoid hemorrhage.

PubMed

Kuo, Chang-Po; Lu, Chueng-He; Wen, Li-Li; Cherng, Chen-Hwan; Wong, Chih-Shung; Borel, Cecil O; Ju, Da-Tong; Chen, Chun-Mei; Wu, Ching-Tang

2011-12-01

Subarachnoid hemorrhage (SAH) causes a high mortality rate and morbidity. It was suggested that oxidant stress plays an important role in neuronal injury after SAH. Therefore, we assessed the effect of curcumin on reducing cerebral vasospasm and neurologic injury in a SAH model in rat. A double-hemorrhage model was used to induce SAH in rats. Groups of animals were treated with intraperitoneal injection of 20 mg/kg curcumin (curcumin group, n = 24) or dimethyl sulfoxide (vehicle group, n = 33), normal saline (SAH group, n = 34) or normal saline (sham group, n = 22), 3 h after SAH induction and daily for 6 days. Glutamate was measured before SAH induction and once daily for 7 days. Glutamate transporter-1, wall thickness and the perimeter of the basilar artery, neurologic scores, neuronal degeneration, malondialdehyde, superoxide dismutase, and catalase activities were assessed. Changes of glutamate levels were lower in the curcumin group versus the SAH and vehicle groups, especially on day 1 (56 folds attenuation vs. vehicle). Correspondingly, glutamate transporter-1 was preserved after SAH in curcumin-treated rats. In the hippocampus and the cortex, malondialdehyde was attenuated (30% and 50%, respectively). Superoxide dismutase (35% and 64%) and catalase (34% and 38%) activities were increased in the curcumin rats compared with the SAH rats. Mortality rate (relative risk: 0.59), wall thickness (30%) and perimeter (31%) of the basilar artery, neuron degeneration scores (39%), and neurologic scores (31%) were improved in curcumin-treated rats. Curcumin in multiple doses is effective against glutamate neurotoxicity and oxidative stress and improves the mortality rate in rats with SAH.

S-adenosylhomocysteine is associated with subclinical atherosclerosis and renal function in a cardiovascular low-risk population.

PubMed

Zawada, Adam M; Rogacev, Kyrill S; Hummel, Björn; Berg, Judith T; Friedrich, Annika; Roth, Heinz J; Obeid, Rima; Geisel, Jürgen; Fliser, Danilo; Heine, Gunnar H

2014-05-01

Although homocysteine has been proposed as a cardiovascular risk factor, interventional trials lowering homocysteine have not consistently demonstrated clinical benefit. Recent evidence proposed the homocysteine metabolite S-adenosylhomocysteine (SAH) rather than homocysteine itself as the real culprit in cardiovascular disease. Of note, SAH is predominantly excreted by the kidneys, and cannot be lowered by vitamin supplementation. Due to its cumbersome measurement, data from large studies on the association between SAH, kidney function and cardiovascular disease are not available. We recruited 420 apparently healthy subjects into our I Like HOMe FU study. Among all study participants, we assessed parameters of C1 metabolism (homocysteine, SAH and S-adenosylmethionine), renal function (estimated glomerular filtration rate [eGFR]) and subclinical atherosclerosis (common carotid intima-media-thickness [IMT]). eGFR was estimated by the CKD-EPIcreat-cys equation. Traditional cardiovascular risk factors and subclinical atherosclerosis were associated with SAH, but not with homocysteine (IMT vs SAH: r = 0.129; p = 0.010; IMT vs homocysteine: r = 0.009; p = 0.853). Moreover, renal function was more closely correlated with SAH than with homocysteine (eGFR vs SAH: r = -0.335; p < 0.001; eGFR vs homocysteine: r = -0.250; p < 0.001). The association between eGFR and SAH remained significant after adjustment for traditional cardiovascular risk factors. In summary, cardiovascular risk factors, subclinical atherosclerosis and eGFR are more strongly associated with SAH than with homocysteine in apparently healthy subjects. Thus, SAH might represent a more promising target to prevent cardiovascular disease than homocysteine. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Analysis of the linker region joining the adenylation and carrier protein domains of the modular nonribosomal peptide synthetases.

PubMed

Miller, Bradley R; Sundlov, Jesse A; Drake, Eric J; Makin, Thomas A; Gulick, Andrew M

2014-10-01

Nonribosomal peptide synthetases (NRPSs) are multimodular proteins capable of producing important peptide natural products. Using an assembly line process, the amino acid substrate and peptide intermediates are passed between the active sites of different catalytic domains of the NRPS while bound covalently to a peptidyl carrier protein (PCP) domain. Examination of the linker sequences that join the NRPS adenylation and PCP domains identified several conserved proline residues that are not found in standalone adenylation domains. We examined the roles of these proline residues and neighboring conserved sequences through mutagenesis and biochemical analysis of the reaction catalyzed by the adenylation domain and the fully reconstituted NRPS pathway. In particular, we identified a conserved LPxP motif at the start of the adenylation-PCP linker. The LPxP motif interacts with a region on the adenylation domain to stabilize a critical catalytic lysine residue belonging to the A10 motif that immediately precedes the linker. Further, this interaction with the C-terminal subdomain of the adenylation domain may coordinate movement of the PCP with the conformational change of the adenylation domain. Through this work, we extend the conserved A10 motif of the adenylation domain and identify residues that enable proper adenylation domain function. © 2014 Wiley Periodicals, Inc.

The PYRIN domain: A member of the death domain-fold superfamily

PubMed Central

Fairbrother, Wayne J.; Gordon, Nathaniel C.; Humke, Eric W.; O'Rourke, Karen M.; Starovasnik, Melissa A.; Yin, Jian-Ping; Dixit, Vishva M.

2001-01-01

PYRIN domains were identified recently as putative protein–protein interaction domains at the N-termini of several proteins thought to function in apoptotic and inflammatory signaling pathways. The ∼95 residue PYRIN domains have no statistically significant sequence homology to proteins with known three-dimensional structure. Using secondary structure prediction and potential-based fold recognition methods, however, the PYRIN domain is predicted to be a member of the six-helix bundle death domain-fold superfamily that includes death domains (DDs), death effector domains (DEDs), and caspase recruitment domains (CARDs). Members of the death domain-fold superfamily are well established mediators of protein–protein interactions found in many proteins involved in apoptosis and inflammation, indicating further that the PYRIN domains serve a similar function. An homology model of the PYRIN domain of CARD7/DEFCAP/NAC/NALP1, a member of the Apaf-1/Ced-4 family of proteins, was constructed using the three-dimensional structures of the FADD and p75 neurotrophin receptor DDs, and of the Apaf-1 and caspase-9 CARDs, as templates. Validation of the model using a variety of computational techniques indicates that the fold prediction is consistent with the sequence. Comparison of a circular dichroism spectrum of the PYRIN domain of CARD7/DEFCAP/NAC/NALP1 with spectra of several proteins known to adopt the death domain-fold provides experimental support for the structure prediction. PMID:11514682

Role of Gap Junctions in Early Brain Injury Following Subarachnoid Hemorrhage

PubMed Central

Ayer, Robert; Chen, Wanqiu; Sugawara, Takashi; Suzuki, Hidenori; Zhang, John H.

2010-01-01

Gap junction inhibition has been demonstrated to reverse the vascular contraction that follows experimental subarachnoid hemorrhage. This study hypothesizes that the use of established gap junction inhibitors: octonal and carbenoxolone, to interrupt cell to cell communication will provide neuroprotection against early brain injury after SAH. The filament perforation model of SAH was performed in male Sprague–Dawley rats weighing between 300 and 380g. Octanol (260.46mg or 781.38 mg/kg), carbenoxolone (100 mg/kg), or vehicles were given via intraperitoneal injection 1 hour after SAH. Neurologic deficits and cerebral apoptosis were assessed 24 and 72 hours after SAH. In addition, Western blot analysis was performed to confirm the in vivo inhibition of CNS gap junctions. The administration of octanol and carbenoxolone both failed to attenuate the neurological deficits induced by SAH, and they did not reduce neuronal apoptosis. Additionally, carbenoloxone increased post SAH mortality and exacerbated SAH induced apoptosis. Despites previous studies that show gap junction inhibitors reverse vasospasm following experimental SAH, they failed to improve clinical outcomes or provide neuroprotection in this study. PMID:20018179

Mutation of domain III and domain VI in L gene conserved domain of Nipah virus

NASA Astrophysics Data System (ADS)

Jalani, Siti Aishah; Ibrahim, Nazlina

2016-11-01

Nipah virus (NiV) is the etiologic agent responsible for the respiratory illness and causes fatal encephalitis in human. NiV L protein subunit is thought to be responsible for the majority of enzymatic activities involved in viral transcription and replication. The L protein which is the viral RNA dependent RNA polymerase has high sequence homology among negative sense RNA viruses. In negative stranded RNA viruses, based on sequence alignment six conserved domain (domain I-IV) have been determined. Each domain is separated on variable regions that suggest the structure to consist concatenated functional domain. To directly address the roles of domains III and VI, site-directed mutations were constructed by the substitution of bases at sequences 2497, 2500, 5528 and 5532. Each mutated L gene can be used in future studies to test the ability for expression on in vitro translation.

Acute convexity subarachnoid haemorrhage and cortical superficial siderosis in probable cerebral amyloid angiopathy without lobar haemorrhage.

PubMed

Charidimou, Andreas; Boulouis, Grégoire; Fotiadis, Panagiotis; Xiong, Li; Ayres, Alison M; Schwab, Kristin M; Gurol, Mahmut Edip; Rosand, Jonathan; Greenberg, Steve M; Viswanathan, Anand

2018-04-01

Acute non-traumatic convexity subarachnoid haemorrhage (cSAH) is increasingly recognised in cerebral amyloid angiopathy (CAA). We investigated: (a) the overlap between acute cSAH and cortical superficial siderosis-a new CAA haemorrhagic imaging signature and (b) whether acute cSAH presents with particular clinical symptoms in patients with probable CAA without lobar intracerebral haemorrhage. MRI scans of 130 consecutive patients meeting modified Boston criteria for probable CAA were analysed for cortical superficial siderosis (focal, ≤3 sulci; disseminated, ≥4 sulci), and key small vessel disease markers. We compared clinical, imaging and cortical superficial siderosis topographical mapping data between subjects with versus without acute cSAH, using multivariable logistic regression. We included 33 patients with probable CAA presenting with acute cSAH and 97 without cSAH at presentation. Patients with acute cSAH were more commonly presenting with transient focal neurological episodes (76% vs 34%; p<0.0001) compared with patients with CAA without cSAH. Patients with acute cSAH were also more often clinically presenting with transient focal neurological episodes compared with cortical superficial siderosis-positive, but cSAH-negative subjects with CAA (76% vs 30%; p<0.0001). Cortical superficial siderosis prevalence (but no other CAA severity markers) was higher among patients with cSAH versus those without, especially disseminated cortical superficial siderosis (49% vs 19%; p<0.0001). In multivariable logistic regression, cortical superficial siderosis burden (OR 5.53; 95% CI 2.82 to 10.8, p<0.0001) and transient focal neurological episodes (OR 11.7; 95% CI 2.70 to 50.6, p=0.001) were independently associated with acute cSAH. This probable CAA cohort provides additional evidence for distinct disease phenotypes, determined by the presence of cSAH and cortical superficial siderosis. © Article author(s) (or their employer(s) unless otherwise stated in the

Hydrolysis by somatic angiotensin-I converting enzyme of basic dipeptides from a cholecystokinin/gastrin and a LH-RH peptide extended at the C-terminus with gly-Arg/Lys-arg, but not from diarginyl insulin.

PubMed

Isaac, R E; Michaud, A; Keen, J N; Williams, T A; Coates, D; Wetsel, W C; Corvol, P

1999-06-01

Endoproteolytic cleavage of protein prohormones often generates intermediates extended at the C-terminus by Arg-Arg or Lys-Arg, the removal of which by a carboxypeptidase (CPE) is normally an important step in the maturation of many peptide hormones. Recent studies in mice that lack CP activity indicate the existence of alternative tissue or plasma enzymes capable of removing C-terminal basic residues from prohormone intermediates. Using inhibitors of angiotensin I-converting enzyme (ACE) and CP, we show that both these enzymes in mouse serum can remove the basic amino acids from the C-terminus of CCK5-GRR and LH-RH-GKR, but only CP is responsible for converting diarginyl insulin to insulin. ACE activity removes C-terminal dipeptides to generate the Gly-extended peptides, whereas CP hydrolysis gives rise to CCK5-GR and LH-RH-GK, both of which are susceptible to the dipeptidyl carboxypeptidase activity of ACE. Somatic ACE has two similar protein domains (the N-domain and the C-domain), each with an active site that can display different substrate specificities. CCK5-GRR is a high-affinity substrate for both the N-domain and C-domain active sites of human sACE (Km of 9.4 microm and 9.0 microm, respectively) with the N-domain showing greater efficiency (kcat : Km ratio of 2.6 in favour of the N-domain). We conclude that somatic forms of ACE should be considered as alternatives to CPs for the removal of basic residues from some Arg/Lys-extended peptides.

Inducible nitric oxide synthase (NOS-2) in subarachnoid hemorrhage: Regulatory mechanisms and therapeutic implications.

PubMed

Iqbal, Sana; Hayman, Erik G; Hong, Caron; Stokum, Jesse A; Kurland, David B; Gerzanich, Volodymyr; Simard, J Marc

2016-01-01

Aneurysmal subarachnoid hemorrhage (SAH) typically carries a poor prognosis. Growing evidence indicates that overabundant production of nitric oxide (NO) may be responsible for a large part of the secondary injury that follows SAH. Although SAH modulates the activity of all three isoforms of nitric oxide synthase (NOS), the inducible isoform, NOS-2, accounts for a majority of NO-mediated secondary injuries after SAH. Here, we review the indispensable physiological roles of NO that must be preserved, even while attempting to downmodulate the pathophysiologic effects of NO that are induced by SAH. We examine the effects of SAH on the function of the various NOS isoforms, with a particular focus on the pathological effects of NOS-2 and on the mechanisms responsible for its transcriptional upregulation. Finally, we review interventions to block NOS-2 upregulation or to counteract its effects, with an emphasis on the potential therapeutic strategies to improve outcomes in patients afflicted with SAH. There is still much to be learned regarding the apparently maladaptive response of NOS-2 and its harmful product NO in SAH. However, the available evidence points to crucial effects that, on balance, are adverse, making the NOS-2/NO/peroxynitrite axis an attractive therapeutic target in SAH.

Neutrophil depletion after subarachnoid hemorrhage improves memory via NMDA receptors.

PubMed

Provencio, Jose Javier; Swank, Valerie; Lu, Haiyan; Brunet, Sylvain; Baltan, Selva; Khapre, Rohini V; Seerapu, Himabindu; Kokiko-Cochran, Olga N; Lamb, Bruce T; Ransohoff, Richard M

2016-05-01

Cognitive deficits after aneurysmal subarachnoid hemorrhage (SAH) are common and disabling. Patients who experience delayed deterioration associated with vasospasm are likely to have cognitive deficits, particularly problems with executive function, verbal and spatial memory. Here, we report neurophysiological and pathological mechanisms underlying behavioral deficits in a murine model of SAH. On tests of spatial memory, animals with SAH performed worse than sham animals in the first week and one month after SAH suggesting a prolonged injury. Between three and six days after experimental hemorrhage, mice demonstrated loss of late long-term potentiation (L-LTP) due to dysfunction of the NMDA receptor. Suppression of innate immune cell activation prevents delayed vasospasm after murine SAH. We therefore explored the role of neutrophil-mediated innate inflammation on memory deficits after SAH. Depletion of neutrophils three days after SAH mitigates tissue inflammation, reverses cerebral vasoconstriction in the middle cerebral artery, and rescues L-LTP dysfunction at day 6. Spatial memory deficits in both the short and long-term are improved and associated with a shift of NMDA receptor subunit composition toward a memory sparing phenotype. This work supports further investigating suppression of innate immunity after SAH as a target for preventative therapies in SAH. Copyright © 2016 Elsevier Inc. All rights reserved.

Enhanced Therapeutic Potential of Nano-Curcumin Against Subarachnoid Hemorrhage-Induced Blood-Brain Barrier Disruption Through Inhibition of Inflammatory Response and Oxidative Stress.

PubMed

Zhang, Zong-Yong; Jiang, Ming; Fang, Jie; Yang, Ming-Feng; Zhang, Shuai; Yin, Yan-Xin; Li, Da-Wei; Mao, Lei-Lei; Fu, Xiao-Yan; Hou, Ya-Jun; Fu, Xiao-Ting; Fan, Cun-Dong; Sun, Bao-Liang

2017-01-01

Curcumin and nano-curcumin both exhibit neuroprotective effects in early brain injury (EBI) after experimental subarachnoid hemorrhage (SAH). However, the mechanism that whether curcumin and its nanoparticles affect the blood-brain barrier (BBB) following SAH remains unclear. This study investigated the effect of curcumin and the poly(lactide-co-glycolide) (PLGA)-encapsulated curcumin nanoparticles (Cur-NPs) on BBB disruption and evaluated the possible mechanism underlying BBB dysfunction in EBI using the endovascular perforation rat SAH model. The results indicated that Cur-NPs showed enhanced therapeutic effects than that of curcumin in improving neurological function, reducing brain water content, and Evans blue dye extravasation after SAH. Mechanically, Cur-NPs attenuated BBB dysfunction after SAH by preventing the disruption of tight junction protein (ZO-1, occludin, and claudin-5). Cur-NPs also up-regulated glutamate transporter-1 and attenuated glutamate concentration of cerebrospinal fluid following SAH. Moreover, inhibition of inflammatory response and microglia activation both contributed to Cur-NPs' protective effects. Additionally, Cur-NPs markedly suppressed SAH-mediated oxidative stress and eventually reversed SAH-induced cell apoptosis in rats. Our findings revealed that the strategy of using Cur-NPs could be a promising way in improving neurological function in EBI after experimental rat SAH.

Domain wall nanoelectronics

NASA Astrophysics Data System (ADS)

Catalan, G.; Seidel, J.; Ramesh, R.; Scott, J. F.

2012-01-01

Domains in ferroelectrics were considered to be well understood by the middle of the last century: They were generally rectilinear, and their walls were Ising-like. Their simplicity stood in stark contrast to the more complex Bloch walls or Néel walls in magnets. Only within the past decade and with the introduction of atomic-resolution studies via transmission electron microscopy, electron holography, and atomic force microscopy with polarization sensitivity has their real complexity been revealed. Additional phenomena appear in recent studies, especially of magnetoelectric materials, where functional properties inside domain walls are being directly measured. In this paper these studies are reviewed, focusing attention on ferroelectrics and multiferroics but making comparisons where possible with magnetic domains and domain walls. An important part of this review will concern device applications, with the spotlight on a new paradigm of ferroic devices where the domain walls, rather than the domains, are the active element. Here magnetic wall microelectronics is already in full swing, owing largely to the work of Cowburn and of Parkin and their colleagues. These devices exploit the high domain wall mobilities in magnets and their resulting high velocities, which can be supersonic, as shown by Kreines’ and co-workers 30 years ago. By comparison, nanoelectronic devices employing ferroelectric domain walls often have slower domain wall speeds, but may exploit their smaller size as well as their different functional properties. These include domain wall conductivity (metallic or even superconducting in bulk insulating or semiconducting oxides) and the fact that domain walls can be ferromagnetic while the surrounding domains are not.

Frequency domain analysis of errors in cross-correlations of ambient seismic noise

NASA Astrophysics Data System (ADS)

Liu, Xin; Ben-Zion, Yehuda; Zigone, Dimitri

2016-12-01

We analyse random errors (variances) in cross-correlations of ambient seismic noise in the frequency domain, which differ from previous time domain methods. Extending previous theoretical results on ensemble averaged cross-spectrum, we estimate confidence interval of stacked cross-spectrum of finite amount of data at each frequency using non-overlapping windows with fixed length. The extended theory also connects amplitude and phase variances with the variance of each complex spectrum value. Analysis of synthetic stationary ambient noise is used to estimate the confidence interval of stacked cross-spectrum obtained with different length of noise data corresponding to different number of evenly spaced windows of the same duration. This method allows estimating Signal/Noise Ratio (SNR) of noise cross-correlation in the frequency domain, without specifying filter bandwidth or signal/noise windows that are needed for time domain SNR estimations. Based on synthetic ambient noise data, we also compare the probability distributions, causal part amplitude and SNR of stacked cross-spectrum function using one-bit normalization or pre-whitening with those obtained without these pre-processing steps. Natural continuous noise records contain both ambient noise and small earthquakes that are inseparable from the noise with the existing pre-processing steps. Using probability distributions of random cross-spectrum values based on the theoretical results provides an effective way to exclude such small earthquakes, and additional data segments (outliers) contaminated by signals of different statistics (e.g. rain, cultural noise), from continuous noise waveforms. This technique is applied to constrain values and uncertainties of amplitude and phase velocity of stacked noise cross-spectrum at different frequencies, using data from southern California at both regional scale (˜35 km) and dense linear array (˜20 m) across the plate-boundary faults. A block bootstrap resampling method

Extending a Flight Management Computer for Simulation and Flight Experiments

NASA Technical Reports Server (NTRS)

Madden, Michael M.; Sugden, Paul C.

2005-01-01

In modern transport aircraft, the flight management computer (FMC) has evolved from a flight planning aid to an important hub for pilot information and origin-to-destination optimization of flight performance. Current trends indicate increasing roles of the FMC in aviation safety, aviation security, increasing airport capacity, and improving environmental impact from aircraft. Related research conducted at the Langley Research Center (LaRC) often requires functional extension of a modern, full-featured FMC. Ideally, transport simulations would include an FMC simulation that could be tailored and extended for experiments. However, due to the complexity of a modern FMC, a large investment (millions of dollars over several years) and scarce domain knowledge are needed to create such a simulation for transport aircraft. As an intermediate alternative, the Flight Research Services Directorate (FRSD) at LaRC created a set of reusable software products to extend flight management functionality upstream of a Boeing-757 FMC, transparently simulating or sharing its operator interfaces. The paper details the design of these products and highlights their use on NASA projects.

Memantine Attenuates Delayed Vasospasm after Experimental Subarachnoid Hemorrhage via Modulating Endothelial Nitric Oxide Synthase.

PubMed

Huang, Chih-Yuan; Wang, Liang-Chao; Shan, Yan-Shen; Pan, Chia-Hsin; Tsai, Kuen-Jer

2015-06-23

Delayed cerebral vasospasm is an important pathological feature of subarachnoid hemorrhage (SAH). The cause of vasospasm is multifactorial. Impairs nitric oxide availability and endothelial nitric oxide synthase (eNOS) dysfunction has been reported to underlie vasospasm. Memantine, a low-affinity uncompetitive N-methyl-d-aspartate (NMDA) blocker has been proven to reduce early brain injury after SAH. This study investigated the effect of memantine on attenuation of vasospasm and restoring eNOS functionality. Male Sprague-Dawley rats weighing 350-450 g were randomly divided into three weight-matched groups, sham surgery, SAH + vehicle, and SAH + memantine groups. The effects of memantine on SAH were evaluated by assessing the severity of vasospasm and the expression of eNOS. Memantine effectively ameliorated cerebral vasospasm by restoring eNOS functionality. Memantine can prevent vasospasm in experimental SAH. Treatment strategies may help combat SAH-induced vasospasm in the future.

[Curcumin alleviates early brain injury following subarachnoid hemorrhage in rats by inhibiting JNK/c-Jun signal pathway].

PubMed

Li, Xia; Zhu, Ji

2018-03-01

Objective To investigate the inhibitory effect of curcumin on early brain injury following subarachnoid hemorrhage (SAH) by inhibiting JNK/ c-Jun signal pathway. Methods Sixty adult male SD rats were randomly divided into four groups: sham operation group (sham group), SAH group, SAH group treated with 100 mg/(kg.d) curcumin and SAH group treated with 200 mg/(kg.d) curcumin, with 15 rats in each group. Endovascular puncture was used to induce SAH model. Nissl staining was used to test whether neurons were broken. TUNEL staining was used to detect apoptosis. Immunohistochemistry was used to investigate the expression of caspase-3. Western blot analysis was used to detect the expressions of p-JNK, JNK, p-c-Jun, c-Jun, and caspase-3. Results Nissl staining indicated the decrease of Nissl bodies in SAH group, but increase of Nissl bodies in SAH group treated with curcumin. TUNEL staining showed that there were more apoptotic neurons in SAH group compared with sham group, while apoptotic neurons decreased after the treatment with curcumin, more obviously in the group treated with 200 mg/(kg.d) curcumin. The expressions of p-JNK, JNK, p-c-Jun, c-Jun, and caspase-3 were up-regulated in SAH group compared with sham group. However, the expressions of those proteins were down-regulated after the treatment with curcumin, especially by higher-dose curcumin treatment. Conclusion Curcumin might suppress early brain injury after SAH by inhibiting JNK/c-Jun signal pathway and neuron apoptosis.

Early Elevation of Serum TNFα is Associated with Poor Outcome in Subarachnoid Hemorrhage

PubMed Central

Chou, Sherry HY.; Feske, Steven K.; Atherton, Juli; Konigsberg, Rachael G.; De Jager, Philip L.; Du, Rose; Lo, Eng H.; Ning, MingMing

2013-01-01

Objective Subarachnoid hemorrhage (SAH) is associated with inflammation which may mediate poor outcome in SAH. We hypothesize that elevated serum tumor necrosis factor-alpha (TNFα) and interleukin-6 (IL-6) are associated with vasospasm and poor outcome in SAH. Methods In 52 consecutive SAH subjects, we compared TNFα and IL-6 levels on post-SAH days 0–1, 2–3, 4–5, 6–8, and 10–14 with respect to vasospasm and to poor outcome at 3- and 6-months. Vasospasm was defined as >50% reduction in vessel caliber on angiography. Poor outcome was defined as modified Rankin score >2. Results Elevated TNFα on post-SAH days 2–3 was associated with poor 3-month outcome (p=0.0004). Global elevation of TNFα over time (post-SAH days 0–14) was independently associated with poor 3-month outcome after adjusting for Hunt-and-Hess grade and age (p=0.02). Neither cross-sectional nor IL-6 levels over time were associated with outcome. Neither TNFα nor IL-6 levels were associated with vasospasm. Conclusions Elevation in serum TNFα on post-SAH days 2–3 and global elevation of TNFα over time are associated with poor outcome but not with angiographic vasospasm in this small cohort. Future studies are needed to define the role of TNFα in SAH-related brain injury and its potential as a SAH outcome biomarker. PMID:22918199

Chemical Synthesis of Hydrocarbon-Stapled Peptides for Protein Interaction Research and Therapeutic Targeting

PubMed Central

Bird, Gregory H.; Crannell, W. Christian; Walensky, Loren D.

2016-01-01

The peptide alpha-helix represents one of Nature’s most featured protein shapes and is employed in a diversity of protein architectures, spanning the very cytoskeletal infrastructure of the cell to the most intimate contact points between crucial signaling proteins. By installing an all-hydrocarbon crosslink into native sequences, we recapitulate the shape and biological activity of natural peptide alpha-helices, yielding a chemical toolbox to both interrogate the protein interactome and modulate interaction networks for potential therapeutic benefit. Here, we describe our latest approach to synthesizing Stabilized Alpha-Helices (SAH) corresponding to key protein interaction domains. We emphasize a stepwise approach to the production of crosslinking non-natural amino acids, their incorporation into peptide templates, and the application of ruthenium-catalyzed ring closing metathesis to generate hydrocarbon-stapled peptides. Through facile derivatization and functionalization steps, SAHs can be tailored for a broad range of applications in biochemical, structural, proteomic, cellular and in vivo studies. PMID:23801563

Extend MANPADS M&S Capabilities to Include Energetic Materials, Fragmentation Effects, and Wing Flutter Response

DTIC Science & Technology

2005-12-31

MANPADS missile is modeled using LSDYNA . It has 187600 nodes, 52802 shell elements with 13 shell materials, 112200 solid elements with 1804 solid...model capability that includes impact, detonation, penetration, and wing flutter response. This work extends an existing body on body missile model...the missile as well as the expansion of the surrounding fluids was modeled in the Eulerian domain. The Jones-Wilkins-Lee (JWL) equation of state was

A functional analysis of TOEFAZ1 uncovers protein domains essential for cytokinesis in Trypanosoma brucei.

PubMed

Sinclair-Davis, Amy N; McAllaster, Michael R; de Graffenried, Christopher L

2017-11-15

The parasite Trypanosoma brucei is highly polarized, including a flagellum that is attached along the cell surface by the flagellum attachment zone (FAZ). During cell division, the new FAZ positions the cleavage furrow, which ingresses from the anterior tip of the cell towards the posterior. We recently identified TOEFAZ1 (for 'Tip of the Extending FAZ protein 1') as an essential protein in trypanosome cytokinesis. Here, we analyzed the localization and function of TOEFAZ1 domains by performing overexpression and RNAi complementation experiments. TOEFAZ1 comprises three domains with separable functions: an N-terminal α-helical domain that may be involved in FAZ recruitment, a central intrinsically disordered domain that keeps the morphogenic kinase TbPLK at the new FAZ tip, and a C-terminal zinc finger domain necessary for TOEFAZ1 oligomerization. Both the N-terminal and C-terminal domains are essential for TOEFAZ1 function, but TbPLK retention at the FAZ is not necessary for cytokinesis. The feasibility of alternative cytokinetic pathways that do not employ TOEFAZ1 are also assessed. Our results show that TOEFAZ1 is a multimeric scaffold for recruiting proteins that control the timing and location of cleavage furrow ingression. © 2017. Published by The Company of Biologists Ltd.

Self-Assembly of Narrowly Dispersed Brush Diblock Copolymers with Domain Spacing more than 100 nm

NASA Astrophysics Data System (ADS)

Gu, Weiyin; Sveinbjornsson, Benjamin; Hong, Sung Woo; Grubbs, Robert; Russell, Thomas

2012-02-01

Self-assembled structures of high molecular weight (MW), narrow molecular weight distribution brush block copolymers containing polylactic acid (PLA) and polystyrene (PS) side chains with similar MWs were studied in both the melt and thin films. The polynorbornene-backbone-based brush diblock copolymers containing approximately equal volume fractions of each block self-assembled into highly ordered lamellae with domain spacing over 100 nm, as revealed by SAXS, GISAXS and AFM. The domain size increased approximately linearly with backbone length, which indicated an extended conformation of the backbone in the ordered state. The length of side chains also played a significant role in terms of controlling the domain size. As the degree of polymerization (DP) increased, the symmetric brush diblock copolymers with longer side chains tended to form larger lamellar microdomains in comparison to those that have the same DP but shorter side chains.

Crystal Structure of the HEAT Domain from the Pre-mRNA Processing Factor Symplekin

PubMed Central

Kennedy, Sarah A.; Frazier, Monica L.; Steiniger, Mindy; Mast, Ann M.; Marzluff, William F.; Redinbo, Matthew R.

2009-01-01

The majority of eukaryotic pre-mRNAs are processed by 3′-end cleavage and polyadenylation, although in metazoa the replication-dependant histone mRNAs are processed by 3′-end cleavage but not polyadenylation. The macromolecular complex responsible for processing both canonical and histone pre-mRNAs contains the ~1,160-residue protein Symplekin. Secondary structural prediction algorithms identified putative HEAT domains in the 300 N-terminal residues of all Symplekins of known sequence. The structure and dynamics of this domain were investigated to begin elucidating the role Symplekin plays in mRNA maturation. The crystal structure of the Drosophila melanogaster Symplekin HEAT domain was determined to 2.4 Å resolution using SAD phasing methods. The structure exhibits 5 canonical HEAT repeats along with an extended 31 amino acid loop (loop 8) between the fourth and fifth repeat that is conserved within closely related Symplekin sequences. Molecular dynamics simulations of this domain show that the presence of loop 8 dampens correlated and anticorrelated motion in the HEAT domain, therefore providing a neutral surface for potential protein-protein interactions. HEAT domains are often employed for such macromolecular contacts. The Symplekin HEAT region not only structurally aligns with several established scaffolding proteins, but also has been reported to contact proteins essential for regulating 3′-end processing. Taken together, these data support the conclusion that the Symplekin HEAT domain serves as a scaffold for protein-protein interactions essential to the mRNA maturation process. PMID:19576221

Factors influencing the incidence and treatment of intracranial aneurysm and subarachnoid hemorrhage: time trends and socioeconomic disparities under an universal healthcare system.

PubMed

Lee, Won Kyung; Oh, Chang Wan; Lee, Heeyoung; Lee, Kun Sei; Park, Hyeonseon

2018-06-22

Despite increasing usage of endovascular treatments for intracranial aneurysms, few research studies have been conducted on the incidence of unruptured aneurysm (UA) and subarachnoid hemorrhage (SAH), and could not show a decrease in the incidence of SAH. Moreover, research on socioeconomic disparities with respect to the diagnosis and treatment of UA and SAH is lacking. Trends in the incidences of newly detected UA and SAH and trends in the treatment modalities used were assessed from 2005 to 2015 using the nationwide database of the Korean National Health Insurance Service in South Korea. We also evaluated the influence of demographic characteristics including socioeconomic factors on the incidence and treatment of UA and SAH. The rates of newly detected UA and SAH were 28.3 and 13.7 per 100 000 of the general population, respectively, in 2015. The incidence of UA increased markedly over the 11-year study period, whereas that of SAH decreased slightly. UA patients were more likely to be female, older, employee-insured, and to have high incomes than SAH patients. In 2015, coiling was the most common treatment modality for both UA and SAH patients. Those who were female, employee-insured, or self-employed, with high income were likely to have a higher probability to be treated for UA and SAH. The marked increase in the detection and treatment of UA might have contributed to the decreasing incidence of SAH, though levels of contribution depend on socioeconomic status despite universal medical insurance coverage. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The extending lithosphere (Arthur Holmes Medal Lecture)

NASA Astrophysics Data System (ADS)

Brun, Jean-Pierre

2017-04-01

Extension of the lithosphere gives birth to a wide range of structures, with characteristic widths between 10 and 1000 km, which includes continental rifts, passive margins, oceanic rifts, core complexes, or back-arc basins. Because the rheology of rocks strongly depends on temperature, this variety of extensional structures falls in two broad categories of extending lithospheres according to the initial Moho temperature TM. "Cold extending systems", with TM < 750°C and mantle-dominated strength, lead to narrow rifts and, if extension is maintained long enough, to passive margins and then mantle core complexes. "Hot extending systems", with TM > 750°C and crustal-dominated strength, lead, depending on strain rate, to either wide rifts or metamorphic core complexes. A much less quoted product of extension is the exhumation of high-pressure (HP ) metamorphic rocks occurring in domains of back-arc extension driven by slab rollback (e.g. Aegean; Appennines-Calabrian) or when the subduction upper plate undergoes extension for plate kinematics reasons (e.g. Norwegian Caledonides; Papua New Guinea). In these tectonic environments, well-documented pressure-temperature-time (P - T - t) paths of HP rocks show a two-stage retrogression path whose the first part corresponds to an isothermal large pressure drop ΔP proportional to the maximum pressure Pmax recorded by the rocks. This linear relation between ΔP and Pmax, which likely results from a stress switch between compression and extension at the onset of exhumation, is in fact observed in all HP metamorphism provinces worldwide, suggesting that the exhumation of HP rocks in extension is a general process rather than an uncommon case. In summary, the modes and products of extension are so diverse that, taken all together, they constitute a very versatile natural laboratory to decipher the rheological complexities of the continental lithosphere and their mechanical implications.

Optimising predictor domains for spatially coherent precipitation downscaling

NASA Astrophysics Data System (ADS)

Radanovics, S.; Vidal, J.-P.; Sauquet, E.; Ben Daoud, A.; Bontron, G.

2012-04-01

resulting optimised domains are analysed for defining regions where neighbouring zones have equal or similar predictor domains and identifying which French river basins contain zones associated with different predictor domains, i.e. are exposed to different meteorological influences. The above analysis will be used (1) to extend the statistical downscaling method of Ben Daoud et al. (2011) to the whole of France and (2) to develop it further in order to achieve spatially coherent forecasts while preserving the predictive skill on the local scale. Ben Daoud, A., Sauquet, E., Lang, M., Bontron, G., and Obled, C. (2011). Precipitation forecasting through an analog sorting technique: a comparative study. Advances in Geosciences, 29:103-107. doi: 10.5194/adgeo-29-103-2011 Obled, C., Bontron, G., and Garçon, R. (2002). Quantitative precipitation forecasts: a statistical adaptation of model outputs through an analogues sorting approach. Atmospheric Research, 63(3-4):303-324. doi: 10.1016/S0169-8095(02)00038-8 Vidal, J.-P., Martin, E., Franchistéguy, L., Baillon, M., and Soubeyroux, J.-M. (2010) A 50-year high-resolution atmospheric reanalysis over France with the Safran system. International Journal of Climatology, 30:1627-1644. doi: 10.1002/joc.2003

Extending the Scope of Speaking Assessment Criteria in a Specific-Purpose Language Test: Operationalizing a Health Professional Perspective

ERIC Educational Resources Information Center

O'Hagan, Sally; Pill, John; Zhang, Ying

2016-01-01

Criticism of specific-purpose language (LSP) tests is often directed at their limited ability to represent fully the demands of the target language use situation. Such criticisms extend to the criteria used to assess test performance, which may fail to capture what matters to participants in the domain of interest. This paper reports on the…

Domain Engineering

NASA Astrophysics Data System (ADS)

Bjørner, Dines

Before software can be designed we must know its requirements. Before requirements can be expressed we must understand the domain. So it follows, from our dogma, that we must first establish precise descriptions of domains; then, from such descriptions, “derive” at least domain and interface requirements; and from those and machine requirements design the software, or, more generally, the computing systems.

Visualizing domain wall and reverse domain superconductivity.

PubMed

Iavarone, M; Moore, S A; Fedor, J; Ciocys, S T; Karapetrov, G; Pearson, J; Novosad, V; Bader, S D

2014-08-28

In magnetically coupled, planar ferromagnet-superconductor (F/S) hybrid structures, magnetic domain walls can be used to spatially confine the superconductivity. In contrast to a superconductor in a uniform applied magnetic field, the nucleation of the superconducting order parameter in F/S structures is governed by the inhomogeneous magnetic field distribution. The interplay between the superconductivity localized at the domain walls and far from the walls leads to effects such as re-entrant superconductivity and reverse domain superconductivity with the critical temperature depending upon the location. Here we use scanning tunnelling spectroscopy to directly image the nucleation of superconductivity at the domain wall in F/S structures realized with Co-Pd multilayers and Pb thin films. Our results demonstrate that such F/S structures are attractive model systems that offer the possibility to control the strength and the location of the superconducting nucleus by applying an external magnetic field, potentially useful to guide vortices for computing application.

Visualizing domain wall and reverse domain superconductivity

PubMed Central

Iavarone, M.; Moore, S. A.; Fedor, J.; Ciocys, S. T.; Karapetrov, G.; Pearson, J.; Novosad, V.; Bader, S. D.

2014-01-01

In magnetically coupled, planar ferromagnet-superconductor (F/S) hybrid structures, magnetic domain walls can be used to spatially confine the superconductivity. In contrast to a superconductor in a uniform applied magnetic field, the nucleation of the superconducting order parameter in F/S structures is governed by the inhomogeneous magnetic field distribution. The interplay between the superconductivity localized at the domain walls and far from the walls leads to effects such as re-entrant superconductivity and reverse domain superconductivity with the critical temperature depending upon the location. Here we use scanning tunnelling spectroscopy to directly image the nucleation of superconductivity at the domain wall in F/S structures realized with Co-Pd multilayers and Pb thin films. Our results demonstrate that such F/S structures are attractive model systems that offer the possibility to control the strength and the location of the superconducting nucleus by applying an external magnetic field, potentially useful to guide vortices for computing application. PMID:25164004

Spatially extended hybrid methods: a review

PubMed Central

2018-01-01

Many biological and physical systems exhibit behaviour at multiple spatial, temporal or population scales. Multiscale processes provide challenges when they are to be simulated using numerical techniques. While coarser methods such as partial differential equations are typically fast to simulate, they lack the individual-level detail that may be required in regions of low concentration or small spatial scale. However, to simulate at such an individual level throughout a domain and in regions where concentrations are high can be computationally expensive. Spatially coupled hybrid methods provide a bridge, allowing for multiple representations of the same species in one spatial domain by partitioning space into distinct modelling subdomains. Over the past 20 years, such hybrid methods have risen to prominence, leading to what is now a very active research area across multiple disciplines including chemistry, physics and mathematics. There are three main motivations for undertaking this review. Firstly, we have collated a large number of spatially extended hybrid methods and presented them in a single coherent document, while comparing and contrasting them, so that anyone who requires a multiscale hybrid method will be able to find the most appropriate one for their need. Secondly, we have provided canonical examples with algorithms and accompanying code, serving to demonstrate how these types of methods work in practice. Finally, we have presented papers that employ these methods on real biological and physical problems, demonstrating their utility. We also consider some open research questions in the area of hybrid method development and the future directions for the field. PMID:29491179

Goal-Based Domain Modeling as a Basis for Cross-Disciplinary Systems Engineering

NASA Astrophysics Data System (ADS)

Jarke, Matthias; Nissen, Hans W.; Rose, Thomas; Schmitz, Dominik

Small and medium-sized enterprises (SMEs) are important drivers for innovation. In particular, project-driven SMEs that closely cooperate with their customers have specific needs in regard to information engineering of their development process. They need a fast requirements capture since this is most often included in the (unpaid) offer development phase. At the same time, they need to maintain and reuse the knowledge and experiences they have gathered in previous projects extensively as it is their core asset. The situation is complicated further if the application field crosses disciplinary boundaries. To bridge the gaps and perspectives, we focus on shared goals and dependencies captured in models at a conceptual level. Such a model-based approach also offers a smarter connection to subsequent development stages, including a high share of automated code generation. In the approach presented here, the agent- and goal-oriented formalism i * is therefore extended by domain models to facilitate information organization. This extension permits a domain model-based similarity search, and a model-based transformation towards subsequent development stages. Our approach also addresses the evolution of domain models reflecting the experiences from completed projects. The approach is illustrated with a case study on software-intensive control systems in an SME of the automotive domain.

Xenon and Other Volatile Anesthetics Change Domain Structure in Model Lipid Raft Membranes

PubMed Central

Weinrich, Michael; Worcester, David L.

2014-01-01

Inhalation anesthetics have been in clinical use for over 160 years, but the molecular mechanisms of action continue to be investigated. Direct interactions with ion channels received much attention after it was found that anesthetics do not change the structure of homogeneous model membranes. However, it was recently found that halothane, a prototypical anesthetic, changes domain structure of a binary lipid membrane. The noble gas xenon is an excellent anesthetic and provides a pivotal test of the generality of this finding, extended to ternary lipid raft mixtures. We report that xenon and conventional anesthetics change the domain equilibrium in two canonical ternary lipid raft mixtures. These findings demonstrate a membrane-mediated mechanism whereby inhalation anesthetics can affect the lipid environment of trans-membrane proteins. PMID:24299622

Optimal Couple Projections for Domain Adaptive Sparse Representation-based Classification.

PubMed

Zhang, Guoqing; Sun, Huaijiang; Porikli, Fatih; Liu, Yazhou; Sun, Quansen

2017-08-29

In recent years, sparse representation based classification (SRC) is one of the most successful methods and has been shown impressive performance in various classification tasks. However, when the training data has a different distribution than the testing data, the learned sparse representation may not be optimal, and the performance of SRC will be degraded significantly. To address this problem, in this paper, we propose an optimal couple projections for domain-adaptive sparse representation-based classification (OCPD-SRC) method, in which the discriminative features of data in the two domains are simultaneously learned with the dictionary that can succinctly represent the training and testing data in the projected space. OCPD-SRC is designed based on the decision rule of SRC, with the objective to learn coupled projection matrices and a common discriminative dictionary such that the between-class sparse reconstruction residuals of data from both domains are maximized, and the within-class sparse reconstruction residuals of data are minimized in the projected low-dimensional space. Thus, the resulting representations can well fit SRC and simultaneously have a better discriminant ability. In addition, our method can be easily extended to multiple domains and can be kernelized to deal with the nonlinear structure of data. The optimal solution for the proposed method can be efficiently obtained following the alternative optimization method. Extensive experimental results on a series of benchmark databases show that our method is better or comparable to many state-of-the-art methods.

Domain Specific vs Domain General: Implications for Dynamic Assessment

ERIC Educational Resources Information Center

Kaniel, Shlomo

2010-01-01

The article responds to the need for evidence-based dynamic assessment. The article is divided into two sections: In Part 1 we examine the scientific answer to the question of how far human mental activities and capabilities are domain general (DG) / domain specific (DS). A highly complex answer emerges from the literature review of domains such…

The relationship between perimesencephalic subarachnoid hemorrhage and deep venous system drainage pattern and calibrations.

PubMed

Buyukkaya, Ramazan; Yıldırım, Nalan; Cebeci, Hakan; Kocaeli, Hasan; Dusak, Abdürrahim; Ocakoğlu, Gökhan; Erdoğan, Cüneyt; Hakyemez, Bahattin

2014-01-01

The purpose of this study is to investigate the relationship between Rosenthal basal vein (BVR) type and diameter and perimesencephalic nonaneurysmal subarachnoid hemorrhage (P-SAH). Aneurysmal subarachnoid hemorrhage (A-SAH), P-SAH, and control groups were evaluated, and BVRs were classified by type. BVR diameters in patients were measured. There was a statistically significant difference of BVR drainage types between groups (P=.002). BVR diameters of patients with normal drainage pattern in P-SAH group were significantly smaller than those in both other groups (P<.001). There is a relationship between P-SAH and BVR primitive drainage type. P-SAH risk increases in parallel with decreasing caliber of BVR in patients with normal drainage pattern. Copyright © 2014 Elsevier Inc. All rights reserved.

Subarachnoid Hemorrhage due to Spinal Cord Schwannoma Presenting Findings Mimicking Meningitis.

PubMed

Zhang, Hong-Mei; Zhang, Yin-Xi; Zhang, Qing; Song, Shui-Jiang; Liu, Zhi-Rong

2016-08-01

Subarachnoid hemorrhage (SAH) of spinal origin is uncommon in clinical practice, and spinal schwannomas associated with SAH are even more rarely reported. We report an unusual case of spinal SAH mimicking meningitis with normal brain computed tomography (CT)/magnetic resonance imaging (MRI) and negative CT angiography. Cerebrospinal fluid examination results were consistent with the manifestation of SAH. Spinal MRI performed subsequently showed an intradural extramedullary mass. The patient received surgery and was finally diagnosed with spinal cord schwannoma. A retrospective chart review of the patient was performed. We describe a case of SAH due to spinal cord schwannoma. Our case highlights the importance of careful history taking and complete evaluation. We emphasize that spinal causes should always be ruled out in patients with angionegative SAH and that schwannoma should be considered in the differential diagnosis of SAH etiologies even though rare. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Molecular dynamics simulations of site point mutations in the TPR domain of cyclophilin 40 identify conformational states with distinct dynamic and enzymatic properties

NASA Astrophysics Data System (ADS)

Gur, Mert; Blackburn, Elizabeth A.; Ning, Jia; Narayan, Vikram; Ball, Kathryn L.; Walkinshaw, Malcolm D.; Erman, Burak

2018-04-01

Cyclophilin 40 (Cyp40) is a member of the immunophilin family that acts as a peptidyl-prolyl-isomerase enzyme and binds to the heat shock protein 90 (Hsp90). Its structure comprises an N-terminal cyclophilin domain and a C-terminal tetratricopeptide (TPR) domain. Cyp40 is overexpressed in prostate cancer and certain T-cell lymphomas. The groove for Hsp90 binding on the TPR domain includes residues Lys227 and Lys308, referred to as the carboxylate clamp, and is essential for Cyp40-Hsp90 binding. In this study, the effect of two mutations, K227A and K308A, and their combinative mutant was investigated by performing a total of 5.76 μs of all-atom molecular dynamics (MD) simulations in explicit solvent. All simulations, except the K308A mutant, were found to adopt two distinct (extended or compact) conformers defined by different cyclophilin-TPR interdomain distances. The K308A mutant was only observed in the extended form which is observed in the Cyp40 X-ray structure. The wild-type, K227A, and combined mutant also showed bimodal distributions. The experimental melting temperature, Tm, values of the mutants correlate with the degree of compactness with the K308A extended mutant having a marginally lower melting temperature. Another novel measure of compactness determined from the MD data, the "coordination shell volume," also shows a direct correlation with Tm. In addition, the MD simulations show an allosteric effect with the mutations in the remote TPR domain having a pronounced effect on the molecular motions of the enzymatic cyclophilin domain which helps rationalise the experimentally observed increase in enzyme activity measured for all three mutations.

Medically induced hypertension, hypervolaemia and haemodilution for the treatment and prophylaxis of vasospasm following aneurysmal subarachnoid haemorrhage: systematic review.

PubMed

Loan, James J M; Wiggins, Anthony N; Brennan, Paul M

2018-01-17

Arterial vasospasm is a major cause of death and long-term disability following subarachnoid haemorrhage (SAH). The use of medically induced hypertension, hypervolaemia and/or haemodilution is widely practiced for prophylaxis and treatment of vasospasm following SAH. We aimed to determine if the quality of available research is adequate to inform use of haemodynamic management strategies to prevent or treat vasospasm following SAH. Individual searches of the following databases were conducted: The Cochrane Database of Systematic Reviews, The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and OpenSIGLE. Pertinent randomised clinical trials and cohort studies comparing any element or combination thereof: medically induced hypertension, hypervolaemia, and haemodilution were included. Data were extracted using standardised proformas and risk of bias assessed using a domain-based risk of bias assessment tool. 348 study reports were identified by our literature search. Eight studies were included, three of which examined both volume expansion and medically induced hypertension. Three randomised clinical trials and two cohort studies examining prophylactic volume expansion were included. Two trials of prophylactic medically induced hypertension and two cohort studies were included. One trial and one cohort study of medically induced hypertension for treatment of established vasospasm was included. These trials demonstrated no significant difference in any of the clinical outcome measures studied. No trials of blood transfusion were included. There is currently insufficient evidence to determine the efficacy or non-efficacy of intravenous volume expansion, medically induced hypertension or blood transfusion for the treatment or prophylaxis of vasospasm following SAH. All of these approaches have been associated with adverse events, of unclear incidence. The current evidence base therefore cannot be used to reliably inform clinical practice. This is a

Extended--and Extending--Literacies

ERIC Educational Resources Information Center

Moje, Elizabeth Birr; Ellison, Tisha Lewis

2016-01-01

We examine the impact of "Becoming a Nation of Readers: The Report of the Commission on Reading" ("BNR") (Anderson, Hiebert, Scott, & Wilkinson, 1985) with the idea of extending literacy learning beyond the early grades, describing present-day conceptions of secondary-school literacy learning, and calling to "further…

Integrating natural language processing and web GIS for interactive knowledge domain visualization

NASA Astrophysics Data System (ADS)

Du, Fangming

Recent years have seen a powerful shift towards data-rich environments throughout society. This has extended to a change in how the artifacts and products of scientific knowledge production can be analyzed and understood. Bottom-up approaches are on the rise that combine access to huge amounts of academic publications with advanced computer graphics and data processing tools, including natural language processing. Knowledge domain visualization is one of those multi-technology approaches, with its aim of turning domain-specific human knowledge into highly visual representations in order to better understand the structure and evolution of domain knowledge. For example, network visualizations built from co-author relations contained in academic publications can provide insight on how scholars collaborate with each other in one or multiple domains, and visualizations built from the text content of articles can help us understand the topical structure of knowledge domains. These knowledge domain visualizations need to support interactive viewing and exploration by users. Such spatialization efforts are increasingly looking to geography and GIS as a source of metaphors and practical technology solutions, even when non-georeferenced information is managed, analyzed, and visualized. When it comes to deploying spatialized representations online, web mapping and web GIS can provide practical technology solutions for interactive viewing of knowledge domain visualizations, from panning and zooming to the overlay of additional information. This thesis presents a novel combination of advanced natural language processing - in the form of topic modeling - with dimensionality reduction through self-organizing maps and the deployment of web mapping/GIS technology towards intuitive, GIS-like, exploration of a knowledge domain visualization. A complete workflow is proposed and implemented that processes any corpus of input text documents into a map form and leverages a web

Subarachnoid Haemorrhage and Sports

PubMed Central

Sousa Nanji, Liliana; Melo, Teresa P.; Canhão, Patrícia; Fonseca, Ana Catarina; Ferro, José Manuel

2015-01-01

Background Some cases of subarachnoid haemorrhage (SAH) have been associated with vigorous physical activity, including sports. Our research aimed to describe the association between SAH and sports and to identify the types of sports that were more frequently found as precipitating factors in a tertiary single-centre SAH register. Methods We retrieved information from a prospectively collected SAH registry and reviewed discharge notes of acute SAH patients admitted to the Stroke Unit of Hospital de Santa Maria, Lisbon, between 1995 and 2014. Results Out of 738 patients included in the analysis, 424 (57.5%) cases of SAH were preceded by physical activity. Nine cases (1.2%) were associated with sports, namely running (2 cases), aerobics (2 cases), cycling, body balance, dance, surf and windsurf. Patients with SAH while practicing sports were younger than controls (average age 43.1 vs. 57.0 years; p = 0.007). In 1 patient, there was a report of trauma to the neck. Patients in the sports group only had Hunt and Hess scale grades 1 (11.1%) or 2 (88.9%) at admission, while patients in the control group had a wider distribution in severity. Conclusions Our findings indicate that SAH precipitated by sports is not very frequent and is uncommonly related to trauma. Patients who suffered SAH associated with sports were younger and apparently had a milder clinical presentation. PMID:26648972

Subarachnoid Haemorrhage and Sports.

PubMed

Sousa Nanji, Liliana; Melo, Teresa P; Canhão, Patrícia; Fonseca, Ana Catarina; Ferro, José Manuel

2015-01-01

Some cases of subarachnoid haemorrhage (SAH) have been associated with vigorous physical activity, including sports. Our research aimed to describe the association between SAH and sports and to identify the types of sports that were more frequently found as precipitating factors in a tertiary single-centre SAH register. We retrieved information from a prospectively collected SAH registry and reviewed discharge notes of acute SAH patients admitted to the Stroke Unit of Hospital de Santa Maria, Lisbon, between 1995 and 2014. Out of 738 patients included in the analysis, 424 (57.5%) cases of SAH were preceded by physical activity. Nine cases (1.2%) were associated with sports, namely running (2 cases), aerobics (2 cases), cycling, body balance, dance, surf and windsurf. Patients with SAH while practicing sports were younger than controls (average age 43.1 vs. 57.0 years; p = 0.007). In 1 patient, there was a report of trauma to the neck. Patients in the sports group only had Hunt and Hess scale grades 1 (11.1%) or 2 (88.9%) at admission, while patients in the control group had a wider distribution in severity. Our findings indicate that SAH precipitated by sports is not very frequent and is uncommonly related to trauma. Patients who suffered SAH associated with sports were younger and apparently had a milder clinical presentation.

Inhibition of mammalian target of rapamycin attenuates early brain injury through modulating microglial polarization after experimental subarachnoid hemorrhage in rats.

PubMed

You, Wanchun; Wang, Zhong; Li, Haiying; Shen, Haitao; Xu, Xiang; Jia, Genlai; Chen, Gang

2016-08-15

Here, we aimed to study the role and underlying mechanism of mTOR in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Experiment 1, the time course of mTOR activation in the cortex following SAH. Experiment 2, the role of mTOR in SAH-induced EBI. Adult SD rats were divided into four groups: sham group (n=18), SAH+vehicle group (n=18), SAH+rapamycin group (n=18), SAH+AZD8055 group (n=18). Experiment 3, we incubated enriched microglia with OxyHb. Rapamycin and AZD8055 were also used to demonstrate the mTOR's role on microglial polarization in vitro. The phosphorylation levels of mTOR and its substrates were significantly increased and peaked at 24h after SAH. Rapamycin or AZD8055 markedly decreased the phosphorylation levels of mTOR and its substrates and the activation of microglia in vivo, and promoted the microglial polarization from M1 phenotype to M2 phenotype. In addition, administration of rapamycin and AZD8055 following SAH significantly ameliorated EBI, including neuronal apoptosis, neuronal necrosis, brain edema and blood-brain barrier permeability. Our findings suggested that the rapamycin and AZD8055 could attenuate the development of EBI in this SAH model, possibly through inhibiting the activation of microglia by mTOR pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

Orientation of Myosin Binding Protein C in the Cardiac Muscle Sarcomere Determined by Domain-Specific Immuno-EM

PubMed Central

Lee, Kyounghwan; Harris, Samantha P.; Sadayappan, Sakthivel; Craig, Roger

2014-01-01

Myosin binding protein-C is a thick filament protein of vertebrate striated muscle. The cardiac isoform (cMyBP-C) is essential for normal cardiac function, and mutations in cMyBP-C cause cardiac muscle disease. The rod-shaped molecule is composed primarily of 11 immunoglobulin- or fibronectin-like domains, and is located at 9 sites, 43 nm apart, in each half of the A-band. To understand how cMyBP-C functions, it is important to know its structural organization in the sarcomere, as this will affect its ability to interact with other sarcomeric proteins. Several models have been proposed, in which cMyBP-C wraps around, extends radially from, or runs axially along the thick filament. Our goal was to define cMyBP-C orientation by determining the relative axial positions of different cMyBP-C domains. Immuno-electron microscopy was performed using mouse cardiac myofibrils labeled with antibodies specific to the N- and C-terminal domains and to the middle of cMyBP-C. Antibodies to all regions of the molecule, except the C-terminus, labeled at the same nine axial positions in each half A-band, consistent with a circumferential and/or radial rather than an axial orientation of the bulk of the molecule. The C-terminal antibody stripes were slightly displaced axially, demonstrating an axial orientation of the C-terminal 3 domains, with the C-terminus closer to the M-line. These results, combined with previous studies, suggest that the C-terminal domains of cMyBP-C run along the thick filament surface, while the N-terminus extends towards neighboring thin filaments. This organization provides a structural framework for understanding cMyBP-C’s modulation of cardiac muscle contraction. PMID:25451032

Habitual Cognitive Reappraisal Was Negatively Related to Perceived Immorality in the Harm and Fairness Domains

PubMed Central

Li, Zhongquan; Wu, Xiaoyuan; Zhang, Lisong; Zhang, Ziyuan

2017-01-01

Emotion plays an important role in moral judgment, and people always use emotion regulation strategies to modulate emotion, consciously or unconsciously. Previous studies had investigated only the relationship between emotion regulation strategies and moral judgment in the Harm domain, and revealed divergent results. Based on Moral Foundations Theory, the present study extended the investigation into moral judgment in all five moral domains and used a set of standardized moral vignettes. Two hundred and six college students filled in the Emotion Regulation Questionnaire and completed emotional ratings and moral judgment on moral vignettes from Moral Foundations Vignettes. Correlation analysis indicated that habitual cognitive reappraisal was negatively related to immorality rating in Harm, Fairness, and Loyalty domains. Regression analysis revealed that after controlling the effect of other variables, cognitive reappraisal negatively predicted immorality ratings in the Harm and Fairness domains. Further mediation analysis showed that emotional valence only partially explained the association between cognitive reappraisal and moral judgment in Harm area. Some other factors beyond emotional valence were suggested for future studies. PMID:29075229

Habitual Cognitive Reappraisal Was Negatively Related to Perceived Immorality in the Harm and Fairness Domains.

PubMed

Li, Zhongquan; Wu, Xiaoyuan; Zhang, Lisong; Zhang, Ziyuan

2017-01-01

Emotion plays an important role in moral judgment, and people always use emotion regulation strategies to modulate emotion, consciously or unconsciously. Previous studies had investigated only the relationship between emotion regulation strategies and moral judgment in the Harm domain, and revealed divergent results. Based on Moral Foundations Theory, the present study extended the investigation into moral judgment in all five moral domains and used a set of standardized moral vignettes. Two hundred and six college students filled in the Emotion Regulation Questionnaire and completed emotional ratings and moral judgment on moral vignettes from Moral Foundations Vignettes. Correlation analysis indicated that habitual cognitive reappraisal was negatively related to immorality rating in Harm, Fairness, and Loyalty domains. Regression analysis revealed that after controlling the effect of other variables, cognitive reappraisal negatively predicted immorality ratings in the Harm and Fairness domains. Further mediation analysis showed that emotional valence only partially explained the association between cognitive reappraisal and moral judgment in Harm area. Some other factors beyond emotional valence were suggested for future studies.

Short forms of the Utrecht-Management of Identity Commitments Scale (U-MICS) with the domains of job, romantic relationship, and region.

PubMed

Schubach, Elisabeth; Zimmermann, Julia; Noack, Peter; Neyer, Franz J

2017-01-01

The U-MICS is a self-report questionnaire designed to assess the identity dimensions from a domain-specific perspective. The present study reports on the development of a short-form version for the domains of job and romantic relationship in young adults from Germany and extends this scale to include the domain of region (n Sample1  = 95, 84% female, mean age 22.45 years; n Sample2  = 1,795, 71% female, mean age 24.53 years). We found the short form to possess adequate psychometric properties and to demonstrate a factor structure congruent to the long-form version. Regarding validity, the small correlations across domains within dimensions support a domain-specific approach to identity. The associations between the different identity domains with personality traits are similar, indicating a consistent pattern of convergent validity for all domains. We conclude that "region" provides a valuable complement to the established domains that can all be reliably assessed with the U-MICS-Short Form. Copyright © 2016 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Effect of 18β-glycyrrhetinic acid on cerebral vasospasm caused by asymmetric dimethylarginine after experimental subarachnoid hemorrhage in rats.

PubMed

Zhao, Dong; Liu, Qi; Ji, Yunxiang; Wang, Ganggang; He, Xuejun; Tian, Weidong; Xu, Hui; Lei, Ting; Wang, Yezhong

2015-06-01

Cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) is characterized by the severe constriction of an artery, which often leads to unfavorable outcomes. CVS after SAH is closely associated with asymmetric dimethylarginine (ADMA) and connexin. The effect of 18β-glycyrrhetinic acid (18β-GA), an inhibitor of gap junction, on ADMA, connexin, and CVS after SAH were investigated. Sprague-Dawley rats (n  =  120), weighing 300-350 g, were divided into the control group, sham, SAH, and SAH + 18β-GA groups. In the SAH group, blood was injected into the prechiasmatic cistern of the rats, and 18β-GA (10 mg/kg) was intraperitoneally injected. The neurological score, basilar artery diameter, ADMA, and connexin protein contents (Cx40, Cx43, and Cx45) were measured using Kaoutzanis scoring system, pressure myograph, enzyme linked immunosorbent assay kit, and Western blot, respectively, 1, 3, 5, 7, and 14 days after SAH. The neurological score significantly decreased 3, 5, 7, and 14 days after SAH. The basilar artery diameter significantly decreased, and the ADMA level in the cerebrospinal fluid (CSF) significantly increased at all time points. The level of Cx40 significantly decreased on days 3, 5, 7, and 14, and the level of Cx43 and Cx45 significantly increased at all time points. ADMA and Cx43 are positively correlated. However, the upregulated level of ADMA, Cx43, and Cx45 were attenuated. The neurology result significantly improved in the SAH + 18β-GA group. Treatment with 18β-GA in SAH rats decreases Cx43 and Cx45 in basilar artery and ADMA in CSF. ADMA is probably involved in the pathophysiological events of CVS after SAH by altering connexin proteins. The mechanism of connexin protein changes caused by ADMA needs to be further studied.

Netrin-1 Preserves Blood-Brain Barrier Integrity Through Deleted in Colorectal Cancer/Focal Adhesion Kinase/RhoA Signaling Pathway Following Subarachnoid Hemorrhage in Rats.

PubMed

Xie, Zongyi; Enkhjargal, Budbazar; Reis, Cesar; Huang, Lei; Wan, Weifeng; Tang, Jiping; Cheng, Yuan; Zhang, John H

2017-05-19

Netrin-1 (NTN-1) has been established to be a novel intrinsic regulator of blood-brain barrier (BBB) maintenance. This study was carried out to investigate the potential roles of exogenous NTN-1 in preserving BBB integrity after experimental subarachnoid hemorrhage (SAH) as well as the underlying mechanisms of its protective effects. A total of 309 male Sprague-Dawley rats were subjected to an endovascular perforation model of SAH. Recombinant NTN-1 was administered intravenously 1 hour after SAH induction. NTN-1 small interfering RNA or Deleted in Colorectal Cancer small interfering RNA was administered intracerebroventricular at 48 hours before SAH. Focal adhesion kinase inhibitor was administered by intraperitoneal injection at 1 hour prior to SAH. Neurological scores, brain water content, BBB permeability, RhoA activity, Western blot, and immunofluorescence staining were evaluated. The expression of endogenous NTN-1 and its receptor Deleted in Colorectal Cancer were increased after SAH. Administration of exogenous NTN-1 significantly reduced brain water content and BBB permeability and ameliorated neurological deficits at 24 and 72 hours after SAH. Exogenous NTN-1 treatment significantly promoted phosphorylated focal adhesion kinase activation and inhibited RhoA activity, as well as upregulated the expression of ZO-1 and Occludin. Conversely, depletion of endogenous NTN-1 aggravated BBB breakdown and neurological impairments at 24 hours after SAH. The protective effects of NTN-1 at 24 hours after SAH were also abolished by pretreatment with Deleted in Colorectal Cancer small interfering RNA and focal adhesion kinase inhibitor. NTN-1 treatment preserved BBB integrity and improved neurological functions through a Deleted in Colorectal Cancer/focal adhesion kinase/RhoA signaling pathway after SAH. Thus, NTN-1 may serve as a promising treatment to alleviate early brain injury following SAH. © 2017 The Authors. Published on behalf of the American Heart

Immunoassay of S-adenosylmethionine and S-adenosylhomocysteine: the methylation index as a biomarker for disease and health status.

PubMed

Hao, Xiujuan; Huang, Yan; Qiu, Ming; Yin, Chunlin; Ren, Huiming; Gan, Hongjie; Li, Huijun; Zhou, Yaxia; Xia, Jiazhi; Li, Wenting; Guo, Lijuan; Angres, Isaac A

2016-11-28

S-Adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH) are relevant to a variety of diseases. Previous reports that quantified SAM and SAH were based on HPLC or LC-MS/MS. No antibody against SAM has been generated, and the antibody against SAH cannot be used with blood samples. Immunoassays have not been used to measure SAM and SAH. In this study, ELISA was used to measure blood SAM and SAH levels. Specific antibodies against SAM were produced for the first time using a stable analog as the antigen. The monoclonal antibodies against SAM and SAH were characterized. No cross-reactivity was detected for the analyzed analogs. For the anti-SAM antibodies, the ELISA sensitivity was ~2 nM, and the affinity was 7.29 × 10 10 L/mol. For the anti-SAH antibodies, the sensitivity was ~15 nM, and the affinity was 2.79 × 10 8 L/mol. Using high-quality antibodies against SAM and SAH, immunoassays for the detection of SAM and SAH levels in blood and tissue samples were developed. Clinical investigations using immunoassays to measure SAM, SAH and the methylation index (MI) in normal and diseased samples indicated that (1) the SAM level is age and gender dependent; (2) the SAM level is associated with the severity of liver diseases, inflammatory reactions and other diseases; and (3) the methylation index (MI) is significantly reduced in many diseases and may serve as a screening biomarker to identify potentially unfavorable health conditions. It is possible to generate antibodies against active small biomolecules with weak immunogenicity, such as SAM and SAH, using traditional hybridoma technology. The antigens and antibodies described here will contribute to the development of immunoassays to measure SAM, SAH and related molecules. These assays enable the MI to be measured specifically, accurately, easily and quickly without costly equipment. This preliminary study indicates that the MI could be an effective indicator of general health, except under conditions that may

Navigation-assisted trans-inferotemporal cortex selective amygdalohippocampectomy for mesial temporal lobe epilepsy; preserving the temporal stem.

PubMed

Kishima, Haruhiko; Kato, Amami; Oshino, Satoru; Tani, Naoki; Maruo, Tomoyuki; Khoo, Hui Ming; Yanagisawa, Takufumi; Edakawa, Kotaro; Kobayashi, Maki; Tanaka, Masataka; Hosomi, Koichi; Hirata, Masayuki; Yoshimine, Toshiki

2017-03-01

Selective amygdalohippocampectomy (SAH) can be used to obtain satisfactory seizure control in patients with mesial temporal lobe epilepsy (MTLE). Several SAH procedures have been reported to achieve satisfactory outcomes for seizure control, but none yield fully satisfactory outcomes for memory function. We hypothesized that preserving the temporal stem might play an important role. To preserve the temporal stem, we developed a minimally invasive surgical procedure, 'neuronavigation-assisted trans-inferotemporal cortex SAH' (TITC-SAH). TITC-SAH was performed in 23 patients with MTLE (MTLE on the language-non-dominant hemisphere, n = 11). The inferior horn of the lateral ventricle was approached via the inferior or middle temporal gyrus along the inferior temporal sulcus under neuronavigation guidance. The hippocampus was dissected in a subpial manner and resected en bloc together with the parahippocampal gyrus. Seizure control at one year and memory function at 6 months postoperatively were evaluated. One year after TITC-SAH, 20 of the 23 patients were seizure-free (ILAE class 1), 2 were class 2, and 1 was class 3. Verbal memory improved significantly in 13 patients with a diagnosis of hippocampal sclerosis, for whom WMS-R scores were available both pre- and post-operatively. Improvements were seen regardless of whether the SAH was on the language-dominant or non-dominant hemisphere. No major complication was observed. Navigation-assisted TITC-SAH performed for MTLE offers a simple, minimally invasive procedure that appears to yield excellent outcomes in terms of seizure control and preservation of memory function, because this procedure does not damage the temporal stem. TITC-SAH should be one of the feasible surgical procedures for MTLE. SAH: Amygdalohippocampectomy; MTLE: Mesial temporal lobe epilepsy (MTLE); TITC-SAH: Ttrans-inferotemporal cortex SAH; ILAE: International League Against Epilepsy (ILAE); MRI: Magnetic resonance imaging; EEG

Influence of experimental subarachnoid hemorrhage on nicotine-induced contraction of the rat basilar artery in relation to arachidonic acid metabolites signaling pathway.

PubMed

Ji, Xu; Wang, Aimin; Trandafir, Cristina C; Kurahashi, Kazuyoshi

2013-10-01

Smoking is one of the most important risk factors for cerebral circulatory disorders. The purpose of this study was to investigate the influence of experimental subarachnoid hemorrhage (SAH) on nicotine-induced contraction (arachidonic acid metabolites) in the basilar arteries of rats. Rats were killed at 1 hour and 1 week after blood injection, and the basilar artery was isolated and cut into a spiral strip. Testing of cyclooxygenase-1 (COX-1) and 5-lipoxygenase (5-LOX) inhibitors revealed no significant differences in their effects on normal and SAH (1 hour and 1 week). Phospholipase C (PLC) inhibitor (1-(6-((17beta-3-methoxyestra-1,3,5(10)-trien-17yl)amino)hexyl)-1H-pyrrole-2,5,-dione [U-73122]) slightly inhibited contraction of SAH (1 hour and 1 week) when compared to controls. Phospholipase A2 (PLA2) inhibitor (manoalide) and cytosolic PLA2 (cPLA2) inhibitor (arachidonyltrifluoromenthylketone [AACOCF3]) more strongly attenuated contraction in SAH (1 hour and 1 week) than in controls. Secreted PLA2 (sPLA2) inhibitor (indoxam), PLC inhibitor (2-nitro-4-carboxyphenyl N, N-diphenylcarbamate [NCDC]), and COX-2 inhibitors (nimesulide, (5-methanesulfonamido-6-(2,4-difluorothiophenyl)-1-indanone) [L-745337], and celecoxib) only slightly inhibited contraction of SAH (1 week) when compared to normal and SAH (1 hour). The calcium-independent PLA2 (iPLA2) inhibitor bromoenol lactone (BEL) showed greater inhibition of contraction in SAH (1 hour) when compared to normal and SAH (1 week). One week after exposure to SAH, PLC, sPLA2, and COX-2 activity were enhanced and cPLA2 activity was inhibited. One hour after exposure to SAH, PLC activity was enhanced and cPLA2 and iPLA2 activity was inhibited. Such changes of inflammatory arachidonic acid metabolites by smoking after SAH may play important roles in fatal cerebral circulatory disorders, suggesting important implications for the etiology and pathogenesis of SAH. Copyright © 2013 National Stroke Association. Published by

Domain-to-domain coupling in voltage-sensing phosphatase.

PubMed

Sakata, Souhei; Matsuda, Makoto; Kawanabe, Akira; Okamura, Yasushi

2017-01-01

Voltage-sensing phosphatase (VSP) consists of a transmembrane voltage sensor and a cytoplasmic enzyme region. The enzyme region contains the phosphatase and C2 domains, is structurally similar to the tumor suppressor phosphatase PTEN, and catalyzes the dephosphorylation of phosphoinositides. The transmembrane voltage sensor is connected to the phosphatase through a short linker region, and phosphatase activity is induced upon membrane depolarization. Although the detailed molecular characteristics of the voltage sensor domain and the enzyme region have been revealed, little is known how these two regions are coupled. In addition, it is important to know whether mechanism for coupling between the voltage sensor domain and downstream effector function is shared among other voltage sensor domain-containing proteins. Recent studies in which specific amino acid sites were genetically labeled using a fluorescent unnatural amino acid have enabled detection of the local structural changes in the cytoplasmic region of Ciona intestinalis VSP that occur with a change in membrane potential. The results of those studies provide novel insight into how the enzyme activity of the cytoplasmic region of VSP is regulated by the voltage sensor domain.

Domain-to-domain coupling in voltage-sensing phosphatase

PubMed Central

Sakata, Souhei; Matsuda, Makoto; Kawanabe, Akira; Okamura, Yasushi

2017-01-01

Voltage-sensing phosphatase (VSP) consists of a transmembrane voltage sensor and a cytoplasmic enzyme region. The enzyme region contains the phosphatase and C2 domains, is structurally similar to the tumor suppressor phosphatase PTEN, and catalyzes the dephosphorylation of phosphoinositides. The transmembrane voltage sensor is connected to the phosphatase through a short linker region, and phosphatase activity is induced upon membrane depolarization. Although the detailed molecular characteristics of the voltage sensor domain and the enzyme region have been revealed, little is known how these two regions are coupled. In addition, it is important to know whether mechanism for coupling between the voltage sensor domain and downstream effector function is shared among other voltage sensor domain-containing proteins. Recent studies in which specific amino acid sites were genetically labeled using a fluorescent unnatural amino acid have enabled detection of the local structural changes in the cytoplasmic region of Ciona intestinalis VSP that occur with a change in membrane potential. The results of those studies provide novel insight into how the enzyme activity of the cytoplasmic region of VSP is regulated by the voltage sensor domain. PMID:28744425

Skyrmion domain wall collision and domain wall-gated skyrmion logic

NASA Astrophysics Data System (ADS)

Xing, Xiangjun; Pong, Philip W. T.; Zhou, Yan

2016-08-01

Skyrmions and domain walls are significant spin textures of great technological relevance to magnetic memory and logic applications, where they can be used as carriers of information. The unique topology of skyrmions makes them display emergent dynamical properties as compared with domain walls. Some studies have demonstrated that the two topologically inequivalent magnetic objects could be interconverted by using cleverly designed geometric structures. Here, we numerically address the skyrmion domain wall collision in a magnetic racetrack by introducing relative motion between the two objects based on a specially designed junction. An electric current serves as the driving force that moves a skyrmion toward a trapped domain wall pair. We see different types of collision dynamics depending on the driving parameters. Most importantly, the modulation of skyrmion transport using domain walls is realized in this system, allowing a set of domain wall-gated logical NOT, NAND, and NOR gates to be constructed. This work provides a skyrmion-based spin-logic architecture that is fully compatible with racetrack memories.

MIT domain of Vps4 is a Ca2+-dependent phosphoinositide-binding domain.

PubMed

Iwaya, Naoko; Takasu, Hirotoshi; Goda, Natsuko; Shirakawa, Masahiro; Tanaka, Toshiki; Hamada, Daizo; Hiroaki, Hidekazu

2013-05-01

The microtubule interacting and trafficking (MIT) domain is a small protein module that is conserved in proteins of diverged function, such as Vps4, spastin and sorting nexin 15 (SNX15). The molecular function of the MIT domain is protein-protein interaction, in which the domain recognizes peptides containing MIT-interacting motifs. Recently, we identified an evolutionarily related domain, 'variant' MIT domain at the N-terminal region of the microtubule severing enzyme katanin p60. We found that the domain was responsible for binding to microtubules and Ca(2+). Here, we have examined whether the authentic MIT domains also bind Ca(2+). We found that the loop between the first and second α-helices of the MIT domain binds a Ca(2+) ion. Furthermore, the MIT domains derived from Vps4b and SNX15a showed phosphoinositide-binding activities in a Ca(2+)-dependent manner. We propose that the MIT domain is a novel membrane-associating domain involved in endosomal trafficking.

Predicting detection performance with model observers: Fourier domain or spatial domain?

PubMed

Chen, Baiyu; Yu, Lifeng; Leng, Shuai; Kofler, James; Favazza, Christopher; Vrieze, Thomas; McCollough, Cynthia

2016-02-27

The use of Fourier domain model observer is challenged by iterative reconstruction (IR), because IR algorithms are nonlinear and IR images have noise texture different from that of FBP. A modified Fourier domain model observer, which incorporates nonlinear noise and resolution properties, has been proposed for IR and needs to be validated with human detection performance. On the other hand, the spatial domain model observer is theoretically applicable to IR, but more computationally intensive than the Fourier domain method. The purpose of this study is to compare the modified Fourier domain model observer to the spatial domain model observer with both FBP and IR images, using human detection performance as the gold standard. A phantom with inserts of various low contrast levels and sizes was repeatedly scanned 100 times on a third-generation, dual-source CT scanner at 5 dose levels and reconstructed using FBP and IR algorithms. The human detection performance of the inserts was measured via a 2-alternative-forced-choice (2AFC) test. In addition, two model observer performances were calculated, including a Fourier domain non-prewhitening model observer and a spatial domain channelized Hotelling observer. The performance of these two mode observers was compared in terms of how well they correlated with human observer performance. Our results demonstrated that the spatial domain model observer correlated well with human observers across various dose levels, object contrast levels, and object sizes. The Fourier domain observer correlated well with human observers using FBP images, but overestimated the detection performance using IR images.

Predicting detection performance with model observers: Fourier domain or spatial domain?

PubMed Central

Chen, Baiyu; Yu, Lifeng; Leng, Shuai; Kofler, James; Favazza, Christopher; Vrieze, Thomas; McCollough, Cynthia

2016-01-01

The use of Fourier domain model observer is challenged by iterative reconstruction (IR), because IR algorithms are nonlinear and IR images have noise texture different from that of FBP. A modified Fourier domain model observer, which incorporates nonlinear noise and resolution properties, has been proposed for IR and needs to be validated with human detection performance. On the other hand, the spatial domain model observer is theoretically applicable to IR, but more computationally intensive than the Fourier domain method. The purpose of this study is to compare the modified Fourier domain model observer to the spatial domain model observer with both FBP and IR images, using human detection performance as the gold standard. A phantom with inserts of various low contrast levels and sizes was repeatedly scanned 100 times on a third-generation, dual-source CT scanner at 5 dose levels and reconstructed using FBP and IR algorithms. The human detection performance of the inserts was measured via a 2-alternative-forced-choice (2AFC) test. In addition, two model observer performances were calculated, including a Fourier domain non-prewhitening model observer and a spatial domain channelized Hotelling observer. The performance of these two mode observers was compared in terms of how well they correlated with human observer performance. Our results demonstrated that the spatial domain model observer correlated well with human observers across various dose levels, object contrast levels, and object sizes. The Fourier domain observer correlated well with human observers using FBP images, but overestimated the detection performance using IR images. PMID:27239086

Barriers and facilitators to hospital pharmacists' engagement in medication safety activities: a qualitative study using the theoretical domains framework.

PubMed

Mekonnen, Alemayehu B; McLachlan, Andrew J; Brien, Jo-Anne E; Mekonnen, Desalew; Abay, Zenahebezu

2018-01-01

Hospital pharmacists play a central role in medication safety activities. However, in Ethiopia, this role has been launched recently and little is known regarding the current status of this extended service. Using the Theoretical Domains Framework (TDF), we aimed to identify the barriers and facilitators to hospital pharmacists' engagement in medication safety activities across various public hospitals in the Amhara region of Ethiopia. Eight focus group discussions, using an interview guide that was drawn upon the TDF, were conducted with 44 hospital pharmacists to explore their beliefs regarding their involvement in clinical services. Group discussions were audio-recorded, transcribed verbatim, and analysed using directed content analysis based on the TDF. Relevant domains were identified by applying relevance criteria to each of the domains in the TDF. Content analysis revealed six domains that influence hospital pharmacists' engagement in medication safety activities. These domains included 'Knowledge', 'Skills', 'Environmental context and resources', 'Motivations and goals', 'Social influences' and 'Social/professional role'. Most hospital pharmacists believed knowledge gap was an issue, as was the lack of training and supportive skills although some expressed as they were competent enough for their skills in identifying medication related problems. Most participants were very much enthusiastic for their extended roles and were positive towards the future of the profession; however, competing priorities along with the lack of remuneration and awareness (of other health care professionals) regarding the profession's role were barriers to service delivery. There were also a number of resource constraints, such as staffing, infrastructure and government funding, and acceptance rate of pharmacist's recommendation that were likely to influence the clinical practice of pharmacists. Using the TDF , this study identified a wide range of barriers and facilitators to

Frequency domain analysis of noise in simple gene circuits

NASA Astrophysics Data System (ADS)

Cox, Chris D.; McCollum, James M.; Austin, Derek W.; Allen, Michael S.; Dar, Roy D.; Simpson, Michael L.

2006-06-01

Recent advances in single cell methods have spurred progress in quantifying and analyzing stochastic fluctuations, or noise, in genetic networks. Many of these studies have focused on identifying the sources of noise and quantifying its magnitude, and at the same time, paying less attention to the frequency content of the noise. We have developed a frequency domain approach to extract the information contained in the frequency content of the noise. In this article we review our work in this area and extend it to explicitly consider sources of extrinsic and intrinsic noise. First we review applications of the frequency domain approach to several simple circuits, including a constitutively expressed gene, a gene regulated by transitions in its operator state, and a negatively autoregulated gene. We then review our recent experimental study, in which time-lapse microscopy was used to measure noise in the expression of green fluorescent protein in individual cells. The results demonstrate how changes in rate constants within the gene circuit are reflected in the spectral content of the noise in a manner consistent with the predictions derived through frequency domain analysis. The experimental results confirm our earlier theoretical prediction that negative autoregulation not only reduces the magnitude of the noise but shifts its content out to higher frequency. Finally, we develop a frequency domain model of gene expression that explicitly accounts for extrinsic noise at the transcriptional and translational levels. We apply the model to interpret a shift in the autocorrelation function of green fluorescent protein induced by perturbations of the translational process as a shift in the frequency spectrum of extrinsic noise and a decrease in its weighting relative to intrinsic noise.

Domain-General and Domain-Specific Strategies for the Assessment of Distress Intolerance

PubMed Central

McHugh, R. Kathryn; Otto, Michael W.

2011-01-01

Recent research has provided evidence that distress intolerance—the perceived inability to tolerate distressing states—varies based on the domain of distress (e.g., pain, anxiety). Although domain-specific assessment strategies may provide information targeted to specific disorders or maladaptive behaviors, domain-general measures have the potential to facilitate comparisons across studies, disorders, and populations. The current study evaluated the utilization of self-report measures of distress intolerance as domain-general measures by examining their association with indices of behavioral avoidance and substance craving. Two groups of participants (N = 55) were recruited including a substance-dependent group and a comparison group equated based on the presence of an affective disorder. Results provided support for the validity of domain-general measures for assessing distress intolerance across varied domains. The importance of both domain-general and domain-specific measurement of distress intolerance is discussed. PMID:21823763

Extended output phasor representation of multi-spectral fluorescence lifetime imaging microscopy

PubMed Central

Campos-Delgado, Daniel U.; Navarro, O. Gutiérrez; Arce-Santana, E. R.; Jo, Javier A.

2015-01-01

In this paper, we investigate novel low-dimensional and model-free representations for multi-spectral fluorescence lifetime imaging microscopy (m-FLIM) data. We depart from the classical definition of the phasor in the complex plane to propose the extended output phasor (EOP) and extended phasor (EP) for multi-spectral information. The frequency domain properties of the EOP and EP are analytically studied based on a multiexponential model for the impulse response of the imaged tissue. For practical implementations, the EOP is more appealing since there is no need to perform deconvolution of the instrument response from the measured m-FLIM data, as in the case of EP. Our synthetic and experimental evaluations with m-FLIM datasets of human coronary atherosclerotic plaques show that low frequency indexes have to be employed for a distinctive representation of the EOP and EP, and to reduce noise distortion. The tissue classification of the m-FLIM datasets by EOP and EP also improves with low frequency indexes, and does not present significant differences by using either phasor. PMID:26114031

Alteration of the C-terminal ligand specificity of the erbin PDZ domain by allosteric mutational effects.

PubMed

Murciano-Calles, Javier; McLaughlin, Megan E; Erijman, Ariel; Hooda, Yogesh; Chakravorty, Nishant; Martinez, Jose C; Shifman, Julia M; Sidhu, Sachdev S

2014-10-23

Modulation of protein binding specificity is important for basic biology and for applied science. Here we explore how binding specificity is conveyed in PDZ (postsynaptic density protein-95/discs large/zonula occludens-1) domains, small interaction modules that recognize various proteins by binding to an extended C terminus. Our goal was to engineer variants of the Erbin PDZ domain with altered specificity for the most C-terminal position (position 0) where a Val is strongly preferred by the wild-type domain. We constructed a library of PDZ domains by randomizing residues in direct contact with position 0 and in a loop that is close to but does not contact position 0. We used phage display to select for PDZ variants that bind to 19 peptide ligands differing only at position 0. To verify that each obtained PDZ domain exhibited the correct binding specificity, we selected peptide ligands for each domain. Despite intensive efforts, we were only able to evolve Erbin PDZ domain variants with selectivity for the aliphatic C-terminal side chains Val, Ile and Leu. Interestingly, many PDZ domains with these three distinct specificities contained identical amino acids at positions that directly contact position 0 but differed in the loop that does not contact position 0. Computational modeling of the selected PDZ domains shows how slight conformational changes in the loop region propagate to the binding site and result in different binding specificities. Our results demonstrate that second-sphere residues could be crucial in determining protein binding specificity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Neuropsychological function after endovascular and neurosurgical treatment of subarachnoid hemorrhage: a systematic review and meta-analysis.

PubMed

Egeto, Peter; Loch Macdonald, R; Ornstein, Tisha J; Schweizer, Tom A

2018-03-01

OBJECTIVE Subarachnoid hemorrhage (SAH) is treated with either surgical clipping or endovascular coiling, though the latter is the preferred treatment method given its more favorable functional outcomes. However, neuropsychological functioning after treatment is rarely taken into account. In this meta-analysis, the authors synthesized relevant data from the literature and compared neuropsychological functioning in patients after coiling and clipping of SAH. They hypothesized that the coiled patients would outperform the clipped patients; that group differences would be greater with higher posterior circulation rupture rates, in older patients, and in more recent publications; that group differences would be smaller with greater rates of middle cerebral artery (MCA) rupture; and that anterior communicating artery (ACoA) rupture rates would not influence effect sizes. METHODS The MEDLINE, Embase, and PsycINFO databases were searched for clinical studies that compared neuropsychological functioning after either endovascular coiling or surgical clipping for SAH. Hedge's g and 95% confidence intervals were calculated using random effects models. Patients who had undergone coiling or clipping were compared on test performance in 8 neuropsychological domains: executive functions, language, attention/processing speed, verbal memory, visual memory, spatial memory, visuospatial functions, and intelligence. Patients were also compared with healthy controls, and meta-regressions were used to explore the relation between effect sizes and publication year, delay between treatment and neuropsychological testing, mean patient age, and rates of posterior circulation, ACoA, and MCA ruptures. RESULTS Thirteen studies with 396 clipped cases, 314 coiled cases, and 169 healthy controls were included in the study. The coil-treated patients outperformed the clip-treated patients on executive function (g = 0.17, 95% CI 0.08-0.25) and language tests (g = 0.23, 95% CI 0.07-0.39), and all

Spatially resolved mapping of electrical conductivity across individual domain (grain) boundaries in graphene.

PubMed

Clark, Kendal W; Zhang, X-G; Vlassiouk, Ivan V; He, Guowei; Feenstra, Randall M; Li, An-Ping

2013-09-24

All large-scale graphene films contain extended topological defects dividing graphene into domains or grains. Here, we spatially map electronic transport near specific domain and grain boundaries in both epitaxial graphene grown on SiC and CVD graphene on Cu subsequently transferred to a SiO2 substrate, with one-to-one correspondence to boundary structures. Boundaries coinciding with the substrate step on SiC exhibit a significant potential barrier for electron transport of epitaxial graphene due to the reduced charge transfer from the substrate near the step edge. Moreover, monolayer-bilayer boundaries exhibit a high resistance that can change depending on the height of substrate step coinciding at the boundary. In CVD graphene, the resistance of a grain boundary changes with the width of the disordered transition region between adjacent grains. A quantitative modeling of boundary resistance reveals the increased electron Fermi wave vector within the boundary region, possibly due to boundary induced charge density variation. Understanding how resistance change with domain (grain) boundary structure in graphene is a crucial first step for controlled engineering of defects in large-scale graphene films.

Phosphodiesterase 5 Inhibition Attenuates Cerebral Vasospasm and Improves Functional Recovery after Experimental Subarachnoid Hemorrhage

PubMed Central

Han, Byung Hee; Vellimana, Ananth Kesav; Zhou, Meng-Liang; Milner, Eric; Zipfel, Gregory Joseph

2014-01-01

Background Cerebral vasospasm is an independent predictor of poor outcome after subarachnoid hemorrhage (SAH). The nitric oxide-cyclic GMP (NO-cGMP) vasodilatory pathway is strongly implicated in its pathophysiology. Preliminary studies suggest that phosphodiesterase 5 (PDE5) – an enzyme that degrades cGMP – may play a role, as the PDE5 inhibitor sildenafil was found to reduce vasospasm after SAH. However, several questions that are critical when considering translational studies remain unanswered. Objective To elucidate the mechanism of action of sildenafil against vasospasm, and to assess whether sildenafil attenuates SAH-induced neuronal cell death, improves functional outcome after SAH, or causes significant physiological side effects when administered at therapeutically relevant doses. Methods SAH was induced via endovascular perforation in male C57BL6 mice. Beginning two hours later, mice received sildenafil citrate (0.7, 2 or 5mg/kg P.O. BID) or vehicle. Neurological outcome was assessed daily. Vasospasm was determined on post-SAH Day 3. Brain PDE5 expression and activity, cGMP content, neuronal cell death, arterial blood pressure (BP), and intracranial pressure (ICP) were examined. Results We found that PDE5 activity (but not expression) is increased after SAH, leading to decreased cGMP levels. Sildenafil attenuates this increase in PDE5 activity and restores cGMP levels after SAH. Post-SAH initiation of sildenafil was found to reduce vasospasm, decrease neuronal cell death, and markedly improve neurological outcome, without causing significant physiological side effects. Conclusion Sildenafil–an FDA-approved drug with a proven track record of safety in humans –is a promising new therapy for vasospasm and neurological deficits following SAH. PMID:21796010

Smoking and elevated blood pressure are the most important risk factors for subarachnoid hemorrhage in the Asia-Pacific region: an overview of 26 cohorts involving 306,620 participants.

PubMed

Feigin, Valery; Parag, Varsha; Lawes, Carlene M M; Rodgers, Anthony; Suh, Il; Woodward, Mark; Jamrozik, Konrad; Ueshima, Hirotsugu

2005-07-01

The cause of subarachnoid hemorrhage (SAH) is poorly understood and there are few large cohort studies of risk factors for SAH. We investigated the risk of SAH mortality and morbidity associated with common cardiovascular risk factors in the Asia-Pacific region and examined whether the strengths of these associations were different in Asian and Australasian (predominantly white) populations. Cohort studies were identified from Internet electronic databases, searches of proceedings of meetings, and personal communication. Hazard ratios (HRs) for systolic blood pressure (SBP), current smoking, total serum cholesterol, body mass index (BMI), and alcohol drinking were calculated from Cox models that were stratified by sex and cohort and adjusted for age at risk. Individual participant data from 26 prospective cohort studies (total number of participants 306,620) that reported incident cases of SAH (fatal and/or nonfatal) were available for analysis. During the median follow-up period of 8.2 years, a total of 236 incident cases of SAH were observed. Current smoking (HR, 2.4; 95% CI, 1.8 to 3.4) and SBP >140 mm Hg (HR, 2.0; 95% CI, 1.5 to 2.7) were significant and independent risk factors for SAH. Attributable risks of SAH associated with current smoking and elevated SBP (> or =140 mm Hg) were 29% and 19%, respectively. There were no significant associations between the risk of SAH and cholesterol, BMI, or drinking alcohol. The strength of the associations of the common cardiovascular risk factors with the risk of SAH did not differ much between Asian and Australasian regions. Cigarette smoking and SBP are the most important risk factors for SAH in the Asia-Pacific region.

Entrapment of metal clusters in metal-organic framework channels by extended hooks anchored at open metal sites.

PubMed

Zheng, Shou-Tian; Zhao, Xiang; Lau, Samuel; Fuhr, Addis; Feng, Pingyun; Bu, Xianhui

2013-07-17

Reported here are the new concept of utilizing open metal sites (OMSs) for architectural pore design and its practical implementation. Specifically, it is shown here that OMSs can be used to run extended hooks (isonicotinates in this work) from the framework walls to the channel centers to effect the capture of single metal ions or clusters, with the concurrent partitioning of the large channel spaces into multiple domains, alteration of the host-guest charge relationship and associated guest-exchange properties, and transfer of OMSs from the walls to the channel centers. The concept of the extended hook, demonstrated here in the multicomponent dual-metal and dual-ligand system, should be generally applicable to a range of framework types.

Apigenin protects blood-brain barrier and ameliorates early brain injury by inhibiting TLR4-mediated inflammatory pathway in subarachnoid hemorrhage rats.

PubMed

Zhang, Tingting; Su, Jingyuan; Guo, Bingyu; Wang, Kaiwen; Li, Xiaoming; Liang, Guobiao

2015-09-01

Early brain injury (EBI) following subarachnoid hemorrhage (SAH) is associated with high morbidity and mortality. Inflammation has been considered as the major contributor to brain damage after SAH. SAH induces a systemic increase in pro-inflammatory cytokines and chemokines. Disruption of blood-brain barrier (BBB) facilitates the influx of inflammatory cells. It has been reported that the activation of toll-like receptor 4 (TLR4)/NF-κB signaling pathway plays a vital role in the central nervous system diseases. Apigenin, a common plant flavonoid, possesses anti-inflammation effect. In this study, we focused on the effects of apigenin on EBI following SAH and its anti-inflammation mechanism. Our results showed that apigenin (20mg/kg) administration significantly attenuated EBI (including brain edema, BBB disruption, neurological deficient, severity of SAH, and cell apoptosis) after SAH in rats by suppressing the expression of TLR4, NF-κB and their downstream pro-inflammatory cytokines in the cortex and by up-regulating the expression of tight junction proteins of BBB. Double immunofluorescence staining demonstrated that TLR4 was activated following SAH in neurons, microglia cells, and endothelial cells but not in astrocytes. Apigenin could suppress the activation of TLR4 induced by SAH and inhibit apoptosis of cells in the cortex. These results suggested that apigenin could attenuate EBI after SAH in rats by suppressing TLR4-mediated inflammation and protecting against BBB disruption. Copyright © 2015 Elsevier B.V. All rights reserved.

Structure of phosphorylated UBL domain and insights into PINK1-orchestrated parkin activation.

PubMed

Aguirre, Jacob D; Dunkerley, Karen M; Mercier, Pascal; Shaw, Gary S

2017-01-10

Mutations in PARK2 and PARK6 genes are responsible for the majority of hereditary Parkinson's disease cases. These genes encode the E3 ubiquitin ligase parkin and the protein kinase PTEN-induced kinase 1 (PINK1), respectively. Together, parkin and PINK1 regulate the mitophagy pathway, which recycles damaged mitochondria following oxidative stress. Native parkin is inactive and exists in an autoinhibited state mediated by its ubiquitin-like (UBL) domain. PINK1 phosphorylation of serine 65 in parkin's UBL and serine 65 of ubiquitin fully activate ubiquitin ligase activity; however, a structural rationale for these observations is not clear. Here, we report the structure of the phosphorylated UBL domain from parkin. We find that destabilization of the UBL results from rearrangements to hydrophobic core packing that modify its structure. Altered surface electrostatics from the phosphoserine group disrupt its intramolecular association, resulting in poorer autoinhibition in phosphorylated parkin. Further, we show that phosphorylation of both the UBL domain and ubiquitin are required to activate parkin by releasing the UBL domain, forming an extended structure needed to facilitate E2-ubiquitin binding. Together, the results underscore the importance of parkin activation by the PINK1 phosphorylation signal and provide a structural picture of the unraveling of parkin's ubiquitin ligase potential.

Arctigenin, a Potent Ingredient of Arctium lappa L., Induces Endothelial Nitric Oxide Synthase and Attenuates Subarachnoid Hemorrhage-Induced Vasospasm through PI3K/Akt Pathway in a Rat Model

PubMed Central

Chang, Chih-Zen; Wu, Shu-Chuan; Chang, Chia-Mao; Kwan, Aij-Lie

2015-01-01

Upregulation of protein kinase B (PKB, also known as Akt) is observed within the cerebral arteries of subarachnoid hemorrhage (SAH) animals. This study is of interest to examine Arctigenin, a potent antioxidant, on endothelial nitric oxide synthase (eNOS) and Akt pathways in a SAH in vitro study. Basilar arteries (BAs) were obtained to examine phosphatidylinositol-3-kinase (PI3K), phospho-PI3K, Akt, phospho-Akt (Western blot) and morphological examination. Endothelins (ETs) and eNOS evaluation (Western blot and immunostaining) were also determined. Arctigenin treatment significantly alleviates disrupted endothelial cells and tortured internal elastic layer observed in the SAH groups (p < 0.01). The reduced eNOS protein and phospho-Akt expression in the SAH groups were relieved by the treatment of Arctigenin (p < 0.01). This result confirmed that Arctigenin might exert dural effects in preventing SAH-induced vasospasm through upregulating eNOS expression via the PI3K/Akt signaling pathway and attenuate endothelins after SAH. Arctigenin shows therapeutic promise in the treatment of cerebral vasospasm following SAH. PMID:26539501

Arctigenin, a Potent Ingredient of Arctium lappa L., Induces Endothelial Nitric Oxide Synthase and Attenuates Subarachnoid Hemorrhage-Induced Vasospasm through PI3K/Akt Pathway in a Rat Model.

PubMed

Chang, Chih-Zen; Wu, Shu-Chuan; Chang, Chia-Mao; Lin, Chih-Lung; Kwan, Aij-Lie

2015-01-01

Upregulation of protein kinase B (PKB, also known as Akt) is observed within the cerebral arteries of subarachnoid hemorrhage (SAH) animals. This study is of interest to examine Arctigenin, a potent antioxidant, on endothelial nitric oxide synthase (eNOS) and Akt pathways in a SAH in vitro study. Basilar arteries (BAs) were obtained to examine phosphatidylinositol-3-kinase (PI3K), phospho-PI3K, Akt, phospho-Akt (Western blot) and morphological examination. Endothelins (ETs) and eNOS evaluation (Western blot and immunostaining) were also determined. Arctigenin treatment significantly alleviates disrupted endothelial cells and tortured internal elastic layer observed in the SAH groups (p < 0.01). The reduced eNOS protein and phospho-Akt expression in the SAH groups were relieved by the treatment of Arctigenin (p < 0.01). This result confirmed that Arctigenin might exert dural effects in preventing SAH-induced vasospasm through upregulating eNOS expression via the PI3K/Akt signaling pathway and attenuate endothelins after SAH. Arctigenin shows therapeutic promise in the treatment of cerebral vasospasm following SAH.

Paravascular pathways contribute to vasculitis and neuroinflammation after subarachnoid hemorrhage independently of glymphatic control

PubMed Central

Luo, C; Yao, X; Li, J; He, B; Liu, Q; Ren, H; Liang, F; Li, M; Lin, H; Peng, J; Yuan, T F; Pei, Z; Su, H

2016-01-01

Subarachnoid hemorrhage (SAH) is a devastating disease with high mortality. The mechanisms underlying its pathological complications have not been fully identified. Here, we investigate the potential involvement of the glymphatic system in the neuropathology of SAH. We demonstrate that blood components rapidly enter the paravascular space following SAH and penetrate into the perivascular parenchyma throughout the brain, causing disastrous events such as cerebral vasospasm, delayed cerebral ischemia, microcirculation dysfunction and widespread perivascular neuroinflammation. Clearance of the paravascular pathway with tissue-type plasminogen activator ameliorates the behavioral deficits and alleviates histological injury of SAH. Interestingly, AQP4−/− mice showed no improvements in neurological deficits and neuroinflammation at day 7 after SAH compared with WT control mice. In conclusion, our study proves that the paravascular pathway dynamically mediates the pathological complications following acute SAH independently of glymphatic control. PMID:27031957

Paravascular pathways contribute to vasculitis and neuroinflammation after subarachnoid hemorrhage independently of glymphatic control.

PubMed

Luo, C; Yao, X; Li, J; He, B; Liu, Q; Ren, H; Liang, F; Li, M; Lin, H; Peng, J; Yuan, T F; Pei, Z; Su, H

2016-03-31

Subarachnoid hemorrhage (SAH) is a devastating disease with high mortality. The mechanisms underlying its pathological complications have not been fully identified. Here, we investigate the potential involvement of the glymphatic system in the neuropathology of SAH. We demonstrate that blood components rapidly enter the paravascular space following SAH and penetrate into the perivascular parenchyma throughout the brain, causing disastrous events such as cerebral vasospasm, delayed cerebral ischemia, microcirculation dysfunction and widespread perivascular neuroinflammation. Clearance of the paravascular pathway with tissue-type plasminogen activator ameliorates the behavioral deficits and alleviates histological injury of SAH. Interestingly, AQP4(-/-) mice showed no improvements in neurological deficits and neuroinflammation at day 7 after SAH compared with WT control mice. In conclusion, our study proves that the paravascular pathway dynamically mediates the pathological complications following acute SAH independently of glymphatic control.

Melatonin mitigate cerebral vasospasm after experimental subarachnoid hemorrhage: a study of synchrotron radiation angiography

NASA Astrophysics Data System (ADS)

Cai, J.; He, C.; Chen, L.; Han, T.; Huang, S.; Huang, Y.; Bai, Y.; Bao, Y.; Zhang, H.; Ling, F.

2013-06-01

Cerebral vasospasm (CV) after subarachnoid hemorrhage (SAH) is a devastating and unsolved clinical issue. In this study, the rat models, which had been induced SAH by prechiasmatic cistern injection, were treated with melatonin. Synchrotron radiation angiography (SRA) was employed to detect and evaluate CV of animal models. Neurological scoring and histological examinations were used to assess the neurological deficits and CV as well. Using SRA techniques and histological analyses, the anterior cerebral artery diameters of SAH rats with melatonin administration were larger than those without melatonin treatment (p < 0.05). The neurological deficits of SAH rats treated with melatonin were less than those without melatonin treatment (p < 0.05). We concluded that SRA was a precise and in vivo tool to observe and evaluate CV of SAH rats; intraperitoneally administration of melatonin could mitigate CV after experimental SAH.

Changes in the level of cardiac troponine and disorders in pulmonary gas exchange as predictors of short- and long-term outcomes of patients with aneurysm subarachnoid haemorrhage.

PubMed

Burzyńska, Małgorzata; Uryga, Agnieszka; Kasprowicz, Magdalena; Kędziora, Jarosław; Szewczyk, Ewa; Woźniak, Jowita; Jarmundowicz, Włodzimierz; Kübler, Andrzej

2017-12-01

Cardiopulmonary abnormalities are common after aneurysmal subarachnoid haemorrhage (aSAH). However, the relationship between short- and long-term outcome is poorly understood. In this paper, we present how cardiac troponine elevations (cTnI) and pulmonary disorders are associated with short- and long-term outcomes assessed by the Glasgow Outcome Scale (GOS) and Extended Glasgow Outcome Scale (GOSE). A total of 104 patients diagnosed with aSAH were analysed in the study. The non-parametric U Mann-Whitney test was used to evaluate the difference between good (GOS IV-V, GOSE V-VIII) and poor (GOS I-III, GOSE I-IV) outcomes in relation to cTnI elevation and pulmonary disorders. Outcome was assessed at discharge from the hospital, and then followed up 6 and 12 months later. Pulmonary disorders were determined by the PaO 2 /FiO 2 ratio and radiography. The areas under the ROC curves (AUCs) were used to determine the predictive power of these factors. In the group with good short-term outcomes cTnI elevation on the second day after aSAH was significantly lower (p = .00007) than in patients with poor short-term outcomes. The same trend was observed after 6 months, although there were different results 12 months from the onset (p = .024 and n.s., respectively). A higher peak of cTnI was observed in the group with a pathological X-ray (p = .008) and pathological PaO 2 /FiO 2 ratio (p ≪ .001). cTnI was an accurate predictor of short-term outcomes (AUC = 0.741, p ≪ .001) and the outcome after 6 months (AUC = 0.688, p = .015). The results showed that cardiopulmonary abnormalities perform well as predictive factors for short- and long-term outcomes after aSAH.

Extended synaptotagmins are Ca2+-dependent lipid transfer proteins at membrane contact sites.

PubMed

Yu, Haijia; Liu, Yinghui; Gulbranson, Daniel R; Paine, Alex; Rathore, Shailendra S; Shen, Jingshi

2016-04-19

Organelles are in constant communication with each other through exchange of proteins (mediated by trafficking vesicles) and lipids [mediated by both trafficking vesicles and lipid transfer proteins (LTPs)]. It has long been known that vesicle trafficking can be tightly regulated by the second messenger Ca(2+), allowing membrane protein transport to be adjusted according to physiological demands. However, it remains unclear whether LTP-mediated lipid transport can also be regulated by Ca(2+) In this work, we show that extended synaptotagmins (E-Syts), poorly understood membrane proteins at endoplasmic reticulum-plasma membrane contact sites, are Ca(2+)-dependent LTPs. Using both recombinant and endogenous mammalian proteins, we discovered that E-Syts transfer glycerophospholipids between membrane bilayers in the presence of Ca(2+) E-Syts use their lipid-accommodating synaptotagmin-like mitochondrial lipid binding protein (SMP) domains to transfer lipids. However, the SMP domains themselves cannot transport lipids unless the two membranes are tightly tethered by Ca(2+)-bound C2 domains. Strikingly, the Ca(2+)-regulated lipid transfer activity of E-Syts was fully recapitulated when the SMP domain was fused to the cytosolic domain of synaptotagmin-1, the Ca(2+)sensor in synaptic vesicle fusion, indicating that a common mechanism of membrane tethering governs the Ca(2+)regulation of lipid transfer and vesicle fusion. Finally, we showed that microsomal vesicles isolated from mammalian cells contained robust Ca(2+)-dependent lipid transfer activities, which were mediated by E-Syts. These findings established E-Syts as a novel class of LTPs and showed that LTP-mediated lipid trafficking, like vesicular transport, can be subject to tight Ca(2+)regulation.

A novel disulfide bond in the SH2 Domain of the C-terminal Src kinase controls catalytic activity.

PubMed

Mills, Jamie E; Whitford, Paul C; Shaffer, Jennifer; Onuchic, Jose N; Adams, Joseph A; Jennings, Patricia A

2007-02-02

The SH2 domain of the C-terminal Src kinase [Csk] contains a unique disulfide bond that is not present in other known SH2 domains. To investigate whether this unusual disulfide bond serves a novel function, the effects of disulfide bond formation on catalytic activity of the full-length protein and on the structure of the SH2 domain were investigated. The kinase activity of full-length Csk decreases by an order of magnitude upon formation of the disulfide bond in the distal SH2 domain. NMR spectra of the fully oxidized and fully reduced SH2 domains exhibit similar chemical shift patterns and are indicative of similar, well-defined tertiary structures. The solvent-accessible disulfide bond in the isolated SH2 domain is highly stable and far from the small lobe of the kinase domain. However, reduction of this bond results in chemical shift changes of resonances that map to a cluster of residues that extend from the disulfide bond across the molecule to a surface that is in direct contact with the small lobe of the kinase domain in the intact molecule. Normal mode analyses and molecular dynamics calculations suggest that disulfide bond formation has large effects on residues within the kinase domain, most notably within the active-site cleft. Overall, the data indicate that reversible cross-linking of two cysteine residues in the SH2 domain greatly impacts catalytic function and interdomain communication in Csk.

Accurate and efficient seismic data interpolation in the principal frequency wavenumber domain

NASA Astrophysics Data System (ADS)

Wang, Benfeng; Lu, Wenkai

2017-12-01

Seismic data irregularity caused by economic limitations, acquisition environmental constraints or bad trace elimination, can decrease the performance of the below multi-channel algorithms, such as surface-related multiple elimination (SRME), though some can overcome the irregularity defects. Therefore, accurate interpolation to provide the necessary complete data is a pre-requisite, but its wide applications are constrained because of its large computational burden for huge data volume, especially in 3D explorations. For accurate and efficient interpolation, the curvelet transform- (CT) based projection onto convex sets (POCS) method in the principal frequency wavenumber (PFK) domain is introduced. The complex-valued PF components can characterize their original signal with a high accuracy, but are at least half the size, which can help provide a reasonable efficiency improvement. The irregularity of the observed data is transformed into incoherent noise in the PFK domain, and curvelet coefficients may be sparser when CT is performed on the PFK domain data, enhancing the interpolation accuracy. The performance of the POCS-based algorithms using complex-valued CT in the time space (TX), principal frequency space, and PFK domains are compared. Numerical examples on synthetic and field data demonstrate the validity and effectiveness of the proposed method. With less computational burden, the proposed method can achieve a better interpolation result, and it can be easily extended into higher dimensions.

Quantum model of a hysteresis in a single-domain magnetically soft ferromagnetic

NASA Astrophysics Data System (ADS)

Ignatiev, V. K.; Lebedev, N. G.; Orlov, A. A.

2018-01-01

A quantum model of a single-domain magnetically soft ferromagnetic is proposed. The α-Fe crystal in a state of the saturation magnetization and a variable magnetic field is considered as a sample. The method of an effective Hamiltonian, including the operators of the Zeeman energy, the spin-orbit interaction and the interaction with the crystal field, is used in the model. An expansion of trial single-electron wave function in a series in small parameter of the spin-orbit interaction is suggested to account for the magnetic anisotropy. Within the framework of the Heisenberg representation, the nonlinear equations of motion for the magnetization and the orbital moment of single domain are obtained. Parameters of the modelling Hamiltonian are found from a comparison with experimental data on the magnetic anisotropy of iron. A phenomenological term of the magnetic friction is introduced into equation of the magnetization motion. Nonlinear equations are solved numerically by the Runge-Kutta method. A dependence of the single domain magnetization on magnetic field intensity has a characteristic form of a hysteresis loop which parameters are quantitatively coordinated with experimental data of researches of magnetic properties of nanoparticles of iron and iron oxide. The method is extended for modelling the magnetization dynamics of multi-domain ferromagnetic in the approximation of a strong crystal field.

Ratchet Effects and Domain Wall Energy Landscapes in Amorphous Magnetic Films with 2D Arrays of Asymmetric Holes

NASA Astrophysics Data System (ADS)

Martin, J. I.; Alija, A.; Sobrado, I.; Perez-Junquera, A.; Rodriguez-Rodriguez, G.; Velez, M.; Alameda, J. M.; Marconi, V. I.; Kolton, A. B.; Parrondo, J. M. R.

2009-03-01

The driven motion of domain walls in extended magnetic films patterned with 2D arrays of asymmetric holes has been found to be subject to two different crossed ratchet effects [1] which results in an inversion of the sign of domain wall motion rectification as a function of the applied magnetic field. This effect can be understood in terms of the competition between drive, elasticity and asymmetric pinning as revealed by a simple 4̂-model. In order to optimize the asymmetric hole design, the relevant energy landscapes for domain wall motion across the array of asymmetric holes have been calculated by micromagnetic simulations as a function of array geometrical characteristics. The effects of a transverse magnetic field on these two crossed ratchet effects will also be discussed in terms of the decrease in domain wall energy per unit area and of the modifications in the magnetostatic barriers for domain wall pinning at the asymmetric inclusions. Work supported by Spanish MICINN.[1] A. Perez-Junquera et al, Phys. Rev. Lett. 100 (2008) 037203

Reductive evolution and the loss of PDC/PAS domains from the genus Staphylococcus

PubMed Central

2013-01-01

tremendous amount of variation in the number of PDC/PAS-containing proteins within genera. This variation extended to the Staphylococcus genus, which had between 6 and 9 PDC/PAS proteins and some of these appear to be previously undescribed signaling proteins. This latter point is important because most staphylococcal proteins that contain PDC/PAS domains regulate virulence factor synthesis or antibiotic resistance. PMID:23902280

Reductive evolution and the loss of PDC/PAS domains from the genus Staphylococcus.

PubMed

Shah, Neethu; Gaupp, Rosmarie; Moriyama, Hideaki; Eskridge, Kent M; Moriyama, Etsuko N; Somerville, Greg A

2013-07-31

number of PDC/PAS-containing proteins within genera. This variation extended to the Staphylococcus genus, which had between 6 and 9 PDC/PAS proteins and some of these appear to be previously undescribed signaling proteins. This latter point is important because most staphylococcal proteins that contain PDC/PAS domains regulate virulence factor synthesis or antibiotic resistance.

A new principle technic for the transformation from frequency domain to time domain

NASA Astrophysics Data System (ADS)

Gao, Ben-Qing

2017-03-01

A principle technic for the transformation from frequency domain to time domain is presented. Firstly, a special type of frequency domain transcendental equation is obtained for an expected frequency domain parameter which is a rational or irrational fraction expression. Secondly, the inverse Laplace transformation is performed. When the two time-domain factors corresponding to the two frequency domain factors at two sides of frequency domain transcendental equation are known quantities, a time domain transcendental equation is reached. At last, the expected time domain parameter corresponding to the expected frequency domain parameter can be solved by the inverse convolution process. Proceeding from rational or irrational fraction expression, all solving process is provided. In the meantime, the property of time domain sequence is analyzed and the strategy for choosing the parameter values is described. Numerical examples are presented to verify the proposed theory and technic. Except for rational or irrational fraction expressions, examples of complex relative permittivity of water and plasma are used as verification method. The principle method proposed in the paper can easily solve problems which are difficult to be solved by Laplace transformation.

Extending Automatic Parallelization to Optimize High-Level Abstractions for Multicore

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

Liao, C; Quinlan, D J; Willcock, J J

2008-12-12

Automatic introduction of OpenMP for sequential applications has attracted significant attention recently because of the proliferation of multicore processors and the simplicity of using OpenMP to express parallelism for shared-memory systems. However, most previous research has only focused on C and Fortran applications operating on primitive data types. C++ applications using high-level abstractions, such as STL containers and complex user-defined types, are largely ignored due to the lack of research compilers that are readily able to recognize high-level object-oriented abstractions and leverage their associated semantics. In this paper, we automatically parallelize C++ applications using ROSE, a multiple-language source-to-source compiler infrastructuremore » which preserves the high-level abstractions and gives us access to their semantics. Several representative parallelization candidate kernels are used to explore semantic-aware parallelization strategies for high-level abstractions, combined with extended compiler analyses. Those kernels include an array-base computation loop, a loop with task-level parallelism, and a domain-specific tree traversal. Our work extends the applicability of automatic parallelization to modern applications using high-level abstractions and exposes more opportunities to take advantage of multicore processors.« less

Radiation comb generation with extended Josephson junctions

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

Solinas, P., E-mail: paolo.solinas@spin.cnr.it; Bosisio, R., E-mail: riccardo.bosisio@nano.cnr.it; NEST, Instituto Nanoscienze-CNR and Scuola Normale Superiore, I-56127 Pisa

2015-09-21

We propose the implementation of a Josephson radiation comb generator based on an extended Josephson junction subject to a time dependent magnetic field. The junction critical current shows known diffraction patterns and determines the position of the critical nodes when it vanishes. When the magnetic flux passes through one of such critical nodes, the superconducting phase must undergo a π-jump to minimize the Josephson energy. Correspondingly, a voltage pulse is generated at the extremes of the junction. Under periodic driving, this allows us to produce a comb-like voltage pulses sequence. In the frequency domain, it is possible to generate upmore » to hundreds of harmonics of the fundamental driving frequency, thus mimicking the frequency comb used in optics and metrology. We discuss several implementations through a rectangular, cylindrical, and annular junction geometries, allowing us to generate different radiation spectra and to produce an output power up to 10 pW at 50 GHz for a driving frequency of 100 MHz.« less

A Logic for Inclusion of Administrative Domains and Administrators in Multi-domain Authorization

NASA Astrophysics Data System (ADS)

Iranmanesh, Zeinab; Amini, Morteza; Jalili, Rasool

Authorization policies for an administrative domain or a composition of multiple domains in multi-domain environments are determined by either one administrator or multiple administrators' cooperation. Several logic-based models for multi-domain environments' authorization have been proposed; however, they have not considered administrators and administrative domains in policies' representation. In this paper, we propose the syntax, proof theory, and semantics of a logic for multi-domain authorization policies including administrators and administrative domains. Considering administrators in policies provides the possibility of presenting composite administration having applicability in many collaborative applications. Indeed, administrators and administrative domains stated in policies can be used in authorization. The presented logic is based on modal logic and utilizes two calculi named the calculus of administrative domains and the calculus of administrators. It is also proved that the logic is sound. A case study is presented signifying the logic application in practical projects.

Extending the half-life of a fab fragment through generation of a humanized anti-human serum albumin Fv domain: An investigation into the correlation between affinity and serum half-life.

PubMed

Adams, Ralph; Griffin, Laura; Compson, Joanne E; Jairaj, Mark; Baker, Terry; Ceska, Tom; West, Shauna; Zaccheo, Oliver; Davé, Emma; Lawson, Alastair Dg; Humphreys, David P; Heywood, Sam

2016-10-01

We generated an anti-albumin antibody, CA645, to link its Fv domain to an antigen-binding fragment (Fab), thereby extending the serum half-life of the Fab. CA645 was demonstrated to bind human, cynomolgus, and mouse serum albumin with similar affinity (1-7 nM), and to bind human serum albumin (HSA) when it is in complex with common known ligands. Importantly for half-life extension, CA645 binds HSA with similar affinity within the physiologically relevant range of pH 5.0 - pH 7.4, and does not have a deleterious effect on the binding of HSA to neonatal Fc receptor (FcRn). A crystal structure of humanized CA645 Fab in complex with HSA was solved and showed that CA645 Fab binds to domain II of HSA. Superimposition with the crystal structure of FcRn bound to HSA confirmed that CA645 does not block HSA binding to FcRn. In mice, the serum half-life of humanized CA645 Fab is 84.2 h. This is a significant extension in comparison with < 1 h for a non-HSA binding CA645 Fab variant. The Fab-HSA structure was used to design a series of mutants with reduced affinity to investigate the correlation between the affinity for albumin and serum half-life. Reduction in the affinity for MSA by 144-fold from 2.2 nM to 316 nM had no effect on serum half-life. Strikingly, despite a reduction in affinity to 62 µM, an extension in serum half-life of 26.4 h was still obtained. CA645 Fab and the CA645 Fab-HSA complex have been deposited in the Protein Data Bank (PDB) with accession codes, 5FUZ and 5FUO, respectively.

Three case studies of the GasNet model in discrete domains.

PubMed

Santos, C L; de Oliveira, P P; Husbands, P; Souza, C R

2001-06-01

A new neural network model - the GasNet - has been recently reported in the literature, which, in addition to the traditional electric type, point-to-point communication between units, also uses communication through a diffilsable chemical modulator. Here we assess the applicability of this model in three different scenarios, the XOR problem, a food gathering task for a simulated robot, and a docking task for a virtual spaceship. All of them represent discrete domains, a contrast with the one where the GasNet was originally introduced, which had an essentially continuous nature. These scenarios are well-known benchmark problems from the literature and, since they exhibit varying degrees of complexity, they impose distinct performance demands on the GasNet. The experiments were primarily intended to better understand the model, by extending the original problem domain where GasNet was introduced. The results reported point at some difficulties with the current GasNet model.

Extended time observations of California marine stratocumulus clouds from GOES for July 1983-1987

NASA Technical Reports Server (NTRS)

Minnis, Patrick; Harrison, Edwin F.; Young, David F.

1990-01-01

One of the goals of the First ISCCP Regional Experiment (FIRE) is to relate the relatively small scale (spatial and temporal) Intensive Field Observations (IFO) to larger time and space domains embodied in the Extended Time Observations (ETO) phase of the experiment. The data analyzed as part of the ETO are to be used to determine some climatological features of the limited area which encompasses the Marine Stratocumulus IFO which took place between 29 June and 19 July 1987 off the coast of southern California.

6-Mercaptopurine reverses experimental vasospasm and alleviates the production of endothelins in NO-independent mechanism-a laboratory study.

PubMed

Chang, Chih-Zen; Wu, Shu-Chuan; Kwan, Aij-Lie; Lin, Chih-Long; Hwang, Shiuh-Lin

2011-04-01

Increased endothelin-1 (ET-1) production and diminished nitric oxide synthase (NOS) bioavailability has been observed in aneurysmal subarachnoid hemorrhage (SAH). The authors previously found that 6-mercaptopurine (6-mp) is effective in preventing and reversing arterial narrowing in a rodent SAH model. This present study is of interest to examine the effect of 6-mp on ET-1/endothelial nitric oxide synthase (eNOS) in this animal model. A rodent double hemorrhage SAH model was employed. Animals were randomly assigned to six groups (sham, SAH only, vehicle, 0.5, 1.0 and 2 mg kg(-1) day(-1) 6-mp treatment). Monoclonal CD45 immunostaining was utilized to evaluate monocytes and microglia. The level of pro-inflammatory cytokines, such as IL-1, IL-6 and TNF-α(RT-PCR), and ET-1 (ELISA) was measured. The basilar arteries (BAs) were harvested and sliced, and their cross-sectional areas were determined. Radiolabeled NOS assay kit was applied to detect eNOS. Morphologically, convolution of internal elastic lamina, endothelial cells distortion, and necrotic smooth muscle were prevalently present in the basilar artery of SAH groups, which was absent in the 1 and 2 mg kg(-1) day(-1) 6-mp plus SAH group or the healthy controls. Significant vasospasm was noted in the vehicle group (lumen patency, 54.6%, p ≤ 0.01 compared with the sham group), but it was less prominent in the 2 mg kg(-1) day(-1) 6-mp treatment group (lumen patency, 87.6%, p < 0.05). In addition, administration with 2 mg kg(-1) day(-1) 6-mp reduced cytokine levels by 11%, 47%, and 34% for IL-1, IL-6, and TNF-α, respectively, and increased ET-1 levels were found in all the animals subject to SAH (SAH only, SAH plus vehicle, SAH plus 0.5 and 1.0 mg kg(-1) day(-1) 6-mp) except in the 2 mg kg(-1) day(-1) 6-mp SAH group, when compared with the healthy controls (no SAH). Meanwhile, treatment with 6-mp did not induce the levels of expressed eNOS in BAs in the 6-mp groups (0.5, 1.0, and 2 mg kg(-1) day(-1) 6-mp

Transmission XMCD-PEEM imaging of an engineered vertical FEBID cobalt nanowire with a domain wall

NASA Astrophysics Data System (ADS)

Wartelle, A.; Pablo-Navarro, J.; Staňo, M.; Bochmann, S.; Pairis, S.; Rioult, M.; Thirion, C.; Belkhou, R.; de Teresa, J. M.; Magén, C.; Fruchart, O.

2018-01-01

Using focused electron-beam-induced deposition, we fabricate a vertical, platinum-coated cobalt nanowire with a controlled three-dimensional structure. The latter is engineered to feature bends along the height: these are used as pinning sites for domain walls, which are obtained at remanence after saturation of the nanostructure in a horizontally applied magnetic field. The presence of domain walls is investigated using x-ray magnetic circular dichroism (XMCD) coupled to photoemission electron microscopy (PEEM). The vertical geometry of our sample combined with the low incidence of the x-ray beam produce an extended wire shadow which we use to recover the wire’s magnetic configuration. In this transmission configuration, the whole sample volume is probed, thus circumventing the limitation of PEEM to surfaces. This article reports on the first study of magnetic nanostructures standing perpendicular to the substrate with XMCD-PEEM. The use of this technique in shadow mode enabled us to confirm the presence of a domain wall without direct imaging of the nanowire.

Reconstituting protein interaction networks using parameter-dependent domain-domain interactions

PubMed Central

2013-01-01

Background We can describe protein-protein interactions (PPIs) as sets of distinct domain-domain interactions (DDIs) that mediate the physical interactions between proteins. Experimental data confirm that DDIs are more consistent than their corresponding PPIs, lending support to the notion that analyses of DDIs may improve our understanding of PPIs and lead to further insights into cellular function, disease, and evolution. However, currently available experimental DDI data cover only a small fraction of all existing PPIs and, in the absence of structural data, determining which particular DDI mediates any given PPI is a challenge. Results We present two contributions to the field of domain interaction analysis. First, we introduce a novel computational strategy to merge domain annotation data from multiple databases. We show that when we merged yeast domain annotations from six annotation databases we increased the average number of domains per protein from 1.05 to 2.44, bringing it closer to the estimated average value of 3. Second, we introduce a novel computational method, parameter-dependent DDI selection (PADDS), which, given a set of PPIs, extracts a small set of domain pairs that can reconstruct the original set of protein interactions, while attempting to minimize false positives. Based on a set of PPIs from multiple organisms, our method extracted 27% more experimentally detected DDIs than existing computational approaches. Conclusions We have provided a method to merge domain annotation data from multiple sources, ensuring large and consistent domain annotation for any given organism. Moreover, we provided a method to extract a small set of DDIs from the underlying set of PPIs and we showed that, in contrast to existing approaches, our method was not biased towards DDIs with low or high occurrence counts. Finally, we used these two methods to highlight the influence of the underlying annotation density on the characteristics of extracted DDIs. Although

Bromovirus RNA Replication Compartment Formation Requires Concerted Action of 1a's Self-Interacting RNA Capping and Helicase Domains

PubMed Central

Diaz, Arturo; Gallei, Andreas

2012-01-01

All positive-strand RNA viruses replicate their genomes in association with rearranged intracellular membranes such as single- or double-membrane vesicles. Brome mosaic virus (BMV) RNA synthesis occurs in vesicular endoplasmic reticulum (ER) membrane invaginations, each induced by many copies of viral replication protein 1a, which has N-terminal RNA capping and C-terminal helicase domains. Although the capping domain is responsible for 1a membrane association and ER targeting, neither this domain nor the helicase domain was sufficient to induce replication vesicle formation. Moreover, despite their potential for mutual interaction, the capping and helicase domains showed no complementation when coexpressed in trans. Cross-linking showed that the capping and helicase domains each form trimers and larger multimers in vivo, and the capping domain formed extended, stacked, hexagonal lattices in vivo. Furthermore, coexpressing the capping domain blocked the ability of full-length 1a to form replication vesicles and replicate RNA and recruited full-length 1a into mixed hexagonal lattices with the capping domain. Thus, BMV replication vesicle formation and RNA replication depend on the direct linkage and concerted action of 1a's self-interacting capping and helicase domains. In particular, the capping domain's strong dominant-negative effects showed that the ability of full-length 1a to form replication vesicles was highly sensitive to disruption by non-productively titrating lattice-forming self-interactions of the capping domain. These and other findings shed light on the roles and interactions of 1a domains in replication compartment formation and support prior results suggesting that 1a induces replication vesicles by forming a capsid-like interior shell. PMID:22090102

Global Federation of Data Services in Seismology: Extending the Concept to Interdisciplinary Science

NASA Astrophysics Data System (ADS)

Ahern, T. K.; Trabant, C. M.; Stults, M.; Van Fossen, M.

2015-12-01

The International Federation of Digital Seismograph Networks (FDSN) sets international standards, formats, and access protocols for global seismology. Recently the availability of an FDSN standard for web services has enabled the development of a federated model of data access. With a growing number of internationally distributed data centers supporting identical web services the task of federation is now fully realizable. This presentation will highlight the advances the seismological community has made in the past year towards federated access to seismological data including waveforms, earthquake event catalogs, and metadata describing seismic stations. As part of the NSF EarthCube project, IRIS and its partners have been extending the concept of standard web services to other domains. Our primary partners include Lamont Doherty Earth Observatory (marine geophysics), Caltech (tectonic plate reconstructions), SDSC (hydrology), UNAVCO (geodesy), and Unidata (atmospheric sciences). Additionally IRIS is working with partners at NOAA's NGDC, NEON, UTEP, WOVODAT, Intermagnet, Global Geodynamics Program, and the Ocean Observatory Initiative (OOI) to develop web services for those domains. The ultimate goal is to allow discovery, access, and utilization of cross-domain data sources. IRIS and a variety of US and European partners have been involved in the Cooperation between Europe and the US (CoopEUS) project where interdisciplinary data integration is a key topic.

Low Temperature Extends the Lifespan of Bursaphelenchus xylophilus through the cGMP Pathway

PubMed Central

Wang, Bowen; Ma, Ling; Wang, Feng; Wang, Buyong; Hao, Xin; Xu, Jiayao; Ma, Yan

2017-01-01

The causal agent of pine wilt disease, pine wood nematode (PWN) (Bursaphelenchus xylophilus), revealed extended lifespan at low temperature. To discover the molecular mechanism of this phenomenon, we attempted to study the molecular characterization, transcript abundance, and functions of three genes of the cyclic guanosine monophosphate (cGMP) pathway from B. xylophilus. Three cGMP pathway genes were identified from B. xylophilus. Bioinformatic software was utilized to analyze the characteristics of the three putative proteins. Function of the three genes in cold tolerance was studied with RNA interference (RNAi). The results showed that the deduced protein of Bx-DAF-11 has an adenylate and guanylate cyclase catalytic domain, indicating an ability to bind to extracellular ligands and synthesizing cGMP. Both Bx-TAX-2 and Bx-TAX-4 have cyclic nucleotide-binding domains and ion transport protein domains, illustrating that they are cGMP-gated ion channels. The transcript level of Bx-daf-11, Bx-tax-2, and Bx-tax-4 increased at low temperature. The survival rates of three gene silenced B. xylophilus revealed a significant decrease at low temperature. This study illustrated that the cGMP pathway plays a key role in low-temperature-induced lifespan extension in B. xylophilus. PMID:29099744

Extended-bandwidth frequency sweeps of a distributed feedback laser using combined injection current and temperature modulation

NASA Astrophysics Data System (ADS)

Hefferman, Gerald; Chen, Zhen; Wei, Tao

2017-07-01

This article details the generation of an extended-bandwidth frequency sweep using a single, communication grade distributed feedback (DFB) laser. The frequency sweep is generated using a two-step technique. In the first step, injection current modulation is employed as a means of varying the output frequency of a DFB laser over a bandwidth of 99.26 GHz. A digital optical phase lock loop is used to lock the frequency sweep speed during current modulation, resulting in a linear frequency chirp. In the second step, the temperature of the DFB laser is modulated, resulting in a shifted starting laser output frequency. A laser frequency chirp is again generated beginning at this shifted starting frequency, resulting in a frequency-shifted spectrum relative to the first recorded data. This process is then repeated across a range of starting temperatures, resulting in a series of partially overlapping, frequency-shifted spectra. These spectra are then aligned using cross-correlation and combined using averaging to form a single, broadband spectrum with a total bandwidth of 510.9 GHz. In order to investigate the utility of this technique, experimental testing was performed in which the approach was used as the swept-frequency source of a coherent optical frequency domain reflectometry system. This system was used to interrogate an optical fiber containing a 20 point, 1-mm pitch length fiber Bragg grating, corresponding to a period of 100 GHz. Using this technique, both the periodicity of the grating in the frequency domain and the individual reflector elements of the structure in the time domain were resolved, demonstrating the technique's potential as a method of extending the sweeping bandwidth of semiconductor lasers for frequency-based sensing applications.

Extended-bandwidth frequency sweeps of a distributed feedback laser using combined injection current and temperature modulation.

PubMed

Hefferman, Gerald; Chen, Zhen; Wei, Tao

2017-07-01

This article details the generation of an extended-bandwidth frequency sweep using a single, communication grade distributed feedback (DFB) laser. The frequency sweep is generated using a two-step technique. In the first step, injection current modulation is employed as a means of varying the output frequency of a DFB laser over a bandwidth of 99.26 GHz. A digital optical phase lock loop is used to lock the frequency sweep speed during current modulation, resulting in a linear frequency chirp. In the second step, the temperature of the DFB laser is modulated, resulting in a shifted starting laser output frequency. A laser frequency chirp is again generated beginning at this shifted starting frequency, resulting in a frequency-shifted spectrum relative to the first recorded data. This process is then repeated across a range of starting temperatures, resulting in a series of partially overlapping, frequency-shifted spectra. These spectra are then aligned using cross-correlation and combined using averaging to form a single, broadband spectrum with a total bandwidth of 510.9 GHz. In order to investigate the utility of this technique, experimental testing was performed in which the approach was used as the swept-frequency source of a coherent optical frequency domain reflectometry system. This system was used to interrogate an optical fiber containing a 20 point, 1-mm pitch length fiber Bragg grating, corresponding to a period of 100 GHz. Using this technique, both the periodicity of the grating in the frequency domain and the individual reflector elements of the structure in the time domain were resolved, demonstrating the technique's potential as a method of extending the sweeping bandwidth of semiconductor lasers for frequency-based sensing applications.

Solution structure of the N-terminal domain of a replication restart primosome factor, PriC, in Escherichia coli

PubMed Central

Aramaki, Takahiko; Abe, Yoshito; Katayama, Tsutomu; Ueda, Tadashi

2013-01-01

In eubacterial organisms, the oriC-independent primosome plays an essential role in replication restart after the dissociation of the replication DNA-protein complex by DNA damage. PriC is a key protein component in the replication restart primosome. Our recent study suggested that PriC is divided into two domains: an N-terminal and a C-terminal domain. In the present study, we determined the solution structure of the N-terminal domain, whose structure and function have remained unknown until now. The revealed structure was composed of three helices and one extended loop. We also observed chemical shift changes in the heteronuclear NMR spectrum and oligomerization in the presence of ssDNA. These abilities may contribute to the PriC-ssDNA complex, which is important for the replication restart primosome. PMID:23868391

Simplifying the construction of domain-specific automatic programming systems: The NASA automated software development workstation project

NASA Technical Reports Server (NTRS)

Allen, Bradley P.; Holtzman, Peter L.

1987-01-01

An overview is presented of the Automated Software Development Workstation Project, an effort to explore knowledge-based approaches to increasing software productivity. The project focuses on applying the concept of domain specific automatic programming systems (D-SAPSs) to application domains at NASA's Johnson Space Center. A version of a D-SAPS developed in Phase 1 of the project for the domain of space station momentum management is described. How problems encountered during its implementation led researchers to concentrate on simplifying the process of building and extending such systems is discussed. Researchers propose to do this by attacking three observed bottlenecks in the D-SAPS development process through the increased automation of the acquisition of programming knowledge and the use of an object oriented development methodology at all stages of the program design. How these ideas are being implemented in the Bauhaus, a prototype workstation for D-SAPS development is discussed.

Simplifying the construction of domain-specific automatic programming systems: The NASA automated software development workstation project

NASA Technical Reports Server (NTRS)

Allen, Bradley P.; Holtzman, Peter L.

1988-01-01

An overview is presented of the Automated Software Development Workstation Project, an effort to explore knowledge-based approaches to increasing software productivity. The project focuses on applying the concept of domain specific automatic programming systems (D-SAPSs) to application domains at NASA's Johnson Space Flight Center. A version of a D-SAPS developed in Phase 1 of the project for the domain of space station momentum management is described. How problems encountered during its implementation led researchers to concentrate on simplifying the process of building and extending such systems is discussed. Researchers propose to do this by attacking three observed bottlenecks in the D-SAPS development process through the increased automation of the acquisition of programming knowledge and the use of an object oriented development methodology at all stages of the program design. How these ideas are being implemented in the Bauhaus, a prototype workstation for D-SAPS development is discussed.

PREFACE: Domain wall dynamics in nanostructures Domain wall dynamics in nanostructures

NASA Astrophysics Data System (ADS)

Marrows, C. H.; Meier, G.

2012-01-01

Domain structures in magnetic materials are ubiquitous and have been studied for decades. The walls that separate them are topological defects in the magnetic order parameter and have a wide variety of complex forms. In general, their investigation is difficult in bulk materials since only the domain structure on the surface of a specimen is visible. Cutting the sample to reveal the interior causes a rearrangement of the domains into a new form. As with many other areas of magnetism, the study of domain wall physics has been revitalised by the advent of nanotechnology. The ability to fabricate nanoscale structures has permitted the formation of simplified and controlled domain patterns; the development of advanced microscopy methods has permitted them to be imaged and then modelled; subjecting them to ultrashort field and current pulses has permitted their dynamics to be explored. The latest results from all of these advances are described in this special issue. Not only has this led to results of great scientific beauty, but also to concepts of great applicability to future information technologies. In this issue the reader will find the latest results for these domain wall dynamics and the high-speed processes of topological structures such as domain walls and magnetic vortices. These dynamics can be driven by the application of magnetic fields, or by flowing currents through spintronic devices using the novel physics of spin-transfer torque. This complexity has been studied using a wide variety of experimental techniques at the edge of the spatial and temporal resolution currently available, and can be described using sophisticated analytical theory and computational modelling. As a result, the dynamics can be engineered to give rise to finely controlled memory and logic devices with new functionality. Moreover, the field is moving to study not only the conventional transition metal ferromagnets, but also complex heterostructures, novel magnets and even other

Dicer cleaves 5'-extended microRNA precursors originating from RNA polymerase II transcription start sites.

PubMed

Sheng, Peike; Fields, Christopher; Aadland, Kelsey; Wei, Tianqi; Kolaczkowski, Oralia; Gu, Tongjun; Kolaczkowski, Bryan; Xie, Mingyi

2018-05-09

MicroRNAs (miRNAs) are approximately 22 nucleotide (nt) long and play important roles in post-transcriptional regulation in both plants and animals. In animals, precursor (pre-) miRNAs are ∼70 nt hairpins produced by Drosha cleavage of long primary (pri-) miRNAs in the nucleus. Exportin-5 (XPO5) transports pre-miRNAs into the cytoplasm for Dicer processing. Alternatively, pre-miRNAs containing a 5' 7-methylguanine (m7G-) cap can be generated independently of Drosha and XPO5. Here we identify a class of m7G-capped pre-miRNAs with 5' extensions up to 39 nt long. The 5'-extended pre-miRNAs are transported by Exportin-1 (XPO1). Unexpectedly, a long 5' extension does not block Dicer processing. Rather, Dicer directly cleaves 5'-extended pre-miRNAs by recognizing its 3' end to produce mature 3p miRNA and extended 5p miRNA both in vivo and in vitro. The recognition of 5'-extended pre-miRNAs by the Dicer Platform-PAZ-Connector (PPC) domain can be traced back to ancestral animal Dicers, suggesting that this previously unrecognized Dicer reaction mode is evolutionarily conserved. Our work reveals additional genetic sources for small regulatory RNAs and substantiates Dicer's essential role in RNAi-based gene regulation.

Photo dynamics of BLUF domain mutant H44R of AppA from Rhodobacter sphaeroides

NASA Astrophysics Data System (ADS)

Zirak, P.; Penzkofer, A.; Hegemann, P.; Mathes, T.

2007-05-01

The photo-cycle dynamics of the H44R mutant of the BLUF domain of the transcriptional anti-repressor protein AppA (AppA-H44R) from the non-sulfur anoxyphototropic purple bacterium Rhodobacter sphaeroides is studied in order to gain information on the involvement of His44 in the photo-cyclic mechanism of the AppA BLUF domain and to add information to the involved processes. The amino acid residue histidine at position 44 is replaced by arginine. A 12 nm red-shifted signalling state is formed upon blue-light excitation, while in wild-type AppA (AppA-wt) the red-shift is 16 nm. The recovery to the receptor dark state is approximately a factor of 2.5 faster ( τrec ≈ 6.5 min) than the recovery of the wild-type counterpart. Extended light exposure of the mutant causes photo-degradation of flavin (mainly free flavin conversion to lumichrome and re-equilibration between free and non-covalently bound flavin) and protein aggregation (showing up as light scattering). No photo-degradation was observed for AppA-wt. The quantum efficiency of signalling-state formation determined by intensity dependent absorption measurements is found to be ϕs ≈ 0.3 (for AppA-wt: ϕs ≈ 0.24). A two-component single-exponential fluorescence relaxation was observed, which is interpreted as fast fluorescence quenching to an equilibrium value by photo-induced electron transfer followed by slower fluorescence decay due to charge recombination. Based on the experimental findings, an extended photo-cycle model for BLUF domains is proposed.

Effects of Meteorological Variables on the Incidence of Rupture of Intracranial Aneurysms in Central New Jersey.

PubMed

Kellogg, Marissa; Petrov, Dimitriy; Agarwal, Nitin; Patel, Nitesh V; Hansberry, David Richard; Agarwal, Prateek; Brimacombe, Michael; Gandhi, Chirag D; Prestigiacomo, Charles

2017-05-01

Introduction  Previous studies have suggested relationships between the rupture of intracranial aneurysms and meteorological variables such as season, barometric pressure, and temperature. Our objective was to examine the relationship between the incidence of hospital admissions secondary to aneurysmal subarachnoid hemorrhage (aSAH) and meteorological variables in central New Jersey. Methods  The study population consisted of 312 patients who presented to University Hospital in Newark, New Jersey, between January 1, 2003, and December 31, 2008, with aSAH. Days in the 6-year period were classified as nonbleed days (no aSAH), bleed days (one or more aSAHs within 1 calendar day), cluster days (two or more aSAHs within 2 calendar days), and multiple-bleed days (two or more aSAHs within 1 calendar day). Results  The only significant meteorological risk factor for the occurrence of multiple-bleed days was high barometric pressure (1018.5 versus 1016.5 millibars [mbars]; p <  0.04), but an increase in barometric pressure (+ 2.8 mbars) over the 2 days prior to the multiple-bleed day, although not statistically significant, may be a risk factor ( p <  0.09). Barometric pressure was also noted to be increased on bleed days (1017.2 versus 1016.5 mbars) and cluster days (1017.7 versus 1016.5 mbars), but this relationship was not significant ( p <  0.1 and p <  0.1, respectively). Although aSAH days demonstrated consistently lower temperatures than non-aSAH days and dropping temperatures were consistently found in the days preceding the aSAH, these relationships were not significant. Conclusion  Among meteorological factors, high barometric pressure and low temperature may be risk factors for the onset of aSAH. Georg Thieme Verlag KG Stuttgart · New York.

How large is the typical subarachnoid hemorrhage? A review of current neurosurgical knowledge.

PubMed

Whitmore, Robert G; Grant, Ryan A; LeRoux, Peter; El-Falaki, Omar; Stein, Sherman C

2012-01-01

Despite the morbidity and mortality of subarachnoid hemorrhage (SAH), the average volume of a typical hemorrhage is not well defined. Animal models of SAH often do not accurately mimic the human disease process. The purpose of this study is to estimate the average SAH volume, allowing standardization of animal models of the disease. We performed a MEDLINE search of SAH volume and erythrocyte counts in human cerebrospinal fluid as well as for volumes of blood used in animal injection models of SAH, from 1956 to 2010. We polled members of the American Association of Neurological Surgeons (AANS) for estimates of typical SAH volume. Using quantitative data from the literature, we calculated the total volume of SAH as equal to the volume of blood clotted in basal cisterns plus the volume of dispersed blood in cerebrospinal fluid. The results of the AANS poll confirmed our estimates. The human literature yielded 322 publications and animal literature, 237 studies. Four quantitative human studies reported blood clot volumes ranging from 0.2 to 170 mL, with a mean of ∼20 mL. There was only one quantitative study reporting cerebrospinal fluid red blood cell counts from serial lumbar puncture after SAH. Dispersed blood volume ranged from 2.9 to 45.9 mL, and we used the mean of 15 mL for our calculation. Therefore, total volume of SAH equals 35 mL. The AANS poll yielded 176 responses, ranging from 2 to 350 mL, with a mean of 33.9 ± 4.4 mL. Based on our estimate of total SAH volume of 35 mL, animal injection models may now become standardized for more accurate portrayal of the human disease process. Copyright © 2012 Elsevier Inc. All rights reserved.

Clinical features of subarachnoid hemorrhage in patients with positive cancer history.

PubMed

Shibahara, Ichiyo; Watanabe, Takashi; Ezura, Masayuki; Inoue, Takashi; Fujimura, Miki; Kimura, Naoto; Inoue, Tomoo; Suzuki, Ichiro; Nishino, Akiko; Nishimura, Shinjitsu; Uenohara, Hiroshi; Tominaga, Teiji

2016-05-01

Advances in cancer treatment have dramatically increased long-term survivors. Prolonged survival increases comorbidity risk, but there is a paucity of studies on how cancer history alters clinical outcomes from subsequent diseases. This study aims to investigate whether positive cancer history influences clinical outcome following subarachnoid hemorrhage (SAH). We retrospectively reviewed consecutive SAH patients admitted between January 2008 and March 2014. Medical histories, known SAH risk factors, and outcome were compared between SAH patients with and without cancer history. Out of the 498 SAH patients, 55 cases had cancer history, 438 cases had no cancer history and 5 cases had an unknown cancer history. Compared with SAH patients without cancer history, those with cancer history had poorer Hunt & Hess grade at SAH presentation (P = 0.021), and poorer modified Rankin Scale (mRS) score at discharge (P < 0.001). After adjustment for age, sex, modified Fisher, previous SAH, history of hypertension, current smoking status, and current alcohol consumption, positive cancer history remained an independent risk factor for poorer mRS0-6 [odds ratio (OR) = 2.25, 95 % confidence interval (CI) 1.28-3.94] and mRS6 (OR = 2.74, 95 % CI 1.40-5.37). Furthermore, stratified analysis by Hunt & Hess grade adjusted by age, sex, and modified Fisher scale, OR of poorer mRS0-6 was 2.12 (95 % CI 0.89-5.05) and OR of mRS6 was 3.68 (95 % CI 1.35-10.04). After adjustment of patients for demographic factors, classical risk factors for SAH and Hunt & Hess grade, previous cancer history is a risk factor for the poor functional outcome of SAH.

Treatment of Spontaneous Subarachnoid Hemorrhage and Self-Reported Neuropsychological Performance at 6 Months - Results of a Prospective Clinical Pilot Study on Good-Grade Patients.

PubMed

Bründl, Elisabeth; Schödel, Petra; Bele, Sylvia; Proescholdt, Martin; Scheitzach, Judith; Zeman, Florian; Brawanski, Alexander; Schebesch, Karl-Michael

2018-01-01

Limited focus has been placed on neuropsychological patient profiles after spontaneous subarachnoid hemorrhage (sSAH). We conducted a prospective controlled study in good-grade sSAH patients to evaluate the time course of treatment-specific differences in cognitive processing after sSAH. Twenty-six consecutive sSAH patients were enrolled (drop out n=5). Nine patients received endovascular aneurysm occlusion (EV), 6 patients were treated microsurgically (MS), and 6 patients with perimesencephalic SAH (pSAH) underwent standardized intensive medical care. No patient experienced serious vasospasm-related ischemic or hemorrhagic complications. All patients were subjected to neuropsychological self-report assessment (36-Item Short Form Health Survey and ICD-10-Symptom-Rating questionnaire) subacutely (day 11 - 35) after the onset of bleeding (t1) and at the 6-month follow-up (FU; t < sub > 2 < /sub > ). From t1 to t < sub > 2 < /sub > , MS and EV patients significantly improved in physical functioning (Pfi; p=.001 each) and the physical component summary (p=.010 vs. p=.015). Bodily pain (Pain; MS p=.034) and general health perceptions (EV p=.014) significantly improved, and nutrition disorder (EV p=.008) worsened. At FU, MS patients reported significantly better Pfi (vs. EV p=.046), less Pain (vs. EV p=.040), and more depression (vs. pSAH p=.035). Group-rate analyses of test differences showed a significant alleviation in nutrition disorder in MS (vs. EV p=.009). All sSAH groups reported a significant deterioration in health. Though both MS and EV patients, improved in several physical items over time, our data suggest a better short-term Pfi, less Pain and improved nutrition disorder in surgically treated patients. pSAH patients performed significantly better in various aspects of physical and psychological functioning than patients with aneurysmal SAH.

Decorin alleviated chronic hydrocephalus via inhibiting TGF-β1/Smad/CTGF pathway after subarachnoid hemorrhage in rats.

PubMed

Yan, Hui; Chen, Yujie; Li, Lingyong; Jiang, Jiaode; Wu, Guangyong; Zuo, Yuchun; Zhang, John H; Feng, Hua; Yan, Xiaoxin; Liu, Fei

2016-01-01

Chronic hydrocephalus is one of the severe complications after subarachnoid hemorrhage (SAH). However, there is no efficient treatment for the prevention of chronic hydrocephalus, partially due to poor understanding of underlying pathogenesis, subarachnoid fibrosis. Transforming growth factor-β1(TGF-β1) is a potent fibrogenic factor implicated in wide range of fibrotic diseases. To investigate whether decorin, a natural antagonist for TGF-β1, protects against subarachnoid fibrosis and chronic hydrocephalus after SAH, two-hemorrhage-injection SAH model was conducted in 6-week-old rats. Recombinant human decorin(rhDecorin) (30ug/2ul) was administered before blood injection and on the 10th day after SAH. TGF-β1, p-Smad2/3, connective tissue growth factor (CTGF), collagen I and pro-collagen I c-terminal propeptide were assessed via western blotting, enzyme-linked immunosorbent assay, radioimmunoassay and immunofluorescence. And neurobehavioral tests and Morris water maze were employed to evaluate long-term neurological functions after SAH. We found that SAH induced heightened activation of TGF-β1/Smad/CTGF axis, presenting as a two peak response of TGF-β1 in cerebrospinal fluid, elevation of TGF-β1, p-Smad2/3, CTGF, collagen I in brain parenchyma and pro-collagen I c-terminal propeptide in cerebrospinal fluid, and increased lateral ventricle index. rhDecorin treatment effectively inhibited up-regulation of TGF-β1, p-Smad2/3, CTGF, collagen I and pro-collagen I c-terminal propeptide after SAH. Moreover, rhDecorin treatment significantly reduced lateral ventricular index and incidence of chronic hydrocephalus after SAH. Importantly, rhDecorin improved neurocognitive deficits after SAH. In conclusion, rhDecorin suppresses extracellular matrix accumulation and following subarachnoid fibrosis via inhibiting TGF-β1/Smad/CTGF pathway, preventing development of hydrocephalus and attenuating long-term neurocognitive defects after SAH. Copyright © 2015 Elsevier B

Search for Extended Sources in the Galactic Plane Using Six Years of Fermi -Large Area Telescope Pass 8 Data above 10 GeV

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

Ackermann, M.; Buehler, R.; Ajello, M.

The spatial extension of a γ -ray source is an essential ingredient to determine its spectral properties, as well as its potential multiwavelength counterpart. The capability to spatially resolve γ -ray sources is greatly improved by the newly delivered Fermi -Large Area Telescope (LAT) Pass 8 event-level analysis, which provides a greater acceptance and an improved point-spread function, two crucial factors for the detection of extended sources. Here, we present a complete search for extended sources located within 7° from the Galactic plane, using 6 yr of Fermi -LAT data above 10 GeV. We find 46 extended sources and providemore » their morphological and spectral characteristics. This constitutes the first catalog of hard Fermi -LAT extended sources, named the Fermi Galactic Extended Source Catalog, which allows a thorough study of the properties of the Galactic plane in the sub-TeV domain.« less

Search for Extended Sources in the Galactic Plane Using Six Years of Fermi-Large Area Telescope Pass 8 Data above 10 GeV

NASA Astrophysics Data System (ADS)

Ackermann, M.; Ajello, M.; Baldini, L.; Ballet, J.; Barbiellini, G.; Bastieri, D.; Bellazzini, R.; Bissaldi, E.; Bloom, E. D.; Bonino, R.; Bottacini, E.; Brandt, T. J.; Bregeon, J.; Bruel, P.; Buehler, R.; Cameron, R. A.; Caragiulo, M.; Caraveo, P. A.; Castro, D.; Cavazzuti, E.; Cecchi, C.; Charles, E.; Chekhtman, A.; Cheung, C. C.; Chiaro, G.; Ciprini, S.; Cohen, J. M.; Costantin, D.; Costanza, F.; Cutini, S.; D'Ammando, F.; de Palma, F.; Desiante, R.; Digel, S. W.; Di Lalla, N.; Di Mauro, M.; Di Venere, L.; Favuzzi, C.; Fegan, S. J.; Ferrara, E. C.; Franckowiak, A.; Fukazawa, Y.; Funk, S.; Fusco, P.; Gargano, F.; Gasparrini, D.; Giglietto, N.; Giordano, F.; Giroletti, M.; Green, D.; Grenier, I. A.; Grondin, M.-H.; Guillemot, L.; Guiriec, S.; Harding, A. K.; Hays, E.; Hewitt, J. W.; Horan, D.; Hou, X.; Jóhannesson, G.; Kamae, T.; Kuss, M.; La Mura, G.; Larsson, S.; Lemoine-Goumard, M.; Li, J.; Longo, F.; Loparco, F.; Lubrano, P.; Magill, J. D.; Maldera, S.; Malyshev, D.; Manfreda, A.; Mazziotta, M. N.; Michelson, P. F.; Mitthumsiri, W.; Mizuno, T.; Monzani, M. E.; Morselli, A.; Moskalenko, I. V.; Negro, M.; Nuss, E.; Ohsugi, T.; Omodei, N.; Orienti, M.; Orlando, E.; Ormes, J. F.; Paliya, V. S.; Paneque, D.; Perkins, J. S.; Persic, M.; Pesce-Rollins, M.; Petrosian, V.; Piron, F.; Porter, T. A.; Principe, G.; Rainò, S.; Rando, R.; Razzano, M.; Razzaque, S.; Reimer, A.; Reimer, O.; Reposeur, T.; Sgrò, C.; Simone, D.; Siskind, E. J.; Spada, F.; Spandre, G.; Spinelli, P.; Suson, D. J.; Tak, D.; Thayer, J. B.; Thompson, D. J.; Torres, D. F.; Tosti, G.; Troja, E.; Vianello, G.; Wood, K. S.; Wood, M.

2017-07-01

The spatial extension of a γ-ray source is an essential ingredient to determine its spectral properties, as well as its potential multiwavelength counterpart. The capability to spatially resolve γ-ray sources is greatly improved by the newly delivered Fermi-Large Area Telescope (LAT) Pass 8 event-level analysis, which provides a greater acceptance and an improved point-spread function, two crucial factors for the detection of extended sources. Here, we present a complete search for extended sources located within 7° from the Galactic plane, using 6 yr of Fermi-LAT data above 10 GeV. We find 46 extended sources and provide their morphological and spectral characteristics. This constitutes the first catalog of hard Fermi-LAT extended sources, named the Fermi Galactic Extended Source Catalog, which allows a thorough study of the properties of the Galactic plane in the sub-TeV domain.

Dislocation dynamics in non-convex domains using finite elements with embedded discontinuities

NASA Astrophysics Data System (ADS)

Romero, Ignacio; Segurado, Javier; LLorca, Javier

2008-04-01

The standard strategy developed by Van der Giessen and Needleman (1995 Modelling Simul. Mater. Sci. Eng. 3 689) to simulate dislocation dynamics in two-dimensional finite domains was modified to account for the effect of dislocations leaving the crystal through a free surface in the case of arbitrary non-convex domains. The new approach incorporates the displacement jumps across the slip segments of the dislocations that have exited the crystal within the finite element analysis carried out to compute the image stresses on the dislocations due to the finite boundaries. This is done in a simple computationally efficient way by embedding the discontinuities in the finite element solution, a strategy often used in the numerical simulation of crack propagation in solids. Two academic examples are presented to validate and demonstrate the extended model and its implementation within a finite element program is detailed in the appendix.

Evaluation of Hematological Parameters in the Differentiation of Subarachnoid Hemorrhage and Other Headache Syndromes.

PubMed

Goktekin, Mehmet C; Yilmaz, Mustafa

2018-06-01

In this research, the aim was to compare hematological data for the differentiation of subarachnoid hemorrhage, migraine attack, and other headache syndromes during consultation in emergency service. In this research, which was designed as retrospective case control study, hematological parameters (WBC, HgB, HCT, PLT, lymphocyte and neutrophile counts and neutrophile/lymphocyte rates) of the patients consulting to emergency service with SAH and migraine and other consulting patients complaining mainly from headache and having normal cranial CT were analysed. Sixty migraine attack patients (F/M:47/13), 57 SAH patients (F/M:30/27), and 53 patients except migraine having normal brain CT (F/M:36/17) who were consulted to emergency service with headache complaint were included in our research. WBC, Hct, HgB, MCV, PLT, MPV, LY, Neu counts, and NY/LY rates were found to differentiate between SAH and migraine. WBC, PLT, MPV, LY, and Neu rates were found to differentiate between SAH and HS patients. Only Hct, HgB, MCV, and NY/LY rates were found to differ meaningfully between SAH and migraine patients but these rates were not found to have meaningful difference between SAH and HS patients. In addition, an increase in WBC counts and NY/LY rates and decrease in MPV counts in ROC analysis were found to be more specific for SAH. WBC, HgB, HCT, PLT, lymphocyte and Neu counts, and NY/LY rates can indicate distinguishing SAH and migraine. WBC, HgB, HCT, PLT, lymphocyte and Neu counts can indicate to the clinician a differentiation of SAH and other headache syndromes.

Sudden death and cervical spine: A new contribution to pathogenesis for sudden death in critical care unit from subarachnoid hemorrhage; first report - An experimental study.

PubMed

Kazdal, Hizir; Kanat, Ayhan; Aydin, Mehmet Dumlu; Yazar, Ugur; Guvercin, Ali Riza; Calik, Muhammet; Gundogdu, Betul

2017-01-01

Sudden death from subarachnoid hemorrhage (SAH) is not uncommon. The goal of this study is to elucidate the effect of the cervical spinal roots and the related dorsal root ganglions (DRGs) on cardiorespiratory arrest following SAH. This was an experimental study conducted on rabbits. This study was conducted on 22 rabbits which were randomly divided into three groups: control ( n = 5), physiologic serum saline (SS; n = 6), SAH groups ( n = 11). Experimental SAH was performed. Seven of 11 rabbits with SAH died within the first 2 weeks. After 20 days, other animals were sacrificed. The anterior spinal arteries, arteriae nervorum of cervical nerve roots (C6-C8), DRGs, and lungs were histopathologically examined and estimated stereologically. Statistical analysis was performed using the PASW Statistics 18.0 for Windows (SPSS Inc., Chicago, Illinois, USA). Intergroup differences were assessed using a one-way ANOVA. The statistical significance was set at P < 0.05. In the SAH group, histopathologically, severe anterior spinal artery (ASA) and arteriae nervorum vasospasm, axonal and neuronal degeneration, and neuronal apoptosis were observed. Vasospasm of ASA did not occur in the SS and control groups. There was a statistically significant increase in the degenerated neuron density in the SAH group as compared to the control and SS groups ( P < 0.05). Cardiorespiratory disturbances, arrest, and lung edema more commonly developed in animals in the SAH group. We noticed interestingly that C6-C8 DRG degenerations were secondary to the vasospasm of ASA, following SAH. Cardiorespiratory disturbances or arrest can be explained with these mechanisms.

Immediate coma and poor outcome in subarachnoid haemorrhage are independently associated with an aneurysmal origin.

PubMed

Tsermoulas, Georgios; Flett, Lisa; Gregson, Barbara; Mitchell, Patrick

2013-08-01

Subarachnoid haemorrhage (SAH) may present with coma and this is known to be associated with aneurysmal origin and blood load. Aneurysmal origin is associated with increased blood load and existing data do not allow us to determine if the association between coma and aneurysmal SAH is wholly due to blood load or if aneurysmal origin has an additional independent effect. The objective of our study is to find if an aneurysmal origin is a predictor of acute onset of coma independent of blood load. A series of consecutive patients with spontaneous SAH were divided into two groups: aneurysmal (aSAH) and non-aneurysmal--angiographically negative SAH (naSAH). Blood load was quantified so that the effect of aneurysmal origin could be resolved from the effect of the amount of blood spilled. Non-parametric regression was used to relate blood load to coma and poor outcome rates for aneurysmal bleeds. We analysed a total of 421 patients presenting during the period 2009-2011. Ninety aneurysmal cases presented with coma, seventy immediately in the early phase and seven shortly after rebleeding. None of the naSAH cases presented with immediate coma and 1 developed delayed coma. Delayed coma was associated with acute hydrocephalus in both groups. Aneurysmal origin was found to be an independent determinant of immediate coma (p=0.02) and poor outcome (p<0.001). Immediate coma and poor outcome in SAH are associated with an aneurysmal origin and do not characterize naSAH. Copyright © 2013 Elsevier B.V. All rights reserved.

Immune and inflammatory gene signature in rat cerebrum in subarachnoid hemorrhage with microarray analysis.

PubMed

Lee, Chu-I; Chou, An-Kuo; Lin, Ching-Chih; Chou, Chia-Hua; Loh, Joon-Khim; Lieu, Ann-Shung; Wang, Chih-Jen; Huang, Chi-Ying F; Howng, Shen-Long; Hong, Yi-Ren

2012-01-01

Cerebral vasospasm following subarachnoid hemorrhage (SAH) has been studied in terms of a contraction of the major cerebral arteries, but the effect of cerebrum tissue in SAH is not yet well understood. To gain insight into the biology of SAH-expressing cerebrum, we employed oligonucleotide microarrays to characterize the gene expression profiles of cerebrum tissue at the early stage of SAH. Functional gene expression in the cerebrum was analyzed 2 h following stage 1-hemorrhage in Sprague-Dawley rats. mRNA was investigated by performing microarray and quantitative real-time PCR analyses, and protein expression was determined by Western blot analysis. In this study, 18 upregulated and 18 downregulated genes displayed at least a 1.5-fold change. Five genes were verified by real-time PCR, including three upregulated genes [prostaglandin E synthase (PGES), CD14 antigen, and tissue inhibitor of metalloproteinase 1 (TIMP1)] as well as two downregulated genes [KRAB-zinc finger protein-2 (KZF-2) and γ-aminobutyric acid B receptor 1 (GABA B receptor)]. Notably, there were functional implications for the three upregulated genes involved in the inflammatory SAH process. However, the mechanisms leading to decreased KZF-2 and GABA B receptor expression in SAH have never been characterized. We conclude that oligonucleotide microarrays have the potential for use as a method to identify candidate genes associated with SAH and to provide novel investigational targets, including genes involved in the immune and inflammatory response. Furthermore, understanding the regulation of MMP9/TIMP1 during the early stages of SAH may elucidate the pathophysiological mechanisms in SAH rats.

Separated matter and antimatter domains with vanishing domain walls

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

Dolgov, A.D.; Godunov, S.I.; Rudenko, A.S.

2015-10-01

We present a model of spontaneous (or dynamical) C and CP violation where it is possible to generate domains of matter and antimatter separated by cosmologically large distances. Such C(CP) violation existed only in the early universe and later it disappeared with the only trace of generated baryonic and/or antibaryonic domains. So the problem of domain walls in this model does not exist. These features are achieved through a postulated form of interaction between inflaton and a new scalar field, realizing short time C(CP) violation.

Natural language processing and visualization in the molecular imaging domain.

PubMed

Tulipano, P Karina; Tao, Ying; Millar, William S; Zanzonico, Pat; Kolbert, Katherine; Xu, Hua; Yu, Hong; Chen, Lifeng; Lussier, Yves A; Friedman, Carol

2007-06-01

Molecular imaging is at the crossroads of genomic sciences and medical imaging. Information within the molecular imaging literature could be used to link to genomic and imaging information resources and to organize and index images in a way that is potentially useful to researchers. A number of natural language processing (NLP) systems are available to automatically extract information from genomic literature. One existing NLP system, known as BioMedLEE, automatically extracts biological information consisting of biomolecular substances and phenotypic data. This paper focuses on the adaptation, evaluation, and application of BioMedLEE to the molecular imaging domain. In order to adapt BioMedLEE for this domain, we extend an existing molecular imaging terminology and incorporate it into BioMedLEE. BioMedLEE's performance is assessed with a formal evaluation study. The system's performance, measured as recall and precision, is 0.74 (95% CI: [.70-.76]) and 0.70 (95% CI [.63-.76]), respectively. We adapt a JAVA viewer known as PGviewer for the simultaneous visualization of images with NLP extracted information.

Exploratory study of the course of posttraumatic stress disorder after aneurysmal subarachnoid hemorrhage.

PubMed

Huenges Wajer, Irene M C; Smits, Anouk R; Rinkel, Gabriel J E; van Zandvoort, Martine J E; Wijngaards-de Meij, Leoniek; Visser-Meily, Johanna M A

2018-05-09

Posttraumatic stress disorder (PTSD) occurs often in aneurysmal subarachnoid hemorrhage (aSAH) survivors, but how PTSD develops over time post-aSAH is still unclear. We examined the course of PTSD symptoms during the first year after aSAH. In this prospective cohort study, the Impact of Event Scale (IES) was applied in 128 patients 3, 6 and 12 months after aSAH. Multilevel modelling was used to assess changes in levels of PTSD symptoms over time and to explore if demographic characteristics, aSAH characteristics, level of education, cognitive functioning and neuroticism are associated to the course of PTSD symptoms. Multilevel analyses showed at group level no differences in the average level of PTSD symptoms between 3, 6 of 12 months post-aSAH (p = 0.22). At individual level, changes in PTSD symptoms over time were present (X 2 (121) = 149.73 p = 0.04). None of the factors could explain the variance in change of PTSD symptoms over time. The course of PTSD appears to differ between individuals after aSAH. We found no factors that explain these differences. There is not one optimal moment in time to assess PTSD. Therefore, it is important to assess PTSD at several time points after aSAH. Copyright © 2018. Published by Elsevier Inc.

Diagnosis of subarachnoid haemorrhage: a survey of Australasian emergency physicians and trainees.

PubMed

Rogers, Andrew; Furyk, Jeremy; Banks, Colin; Chu, Kevin

2014-10-01

This study aims to establish current practice among Australasian emergency physicians and trainees on several aspects of the investigation of suspected subarachnoid haemorrhage (SAH). An electronic questionnaire (SurveyMonkey™) was distributed to emergency physicians and trainees by email through the ACEM. Survey recipients were asked about demographics, followed by a series of questions relating to the investigation of SAH. There were 878 survey respondents (response rate 24%). Our data showed that 47.3% of respondents agreed or strongly agreed that a CT brain within 6 h of headache onset is sufficient to exclude a diagnosis of SAH. For a CT performed within 12 h of ictus, 14.4% were satisfied that SAH could be excluded. After a negative CT scan, for further investigation of SAH, 88% of respondents preferred lumbar puncture to CT angiography. For detection of xanthochromia in the cerebrospinal fluid, 57.7% of respondents felt that spectrophotometry (vs visual inspection) is necessary to accurately diagnose SAH. A range of information was collected regarding the investigation of suspected SAH. We report significant differences in the diagnostic approach of Australasian emergency physicians and trainees to this condition, in particular the utility of CT within 6 h for exclusion of SAH. © 2014 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine.

Entry into the nuclear pore complex is controlled by a cytoplasmic exclusion zone containing dynamic GLFG-repeat nucleoporin domains.

PubMed

Fiserova, Jindriska; Spink, Matthew; Richards, Shane A; Saunter, Christopher; Goldberg, Martin W

2014-01-01

Nuclear pore complexes (NPCs) mediate nucleocytoplasmic movement. The central channel contains proteins with phenylalanine-glycine (FG) repeats, or variations (GLFG, glycine-leucine-phenylalanine-glycine). These are 'intrinsically disordered' and often represent weak interaction sites that become ordered upon interaction. We investigated this possibility during nuclear transport. Using electron microscopy of S. cerevisiae, we show that NPC cytoplasmic filaments form a dome-shaped structure enclosing GLFG domains. GLFG domains extend out of this structure and are part of an 'exclusion zone' that might act as a partial barrier to entry of transport-inert proteins. The anchor domain of a GLFG nucleoporin locates exclusively to the central channel. By contrast, the localisation of the GLFG domains varied between NPCs and could be cytoplasmic, central or nucleoplasmic and could stretch up to 80 nm. These results suggest a dynamic exchange between ordered and disordered states. In contrast to diffusion through the NPC, transport cargoes passed through the exclusion zone and accumulated near the central plane. We also show that movement of cargo through the NPC is accompanied by relocation of GLFG domains, suggesting that binding, restructuring and movement of these domains could be part of the translocation mechanism.

Internationalized Domain Names.

ERIC Educational Resources Information Center

Wielansky, Marc D.

2002-01-01

Reports on an investigation of what may appear at first to be an arcane topic--the internationalization of domain names on the Internet. Concludes that expanding domain names internationally poses challenges to the inherent open structure of the Internet; to its ease of use for those accustomed to Latin-alphabet-only domain names; and to corporate…

An Autoinhibitory Role for the Pleckstrin Homology Domain of Interleukin-2-Inducible Tyrosine Kinase and Its Interplay with Canonical Phospholipid Recognition.

PubMed

Devkota, Sujan; Joseph, Raji E; Boyken, Scott E; Fulton, D Bruce; Andreotti, Amy H

2017-06-13

Pleckstrin homology (PH) domains are well-known as phospholipid binding modules, yet evidence that PH domain function extends beyond lipid recognition is mounting. In this work, we characterize a protein binding function for the PH domain of interleukin-2-inducible tyrosine kinase (ITK), an immune cell specific signaling protein that belongs to the TEC family of nonreceptor tyrosine kinases. Its N-terminal PH domain is a well-characterized lipid binding module that localizes ITK to the membrane via phosphatidylinositol 3,4,5-trisphosphate (PIP 3 ) binding. Using a combination of nuclear magnetic resonance spectroscopy and mutagenesis, we have mapped an autoregulatory protein interaction site on the ITK PH domain that makes direct contact with the catalytic kinase domain of ITK, inhibiting the phospho-transfer reaction. Moreover, we have elucidated an important interplay between lipid binding by the ITK PH domain and the stability of the autoinhibitory complex formed by full length ITK. The ITK activation loop in the kinase domain becomes accessible to phosphorylation to the exogenous kinase LCK upon binding of the ITK PH domain to PIP 3 . By clarifying the allosteric role of the ITK PH domain in controlling ITK function, we have expanded the functional repertoire of the PH domain generally and opened the door to alternative strategies to target this specific kinase in the context of immune cell signaling.

Comparison of frequency-domain and time-domain rotorcraft vibration control methods

NASA Technical Reports Server (NTRS)

Gupta, N. K.

1984-01-01

Active control of rotor-induced vibration in rotorcraft has received significant attention recently. Two classes of techniques have been proposed. The more developed approach works with harmonic analysis of measured time histories and is called the frequency-domain approach. The more recent approach computes the control input directly using the measured time history data and is called the time-domain approach. The report summarizes the results of a theoretical investigation to compare the two approaches. Five specific areas were addressed: (1) techniques to derive models needed for control design (system identification methods), (2) robustness with respect to errors, (3) transient response, (4) susceptibility to noise, and (5) implementation difficulties. The system identification methods are more difficult for the time-domain models. The time-domain approach is more robust (e.g., has higher gain and phase margins) than the frequency-domain approach. It might thus be possible to avoid doing real-time system identification in the time-domain approach by storing models at a number of flight conditions. The most significant error source is the variation in open-loop vibrations caused by pilot inputs, maneuvers or gusts. The implementation requirements are similar except that the time-domain approach can be much simpler to implement if real-time system identification were not necessary.

Necrostatin-1 attenuates early brain injury after subarachnoid hemorrhage in rats by inhibiting necroptosis.

PubMed

Chen, Fuxiang; Su, Xingfen; Lin, Zhangya; Lin, Yuanxiang; Yu, Lianghong; Cai, Jiawei; Kang, Dezhi; Hu, Liwen

2017-01-01

Necroptosis is programmed cell death that has been recently proposed and reported to be involved in several neurologic diseases. However, the role of necroptosis in early brain injury after subarachnoid hemorrhage (SAH) is still unknown. The purpose of this study was to investigate whether necroptosis was involved in SAH-induced early brain injury, and to assess the possible neuroprotective effect of necrostatin-1 using an endovascular perforation rat model of SAH. Our results showed that the expression levels of necroptosis-related proteins including RIP1, RIP3 and MLKL in the basal cortex all increased at 3 hours after SAH ( P <0.05) and peaked at 48 hours after SAH ( P <0.05). However, they were greatly reduced after treatment with necrostatin-1 ( P <0.05). Concurrently, neurologic outcomes were significantly improved after necrostatin-1 treatment ( P <0.05). Furthermore, brain edema, blood-brain barrier disruption, necrotic cell death and neuroinflammation were also greatly inhibited after necrostatin-1 treatment. These results indicate that necroptosis is an important mechanism of cell death involved in the early brain injury after experimental SAH. Necrostatin-1 perhaps can serve as a promising neuroprotective agent for SAH treatment.

Domain learning naming game for color categorization.

PubMed

Li, Doujie; Fan, Zhongyan; Tang, Wallace K S

2017-01-01

Naming game simulates the evolution of vocabulary in a population of agents. Through pairwise interactions in the games, agents acquire a set of vocabulary in their memory for object naming. The existing model confines to a one-to-one mapping between a name and an object. Focus is usually put onto name consensus in the population rather than knowledge learning in agents, and hence simple learning model is usually adopted. However, the cognition system of human being is much more complex and knowledge is usually presented in a complicated form. Therefore, in this work, we extend the agent learning model and design a new game to incorporate domain learning, which is essential for more complicated form of knowledge. In particular, we demonstrate the evolution of color categorization and naming in a population of agents. We incorporate the human perceptive model into the agents and introduce two new concepts, namely subjective perception and subliminal stimulation, in domain learning. Simulation results show that, even without any supervision or pre-requisition, a consensus of a color naming system can be reached in a population solely via the interactions. Our work confirms the importance of society interactions in color categorization, which is a long debate topic in human cognition. Moreover, our work also demonstrates the possibility of cognitive system development in autonomous intelligent agents.

Domain learning naming game for color categorization

PubMed Central

2017-01-01

Naming game simulates the evolution of vocabulary in a population of agents. Through pairwise interactions in the games, agents acquire a set of vocabulary in their memory for object naming. The existing model confines to a one-to-one mapping between a name and an object. Focus is usually put onto name consensus in the population rather than knowledge learning in agents, and hence simple learning model is usually adopted. However, the cognition system of human being is much more complex and knowledge is usually presented in a complicated form. Therefore, in this work, we extend the agent learning model and design a new game to incorporate domain learning, which is essential for more complicated form of knowledge. In particular, we demonstrate the evolution of color categorization and naming in a population of agents. We incorporate the human perceptive model into the agents and introduce two new concepts, namely subjective perception and subliminal stimulation, in domain learning. Simulation results show that, even without any supervision or pre-requisition, a consensus of a color naming system can be reached in a population solely via the interactions. Our work confirms the importance of society interactions in color categorization, which is a long debate topic in human cognition. Moreover, our work also demonstrates the possibility of cognitive system development in autonomous intelligent agents. PMID:29136661

Frequency and time-domain inspiral templates for comparable mass compact binaries in eccentric orbits

NASA Astrophysics Data System (ADS)

Tanay, Sashwat; Haney, Maria; Gopakumar, Achamveedu

2016-03-01

Inspiraling compact binaries with non-negligible orbital eccentricities are plausible gravitational wave (GW) sources for the upcoming network of GW observatories. In this paper, we present two prescriptions to compute post-Newtonian (PN) accurate inspiral templates for such binaries. First, we adapt and extend the postcircular scheme of Yunes et al. [Phys. Rev. D 80, 084001 (2009)] to obtain a Fourier-domain inspiral approximant that incorporates the effects of PN-accurate orbital eccentricity evolution. This results in a fully analytic frequency-domain inspiral waveform with Newtonian amplitude and 2PN-order Fourier phase while incorporating eccentricity effects up to sixth order at each PN order. The importance of incorporating eccentricity evolution contributions to the Fourier phase in a PN-consistent manner is also demonstrated. Second, we present an accurate and efficient prescription to incorporate orbital eccentricity into the quasicircular time-domain TaylorT4 approximant at 2PN order. New features include the use of rational functions in orbital eccentricity to implement the 1.5PN-order tail contributions to the far-zone fluxes. This leads to closed form PN-accurate differential equations for evolving eccentric orbits, and the resulting time-domain approximant is accurate and efficient to handle initial orbital eccentricities ≤0.9 . Preliminary GW data analysis implications are probed using match estimates.

Does expert perceptual anticipation transfer to a dissimilar domain?

PubMed

Müller, Sean; McLaren, Michelle; Appleby, Brendyn; Rosalie, Simon M

2015-06-01

The purpose of this experiment was to extend theoretical understanding of transfer of learning by investigating whether expert perceptual anticipation skill transfers to a dissimilar domain. The capability of expert and near-expert rugby players as well as novices to anticipate skill type within rugby (learning sport) was first examined using a temporal occlusion paradigm. Participants watched video footage of an opponent performing rugby skill types that were temporally occluded at different points in the opponent's action and then made a written prediction. Thereafter, the capability of participants to transfer their anticipation skill to predict pitch type in baseball (transfer sport) was examined. Participants watched video footage of a pitcher throwing different pitch types that were temporally occluded and made a written prediction. Results indicated that expert and near-expert rugby players anticipated significantly better than novices across all occlusion conditions. However, none of the skill groups were able to transfer anticipation skill to predict pitch type in baseball. The findings of this paper, along with existing literature, support the theoretical prediction that transfer of perceptual anticipation is expertise dependent and restricted to similar domains. (c) 2015 APA, all rights reserved).

Predicting chroma from luma with frequency domain intra prediction

NASA Astrophysics Data System (ADS)

Egge, Nathan E.; Valin, Jean-Marc

2015-03-01

This paper describes a technique for performing intra prediction of the chroma planes based on the reconstructed luma plane in the frequency domain. This prediction exploits the fact that while RGB to YUV color conversion has the property that it decorrelates the color planes globally across an image, there is still some correlation locally at the block level.1 Previous proposals compute a linear model of the spatial relationship between the luma plane (Y) and the two chroma planes (U and V).2 In codecs that use lapped transforms this is not possible since transform support extends across the block boundaries3 and thus neighboring blocks are unavailable during intra- prediction. We design a frequency domain intra predictor for chroma that exploits the same local correlation with lower complexity than the spatial predictor and which works with lapped transforms. We then describe a low- complexity algorithm that directly uses luma coefficients as a chroma predictor based on gain-shape quantization and band partitioning. An experiment is performed that compares these two techniques inside the experimental Daala video codec and shows the lower complexity algorithm to be a better chroma predictor.

Global Federation of Data Services in Seismology: Extending the Concept to Interdisciplinary Science

NASA Astrophysics Data System (ADS)

Ahern, Tim; Trabant, Chad; Stults, Mike; VanFossen, Mick

2016-04-01

The International Federation of Digital Seismograph Networks (FDSN) sets international standards, formats, and access protocols for global seismology. Recently the availability of an FDSN standard for web services has enabled the development of a federated model of data access. With a growing number of internationally distributed data centers supporting compatible web services the task of federation is now fully realizable. The utility of this approach is already starting to bear fruit in seismology. This presentation will highlight the advances the seismological community has made in the past year towards federated access to seismological data including waveforms, earthquake event catalogs, and metadata describing seismic stations. It will include a discussion of an IRIS Federator as well as an emerging effort to develop an FDSN Federator that will allow seamless access to seismological information across multiple FDSN data centers. As part of the NSF EarthCube initiative as well as the US-European data coordination project (COOPEUS), IRIS and several partners, collectively called GeoWS, have been extending the concept of standard web services to other domains. Our primary partners include Lamont Doherty Earth Observatory (marine geophysics), Caltech (tectonic plate reconstructions), SDSC (hydrology), UNAVCO (geodesy), and Unidata (atmospheric sciences). Additionally, IRIS is working with partners at NOAA's National Centers for Environmental Information (NCEI) , NEON, UTEP, WOVOdat, INTERMAGNET, Global Geodynamics Program, and the Ocean Observatory Initiative (OOI) to develop web services for those domains. The ultimate goal is to allow discovery, access, and utilization of cross-domain data sources. One of the significant outcomes of this effort is the development of a simple text and metadata representation for tabular data called GeoCSV, that allows straightforward interpretation of information from multiple domains by non-domain experts.

A thermophilic mini-chaperonin contains a conserved polypeptide-binding surface: combined crystallographic and NMR studies of the GroEL Apical Domain with implications for substrate interactions

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

Hua, Q. X. H.; Dementieva, I. S. D.; Walsh, M. A. W.

2001-02-23

A homologue of the Escherichia coli GroEL apical domain was obtained from thermophilic eubacterium Thermus thermophilus. The domains share 70 % sequence identity (101 out of 145 residues). The thermal stability of the T. thermophilus apical domain (T{sub m}>100{sup o}C as evaluated by circular dichroism) is at least 35{sup o}C greater than that of the E. coli apical domain (T{sub m}=65{sup o}C). The crystal structure of a selenomethione-substituted apical domain from T. thermophilus was determined to a resolution of 1.78 {angstrom} using multiwavelength-anomalous-diffraction phasing. The structure is similar to that of the E. coli apical domain (root-mean-square deviation 0.45 {angstrom}more » based on main-chain atoms). The thermophilic structure contains seven additional salt bridges of which four contain charge-stabilized hydrogen bonds. Only one of the additional salt bridges would face the 'Anfinsen cage' in GroEL. High temperatures were exploited to map sites of interactions between the apical domain and molten globules. NMR footprints of apical domain-protein complexes were obtained at elevated temperature using {sup 15}N-{sup 1}H correlation spectra of {sup 15}N-labeled apical domain. Footprints employing two polypeptides unrelated in sequence or structure (an insulin monomer and the SRY high-mobility-group box, each partially unfolded at 50{sup o}C) are essentially the same and consistent with the peptide-binding surface previously defined in E. coli GroEL and its apical domain-peptide complexes. An additional part of this surface comprising a short N-terminal {alpha}-helix is observed. The extended footprint rationalizes mutagenesis studies of intact GroEL in which point mutations affecting substrate binding were found outside the 'classical' peptide-binding site. Our results demonstrate structural conservation of the apical domain among GroEL homologues and conservation of an extended non-polar surface recognizing diverse polypeptides.« less

Convexity Subarachnoid Hemorrhage Due to Cardioembolic Stroke in a Woman with Thyrotoxicosis: Α Case Report.

PubMed

Spanou, Ioanna; Vassilopoulou, Sophia; Koroboki, Eleni; Tountopoulou, Argyro; Velonakis, Georgios; Mitsikostas, Dimos Dimitrios

2017-10-01

Non-traumatic convexity subarachnoid hemorrhage (cSAH) is a rarely reported condition with a wide spectrum of etiologies. Cerebral ischemia secondary to extracranial or intracranial atherosclerotic disease has been identified as a relatively uncommon cause of cSAH. We report a case of cSAH caused by cardioembolic stroke. A 69-year old female patient developed suddenly left-sided face and body weakness and numbness and visual neglect on the left. She was newly detected with paroxysmal atrial fibrillation on the ground of thyrotoxicosis. Brain magnetic resonance imaging revealed ischemia of embolic pattern with cSAH. Further evaluation excluded other cause of hemorrhage. Dilation of leptomeningeal collateral vessels and rupture of pial vessels in distal cortical arteries may caused cSAH. Full anticoagulation was initiated. After one month, her condition improved significantly (NIHSS from 6 to 2). cSAH may be a rare complication of cardioembolic stroke. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Low-lying Photoexcited States of a One-Dimensional Ionic Extended Hubbard Model

NASA Astrophysics Data System (ADS)

Yokoi, Kota; Maeshima, Nobuya; Hino, Ken-ichi

2017-10-01

We investigate the properties of low-lying photoexcited states of a one-dimensional (1D) ionic extended Hubbard model at half-filling. Numerical analysis by using the full and Lanczos diagonalization methods shows that, in the ionic phase, there exist low-lying photoexcited states below the charge transfer gap. As a result of comparison with numerical data for the 1D antiferromagnetic (AF) Heisenberg model, it was found that, for a small alternating potential Δ, these low-lying photoexcited states are spin excitations, which is consistent with a previous analytical study [Katsura et al., Phys. Rev. Lett. 103, 177402 (2009)]. As Δ increases, the spectral intensity of the 1D ionic extended Hubbard model rapidly deviates from that of the 1D AF Heisenberg model and it is clarified that this deviation is due to the neutral-ionic domain wall, an elementary excitation near the neutral-ionic transition point.

Extracting and compensating dispersion mismatch in ultrahigh-resolution Fourier domain OCT imaging of the retina

PubMed Central

Choi, WooJhon; Baumann, Bernhard; Swanson, Eric A.; Fujimoto, James G.

2012-01-01

We present a numerical approach to extract the dispersion mismatch in ultrahigh-resolution Fourier domain optical coherence tomography (OCT) imaging of the retina. The method draws upon an analogy with a Shack-Hartmann wavefront sensor. By exploiting mathematical similarities between the expressions for aberration in optical imaging and dispersion mismatch in spectral / Fourier domain OCT, Shack-Hartmann principles can be extended from the two-dimensional paraxial wavevector space (or the x-y plane in the spatial domain) to the one-dimensional wavenumber space (or the z-axis in the spatial domain). For OCT imaging of the retina, different retinal layers, such as the retinal nerve fiber layer (RNFL), the photoreceptor inner and outer segment junction (IS/OS), or all the retinal layers near the retinal pigment epithelium (RPE) can be used as point source beacons in the axial direction, analogous to point source beacons used in conventional two-dimensional Shack-Hartman wavefront sensors for aberration characterization. Subtleties regarding speckle phenomena in optical imaging, which affect the Shack-Hartmann wavefront sensor used in adaptive optics, also occur analogously in this application. Using this approach and carefully suppressing speckle, the dispersion mismatch in spectral / Fourier domain OCT retinal imaging can be successfully extracted numerically and used for numerical dispersion compensation to generate sharper, ultrahigh-resolution OCT images. PMID:23187353

MiDas: Automatic Extraction of a Common Domain of Discourse in Sleep Medicine for Multi-center Data Integration

PubMed Central

Sahoo, Satya S.; Ogbuji, Chimezie; Luo, Lingyun; Dong, Xiao; Cui, Licong; Redline, Susan S.; Zhang, Guo-Qiang

2011-01-01

Clinical studies often use data dictionaries with controlled sets of terms to facilitate data collection, limited interoperability and sharing at a local site. Multi-center retrospective clinical studies require that these data dictionaries, originating from individual participating centers, be harmonized in preparation for the integration of the corresponding clinical research data. Domain ontologies are often used to facilitate multi-center data integration by modeling terms from data dictionaries in a logic-based language, but interoperability among domain ontologies (using automated techniques) is an unresolved issue. Although many upper-level reference ontologies have been proposed to address this challenge, our experience in integrating multi-center sleep medicine data highlights the need for an upper level ontology that models a common set of terms at multiple-levels of abstraction, which is not covered by the existing upper-level ontologies. We introduce a methodology underpinned by a Minimal Domain of Discourse (MiDas) algorithm to automatically extract a minimal common domain of discourse (upper-domain ontology) from an existing domain ontology. Using the Multi-Modality, Multi-Resource Environment for Physiological and Clinical Research (Physio-MIMI) multi-center project in sleep medicine as a use case, we demonstrate the use of MiDas in extracting a minimal domain of discourse for sleep medicine, from Physio-MIMI’s Sleep Domain Ontology (SDO). We then extend the resulting domain of discourse with terms from the data dictionary of the Sleep Heart and Health Study (SHHS) to validate MiDas. To illustrate the wider applicability of MiDas, we automatically extract the respective domains of discourse from 6 sample domain ontologies from the National Center for Biomedical Ontologies (NCBO) and the OBO Foundry. PMID:22195180

MiDas: automatic extraction of a common domain of discourse in sleep medicine for multi-center data integration.

PubMed

Sahoo, Satya S; Ogbuji, Chimezie; Luo, Lingyun; Dong, Xiao; Cui, Licong; Redline, Susan S; Zhang, Guo-Qiang

2011-01-01

Clinical studies often use data dictionaries with controlled sets of terms to facilitate data collection, limited interoperability and sharing at a local site. Multi-center retrospective clinical studies require that these data dictionaries, originating from individual participating centers, be harmonized in preparation for the integration of the corresponding clinical research data. Domain ontologies are often used to facilitate multi-center data integration by modeling terms from data dictionaries in a logic-based language, but interoperability among domain ontologies (using automated techniques) is an unresolved issue. Although many upper-level reference ontologies have been proposed to address this challenge, our experience in integrating multi-center sleep medicine data highlights the need for an upper level ontology that models a common set of terms at multiple-levels of abstraction, which is not covered by the existing upper-level ontologies. We introduce a methodology underpinned by a Minimal Domain of Discourse (MiDas) algorithm to automatically extract a minimal common domain of discourse (upper-domain ontology) from an existing domain ontology. Using the Multi-Modality, Multi-Resource Environment for Physiological and Clinical Research (Physio-MIMI) multi-center project in sleep medicine as a use case, we demonstrate the use of MiDas in extracting a minimal domain of discourse for sleep medicine, from Physio-MIMI's Sleep Domain Ontology (SDO). We then extend the resulting domain of discourse with terms from the data dictionary of the Sleep Heart and Health Study (SHHS) to validate MiDas. To illustrate the wider applicability of MiDas, we automatically extract the respective domains of discourse from 6 sample domain ontologies from the National Center for Biomedical Ontologies (NCBO) and the OBO Foundry.

Search for Extended Sources in the Galactic Plane Using Six Years of Fermi-Large Area Telescope Pass 8 Data above 10 GeV

DOE PAGES

Ackermann, M.; Ajello, M.; Baldini, L.; ...

2017-07-10

The spatial extension of a γ-ray source is an essential ingredient to determine its spectral properties, as well as its potential multiwavelength counterpart. The capability to spatially resolve γ-ray sources is greatly improved by the newly delivered Fermi-Large Area Telescope (LAT) Pass 8 event-level analysis, which provides a greater acceptance and an improved point-spread function, two crucial factors for the detection of extended sources. Here, we present a complete search for extended sources located within 7° from the Galactic plane, using 6 yr of Fermi-LAT data above 10 GeV. We find 46 extended sources and provide their morphological and spectralmore » characteristics. As a result, this constitutes the first catalog of hard Fermi-LAT extended sources, named the Fermi Galactic Extended Source Catalog, which allows a thorough study of the properties of the Galactic plane in the sub-TeV domain.« less

Search for Extended Sources in the Galactic Plane Using Six Years of Fermi-Large Area Telescope Pass 8 Data above 10 GeV

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

Ackermann, M.; Ajello, M.; Baldini, L.

The spatial extension of a γ-ray source is an essential ingredient to determine its spectral properties, as well as its potential multiwavelength counterpart. The capability to spatially resolve γ-ray sources is greatly improved by the newly delivered Fermi-Large Area Telescope (LAT) Pass 8 event-level analysis, which provides a greater acceptance and an improved point-spread function, two crucial factors for the detection of extended sources. Here, we present a complete search for extended sources located within 7° from the Galactic plane, using 6 yr of Fermi-LAT data above 10 GeV. We find 46 extended sources and provide their morphological and spectralmore » characteristics. As a result, this constitutes the first catalog of hard Fermi-LAT extended sources, named the Fermi Galactic Extended Source Catalog, which allows a thorough study of the properties of the Galactic plane in the sub-TeV domain.« less

Delayed Vasospasm after Aneurysmal Subarachnoid Hemorrhage in Behcet Syndrome.

PubMed

Kim, Jun Hak; Lee, Si-Un; Huh, Choonwoong; Oh, Chang Wan; Bang, Jae Seung; Kim, Tackeun

2016-03-01

A man visited the emergency room with a headache. Brain computed tomography showed aneurysmal subarachnoid hemorrhage (SAH) and multiple aneurysms. After aneurysm clipping surgery, the patient was discharged. After 5 days, he was admitted to the hospital with skin ulceration and was diagnosed with Behcet syndrome. An angiogram taken 7 weeks after aneurysmal SAH showed intracranial vasospasm. Because inflammation in Behcet syndrome may aggravate intracranial vasospasm, intracranial vasospasm after aneurysmal SAH in Behcet syndrome should be monitored for longer compared to general aneurysmal SAH.

Delayed Vasospasm after Aneurysmal Subarachnoid Hemorrhage in Behcet Syndrome

PubMed Central

Kim, Jun Hak; Lee, Si-Un; Huh, Choonwoong; Oh, Chang Wan; Bang, Jae Seung

2016-01-01

A man visited the emergency room with a headache. Brain computed tomography showed aneurysmal subarachnoid hemorrhage (SAH) and multiple aneurysms. After aneurysm clipping surgery, the patient was discharged. After 5 days, he was admitted to the hospital with skin ulceration and was diagnosed with Behcet syndrome. An angiogram taken 7 weeks after aneurysmal SAH showed intracranial vasospasm. Because inflammation in Behcet syndrome may aggravate intracranial vasospasm, intracranial vasospasm after aneurysmal SAH in Behcet syndrome should be monitored for longer compared to general aneurysmal SAH. PMID:27114963

Whether the decadal shift of South Asia High intensity around the late 1970s exists or not

NASA Astrophysics Data System (ADS)

Xue, Xu; Chen, Wen; Nath, Debashis; Zhou, Dingwen

2015-05-01

This study compares the decadal means of the seasonal (June-July-August (JJA)) mean geopotential heights available from the NCEP1 and ERA-40 reanalysis data in the Northern Hemisphere. The interdecadal changes in the South Asia High (SAH) intensity derived from the reanalysis data are also compared with ground-based radiosonde observations and atmospheric model outputs. The JJA mean geopotential heights in the 1980s are distinctly larger than the 1970s in NCEP1 over most of the regions in the Northern Hemisphere, while no obvious difference is observed in ERA-40. The interannual variation of the SAH strength is very close in the two reanalysis data, so that it is appropriate to utilize the reanalysis data to study the interannual variation of SAH strength after removing the interdecadal trend. However, the discrepancy in SAH intensity between NCEP1 and ERA-40 mainly exists on the interdecadal time scale. The SAH intensity in the NCEP1 was close to that in the ERA-40 before the late 1970s but became remarkably stronger after the late 1970s, leading to a much larger decadal strengthening during the period 1970-1990. Based on the six radiosonde observation stations in the area of the SAH, the results indicate that the decadal reinforcing in the SAH strength occurs around the mid-1980s. Thus, NCEP1 may overestimate the decadal shift in the SAH intensity around the late 1970s, while ERA-40 may underestimate it. Much attention needs to be paid when we use the reanalysis data to study the decadal variability of the SAH intensity.

Sudden death and cervical spine: A new contribution to pathogenesis for sudden death in critical care unit from subarachnoid hemorrhage; first report – An experimental study

PubMed Central

Kazdal, Hizir; Kanat, Ayhan; Aydin, Mehmet Dumlu; Yazar, Ugur; Guvercin, Ali Riza; Calik, Muhammet; Gundogdu, Betul

2017-01-01

Context: Sudden death from subarachnoid hemorrhage (SAH) is not uncommon. Aims: The goal of this study is to elucidate the effect of the cervical spinal roots and the related dorsal root ganglions (DRGs) on cardiorespiratory arrest following SAH. Settings and Design: This was an experimental study conducted on rabbits. Materials and Methods: This study was conducted on 22 rabbits which were randomly divided into three groups: control (n = 5), physiologic serum saline (SS; n = 6), SAH groups (n = 11). Experimental SAH was performed. Seven of 11 rabbits with SAH died within the first 2 weeks. After 20 days, other animals were sacrificed. The anterior spinal arteries, arteriae nervorum of cervical nerve roots (C6–C8), DRGs, and lungs were histopathologically examined and estimated stereologically. Statistical Analysis Used: Statistical analysis was performed using the PASW Statistics 18.0 for Windows (SPSS Inc., Chicago, Illinois, USA). Intergroup differences were assessed using a one-way ANOVA. The statistical significance was set at P < 0.05. Results: In the SAH group, histopathologically, severe anterior spinal artery (ASA) and arteriae nervorum vasospasm, axonal and neuronal degeneration, and neuronal apoptosis were observed. Vasospasm of ASA did not occur in the SS and control groups. There was a statistically significant increase in the degenerated neuron density in the SAH group as compared to the control and SS groups (P < 0.05). Cardiorespiratory disturbances, arrest, and lung edema more commonly developed in animals in the SAH group. Conclusion: We noticed interestingly that C6–C8 DRG degenerations were secondary to the vasospasm of ASA, following SAH. Cardiorespiratory disturbances or arrest can be explained with these mechanisms. PMID:28250634

A Dual Super-Element Domain Decomposition Approach for Parallel Nonlinear Finite Element Analysis

NASA Astrophysics Data System (ADS)

Jokhio, G. A.; Izzuddin, B. A.

2015-05-01

This article presents a new domain decomposition method for nonlinear finite element analysis introducing the concept of dual partition super-elements. The method extends ideas from the displacement frame method and is ideally suited for parallel nonlinear static/dynamic analysis of structural systems. In the new method, domain decomposition is realized by replacing one or more subdomains in a "parent system," each with a placeholder super-element, where the subdomains are processed separately as "child partitions," each wrapped by a dual super-element along the partition boundary. The analysis of the overall system, including the satisfaction of equilibrium and compatibility at all partition boundaries, is realized through direct communication between all pairs of placeholder and dual super-elements. The proposed method has particular advantages for matrix solution methods based on the frontal scheme, and can be readily implemented for existing finite element analysis programs to achieve parallelization on distributed memory systems with minimal intervention, thus overcoming memory bottlenecks typically faced in the analysis of large-scale problems. Several examples are presented in this article which demonstrate the computational benefits of the proposed parallel domain decomposition approach and its applicability to the nonlinear structural analysis of realistic structural systems.

Theoretical study of optical properties of anti phase domains in GaP

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

Tea, E., E-mail: etea.contact@gmail.com; FOTON INSA-Rennes; Vidal, J.

III-V/Si heterostructures are currently investigated for silicon photonics and solar energy conversion. In particular, dilute nitride alloy GaAsPN grown on a GaP/Si platform exhibits lattice match with Si and an optimal band gap configuration for tandem solar cell devices. However, monolithic “coherent” growth of the GaP thin layer on Si suffers from the nucleation of extended structural defects, which can hamper device operation as well as the GaP/Si interface level and through their propagation inside the overall heterostructure. However, the effect of such structural defects on optical and transport properties is actually not well understood in details. In this letter,more » we investigate the anti phase domains defect (also called inversion domains) by means of ab initio calculations giving insights into the alteration of optical and transport properties of GaP due to the defective GaP/Si interface.« less

PalymSys (TM): An extended version of CLIPS for construction and reasoning using blackboards

NASA Technical Reports Server (NTRS)

Bryson, Travis; Ballard, Dan

1994-01-01

This paper describes PalymSys(TM) -- an extended version of the CLIPS language that is designed to facilitate the implementation of blackboard systems. The paper first describes the general characteristics of blackboards and shows how a control blackboard architecture can be used by AI systems to examine their own behavior and adapt to real-time problem-solving situations by striking a balance between domain and control reasoning. The paper then describes the use of PalymSys in the development of a situation assessment subsystem for use aboard Army helicopters. This system performs real-time inferencing about the current battlefield situation using multiple domain blackboards as well as a control blackboard. A description of the control and domain blackboards and their implementation is presented. The paper also describes modifications made to the standard CLIPS 6.02 language in PalymSys(TM) 2.0. These include: (1) a dynamic Dempster-Shafer belief network whose structure is completely specifiable at run-time in the consequent of a PalymSys(TM) rule, (2) extension of the run command including a continuous run feature that enables the system to run even when the agenda is empty, and (3) a built-in communications link that uses shared memory to communicate with other independent processes.

Adaptation and Validation of the Spanish Version of OSA-18, a Quality of Life Questionnaire for Evaluation of Children with Sleep Apnea-Hypopnea Syndrome.

PubMed

Chiner, Eusebi; Landete, Pedro; Sancho-Chust, José Norberto; Martínez-García, Miguel Ángel; Pérez-Ferrer, Patricia; Pastor, Esther; Senent, Cristina; Arlandis, Mar; Navarro, Cristina; Selma, María José

2016-11-01

To analyze the reliability and validity of the Spanish version of the OSA-18 quality of life questionnaire in children with apnea-hypopnea syndrome (SAHS). Children with suspected SAHS were studied with polysomnography (PSG) before and after adenotonsillectomy (AA). Age, gender, clinical data, PSG, anthropometric data, and Mallampati and Brodsky scales were analyzed. OSA-18 was administered at baseline and 3-6months post AA. After translation and backtranslation by bilingual professionals, the internal consistency, reliability, construct validity, concurrent validity, predictive validity and sensitivity to change of the questionnaire was assessed. In total, 45 boys and 15 girls were evaluated, showing BMI 18±4, neck 28±5, Brodsky (0: 7%; <25%: 12%; 25-50%: 27%; >50 to <75%: 45%; >75%: 6%), AHI 12±7 pre AA. Global Cronbach alpha was 0.91. Correlations between domains were significant except for emotional aspects, although the total scores correlated with all domains (0.50 to 0.90). The factorial analysis was virtually identical to the original structure. The total scores showed good correlation for concurrent validity (0.2-0.45). With regard to predictive validity, the questionnaire adequately differentiated levels of severity according to Mallampati (ANOVA P=.002) and apnea-hypopnea index (ANOVA P=.006). Test-retest reliability was excellent, as was sensitivity to change, both in the total scores (P<.001) and in each domain (P<.001). The Spanish adaptation of the OSA-18 and its psychometric characteristics suggest that the Spanish version is equivalent to the original and can be used in Spanish-speaking countries. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Extended family medicine training

PubMed Central

Slade, Steve; Ross, Shelley; Lawrence, Kathrine; Archibald, Douglas; Mackay, Maria Palacios; Oandasan, Ivy F.

2016-01-01

Abstract Objective To examine trends in family medicine training at a time when substantial pedagogic change is under way, focusing on factors that relate to extended family medicine training. Design Aggregate-level secondary data analysis based on the Canadian Post-MD Education Registry. Setting Canada. Participants All Canadian citizens and permanent residents who were registered in postgraduate family medicine training programs within Canadian faculties of medicine from 1995 to 2013. Main outcome measures Number and proportion of family medicine residents exiting 2-year and extended (third-year and above) family medicine training programs, as well as the types and numbers of extended training programs offered in 2015. Results The proportion of family medicine trainees pursuing extended training almost doubled during the study period, going from 10.9% in 1995 to 21.1% in 2013. Men and Canadian medical graduates were more likely to take extended family medicine training. Among the 5 most recent family medicine exit cohorts (from 2009 to 2013), 25.9% of men completed extended training programs compared with 18.3% of women, and 23.1% of Canadian medical graduates completed extended training compared with 13.6% of international medical graduates. Family medicine programs vary substantially with respect to the proportion of their trainees who undertake extended training, ranging from a low of 12.3% to a high of 35.1% among trainees exiting from 2011 to 2013. Conclusion New initiatives, such as the Triple C Competency-based Curriculum, CanMEDS–Family Medicine, and Certificates of Added Competence, have emerged as part of family medicine education and credentialing. In acknowledgment of the potential effect of these initiatives, it is important that future research examine how pedagogic change and, in particular, extended training shapes the care family physicians offer their patients. As part of that research it will be important to measure the breadth and uptake of

Changes in children's self-competence and values: gender and domain differences across grades one through twelve.

PubMed

Jacobs, Janis E; Lanza, Stephanie; Osgood, D Wayne; Eccles, Jacquelynne S; Wigfield, Allan

2002-01-01

This study extended previous research on changes in children's self-beliefs by documenting domain-specific growth trajectories for 761 children across grades 1 through 12 in a longitudinal study of perceptions of self-competence and task values. Hierarchical Linear Modeling was used to (1) describe changes in beliefs across childhood and adolescence within the domains of mathematics, language arts, and sports; (2) examine the impact of changes in competence beliefs on changes in values over time in the same domains; and (3) describe gender differences in mean levels and trajectories of change in competence beliefs and values. The most striking finding across all domains was that self-perceptions of competence and subjective task values declined as children got older, although the extent and rate of decline varied across domains. For example, in language arts, competence beliefs declined rapidly during the elementary school years, but then leveled off or increased to some extent; whereas the decline in self-competence beliefs in sports accelerated during the high school years. Significant gender differences in beliefs were found in most domains; however, the gender differences in developmental trajectories appeared to be domain specific rather than global. Importantly, the gender differences between boys and girls did not systematically increase with age, as predicted by some socialization perspectives. Adding competence beliefs as an explanatory variable to the model for task values revealed that changes in competence beliefs accounted for much of the age-related decline in task values. In addition, competence beliefs accounted for most of the gender differences in task values for language arts and sports.

The HIV-1 late domain-2 S40A polymorphism in antiretroviral (or ART)-exposed individuals influences protease inhibitor susceptibility.

PubMed

Watanabe, Susan M; Simon, Viviana; Durham, Natasha D; Kemp, Brittney R; Machihara, Satoshi; Kemal, Kimdar Sherefa; Shi, Binshan; Foley, Brian; Li, Hongru; Chen, Benjamin K; Weiser, Barbara; Burger, Harold; Anastos, Kathryn; Chen, Chaoping; Carter, Carol A

2016-09-06

The p6 region of the HIV-1 structural precursor polyprotein, Gag, contains two motifs, P7TAP11 and L35YPLXSL41, designated as late (L) domain-1 and -2, respectively. These motifs bind the ESCRT-I factor Tsg101 and the ESCRT adaptor Alix, respectively, and are critical for efficient budding of virus particles from the plasma membrane. L domain-2 is thought to be functionally redundant to PTAP. To identify possible other functions of L domain-2, we examined this motif in dominant viruses that emerged in a group of 14 women who had detectable levels of HIV-1 in both plasma and genital tract despite a history of current or previous antiretroviral therapy. Remarkably, variants possessing mutations or rare polymorphisms in the highly conserved L domain-2 were identified in seven of these women. A mutation in a conserved residue (S40A) that does not reduce Gag interaction with Alix and therefore did not reduce budding efficiency was further investigated. This mutation causes a simultaneous change in the Pol reading frame but exhibits little deficiency in Gag processing and virion maturation. Whether introduced into the HIV-1 NL4-3 strain genome or a model protease (PR) precursor, S40A reduced production of mature PR. This same mutation also led to high level detection of two extended forms of PR that were fairly stable compared to the WT in the presence of IDV at various concentrations; one of the extended forms was effective in trans processing even at micromolar IDV. Our results indicate that L domain-2, considered redundant in vitro, can undergo mutations in vivo that significantly alter PR function. These may contribute fitness benefits in both the absence and presence of PR inhibitor.

Domain shape instabilities and dendrite domain growth in uniaxial ferroelectrics

NASA Astrophysics Data System (ADS)

Shur, Vladimir Ya.; Akhmatkhanov, Andrey R.

2018-01-01

The effects of domain wall shape instabilities and the formation of nanodomains in front of moving walls obtained in various uniaxial ferroelectrics are discussed. Special attention is paid to the formation of self-assembled nanoscale and dendrite domain structures under highly non-equilibrium switching conditions. All obtained results are considered in the framework of the unified kinetic approach to domain structure evolution based on the analogy with first-order phase transformation. This article is part of the theme issue `From atomistic interfaces to dendritic patterns'.

Contributions of the Central Extended Amygdala to Fear and Anxiety

PubMed Central

2016-01-01

It is widely thought that phasic and sustained responses to threat reflect dissociable circuits centered on the central nucleus of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST), the two major subdivisions of the central extended amygdala. Early versions of this hypothesis remain highly influential and have been incorporated into the National Institute of Mental Health Research Research Domain Criteria framework. However, new observations encourage a different perspective. Anatomical studies show that the Ce and BST form a tightly interconnected unit, where different kinds of threat-relevant information can be integrated and used to assemble states of fear and anxiety. Imaging studies in humans and monkeys show that the Ce and BST exhibit similar functional profiles. Both regions are sensitive to a range of aversive challenges, including uncertain or temporally remote threat; both covary with concurrent signs and symptoms of fear and anxiety; both show phasic responses to short-lived threat; and both show heightened activity during sustained exposure to diffusely threatening contexts. Mechanistic studies demonstrate that both regions can control the expression of fear and anxiety during sustained exposure to diffuse threat. These observations compel a reconsideration of the central extended amygdala's contributions to fear and anxiety and its role in neuropsychiatric disease. PMID:27488625

Structural changes in the BH3 domain of SOUL protein upon interaction with the anti-apoptotic protein Bcl-xL

PubMed Central

Ambrosi, Emmanuele; Capaldi, Stefano; Bovi, Michele; Saccomani, Gianmaria; Perduca, Massimiliano; Monaco, Hugo L.

2011-01-01

The SOUL protein is known to induce apoptosis by provoking the mitochondrial permeability transition, and a sequence homologous with the BH3 (Bcl-2 homology 3) domains has recently been identified in the protein, thus making it a potential new member of the BH3-only protein family. In the present study, we provide NMR, SPR (surface plasmon resonance) and crystallographic evidence that a peptide spanning residues 147–172 in SOUL interacts with the anti-apoptotic protein Bcl-xL. We have crystallized SOUL alone and the complex of its BH3 domain peptide with Bcl-xL, and solved their three-dimensional structures. The SOUL monomer is a single domain organized as a distorted β-barrel with eight anti-parallel strands and two α-helices. The BH3 domain extends across 15 residues at the end of the second helix and eight amino acids in the chain following it. There are important structural differences in the BH3 domain in the intact SOUL molecule and the same sequence bound to Bcl-xL. PMID:21639858

Increasing numbers of nonaneurysmal subarachnoid hemorrhage in the last 15 years: antithrombotic medication as reason and prognostic factor?

PubMed

Konczalla, Juergen; Kashefiolasl, Sepide; Brawanski, Nina; Senft, Christian; Seifert, Volker; Platz, Johannes

2016-06-01

OBJECT Subarachnoid hemorrhage (SAH) is usually caused by a ruptured intracranial aneurysm, but in some patients no source of hemorrhage can be detected. More recent data showed increasing numbers of cases of spontaneous nonaneurysmal SAH (NASAH). The aim of this study was to analyze factors, especially the use of antithrombotic medications such as systemic anticoagulation or antiplatelet agents (aCPs), influencing the increasing numbers of cases of NASAH and the clinical outcome. METHODS Between 1999 and 2013, 214 patients who were admitted to the authors' institution suffered from NASAH, 14% of all patients with SAH. Outcome was assessed according to the modified Rankin Scale (mRS) at 6 months. Risk factors were identified based on the outcome. RESULTS The number of patients with NASAH increased significantly in the last 15 years of the study period. There was a statistically significant increase in the rate of nonperimesencephalic (NPM)-SAH occurrence and aCP use, while the proportion of elderly patients remained stable. Favorable outcome (mRS 0-2) was achieved in 85% of cases, but patients treated with aCPs had a significantly higher risk for an unfavorable outcome. Further analysis showed that elderly patients, and especially the subgroup with a Fisher Grade 3 bleeding pattern, had a high risk for an unfavorable outcome, whereas the subgroup of NPM-SAH without a Fisher Grade 3 bleeding pattern had a favorable outcome, similar to perimesencephalic (PM)-SAH. CONCLUSIONS Over the years, a significant increase in the number of patients with NASAH has been observed. Also, the rate of aCP use has increased significantly. Risk factors for an unfavorable outcome were age > 65 years, Fisher Grade 3 bleeding pattern, and aCP use. Both "PM-SAH" and "NPM-SAH without a Fisher Grade 3 bleeding pattern" had excellent outcomes. Patients with NASAH and a Fisher Grade 3 bleeding pattern had a significantly higher risk for an unfavorable outcome and death. Therefore, for further

Preliminary frequency-domain analysis for the reconstructed spatial resolution of muon tomography

NASA Astrophysics Data System (ADS)

Yu, B.; Zhao, Z.; Wang, X.; Wang, Y.; Wu, D.; Zeng, Z.; Zeng, M.; Yi, H.; Luo, Z.; Yue, X.; Cheng, J.

2014-11-01

Muon tomography is an advanced technology to non-destructively detect high atomic number materials. It exploits the multiple Coulomb scattering information of muon to reconstruct the scattering density image of the traversed object. Because of the statistics of muon scattering, the measurement error of system and the data incompleteness, the reconstruction is always accompanied with a certain level of interference, which will influence the reconstructed spatial resolution. While statistical noises can be reduced by extending the measuring time, system parameters determine the ultimate spatial resolution that one system can reach. In this paper, an effective frequency-domain model is proposed to analyze the reconstructed spatial resolution of muon tomography. The proposed method modifies the resolution analysis in conventional computed tomography (CT) to fit the different imaging mechanism in muon scattering tomography. The measured scattering information is described in frequency domain, then a relationship between the measurements and the original image is proposed in Fourier domain, which is named as "Muon Central Slice Theorem". Furthermore, a preliminary analytical expression of the ultimate reconstructed spatial is derived, and the simulations are performed for validation. While the method is able to predict the ultimate spatial resolution of a given system, it can also be utilized for the optimization of system design and construction.

Stress fields around two pores in an elastic body: exact quadrature domain solutions.

PubMed

Crowdy, Darren

2015-08-08

Analytical solutions are given for the stress fields, in both compression and far-field shear, in a two-dimensional elastic body containing two interacting non-circular pores. The two complex potentials governing the solutions are found by using a conformal mapping from a pre-image annulus with those potentials expressed in terms of the Schottky-Klein prime function for the annulus. Solutions for a three-parameter family of elastic bodies with two equal symmetric pores are presented and the compressibility of a special family of pore pairs is studied in detail. The methodology extends to two unequal pores. The importance for boundary value problems of plane elasticity of a special class of planar domains known as quadrature domains is also elucidated. This observation provides the route to generalization of the mathematical approach here to finding analytical solutions for the stress fields in bodies containing any finite number of pores.

The Biochemical Basis of Hydroxymethylglutaryl-CoA Reductase Inhibitors as Neuroprotective Agents in Aneurysmal Subarachnoid Hemorrhage

PubMed Central

Wong, George Kwok Chu; Poon, Wai Sang

2010-01-01

Aneurysmal subarachnoid hemorrhage (SAH) has the highest morbidity and mortality rates of all types of stroke. Many aneurysmal SAH patients continue to suffer from significant neurological morbidity and mortality directly related to delayed cerebral ischemia. Pilot clinical studies of the use of Hydroxymethylglutaryl-CoA Reductase Inhibitors (statins) in aneurysmal SAH patients have reported a reduction in delayed cerebral ischemia and better clinical outcomes. We review the biochemical effects of statins on endothelium vascular function, glutamate-mediated neurotoxicity, inflammatory changes, and oxidative injuries, with reference to their possible neuroprotective effects in aneurysmal SAH.

The Arctic Marine Pulses Model: Linking Contiguous Domains in the Pacific Arctic Region

NASA Astrophysics Data System (ADS)

Moore, S. E.; Stabeno, P. J.

2016-02-01

The Pacific Arctic marine ecosystem extends from the northern Bering Sea, across the Chukchi and into the East Siberian and Beaufort seas. Food webs in this domain are short, a simplicity that belies the biophysical complexity underlying trophic linkages from primary production to humans. Existing biophysical models, such as pelagic-benthic coupling and advective processes, provide frameworks for connecting certain aspects of the marine food web, but do not offer a full accounting of events that occur seasonally across the Pacific Arctic. In the course of the Synthesis of Arctic Research (SOAR) project, a holistic Arctic Marine Pulses (AMP) model was developed that depicts seasonal biophysical `pulses' across a latitudinal gradient, and linking four previously-described contiguous domains, including the: (i) Pacific-Arctic domain = the focal region; (ii) seasonal ice zone domain; (iii) Pacific marginal domain; and (iv) riverine coastal domain. The AMP model provides a spatial-temporal framework to guide research on dynamic ecosystem processes during this period of rapid biophysical changes in the Pacific Arctic. Some of the processes included in the model, such as pelagic-benthic coupling in the Northern Bering and Chukchi seas, and advection and upwelling along the Beaufort shelf, are already the focus of sampling via the Distributed Biological Observatory (DBO) and other research programs. Other aspects such as biological processes associated with the seasonal ice zone and trophic responses to riverine outflow have received less attention. The AMP model could be enhanced by the application of visualization tools to provide a means to watch a season unfold in space and time. The capability to track sea ice dynamics and water masses and to move nutrients, prey and upper-trophic predators in space and time would provide a strong foundation for the development of predictive human-inclusive ecosystem models for the Pacific Arctic.

Possible Role of Inflammation and Galectin-3 in Brain Injury after Subarachnoid Hemorrhage

PubMed Central

2018-01-01

Aneurysmal subarachnoid hemorrhage (SAH) is known as one of the most devastating diseases in the central nervous system. In the past few decades, research on SAH has focused on cerebral vasospasm to prevent post-SAH delayed cerebral ischemia (DCI) and to improve outcomes. However, increasing evidence has suggested that early brain injury (EBI) is an important mechanism contributing to DCI, cerebral vasospasm as well as poor outcomes. Though the mechanism of EBI is very complex, inflammation is thought to play a pivotal role in EBI. Galectin-3 is a unique chimera type in the galectin family characterized by its β-galactoside-binding lectin, which mediates various pathologies, such as fibrosis, cell adhesion, and inflammation. Recently, two clinical studies revealed galectin-3 to be a possible prognostic biomarker in SAH patients. In addition, our recent report suggested that higher acute-stage plasma galectin-3 levels correlated with subsequent development of delayed cerebral infarction that was not associated with vasospasm in SAH patients. We review the possible role and molecular mechanisms of inflammation as well as galectin-3 in brain injuries, especially focusing on EBI after SAH, and discuss galectin-3 as a potential new therapeutic or research target in post-SAH brain injuries. PMID:29414883

Sulforaphane activates the cerebral vascular Nrf2-ARE pathway and suppresses inflammation to attenuate cerebral vasospasm in rat with subarachnoid hemorrhage.

PubMed

Zhao, Xudong; Wen, Liting; Dong, Min; Lu, Xiaojie

2016-12-15

Nrf2-ARE pathway reportedly plays a protective role in several central nervous system diseases. No study has explored the role of the Nrf2-ARE pathway in cerebral vasospasm(CVS) after subarachnoid hemorrhage(SAH). The purpose of the present study was to investigate the activation of the cerebral vascular Nrf2-ARE pathway and to determine the potential role of this pathway in the development of CVS following SAH. We investigated whether the administration of sulforaphane (SFN, a specific Nrf2 activator) modulated vascular caliber, Nrf2-ARE pathway activity, proinflammatory cytokine expression, and clinical behavior in a rat model of SAH. A two-hemorrhage protocol was used to generate an animal model of SAH in male Sprague-Dawley rats. Administration of SFN to these rats following SAH enhanced the activity of the Nrf2-ARE pathway and suppressed the release of proinflammatory cytokines. Vasospasm was markedly attenuated in the basilar arteries after SFN therapy. Additionally, SFN administration significantly ameliorated two behavioral functions disrupted by SAH. These results suggest that SFN has a therapeutic benefit in post-SAH, and this may be due to elevated Nrf2-ARE pathway activity and inhibition of cerebral vascular proinflammatory cytokine expression. Copyright © 2016. Published by Elsevier B.V.

Curcumin attenuates blood-brain barrier disruption after subarachnoid hemorrhage in mice.

PubMed

Yuan, Jichao; Liu, Wei; Zhu, Haitao; Zhang, Xuan; Feng, Yang; Chen, Yaxing; Feng, Hua; Lin, Jiangkai

2017-01-01

Early brain injury, one of the most important mechanisms underlying subarachnoid hemorrhage (SAH), comprises edema formation and blood-brain barrier (BBB) disruption. Curcumin, an active extract from the rhizomes of Curcuma longa, alleviates neuroinflammation by as yet unknown neuroprotective mechanisms. In this study, we examined whether curcumin treatment ameliorates SAH-induced brain edema and BBB permeability changes, as well as the mechanisms underlying this phenomenon. We induced SAH in mice via endovascular perforation, administered curcumin 15 min after surgery and evaluated neurologic scores, brain water content, Evans blue extravasation, Western blot assay results, and immunohistochemical analysis results 24 h after surgery. Curcumin significantly improved neurologic scores and reduced brain water content in treated mice compared with SAH mice. Furthermore, curcumin decreased Evans blue extravasation, matrix metallopeptidase-9 expression, and the number of Iba-1-positive microglia in treated mice compared with SAH mice. At last, curcumin treatment increased the expression of the tight junction proteins zonula occludens-1 and occludin in treated mice compared with vehicle-treated and sample SAH mice. We demonstrated that curcumin inhibits microglial activation and matrix metallopeptidase-9 expression, thereby reducing brain edema and attenuating post-SAH BBB disruption in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

Associations between Temperature and Hospital Admissions for Subarachnoid Hemorrhage in Korea

PubMed Central

Lee, Suji; Guth, Matthias

2017-01-01

The relationship between temperature and subarachnoid hemorrhage (SAH) is less studied than that between temperature and myocardial infarction or other cardiovascular diseases. This study investigated the association between daily temperature and risk of SAH by analyzing the hospital admission records of 111,316 SAH patients from 2004 to 2012 in Korea. A Poisson regression model was used to examine the association between temperature and daily SAH hospital admissions. To analyze data and identify vulnerable groups, we used the following subgroups: sex, age, insurance type, area (rural or urban), and different climate zones. We confirmed a markedly higher SAH risk only for people of low socioeconomic status in both hot and cold temperatures; the relative risk (RR) in the Medicaid group was significantly increased and ranged from 1.04 to 1.11 for cold temperatures and 1.10 to 1.11 for hot temperatures. For the National Health Insurance group, the RR was increased to 1.02 for the maximum temperature only. The increased risk for SAH was highest in the temperate zone. An increase above the heat threshold temperature and a decrease below the cold threshold temperature were correlated with an increased risk of SAH in susceptible populations and were associated with different lag effects and RRs. PMID:28430143

The effects of intrathecal nicergoline and nimodipine in cerebral vasospasm: an experimental study in rabbits.

PubMed

Solmaz, Ilker; Onal, Mehmet Bulent; Civelek, Erdinc; Kircelli, Atilla; Ongoru, Onder; Ugurel, Sahin; Erdogan, Ersin; Gonul, Engin

2011-01-01

the aim of this study was to assess and to compare the ability of intrathecal nicergoline and nimodipine in prevention of cerebral vasospasm in a rabbit model of subarachnoid hemorrhage (SAH). twenty male New Zealand white rabbits were allocated into four groups randomly. Subarachnoid hemorrhage was induced by injecting autologous blood into the cisterna magna. The treatment groups were as follows: (1) control [no SAH (n = 5)], (2) SAH only (n = 5), (3) SAH plus nimodipine (n = 5), and (4) SAH plus nicergoline (n = 5). there was a statistically significant difference between the mean basilar artery cross-sectional areas and the mean arterial wall thickness measurements of the control and SAH-only groups (p < 0.05). Basilar artery vessel diameter and luminal section areas in group 3 were significantly higher than in group 2 (p < 0.05). Basilar artery vessel diameter and basilar artery luminal section areas in group 4 were significantly higher than in group 2 (p < 0.05). There was no significant difference between basilar artery vessel diameter and basilar artery luminal section areas in group 3 and group 4. these findings demonstrate that intrathecal nicergoline has a vasodilatatory effect in an experimental model of SAH in rabbits but not more than that of nimodipine.

Domain-Generality versus Domain-Specificity: The Life and Impending Death of a False Dichotomy.

ERIC Educational Resources Information Center

Sternberg, Robert J.

1989-01-01

Argues that the question of whether information representation and processing are domain-general or domain-specific is neither meaningful nor answerable. Researchers should be asking questions about ways in which representation and processing are domain-general and ways in which they are domain-specific. (RH)

Adverse lipid profile elevates risk for subarachnoid hemorrhage: A prospective population-based cohort study.

PubMed

Lindbohm, Joni; Korja, Miikka; Jousilahti, Pekka; Salomaa, Veikko; Kaprio, Jaakko

2018-05-05

Studies report that both high and low total cholesterol (TC) elevates SAH risk. There are few prospective studies on high-density lipoproteins (HDL-C) and low-density lipoproteins (LDL-C), and apparently none concerns apolipoproteins A and B. We aimed to clarify the association between lipid profile and SAH risk. The National FINRISK study provided risk-factor data recorded at enrolment between 1972 and 2007. During 1.52 million person-years of follow-up until 2014, 543 individuals suffered from incident hospitalized SAH or outside-hospital-fatal SAH. Cox proportional hazards model was used to calculate the hazard ratios and multiple imputation predicted ApoA1, ApoB, and LDL-C values for cohorts from a time before apolipoprotein-measurement methods were available. One SD elevation (1.28 mmol/l) in TC elevated SAH risk in men (hazard ratio (HR) 1.15 (95% CIs 1.00-1.32)). Low HDL-C levels increased SAH risk, as each SD decrease (0.37 mmol/l) in HDL-C raised the risk in women (HR 1.29 (95% CIs 1.07-1.55)) and men (HR 1.20 (95% CIs 1.14-1.27)). Each SD increase (0.29 g/l) in ApoA1 decreased SAH risk in women (HR 0.85 (95% CIs 0.74-0.97)) and men (HR 0.88 (95% CIs 0.76-1.02)). LDL-C (SD 1.07 mmol/l) and ApoB (SD 0.28 g/l) elevated SAH risk in men with HR 1.15 (95% CIs 1.01-1.31) and HR 1.26 (95% CIs 1.10-1.44) per one SD increase. Age did not change these findings. An adverse lipid profile seems to elevate SAH risk similar to its effect in other cardiovascular diseases, especially in men. Whether SAH incidence diminishes with increasing statin use remains to be studied. Copyright © 2018 Elsevier B.V. All rights reserved.

Between-domain relations of students' academic emotions and their judgments of school domain similarity

PubMed Central

Goetz, Thomas; Haag, Ludwig; Lipnevich, Anastasiya A.; Keller, Melanie M.; Frenzel, Anne C.; Collier, Antonie P. M.

2014-01-01

With the aim to deepen our understanding of the between-domain relations of academic emotions, a series of three studies was conducted. We theorized that between-domain relations of trait (i.e., habitual) emotions reflected students' judgments of domain similarities, whereas between-domain relations of state (i.e., momentary) emotions did not. This supposition was based on the accessibility model of emotional self-report, according to which individuals' beliefs tend to strongly impact trait, but not state emotions. The aim of Study 1 (interviews; N = 40; 8th and 11th graders) was to gather salient characteristics of academic domains from students' perspective. In Study 2 (N = 1709; 8th and 11th graders) the 13 characteristics identified in Study 1 were assessed along with academic emotions in four different domains (mathematics, physics, German, and English) using a questionnaire-based trait assessment. With respect to the same domains, state emotions were assessed in Study 3 (N = 121; 8th and 11th graders) by employing an experience sampling approach. In line with our initial assumptions, between-domain relations of trait but not state academic emotions reflected between-domain relations of domain characteristics. Implications for research and practice are discussed. PMID:25374547

Spontaneous Subarachnoid Hemorrhage: A Systematic Review and Meta-analysis Describing the Diagnostic Accuracy of History, Physical Examination, Imaging, and Lumbar Puncture With an Exploration of Test Thresholds.

PubMed

Carpenter, Christopher R; Hussain, Adnan M; Ward, Michael J; Zipfel, Gregory J; Fowler, Susan; Pines, Jesse M; Sivilotti, Marco L A

2016-09-01

Spontaneous subarachnoid hemorrhage (SAH) is a rare, but serious etiology of headache. The diagnosis of SAH is especially challenging in alert, neurologically intact patients, as missed or delayed diagnosis can be catastrophic. The objective was to perform a diagnostic accuracy systematic review and meta-analysis of history, physical examination, cerebrospinal fluid (CSF) tests, computed tomography (CT), and clinical decision rules for spontaneous SAH. A secondary objective was to delineate probability of disease thresholds for imaging and lumbar puncture (LP). PubMed, Embase, Scopus, and research meeting abstracts were searched up to June 2015 for studies of emergency department patients with acute headache clinically concerning for spontaneous SAH. QUADAS-2 was used to assess study quality and, when appropriate, meta-analysis was conducted using random effects models. Outcomes were sensitivity, specificity, and positive (LR+) and negative (LR-) likelihood ratios. To identify test and treatment thresholds, we employed the Pauker-Kassirer method with Bernstein test indication curves using the summary estimates of diagnostic accuracy. A total of 5,022 publications were identified, of which 122 underwent full-text review; 22 studies were included (average SAH prevalence = 7.5%). Diagnostic studies differed in assessment of history and physical examination findings, CT technology, analytical techniques used to identify xanthochromia, and criterion standards for SAH. Study quality by QUADAS-2 was variable; however, most had a relatively low risk of biases. A history of neck pain (LR+ = 4.1; 95% confidence interval [CI] = 2.2 to 7.6) and neck stiffness on physical examination (LR+ = 6.6; 95% CI = 4.0 to 11.0) were the individual findings most strongly associated with SAH. Combinations of findings may rule out SAH, yet promising clinical decision rules await external validation. Noncontrast cranial CT within 6 hours of headache onset accurately ruled in (LR+ = 230; 95

Spontaneous Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis Describing the Diagnostic Accuracy of History, Physical Exam, Imaging, and Lumbar Puncture with an Exploration of Test Thresholds

PubMed Central

Carpenter, Christopher R.; Hussain, Adnan M.; Ward, Michael J.; Zipfel, Gregory J.; Fowler, Susan; Pines, Jesse M.; Sivilotti, Marco L.A.

2016-01-01

Background Spontaneous subarachnoid hemorrhage (SAH) is a rare, but serious etiology of headache. The diagnosis of SAH is especially challenging in alert, neurologically intact patients, as missed or delayed diagnosis can be catastrophic. Objectives To perform a diagnostic accuracy systematic review and meta-analysis of history, physical examination, cerebrospinal fluid (CSF) tests, computed tomography (CT), and clinical decision rules for spontaneous SAH. A secondary objective was to delineate probability of disease thresholds for imaging and lumbar puncture (LP). Methods PUBMED, EMBASE, SCOPUS, and research meeting abstracts were searched up to June 2015 for studies of emergency department (ED) patients with acute headache clinically concerning for spontaneous SAH. QUADAS-2 was used to assess study quality and, when appropriate, meta-analysis was conducted using random effects models. Outcomes were sensitivity, specificity, positive (LR+) and negative (LR−) likelihood ratios. To identify test- and treatment-thresholds, we employed the Pauker-Kassirer method with Bernstein test-indication curves using the summary estimates of diagnostic accuracy. Results A total of 5,022 publications were identified, of which 122 underwent full text-review; 22 studies were included (average SAH prevalence 7.5%). Diagnostic studies differed in assessment of history and physical exam findings, CT technology, analytical techniques used to identify xanthochromia, and criterion standards for SAH. Study quality by QUADAS-2 was variable; however, most had a relatively low-risk of biases. A history of neck pain (LR+ 4.1 [95% CI 2.2-7.6]) and neck stiffness on physical exam (LR+ 6.6 [4.0-11.0]) were the individual findings most strongly associated with SAH. Combinations of findings may rule out SAH, yet promising clinical decision rules await external validation. Non-contrast cranial CT within 6 hours of headache onset accurately ruled-in (LR+ 230 [6-8700]) and ruled-out SAH (LR− 0

Inference of domain-disease associations from domain-protein, protein-disease and disease-disease relationships.

PubMed

Zhang, Wangshu; Coba, Marcelo P; Sun, Fengzhu

2016-01-11

Protein domains can be viewed as portable units of biological function that defines the functional properties of proteins. Therefore, if a protein is associated with a disease, protein domains might also be associated and define disease endophenotypes. However, knowledge about such domain-disease relationships is rarely available. Thus, identification of domains associated with human diseases would greatly improve our understanding of the mechanism of human complex diseases and further improve the prevention, diagnosis and treatment of these diseases. Based on phenotypic similarities among diseases, we first group diseases into overlapping modules. We then develop a framework to infer associations between domains and diseases through known relationships between diseases and modules, domains and proteins, as well as proteins and disease modules. Different methods including Association, Maximum likelihood estimation (MLE), Domain-disease pair exclusion analysis (DPEA), Bayesian, and Parsimonious explanation (PE) approaches are developed to predict domain-disease associations. We demonstrate the effectiveness of all the five approaches via a series of validation experiments, and show the robustness of the MLE, Bayesian and PE approaches to the involved parameters. We also study the effects of disease modularization in inferring novel domain-disease associations. Through validation, the AUC (Area Under the operating characteristic Curve) scores for Bayesian, MLE, DPEA, PE, and Association approaches are 0.86, 0.84, 0.83, 0.83 and 0.79, respectively, indicating the usefulness of these approaches for predicting domain-disease relationships. Finally, we choose the Bayesian approach to infer domains associated with two common diseases, Crohn's disease and type 2 diabetes. The Bayesian approach has the best performance for the inference of domain-disease relationships. The predicted landscape between domains and diseases provides a more detailed view about the disease

The rabbit blood-shunt model for the study of acute and late sequelae of subarachnoid hemorrhage: technical aspects.

PubMed

Andereggen, Lukas; Neuschmelting, Volker; von Gunten, Michael; Widmer, Hans Rudolf; Takala, Jukka; Jakob, Stephan M; Fandino, Javier; Marbacher, Serge

2014-10-02

Early brain injury and delayed cerebral vasospasm both contribute to unfavorable outcomes after subarachnoid hemorrhage (SAH). Reproducible and controllable animal models that simulate both conditions are presently uncommon. Therefore, new models are needed in order to mimic human pathophysiological conditions resulting from SAH. This report describes the technical nuances of a rabbit blood-shunt SAH model that enables control of intracerebral pressure (ICP). An extracorporeal shunt is placed between the arterial system and the subarachnoid space, which enables examiner-independent SAH in a closed cranium. Step-by-step procedural instructions and necessary equipment are described, as well as technical considerations to produce the model with minimal mortality and morbidity. Important details required for successful surgical creation of this robust, simple and consistent ICP-controlled SAH rabbit model are described.

The intrinsically disordered C-terminal domain of the measles virus nucleoprotein interacts with the C-terminal domain of the phosphoprotein via two distinct sites and remains predominantly unfolded

PubMed Central

Bourhis, Jean-Marie; Receveur-Bréchot, Véronique; Oglesbee, Michael; Zhang, Xinsheng; Buccellato, Matthew; Darbon, Hervé; Canard, Bruno; Finet, Stéphanie; Longhi, Sonia

2005-01-01

Measles virus is a negative-sense, single-stranded RNA virus within theMononegavirales order,which includes several human pathogens, including rabies, Ebola, Nipah, and Hendra viruses. Themeasles virus nucleoprotein consists of a structured N-terminal domain, and of an intrinsically disordered C-terminal domain, NTAIL (aa 401–525), which undergoes induced folding in the presence of the C-terminal domain (XD, aa 459–507) of the viral phosphoprotein. With in NTAIL, an α-helical molecular recognition element (α-MoRE, aa 488–499) involved in binding to P and in induced folding was identified and then observed in the crystal structure of XD. Using small-angle X-ray scattering, we have derived a low-resolution structural model of the complex between XD and NTAIL, which shows that most of NTAIL remains disordered in the complex despite P-induced folding within the α-MoRE. The model consists of an extended shape accommodating the multiple conformations adopted by the disordered N-terminal region of NTAIL, and of a bulky globular region, corresponding to XD and to the C terminus of NTAIL (aa 486–525). Using surface plasmon resonance, circular dichroism, fluorescence spectroscopy, and heteronuclear magnetic resonance, we show that NTAIL has an additional site (aa 517–525) involved in binding to XD but not in the unstructured-to-structured transition. This work provides evidence that intrinsically disordered domains can establish complex interactions with their partners, and can contact them through multiple sites that do not all necessarily gain regular secondary structure. PMID:16046624

Computation of forces arising from the polarizable continuum model within the domain-decomposition paradigm

NASA Astrophysics Data System (ADS)

Gatto, Paolo; Lipparini, Filippo; Stamm, Benjamin

2017-12-01

The domain-decomposition (dd) paradigm, originally introduced for the conductor-like screening model, has been recently extended to the dielectric Polarizable Continuum Model (PCM), resulting in the ddPCM method. We present here a complete derivation of the analytical derivatives of the ddPCM energy with respect to the positions of the solute's atoms and discuss their efficient implementation. As it is the case for the energy, we observe a quadratic scaling, which is discussed and demonstrated with numerical tests.

Improving the Effectiveness of Speaker Verification Domain Adaptation With Inadequate In-Domain Data

DTIC Science & Technology

2017-08-20

Improving the Effectiveness of Speaker Verification Domain Adaptation With Inadequate In-Domain Data Bengt J. Borgström1, Elliot Singer1, Douglas...ll.mit.edu.edu, dar@ll.mit.edu, es@ll.mit.edu, omid.sadjadi@nist.gov Abstract This paper addresses speaker verification domain adaptation with...contain speakers with low channel diversity. Existing domain adaptation methods are reviewed, and their shortcomings are discussed. We derive an

Evolution of domain promiscuity in eukaryotic genomes—a perspective from the inferred ancestral domain architectures†

PubMed Central

Cohen-Gihon, Inbar; Fong, Jessica H.; Sharan, Roded; Nussinov, Ruth

2012-01-01

Most eukaryotic proteins are composed of two or more domains. These assemble in a modular manner to create new proteins usually by the acquisition of one or more domains to an existing protein. Promiscuous domains which are found embedded in a variety of proteins and co-exist with many other domains are of particular interest and were shown to have roles in signaling pathways and mediating network communication. The evolution of domain promiscuity is still an open problem, mostly due to the lack of sequenced ancestral genomes. Here we use inferred domain architectures of ancestral genomes to trace the evolution of domain promiscuity in eukaryotic genomes. We find an increase in average promiscuity along many branches of the eukaryotic tree. Moreover, domain promiscuity can proceed at almost a steady rate over long evolutionary time or exhibit lineage-specific acceleration. We also observe that many signaling and regulatory domains gained domain promiscuity around the Bilateria divergence. In addition we show that those domains that played a role in the creation of two body axes and existed before the divergence of the bilaterians from fungi/metazoan achieve a boost in their promiscuities during the bilaterian evolution. PMID:21127809

Socioeconomic Disadvantage Is Associated with a Higher Incidence of Aneurysmal Subarachnoid Hemorrhage.

PubMed

Nichols, Linda; Stirling, Christine; Otahal, Petr; Stankovich, Jim; Gall, Seana

2018-03-01

Aneurysmal subarachnoid hemorrhage (aSAH) incidence is not well studied. Varied definitions of "subarachnoid hemorrhage" have led to a lack of clarity regarding aSAH incidence. The impact of area-level socioeconomic disadvantage and geographical location on the incidence of aSAH also remains unclear. Using a population-based statewide study, we examined the incidence of aSAH in relation to socioeconomic disadvantage and geographical location. A retrospective cohort study of nontraumatic subarachnoid hemorrhages from 2010 to 2014 was undertaken. Researchers manually collected data from multiple overlapping sources including statewide administrative databases, individual digital medical records, and death registers. Age-standardized rates (ASRs) per 100,000 person years were calculated using the 2001 Australian population. Differences in incidence rate ratios were calculated by age, sex, area-level socioeconomic status, and geographical location using Poisson regression. The cohort of 237 cases (mean age, 61.0 years) with a female predominance of 166 (70.04%) included 159 confirmed aSAH, 52 community-based deaths, and 26 probable cases. The ASR for aSAH was 9.99 (95% confidence interval [CI], 8.69-11.29). A significant association between area-level socioeconomic disadvantage and incidence was observed, with the rate of aSAH in disadvantaged geographical areas being 1.40 times higher than that in advantaged areas (95% CI, 1.11-1.82; P = .012). This study uses a comprehensive search of multiple data sources to define a new baseline of aSAH within an Australian population. This study presents a higher incidence rate of aSAH with socioeconomic variations. As a key risk factor that may explain this paradox, addressing socioeconomic inequalities is important for effective prevention and management interventions. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Patterns of convexal subarachnoid haemorrhage: clinical, radiological and outcome differences between cerebral amyloid angiopathy and other causes.

PubMed

Calviere, Lionel; Raposo, Nicolas; Cuvinciuc, Victor; Cognard, Christophe; Bonneville, Fabrice; Viguier, Alain

2018-01-01

Cerebral amyloid angiopathy (CAA) is a common aetiology of convexal subarachnoid haemorrhage (cSAH) but little is known about its specific characteristics in comparison with cSAH from other causes. In this study we compared patients with CAA vs. non-CAA-related cSAH. Retrospective review of baseline and follow-up data of consecutive patients admitted with a symptomatic acute cSAH. Sixty-two patients were included (mean age 66.2 ± 14.1 years), of whom 31 with probable CAA. CAA patients presented more frequently with transient symptoms (83.9 vs. 19.3%; p < 0.001) usually without headache (19.0 vs. 58.1%; p = 0.002). In CAA, these were essentially positive sensory disturbance that met the criteria of transient focal neurological episodes (TFNE). CAA was more often associated with cortical superficial siderosis (cSS) (80.6 vs. 0%; p < 0.001) and lobar cerebral microbleeds (83.4 vs. 9%; p < 0.001). During a mean of 22 months of follow-up, recurrent symptomatic cSAH occurred in 4/27 (12.9%) CAA patients and in 0/27 non-CAA patients. Among 40 patients with MRI follow-up, cSAH recurrences were observed in 44% of CAA patients vs. 13.3% of other cases (p = 0.08) and extension of cSS was detected only in CAA (60%) (p < 0.001). Acute cSAH evolved to cSS in 96 and 73.3% of CAA and non-CAA patients, respectively (p = 0.06). CAA differs from other cSAH in having TFNE as a frequent clinical presentation, a high prevalence of cSS and an increased risk of recurrent subarachnoid bleeding. However, evolution from acute cSAH to focal cSS may not be specific to CAA.

Consequences and coping strategies six years after a subarachnoid hemorrhage – A qualitative study

PubMed Central

Törnbom, Karin; Sunnerhagen, Katharina S.; Törnbom, Marie

2017-01-01

Background After a subarachnoid haemorrhage (SAH), continuing impairment is common and may impact the person’s life. There is a lack of knowledge regarding long-term consequences experienced. Purpose To explore experiences of the care and rehabilitation as well as the consequences and strategies used to cope with everyday life six years post SAH. Methods An explorative interview study with a qualitative design. Individual interviews, with open ended questions, using an interview guide were performed with sixteen participants (mean age 63, 8 men, 8 women) six years post SAH. Data was analyzed according to a descriptive thematic analysis, and themes were discovered inductively. Results Two major themes from the analysis, both including four sub-themes, were identified; these themes were consequences of the SAH and coping strategies. Participants were grateful to have survived the SAH and most were satisfied with their acute medical care. If discharged directly from the neurosurgical unit participants can feel abandoned. In contrast, participants who were referred to a rehabilitation clinic felt supported and informed. Cognitive problems, such as impaired memory and mental fatigue, were reported as still present six years post SAH. Coping strategies were; receiving support from family, society, employers, or technical equipment. At work, talking to colleagues and to taking breaks were common. Participants described hiding their symptoms from employers and friends, as well as trying to continue doing tasks in the same manner as prior to the SAH. If this was not possible, some refrained from doing these tasks. They went through a mourning process, fear, and worries. Conclusions Participants reported several long-term consequences which impacted on their daily lives post SAH, and different coping strategies were used to cope with these problems. Participants reported lack of awareness regarding the consequences of SAH and stressed the importance of structured

Association of Recreational Marijuana Use with Aneurysmal Subarachnoid Hemorrhage.

PubMed

Rumalla, Kavelin; Reddy, Adithi Y; Mittal, Manoj K

2016-02-01

Our objective was to evaluate the effect of cannabis use on hospitalizations for aneurysmal subarachnoid hemorrhage (aSAH). The Nationwide Inpatient Sample (2004-2011) was used to identify all patients (age 15-54) with a primary diagnosis of aSAH (International Classification of Diseases, Ninth Edition, Clinical Modification 430). We identified patients testing positive for cannabis use using all available diagnosis fields. The incidence and characteristics of aSAH hospitalizations among cannabis users were examined. Bivariate and multivariate analyses were performed to determine the effect of cannabis use on aSAH and in-hospital outcomes. Prior to adjustment, the incidence of aSAH in the cannabis cohort was slightly increased relative to the noncannabis cohort (relative risk: 1.07, 95% confidence interval [CI]: 1.02-1.11). Cannabis use in aSAH was more frequent among younger patients (40.44 ± 10.17 versus 43.74 ± 8.68, P < .0001), males (53.3% versus 40.76%, P < .0001), black patients (35.92% versus 19.10%, P < .0001), and Medicaid enrollees (31.13% versus 18.31%, P < .0001). The cannabis use cohort had greater overall illicit drug use but fewer medical risk factors for aSAH. Cannabis use (odds ratio: 1.18, 95% CI: 1.12-1.24) was found to be an independent predictor of aSAH when adjusting for demographics, substance use, and risk factors. Cannabis use was not associated with symptomatic cerebral vasospasm, inpatient mortality, or adverse discharge disposition. Our analysis suggests that recreational marijuana use is independently associated with an 18% increased likelihood of aSAH. Further case-control studies may analyze inpatient outcomes and other understudied mechanisms behind cannabis-associated stroke. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

30-day mortality and readmission after hemorrhagic stroke among Medicare beneficiaries in Joint Commission primary stroke center-certified and noncertified hospitals.

PubMed

Lichtman, Judith H; Jones, Sara B; Leifheit-Limson, Erica C; Wang, Yun; Goldstein, Larry B

2011-12-01

Ischemic stroke patients treated at Joint Commission Primary Stroke Center (JC-PSC)-certified hospitals have better outcomes. Data reflecting the impact of JC-PSC status on outcomes after hemorrhagic stroke are limited. We determined whether 30-day mortality and readmission rates after hemorrhagic stroke differed for patients treated at JC-PSC-certified versus noncertified hospitals. The study included all fee-for-service Medicare beneficiaries aged 65 years or older with a primary discharge diagnosis of subarachnoid hemorrhage (SAH) or intracerebral hemorrhage (ICH) in 2006. Covariate-adjusted logistic and Cox proportional hazards regression assessed the effect of care at a JC-PSC-certified hospital on 30-day mortality and readmission. There were 2305 SAH and 8708 ICH discharges from JC-PSC-certified hospitals and 3892 SAH and 22 564 ICH discharges from noncertified hospitals. Unadjusted in-hospital mortality (SAH: 27.5% versus 33.2%, P<0.0001; ICH: 27.9% versus 29.6%, P=0.003) and 30-day mortality (SAH: 35.1% versus 44.0%, P<0.0001; ICH: 39.8% versus 42.4%, P<0.0001) were lower in JC-PSC hospitals, but 30-day readmission rates were similar (SAH: 17.0% versus 17.0%, P=0.97; ICH: 16.0% versus 15.5%, P=0.29). Risk-adjusted 30-day mortality was 34% lower (odds ratio, 0.66; 95% confidence interval, 0.58-0.76) after SAH and 14% lower (odds ratio, 0.86; 95% confidence interval, 0.80-0.92) after ICH for patients discharged from JC-PSC-certified hospitals. There was no difference in 30-day risk-adjusted readmission rates for SAH or ICH based on JC-PSC status. Patients treated at JC-PSC-certified hospitals had lower risk-adjusted mortality rates for both SAH and ICH but similar 30-day readmission rates as compared with noncertified hospitals.

Life satisfaction and return to work after aneurysmal subarachnoid hemorrhage.

PubMed

Passier, Patricia E C A; Visser-Meily, Johanna M A; Rinkel, Gabriel J E; Lindeman, Eline; Post, Marcel W M

2011-01-01

This study was conducted to investigate life satisfaction and employment status after aneurysmal subarachnoid hemorrhage (SAH) and to explain the associations between life satisfaction and demographic, disease-related, psychological, and personality characteristics. Subjects with SAH (n = 141) living at home 2-4 years after the SAH responded to a mailed questionnaire. Outcomes were life satisfaction, as measured with the Life Satisfaction Questionnaire 9 (LiSat-9), and employment status. Determinants in multiple regression analysis were demographic and SAH characteristics, subjective complaints (eg, mood disorder, fatigue, cognitive complaints), and personality characteristics (eg, neuroticism, passive coping style). Of the 141 subjects, 64 (46.7%) had a Glasgow Outcome Scale score of V (good outcome) at discharge. Mean subject age was 51.4 ± 12.3 years, and mean time after SAH was 36.1 ± 7.9 months. Of the 88 subjects who were working at the time of the SAH, 54 (61.4%) returned to work, but only 31 (35.2%) resumed their work completely. The subjects were least satisfied with their vocational situation (51.9% satisfied) and sexual life (51.7%) and were most satisfied with their relationships (75.2%-88.7%) and self-care ability (88.6%). Age (β value = 0.17), return to work after SAH (0.19), disability at hospital discharge (0.25), worsened mood (-0.37), and passive coping (-0.25) together accounted for 47.2% of the life satisfaction scores. Our data indicate that return to work is a major issue for individuals who survive an SAH. Not returning to work, disability, depression, and passive coping are associated with reduced life satisfaction. Thus, vocational reintegration after SAH merits more attention during rehabilitation. Copyright © 2011 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Lifetime risks for aneurysmal subarachnoid haemorrhage: multivariable risk stratification.

PubMed

Vlak, Monique H M; Rinkel, Gabriel J E; Greebe, Paut; Greving, Jacoba P; Algra, Ale

2013-06-01

The overall incidence of aneurysmal subarachnoid haemorrhage (aSAH) in western populations is around 9 per 100 000 person-years, which confers to a lifetime risk of around half per cent. Risk factors for aSAH are usually expressed as relative risks and suggest that absolute risks vary considerably according to risk factor profiles, but such estimates are lacking. We aimed to estimate incidence and lifetime risks of aSAH according to risk factor profiles. We used data from 250 patients admitted with aSAH and 574 sex-matched and age-matched controls, who were randomly retrieved from general practitioners files. We determined independent prognostic factors with multivariable logistic regression analyses and assessed discriminatory performance using the area under the receiver operating characteristic curve. Based on the prognostic model we predicted incidences and lifetime risks of aSAH for different risk factor profiles. The four strongest independent predictors for aSAH, namely current smoking (OR 6.0; 95% CI 4.1 to 8.6), a positive family history for aSAH (4.0; 95% CI 2.3 to 7.0), hypertension (2.4; 95% CI 1.5 to 3.8) and hypercholesterolaemia (0.2; 95% CI 0.1 to 0.4), were used in the final prediction model. This model had an area under the receiver operating characteristic curve of 0.73 (95% CI 0.69 to 0.76). Depending on sex, age and the four predictors, the incidence of aSAH ranged from 0.4/100 000 to 298/100 000 person-years and lifetime risk between 0.02% and 7.2%. The incidence and lifetime risk of aSAH in the general population varies widely according to risk factor profiles. Whether persons with high risks benefit from screening should be assessed in cost-effectiveness studies.