Description and physical localization of the bovine survival of motor neuron gene (SMN).

PubMed

Pietrowski, D; Goldammer, T; Meinert, S; Schwerin, M; Förster, M

1998-01-01

Proximal spinal muscular atrophy (SMA) is an autosomal recessive disease in humans and other mammals, characterized by degeneration of anterior horn cells of the spinal cord. In humans, the survival of motor neuron gene (SMN) has been recognized as the SMA-determining gene and has been mapped to 5q13. In cattle, SMA is a recurrent, inherited disease that plays an important economic role in breeding programs of Brown Swiss stock. Now we have identified the full- length cDNA sequence of the bovine SMN gene. Molecular analysis and characterization of the sequence documents 85% identity to its human counterpart and three evolutionarily conserved domains in different species. Physical mapping data reveals that bovine SMN is localized to chromosome region 20q12-->q13, supporting the conserved synteny of this chromosomal region between humans and cattle.

Investigations on Vibration Characteristics of Sma Embedded Horizontal Axis Wind Turbine Blade

NASA Astrophysics Data System (ADS)

Jagadeesh, V.; Yuvaraja, M.; Chandhru, A.; Viswanathan, P.; Senthil kumar, M.

2018-02-01

Vibration induced in wind turbine blade is a solemn problem as it reduces the life of the blade and also it can create critical vibration onto the tower, which may cause serious damage to the tower. The aim of this paper is to investigate the vibration characteristics of the prototype horizontal axis wind turbine blade. Shape memory alloys (SMA), with its variable physical properties, provides an alternative actuating mechanism. Heating an SMA causes a change in the elastic modulus of the material and hence SMAs are used as a damping material. A prototype blade with S1223 profile has been manufactured and the natural frequency is found. The natural frequency is found by incorporating the single SMA wire of 0.5mm diameter over the surface of the blade for a length of 240 mm. Similarly, number of SMA wires over the blade is increased up to 3 and the natural frequency is found. Frequency responses showed that the embedment of SMA over the blade’s surface will increase the natural frequency and reduce the amplitude of vibration. This is because of super elastic nature of SMA. In this paper, when SMA wire of 0.5 mm diameter and of length of 720 mm is embedded on the blade, an increase in the natural frequency by 6.3% and reducing the amplitude by 64.8%. Results of the experimental modal and harmonic indicates the effectiveness of SMA as a passive vibration absorber and that it has potential as a modest and high-performance method for controlling vibration of the blade.

Preisach modeling and compensation for smart material hysteresis

NASA Astrophysics Data System (ADS)

Hughes, Declan C.; Wen, John T.

1995-02-01

Many of the Smart materials being investigated (e.g., Shape Memory Alloys (SMAs), piezoceramics, and magnetostrictives) exhibit significant hysteresis effects, especially when driven with large control signals. In this paper the similarity between the microscopic domain kinematics that generate static hysteresis effects, or ferromagnetics, piezoceramics and SMAs is noted. The Preisach independent domain hysteresis model, and its derivatives, have been shown to be a comprehensive class of hysteresis operator that captures the major features of ferromagnetic hysteresis, and hence it is proposed here as a suitable model for piezoceramic and SMA hysteresis also. This basic Preisach model is used to model piezoceramic sheet actuators bonded to a flexible aluminum beam, and a Nitinol SMA wire muscle that applies a bending force to the end of the beam. A numerical inverse Preisach hysteresis series compensator is also proposed and applied in a real time experiment thereby reducing the apparent nonlinear hysteresis effects for the piezoceramic actuator quasi-static case.

The Survival Motor Neuron Protein Forms Soluble Glycine Zipper Oligomers

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

Martin, Renee; Gupta, Kushol; Ninan, Nisha S.

2012-11-01

The survival motor neuron (SMN) protein forms the oligomeric core of a multiprotein complex that functions in spliceosomal snRNP biogenesis. Loss of function mutations in the SMN gene cause spinal muscular atrophy (SMA), a leading genetic cause of infant mortality. Nearly half of the known SMA patient missense mutations map to the SMN YG-box, a highly conserved oligomerization domain of unknown structure that contains a (YxxG)3 motif. Here, we report that the SMN YG-box forms helical oligomers similar to the glycine zippers found in transmembrane channel proteins. A network of tyrosine-glycine packing between helices drives formation of soluble YG-box oligomers,more » providing a structural basis for understanding SMN oligomerization and for relating defects in oligomerization to the mutations found in SMA patients. These results have important implications for advancing our understanding of SMN function and glycine zipper-mediated helix-helix interactions.« less

Effect of multi-adhesive layering on retention of extraoral maxillofacial silicone prostheses in vivo.

PubMed

Kiat-Amnuay, Sudarat; Gettleman, Lawrence; Goldsmith, L Jane

2004-09-01

Loss of retention of maxillofacial prostheses often makes the margin visible or the prosthesis dislodge. Using several medical adhesives in combination may improve retention. The purpose of this study was to investigate the effect of single- and multi-adhesive layering of 2 adhesives on the retention of maxillofacial silicone elastomer strips adhered to the skin of human forearms using a peel test. Power analysis from a previous study and a pilot trial specified at least 20 subjects. Eight Silastic Adhesive A/MDX4-4210 silicone rubber strips (N=240) were applied in a predetermined random order to the left and right ventral forearms of 30 IRB-approved human subjects. Skin-Prep Protective Dressing was applied. Secure 2 Medical Adhesive (SMA) and Epithane-3 (E3) adhesive were used alone or as SMA/E3 or E3/SMA sandwiches (from skin to prosthesis) to adhere strips. Strips were peeled 6 hours later in a universal testing machine at 10 cm/min and data reported in N/m. Paired t tests were used to evaluate left and right arm differences. A Friedman test for nonparametric correlated data with within-subject design was performed, determining differences between both adhesives singly and in combination (alpha=.05). Tests of left-right differences were insignificant ( P =0.43), so the data from both arms were combined. Many strips with E3 did not adhere before testing and were counted as 0 adhesion. Median peel strengths (and 25th and 75th percentiles) in N/m were: SMA = 76.1 (47.1-107), E3 = 6.75 (0.0-25.9), SMA/E3 = 107 (78.0-132), and E3/SMA= 19.6 (6.99-42.4). All 4 variables were significantly different ( P <.0005). The multi-adhesive combination of SMA/E3 had the highest adhesion, followed, in order, by SMA alone, E3/ SMA, and E3 alone. Both E3 groups left a difficult-to-remove residue on the skin. SMA/E3 left a halo-like residue on the skin at the periphery of the strips from the E3 leaking around the SMA. SMA remained adherent to the prosthetic material.

Working Memory Deficits After Lesions Involving the Supplementary Motor Area.

PubMed

Cañas, Alba; Juncadella, Montserrat; Lau, Ruth; Gabarrós, Andreu; Hernández, Mireia

2018-01-01

The Supplementary Motor Area (SMA)-located in the superior and medial aspects of the superior frontal gyrus-is a preferential site of certain brain tumors and arteriovenous malformations, which often provoke the so-called SMA syndrome. The bulk of the literature studying this syndrome has focused on two of its most apparent symptoms: contralateral motor and speech deficits. Surprisingly, little attention has been given to working memory (WM) even though neuroimaging studies have implicated the SMA in this cognitive process. Given its relevance for higher-order functions, our main goal was to examine whether WM is compromised in SMA lesions. We also asked whether WM deficits might be reducible to processing speed (PS) difficulties. Given the connectivity of the SMA with prefrontal regions related to executive control (EC), as a secondary goal we examined whether SMA lesions also hampered EC. To this end, we tested 12 patients with lesions involving the left (i.e., the dominant) SMA. We also tested 12 healthy controls matched with patients for socio-demographic variables. To ensure that the results of this study can be easily transferred and implemented in clinical practice, we used widely-known clinical neuropsychological tests: WM and PS were measured with their respective Wechsler Adult Intelligence Scale indexes, and EC was tested with phonemic and semantic verbal fluency tasks. Non-parametric statistical methods revealed that patients showed deficits in the executive component of WM: they were able to sustain information temporarily but not to mentally manipulate this information. Such WM deficits were not subject to patients' marginal PS impairment. Patients also showed reduced phonemic fluency, which disappeared after controlling for the influence of WM. This observation suggests that SMA damage does not seem to affect cognitive processes engaged by verbal fluency other than WM. In conclusion, WM impairment needs to be considered as part of the SMA syndrome. These findings represent the first evidence about the cognitive consequences (other than language) of damage to the SMA. Further research is needed to establish a more specific profile of WM impairment in SMA patients and determine the consequences of SMA damage for other cognitive functions.

The clinical landscape for SMA in a new therapeutic era

PubMed Central

Talbot, K; Tizzano, E F

2017-01-01

Despite significant advances in basic research, the treatment of degenerative diseases of the nervous system remains one of the greatest challenges for translational medicine. The childhood onset motor neuron disorder spinal muscular atrophy (SMA) has been viewed as one of the more tractable targets for molecular therapy due to a detailed understanding of the molecular genetic basis of the disease. In SMA, inactivating mutations in the SMN1 gene can be partially compensated for by limited expression of SMN protein from a variable number of copies of the SMN2 gene, which provides both a molecular explanation for phenotypic severity and a target for therapy. The advent of the first tailored molecular therapy for SMA, based on modulating the splicing behaviour of the SMN2 gene provides, for the first time, a treatment which alters the natural history of motor neuron degeneration. Here we consider how this will change the landscape for diagnosis, clinical management and future therapeutic trials in SMA, as well as the implications for the molecular therapy of other neurological diseases. PMID:28644430

Dynamic Analysis for a Geared Turbofan Engine with Variable Area Fan Nozzle

NASA Technical Reports Server (NTRS)

Csank, Jeffrey T.; Thomas, George L.

2017-01-01

Aggressive design goals have been set for future aero-propulsion systems with regards to fuel economy, noise, and emissions. To meet these challenging goals, advanced propulsion concepts are being explored and current operating margins are being re-evaluated to find additional concessions that can be made. One advanced propulsion concept being evaluated is a geared turbofan with a variable area fan nozzle (VAFN), developed by NASA. This engine features a small core, a fan driven by the low pressure turbine through a reduction gearbox, and a shape memory alloy (SMA)-actuated VAFN. The VAFN is designed to allow both a small exit area for efficient operation at cruise, while being able to open wider at high power conditions to reduce backpressure on the fan and ensure a safe level of stall margin is maintained. The VAFN is actuated via a SMA-based system instead of a conventional system to decrease overall weight of the system, however, SMA-based actuators respond relatively slowly, which introduces dynamic issues that are investigated in this work. This paper describes both a control system designed specifically for issues associated with SMAs, and dynamic analysis of the geared turbofan VAFN with the SMA actuators. Also, some future recommendations are provided for this type of propulsion system.

Superelastic tension and bending characteristics of shape memory alloys

NASA Astrophysics Data System (ADS)

Bundara, B.; Tokuda, M.; Kuselj, B.; Ule, B.; Tuma, J. V.

2000-08-01

The objective of this study was to develop a numerical model of the superelastic behavior of shape memory alloys (SMA) on a macro-scale level. Results from a study on this behavior under tension and pure bending tests are presented and discussed. Two SMA samples were used in the experimental work and subjected to various loading paths in tension and pure bending: a single crystalline CuZnAl alloy and polycrystalline NiTi wire. Bending tests were performed under a pure bending loading condition on a new testing apparatus designed for the specific needs of this study. The experimental part of this study focused mainly on the response of the SMA to the loading paths in a quasi-plastic domain where the deformation mechanism is dominantly governed by the stress-induced martensitic transformation. Experimental results obtained from the NiTi polycrystals by tensile tests indicate that the superelastic SMA exhibits sufficient repeatability useful enough for a modeling task, while similar results obtained from the single crystalline CuZnAl indicate that the same modeling approach is not easily feasible. The facts have been qualitatively verified by the experimental data from pure bending tests, and a further area as study is suggested.

Functional Haplotypes of Fc gamma (Fcγ) receptor (FcγRIIA and FcγRIIIB) predict risk to repeated episodes of severe malarial anemia and mortality in Kenyan children

PubMed Central

Ouma, Collins; Davenport, Gregory C.; Garcia, Steven; Kempaiah, Prakasha; Chaudhary, Ateefa; Were, Tom; Anyona, Samuel B.; Raballah, Evans; Konah, Stephen N.; Hittner, James B.; Vulule, John M.; Ong’echa, John M.; Perkins, Douglas J.

2011-01-01

Development of protective immunity against Plasmodium falciparum is partially mediated through binding of malaria-specific IgG to Fc gamma (γ) receptors. Variation in human FcγRIIA-H/R-131 and FcγRIIIB-NA1/NA2 affect differential binding of IgG sub-classes. Since variability in FcγR may play an important role in severe malarial anemia (SMA) pathogenesis by mediating phagocytosis of red blood cells and triggering cytokine production, the relationship between FcγRIIA-H/R131 and FcγRIIIB-NA1/NA2 haplotypes and susceptibility to SMA (Hb<6.0g/dL) was investigated in Kenyan children (n=528) with acute malaria residing in a holoendemic P. falciparum transmission region. In addition, the association between carriage of the haplotypes and repeated episodes of SMA and all-cause mortality were investigated over a three-year follow-up period. Since variability in FcγR can alter interferon (IFN)-γ production, a mediator of innate and adaptive immune responses, functional associations between the haplotypes and IFN-γ were also explored. During acute malaria, children with SMA had elevated peripheral IFN-γ levels (P=0.006). Although multivariate logistic regression analyses (controlling for covariates) revealed no associations between the FcγR haplotypes and susceptibility to SMA during acute infection, the FcγRIIA-131H/FcγRIIIB-NA1 haplotype was associated with decreased peripheral IFN-γ (P=0.046). Longitudinal analyses showed that carriage of the FcγRIIA-131H/FcγRIIIB-NA1 haplotype was associated with reduced risk of SMA (RR; 0.65, 95%CI, 0.46-0.90; P=0.012) and all-cause mortality (P=0.002). In contrast, carriers of the FcγRIIA-131H/FcγRIIIB-NA2 haplotype had increased susceptibility to SMA (RR; 1.47, 95%CI, 1.06-2.04; P=0.020). Results here demonstrate that variation in the FcγR gene alters susceptibility to repeated episodes of SMA and mortality, as well as functional changes in IFN-γ production. PMID:21818580

Epithelial Markers aSMA, Krt14, and Krt19 Unveil Elements of Murine Lacrimal Gland Morphogenesis and Maturation.

PubMed

Kuony, Alison; Michon, Frederic

2017-01-01

As an element of the lacrimal apparatus, the lacrimal gland (LG) produces the aqueous part of the tear film, which protects the eye surface. Therefore, a defective LG can lead to serious eyesight impairment. Up to now, little is known about LG morphogenesis and subsequent maturation. In this study, we delineated elements of the cellular and molecular events involved in LG formation by using three epithelial markers, namely aSMA, Krt14, and Krt19. While aSMA marked a restricted epithelial population of the terminal end buds (TEBs) in the forming LG, Krt14 was found in the whole embryonic LG epithelial basal cell layer. Interestingly, Krt19 specifically labeled the presumptive ductal domain and subsequently, the luminal cell layer. By combining these markers, the Fucci reporter mouse strain and genetic fate mapping of the Krt14 + population, we demonstrated that LG epithelium expansion is fuelled by a patterned cell proliferation, and to a lesser extent by epithelial reorganization and possible mesenchymal-to-epithelial transition. We pointed out that this epithelial reorganization, which is associated with apoptosis, regulated the lumen formation. Finally, we showed that the inhibition of Notch signaling prevented the ductal identity from setting, and led to a LG covered by ectopic TEBs. Taken together our results bring a deeper understanding on LG morphogenesis, epithelial domain identity, and organ expansion.

Epithelial Markers aSMA, Krt14, and Krt19 Unveil Elements of Murine Lacrimal Gland Morphogenesis and Maturation

PubMed Central

Kuony, Alison; Michon, Frederic

2017-01-01

As an element of the lacrimal apparatus, the lacrimal gland (LG) produces the aqueous part of the tear film, which protects the eye surface. Therefore, a defective LG can lead to serious eyesight impairment. Up to now, little is known about LG morphogenesis and subsequent maturation. In this study, we delineated elements of the cellular and molecular events involved in LG formation by using three epithelial markers, namely aSMA, Krt14, and Krt19. While aSMA marked a restricted epithelial population of the terminal end buds (TEBs) in the forming LG, Krt14 was found in the whole embryonic LG epithelial basal cell layer. Interestingly, Krt19 specifically labeled the presumptive ductal domain and subsequently, the luminal cell layer. By combining these markers, the Fucci reporter mouse strain and genetic fate mapping of the Krt14+ population, we demonstrated that LG epithelium expansion is fuelled by a patterned cell proliferation, and to a lesser extent by epithelial reorganization and possible mesenchymal-to-epithelial transition. We pointed out that this epithelial reorganization, which is associated with apoptosis, regulated the lumen formation. Finally, we showed that the inhibition of Notch signaling prevented the ductal identity from setting, and led to a LG covered by ectopic TEBs. Taken together our results bring a deeper understanding on LG morphogenesis, epithelial domain identity, and organ expansion. PMID:29033846

Macroscopic models for shape memory alloy characterization and design

NASA Astrophysics Data System (ADS)

Massad, Jordan Elias

Shape memory alloys (SMAs) are being considered for a number of high performance applications, such as deformable aircraft wings, earthquake-resistant structures, and microdevices, due to their capability to achieve very high work densities, produce large deformations, and generate high stresses. In general, the material behavior of SMAs is nonlinear and hysteresic. To achieve the full potential of SMA actuators, it is necessary to develop models that characterize the nonlinearities and hysteresis inherent in the constituent materials. Additionally, the design of SMA actuators necessitates the development of control algorithms based on those models. We develop two models that quantify the nonlinearities and hysteresis inherent to SMAs, each in formulations suitable for subsequent control design. In the first model, we employ domain theory to quantify SMA behavior under isothermal conditions. The model involves a single first-order, nonlinear ordinary differential equation and requires as few as seven parameters that are identifiable from measurements. We develop the second model using the Muller-Achenbach-Seelecke framework where a transition state theory of nonequilibrium processes is used to derive rate laws for the evolution of material phase fractions. The fully thermomechanical model predicts rate-dependent, polycrystalline SMA behavior, and it accommodates heat transfer issues pertinent to thin-film SMAs. Furthermore, the model admits a low-order formulation and has a small number of parameters which can be readily identified using attributes of measured data. We illustrate aspects of both models through comparison with experimental bulk and thin-film SMA data.

Spinal Muscular Atrophy: Current Therapeutic Strategies

NASA Astrophysics Data System (ADS)

Kiselyov, Alex S.; Gurney, Mark E.

Proximal spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by death of motor neurons in the spinal cord. SMA is caused by deletion and/or mutation of the survival motor neuron gene (SMN1) on chromosome 5q13. There are variable numbers of copies of a second, related gene named SMN2 located in the proximity to SMN1. Both genes encode the same protein (Smn). Loss of SMN1 and incorrect splicing of SMN2 affect cellular levels of Smn triggering death of motor neurons. The severity of SMA is directly related to the normal number of copies of SMN2 carried by the patient. A considerable effort has been dedicated to identifying modalities including both biological and small molecule agents that increase SMN2 promoter activity to upregulate gene transcription and produce increased quantities of full-length Smn protein. This review summarizes recent progress in the area and suggests potential target product profile for an SMA therapeutic.

Curvature effect on the mechanical behaviour of a martensitic shape-memory-alloy wire for applications in civil engineering

NASA Astrophysics Data System (ADS)

Tran, Hanh; Balandraud, Xavier; Destrebecq, Jean-François

2015-02-01

The mechanical response of a bent shape memory alloy (SMA) wire is a key point for the understanding of the process of the creation of confining effects in a wrapped concrete cylinder for example. The objective of the present study is to model the phenomena involved in the bending of a martensitic SMA wire. The mechanism of martensite reorientation is considered in the model, which also takes into account the asymmetry between tension and compression. For validation purposes, experiments were performed on Ni-Ti wires: measurement of residual curvatures after bending release and tensile tests on pre-bent wires. In particular, the analysis shows a variation in axial stiffness as a function of the preliminary curvature. This result shows the necessity of modelling the distributions of the state variables within the wire cross-section for the simulation of confinement processes using SMA wires. It also opens prospects to potential application to the bending of SMA fibres in smart textiles.

Prosthetic leg powered by MR brake and SMA wires

NASA Astrophysics Data System (ADS)

Nguyen, The; Munguia, Vicente; Calderon, Jose

2014-04-01

Current knee designs for prosthetic legs rely on electric motors for both moving and stationary states. The electric motors draw an especially high level of current to sustain a fixed position. The advantage of using magnetorheological (MR) fluid is that it requires less current and can have a variable braking torque. Besides, the proposed prosthetic leg is actuated by NiTinol wire, a popular shape memory alloy (SMA). The incorporation of NiTinol gives the leg more realistic weight distribution with appropriate arrangement of the batteries and wires. The prosthesis in this research was designed with MR brake as stopping component and SMA wire network as actuating component at the knee. The MR brake was designed with novel non-circular shape for the rotor that improved the braking torque while minimizing the power consumption. The design also helped simplify the control of braking process. The SMA wire network was design so that the knee motion was actively rotated in both directions. The SMA wires were arranged and played very similar role as the leg's muscles. The study started with the overall solid design of the knee including both MR and SMA parts. Theoretical models were derived and programmed in Simulink for both components. The simulation was capable of predicting the power required for moving the leg or hold it in a fixed position for a certain amount of time. Subsequently, the design was prototyped and tested to validate the theoretical prediction. The theoretical models were updated accordingly to correlate with the experimental data.

Design of an antagonistic shape memory alloy actuator for flap type control surfaces

NASA Astrophysics Data System (ADS)

Dönmez, Burcu; Özkan, Bülent

2011-03-01

This paper deals with the flap control of unmanned aerial vehicles (UAVs) using shape memory alloy (SMA) actuators in an antagonistic configuration. The use of SMA actuators has the advantage of significant weight and cost reduction over the conventional actuation of the UAV flaps by electric motors or hydraulic actuators. In antagonistic configuration, two SMA actuators are used: one to rotate the flap clockwise and the other to rotate the flap counterclockwise. In this content, mathematical modeling of strain and power dissipation of SMA wire is obtained through characterization tests. Afterwards, the model of the antagonistic flap mechanism is derived. Later, based on these models both flap angle and power dissipation of the SMA wire are controlled in two different loops employing proportional-integral type and neural network based control schemes. The angle commands are converted to power commands through the outer loop controller later, which are updated using the error in the flap angle induced because of the indirect control and external effects. In this study, power consumption of the wire is introduced as a new internal feedback variable. Constructed simulation models are run and performance specifications of the proposed control systems are investigated. Consequently, it is shown that proposed controllers perform well in terms of achieving small tracking errors.

Heart rate variability and hemodynamic change in the superior mesenteric artery by acupuncture stimulation of lower limb points: a randomized crossover trial.

PubMed

Kaneko, Soichiro; Watanabe, Masashi; Takayama, Shin; Numata, Takehiro; Seki, Takashi; Tanaka, Junichi; Kanemura, Seiki; Kagaya, Yutaka; Ishii, Tadashi; Kimura, Yoshitaka; Yaegashi, Nobuo

2013-01-01

Objective. We investigated the relationship between superior mesenteric artery blood flow volume (SMA BFV) and autonomic nerve activity in acupuncture stimulation of lower limb points through heart rate variability (HRV) evaluations. Methods. Twenty-six healthy volunteers underwent crossover applications of bilateral manual acupuncture stimulation at ST36 or LR3 or no stimulation. Heart rate, blood pressure, cardiac index, systemic vascular resistance index, SMA BFV, and HRV at rest and 30 min after the intervention were analyzed. Results. SMA BFV showed a significant increase after ST36 stimulation (0% to 14.1% ± 23.4%, P = 0.007); very low frequency (VLF), high frequency (HF), low frequency (LF), and LF/HF were significantly greater than those at rest (0% to 479.4% ± 1185.6%, P = 0.045; 0% to 78.9% ± 197.6%, P = 0.048; 0% to 123.9% ± 217.1%, P = 0.006; 0% to 71.5% ± 171.1%, P = 0.039). Changes in HF and LF also differed significantly from those resulting from LR3 stimulation (HF: 78.9% ± 197.6% versus -18.2% ± 35.8%, P = 0.015; LF: 123.9% ± 217.1% versus 10.6% ± 70.6%, P = 0.013). Conclusion. Increased vagus nerve activity after ST36 stimulation resulted in increased SMA BFV. This partly explains the mechanism of acupuncture-induced BFV changes.

Heart Rate Variability and Hemodynamic Change in the Superior Mesenteric Artery by Acupuncture Stimulation of Lower Limb Points: A Randomized Crossover Trial

PubMed Central

Watanabe, Masashi; Tanaka, Junichi; Kanemura, Seiki; Kagaya, Yutaka; Ishii, Tadashi; Kimura, Yoshitaka; Yaegashi, Nobuo

2013-01-01

Objective. We investigated the relationship between superior mesenteric artery blood flow volume (SMA BFV) and autonomic nerve activity in acupuncture stimulation of lower limb points through heart rate variability (HRV) evaluations. Methods. Twenty-six healthy volunteers underwent crossover applications of bilateral manual acupuncture stimulation at ST36 or LR3 or no stimulation. Heart rate, blood pressure, cardiac index, systemic vascular resistance index, SMA BFV, and HRV at rest and 30 min after the intervention were analyzed. Results. SMA BFV showed a significant increase after ST36 stimulation (0% to 14.1% ± 23.4%, P = 0.007); very low frequency (VLF), high frequency (HF), low frequency (LF), and LF/HF were significantly greater than those at rest (0% to 479.4% ± 1185.6%, P = 0.045; 0% to 78.9% ± 197.6%, P = 0.048; 0% to 123.9% ± 217.1%, P = 0.006; 0% to 71.5% ± 171.1%, P = 0.039). Changes in HF and LF also differed significantly from those resulting from LR3 stimulation (HF: 78.9% ± 197.6% versus −18.2% ± 35.8%, P = 0.015; LF: 123.9% ± 217.1% versus 10.6% ± 70.6%, P = 0.013). Conclusion. Increased vagus nerve activity after ST36 stimulation resulted in increased SMA BFV. This partly explains the mechanism of acupuncture-induced BFV changes. PMID:24381632

A Heart Failure Management Program Using Shared Medical Appointments.

PubMed

Carroll, Allison J; Howrey, Hillary L; Payvar, Susan; Deshida-Such, Kristen; Kansal, Mayank; Brar, Charanjit K

2017-04-01

Disease management programs for heart failure (HF) effectively reduce HF-related hospitalization rates and mortality. Shared medical appointments (SMAs) offer a cost-effective delivery method for HF disease management programs. However, few studies have evaluated this cost-effective delivery method of HF disease management among Veterans with acute HF. We hypothesized that Veterans who attended a multidisciplinary HF-SMA clinic promoting HF self-management, compared those who only received individual treatment through the HF specialty clinic, would have better 12-month hospitalization outcomes. We completed a retrospective review of the VA electronic health record for HF-SMA clinic appointments (1/1/2012 to 12/31/2013). The multidisciplinary HF-SMA program comprised 4 weekly sessions covering topics including HF disease, HF medications, diet adherence, physical activity, psychological well-being, and stress management. Patients who attended the HF-SMA clinic ( n =54) were compared to patients who were scheduled for an HF-SMA appointment but never attended and were followed only in the HF clinic ( n =37). Outcomes were 12-month HF-related and all-cause hospitalization rates, days in the hospital, and time to first hospitalization. Of 141 patients scheduled for an HF-SMA clinic appointment, 54 met criteria for the HF-SMA clinic group and 37 were included in the HF clinic group. The groups did not significantly differ on any sociodemographic variables. Furthermore, no significant differences were observed between the HF-SMA group and the HF clinic group on demographics or hospitalization outcomes, p >.05 for all comparisons. Our results did not support our hypothesis that offering multidisciplinary, HF-SMAs promoting HF self-management skills, above and beyond the individual disease management care provided in an HF specialty clinic, would improve hospitalization outcomes among Veterans with acute HF. Limitations of the present study and recommendations for HF self-management programs for Veterans are discussed.

Shared medical appointments for patients with diabetes mellitus: a systematic review.

PubMed

Edelman, David; Gierisch, Jennifer M; McDuffie, Jennifer R; Oddone, Eugene; Williams, John W

2015-01-01

Shared medical appointments (SMAs) are an increasingly used system-redesign strategy for improving access to and quality of chronic illness care. We conducted a systematic review of the existing literature on SMA interventions for patients with diabetes in order to understand their impact on outcomes. MEDLINE, EMBASE, CINAHL, PsycINFO, and Web of Science from January 1996 through April 2012. PubMed search updated June 2013. English-language peer-reviewed publications of randomized controlled trials (RCTs), nonrandomized cluster controlled trials, controlled before-and-after studies, or interrupted time-series designs conducted among adult patients with diabetes. Two independent reviewers used prespecified criteria to screen titles and abstracts for full text review. Two different reviewers abstracted data and rated study quality and strength of evidence. When possible, we used random-effects models to synthesize the effects quantitatively, reporting by a weighted difference of the means when the same scale was used across studies, and a standardized mean difference when the scales differed. We measured heterogeneity in study effects using Forest Plots, Cochran's Q, and I(2), and explored heterogeneity by using subgroup analyses for categorical variables and meta-regression analyses for continuous or discrete variables. Outcomes not suitable to meta-analysis were summarized qualitatively. Twenty-five articles representing 17 unique studies compared SMA interventions with usual care. Among patients with diabetes, SMAs improved hemoglobin A1c (∆ = -0.55 percentage points [95 % CI, -0.11 to -0.99]); improved systolic blood pressure (∆ = -5.2 mmHg [95 % CI, -3.0 to -7.4]); and did not improve LDL cholesterol (∆ = -6.6 mg/dl [95 % CI, 2.8 to -16.1]). Nonbiophysical outcomes, including economic outcomes, were reported too infrequently to meta-analyze, or to draw conclusions from. The A1c result had significant heterogeneity among studies, likely secondary to the heterogeneity among included SMA interventions. Heterogeneity among the components of diabetes SMAs leads to uncertainty about what makes a particular SMA successful. SMA interventions improve biophysical outcomes among patients with diabetes. There was inadequate literature to determine SMA effects on patient experience, utilization, and costs.

Time domain nonlinear SMA damper force identification approach and its numerical validation

NASA Astrophysics Data System (ADS)

Xin, Lulu; Xu, Bin; He, Jia

2012-04-01

Most of the currently available vibration-based identification approaches for structural damage detection are based on eigenvalues and/or eigenvectors extracted from vibration measurements and, strictly speaking, are only suitable for linear system. However, the initiation and development of damage in engineering structures under severe dynamic loadings are typical nonlinear procedure. Studies on the identification of restoring force which is a direct indicator of the extent of the nonlinearity have received increasing attention in recent years. In this study, a date-based time domain identification approach for general nonlinear system was developed. The applied excitation and the corresponding response time series of the structure were used for identification by means of standard least-square techniques and a power series polynomial model (PSPM) which was utilized to model the nonlinear restoring force (NRF). The feasibility and robustness of the proposed approach was verified by a 2 degree-of-freedoms (DOFs) lumped mass numerical model equipped with a shape memory ally (SMA) damper mimicking nonlinear behavior. The results show that the proposed data-based time domain method is capable of identifying the NRF in engineering structures without any assumptions on the mass distribution and the topology of the structure, and provides a promising way for damage detection in the presence of structural nonlinearities.

Digital Beam Steering Device Based on Decoupled Birefringent Prism Deflector and Polarization Rotator

NASA Technical Reports Server (NTRS)

Pishnyak, Oleg; Kreminska, Lyubov; Laventovich, Oleg D.; Pouch, John J.; Miranda, Felix A.; Winker, Bruce K.

2004-01-01

We describe digital beam deflectors (DBDs) based on liquid crystals. Each stage of the device comprises a polarization rotator and a birefringent prism deflector. The birefringent prism deflects the beam by an angle that depends on polarization of the incident beam. The prism can be made of the uniaxial smectic A (SmA) liquid crystal (LC) or a solid crystal such as yttrium orthovanadate (YVO4). SmA prisms have high birefringence and can be constructed in a variety of shapes, including single prisms and prismatic blazed gratings of different angles and profiles. We address the challenges of uniform alignment of SmA, such as elimination of focal conic domains. Rotation of linear polarization is achieved by an electrically switched twisted nematic (TN) cell. A DBD composed of N rotator-deflector pairs steers the beam into 2(sup N) directions. As an example, we describe a four-stage DBD deflecting normally incident laser beam within the range of +/- 56 mrad with 8 mrad steps. Redirection of the beam is achieved by switching the TN cells.

Solubilization of human cells by the styrene-maleic acid copolymer: Insights from fluorescence microscopy.

PubMed

Dörr, Jonas M; van Coevorden-Hameete, Marleen H; Hoogenraad, Casper C; Killian, J Antoinette

2017-11-01

Extracting membrane proteins from biological membranes by styrene-maleic acid copolymers (SMAs) in the form of nanodiscs has developed into a powerful tool in membrane research. However, the mode of action of membrane (protein) solubilization in a cellular context is still poorly understood and potential specificity for cellular compartments has not been investigated. Here, we use fluorescence microscopy to visualize the process of SMA solubilization of human cells, exemplified by the immortalized human HeLa cell line. Using fluorescent protein fusion constructs that mark distinct subcellular compartments, we found that SMA solubilizes membranes in a concentration-dependent multi-stage process. While all major intracellular compartments were affected without a strong preference, plasma membrane solubilization was found to be generally slower than the solubilization of organelle membranes. Interestingly, some plasma membrane-localized proteins were more resistant against solubilization than others, which might be explained by their presence in specific membrane domains with differing properties. Our results support the general applicability of SMA for the isolation of membrane proteins from different types of (sub)cellular membranes. Copyright © 2017 Elsevier B.V. All rights reserved.

Design of shape memory alloy actuated intelligent parabolic antenna for space applications

NASA Astrophysics Data System (ADS)

Kalra, Sahil; Bhattacharya, Bishakh; Munjal, B. S.

2017-09-01

The deployment of large flexible antennas is becoming critical for space applications today. Such antenna systems can be reconfigured in space for variable antenna footprint, and hence can be utilized for signal transmission to different geographic locations. Due to quasi-static shape change requirements, coupled with the demand of large deflection, shape memory alloy (SMA) based actuators are uniquely suitable for this system. In this paper, we discuss the design and development of a reconfigurable parabolic antenna structure. The reflector skin of the antenna is vacuum formed using a metalized polycarbonate shell. Two different strategies are chosen for the antenna actuation. Initially, an SMA wire based offset network is formed on the back side of the reflector. A computational model is developed using equivalent coefficient of thermal expansion (ECTE) for the SMA wire. Subsequently, the interaction between the antenna and SMA wire is modeled as a constrained recovery system, using a 1D modified Brinson model. Joule effect based SMA phase transformation is considered for the relationship between input voltage and temperature at the SMA wire. The antenna is modeled using ABAQUS based finite element methodology. The deflection found through the computational model is compared with that measured in experiment. Subsequently, a point-wise actuation system is developed for higher deflection. For power-minimization, an auto-locking device is developed. The performance of the new configuration is compared with the offset-network configuration. It is envisaged that the study will provide a comprehensive procedure for the design of intelligent flexible structures especially suitable for space applications.

Re-centering variable friction device for vibration control of structures subjected to near-field earthquakes

NASA Astrophysics Data System (ADS)

Ozbulut, Osman E.; Hurlebaus, Stefan

2011-11-01

This paper proposes a re-centering variable friction device (RVFD) for control of civil structures subjected to near-field earthquakes. The proposed hybrid device has two sub-components. The first sub-component of this hybrid device consists of shape memory alloy (SMA) wires that exhibit a unique hysteretic behavior and full recovery following post-transformation deformations. The second sub-component of the hybrid device consists of variable friction damper (VFD) that can be intelligently controlled for adaptive semi-active behavior via modulation of its voltage level. In general, installed SMA devices have the ability to re-center structures at the end of the motion and VFDs can increase the energy dissipation capacity of structures. The full realization of these devices into a singular, hybrid form which complements the performance of each device is investigated in this study. A neuro-fuzzy model is used to capture rate- and temperature-dependent nonlinear behavior of the SMA components of the hybrid device. An optimal fuzzy logic controller (FLC) is developed to modulate voltage level of VFDs for favorable performance in a RVFD hybrid application. To obtain optimal controllers for concurrent mitigation of displacement and acceleration responses, tuning of governing fuzzy rules is conducted by a multi-objective heuristic optimization. Then, numerical simulation of a multi-story building is conducted to evaluate the performance of the hybrid device. Results show that a re-centering variable friction device modulated with a fuzzy logic control strategy can effectively reduce structural deformations without increasing acceleration response during near-field earthquakes.

SMA-Causing Missense Mutations in Survival motor neuron (Smn) Display a Wide Range of Phenotypes When Modeled in Drosophila

PubMed Central

Praveen, Kavita; Wen, Ying; Gray, Kelsey M.; Noto, John J.; Patlolla, Akash R.; Van Duyne, Gregory D.; Matera, A. Gregory

2014-01-01

Mutations in the human survival motor neuron 1 (SMN) gene are the primary cause of spinal muscular atrophy (SMA), a devastating neuromuscular disorder. SMN protein has a well-characterized role in the biogenesis of small nuclear ribonucleoproteins (snRNPs), core components of the spliceosome. Additional tissue-specific and global functions have been ascribed to SMN; however, their relevance to SMA pathology is poorly understood and controversial. Using Drosophila as a model system, we created an allelic series of twelve Smn missense mutations, originally identified in human SMA patients. We show that animals expressing these SMA-causing mutations display a broad range of phenotypic severities, similar to the human disease. Furthermore, specific interactions with other proteins known to be important for SMN's role in RNP assembly are conserved. Intragenic complementation analyses revealed that the three most severe mutations, all of which map to the YG box self-oligomerization domain of SMN, display a stronger phenotype than the null allele and behave in a dominant fashion. In support of this finding, the severe YG box mutants are defective in self-interaction assays, yet maintain their ability to heterodimerize with wild-type SMN. When expressed at high levels, wild-type SMN is able to suppress the activity of the mutant protein. These results suggest that certain SMN mutants can sequester the wild-type protein into inactive complexes. Molecular modeling of the SMN YG box dimer provides a structural basis for this dominant phenotype. These data demonstrate that important structural and functional features of the SMN YG box are conserved between vertebrates and invertebrates, emphasizing the importance of self-interaction to the proper functioning of SMN. PMID:25144193

SMA-causing missense mutations in survival motor neuron (Smn) display a wide range of phenotypes when modeled in Drosophila.

PubMed

Praveen, Kavita; Wen, Ying; Gray, Kelsey M; Noto, John J; Patlolla, Akash R; Van Duyne, Gregory D; Matera, A Gregory

2014-08-01

Mutations in the human survival motor neuron 1 (SMN) gene are the primary cause of spinal muscular atrophy (SMA), a devastating neuromuscular disorder. SMN protein has a well-characterized role in the biogenesis of small nuclear ribonucleoproteins (snRNPs), core components of the spliceosome. Additional tissue-specific and global functions have been ascribed to SMN; however, their relevance to SMA pathology is poorly understood and controversial. Using Drosophila as a model system, we created an allelic series of twelve Smn missense mutations, originally identified in human SMA patients. We show that animals expressing these SMA-causing mutations display a broad range of phenotypic severities, similar to the human disease. Furthermore, specific interactions with other proteins known to be important for SMN's role in RNP assembly are conserved. Intragenic complementation analyses revealed that the three most severe mutations, all of which map to the YG box self-oligomerization domain of SMN, display a stronger phenotype than the null allele and behave in a dominant fashion. In support of this finding, the severe YG box mutants are defective in self-interaction assays, yet maintain their ability to heterodimerize with wild-type SMN. When expressed at high levels, wild-type SMN is able to suppress the activity of the mutant protein. These results suggest that certain SMN mutants can sequester the wild-type protein into inactive complexes. Molecular modeling of the SMN YG box dimer provides a structural basis for this dominant phenotype. These data demonstrate that important structural and functional features of the SMN YG box are conserved between vertebrates and invertebrates, emphasizing the importance of self-interaction to the proper functioning of SMN.

Neural noise and movement-related codes in the macaque supplementary motor area.

PubMed

Averbeck, Bruno B; Lee, Daeyeol

2003-08-20

We analyzed the variability of spike counts and the coding capacity of simultaneously recorded pairs of neurons in the macaque supplementary motor area (SMA). We analyzed the mean-variance functions for single neurons, as well as signal and noise correlations between pairs of neurons. All three statistics showed a strong dependence on the bin width chosen for analysis. Changes in the correlation structure of single neuron spike trains over different bin sizes affected the mean-variance function, and signal and noise correlations between pairs of neurons were much smaller at small bin widths, increasing monotonically with the width of the bin. Analyses in the frequency domain showed that the noise between pairs of neurons, on average, was most strongly correlated at low frequencies, which explained the increase in noise correlation with increasing bin width. The coding performance was analyzed to determine whether the temporal precision of spike arrival times and the interactions within and between neurons could improve the prediction of the upcoming movement. We found that in approximately 62% of neuron pairs, the arrival times of spikes at a resolution between 66 and 40 msec carried more information than spike counts in a 200 msec bin. In addition, in 19% of neuron pairs, inclusion of within (11%)- or between-neuron (8%) correlations in spike trains improved decoding accuracy. These results suggest that in some SMA neurons elements of the spatiotemporal pattern of activity may be relevant for neural coding.

Submillimeter Array reveals molecular complexity of dying stars

NASA Astrophysics Data System (ADS)

Tomasz

2018-01-01

The unique capabilities of the Submillimeter Array (SMA) have allowed unprecedented studies of cool evolved stars at submillimeter wavelengths. In particular, the SMA now offers the possibility to image multiple molecular transitions at once, owing to the 32-GHz wide instantaneous bandwidth of SWARM, the SMA’s new correlator. Molecular gas located far and very close to the photosphere of an asymptotic-giant branch (AGB) star, a red supergiant, or a pre-planetary nebula can now be examined in transitions observed simultaneously from a wide range of energy levels. This allows a very detailed quantitative investigation of physical and chemical conditions around these variable objects. Several imaging line surveys have been obtained with the SMA to reveal the beautiful complexity of these evolved systems. The surveys resulted in first submillimeter-wave identifications of molecules of prime astrophysical interest, e.g. of TiO, TiO2, and of rotational transitions at excited vibrational states of CO. An overview of recent SMA observations of cool evolved stars will be given with an emphasize on the interferometric line surveys. We will demonstrate their importance in unraveling the mass-loss phenomena, propagation of shocks in the circumstellar medium, and production of dust at elevated temperatures. The SMA studies of these molecular factories have a direct impact on our understanding of the chemical evolution of the Galaxy and stellar evolution at low and high masses.

Immunohistochemical characterisation of the hepatic stem cell niche in feline hepatic lipidosis: a preliminary morphological study.

PubMed

Valtolina, Chiara; Robben, Joris H; Favier, Robert P; Rothuizen, Jan; Grinwis, Guy Cm; Schotanus, Baukje A; Penning, Louis C

2018-05-01

Objectives The aim of this study was to describe the cellular and stromal components of the hepatic progenitor cell niche in feline hepatic lipidosis (FHL). Methods Immunohistochemical staining for the progenitor/bile duct marker (K19), activated Kupffer cells (MAC387), myofibroblasts (alpha-smooth muscle actin [α-SMA]) and the extracellular matrix component laminin were used on seven liver biopsies of cats with FHL and three healthy cats. Double immunofluorescence stainings were performed to investigate co-localisation of different cell types in the hepatic progenitor cell (HPC) niche. Results HPCs, Kupffer cells, myofibroblasts and laminin deposition were observed in the liver samples of FHL, although with variability in the expression and positivity of the different immunostainings between different samples. When compared with the unaffected cats where K19 positivity and minimal α-SMA and laminin positivity were seen mainly in the portal area, in the majority of FHL samples K19 and α-SMA-positive cells and laminin positivity were seen also in the periportal and parenchymatous area. MAC387-positive cells were present throughout the parenchyma. Conclusions and relevance This is a preliminary morphological study to describe the activation and co-localisation of components of the HPC niche in FHL. Although the HPC niche in FHL resembles that described in hepatopathies in dogs and in feline lymphocytic cholangitis, the expression of K19, α-SMA, MAC387 and lamin is more variable in FHL, and a common pattern of activation could not be established. Nevertheless, when HPCs were activated, a spatial association between HPCs and their niche could be demonstrated.

Neural Systems Underlying Emotional and Non-emotional Interference Processing: An ALE Meta-Analysis of Functional Neuroimaging Studies

PubMed Central

Xu, Min; Xu, Guiping; Yang, Yang

2016-01-01

Understanding how the nature of interference might influence the recruitments of the neural systems is considered as the key to understanding cognitive control. Although, interference processing in the emotional domain has recently attracted great interest, the question of whether there are separable neural patterns for emotional and non-emotional interference processing remains open. Here, we performed an activation likelihood estimation meta-analysis of 78 neuroimaging experiments, and examined common and distinct neural systems for emotional and non-emotional interference processing. We examined brain activation in three domains of interference processing: emotional verbal interference in the face-word conflict task, non-emotional verbal interference in the color-word Stroop task, and non-emotional spatial interference in the Simon, SRC and Flanker tasks. Our results show that the dorsal anterior cingulate cortex (ACC) was recruited for both emotional and non-emotional interference. In addition, the right anterior insula, presupplementary motor area (pre-SMA), and right inferior frontal gyrus (IFG) were activated by interference processing across both emotional and non-emotional domains. In light of these results, we propose that the anterior insular cortex may serve to integrate information from different dimensions and work together with the dorsal ACC to detect and monitor conflicts, whereas pre-SMA and right IFG may be recruited to inhibit inappropriate responses. In contrast, the dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC) showed different degrees of activation and distinct lateralization patterns for different processing domains, which suggests that these regions may implement cognitive control based on the specific task requirements. PMID:27895564

Analysis-Driven Design Optimization of a SMA-Based Slat-Cove Filler for Aeroacoustic Noise Reduction

NASA Technical Reports Server (NTRS)

Scholten, William; Hartl, Darren; Turner, Travis

2013-01-01

Airframe noise is a significant component of environmental noise in the vicinity of airports. The noise associated with the leading-edge slat of typical transport aircraft is a prominent source of airframe noise. Previous work suggests that a slat-cove filler (SCF) may be an effective noise treatment. Hence, development and optimization of a practical slat-cove-filler structure is a priority. The objectives of this work are to optimize the design of a functioning SCF which incorporates superelastic shape memory alloy (SMA) materials as flexures that permit the deformations involved in the configuration change. The goal of the optimization is to minimize the actuation force needed to retract the slat-SCF assembly while satisfying constraints on the maximum SMA stress and on the SCF deflection under static aerodynamic pressure loads, while also satisfying the condition that the SCF self-deploy during slat extension. A finite element analysis model based on a physical bench-top model is created in Abaqus such that automated iterative analysis of the design could be performed. In order to achieve an optimized design, several design variables associated with the current SCF configuration are considered, such as the thicknesses of SMA flexures and the dimensions of various components, SMA and conventional. Designs of experiment (DOE) are performed to investigate structural response to an aerodynamic pressure load and to slat retraction and deployment. DOE results are then used to inform the optimization process, which determines a design minimizing actuator forces while satisfying the required constraints.

Applicability of Shape Memory Alloy Wire for an Active, Soft Orthotic

NASA Astrophysics Data System (ADS)

Stirling, Leia; Yu, Chih-Han; Miller, Jason; Hawkes, Elliot; Wood, Robert; Goldfield, Eugene; Nagpal, Radhika

2011-07-01

Current treatments for gait pathologies associated with neuromuscular disorders may employ a passive, rigid brace. While these provide certain benefits, they can also cause muscle atrophy. In this study, we examined NiTi shape memory alloy (SMA) wires that were annealed into springs to develop an active, soft orthotic (ASO) for the knee. Actively controlled SMA springs may provide variable assistances depending on factors such as when, during the gait cycle, the springs are activated; ongoing muscle activity level; and needs of the wearer. Unlike a passive brace, an active orthotic may provide individualized control, assisting the muscles so that they may be used more appropriately, and possibly leading to a re-education of the neuro-motor system and eventual independence from the orthotic system. A prototype was tested on a suspended, robotic leg to simulate the swing phase of a typical gait. The total deflection generated by the orthotic depended on the knee angle and the total number of actuators triggered, with a max deflection of 35°. While SMA wires have a high energy density, they require a significant amount of power. Furthermore, the loaded SMA spring response times were much longer than the natural frequency of an average gait for the power conditions tested. While the SMA wires are not appropriate for correction of gait pathologies as currently implemented, the ability to have a soft, actuated material could be appropriate for slower timescale applications.

Development of shape memory alloy (SMA) torsional actuators for variable twist tilt rotor (VTTR) blades

NASA Astrophysics Data System (ADS)

Prahlad, Harsha

This dissertation presents the development of a torsional actuator to alter the twist distributions of a tiltrotor blade between hover and forward flight. The actuator uses a Shape Memory Alloy (SMA) tube as its active element. The historical development of the tiltrotor aircraft is discussed, with emphasis on advanced tiltrotor concepts. The central theme in these concepts is to reduce the compromises for tiltrotor blade design, thereby improving performance of the aircraft in both hover and forward flight modes. A survey of research conducted in the application of smart structures to performance enhancement of aircraft is conducted. A review of other torsional actuators that are based on SMAs is presented. An assessment of the state-of-the-art in SMA modeling and characterization, both in mechanical tensile and torsional loading, is also discussed. Shape Memory Alloys are "smart" actuation materials that are capable of providing high stroke and high force of actuation at relatively low bandwidth. However, their behavior is complex, and influenced by material non-linearities, thermo-mechanical conditions and history of loading. In addition, the behavior of torsional SMA actuators has not been investigated in detail. In order to address these issues, the current research carries out a comprehensive characterization of SMAs. Experimental characteristics of SMA wires under extensional loading, and SMA rods and tubes in both extensional and torsional loading under a variety of thermo-mechanical conditions are presented in this dissertation. It is demonstrated that the uniaxial quasistatic SMA models show good overall agreement with the experimental behavior of an SMA wire under extensional loading. In addition, an approach that incorporates these models with radial non-uniformity due to torsional deflections is shown to provide good predictions of torsional characteristics of SMA rods and tubes. Several differences of the material response under non-quasistatic loading conditions are also shown. A modeling technique that predicts these effects by coupling the material phenomenology with an energy equilibrium analysis is proposed. In addition, a theoretical and experimental study involving composite laminates with embedded SMAs is also presented in this work. The concept of tuning the natural frequencies of a composite structure using embedded SMAs is demonstrated, and associated manufacturing issues discussed. Using the concepts developed in the study on SMAs, a torsional actuator involving an SMA tube is developed for the proposed application. The design of the heat transfer and torque transfer assemblies for the actuator is described. Benchtop testing of the actuator shows the feasibility of this actuator in applications involving large recovery torques of actuation. It is demonstrated that using the current concept, one actuator is not sufficient to meet the twist actuation requirements for a full-scale tiltrotor blade. However, a modification in the blade torsional stiffness, in conjunction with the use of two discrete SMA actuators, may render the concept feasible for a full-scale tiltrotor.

Assessing upper limb function in nonambulant SMA patients: development of a new module.

PubMed

Mazzone, Elena; Bianco, Flaviana; Martinelli, Diego; Glanzman, Allan M; Messina, Sonia; De Sanctis, Roberto; Main, Marion; Eagle, Michelle; Florence, Julaine; Krosschell, Kristin; Vasco, Gessica; Pelliccioni, Marco; Lombardo, Marilena; Pane, Marika; Finkel, Richard; Muntoni, Francesco; Bertini, Enrico; Mercuri, Eugenio

2011-06-01

We report the development of a module specifically designed for assessing upper limb function in nonambulant SMA patients, including young children and those with severe contractures. The application of the module to a preschool cohort of 40 children (age 30-48 months) showed that all the items could be completed by 30 months. The module was also used in 45 nonambulant SMA patients (age 30 months to 27 years). Their scores were more variable than in the preschool cohort, ranging from 0 to 18. The magnitude of scores was not related to age (r=-0.19). The upper limb scores had a good correlation with the Hammersmith Functional Motor Scale, r=0.75, but the upper limb function did not always strictly follow the overall gross motor function. These findings suggest that even some of the very weak nonambulant children possess upper limb skills that can be measured. Copyright © 2011 Elsevier B.V. All rights reserved.

Probabilistic fiber tracking of the language and motor white matter pathways of the supplementary motor area (SMA) in patients with brain tumors.

PubMed

Jenabi, Mehrnaz; Peck, Kyung K; Young, Robert J; Brennan, Nicole; Holodny, Andrei I

2014-12-01

Accurate localization of anatomically and functionally separate SMA tracts is important to improve planning prior to neurosurgery. Using fMRI and probabilistic DTI techniques, we assessed the connectivity between the frontal language area (Broca's area) and the rostral pre-SMA (language SMA) and caudal SMA proper (motor SMA). Twenty brain tumor patients completed motor and language fMRI paradigms and DTI. Peaks of functional activity in the language SMA, motor SMA and Broca's area were used to define seed regions for probabilistic tractography. fMRI and probabilistic tractography identified separate and unique pathways connecting the SMA to Broca's area - the language SMA pathway and the motor SMA pathway. For all subjects, the language SMA pathway had a larger number of voxels (P<0.0001) and higher connectivity (P<0.0001) to Broca's area than did the motor SMA pathway. In each patient, the number of voxels was greater in the language and motor SMA pathways than in background pathways (P<0.0001). No differences were found between patients with ipsilateral and those with contralateral tumors for either the language SMA pathway (degree of connectivity: P<0.36; number of voxels: 0.35) or the motor SMA pathway (degree of connectivity, P<0.28; number of voxels, P<0.74). Probabilistic tractography can identify unique white matter tracts that connect language SMA and motor SMA to Broca's area. The language SMA is more significantly connected to Broca's area than is the motor subdivision of the SMA proper. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Tumor location and IDH1 mutation may predict intraoperative seizures during awake craniotomy.

PubMed

Gonen, Tal; Grossman, Rachel; Sitt, Razi; Nossek, Erez; Yanaki, Raneen; Cagnano, Emanuela; Korn, Akiva; Hayat, Daniel; Ram, Zvi

2014-11-01

Intraoperative seizures during awake craniotomy may interfere with patients' ability to cooperate throughout the procedure, and it may affect their outcome. The authors have assessed the occurrence of intraoperative seizures during awake craniotomy in regard to tumor location and the isocitrate dehydrogenase 1 (IDH1) status of the tumor. Data were collected in 137 consecutive patients who underwent awake craniotomy for removal of a brain tumor. The authors performed a retrospective analysis of the incidence of seizures based on the tumor location and its IDH1 mutation status, and then compared the groups for clinical variables and surgical outcome parameters. Tumor location was strongly associated with the occurrence of intraoperative seizures. Eleven patients (73%) with tumor located in the supplementary motor area (SMA) experienced intraoperative seizures, compared with 17 (13.9%) with tumors in the other three non-SMA brain regions (p < 0.0001). Interestingly, there was no significant association between history of seizures and tumor location (p = 0.44). Most of the patients (63.6%) with tumor in the SMA region harbored an IDH1 mutation compared with those who had tumors in non-SMA regions. Thirty-one of 52 patients (60%) with a preoperative history of seizures had an IDH1 mutation (p = 0.02), and 15 of 22 patients (68.2%) who experienced intraoperative seizures had an IDH1 mutation (p = 0.03). In a multivariate analysis, tumor location was found as a significant predictor of intraoperative seizures (p = 0.002), and a trend toward IDH1 mutation as such a predictor was found as well (p = 0.06). Intraoperative seizures were not associated with worse outcome. Patients with tumors located in the SMA are more prone to develop intraoperative seizures during awake craniotomy compared with patients who have a tumor in non-SMA frontal areas and other brain regions. The IDH1 mutation was more common in SMA region tumors compared with other brain regions, and may be an additional risk factor for the occurrence of intraoperative seizures.

SMA-MAP: a plasma protein panel for spinal muscular atrophy.

PubMed

Kobayashi, Dione T; Shi, Jing; Stephen, Laurie; Ballard, Karri L; Dewey, Ruth; Mapes, James; Chung, Brett; McCarthy, Kathleen; Swoboda, Kathryn J; Crawford, Thomas O; Li, Rebecca; Plasterer, Thomas; Joyce, Cynthia; Chung, Wendy K; Kaufmann, Petra; Darras, Basil T; Finkel, Richard S; Sproule, Douglas M; Martens, William B; McDermott, Michael P; De Vivo, Darryl C; Walker, Michael G; Chen, Karen S

2013-01-01

Spinal Muscular Atrophy (SMA) presents challenges in (i) monitoring disease activity and predicting progression, (ii) designing trials that allow rapid assessment of candidate therapies, and (iii) understanding molecular causes and consequences of the disease. Validated biomarkers of SMA motor and non-motor function would offer utility in addressing these challenges. Our objectives were (i) to discover additional markers from the Biomarkers for SMA (BforSMA) study using an immunoassay platform, and (ii) to validate the putative biomarkers in an independent cohort of SMA patients collected from a multi-site natural history study (NHS). BforSMA study plasma samples (N = 129) were analyzed by immunoassay to identify new analytes correlating to SMA motor function. These immunoassays included the strongest candidate biomarkers identified previously by chromatography. We selected 35 biomarkers to validate in an independent cohort SMA type 1, 2, and 3 samples (N = 158) from an SMA NHS. The putative biomarkers were tested for association to multiple motor scales and to pulmonary function, neurophysiology, strength, and quality of life measures. We implemented a Tobit model to predict SMA motor function scores. 12 of the 35 putative SMA biomarkers were significantly associated (p<0.05) with motor function, with a 13(th) analyte being nearly significant. Several other analytes associated with non-motor SMA outcome measures. From these 35 biomarkers, 27 analytes were selected for inclusion in a commercial panel (SMA-MAP) for association with motor and other functional measures. Discovery and validation using independent cohorts yielded a set of SMA biomarkers significantly associated with motor function and other measures of SMA disease activity. A commercial SMA-MAP biomarker panel was generated for further testing in other SMA collections and interventional trials. Future work includes evaluating the panel in other neuromuscular diseases, for pharmacodynamic responsiveness to experimental SMA therapies, and for predicting functional changes over time in SMA patients.

Satellite sensor requirements for monitoring essential biodiversity variables of coastal ecosystems

EPA Science Inventory

The biodiversity and high productivity of coastal terrestrial and aquatic habitats are the foundation for important benefits to human societies around the world. These globally distributed habitats need frequent and broad systematic assessments, but field surveys only cover a sma...

A fuzzy model of superelastic shape memory alloys for vibration control in civil engineering applications

NASA Astrophysics Data System (ADS)

Ozbulut, O. E.; Mir, C.; Moroni, M. O.; Sarrazin, M.; Roschke, P. N.

2007-06-01

Two experimental test programs are conducted to collect data and simulate the dynamic behavior of CuAlBe shape memory alloy (SMA) wires. First, in order to evaluate the effect of temperature changes on superelastic SMA wires, a large number of cyclic, sinusoidal, tensile tests are performed at 1 Hz. These tests are conducted in a controlled environment at 0, 25 and 50 °C with three different strain amplitudes. Second, in order to assess the dynamic effects of the material, a series of laboratory experiments is conducted on a shake table with a scale model of a three-story structure that is stiffened with SMA wires. Data from these experiments are used to create fuzzy inference systems (FISs) that can predict hysteretic behavior of CuAlBe wire. Both fuzzy models employ a total of three input variables (strain, strain-rate, and temperature or pre-stress) and an output variable (predicted stress). Gaussian membership functions are used to fuzzify data for each of the input and output variables. Values of the initially assigned membership functions are adjusted using a neural-fuzzy procedure to more accurately predict the correct stress level in the wires. Results of the trained FISs are validated using test results from experimental records that had not been previously used in the training procedure. Finally, a set of numerical simulations is conducted to illustrate practical use of these wires in a civil engineering application. The results reveal the applicability for structural vibration control of pseudoelastic CuAlBe wire whose highly nonlinear behavior is modeled by a simple, accurate, and computationally efficient FIS.

Developing Methods for Fraction Cover Estimation Toward Global Mapping of Ecosystem Composition

NASA Astrophysics Data System (ADS)

Roberts, D. A.; Thompson, D. R.; Dennison, P. E.; Green, R. O.; Kokaly, R. F.; Pavlick, R.; Schimel, D.; Stavros, E. N.

2016-12-01

Terrestrial vegetation seldom covers an entire pixel due to spatial mixing at many scales. Estimating the fractional contributions of photosynthetic green vegetation (GV), non-photosynthetic vegetation (NPV), and substrate (soil, rock, etc.) to mixed spectra can significantly improve quantitative remote measurement of terrestrial ecosystems. Traditional methods for estimating fractional vegetation cover rely on vegetation indices that are sensitive to variable substrate brightness, NPV and sun-sensor geometry. Spectral mixture analysis (SMA) is an alternate framework that provides estimates of fractional cover. However, simple SMA, in which the same set of endmembers is used for an entire image, fails to account for natural spectral variability within a cover class. Multiple Endmember Spectral Mixture Analysis (MESMA) is a variant of SMA that allows the number and types of pure spectra to vary on a per-pixel basis, thereby accounting for endmember variability and generating more accurate cover estimates, but at a higher computational cost. Routine generation and delivery of GV, NPV, and substrate (S) fractions using MESMA is currently in development for large, diverse datasets acquired by the Airborne Visible Infrared Imaging Spectrometer (AVIRIS). We present initial results, including our methodology for ensuring consistency and generalizability of fractional cover estimates across a wide range of regions, seasons, and biomes. We also assess uncertainty and provide a strategy for validation. GV, NPV, and S fractions are an important precursor for deriving consistent measurements of ecosystem parameters such as plant stress and mortality, functional trait assessment, disturbance susceptibility and recovery, and biomass and carbon stock assessment. Copyright 2016 California Institute of Technology. All Rights Reserved. We acknowledge support of the US Government, NASA, the Earth Science Division and Terrestrial Ecology program.

Stimulating neural plasticity with real-time fMRI neurofeedback in Huntington's disease: A proof of concept study.

PubMed

Papoutsi, Marina; Weiskopf, Nikolaus; Langbehn, Douglas; Reilmann, Ralf; Rees, Geraint; Tabrizi, Sarah J

2018-03-01

Novel methods that stimulate neuroplasticity are increasingly being studied to treat neurological and psychiatric conditions. We sought to determine whether real-time fMRI neurofeedback training is feasible in Huntington's disease (HD), and assess any factors that contribute to its effectiveness. In this proof-of-concept study, we used this technique to train 10 patients with HD to volitionally regulate the activity of their supplementary motor area (SMA). We collected detailed behavioral and neuroimaging data before and after training to examine changes of brain function and structure, and cognitive and motor performance. We found that patients overall learned to increase activity of the target region during training with variable effects on cognitive and motor behavior. Improved cognitive and motor performance after training predicted increases in pre-SMA grey matter volume, fMRI activity in the left putamen, and increased SMA-left putamen functional connectivity. Although we did not directly target the putamen and corticostriatal connectivity during neurofeedback training, our results suggest that training the SMA can lead to regulation of associated networks with beneficial effects in behavior. We conclude that neurofeedback training can induce plasticity in patients with Huntington's disease despite the presence of neurodegeneration, and the effects of training a single region may engage other regions and circuits implicated in disease pathology. © 2017 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.

A two-site ELISA can quantify upregulation of SMN protein by drugs for spinal muscular atrophy.

PubMed

Nguyen thi Man; Humphrey, E; Lam, L T; Fuller, H R; Lynch, T A; Sewry, C A; Goodwin, P R; Mackenzie, A E; Morris, G E

2008-11-25

Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by loss of lower motor neurons during early or postnatal development. Severity is variable and is inversely related to the levels of survival of motor neurons (SMN) protein. The aim of this study was to produce a two-site ELISA capable of measuring both the low, basal levels of SMN protein in cell cultures from patients with severe SMA and small increases in these levels after treatment of cells with drugs. A monoclonal antibody against recombinant SMN, MANSMA1, was selected for capture of SMN onto microtiter plates. A selected rabbit antiserum against refolded recombinant SMN was used for detection of the captured SMN. The ratio of SMN levels in control fibroblasts to levels in SMA fibroblasts was greater than 3.0, consistent with Western blot data. The limit of detection was 0.13 ng/mL and SMN could be measured in human NT-2 neuronal precursor cells grown in 96-well culture plates (3 x 10(4) cells per well). Increases in SMN levels of 50% were demonstrable by ELISA after 24 hours treatment of 10(5) SMA fibroblasts with valproate or phenylbutyrate. A rapid and specific two-site, 96-well ELISA assay, available in kit format, can now quantify the effects of drugs on survival of motor neurons protein levels in cell cultures.

Effective connectivity within the frontoparietal control network differentiates cognitive control and working memory.

PubMed

Harding, Ian H; Yücel, Murat; Harrison, Ben J; Pantelis, Christos; Breakspear, Michael

2015-02-01

Cognitive control and working memory rely upon a common fronto-parietal network that includes the inferior frontal junction (IFJ), dorsolateral prefrontal cortex (dlPFC), pre-supplementary motor area/dorsal anterior cingulate cortex (pSMA/dACC), and intraparietal sulcus (IPS). This network is able to flexibly adapt its function in response to changing behavioral goals, mediating a wide range of cognitive demands. Here we apply dynamic causal modeling to functional magnetic resonance imaging data to characterize task-related alterations in the strength of network interactions across distinct cognitive processes. Evidence in favor of task-related connectivity dynamics was accrued across a very large space of possible network structures. Cognitive control and working memory demands were manipulated using a factorial combination of the multi-source interference task and a verbal 2-back working memory task, respectively. Both were found to alter the sensitivity of the IFJ to perceptual information, and to increase IFJ-to-pSMA/dACC connectivity. In contrast, increased connectivity from the pSMA/dACC to the IPS, as well as from the dlPFC to the IFJ, was uniquely driven by cognitive control demands; a task-induced negative influence of the dlPFC on the pSMA/dACC was specific to working memory demands. These results reflect a system of both shared and unique context-dependent dynamics within the fronto-parietal network. Mechanisms supporting cognitive engagement, response selection, and action evaluation may be shared across cognitive domains, while dynamic updating of task and context representations within this network are potentially specific to changing demands on cognitive control. Copyright © 2014 Elsevier Inc. All rights reserved.

Full-scale flight tests of aircraft morphing structures using SMA actuators

NASA Astrophysics Data System (ADS)

Mabe, James H.; Calkins, Frederick T.; Ruggeri, Robert T.

2007-04-01

In August of 2005 The Boeing Company conducted a full-scale flight test utilizing Shape Memory Alloy (SMA) actuators to morph an engine's fan exhaust to correlate exhaust geometry with jet noise reduction. The test was conducted on a 777-300ER with GE-115B engines. The presence of chevrons, serrated aerodynamic surfaces mounted at the trailing edge of the thrust reverser, have been shown to greatly reduce jet noise by encouraging advantageous mixing of the free, and fan streams. The morphing, or Variable Geometry Chevrons (VGC), utilized compact, light weight, and robust SMA actuators to morph the chevron shape to optimize the noise reduction or meet acoustic test objectives. The VGC system was designed for two modes of operation. The entirely autonomous operation utilized changes in the ambient temperature from take-off to cruise to activate the chevron shape change. It required no internal heaters, wiring, control system, or sensing. By design this provided one tip immersion at the warmer take-off temperatures to reduce community noise and another during the cooler cruise state for more efficient engine operation, i.e. reduced specific fuel consumption. For the flight tests a powered mode was added where internal heaters were used to individually control the VGC temperatures. This enabled us to vary the immersions and test a variety of chevron configurations. The flight test demonstrated the value of SMA actuators to solve a real world aerospace problem, validated that the technology could be safely integrated into the airplane's structure and flight system, and represented a large step forward in the realization of SMA actuators for production applications. In this paper the authors describe the development of the actuator system, the steps required to integrate the morphing structure into the thrust reverser, and the analysis and testing that was required to gain approval for flight. Issues related to material strength, thermal environment, vibration, electrical power, controls, data acquisition, and engine operability are discussed. Furthermore the authors layout a road map for the next stage of development of SMA aerospace actuators. A detailed look at the requirements and specifications that may define a production SMA actuator and the technology development required to meet them are presented. A path for meeting production requirements and achieving the next level of technology readiness for both autonomous and controlled SMA actuators is proposed. This path relies strongly on cross functional and organizational teaming including industry, academia, and government.

Supplementary motor area activation in patients with frontal lobe tumors and arteriovenous malformations.

PubMed

Sailor, Janet; Meyerand, M Elizabeth; Moritz, Chad H; Fine, Jason; Nelson, Lindsey; Badie, Behnam; Haughton, Victor M

2003-10-01

Some patients who undergo surgical resection of portions of the supplementary motor area (SMA) have severe postoperative motor and language deficits, whereas others have no deficits. We tested the hypothesis that in some patients with lesions affecting the SMA, the contralateral SMA exhibits some of the activation normally associated with the ipsilateral SMA. Functional MR imaging studies in seven healthy volunteers and 19 patients with frontal lobe tumors or arteriovenous malformations were reviewed retrospectively. The hemisphere in which the SMA activation predominated was tabulated for right and left motor tasks. The relative hemispheric dominance in the SMA for the right and left motor tasks was compared in the healthy and patient groups and with the location of the lesion in the patient group. None of the control subjects performing a right hand motor task activated predominantly the right SMA. Fifty percent of the patients with lesions overlapping the left SMA performing the right motor task activated predominantly the right SMA. Fifty-seven percent of control subjects performing the left hand motor task activated the left SMA predominantly. One hundred percent of patients with lesions overlapping the right frontal SMA performing the left motor task activated the left SMA predominantly. Differences between patients and controls were statistically significant. A lesion that contacts or overlaps the SMA is associated with an increased functional MR imaging response within the contralateral SMA.

Centrality of prefrontal and motor preparation cortices to Tourette Syndrome revealed by meta-analysis of task-based neuroimaging studies.

PubMed

Polyanska, Liliana; Critchley, Hugo D; Rae, Charlotte L

2017-01-01

Tourette Syndrome (TS) is a neurodevelopmental condition characterized by chronic multiple tics, which are experienced as compulsive and 'unwilled'. Patients with TS can differ markedly in the frequency, severity, and bodily distribution of tics. Moreover, there are high comorbidity rates with attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), anxiety disorders, and depression. This complex clinical profile may account for apparent variability of findings across neuroimaging studies that connect neural function to cognitive and motor behavior in TS. Here we crystalized information from neuroimaging regarding the functional circuitry of TS, and furthermore, tested specifically for neural determinants of tic severity, by applying activation likelihood estimation (ALE) meta-analyses to neuroimaging (activation) studies of TS. Fourteen task-based studies (13 fMRI and one H2O-PET) met rigorous inclusion criteria. These studies, encompassing 25 experiments and 651 participants, tested for differences between TS participants and healthy controls across cognitive, motor, perceptual and somatosensory domains. Relative to controls, TS participants showed distributed differences in the activation of prefrontal (inferior, middle, and superior frontal gyri), anterior cingulate, and motor preparation cortices (lateral premotor cortex and supplementary motor area; SMA). Differences also extended into sensory (somatosensory cortex and the lingual gyrus; V4); and temporo-parietal association cortices (posterior superior temporal sulcus, supramarginal gyrus, and retrosplenial cortex). Within TS participants, tic severity (reported using the Yale Global Tic Severity Scale; YGTSS) selectively correlated with engagement of SMA, precentral gyrus, and middle frontal gyrus across tasks. The dispersed involvement of multiple cortical regions with differences in functional reactivity may account for heterogeneity in the symptomatic expression of TS and its comorbidities. More specifically for tics and tic severity, the findings reinforce previously proposed contributions of premotor and lateral prefrontal cortices to tic expression.

Structural Equation Modelling with Three Schemes Estimation of Score Factors on Partial Least Square (Case Study: The Quality Of Education Level SMA/MA in Sumenep Regency)

NASA Astrophysics Data System (ADS)

Anekawati, Anik; Widjanarko Otok, Bambang; Purhadi; Sutikno

2017-06-01

Research in education often involves a latent variable. Statistical analysis technique that has the ability to analyze the pattern of relationship among latent variables as well as between latent variables and their indicators is Structural Equation Modeling (SEM). SEM partial least square (PLS) was developed as an alternative if these conditions are met: the theory that underlying the design of the model is weak, does not assume a certain scale measurement, the sample size should not be large and the data does not have the multivariate normal distribution. The purpose of this paper is to compare the results of modeling of the educational quality in high school level (SMA/MA) in Sumenep Regency with structural equation modeling approach partial least square with three schemes estimation of score factors. This paper is a result of explanatory research using secondary data from Sumenep Education Department and Badan Pusat Statistik (BPS) Sumenep which was data of Sumenep in the Figures and the District of Sumenep in the Figures for the year 2015. The unit of observation in this study were districts in Sumenep that consists of 18 districts on the mainland and 9 districts in the islands. There were two endogenous variables and one exogenous variable. Endogenous variables are the quality of education level of SMA/MA (Y1) and school infrastructure (Y2), whereas exogenous variable is socio-economic condition (X1). In this study, There is one improved model which represented by model from path scheme because this model is a consistent, all of its indicators are valid and its the value of R-square increased which is: Y1=0.651Y2. In this model, the quality of education influenced only by the school infrastructure (0.651). The socio-economic condition did not affect neither the school infrastructure nor the quality of education. If the school infrastructure increased 1 point, then the quality of education increased 0.651 point. The quality of education had an R2 of 0.418, which indicates that 41.8 percent of variance in the quality of education is explained by the school infrastructure, the remaining 58.2% is explained by the other factors which were not investigated in this work.

Prediction and Measurement of the Vibration and Acoustic Radiation of Panels Subjected to Acoustic Loading

NASA Technical Reports Server (NTRS)

Turner, Travis L.; Rizzi, Stephen A.

1995-01-01

Interior noise and sonic fatigue are important issues in the development and design of advanced subsonic and supersonic aircraft. Conventional aircraft typically employ passive treatments, such as constrained layer damping and acoustic absorption materials, to reduce the structural response and resulting acoustic levels in the aircraft interior. These techniques require significant addition of mass and only attenuate relatively high frequency noise transmitted through the fuselage. Although structural acoustic coupling is in general very important in the study of aircraft fuselage interior noise, analysis of noise transmission through a panel supported in an infinite rigid baffle (separating two semi-infinite acoustic domains) can be useful in evaluating the effects of active/adaptive materials, complex loading, etc. Recent work has been aimed at developing adaptive and/or active methods of controlling the structural acoustic response of panels to reduce the transmitted noise1. A finite element formulation was recently developed to study the dynamic response of shape memory alloy (SMA) hybrid composite panels (conventional composite panel with embedded SMA fibers) subject to combined acoustic and thermal loads2. Further analysis has been performed to predict the far-field acoustic radiation using the finite element dynamic panel response prediction3. The purpose of the present work is to validate the panel vibration and acoustic radiation prediction methods with baseline experimental results obtained from an isotropic panel, without the effect of SMA.

Genetic Correction of Human Induced Pluripotent Stem Cells from Patients with Spinal Muscular Atrophy

PubMed Central

Corti, Stefania; Nizzardo, Monica; Simone, Chiara; Falcone, Marianna; Nardini, Martina; Ronchi, Dario; Donadoni, Chiara; Salani, Sabrina; Riboldi, Giulietta; Magri, Francesca; Menozzi, Giorgia; Bonaglia, Clara; Rizzo, Federica; Bresolin, Nereo; Comi, Giacomo P.

2016-01-01

Spinal muscular atrophy (SMA) is among the most common genetic neurological diseases that cause infant mortality. Induced pluripotent stem cells (iPSCs) generated from skin fibroblasts from SMA patients and genetically corrected have been proposed to be useful for autologous cell therapy. We generated iPSCs from SMA patients (SMA-iPSCs) using nonviral, nonintegrating episomal vectors and used a targeted gene correction approach based on single-stranded oligonucleotides to convert the survival motor neuron 2 (SMN2) gene into an SMN1-like gene. Corrected iPSC lines contained no exogenous sequences. Motor neurons formed by differentiation of uncorrected SMA-iPSCs reproduced disease-specific features. These features were ameliorated in motor neurons derived from genetically corrected SMA-iPSCs. The different gene splicing profile in SMA-iPSC motor neurons was rescued after genetic correction. The transplantation of corrected motor neurons derived from SMA-iPSCs into an SMA mouse model extended the life span of the animals and improved the disease phenotype. These results suggest that generating genetically corrected SMA-iPSCs and differentiating them into motor neurons may provide a source of motor neurons for therapeutic transplantation for SMA. PMID:23253609

Limitations of commonly used internal controls for real-time RT-PCR analysis of renal epithelial-mesenchymal cell transition.

PubMed

Elberg, Gerard; Elberg, Dorit; Logan, Charlotte J; Chen, Lijuan; Turman, Martin A

2006-01-01

Progressive renal fibrotic disease is accompanied by the massive accumulation of myofibroblasts as defined by alpha smooth muscle actin (alphaSMA) expression. We quantitated gene expression using real-time RT-PCR analysis during conversion of primary cultured human renal tubular cells (RTC) to myofibroblasts after treatment with transforming growth factor-beta1 (TGF-beta1). We report herein the limitations of commonly used reference genes for mRNA quantitation. We determined the expression of alphaSMA and megakaryoblastic leukemia-1 (MKL1), a transcriptional regulator of alphaSMA, by quantitative real-time PCR using three common internal controls, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), cyclophilin A and 18S rRNA. Expression of GAPDH mRNA and cyclophilin A mRNA, and to a lesser extent, 18S rRNA levels varied over time in culture and with exposure to TGF-beta1. Thus, depending on which reference gene was used, TGF-beta1 appeared to have different effects on expression of MKL1 and alphaSMA. RTC converting to myofibroblasts in primary culture is a valuable system to study renal fibrosis in humans. However, variability in expression of reference genes with TGF-beta1 treatment illustrates the need to validate mRNA quantitation with multiple reference genes to provide accurate interpretation of fibrosis studies in the absence of a universal internal standard for mRNA expression. 2006 S. Karger AG, Basel.

Survival motor neuron protein in motor neurons determines synaptic integrity in spinal muscular atrophy.

PubMed

Martinez, Tara L; Kong, Lingling; Wang, Xueyong; Osborne, Melissa A; Crowder, Melissa E; Van Meerbeke, James P; Xu, Xixi; Davis, Crystal; Wooley, Joe; Goldhamer, David J; Lutz, Cathleen M; Rich, Mark M; Sumner, Charlotte J

2012-06-20

The inherited motor neuron disease spinal muscular atrophy (SMA) is caused by deficient expression of survival motor neuron (SMN) protein and results in severe muscle weakness. In SMA mice, synaptic dysfunction of both neuromuscular junctions (NMJs) and central sensorimotor synapses precedes motor neuron cell death. To address whether this synaptic dysfunction is due to SMN deficiency in motor neurons, muscle, or both, we generated three lines of conditional SMA mice with tissue-specific increases in SMN expression. All three lines of mice showed increased survival, weights, and improved motor behavior. While increased SMN expression in motor neurons prevented synaptic dysfunction at the NMJ and restored motor neuron somal synapses, increased SMN expression in muscle did not affect synaptic function although it did improve myofiber size. Together these data indicate that both peripheral and central synaptic integrity are dependent on motor neurons in SMA, but SMN may have variable roles in the maintenance of these different synapses. At the NMJ, it functions at the presynaptic terminal in a cell-autonomous fashion, but may be necessary for retrograde trophic signaling to presynaptic inputs onto motor neurons. Importantly, SMN also appears to function in muscle growth and/or maintenance independent of motor neurons. Our data suggest that SMN plays distinct roles in muscle, NMJs, and motor neuron somal synapses and that restored function of SMN at all three sites will be necessary for full recovery of muscle power.

crm-1 facilitates BMP signaling to control body size in Caenorhabditis elegans.

PubMed

Fung, Wong Yan; Fat, Ko Frankie Chi; Eng, Cheah Kathryn Song; Lau, Chow King

2007-11-01

We have identified in Caenorhabditis elegans a homologue of the vertebrate Crim1, crm-1, which encodes a putative transmembrane protein with multiple cysteine-rich (CR) domains known to have bone morphogenetic proteins (BMPs) binding activity. Using the body morphology of C. elegans as an indicator, we showed that attenuation of crm-1 activity leads to a small body phenotype reminiscent of that of BMP pathway mutants. We showed that the crm-1 loss-of-function phenotype can be rescued by constitutive supply of sma-4 activity. crm-1 can enhance BMP signaling and this activity is dependent on the presence of the DBL-1 ligand and its receptors. crm-1 is expressed in neurons at the ventral nerve cord, where the DBL-1 ligand is produced. However, ectopic expression experiments reveal that crm-1 gene products act outside the DBL-1 producing cells and function non-autonomously to facilitate dbl/sma pathway signaling to control body size.

Electro-Optical Characterization of Bistable Smectic A Liquid Crystal Displays

NASA Astrophysics Data System (ADS)

Buyuktanir, Ebru Aylin

My dissertation focuses the characterization and optimization of the electro-optical properties of smectic A (SmA) based liquid crystal (LC) displays. I present the development of robust and flexible bistable SmA LC displays utilizing polymer dispersed liquid crystal (PDLC) technology. The SmA PDLC displays produced on plastic substrates present electrically reversible memory, high contrast ratio, paper-like sunlight readability, and wide viewing angle characteristics. In order to optimize the SmA PDLC display, I investigated polymerization conditions, such as polymer concentration effect, polymerization temperature, and UV-light intensity variations. I characterized the electro-optical responses-such as static-response, time-response, threshold characteristics, and contrast ratio values' of the optimized SmA PDLC display and compared them to those of the pure SmA LC. The best electro-optical performance of SmA PDLC formulation was obtained using the combination of low mW/cm 2 and high mW/cm2 UV-light curing intensity. The contrast ratio of the optimum SmA PDLC at a 5o collection angle was 83% of that of the pure SmA material on plastic substrates. I fabricated 2.5 x 2.5 in., 4 x 4 in., and 6 x 6 in. sized monochrome flexible SmA PDLC displays, as well as red, yellow, and fluorescent dyes colored SmA PDLC displays on plastic substrates. The electro-optic performance of the bistable SmA LC display consisting of a patterned field-induced polymer wall infrastructure was also studied and compared to those of pure SmA material. I found that the contrast ratio of the SmA LC encapsulated between polymer walls was much greater than that of the SmA PDLC system, approaching the contrast ratio value of the pure SmA material. I also improved the electro-optical characteristics of bistable SmA LC displays by adding ferroparticles into the system. Finally, I illustrated the unique capabilities of polarized confocal Raman microscopy (CRM) to resolve the orientational order of SmA LCs in three-dimension by investigating the characteristic vibrational bands of LC molecules. CRM provides a precise characterization of the molecular order at different depths of the LC films. I examined the director patterns of focal conic defects of smectic A LC, colloidal smectic A LC systems, and the field-oriented nematic LC in the horizontal and vertical planes.

Influence of Embedding SMA Fibres and SMA Fibre Surface Modification on the Mechanical Performance of BFRP Composite Laminates

PubMed Central

Liu, Yanfei; Wang, Zhenqing; Li, Hao; Sun, Min; Wang, Fangxin; Chen, Bingjie

2018-01-01

In this paper, a new shape memory alloy (SMA) hybrid basalt fibre reinforced polymer (BFRP) composite laminate was fabricated and a new surface modification method with both silane coupling agent KH550 and Al2O3 nanoparticles was conducted to enhance the interface performance. The mechanical performance of BFRP composite laminates with and without SMA fibres and the influence of SMA surface modification were studied in this paper. Different SMA fibre surface treatment methods, including etching with both H2SO4 and NaOH, modification with the silane coupling agent KH550 and new modification method with both KH550 and Al2O3 nanoparticles, were conducted to enhance the bonding between the SMA fibres and polymer matrix. Scanning electron microscopy (SEM) was used to observe the micromorphology of the SMA fibre surfaces exposed to different treatments and the damage morphology of composite laminates. The mechanical performance of the composites was investigated with tensile, three-point bending and low-velocity impact tests to study the influence of embedded SMA fibres and the different surface modifications of the SMA fibres. The results demonstrated that the embedded Ni-Ti SMA fibres can significantly enhance the mechanical performance of BFRP composite laminates. SMA fibres modified with both the silane coupling agent KH550 and Al2O3 nanoparticles illustrate the best mechanical performance among all samples. PMID:29300321

Tensile and fatigue behavior of polymer composites reinforced with superelastic SMA strands

NASA Astrophysics Data System (ADS)

Daghash, Sherif M.; Ozbulut, Osman E.

2018-06-01

This study explores the use of superelastic shape memory alloy (SMA) strands, which consist of seven individual small-diameter wires, in an epoxy matrix and characterizes the tensile and fatigue responses of the developed SMA/epoxy composites. Using a vacuum assisted hand lay-up technique, twelve SMA fiber reinforced polymer (FRP) specimens were fabricated. The developed SMA-FRP composites had a fiber volume ratio of 50%. Tensile response of SMA-FRP specimens were characterized under both monotonic loading and increasing amplitude loading and unloading cycles. The degradation in superelastic properties of the developed SMA-FRP composites during fatigue loading at different strain amplitudes was investigated. The effect of loading rate on the fatigue response of SMA-FRP composites was also explored. In addition, fractured specimens were examined using the scanning electron microscopy (SEM) technique to study the failure mechanisms of the tested specimens. A good interfacial bonding between the SMA strands and epoxy matrix was observed. The developed SMA-FRP composites exhibited good superelastic behavior at different strain amplitudes up to at least 800 cycle after which significant degradation occurred.

Time-Reversal Based Range Extension Technique for Ultra-Wideband (UWB) Sensors and Applications in Tactical Communications and Networking

DTIC Science & Technology

2009-07-16

Frequency (MHz) Figure 3.4: CABLE SMA/SMA 24" RG-316DS. CABLE SMA PLUG-PLUG HF -.086 8" 3.1. TRANSMITTER IMPLEMENTATION 13 Length: 8.0" (203.2mm) Color...Gray RG Type: Hand Formable .086 Connector: Type SMA Male to SMA Male Features: Shielded "• JI Figure 3.5: CABLE SMA PLUG-PLUG HF -.086 8...34 . • CABLE SMA PLUG-PLUG HF -.141 8" Length: 8.0" (203.2mm) Color: Gray RG Type: Hand Formable .141 14 CHAPTER 3. 2 BY I MISO SYSTEM DEVELOPMENT

The confining effectiveness of NiTiNb and NiTi SMA wire jackets for concrete

NASA Astrophysics Data System (ADS)

Choi, Eunsoo; Chung, Young-Soo; Choi, Jun-Hyeok; Kim, Hong-Taek; Lee, Hacksoo

2010-03-01

The purpose of this study is to assess the confining effectiveness of shape memory alloy (SMA) wire jackets for concrete. The performance of SMA wire jackets was compared to that of steel jackets. A prestrained martensitic SMA wire was wrapped around a concrete cylinder and then heated by a heating jacket. In the process, a confining stress around the cylinder was developed in the SMA wire due to the shape memory effect; this jacketing method can increase the strength and ductility of the cylinder under an axial compressive load. In this study, NiTi and NiTiNb SMA wires of 1.0 mm in diameter were used for the confinement. Recovery tests were conducted on the wires to assess their recovery and residual stress. The confinement by SMA wire jackets increased the strength slightly and greatly increased the ductility compared to the strength and ductility of plain concrete cylinders. The NiTiNb SMA wire jacket showed better performance than that of the NiTi SMA wire jacket. The confining effectiveness of the SMA wire jackets of this study was estimated to be similar to that of the steel jackets. This study showed the potential of the SMA wire jacketing method to retrofit reinforced concrete columns and protect them from seismic risks.

Medical Issues: Orthopedics

MedlinePlus

... Cure SMA Store Volunteer Donate Learn About SMA Research Support & Care Get Involved Donate About Us News www.curesma.org > support & care > living with sma > medical issues > orthopedics Orthopedics In SMA, muscle weakness can cause several ...

Contralateral functional reorganization of the speech supplementary motor area following neurosurgical tumor resection.

PubMed

Chivukula, Srinivas; Pikul, Brian K; Black, Keith L; Pouratian, Nader; Bookheimer, Susan Y

2018-05-18

We evaluated plasticity in speech supplemental motor area (SMA) tissue in two patients using functional magnetic resonance imaging (fMRI), following resection of tumors in or associated with the dominant hemisphere speech SMA. Patient A underwent resection of a anaplastic astrocytoma NOS associated with the left speech SMA, experienced SMA syndrome related mutism postoperatively, but experienced full recovery 14 months later. FMRI performed 32 months after surgery demonstrated a migration of speech SMA to homologous contralateral hemispheric regional tissue. Patient B underwent resection of a oligodendroglioma NOS in the left speech SMA, and postoperatively experienced speech hesitancy, latency and poor fluency, which gradually resolved over 18 months. FMRI performed at 64 months after surgery showed a reorganization of speech SMA to the contralateral hemisphere. These data support the hypothesis of dynamic, time based plasticity in speech SMA tissue, and may represent a noninvasive neural marker for SMA syndrome recovery. Copyright © 2018 Elsevier Inc. All rights reserved.

Shape memory alloy/shape memory polymer tools

DOEpatents

Seward, Kirk P.; Krulevitch, Peter A.

2005-03-29

Micro-electromechanical tools for minimally invasive techniques including microsurgery. These tools utilize composite shape memory alloy (SMA), shape memory polymer (SMP) and combinations of SMA and SMP to produce catheter distal tips, actuators, etc., which are bistable. Applications for these structures include: 1) a method for reversible fine positioning of a catheter tip, 2) a method for reversible fine positioning of tools or therapeutic catheters by a guide catheter, 3) a method for bending articulation through the body's vasculature, 4) methods for controlled stent delivery, deployment, and repositioning, and 5) catheters with variable modulus, with vibration mode, with inchworm capability, and with articulated tips. These actuators and catheter tips are bistable and are opportune for in vivo usage because the materials are biocompatible and convenient for intravascular use as well as other minimal by invasive techniques.

Recent developments on SMA actuators: predicting the actuation fatigue life for variable loading schemes

NASA Astrophysics Data System (ADS)

Wheeler, Robert W.; Lagoudas, Dimitris C.

2017-04-01

Shape memory alloys (SMAs), due to their ability to repeatably recover substantial deformations under applied mechanical loading, have the potential to impact the aerospace, automotive, biomedical, and energy industries as weight and volume saving replacements for conventional actuators. While numerous applications of SMA actuators have been flight tested and can be found in industrial applications, these actuators are generally limited to non-critical components, are not widely implemented and frequently one-off designs, and are generally overdesigned due to a lack of understanding of the effect of the loading path on the fatigue life and the lack of an accurate method for predicting actuator lifetimes. In recent years, multiple research efforts have increased our understanding of the actuation fatigue process of SMAs. These advances can be utilized to predict the fatigue lives and failure loads in SMA actuators. Additionally, these prediction methods can be implemented in order to intelligently design actuators in accordance with their fatigue and failure limits. In the following paper, both simple and complex thermomechanical loading paths have been considered. Experimental data was utilized from two material systems: equiatomic Nickel-Titanium and Nickelrich Nickel-Titanium.

Physical and genetic map of Streptococcus thermophilus A054.

PubMed Central

Roussel, Y; Pebay, M; Guedon, G; Simonet, J M; Decaris, B

1994-01-01

The three restriction endonucleases SfiI, BssHII, and SmaI were found to generate fragments with suitable size distributions for mapping the genome of Streptococcus thermophilus A054. A total of 5, 8, and 24 fragments were produced with SfiI, BssHII, and SmaI, respectively. An average genome size of 1,824 kb was determined by summing the total fragment sizes obtained by digestions with these three enzymes. Partial and multiple digestions of genomic DNA in conjunction with Southern hybridization were used to map SfiI, BssHII, and SmaI fragments. All restriction fragments were arranged in a unique circular chromosome. Southern hybridization analysis with specific probes allowed 23 genetic markers to be located on the restriction map. Among them, six rrn loci were precisely located. The area of the chromosome containing the ribosomal operons was further detailed by mapping some of the ApaI and SgrAI sites. Comparison of macrorestriction patterns from three clones derived from strain A054 revealed two variable regions in the chromosome. One was associated with the tandem rrnD and rrnE loci, and the other was mapped in the region of the lactose operon. Images PMID:8002562

Renal alpha-smooth muscle actin: a new prognostic factor for lupus nephritis.

PubMed

Makni, Kaouthar; Jarraya, Faïçal; Khabir, Abdelmajid; Hentati, Basma; Hmida, Mohamed Ben; Makni, Hafedh; Boudawara, Tahia; Jlidi, Rchid; Hachicha, Jamil; Ayadi, Hammadi

2009-08-01

Systemic lupus erythematosus (SLE) is the prototype of autoimmune disease where renal involvement is frequent and always severe. Histological prognostic factors proposed for lupus nephritis (LN) including the World Health Organization and International Society of Nephrology/Renal Pathology Society--Working Group on the Classification classifications, active (AI) and chronicity (CI) indices may not predict response to treatment. The aim of this study was to correlate alpha-smooth muscle actin (alpha-SMA) expression, an early marker of glomerular and interstitial response to injury, to AI and CI, renal scarring progression and response to treatment. Fifty-seven kidney biopsy specimens obtained from 32 patients suffering from LN were studied. Twenty patients with class IV LN at first biopsy were identified to study renal progression to chronic renal failure until the use of immunosuppressive treatment. Interstitial alpha-SMA (I-alpha-SMA) was correlated only with CI (P < 0.001) whereas mesangial alpha-SMA (M-alpha-SMA) was correlated with neither LN activity (P = 0.126) nor sclerosis (P = 0.297). Only I-alpha-SMA was correlated with renal failure (P = 0.01). We divided patients with class IV LN into progressors and non-progressors based on the slope of serum creatinine. At first biopsy, M-alpha-SMA and I-alpha-SMA, but not AI and CI, were correlated with renal failure progression (M-alpha-SMA, 9.7b1.1 vs 7.8b1.4, P = 0.004; and I-alpha-SMA, 9.3b1.1 vs 6.5b3.2, P = 0.011). The study data highlight that I-alpha-SMA immunostain in class IV LN patients was correlated with chronicity indices. Moreover, M-alpha-SMA and I-alpha-SMA expression in first biopsy predicted renal progression modality. alpha-SMA expression may therefore be a useful marker to predict renal prognosis in LN.

Comparative Life Cycle Assessment between Warm SMA and Conventional SMA

DOT National Transportation Integrated Search

2011-09-01

This report presents the comparative life cycle assessment (LCA) between warm stone mastic asphalt (SMA) and conventional : SMA. Specifically, the study evaluated and compared the life cycle environmental and economic performances of two mixtures: a ...

Confinement of NORMAL- AND HIGH-STRENGTH CONCRETE by Shape Memory Alloy (SMA) Spirals

NASA Astrophysics Data System (ADS)

Gholampour, A.; Ozbakkaloglu, T.

2018-01-01

This paper presents the results of an experimental study on the axial compressive behaviour of normal- and high-strength concrete (NSC and HSC) confined by shape memory alloy (SMA) spirals. A spiral pitch space of 36 and 20 mm was used for SMA confinement of NSC and HSC columns, respectively. The confining pressure was applied on the concrete cylinders by SMA spirals that were prestrained at 0, 5.5, and 9.5%. The compression test results on the SMA-confined specimens indicate that the prestrain level of SMA significantly affects the axial compressive behaviour of both NSC and HSC. An increase in the level of prestrain leads to an increase in the peak axial stress and corresponding strain of SMA-confined concrete.

New design for a rotatory joint actuator made with shape memory alloy contractile wire

NASA Astrophysics Data System (ADS)

Wang, Guoping; Shahinpoor, Mohsen

1996-05-01

A design approach for a rotatory joint actuator using a contractile shape memory alloy (SMA) wire is presented and an example design is followed. In this example, the output torque of the actuator is 18 Newton-meters, and its angular range is 30 degrees. Compared with a SMA spring type actuating component, a SMA wire type actuating component uses less SMA material and uses less electrical energy when it is electrically powered. On the other hand, a SMA wire type actuating component must have a large SMA wire length to produce a required amount of angular rotation of the joint. When pulleys are used to arrange a lengthy SMA wire in a small space, the friction between pulleys and pins is introduced and the performance of the joint actuator is degenerated to some degree. The investigated joint actuator provides a good chance for developing powered orthoses with SMA actuators for disabled individuals. It can relieve the weight concern with hydraulic and motor-powered orthoses and the safety concern with motor-powered orthoses. When electrically powered, a SMA actuator has the disadvantage of low energy efficiency.

Bioconjugation of laminin peptide YIGSR with poly(styrene co-maleic acid) increases its antimetastatic effect on lung metastasis of B16-BL6 melanoma cells.

PubMed

Mu, Y; Kamada, H; Kaneda, Y; Yamamoto, Y; Kodaira, H; Tsunoda, S; Tsutsumi, Y; Maeda, M; Kawasaki, K; Nomizu, M; Yamada, Y; Mayumi, T

1999-02-05

A comb-shaped polymeric modifier, SMA [poly(styrene comaleic anhydride)], which binds to plasma albumin in blood was used to modify the synthetic cell-adhesive laminin peptide YIGSR, and its inhibitory effect on experimental lung metastasis of B16-BL6 melanoma cells was examined. YIGSR was chemically conjugated with SMA via formation of an amide bond between the N-terminal amino group of YIGSR and the carboxyl anhydride of SMA. The antimetastatic effect of SMA-conjugated YIGSR was approximately 50-fold greater than that of native YIGSR. When injected intravenously, SMA-YIGSR showed a 10-fold longer plasma half-life than native YIGSR in vivo. In addition, SMA-YIGSR had the same binding affinity to plasma albumin as SMA, while native YIGSR did not bind to albumin. These findings suggested that the enhanced antimetastatic effect of SMA-YIGSR may be due to its prolonged plasma half-life by binding to plasma albumin, and that bioconjugation of in vivo unstable peptides with SMA may facilitate their therapeutic use. Copyright 1999 Academic Press.

Molecular Analysis of Spinal Muscular Atrophy: A genotyping protocol based on TaqMan(®) real-time PCR.

PubMed

de Souza Godinho, Fernanda Marques; Bock, Hugo; Gheno, Tailise Conte; Saraiva-Pereira, Maria Luiza

2012-12-01

Spinal muscular atrophy (SMA) is an autosomal recessive inherited disorder caused by alterations in the survival motor neuron I (SMN1) gene. SMA patients are classified as type I-IV based on severity of symptoms and age of onset. About 95% of SMA cases are caused by the homozygous absence of SMN1 due to gene deletion or conversion into SMN2. PCR-based methods have been widely used in genetic testing for SMA. In this work, we introduce a new approach based on TaqMan(®)real-time PCR for research and diagnostic settings. DNA samples from 100 individuals with clinical signs and symptoms suggestive of SMA were analyzed. Mutant DNA samples as well as controls were confirmed by DNA sequencing. We detected 58 SMA cases (58.0%) by showing deletion of SMN1 exon 7. Considering clinical information available from 56 of them, the patient distribution was 26 (46.4%) SMA type I, 16 (28.6%) SMA type II and 14 (25.0%) SMA type III. Results generated by the new method was confirmed by PCR-RFLP and by DNA sequencing when required. In conclusion, a protocol based on real-time PCR was shown to be effective and specific for molecular analysis of SMA patients.

Shape memory alloy wires turn composites into smart structures: I. Material requirements

NASA Astrophysics Data System (ADS)

Schrooten, Jan; Michaud, Veronique J.; Zheng, Yanjun; Balta-Neumann, J. Antonio; Manson, Jan-Anders E.

2002-07-01

Composites containing thin Shape Memory Alloy (SMA) wires show great potential as materials able to adapt their shape, thermal behavior or vibrational properties to external stimuli. The functional properties of SMA-composites are directly related to the constraining effect of the matrix on the reversible martensitic transformation of the embedded pre-strained SMA wires. The present work reports results of a concerted European effort towards a fundamental understanding of the manufacturing and design of SMA composites. This first part investigates the transformational behavior of constrained SMA wires and its translation into functional properties of SMA composites. Thermodynamic and thermomechanical experiments were performed on SMA wires. A model was developed to simulate the thermomechanical behavior of the wires. From the screening of potential wires it was concluded that NiTiCu, as well as R-phase NiTi appeared as best candidates. Requirements for the host composite materials were surveyed. A Kevlar-epoxy system was chosen. Finally, the quality of the SMA wire-resin interface was assessed by two different techniques. These indicated that a thin oxide layer seems to provide the best interfacial strength. A temperature window in which SMA composites can be safely used was also defined. The manufacturing and properties of the SMA composites will be discussed in Part II.

[Expression of FAP and alpha-SMA during the incised wound healing in mice skin].

PubMed

Gao, Yang; Peng, Xue; Jin, Zhan-Fen; Fu, Zhi-Jun

2009-12-01

OBJECTIVE To investigate the time-dependent expression of fibroblast activation protein (FAP) and alpha-smooth muscle actin(alpha-SMA) during the incised wound healing of the skin in mice. The expression of FAP and alpha-SMA in incised wound of mice skin was detected by immunohistochemistry and Western blot. By immunohistochemistry, the expression of FAP and alpha-SMA in the normal skin and the skin 1 h after injury maintained at a very low level, but the positive cells expressing FAP and alpha-SMA started to elevate 6 h after injury and reached its peak on 5 d for FAP and on 3 d for alpha-SMA, then gradually decreased to the normal level on 14 d. The expression of FAP and alpha-SMA was observed throughout the wound healing stages 1 d after injuries by Western blot as well with a peak expression occurring on 5 d for FAP and on 3 d for alpha-SMA after injury. FAP may be a potentially useful marker for wound age determination and alpha-SMA may be used as an effective indicator for the mid- and late stage incised wound of mice skin. The combination use of FAP and alpha-SMA may be potentially effective indicators for wound age determination.

Motor neuron mitochondrial dysfunction in spinal muscular atrophy

PubMed Central

Miller, Nimrod; Shi, Han; Zelikovich, Aaron S.; Ma, Yong-Chao

2016-01-01

Spinal muscular atrophy (SMA), the leading genetic cause of infant mortality, predominantly affects high metabolic tissues including motor neurons, skeletal muscles and the heart. Although the genetic cause of SMA has been identified, mechanisms underlying tissue-specific vulnerability are not well understood. To study these mechanisms, we carried out a deep sequencing analysis of the transcriptome of spinal motor neurons in an SMA mouse model, in which we unexpectedly found changes in many genes associated with mitochondrial bioenergetics. Importantly, functional measurement of mitochondrial activities showed decreased basal and maximal mitochondrial respiration in motor neurons from SMA mice. Using a reduction-oxidation sensitive GFP and fluorescence sensors specifically targeted to mitochondria, we found increased oxidative stress level and impaired mitochondrial membrane potential in motor neurons affected by SMA. In addition, mitochondrial mobility was impaired in SMA disease conditions, with decreased retrograde transport but no effect on anterograde transport. We also found significantly increased fragmentation of the mitochondrial network in primary motor neurons from SMA mice, with no change in mitochondria density. Electron microscopy study of SMA mouse spinal cord revealed mitochondria fragmentation, edema and concentric lamellar inclusions in motor neurons affected by the disease. Intriguingly, these functional and structural deficiencies in the SMA mouse model occur during the presymptomatic stage of disease, suggesting a role in initiating SMA. Altogether, our findings reveal a critical role for mitochondrial defects in SMA pathogenesis and suggest a novel target for improving tissue health in the disease. PMID:27488123

Non-Aggregating Tau Phosphorylation by Cyclin-Dependent Kinase 5 Contributes to Motor Neuron Degeneration in Spinal Muscular Atrophy

PubMed Central

Miller, Nimrod; Feng, Zhihua; Edens, Brittany M.; Yang, Ben; Shi, Han; Sze, Christie C.; Hong, Benjamin Taige; Su, Susan C.; Cantu, Jorge A.; Topczewski, Jacek; Crawford, Thomas O.; Ko, Chien-Ping; Sumner, Charlotte J.; Ma, Long

2015-01-01

Mechanisms underlying motor neuron degeneration in spinal muscular atrophy (SMA), the leading inherited cause of infant mortality, remain largely unknown. Many studies have established the importance of hyperphosphorylation of the microtubule-associated protein tau in various neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. However, tau phosphorylation in SMA pathogenesis has yet to be investigated. Here we show that tau phosphorylation on serine 202 (S202) and threonine 205 (T205) is increased significantly in SMA motor neurons using two SMA mouse models and human SMA patient spinal cord samples. Interestingly, phosphorylated tau does not form aggregates in motor neurons or neuromuscular junctions (NMJs), even at late stages of SMA disease, distinguishing it from other tauopathies. Hyperphosphorylation of tau on S202 and T205 is mediated by cyclin-dependent kinase 5 (Cdk5) in SMA disease condition, because tau phosphorylation at these sites is significantly reduced in Cdk5 knock-out mice; genetic knock-out of Cdk5 activating subunit p35 in an SMA mouse model also leads to reduced tau phosphorylation on S202 and T205 in the SMA;p35−/− compound mutant mice. In addition, expression of the phosphorylation-deficient tauS202A,T205A mutant alleviates motor neuron defects in a zebrafish SMA model in vivo and mouse motor neuron degeneration in culture, whereas expression of phosphorylation-mimetic tauS202E,T205E promotes motor neuron defects. More importantly, genetic knock-out of tau in SMA mice rescues synapse stripping on motor neurons, NMJ denervation, and motor neuron degeneration in vivo. Altogether, our findings suggest a novel mechanism for SMA pathogenesis in which hyperphosphorylation of non-aggregating tau by Cdk5 contributes to motor neuron degeneration. PMID:25878277

Model and Simulation of an SMA Enhanced Lip Seal

NASA Astrophysics Data System (ADS)

Qiao, Rui; Gao, Xiujie; Brinson, L. Catherine

2011-07-01

The feasibility of using SMA wires to improve the seal effectiveness has been studied experimentally and numerically. In this article, we present only the numerical study of simulating the thermo-mechanical behavior for an SMA enhanced lip seal, leaving the test setup and results in the experimental counterpart. A pseudo 3D SMA model, considering 1D SMA behavior in the major loading direction and elastic response in other directions, was used to capture the thermo-mechanical behavior of SMA wires. The model was then implemented into ABAQUS using the user-defined material subroutine to inherit most features of the commercial finite element package. Two-way shape memory effect was also considered since the SMA material exhibits strong two-way effects. An axisymmetric finite element model was constructed to simulate a seal mounting on a shaft and the sealing pressure was calculated for both the regular seal and the SMA enhanced seal. Finally, the result was qualitatively compared with the experimental observation.

Prestressing effect of cold-drawn short NiTi SMA fibres in steel reinforced mortar beams

NASA Astrophysics Data System (ADS)

Choi, Eunsoo; Kim, Dong Joo; Hwang, Jin-Ha; Kim, Woo Jin

2016-08-01

This study investigated the prestressing effect of cold-drawn short NiTi shape memory alloy (SMA) fibres in steel reinforced mortar beams. The SMA fibres were mixed with 1.5% volume content in a mortar matrix with the compressive strength of 50 MPa. The SMA fibres had an average length of 34 mm, and they were manufactured with a dog-bone shape: the diameters of the end- and middle-parts were 1.024 and 1.0 mm, respectively. Twenty mortar beams with the dimensions of 40 mm × 40 mm × 160 mm (B × H × L) were prepared. Two types of tests were conducted. One was to investigate the prestressing effect of the SMA fibres, and the beams with the SMA fibres were heated at the bottom. The other was to assess the bending behaviour of the beams prestressed by the SMA fibres. The SMA fibres induced upward deflection and cracking at the top surface by heating at the bottom; thus, they achieved an obvious prestressing effect. The beams that were prestressed by the SMA fibres did not show a significant difference in bending behaviour from that of the SMA fibre reinforced beams that were not subjected to heating. Stress analysis of the beams indicated that the prestressing effect decreased in relation to the cooling temperature.

Aneurysmal and haemangiopericytoma-like fibrous histiocytoma.

PubMed Central

Zelger, B W; Zelger, B G; Steiner, H; Ofner, D

1996-01-01

AIM: To describe the clinicopathological features of 33 aneurysmal fibrous histiocytomas (AFH), including five cases with a haemangiopericytoma-like pattern. METHODS: Thirty three cases of AFH were studied by using routine histology and immunohistochemistry for factor XIIIa, the "cell activity marker" E9 (anti-metallothionein), NK1C3 (CD57), smooth muscle actin (SMA), factor VIII, ulex europaeus agglutinin, JC70A (CD31), and QBEND10 (CD34). The time dependent variation in histopathological features was evaluated by statistical methods (Pearson chi 2, likelihood ratio chi 2). RESULTS: Of the AFHs, 29 of 33 occurred on the extremities of adults (age range 30 to 50 years), six of which were associated with rapid growth, probably caused by trauma, and pain. Twenty one lesions were thought to be vascular and/or melanocytic lesions, including two melanomas, because of a bluish-black and/or cystic appearance. Histologically, large areas of haemorrhage, up to 50% of the tumour bulk, lacking an endothelial lining were seen in otherwise typical fibrous histiocytomas. Five cases resembled nodular stages of Kaposi's sarcoma. Variable haemosiderin deposition in histiocytes (18/33) and giant cells (11/33) was suggestive of haemosiderotic histiocytoma. A haemangiopericytoma-like pattern was seen in five otherwise indistinguishable cases. On immunohistochemistry, variable reactivity was seen for factor XIIIa (18/30), with E9 (18/30), NK1C3 (19/30), and for SMA (14/30), but labelling for vascular markers was not detected. Early lesions without iron deposition were factor XIIIa positive; late lesions with iron deposition were factor XIIIa negative. Labelling for SMA correlated with prominent sclerosis. CONCLUSION: AFHs, including a haemangiopericytoma-like variant, have a characteristic time dependent histological and immunophenotypic profile, clearly different from nodular type Kaposi's sarcoma. Images PMID:8655708

Cortical Thickness of Neural Substrates Supporting Cognitive Empathy in Individuals with Schizophrenia

PubMed Central

Massey, Suena H.; Stern, Daniel; Alden, Eva C.; Petersen, Julie E.; Cobia, Derin J.; Wang, Lei; Csernansky, John G.; Smith, Matthew J.

2016-01-01

Background Cognitive empathy is supported by the inferior frontal gyrus (IFG), anterior mid-cingulate cortex (aMCC), insula (INS), supplementary motor area (SMA), medial prefrontal cortex (mPFC), right temporo-parietal junction (TPJ), and precuneus (PREC). In healthy controls, cortical thickness in these regions has been linked to cognitive empathy. As cognitive empathy is impaired in schizophrenia, we examined whether reduced cortical thickness in these regions was associated with poorer cognitive empathy in this population. Methods 41 clinically-stable community-dwelling individuals with schizophrenia and 46 healthy controls group-matched on demographic variables completed self-report empathy questionnaires, a cognitive empathy task, and structural magnetic resonance imaging. We examined between-group differences in study variables using t-tests and analyses of variance. Next, we used Pearson correlations to evaluate the relationship between cognitive empathy and cortical thickness in the mPFC, IFG, aMCC, INS, SMA, TPJ, and PREC in both groups. Results Individuals with schizophrenia demonstrated cortical thinning in the IFG, INS, SMA, TPJ, and PREC (all p<0.05) and impaired cognitive empathy across all measures (all p<0.01) relative to controls. While cortical thickness in the mPFC, IFC, aMCC, and INS (all p<0.05) was related to cognitive empathy in controls, we did not observe these relationships in individuals with schizophrenia (all p>0.10). Conclusions Individuals with schizophrenia have reduced cortical thickness in empathy-related neural regions and significant impairments in cognitive empathy. Interestingly, cortical thickness was related to cognitive empathy in controls but not in the schizophrenia group. We discuss other mechanisms that may account for cognitive empathy impairment in schizophrenia. PMID:27665257

Cortical thickness of neural substrates supporting cognitive empathy in individuals with schizophrenia.

PubMed

Massey, Suena H; Stern, Daniel; Alden, Eva C; Petersen, Julie E; Cobia, Derin J; Wang, Lei; Csernansky, John G; Smith, Matthew J

2017-01-01

Cognitive empathy is supported by the medial prefrontal cortex (mPFC), inferior frontal gyrus (IFG), anterior mid-cingulate cortex (aMCC), insula (INS), supplementary motor area (SMA), right temporo-parietal junction (TPJ), and precuneus (PREC). In healthy controls, cortical thickness in these regions has been linked to cognitive empathy. As cognitive empathy is impaired in schizophrenia, we examined whether reduced cortical thickness in these regions was associated with poorer cognitive empathy in this population. 41 clinically-stable community-dwelling individuals with schizophrenia and 46 healthy controls group-matched on demographic variables completed self-report empathy questionnaires, a cognitive empathy task, and structural magnetic resonance imaging. We examined between-group differences in study variables using t-tests and analyses of variance. Next, we used Pearson correlations to evaluate the relationship between cognitive empathy and cortical thickness in the mPFC, IFG, aMCC, INS, SMA, TPJ, and PREC in both groups. Individuals with schizophrenia demonstrated cortical thinning in the IFG, INS, SMA, TPJ, and PREC (all p<0.05) and impaired cognitive empathy across all measures (all p<0.01) relative to controls. While cortical thickness in the mPFC, IFC, aMCC, and INS (all p<0.05) was related to cognitive empathy in controls, we did not observe these relationships in individuals with schizophrenia (all p>0.10). Individuals with schizophrenia have reduced cortical thickness in empathy-related neural regions and significant impairments in cognitive empathy. Interestingly, cortical thickness was related to cognitive empathy in controls but not in the schizophrenia group. We discuss other mechanisms that may account for cognitive empathy impairment in schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

Shape memory alloy actuation for a variable area fan nozzle

NASA Astrophysics Data System (ADS)

Rey, Nancy; Tillman, Gregory; Miller, Robin M.; Wynosky, Thomas; Larkin, Michael J.; Flamm, Jeffrey D.; Bangert, Linda S.

2001-06-01

The ability to control fan nozzle exit area is an enabling technology for next generation high-bypass-ratio turbofan engines. Performance benefits for such designs are estimated at up to 9% in thrust specific fuel consumption (TSFC) relative to current fixed-geometry engines. Conventionally actuated variable area fan nozzle (VAN) concepts tend to be heavy and complicated, with significant aircraft integration, reliability and packaging issues. The goal of this effort was to eliminate these undesirable features and formulate a design that meets or exceeds leakage, durability, reliability, maintenance and manufacturing cost goals. A Shape Memory Alloy (SMA) bundled cable actuator acting to move an array of flaps around the fan nozzle annulus is a concept that meets these requirements. The SMA bundled cable actuator developed by the United Technologies Corporation (Patents Pending) provides significant work output (greater than 2200 in-lb per flap, through the range of motion) in a compact package and minimizes system complexity. Results of a detailed design study indicate substantial engine performance, weight, and range benefits. The SMA- based actuation system is roughly two times lighter than a conventional mechanical system, with significant aircraft direct operating cost savings (2-3%) and range improvements (5-6%) relative to a fixed-geometry nozzle geared turbofan. A full-scale sector model of this VAN system was built and then tested at the Jet Exit Test Facility at NASA Langley to demonstrate the system's ability to achieve 20% area variation of the nozzle under full scale aerodynamic loads. The actuator exceeded requirements, achieving repeated actuation against full-scale loads representative of typical cruise as well as greater than worst-case (ultimate) aerodynamic conditions. Based on these encouraging results, work is continuing with the goal of a flight test on a C-17 transport aircraft.

Characterization and modeling of three-dimensional self-healing shape memory alloy-reinforced metal-matrix composites

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

Zhu, Pingping; Cui, Zhiwei; Kesler, Michael S.

In this paper, three-dimensional metal-matrix composites (MMCs) reinforced by shape memory alloy (SMA) wires are modeled and simulated, by adopting an SMA constitutive model accounting for elastic deformation, phase transformation and plastic behavior. A modeling method to create composites with pre-strained SMA wires is also proposed to improve the self-healing ability. Experimental validation is provided with a composite under three-point bending. This modeling method is applied in a series of finite element simulations to investigate the self-healing effects in pre-cracked composites, especially the role of the SMA reinforcement, the softening property of the matrix, and the effect of pre-strain inmore » the SMA. The results demonstrate that SMA reinforcements provide stronger shape recovery ability than other, non-transforming materials. The softening property of the metallic matrix and the pre-strain in SMA are also beneficial to help crack closure and healing. This modeling approach can serve as an efficient tool to design SMA-reinforced MMCs with optimal self-healing properties that have potential applications in components needing a high level of reliability.« less

Role of medial premotor areas in action language processing in relation to motor skills.

PubMed

Courson, Melody; Macoir, Joël; Tremblay, Pascale

2017-10-01

The literature reports that the supplementary motor area (SMA) and pre-supplementary motor area (pre-SMA) are involved in motor planning and execution, and in motor-related cognitive functions such as motor imagery. However, their specific role in action language processing remains unclear. In the present study, we investigated the impact of repetitive transcranial magnetic stimulation (rTMS) over SMA and pre-SMA during an action semantic analogy task (SAT) in relation with fine motor skills (i.e., manual dexterity) and motor imagery abilities in healthy non-expert adults. The impact of rTMS over SMA (but not pre-SMA) on reaction times (RT) during SAT was correlated with manual dexterity. Specifically, results show that rTMS over SMA modulated RT for those with lower dexterity skills. Our results therefore demonstrate a causal involvement of SMA in action language processing, as well as the existence of inter-individual differences in this involvement. We discuss these findings in light of neurolinguistic theories of language processing. Copyright © 2017 Elsevier Ltd. All rights reserved.

Dysfunction of the neuromuscular junction in spinal muscular atrophy types 2 and 3.

PubMed

Wadman, Renske I; Vrancken, Alexander F J E; van den Berg, Leonard H; van der Pol, W Ludo

2012-11-13

Spinal muscular atrophy (SMA) is pathologically characterized by degeneration of anterior horn cells. Recent observations in animal models of SMA and muscle tissue from patients with SMA suggest additional abnormalities in the development and maturation of the neuromuscular junction. We therefore evaluated neuromuscular junction function in SMA with repetitive nerve stimulation. In this case-control study, repetitive nerve stimulation was performed in 35 patients with SMA types 2, 3, and 4, 20 healthy controls, and 5 controls with motor neuron disease. Pathologic decremental responses (>10%) during 3-Hz repetitive nerve stimulation were observed in 17 of 35 patients (49%) with SMA types 2 and 3, but not in healthy controls or controls with motor neuron disease. None of the patients or controls had an abnormal incremental response of >60%. The presence of an abnormal decremental response was not specific for the type of SMA, nor was it associated with compound muscle action potential amplitude, clinical scores, or disease duration. Two of 4 patients with SMA type 3 who tried pyridostigmine reported increased stamina. These data suggest dysfunction of the neuromuscular junction in patients with SMA types 2 and 3. Therefore, drugs that facilitate neuromuscular transmission are candidate drugs for evaluation in carefully designed, placebo-controlled, clinical trials.

Investigation on low velocity impact resistance of SMA composite material

NASA Astrophysics Data System (ADS)

Hu, Dianyin; Zhang, Long; Wang, Rongqiao; Zhang, Xiaoyong

2016-04-01

A method to improve low velocity impact resistance of aeroengine composite casing using shape memory alloy's properties of shape memory(SM) and super-elasticity(SE) is proposed in this study. Firstly, a numerical modeling of SMA reinforced composite laminate under low velocity impact load with impact velocity of 10 m/s is established based on its constitutive model implemented by the VUMAT subroutine of commercial software ABAQUS. Secondly, the responses of SMA composite laminate including stress and deflection distributions were achieved through transient analysis under low velocity impact load. Numerical results show that both peak stress and deflection values of SMA composite laminate are less than that without SMA, which proves that embedding SMA into the composite structure can effectively improve the low velocity impact performance of composite structure. Finally, the influence of SM and SE on low velocity impact resistance is quantitatively investigated. The values of peak stress and deflection of SMA composite based on SM property decrease by 18.28% and 9.43% respectively, compared with those without SMA, instead of 12.87% and 5.19% based on SE. In conclusion, this proposed model described the impact damage of SMA composite structure and turned to be a more beneficial method to enhance the impact resistance by utilizing SM effect.

Development of damage suppression system using embedded SMA foil in CFRP laminates

NASA Astrophysics Data System (ADS)

Ogisu, Toshimichi; Nomura, Masato; Ando, Norio; Takaki, Junji; Kobayashi, Masakazu; Okabe, Tomonaga; Takeda, Nobuo

2001-07-01

Some recent studies have suggested possible applications of Shape Memory Alloy (SMA) for a smart health monitoring and suppression of damage growth. The authors have been conducting research and development studies on applications of embedded SMA foil actuators in CFRP laminates as the basic research for next generation aircrafts. First the effective surface treatment for improvement of bonding properties between SMA and CFRP was studied. It was certified that the anodic oxide treatment by 10% NaOH solution was the most effective treatment from the results of peel resistance test and shear strength test. Then, CFRP laminates with embedded SMA foils were successfully fabricated using this effective surface treatment. The damage behavior of quasi-isotropic CFRP laminates with embedded SMA foils was characterized in both quasi-static load-unload and fatigue tests. The relationship between crack density and applied strain was obtained. The recovery stress generated by embedded SMA foils could increase the onset strain of transverse cracking by 0.2%. The onset strain of delmination in CFRP laminates was also increased accordingly. The shear-lag analysis was also conducted to predict the damage evolution in CFRP laminates with embedded SMA foils. The adhesive layers on both sides of SMA foils were treated as shear elements. The theoretical analysis successfully predicted the experimental results.

Astrocytes influence the severity of spinal muscular atrophy

PubMed Central

Rindt, Hansjörg; Feng, Zhihua; Mazzasette, Chiara; Glascock, Jacqueline J.; Valdivia, David; Pyles, Noah; Crawford, Thomas O.; Swoboda, Kathryn J.; Patitucci, Teresa N.; Ebert, Allison D.; Sumner, Charlotte J.; Ko, Chien-Ping; Lorson, Christian L.

2015-01-01

Systemically low levels of survival motor neuron-1 (SMN1) protein cause spinal muscular atrophy (SMA). α-Motor neurons of the spinal cord are considered particularly vulnerable in this genetic disorder and their dysfunction and loss cause progressive muscle weakness, paralysis and eventually premature death of afflicted individuals. Historically, SMA was therefore considered a motor neuron-autonomous disease. However, depletion of SMN in motor neurons of normal mice elicited only a very mild phenotype. Conversely, restoration of SMN to motor neurons in an SMA mouse model had only modest effects on the SMA phenotype and survival. Collectively, these results suggested that additional cell types contribute to the pathogenesis of SMA, and understanding the non-autonomous requirements is crucial for developing effective therapies. Astrocytes are critical for regulating synapse formation and function as well as metabolic support for neurons. We hypothesized that astrocyte functions are disrupted in SMA, exacerbating disease progression. Using viral-based restoration of SMN specifically to astrocytes, survival in severe and intermediate SMA mice was observed. In addition, neuromuscular circuitry was improved. Astrogliosis was prominent in end-stage SMA mice and in post-mortem patient spinal cords. Increased expression of proinflammatory cytokines was partially normalized in treated mice, suggesting that astrocytes contribute to the pathogenesis of SMA. PMID:25911676

Machine learning algorithms to classify spinal muscular atrophy subtypes.

PubMed

Srivastava, Tuhin; Darras, Basil T; Wu, Jim S; Rutkove, Seward B

2012-07-24

The development of better biomarkers for disease assessment remains an ongoing effort across the spectrum of neurologic illnesses. One approach for refining biomarkers is based on the concept of machine learning, in which individual, unrelated biomarkers are simultaneously evaluated. In this cross-sectional study, we assess the possibility of using machine learning, incorporating both quantitative muscle ultrasound (QMU) and electrical impedance myography (EIM) data, for classification of muscles affected by spinal muscular atrophy (SMA). Twenty-one normal subjects, 15 subjects with SMA type 2, and 10 subjects with SMA type 3 underwent EIM and QMU measurements of unilateral biceps, wrist extensors, quadriceps, and tibialis anterior. EIM and QMU parameters were then applied in combination using a support vector machine (SVM), a type of machine learning, in an attempt to accurately categorize 165 individual muscles. For all 3 classification problems, normal vs SMA, normal vs SMA 3, and SMA 2 vs SMA 3, use of SVM provided the greatest accuracy in discrimination, surpassing both EIM and QMU individually. For example, the accuracy, as measured by the receiver operating characteristic area under the curve (ROC-AUC) for the SVM discriminating SMA 2 muscles from SMA 3 muscles was 0.928; in comparison, the ROC-AUCs for EIM and QMU parameters alone were only 0.877 (p < 0.05) and 0.627 (p < 0.05), respectively. Combining EIM and QMU data categorizes individual SMA-affected muscles with very high accuracy. Further investigation of this approach for classifying and for following the progression of neuromuscular illness is warranted.

Mechanisms of smooth muscle antibody production: a clinical study in children with infections, haemolytic syndromes, and idiopathic thrombocytopenic purpura.

PubMed Central

Kanakoudi-Tsakalidis, F; Cassimos, C; Papastavrou-Mavroudi, T; Akoglu, T; Toh, B H; Yildiz, A; Osung, O; Holborow, E J; Sotelo, J

1979-01-01

Sera from 530 children suffering from various diseases and from 64 controls were tested for smooth muscle autoantibodies (SMA) by indirect immunofluorescence. A high incidence of SMA (51-86%) was found in patients with viral and bacterial infections (viral hepatitis, infectious mononucleosis, measles, mumps, chickenpox, typhoid fever, and brucellosis), independently of liver invovlvement, and in patients with acute haemolytic anaemia due to G-6-PD deficiency (48%). By contrast, the incidence of SMA from patients with beta-thalassaemia major and idiopathic thrombocytopenic purpura was no higher than in the controls. The discrepancy in incidence in haemolytic anaemias due to different causes may reflect the effect of endogenous and extrinsic agents. In the viral infections, SMA were mainly of the IgM class and gave an 'SMA-V' staining pattern. In bacterial infections (typhoid fever and brucellosis), SMA were either IgG only or IgM and IgG, and the staining pattern was also mainly 'SMA-V'. In infections which affect or may affect the liver (viral hepatitis, infectious mononucleosis, typhoid fever, and brucellosis), SMA was present at high titres (1:80-1:320), whereas in infections not affecting the liver (measles, mumps, and chickenpox) the titres were lower (less than or equal to 1:80). In most patients SMA occurred transiently and without apparent pathogenetic significance. The antigen against which infection-induced SMA is directed is not actin; its nature has yet to be identified. PMID:575362

A uniaxial constitutive model for superelastic NiTi SMA including R-phase and martensite transformations and thermal effects

NASA Astrophysics Data System (ADS)

Helbert, Guillaume; Saint-Sulpice, Luc; Arbab Chirani, Shabnam; Dieng, Lamine; Lecompte, Thibaut; Calloch, Sylvain; Pilvin, Philippe

2017-02-01

The well-known martensitic transformation is not always the unique solid-solid phase change in NiTi shape memory alloys (SMA). For this material, R-phase can occur from both austenite and martensite. In some applications, macroscopic strain of the material can be limited to 2%. In these cases, R-phase contribution can not be neglected anymore when compared with martensite. Furthermore, different thermomechanical couplings have to be taken into account to carefully predict strain rate effects and to better describe application conditions. In this paper, a new model taking into account various phase transformations with thermomechanical couplings is presented. This model is based on several transformation criteria. In most applications, SMA are used as wires, submitted to tensile-tensile loadings, in the superelasticity working range. Consequently, a uniaxial reduction of the model is presented for its simplicity. A thermodynamic framework is proposed. It enables to describe the internal variables evolution laws. The simple and fast identification process of model parameters is briefly presented. To verify the validity of the proposed model, simulation results are compared with experimental ones. The influences of testing temperature and strain amplitude on the material behavior is discussed. The damping capacity is also studied, using an energy-based criterion.

New multiplex real-time PCR approach to detect gene mutations for spinal muscular atrophy.

PubMed

Liu, Zhidai; Zhang, Penghui; He, Xiaoyan; Liu, Shan; Tang, Shi; Zhang, Rong; Wang, Xinbin; Tan, Junjie; Peng, Bin; Jiang, Li; Hong, Siqi; Zou, Lin

2016-08-17

Spinal muscular atrophy (SMA) is the most common autosomal recessive disease in children, and the diagnosis is complicated and difficult, especially at early stage. Early diagnosis of SMA is able to improve the outcome of SMA patients. In our study, Real-time PCR was developed to measure the gene mutation or deletion of key genes for SMA and to further analyse genotype-phenotype correlation. The multiple real-time PCR for detecting the mutations of survival of motor neuron (SMN), apoptosis inhibitory protein (NAIP) and general transcription factor IIH, polypeptide 2 gene (GTF2H2) was established and confirmed by DNA sequencing and multiplex ligation-dependent probe amplification (MLPA). The diagnosis and prognosis of 141 hospitalized children, 100 normal children and further 2000 cases of dry blood spot (DBS) samples were analysed by this multiple real-time PCR. The multiple real-time PCR was established and the accuracy of it to detect the mutations of SMN, NAIP and GTF2H2 was at least 98.8 % comparing with DNA sequencing and MLPA. Among 141 limb movement disorders children, 75 cases were SMA. 71 cases of SMA (94.67 %) were with SMN c.840 mutation, 9 cases (12 %) with NAIP deletion and 3 cases (4 %) with GTF2H2 deletion. The multiple real-time PCR was able to diagnose and predict the prognosis of SMA patients. Simultaneously, the real-time PCR was applied to detect trace DNA from DBS and able to make an early diagnosis of SMA. The clinical and molecular characteristics of SMA in Southwest of China were presented. Our work provides a novel way for detecting SMA in children by using real-time PCR and the potential usage in newborn screening for early diagnosis of SMA.

Self-medication practices with antibiotics among Chinese university students.

PubMed

Zhu, X; Pan, H; Yang, Z; Cui, B; Zhang, D; Ba-Thein, W

2016-01-01

Self-medication with antibiotics (SMA) is a serious global health problem. We sought to investigate SMA behaviors and risk factors among Chinese university students, and further explore the association between SMA practices and adverse drug events (ADEs). Cross-sectional study. An online survey was conducted at Jiangsu University (JSU) in eastern China in July 2011 using a pretested questionnaire. Out of 2608 website visitors, 1086 participated in the survey (response rate: 41.6%), 426 respondents were excluded for not being a JSU student or repeat participation, 660 (2.2% of JSU students) were included in analysis, and 316 students (47.9%) had a lifetime history of SMA. Among self-treated students, 43.5% believed that antibiotic was suitable for viral infections, 65.9% had more than one SMA episode in the previous year, 73.5% self-medicated with at least two different antibiotics, 57.1% and 64.4% changed antibiotic dosage and antibiotics during the course, respectively. Female gender, older age, and prior knowledge of antibiotics (PKA) were identified as independent risk factors of SMA. There was no difference between students with and without PKA regarding SMA frequency, use of polyantibiotics, and switching antibiotic dosage or antibiotics. ADEs happened to 13.3% of self-medicated students. Frequent change of dosage and simultaneous use of the same antibiotic with different names were independent risk practices associated with an ADE. Our findings substantiate high SMA prevalence among Chinese university students. Older age and PKA are independent SMA risk factors common to Chinese university students and female gender is exclusive SMA risk factor for JSU students. Poor SMA practices are associated with ADEs. Strict regulations on antibiotic sales and public education reinforced by further health care reform are recommended. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Dissociating the Role of the pre-SMA in Response Inhibition and Switching: A Combined Online and Offline TMS Approach

PubMed Central

Obeso, Ignacio; Robles, Noemí; Marrón, Elena M.; Redolar-Ripoll, Diego

2013-01-01

The pre-supplementary motor area (pre-SMA) is considered to be a key node in the cognitive control of actions that require rapid updating, inhibition, or switching, as well as working memory. It is now recognized that the pre-SMA is part of a “cognitive control” network involving the inferior frontal gyrus (IFG) and subcortical regions, such as the striatum and subthalamic nucleus. However, two important questions remain to be addressed. First, it is not clear if the main role of the pre-SMA in cognitive control lies in inhibition or switching of actions. From imaging evidence, the right pre-SMA is consistently recruited during inhibition and switching, but the extent to which it participates specifically in either of these processes is unknown. Secondly, the pre-SMA may perform inhibition and switching alone or as part of a larger brain network. The present study used online and offline transcranial magnetic stimulation (TMS) to dissociate the roles of pre-SMA in cognitive control, but also to investigate the potential contribution of connectivity between the pre-SMA and IFG. We applied continuous theta burst stimulation (cTBS) over the right IFG before participants performed a stop switching task while receiving single TMS pulses over the right pre-SMA. The results were compared to a sham cTBS session and pulses applied over the vertex region. Significant worsening of inhibition as well as response adaptation during inhibition was found when applying pulses over the pre-SMA. However, no such worsening was observed in switch trials. Additionally, after cTBS over the IFG, inhibition was also delayed, suggesting its critical necessity in stopping of actions. The results reveal a key contribution of the pre-SMA in inhibition and could suggest a dissociative role in the switching of actions. These findings indicate there is an essential union between IFG and pre-SMA during inhibition. PMID:23616761

[Protective effect of pretreatment of Salvia miltiorrhiza Bunge. f. alba plasma against oxygen-glucose deprivation-induced injury of cultured rat hippocampal neurons by inhibiting apoptosis].

PubMed

Li, Mei-Yi; Zhang, Yan-Bo; Zuo, Huan; Liu, Li-Li; Niu, Jing-Zhong

2012-02-25

The present study was to investigate the effect of Salvia miltiorrhiza Bunge. f. alba (SMA) pharmacological pretreatment on apoptosis of cultured hippocampal neurons from neonate rats under oxygen-glucose deprivation (OGD). Cultured hippocampal neurons were randomly divided into five groups (n = 6): normal plasma group, low dose SMA plasma (2.5%) group, middle dose SMA plasma (5%) group, high dose SMA plasma (10%) group and control group. The hippocampal neurons were cultured and treated with plasma from adult Wistar rats intragastrically administered with saline or aqueous extract of SMA. The apoptosis of neurons was induced by glucose-free Earle's solution containing 1 mmol/L Na2S2O4 and labeled by MTT and Annexin V/PI double staining. Moreover, protein expressions of Bcl-2 and Bax were detected by immunofluorescence. The results showed that few apoptotic cells were observed in control group, whereas the number of apoptotic cells was greatly increased in normal plasma group and low dose SMA plasma group. Both middle and high dose SMA plasma could protect cultured hippocampal neurons from apoptosis induced by OGD (P < 0.05). The protective effect of high dose SMA plasma was stronger than that of middle one (P < 0.05). Compared to control, normal plasma and low dose SMA plasma groups, middle and high dose SMA plasma groups both showed significantly higher levels of Bcl-2 (P < 0.05 or 0.01), whereas expressions of Bax was opposite. There were no significant differences of Bcl-2 and Bax expressions between middle and high dose SMA plasma groups. Number of Bcl-2- and Bax-positive cells had similar tendency. Bcl-2/Bax (number of positive cells) ratio was higher in high dose SMA plasma group than those of all the other groups (P < 0.05 or 0.01). These results suggest that pharmacological pretreatment of blood plasma containing middle and high dose SMA could raise viability and inhibit apoptosis of OGD-injured hippocampal neurons by up-regulating the expression of Bcl-2 and down-regulating the expression of Bax.

Miga Aero Actuator and 2D Machined Mechanical Binary Latch

NASA Technical Reports Server (NTRS)

Gummin, Mark A.

2013-01-01

Shape memory alloy (SMA) actuators provide the highest force-to-weight ratio of any known actuator. They can be designed for a wide variety of form factors from flat, thin packages, to form-matching packages for existing actuators. SMA actuators can be operated many thousands of times, so that ground testing is possible. Actuation speed can be accurately controlled from milliseconds to position and hold, and even electronic velocity-profile control is possible. SMA actuators provide a high degree of operational flexibility, and are truly smart actuators capable of being accurately controlled by onboard microprocessors across a wide range of voltages. The Miga Aero actuator is a SMA actuator designed specifically for spaceflight applications. Providing 13 mm of stroke with either 20- or 40-N output force in two different models, the Aero actuator is made from low-outgassing PEEK (polyether ether ketone) plastic, stainless steel, and nickel-titanium SMA wires. The modular actuator weighs less than 28 grams. The dorsal output attachment allows the Aero to be used in either PUSH or PULL modes by inverting the mounting orientation. The SPA1 actuator utilizes commercially available SMA actuator wire to provide 3/8-in. (approx. =.1 cm) of stroke at a force of over 28 lb (approx. = .125 N). The force is provided by a unique packaging of the single SMA wire that provides the output force of four SMA wires mechanically in parallel. The output load is shared by allowing the SMA wire to slip around the output attachment end to adjust or balance the load, preventing any individual wire segment from experiencing high loads during actuation. A built-in end limit switch prevents overheating of the SMA element following actuation when used in conjunction with the Miga Analog Driver [a simple MOSFET (metal oxide semiconductor field-effect transistor) switching circuit]. A simple 2D machined mechanical binary latch has been developed to complement the capabilities of SMA wire actuators. SMA actuators typically perform ideally as latch-release devices, wherein a spring-loaded device is released when the SMA actuator actuates in one direction. But many applications require cycling between two latched states open and closed.

Seismic margin assessment of the Edwin I. Hatch Nuclear Plant, Unit 1

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

Barr, W.T.; Moore, D.P.; Smith, J.E.

1991-06-01

This summary presents the results and lessons learned from the seismic margin assessment (SMA) of Unit 1 of the Hatch Nuclear Plant. The primary purpose of this SMA was to assess the practicality of the EPRI SMA methodology on a BWR on a soil site such as Hatch. The major findings from the Hatch SMA are briefly described along with the lessons learned during the project implementation. The experience gained on the Hatch SMA is expected to benefit others in the performance of future SMAs. 12 refs.

Expression of transforming growth factor-beta1, -beta2 and -beta3 in normal and diseased canine mitral valves.

PubMed

Aupperle, H; März, I; Thielebein, J; Schoon, H-A

2008-01-01

The pathogenesis of chronic valvular disease (CVD) in dogs remains unclear, but activation and proliferation of valvular stromal cells (VSC) and their transdifferentiation into myofibroblast-like cells has been described. These alterations may be influenced by transforming growth factor-beta (TGF-beta), a cytokine involved in extracellular matrix (ECM) regulation and mesenchymal cell differentiation. The present study investigates immunohistochemically the expression of TGF-beta1, -beta2, -beta3 and smooth muscle alpha actin (alpha-SMA) in normal canine mitral valves (MVs) (n=10) and in the valves of dogs with mild (n=7), moderate (n=14) and severe (n=9) CVD. In normal mitral valves there was no expression of alpha-SMA but VSC displayed variable expression of TGF-beta1 (10% of VSC labelled), TGF-beta2 (1-5% labelled) and TGF-beta3 (50% labelled). In mild CVD the affected atrialis contain activated and proliferating alpha-SMA-positive VSC, which strongly expressed TGF-beta1 and -beta3, but only 10% of these cells expressed TGF-beta2. In unaffected areas of the leaflet there was selective increase in expression of TGF-beta1 and -beta3. In advanced CVD the activated subendothelial VSC strongly expressed alpha-SMA, TGF-beta1 and -beta3. Inactive VSC within the centre of the nodules had much less labelling for TGF-beta1 and -beta3. TGF-beta1 labelling was strong within the ECM. These data suggest that TGF-beta plays a role in the pathogenesis of CVD by inducing myofibroblast-like differentiation of VSC and ECM secretion. Changed haemodynamic forces and expression of matrix metalloproteinases (MMPs) may in turn regulate TGF-beta expression.

Gastroschisis in the rat model is associated with a delayed maturation of intestinal pacemaker cells and smooth muscle cells.

PubMed

Midrio, P; Faussone-Pellegrini, M S; Vannucchi, M G; Flake, A W

2004-10-01

A pacemaker system is required for peristalsis generation. The interstitial cells of Cajal (ICC) are considered the intestinal pacemaker, and are identified by expression of the c-kit gene--encoded protein. Gastroschisis is characterized by a severe gastrointestinal dysmotility in newborns. In spite of this clinical picture, few studies have focused on smooth muscle cells (SMC) morphology and none on ICC. Therefore, their morphology has been studied in fetuses at term in the rat model of gastroschisis. At 18.5 day's gestation (E18.5), 10 rat fetuses were killed, 10 underwent surgical creation of gastroschisis, and 10 underwent manipulation only. The small intestine of the latter 2 groups was harvested at E21.5. Specimens were processed for H&E, c-kit and actin (alpha smooth muscle antibody [alpha-SMA]) immunohistochemistry, and transmission electron microscopy (TEM). In the controls, SMC were c-kit+ and alpha-SMA+, with labeling intensity increasing by age. At E21.5, some cells around the Auerbach's plexus were more intensely c-kit+, and differentiating ICC were seen under TEM at this level. Gastroschisis fetuses had no c-kit+ cells referable to ICC. In the more damaged loops, SMC were very faintly c-kit+ and alpha-SMA+. Under TEM, there were few differentiated SMC and no presumptive ICC. In the less-damaged loops, SMC were faintly c-kit+ and alpha-SMA+ and had ultrastructural features intermediate between those of E18.5 and E21.5 controls; ICC were very immature. ICC and SMC differentiation is delayed in gastroschisis with the most damaged loops showing the most incomplete picture. These findings might help in understanding the delayed onset of peristalsis and the variable time-course of the recover seen in babies affected by gastroschisis.

Oligomeric Properties of Survival Motor Neuron·Gemin2 Complexes*

PubMed Central

Gupta, Kushol; Martin, Renee; Sharp, Robert; Sarachan, Kathryn L.; Ninan, Nisha S.; Van Duyne, Gregory D.

2015-01-01

The survival motor neuron (SMN) protein forms the oligomeric core of a multiprotein complex required for the assembly of spliceosomal small nuclear ribonucleoproteins. Deletions and mutations in the SMN1 gene are associated with spinal muscular atrophy (SMA), a devastating neurodegenerative disease that is the leading heritable cause of infant mortality. Oligomerization of SMN is required for its function, and some SMA patient mutations disrupt the ability of SMN to self-associate. Here, we investigate the oligomeric nature of the SMN·Gemin2 complexes from humans and fission yeast (hSMN·Gemin2 and ySMN·Gemin2). We find that hSMN·Gemin2 forms oligomers spanning the dimer to octamer range. The YG box oligomerization domain of SMN is both necessary and sufficient to form these oligomers. ySMN·Gemin2 exists as a dimer-tetramer equilibrium with Kd = 1.0 ± 0.9 μm. A 1.9 Å crystal structure of the ySMN YG box confirms a high level of structural conservation with the human ortholog in this important region of SMN. Disulfide cross-linking experiments indicate that SMN tetramers are formed by self-association of stable, non-dissociating dimers. Thus, SMN tetramers do not form symmetric helical bundles such as those found in glycine zipper transmembrane oligomers. The dimer-tetramer nature of SMN complexes and the dimer of dimers organization of the SMN tetramer provide an important foundation for ongoing studies to understand the mechanism of SMN-assisted small nuclear ribonucleoprotein assembly and the underlying causes of SMA. PMID:26092730

Cryogenic optical testing results of JWST aspheric test plate lens

NASA Astrophysics Data System (ADS)

Smith, Koby Z.; Towell, Timothy C.

2011-09-01

The James Webb Space Telescope (JWST) Secondary Mirror Assembly (SMA) is a circular 740mm diameter beryllium convex hyperboloid that has a 23.5nm-RMS (λ/27 RMS) on-orbit surface figure error requirement. The radius of curvature of the SMA is 1778.913mm+/-0.45mm and has a conic constant of -1.6598+/-0.0005. The on-orbit operating temperature of the JWST SMA is 22.5K. Ball Aerospace & Technologies Corp. (BATC) is under contract to Northrop Grumman Aerospace Systems (NGAS) to fabricate, assemble, and test the JWST SMA to its on-orbit requirements including the optical testing of the SMA at its cryogenic operating temperature. BATC has fabricated and tested an Aspheric Test Plate Lens (ATPL) that is an 870mm diameter fused silica lens used as the Fizeau optical reference in the ambient and cryogenic optical testing of the JWST Secondary Mirror Assembly (SMA). As the optical reference for the SMA optical test, the concave optical surface of the ATPL is required to be verified at the same 20K temperature range required for the SMA. In order to meet this objective, a state-of-the-art helium cryogenic testing facility was developed to support the optical testing requirements of a number of the JWST optical testing needs, including the ATPL and SMA. With the implementation of this cryogenic testing facility, the ATPL was successfully cryogenically tested and performed to less than 10nm-RMS (λ/63 RMS) surface figure uncertainty levels for proper reference backout during the SMA optical testing program.

The supplementary motor area contributes to the timing of the anticipatory postural adjustment during step initiation in participants with and without Parkinson's disease.

PubMed

Jacobs, J V; Lou, J S; Kraakevik, J A; Horak, F B

2009-12-01

The supplementary motor area (SMA) is thought to contribute to the generation of anticipatory postural adjustments (APAs, which act to stabilize supporting body segments prior to movement), but its precise role remains unclear. In addition, participants with Parkinson's disease (PD) exhibit impaired function of the SMA as well as decreased amplitudes and altered timing of the APA during step initiation, but the contribution of the SMA to these impairments also remains unclear. To determine how the SMA contributes to generating the APA and to the impaired APAs of participants with PD, we examined the voluntary steps of eight participants with PD and eight participants without PD, before and after disrupting the SMA and dorsolateral premotor cortex (dlPMC), in separate sessions, with 1-Hz repetitive transcranial magnetic stimulation (rTMS). Both groups exhibited decreased durations of their APAs after rTMS over the SMA but not over the dlPMC. Peak amplitudes of the APAs were unaffected by rTMS to either site. The symptom severity of the participants with PD positively correlated with the extent that rTMS over the SMA affected the durations of their APAs. The results suggest that the SMA contributes to the timing of the APA and that participants with PD exhibit impaired timing of their APAs, in part, due to progressive dysfunction of circuits associated with the SMA.

Microsurgical and Tractographic Anatomy of the Supplementary Motor Area Complex in Humans.

PubMed

Bozkurt, Baran; Yagmurlu, Kaan; Middlebrooks, Erik H; Karadag, Ali; Ovalioglu, Talat Cem; Jagadeesan, Bharathi; Sandhu, Gauravjot; Tanriover, Necmettin; Grande, Andrew W

2016-11-01

To evaluate the microsurgical anatomy of the fiber tract connections of the supplementary motor area (SMA) and pre-SMA, and examine its potential functional role with reference to clinical trials in the literature. Ten postmortem formalin-fixed human brains (20 sides) and 1 cadaveric head were prepared following Klingler's method. The fiber dissection was performed in a stepwise fashion, from lateral to medial and also from medial to lateral, under an operating microscope, with 3D images captured at each stage. Our findings were supported by in vivo magnetic resonance imaging tractography in 2 healthy subjects. The connections of the SMA complex, composed of the pre-SMA and the SMA proper, are composed of short "U" association fibers and the superior longitudinal fasciculus I, cingulum, claustrocortical fibers, callosal fibers, corticospinal tract, frontal aslant tract, and frontostriatal tract. The claustrocortical fibers may play an important role in the integration of motor, language, and limbic functions of the SMA complex. The frontostriatal tract connects the pre-SMA to the putamen and caudate nucleus, and also forms parts of both the internal capsule and the dorsal external capsule. The SMA complex has numerous connections throughout the cerebrum. An understanding of these connections is important for presurgical planning for lesions in the frontal lobe and helps explain symptoms related to SMA injury. Copyright © 2016 Elsevier Inc. All rights reserved.

A novel population of α-smooth muscle actin-positive cells activated in a rat model of stroke: an analysis of the spatio-temporal distribution in response to ischemia.

PubMed

Sharma, Varun; Ling, Tina W; Rewell, Sarah S; Hare, David L; Howells, David W; Kourakis, Angela; Wookey, Peter J

2012-11-01

In a rat model of stroke, the spatio-temporal distribution of α-smooth muscle actin-positive, (αSMA+) cells was investigated in the infarcted hemisphere (ipsilateral) and compared with the contralateral hemisphere. At day 3 postischemia, αSMA+ cells were concentrated in two main loci within the ipsilateral hemisphere (Area A) in the medial corpus callosum and (Area B) midway through the striatum adjacent to the lateral ventricle. By day 7 and further by day 14, fewer αSMA+ cells remained in Areas A and B but a steady increase in the peri-infarct was observed. αSMA+ cells also expressed glial acidic fibrillary protein [GFAP: αSMA+/GFAP+ (29%); αSMA+/GFAP- (71%) phenotypes] and feline leukemia virus C receptor 2 (FLVCR2), but not ED1(microglia) and established markers of pericytes normally located in vascular wall. αSMA+ cells were also located close to the subventricular zones (SVZ) adjacent to Areas A and B. In conclusion, αSMA+ cells have been identified in a spatial and temporal sequence from the SVZ, at intermediate loci and in the vicinity of the peri-infarct. It is hypothesized that novel populations of αSMA+ precursors of pericytes are born on the SVZ, migrate into the peri-infarct region and are incorporated into new vessels of the peri-infarct regions.

Relationship between input power and power density of SMA spring

NASA Astrophysics Data System (ADS)

Park, Cheol Hoon; Ham, Sang Yong; Son, Young Su

2016-04-01

The important required characteristics of an artificial muscle for a human arm-like manipulator are high strain and high power density. From this viewpoint, an SMA (shape memory alloy) spring is a good candidate for the actuator of a robotic manipulator that utilizes an artificial muscle. In this study, the maximum power density of an SMA spring was evaluated with respect to the input power. The spring samples were fabricated from SMA wires of different diameters ranging between 0.1 and 0.3 mm. For each diameter, two types of wires with different transition temperatures were used. The relationship between the transition temperature and maximum power density was also evaluated. Each SMA spring was stretched downward by an attached weight and the temperature was increased through the application of an electric current. The displacement, velocity, and temperature of the SMA spring were measured by laser displacement sensors and a thermocouple. Based on the experimental data, it was determined that the maximum power densities of the different SMA springs ranged between 1,300 and 5,500 W/kg. This confirmed the applicability of an SMA spring to human arm-like robotic manipulators. The results of this study can be used as reference for design.

Evaluating the ductility characteristics of self-centering buckling-restrained shape memory alloy braces

NASA Astrophysics Data System (ADS)

Abou-Elfath, Hamdy

2017-05-01

Recently, self-centering earthquake resistant systems have attracted attention because of their promising potential in controlling the residual drifts and reducing repair costs after earthquake events. Considerable portion of self-centering research is based on using short-segment superelastic shape memory alloy (SMA) braces as strengthening technique because of the lower modulus of elasticity of SMA in comparison with that of steel. The goal of this study is to investigate the ductility characteristics of these newly proposed short-segment SMA braces to evaluate their safety levels against fracture failures under earthquake loading. This goal has been achieved by selecting an appropriate seismic performance criterion for steel frames equipped with SMA braces, defining the level of strain capacity of SMA and calculating the strain demands in the SMA braces by conducting a series of pushover and earthquake time history analyzes on typical frame structure. The results obtained in this study indicated the inability of short-segment SMA designs to provide adequate ductility to the lateral resistant systems. An alternative approach is introduced by using hybrid steel-SMA braces that are capable of controlling the residual drifts and providing the structure with adequate lateral stiffness.

Numerical Investigation of the Macroscopic Mechanical Behavior of NiTi-Hybrid Composites Subjected to Static Load-Unload-Reload Path

NASA Astrophysics Data System (ADS)

Taheri-Behrooz, Fathollah; Kiani, Ali

2017-04-01

Shape memory alloys (SMAs) are a type of shape memory materials that recover large deformation and return to their primary shape by rising temperature. In the current research, the effect of embedding SMA wires on the macroscopic mechanical behavior of glass-epoxy composites is investigated through finite element simulations. A perfect interface between SMA wires and the host composite is assumed. Effects of various parameters such as SMA wires volume fraction, SMA wires pre-strain and temperature are investigated during loading-unloading and reloading steps by employing ANSYS software. In order to quantify the extent of induced compressive stress in the host composite and residual tensile stress in the SMA wires, a theoretical approach is presented. Finally, it was shown that smart structures fabricated using composite layers and pre-strained SMA wires exhibited overall stiffness reduction at both ambient and elevated temperatures which were increased by adding SMA volume fraction. Also, the induced compressive stress on the host composite was increased remarkably using 4% pre-strained SMA wires at elevated temperature. Results obtained by FE simulations were in good correlation with the rule of mixture predictions and available experimental data in the literature.

Performance range of SMA actuator wires and SMA-FRP structure in terms of manufacturing, modeling and actuation

NASA Astrophysics Data System (ADS)

Hübler, M.; Gurka, M.; Schmeer, S.; Breuer, U. P.

2013-09-01

In this contribution we present a comprehensive theoretical and experimental description of an active shape memory alloy (SMA) fiber reinforced composite (FRP) hybrid structure. The major influences on actuation performance arising from variations in the design and manufacturing process are discussed, utilizing a new phenomenological model to describe the actuating SMA material. The different material properties for the activated, respective the unactivated, SMA as well as the influence of different loading conditions or pre-treatment of the material are taken into account in this model. To validate our material model we performed new actuation experiments with an exemplary SMA-FRP structure, which we compared to finite element (FE) simulation results. Our FE-model is based on a material model for the actuating SMA elements derived from experiments and data on the actual microscopic geometry of the hybrid composite. Therefore it is able to predict very precisely the actuation behavior of a typical FRP structure for industrial use cases: a thin walled CFRP sheet with SMA wires attached to the top for performing a bending motion with a maximum deflection of approx. 25% of its length.

Intracellular uptake and behavior of two types zinc protoporphyrin (ZnPP) micelles, SMA-ZnPP and PEG-ZnPP as anticancer agents; unique intracellular disintegration of SMA micelles.

PubMed

Nakamura, Hideaki; Fang, Jun; Gahininath, Bharate; Tsukigawa, Kenji; Maeda, Hiroshi

2011-11-07

SMA-ZnPP and PEG-ZnPP are micellar drugs, encapsulating zinc protoporphyrin IX (ZnPP) with styrene maleic acid copolymer (SMA) and covalent conjugate of ZnPP with polyethylene glycol (PEG) respectively. Their intracellular uptake rate and subcellular localization were investigated. We found SMA-ZnPP showed higher and more efficient (about 2.5 times) intracellular uptake rate than PEG-ZnPP, although both SMA-ZnPP and PEG-ZnPP micelles were localized at endoplasmic reticulum (ER) and inhibited the target enzyme heme oxygenase 1 (HO-1) similarly. Both micellar ZnPP were taken up into the tumor cells by endocytosis. Furthermore SMA-ZnPP and PEG-ZnPP were examined for their drug releasing mechanisms. Liberation of ZnPP from the SMA micelle appears to depend on cellular amphiphilic components such as lecithin, while that for PEG-ZnPP depends on hydrolytic cleavage. These results indicate that these micelle formulations make water insoluble ZnPP to water soluble practical anticancer agents. Copyright © 2011 Elsevier B.V. All rights reserved.

Emerging treatment options for spinal muscular atrophy.

PubMed

Burnett, Barrington G; Crawford, Thomas O; Sumner, Charlotte J

2009-03-01

The motor neuron disease spinal muscular atrophy (SMA) is one of the leading genetic killers of infants worldwide. SMA is caused by mutation of the survival motor neuron 1 (SMN1) gene and deficiency of the survival motor neuron (SMN) protein. All patients retain one or more copies of the SMN2 gene, which (by producing a small amount of the SMN protein) rescues embryonic lethality and modifies disease severity. Rapid progress continues in dissecting the cellular functions of the SMN protein, but the mechanisms linking SMN deficiency with dysfunction and loss of functioning motor units remain poorly defined. Clinically, SMA should to be distinguished from other neuromuscular disorders, and the diagnosis can be readily confirmed with genetic testing. Quality of life and survival of SMA patients are improved with aggressive supportive care including optimized respiratory and nutritional care and management of scoliosis and contractures. Because SMA is caused by inadequate amounts of SMN protein, one aim of current SMA therapeutics development is to increase SMN protein levels in SMA patients by activating SMN2 gene expression and/or increasing levels of full-length SMN2 transcripts. Several potential therapeutic compounds are currently being studied in clinical trials in SMA patients.

Motor neuron cell-nonautonomous rescue of spinal muscular atrophy phenotypes in mild and severe transgenic mouse models

PubMed Central

Liu, Ying Hsiu; Sahashi, Kentaro; Rigo, Frank; Bennett, C. Frank

2015-01-01

Survival of motor neuron (SMN) deficiency causes spinal muscular atrophy (SMA), but the pathogenesis mechanisms remain elusive. Restoring SMN in motor neurons only partially rescues SMA in mouse models, although it is thought to be therapeutically essential. Here, we address the relative importance of SMN restoration in the central nervous system (CNS) versus peripheral tissues in mouse models using a therapeutic splice-switching antisense oligonucleotide to restore SMN and a complementary decoy oligonucleotide to neutralize its effects in the CNS. Increasing SMN exclusively in peripheral tissues completely rescued necrosis in mild SMA mice and robustly extended survival in severe SMA mice, with significant improvements in vulnerable tissues and motor function. Our data demonstrate a critical role of peripheral pathology in the mortality of SMA mice and indicate that peripheral SMN restoration compensates for its deficiency in the CNS and preserves motor neurons. Thus, SMA is not a cell-autonomous defect of motor neurons in SMA mice. PMID:25583329

The role of the supplementary motor area for speech and language processing.

PubMed

Hertrich, Ingo; Dietrich, Susanne; Ackermann, Hermann

2016-09-01

Apart from its function in speech motor control, the supplementary motor area (SMA) has largely been neglected in models of speech and language processing in the brain. The aim of this review paper is to summarize more recent work, suggesting that the SMA has various superordinate control functions during speech communication and language reception, which is particularly relevant in case of increased task demands. The SMA is subdivided into a posterior region serving predominantly motor-related functions (SMA proper) whereas the anterior part (pre-SMA) is involved in higher-order cognitive control mechanisms. In analogy to motor triggering functions of the SMA proper, the pre-SMA seems to manage procedural aspects of cognitive processing. These latter functions, among others, comprise attentional switching, ambiguity resolution, context integration, and coordination between procedural and declarative memory structures. Regarding language processing, this refers, for example, to the use of inner speech mechanisms during language encoding, but also to lexical disambiguation, syntax and prosody integration, and context-tracking. Copyright © 2016 Elsevier Ltd. All rights reserved.

Numerical tool for SMA material simulation: application to composite structure design

NASA Astrophysics Data System (ADS)

Chemisky, Yves; Duval, Arnaud; Piotrowski, Boris; Ben Zineb, Tarak; Tahiri, Vanessa; Patoor, Etienne

2009-10-01

Composite materials based on shape memory alloys (SMA) have received growing attention over these last few years. In this paper, two particular morphologies of composites are studied. The first one is an SMA/elastomer composite in which a snake-like wire NiTi SMA is embedded into an elastomer ribbon. The second one is a commercial Ni47Ti44Nb9 which presents elastic-plastic inclusions in an NiTi SMA matrix. In both cases, the design of such composites required the development of an SMA design tool, based on a macroscopic 3D constitutive law for NiTi alloys. Two different strategies are then applied to compute these composite behaviors. For the SMA/elastomer composite, the macroscopic behavior law is implemented in commercial FEM software, and for the Ni47Ti44Nb9 a scale transition approach based on the Mori-Tanaka scheme is developed. In both cases, simulations are compared to experimental data.

Miniature High-Force, Long-Stroke SMA Linear Actuators

NASA Technical Reports Server (NTRS)

Cummin, Mark A.; Donakowski, William; Cohen, Howard

2008-01-01

Improved long-stroke shape-memory-alloy (SMA) linear actuators are being developed to exert significantly higher forces and operate at higher activation temperatures than do prior SMA actuators. In these actuators, long linear strokes are achieved through the principle of displacement multiplication, according to which there are multiple stages, each intermediate stage being connected by straight SMA wire segments to the next stage so that relative motions of stages are additive toward the final stage, which is the output stage. Prior SMA actuators typically include polymer housings or shells, steel or aluminum stages, and polymer pads between successive stages of displacement-multiplication assemblies. Typical output forces of prior SMA actuators range from 10 to 20 N, and typical strokes range from 0.5 to 1.5 cm. An important disadvantage of prior SMA wire actuators is relatively low cycle speed, which is related to actuation temperature as follows: The SMA wires in prior SMA actuators are typically made of a durable nickel/titanium alloy that has a shape-memory activation temperature of 80 C. An SMA wire can be heated quickly from below to above its activation temperature to obtain a stroke in one direction, but must then be allowed to cool to somewhat below its activation temperature (typically, less than or equal to 60 C in the case of an activation temperature of 80 C) to obtain a stroke in the opposite direction (return stroke). At typical ambient temperatures, cooling times are of the order of several seconds. Cooling times thus limit cycle speeds. Wires made of SMA alloys having significantly higher activation temperatures [denoted ultra-high-temperature (UHT) SMA alloys] cool to the required lower return-stroke temperatures more rapidly, making it possible to increase cycle speeds. The present development is motivated by a need, in some applications (especially aeronautical and space-flight applications) for SMA actuators that exert higher forces, operate at greater cycle speeds, and have stronger housings that can withstand greater externally applied forces and impacts. The main novel features of the improved SMA actuators are the following: 1) The ends of the wires are anchored in compact crimps made from short steel tubes. Each wire end is inserted in a tube, the tube is flattened between planar jaws to make the tube grip the wire, the tube is compressed to a slight U-cross-section deformation to strengthen the grip, then the crimp is welded onto one of the actuator stages. The pull strength of a typical crimp is about 125 N -- comparable to the strength of the SMA wire and greater than the typical pull strengths of wire-end anchors in prior SMA actuators. Greater pull strength is one of the keys to achievement of higher actuation force; 2) For greater strength and resistance to impacts, housings are milled from aluminum instead of being made from polymers. Each housing is made from two pieces in a clamshell configuration. The pieces are anodized to reduce sliding friction; 3) Stages are made stronger (to bear greater compression loads without excessive flexing) by making them from steel sheets thicker than those used in prior SMA actuators. The stages contain recessed pockets to accommodate the crimps. Recessing the pockets helps to keep overall dimensions as small as possible; and, 4) UHT SMA wires are used to satisfy the higher-speed/higher-temperature requirement.

Shape memory alloy heat engines and energy harvesting systems

DOEpatents

Browne, Alan L; Johnson, Nancy L; Keefe, Andrew C; Alexander, Paul W; Sarosi, Peter Maxwell; Herrera, Guillermo A; Yates, James Ryan

2013-12-17

A heat engine includes a first rotatable pulley and a second rotatable pulled spaced from the first rotatable pulley. A shape memory alloy (SMA) element is disposed about respective portions of the pulleys at an SMA pulley ratio. The SMA element includes first spring coil and a first fiber core within the first spring coil. A timing cable is disposed about disposed about respective portions of the pulleys at a timing pulley ratio, which is different than the SMA pulley ratio. The SMA element converts a thermal energy gradient between the hot region and the cold region into mechanical energy.

SMA CARNI-VAL trial part I: double-blind, randomized, placebo-controlled trial of L-carnitine and valproic acid in spinal muscular atrophy.

PubMed

Swoboda, Kathryn J; Scott, Charles B; Crawford, Thomas O; Simard, Louise R; Reyna, Sandra P; Krosschell, Kristin J; Acsadi, Gyula; Elsheik, Bakri; Schroth, Mary K; D'Anjou, Guy; LaSalle, Bernard; Prior, Thomas W; Sorenson, Susan L; Maczulski, Jo Anne; Bromberg, Mark B; Chan, Gary M; Kissel, John T

2010-08-19

Valproic acid (VPA) has demonstrated potential as a therapeutic candidate for spinal muscular atrophy (SMA) in vitro and in vivo. Two cohorts of subjects were enrolled in the SMA CARNIVAL TRIAL, a non-ambulatory group of "sitters" (cohort 1) and an ambulatory group of "walkers" (cohort 2). Here, we present results for cohort 1: a multicenter phase II randomized double-blind intention-to-treat protocol in non-ambulatory SMA subjects 2-8 years of age. Sixty-one subjects were randomized 1:1 to placebo or treatment for the first six months; all received active treatment the subsequent six months. The primary outcome was change in the modified Hammersmith Functional Motor Scale (MHFMS) score following six months of treatment. Secondary outcomes included safety and adverse event data, and change in MHFMS score for twelve versus six months of active treatment, body composition, quantitative SMN mRNA levels, maximum ulnar CMAP amplitudes, myometry and PFT measures. At 6 months, there was no difference in change from the baseline MHFMS score between treatment and placebo groups (difference = 0.643, 95% CI = -1.22-2.51). Adverse events occurred in >80% of subjects and were more common in the treatment group. Excessive weight gain was the most frequent drug-related adverse event, and increased fat mass was negatively related to change in MHFMS values (p = 0.0409). Post-hoc analysis found that children ages two to three years that received 12 months treatment, when adjusted for baseline weight, had significantly improved MHFMS scores (p = 0.03) compared to those who received placebo the first six months. A linear regression analysis limited to the influence of age demonstrates young age as a significant factor in improved MHFMS scores (p = 0.007). This study demonstrated no benefit from six months treatment with VPA and L-carnitine in a young non-ambulatory cohort of subjects with SMA. Weight gain, age and treatment duration were significant confounding variables that should be considered in the design of future trials. Clinicaltrials.gov NCT00227266.

Computer-assisted study of the axial orientation and distances between renovisceral arteries ostia.

PubMed

Lawton, James; Touma, Joseph; Sénémaud, Jean; de Boissieu, Paul; Brossier, Julien; Kobeiter, Hicham; Desgranges, Pascal

2017-02-01

Endovascular navigation in aortic, renal and visceral procedures are based on precise knowledge of arterial anatomy. Our aim was to define the anatomical localization of the ostia of renovisceral arteries and their distribution to establish anatomical landmarks for endovascular catheterization. Computer-assisted measurements performed on 55 CT scans and patients features (age, sex, aortic diameter) were analyzed. p values <0.05 were considered statistically significant. The mean axial angulation of CeT and the SMA origin was 21.8° ± 10.1° and 9.9° ± 10.5°, respectively. The ostia were located on the left anterior edge of the aorta in 96 % of cases for the CeT and 73 % for the SMA. CeT and SMA angles followed Gaussian distribution. Left renal artery (LRA) rose at 96° ± 15° and in 67 % of cases on the left posterior edge. The right renal artery (RRA) rose at -62° ± 16.5° and in 98 % of cases on the right anterior edge of the aorta. RRA angle measurements and cranio-caudal RRA-LRA distance measurements did not follow Gaussian distribution. The mean distances between the CeT and the SMA, LRA, and RRA were 16.7 ± 5.0, 30.7 ± 7.9 and 30.5 ± 7.7 mm, respectively. CeT-SMA distance showed correlation with age and aortic diameter (p = 0.03). CeT-LRA distance showed correlation with age (p = 0.04). The mean distance between the renal ostia was 3.75 ± 0.21 mm. The RRA ostium was higher than the LRA ostium in 52 % of cases. RRA and LRA origins were located at the same level in 7 % of cases. Our results illustrate aortic elongation with ageing and high anatomical variability of renal arteries. Our findings are complementary to anatomical features previously published and might contribute to enhance endovascular procedures safety and efficacy for vascular surgeons and interventional radiologists.

Established Stem Cell Model of Spinal Muscular Atrophy Is Applicable in the Evaluation of the Efficacy of Thyrotropin-Releasing Hormone Analog

PubMed Central

Ohuchi, Kazuki; Kato, Zenichiro; Seki, Junko; Kawase, Chizuru; Tamai, Yuya; Ono, Yoko; Nagahara, Yuki; Noda, Yasuhiro; Kameyama, Tsubasa; Ando, Shiori; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Hara, Hideaki; Kaneko, Hideo

2016-01-01

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by the degeneration of spinal motor neurons. This disease is mainly caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. Currently, no effective treatment is available, and only symptomatic treatment can be provided. Our purpose in the present study was to establish a human SMA-derived induced pluripotent stem cell (SMA-iPSC) disease model and assay a therapeutic drug in preparation for the development of a novel treatment of SMA. We generated iPSCs from the skin fibroblasts of a patient with SMA and confirmed that they were pluripotent and undifferentiated. The neural differentiation of SMA-iPSCs shortened the dendrite and axon length and increased the apoptosis of the spinal motor neurons. In addition, we found activated astrocytes in differentiated SMA-iPSCs. Using this model, we confirmed that treatment with the thyrotropin-releasing hormone (TRH) analog, 5-oxo-l-prolyl-l-histidyl-l-prolinamide, which had marginal effects in clinical trials, increases the SMN protein level. This increase was mediated through the transcriptional activation of the SMN2 gene and inhibition of glycogen synthase kinase-3β activity. Finally, the TRH analog treatment resulted in dendrite and axon development of spinal motor neurons in differentiated SMA-iPSCs. These results suggest that this human in vitro disease model stimulates SMA pathology and reveal the potential efficacy of TRH analog treatment for SMA. Therefore, we can screen novel therapeutic drugs such as TRH for SMA easily and effectively using the human SMA-iPSC model. Significance Platelet-derived growth factor (PDGF) has recently been reported to produce the greatest increase in survival motor neuron protein levels by inhibiting glycogen synthase kinase (GSK)-3β; however, motor neurons lack PDGF receptors. A human in vitro spinal muscular atrophy-derived induced pluripotent stem cell model was established, which showed that the thyrotropin releasing hormone (TRH) analog promoted transcriptional activation of the SMN2 gene and inhibition of GSK-3β activity, resulting in the increase and stabilization of the SMN protein and axon elongation of spinal motor neurons. These results reveal the potential efficacy of TRH analog treatment for SMA. PMID:26683872

Established Stem Cell Model of Spinal Muscular Atrophy Is Applicable in the Evaluation of the Efficacy of Thyrotropin-Releasing Hormone Analog.

PubMed

Ohuchi, Kazuki; Funato, Michinori; Kato, Zenichiro; Seki, Junko; Kawase, Chizuru; Tamai, Yuya; Ono, Yoko; Nagahara, Yuki; Noda, Yasuhiro; Kameyama, Tsubasa; Ando, Shiori; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Hara, Hideaki; Kaneko, Hideo

2016-02-01

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by the degeneration of spinal motor neurons. This disease is mainly caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. Currently, no effective treatment is available, and only symptomatic treatment can be provided. Our purpose in the present study was to establish a human SMA-derived induced pluripotent stem cell (SMA-iPSC) disease model and assay a therapeutic drug in preparation for the development of a novel treatment of SMA. We generated iPSCs from the skin fibroblasts of a patient with SMA and confirmed that they were pluripotent and undifferentiated. The neural differentiation of SMA-iPSCs shortened the dendrite and axon length and increased the apoptosis of the spinal motor neurons. In addition, we found activated astrocytes in differentiated SMA-iPSCs. Using this model, we confirmed that treatment with the thyrotropin-releasing hormone (TRH) analog, 5-oxo-l-prolyl-l-histidyl-l-prolinamide, which had marginal effects in clinical trials, increases the SMN protein level. This increase was mediated through the transcriptional activation of the SMN2 gene and inhibition of glycogen synthase kinase-3β activity. Finally, the TRH analog treatment resulted in dendrite and axon development of spinal motor neurons in differentiated SMA-iPSCs. These results suggest that this human in vitro disease model stimulates SMA pathology and reveal the potential efficacy of TRH analog treatment for SMA. Therefore, we can screen novel therapeutic drugs such as TRH for SMA easily and effectively using the human SMA-iPSC model. Significance: Platelet-derived growth factor (PDGF) has recently been reported to produce the greatest increase in survival motor neuron protein levels by inhibiting glycogen synthase kinase (GSK)-3β; however, motor neurons lack PDGF receptors. A human in vitro spinal muscular atrophy-derived induced pluripotent stem cell model was established, which showed that the thyrotropin releasing hormone (TRH) analog promoted transcriptional activation of the SMN2 gene and inhibition of GSK-3β activity, resulting in the increase and stabilization of the SMN protein and axon elongation of spinal motor neurons. These results reveal the potential efficacy of TRH analog treatment for SMA. ©AlphaMed Press.

pH-sensitive polymeric cisplatin-ion complex with styrene-maleic acid copolymer exhibits tumor-selective drug delivery and antitumor activity as a result of the enhanced permeability and retention effect.

PubMed

Saisyo, Atsuyuki; Nakamura, Hideaki; Fang, Jun; Tsukigawa, Kenji; Greish, Khaled; Furukawa, Hiroyuki; Maeda, Hiroshi

2016-02-01

Cisplatin (CDDP) is widely used to treat various cancers. However, its distribution to normal tissues causes serious adverse effects. For this study, we synthesized a complex of styrene-maleic acid copolymer (SMA) and CDDP (SMA-CDDP), which formed polymeric micelles, to achieve tumor-selective drug delivery based on the enhanced permeability and retention (EPR) effect. SMA-CDDP is obtained by regulating the pH of the reaction solution of SMA and CDDP. The mean SMA-CDDP particle size was 102.5 nm in PBS according to electrophoretic light scattering, and the CDDP content was 20.1% (w/w). The release rate of free CDDP derivatives from the SMA-CDDP complex at physiological pH was quite slow (0.75%/day), whereas it was much faster at pH 5.5 (4.4%/day). SMA-CDDP thus had weaker in vitro toxicity at pH 7.4 but higher cytotoxicity at pH 5.5. In vivo pharmacokinetic studies showed a 5-fold higher tumor concentration of SMA-CDDP than of free CDDP. SMA-CDDP had more effective antitumor potential but lower toxicity than did free CDDP in mice after i.v. administration. Administration of parental free CDDP at 4 mg/kg×3 caused a weight loss of more than 5%; SMA-CDDP at 60 mg/kg (CDDP equivalent)×3 caused no significant weight change but markedly suppressed S-180 tumor growth. These findings together suggested using micelles of the SMA-CDDP complex as a cancer chemotherapeutic agent because of beneficial properties-tumor-selective accumulation and relatively rapid drug release at the acidic pH of the tumor-which resulted in superior antitumor effects and fewer side effects compared with free CDDP. Copyright © 2015 Elsevier B.V. All rights reserved.

Acquisition through Horizontal Gene Transfer of Plasmid pSMA198 by Streptococcus macedonicus ACA-DC 198 Points towards the Dairy Origin of the Species

PubMed Central

Papadimitriou, Konstantinos; Anastasiou, Rania; Maistrou, Eleni; Plakas, Thomas; Papandreou, Nikos C.; Hamodrakas, Stavros J.; Ferreira, Stéphanie; Supply, Philip; Renault, Pierre; Pot, Bruno; Tsakalidou, Effie

2015-01-01

Background Streptococcus macedonicus is an intriguing streptococcal species whose most frequent source of isolation is fermented foods similarly to Streptococcus thermophilus. However, S. macedonicus is closely related to commensal opportunistic pathogens of the Streptococcus bovis/Streptococcus equinus complex. Methodology/Principal Findings We analyzed the pSMA198 plasmid isolated from the dairy strain Streptococcus macedonicus ACA-DC 198 in order to provide novel clues about the main ecological niche of this bacterium. pSMA198 belongs to the narrow host range pCI305/pWV02 family found primarily in lactococci and to the best of our knowledge it is the first such plasmid to be reported in streptococci. Comparative analysis of the pSMA198 sequence revealed a high degree of similarity with plasmids isolated from Lactococcus lactis strains deriving from milk or its products. Phylogenetic analysis of the pSMA198 Rep showed that the vast majority of closely related proteins derive from lactococcal dairy isolates. Additionally, cloning of the pSMA198 ori in L. lactis revealed a 100% stability of replication over 100 generations. Both pSMA198 and the chromosome of S. macedonicus exhibit a high percentage of potential pseudogenes, indicating that they have co-evolved under the same gene decay processes. We identified chromosomal regions in S. macedonicus that may have originated from pSMA198, also supporting a long co-existence of the two replicons. pSMA198 was also found in divergent biotypes of S. macedonicus and in strains isolated from dispersed geographic locations (e.g. Greece and Switzerland) showing that pSMA198’s acquisition is not a recent event. Conclusions/Significance Here we propose that S. macedonicus acquired plasmid pSMA198 from L. lactis via an ancestral genetic exchange event that took place most probably in milk or dairy products. We provide important evidence that point towards the dairy origin of this species. PMID:25584532

Revised Hammersmith Scale for spinal muscular atrophy: A SMA specific clinical outcome assessment tool.

PubMed

Ramsey, Danielle; Scoto, Mariacristina; Mayhew, Anna; Main, Marion; Mazzone, Elena S; Montes, Jacqueline; de Sanctis, Roberto; Dunaway Young, Sally; Salazar, Rachel; Glanzman, Allan M; Pasternak, Amy; Quigley, Janet; Mirek, Elizabeth; Duong, Tina; Gee, Richard; Civitello, Matthew; Tennekoon, Gihan; Pane, Marika; Pera, Maria Carmela; Bushby, Kate; Day, John; Darras, Basil T; De Vivo, Darryl; Finkel, Richard; Mercuri, Eugenio; Muntoni, Francesco

2017-01-01

Recent translational research developments in Spinal Muscular Atrophy (SMA), outcome measure design and demands from regulatory authorities require that clinical outcome assessments are 'fit for purpose'. An international collaboration (SMA REACH UK, Italian SMA Network and PNCRN USA) undertook an iterative process to address discontinuity in the recorded performance of the Hammersmith Functional Motor Scale Expanded and developed a revised functional scale using Rasch analysis, traditional psychometric techniques and the application of clinical sensibility via expert panels. Specifically, we intended to develop a psychometrically and clinically robust functional clinician rated outcome measure to assess physical abilities in weak SMA type 2 through to strong ambulant SMA type 3 patients. The final scale, the Revised Hammersmith Scale (RHS) for SMA, consisting of 36 items and two timed tests, was piloted in 138 patients with type 2 and 3 SMA in an observational cross-sectional multi-centre study across the three national networks. Rasch analysis demonstrated very good fit of all 36 items to the construct of motor performance, good reliability with a high Person Separation Index PSI 0.98, logical and hierarchical scoring in 27/36 items and excellent targeting with minimal ceiling. The RHS differentiated between clinically different groups: SMA type, World Health Organisation (WHO) categories, ambulatory status, and SMA type combined with ambulatory status (all p < 0.001). Construct and concurrent validity was also confirmed with a strong significant positive correlation with the WHO motor milestones rs = 0.860, p < 0.001. We conclude that the RHS is a psychometrically sound and versatile clinical outcome assessment to test the broad range of physical abilities of patients with type 2 and 3 SMA. Further longitudinal testing of the scale with regards change in scores over 6 and 12 months are required prior to its adoption in clinical trials.

Acquisition through horizontal gene transfer of plasmid pSMA198 by Streptococcus macedonicus ACA-DC 198 points towards the dairy origin of the species.

PubMed

Papadimitriou, Konstantinos; Anastasiou, Rania; Maistrou, Eleni; Plakas, Thomas; Papandreou, Nikos C; Hamodrakas, Stavros J; Ferreira, Stéphanie; Supply, Philip; Renault, Pierre; Pot, Bruno; Tsakalidou, Effie

2015-01-01

Streptococcus macedonicus is an intriguing streptococcal species whose most frequent source of isolation is fermented foods similarly to Streptococcus thermophilus. However, S. macedonicus is closely related to commensal opportunistic pathogens of the Streptococcus bovis/Streptococcus equinus complex. We analyzed the pSMA198 plasmid isolated from the dairy strain Streptococcus macedonicus ACA-DC 198 in order to provide novel clues about the main ecological niche of this bacterium. pSMA198 belongs to the narrow host range pCI305/pWV02 family found primarily in lactococci and to the best of our knowledge it is the first such plasmid to be reported in streptococci. Comparative analysis of the pSMA198 sequence revealed a high degree of similarity with plasmids isolated from Lactococcus lactis strains deriving from milk or its products. Phylogenetic analysis of the pSMA198 Rep showed that the vast majority of closely related proteins derive from lactococcal dairy isolates. Additionally, cloning of the pSMA198 ori in L. lactis revealed a 100% stability of replication over 100 generations. Both pSMA198 and the chromosome of S. macedonicus exhibit a high percentage of potential pseudogenes, indicating that they have co-evolved under the same gene decay processes. We identified chromosomal regions in S. macedonicus that may have originated from pSMA198, also supporting a long co-existence of the two replicons. pSMA198 was also found in divergent biotypes of S. macedonicus and in strains isolated from dispersed geographic locations (e.g. Greece and Switzerland) showing that pSMA198's acquisition is not a recent event. Here we propose that S. macedonicus acquired plasmid pSMA198 from L. lactis via an ancestral genetic exchange event that took place most probably in milk or dairy products. We provide important evidence that point towards the dairy origin of this species.

Spinal Muscular Atrophy (SMA)

MedlinePlus

... forms of SMA still shorten life span, new approaches to ventilation and feeding have expanded what’s possible. ... 5-linked SMA in the last decade. Other approaches include less specific methods of helping motor neurons ...

Left-lateralization of resting state functional connectivity between the presupplementary motor area and primary language areas.

PubMed

Lou, William; Peck, Kyung K; Brennan, Nicole; Mallela, Arka; Holodny, Andrei

2017-07-05

An abundance of evidence points to the role of a presupplementary motor area (pre-SMA) in human language. This study explores the pre-SMA resting state connectivity network and the nature of its connections to known language areas. We tested the hypothesis that by seeding the pre-SMA, one would be able to establish language laterality to known cortical and subcortical language areas. We analyzed data from 30 right-handed healthy controls and performed the resting state functional MRI. A seed-based analysis using a manually drawn pre-SMA region of interest template was applied. Time-course signals in the pre-SMA region of interest were averaged and cross-correlated to every voxel in the brain. Results show that the pre-SMA has significant left-lateralized functional connectivity to the pars opercularis within Broca's area. Among cortical regions, pre-SMA functional connectivity is strongest to the pars opercularis In addition, pre-SMA connectivity was shown to exist to other cortical language-association regions, including Wernicke's Area, supramarginal gyri, angular gyri, and middle frontal gyri. Among subcortical areas, considerable left-lateralized functional connectivity occurs to the caudate and thalamus, whereas cerebellar subregions show right lateralization. The current study shows that the pre-SMA most strongly connects to the pars opercularis within Broca's area and that cortical connections to language areas are left lateralized among a sample of right-handed patients. We provide resting state functional MRI evidence that the functional connectivity of the pre-SMA is involved in semantic language processing and that this identification may be useful for establishing language laterality in preoperative neurosurgical planning.

Neurocalcin Delta Suppression Protects against Spinal Muscular Atrophy in Humans and across Species by Restoring Impaired Endocytosis.

PubMed

Riessland, Markus; Kaczmarek, Anna; Schneider, Svenja; Swoboda, Kathryn J; Löhr, Heiko; Bradler, Cathleen; Grysko, Vanessa; Dimitriadi, Maria; Hosseinibarkooie, Seyyedmohsen; Torres-Benito, Laura; Peters, Miriam; Upadhyay, Aaradhita; Biglari, Nasim; Kröber, Sandra; Hölker, Irmgard; Garbes, Lutz; Gilissen, Christian; Hoischen, Alexander; Nürnberg, Gudrun; Nürnberg, Peter; Walter, Michael; Rigo, Frank; Bennett, C Frank; Kye, Min Jeong; Hart, Anne C; Hammerschmidt, Matthias; Kloppenburg, Peter; Wirth, Brunhilde

2017-02-02

Homozygous SMN1 loss causes spinal muscular atrophy (SMA), the most common lethal genetic childhood motor neuron disease. SMN1 encodes SMN, a ubiquitous housekeeping protein, which makes the primarily motor neuron-specific phenotype rather unexpected. SMA-affected individuals harbor low SMN expression from one to six SMN2 copies, which is insufficient to functionally compensate for SMN1 loss. However, rarely individuals with homozygous absence of SMN1 and only three to four SMN2 copies are fully asymptomatic, suggesting protection through genetic modifier(s). Previously, we identified plastin 3 (PLS3) overexpression as an SMA protective modifier in humans and showed that SMN deficit impairs endocytosis, which is rescued by elevated PLS3 levels. Here, we identify reduction of the neuronal calcium sensor Neurocalcin delta (NCALD) as a protective SMA modifier in five asymptomatic SMN1-deleted individuals carrying only four SMN2 copies. We demonstrate that NCALD is a Ca 2+ -dependent negative regulator of endocytosis, as NCALD knockdown improves endocytosis in SMA models and ameliorates pharmacologically induced endocytosis defects in zebrafish. Importantly, NCALD knockdown effectively ameliorates SMA-associated pathological defects across species, including worm, zebrafish, and mouse. In conclusion, our study identifies a previously unknown protective SMA modifier in humans, demonstrates modifier impact in three different SMA animal models, and suggests a potential combinatorial therapeutic strategy to efficiently treat SMA. Since both protective modifiers restore endocytosis, our results confirm that endocytosis is a major cellular mechanism perturbed in SMA and emphasize the power of protective modifiers for understanding disease mechanism and developing therapies. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Thermal Powered Reciprocating-Force Motor

NASA Technical Reports Server (NTRS)

Tatum, III, Paul F. (Inventor); McDow Elliott, Amelia (Inventor)

2015-01-01

A thermal-powered reciprocating-force motor includes a shutter switchable between a first position that passes solar energy and a second position that blocks solar energy. A shape memory alloy (SMA) actuator is coupled to the shutter to control switching thereof between the shutter's first and second position. The actuator is positioned with respect to the shutter such that (1) solar energy impinges on the SMA when the shutter is in its first position so that the SMA experiences contraction in length until the shutter is switched to its second position, and (2) solar energy is impeded from impingement on the SMA when the shutter is in its second position so that the SMA experiences extension in length. Elastic members coupled to the actuator apply a force to the SMA that aids in its extension in length until the shutter is switched to its first position.

Crack-closing of cement mortar beams using NiTi cold-drawn SMA short fibers

NASA Astrophysics Data System (ADS)

Choi, Eunsoo; Kim, Dong Joo; Chung, Young-Soo; Kim, Hee Sun; Jung, Chungsung

2015-01-01

In this study, crack-closing tests of mortar beams reinforced by shape memory alloy (SMA) short fibers were performed. For this purpose, NiTi SMA fibers with a diameter of 0.965 mm and a length of 30 mm were made from SMA wires of 1.0 mm diameter by cold drawing. Four types of SMA fibers were prepared, namely, straight and dog-bone-shaped fiber and the two types of fibers with paper wrapping in the middle of the fibers. The paper provides an unbonded length of 15 mm. For bending tests, six types of mortar beams with the dimensions of 40 mm × 40 mm × 160 mm (B×H×L) were prepared. The SMA fibers were placed at the bottom center of the beams along with an artificial crack of 10 mm depth and 1 mm thickness. This study investigated the influence of SMA fibers on the flexural strength of the beams from the measured force- deflection curves. After cracking, the beams were heated at the bottom by fire to activate the SMA fibers. Then, the beams recovered the deflection, and the cracks were closed. This study evaluated crack-closing capacity using the degree of crack recovery and deflection-recovery factor. The first factor is estimated from the crack-width before and after crack-closing, and the second one is obtained from the downward deflection due to loading and the upward deflection due to the closing force of the SMA fibers.

Encoding of speed and direction of movement in the human supplementary motor area

PubMed Central

Tankus, Ariel; Yeshurun, Yehezkel; Flash, Tamar; Fried, Itzhak

2010-01-01

Object The supplementary motor area (SMA) plays an important role in planning, initiation, and execution of motor acts. Patients with SMA lesions are impaired in various kinematic parameters, such as velocity and duration of movement. However, the relationships between neuronal activity and these parameters in the human brain have not been fully characterized. This is a study of single-neuron activity during a continuous volitional motor task, with the goal of clarifying these relationships for SMA neurons and other frontal lobe regions in humans. Methods The participants were 7 patients undergoing evaluation for epilepsy surgery requiring implantation of intracranial depth electrodes. Single-unit recordings were conducted while the patients played a computer game involving movement of a cursor in a simple maze. Results In the SMA proper, most of the recorded units exhibited a monotonic relationship between the unit firing rate and hand motion speed. The vast majority of SMA proper units with this property showed an inverse relation, that is, firing rate decrease with speed increase. In addition, most of the SMA proper units were selective to the direction of hand motion. These relationships were far less frequent in the pre-SMA, anterior cingulate gyrus, and orbitofrontal cortex. Conclusions The findings suggest that the SMA proper takes part in the control of kinematic parameters of end-effector motion, and thus lend support to the idea of connecting neuroprosthetic devices to the human SMA. PMID:19231930

Correlation between Fibrillin-1 Degradation and mRNA Downregulation and Myofibroblast Differentiation in Cultured Human Dental Pulp Tissue

PubMed Central

Yoshiba, Nagako; Yoshiba, Kunihiko; Ohkura, Naoto; Takei, Erika; Edanami, Naoki; Oda, Youhei; Hosoya, Akihiro; Nakamura, Hiroaki; Okiji, Takashi

2015-01-01

Myofibroblasts and extracellular matrix are important components in wound healing. Alpha-smooth muscle actin (α-SMA) is a marker of myofibroblasts. Fibrillin-1 is a major constituent of microfibrils and an extracellular-regulator of TGF-β1, an important cytokine in the transdifferentiation of resident fibroblasts into myofibroblasts. To study the correlation between changes in fibrillin-1 expression and myofibroblast differentiation, we examined alterations in fibrillin-1 and α-SMA expression in organotypic cultures of dental pulp in vitro. Extracted healthy human teeth were cut to 1-mm-thick slices and cultured for 7 days. In intact dental pulp, fibrillin-1 was broadly distributed, and α-SMA was observed in pericytes and vascular smooth muscle cells. After 7 days of culture, immunostaining for fibrillin-1 became faint concomitant with a downregulation in its mRNA levels. Furthermore, fibroblasts, odontoblasts and Schwann cells were immunoreactive for α-SMA with a significant increase in α-SMA mRNA expression. Double immunofluorescence staining was positive for pSmad2/3, central mediators of TGF-β signaling, and α-SMA. The administration of inhibitors for extracellular matrix proteases recovered fibrillin-1 immunostaining; moreover, fibroblasts lost their immunoreactivity for α-SMA along with a downregulation in α-SMA mRNA. These findings suggest that the expression of α-SMA is TGF-β1 dependent, and fibrillin-1 degradation and downregulation might be implicated in the differentiation of myofibroblasts in dental pulp wound healing. PMID:25805839

Mapping of the bovine spinal muscular atrophy locus to Chromosome 24.

PubMed

Medugorac, Ivica; Kemter, Juliane; Russ, Ingolf; Pietrowski, Detlef; Nüske, Stefan; Reichenbach, Horst-Dieter; Schmahl, Wolfgang; Förster, Martin

2003-06-01

A hereditary form of spinal muscular atrophy (SMA) caused by an autosomal recessive gene has been reported for American Brown-Swiss cattle and in advanced backcrosses between American Brown-Swiss and many European brown cattle breeds. Bovine SMA (bovSMA) bears remarkable resemblance to the human SMA (SMA1). Affected homozygous calves also show progressive symmetric weakness and neurogenic atrophy of proximal muscles. The condition is characterized by severe muscle atrophy, quadriparesis, and sternal recumbency as result of neurogenic atrophy. We report on the localization of the gene causing bovSMA within a genomic interval between the microsatellite marker URB031 and the telomeric end of bovine Chromosome (Chr) 24 (BTA24). Linkage analysis of a complex pedigree of German Braunvieh cattle revealed a recombination fraction of 0.06 and a three-point lod score of 11.82. The results of linkage and haplotyping analysis enable a marker-assisted selection against bovSMA based on four microsatellite markers most telomeric on BTA24 to a moderate accuracy of 89-94%. So far, this region is not orthologous to any human chromosome segments responsible for twelve distinct disease phenotypes of autosomal neuropathies. Our results indicate the apoptosis-inhibiting protein BCL2 as the most promising positional candidate gene causing bovSMA. Our findings offer an attractive animal model for a better understanding of human forms of SMA and for a probable anti-apoptotic synergy of SMN-BCL2 aggregates in mammals.

Edaravone is a candidate agent for spinal muscular atrophy: In vitro analysis using a human induced pluripotent stem cells-derived disease model.

PubMed

Ando, Shiori; Funato, Michinori; Ohuchi, Kazuki; Kameyama, Tsubasa; Inagaki, Satoshi; Seki, Junko; Kawase, Chizuru; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Kaneko, Hideo; Hara, Hideaki

2017-11-05

Spinal muscular atrophy (SMA) is an intractable disease characterized by a progressive loss of spinal motor neurons, which leads to skeletal muscle weakness and atrophy. Currently, there are no curative agents for SMA, although it is understood to be caused by reduced levels of survival motor neuron (SMN) protein. Additionally, why reduced SMN protein level results in selective apoptosis in spinal motor neurons is still not understood. Our purpose in this study was to evaluate the therapeutic potential of edaravone, a free radical scavenger, by using induced pluripotent stem cells from an SMA patient (SMA-iPSCs) and to address oxidative stress-induced apoptosis in spinal motor neurons. We first found that edaravone could improve impaired neural development of SMA-iPSCs-derived spinal motor neurons with limited effect on nuclear SMN protein expression. Furthermore, edaravone inhibited the generation of reactive oxygen species and mitochondrial reactive oxygen species upregulated in SMA-iPSCs-derived spinal motor neurons, and reversed oxidative-stress induced apoptosis. In this study, we suggest that oxidative stress might be partly the reason for selective apoptosis in spinal motor neurons in SMA pathology, and that oxidative stress-induced apoptosis might be the therapeutic target of SMA. Copyright © 2017 Elsevier B.V. All rights reserved.

Electrical/Mechanical Monitoring of Shape Memory Alloy Reinforcing Fibers Obtained by Pullout Tests in SMA/Cement Composite Materials.

PubMed

Kim, Eui-Hyun; Lee, Hyunbae; Kim, Jae-Hwan; Bae, Seung-Muk; Hwang, Heesu; Yang, Heesun; Choi, Eunsoo; Hwang, Jin-Ha

2018-02-22

Self-healing is an essential property of smart concrete structures. In contrast to other structural metals, shape memory alloys (SMAs) offer two unique effects: shape memory effects, and superelastic effects. Composites composed of SMA wires and conventional cements can overcome the mechanical weaknesses associated with tensile fractures in conventional concretes. Under specialized environments, the material interface between the cementitious component and the SMA materials plays an important role in achieving the enhanced mechanical performance and robustness of the SMA/cement interface. This material interface is traditionally evaluated in terms of mechanical aspects, i.e., strain-stress characteristics. However, the current work attempts to simultaneously characterize the mechanical load-displacement relationships synchronized with impedance spectroscopy as a function of displacement. Frequency-dependent impedance spectroscopy is tested as an in situ monitoring tool for structural variations in smart composites composed of non-conducting cementitious materials and conducting metals. The artificial geometry change in the SMA wires is associated with an improved anchoring action that is compatible with the smallest variation in resistance compared with prismatic SMA wires embedded into a cement matrix. The significant increase in resistance is interpreted to be associated with the slip of the SMA fibers following the elastic deformation and the debonding of the SMA fiber/matrix.

Abnormalities in early markers of muscle involvement support a delay in myogenesis in spinal muscular atrophy.

PubMed

Martínez-Hernández, Rebeca; Bernal, Sara; Alias, Laura; Tizzano, Eduardo F

2014-06-01

Spinal muscular atrophy (SMA) is characterized by loss of motor neurons in the spinal cord that results in muscle denervation and profound weakness in affected patients. We sought evidence for primary muscle involvement in the disease during human development by analyzing the expression of several muscle cytoskeletal components (i.e. slow, fast, and developmental myosin, desmin, and vimentin) in fetal or postnatal skeletal muscle samples from 5 SMA cases and 6 controls. At 14 weeks' gestation, SMA samples had higher percentages of myotubes expressing fast myosin and lower percentages of myotubes expressing slow myosin versus control samples. Desmin and vimentin were highly expressed at prenatal stages without notable differences between control and SMA samples, although both proteins showed persistent immunostaining in atrophic fibers in postnatal SMA samples. We also studied the expression of Pax7-positive nuclei as a marker of satellite cells and found no differences between control and SMA prenatal samples. There was, however, a significant increase in satellite cells in postnatal atrophic SMA fibers, suggesting an abnormal myogenic process. Together, these results support the hypothesis of a delay in muscle maturation as one of the primary pathologic components of SMA. Furthermore, myosins and Pax7 may be useful research markers of muscle involvement in this disease.

Genetic inhibition of JNK3 ameliorates spinal muscular atrophy.

PubMed

Genabai, Naresh K; Ahmad, Saif; Zhang, Zhanying; Jiang, Xiaoting; Gabaldon, Cynthia A; Gangwani, Laxman

2015-12-15

Mutation of the Survival Motor Neuron 1 (SMN1) gene causes spinal muscular atrophy (SMA), an autosomal recessive neurodegenerative disorder that occurs in early childhood. Degeneration of spinal motor neurons caused by SMN deficiency results in progressive muscle atrophy and death in SMA. The molecular mechanism underlying neurodegeneration in SMA is unknown. No treatment is available to prevent neurodegeneration and reduce the burden of illness in SMA. We report that the c-Jun NH2-terminal kinase (JNK) signaling pathway mediates neurodegeneration in SMA. The neuron-specific isoform JNK3 is required for neuron degeneration caused by SMN deficiency. JNK3 deficiency reduces degeneration of cultured neurons caused by low levels of SMN. Genetic inhibition of JNK pathway in vivo by Jnk3 knockout results in amelioration of SMA phenotype. JNK3 deficiency prevents the loss of spinal cord motor neurons, reduces muscle degeneration, improves muscle fiber thickness and muscle growth, improves motor function and overall growth and increases lifespan of mice with SMA that shows a systemic rescue of phenotype by a SMN-independent mechanism. JNK3 represents a potential (non-SMN) therapeutic target for the treatment of SMA. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Pulse width modulation-based temperature tracking for feedback control of a shape memory alloy actuator.

PubMed

Ayvali, Elif; Desai, Jaydev P

2014-04-01

This work presents a temperature-feedback approach to control the radius of curvature of an arc-shaped shape memory alloy (SMA) wire. The nonlinear properties of the SMA such as phase transformation and its dependence on temperature and stress make SMA actuators difficult to control. Tracking a desired trajectory is more challenging than controlling just the position of the SMA actuator since the desired path is continuously changing. Consequently, tracking the desired strain directly or tracking the parameters such as temperature and electrical resistance that are related to strain with a model is a challenging task. Temperature-feedback is an attractive approach when direct measurement of strain is not practical. Pulse width modulation (PWM) is an effective method for SMA actuation and it can be used along with a compensator to control the temperature of the SMA. Using the constitutive model of the SMA, the desired temperature profile can be obtained for a given strain trajectory. A PWM-based nonlinear PID controller with a feed-forward heat transfer model is proposed to use temperature-feedback for tracking a desired temperature trajectory. The proposed controller is used during the heating phase of the SMA actuator. The controller proves to be effective in tracking step-wise and continuous trajectories.

SMA Foils for MEMS: From Material Properties to the Engineering of Microdevices

NASA Astrophysics Data System (ADS)

Kohl, Manfred; Ossmer, Hinnerk; Gueltig, Marcel; Megnin, Christof

2018-03-01

In the early nineties, microelectromechanical systems (MEMS) technology has been still in its infancy. As silicon (Si) is not a transducer material, it was clear at the very beginning that mechanically active materials had to be introduced to MEMS in order to enable functional microdevices with actuation capability beyond electrostatics. At that time, shape memory alloys (SMAs) have been available in bulk form, mainly as SMA wires and SMA plates. On the macro scale, these materials show highest work densities compared to other actuation principles in the order of 107 J/m3, which stimulated research on the integration of SMA to MEMS. Subsequently, two approaches for producing planar materials have been initiated (1) magnetron sputtering of SMA thin films and (2) the integration of rolled SMA foils, which both turned out to be very successful creating a paradigm change in microactuation technology. The following review covers important milestones of the research and development of SMA foil-based microactuators including materials characterization, design engineering, technology, and demonstrator development as well as first commercial products.

SMA Foils for MEMS: From Material Properties to the Engineering of Microdevices

NASA Astrophysics Data System (ADS)

Kohl, Manfred; Ossmer, Hinnerk; Gueltig, Marcel; Megnin, Christof

2017-12-01

In the early nineties, microelectromechanical systems (MEMS) technology has been still in its infancy. As silicon (Si) is not a transducer material, it was clear at the very beginning that mechanically active materials had to be introduced to MEMS in order to enable functional microdevices with actuation capability beyond electrostatics. At that time, shape memory alloys (SMAs) have been available in bulk form, mainly as SMA wires and SMA plates. On the macro scale, these materials show highest work densities compared to other actuation principles in the order of 107 J/m3, which stimulated research on the integration of SMA to MEMS. Subsequently, two approaches for producing planar materials have been initiated (1) magnetron sputtering of SMA thin films and (2) the integration of rolled SMA foils, which both turned out to be very successful creating a paradigm change in microactuation technology. The following review covers important milestones of the research and development of SMA foil-based microactuators including materials characterization, design engineering, technology, and demonstrator development as well as first commercial products.

Feasibility study of an active soft catheter actuated by SMA wires

NASA Astrophysics Data System (ADS)

Konh, Bardia; Karimi, Saeed; Miller, Scott

2018-03-01

This study aims to assess the feasibility of using a combination of thin elastomer tubes and SMA wires to develop an active catheter. Cardiac catheters have been widely used in investigational and interventional procedures such as angiography, angioplasty, electro- physiology, and endocardial ablation. The commercial models manually steer inside the patient's body via internally installed pull wires. Active catheters, on the other hand, have the potential to revolutionize surgical procedures because of their computer-controlled and enhanced motion. Shape memory alloys have been used for almost a decade as a trustworthy actuator for biomedical applications. In this work, SMA wires were attached to a small pressurized elastomer tube to realize deflection. The tube was pressurized to maintain a constant stress on the SMA wires. The tip motion via actuation of SMA wires was then measured and reported. The results of this study showed that by adopting an appropriate training process for the SMA wires prior to performing the experiments and adopting an appropriate internal pressure for the elastomer tube, less external loads on SMA wires would be needed for a consistent actuation.

A two-degrees-of-freedom miniature manipulator actuated by antagonistic shape memory alloys

NASA Astrophysics Data System (ADS)

Lai, Chih-Ming; Chu, Cheng-Yu; Lan, Chao-Chieh

2013-08-01

This paper presents a miniature manipulator that can provide rotations around two perpendicularly intersecting axes. Each axis is actuated by a pair of shape memory alloy (SMA) wires. SMA wire actuators are known for their large energy density and ease of actuation. These advantages make them ideal for applications that have stringent size and weight constraints. SMA actuators can be temperature-controlled to contract and relax like muscles. When correctly designed, antagonistic SMA actuators have a faster response and larger range of motion than bias-type SMA actuators. This paper proposes an antagonistic actuation model to determine the manipulator parameters that are required to generate sufficient workspace. Effects of SMA prestrain and spring stiffness on the manipulator are investigated. Taking advantage of proper prestrain, the actuator size can be made much smaller while maintaining the same motion. The use of springs in series with SMA can effectively reduce actuator stress. A controller and an anti-slack algorithm are developed to ensure fast and accurate motion. Speed, stress, and loading experiments are conducted to demonstrate the performance of the manipulator.

Probing molecular interactions of poly(styrene-co-maleic acid) with lipid matrix models to interpret the therapeutic potential of the co-polymer.

PubMed

Banerjee, Shubhadeep; Pal, Tapan K; Guha, Sujoy K

2012-03-01

To understand and maximize the therapeutic potential of poly(styrene-co-maleic acid) (SMA), a synthetic, pharmacologically-active co-polymer, its effect on conformation, phase behavior and stability of lipid matrix models of cell membranes were investigated. The modes of interaction between SMA and lipid molecules were also studied. While, attenuated total reflection-Fourier-transform infrared (ATR-FTIR) and static (31)P nuclear magnetic resonance (NMR) experiments detected SMA-induced conformational changes in the headgroup region, differential scanning calorimetry (DSC) studies revealed thermotropic phase behavior changes of the membranes. (1)H NMR results indicated weak immobilization of SMA within the bilayers. Molecular interpretation of the results indicated the role of hydrogen-bond formation and hydrophobic forces between SMA and zwitterionic phospholipid bilayers. The extent of membrane fluidization and generation of isotropic phases were affected by the surface charge of the liposomes, and hence suggested the role of electrostatic interactions between SMA and charged lipid headgroups. SMA was thus found to directly affect the structural integrity of model membranes. Copyright © 2011 Elsevier B.V. All rights reserved.

Capillary pericytes express α-smooth muscle actin, which requires prevention of filamentous-actin depolymerization for detection.

PubMed

Alarcon-Martinez, Luis; Yilmaz-Ozcan, Sinem; Yemisci, Muge; Schallek, Jesse; Kılıç, Kıvılcım; Can, Alp; Di Polo, Adriana; Dalkara, Turgay

2018-03-21

Recent evidence suggests that capillary pericytes are contractile and play a crucial role in the regulation of microcirculation. However, failure to detect components of the contractile apparatus in capillary pericytes, most notably α-smooth muscle actin (α-SMA), has questioned these findings. Using strategies that allow rapid filamentous-actin (F-actin) fixation (i.e. snap freeze fixation with methanol at -20°C) or prevent F-actin depolymerization (i.e. with F-actin stabilizing agents), we demonstrate that pericytes on mouse retinal capillaries, including those in intermediate and deeper plexus, express α-SMA. Junctional pericytes were more frequently α-SMA-positive relative to pericytes on linear capillary segments. Intravitreal administration of short interfering RNA (α-SMA-siRNA) suppressed α-SMA expression preferentially in high order branch capillary pericytes, confirming the existence of a smaller pool of α-SMA in distal capillary pericytes that is quickly lost by depolymerization. We conclude that capillary pericytes do express α-SMA, which rapidly depolymerizes during tissue fixation thus evading detection by immunolabeling. © 2018, Alarcon-Martinez et al.

Development of a shape memory alloy actuated biomimetic vehicle

NASA Astrophysics Data System (ADS)

Garner, L. J.; Wilson, L. N.; Lagoudas, D. C.; Rediniotis, O. K.

2000-10-01

The development of a biomimetic active hydrofoil that utilizes shape memory alloy (SMA) actuator technology is presented. This work is the first stage prototype of a vehicle that will consist of many actuated body segments. The current work describes the design, modeling and testing of a single-segment demonstration SMA actuated hydrofoil. The SMA actuation elements are two sets of thin wires on either side of an elastomeric component that joins together the leading and trailing edges of the hydrofoil. Controlled heating and cooling of the two wire sets generates bi-directional bending of the elastomer, which in turn deflects the trailing edge of the hydrofoil. In this paper the design of the hydrofoil and the experimental tests preformed thereon are explained. A detailed account of SMA actuator preparation (training) and material characterization is given. Finite-element method (FEM) modeling of hydrofoil response to electrical heating of the SMA actuators is carried out using a thermomechanical constitutive model for the SMA with input from the material characterization. The modeling predictions are finally compared with experimental measurements of the trailing edge deflection and the SMA actuator temperature.

Thematic mapper flight model preshipment review data package. Volume 4: Appendix. Part B: Scan mirror assembly data

NASA Technical Reports Server (NTRS)

1982-01-01

Data from the thematic mapper scan mirror assembly (SMA) acceptance test are presented. Documentation includes: (1) a list of the acceptance test discrepancies; (2) flight 1 SMA test data book; (3) flight 1 SMA environmental report; (4) the configuration verification index; (5) the flight 1 SMA test failure reports; (6) the flight 1 data tapes log; and (7) the requests for deviation/waivers.

Newborn screening for spinal muscular atrophy: Anticipating an imminent need.

PubMed

Phan, Han C; Taylor, Jennifer L; Hannon, Harry; Howell, Rodney

2015-04-01

Spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality. Children with type I SMA typically die by the age of 2 years. Recent progress in gene modification and other innovative therapies suggest that improved outcomes may soon be forthcoming. In animal models, therapeutic intervention initiated before the loss of motor neurons alters SMA phenotype and increases lifespan. Presently, supportive care including respiratory, nutritional, physiatry, and orthopedic management can ameliorate clinical symptoms and improve survival rates if SMA is diagnosed early in life. Newborn screening could help optimize these potential benefits. A recent report demonstrated that SMA detection can be multiplexed at minimal additional cost with the assay for severe combined immunodeficiency, already implemented by many newborn screening programs. The public health community should remain alert to the rapidly changing developments in early detection and treatment of SMA. Copyright © 2015 Elsevier Inc. All rights reserved.

Parental attitudes toward newborn screening for Duchenne/Becker muscular dystrophy and spinal muscular atrophy.

PubMed

Wood, Molly F; Hughes, Sarah C; Hache, Lauren P; Naylor, Edwin W; Abdel-Hamid, Hoda Z; Barmada, M Michael; Dobrowolski, Steven F; Stickler, David E; Clemens, Paula R

2014-06-01

Disease inclusion in the newborn screening (NBS) panel should consider the opinions of those most affected by the outcome of screening. We assessed the level and factors that affect parent attitudes regarding NBS panel inclusion of Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and spinal muscular atrophy (SMA). The attitudes toward NBS for DMD, BMD, and SMA were surveyed and compared for 2 categories of parents, those with children affected with DMD, BMD, or SMA and expectant parents unselected for known family medical history. The level of support for NBS for DMD, BMD, and SMA was 95.9% among parents of children with DMD, BMD, or SMA and 92.6% among expectant parents. There was strong support for NBS for DMD, BMD, and SMA in both groups of parents. Given advances in diagnostics and promising therapeutic approaches, discussion of inclusion in NBS should continue. Copyright © 2013 Wiley Periodicals, Inc.

Survival probabilities of patients with childhood spinal muscle atrophy.

PubMed

Mannaa, Mohannad M; Kalra, Maninder; Wong, Brenda; Cohen, Aliza P; Amin, Raouf S

2009-03-01

Medical and technological advances over the past 2 decades have resulted in improved patient care for children with spinal muscular atrophy (SMA). The objective of the present study was to describe changes in the life expectancy of pediatric patients with SMA over time and to compare these findings with previously reported survival patterns. Medical records of all patients diagnosed with SMA over a 16-year period (1989-2005) at Cincinnati Children's Hospital Medical Center were reviewed. Data pertaining to date of birth, type of SMA, medical and surgical interventions, pulmonary complications, and date of death were obtained. Kaplan-Meier survival analyses showed a significant improvement in survival probabilities in the severest form of SMA. We found a positive trend in the survival of patients with severe SMA. Although we cannot attribute this trend to any single factor, it is likely that advances in pulmonary care and aggressive nutritional support have played a significant role.

Stimulating neural plasticity with real‐time fMRI neurofeedback in Huntington's disease: A proof of concept study

PubMed Central

Papoutsi, Marina; Weiskopf, Nikolaus; Langbehn, Douglas; Reilmann, Ralf; Rees, Geraint

2017-01-01

Abstract Novel methods that stimulate neuroplasticity are increasingly being studied to treat neurological and psychiatric conditions. We sought to determine whether real‐time fMRI neurofeedback training is feasible in Huntington's disease (HD), and assess any factors that contribute to its effectiveness. In this proof‐of‐concept study, we used this technique to train 10 patients with HD to volitionally regulate the activity of their supplementary motor area (SMA). We collected detailed behavioral and neuroimaging data before and after training to examine changes of brain function and structure, and cognitive and motor performance. We found that patients overall learned to increase activity of the target region during training with variable effects on cognitive and motor behavior. Improved cognitive and motor performance after training predicted increases in pre‐SMA grey matter volume, fMRI activity in the left putamen, and increased SMA–left putamen functional connectivity. Although we did not directly target the putamen and corticostriatal connectivity during neurofeedback training, our results suggest that training the SMA can lead to regulation of associated networks with beneficial effects in behavior. We conclude that neurofeedback training can induce plasticity in patients with Huntington's disease despite the presence of neurodegeneration, and the effects of training a single region may engage other regions and circuits implicated in disease pathology. PMID:29239063

New laser machining processes for shape memory alloys

NASA Astrophysics Data System (ADS)

Haferkamp, Heinz; Paschko, Stefan; Goede, Martin

2001-04-01

Due to special material properties, shape memory alloys (SMA) are finding increasing attention in micro system technology. However, only a few processes are available for the machining of miniaturized SMA-components. In this connection, laser material processing offers completely new possibilities. This paper describes the actual status of two projects that are being carried out to qualify new methods to machine SMA components by means of laser radiation. Within one project, the laser material ablation process of miniaturized SMA- components using ultra-short laser pulses (pulse duration: approx. 200 fs) in comparison to conventional laser material ablation is being investigated. Especially for SMA micro- sensors and actuators, it is important to minimize the heat affected zone (HAZ) to maintain the special mechanical properties. Light-microscopic investigations of the grain texture of SMA devices processed with ultra-short laser pulses show that the HAZ can be neglected. Presently, the main goal of the project is to qualify this new processing technique for the micro-structuring of complex SMA micro devices with high precision. Within a second project, investigations are being carried out to realize the induction of the two-way memory effect (TWME) into SMA components using laser radiation. By precisely heating SMA components with laser radiation, local tensions remain near the component surface. In connection with the shape memory effect, these tensions can be used to make the components execute complicated movements. Compared to conventional training methods to induce the TWME, this procedure is faster and easier. Furthermore, higher numbers of thermal cycling are expected because of the low dislocation density in the main part of the component.

Primary motor cortex activity reduction under the regulation of SMA by real-time fMRI

NASA Astrophysics Data System (ADS)

Guo, Jia; Zhao, Xiaojie; Li, Yi; Yao, Li; Chen, Kewei

2012-03-01

Real-time fMRI (rtfMRI) is a new technology which allows human subjects to observe and control their own BOLD signal change from one or more localized brain regions during scanning. Current rtfMRI-neurofeedback studies mainly focused on the target region itself without considering other related regions influenced by the real-time feedback. However, there always exits important directional influence between many of cooperative regions. On the other hand, rtfMRI based on motor imagery mainly aimed at somatomotor cortex or primary motor area, whereas supplement motor area (SMA) was a relatively more integrated and pivotal region. In this study, we investigated whether the activities of SMA can be controlled utilizing different motor imagery strategies, and whether there exists any possible impact on an unregulated but related region, primary motor cortex (M1). SMA was first localized using overt finger tapping task, the activities of SMA were feedback to subjects visually on line during each of two subsequent imagery motor movement sessions. All thirteen healthy participants were found to be able to successfully control their SMA activities by self-fit imagery strategies which involved no actual motor movements. The activation of right M1 was also found to be significantly reduced in both intensity and extent with the neurofeedback process targeted at SMA, suggestive that not only the part of motor cortex activities were influenced under the regulation of a key region SMA, but also the increased difference between SMA and M1 might reflect the potential learning effect.

Increased IGF-1 in muscle modulates the phenotype of severe SMA mice

PubMed Central

Bosch-Marcé, Marta; Wee, Claribel D.; Martinez, Tara L.; Lipkes, Celeste E.; Choe, Dong W.; Kong, Lingling; Van Meerbeke, James P.; Musarò, Antonio; Sumner, Charlotte J.

2011-01-01

Spinal muscular atrophy (SMA) is an inherited motor neuron disease caused by the mutation of the survival motor neuron 1 (SMN1) gene and deficiency of the SMN protein. Severe SMA mice have abnormal motor function and small, immature myofibers early in development suggesting that SMN protein deficiency results in retarded muscle growth. Insulin-like growth factor 1 (IGF-1) stimulates myoblast proliferation, induces myogenic differentiation and generates myocyte hypertrophy in vitro and in vivo. We hypothesized that increased expression of IGF-1 specifically in skeletal muscle would attenuate disease features of SMAΔ7 mice. SMAΔ7 mice overexpressing a local isoform of IGF-1 (mIGF-1) in muscle showed enlarged myofibers and a 40% increase in median survival compared with mIGF-1-negative SMA littermates (median survival = 14 versus 10 days, respectively, log-rank P = 0.025). Surprisingly, this was not associated with a significant improvement in motor behavior. Treatment of both mIGF-1NEG and mIGF-1POS SMA mice with the histone deacetylase inhibitor, trichostatin A (TSA), resulted in a further extension of survival and improved motor behavior, but the combination of mIGF-1 and TSA treatment was not synergistic. These results show that increased mIGF-1 expression restricted to muscle can modulate the phenotype of SMA mice indicating that therapeutics targeted to muscle alone should not be discounted as potential disease-modifying therapies in SMA. IGF-1 may warrant further investigation in mild SMA animal models and perhaps SMA patients. PMID:21325354

Superior Mesenteric Artery Syndrome Improved by Enteral Nutritional Therapy according to the Controlling Nutritional Status Score.

PubMed

Takehara, Kazuhiro; Sakamoto, Kazuhiro; Takahashi, Rina; Kawai, Masaya; Kawano, Shingo; Munakata, Shinya; Sugimoto, Kiichi; Takahashi, Makoto; Kojima, Yutaka; Fukunaga, Tetsu; Kajiyama, Yoshiaki; Kawasaki, Seiji

2017-01-01

Superior mesenteric artery syndrome (SMAS) is a relatively rare disease that involves bowel obstruction symptoms, such as vomiting and gastric distension, owing to the compression of the third portion of the duodenum from the front by the superior mesenteric artery (SMA) and from the rear by the abdominal aorta and the spine. SMAS is diagnosed on the basis of an upper gastrointestinal examination series indicating the obstruction of the third portion of the duodenum or a computed tomography scan indicating the narrowing of the branch angle between the aorta and the SMA (i.e., the aorta-SMA angle). Here, we report the case of a 78-year-old woman diagnosed with SMAS after a laparoscopic right hemicolectomy for cecal cancer, whose condition was improved by enteral nutritional therapy. We used her controlling nutritional status (CONUT) score as a nutrition assessment and noted the changes in the aorta-SMA angle over the course of the disease. This patient appeared to develop SMAS, on the basis of a worsened CONUT score and a decreased aorta-SMA angle, owing to the inflammation resulting from the intraoperative dissection of the tissues around the SMA and prolonged postoperative fasting. After the initiation of enteral nutritional therapy, the patient exhibited body weight gain and an improved aorta-SMA angle and CONUT score. Hence, assessment of the aorta-SMA angle and CONUT score is an important preoperative consideration.

Systemic restoration of UBA1 ameliorates disease in spinal muscular atrophy

PubMed Central

Powis, Rachael A.; Karyka, Evangelia; Boyd, Penelope; Côme, Julien; Jones, Ross A.; Zheng, Yinan; Szunyogova, Eva; Groen, Ewout J.N.; Hunter, Gillian; Thomson, Derek; Wishart, Thomas M.; Becker, Catherina G.; Parson, Simon H.; Martinat, Cécile; Azzouz, Mimoun; Gillingwater, Thomas H.

2016-01-01

The autosomal recessive neuromuscular disease spinal muscular atrophy (SMA) is caused by loss of survival motor neuron (SMN) protein. Molecular pathways that are disrupted downstream of SMN therefore represent potentially attractive therapeutic targets for SMA. Here, we demonstrate that therapeutic targeting of ubiquitin pathways disrupted as a consequence of SMN depletion, by increasing levels of one key ubiquitination enzyme (ubiquitin-like modifier activating enzyme 1 [UBA1]), represents a viable approach for treating SMA. Loss of UBA1 was a conserved response across mouse and zebrafish models of SMA as well as in patient induced pluripotent stem cell–derive motor neurons. Restoration of UBA1 was sufficient to rescue motor axon pathology and restore motor performance in SMA zebrafish. Adeno-associated virus serotype 9–UBA1 (AAV9-UBA1) gene therapy delivered systemic increases in UBA1 protein levels that were well tolerated over a prolonged period in healthy control mice. Systemic restoration of UBA1 in SMA mice ameliorated weight loss, increased survival and motor performance, and improved neuromuscular and organ pathology. AAV9-UBA1 therapy was also sufficient to reverse the widespread molecular perturbations in ubiquitin homeostasis that occur during SMA. We conclude that UBA1 represents a safe and effective therapeutic target for the treatment of both neuromuscular and systemic aspects of SMA. PMID:27699224

Cervical Spinal Cord Atrophy Profile in Adult SMN1-Linked SMA

PubMed Central

El Mendili, Mohamed-Mounir; Lenglet, Timothée; Stojkovic, Tanya; Behin, Anthony; Guimarães-Costa, Raquel; Salachas, François; Meininger, Vincent; Bruneteau, Gaelle; Le Forestier, Nadine; Laforêt, Pascal; Lehéricy, Stéphane; Benali, Habib; Pradat, Pierre-François

2016-01-01

Purpose The mechanisms underlying the topography of motor deficits in spinal muscular atrophy (SMA) remain unknown. We investigated the profile of spinal cord atrophy (SCA) in SMN1-linked SMA, and its correlation with the topography of muscle weakness. Materials and Methods Eighteen SMN1-linked SMA patients type III/V and 18 age/gender-matched healthy volunteers were included. Patients were scored on manual muscle testing and functional scales. Spinal cord was imaged using 3T MRI system. Radial distance (RD) and cord cross-sectional area (CSA) measurements in SMA patients were compared to those in controls and correlated with strength and disability scores. Results CSA measurements revealed a significant cord atrophy gradient mainly located between C3 and C6 vertebral levels with a SCA rate ranging from 5.4% to 23% in SMA patients compared to controls. RD was significantly lower in SMA patients compared to controls in the anterior-posterior direction with a maximum along C4 and C5 vertebral levels (p-values < 10−5). There were no correlations between atrophy measurements, strength and disability scores. Conclusions Spinal cord atrophy in adult SMN1-linked SMA predominates in the segments innervating the proximal muscles. Additional factors such as neuromuscular junction or intrinsic skeletal muscle defects may play a role in more complex mechanisms underlying weakness in these patients. PMID:27089520

District nurses' use for an assessment tool in their daily work with elderly patients' medication management.

PubMed

Gusdal, Annelie K; Beckman, Christel; Wahlström, Rolf; Törnkvist, Lena

2011-06-01

To explore the capability of the Safe Medication Assessment (SMA) tool in identifying factors highly related to unsafe medication management among elderly patients and to investigate the district nurses' (DNs) opinions of the SMA's usefulness as a tool in their daily primary healthcare practice. Elderly patients who experience many medical conditions often use multiple drugs. As well as the combined decline in physical and cognitive functions, the elderly are at high risk for medication-related problems. It is essential to develop a screening procedure to distinguish elderly at risk of an unsafe medication management. An explorative study. During a 3-6-month period, 25 voluntary DNs used SMA with 160 patients (consecutively chosen and meeting four specified criteria) in their daily practice. Furthermore, DNs responded to questions regarding SMA's usefulness. The result showed that SMA had the capability to identify factors highly related to unsafe medication management among the elderly included in the study. In 64% of assessments DNs identified areas of new information and in 23% of the assessments DNs intervened. They found SMA to be satisfactory regarding its level of simplicity, relevance, completeness, intelligibility, and time for implementation. SMA alerted the DNs to patients' attitudes about medication and empowered them in identifying elderly patients who had unsafe medication management. SMA was also perceived as a useful assessment tool by the DNs.

Analysis and Evaluation of the Dynamic Performance of SMA Actuators for Prosthetic Hand Design

NASA Astrophysics Data System (ADS)

O'Toole, Kevin T.; McGrath, Mark M.; Coyle, Eugene

2009-08-01

It is widely acknowledged within the biomedical engineering community that shape memory alloys (SMAs) exhibit great potential for application in the actuation of upper limb prosthesis designs. These lightweight actuators are particularly suitable for prosthetic hand solutions. A four-fingered, 12 degree-of-freedom prosthetic hand has been developed featuring SMA bundle actuators embedded within the palmar structure. Joule heating of the SMA bundle actuators generates sufficient torque at the fingers to allow a wide range of everyday tasks to be carried out. Transient characterization of SMA bundles has shown that performance/response during heating and cooling differs substantially. Natural convection is insufficient to provide for adequate cooling during elongation of the actuators. An experimental test-bed has been developed to facilitate analysis of the heat transfer characteristics of the appropriately sized SMA bundle actuators for use within the prosthetic hand design. Various modes of heat sinking are evaluated so that the most effective wire-cooling solution can be ascertained. SMA bundles of varying size will be used so that a generalized model of the SMA displacement performance under natural and forced cooling conditions can be obtained. The optimum cooling solution will be implemented onto the mechanical hand framework in future work. These results, coupled with phenomenological models of SMA behavior, will be used in the development of an effective control strategy for this application in future work.

Spooled packaging of shape memory alloy actuators

NASA Astrophysics Data System (ADS)

Redmond, John A.

A vast cross-section of transportation, manufacturing, consumer product, and medical technologies rely heavily on actuation. Accordingly, progress in these industries is often strongly coupled to the advancement of actuation technologies. As the field of actuation continues to evolve, smart materials show significant promise for satisfying the growing needs of industry. In particular, shape memory alloy (SMA) wire actuators present an opportunity for low-cost, high performance actuation, but until now, they have been limited or restricted from use in many otherwise suitable applications by the difficulty in packaging the SMA wires within tight or unusually shaped form constraints. To address this packaging problem, SMA wires can be spool-packaged by wrapping around mandrels to make the actuator more compact or by redirecting around multiple mandrels to customize SMA wire pathways to unusual form factors. The goal of this dissertation is to develop the scientific knowledge base for spooled packaging of low-cost SMA wire actuators that enables high, predictable performance within compact, customizable form factors. In developing the scientific knowledge base, this dissertation defines a systematic general representation of single and multiple mandrel spool-packaged SMA actuators and provides tools for their analysis, understanding, and synthesis. A quasi-static analytical model distills the underlying mechanics down to the three effects of friction, bending, and binding, which enables prediction of the behavior of generic spool-packaged SMA actuators with specifiable geometric, loading, frictional, and SMA material parameters. An extensive experimental and simulation-based parameter study establishes the necessary understanding of how primary design tradeoffs between performance, packaging, and cost are governed by the underlying mechanics of spooled actuators. A design methodology outlines a systematic approach to synthesizing high performance SMA wire actuators with mitigated material, power, and packaging costs and compact, customizable form factors. By examining the multi-faceted connections between performance, packaging, and cost, this dissertation builds a knowledge base that goes beyond implementing SMA actuators for particular applications. Rather, it provides a well-developed strategy for realizing the advantages of SMA actuation for a broadened range of applications, thereby enabling opportunities for new functionality and capabilities in industry.

The utilization of video-conference shared medical appointments in rural diabetes care.

PubMed

Tokuda, Lisa; Lorenzo, Lenora; Theriault, Andre; Taveira, Tracey H; Marquis, Lynn; Head, Helene; Edelman, David; Kirsh, Susan R; Aron, David C; Wu, Wen-Chih

2016-09-01

To explore whether Video-Shared Medical Appointments (video-SMA), where group education and medication titration were provided remotely through video-conferencing technology would improve diabetes outcomes in remote rural settings. We conducted a pilot where a team of a clinical pharmacist and a nurse practitioner from Honolulu VA hospital remotely delivered video-SMA in diabetes to Guam. Patients with diabetes and HbA1c ≥7% were enrolled into the study during 2013-2014. Six groups of 4-6 subjects attended 4 weekly sessions, followed by 2 bi-monthly booster video-SMA sessions for 5 months. Patients with HbA1c ≥7% that had primary care visits during the study period but not referred/recruited for video-SMA were selected as usual-care comparators. We compared changes from baseline in HbA1c, blood-pressure, and lipid levels using mixed-effect modeling between video-SMA and usual care groups. We also analyzed emergency department (ED) visits and hospitalizations. Focus groups were conducted to understand patient's perceptions. Thirty-one patients received video-SMA and charts of 69 subjects were abstracted as usual-care. After 5 months, there was a significant decline in HbA1c in video-SMA vs. usual-care (9.1±1.9 to 8.3±1.8 vs. 8.6±1.4 to 8.7±1.6, P=0.03). No significant change in blood-pressure or lipid levels was found between the groups. Patients in the video-SMA group had significantly lower rates of ED visits (3.2% vs. 17.4%, P=0.01) than usual-care but similar hospitalization rates. Focus groups suggested patient satisfaction with video-SMA and increase in self-efficacy in diabetes self-care. Video-SMA is feasible, well-perceived and has the potential to improve diabetes outcomes in a rural setting. Published by Elsevier Ireland Ltd.

Histochemical and Immunohistochemical Study of α-SMA, Collagen, and PCNA in Epithelial Ovarian Neoplasm

PubMed

Anggorowati, Nungki; Ratna Kurniasari, Chatarina; Damayanti, Karina; Cahyanti, Titik; Widodo, Irianiwati; Ghozali, Ahmad; Romi, Muhammad Mansyur; Sari, Dwi Cahyani Ratna; Arfian, Nur

2017-03-01

Background: Alpha-smooth muscle actin (α-SMA) is an isoform of actin, positive in myofibroblasts and is an epithelial to mesenchymal transition (EMT) marker. EMT is a process by which tumor cells develop to be more hostile and able to metastasize. Progression of tumor cells is always followed by cell composition and extracellular matrix component alteration. Increased α-SMA expression and collagen alteration may predict the progressivity of ovarian neoplasms. Objective: The aim of this research was to analyse the characteristic of α-SMA and collagen in tumor cells and stroma of ovarian neoplasms. In this study, PCNA (proliferating cell nuclear antigen) expression was also investigated. Methods: Thirty samples were collected including serous, mucinous, endometrioid, and clear cell subtypes. The expression of α-SMA and PCNA were calculated in cells and stroma of ovarian tumors. Collagen was detected using Sirius Red staining and presented as area fraction. Results: The overexpressions of α-SMA in tumor cells were only detected in serous and clear cell ovarian carcinoma. The histoscore of α-SMA was higher in malignant than in benign or borderline ovarian epithelial neoplasms (105.3±129.9 vs. 17.3±17.1, P=0.011; mean±SD). Oppositely, stromal α-SMA and collagen area fractions were higher in benign than in malignant tumors (27.2±6.6 vs 20.5±8.4, P=0.028; 31.0±5.6 vs. 23.7±6.4, P=0.04). The percentages of epithelial and stromal PCNA expressions were not significantly different between benign and malignant tumors. Conclusion: Tumor cells of serous and clear cell ovarian carcinoma exhibit mesenchymal characteristic as shown by α-SMA positive expression. This expression might indicate that these subtypes were more aggressive. This research showed that collagen and α-SMA area fractions in stroma were higher in benign than in malignant neoplasms. 10.22034/APJCP.2017.18.3.667

Behavior of NiTiNb SMA wires under recovery stress or prestressing.

PubMed

Choi, Eunsoo; Nam, Tae-Hyun; Chung, Young-Soo; Kim, Yeon-Wook; Lee, Seung-Yong

2012-01-05

The recovery stress of martensitic shape-memory alloy [SMA] wires can be used to confine concrete, and the confining effectiveness of the SMA wires was previously proved through experimental tests. However, the behavior of SMA wires under recovery stress has not been seriously investigated. Thus, this study conducted a series of tests of NiTiNb martensitic SMA wires under recovery stress with varying degrees of prestrain on the wires and compared the behavior under recovery stress with that under prestressing of the wires. The remaining stress was reduced by the procedure of additional strain loading and unloading. More additional strains reduced more remaining stresses. When the SMA wires were heated up to the transformation temperature under prestress, the stress on the wires increased due to the state transformation. Furthermore, the stress decreased with a decreasing temperature of the wires down to room temperature. The stress of the NiTiNb wires was higher than the prestress, and the developed stress seemed to depend on the composition of the SMAs. When an additional strain was subsequently loaded and unloaded on the prestressed SMA wires, the remaining stress decreased. Finally, the remaining stress becomes zero when loading and unloading a specific large strain.

Fabrication and testing of SMA composite beam with shape control

NASA Astrophysics Data System (ADS)

Noolvi, Basavaraj; S, Raja; Nagaraj, Shanmukha; Mudradi, Varada Raj

2017-07-01

Smart materials are the advanced materials that have characteristics of sensing and actuation in response to the external stimuli like pressure, heat or electric charge etc. These materials can be integrated in to any structure to make it smart. From the different types of smart materials available, Shape Memory Alloy (SMA) is found to be more useful in designing new applications, which can offer more actuating speed, reduce the overall weight of the structure. The unique property of SMA is the ability to remember and recover from large strains of upto 8% without permanent deformation. Embedding the SMA wire/sheet in fiber-epoxy/flexible resin systems has many potential applications in Aerospace, Automobile, Medical, Robotics and various other fields. In this work the design, fabrication, and testing of smart SMA composite beam has been carried out. Two types of epoxy based resin systems namely LY 5210 resin system and EPOLAM 2063 resin system are used in fabricating the SMA composite specimens. An appropriate mould is designed and fabricated to retain the pre-strain of SMA wire during high temperature post curing of composite specimens. The specimens are fabricated using vacuum bag technique.

Establishing a reference dataset for the authentication of spinal muscular atrophy cell lines using STR profiling and digital PCR.

PubMed

Stabley, Deborah L; Holbrook, Jennifer; Harris, Ashlee W; Swoboda, Kathryn J; Crawford, Thomas O; Sol-Church, Katia; Butchbach, Matthew E R

2017-05-01

Fibroblasts and lymphoblastoid cell lines (LCLs) derived from individuals with spinal muscular atrophy (SMA) have been and continue to be essential for translational SMA research. Authentication of cell lines helps ensure reproducibility and rigor in biomedical research. This quality control measure identifies mislabeling or cross-contamination of cell lines and prevents misinterpretation of data. Unfortunately, authentication of SMA cell lines used in various studies has not been possible because of a lack of a reference. In this study, we provide said reference so that SMA cell lines can be subsequently authenticated. We use short tandem repeat (STR) profiling and digital PCR (dPCR), which quantifies SMN1 and SMN2 copy numbers, to generate molecular identity codes for fibroblasts and LCLs that are commonly used in SMA research. Using these molecular identity codes, we clarify the familial relationships within a set of fibroblasts commonly used in SMA research. This study presents the first cell line reference set for the SMA research community and demonstrates its usefulness for re-identification and authentication of lines commonly used as in vitro models for future studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Energy-dissipating and self-repairing SMA-ECC composite material system

NASA Astrophysics Data System (ADS)

Li, Xiaopeng; Li, Mo; Song, Gangbing

2015-02-01

Structural component ductility and energy dissipation capacity are crucial factors for achieving reinforced concrete structures more resistant to dynamic loading such as earthquakes. Furthermore, limiting post-event residual damage and deformation allows for immediate re-operation or minimal repairs. These desirable characteristics for structural ‘resilience’, however, present significant challenges due to the brittle nature of concrete, its deformation incompatibility with ductile steel, and the plastic yielding of steel reinforcement. Here, we developed a new composite material system that integrates the unique ductile feature of engineered cementitious composites (ECC) with superelastic shape memory alloy (SMA). In contrast to steel reinforced concrete (RC) and SMA reinforced concrete (SMA-RC), the SMA-ECC beams studied in this research exhibited extraordinary energy dissipation capacity, minimal residual deformation, and full self-recovery of damage under cyclic flexural loading. We found that the tensile strain capacity of ECC, tailored up to 5.5% in this study, allows it to work compatibly with superelastic SMA. Furthermore, the distributed microcracking damage mechanism in ECC is critical for sufficient and reliable recovery of damage upon unloading. This research demonstrates the potential of SMA-ECC for improving resilience of concrete structures under extreme hazard events.

X-linked infantile spinal muscular atrophy: clinical definition and molecular mapping.

PubMed

Dressman, Devin; Ahearn, Mary Ellen; Yariz, Kemal O; Basterrecha, Hugo; Martínez, Francisco; Palau, Francesc; Barmada, M Michael; Clark, Robin Dawn; Meindl, Alfons; Wirth, Brunhilde; Hoffman, Eric P; Baumbach-Reardon, Lisa

2007-01-01

X-linked infantile spinal-muscular atrophy (XL-SMA) is a rare disorder, which presents with the clinical characteristics of hypotonia, areflexia, and multiple congenital contractures (arthrogryposis) associated with loss of anterior horn cells and death in infancy. We have previously reported a single family with XL-SMA that mapped to Xp11.3-q11.2. Here we report further clinical description of XL-SMA plus an additional seven unrelated (XL-SMA) families from North America and Europe that show linkage data consistent with the same region. We first investigated linkage to the candidate disease gene region using microsatellite repeat markers. We further saturated the candidate disease gene region using polymorphic microsatellite repeat markers and single nucleotide polymorphisms in an effort to narrow the critical region. Two-point and multipoint linkage analysis was performed using the Allegro software package. Linkage analysis of all XL-SMA families displayed linkage consistent with the original XL-SMA region. The addition of new families and new markers has narrowed the disease gene interval for a XL-SMA locus between SNP FLJ22843 near marker DXS 8080 and SNP ARHGEF9 which is near DXS7132 (Xp11.3-Xq11.1).

Shape memory alloy resistance behaviour at high altitude for feedback control

NASA Astrophysics Data System (ADS)

Ng, W. T.; Sedan, M. F.; Abdullah, E. J.; Azrad, S.; Harithuddin, A. S. M.

2017-12-01

Many recent aerospace technologies are using smart actuators to reduce the system's complexity and increase its reliability. One such actuator is shape memory alloy (SMA) actuator, which is lightweight, produces high force and large deflection. However, some disadvantages in using SMA actuators have been identified and they include nonlinear response of the strain to input current, hysteresis characteristic that results in inaccurate control and less than optimum system performance, high operating temperatures, slow response and also high requirement of electrical power to obtain the desired actuation forces. It is still unknown if the SMA actuators can perform effectively at high altitude with low surrounding temperature. The work presented here covers the preliminary process of verifying the feasibility of using resistance as feedback control at high altitude for aerospace applications. Temperature and resistance of SMA actuator at high altitude is investigated by conducting an experiment onboard a high altitude balloon. The results from the high altitude experiment indicate that the resistance or voltage drop of the SMA wire is not significantly affected by the low surrounding temperature at high altitude as compared to the temperature of SMA. Resistance feedback control for SMA actuators may be suitable for aerospace applications.

Development of damage suppression system using embedded SMA foil sensor and actuator

NASA Astrophysics Data System (ADS)

Ogisu, Toshimichi; Nomura, Masato; Ando, Norio; Takaki, Junji; Song, Dong Y.; Takeda, Nobuo

2000-06-01

The recent studies suggest possible applications of shape memory alloy (SMA) for a smart health monitoring and suppression of damage growth. The authors have been conducting research and development studies on applications of embedded SMA foil sensors and actuators in CFRP laminates. The goal of this research is suppression of damage growth in CFRP laminates. At first, the authors proposed a concept of damage suppression in CFRP laminates. Then, the development studies are conducted in three phases. The first phase is the improvement of interlaminar shear strength between SMA and CFRP laminates. Some surface treatments were investigated for the improvement of bonding property by peel resistance test and single lap shear strength test. The second phase is the investigation of fabrication technique for producing a CFRP panel with embedded SMA foils. Fixture jigs were devised to introduce tensile loads during the fabrication process. The third phase is the strength demonstration of CFRP laminates with embedded SMA foils. Some strength test were conducted to obtain the design data for aircraft structures. It is confirmed that the shrinking force of pre-strained SMA influences to the strength and the crack density of CFRP panel.

Potentiation of motor sub-networks for motor control but not working memory: Interaction of dACC and SMA revealed by resting-state directed functional connectivity

PubMed Central

Diwadkar, Vaibhav A.; Asemi, Avisa; Burgess, Ashley; Chowdury, Asadur; Bressler, Steven L.

2017-01-01

The dorsal Anterior Cingulate Cortex (dACC) and the Supplementary Motor Area (SMA) are known to interact during motor coordination behavior. We previously discovered that the directional influences underlying this interaction in a visuo-motor coordination task are asymmetric, with the dACC→SMA influence being significantly greater than that in the reverse direction. To assess the specificity of this effect, here we undertook an analysis of the interaction between dACC and SMA in two distinct contexts. In addition to the motor coordination task, we also assessed these effects during a (n-back) working memory task. We applied directed functional connectivity analysis to these two task paradigms, and also to the rest condition of each paradigm, in which rest blocks were interspersed with task blocks. We report here that the previously known asymmetric interaction between dACC and SMA, with dACC→SMA dominating, was significantly larger in the motor coordination task than the memory task. Moreover the asymmetry between dACC and SMA was reversed during the rest condition of the motor coordination task, but not of the working memory task. In sum, the dACC→SMA influence was significantly greater in the motor task than the memory task condition, and the SMA→dACC influence was significantly greater in the motor rest than the memory rest condition. We interpret these results as suggesting that the potentiation of motor sub-networks during the motor rest condition supports the motor control of SMA by dACC during the active motor task condition. PMID:28278267

Preoperative mapping of the supplementary motor area in patients harboring tumors in the medial frontal lobe.

PubMed

Nelson, Lindsey; Lapsiwala, Samir; Haughton, Victor M; Noyes, Jane; Sadrzadeh, Amir H; Moritz, Chad H; Meyerand, M Elizabeth; Badie, Behnam

2002-11-01

Injury to the supplementary motor area (SMA) is thought to be responsible for transient motor and speech deficits following resection of tumors involving the medial frontal lobe. Because direct intraoperative localization of SMA is difficult, the authors hypothesized that functional magnetic resonance (fMR) imaging might be useful in predicting the risk of postoperative deficits in patients who undergo resection of tumors in this region. Twelve patients who had undergone fMR imaging mapping while performing speech and motor tasks prior to excision of their tumor, that is, based on anatomical landmarks involving the SMA, were included in this study. The distance between the edge of the tumor and the center of SMA activation was measured and was correlated with the risk of incurring postoperative neurological deficits. In every patient, SMA activation was noted in the superior frontal gyrus on preoperative fMR imaging. Two speech and two motor deficits typical of SMA injury were observed in three of the 12 patients. The two speech deficits occurred in patients with tumors involving the dominant hemisphere, whereas one of the motor deficits occurred in a patient with a tumor in the nondominant hemisphere. The risk of developing a postoperative speech or motor deficit was 100% when the distance between the SMA and the tumor was 5 mm or less. When the distance between SMA activation and the lesion was greater than 5 mm, the risk of developing a motor or a speech deficit was 0% (p = 0.0007). Early data from this study indicated that fMR imaging might be useful in localizing the SMA and in determining the risk of postoperative deficits in patients who undergo resection of tumors located in the medial frontal lobe.

SMA spring-based artificial muscle actuated by hot and cool water using faucet-like valve

NASA Astrophysics Data System (ADS)

Park, Cheol Hoon; Son, Young Su

2017-04-01

An artificial muscle for a human arm-like manipulator with high strain and high power density are under development, and an SMA(Shape memory alloy) spring is a good actuator for this application. In this study, an artificial muscle composed of a silicon tube and a bundle of SMA(Shape memory alloy) springs is evaluated. A bundle of SMA springs consists of five SMA springs which are fabricated by using SMA wires with a diameter of 0.5 mm, and hot and cool water actuates it by heating and cooling SMA springs. A faucet-like valve was also developed to mix hot water and cool water and control the water temperature. The mass of silicon tube and a bundle of SMA springs is only 3.3 g and 2.25 g, respectively, and the total mass of artificial muscle is 5.55 g. It showed good actuating performance for a load with a mass of 2.3 kg and the power density was more than 800 W/kg for continuous valve switching with a cycle of 0.6 s. The faucet-like valve can switch a water output from hot water to cold water within 0.3s, and the artificial muscle is actuated well in response to the valve position and speed. It is also presented that the temperature of the mixed water can be controlled depending on the valve position, and the displacement of the artificial muscle can be controlled well by the mixed water. Based on these results, SMA spring-based artificial muscle actuated by hot and cool water could be applicable to the human arm-like robot manipulators.

Cortico-Cortical White Matter Motor Pathway Microstructure Is Related to Psychomotor Retardation in Major Depressive Disorder

PubMed Central

Bracht, Tobias; Federspiel, Andrea; Schnell, Susanne; Horn, Helge; Höfle, Oliver; Wiest, Roland; Dierks, Thomas; Strik, Werner; Müller, Thomas J.; Walther, Sebastian

2012-01-01

Alterations of brain structure and function have been associated with psychomotor retardation in major depressive disorder (MDD). However, the association of motor behaviour and white matter integrity of motor pathways in MDD is unclear. The aim of the present study was to first investigate structural connectivity of white matter motor pathways in MDD. Second, we explore the relation of objectively measured motor activity and white matter integrity of motor pathways in MDD. Therefore, 21 patients with MDD and 21 healthy controls matched for age, gender, education and body mass index underwent diffusion tensor imaging and 24 hour actigraphy (measure of the activity level) the same day. Applying a probabilistic fibre tracking approach we extracted connection pathways between the dorsolateral prefrontal cortex (dlPFC), the rostral anterior cingulate cortex (rACC), the pre-supplementary motor area (pre-SMA), the SMA-proper, the primary motor cortex (M1), the caudate nucleus, the putamen, the pallidum and the thalamus. Patients had lower activity levels and demonstrated increased mean diffusivity (MD) in pathways linking left pre-SMA and SMA-proper, and right SMA-proper and M1. Exploratory analyses point to a positive association of activity level and mean-fractional anisotropy in the right rACC-pre-SMA connection in MDD. Only MDD patients with low activity levels had a negative linear association of activity level and mean-MD in the left dlPFC-pre-SMA connection. Our results point to structural alterations of cortico-cortical white matter motor pathways in MDD. Altered white matter organisation of rACC-pre-SMA and dlPFC-pre-SMA pathways may contribute to movement initiation in MDD. PMID:23284950

The effectiveness of styrene-maleic acid (SMA) copolymers for solubilisation of integral membrane proteins from SMA-accessible and SMA-resistant membranes.

PubMed

Swainsbury, David J K; Scheidelaar, Stefan; Foster, Nicholas; van Grondelle, Rienk; Killian, J Antoinette; Jones, Michael R

2017-10-01

Solubilisation of biological lipid bilayer membranes for analysis of their protein complement has traditionally been carried out using detergents, but there is increasing interest in the use of amphiphilic copolymers such as styrene maleic acid (SMA) for the solubilisation, purification and characterisation of integral membrane proteins in the form of protein/lipid nanodiscs. Here we survey the effectiveness of various commercially-available formulations of the SMA copolymer in solubilising Rhodobacter sphaeroides reaction centres (RCs) from photosynthetic membranes. We find that formulations of SMA with a 2:1 or 3:1 ratio of styrene to maleic acid are almost as effective as detergent in solubilising RCs, with the best solubilisation by short chain variants (<30kDa weight average molecular weight). The effectiveness of 10kDa 2:1 and 3:1 formulations of SMA to solubilise RCs gradually declined when genetically-encoded coiled-coil bundles were used to artificially tether normally monomeric RCs into dimeric, trimeric and tetrameric multimers. The ability of SMA to solubilise reaction centre-light harvesting 1 (RC-LH1) complexes from densely packed and highly ordered photosynthetic membranes was uniformly low, but could be increased through a variety of treatments to increase the lipid:protein ratio. However, proteins isolated from such membranes comprised clusters of complexes in small membrane patches rather than individual proteins. We conclude that short-chain 2:1 and 3:1 formulations of SMA are the most effective in solubilising integral membrane proteins, but that solubilisation efficiencies are strongly influenced by the size of the target protein and the density of packing of proteins in the membrane. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Cortico-cortical white matter motor pathway microstructure is related to psychomotor retardation in major depressive disorder.

PubMed

Bracht, Tobias; Federspiel, Andrea; Schnell, Susanne; Horn, Helge; Höfle, Oliver; Wiest, Roland; Dierks, Thomas; Strik, Werner; Müller, Thomas J; Walther, Sebastian

2012-01-01

Alterations of brain structure and function have been associated with psychomotor retardation in major depressive disorder (MDD). However, the association of motor behaviour and white matter integrity of motor pathways in MDD is unclear. The aim of the present study was to first investigate structural connectivity of white matter motor pathways in MDD. Second, we explore the relation of objectively measured motor activity and white matter integrity of motor pathways in MDD. Therefore, 21 patients with MDD and 21 healthy controls matched for age, gender, education and body mass index underwent diffusion tensor imaging and 24 hour actigraphy (measure of the activity level) the same day. Applying a probabilistic fibre tracking approach we extracted connection pathways between the dorsolateral prefrontal cortex (dlPFC), the rostral anterior cingulate cortex (rACC), the pre-supplementary motor area (pre-SMA), the SMA-proper, the primary motor cortex (M1), the caudate nucleus, the putamen, the pallidum and the thalamus. Patients had lower activity levels and demonstrated increased mean diffusivity (MD) in pathways linking left pre-SMA and SMA-proper, and right SMA-proper and M1. Exploratory analyses point to a positive association of activity level and mean-fractional anisotropy in the right rACC-pre-SMA connection in MDD. Only MDD patients with low activity levels had a negative linear association of activity level and mean-MD in the left dlPFC-pre-SMA connection. Our results point to structural alterations of cortico-cortical white matter motor pathways in MDD. Altered white matter organisation of rACC-pre-SMA and dlPFC-pre-SMA pathways may contribute to movement initiation in MDD.

Does depression treatment improve the survival of depressed patients with cancer? A long-term follow-up of participants in the SMaRT Oncology-2 and 3 trials.

PubMed

Mulick, Amy; Walker, Jane; Puntis, Stephen; Burke, Katy; Symeonides, Stefan; Gourley, Charlie; Wanat, Marta; Frost, Chris; Sharpe, Michael

2018-04-01

Comorbid major depression has been associated with worse survival in patients with cancer. However, we do not know if treating depression improves survival. In the SMaRT Oncology-2 (good prognosis cancers) and SMaRT Oncology-3 (lung cancer, a poor prognosis cancer) trials, we found that a depression treatment programme, Depression Care for People with Cancer (DCPC), was effective in reducing comorbid major depression. In this analysis, we aimed to identify whether DCPC also had an effect on survival. The trials were conducted in three cancer centres and their associated clinics in Scotland, UK. In SMaRT Oncology-2, outpatients with good prognosis cancers and major depression were randomly assigned in a 1:1 ratio to DCPC or usual care, with stratification (by trial centre) and minimisation (by age, primary cancer, and sex) with allocation concealment. In SMaRT Oncology-3, outpatients with lung cancer and major depression were randomly assigned (1:1 ratio) to DCPC or usual care with stratification (by trial centre) and minimisation (by age, sex, and cancer type) with allocation concealment. For this analysis, we obtained long-term data on deaths (all causes) in the SMaRT Oncology-2 and 3 trial participants, censored at July 31, 2015, and analysed survival as a trial outcome. We estimated unadjusted hazard ratios (HRs) for each trial using Cox regression, and pooled the log HRs in a fixed-effects meta-analysis. We recruited 642 participants; between May 12, 2008, and May 13, 2011, 500 participants were recruited to the SMaRT Oncology-2 trial and between Jan 5, 2009, and Sept 9, 2011, 142 participants were recruited to the SMaRT Oncology-3 trial. We followed up SMaRT Oncology-2 and SMaRT Oncology-3 participants for a median of 5 years and 1 year, respectively. 135 (27%) of 500 SMaRT Oncology-2 participants and 114 (80%) of 142 SMaRT Oncology-3 participants died within this period. We found no significant effect of DCPC on survival in the total follow-up period for either SMaRT Oncology 2 (HR 1·02, 95% CI 0·72-1·42, p=0·93) or SMaRT Oncology-3 (HR 0·82, 95% CI 0·56-1·18, p=0·28; pooled HR 0·92, 95% CI 0·72-1·18, p=0·51). DCPC is highly effective in improving depression and quality of life in depressed patients with cancer, but there was no evidence for a significant effect on survival. Despite the absence of an effect on length of life, the management of depression remains important for its beneficial effect on quality of life. NIHR CLAHRC Oxford, Cancer Research UK, and the Chief Scientist Office of the Scottish Government. Copyright © 2018 Elsevier Ltd. All rights reserved.

Shape memory alloy heat engines and energy harvesting systems

DOEpatents

Browne, Alan L; Johnson, Nancy L; Shaw, John Andrew; Churchill, Christopher Burton; Keefe, Andrew C; McKnight, Geoffrey P; Alexander, Paul W; Herrera, Guillermo A; Yates, James Ryan; Brown, Jeffrey W

2014-09-30

A heat engine includes a first rotatable pulley and a second rotatable pulley spaced from the first rotatable pulley. A shape memory alloy (SMA) element is disposed about respective portions of the pulleys at an SMA pulley ratio. The SMA element includes a first wire, a second wire, and a matrix joining the first wire and the second wire. The first wire and the second wire are in contact with the pulleys, but the matrix is not in contact with the pulleys. A timing cable is disposed about respective portions of the pulleys at a timing pulley ratio, which is different than the SMA pulley ratio. The SMA element converts a thermal energy gradient between the hot region and the cold region into mechanical energy.

Finite Element Analysis of Adaptive-Stiffening and Shape-Control SMA Hybrid Composites

NASA Technical Reports Server (NTRS)

Gao, Xiujie; Burton, Deborah; Turner, Travis L.; Brinson, Catherine

2005-01-01

Shape memory alloy hybrid composites with adaptive-stiffening or morphing functions are simulated using finite element analysis. The composite structure is a laminated fiber-polymer composite beam with embedded SMA ribbons at various positions with respect to the neutral axis of the beam. Adaptive stiffening or morphing is activated via selective resistance heating of the SMA ribbons or uniform thermal loads on the beam. The thermomechanical behavior of these composites was simulated in ABAQUS using user-defined SMA elements. The examples demonstrate the usefulness of the methods for the design and simulation of SMA hybrid composites. Keywords: shape memory alloys, Nitinol, ABAQUS, finite element analysis, post-buckling control, shape control, deflection control, adaptive stiffening, morphing, constitutive modeling, user element

Smart flight control

NASA Astrophysics Data System (ADS)

Larson, Brett; Bartlett, James P.; O'Hearn, Steve; Adams, Clinton

2001-04-01

Shape Memory Alloy (SMA) wire technology was used as primary flight control actuators on a 99-inch wingspan remote controlled aircraft. Modifications were made to a Dynaflite Butterfly and its Futaba remote control system. Comparisons were recorded between the original Futaba electric motor servo system and the SMA actuator system in terms of input power requirement, response time, actuation geometry, output power, and proportional control characteristics. The advantages and limitations of this application of SMA technology were exposed. This project shed light on further possibilities for use of SMA technology that could eliminate much of the weight, complexity, and cost associated with current use of remote actuation and linkage systems. It is the author's hope that the information presented herein will help facilitate further development of SMA in highly critical miniature applications.

Protostellar accretion traced with chemistry. High-resolution C18O and continuum observations towards deeply embedded protostars in Perseus

NASA Astrophysics Data System (ADS)

Frimann, Søren; Jørgensen, Jes K.; Dunham, Michael M.; Bourke, Tyler L.; Kristensen, Lars E.; Offner, Stella S. R.; Stephens, Ian W.; Tobin, John J.; Vorobyov, Eduard I.

2017-06-01

Context. Understanding how accretion proceeds is a key question of star formation, with important implications for both the physical and chemical evolution of young stellar objects. In particular, very little is known about the accretion variability in the earliest stages of star formation. Aims: Our aim is to characterise protostellar accretion histories towards individual sources by utilising sublimation and freeze-out chemistry of CO. Methods: A sample of 24 embedded protostars are observed with the Submillimeter Array (SMA) in context of the large program "Mass Assembly of Stellar Systems and their Evolution with the SMA" (MASSES). The size of the C18O-emitting region, where CO has sublimated into the gas-phase, is measured towards each source and compared to the expected size of the region given the current luminosity. The SMA observations also include 1.3 mm continuum data, which are used to investigate whether or not a link can be established between accretion bursts and massive circumstellar disks. Results: Depending on the adopted sublimation temperature of the CO ice, between 20% and 50% of the sources in the sample show extended C18O emission indicating that the gas was warm enough in the past that CO sublimated and is currently in the process of refreezing; something which we attribute to a recent accretion burst. Given the fraction of sources with extended C18O emission, we estimate an average interval between bursts of 20 000-50 000 yr, which is consistent with previous estimates. No clear link can be established between the presence of circumstellar disks and accretion bursts, however the three closest known binaries in the sample (projected separations <20 AU) all show evidence of a past accretion burst, indicating that close binary interactions may also play a role in inducing accretion variability.

A 1.3 mm SMA survey of 29 variable young stellar objects

NASA Astrophysics Data System (ADS)

Liu, Hauyu Baobab; Dunham, Michael M.; Pascucci, Ilaria; Bourke, Tyler L.; Hirano, Naomi; Longmore, Steven; Andrews, Sean; Carrasco-González, Carlos; Forbrich, Jan; Galván-Madrid, Roberto; Girart, Josep M.; Green, Joel D.; Juárez, Carmen; Kóspál, Ágnes; Manara, Carlo F.; Palau, Aina; Takami, Michihiro; Testi, Leonardo; Vorobyov, Eduard I.

2018-04-01

Context. Young stellar objects (YSOs) may undergo periods of active accretion (outbursts), during which the protostellar accretion rate is temporarily enhanced by a few orders of magnitude. Whether or not these accretion outburst YSOs possess similar dust and gas reservoirs to each other, and whether or not their dust and gas reservoirs are similar as quiescent YSOs, are issues yet to be clarified. Aims: The aim of this work is to characterize the millimeter thermal dust emission properties of a statistically significant sample of long and short duration accretion outburst YSOs (i.e., FUors and EXors) and the spectroscopically identified candidates of accretion outbursting YSOs (i.e., FUor-like objects). Methods: We have carried out extensive Submillimeter Array (SMA) observations mostly at 225 GHz (1.33 mm) and 272 GHz (1.10 mm), from 2008 to 2017. We covered accretion outburst YSOs located at <1 kpc distances from the solar system. Results: We analyze all the existing SMA data of such objects, both published and unpublished, in a coherent way to present a millimeter interferometric database of 29 objects. We obtained 21 detections at >3σ significance. Detected sources except for the two cases of V883 Ori and NGC 2071 MM3 were observed with 1″ angular resolution. Overall our observed targets show a systematically higher millimeter luminosity distribution than those of the M* > 0.3 M⊙ Class II YSOs in the nearby (≲400 pc) low-mass star-forming molecular clouds (e.g., Taurus, Lupus, Upp Scorpio, and Chameleon I). In addition, at 1 mm our observed confirmed binaries or triple-system sources are systematically fainter than the rest of the sources even though their 1 mm fluxes are broadly distributed. We may have detected 30-60% millimeter flux variability from V2494 Cyg and V2495 Cyg, from the observations separated by approximately one year.

Human Medial Frontal Cortex Mediates Unconscious Inhibition of Voluntary Action

PubMed Central

Sumner, Petroc; Nachev, Parashkev; Morris, Peter; Peters, Andrew M.; Jackson, Stephen R.; Kennard, Christopher; Husain, Masud

2007-01-01

Summary Within the medial frontal cortex, the supplementary eye field (SEF), supplementary motor area (SMA), and pre-SMA have been implicated in the control of voluntary action, especially during motor sequences or tasks involving rapid choices between competing response plans. However, the precise roles of these areas remain controversial. Here, we study two extremely rare patients with microlesions of the SEF and SMA to demonstrate that these areas are critically involved in unconscious and involuntary motor control. We employed masked-prime stimuli that evoked automatic inhibition in healthy people and control patients with lateral premotor or pre-SMA damage. In contrast, our SEF/SMA patients showed a complete reversal of the normal inhibitory effect—ocular or manual—corresponding to the functional subregion lesioned. These findings imply that the SEF and SMA mediate automatic effector-specific suppression of motor plans. This automatic mechanism may contribute to the participation of these areas in the voluntary control of action. PMID:17553420

Rapid prototyping prosthetic hand acting by a low-cost shape-memory-alloy actuator.

PubMed

Soriano-Heras, Enrique; Blaya-Haro, Fernando; Molino, Carlos; de Agustín Del Burgo, José María

2018-06-01

The purpose of this article is to develop a new concept of modular and operative prosthetic hand based on rapid prototyping and a novel shape-memory-alloy (SMA) actuator, thus minimizing the manufacturing costs. An underactuated mechanism was needed for the design of the prosthesis to use only one input source. Taking into account the state of the art, an underactuated mechanism prosthetic hand was chosen so as to implement the modifications required for including the external SMA actuator. A modular design of a new prosthesis was developed which incorporated a novel SMA actuator for the index finger movement. The primary objective of the prosthesis is achieved, obtaining a modular and functional low-cost prosthesis based on additive manufacturing executed by a novel SMA actuator. The external SMA actuator provides a modular system which allows implementing it in different systems. This paper combines rapid prototyping and a novel SMA actuator to develop a new concept of modular and operative low-cost prosthetic hand.

Mouse strains to study cold-inducible beige progenitors and beige adipocyte formation and function

PubMed Central

Berry, Daniel C.; Jiang, Yuwei; Graff, Jonathan M.

2016-01-01

Cold temperatures induce formation of beige adipocytes, which convert glucose and fatty acids to heat, and may increase energy expenditure, reduce adiposity and lower blood glucose. This therapeutic potential is unrealized, hindered by a dearth of genetic tools to fate map, track and manipulate beige progenitors and ‘beiging'. Here we examined 12 Cre/inducible Cre mouse strains that mark adipocyte, muscle and mural lineages, three proposed beige origins. Among these mouse strains, only those that marked perivascular mural cells tracked the cold-induced beige lineage. Two SMA-based strains, SMA-CreERT2 and SMA-rtTA, fate mapped into the majority of cold-induced beige adipocytes and SMA-marked progenitors appeared essential for beiging. Disruption of the potential of the SMA-tracked progenitors to form beige adipocytes was accompanied by an inability to maintain body temperature and by hyperglycaemia. Thus, SMA-engineered mice may be useful to track and manipulate beige progenitors, beige adipocyte formation and function. PMID:26729601

Motor Neuron Rescue in Spinal Muscular Atrophy Mice Demonstrates That Sensory-Motor Defects Are a Consequence, Not a Cause, of Motor Neuron Dysfunction

PubMed Central

Gogliotti, Rocky G.; Quinlan, Katharina A.; Barlow, Courtenay B.; Heier, Christopher R.; Heckman, C. J.

2012-01-01

The loss of motor neurons (MNs) is a hallmark of the neuromuscular disease spinal muscular atrophy (SMA); however, it is unclear whether this phenotype autonomously originates within the MN. To address this question, we developed an inducible mouse model of severe SMA that has perinatal lethality, decreased motor function, motor unit pathology, and hyperexcitable MNs. Using an Hb9-Cre allele, we increased Smn levels autonomously within MNs and demonstrate that MN rescue significantly improves all phenotypes and pathologies commonly described in SMA mice. MN rescue also corrects hyperexcitability in SMA motor neurons and prevents sensory-motor synaptic stripping. Survival in MN-rescued SMA mice is extended by only 5 d, due in part to failed autonomic innervation of the heart. Collectively, this work demonstrates that the SMA phenotype autonomously originates in MNs and that sensory-motor synapse loss is a consequence, not a cause, of MN dysfunction. PMID:22423102

Modeling and development of a twisting wing using inductively heated shape memory alloy actuators

NASA Astrophysics Data System (ADS)

Saunders, Robert N.; Hartl, Darren J.; Boyd, James G.; Lagoudas, Dimitris C.

2015-04-01

Wing twisting has been shown to improve aircraft flight performance. The potential benefits of a twisting wing are often outweighed by the mass of the system required to twist the wing. Shape memory alloy (SMA) actuators repeatedly demonstrate abilities and properties that are ideal for aerospace actuation systems. Recent advances have shown an SMA torsional actuator that can be manufactured and trained with the ability to generate large twisting deformations under substantial loading. The primary disadvantage of implementing large SMA actuators has been their slow actuation time compared to conventional actuators. However, inductive heating of an SMA actuator allows it to generate a full actuation cycle in just seconds rather than minutes while still . The aim of this work is to demonstrate an experimental wing being twisted to approximately 10 degrees by using an inductively heated SMA torsional actuator. This study also considers a 3-D electromagnetic thermo-mechanical model of the SMA-wing system and compare these results to experiments to demonstrate modeling capabilities.

Strategies employed by sexual minority adolescents to cope with minority stress.

PubMed

Goldbach, J T; Gibbs, J J

2015-09-01

Sexual minority adolescents (SMA) experience disparities in health and behavioral health outcomes, including high rates of depression, anxiety, self-harm, substance use, HIV risk behavior, suicidal ideation, and suicide attempts. These outcomes are commonly attributed to minority stress. Stress experiences are different for SMA than their adult counterparts. For example, disclosing their sexual orientation may be more likely to result in homelessness because these youth more often live with parents or other family members. Although stress in this population has been explored in previous research, very little is known about how SMA cope. Relying upon an adolescent coping model, this study examined the coping strategies, responses, and resources of SMA related to stress. Forty-eight racially and ethnically diverse SMA (age 14-19) were recruited for 90-minute tape-recorded interviews. The semi-structured interviews were guided by a life history calendar. Recordings were transcribed verbatim and entered into QSR NVivo. All transcripts were coded by two members of the research team and went through a consensus process. Forty-three unique coping statements emerged that fit with the Compas model of adolescent coping. SMA cope with minority stress in similar ways to heterosexual youth coping with general stress, but findings suggest that SMA may also use different kinds of coping resources. Although further research is needed, the present study identified a variety of ways SMA cope with stress and can inform future research on the development interventions.

Antitumor activity of 7-O-succinyl macrolactin A tromethamine salt in the mouse glioma model.

PubMed

Jin, Jun; Choi, Suh Hee; Lee, Jung Eun; Joo, Jin-Deok; Han, Jung Ho; Park, Su-Young; Kim, Chae-Yong

2017-05-01

Chemoradiotherapy with temozolomide is the current standard treatment option for patients with glioblastoma. However, the majority of patients with glioblastoma survive for <2 years. Therefore, it is necessary to develop more effective therapeutic strategies for the treatment of glioblastoma. 7-O-succinyl macrolactin A tromethamine salt (SMA salt), a macrolactin compound, is known to possess an antiangiogenic activity. The present study investigated the antitumor effects of SMA salt in the treatment of glioblastoma by evaluating in vitro and in vivo antitumor effects of SMA salt in an experimental glioblastoma model. The antitumor effects of the drug on human glioblastoma U87MG, U251MG and LN229 cell lines were assessed using in vitro cell viability, migration and invasion assays. Nude mice with established U87MG glioblastoma were assigned to either the control or SMA salt treatment group. The volume of tumors and the duration of survival were also measured. SMA salt affected cell viability and caused a concentration-dependent inhibition effect on the migration and invasion of glioblastoma cell lines. Animals in the SMA salt treatment group demonstrated a significant reduction in tumor volume and an increase in survival (P<0.05). Treatment with SMA salt presented more cytotoxic effects as well as anti-migration and anti-invasion activity compared with the control group in vitro and in vivo . These results suggest that SMA salt has significant antitumor effects on glioblastoma.

Development and Verification of Sputtered Thin-Film Nickel-Titanium (NiTi) Shape Memory Alloy (SMA)

DTIC Science & Technology

2015-08-01

Shape Memory Alloy (SMA) by Cory R Knick and Christopher J Morris Approved for public release; distribution unlimited...Laboratory Development and Verification of Sputtered Thin-Film Nickel-Titanium (NiTi) Shape Memory Alloy (SMA) by Cory R Knick and Christopher

Preisach modeling of piezoceramic and shape memory alloy hysteresis

NASA Astrophysics Data System (ADS)

Hughes, Declan; Wen, John T.

1997-06-01

Smart materials such as piezoceramics, magnetostrictive materials, and shape memory alloys exhibit hysteresis, and the larger the input signal the larger the effect. Hysteresis can lead to unwanted harmonics, inaccuracy in open loop control, and instability in closed loop control. The Preisach independent domain hysteresis model has been shown to capture the major features of hysteresis arising in ferromagnetic materials. Noting the similarity between the microscopic domain kinematics that generate static hysteresis effects in ferromagnetics, piezoceramics, and shape memory alloys (SMAs), we apply the Preisach model for the hysteresis in piezoceramic and shape memory alloy materials. This paper reviews the basic properties of the Preisach model, discusses control-theoretic issues such as identification, simulation, and inversion, and presents experimental results for piezoceramic sheet actuators bonded to a flexible aluminum beam, and a Nitinol SMA wire muscle that applies a bending force to the end of a beam.

Preisach modeling of piezoceramic and shape memory alloy hysteresis

NASA Astrophysics Data System (ADS)

Hughes, Declan C.; Wen, John T.

1996-05-01

Smart materials such as piezoceramics, magnetostrictive materials, and shape memory alloys exhibit significant hysteresis, especially when driven with large input signals. Hysteresis can lead to unwanted harmonics, inaccuracy in open loop control, and instability in closed loop control. The Preisach independent domain hysteresis model has been shown to capture the major features of hysteresis arising in ferromagnetic materials. Noting the similarity between the microscopic domain kinematics that generate static hysteresis effects in ferromagnetics, piezoceramics, and shape memory alloys, we apply the Preisach model for the hysteresis in piezoceramic and shape memory alloy materials. This paper reviews the basic properties of the Preisach model, discusses control-theoretic issues such as identification, simulation, and inversion, and presents experimental results for piezoceramic sheet actuators bonded to a flexible aluminum beam, and a Nitinol SMA wire muscle that applies a bending force to the end of a beam.

The influence of expertise on brain activation of the action observation network during anticipation of tennis and volleyball serves.

PubMed

Balser, Nils; Lorey, Britta; Pilgramm, Sebastian; Naumann, Tim; Kindermann, Stefan; Stark, Rudolf; Zentgraf, Karen; Williams, A Mark; Munzert, Jörn

2014-01-01

In many daily activities, and especially in sport, it is necessary to predict the effects of others' actions in order to initiate appropriate responses. Recently, researchers have suggested that the action-observation network (AON) including the cerebellum plays an essential role during such anticipation, particularly in sport expert performers. In the present study, we examined the influence of task-specific expertise on the AON by investigating differences between two expert groups trained in different sports while anticipating action effects. Altogether, 15 tennis and 16 volleyball experts anticipated the direction of observed tennis and volleyball serves while undergoing functional magnetic resonance imaging (fMRI). The expert group in each sport acted as novice controls in the other sport with which they had only little experience. When contrasting anticipation in both expertise conditions with the corresponding untrained sport, a stronger activation of AON areas (SPL, SMA), and particularly of cerebellar structures, was observed. Furthermore, the neural activation within the cerebellum and the SPL was linearly correlated with participant's anticipation performance, irrespective of the specific expertise. For the SPL, this relationship also holds when an expert performs a domain-specific anticipation task. Notably, the stronger activation of the cerebellum as well as of the SMA and the SPL in the expertise conditions suggests that experts rely on their more fine-tuned perceptual-motor representations that have improved during years of training when anticipating the effects of others' actions in their preferred sport. The association of activation within the SPL and the cerebellum with the task achievement suggests that these areas are the predominant brain sites involved in fast motor predictions. The SPL reflects the processing of domain-specific contextual information and the cerebellum the usage of a predictive internal model to solve the anticipation task.

Callosal connections of dorso-lateral premotor cortex.

PubMed

Marconi, B; Genovesio, A; Giannetti, S; Molinari, M; Caminiti, R

2003-08-01

This study investigated the organization of the callosal connections of the two subdivisions of the monkey dorsal premotor cortex (PMd), dorso-rostral (F7) and dorso-caudal (F2). In one animal, Fast blue and Diamidino yellow were injected in F7 and F2, respectively; in a second animal, the pattern of injections was reversed. F7 and F2 receive a major callosal input from their homotopic counterpart. The heterotopic connections of F7 originate mainly from F2, with smaller contingent from pre-supplementary motor area (pre-SMA, F6), area 8 (frontal eye fields), and prefrontal cortex (area 46), while those of F2 originate from F7, with smaller contributions from ventral premotor areas (F5, F4), SMA-proper (F3), and primary motor cortex (M1). Callosal cells projecting homotopically are mostly located in layers II-III, those projecting heterotopically occupy layers II-III and V-VI. A spectral analysis was used to characterize the spatial fluctuations of the distribution of callosal neurons, in both F7 and F2, as well as in adjacent cortical areas. The results revealed two main periodic components. The first, in the domain of the low spatial frequencies, corresponds to periodicities of cell density with peak-to-peak distances of approximately 10 mm, and suggests an arrangement of callosal cells in the form of 5-mm wide bands. The second corresponds to periodicities of approximately 2 mm, and probably reflects a 1-mm columnar-like arrangement. Coherency and phase analyses showed that, although similar in their spatial arrangements, callosal cells projecting to dorsal premotor areas are segregated in the tangential cortical domain.

Lung tissue remodelling in MCT-induced pulmonary hypertension: a proposal for a novel scoring system and changes in extracellular matrix and fibrosis associated gene expression.

PubMed

Franz, Marcus; Grün, Katja; Betge, Stefan; Rohm, Ilonka; Ndongson-Dongmo, Bernadin; Bauer, Reinhard; Schulze, P Christian; Lichtenauer, Michael; Petersen, Iver; Neri, Dario; Berndt, Alexander; Jung, Christian

2016-12-06

Pulmonary hypertension (PH) is associated with vasoconstriction and remodelling. We studied lung tissue remodelling in a rat model of PH with special focus on histology and extracellular matrix (ECM) remodelling. After induction of PH by monocrotaline, lung tissue was analysed histologically, by gene expression analysis and immunofluorescence labelling of ED-A domain containing fibronectin (ED-A+ Fn), B domain containing tenascin-C (B+ Tn-C) as well as alpha-smooth muscle actin (α-SMA). Serum concentrations of ED-A+ Fn were determined by ELISA. Systolic right ventricular pressure (RVPsys) values were significantly elevated in PH (n = 18; 75 ± 26.4 mmHg) compared to controls (n = 10; 29 ± 19.3 mmHg; p = 0.015). The histological sum-score was significantly increased in PH (8.0 ± 2.2) compared to controls (2.5 ± 1.6; p < 0.001). Gene expression analysis revealed relevant induction of several key genes of extracellular matrix remodelling. Increased protein deposition of ED-A+ Fn but not of B+ Tn-C and α-SMA in lung tissue was found in PH (2.88 ± 3.19 area%) compared to controls (1.32 ± 0.16 area%; p = 0.030). Serum levels of ED-A+ Fn were significantly higher in PH (p = 0.007) positively correlating with RVPsys (r = 0.618, p = 0.019). We here present a novel histological scoring system to assess lung tissue remodelling in PH. Gene expression analysis revealed induction of candidate genes involved in collagen matrix turnover, fibrosis and vascular remodelling. The stable increased tissue deposition of ED-A+ Fn in PH as well as its dynamics in serum suggests a role as a promising novel biomarker and potential therapeutic target.

Effects of Increasing Neuromuscular Electrical Stimulation Current Intensity on Cortical Sensorimotor Network Activation: A Time Domain fNIRS Study

PubMed Central

Zucchelli, Lucia; Perrey, Stephane; Contini, Davide; Caffini, Matteo; Spinelli, Lorenzo; Kerr, Graham; Quaresima, Valentina; Ferrari, Marco; Torricelli, Alessandro

2015-01-01

Neuroimaging studies have shown neuromuscular electrical stimulation (NMES)-evoked movements activate regions of the cortical sensorimotor network, including the primary sensorimotor cortex (SMC), premotor cortex (PMC), supplementary motor area (SMA), and secondary somatosensory area (S2), as well as regions of the prefrontal cortex (PFC) known to be involved in pain processing. The aim of this study, on nine healthy subjects, was to compare the cortical network activation profile and pain ratings during NMES of the right forearm wrist extensor muscles at increasing current intensities up to and slightly over the individual maximal tolerated intensity (MTI), and with reference to voluntary (VOL) wrist extension movements. By exploiting the capability of the multi-channel time domain functional near-infrared spectroscopy technique to relate depth information to the photon time-of-flight, the cortical and superficial oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin concentrations were estimated. The O2Hb and HHb maps obtained using the General Linear Model (NIRS-SPM) analysis method, showed that the VOL and NMES-evoked movements significantly increased activation (i.e., increase in O2Hb and corresponding decrease in HHb) in the cortical layer of the contralateral sensorimotor network (SMC, PMC/SMA, and S2). However, the level and area of contralateral sensorimotor network (including PFC) activation was significantly greater for NMES than VOL. Furthermore, there was greater bilateral sensorimotor network activation with the high NMES current intensities which corresponded with increased pain ratings. In conclusion, our findings suggest that greater bilateral sensorimotor network activation profile with high NMES current intensities could be in part attributable to increased attentional/pain processing and to increased bilateral sensorimotor integration in these cortical regions. PMID:26158464

Effects of Increasing Neuromuscular Electrical Stimulation Current Intensity on Cortical Sensorimotor Network Activation: A Time Domain fNIRS Study.

PubMed

Muthalib, Makii; Re, Rebecca; Zucchelli, Lucia; Perrey, Stephane; Contini, Davide; Caffini, Matteo; Spinelli, Lorenzo; Kerr, Graham; Quaresima, Valentina; Ferrari, Marco; Torricelli, Alessandro

2015-01-01

Neuroimaging studies have shown neuromuscular electrical stimulation (NMES)-evoked movements activate regions of the cortical sensorimotor network, including the primary sensorimotor cortex (SMC), premotor cortex (PMC), supplementary motor area (SMA), and secondary somatosensory area (S2), as well as regions of the prefrontal cortex (PFC) known to be involved in pain processing. The aim of this study, on nine healthy subjects, was to compare the cortical network activation profile and pain ratings during NMES of the right forearm wrist extensor muscles at increasing current intensities up to and slightly over the individual maximal tolerated intensity (MTI), and with reference to voluntary (VOL) wrist extension movements. By exploiting the capability of the multi-channel time domain functional near-infrared spectroscopy technique to relate depth information to the photon time-of-flight, the cortical and superficial oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin concentrations were estimated. The O2Hb and HHb maps obtained using the General Linear Model (NIRS-SPM) analysis method, showed that the VOL and NMES-evoked movements significantly increased activation (i.e., increase in O2Hb and corresponding decrease in HHb) in the cortical layer of the contralateral sensorimotor network (SMC, PMC/SMA, and S2). However, the level and area of contralateral sensorimotor network (including PFC) activation was significantly greater for NMES than VOL. Furthermore, there was greater bilateral sensorimotor network activation with the high NMES current intensities which corresponded with increased pain ratings. In conclusion, our findings suggest that greater bilateral sensorimotor network activation profile with high NMES current intensities could be in part attributable to increased attentional/pain processing and to increased bilateral sensorimotor integration in these cortical regions.

Potential of using stone matrix asphalt (SMA) for thin overlays

DOT National Transportation Integrated Search

2003-04-01

Stone matrix asphalt (SMA) has been used within the U.S. since 1991. To date almost all of the SMA mixes have had either a 12.5 or 19.0 mm nominal maximum aggregate size (NMAS). These two NMASs have been predominant because they conform to informatio...

Inhibition of Pre-Supplementary Motor Area by Continuous Theta Burst Stimulation Leads to More Cautious Decision-making and More Efficient Sensory Evidence Integration.

PubMed

Tosun, Tuğçe; Berkay, Dilara; Sack, Alexander T; Çakmak, Yusuf Ö; Balcı, Fuat

2017-08-01

Decisions are made based on the integration of available evidence. The noise in evidence accumulation leads to a particular speed-accuracy tradeoff in decision-making, which can be modulated and optimized by adaptive decision threshold setting. Given the effect of pre-SMA activity on striatal excitability, we hypothesized that the inhibition of pre-SMA would lead to higher decision thresholds and an increased accuracy bias. We used offline continuous theta burst stimulation to assess the effect of transient inhibition of the right pre-SMA on the decision processes in a free-response two-alternative forced-choice task within the drift diffusion model framework. Participants became more cautious and set higher decision thresholds following right pre-SMA inhibition compared with inhibition of the control site (vertex). Increased decision thresholds were accompanied by an accuracy bias with no effects on post-error choice behavior. Participants also exhibited higher drift rates as a result of pre-SMA inhibition compared with the vertex inhibition. These results, in line with the striatal theory of speed-accuracy tradeoff, provide evidence for the functional role of pre-SMA activity in decision threshold modulation. Our results also suggest that pre-SMA might be a part of the brain network associated with the sensory evidence integration.

Contribution of the pre-SMA to the production of words and non-speech oral motor gestures, as revealed by repetitive transcranial magnetic stimulation (rTMS).

PubMed

Tremblay, Pascale; Gracco, Vincent L

2009-05-01

An emerging theoretical perspective, largely based on neuroimaging studies, suggests that the pre-SMA is involved in planning cognitive aspects of motor behavior and language, such as linguistic and non-linguistic response selection. Neuroimaging studies, however, cannot indicate whether a brain region is equally important to all tasks in which it is activated. In the present study, we tested the hypothesis that the pre-SMA is an important component of response selection, using an interference technique. High frequency repetitive TMS (10 Hz) was used to interfere with the functioning of the pre-SMA during tasks requiring selection of words and oral gestures under different selection modes (forced, volitional) and attention levels (high attention, low attention). Results show that TMS applied to the pre-SMA interferes selectively with the volitional selection condition, resulting in longer RTs. The low- and high-attention forced selection conditions were unaffected by TMS, demonstrating that the pre-SMA is sensitive to selection mode but not attentional demands. TMS similarly affected the volitional selection of words and oral gestures, reflecting the response-independent nature of the pre-SMA contribution to response selection. The implications of these results are discussed.

Insights into deregulated TNF and IL-10 production in malaria: implications for understanding severe malarial anaemia.

PubMed

Boeuf, Philippe S; Loizon, Séverine; Awandare, Gordon A; Tetteh, John K A; Addae, Michael M; Adjei, George O; Goka, Bamenla; Kurtzhals, Jørgen A L; Puijalon, Odile; Hviid, Lars; Akanmori, Bartholomew D; Behr, Charlotte

2012-08-01

Severe malarial anaemia (SMA) is a major life-threatening complication of paediatric malaria. Protracted production of pro-inflammatory cytokines promoting erythrophagocytosis and depressing erythropoiesis is thought to play an important role in SMA, which is characterized by a high TNF/IL-10 ratio. Whether this TNF/IL-10 imbalance results from an intrinsic incapacity of SMA patients to produce IL-10 or from an IL-10 unresponsiveness to infection is unknown. Monocytes and T cells are recognized as the main sources of TNF and IL-10 in vivo, but little is known about the activation status of those cells in SMA patients. The IL-10 and TNF production capacity and the activation phenotype of monocytes and T cells were compared in samples collected from 332 Ghanaian children with non-overlapping SMA (n = 108), cerebral malaria (CM) (n = 144) or uncomplicated malaria (UM) (n = 80) syndromes. Activation status of monocytes and T cells was ascertained by measuring HLA-DR+ and/or CD69+ surface expression by flow cytometry. The TNF and IL-10 production was assessed in a whole-blood assay after or not stimulation with lipopolysaccharide (LPS) or phytohaemaglutinin (PHA) used as surrogate of unspecific monocyte and T cell stimulant. The number of circulating pigmented monocytes was also determined. Monocytes and T cells from SMA and CM patients showed similar activation profiles with a comparable decreased HLA-DR expression on monocytes and increased frequency of CD69+ and HLA-DR+ T cells. In contrast, the acute-phase IL-10 production was markedly decreased in SMA compared to CM (P = .003) and UM (P = .004). Although in SMA the IL-10 response to LPS-stimulation was larger in amplitude than in CM (P = .0082), the absolute levels of IL-10 reached were lower (P = .013). Both the amplitude and levels of TNF produced in response to LPS-stimulation were larger in SMA than CM (P = .019). In response to PHA-stimulation, absolute levels of IL-10 produced in SMA were lower than in CM (P = .005) contrasting with TNF levels, which were higher (P = .001). These data reveal that SMA patients have the potential to mount efficient IL-10 responses and that the TNF/IL-10 imbalance may reflect a specific monocyte and T cell programming/polarization pattern in response to infection.

Type 0 Spinal Muscular Atrophy: Further Delineation of Prenatal and Postnatal Features in 16 Patients.

PubMed

Grotto, Sarah; Cuisset, Jean-Marie; Marret, Stéphane; Drunat, Séverine; Faure, Patricia; Audebert-Bellanger, Séverine; Desguerre, Isabelle; Flurin, Vincent; Grebille, Anne-Gaëlle; Guerrot, Anne-Marie; Journel, Hubert; Morin, Gilles; Plessis, Ghislaine; Renolleau, Sylvain; Roume, Joëlle; Simon-Bouy, Brigitte; Touraine, Renaud; Willems, Marjolaine; Frébourg, Thierry; Verspyck, Eric; Saugier-Veber, Pascale

2016-11-29

Spinal muscular atrophy (SMA) is caused by homozygous inactivation of the SMN1 gene. The SMN2 copy number modulates the severity of SMA. The 0SMN1/1SMN2 genotype, the most severe genotype compatible with life, is expected to be associated with the most severe form of the disease, called type 0 SMA, defined by prenatal onset. The aim of the study was to review clinical features and prenatal manifestations in this rare SMA subtype. SMA patients with the 0SMN1/1SMN2 genotype were retrospectively collected using the UMD-SMN1 France database. Data from 16 patients were reviewed. These 16 patients displayed type 0 SMA. At birth, a vast majority had profound hypotonia, severe muscle weakness, severe respiratory distress, and cranial nerves involvement (inability to suck/swallow, facial muscles weakness). They showed characteristics of fetal akinesia deformation sequence and congenital heart defects. Recurrent episodes of bradycardia were observed. Death occurred within the first month. At prenatal stage, decreased fetal movements were frequently reported, mostly only by mothers, in late stages of pregnancy; increased nuchal translucency was reported in about half of the cases; congenital heart defects, abnormal amniotic fluid volume, or joint contractures were occasionally reported. Despite a prenatal onset attested by severity at birth and signs of fetal akinesia deformation sequence, prenatal manifestations of type 0 SMA are not specific and not constant. As illustrated by the frequent association with congenital heart defects, type 0 SMA physiopathology is not restricted to motor neuron, highlighting that SMN function is critical for organogenesis.

Protective effects of butyrate-based compounds on a mouse model for spinal muscular atrophy.

PubMed

Butchbach, Matthew E R; Lumpkin, Casey J; Harris, Ashlee W; Saieva, Luciano; Edwards, Jonathan D; Workman, Eileen; Simard, Louise R; Pellizzoni, Livio; Burghes, Arthur H M

2016-05-01

Proximal spinal muscular atrophy (SMA) is a childhood-onset degenerative disease resulting from the selective loss of motor neurons in the spinal cord. SMA is caused by the loss of SMN1 (survival motor neuron 1) but retention of SMN2. The number of copies of SMN2 modifies disease severity in SMA patients as well as in mouse models, making SMN2 a target for therapeutics development. Sodium butyrate (BA) and its analog (4PBA) have been shown to increase SMN2 expression in SMA cultured cells. In this study, we examined the effects of BA, 4PBA as well as two BA prodrugs-glyceryl tributyrate (BA3G) and VX563-on the phenotype of SMNΔ7 SMA mice. Treatment with 4PBA, BA3G and VX563 but not BA beginning at PND04 significantly improved the lifespan and delayed disease end stage, with administration of VX563 also improving the growth rate of these mice. 4PBA and VX563 improved the motor phenotype of SMNΔ7 SMA mice and prevented spinal motor neuron loss. Interestingly, neither 4PBA nor VX563 had an effect on SMN expression in the spinal cords of treated SMNΔ7 SMA mice; however, they inhibited histone deacetylase (HDAC) activity and restored the normal phosphorylation states of Akt and glycogen synthase kinase 3β, both of which are altered by SMN deficiency in vivo. These observations show that BA-based compounds with favorable pharmacokinetics ameliorate SMA pathology possibly by modulating HDAC and Akt signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

Defining functional SMA and pre-SMA subregions in human MFC using resting state fMRI: functional connectivity-based parcellation method.

PubMed

Kim, Jae-Hun; Lee, Jong-Min; Jo, Hang Joon; Kim, Sook Hui; Lee, Jung Hee; Kim, Sung Tae; Seo, Sang Won; Cox, Robert W; Na, Duk L; Kim, Sun I; Saad, Ziad S

2010-02-01

Noninvasive parcellation of the human cerebral cortex is an important goal for understanding and examining brain functions. Recently, the patterns of anatomical connections using diffusion tensor imaging (DTI) have been used to parcellate brain regions. Here, we present a noninvasive parcellation approach that uses "functional fingerprints" obtained by correlation measures on resting state functional magnetic resonance imaging (fMRI) data to parcellate brain regions. In other terms, brain regions are parcellated based on the similarity of their connection--as reflected by correlation during resting state--to the whole brain. The proposed method was used to parcellate the medial frontal cortex (MFC) into supplementary motor areas (SMA) and pre-SMA subregions. In agreement with anatomical landmark-based parcellation, we find that functional fingerprint clustering of the MFC results in anterior and posterior clusters. The probabilistic maps from 12 subjects showed that the anterior cluster is mainly located rostral to the vertical commissure anterior (VCA) line, whereas the posterior cluster is mainly located caudal to VCA line, suggesting the homologues of pre-SMA and SMA. The functional connections from the putative pre-SMA cluster were connected to brain regions which are responsible for complex/cognitive motor control, whereas those from the putative SMA cluster were connected to brain regions which are related to the simple motor control. These findings demonstrate the feasibility of the functional connectivity-based parcellation of the human cerebral cortex using resting state fMRI. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Shape-retainment control using an antagonistic shape memory alloy system

NASA Astrophysics Data System (ADS)

Ikeda, T.; Sawamura, K.; Senba, A.; Tamayama, M.

2015-04-01

Since shape memory alloy (SMA) actuators can generate large force per unit weight, they are expected as one of the next generation actuators for aircraft. To keep a position of conventional control surfaces or morphing wings with SMA actuators, the SMA actuators must keep being heated, and the heating energy is not small. To save the energy, a new control method proposed for piezoelectric actuators utilizing hysteresis in deformation [Ikeda and Takahashi, Proc. SPIE 8689 (2013), 86890C] is applied to an antagonistic SMA system. By using the control method any position can be an equilibrium point within hysteresis of stress-strain diagrams. To confirm a feasibility of the control method, a fundamental experiment is performed. The SMA wires are heated by applying electric current to the wires. When a pulsed current is applied to the two SMA wires alternately, the equilibrium position changes between two positions alternately, and when a series of pulse whose amplitude increases gradually is applied to one SMA wire, the equilibrium position changes like a staircase. However, just after the pulse the position returns slightly, that is, overshoot takes place. To investigate such a behavior of the system, numerical simulation is also performed. The one-dimensional phase transformation model [Ikeda, Proc. SPIE 5757 (2005), 344-352] is used for a constitutive model of the SMA wires. The simulated result agrees with the experiment qualitatively, including the overshoot. By examining volume fraction of each phase, it is found that the overshoot is caused by that austenite phase transforms into stress-induced martensite phase during the cooling process after the pulse.

An analysis of chemical and meteorological characteristics of haze events in the Seoul metropolitan area during January 12-18, 2013

NASA Astrophysics Data System (ADS)

Koo, Youn-Seo; Yun, Hui-Young; Choi, Dae-Ryun; Han, Jin-Seok; Lee, Jae-Bum; Lim, Yong-Jae

2018-04-01

The chemical characteristics of secondary inorganic and carbonaceous aerosols as well as their formation mechanisms during the haze event of January 12-18, 2013, in the Seoul Metropolitan Area (SMA) were investigated using measurements at the Baengnyeong and Seoul supersites with data available from LIDAR, meteorology, and modeling. An extraordinary haze event that occurred in northern China during that period extended to the Korean Peninsula and initiated the haze event in the SMA. Local emissions of primary aerosol and gaseous precursors in the SMA then made the situation worse under adverse meteorological conditions. OM (Organic Matter) and SO42- were the major long-range transport (LRT) aerosols from the Beijing, Tianjin and Hebei province (BTH) area to the SMA during the initial stage of the haze event. The LRT of SO42- from the BTH area, which was detected at Baengnyeong Island, was mostly acidic, while in Seoul, it was fully neutralized to (NH4)2SO4. The SIAs (Secondary Inorganic Aerosols) consisting of 56.5% PM2.5 during the haze period were the major chemical species causing haze problems in the SMA. NO3- was the most dominant chemical species among the SIAs and was locally formed by a heavy burden of NOx emissions from mobile sources in the SMA. Carbonaceous aerosols of OM and EC (Elemental Carbon) in the SMA during the haze period consisted of 18.9% PM2.5, but secondary organic carbon (SOC) was not the key species inducing the haze event during the January episode in the SMA.

Non-linear Relationship between BOLD Activation and Amplitude of Beta Oscillations in the Supplementary Motor Area during Rhythmic Finger Tapping and Internal Timing.

PubMed

Gompf, Florian; Pflug, Anja; Laufs, Helmut; Kell, Christian A

2017-01-01

Functional imaging studies using BOLD contrasts have consistently reported activation of the supplementary motor area (SMA) both during motor and internal timing tasks. Opposing findings, however, have been shown for the modulation of beta oscillations in the SMA. While movement suppresses beta oscillations in the SMA, motor and non-motor tasks that rely on internal timing increase the amplitude of beta oscillations in the SMA. These independent observations suggest that the relationship between beta oscillations and BOLD activation is more complex than previously thought. Here we set out to investigate this rapport by examining beta oscillations in the SMA during movement with varying degrees of internal timing demands. In a simultaneous EEG-fMRI experiment, 20 healthy right-handed subjects performed an auditory-paced finger-tapping task. Internal timing was operationalized by including conditions with taps on every fourth auditory beat, which necessitates generation of a slow internal rhythm, while tapping to every auditory beat reflected simple auditory-motor synchronization. In the SMA, BOLD activity increased and power in both the low and the high beta band decreased expectedly during each condition compared to baseline. Internal timing was associated with a reduced desynchronization of low beta oscillations compared to conditions without internal timing demands. In parallel with this relative beta power increase, internal timing activated the SMA more strongly in terms of BOLD. This documents a task-dependent non-linear relationship between BOLD and beta-oscillations in the SMA. We discuss different roles of beta synchronization and desynchronization in active processing within the same cortical region.

Protective Effects of Butyrate-based Compounds on a Mouse Model for Spinal Muscular Atrophy

PubMed Central

Butchbach, Matthew E. R.; Lumpkin, Casey J.; Harris, Ashlee W.; Saieva, Luciano; Edwards, Jonathan D.; Workman, Eileen; Simard, Louise R.; Pellizzoni, Livio; Burghes, Arthur H. M.

2016-01-01

Proximal spinal muscular atrophy (SMA) is a childhood-onset degenerative disease resulting from the selective loss of motor neurons in the spinal cord. SMA is caused by the loss of SMN1 (survival motor neuron 1) but retention of SMN2. The number of copies of SMN2 modifies disease severity in SMA patients as well as in mouse models, making SMN2 a target for therapeutics development. Sodium butyrate (BA) and its analogue (4PBA) have been shown to increase SMN2 expression in SMA cultured cells. In this study, we examined the effects of BA, 4PBA as well as two BA prodrugs—glyceryl tributyrate (BA3G) and VX563—on the phenotype of SMNΔ7 SMA mice. Treatment with 4PBA, BA3G and VX563 but not BA beginning at PND04 significantly improved the lifespan and delayed disease end stage, with administration of VX563 also improving the growth rate of these mice. 4PBA and VX563 improved the motor phenotype of SMNΔ7 SMA mice and prevented spinal motor neuron loss. Interestingly, neither 4PBA nor VX563 had an effect on SMN expression in the spinal cords of treated SMNΔ7 SMA mice; however, they inhibited histone deacetylase (HDAC) activity and restored the normal phosphorylation states of Akt and glycogen synthase kinase 3β, both of which are altered by SMN deficiency in vivo. These observations show that BA-based compounds with favourable pharmacokinetics ameliorate SMA pathology possibly by modulating HDAC and Akt signaling. PMID:26892876

Development of a flexible pavement database for local calibration of the MEPDG : part 2, evaluation of ODOT SMA mixtures.

DOT National Transportation Integrated Search

2011-03-01

There has been some reluctance on the part of some in Oklahoma to use SMA mixtures. There are several factors that could be involved in the slow acceptance of SMA mixtures in Oklahoma. These factors are 1) the extra expense associated with the higher...

Optimization of Spinal Muscular Atrophy subject's muscle activity during gait

NASA Astrophysics Data System (ADS)

Umat, Gazlia; Rambely, Azmin Sham

2014-06-01

Spinal Muscular Atrophy (SMA) is a hereditary disease related muscle nerve disorder caused by degeneration of the anterior cells of the spinal cord. SMA is divided into four types according to the degree of seriousness. SMA patients show different gait with normal people. Therefore, this study focused on the effects of SMA patient muscle actions and the difference that exists between SMA subjects and normal subjects. Therefore, the electromyography (EMG) test will be used to track the behavior of muscle during walking and optimization methods are used to get the muscle stress that is capable of doing the work while walking. Involved objective function is non-linear function of the quadratic and cubic functions. The study concludes with a comparison of the objective function using the force that sought to use the moment of previous studies and the objective function using the data obtained from EMG. The results shows that the same muscles, peroneus longus and bisepsfemoris, were used during walking activity by SMA subjects and control subjects. Muscle stress force best solution achieved from part D in simulation carried out.

Comparison of myofibroblasts expression in oral squamous cell carcinoma, verrucous carcinoma, high risk epithelial dysplasia, low risk epithelial dysplasia and normal oral mucosa.

PubMed

Chaudhary, Minal; Gadbail, Amol Ramchandra; Vidhale, Gaurav; Mankar Gadbail, Mugdha P; Gondivkar, Shailesh M; Gawande, Madhuri; Patil, Swati

2012-09-01

The aim was to evaluate and compare the presence of myofibroblasts in oral squamous cell carcinoma (OSCC), verrucous carcinoma (VC), high-risk epithelial dysplasia (HRED), low-risk epithelial dysplasia (LRED), and normal oral mucosa (NOM). The study consisted of 37 OSCC, 15 VC, 15 HRED, 15 LRED and 15 NOM. α-smooth muscle actin (α-SMA) antibody was used to identify myofibroblasts. The α-SMA expression was not observed in NOM and LRED. The α-SMA was expressed in 97.29% of OSCC, 86.66% of VC, 46.66 % of HRED. The α-SMA expression was significantly higher in OSCC than VC (p = 0.023) and HRED (p < 0.000). The α-SMA expression was significantly higher in VC than HRED (p = 0.043). Myofibroblastic expression, as highlighted by α-SMA, is undetectable in NOM and LRED but increases as the disease progresses from potentially malignant disorders, as HRED to VC to invasive OSCC. Thus, proliferation of myofibroblasts may be used as a stromal marker of oral premalignancy and malignancy.

Acoustic transmission and radiation analysis of adaptive shape-memory alloy reinforced laminated plates

NASA Astrophysics Data System (ADS)

Liang, C.; Rogers, C. A.; Fuller, C. R.

1991-02-01

A theoretical analysis of sound transmission/radiation of shape-memory alloy (SMA) hybrid composite panels is presented. Unlike other composite materials, SMA hybrid composite is dynamically tunable by electrical activation of the SMA fibers and has numerous active control capabilities. Two of the concepts that will be briefly described and utilized in this paper are referred to as active property tuning (APT) and active strain energy tuning (ASET). Tuning or activating the embedded shape-memory alloy fibers in conventional composite materials changes the overall stiffness of the SMA hybrid composite structure and consequently changes natural frequency and mode shapes. The sound transmission and radiation from a composite panel is related to its frequency and mode shapes. Because of the capability to change both the natural frequency and mode shapes, the acoustic characteristics of SMA hybrid composite plates can be changed as well. The directivity pattern, radiation efficiency, and transmission loss of laminated composite materials are investigated based on 'composite' mode shapes in order to derive a basic understanding of the nature and authority of acoustic control by use of SMA hybrid composites.

Inhibition of myostatin does not ameliorate disease features of severe spinal muscular atrophy mice.

PubMed

Sumner, Charlotte J; Wee, Claribel D; Warsing, Leigh C; Choe, Dong W; Ng, Andrew S; Lutz, Cathleen; Wagner, Kathryn R

2009-09-01

There is currently no treatment for the inherited motor neuron disease, spinal muscular atrophy (SMA). Severe SMA causes lower motor neuron loss, impaired myofiber development, profound muscle weakness and early mortality. Myostatin is a transforming growth factor-beta family member that inhibits muscle growth. Loss or blockade of myostatin signaling increases muscle mass and improves muscle strength in mouse models of primary muscle disease and in the motor neuron disease, amyotrophic lateral sclerosis. In this study, we evaluated the effects of blocking myostatin signaling in severe SMA mice (hSMN2/delta7SMN/mSmn(-/-)) by two independent strategies: (i) transgenic overexpression of the myostatin inhibitor follistatin and (ii) post-natal administration of a soluble activin receptor IIB (ActRIIB-Fc). SMA mice overexpressing follistatin showed little increase in muscle mass and no improvement in motor function or survival. SMA mice treated with ActRIIB-Fc showed minimal improvement in motor function, and no extension of survival compared with vehicle-treated mice. Together these results suggest that inhibition of myostatin may not be a promising therapeutic strategy in severe forms of SMA.

Safety and Mission Assurance for In-House Design Lessons Learned from Ares I Upper Stage

NASA Technical Reports Server (NTRS)

Anderson, Joel M.

2011-01-01

This viewgraph presentation identifies lessons learned in the course of the Ares I Upper Stage design and in-house development effort. The contents include: 1) Constellation Organization; 2) Upper Stage Organization; 3) Presentation Structure; 4) Lesson-Importance of Systems Engineering/Integration; 5) Lesson-Importance of Early S&MA Involvement; 6) Lesson-Importance of Appropriate Staffing Levels; 7) Lesson-Importance S&MA Team Deployment; 8) Lesson-Understanding of S&MA In-Line Engineering versus Assurance; 9) Lesson-Importance of Close Coordination between Supportability and Reliability/Maintainability; 10) Lesson-Importance of Engineering Data Systems; 11) Lesson-Importance of Early Development of Supporting Databases; 12) Lesson-Importance of Coordination with Safety Assessment/Review Panels; 13) Lesson-Implementation of Software Reliability; 14) Lesson-Implementation of S&MA Technical Authority/Chief S&MA Officer; 15) Lesson-Importance of S&MA Evaluation of Project Risks; 16) Lesson-Implementation of Critical Items List and Government Mandatory Inspections; 17) Lesson-Implementation of Critical Items List Mandatory Inspections; 18) Lesson-Implementation of Test Article Safety Analysis; and 19) Lesson-Importance of Procurement Quality.

Optimal design of damping layers in SMA/GFRP laminated hybrid composites

NASA Astrophysics Data System (ADS)

Haghdoust, P.; Cinquemani, S.; Lo Conte, A.; Lecis, N.

2017-10-01

This work describes the optimization of the shape profiles for shape memory alloys (SMA) sheets in hybrid layered composite structures, i.e. slender beams or thinner plates, designed for the passive attenuation of flexural vibrations. The paper starts with the description of the material and architecture of the investigated hybrid layered composite. An analytical method, for evaluating the energy dissipation inside a vibrating cantilever beam is developed. The analytical solution is then followed by a shape profile optimization of the inserts, using a genetic algorithm to minimize the SMA material layer usage, while maintaining target level of structural damping. Delamination problem at SMA/glass fiber reinforced polymer interface is discussed. At the end, the proposed methodology has been applied to study the hybridization of a wind turbine layered structure blade with SMA material, in order to increase its passive damping.

Perceptions of equine-assisted activities and therapies by parents and children with spinal muscular atrophy.

PubMed

Lemke, Danielle; Rothwell, Erin; Newcomb, Tara M; Swoboda, Kathryn J

2014-01-01

To identify the physical and psychosocial effects of equine-assisted activities and therapies (EAATs) on children with spinal muscular atrophy (SMA) from the perspective of the children and their parents. The families of all eligible children with SMA, who reported participation in EAAT, from a Western metropolitan academic center were contacted and invited to participate. This study implemented qualitative, semistructured interviews of children with SMA and their parents. Three themes emerged from the qualitative content analysis: physical/psychosocial benefits; relationship development with the horses, instructors, and children; and barriers to continued EAAT engagement. The data suggest that the overall EAAT experience was a source of enjoyment, self-confidence, and normalcy for the children with SMA. The results of this study provide preliminary support for the use of EAAT among children with SMA.

Finite Element Analysis of Adaptive-Stiffening and Shape-Control SMA Hybrid Composites

NASA Technical Reports Server (NTRS)

Gao, Xiu-Jie; Turner, Travis L.; Burton, Deborah; Brinson, L. Catherine

2005-01-01

The usage of shape memory materials has extended rapidly to many fields, including medical devices, actuators, composites, structures and MEMS devices. For these various applications, shape memory alloys (SMAs) are available in various forms: bulk, wire, ribbon, thin film, and porous. In this work, the focus is on SMA hybrid composites with adaptive-stiffening or morphing functions. These composites are created by using SMA ribbons or wires embedded in a polymeric based composite panel/beam. Adaptive stiffening or morphing is activated via selective resistance heating or uniform thermal loads. To simulate the thermomechanical behavior of these composites, a SMA model was implemented using ABAQUS user element interface and finite element simulations of the systems were studied. Several examples are presented which show that the implemented model can be a very useful design and simulation tool for SMA hybrid composites.

Fabrication of a smart air intake structure using shape memory alloy wire embedded composite

NASA Astrophysics Data System (ADS)

Jung, Beom-Seok; Kim, Min-Saeng; Kim, Ji-Soo; Kim, Yun-Mi; Lee, Woo-Yong; Ahn, Sung-Hoon

2010-05-01

Shape memory alloys (SMAs) have been actively studied in many fields utilizing their high energy density. Applying SMA wire-embedded composite to aerospace structures, such as air intake of jet engines and guided missiles, is attracting significant attention because it could generate a comparatively large actuating force. In this research, a scaled structure of SMA wire-embedded composite was fabricated for the air intake of aircraft. The structure was composed of several prestrained Nitinol (Ni-Ti) SMA wires embedded in ∩-shape glass fabric reinforced plastic (GFRP), and it was cured at room temperature for 72 h. The SMA wire-embedded GFRP could be actuated by applying electric current through the embedded SMA wires. The activation angle generated from the composite structure was large enough to make a smart air intake structure.

Copy Number Variations in the Survival Motor Neuron Genes: Implications for Spinal Muscular Atrophy and Other Neurodegenerative Diseases

PubMed Central

Butchbach, Matthew E. R.

2016-01-01

Proximal spinal muscular atrophy (SMA), a leading genetic cause of infant death worldwide, is an early-onset, autosomal recessive neurodegenerative disease characterized by the loss of spinal α-motor neurons. This loss of α-motor neurons is associated with muscle weakness and atrophy. SMA can be classified into five clinical grades based on age of onset and severity of the disease. Regardless of clinical grade, proximal SMA results from the loss or mutation of SMN1 (survival motor neuron 1) on chromosome 5q13. In humans a large tandem chromosomal duplication has lead to a second copy of the SMN gene locus known as SMN2. SMN2 is distinguishable from SMN1 by a single nucleotide difference that disrupts an exonic splice enhancer in exon 7. As a result, most of SMN2 mRNAs lack exon 7 (SMNΔ7) and produce a protein that is both unstable and less than fully functional. Although only 10–20% of the SMN2 gene product is fully functional, increased genomic copies of SMN2 inversely correlates with disease severity among individuals with SMA. Because SMN2 copy number influences disease severity in SMA, there is prognostic value in accurate measurement of SMN2 copy number from patients being evaluated for SMA. This prognostic value is especially important given that SMN2 copy number is now being used as an inclusion criterion for SMA clinical trials. In addition to SMA, copy number variations (CNVs) in the SMN genes can affect the clinical severity of other neurological disorders including amyotrophic lateral sclerosis (ALS) and progressive muscular atrophy (PMA). This review will discuss how SMN1 and SMN2 CNVs are detected and why accurate measurement of SMN1 and SMN2 copy numbers is relevant for SMA and other neurodegenerative diseases. PMID:27014701

Sex-related shape dimorphism in the human radiocarpal and midcarpal joints.

PubMed

Kivell, Tracy L; Guimont, Isabelle; Wall, Christine E

2013-01-01

Previous research has revealed significant size differences between human male and female carpal bones but it is unknown if there are significant shape differences as well. This study investigated sex-related shape variation and allometric patterns in five carpal bones that make up the radiocarpal and midcarpal joints in modern humans. We found that many aspects of carpal shape (76% of all variables quantified) were similar between males and females, despite variation in size. However, 10 of the shape ratios were significantly different between males and females, with at least one significant shape difference observed in each carpal bone. Within-sex standard major axis regressions (SMA) of the numerator (i.e., the linear variables) on the denominator (i.e., the geometric mean) for each significantly different shape ratio indicated that most linear variables scaled with positive allometry in both males and females, and that for eight of the shape ratios, sex-related shape variation is associated with statistically similar sex-specific scaling relationships. Only the length of the scaphoid body and the height of the lunate triquetrum facet showed a significantly higher SMA slope in females compared with males. These findings indicate that the significant differences in the majority of the shape ratios are a function of subtle (i.e., not statistically significant) scaling differences between males and females. There are a number of potential developmental, functional, and evolutionary factors that may cause sex-related shape differences in the human carpus. The results highlight the potential for subtle differences in scaling to result in functionally significant differences in shape. Copyright © 2012 Wiley Periodicals, Inc.

Germination and growth of wheat in simulated Martian atmospheres

NASA Technical Reports Server (NTRS)

Schwartzkopf, Steven H.; Mancinelli, Rocco L.

1991-01-01

One design for a manned Mars base incorporates a bioregenerative life support system based upon growing higher plants at a low atmospheric pressure in a greenhouse on the Martian surface. To determine the concept's feasibility, the germination and initial growth of wheat (Triticum aestivum) was evaluated at low atmospheric pressures in simulated Martian atmosphere (SMA) and in SMA supplemented with oxygen. Total atmospheric pressures ranged from 10 to 1013 mb. No seeds germinated in pure SMA, regardless of atmospheric pressure. In SMA plus oxygen at 60 mb total pressure, germination and growth occurred but were lower than in the earth atmosphere controls.

[The role of RNA splicing in the pathogenesis of spinal muscular atrophy and development of its therapeutics].

PubMed

Sahashi, Kentaro; Sobue, Gen

2014-12-01

Loss-of-function mutations in SMN1 cause spinal muscular atrophy (SMA), a leading genetic cause of infant mortality. Degeneration of alpha-motor neurons that results in progressive paralysis is a pathological hallmark of SMA. Recently, peripheral-tissue involvement has also been reported in SMA. Patients have low levels of functional SMN which is attributed to alternative splicing in SMN2, a gene closely-related to SMN1. This decrease in the expression of SMN, a ubiquitously expressed protein involved in promoting snRNP assembly required for splicing, is responsible for SMA. However, the mechanism through which decrease in SMN levels causes SMA remains unclear. Currently, no curative treatment is available for SMA, but SMN restoration is thought to be necessary and sufficient for cure. Antisense oligonucleotides (ASOs) can be designed to specifically alter splicing patterns of target pre-mRNAs. We identified an ASO that redirects SMN2 splicing and is currently in clinical trials for use as RNA-targeting therapeutics. Further, we have also reported a novel application of splicing-modulating ASOs--creation of animal phenocopy models of diseases by inducing mis-splicing. Exploring the relationship between the spatial and temporal effects of therapeutic and pathogenic ASOs yields relevant insights into the roles of SMN in SMA pathogenesis and into its normal physiological functions. This knowledge, in turn, contributes to the ongoing development of targeted therapeutics.

Cerebrovascular Smooth Muscle Actin Is Increased in Non-Demented Subjects with Frequent Senile Plaques at Autopsy: Implications for the Pathogenesis of Alzheimer Disease

PubMed Central

Hulette, Christine M.; Ervin, John F.; Edmonds, Yvette; Antoine, Samantha; Stewart, Nicolas; Szymanski, Mari H.; Hayden, Kathleen M; Pieper, Carl F.; Burke, James R.; Welsh-Bohmer, Kathleen A.

2009-01-01

We previously found that vascular smooth muscle actin (SMA) is reduced in the brains of patients with late stage Alzheimer disease (AD) compared to brains of non-demented, neuropathologically normal subjects. To assess the pathogenetic significance and disease specificity of this finding, we studied 3 additional patient groups: non-demented subjects without significant AD type pathology (“Normal”, n = 20); non-demented subjects with frequent senile plaques at autopsy (“Preclinical AD”, n = 20); and subjects with frontotemporal dementia, (“FTD”, n = 10). The groups were matched for gender and age with those previously reported; SMA immunohistochemistry and image analysis were performed as previously described. Surprisingly, SMA expression in arachnoid, cerebral cortex and white matter arterioles was greater in the Preclinical AD group than in the Normal and FTD groups. The plaques were not associated with amyloid angiopathy or other vascular disease in this group. SMA expression in the brains of the Normal group was intermediate between the Preclinical AD and FTD groups. All 3 groups exhibited much greater SMA expression than in our previous report. The presence of frequent plaques and increased arteriolar SMA expression in the brains of non-demented subjects suggest that increased SMA expression might represent a physiologic response to neurodegeneration that could prevent or delay overt expression dementia in AD. PMID:19287310

Properties of styrene-maleic anhydride copolymers containing wood-based fillers

Treesearch

John Simonsen; Rodney Jacobson; Roger Rowell

1998-01-01

Recycled newsprint (ONP) and dry process aspen fiber were combined with styrene maleic anhydride (SMA) copolymers containing either 7 or 14 percent maleic anhydride. The fiber-filled SMA composites were equivalent or superior to unfilled SMA in strength, stiffness, and notched Izod impact strength. ONP performed surprisingly well as a filler. Unnotched Izod impact...

Design of Active Composites

DTIC Science & Technology

2009-03-30

SMA and piezoelectric ceramics(SMA-piezo composite) for fast-responsive actuator, (iii) SMA-piezo composite for thermal energy harvester , and (iv...Composite for Thermal Energy Harvesting Piezoelectric materials and shape memory alloys (SMAs) are very common materials for actuators and sensors; however...their composites as electrical generators is least explored, although use of piezoelectric as the mechanical energy harvester is increasingly popular

Styrene maleic acid encapsulated raloxifene micelles for management of inflammatory bowel disease.

PubMed

Greish, Khaled; Taha, Safa; Jasim, Anfal; Elghany, Sara Abd; Sultan, Ameera; AlKhateeb, Ali; Othman, Manal; Jun, Fang; Taurin, Sebastien; Bakhiet, Moiz

2017-12-01

Inflammatory bowel disease (IBD) comprises a group of disorders that manifest through chronic inflammation of the colon and small intestine. Although the exact cause of IBD is still unclear, dysfunctional immunoregulation involving overproduction of inflammatory cytokines such as TNF-α, and IL-6 have been implicated in pathogenesis. Current therapy relies on immunosuppression, cytotoxic drugs, and monoclonal antibodies against TNF-α. These classes of drugs have severe side-effects, especially when used for long duration. Our previous work with raloxifene, a selective estrogen receptor modulator, has shown that the drug, and to a greater extent its micellar formulation, has a significant suppressive effect on NF-κB, an essential immune-regulator. This finding directed the current work towards testing the anti-inflammatory and immunomodulatory effects of raloxifene using cell lines, as well as testing the potential use of the styrene maleic acid (SMA) micelles loaded with raloxifene (SMA-Ral) against dextran sulfate sodium (DSS) induced colitis in an in vivo model of IBD. Treatment of MCF-7 cells with TNF-α was shown to protect the cells from the cytotoxic effect of raloxifene (42 vs. 10% cell death, with TNF-α. Treating CaCo-2 cells with both free and SMA-Ral improved cell survival after exposure to 2% DDS with significantly higher protection with SMA-Ral. Treatment of U-937 with SMA-Ral and free-Ral resulted in down-regulation of TNF-α, IL-1β, IL-6, and MIP1α, with greater inhibition of the SMA-Ral, compared to free Ral. Balb/c mice treated with raloxifene and SMA-Ral showed weight gain at 14 days, compared to the control group (122, and 115% respectively). Treatment with raloxifene prevented DSS-induced diarrhea in 6/6 of free raloxifene treated mice and in 5/6 mice treated with SMA-Ral. Control group of DSS-treated mice showed average colon length of 7.4 cm compared to 13 cm in the control group. The average colon length was 12.3 and 11.5 cm for raloxifene and SMA-Ral treated groups, respectively. Furthermore, inflammatory cytokines such as IL-6 and TNF-α were reduced in serum of animals treated with free-Ral and SMA-Ral. Raloxifene and its micellar formulation warrants further studies to understand their effect on the treatment of colitis. Graphical abstract SMA-Raloxifene preparation and its in vivo and in vitro effect on colitis.

Experimental Studies on Dynamic Vibration Absorber using Shape Memory Alloy (NiTi) Springs

NASA Astrophysics Data System (ADS)

Kumar, V. Raj; Kumar, M. B. Bharathi Raj; Kumar, M. Senthil

2011-10-01

Shape memory alloy (SMA) springs have been used as actuators in many applications although their use in the vibration control area is very recent. Since shape memory alloys differ from conventional alloy materials in many ways, the traditional design approach for springs is not completely suitable for designing SMA springs. Some vibration control concepts utilizing unique characteristics of SMA's will be presented in this paper. A dynamic vibration absorber (DVA) using shape memory alloy (SMA) actuator is developed for attenuation of vibration in a cantilever beam. The design procedure of the DVA is presented. The system consists of a cantilever beam which is considered to generate the real-time vibration using shaker. A SMA spring is used with a mass attached to its end. The stiffness of the SMA spring is dynamically varied in such a way to attenuate the vibration. Both simulation and experimentation are carried out using PID controller. The experiments were carried out by interfacing the experimental setup with a computer using LabVIEW software, Data acquisition and control are implemented using a PCI data acquisition card. Standard PID controllers have been used to control the vibration of the beam. Experimental results are used to demonstrate the effectiveness of the controllers designed and the usefulness of the proposed test platform by exciting the structure at resonance. In experimental setup, an accelerometer is used to measure the vibration which is fed to computer and correspondingly the SMA spring is actuated to change its stiffness to control the vibration. The results obtained illustrate that the developed DVA using SMA actuator is very effective in reducing structural response and have great potential to be an active vibration control medium.

An efficient method for automatic morphological abnormality detection from human sperm images.

PubMed

Ghasemian, Fatemeh; Mirroshandel, Seyed Abolghasem; Monji-Azad, Sara; Azarnia, Mahnaz; Zahiri, Ziba

2015-12-01

Sperm morphology analysis (SMA) is an important factor in the diagnosis of human male infertility. This study presents an automatic algorithm for sperm morphology analysis (to detect malformation) using images of human sperm cells. The SMA method was used to detect and analyze different parts of the human sperm. First of all, SMA removes the image noises and enhances the contrast of the image to a great extent. Then it recognizes the different parts of sperm (e.g., head, tail) and analyzes the size and shape of each part. Finally, the algorithm classifies each sperm as normal or abnormal. Malformations in the head, midpiece, and tail of a sperm, can be detected by the SMA method. In contrast to other similar methods, the SMA method can work with low resolution and non-stained images. Furthermore, an image collection created for the SMA, has also been described in this study. This benchmark consists of 1457 sperm images from 235 patients, and is known as human sperm morphology analysis dataset (HSMA-DS). The proposed algorithm was tested on HSMA-DS. The experimental results show the high ability of SMA to detect morphological deformities from sperm images. In this study, the SMA algorithm produced above 90% accuracy in sperm abnormality detection task. Another advantage of the proposed method is its low computation time (that is, less than 9s), as such, the expert can quickly decide to choose the analyzed sperm or select another one. Automatic and fast analysis of human sperm morphology can be useful during intracytoplasmic sperm injection for helping embryologists to select the best sperm in real time. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Altered cortico-basal ganglia motor pathways reflect reduced volitional motor activity in schizophrenia.

PubMed

Bracht, Tobias; Schnell, Susanne; Federspiel, Andrea; Razavi, Nadja; Horn, Helge; Strik, Werner; Wiest, Roland; Dierks, Thomas; Müller, Thomas J; Walther, Sebastian

2013-02-01

Little is known about the neurobiology of hypokinesia in schizophrenia. Therefore, the aim of this study was to investigate alterations of white matter motor pathways in schizophrenia and to relate our findings to objectively measured motor activity. We examined 21 schizophrenia patients and 21 healthy controls using diffusion tensor imaging and actigraphy. We applied a probabilistic fibre tracking approach to investigate pathways connecting the dorsolateral prefrontal cortex (dlPFC), the rostral anterior cingulate cortex (rACC), the pre-supplementary motor area (pre-SMA), the supplementary motor area proper (SMA-proper), the primary motor cortex (M1), the caudate nucleus, the striatum, the pallidum and the thalamus. Schizophrenia patients had lower activity levels than controls. In schizophrenia we found higher probability indices forming part of a bundle of interest (PIBI) in pathways connecting rACC, pre-SMA and SMA-proper as well as in pathways connecting M1 and pre-SMA with caudate nucleus, putamen, pallidum and thalamus and a reduced spatial extension of motor pathways in schizophrenia. There was a positive correlation between PIBI and activity level in the right pre-SMA-pallidum and the left M1-thalamus connection in healthy controls, and in the left pre-SMA-SMA-proper pathway in schizophrenia. Our results point to reduced volitional motor activity and altered motor pathway organisation in schizophrenia. The identified associations between the amount of movement and structural connectivity of motor pathways suggest dysfunction of cortico-basal ganglia pathways in the pathophysiology of hypokinesia in schizophrenia. Schizophrenia patients may use cortical pathways involving the supplementary motor area to compensate for basal ganglia dysfunction. Copyright © 2012 Elsevier B.V. All rights reserved.

ROCK inhibition as a therapy for spinal muscular atrophy: understanding the repercussions on multiple cellular targets

PubMed Central

Coque, Emmanuelle; Raoul, Cédric; Bowerman, Mélissa

2014-01-01

Spinal muscular atrophy (SMA) is the most common genetic disease causing infant death, due to an extended loss of motoneurons. This neuromuscular disorder results from deletions and/or mutations within the Survival Motor Neuron 1 (SMN1) gene, leading to a pathological decreased expression of functional full-length SMN protein. Emerging studies suggest that the small GTPase RhoA and its major downstream effector Rho kinase (ROCK), which both play an instrumental role in cytoskeleton organization, contribute to the pathology of motoneuron diseases. Indeed, an enhanced activation of RhoA and ROCK has been reported in the spinal cord of an SMA mouse model. Moreover, the treatment of SMA mice with ROCK inhibitors leads to an increased lifespan as well as improved skeletal muscle and neuromuscular junction pathology, without preventing motoneuron degeneration. Although motoneurons are the primary target in SMA, an increasing number of reports show that other cell types inside and outside the central nervous system contribute to SMA pathogenesis. As administration of ROCK inhibitors to SMA mice was systemic, the improvement in survival and phenotype could therefore be attributed to specific effects on motoneurons and/or on other non-neuronal cell types. In the present review, we will present the various roles of the RhoA/ROCK pathway in several SMA cellular targets including neurons, myoblasts, glial cells, cardiomyocytes and pancreatic cells as well as discuss how ROCK inhibition may ameliorate their health and function. It is most likely a concerted influence of ROCK modulation on all these cell types that ultimately lead to the observed benefits of pharmacological ROCK inhibition in SMA mice. PMID:25221469

The design, hysteresis modeling and control of a novel SMA-fishing-line actuator

NASA Astrophysics Data System (ADS)

Xiang, Chaoqun; Yang, Hui; Sun, Zhiyong; Xue, Bangcan; Hao, Lina; Asadur Rahoman, M. D.; Davis, Steve

2017-03-01

Fishing line can be combined with shape memory alloy (SMA) to form novel artificial muscle actuators which have low cost, are lightweight and soft. They can be applied in bionic, wearable and rehabilitation robots, and can reduce system weight and cost, increase power-to-weight ratio and offer safer physical human-robot interaction. However, these actuators possess several disadvantages, for example fishing line based actuators possess low strength and are complex to drive, and SMA possesses a low percentage contraction and has high hysteresis. This paper presents a novel artificial actuator (known as an SMA-fishing-line) made of fishing line and SMA twisted then coiled together, which can be driven directly by an electrical voltage. Its output force can reach 2.65 N at 7.4 V drive voltage, and the percentage contraction at 4 V driven voltage with a 3 N load is 7.53%. An antagonistic bionic joint driven by the novel SMA-fishing-line actuators is presented, and based on an extended unparallel Prandtl-Ishlinskii (EUPI) model, its hysteresis behavior is established, and the error ratio of the EUPI model is determined to be 6.3%. A Joule heat model of the SMA-fishing-line is also presented, and the maximum error of the established model is 0.510 mm. Based on this accurate hysteresis model, a composite PID controller consisting of PID and an integral inverse (I-I) compensator is proposed and its performance is compared with a traditional PID controller through simulations and experimentation. These results show that the composite PID controller possesses higher control precision than basic PID, and is feasible for implementation in an SMA-fishing-line driven antagonistic bionic joint.

Development of an extended Kalman filter for the self-sensing application of a spring-biased shape memory alloy wire actuator

NASA Astrophysics Data System (ADS)

Gurung, H.; Banerjee, A.

2016-02-01

This report presents the development of an extended Kalman filter (EKF) to harness the self-sensing capability of a shape memory alloy (SMA) wire, actuating a linear spring. The stress and temperature of the SMA wire, constituting the state of the system, are estimated using the EKF, from the measured change in electrical resistance (ER) of the SMA. The estimated stress is used to compute the change in length of the spring, eliminating the need for a displacement sensor. The system model used in the EKF comprises the heat balance equation and the constitutive relation of the SMA wire coupled with the force-displacement behavior of a spring. Both explicit and implicit approaches are adopted to evaluate the system model at each time-update step of the EKF. Next, in the measurement-update step, estimated states are updated based on the measured electrical resistance. It has been observed that for the same time step, the implicit approach consumes less computational time than the explicit method. To verify the implementation, EKF estimated states of the system are compared with those of an established model for different inputs to the SMA wire. An experimental setup is developed to measure the actual spring displacement and ER of the SMA, for any time-varying voltage applied to it. The process noise covariance is decided using a heuristic approach, whereas the measurement noise covariance is obtained experimentally. Finally, the EKF is used to estimate the spring displacement for a given input and the corresponding experimentally obtained ER of the SMA. The qualitative agreement between the EKF estimated displacement with that obtained experimentally reveals the true potential of this approach to harness the self-sensing capability of the SMA.

Early and late changes in the distal forelimb representation of the supplementary motor area after injury to frontal motor areas in the squirrel monkey.

PubMed

Eisner-Janowicz, Ines; Barbay, Scott; Hoover, Erica; Stowe, Ann M; Frost, Shawn B; Plautz, Erik J; Nudo, Randolph J

2008-09-01

Neuroimaging studies in stroke survivors have suggested that adaptive plasticity occurs following stroke. However, the complex temporal dynamics of neural reorganization after injury make the interpretation of functional imaging studies equivocal. In the present study in adult squirrel monkeys, intracortical microstimulation (ICMS) techniques were used to monitor changes in representational maps of the distal forelimb in the supplementary motor area (SMA) after a unilateral ischemic infarct of primary motor (M1) and premotor distal forelimb representations (DFLs). In each animal, ICMS maps were derived at early (3 wk) and late (13 wk) postinfarct stages. Lesions resulted in severe deficits in motor abilities on a reach and retrieval task. Limited behavioral recovery occurred and plateaued at 3 wk postinfarct. At both early and late postinfarct stages, distal forelimb movements could still be evoked by ICMS in SMA at low current levels. However, the size of the SMA DFL changed after the infarct. In particular, wrist-forearm representations enlarged significantly between early and late stages, attaining a size substantially larger than the preinfarct area. At the late postinfarct stage, the expansion in the SMA DFL area was directly proportional to the absolute size of the lesion. The motor performance scores were positively correlated to the absolute size of the SMA DFL at the late postinfarct stage. Together, these data suggest that, at least in squirrel monkeys, descending output from M1 and dorsal and ventral premotor cortices is not necessary for SMA representations to be maintained and that SMA motor output maps undergo delayed increases in representational area after damage to other motor areas. Finally, the role of SMA in recovery of function after such lesions remains unclear because behavioral recovery appears to precede neurophysiological map changes.

Normalization of Patient-Identified Plasma Biomarkers in SMNΔ7 Mice following Postnatal SMN Restoration

PubMed Central

Arnold, W. David; Duque, Sandra; Iyer, Chitra C.; Zaworski, Phillip; McGovern, Vicki L.; Taylor, Shannon J.; von Herrmann, Katharine M.; Kobayashi, Dione T.; Chen, Karen S.; Kolb, Stephen J.; Paushkin, Sergey V.; Burghes, Arthur H. M.

2016-01-01

Introduction and Objective Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disorder. SMA is caused by homozygous loss of the SMN1 gene and retention of the SMN2 gene resulting in reduced levels of full length SMN protein that are insufficient for motor neuron function. Various treatments that restore levels of SMN are currently in clinical trials and biomarkers are needed to determine the response to treatment. Here, we sought to investigate in SMA mice a set of plasma analytes, previously identified in patients with SMA to correlate with motor function. The goal was to determine whether levels of plasma markers were altered in the SMNΔ7 mouse model of SMA and whether postnatal SMN restoration resulted in normalization of the biomarkers. Methods SMNΔ7 and control mice were treated with antisense oligonucleotides (ASO) targeting ISS-N1 to increase SMN protein from SMN2 or scramble ASO (sham treatment) via intracerebroventricular injection on postnatal day 1 (P1). Brain, spinal cord, quadriceps muscle, and liver were analyzed for SMN protein levels at P12 and P90. Ten plasma biomarkers (a subset of biomarkers in the SMA-MAP panel available for analysis in mice) were analyzed in plasma obtained at P12, P30, and P90. Results Of the eight plasma biomarkers assessed, 5 were significantly changed in sham treated SMNΔ7 mice compared to control mice and were normalized in SMNΔ7 mice treated with ASO. Conclusion This study defines a subset of the SMA-MAP plasma biomarker panel that is abnormal in the most commonly used mouse model of SMA. Furthermore, some of these markers are responsive to postnatal SMN restoration. These findings support continued clinical development of these potential prognostic and pharmacodynamic biomarkers. PMID:27907033

Effect of the self-monitoring approach on exercise maintenance during cardiac rehabilitation: a randomized, controlled trial.

PubMed

Izawa, Kazuhiro P; Watanabe, Satoshi; Omiya, Kazuto; Hirano, Yasuyuki; Oka, Koichiro; Osada, Naohiko; Iijima, Setsu

2005-05-01

To evaluate the effect of the self-monitoring approach (SMA) on self-efficacy for physical activity (SEPA), exercise maintenance, and objective physical activity level over a 6-mo period after a supervised 6-mo cardiac rehabilitation (CR) program. We conducted a randomized, controlled trial with 45 myocardial infarction patients (38 men, seven women; mean age, 64.2 yrs) recruited after completion of an acute-phase, exercise-based CR program. Patients were randomly assigned to an SMA group (n = 24) or control group (n = 21). Along with CR, the subjects in the SMA group self-monitored their weight and physical activity for 6 mos. The SMA used in this study was based on Bandura's self-efficacy theory and was designed to enhance confidence for exercise maintenance. The control group participated in CR only. All patients were evaluated with the SEPA assessment tool. Exercise maintenance, SEPA scores, and objective physical activity (average steps per week) as a caloric expenditure were assessed at baseline and during a 6-mo period after the supervised CR program. Mean period from myocardial infarction onset did not differ significantly between the SMA and control groups (12.1 +/- 1.3 vs. 12.2 +/- 1.2 mos, P = 0.692). All patients maintained their exercise routine in the SMA group. Mean SEPA score (90.5 vs. 72.7 points, P < 0.001) and mean objective physical activity (10,458.7 vs. 6922.5 steps/wk, P < 0.001) at 12 mos after myocardial infarction onset were significantly higher in the SMA than control group. SEPA showed significant positive correlation with objective physical activity (r = 0.642, P < 0.001). SMA during supervised CR may effectively increase exercise maintenance, SEPA, and objective physical activity at 12 mos after myocardial infarction onset.

Non-linear Relationship between BOLD Activation and Amplitude of Beta Oscillations in the Supplementary Motor Area during Rhythmic Finger Tapping and Internal Timing

PubMed Central

Gompf, Florian; Pflug, Anja; Laufs, Helmut; Kell, Christian A.

2017-01-01

Functional imaging studies using BOLD contrasts have consistently reported activation of the supplementary motor area (SMA) both during motor and internal timing tasks. Opposing findings, however, have been shown for the modulation of beta oscillations in the SMA. While movement suppresses beta oscillations in the SMA, motor and non-motor tasks that rely on internal timing increase the amplitude of beta oscillations in the SMA. These independent observations suggest that the relationship between beta oscillations and BOLD activation is more complex than previously thought. Here we set out to investigate this rapport by examining beta oscillations in the SMA during movement with varying degrees of internal timing demands. In a simultaneous EEG-fMRI experiment, 20 healthy right-handed subjects performed an auditory-paced finger-tapping task. Internal timing was operationalized by including conditions with taps on every fourth auditory beat, which necessitates generation of a slow internal rhythm, while tapping to every auditory beat reflected simple auditory-motor synchronization. In the SMA, BOLD activity increased and power in both the low and the high beta band decreased expectedly during each condition compared to baseline. Internal timing was associated with a reduced desynchronization of low beta oscillations compared to conditions without internal timing demands. In parallel with this relative beta power increase, internal timing activated the SMA more strongly in terms of BOLD. This documents a task-dependent non-linear relationship between BOLD and beta-oscillations in the SMA. We discuss different roles of beta synchronization and desynchronization in active processing within the same cortical region. PMID:29249950

Usefulness of multidetector-row CT (MDCT) for the diagnosis of non-occlusive mesenteric ischemia (NOMI): assessment of morphology and diameter of the superior mesenteric artery (SMA) on multi-planar reconstructed (MPR) images.

PubMed

Woodhams, Reiko; Nishimaki, Hiroshi; Fujii, Kaoru; Kakita, Satoko; Hayakawa, Kazushige

2010-10-01

The purpose of this study was to assess the efficacy of multidetector-row CT (MDCT) for the diagnosis of non-occlusive mesenteric ischemia (NOMI) by analyzing morphology and diameter of superior mesenteric artery (SMA). We assessed whether MDCT was as useful as angiography for the diagnosis of NOMI. Four patients who were diagnosed with NOMI were retrospectively analyzed. All patients had 8-row MDCT followed by laparotomy. Two of them underwent angiography after MDCT. The morphology and diameter of SMA of these cases was analyzed on multi-planar reconstructed (MPR) images. The mean diameter of SMA of NOMI cases was compared to that of 13 control cases. MPR images of all NOMI cases showed irregular narrowing of the SMA, spasm of the arcades of SMA, and poor demonstration of intramural vessels. MPR images of two patients who had angiography were concordant with their angiograms. The mean diameter of SMA of NOMI patients was 3.4±1.1mm, which was statistically smaller than that of 13 control patients, 6.0±1.5mm (P<0.05, Wilcoxon rank sum tests). Angiography has been recognized essential for the diagnosis of NOMI. This study shows the possibility of MDCT to be an equivalently useful modality compared to angiography for the diagnosis of NOMI by interpreting morphologic appearance and diameter of SMA. Introduction of MDCT in the decision tree of NOMI treatment may bring the benefit of prompt diagnosis and subsequent early and efficient initiation of therapy, which may improve the mortality. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

The use of plastic optical fibres and shape memory alloys for damage assessment and damping control in composite materials

NASA Astrophysics Data System (ADS)

Kuang, K. S. C.; Cantwell, W. J.

2003-08-01

This paper reports the use of a plastic fibre sensor for detecting impact damage in carbon fibre epoxy cantilever beams by monitoring their damping response under free vibration loading conditions. The composite beams were impacted at impact energies up to 8 J. The residual strengths and stiffnesses of the damaged laminates were measured in order to relate reductions in their mechanical properties to changes in their damping characteristics. Here, optical fibre sensors were surface bonded to carbon fibre composite beams which were subjected to free vibration tests to monitor their dynamic response. In the second part of this study, Ni-Ti shape memory alloy (SMA) wires were employed to control and modify the damping response of a composite beam. The SMA wires were initially trained to obtain the desired shape when activated. Here, the trained SMA wires were heated locally using a nickel/chromium wire that was wrapped around the trained region of the SMA. By using this method to activate the SMA wire (as opposed to direct electrical heating), it is possible to obtain localized actuation without heating the entire length of the wire. This procedure minimizes any damage to the host material that may result from local heat transfer between the SMA wire and the composite structure. In addition, the reduction in power requirements to achieve SMA activation permits the use of small-size power packs which can in turn lead to a potential weight reduction in weight-critical applications. The findings of this study demonstrate that a trained SMA offers a superior damping capability to that exhibited by an 'as-supplied' flat-annealed wire.

Experimental Studies on Dynamic Vibration Absorber using Shape Memory Alloy (NiTi) Springs

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

Kumar, V. Raj; Kumar, M. B. Bharathi Raj; Kumar, M. Senthil

2011-10-20

Shape memory alloy (SMA) springs have been used as actuators in many applications although their use in the vibration control area is very recent. Since shape memory alloys differ from conventional alloy materials in many ways, the traditional design approach for springs is not completely suitable for designing SMA springs. Some vibration control concepts utilizing unique characteristics of SMA's will be presented in this paper.A dynamic vibration absorber (DVA) using shape memory alloy (SMA) actuator is developed for attenuation of vibration in a cantilever beam. The design procedure of the DVA is presented. The system consists of a cantilever beammore » which is considered to generate the real-time vibration using shaker. A SMA spring is used with a mass attached to its end. The stiffness of the SMA spring is dynamically varied in such a way to attenuate the vibration. Both simulation and experimentation are carried out using PID controller. The experiments were carried out by interfacing the experimental setup with a computer using LabVIEW software, Data acquisition and control are implemented using a PCI data acquisition card. Standard PID controllers have been used to control the vibration of the beam. Experimental results are used to demonstrate the effectiveness of the controllers designed and the usefulness of the proposed test platform by exciting the structure at resonance. In experimental setup, an accelerometer is used to measure the vibration which is fed to computer and correspondingly the SMA spring is actuated to change its stiffness to control the vibration. The results obtained illustrate that the developed DVA using SMA actuator is very effective in reducing structural response and have great potential to be an active vibration control medium.« less

Utility of Survival Motor Neuron ELISA for Spinal Muscular Atrophy Clinical and Preclinical Analyses

PubMed Central

Kobayashi, Dione T.; Olson, Rory J.; Sly, Laurel; Swanson, Chad J.; Chung, Brett; Naryshkin, Nikolai; Narasimhan, Jana; Bhattacharyya, Anuradha; Mullenix, Michael; Chen, Karen S.

2011-01-01

Objectives Genetic defects leading to the reduction of the survival motor neuron protein (SMN) are a causal factor for Spinal Muscular Atrophy (SMA). While there are a number of therapies under evaluation as potential treatments for SMA, there is a critical lack of a biomarker method for assessing efficacy of therapeutic interventions, particularly those targeting upregulation of SMN protein levels. Towards this end we have engaged in developing an immunoassay capable of accurately measuring SMN protein levels in blood, specifically in peripheral blood mononuclear cells (PBMCs), as a tool for validating SMN protein as a biomarker in SMA. Methods A sandwich enzyme-linked immunosorbent assay (ELISA) was developed and validated for measuring SMN protein in human PBMCs and other cell lysates. Protocols for detection and extraction of SMN from transgenic SMA mouse tissues were also developed. Results The assay sensitivity for human SMN is 50 pg/mL. Initial analysis reveals that PBMCs yield enough SMN to analyze from blood volumes of less than 1 mL, and SMA Type I patients' PBMCs show ∼90% reduction of SMN protein compared to normal adults. The ELISA can reliably quantify SMN protein in human and mouse PBMCs and muscle, as well as brain, and spinal cord from a mouse model of severe SMA. Conclusions This SMN ELISA assay enables the reliable, quantitative and rapid measurement of SMN in healthy human and SMA patient PBMCs, muscle and fibroblasts. SMN was also detected in several tissues in a mouse model of SMA, as well as in wildtype mouse tissues. This SMN ELISA has general translational applicability to both preclinical and clinical research efforts. PMID:21904622

The Upturned Superior Mesenteric Artery Sign for First-Trimester Detection of Congenital Diaphragmatic Hernia and Omphalocele.

PubMed

Lakshmy, Ravi Selvaraj; Agnees, Joy; Rose, Nity

2017-03-01

The aim of this study was to follow the course of the superior mesenteric artery (SMA) in first-trimester fetuses to predict the location of the small bowel. Its abnormal course aids in early detection of congenital diaphragmatic hernia (CDH) and assessment of the contents of omphalocele. The SMA can be easily identified in a sagittal section of the fetus by using color Doppler sonography at the 11- to 14-week scan, and normally, it has a downward course caudally to supply the intestines. The course of the SMA points to the location of the bowel. We report a series of 7 cases detected in first trimester with an abnormal course of the SMA, 3 of which had CDH and 4 of which had omphalocele. In CDH, the intestines herniate into the thoracic cavity; hence, the SMA tends to have an upward course toward the thorax. In 4 cases of omphalocele, the SMA follows the exteriorized bowel into the base of the umbilical cord. Second-trimester sonography for detection of congenital malformations is a standardized protocol, but a careful anatomic survey at the 11- to 14-week scan is often rewarding. When there is a suspicion of an intrathoracic mass or a mediastinal shift, the upturned course of SMA serves as a valuable sign in confirmation of CDH. Chromosomal abnormalities are often reported in cases of omphalocele containing small bowel only, and the upward course of the SMA toward the base of the cord helps in its early prenatal diagnosis, which facilitates early genetic assessment in these fetuses. © 2017 by the American Institute of Ultrasound in Medicine.

Suppression of α Smooth Muscle Actin Accumulation by Bovine Fetal Dermal Collagen Matrix in Full Thickness Skin Wounds

PubMed Central

Lineaweaver, William; Bush, Katie; James, Kenneth

2015-01-01

Abstract The suppression of elements associated with wound contracture and unfavorable scarring is a potentially important strategy in clinical wound management. In this study, the presence of α smooth muscle actin (αSMA), a protein involved in wound contraction, was analyzed in a series of wounds in which bovine fetal collagen (BFC) acellular dermal matrix (PriMatrix) was used in staged split thickness skin graft procedures. The results obtained through histological and quantitative image analyses of incidental biopsies from these wounds demonstrated a suppression of αSMA in the wound regions occupied by assimilated BFC relative to increased levels of αSMA found in other areas of the wound. The αSMA levels found in assimilated BFC were similar to αSMA levels in uninjured human dermis. These findings suggest a mechanism by which application of BFC could decrease contraction of full thickness skin wounds. PMID:25695450

Numerical model for an epoxy beam reinforced with superelastic shape memory alloy wires

NASA Astrophysics Data System (ADS)

Viet, N. V.; Zaki, W.; Umer, R.

2018-03-01

We present a numerical solution for a smart composite beam consisting of an epoxy matrix reinforced with unidirectional superelastic shape memory alloy (SMA) fibers with uniform circular cross section. The beam is loaded by a tip load, which is then removed resulting in shape recovery due to superelasticity of the SMA wires. The analysis is carried out considering a representative volume element (RVE) of the beam consisting of one SMA wire embedded in epoxy. The analytical model is developed for a superelastic SMA/epoxy composite beam subjected to a complete loading cycle in bending. Using the proposed model, the moment-curvature profile, martensite volume fraction variation, and axial stress are determined. The results are validated against three-dimensional finite element analysis (3D FEA) for the same conditions. The proposed work is a contribution toward better understanding of the bending behavior of superelastic SMA-reinforced composites.

Confining jackets for concrete cylinders using NiTiNb and NiTi shape memory alloy wires

NASA Astrophysics Data System (ADS)

Choi, Eunsoo; Nam, Tae-Hyun; Yoon, Soon-Jong; Cho, Sun-Kyu; Park, Joonam

2010-05-01

This study used prestrained NiTiNb and NiTi shape memory alloy (SMA) wires to confine concrete cylinders. The recovery stress of the wires was measured with respect to the maximal prestrain of the wires. SMA wires were preelongated during the manufacturing process and then wrapped around concrete cylinders of 150 mm×300 mm (phi×L). Unconfined concrete cylinders were tested for compressive strength and the results were compared to those of cylinders confined by SMA wires. NiTiNb SMA wires increased the compressive strength and ductility of the cylinders due to the confining effect. NiTiNb wires were found to be more effective in increasing the peak strength of the cylinders and dissipating energy than NiTi wires. This study showed the potential of the proposed method to retrofit reinforced concrete columns using SMA wires to protect them from earthquakes.

Suppression of α Smooth Muscle Actin Accumulation by Bovine Fetal Dermal Collagen Matrix in Full Thickness Skin Wounds.

PubMed

Lineaweaver, William; Bush, Katie; James, Kenneth

2015-06-01

The suppression of elements associated with wound contracture and unfavorable scarring is a potentially important strategy in clinical wound management. In this study, the presence of α smooth muscle actin (αSMA), a protein involved in wound contraction, was analyzed in a series of wounds in which bovine fetal collagen (BFC) acellular dermal matrix (PriMatrix) was used in staged split thickness skin graft procedures. The results obtained through histological and quantitative image analyses of incidental biopsies from these wounds demonstrated a suppression of αSMA in the wound regions occupied by assimilated BFC relative to increased levels of αSMA found in other areas of the wound. The αSMA levels found in assimilated BFC were similar to αSMA levels in uninjured human dermis. These findings suggest a mechanism by which application of BFC could decrease contraction of full thickness skin wounds.

Application study on aircraft structures of CFRP laminates with embedded SMA foils

NASA Astrophysics Data System (ADS)

Ogisu, Toshimichi; Nomura, Masato; Ando, Norio; Takaki, Junji; Takeda, Nobuo

2002-07-01

This paper reports some research results for the application study of the smart materials an structural using Shape Memory Alloy (SMA) foils. First, the authors acquired the recovery strain of CFRP laminates generated by the recovery stress of the pre-strained SMA foils. Then, the quasi-static load-unload tests were conducted using several kinds of quasi-isotropic CFRP laminates with embedded SMA foils. Micro-mechanics of damage behavior due to the effects of the recovery strain and the first transverse crack strain were discussed. The improvement of maximum 40 percent for the onset strain of the transverse cracks and maximum 60 percent for the onset strain of delamination were achieved for CFRP laminates with embedded pre-strained SMA foils compared with standard CFRP laminates. Furthermore, the authors conducted the structural element test for application to actual structures. Testing technique and the manufacturing technique of the structural element specimen were established.

FE analysis of SMA-based bio-inspired bone-joint system

NASA Astrophysics Data System (ADS)

Yang, S.; Seelecke, S.

2009-10-01

This paper presents the finite element (FE) analysis of a bio-inspired bone-joint system. Motivated by the BATMAV project, which aims at the development of a micro-air-vehicle platform that implements bat-like flapping flight capabilities, we study the actuation of a typical elbow joint, using shape memory alloy (SMA) in a dual manner. Micro-scale martensitic SMA wires are used as 'metal muscles' to actuate a system of humerus, elbow joint and radius, in concert with austenitic wires, which operate as flexible joints due to their superelastic character. For the FE analysis, the humerus and radius are modeled as standard elastic beams, while the elbow joint and muscle wires use the Achenbach-Muller-Seelecke SMA model as beams and cable elements, respectively. The particular focus of the paper is on the implementation of the above SMA model in COMSOL.

Perceptions of Equine Assisted Activities and Therapies by Parents and Children with Spinal Muscular Atrophy

PubMed Central

Lemke, Danielle; Rothwell, Erin; Newcomb, Tara M.; Swoboda, Kathryn J.

2014-01-01

Purpose To identify the physical and psychosocial effects of equine assisted activities and therapies (EAAT) on children with Spinal Muscular Atrophy (SMA) from the perspective of the child and their parents. Methods The families of all eligible children with SMA, who reported participation in EAAT, from a western metropolitan academic center were contacted and invited to participate. This study implemented qualitative, semi-structured interviews of children with SMA and their parents. Results Three themes emerged from the qualitative content analysis: physical/psychosocial benefits; relationship development with the horses, instructors, and children; and barriers to continued EAAT engagement. Conclusions The data suggest the overall EAAT experience was a source of enjoyment, self-confidence, and normalcy for the children with SMA. The results of this study provide preliminary support for the use of EAAT among children with SMA. PMID:24675128

Superelastic SMA U-shaped dampers with self-centering functions

NASA Astrophysics Data System (ADS)

Wang, Bin; Zhu, Songye

2018-05-01

As high-performance metallic materials, shape memory alloys (SMAs) have been investigated increasingly by the earthquake engineering community in recent years, because of their remarkable self-centering (SC) and energy-dissipating capabilities. This paper systematically presents an experimental study on a novel superelastic SMA U-shaped damper (SMA-UD) with SC function under cyclic loading. The mechanical properties, including strength, SC ability, and energy-dissipating capability with varying loading amplitudes and strain rates are evaluated. Test results show that excellent and stable flag-shaped hysteresis loops are exhibited in multiple loading cycles. Strain rate has a negligible effect on the cyclic behavior of the SMA-UD within the dynamic frequency range of typical interest in earthquake engineering. Furthermore, a numerical investigation is performed to understand the mechanical behavior of the SMA-UD. The numerical model is calibrated against the experimental results with reasonable accuracy. Then, the stress–strain states with different phase transformations are also discussed.

Adaptive online inverse control of a shape memory alloy wire actuator using a dynamic neural network

NASA Astrophysics Data System (ADS)

Mai, Huanhuan; Song, Gangbing; Liao, Xiaofeng

2013-01-01

Shape memory alloy (SMA) actuators exhibit severe hysteresis, a nonlinear behavior, which complicates control strategies and limits their applications. This paper presents a new approach to controlling an SMA actuator through an adaptive inverse model based controller that consists of a dynamic neural network (DNN) identifier, a copy dynamic neural network (CDNN) feedforward term and a proportional (P) feedback action. Unlike fixed hysteresis models used in most inverse controllers, the proposed one uses a DNN to identify online the relationship between the applied voltage to the actuator and the displacement (the inverse model). Even without a priori knowledge of the SMA hysteresis and without pre-training, the proposed controller can precisely control the SMA wire actuator in various tracking tasks by identifying online the inverse model of the SMA actuator. Experiments were conducted, and experimental results demonstrated real-time modeling capabilities of DNN and the performance of the adaptive inverse controller.

Shape Memory Alloy Modeling and Applications to Porous and Composite Structures

NASA Astrophysics Data System (ADS)

Zhu, Pingping

There has been a growing concern about an exciting class of advanced material -- shape memory alloys (SMAs) since their discovery several decades ago. SMAs exhibit large reversible stresses and strains owing to a thermoelastic phase transformation. They have been widely used in many engineering fields including aerospace, biomedical, and automotive engineering, especially as sensors, actuators, bone implants and deployable switches. The behavior of SMAs is very complex due to the coupling between thermal and mechanical effects. Theoretical and computational tools are used in this dissertation to investigate the mechanical behavior of SMA and its related structures for seeking better and wider application of this material. In the first part of this dissertation, we proposed an improved macroscopic phenomenological constitutive model of SMA that accounts for all major mechanical behaviors including elasticity, phase transformation, reorientation and plasticity. The model is based on some previous work developed in the Brinson group, and the current efforts are focused on plasticity, the application of a pre-defined strain, unification of notations, and other coding-related work. A user subroutine script VUMAT is developed to implement the constitutive model to the commercial finite element software Abaqus. Typical simulation results based on the model are presented, as well as verification with some experimental results. In the second part, we apply the developed constitutive model to a series of two-dimensional SMA plates with structured arrays of pores to investigate the structural response, especially the stress, strain, phase transformation, and plastic fields. Results are documented about the coupling of the elastic, transformation and plastic fields about the arrays of pores. Theoretical and experimental DIC results are also utilized to validate some simulation results. Conclusions are then drawn to provide understanding in the effect of pores and the underlying mechanism of pore interactions in the SMA foams. Additionally, the influence of geometric features including the number, size and locations of pores are studied to guide the design and optimization of porous SMAs. Thirdly, modeling and simulation are performed on a series of cracked self-healing SMA composite systems. These composites are to be applied in aeronautic structures where fatigue crack initiation and propagation is a significant safety and economic concern, based on a liquid-assisted SMA self-healing technology. We develop a modeling approach in Abaqus to create composite models with the as-is or pre-strained SMA wires. The modeling approach is validated by two simulation cases following the experiment setups. The amount of crack closure in the SMA-reinforced MMC is then focused, especially on the role of the SMA reinforcement, the softening property of the matrix, and the effect of pre-strain in the SMA. Composites with various geometric configurations of SMA are also created to study how the number, location, length and orientation of the SMA wires would affect the crack closure and self-healing behavior. These studies, from three aspects, provide deep insights to SMA and its related applications from the modeling and simulation point of view, which can further guide the development and application of this unique material.

Self-Monitoring of Attention versus Self-Monitoring of Performance: Effects on Attention and Academic Performance.

ERIC Educational Resources Information Center

Reid, Robert; Harris, Karen R.

1993-01-01

Twenty-eight students (ages 9-12) with learning disabilities were taught a spelling study procedure (SSP), followed by instruction in self-monitoring of performance (SMP) and self-monitoring of attention (SMA). On-task behavior was significantly higher in both SMA and SMP than in SSP. Neither SMP nor SMA were inherently superior across subjects,…

Switchable Shape Memory Alloys (SMA) Thermal Materials Project

NASA Technical Reports Server (NTRS)

Falker, John; Zeitlin, Nancy; Williams, Martha; Fesmire, James

2014-01-01

Develop 2-way switchable thermal systems for use in systems that function in cold to hot temperature ranges using different alloy designs for SMA system concepts. In this project, KSC will specifically address designs of two proof of concept SMA systems with transition temperatures in the 65-95 C range and investigate cycle fatigue and "memory loss" due to thermal cycling.

Changing the S and MA [Safety and Mission Assurance] Paradigm

NASA Technical Reports Server (NTRS)

Malone, Roy W., Jr.

2010-01-01

Objectives: 1) Optimize S&MA organization to best facilitate Shuttle transition in 2010, successfully support Ares developmental responsibilities, and minimize the impacts of the gap between last Shuttle flight and start of Ares V Project. 2) Improve leveraging of critical skills and experience between Shuttle and Ares. 3) Split technical and supervisory functions to facilitate technical penetration. 4) Create Chief Safety and Mission Assurance Officer (CSO) stand-alone position for successfully implementation of S&MA Technical Authority. 5) Minimize disruption to customers. 6) Provide early involvement of S&MA leadership team and frequent/open communications with S&MA team members and steak-holders.

The drastic reduction of SMN protein in SMA I spinal cord motor neurons is not due to inefficient transcription.

PubMed

Mirabella, M; Servidei, S; Broccolini, A; Gandolfi, N; Ricci, E; Neri, G; Tonali, P; Brahe, C

1999-04-01

Spinal muscular atrophy (SMA) is caused by homozygous absence of the telomeric copy of the survival motor neuron (SMNt) gene. SMNt and its homologous centromeric copy (SMNc) encode the SMN protein, which is markedly reduced in SMA I patients. We have performed SMN transcript and protein studies on spinal cord sections of an SMA I patient using in situ hybridization and immunofluorescence. While the amount of protein was negligible, the level of transcripts was comparable with that of controls. These findings suggest that the reduced protein level is not caused by a deficient transcription of the SMNc gene.

VizieR Online Data Catalog: 340GHz SMA obs. of 50 nearby protoplanetary disks (Tripathi+, 2017)

NASA Astrophysics Data System (ADS)

Tripathi, A.; Andrews, S. M.; Birnstiel, T.; Wilner, D. J.

2018-03-01

A sample of 50 nearby (d<=200pc) disk targets was collated from the archived catalog of ~340GHz (880um) continuum measurements made with the Submillimeter Array (SMA), since the start of science operations in 2004. Of the 50 disks in our survey, 10 were recently observed by us expressly for the purposes of the present study. To our knowledge, the SMA observations of 18 targets have not yet been published elsewhere. Table 1 is a brief SMA observation log, with references for where the data originally appeared (observations span 2005 jun 12 to 2015 Jan 19). (3 data files).

Active Vibration Control of Elastic Beam by Means of Shape Memory Alloy Layers

NASA Technical Reports Server (NTRS)

Chen, Q.; Levy, C.

1996-01-01

The mathematical model of a flexible beam covered with shape memory alloy (SMA) layers is presented. The SMA layers are used as actuators, which are capable of changing their elastic modulus and recovery stress, thus changing the natural frequency of, and adjusting the excitation to, the vibrating beam. The frequency factor variation as a function of SMA Young's modulus, SMA layer thickness and beam thickness is discussed. Also control of the beam employing an optimal linear control law is evaluated. The control results indicate how the system reacts to various levels of excitation input through the non-homogeneous recovery shear term of the governing differential equation.

Simulated and Experimental Damping Properties of a SMA/Fiber Glass Laminated Composite

NASA Astrophysics Data System (ADS)

Arnaboldi, S.; Bassani, P.; Biffi, C. A.; Tuissi, A.; Carnevale, M.; Lecis, N.; Loconte, A.; Previtali, B.

2011-07-01

In this article, an advanced laminated composite is developed, combining the high damping properties of shape memory alloy (SMA) with mechanical properties and light weight of a glass-fiber reinforced polymer. The composite is formed by stacking a glass-fiber reinforced epoxy core between two thin patterned strips of SMA alloy, and two further layers of fiber-glass reinforced epoxy. The bars of the laminated composite were assembled and cured in autoclave. The patterning was designed to enhance the interface adhesion between matrix and SMA inserts and optimally exploit the damping capacity of the SMA thin ribbons. The patterned ribbons of the SMA alloy were cut by means of a pulsed fiber laser source. Damping properties at different amplitudes on full scale samples were investigated at room temperature with a universal testing machine through dynamic tension tests, while temperature dependence was investigated by dynamic mechanical analyses (DMA) on smaller samples. Experimental results were used in conjunction with FEM analysis to optimize the geometry of the inserts. Experimental decay tests on the laminated composite have been carried out to identify the adimensional damping value related to their first flexural mode.

Shape memory alloy smart knee spacer to enhance knee functionality: model design and finite element analysis.

PubMed

Gautam, Arvind; Rani, A Bhargavi; Callejas, Miguel A; Acharyya, Swati Ghosh; Acharyya, Amit; Biswas, Dwaipayan; Bhandari, Vasundhra; Sharma, Paresh; Naik, Ganesh R

2016-08-01

In this paper we introduce Shape Memory Alloy (SMA) for designing the tibial part of Total Knee Arthroplasty (TKA) by exploiting the shape-memory and pseudo-elasticity property of the SMA (e.g. NiTi). This would eliminate the drawbacks of the state-of-the art PMMA based knee-spacer including fracture, sustainability, dislocation, tilting, translation and subluxation for tackling the Osteoarthritis especially for the aged people of 45-plus or the athletes. In this paper a Computer Aided Design (CAD) model using SolidWorks for the knee-spacer is presented based on the proposed SMA adopting the state-of-the art industry-standard geometry that is used in the PMMA based spacer design. Subsequently Ansys based Finite Element Analysis is carried out to measure and compare the performance between the proposed SMA based model with the state-of-the art PMMA ones. 81% more bending is noticed in the PMMA based spacer compared to the proposed SMA that would eventually cause fracture and tilting or translation of spacer. Permanent shape deformation of approximately 58.75% in PMMA based spacer is observed compared to recoverable 11% deformation in SMA when same load is applied on both separately.

cTBS disruption of the supplementary motor area perturbs cortical sequence representation but not behavioural performance.

PubMed

Solopchuk, Oleg; Alamia, Andrea; Dricot, Laurence; Duque, Julie; Zénon, Alexandre

2017-12-01

Neuroimaging studies have repeatedly emphasized the role of the supplementary motor area (SMA) in motor sequence learning, but interferential approaches have led to inconsistent findings. Here, we aimed to test the role of the SMA in motor skill learning by combining interferential and neuroimaging techniques. Sixteen subjects were trained on simple finger movement sequences for 4 days. Afterwards, they underwent two neuroimaging sessions, in which they executed both trained and novel sequences. Prior to entering the scanner, the subjects received inhibitory transcranial magnetic stimulation (TMS) over the SMA or a control site. Using multivariate fMRI analysis, we confirmed that motor training enhances the neural representation of motor sequences in the SMA, in accordance with previous findings. However, although SMA inhibition altered sequence representation (i.e. between-sequence decoding accuracy) in this area, behavioural performance remained unimpaired. Our findings question the causal link between the neuroimaging correlate of elementary motor sequence representation in the SMA and sequence generation, calling for a more thorough investigation of the role of this region in performance of learned motor sequences. Copyright © 2017 Elsevier Inc. All rights reserved.

Performance of SMA-reinforced composites in an aerodynamic profile

NASA Astrophysics Data System (ADS)

Simpson, John; Boller, Christian

2002-07-01

Within the European collaborative applied fundamental research project ADAPT, fundamentals of SMA-reinforced composites were evaluated and the specific manufacturing techniques for these composites developed and realised. The involved partners are listed at the end. To demonstrate applicability of these composites a realistically scaled aerodynamic profile of around 0.5m span by 0.5m root chord was designed, manufactured and assembled. The curved skins were manufactured as SMA composites with two layers of SMA-wires integrated into the layup of aramid fibre prepregs. All SMA wires were connected such that they can be operated as individual sets of wires and at low voltages, similar to the conditions for electrical energy generation in a real aircraft. The profile was then mounted on a vibration test rig and activated and excited by a shaker at its tip which allowed to test the dynamic performance of the profile under different external loading conditions with various internal actuation conditions through the SMA wires. The paper includes some background of the design and manufacturing of the aerodynamic profile and will discuss some of the results determined recently on the test rig. A view with regard to future wind tunnel testing will be given as well.

Inhibition of myostatin does not ameliorate disease features of severe spinal muscular atrophy mice

PubMed Central

Sumner, Charlotte J.; Wee, Claribel D.; Warsing, Leigh C.; Choe, Dong W.; Ng, Andrew S.; Lutz, Cathleen; Wagner, Kathryn R.

2009-01-01

There is currently no treatment for the inherited motor neuron disease, spinal muscular atrophy (SMA). Severe SMA causes lower motor neuron loss, impaired myofiber development, profound muscle weakness and early mortality. Myostatin is a transforming growth factor-β family member that inhibits muscle growth. Loss or blockade of myostatin signaling increases muscle mass and improves muscle strength in mouse models of primary muscle disease and in the motor neuron disease, amyotrophic lateral sclerosis. In this study, we evaluated the effects of blocking myostatin signaling in severe SMA mice (hSMN2/delta7SMN/mSmn−/−) by two independent strategies: (i) transgenic overexpression of the myostatin inhibitor follistatin and (ii) post-natal administration of a soluble activin receptor IIB (ActRIIB-Fc). SMA mice overexpressing follistatin showed little increase in muscle mass and no improvement in motor function or survival. SMA mice treated with ActRIIB-Fc showed minimal improvement in motor function, and no extension of survival compared with vehicle-treated mice. Together these results suggest that inhibition of myostatin may not be a promising therapeutic strategy in severe forms of SMA. PMID:19477958

Towards High-Frequency Shape Memory Alloy Actuators Incorporating Liquid Metal Energy Circuits

NASA Astrophysics Data System (ADS)

Hartl, Darren; Mingear, Jacob; Bielefeldt, Brent; Rohmer, John; Zamarripa, Jessica; Elwany, Alaa

2017-12-01

Large shape memory alloy (SMA) actuators are currently limited to applications with low cyclic actuation frequency requirements due to their generally poor heat transfer rates. This limitation can be overcome through the use of distributed body heating methods such as induction heating or by accelerated cooling methods such as forced convection in internal cooling channels. In this work, a monolithic SMA beam actuator containing liquid gallium-indium alloy-filled channels is fabricated through additive manufacturing. These liquid metal channels enable a novel multi-physical thermal control system, allowing for increased heating and cooling rates to facilitate an increased cyclic actuation frequency. Liquid metal flowing in the channels performs the dual tasks of inductively heating the surrounding SMA material and then actively cooling the SMA via forced internal fluid convection. A coupled thermoelectric model, implemented in COMSOL, predicts a possible fivefold increase in the cyclic actuation frequency due to these increased thermal transfer rates when compared to conventional SMA forms having external heating coils and being externally cooled via forced convection. The first ever experimental prototype SMA actuator of this type is described and, even at much lower flow rates, is shown to exhibit a decrease in cooling time of 40.9%.

Shape memory alloy actuated accumulator for ultra-deepwater oil and gas exploration

NASA Astrophysics Data System (ADS)

Patil, Devendra; Song, Gangbing

2016-04-01

As offshore oil and gas exploration moves further offshore and into deeper waters to reach hydrocarbon reserves, it is becoming essential for the industry to develop more reliable and efficient hydraulic accumulators to supply pressured hydraulic fluid for various control and actuation operations, such as closing rams of blowout preventers and controlling subsea valves on the seafloor. By utilizing the shape memory effect property of nitinol, which is a type of shape memory alloy (SMA), an innovative SMA actuated hydraulic accumulator prototype has been developed and successfully tested at Smart Materials and Structure Laboratory at the University of Houston. Absence of gas in the developed SMA accumulator prototype makes it immune to hydrostatic head loss caused by water depth and thus reduces the number of accumulators required in deep water operations. Experiments with a feedback control have demonstrated that the proposed SMA actuated accumulator can provide precisely regulated pressurized fluids. Furthermore the potential use of ultracapacitors along with an embedded system to control the electric power supplied to SMA allows this accumulator to be an autonomous device for deployment. The developed SMA accumulator will make deepwater oil extraction systems more compact and cost effective.

Hydroxyurea enhances SMN2 gene expression through nitric oxide release.

PubMed

Xu, Cheng; Chen, Xin; Grzeschik, Susanna M; Ganta, Madhuri; Wang, Ching H

2011-02-01

Small molecules that increase full-length survivor motor neuron (SMN) gene transcript are promising therapeutic candidates for spinal muscular atrophy (SMA). Hydroxyurea (HU) has recently been shown to increase full-length SMN transcript in cultured lymphocytes from patients with SMA. We investigate the mechanism by which HU enhances full-length SMN2 gene expression in SMA lymphocytes. Nitric oxide (NO) is a major intracellular metabolite of HU. We test whether NO donors can themselves enhance full-length SMN2 expression. Eighteen cell lines (five type I, five type II, six type III SMA, and two non-SMA controls) were treated with or without NO donors for 48 h. SMA cells treated with HU and three NO donors: two long-acting donors, Deta-NONOate and S-nitrosoglutathione, and one short-acting donor, 3-ethyl-3-(ethylaminoethyl)-1-hydroxy-2-oxo-1-triazene, resulted in significant increase in full-length SMN2 mRNA. These effects were abolished by co-treatment with an NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide. One short-acting NO donor, S-nitroso-N-acetyl-DL-penicillamine, failed to show significant effect on full-length SMN2 expression, possibly due to high degree of cytotoxicity. These results were observed using both densitometry and quantitative PCR methods. We conclude that HU enhances SMN2 expression through the release of NO. NO donors may themselves be considered as new therapeutic candidates for SMA.

Effect of Substrate Roughness on Adhesion and Structural Properties of Ti-Ni Shape Memory Alloy Thin Film.

PubMed

Kim, Donghwan; Lee, Hyunsuk; Bae, Joohyeon; Jeong, Hyomin; Choi, Byeongkeun; Nam, Taehyun; Noh, Jungpil

2018-09-01

Ti-Ni shape memory alloy (SMA) thin films are very attractive material for industrial and medical applications such as micro-actuator, micro-sensors, and stents for blood vessels. An important property besides shape memory effect in the application of SMA thin films is the adhesion between the film and the substrate. When using thin films as micro-actuators or micro-sensors in MEMS, the film must be strongly adhered to the substrate. On the other hand, when using SMA thin films in medical devices such as stents, the deposited alloy thin film must be easily separable from the substrate for efficient processing. In this study, we investigated the effect of substrate roughness on the adhesion of Ti-Ni SMA thin films, as well as the structural properties and phase-transformation behavior of the fabricated films. Ti-Ni SMA thin films were deposited onto etched glass substrates with magnetron sputtering. Radio frequency plasma was used for etching the substrate. The adhesion properties were investigated through progressive scratch test. Structural properties of the films were determined via Feld emission scanning electron microscopy, X-ray diffraction measurements (XRD) and Energy-dispersive X-ray spectroscopy analysis. Phase transformation behaviors were observed with differential scanning calorimetry and low temperature-XRD. Ti-Ni SMA thin film deposited onto rough substrate provides higher adhesive strength than smooth substrate. However the roughness of the substrate has no influence on the growth and crystallization of the Ti-Ni SMA thin films.

Deletion of atrophy enhancing genes fails to ameliorate the phenotype in a mouse model of spinal muscular atrophy.

PubMed

Iyer, Chitra C; McGovern, Vicki L; Wise, Dawnne O; Glass, David J; Burghes, Arthur H M

2014-05-01

Spinal muscular atrophy (SMA) is an autosomal recessive disease causing degeneration of lower motor neurons and muscle atrophy. One therapeutic avenue for SMA is targeting signaling pathways in muscle to ameliorate atrophy. Muscle Atrophy F-box, MAFbx, and Muscle RING Finger 1, MuRF1, are muscle-specific ubiquitin ligases upregulated in skeletal and cardiac muscle during atrophy. Homozygous knock-out of MAFbx or MuRF1 causes muscle sparing in adult mice subjected to atrophy by denervation. We wished to determine whether blockage of the major muscle atrophy pathways by deletion of MAFbx or MuRF1 in a mouse model of SMA would improve the phenotype. Deletion of MAFbx in the Δ7 SMA mouse model had no effect on the weight and the survival of the mice while deletion of MuRF1 was deleterious. MAFbx(-/-)-SMA mice showed a significant alteration in fiber size distribution tending towards larger fibers. In skeletal and cardiac tissue MAFbx and MuRF1 transcripts were upregulated whereas MuRF2 and MuRF3 levels were unchanged in Δ7 SMA mice. We conclude that deletion of the muscle ubiquitin ligases does not improve the phenotype of a Δ7 SMA mouse. Furthermore, it seems unlikely that the beneficial effect of HDAC inhibitors is mediated through inhibition of MAFbx and MuRF1. Copyright © 2014 Elsevier B.V. All rights reserved.

Evidence for a role of TGF-beta1 in the expression and regulation of alpha-SMA in fetal growth restricted placentae.

PubMed

Todros, T; Marzioni, D; Lorenzi, T; Piccoli, E; Capparuccia, L; Perugini, V; Cardaropoli, S; Romagnoli, R; Gesuita, R; Rolfo, A; Paulesu, L; Castellucci, M

2007-01-01

There is evidence that alpha-smooth muscle actin (alpha-SMA) is a protein that plays a pivotal role in the production of contractile forces and it is induced by transforming growth factor-beta1 (TGF-beta1). We have analysed the expression of alpha-SMA, TGF-beta1, its receptor RI and the activator phospho-Smad2 in (a) fetal growth restriction pre-eclamptic placentae characterised by early onset and absence of end diastolic velocities in the umbilical arteries (FGR-AED) and (b) control placentae accurately matched for gestational age. The study was performed by immunohistochemical, quantitative Western blotting, ELISA, RT-PCR and in vitro analyses. We found that TGF-beta1 stimulates alpha-SMA production in chorionic villi cultured in vitro. In addition, we observed that in vivo TGF-beta1 concentration is significantly higher in FGR-AED placental samples than in control placentae and that this growth factor could have a paracrine action on villous stroma myofibroblasts expressing TGF-beta1 receptors and phospho-Smad2. Indeed, we report that alpha-SMA undergoes a redistribution in FGR-AED placental villous tree, i.e. we show that alpha-SMA is enhanced in medium and small stem villi and significantly decreased in the peripheral villi. Our data allow us to consider TGF-beta1 and alpha-SMA as key molecules related to FGR-AED placental villous tree phenotypic changes responsible for increased impedance to blood flow observable in this pathology.

Analysis of the fibroblast growth factor system reveals alterations in a mouse model of spinal muscular atrophy.

PubMed

Hensel, Niko; Ratzka, Andreas; Brinkmann, Hella; Klimaschewski, Lars; Grothe, Claudia; Claus, Peter

2012-01-01

The monogenetic disease Spinal Muscular Atrophy (SMA) is characterized by a progressive loss of motoneurons leading to muscle weakness and atrophy due to severe reduction of the Survival of Motoneuron (SMN) protein. Several models of SMA show deficits in neurite outgrowth and maintenance of neuromuscular junction (NMJ) structure. Survival of motoneurons, axonal outgrowth and formation of NMJ is controlled by neurotrophic factors such as the Fibroblast Growth Factor (FGF) system. Besides their classical role as extracellular ligands, some FGFs exert also intracellular functions controlling neuronal differentiation. We have previously shown that intracellular FGF-2 binds to SMN and regulates the number of a subtype of nuclear bodies which are reduced in SMA patients. In the light of these findings, we systematically analyzed the FGF-system comprising five canonical receptors and 22 ligands in a severe mouse model of SMA. In this study, we demonstrate widespread alterations of the FGF-system in both muscle and spinal cord. Importantly, FGF-receptor 1 is upregulated in spinal cord at a pre-symptomatic stage as well as in a mouse motoneuron-like cell-line NSC34 based model of SMA. Consistent with that, phosphorylations of FGFR-downstream targets Akt and ERK are increased. Moreover, ERK hyper-phosphorylation is functionally linked to FGFR-1 as revealed by receptor inhibition experiments. Our study shows that the FGF system is dysregulated at an early stage in SMA and may contribute to the SMA pathogenesis.

Synthesis and therapeutic effect of styrene–maleic acid copolymer-conjugated pirarubicin

PubMed Central

Tsukigawa, Kenji; Liao, Long; Nakamura, Hideaki; Fang, Jun; Greish, Khaled; Otagiri, Masaki; Maeda, Hiroshi

2015-01-01

Previously, we prepared a pirarubicin (THP)-encapsulated micellar drug using styrene–maleic acid copolymer (SMA) as the drug carrier, in which active THP was non-covalently encapsulated. We have now developed covalently conjugated SMA-THP (SMA-THP conjugate) for further investigation toward clinical development, because covalently linked polymer–drug conjugates are known to be more stable in circulation than drug-encapsulated micelles. The SMA-THP conjugate also formed micelles and showed albumin binding capacity in aqueous solution, which suggested that this conjugate behaved as a macromolecule during blood circulation. Consequently, SMA-THP conjugate showed significantly prolonged circulation time compared to free THP and high tumor-targeting efficiency by the enhanced permeability and retention (EPR) effect. As a result, remarkable antitumor effect was achieved against two types of tumors in mice without apparent adverse effects. Significantly, metastatic lung tumor also showed the EPR effect, and this conjugate reduced metastatic tumor in the lung almost completely at 30 mg/kg once i.v. (less than one-fifth of the maximum tolerable dose). Although SMA-THP conjugate per se has little cytotoxicity in vitro (1/100 of free drug THP), tumor-targeted accumulation by the EPR effect ensures sufficient drug concentrations in tumor to produce an antitumor effect, whereas toxicity to normal tissues is much less. These findings suggest the potential of SMA-THP conjugate as a highly favorable candidate for anticancer nanomedicine with good stability and tumor-targeting properties in vivo. PMID:25529761

Differential responses of EGFR-/AGT-expressing cells to the "combi-triazene" SMA41.

PubMed

Matheson, Stephanie L; McNamee, James P; Jean-Claude, Bertrand J

2003-01-01

Previous studies have demonstrated enhanced potency associated with the binary [DNA/epidermal growth factor receptor (EGFR)] targeting properties of SMA41 (a chimeric 3-(alkyl)-1,2,3-triazene linked to a 4-anilinoquinazoline backbone) in the A431 (epidermal carcinoma of the vulva) cell line. We now report on the dependence of its antiproliferative effects (e.g. DNA damage, cell survival) on the EGFR and the DNA repair protein O6-alkylguanine DNA alkyltransferase (AGT) contents of 12 solid tumor cell lines, two of which, NIH3T3 and NIH3T3 HER14 (engineered to overexpress EGFR), were isogenic. Receptor type specificity was determined using ELISA for competitive binding, as well as growth factor-stimulation assays. DNA damage was studied using single-cell microelectrophoresis (comet) assays, and levels of EGFR were determined by Western blotting. The effects of SMA41 on the cell cycle of NIH3T3 cells were investigated using univariate flow cytometry. Studies of receptor type specificity showed that SMA41: (a) preferentially inhibited the kinase activity of EGFR over those of Src, insulin receptor and protein kinase C (PKC, a serine/threonine kinase), (b) induced stronger inhibition of growth stimulated with EGF than of growth stimulated with platelet-derived growth factor (PDGF) or fetal bovine serum (FBS). Despite the EGFR specificity of SMA41, there was an absence of a linear correlation between the EGFR status of our solid tumor cell lines and levels of DNA damage induced by the alkylating component. Similarly, EGFR levels did not correlate with IC(50) values. The antiproliferative activities of SMA41 correlated more with the AGT status of these cells and paralleled those of the clinical triazene temozolomide (TEM). However, throughout the panel, tumor cell sensitivity to SMA41 was consistently stronger than to its closest analogue TEM. Experiments performed with the isogenic cells showed that SMA41 was capable of inducing twofold higher levels of DNA damage in the EGFR transfectant and delayed cell entry to G(2)/M in both cell types. When the cells were starved and growth-stimulated with FBS (conditions under which both cell types were growth-stimulated), in contrast to TEM, SMA41 and its hydrolytic metabolite SMA52 exhibited approximately nine- and threefold stronger inhibition of growth of the EGFR transfectant. These results suggest that, in addition to its ability to induce DNA damage and cell cycle perturbations, SMA41 is capable of selectively targeting the cells with a growth advantage conferred by EGFR transfection. When compared with the monoalkyltriazene prodrug TEM, its potency may be further enhanced by its ability to hydrolyze to another signal transduction inhibitor (SMA52) plus a DNA alkylating agent that may further contribute to chemosensitivity. Thus, our new "combi-targeting" strategy may well represent a tandem approach to selectively blocking receptor tyrosine kinase-mediated growth signaling while inducing significant levels of cytotoxic DNA lesions in refractory tumors.

Myofibroblast distribution in Dupuytren's cords: correlation with digital contracture.

PubMed

Verjee, Liaquat Suleman; Midwood, Kim; Davidson, Dominique; Essex, David; Sandison, Ann; Nanchahal, Jagdeep

2009-12-01

Dupuytren's tissue has typically been described as being composed of myofibroblast-rich palmar nodules and relatively acellular tendon-like cords. We aimed to determine myofibroblast distribution (alpha-smooth muscle actin [alpha-SMA] positive cells) within Dupuytren's tissue and to correlate histologically defined alpha-SMA-positive nodules with digital contracture and recurrent disease. One hundred and three digital Dupuytren's cords (72 fasciectomy, 31 dermofasciectomy) were stained with anti-alpha-SMA antibody. The presence of alpha-SMA-positive nodules, their surface area, and alpha-SMA-positive cells were quantified throughout excised Dupuytren's tissue. Clinical data on diathesis, flexion deformity, and previous surgeries were collected. Cords were nodular (66%) or non-nodular (34%). Nodular cords contained 1 (55%), 2 (33%), or 3 or more nodules (12%) composed of localized collections of cells. The mean total nodule surface area was 23 mm(2) (range, 1.3-105 mm(2)). Nodules contained the highest number of alpha-SMA-positive cells (mean 97%, 2374 cells/mm(2)) compared to peri-nodular areas (mean 32%, 763 cells/mm(2)), and more distant cord (mean 8%, 495 cells/mm(2)). Non-nodular cords contained 9% to 17% alpha-SMA-positive cells (mean 475-663 cells/mm(2)), with higher numbers distally. There was greater digital contracture in patients with non-nodular cords. Thirty-six of 38 proximal interphalangeal (PIP) joint-marked samples had a nodule that co-localized with the PIP joint. Nodule size did not correlate with flexion deformity or with primary or recurrent disease. We found that two thirds of digital cords were nodular. Nodules were hypercellular, the majority being alpha-SMA-positive cells. Nodules varied in size and co-localized with the PIP joint. Cord was relatively cellular throughout; a proportion of these cells were alpha-SMA-positive and cells aligned with collagen fibers. Non-nodular cords correlated with significantly greater digital flexion contracture. We propose that cells in nodular cords contract and deposit extracellular matrix components. The matrix is then remodeled in shortened configuration, and as fixed flexion deformity develops, stress shielding eventually leads to myofibroblast apoptosis, and cord becomes less cellular.

Investigation of residual stresses in shape memory alloy (SMA) composites

NASA Astrophysics Data System (ADS)

Berman, Justin Bradley

Shape memory alloy (SMA) composites are a class of smart materials in which SMA actuators are embedded in a host matrix. The shape memory effect allows for stress induced phase transformations and large recoverable strains that make SMA composites promising candidates for structural shape/vibration control, impact absorption, aircraft deicing or in-flight airfoil shape control systems. However, the difference in thermal expansion between the SMA and the host material leads to residual stresses during processing. In addition, the SMA transformation from martensite to austenite, or the reverse, also generate stresses. These stresses acting in combination can lead to SMA/polymer interfacial debonding or microcracking of the host matrix. The present work was undertaken to study the behavior of nitinol shape memory alloys embedded in epoxy and glass/epoxy matrices and to investigate the development of residual stresses during their manufacture and actuation. A three-phase concentric cylinder micromechanics model and an SMA composite thermoelastic beam theory were developed to analyze the micromechanical and structural-level thermal and transformational stresses for nitinol composites induced by nitinol wires embedded in a host matrix. A series of warpage experiments were conducted on nitinol composite beams during heating cycles to provide experimental validation of model predictions and to assess their thermoelastic structural behavior under non-mechanical loading. Micromechanical model results indicate that excessive residual hoop stresses in nitino/graphite/epoxy composites leads to radial cracking around the embedded nitinol wires. Based on modeling results, the most important factor in reducing residual stresses (and thereby preventing radial cracking) is increasing the level of recovery strain for the nitinol wire. The SMA composite beam model agrees well with experimental data captured for the nitinol/epoxy beam series. Warpage experiments on nitinol/glass/epoxy beams showed a large increase in the effective austenitic start temperature (As) of 9.3°C. The elevation of the effective As together with other observations of warpage development indicates that plastic flow may have occurred in nitinol wires when embedded in glass/epoxy. These observations reinforce the need to train nitinol wires at modest recovery levels when embedding in relatively stiff materials.

Deficiency of the Survival of Motor Neuron Protein Impairs mRNA Localization and Local Translation in the Growth Cone of Motor Neurons.

PubMed

Fallini, Claudia; Donlin-Asp, Paul G; Rouanet, Jeremy P; Bassell, Gary J; Rossoll, Wilfried

2016-03-30

Spinal muscular atrophy (SMA) is a neurodegenerative disease primarily affecting spinal motor neurons. It is caused by reduced levels of the survival of motor neuron (SMN) protein, which plays an essential role in the biogenesis of spliceosomal small nuclear ribonucleoproteins in all tissues. The etiology of the specific defects in the motor circuitry in SMA is still unclear, but SMN has also been implicated in mediating the axonal localization of mRNA-protein complexes, which may contribute to the axonal degeneration observed in SMA. Here, we report that SMN deficiency severely disrupts local protein synthesis within neuronal growth cones. We also identify the cytoskeleton-associated growth-associated protein 43 (GAP43) mRNA as a new target of SMN and show that motor neurons from SMA mouse models have reduced levels ofGAP43mRNA and protein in axons and growth cones. Importantly, overexpression of two mRNA-binding proteins, HuD and IMP1, restoresGAP43mRNA and protein levels in growth cones and rescues axon outgrowth defects in SMA neurons. These findings demonstrate that SMN plays an important role in the localization and local translation of mRNAs with important axonal functions and suggest that disruption of this function may contribute to the axonal defects observed in SMA. The motor neuron disease spinal muscular atrophy (SMA) is caused by reduced levels of the survival of motor neuron (SMN) protein, which plays a key role in assembling RNA/protein complexes that are essential for mRNA splicing. It remains unclear whether defects in this well characterized housekeeping function cause the specific degeneration of spinal motor neurons observed in SMA. Here, we describe an additional role of SMN in regulating the axonal localization and local translation of the mRNA encoding growth-associated protein 43 (GAP43). This study supports a model whereby SMN deficiency impedes transport and local translation of mRNAs important for neurite outgrowth and stabilization, thus contributing to axon degeneration, muscle denervation, and motor neuron cell death in SMA. Copyright © 2016 the authors 0270-6474/16/363811-10$15.00/0.

Variable area nozzle including a plurality of convexly vanes with a crowned contour, in a vane to vane sealing arrangement and with nonuniform lengths

NASA Technical Reports Server (NTRS)

Arnold, Steven M. (Inventor); Penney, Nicholas (Inventor)

2008-01-01

A variable area nozzle comprising a concentric support and a plurality of convexly contoured self sealing vanes is disclosed and claimed. The vanes are circumferentially and rotatably mounted to the concentric support forming a nozzle infinitely positionable between a first position corresponding to a minimum area nozzle and a second position corresponding to a maximum area nozzle. A closer, which is preferably a shape memory alloy (SMA), urges the nozzle toward the first position corresponding to a minimum area nozzle. Periodically spaced openers act between adjacent vanes to urge the nozzle to a second position corresponding to a maximum area nozzle.

Design of SMA - 13 asphalt mixture ratio on Z3and Z18 of the capital airport

NASA Astrophysics Data System (ADS)

Tian, Shuaituan; Ye, Song; Kong, Fandong

2017-12-01

According to the demand of T2 terminal airlines to operate A380 models, to meet the smooth running of the A380 airliner at the west end of the Capital Airport, So Z3 and Z18 taxiway area of the transformation is imperative. According to the design, the upper layer of this project adopts SMA - 13 modified asphalt mastic macadam mixture. We design the SMA-13 modified asphalt mixture on Z3 and Z18 of the capital airport from any respects, including coarse and fine aggregate, filler, asphalt, fiber and anti-rutting agent, and we hope we can find the best SMA-13 modified asphalt mixture.

Shape Morphing Adaptive Radiator Technology (SMART) Updates to Techport Entry

NASA Technical Reports Server (NTRS)

Erickson, Lisa; Bertagne, Christopher; Hartl, Darren; Witcomb, John; Cognata, Thomas

2017-01-01

The Shape-Morphing Adaptive Radiator Technology (SMART) project builds off the FY16 research effort that developed a flexible composite radiator panel and demonstrated its ability to actuate from SMA's attached to it. The proposed FY17 Shape-Morphing Adaptive Radiator Technology (SMART) project's goal is to 1) develop a practical radiator design with shape memory alloys (SMAs) bonded to the radiator's panel, and 2) build a multi-panel radiator prototype for subsequent system level thermal vacuum tests. The morphing radiator employs SMA materials to passively change its shape to adapt its rate of heat rejection to vehicle requirements. Conceptually, the radiator panel has a naturally closed position (like a cylinder) in a cold environment. Whenever the radiator's temperature gradually rises, SMA's affixed to the face sheet will pull the face sheet open a commensurate amount - increasing the radiators view to space and causing it to reject more heat. In a vehicle, the radiator's variable heat rejection capabilities would reduce the number of additional heat rejection devices in a vehicle's thermal control system. This technology aims to help achieve the required maximum to minimum heat rejection ratio required for manned space vehicles to adopt a lighter, simpler, single loop thermal control architecture (ATCS). Single loop architectures are viewed as an attractive means to reduce mass and complexity over traditional dual-loop solutions. However, fluids generally considered safe enough to flow within crewed cabins (e.g. propylene glycol-water mixtures) have much higher freezing points and viscosities than those used in the external sides of dual loop ATCSs (e.g. Ammonia and HFE7000).

Optimization of Fermentation Conditions and Rheological Properties of Exopolysaccharide Produced by Deep-Sea Bacterium Zunongwangia profunda SM-A87

PubMed Central

Liu, Sheng-Bo; Qiao, Li-Ping; He, Hai-Lun; Zhang, Qian; Chen, Xiu-Lan; Zhou, Wei-Zhi; Zhou, Bai-Cheng; Zhang, Yu-Zhong

2011-01-01

Zunongwangia profunda SM-A87 isolated from deep-sea sediment can secrete large quantity of exopolysaccharide (EPS). Response surface methodology was applied to optimize the culture conditions for EPS production. Single-factor experiment showed that lactose was the best carbon source. Based on the Plackett–Burman design, lactose, peptone and temperature were selected as significant variables, which were further optimized by the steepest ascent (descent) method and central composite design. The optimal culture conditions for EPS production and broth viscosity were determined as 32.21 g/L lactose, 8.87 g/L peptone and an incubation temperature of 9.8°C. Under these conditions, the maximum EPS yield and broth viscosity were 8.90 g/L and 6551 mPa•s, respectively, which is the first report of such high yield of EPS from a marine bacterium. The aqueous solution of the EPS displayed high viscosity, interesting shearing thinning property and great tolerance to high temperature, a wide range of pH, and high salinity. PMID:22096500

Desertification Assessment and Monitoring Based on Remote Sensing

NASA Astrophysics Data System (ADS)

Gao, Z.; del Barrio, G.; Li, X.

2016-08-01

The objective of Dragon 3 Project 10367 is the development of techniques research for desertification assessment and monitoring in China using remote sensing data in combination with climate and environmental-related data. The main achievements acquired during the last two years could be summarized as follows:(1) Photosynthetic vegetation (PV) and non-photosynthetic vegetation (NPV) were estimated in Otindag sandy land by comparison of the pixel-invariant (Spectral Mixture Analysis, SMA) and pixel-variable (Multi-Endmember Spectral Mixture Analysis, MESMA, Automated Monte Carlo Unmixing Analysis, AutoMCU) methods, based on GF-1 data and field measured spectral library.(2) Based on GF-1 data, SMA was applied to solve vegetation cover and transitional sandy land detection in Zhenglan Banner, Inner Mongolia, China.(3) By defined a new indictor, Moisture-responded NPP(MNPP), a new method for identification of degraded lands was put forward, and the land degradation in Xinlin Gol league, Inner Mongolia Autonomous Region, China was assessed preliminarily. (4) The 2dRUE proved to be a good indicator for land degradation, based on which, land degradation status in the general potential extent of desertification in China (PEDC) was assessed.

Feedback Control of a Morphing Chevron for Takeoff and Cruise Noise Reduction

NASA Technical Reports Server (NTRS)

Cabell, Randolph H.; Schiller, Noah H.; Mabe, James H.; Ruggeri, Robert T.; Butler, G. W.

2004-01-01

Noise from commercial high-bypass ratio turbofan engines is generated by turbulent mixing of the hot jet exhaust, fan stream, and ambient air. Serrated aerodynamic devices, known as chevrons, along the trailing edges of a jet engine primary and secondary exhaust nozzle have been shown to reduce jet noise at takeoff and shock-cell noise at cruise conditions. Their optimum shape is a finely tuned compromise between noise-benefit and thrust-loss. The design of a full scale Variable Geometry Chevron (VGC) fan-nozzle incorporating Shape Memory Alloy (SMA) actuators is described in a companion paper. This paper describes the development and testing of a proportional-integral control system that regulates the heating of the SMA actuators to control the VGC s tip immersion. The VGC and control system were tested under representative flow conditions in Boeing s Nozzle Test Facility (NTF). Results from the NTF test which demonstrate controllable immersion of the VGC are described. The paper also describes the correlation between strains and temperatures on the chevron with a photogrammetric measurement of the chevron's tip immersion.

Comparison of the effects of intraocular irrigating solutions on the corneal endothelium in intraocular lens implantation.

PubMed Central

Matsuda, M; Kinoshita, S; Ohashi, Y; Shimomura, Y; Ohguro, N; Okamoto, H; Omoto, T; Hosotani, H; Yoshida, H

1991-01-01

We conducted a randomised prospective controlled study to determine the effects of a glucose glutathione bicarbonate solution (BSS Plus) and a citrate acetate bicarbonate solution (S-MA2) on the corneal endothelium in patients undergoing extracapsular cataract extraction with posterior chamber lens implantation. One eye of each patient was randomly assigned to receive BSS Plus, and the other eye to receive S-MA2. BSS Plus caused significantly less corneal swelling on the first postoperative day than did S-MA2. There was no difference between the two solutions in their effect on corneal thickness one week and one month postoperatively. Computer assisted morphometric analysis of wide-field specular microscopic photographs demonstrated minimal changes in endothelial morphological characteristics in the eyes irrigated with BSS Plus. By comparison S-MA2, caused a significant loss of endothelial cells and a marked reduction in the figure coefficient. These results indicated that BSS Plus has a clinical advantage over S-MA2 with respect to the corneal endothelium. PMID:1873266

Design and testing of shape memory alloy actuation mechanism for flapping wing micro unmanned aerial vehicles

NASA Astrophysics Data System (ADS)

Kamaruzaman, N. F.; Abdullah, E. J.

2017-12-01

Shape memory alloy (SMA) actuator offers great solution for aerospace applications with low weight being its most attractive feature. A SMA actuation mechanism for the flapping micro unmanned aerial vehicle (MAV) is proposed in this study, where SMA material is the primary system that provides the flapping motion to the wings. Based on several established design criteria, a design prototype has been fabricated to validate the design. As a proof of concept, an experiment is performed using an electrical circuit to power the SMA actuator to evaluate the flapping angle. During testing, several problems have been observed and their solutions for future development are proposed. Based on the experiment, the average recorded flapping wing angle is 14.33° for upward deflection and 12.12° for downward deflection. This meets the required design criteria and objective set forth for this design. The results prove the feasibility of employing SMA actuators in flapping wing MAV.

Impact damage resistance and damage suppression properties of shape memory alloys in hybrid composites—a review

NASA Astrophysics Data System (ADS)

Angioni, S. L.; Meo, M.; Foreman, A.

2011-01-01

Composite materials are known to have a poor resistance to through-the-thickness impact loading. There are various methods for improving their impact damage tolerance, such as fiber toughening, matrix toughening, interface toughening, through-the-thickness reinforcements, and selective interlayers and hybrids. Hybrid composites with improved impact resistance are particularly useful in military and commercial civil applications. Hybridizing composites using shape memory alloys (SMA) is one solution since SMA materials can absorb the energy of the impact through superelastic deformation or recovery stress, reducing the effects of the impact on the composite structure. The SMA material may be embedded in the hybrid composites (SMAHC) in many different forms and also the characteristics of the fiber reinforcements may vary, such as SMA wires in woven laminates or SMA foils in unidirectional laminates, only to cite two examples. We will review the state of the art of SMAHC for the purpose of damage suppression. Both the active and passive damage suppression mechanisms will be considered.

Increasing expression and decreasing degradation of SMN ameliorate the spinal muscular atrophy phenotype in mice

PubMed Central

Kwon, Deborah Y.; Motley, William W.; Fischbeck, Kenneth H.; Burnett, Barrington G.

2011-01-01

Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by reduced levels of the survival motor neuron (SMN) protein. Here we show that the proteasome inhibitor, bortezomib, increases SMN in cultured cells and in peripheral tissues of SMA model mice. Bortezomib-treated animals had improved motor function, which was associated with reduced spinal cord and muscle pathology and improved neuromuscular junction size, but no change in survival. Combining bortezomib with the histone deacetylase inhibitor trichostatin A (TSA) resulted in a synergistic increase in SMN protein levels in mouse tissue and extended survival of SMA mice more than TSA alone. Our results demonstrate that a combined regimen of drugs that decrease SMN protein degradation and increase SMN gene transcription synergistically increases SMN levels and improves the lifespan of SMA model mice. Moreover, this study indicates that while increasing SMN levels in the central nervous system may help extend survival, peripheral tissues can also be targeted to improve the SMA disease phenotype. PMID:21693563

Active shape control of composite blades using shape memory actuation

NASA Astrophysics Data System (ADS)

Chandra, Ramesh

2001-10-01

This paper presents active shape control of composite beams using shape memory actuation. Shape memory alloy (SMA) bender elements trained to memorize bending shape were used to induce bending and twisting deformations in composite beams. Bending-torsion coupled graphite-epoxy and kevlar-epoxy composite beams with Teflon inserts were manufactured using an autoclave-molding technique. Teflon inserts were replaced by trained SMA bender elements. Composite beams with SMA bender elements were activated by heating these using electrical resistive heating and the bending and twisting deformations of the beams were measured using a mirror and laser system. The structural response of the composite beams activated by SMA elements was predicted using the Vlasov theory, where these beams were modeled as open sections with many branches. The bending moment induced by a SMA bender element was calculated from its experimentally determined memorized shape. The bending, torsion, and bending-torsion coupling stiffness coefficients of these beams were obtained using analytical formulation of an open-section composite beam with many branches (Vlasov theory).

Superhydrophobic NiTi shape memory alloy surfaces fabricated by anodization and surface mechanical attrition treatment

NASA Astrophysics Data System (ADS)

Ou, Shih-Fu; Wang, Kuang-Kuo; Hsu, Yen-Chi

2017-12-01

This paper describes the fabrication of superhydrophobic NiTi shape memory alloy (SMA) surfaces using an environmentally friendly method based on an economical anodizing process. Perfluorooctyltriethoxysilane was used to reduce the surface energy of the anodized surfaces. The wettability, morphology, composition, and microstructure of the surfaces were investigated by scanning electron microscopy, transmission electron microscopy, and x-ray photoelectron spectroscopy. The surface of the treated NiTi SMA exhibited superhydrophobicity, with a water contact angle of 150.6° and sliding angle of 8°. The anodic film on the NiTi SMA comprised of TiO2 and NiO, as well as traces of TiCl3. In addition, before the NiTi SMA was anodized, it underwent a surface mechanical attrition treatment to grain-refine its surface. This method efficiently enhanced the growth rate of the anodic oxide film, and improved the hydrophobic uniformity of the anodized NiTi-SMA-surface.

Design of a shape adaptive airfoil actuated by a Shape Memory Alloy strip for airplane tail

NASA Astrophysics Data System (ADS)

Shirzadeh, R.; Raissi Charmacani, K.; Tabesh, M.

2011-04-01

Of the factors that mainly affect the efficiency of the wing during a special flow regime, the shape of its airfoil cross section is the most significant. Airfoils are generally designed for a specific flight condition and, therefore, are not fully optimized in all flight conditions. It is very desirable to have an airfoil with the ability to change its shape based on the current regime. Shape memory alloy (SMA) actuators activate in response to changes in the temperature and can recover their original configuration after being deformed. This study presents the development of a method to control the shape of an airfoil using SMA actuators. To predict the thermomechanical behaviors of an SMA thin strip, 3D incremental formulation of the SMA constitutive model is implemented in FEA software package ABAQUS. The interactions between the airfoil structure and SMA thin strip actuator are investigated. Also, the aerodynamic performance of a standard airfoil with a plain flap is compared with an adaptive airfoil.

VPAC2 receptor agonist BAY 55-9837 increases SMN protein levels and moderates disease phenotype in severe spinal muscular atrophy mouse models.

PubMed

Hadwen, Jeremiah; MacKenzie, Duncan; Shamim, Fahad; Mongeon, Kevin; Holcik, Martin; MacKenzie, Alex; Farooq, Faraz

2014-01-09

Spinal Muscular Atrophy (SMA) is one of the most common inherited causes of infant death and is caused by the loss of functional survival motor neuron (SMN) protein due to mutations or deletion in the SMN1 gene. One of the treatment strategies for SMA is to induce the expression of the protein from the homologous SMN2 gene, a rescuing paralog for SMA. Here we demonstrate the promise of pharmacological modulation of SMN2 gene by BAY 55-9837, an agonist of the vasoactive intestinal peptide receptor 2 (VPAC2), a member of G protein coupled receptor family. Treatment with BAY 55-9837 lead to induction of SMN protein levels via activation of MAPK14 or p38 pathway in vitro. Importantly, BAY 55-9837 also ameliorated disease phenotype in severe SMA mouse models. Our findings suggest the VPAC2 pathway is a potential SMA therapeutic target.

Induction of fibroblast senescence generates a non-fibrogenic myofibroblast phenotype that differentially impacts on cancer prognosis

PubMed Central

Thirdborough, Steve; Mellows, Toby; Garcia, Edwin; Woo, Jeongmin; Tod, Joanne; Frampton, Steve; Jenei, Veronika; Moutasim, Karwan A.; Kabir, Tasnuva D.; Brennan, Peter A; Venturi, Giulia; Ford, Kirsty; Herranz, Nicolas; Lim, Kue Peng; Clarke, James; Lambert, Daniel W.; Prime, Stephen S.; Underwood, Timothy J.; Vijayanand, Pandurangan; Eliceiri, Kevin W.; Woelk, Christopher; King, Emma V.; Gil, Jesus; Ottensmeier, Christian H.; Thomas, Gareth J.

2017-01-01

Cancer-associated fibroblasts (CAF) remain a poorly characterized, heterogeneous cell population. Here we characterized two previously described tumor-promoting CAF sub-types, smooth muscle actin (SMA)-positive myofibroblasts and senescent fibroblasts, identifying a novel link between the two. Analysis of CAF cultured ex vivo, showed that senescent CAF are predominantly SMA-positive; this was confirmed by immunochemistry in head & neck (HNSCC) and esophageal (EAC) cancers. In vitro, we found that fibroblasts induced to senesce develop molecular, ultrastructural and contractile features typical of myofibroblasts and this is dependent on canonical TGF-β signaling. Similar to TGF-β1-generated myofibroblasts, these cells secrete soluble factors that promote tumor cell motility. However, RNA-sequencing revealed significant transcriptomic differences between the two SMA-positive CAF groups, particularly in genes associated with extracellular matrix (ECM) deposition and organization, which differentially promote tumor cell invasion. Notably, second harmonic generation imaging and bioinformatic analysis of SMA-positive human HNSCC and EAC showed that collagen fiber organization correlates with poor prognosis, indicating that heterogeneity within the SMA-positive CAF population differentially impacts on survival. These results show that non-fibrogenic, SMA-positive myofibroblasts can be directly generated through induction of fibroblast senescence and suggest that senescence and myofibroblast differentiation are closely linked processes. PMID:27992856

Disease Mechanisms and Therapeutic Approaches in Spinal Muscular Atrophy

PubMed Central

Tisdale, Sarah

2015-01-01

Motor neuron diseases are neurological disorders characterized primarily by the degeneration of spinal motor neurons, skeletal muscle atrophy, and debilitating and often fatal motor dysfunction. Spinal muscular atrophy (SMA) is an autosomal-recessive motor neuron disease of high incidence and severity and the most common genetic cause of infant mortality. SMA is caused by homozygous mutations in the survival motor neuron 1 (SMN1) gene and retention of at least one copy of the hypomorphic gene paralog SMN2. Early studies established a loss-of-function disease mechanism involving ubiquitous SMN deficiency and suggested SMN upregulation as a possible therapeutic approach. In recent years, greater knowledge of the central role of SMN in RNA processing combined with deep characterization of animal models of SMA has significantly advanced our understanding of the cellular and molecular basis of the disease. SMA is emerging as an RNA disease not limited to motor neurons, but one that involves dysfunction of motor circuits that comprise multiple neuronal subpopulations and possibly other cell types. Advances in SMA research have also led to the development of several potential therapeutics shown to be effective in animal models of SMA that are now in clinical trials. These agents offer unprecedented promise for the treatment of this still incurable neurodegenerative disease. PMID:26063904

Induction of fibroblast senescence generates a non-fibrogenic myofibroblast phenotype that differentially impacts on cancer prognosis.

PubMed

Mellone, Massimiliano; Hanley, Christopher J; Thirdborough, Steve; Mellows, Toby; Garcia, Edwin; Woo, Jeongmin; Tod, Joanne; Frampton, Steve; Jenei, Veronika; Moutasim, Karwan A; Kabir, Tasnuva D; Brennan, Peter A; Venturi, Giulia; Ford, Kirsty; Herranz, Nicolas; Lim, Kue Peng; Clarke, James; Lambert, Daniel W; Prime, Stephen S; Underwood, Timothy J; Vijayanand, Pandurangan; Eliceiri, Kevin W; Woelk, Christopher; King, Emma V; Gil, Jesus; Ottensmeier, Christian H; Thomas, Gareth J

2016-12-15

Cancer-associated fibroblasts (CAF) remain a poorly characterized, heterogeneous cell population. Here we characterized two previously described tumor-promoting CAF sub-types, smooth muscle actin (SMA)-positive myofibroblasts and senescent fibroblasts, identifying a novel link between the two. Analysis of CAF cultured ex vivo , showed that senescent CAF are predominantly SMA-positive; this was confirmed by immunochemistry in head & neck (HNSCC) and esophageal (EAC) cancers. In vitro , we found that fibroblasts induced to senesce develop molecular, ultrastructural and contractile features typical of myofibroblasts and this is dependent on canonical TGF-β signaling. Similar to TGF-β1-generated myofibroblasts, these cells secrete soluble factors that promote tumor cell motility. However, RNA-sequencing revealed significant transcriptomic differences between the two SMA-positive CAF groups, particularly in genes associated with extracellular matrix (ECM) deposition and organization, which differentially promote tumor cell invasion. Notably, second harmonic generation imaging and bioinformatic analysis of SMA-positive human HNSCC and EAC showed that collagen fiber organization correlates with poor prognosis, indicating that heterogeneity within the SMA-positive CAF population differentially impacts on survival. These results show that non-fibrogenic, SMA-positive myofibroblasts can be directly generated through induction of fibroblast senescence and suggest that senescence and myofibroblast differentiation are closely linked processes.

Effect of styrene maleic acid WIN55,212-2 micelles on neuropathic pain in a rat model.

PubMed

Linsell, Oliver; Brownjohn, Philip W; Nehoff, Hayley; Greish, Khaled; Ashton, John C

2015-05-01

Cannabinoid receptor agonists are moderately effective at reducing neuropathic pain but are limited by psychoactivity. We developed a styrene maleic acid (SMA) based on the cannabinoid WIN 55,212-2 (WIN) and tested in a rat model of neuropathic pain and in the rotarod test. We hypothesized that miceller preparation can ensure prolonged plasma half-life being above the renal threshold of excretion. Furthermore, SMA-WIN could potentially reduce the central nervous system effects of encapsulated WIN by limiting its transport across the blood-brain barrier. Using the chronic constriction injury model of sciatic neuropathy, the SMA-WIN micelles were efficacious in the treatment of neuropathic pain for a prolonged period compared to control (base WIN). Attenuation of chronic constriction injury-induced mechanical allodynia occurred for up to 8 h at a dose of 11.5 mg/kg of SMA-WIN micelles. To evaluate central effects on motor function, the rotarod assessment was utilized. Results showed initial impairment caused by SMA-WIN micelles to be identical to WIN control for up to 1.5 h. Despite this, the SMA-WIN micelle formulation was able to produce prolonged analgesia over a time when there was decreased impairment in the rotarod test compared with base WIN.

Protective effects of long-term lithium administration in a slowly progressive SMA mouse model.

PubMed

Biagioni, Francesca; Ferrucci, Michela; Ryskalin, Larisa; Fulceri, Federica; Lazzeri, Gloria; Calierno, Maria Teresa; Busceti, Carla L; Ruffoli, Riccardo; Fornai, Francesco

2017-12-01

In the present study we evaluated the long-term effects of lithium administration to a knock-out double transgenic mouse model (Smn-/-; SMN1A2G+/-; SMN2+/+) of Spinal Muscle Atrophy type III (SMA-III). This model is characterized by very low levels of the survival motor neuron protein, slow disease progression and motor neuron loss, which enables to detect disease-modifying effects at delayed time intervals. Lithium administration attenuates the decrease in motor activity and provides full protection from motor neuron loss occurring in SMA-III mice, throughout the disease course. In addition, lithium prevents motor neuron enlargement and motor neuron heterotopy and suppresses the occurrence of radial-like glial fibrillary acidic protein immunostaining in the ventral white matter of SMA-III mice. In SMA-III mice long-term lithium administration determines a dramatic increase of survival motor neuron protein levels in the spinal cord. These data demonstrate that long-term lithium administration during a long-lasting motor neuron disorder attenuates behavioural deficit and neuropathology. Since low level of survival motor neuron protein is bound to disease severity in SMA, the robust increase in protein level produced by lithium provides solid evidence which calls for further investigations considering lithium in the long-term treatment of spinal muscle atrophy.

Model Based Mission Assurance in a Model Based Systems Engineering (MBSE) Framework: State-of-the-Art Assessment

NASA Technical Reports Server (NTRS)

Cornford, Steven L.; Feather, Martin S.

2016-01-01

This report explores the current state of the art of Safety and Mission Assurance (S&MA) in projects that have shifted towards Model Based Systems Engineering (MBSE). Its goal is to provide insight into how NASA's Office of Safety and Mission Assurance (OSMA) should respond to this shift. In MBSE, systems engineering information is organized and represented in models: rigorous computer-based representations, which collectively make many activities easier to perform, less error prone, and scalable. S&MA practices must shift accordingly. The "Objective Structure Hierarchies" recently developed by OSMA provide the framework for understanding this shift. Although the objectives themselves will remain constant, S&MA practices (activities, processes, tools) to achieve them are subject to change. This report presents insights derived from literature studies and interviews. The literature studies gleaned assurance implications from reports of space-related applications of MBSE. The interviews with knowledgeable S&MA and MBSE personnel discovered concerns and ideas for how assurance may adapt. Preliminary findings and observations are presented on the state of practice of S&MA with respect to MBSE, how it is already changing, and how it is likely to change further. Finally, recommendations are provided on how to foster the evolution of S&MA to best fit with MBSE.

Co-rotational thermo-mechanically coupled multi-field framework and finite element for the large displacement analysis of multi-layered shape memory alloy beam-like structures

NASA Astrophysics Data System (ADS)

Solomou, Alexandros G.; Machairas, Theodoros T.; Karakalas, Anargyros A.; Saravanos, Dimitris A.

2017-06-01

A thermo-mechanically coupled finite element (FE) for the simulation of multi-layered shape memory alloy (SMA) beams admitting large displacements and rotations (LDRs) is developed to capture the geometrically nonlinear effects which are present in many SMA applications. A generalized multi-field beam theory implementing a SMA constitutive model based on small strain theory, thermo-mechanically coupled governing equations and multi-field kinematic hypotheses combining first order shear deformation assumptions with a sixth order polynomial temperature field through the thickness of the beam section are extended to admit LDRs. The co-rotational formulation is adopted, where the motion of the beam is decomposed to rigid body motion and relative small deformation in the local frame. A new generalized multi-layered SMA FE is formulated. The nonlinear transient spatial discretized equations of motion of the SMA structure are synthesized and solved using the Newton-Raphson method combined with an implicit time integration scheme. Correlations of models incorporating the present beam FE with respective results of models incorporating plane stress SMA FEs, demonstrate excellent agreement of the predicted LDRs response, temperature and phase transformation fields, as well as, significant gains in computational time.

PreSMA stimulation changes task-free functional connectivity in the fronto-basal-ganglia that correlates with response inhibition efficiency

PubMed Central

Xu, Benjamin; Sandrini, Marco; Wang, Wen-tung; Smith, Jason F.; Sarlls, Joelle E.; Awosika, Oluwole; Butman, John A.; Horwitz, Barry; Cohen, Leonardo G.

2016-01-01

Previous work using transcranial magnetic stimulation (TMS) demonstrated that the right pre-supplementary motor area (preSMA), a node in the fronto-basal-ganglia network, is critical for response inhibition. However, TMS influences interconnected regions, raising the possibility of a link between the preSMA activity and the functional connectivity within the network. To understand this relationship, we applied single-pulse TMS to the right preSMA during functional magnetic resonance imaging when the subjects were at rest to examine changes in neural activity and functional connectivity within the network in relation to the efficiency of response inhibition evaluated with a stop-signal task. The results showed that preSMA-TMS increased activation in the right inferior-frontal cortex (rIFC) and basal ganglia and modulated their task-free functional connectivity. Both the TMS-induced changes in the basal-ganglia activation and the functional connectivity between rIFC and left striatum, and of the overall network correlated with the efficiency of response inhibition and with the white-matter microstructure along the preSMA – rIFC pathway. These results suggest that the task-free functional and structural connectivity between the rIFCop and basal ganglia are critical to the efficiency of response inhibition. PMID:27144466

Bioenergetic status modulates motor neuron vulnerability and pathogenesis in a zebrafish model of spinal muscular atrophy

PubMed Central

Boyd, Penelope J.; Shorrock, Hannah K.; Carter, Roderick N.; Powis, Rachael A.; Thomson, Sophie R.; Thomson, Derek; Graham, Laura C.; Motyl, Anna A. L.; Highley, J. Robin; Becker, Thomas; Becker, Catherina G.; Heath, Paul R.

2017-01-01

Degeneration and loss of lower motor neurons is the major pathological hallmark of spinal muscular atrophy (SMA), resulting from low levels of ubiquitously-expressed survival motor neuron (SMN) protein. One remarkable, yet unresolved, feature of SMA is that not all motor neurons are equally affected, with some populations displaying a robust resistance to the disease. Here, we demonstrate that selective vulnerability of distinct motor neuron pools arises from fundamental modifications to their basal molecular profiles. Comparative gene expression profiling of motor neurons innervating the extensor digitorum longus (disease-resistant), gastrocnemius (intermediate vulnerability), and tibialis anterior (vulnerable) muscles in mice revealed that disease susceptibility correlates strongly with a modified bioenergetic profile. Targeting of identified bioenergetic pathways by enhancing mitochondrial biogenesis rescued motor axon defects in SMA zebrafish. Moreover, targeting of a single bioenergetic protein, phosphoglycerate kinase 1 (Pgk1), was found to modulate motor neuron vulnerability in vivo. Knockdown of pgk1 alone was sufficient to partially mimic the SMA phenotype in wild-type zebrafish. Conversely, Pgk1 overexpression, or treatment with terazosin (an FDA-approved small molecule that binds and activates Pgk1), rescued motor axon phenotypes in SMA zebrafish. We conclude that global bioenergetics pathways can be therapeutically manipulated to ameliorate SMA motor neuron phenotypes in vivo. PMID:28426667

The DcpS inhibitor RG3039 improves motor function in SMA mice

PubMed Central

Van Meerbeke, James P.; Gibbs, Rebecca M.; Plasterer, Heather L.; Miao, Wenyan; Feng, Zhihua; Lin, Ming-Yi; Rucki, Agnieszka A.; Wee, Claribel D.; Xia, Bing; Sharma, Shefali; Jacques, Vincent; Li, Darrick K.; Pellizzoni, Livio; Rusche, James R.; Ko, Chien-Ping; Sumner, Charlotte J.

2013-01-01

Spinal muscular atrophy (SMA) is caused by mutations of the survival motor neuron 1 (SMN1) gene, retention of the survival motor neuron 2 (SMN2) gene and insufficient expression of full-length survival motor neuron (SMN) protein. Quinazolines increase SMN2 promoter activity and inhibit the ribonucleic acid scavenger enzyme DcpS. The quinazoline derivative RG3039 has advanced to early phase clinical trials. In preparation for efficacy studies in SMA patients, we investigated the effects of RG3039 in severe SMA mice. Here, we show that RG3039 distributed to central nervous system tissues where it robustly inhibited DcpS enzyme activity, but minimally activated SMN expression or the assembly of small nuclear ribonucleoproteins. Nonetheless, treated SMA mice showed a dose-dependent increase in survival, weight and motor function. This was associated with improved motor neuron somal and neuromuscular junction synaptic innervation and function and increased muscle size. RG3039 also enhanced survival of conditional SMA mice in which SMN had been genetically restored to motor neurons. As this systemically delivered drug may have therapeutic benefits that extend beyond motor neurons, it could act additively with SMN-restoring therapies delivered directly to the central nervous system such as antisense oligonucleotides or gene therapy. PMID:23727836

Age-associated and therapy-induced alterations in the cellular microenvironment of experimental gliomas.

PubMed

Schneider, Hannah; Lohmann, Birthe; Wirsching, Hans-Georg; Hasenbach, Kathy; Rushing, Elisabeth J; Frei, Karl; Pruschy, Martin; Tabatabai, Ghazaleh; Weller, Michael

2017-10-20

The poor prognosis associated with advanced age in patients with glioblastoma remains poorly understood. Glioblastoma in the elderly has been particularly associated with vascular endothelial growth factor (VEGF)-dependent angiogenesis, and early uncontrolled studies suggested that the anti-angiogenic agent bevacizumab (BEV), an antibody to VEGF, might be preferentially active in this patient population. Accordingly, we explored host age-dependent differences in survival and benefit from radiotherapy (RT) or BEV in syngeneic mouse glioma models. Survival was inferior in older mice in the SMA-540 and and less so in SMA-560, but not in the SMA-497 or GL-261 models. Detailed flow cytometric studies revealed increased myeloid and decreased effector T cell population frequencies in SMA-540 tumors of old compared to young mice, but no such difference in the SMA-497 model. Bone marrow transplantation (BMT) from young to old mice had no effect, whereas survival was reduced with BMT from old to young mice. BEV significantly decreased vessel densities in gliomas of old, but not young mice. Accordingly, old, but not young SMA-540 tumor-bearing mice benefited from BEV alone or in combination with RT. End-stage tumors of old BEV- and BEV/RT-treated mice exhibited increased infiltration of T helper and cytotoxic T cells compared to tumors of young mice. The SMA-540 model may provide a valuable tool to evaluate the influence of host age on glioblastoma progression and treatment response. The biological host factors that modulate glioma growth in old as opposed to young mice remain to be identified.

Human pericytes adopt myofibroblast properties in the microenvironment of the IPF lung.

PubMed

Sava, Parid; Ramanathan, Anand; Dobronyi, Amelia; Peng, Xueyan; Sun, Huanxing; Ledesma-Mendoza, Adrian; Herzog, Erica L; Gonzalez, Anjelica L

2017-12-21

Idiopathic pulmonary fibrosis (IPF) is a fatal disease of unknown etiology characterized by a compositionally and mechanically altered extracellular matrix. Poor understanding of the origin of α-smooth muscle actin (α-SMA) expressing myofibroblasts has hindered curative therapies. Though proposed as a source of myofibroblasts in mammalian tissues, identification of microvascular pericytes (PC) as contributors to α-SMA-expressing populations in human IPF and the mechanisms driving this accumulation remain unexplored. Here, we demonstrate enhanced detection of α-SMA+ cells coexpressing the PC marker neural/glial antigen 2 in the human IPF lung. Isolated human PC cultured on decellularized IPF lung matrices adopt expression of α-SMA, demonstrating that these cells undergo phenotypic transition in response to direct contact with the extracellular matrix (ECM) of the fibrotic human lung. Using potentially novel human lung-conjugated hydrogels with tunable mechanical properties, we decoupled PC responses to matrix composition and stiffness to show that α-SMA+ PC accumulate in a mechanosensitive manner independent of matrix composition. PC activated with TGF-β1 remodel the normal lung matrix, increasing tissue stiffness to facilitate the emergence of α-SMA+ PC via MKL-1/MTRFA mechanotranduction. Nintedanib, a tyrosine-kinase inhibitor approved for IPF treatment, restores the elastic modulus of fibrotic lung matrices to reverse the α-SMA+ phenotype. This work furthers our understanding of the role that microvascular PC play in the evolution of IPF, describes the creation of an ex vivo platform that advances the study of fibrosis, and presents a potentially novel mode of action for a commonly used antifibrotic therapy that has great relevance for human disease.

Folic acid-conjugated amphiphilic alternating copolymer as a new active tumor targeting drug delivery platform.

PubMed

Li, Xia; Szewczuk, Myron R; Malardier-Jugroot, Cecile

2016-01-01

Targeted drug delivery using polymeric nanostructures is an emerging cancer research area, engineered for safer, more efficient, and effective use of chemotherapeutic drugs. A pH-responsive, active targeting delivery system was designed using folic acid functionalized amphiphilic alternating copolymer poly(styrene-alt-maleic anhydride) (FA-DABA-SMA) via a biodegradable linker 2,4-diaminobutyric acid (DABA). The polymeric template is pH responsive, forming amphiphilic nanostructures at pH 7, allowing the encapsulation of hydrophobic drugs on its interior. Moreover, the structure is stable only at neutral pH and collapses in the acidic tumor microenvironment, releasing drugs on-site from its core. The delivery vehicle is investigated using human pancreatic PANC-1 cancer cells and RAW-Blue™ mouse macrophage reporter cell line, both of which have overly expression of folic acid receptors. To trace the cellular uptake by both cell lines, curcumin was selected as a dye and drug mimic owing to its fluorescence nature and hydrophobic properties. Fluorescent microscopy of FA-DABA-SMA loaded with curcumin revealed a significant internalization of the dye by human pancreatic PANC-1 cancer cells compared to those with unfunctionalized polymers (SMA). Moreover, the FA-DABA-SMA polymers exhibit rodlike association specific to the cells. Both empty SMA and FA-DABA-SMA show little toxicity to PANC-1 cells as characterized by WST-1 cell proliferation assay. These results clearly indicate that FA-DABA-SMA polymers show potential as an active tumor targeting drug delivery system with the ability to internalize hydrophobic chemotherapeutics after they specifically attach to cancer cells.

Health monitoring and rehabilitation of a concrete structure using intelligent materials

NASA Astrophysics Data System (ADS)

Song, G.; Mo, Y. L.; Otero, K.; Gu, H.

2006-04-01

This paper presents the concept of an intelligent reinforced concrete structure (IRCS) and its application in structural health monitoring and rehabilitation. The IRCS has multiple functions which include self-rehabilitation, self-vibration damping, and self-structural health monitoring. These functions are enabled by two types of intelligent (smart) materials: shape memory alloys (SMAs) and piezoceramics. In this research, Nitinol type SMA and PZT (lead zirconate titanate) type piezoceramics are used. The proposed concrete structure is reinforced by martensite Nitinol cables using the method of post-tensioning. The martensite SMA significantly increases the concrete's damping property and its ability to handle large impact. In the presence of cracks due to explosions or earthquakes, by electrically heating the SMA cables, the SMA cables contract and close up the cracks. In this research, PZT patches are embedded in the concrete structure to detect possible cracks inside the concrete structure. The wavelet packet analysis method is then applied as a signal-processing tool to analyze the sensor signals. A damage index is defined to describe the damage severity for health monitoring purposes. In addition, by monitoring the electric resistance change of the SMA cables, the crack width can be estimated. To demonstrate this concept, a concrete beam specimen with reinforced SMA cables and with embedded PZT patches is fabricated. Experiments demonstrate that the IRC has the ability of self-sensing and self-rehabilitation. Three-point bending tests were conducted. During the loading process, a crack opens up to 0.47 inches. Upon removal of the load and heating the SMA cables, the crack closes up. The damage index formed by wavelet packet analysis of the PZT sensor data predicts and confirms the onset and severity of the crack during the loading. Also during the loading, the electrical resistance value of the SMA cable changes by up to 27% and this phenomenon is used to monitor the crack width.

Solution Mask Liquid Lithography (SMaLL) for One-Step, Multimaterial 3D Printing.

PubMed

Dolinski, Neil D; Page, Zachariah A; Callaway, E Benjamin; Eisenreich, Fabian; Garcia, Ronnie V; Chavez, Roberto; Bothman, David P; Hecht, Stefan; Zok, Frank W; Hawker, Craig J

2018-06-21

A novel methodology for printing 3D objects with spatially resolved mechanical and chemical properties is reported. Photochromic molecules are used to control polymerization through coherent bleaching fronts, providing large depths of cure and rapid build rates without the need for moving parts. The coupling of these photoswitches with resin mixtures containing orthogonal photo-crosslinking systems allows simultaneous and selective curing of multiple networks, providing access to 3D objects with chemically and mechanically distinct domains. The power of this approach is showcased through the one-step fabrication of bioinspired soft joints and mechanically reinforced "brick-and-mortar" structures. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Distinct Regions within Medial Prefrontal Cortex Process Pain and Cognition

PubMed Central

Jahn, Andrew; Nee, Derek Evan; Alexander, William H.

2016-01-01

Neuroimaging studies of the medial prefrontal cortex (mPFC) suggest that the dorsal anterior cingulate cortex (dACC) region is responsive to a wide variety of stimuli and psychological states, such as pain, cognitive control, and prediction error (PE). In contrast, a recent meta-analysis argues that the dACC is selective for pain, whereas the supplementary motor area (SMA) and pre-SMA are specifically associated with higher-level cognitive processes (Lieberman and Eisenberger, 2015). To empirically test this claim, we manipulated effects of pain, conflict, and PE in a single experiment using human subjects. We observed a robust dorsal-ventral dissociation within the mPFC with cognitive effects of PE and conflict overlapping dorsally and pain localized more ventrally. Classification of subjects based on the presence or absence of a paracingulate sulcus showed that PE effects extended across the dorsal area of the dACC and into the pre-SMA. These results begin to resolve recent controversies by showing the following: (1) the mPFC includes dissociable regions for pain and cognitive processing; and (2) meta-analyses are correct in localizing cognitive effects to the dACC, although these effects extend to the pre-SMA as well. These results both provide evidence distinguishing between different theories of mPFC function and highlight the importance of taking individual anatomical variability into account when conducting empirical studies of the mPFC. SIGNIFICANCE STATEMENT Decades of neuroimaging research have shown the mPFC to represent a wide variety of stimulus processing and cognitive states. However, recently it has been argued whether distinct regions of the mPFC separately process pain and cognitive phenomena. To address this controversy, this study directly compared pain and cognitive processes within subjects. We found a double dissociation within the mPFC with pain localized ventral to the cingulate sulcus and cognitive effects localized more dorsally within the dACC and spreading into the pre-supplementary motor area. This provides empirical evidence to help resolve the current debate about the functional architecture of the mPFC. PMID:27807031

A weakly-constrained data assimilation approach to address rainfall-runoff model structural inadequacy in streamflow prediction

NASA Astrophysics Data System (ADS)

Lee, Haksu; Seo, Dong-Jun; Noh, Seong Jin

2016-11-01

This paper presents a simple yet effective weakly-constrained (WC) data assimilation (DA) approach for hydrologic models which accounts for model structural inadequacies associated with rainfall-runoff transformation processes. Compared to the strongly-constrained (SC) DA, WC DA adjusts the control variables less while producing similarly or more accurate analysis. Hence the adjusted model states are dynamically more consistent with those of the base model. The inadequacy of a rainfall-runoff model was modeled as an additive error to runoff components prior to routing and penalized in the objective function. Two example modeling applications, distributed and lumped, were carried out to investigate the effects of the WC DA approach on DA results. For distributed modeling, the distributed Sacramento Soil Moisture Accounting (SAC-SMA) model was applied to the TIFM7 Basin in Missouri, USA. For lumped modeling, the lumped SAC-SMA model was applied to nineteen basins in Texas. In both cases, the variational DA (VAR) technique was used to assimilate discharge data at the basin outlet. For distributed SAC-SMA, spatially homogeneous error modeling yielded updated states that are spatially much more similar to the a priori states, as quantified by Earth Mover's Distance (EMD), than spatially heterogeneous error modeling by up to ∼10 times. DA experiments using both lumped and distributed SAC-SMA modeling indicated that assimilating outlet flow using the WC approach generally produce smaller mean absolute difference as well as higher correlation between the a priori and the updated states than the SC approach, while producing similar or smaller root mean square error of streamflow analysis and prediction. Large differences were found in both lumped and distributed modeling cases between the updated and the a priori lower zone tension and primary free water contents for both WC and SC approaches, indicating possible model structural deficiency in describing low flows or evapotranspiration processes for the catchments studied. Also presented are the findings from this study and key issues relevant to WC DA approaches using hydrologic models.

Insights from the supplementary motor area syndrome in balancing movement initiation and inhibition

PubMed Central

Potgieser, A. R. E.; de Jong, B. M.; Wagemakers, M.; Hoving, E. W.; Groen, R. J. M.

2014-01-01

The supplementary motor area (SMA) syndrome is a characteristic neurosurgical syndrome that can occur after unilateral resection of the SMA. Clinical symptoms may vary from none to a global akinesia, predominantly on the contralateral side, with preserved muscle strength and mutism. A remarkable feature is that these symptoms completely resolve within weeks to months, leaving only a disturbance in alternating bimanual movements. In this review we give an overview of the old and new insights from the SMA syndrome and extrapolate these findings to seemingly unrelated diseases and symptoms such as Parkinson’s disease (PD) and tics. Furthermore, we integrate findings from lesion, stimulation and functional imaging studies to provide insight in the motor function of the SMA. PMID:25506324

Structural Covariance of the Prefrontal-Amygdala Pathways Associated with Heart Rate Variability.

PubMed

Wei, Luqing; Chen, Hong; Wu, Guo-Rong

2018-01-01

The neurovisceral integration model has shown a key role of the amygdala in neural circuits underlying heart rate variability (HRV) modulation, and suggested that reciprocal connections from amygdala to brain regions centered on the central autonomic network (CAN) are associated with HRV. To provide neuroanatomical evidence for these theoretical perspectives, the current study used covariance analysis of MRI-based gray matter volume (GMV) to map structural covariance network of the amygdala, and then determined whether the interregional structural correlations related to individual differences in HRV. The results showed that covariance patterns of the amygdala encompassed large portions of cortical (e.g., prefrontal, cingulate, and insula) and subcortical (e.g., striatum, hippocampus, and midbrain) regions, lending evidence from structural covariance analysis to the notion that the amygdala was a pivotal node in neural pathways for HRV modulation. Importantly, participants with higher resting HRV showed increased covariance of amygdala to dorsal medial prefrontal cortex and anterior cingulate cortex (dmPFC/dACC) extending into adjacent medial motor regions [i.e., pre-supplementary motor area (pre-SMA)/SMA], demonstrating structural covariance of the prefrontal-amygdala pathways implicated in HRV, and also implying that resting HRV may reflect the function of neural circuits underlying cognitive regulation of emotion as well as facilitation of adaptive behaviors to emotion. Our results, thus, provide anatomical substrates for the neurovisceral integration model that resting HRV may index an integrative neural network which effectively organizes emotional, cognitive, physiological and behavioral responses in the service of goal-directed behavior and adaptability.

The Submillimeter Array – current status and future plans

NASA Astrophysics Data System (ADS)

Blundell, Raymond

2018-01-01

The current SMA receiver systems were designed in the mid-1990s and have been operating for more than fifteen years. With regular upgrades to receivers, deployment of the SWARM correlator, expansion of the IF signal transport bandwidth via improvements to the analog IF signal processing hardware, and many other enhancements, the SMA currently greatly outperforms its original specifications in terms of sensitivity, instantaneous bandwidth, and availability of observing modes such as full-Stokes polarization and dual frequency operation.We have recently started to implement a three-year instrument upgrade plan, which we are calling the wSMA. The wSMA will offer even wider bandwidth operation than the current SMA and improved sensitivity. The major subsystems that will form the wSMA include significantly improved, dual polarization receiver cartridges housed in a new cryostat; local oscillator units incorporating modern mm-wave technology; an upgraded signal transmission system; and a further expansion of the SWARM correlator. The cryostat will be cooled by a low-maintenance pulse-tube cryocooler. Two dual-polarization receiver cartridges will cover approximately the same sky frequencies as the current receiver sets; the low-band receiver will be fed by an LO unit covering 210-270 GHz, and the high-band receiver will be fed by an LO covering 280-360 GHz. With a receiver IF band of 4-20 GHz, this will enable continuous sky frequency coverage from 190 GHz to 380 GHz.Details of the upgrade plans will be presented together with a discussion of scientific opportunities afforded by this upgrade, which, once implemented, will enable the SMA to continue to produce the highest quality science throughout the next decade.

Pharmacokinetics, pharmacodynamics, and efficacy of a small-molecule SMN2 splicing modifier in mouse models of spinal muscular atrophy

PubMed Central

Zhao, Xin; Feng, Zhihua; Ling, Karen K. Y.; Mollin, Anna; Sheedy, Josephine; Yeh, Shirley; Petruska, Janet; Narasimhan, Jana; Dakka, Amal; Welch, Ellen M.; Karp, Gary; Chen, Karen S.; Metzger, Friedrich; Ratni, Hasane; Lotti, Francesco; Tisdale, Sarah; Naryshkin, Nikolai A.; Pellizzoni, Livio; Paushkin, Sergey; Ko, Chien-Ping; Weetall, Marla

2016-01-01

Spinal muscular atrophy (SMA) is caused by the loss or mutation of both copies of the survival motor neuron 1 (SMN1) gene. The related SMN2 gene is retained, but due to alternative splicing of exon 7, produces insufficient levels of the SMN protein. Here, we systematically characterize the pharmacokinetic and pharmacodynamics properties of the SMN splicing modifier SMN-C1. SMN-C1 is a low-molecular weight compound that promotes the inclusion of exon 7 and increases production of SMN protein in human cells and in two transgenic mouse models of SMA. Furthermore, increases in SMN protein levels in peripheral blood mononuclear cells and skin correlate with those in the central nervous system (CNS), indicating that a change of these levels in blood or skin can be used as a non-invasive surrogate to monitor increases of SMN protein levels in the CNS. Consistent with restored SMN function, SMN-C1 treatment increases the levels of spliceosomal and U7 small-nuclear RNAs and corrects RNA processing defects induced by SMN deficiency in the spinal cord of SMNΔ7 SMA mice. A 100% or greater increase in SMN protein in the CNS of SMNΔ7 SMA mice robustly improves the phenotype. Importantly, a ∼50% increase in SMN leads to long-term survival, but the SMA phenotype is only partially corrected, indicating that certain SMA disease manifestations may respond to treatment at lower doses. Overall, we provide important insights for the translation of pre-clinical data to the clinic and further therapeutic development of this series of molecules for SMA treatment. PMID:26931466

Finite Element Analysis of a Copper Single Crystal Shape Memory Alloy-Based Endodontic Instruments

NASA Astrophysics Data System (ADS)

Vincent, Marin; Thiebaud, Frédéric; Bel Haj Khalifa, Saifeddine; Engels-Deutsch, Marc; Ben Zineb, Tarak

2015-10-01

The aim of the present paper is the development of endodontic Cu-based single crystal Shape Memory Alloy (SMA) instruments in order to eliminate the antimicrobial and mechanical deficiencies observed with the conventional Nickel-Titane (NiTi) SMA files. A thermomechanical constitutive law, already developed and implemented in a finite element code by our research group, is adopted for the simulation of the single crystal SMA behavior. The corresponding material parameters were identified starting from experimental results for a tensile test at room temperature. A computer-aided design geometry has been achieved and considered for a finite element structural analysis of the endodontic Cu-based single crystal SMA files. They are meshed with tetrahedral continuum elements to improve the computation time and the accuracy of results. The geometric parameters tested in this study are the length of the active blade, the rod length, the pitch, the taper, the tip diameter, and the rod diameter. For each set of adopted parameters, a finite element model is built and tested in a combined bending-torsion loading in accordance with ISO 3630-1 norm. The numerical analysis based on finite element procedure allowed purposing an optimal geometry suitable for Cu-based single crystal SMA endodontic files. The same analysis was carried out for the classical NiTi SMA files and a comparison was made between the two kinds of files. It showed that Cu-based single crystal SMA files are less stiff than the NiTi files. The Cu-based endodontic files could be used to improve the root canal treatments. However, the finite element analysis brought out the need for further investigation based on experiments.

The anterior visceral branches of the abdominal aorta and their relationship to the renal arteries.

PubMed

Pennington, Neil; Soames, Roger W

2005-12-01

Variations in the anatomy of the abdominal aorta and its branches are of interest as vessel geometry not only determines flow dynamics, but is also crucial in the pathogenesis of vascular disease. The relationship between the anterior visceral and renal arteries is important when undertaking diagnostic arteriography and endovascular interventions. To examine these relationships, the length of the abdominal aorta was determined and measurements taken of the position of origin of the celiac artery, superior mesenteric artery (SMA), inferior mesenteric artery (IMA) and renal arteries, as well as the three-dimensional projection of each vessel from the aorta. The mean level of bifurcation of the aorta was at the lower third of the body of L4, with the celiac artery, SMA, renal arteries and IMA arising at the level of the T12/L1 intervertebral disc, upper third of the body of L1, lower third of the body of L1 and lower third of the body of L3, respectively. The horizontal projection of the celiac artery, SMA and IMA was to the left of the midline; in the sagittal plane, the celiac artery and SMA projected anteriorly and the IMA posteriorly; in the coronal plane all vessels projected inferiorly, with the SMA to the right and the IMA to the left. The celiac artery, SMA and both renal arteries all arise from the proximal half of the abdominal aorta within 45 mm of each other, with the origins of the renal arteries being remarkably consistent. It is concluded that the celiac artery and SMA are both useful landmarks for determining the position of the renal arteries.

Area- and band-specific representations of hand movements by local field potentials in caudal cingulate motor area and supplementary motor area of monkeys

PubMed Central

Yokoyama, Osamu; Nakayama, Yoshihisa

2016-01-01

The caudal cingulate motor area (CMAc) and the supplementary motor area (SMA) play important roles in movement execution. The present study examined the neural mechanisms underlying these roles by investigating local field potentials (LFPs) from these areas while monkeys pressed buttons with either their left or right hand. During hand movement, power increases in the high-gamma (80–120 Hz) and theta (3–8 Hz) bands and a power decrease in the beta (12–30 Hz) band were observed in both the CMAc and SMA. High-gamma and beta activity in the SMA predominantly represented contralateral hand movements, whereas activity in the CMAc preferentially represented movement of either hand. Theta activity in both brain regions most frequently reflected movement of either hand, but a contralateral hand bias was more evident in the SMA than in the CMAc. An analysis of the relationships of the laterality representations between the high-gamma and theta bands at each recording site revealed that, irrespective of the hand preference for the theta band, the high-gamma band in the SMA preferentially represented contralateral hand movement, whereas the high-gamma band in the CMAc represented movement of either hand. These findings suggest that the input-output relationships for ipsilateral and contralateral hand movements in the CMAc and SMA differ in terms of their functionality. The CMAc may transform the input signals representing general aspects of movement into commands to perform movements with either hand, whereas the SMA may transform the input signals into commands to perform movement with the contralateral hand. PMID:26792884

Thermotropic properties of phosphatidylcholine nanodiscs bounded by styrene-maleic acid copolymers.

PubMed

Dominguez Pardo, J J; Dörr, J M; Renne, M F; Ould-Braham, T; Koorengevel, M C; van Steenbergen, M J; Killian, J A

2017-11-01

Styrene-maleic acid copolymers (SMA) have been gaining interest in the field of membrane research due to their ability to solubilize membranes into nanodics. The SMA molecules act as an amphipathic belt that surrounds the nanodiscs, whereby the hydrophobic styrene moieties can insert in between the lipid acyl chains. Here we used SMA variants with different styrene-to-maleic acid ratio (i.e. 2:1, 3:1 and 4:1) to investigate how lipid packing in the nanodiscs is affected by the presence of the polymers and how it depends on polymer composition. This was done by analyzing the thermotropic properties of a series of saturated phosphatidylcholines in nanodiscs using laurdan fluorescence and differential scanning calorimetry. In all cases it was found that the temperature of the main phase transition (T m ) of the lipids in the nanodiscs is downshifted and that its cooperativity is strongly reduced as compared to the situation in vesicles. These effects were least pronounced for lipids in nanodiscs bounded by SMA 2:1. Unexpected trends were observed for the calorimetric enthalpy of the transition, suggesting that the polymer itself contributes, possibly by rearranging around the nanodiscs when the lipids adopt the fluid phase. Finally, distinct differences in morphology were observed for nanodiscs at relatively high polymer concentrations, depending on the SMA variant used. Overall, the results suggest that the extent of preservation of native thermodynamic properties of the lipids as well as the stability of the nanodiscs at high polymer concentrations is better for SMA 2:1 than for the other SMA variants. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

The DcpS inhibitor RG3039 improves survival, function and motor unit pathologies in two SMA mouse models

PubMed Central

Gogliotti, Rocky G.; Cardona, Herminio; Singh, Jasbir; Bail, Sophie; Emery, Carina; Kuntz, Nancy; Jorgensen, Michael; Durens, Madel; Xia, Bing; Barlow, Courtenay; Heier, Christopher R.; Plasterer, Heather L.; Jacques, Vincent; Kiledjian, Megerditch; Jarecki, Jill; Rusche, James; DiDonato, Christine J.

2013-01-01

Spinal muscular atrophy (SMA) is caused by insufficient levels of the survival motor neuron (SMN) protein due to the functional loss of the SMN1 gene and the inability of its paralog, SMN2, to fully compensate due to reduced exon 7 splicing efficiency. Since SMA patients have at least one copy of SMN2, drug discovery campaigns have sought to identify SMN2 inducers. C5-substituted quinazolines increase SMN2 promoter activity in cell-based assays and a derivative, RG3039, has progressed to clinical testing. It is orally bioavailable, brain-penetrant and has been shown to be an inhibitor of the mRNA decapping enzyme, DcpS. Our pharmacological characterization of RG3039, reported here, demonstrates that RG3039 can extend survival and improve function in two SMA mouse models of varying disease severity (Taiwanese 5058 Hemi and 2B/− SMA mice), and positively impacts neuromuscular pathologies. In 2B/− SMA mice, RG3039 provided a >600% survival benefit (median 18 days to >112 days) when dosing began at P4, highlighting the importance of early intervention. We determined the minimum effective dose and the associated pharmacokinetic (PK) and exposure relationship of RG3039 and DcpS inhibition ex vivo. These data support the long PK half-life with extended pharmacodynamic outcome of RG3039 in 2B/− SMA mice. In motor neurons, RG3039 significantly increased both the average number of cells with gems and average number of gems per cell, which is used as an indirect measure of SMN levels. These studies contribute to dose selection and exposure estimates for the first studies with RG3039 in human subjects. PMID:23736298

[Experimental study of an intratracheal stent made of shape memory alloy].

PubMed

Yoshimura, M; Tsugawa, C; Tsubota, N

1994-11-01

To develop a new prosthesis for treating tracheal stenosis and tracheobronchomalacia, we examined the usefulness of an intratracheal stent made of shape memory alloy (SMA), a titanium-nickel alloy composed of 50% of each metal. At its recovery temperature (37 degrees C), the SMA stent was designed to recall the memorized shape of a coil with a diameter of 5 or 6 mm and a length of 10 mm. For the present experiment, it was transformed to a smaller coil 3 mm in diameter at a low temperature (-50 degrees C) and then loaded into the prosthesis introducer tube. An experimental model of potentially fatal tracheomalacia was made surgically by cutting and fracturing the tracheal cartilages of rabbits and tracheal collapse was confirmed by rigid bronchoscope. The introducer tube with the SMA stent was inserted and then the prosthesis was advanced into the collapsed segment of the trachea using the stent pusher. The SMA stent warmed bo body temperature and recovered its memorized shape after 1-2 min. In 3 out of 8 rabbits, follow-up bronchoscopy performed at 6, 8, and 10 months after implantation revealed satisfactory patency of the SMA stent and the trachea. After follow-up, 3 animals were sacrificed for histological observation, which showed little proliferation of granulation tissue and no dislocation of the SMA stent from the malacic portion. The remaining 5 rabbits have been followed for 18-24 months and are doing well. We conclude that the SMA stent maintains good tracheal patency, causes little reaction in the tracheal wall, and is easy to handle. Thus, it shows the potential for clinical application.

Focus scanning with feedback control for fiber-optic nonlinear endomicroscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Li, Ang; Liang, Wenxuan; Li, Xingde

2017-02-01

Fiber-optic nonlinear endomicroscopy represents a strong promise to enable translation of nonlinear microscopy technologies to in vivo applications, particularly imaging of internal organs. Two-dimensional imaging beam scanning has been accomplished by using fiber-optic scanners or MEMS scanners. Yet nonlinear endomicroscopy still cannot perform rapid and reliable depth or focus scanning while maintaining a small form factor. Shape memory alloy (SMA) wire had shown promise in extending 2D endoscopic imaging to the third dimension. By Joule heating, the SMA wire would contract and move the endomicroscope optics to change beam focus. However, this method suffered from hysteresis, and was susceptible to change in ambient temperature, making it difficult to achieve accurate and reliable depth scanning. Here we present a feedback-controlled SMA actuator which addressed these challenges. The core of the feedback loop was a Hall effect sensor. By measuring the magnetic flux density from a tiny magnet attached to the SMA wire, contraction distance of the SMA wire could be tracked in real time. The distance was then fed to the PID algorithm running in a microprocessor, which computed the error between the command position and the current position of the actuator. The current running through the SMA wire was adjusted accordingly. Our feedback-controlled SMA actuator had a tube-like shape with outer diameter of 5.5 mm and length of 25 mm, and was designed to house the endomicroscope inside. Initial test showed that it allowed more than 300 microns of travel distance, with an average positioning error of less than 2 microns. 3D imaging experiments with the endomicroscope is underway, and its imaging performance will be assessed and discussed.

Thermal response of novel shape memory polymer-shape memory alloy hybrids

NASA Astrophysics Data System (ADS)

Rossiter, Jonathan; Takashima, Kazuto; Mukai, Toshiharu

2014-03-01

Shape memory polymers (SMP) and shape memory alloys (SMA) have both been proven important smart materials in their own fields. Shape memory polymers can be formed into complex three-dimensional structures and can undergo shape programming and large strain recovery. These are especially important for deployable structures including those for space applications and micro-structures such as stents. Shape memory alloys on the other hand are readily exploitable in a range of applications where simple, silent, light-weight and low-cost repeatable actuation is required. These include servos, valves and mobile robotic artificial muscles. Despite their differences, one important commonality between SMPs and SMAs is that they are both typically activated by thermal energy. Given this common characteristic it is important to consider how these two will behave when in close environmental proximity, and hence exposed to the same thermal stimulus, and when they are incorporated into a hybrid SMA-SMP structure. In this paper we propose and examine the operation of SMA-SMP hybrids. The relationship between the two temperatures Tg, the glass transition temperature of the polymer, and Ta, the nominal austenite to martensite transition temperature of the alloy is considered. We examine how the choice of these two temperatures affects the thermal response of the hybrid. Electrical stimulation of the SMA is also considered as a method not only of actuating the SMA but also of inducing heating in the surrounding polymer, with consequent effects on actuator behaviour. Likewise by varying the rate and degree of thermal stimulation of the SMA significantly different actuation and structural stiffness can be achieved. Novel SMP-SMA hybrid actuators and structures have many ready applications in deployable structures, robotics and tuneable engineering systems.

Spatially and chemically resolved source apportionment analysis: Case study of high particulate matter event

NASA Astrophysics Data System (ADS)

Kim, Byeong-Uk; Bae, Changhan; Kim, Hyun Cheol; Kim, Eunhye; Kim, Soontae

2017-08-01

This article presents the results of a detailed source apportionment study of the high particulate matter (PM) event in the Seoul Metropolitan Area (SMA), South Korea, during late February 2014. Using the Comprehensive Air Quality Model with Extensions with its Particulate Source Apportionment Technology (CAMx-PSAT), we defined 10 source regions, including five in China, for spatially and chemically resolved analyses. During the event, the spatially averaged PM10 concentration at all PM10 monitors in the SMA was 129 μg/m3, while the PM10 and PM2.5 concentrations at the BulGwang Supersite were 143 μg/m3 and 123 μg/m3, respectively. CAMx-PSAT showed reasonably good PM model performance in both China and the SMA. For February 23-27, CAMx-PSAT estimated that Chinese contributions to the SMA PM10 and PM2.5 were 84.3 μg/m3 and 80.0 μg/m3, respectively, or 64% and 70% of the respective totals, while South Korea's respective domestic contributions were 36.5 μg/m3 and 23.3 μg/m3. We observed that the spatiotemporal pattern of PM constituent concentrations and contributions did not necessarily follow that of total PM10 and PM2.5 concentrations. For example, Beijing-Tianjin-Hebei produced high nitrate concentrations, but the two most-contributing regions to PM in the SMA were the Near Beijing area and South Korea. In addition, we noticed that the relative contributions from each region changed over time. We found that most ammonium mass that neutralized Chinese sulfate mass in the SMA came from South Korean sources, indicating that secondary inorganic aerosol in the SMA, especially ammonium sulfates, during this event resulted from different major precursors originating from different regions.

PreSMA stimulation changes task-free functional connectivity in the fronto-basal-ganglia that correlates with response inhibition efficiency.

PubMed

Xu, Benjamin; Sandrini, Marco; Wang, Wen-Tung; Smith, Jason F; Sarlls, Joelle E; Awosika, Oluwole; Butman, John A; Horwitz, Barry; Cohen, Leonardo G

2016-09-01

Previous work using transcranial magnetic stimulation (TMS) demonstrated that the right presupplementary motor area (preSMA), a node in the fronto-basal-ganglia network, is critical for response inhibition. However, TMS influences interconnected regions, raising the possibility of a link between the preSMA activity and the functional connectivity within the network. To understand this relationship, we applied single-pulse TMS to the right preSMA during functional magnetic resonance imaging when the subjects were at rest to examine changes in neural activity and functional connectivity within the network in relation to the efficiency of response inhibition evaluated with a stop-signal task. The results showed that preSMA-TMS increased activation in the right inferior-frontal cortex (rIFC) and basal ganglia and modulated their task-free functional connectivity. Both the TMS-induced changes in the basal-ganglia activation and the functional connectivity between rIFC and left striatum, and of the overall network correlated with the efficiency of response inhibition and with the white-matter microstructure along the preSMA-rIFC pathway. These results suggest that the task-free functional and structural connectivity between the rIFCop and basal ganglia are critical to the efficiency of response inhibition. Hum Brain Mapp 37:3236-3249, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Quantitative analysis of SMN1 gene and estimation of SMN1 deletion carrier frequency in Korean population based on real-time PCR.

PubMed

Lee, Tae-Mi; Kim, Sang-Wun; Lee, Kwang-Soo; Jin, Hyun-Seok; Koo, Soo Kyung; Jo, Inho; Kang, Seongman; Jung, Sung-Chul

2004-12-01

Spinal muscular atrophy (SMA) is an autosomal recessive disorder, caused by homozygous absence of the survival motor neuron gene (SMN1) in approximately 94% of patients. Since most carriers have only one SMN1 gene copy, several SMN1 quantitative analyses have been used for the SMA carrier detection. We developed a reliable quantitative real-time PCR with SYBR Green I dye and studied 13 patients with SMA and their 24 parents, as well as 326 healthy normal individuals. The copy number of the SMN1 gene was determined by the comparative threshold cycle (Ct) method and albumin was used as a reference gene. The homozygous SMN1 deletion ratio of patients was 0.00 and the hemizygous SMN1 deletion ratio of parents ranged from 0.39 to 0.59. The deltadelta Ct ratios of 7 persons among 326 normal individuals were within the carrier range, 0.41-0.57. According to these data, we estimated the carrier and disease prevalence of SMA at 1/47 and 1/8,496 in Korean population, respectively. These data indicated that there would be no much difference in disease prevalence of SMA compared with western countries. Since the prevalence of SMA is higher than other autosomal recessive disorders, the carrier detection method using real-time PCR could be a useful tool for genetic counseling.

Fabrication and characterization of an SU-8 gripper actuated by a shape memory alloy thin film

NASA Astrophysics Data System (ADS)

Roch, I.; Bidaud, Ph; Collard, D.; Buchaillot, L.

2003-03-01

In this paper, we present the fabrication process of a shape memory alloy (SMA) thin film in both monolithic and hybrid configurations. This provides an effective actuation part for a gripper made of SU-8 thick photoresist. We also extensively describe and discuss the assembly of the SMA thin film with the SU-8 mechanism. Measurements show that the SU-8 gripper is able to achieve an opening action of 500 mum in amplitude at a frequency of 1 Hz. Finite element model simulations indicate that a force of 50 mN, corresponding to 400 mum of opening amplitude, should be produced by the SMA actuator. Although the assembly of the TiNi SMA thin film with the SU-8 mechanism is demonstrated, the bond reliability needs further development in order to improve the thermal behavior of the interface. In this paper, we show that SU-8 is well suited as a structural material for microelectromechanical systems (MEMS) applications. An attractive feature in the MEMS design is that the SMA generated force is well matched with the elastic properties of SU-8. From the application point of view, a SMA-actuated SU-8 high-aspect-ratio microgripper can serve as a secure means to transport microelectronics device, because it provides good grasping and safe insulation. This is also a preliminary result for the future development of biogrippers.

SMN1 and SMN2 copy numbers in cell lines derived from patients with spinal muscular atrophy as measured by array digital PCR.

PubMed

Stabley, Deborah L; Harris, Ashlee W; Holbrook, Jennifer; Chubbs, Nicholas J; Lozo, Kevin W; Crawford, Thomas O; Swoboda, Kathryn J; Funanage, Vicky L; Wang, Wenlan; Mackenzie, William; Scavina, Mena; Sol-Church, Katia; Butchbach, Matthew E R

2015-07-01

Proximal spinal muscular atrophy (SMA) is an early-onset motor neuron disease characterized by loss of α-motor neurons and associated muscle atrophy. SMA is caused by deletion or other disabling mutation of survival motor neuron 1 (SMN1). In the human genome, a large duplication of the SMN-containing region gives rise to a second copy of this gene (SMN2) that is distinguishable by a single nucleotide change in exon 7. Within the SMA population, there is substantial variation in SMN2 copy number; in general, those individuals with SMA who have a high SMN2 copy number have a milder disease. Because SMN2 functions as a disease modifier, its accurate copy number determination may have clinical relevance. In this study, we describe the development of an assay to assess SMN1 and SMN2 copy numbers in DNA samples using an array-based digital PCR (dPCR) system. This dPCR assay can accurately and reliably measure the number of SMN1 and SMN2 copies in DNA samples. In a cohort of SMA patient-derived cell lines, the assay confirmed a strong inverse correlation between SMN2 copy number and disease severity. Array dPCR is a practical technique to determine, accurately and reliably, SMN1 and SMN2 copy numbers from SMA samples.

Incremental dynamic analysis of concrete moment resisting frames reinforced with shape memory composite bars

NASA Astrophysics Data System (ADS)

Zafar, Adeel; Andrawes, Bassem

2012-02-01

Fiber reinforced polymer (FRP) reinforcing bars have been used in concrete structures as an alternative to conventional steel reinforcement, in order to overcome corrosion problems. However, due to the linear behavior of the commonly used reinforcing fibers, they are not considered in structures which require ductility and damping characteristics. The use of superelastic shape memory alloy (SMA) fibers with their nonlinear elastic behavior as reinforcement in the composite could potentially provide a solution for this problem. Small diameter SMA wires are coupled with polymer matrix to produce SMA-FRP composite, which is sought in this research as reinforcing bars. SMA-FRP bars are sought in this study to enhance the seismic performance of reinforced concrete (RC) moment resisting frames (MRFs) in terms of reducing their residual inter-story drifts while still maintaining the elastic characteristics associated with conventional FRP. Three story one bay and six story two bay RC MRF prototype structures are designed with steel, SMA-FRP and glass-FRP reinforcement. The incremental dynamic analysis technique is used to investigate the behaviors of the two frames with the three different reinforcement types under a suite of ground motion records. It is found that the frames with SMA-FRP composite reinforcement exhibit higher performance levels including lower residual inter-story drifts, high energy dissipation and thus lower damage, which are important for structures in highly seismic zones.

The use of single-date MODIS imagery for estimating large-scale urban impervious surface fraction with spectral mixture analysis and machine learning techniques

NASA Astrophysics Data System (ADS)

Deng, Chengbin; Wu, Changshan

2013-12-01

Urban impervious surface information is essential for urban and environmental applications at the regional/national scales. As a popular image processing technique, spectral mixture analysis (SMA) has rarely been applied to coarse-resolution imagery due to the difficulty of deriving endmember spectra using traditional endmember selection methods, particularly within heterogeneous urban environments. To address this problem, we derived endmember signatures through a least squares solution (LSS) technique with known abundances of sample pixels, and integrated these endmember signatures into SMA for mapping large-scale impervious surface fraction. In addition, with the same sample set, we carried out objective comparative analyses among SMA (i.e. fully constrained and unconstrained SMA) and machine learning (i.e. Cubist regression tree and Random Forests) techniques. Analysis of results suggests three major conclusions. First, with the extrapolated endmember spectra from stratified random training samples, the SMA approaches performed relatively well, as indicated by small MAE values. Second, Random Forests yields more reliable results than Cubist regression tree, and its accuracy is improved with increased sample sizes. Finally, comparative analyses suggest a tentative guide for selecting an optimal approach for large-scale fractional imperviousness estimation: unconstrained SMA might be a favorable option with a small number of samples, while Random Forests might be preferred if a large number of samples are available.

[Molecular diagnosis of spinal muscular atrophy by multiplex ligation-dependent probe amplification].

PubMed

Zeng, Jian; Ke, Long-feng; Deng, Xiao-jun; Cai, Mei-ying; Tu, Xiang-dong; Lan, Feng-hua

2008-12-16

To investigate the effect of multiplex ligation-dependent probe amplification (MLPA) in molecular diagnosis of spinal muscular atrophy (SMA). Peripheral blood samples were collected from 13 SMA patients, 31 parents of SMA patients, 50 healthy individuals without family history of SMA, and 10 specimens of amniotic fluid from these families were collected too. Genomic DNA was analyzed by MLPA, conventional PCR-RFLP, and allele-specific PCR. In complete agreement with the results of conventional PCR-RFLP and allele-specific PCR, MLPA analysis showed that all of the 13 patients had homozygous deletion of the survival of motor neuron 1 (SMN1) gene, and there was significant difference between the SMA severity (type I to type III) and SMN2 copy number (P < 0.05). Of the 31 parents 29 (93.5%) had 1 copy of SMN1, 2 (6.5%) had 2 copies of SMN1. Of the 50 healthy individuals, 1 (2.0%) had 1 copy of SMN1, 48 (96.0%) had 2 copies of SMN1, and 1 (2.0%) had 3 copies. The SMN1 copy number of the parents was significantly higher than that of the healthy individuals (P < 0.01). Two of the 10 fetuses had homozygous deletion of SMN1. The MLPA technique has proved to be an accurate and reliable tool for the molecular diagnosis of SMA, both in patients and in healthy carriers.

Styrene maleic acid-encapsulated RL71 micelles suppress tumor growth in a murine xenograft model of triple negative breast cancer.

PubMed

Martey, Orleans; Nimick, Mhairi; Taurin, Sebastien; Sundararajan, Vignesh; Greish, Khaled; Rosengren, Rhonda J

2017-01-01

Patients with triple negative breast cancer have a poor prognosis due in part to the lack of targeted therapies. In the search for novel drugs, our laboratory has developed a second-generation curcumin derivative, 3,5-bis(3,4,5-trimethoxybenzylidene)-1-methylpiperidine-4-one (RL71), that exhibits potent in vitro cytotoxicity. To improve the clinical potential of this drug, we have encapsulated it in styrene maleic acid (SMA) micelles. SMA-RL71 showed improved biodistribution, and drug accumulation in the tumor increased 16-fold compared to control. SMA-RL71 (10 mg/kg, intravenously, two times a week for 2 weeks) also significantly suppressed tumor growth compared to control in a xenograft model of triple negative breast cancer. Free RL71 was unable to alter tumor growth. Tumors from SMA-RL71-treated mice showed a decrease in angiogenesis and an increase in apoptosis. The drug treatment also modulated various cell signaling proteins including the epidermal growth factor receptor, with the mechanisms for tumor suppression consistent with previous work with RL71 in vitro. The nanoformulation was also nontoxic as shown by normal levels of plasma markers for liver and kidney injury following weekly administration of SMA-RL71 (10 mg/kg) for 90 days. Thus, we report clinical potential following encapsulation of a novel curcumin derivative, RL71, in SMA micelles.

The implementation of discovery learning model based on lesson study to increase student's achievement in colloid

NASA Astrophysics Data System (ADS)

Suyanti, Retno Dwi; Purba, Deby Monika

2017-03-01

The objectives of this research are to get the increase student's achievement on the discovery learning model based on lesson study. Beside of that, this research also conducted to know the cognitive aspect. This research was done in three school that are SMA N 3 Medan. Population is all the students in SMA N 11 Medan which taken by purposive random sampling. The research instruments are achievement test instruments that have been validated. The research data analyzed by statistic using Ms Excell. The result data shows that the student's achievement taught by discovery learning model based on Lesson study higher than the student's achievement taught by direct instructional method. It can be seen from the average of gain and also proved with t-test, the normalized gain in experimental class of SMA N 11 is (0.74±0.12) and control class (0.45±0.12), at significant level α = 0.05, Ha is received and Ho is refused where tcount>ttable in SMA N 11 (9.81>1,66). Then get the improvement cognitive aspect from three of school is C2 where SMA N 11 is 0.84(high). Then the observation sheet result of lesson study from SMA N 11 92 % of student working together while 67% less in active using media.

Theoretical modelling of residual and transformational stresses in SMA composites

NASA Astrophysics Data System (ADS)

Berman, J. B.; White, S. R.

1996-12-01

SMA composites are a class of smart materials in which shape memory alloy (SMA) actuators are embedded in a polymer matrix composite. The difference in thermal expansion between the SMA and the host material leads to residual stresses during processing. Similarly, the SMA transformations from martensite to austenite, or the reverse, also generate stresses. These stresses acting in combination can lead to SMA/epoxy interfacial debonding or microcracking of the composite phase. In this study the residual and transformational stresses are investigated for a nitinol wire embedded in a graphite/epoxy composite. A three-phase micromechanical model is developed. The nitinol wire is assumed to behave as a thermoelastic material. Nitinol austenitic and martensitic transformations are modelled using linear piecewise interpolation of experimental data. The interphase is modelled as a thermoelastic polymer. A transversely isotropic thermoelastic composite is used for the outer phase. Stress-free conditions are assumed immediately before cool down from the cure temperature. The effect of nitinol, coating and composite properties on residual and transformational stresses are evaluated. Fiber architectures favoring the axial direction decrease the magnitude of all residual stresses. A decrease in stresses at the composite/coating interface is also predicted through the use of thick, compliant coatings. Reducing the recovery strain and moving the transformation to higher temperatures were found to be most effective in reducing residual stresses.

Use of orthoses and orthopaedic technical devices in proximal spinal muscular atrophy. Results of survey in 194 SMA patients.

PubMed

Fujak, Albert; Kopschina, Carsten; Forst, Raimund; Mueller, Lutz Arne; Forst, Jürgen

2011-01-01

The purpose of this study is to determine the use of orthopaedic and assistive devices for Spinal muscular atrophy (SMA) patients, following a survey of 194 patients. The use of wheelchairs, corsets and orthoses was evaluated in 194 SMA patients whose mean age was 12.6 (SD 7.2, 0.7-41.1). There were 14 patients with SMA type Ib (age range 1.7-36.9), 133 with type II (age range 0.7-37.7), 42 with type IIIa (age range 3.2-41.1) and 5 with type IIIb (age range 8.0-20.0). One hundred and sixteen patients (60%) had powered and 29 patients (15%) manual wheelchairs. Nineteen patients (10%) used long leg orthoses. Ten patients (5%) used swivel walkers and 26 (13%) had standing frames. Twenty-six patients (13%) received lower leg orthoses because of foot deformities. Eight patients (4%) used night splints for the lower limbs. One hundred and fifteen patients (59%) were fitted with corsets because of progressive scoliosis. This is the first study about the provision of orthopaedic and assistive devices in a large group of SMA patients. Following the results of this survey we can optimise the strategy of providing orthoses and assistive devices for SMA patients and better adapt them to the patient's individual needs.

Influence of TiN coating on the biocompatibility of medical NiTi alloy.

PubMed

Jin, Shi; Zhang, Yang; Wang, Qiang; Zhang, Dan; Zhang, Song

2013-01-01

The biocompatibility of TiN coated nickel-titanium shape memory alloy (NiTi-SMA) was evaluated to compare with that of the uncoated NiTi-SMA. Based on the orthodontic clinical application, the surface properties and biocompatibility were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), wettability test, mechanical test and in vitro tests including MTT, cell apoptosis and cell adhesion tests. It was observed that the bonding between the substrate and TiN coating is excellent. The roughness and wettability increased as for the TiN coating compared with the uncoated NiTi-SMA. MTT test showed no significant difference between the coated and uncoated NiTi-SMA, however the percentage of early cell apoptosis was significantly higher as for the uncoated NiTi alloy. SEM results showed that TiN coating could enhance the cell attachment, spreading and proliferation on NiTi-SMA. The results indicated that TiN coating bonded with the substrate well and could lead to a better biocompatibility. Copyright © 2012 Elsevier B.V. All rights reserved.

Sensory neurons do not induce motor neuron loss in a human stem cell model of spinal muscular atrophy.

PubMed

Schwab, Andrew J; Ebert, Allison D

2014-01-01

Spinal muscular atrophy (SMA) is an autosomal recessive disorder leading to paralysis and early death due to reduced SMN protein. It is unclear why there is such a profound motor neuron loss, but recent evidence from fly and mouse studies indicate that cells comprising the whole sensory-motor circuit may contribute to motor neuron dysfunction and loss. Here, we used induced pluripotent stem cells derived from SMA patients to test whether sensory neurons directly contribute to motor neuron loss. We generated sensory neurons from SMA induced pluripotent stem cells and found no difference in neuron generation or survival, although there was a reduced calcium response to depolarizing stimuli. Using co-culture of SMA induced pluripotent stem cell derived sensory neurons with control induced pluripotent stem cell derived motor neurons, we found no significant reduction in motor neuron number or glutamate transporter boutons on motor neuron cell bodies or neurites. We conclude that SMA sensory neurons do not overtly contribute to motor neuron loss in this human stem cell system.

Reliability and Validity of the TIMPSI for Infants With Spinal Muscular Atrophy Type I

PubMed Central

Krosschell, Kristin J.; Maczulski, Jo Anne; Scott, Charles; King, Wendy; Hartman, Jill T.; Case, Laura E.; Viazzo-Trussell, Donata; Wood, Janine; Roman, Carolyn A.; Hecker, Eva; Meffert, Marianne; Léveillé, Maude; Kienitz, Krista; Swoboda, Kathryn J.

2014-01-01

Purpose This study examined the reliability and validity of the Test of Infant Motor Performance Screening Items (TIMPSI) in infants with type I spinal muscular atrophy (SMA). Methods After training, 12 evaluators scored 4 videos of infants with type I SMA to assess interrater reliability. Intrarater and test-retest reliability was further assessed for 9 evaluators during a SMA type I clinical trial, with 9 evaluators testing a total of 38 infants twice. Relatedness of the TIMPSI score to ability to reach and ventilatory support was also examined. Results Excellent interrater video score reliability was noted (intraclass correlation coefficient, 0.97–0.98). Intrarater reliability was excellent (intraclass correlation coefficient, 0.91–0.98) and test-retest reliability ranged from r = 0.82 to r = 0.95. The TIMPSI score was related to the ability to reach (P ≤ .05). Conclusion The TIMPSI can reliably be used to assess motor function in infants with type I SMA. In addition, the TIMPSI scores are related to the ability to reach, an important functional skill in children with type I SMA. PMID:23542189

Shape memory alloy wire for self-sensing servo actuation

NASA Astrophysics Data System (ADS)

Josephine Selvarani Ruth, D.; Dhanalakshmi, K.

2017-01-01

This paper reports on the development of a straightforward approach to realise self-sensing shape memory alloy (SMA) wire actuated control. A differential electrical resistance measurement circuit (the sensorless signal conditioning (SSC) circuit) is designed; this sensing signal is directly used as the feedback for control. Antagonistic SMA wire actuators designed for servo actuation is realized in self-sensing actuation (SSA) mode for direct control with the differential electrical resistance feedback. The self-sensing scheme is established on a 1-DOF manipulator with the discrete time sliding mode controls which demonstrates good control performance, whatever be the disturbance and loading conditions. The uniqueness of this work is the design of the generic electronic SSC circuit for SMA actuated system, for measurement and control. With a concern to the implementation of self-sensing technique in SMA, this scheme retains the systematic control architecture by using the sensing signal (self-sensed, electrical resistance corresponding to the system position) for feedback, without requiring any processing as that of the methods adopted and reported previously for SSA techniques of SMA.

Transcranial direct current stimulation (tDCS) to the supplementary motor area (SMA) influences performance on motor tasks.

PubMed

Hupfeld, K E; Ketcham, C J; Schneider, H D

2017-03-01

The supplementary motor area (SMA) is believed to be highly involved in the planning and execution of both simple and complex motor tasks. This study aimed to examine the role of the SMA in planning the movements required to complete reaction time, balance, and pegboard tasks using anodal transcranial direct current stimulation (tDCS), which passes a weak electrical current between two electrodes, in order to modulate neuronal activity. Twenty healthy adults were counterbalanced to receive either tDCS (experimental condition) or no tDCS (control condition) for 3 days. During administration of tDCS, participants performed a balance task significantly faster than controls. After tDCS, subjects significantly improved their simple and choice reaction time. These results demonstrate that the SMA is highly involved in planning and executing fine and gross motor skill tasks and that tDCS is an effective modality for increasing SMA-related performance on these tasks. The findings may be generalizable and therefore indicate implications for future interventions using tDCS as a therapeutic tool.

Deregulation of ZPR1 causes respiratory failure in spinal muscular atrophy.

PubMed

Genabai, Naresh K; Kannan, Annapoorna; Ahmad, Saif; Jiang, Xiaoting; Bhatia, Kanchan; Gangwani, Laxman

2017-08-15

Spinal muscular atrophy (SMA) is caused by the low levels of survival motor neuron (SMN) protein and is characterized by motor neuron degeneration and muscle atrophy. Respiratory failure causes death in SMA but the underlying molecular mechanism is unknown. The zinc finger protein ZPR1 interacts with SMN. ZPR1 is down regulated in SMA patients. We report that ZPR1 functions downstream of SMN to regulate HoxA5 levels in phrenic motor neurons that control respiration. Spatiotemporal inactivation of Zpr1 gene in motor neurons down-regulates HoxA5 and causes defects in the function of phrenic motor neurons that results in respiratory failure and perinatal lethality in mice. Modulation in ZPR1 levels directly correlates and influences levels of HoxA5 transcription. In SMA mice, SMN-deficiency causes down-regulation of ZPR1 and HoxA5 that result in degeneration of phrenic motor neurons. Identification of ZPR1 and HoxA5 as potential targets provides a paradigm for developing strategies to treat respiratory distress in SMA.

Molecular Mechanisms of Neurodegeneration in Spinal Muscular Atrophy.

PubMed

Ahmad, Saif; Bhatia, Kanchan; Kannan, Annapoorna; Gangwani, Laxman

2016-01-01

Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease with a high incidence and is the most common genetic cause of infant mortality. SMA is primarily characterized by degeneration of the spinal motor neurons that leads to skeletal muscle atrophy followed by symmetric limb paralysis, respiratory failure, and death. In humans, mutation of the Survival Motor Neuron 1 (SMN1) gene shifts the load of expression of SMN protein to the SMN2 gene that produces low levels of full-length SMN protein because of alternative splicing, which are sufficient for embryonic development and survival but result in SMA. The molecular mechanisms of the (a) regulation of SMN gene expression and (b) degeneration of motor neurons caused by low levels of SMN are unclear. However, some progress has been made in recent years that have provided new insights into understanding of the cellular and molecular basis of SMA pathogenesis. In this review, we have briefly summarized recent advances toward understanding of the molecular mechanisms of regulation of SMN levels and signaling mechanisms that mediate neurodegeneration in SMA.

[Retrieval of crown closure of moso bamboo forest using unmanned aerial vehicle (UAV) remotely sensed imagery based on geometric-optical model].

PubMed

Wang, Cong; Du, Hua-qiang; Zhou, Guo-mo; Xu, Xiao-jun; Sun, Shao-bo; Gao, Guo-long

2015-05-01

This research focused on the application of remotely sensed imagery from unmanned aerial vehicle (UAV) with high spatial resolution for the estimation of crown closure of moso bamboo forest based on the geometric-optical model, and analyzed the influence of unconstrained and fully constrained linear spectral mixture analysis (SMA) on the accuracy of the estimated results. The results demonstrated that the combination of UAV remotely sensed imagery and geometric-optical model could, to some degrees, achieve the estimation of crown closure. However, the different SMA methods led to significant differentiation in the estimation accuracy. Compared with unconstrained SMA, the fully constrained linear SMA method resulted in higher accuracy of the estimated values, with the coefficient of determination (R2) of 0.63 at 0.01 level, against the measured values acquired during the field survey. Root mean square error (RMSE) of approximate 0.04 was low, indicating that the usage of fully constrained linear SMA could bring about better results in crown closure estimation, which was closer to the actual condition in moso bamboo forest.

Development of shape memory metal as the actuator of a fail safe mechanism

NASA Technical Reports Server (NTRS)

Ford, V. G.; Johnson, M. R.; Orlosky, S. D.

1990-01-01

A small, compact, lightweight device was developed using shape memory alloy (SMA) in wire form to actuate a pin-puller that decouples the flanges of two shafts. When the SMA is heated it contracts producing a useful force and stroke. As it cools, it can be reset (elongated in this case) by applying a relatively small force. Resistive heating is accomplished by running a current through the SMA wire for a controlled length of time. The electronics to drive the device are not elaborate or complicated, consisting of a timed current source. The total available contraction is 3 percent of the length of the wire. This device, the engineering properties of the SMA, and the tests performed to verify the design concept are described.

Note: A component-level frequency tunable isolator for vibration-sensitive chips using SMA beams.

PubMed

Zhang, Xiaoyong; Ding, Xin; Wu, Di; Qi, Junlei; Wang, Ruixin; Lu, Siwei; Yan, Xiaojun

2016-06-01

This note presents a component-level frequency tunable isolator for vibration-sensitive chips. The isolator employed 8 U-shaped shape memory alloy (SMA) beams to support an isolation island (used for mounting chips). Due to the temperature-induced Young's modulus variation of SMA, the system stiffness of the isolator can be controlled through heating the SMA beams. In such a way, the natural frequency of the isolator can be tuned. A prototype was fabricated to evaluate the concept. The test results show that the natural frequency of the isolator can be tuned in the range of 64 Hz-97 Hz by applying different heating strategies. Moreover, resonant vibration can be suppressed significantly (the transmissibility decreases about 65% near the resonant frequency) using a real-time tuning method.

Modeling of vibrations isolation and arrest by shape memory parts and permanent magnets

NASA Astrophysics Data System (ADS)

Belyaev, Fedor S.; Volkov, Aleksandr E.; Evard, Margarita E.; Vikulenkov, Andrey V.; Uspenskiy, Evgeniy S.

2018-05-01

A vibration protection system under consideration consists of a payload connected to a vibrating housing by shape memory alloy (SMA) slotted springs. To provide an arrest function two permanent magnets are inserted into the system. The slotted SMA elements are preliminary deformed in the martensitic state. Activation of one element by heating initiates force and displacement generation, which provide an arrest of the payload by magnets. The magnets also secure the arrest mode after cooling of the SMA element. Activation of the other element results in uncaging of the payload and switching to the vibration isolation mode. Computer simulations of arrest and uncaging when the housing is quiescent or producing sine-wave displacements were carried out. Functional-mechanical behavior of SMA parts was described by means of a microstructural model.

The influence of expertise on brain activation of the action observation network during anticipation of tennis and volleyball serves

PubMed Central

Balser, Nils; Lorey, Britta; Pilgramm, Sebastian; Naumann, Tim; Kindermann, Stefan; Stark, Rudolf; Zentgraf, Karen; Williams, A. Mark; Munzert, Jörn

2014-01-01

In many daily activities, and especially in sport, it is necessary to predict the effects of others' actions in order to initiate appropriate responses. Recently, researchers have suggested that the action–observation network (AON) including the cerebellum plays an essential role during such anticipation, particularly in sport expert performers. In the present study, we examined the influence of task-specific expertise on the AON by investigating differences between two expert groups trained in different sports while anticipating action effects. Altogether, 15 tennis and 16 volleyball experts anticipated the direction of observed tennis and volleyball serves while undergoing functional magnetic resonance imaging (fMRI). The expert group in each sport acted as novice controls in the other sport with which they had only little experience. When contrasting anticipation in both expertise conditions with the corresponding untrained sport, a stronger activation of AON areas (SPL, SMA), and particularly of cerebellar structures, was observed. Furthermore, the neural activation within the cerebellum and the SPL was linearly correlated with participant's anticipation performance, irrespective of the specific expertise. For the SPL, this relationship also holds when an expert performs a domain-specific anticipation task. Notably, the stronger activation of the cerebellum as well as of the SMA and the SPL in the expertise conditions suggests that experts rely on their more fine-tuned perceptual-motor representations that have improved during years of training when anticipating the effects of others' actions in their preferred sport. The association of activation within the SPL and the cerebellum with the task achievement suggests that these areas are the predominant brain sites involved in fast motor predictions. The SPL reflects the processing of domain-specific contextual information and the cerebellum the usage of a predictive internal model to solve the anticipation task. PMID:25136305

[Intramuscular injection of lentivirus-mediated EPAS1 gene improves hind limb ischemia and its mechanism in a rat model of peripheral artery vascular disease].

PubMed

Wang, Zhihong; Gu, Hongbin; Yang, Fan; Xie, Huajie; Sheng, Lei; Li, Mingfei

2017-11-01

Objective To investigate the effect of over-expressed endothelial Per-Arnt-Sim domain protein 1 (EPAS1) on peripheral arterial disease (PAD) in a rat model. Methods PAD rat model was established by external iliac artery ligation followed by lentivirus-mediated EPAS1 gene injection into rat right adductor magnus. The models were evaluated by quantitative analysis of gait disturbance. The changes of blood flow in the posterior extremity of the rats were detected using laser Doppler. The expressions of EPAS1, hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) mRNAs were tested by real-time quantitative PCR. The expression of α-smooth muscle actin (αSMA) was detected by immunohistochemical staining. Results Compared with lenti-EGFP group, rat hind limb function and circulation got recovered obviously 7 days after lenti-EPAS1 injection. The mRNA expressions of EPAS1, HGF, bFGF, and VEGF were up-regulated in the lenti-EPAS1-treated sites.The expression of αSMA showed an obvious increase in the lenti-EPAS1-treated muscles. Conclusion Over-expressed lenti-EPAS1 can promote angiogenesis via the up-regulation of EPAS1-related angiogenic factors in the muscles of the affected hind limb and reduce gait disturbance.

Solution structure of the core SMN–Gemin2 complex

PubMed Central

Sarachan, Kathryn L.; Valentine, Kathleen G.; Gupta, Kushol; Moorman, Veronica R.; Gledhill, John M.; Bernens, Matthew; Tommos, Cecilia; Wand, A. Joshua; Van Duyne, Gregory D.

2012-01-01

In humans, assembly of spliceosomal snRNPs (small nuclear ribonucleoproteins) begins in the cytoplasm where the multi-protein SMN (survival of motor neuron) complex mediates the formation of a seven-membered ring of Sm proteins on to a conserved site of the snRNA (small nuclear RNA). The SMN complex contains the SMN protein Gemin2 and several additional Gemins that participate in snRNP biosynthesis. SMN was first identified as the product of a gene found to be deleted or mutated in patients with the neurodegenerative disease SMA (spinal muscular atrophy), the leading genetic cause of infant mortality. In the present study, we report the solution structure of Gemin2 bound to the Gemin2-binding domain of SMN determined by NMR spectroscopy. This complex reveals the structure of Gemin2, how Gemin2 binds to SMN and the roles of conserved SMN residues near the binding interface. Surprisingly, several conserved SMN residues, including the sites of two SMA patient mutations, are not required for binding to Gemin2. Instead, they form a conserved SMN/Gemin2 surface that may be functionally important for snRNP assembly. The SMN–Gemin2 structure explains how Gemin2 is stabilized by SMN and establishes a framework for structure–function studies to investigate snRNP biogenesis as well as biological processes involving Gemin2 that do not involve snRNP assembly. PMID:22607171

Impaired Muscle Mitochondrial Biogenesis and Myogenesis in Spinal Muscular Atrophy

PubMed Central

Ripolone, Michela; Ronchi, Dario; Violano, Raffaella; Vallejo, Dionis; Fagiolari, Gigliola; Barca, Emanuele; Lucchini, Valeria; Colombo, Irene; Villa, Luisa; Berardinelli, Angela; Balottin, Umberto; Morandi, Lucia; Mora, Marina; Bordoni, Andreina; Fortunato, Francesco; Corti, Stefania; Parisi, Daniela; Toscano, Antonio; Sciacco, Monica; DiMauro, Salvatore; Comi, Giacomo P.; Moggio, Maurizio

2016-01-01

IMPORTANCE The important depletion of mitochondrial DNA (mtDNA) and the general depression of mitochondrial respiratory chain complex levels (including complex II) have been confirmed, implying an increasing paucity of mitochondria in the muscle from patients with types I, II, and III spinal muscular atrophy (SMA-I, -II, and -III, respectively). OBJECTIVE To investigate mitochondrial dysfunction in a large series of muscle biopsy samples from patients with SMA. DESIGN, SETTING, AND PARTICIPANTS We studied quadriceps muscle samples from 24 patients with genetically documented SMA and paraspinal muscle samples from 3 patients with SMA-II undergoing surgery for scoliosis correction. Postmortem muscle samples were obtained from 1 additional patient. Age-matched controls consisted of muscle biopsy specimens from healthy children aged 1 to 3 years who had undergone analysis for suspected myopathy. Analyses were performed at the Neuromuscular Unit, Istituto di Ricovero e Cura a Carattere Scientifico Foundation Ca’ Granda Ospedale Maggiore Policlinico-Milano, from April 2011 through January 2015. EXPOSURES We used histochemical, biochemical, and molecular techniques to examine the muscle samples. MAIN OUTCOMES AND MEASURES Respiratory chain activity and mitochondrial content. RESULTS Results of histochemical analysis revealed that cytochrome-c oxidase (COX) deficiency was more evident in muscle samples from patients with SMA-I and SMA-II. Residual activities for complexes I, II, and IV in muscles from patients with SMA-I were 41%, 27%, and 30%, respectively, compared with control samples (P < .005). Muscle mtDNA content and cytrate synthase activity were also reduced in all 3 SMA types (P < .05). We linked these alterations to downregulation of peroxisome proliferator–activated receptor coactivator 1α, the transcriptional activators nuclear respiratory factor 1 and nuclear respiratory factor 2, mitochondrial transcription factor A, and their downstream targets, implying depression of the entire mitochondrial biogenesis. Results of Western blot analysis confirmed the reduced levels of the respiratory chain subunits that included mitochondrially encoded COX1 (47.5%; P = .004), COX2 (32.4%; P < .001), COX4 (26.6%; P < .001), and succinate dehydrogenase complex subunit A (65.8%; P = .03) as well as the structural outer membrane mitochondrial porin (33.1%; P < .001). Conversely, the levels of expression of 3 myogenic regulatory factors—muscle-specificmyogenic factor 5, myoblast determination 1, and myogenin—were higher in muscles from patients with SMA compared with muscles from age-matched controls (P < .05). CONCLUSIONS AND RELEVANCE Our results strongly support the conclusion that an altered regulation of myogenesis and a downregulated mitochondrial biogenesis contribute to pathologic change in the muscle of patients with SMA. Therapeutic strategies should aim at counteracting these changes. PMID:25844556

Medical Issues: Equipment

MedlinePlus

... support & care > living with sma > medical issues > equipment Equipment Individuals with SMA often require a range of ... you can submit an equipment pool request. Helpful Equipment The following is a list of equipment that ...

The Development of Learning Model Based on Problem Solving to Construct High-Order Thinking Skill on the Learning Mathematics of 11th Grade in SMA/MA

ERIC Educational Resources Information Center

Syahputra, Edi; Surya, Edy

2017-01-01

This paper is a summary study of team Postgraduate on 11th grade. The objective of this study is to develop a learning model based on problem solving which can construct high-order thinking on the learning mathematics in SMA/MA. The subject of dissemination consists of Students of 11th grade in SMA/MA in 3 kabupaten/kota in North Sumatera, namely:…

Percutaneous Retrograde Recanalization of the Celiac Artery by Way of the Superior Mesenteric Artery for Chronic Mesenteric Ischemia

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

Joseph, George, E-mail: joseph59@gmail.com; Chacko, Sujith Thomas

2013-02-15

A 52-year-old man presented with recurrent postprandial abdominal pain, sitophobia, and progressive weight loss. Chronic mesenteric ischemia (CMI) due to subtotal occlusion of the superior mesenteric artery (SMA) and flush occlusion of the celiac artery (CA) was diagnosed. Retrograde recanalization of the CA by way of a collateral channel from the SMA was performed using contemporary recanalization equipment. The CA and SMA were then stented, resulting in sustained resolution of CMI-related symptoms.

Effemeridi del transito meridiano 2017-2020 per la basilica di Santa Maria degli Angeli in Roma

NASA Astrophysics Data System (ADS)

Sigismondi, Costantino

2016-12-01

The meridian transit time is computed using the ephemerides of IMCCE and the position of the image's center on the 1702 meridian line is corrected for the average atmospheric refraction at the site of Santa Maria degli Angeli, SMA, in Rome. The ephemerides for 2017-2020 are public on http://www.icra.it/gerbertus/2016/effem-SMA.pdf The measurement at SMA of DUT1=-0.34s on Dec 2016 is in agreement with IERS bullettin D132.

Spinal Muscular Atrophy (SMA)

MedlinePlus

... kids of the same age or have trouble lifting things. Kids with SMA can develop scoliosis (a ... Nervous System Your Muscles Wheelchairs Scoliosis Steven's Story: Power Player Kyphosis Muscular Dystrophy Spinal Muscular Atrophy: Steven's ...

Spinal Muscular Atrophy FAQ

MedlinePlus

... in SMA. What is Spinal Muscular Atrophy with Respiratory Distress (SMARD)? SMARD and SMA are separate diseases ... muscle weakness and atrophy. Spinal Muscular Atrophy with Respiratory Distress (SMARD) is a rare neuromuscular disease that ...

Sense of agency is related to gamma band coupling in an inferior parietal-preSMA circuitry

PubMed Central

Ritterband-Rosenbaum, Anina; Nielsen, Jens B.; Christensen, Mark S.

2014-01-01

In the present study we tested whether sense of agency (SoA) is reflected by changes in coupling between right medio-frontal/supplementary motor area (SMA) and inferior parietal cortex (IPC). Twelve healthy adult volunteers participated in the study. They performed a variation of a line-drawing task (Nielsen, 1963; Fourneret and Jeannerod, 1998), in which they moved a cursor on a digital tablet with their right hand without seeing the hand. Visual feedback displayed on a computer monitor was either in correspondence with or deviated from the actual movement. This made participants uncertain as to the agent of the movement and they reported SoA in approximately 50% of trials when the movement was computer-generated. We tested whether IPC-preSMA coupling was associated with SoA, using dynamic causal modeling (DCM) for induced responses (Chen et al., 2008; Herz et al., 2012). Nine different DCMs were constructed for the early and late phases of the task, respectively. All models included two regions: a superior medial gyrus (preSMA) region and a right supramarginal gyrus (IPC) region. Bayesian models selection (Stephan et al., 2009) favored a model with input to IPC and modulation of the forward connection to SMA in the late task phase, and a model with input to preSMA and modulation of the backward connection was favored for the early task phase. The analysis shows that IPC source activity in the 50–60 Hz range modulated preSMA source activity in the 40–70 Hz range in the presence of SoA compared with no SoA in the late task phase, but the test of the early task phase did not reveal any differences between presence and absence of SoA. We show that SoA is associated with a directionally specific between frequencies coupling from IPC to preSMA in the higher gamma (ɣ) band in the late task phase. This suggests that SoA is a retrospective perception, which is highly dependent on interpretation of the outcome of the performed action. PMID:25076883

[Mesenteric flow in an experimental model of ischaemia-reperfusion in rats].

PubMed

Cáceres, F; Castañon, M; Lerena, J; Cusi, V; Badosa, J; Morales, L

2014-03-01

Maintained acute occlusion followed by reperfusion of the superior mesenteric artery (SMA) in a few hours can trigger irreversible bowel damage. The aim of the study was to determine the changes in mesenteric flow measured by colour Doppler Ultrasound and correlating with histological lesions in an experimental model of ischaemia-reperfusion. Three groups of Sprague-Dawley 17 day-old rats were studied (control, ischemia and reperfusion). The model used was ischaemia-reperfusion over the SMA. Intra-abdominal ultrasound was then performed. The parameters recorded were: Maximum systolic velocity (MSV), pulsatility index (PI), resistance (RI) and systole-diastole (S/D). The histological variables were: intestinal lesion (Wallace/Keenan-Chiu scale), morphometrics (mean villus height [MVH]), and goblet cells. The Spearman (rs) correlation was used. The MSV in the reperfusion group was 74.3 cm/s, the PI 7.33 and S/D 25.75 in the SMA, which were higher than the controls (41.35 cm/s; 3.12 and 12.45, respectively). A direct association (P<.01) was found between MSV, PI and S/D regarding: Wallace/Kennan scoring system (rs = 0.655; rs = 0.593; rs = 0.63) and the Chiu (rs = 0.569; rs = 0.522; rs = 0.47). While the correlation was the reverse (P<.01) when associated with the MVH (rs = -0,495; rs = -0,452; rs = -0,459) and goblet cells of the colon (rs = -0,525; rs = -0,45; rs = -0,518). The reperfusion phase increased mesenteric flow expressed by the MSV and PI and could significantly predict the potential bowel damage at macroscopic and microscopic level. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

How feedback, motor imagery, and reward influence brain self-regulation using real-time fMRI.

PubMed

Sepulveda, Pradyumna; Sitaram, Ranganatha; Rana, Mohit; Montalba, Cristian; Tejos, Cristian; Ruiz, Sergio

2016-09-01

The learning process involved in achieving brain self-regulation is presumed to be related to several factors, such as type of feedback, reward, mental imagery, duration of training, among others. Explicitly instructing participants to use mental imagery and monetary reward are common practices in real-time fMRI (rtfMRI) neurofeedback (NF), under the assumption that they will enhance and accelerate the learning process. However, it is still not clear what the optimal strategy is for improving volitional control. We investigated the differential effect of feedback, explicit instructions and monetary reward while training healthy individuals to up-regulate the blood-oxygen-level dependent (BOLD) signal in the supplementary motor area (SMA). Four groups were trained in a two-day rtfMRI-NF protocol: GF with NF only, GF,I with NF + explicit instructions (motor imagery), GF,R with NF + monetary reward, and GF,I,R with NF + explicit instructions (motor imagery) + monetary reward. Our results showed that GF increased significantly their BOLD self-regulation from day-1 to day-2 and GF,R showed the highest BOLD signal amplitude in SMA during the training. The two groups who were instructed to use motor imagery did not show a significant learning effect over the 2 days. The additional factors, namely motor imagery and reward, tended to increase the intersubject variability in the SMA during the course of training. Whole brain univariate and functional connectivity analyses showed common as well as distinct patterns in the four groups, representing the varied influences of feedback, reward, and instructions on the brain. Hum Brain Mapp 37:3153-3171, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Hypoxia-inducible vascular endothelial growth factor gene therapy using the oxygen-dependent degradation domain in myocardial ischemia.

PubMed

Kim, Hyun Ah; Lim, Soyeon; Moon, Hyung-Ho; Kim, Sung Wan; Hwang, Ki-Chul; Lee, Minhyung; Kim, Sun Hwa; Choi, Donghoon

2010-10-01

A hypoxia-inducible VEGF expression system with the oxygen-dependent degradation (ODD) domain was constructed and tested to be used in gene therapy for ischemic myocardial disease. Luciferase and VEGF expression vector systems were constructed with or without the ODD domain: pEpo-SV-Luc (or pEpo-SV-VEGF) and pEpo-SV-Luc-ODD (or pEpo-SV-VEGF-ODD). In vitro gene expression efficiency of each vector type was evaluated in HEK 293 cells under both hypoxic and normoxic conditions. The amount of VEGF protein was estimated by ELISA. The VEGF expression vectors with or without the ODD domain were injected into ischemic rat myocardium. Fibrosis, neovascularization, and cardiomyocyte apoptosis were assessed using Masson's trichrome staining, α-smooth muscle actin (α-SMA) immunostaining, and the TUNEL assay, respectively. The plasmid vectors containing ODD significantly improved the expression level of VEGF protein in hypoxic conditions. The enhancement of VEGF protein production was attributed to increased protein stability due to oxygen deficiency. In a rat model of myocardial ischemia, the pEpo-SV-VEGF-ODD group exhibited less myocardial fibrosis, higher microvessel density, and less cardiomyocyte apoptosis compared to the control groups (saline and pEpo-SV-VEGF treatments). An ODD-mediated VEGF expression system that facilitates VEGF-production under hypoxia may be useful in the treatment of ischemic heart disease.

Surveying Low-Mass Star Formation with the Submillimeter Array

NASA Astrophysics Data System (ADS)

Dunham, Michael

2018-01-01

Large astronomical surveys yield important statistical information that can’t be derived from single-object and small-number surveys. In this talk I will review two recent surveys in low-mass star formation undertaken by the Submillimeter Array (SMA): a millimeter continuum survey of disks surrounding variably accreting young stars, and a complete continuum and molecular line survey of all protostars in the nearby Perseus Molecular Cloud. I will highlight several new insights into the processes by which low-mass stars gain their mass that have resulted from the statistical power of these surveys.

Cure SMA

MedlinePlus

... Funding Opportunities Research Conference Recruit for Clinical Trials Research Publications Spinraza Support & Care For Newly Diagnosed Care Packages Information Packets Equipment Pool Living With SMA Medical Issues Palliative Breathing Orthopedics Nutrition Equipment Daily Life At School At Home ...

Fatigue behavior of a thermally-activated NiTiNb SMA-FRP patch

NASA Astrophysics Data System (ADS)

El-Tahan, M.; Dawood, M.

2016-01-01

This paper presents the details of an experimental study that was conducted to characterize the fatigue behavior of a thermally-activated shape memory alloy (SMA)/carbon fiber reinforced polymer (CFRP) patch that can be used to repair cracked steel members. A total of 14 thermally-activated patches were fabricated and tested to evaluate the stability of the prestress under fatigue loading. The parameters considered in this study are the prestress level in the nickel-titanium-niobium SMA wires and the applied force range. An empirical model to predict the degradation of the prestress is also presented. The results indicate that patches for which the maximum applied loads in a fatigue cycle did not cause debonding of the SMA wires from the CFRP sustained two million loading cycles with less than 20% degradation of the prestress.

Determination of strain fields in porous shape memory alloys using micro-computed tomography

NASA Astrophysics Data System (ADS)

Bormann, Therese; Friess, Sebastian; de Wild, Michael; Schumacher, Ralf; Schulz, Georg; Müller, Bert

2010-09-01

Shape memory alloys (SMAs) belong to 'intelligent' materials since the metal alloy can change its macroscopic shape as the result of the temperature-induced, reversible martensite-austenite phase transition. SMAs are often applied for medical applications such as stents, hinge-less instruments, artificial muscles, and dental braces. Rapid prototyping techniques, including selective laser melting (SLM), allow fabricating complex porous SMA microstructures. In the present study, the macroscopic shape changes of the SMA test structures fabricated by SLM have been investigated by means of micro computed tomography (μCT). For this purpose, the SMA structures are placed into the heating stage of the μCT system SkyScan 1172™ (SkyScan, Kontich, Belgium) to acquire three-dimensional datasets above and below the transition temperature, i.e. at room temperature and at about 80°C, respectively. The two datasets were registered on the basis of an affine registration algorithm with nine independent parameters - three for the translation, three for the rotation and three for the scaling in orthogonal directions. Essentially, the scaling parameters characterize the macroscopic deformation of the SMA structure of interest. Furthermore, applying the non-rigid registration algorithm, the three-dimensional strain field of the SMA structure on the micrometer scale comes to light. The strain fields obtained will serve for the optimization of the SLM-process and, more important, of the design of the complex shaped SMA structures for tissue engineering and medical implants.

Characterization of NiTinol under torsional loads through a numerical implementation of the Boyd Lagoudas constitutive model and comparison of the results with experimental data

NASA Astrophysics Data System (ADS)

Vitiello, Antonio; Squillace, Antonino; Prisco, Umberto

2007-02-01

Shape memory alloys (SMA) are a particular family of materials, discovered during the 1930s and only now used in technological applications, with the property of returning to an imposed shape after a deformation and heating process. The study of the mechanical behaviour of SMA, through a proper constitutive model, and the possible ensuing applications form the core of an interesting research field, developed in the last few years and still now subject to studies driven by the aim of understanding and characterizing the peculiar properties of these materials. The aim of this work is to study the behaviour of SMA under torsional loads. To obtain a forecast of the mechanical response of the SMA, we utilized a numerical algorithm based on the Boyd-Lagoudas model and then we compared the results with those from some experimental tests. The experiments were conducted by subjecting helicoidal springs with a constant cross section to a traction load. It is well known, in fact, that in such springs the main stress under traction loads is almost completely a pure torsional stress field. The interest in these studies is due to the absence of data on such tests in the literature for SMA, and because there are an increasing number of industrial applications where SMA are subjected to torsional load, in particular in medicine, and especially in orthodontic drills which usually work under torsional loads.

Towards the development of a triple SMA actuated vertical tube

NASA Astrophysics Data System (ADS)

Karimi, Saeed; Konh, Bardia; Seidi, Ebrahim

2018-03-01

In this work an active vertically hung tube has been designed, fabricated and tested. The active tube was made of three separate 3D printed parts assembled and glued together. Shape Memory Alloy (SMA) wires were embedded as actuators in the body of the tube to privilege from their robust actuation and high energy density. Three SMA wires were trained and installed evenly on the exterior peripheral side of the tubes to realize motion in multiple directions. A deadweight was hung to one end of the tube to exert a certain amount of pre-stress on actuators. This design offers a restricted actuation because the two wires on the opposite side always resist the intended deflection. Hence, for a proper actuation, each wire was stressed to a certain level to exhibit either expansion or contraction upon demand. This amount of stress was selected based on rigorous experimental data. Power supply units were integrated and linked to a python program to control the amount of power passed through each SMA wire. The active tube was tested, and its movement was captured via a camera and analyzed by ImageJ software for the two cases free of stress and with an applied external load. The electrical resistance of the each SMA wire was measured and used for controlling the tube's deflection in each direction. This work demonstrated the feasibility of using three evenly distributed SMA wires on a tube to create motion in 3D direction.

MT1-MMP Responsive Doxorubicin Conjugated Poly(lactic-co-glycolic Acid)/Poly(styrene-alt-maleic Anhydride) Core/Shell Microparticles for Intrahepatic Arterial Chemotherapy of Hepatic Cancer.

PubMed

Davaa, Enkhzaya; Lee, Junghan; Jenjob, Ratchapol; Yang, Su-Geun

2017-01-11

In this study, we demonstrated that the MT1-MMP-responsive peptide (sequence: GPLPLRSWGLK) and doxorubicin-conjugated poly(lactic-co-glycolic acid/poly(styrene-alt-maleic anhydride) core/shell microparticles (PLGA/pSMA MPs) can be applied for intrahepatic arterial injection for hepatocellular carcinoma (HCC). PLGA/pSMA MPs were prepared with a capillary-focused microfluidic device. The particle size, observed by scanning electron microscopy (SEM), was around 22 ± 3 μm. MT1-MMP-responsive peptide and doxorubicin (DOX) were chemically conjugated with pSMA segments on the shell of MPs to form a PLGA/pSMA-peptide-DOX complex, resulting in high encapsulation efficiency (91.1%) and loading content (2.9%). DOX was released from PLGA/pSMA-peptide-DOX MPs in a pH-dependent manner (∼25% at pH 5.4 and ∼8% at pH 7.4) and accumulated significantly in an MT1-MMP-overexpressing Hep3B cell line. An in vivo intrahepatic injection study showed localization of MPs on the hepatic vessels and hepatic lobes up to 24 h after the injection without any shunting to the lung. Moreover, MPs efficiently inhibited tumor growth of Hep3B hepatic tumor xenografted mouse models. We expect that PLGA/pSMA-peptide-DOX MPs can be utilized as an effective intrahepatic drug delivery system for the treatment of HCC.

A qualitative study of perceptions of meaningful change in spinal muscular atrophy.

PubMed

McGraw, Sarah; Qian, Ying; Henne, Jeff; Jarecki, Jill; Hobby, Kenneth; Yeh, Wei-Shi

2017-04-04

This qualitative study examined how individuals with Spinal Muscular Atrophy (SMA), their caregivers, and clinicians defined meaningful change, primarily in the Type II and non-ambulant type III patient populations, associated with treatment of this condition. In addition, we explored participants' views about two measures of motor function routinely used in clinical trials for these SMA subtypes, namely the expanded version of the Hammersmith Functional Motor Scale (HFMSE) and the Upper Limb Module (ULM). The 123 participants (21 with SMA, 64 parents, and 11 clinicians), recruited through SMA advocacy organizations, participated in one of 16 focus groups or 37 interviews. The sessions were audio-recorded, and verbatim transcripts were analyzed using a grounded theory approach. For the participants, meaningful change was relative to functional ability, and small changes in motor function could have an important impact on quality of life. Because patients and families feared progressive loss of functional ability, the participants saw maintenance of abilities as a meaningful outcome. They believed that measures of motor function covered important items, but worried that the HFMSE and ULM might not be sensitive enough to capture small changes. In addition, they felt that outcome measures should assess other important features of life with SMA, including the ability to perform daily activities, respiratory function, swallowing, fatigue, and endurance. Given the heterogeneity of SMA, it is important to expand the assessment of treatment effects to a broader range of outcomes using measures sensitive enough to detect small changes.

Seamless Genetic Conversion of SMN2 to SMN1 via CRISPR/Cpf1 and Single-Stranded Oligodeoxynucleotides in Spinal Muscular Atrophy Patient-Specific Induced Pluripotent Stem Cells.

PubMed

Zhou, Miaojin; Hu, Zhiqing; Qiu, Liyan; Zhou, Tao; Feng, Mai; Hu, Qian; Zeng, Baitao; Li, Zhuo; Sun, Qianru; Wu, Yong; Liu, Xionghao; Wu, Lingqian; Liang, Desheng

2018-05-09

Spinal muscular atrophy (SMA) is a kind of neuromuscular disease characterized by progressive motor neuron loss in the spinal cord. It is caused by mutations in the survival motor neuron 1 (SMN1) gene. SMN1 has a paralogous gene, survival motor neuron 2 (SMN2), in humans that is present in almost all SMA patients. The generation and genetic correction of SMA patient-specific induced pluripotent stem cells (iPSCs) is a viable, autologous therapeutic strategy for the disease. Here, c-Myc-free and non-integrating iPSCs were generated from the urine cells of an SMA patient using an episomal iPSC reprogramming vector, and a unique crRNA was designed that does not have similar sequences (≤3 mismatches) anywhere in the human reference genome. In situ gene conversion of the SMN2 gene to an SMN1-like gene in SMA-iPSCs was achieved using CRISPR/Cpf1 and single-stranded oligodeoxynucleotide with a high efficiency of 4/36. Seamlessly gene-converted iPSC lines contained no exogenous sequences and retained a normal karyotype. Significantly, the SMN expression and gems localization were rescued in the gene-converted iPSCs and their derived motor neurons. This is the first report of an efficient gene conversion mediated by Cpf1 homology-directed repair in human cells and may provide a universal gene therapeutic approach for most SMA patients.

Standardization of shape memory alloy test methods toward certification of aerospace applications

NASA Astrophysics Data System (ADS)

Hartl, D. J.; Mabe, J. H.; Benafan, O.; Coda, A.; Conduit, B.; Padan, R.; Van Doren, B.

2015-08-01

The response of shape memory alloy (SMA) components employed as actuators has enabled a number of adaptable aero-structural solutions. However, there are currently no industry or government-accepted standardized test methods for SMA materials when used as actuators and their transition to commercialization and production has been hindered. This brief fast track communication introduces to the community a recently initiated collaborative and pre-competitive SMA specification and standardization effort that is expected to deliver the first ever regulatory agency-accepted material specification and test standards for SMA as employed as actuators for commercial and military aviation applications. In the first phase of this effort, described herein, the team is working to review past efforts and deliver a set of agreed-upon properties to be included in future material certification specifications as well as the associated experiments needed to obtain them in a consistent manner. Essential for the success of this project is the participation and input from a number of organizations and individuals, including engineers and designers working in materials and processing development, application design, SMA component fabrication, and testing at the material, component, and system level. Going forward, strong consensus among this diverse body of participants and the SMA research community at large is needed to advance standardization concepts for universal adoption by the greater aerospace community and especially regulatory bodies. It is expected that the development and release of public standards will be done in collaboration with an established standards development organization.

Embedding of Superelastic SMA Wires into Composite Structures: Evaluation of Impact Properties

NASA Astrophysics Data System (ADS)

Pappadà, Silvio; Rametta, Rocco; Toia, Luca; Coda, Alberto; Fumagalli, Luca; Maffezzoli, Alfonso

2009-08-01

Shape memory alloy (SMA) represents the most versatile way to realize smart materials with sensing, controlling, and actuating functions. Due to their unique mechanical and thermodynamic properties and to the possibility to obtain SMA wires with very small diameters, they are used as smart components embedded into the conventional resins or composites, obtaining active abilities, tunable properties, self-healing properties, and damping capacity. Moreover, superelastic SMAs are used to increase the impact resistance properties of composite materials. In this study, the influence of the integration of thin superelastic wires to suppress propagating damage of composite structures has been investigated. Superelastic SMAs have very high strain to failure and recoverable elastic strain, due to a stress-induced martensitic phase transition creating a plateau region in the stress-strain curve. NiTi superelastic wires ( A f = -15 °C fully annealed) of 0.10 mm in diameter have been produced and characterized by SAES Getters. The straight annealed wire shows the typical flag stress-strain behavior. The measured loading plateau is about 450 MPa at ambient temperature with a recoverable elastic strain of more than 6%. For these reasons superelastic SMA fibers can absorb much more strain energy than other fibers before their failure, partly with a constant stress level. In this paper, the improvement of composite laminates impact properties by embedding SMA wires is evaluated and indications for design and manufacturing of SMA composites with high-impact properties are also given.

Buckling of a circular plate made of a shape memory alloy due to a reverse thermoelastic martensite transformation

NASA Astrophysics Data System (ADS)

Movchan, A. A.; Sil'chenko, L. G.

2008-02-01

We solve the axisymmetric buckling problem for a circular plate made of a shape memory alloy undergoing reverse martensite transformation under the action of a compressing load, which occurs after the direct martensite transformation under the action of a generally different (extending or compressing) load. The problem was solved without any simplifying assumptions concerning the transverse dimension of the supplementary phase transition region related to buckling. The mathematical problem was reduced to a nonlinear eigenvalue problem. An algorithm for solving this problem was proposed. It was shown that the critical buckling load under the reverse transition, which is obtained by taking into account the evolution of the phase strains, can be many times lower than the same quantity obtained under the assumption that the material behavior is elastic even for the least (martensite) values of the elastic moduli. The critical buckling force decreases with increasing modulus of the load applied at the preliminary stage of direct transition and weakly depends on whether this load was extending or compressing. In shape memory alloys (SMA), mutually related processes of strain and direct (from the austenitic into the martensite phase) or reverse thermoelastic phase transitions may occur. The direct transition occurs under cooling and (or) an increase in stresses and is accompanied by a significant decrease (nearly by a factor of three in titan nickelide) of the Young modulus. If the direct transition occurs under the action of stresses with nonzero deviator, then it is accompanied by accumulation of macroscopic phase strains, whose intensity may reach 8%. Under the reverse transition, which occurs under heating and (or) unloading, the moduli increase and the accumulated strain is removed. For plates compressed in their plane, in the case of uniform temperature distribution over the thickness, one can separate trivial processes under which the strained plate remains plane and the phase ratio has a uniform distribution over the thickness. For sufficiently high compressing loads, the trivial process of uniform compression may become unstable in the sense that, for small perturbations of the plate deflection, temperature, the phase ratio, or the load, the difference between the corresponding perturbed process and the unperturbed process may be significant. The results of several experiments concerning the buckling of SMA elements are given in [1, 2], and the statement and solution of the corresponding boundary value problems can be found in [3-11]. The experimental studies [2] and several analytic solutions obtained for the Shanley column [3, 4], rods [5-7], rectangular plates under direct [8] and reverse [9] transitions showed that the processes of thermoelastic phase transitions can significantly (by several times) decrease the critical buckling loads compared with their elastic values calculated for the less rigid martensite state of the material. Moreover, buckling does not occur in the one-phase martensite state in which the elastic moduli are minimal but in the two-phase state in which the values of the volume fractions of the austenitic and martensite phase are approximately equal to each other. This fact is most astonishing for buckling, studied in the present paper, under the reverse transition in which the Young modulus increases approximately half as much from the beginning of the phase transition to the moment of buckling. In [3-9] and in the present paper, the static buckling criterion is used. Following this criterion, the critical load is defined to be the load such that a nontrivial solution of the corresponding quasistatic problem is possible under the action of this load. If, in the problems of stability of rods and SMA plates, small perturbations of the external load are added to small perturbations of the deflection (the critical force is independent of the amplitude of the latter), then the critical forces vary depending on the value of perturbations of the external load [5, 8, 9]. Thus, in the case of small perturbations of the load, the problem of stability of SMA elements becomes indeterminate. The solution of the stability problem for SMA elements also depends on whether the small perturbations of the phase ratio and the phase strain tensor are taken into account. According to this, the problem of stability of SMA elements can be solved in the framework of several statements (concepts, hypotheses) which differ in the set of quantities whose perturbations are admissible (taken into account) in the process of solving the problem. The variety of these statements applied to the problem of buckling of SMA elements under direct martensite transformation is briefly described in [4, 5]. But, in the problem of buckling under the reverse transformation, some of these statements must be changed. The main question which we should answer when solving the problem of stability of SMA elements is whether small perturbations of the phase ratio (the volume fraction of the martensite phase q) are taken into account, because an appropriate choice significantly varies the results of solving the stability problem. If, under the transition to the adjacent form of equilibrium, the phase ratio of all points of the body is assumed to remain the same, then we deal with the "fixed phase atio" concept. The opposite approach can be classified as the "supplementary phase transition" concept (which occurs under the transition to the adjacent form of equilibrium). It should be noted that, since SMA have temperature hysteresis, the phase ratio in SMA can endure only one-sided small variations. But if we deal with buckling under the inverse transformation, then the variation in the volume fraction of the martensite phase cannot be positive. The phase ratio is not an independent variable, like loads or temperature, but, due to the constitutive relations, its variations occur together with the temperature variations and, in the framework of connected models for a majority of SMA, together with variations in the actual stresses. Therefore, the presence or absence of variations in q is determined by the presence or absence of variations in the temperature, deflection, and load, as well as by the system of constitutive relations used in this particular problem. In the framework of unconnected models which do not take the influence of actual stresses on the phase ratio into account, the "fixed phase ratio" concept corresponds to the case of absence of temperature variations. The variations in the phase ratio may also be absent in connected models in the case of specially chosen values of variations in the temperature and (or) in the external load, as well as in the case of SMA of CuMn type, for which the influence of the actual stresses on the phase compound is absent or negligible. In the framework of the "fixed phase ratio" hypothesis, the stability problem for SMA elements has a solution coinciding in form with the solution of the corresponding elastic problem, with the elastic moduli replaced by the corresponding functions of the phase ratio. In the framework of the supplementary phase transition" concept, the result of solving the stability problem essentially depends on whether the small perturbations of the external loads are taken into account in the process of solving the problem. The point is that, when solving the problem in the connected setting, the supplementary phase transition region occupies, in general, not the entire cross-section of the plate but only part of it, and the location of the boundary of this region depends on the existence and the value of these small perturbations. More precisely, the existence of arbitrarily small perturbations of the actual load can result in finite changes of the configuration of the supplementary phase transition region and hence in finite change of the critical values of the load. Here we must distinguish the "fixed load" hypothesis where no perturbations of the external loads are admitted and the "variable load" hypothesis in the opposite case. The conditions that there no variations in the external loads imply additional equations for determining the boundary of the supplementary phase transition region. If the "supplementary phase transition" concept and the "fixed load" concept are used together, then the solution of the stability problem of SMA is uniquely determined in the same sense as the solution of the elastic stability problem under the static approach. In the framework of the "variable load" concept, the result of solving the stability problem for SMA ceases to be unique. But one can find the upper and lower bounds for the critical forces which correspond to the cases of total absence of the supplementary phase transition: the upper bound corresponds to the critical load coinciding with that determined in the framework of the "fixed phase ratio" concept, and the lower bound corresponds to the case where the entire cross-section of the plate experiences the supplementary phase transition. The first version does not need any additional name, and the second version can be called as the "all-round supplementary phase transition" hypothesis. In the present paper, the above concepts are illustrated by examples of solving problems about axisymmetric buckling of a circular freely supported or rigidly fixed plate experiencing reverse martensite transformation under the action of an external force uniformly distributed over the contour. We find analytic solutions in the framework of all the above-listed statements except for the case of free support in the "fixed load" concept, for which we obtain a numerical solution.

Coordinated Multiwavelength Observations of PKS 0528+134 in Quiescence

NASA Astrophysics Data System (ADS)

Boettcher, Markus; Palma, N.

2011-01-01

We report results of an intensive multiwavelength campaign on the prominent high-redshift (z = 2.06) gamma-ray bright blazar PKS 0528+134 in September - October 2009. The campaign was centered on four 30 ksec pointings with XMM-Newton, supplemented with ground-based optical (MDM, Perkins) and radio (UMRAO, Medicina, Metsaehovi, Noto, SMA) observations as well as long-term X-ray monitoring with RXTE and gamma-ray monitoring by Fermi. We find significant variability on 1 day time scales in the optical regime, accompanied by a weak redder-when-brighter trend. X-ray variability is found on longer ( 1 week) time scales, while the Fermi light curve shows no evidence for variability, neither in flux nor spectral index. We constructed four simultaneous spectral energy distributions, which can all be fit satisfactorily with a one-zone leptonic jet model. This work was supported by NASA through XMM-Newton Guest Observer Grant NNX09AV45G.

Shortening rate of the NW-Himalaya, across the Surin Mastgarh Anticline, Chenab Re-entrant, Jammu

NASA Astrophysics Data System (ADS)

Anilkumar, A.

2016-12-01

Within the foreland basin of NW Himalaya, a frontal fold, the Surin Mastgarh anticline, SMA extends continuously for about 180 km along strike, between River Beas in the east and River Munawartawi in the west. It extends for such a long distance without an emergent frontal thrust cutting the forelimb of SMA, depicting an unknown geometry with the underlying decollement. In the hinterland of the SMA the Medlicott-Wadia Thrust accommodates shortening at a rate of 11+3.8 mm/yr, Vassallo et al, 2015. Using the excess area method given by Hossack et al, Vassallo et al further estimated a 9+3.2mm/yr shortening rate for SMA in Reasi region. The sum of the total shortening rates between these active structures (Vassallo et al., 2015) however, exceeds the 16-mm/yr convergence rates reported by geodetic studies within Kashmir Himalaya (Schiffman et al, 2013; Kundu et al, 2014). Another parallel study by Gavillot et al, 2016) documents a 4-6 mm/year shortening interpreted from restored cross section taken across the SMA along River Chenab. Since, a discrepancy exits in the previously documented shortening rates for the SMA; we have utilized the morphology of the terraces of Chenab to estimate shortening within the SMA. We surveyed the terraces in the valley using Real Time Kinematic GPS for obtaining topographic profiles. The strath terraces were sampled for dating by Optically Stimulated Luminescence technique. The morphology of the terraces suggests that they are progressively folded and uplifted above the present course of River Chenab. We adapted the method given by Rockwell et al 2008. In this method the anticline is considered obeying a Sine function. The arc-length of the limb, L can be evaluated from two parameters; the horizontal distance of the limb-D and slope of curve at point of inflection point-θ. By using arc line method shortening amount of 124.85m is inferred. Consequently a geological shortening rate of 6.57+1.39 mm/yr is estimated for the SMA using abandonment ages of the terrace. This value falls well within the 16 mm/year convergence rate of Kashmir Himalaya and suggests that 30-40 % of this convergence is taken for shortening within the SMA. This anticline extends in the seismic gap of 1905 Kangra and 2005 Kashmir earthquakes, it holds a significant potential for hazard in a populated region of Jammu and Punjab.

Cognitive and neural foundations of discrete sequence skill: a TMS study.

PubMed

Ruitenberg, Marit F L; Verwey, Willem B; Schutter, Dennis J L G; Abrahamse, Elger L

2014-04-01

Executing discrete movement sequences typically involves a shift with practice from a relatively slow, stimulus-based mode to a fast mode in which performance is based on retrieving and executing entire motor chunks. The dual processor model explains the performance of (skilled) discrete key-press sequences in terms of an interplay between a cognitive processor and a motor system. In the present study, we tested and confirmed the core assumptions of this model at the behavioral level. In addition, we explored the involvement of the pre-supplementary motor area (pre-SMA) in discrete sequence skill by applying inhibitory 20 min 1-Hz off-line repetitive transcranial magnetic stimulation (rTMS). Based on previous work, we predicted pre-SMA involvement in the selection/initiation of motor chunks, and this was confirmed by our results. The pre-SMA was further observed to be more involved in more complex than in simpler sequences, while no evidence was found for pre-SMA involvement in direct stimulus-response translations or associative learning processes. In conclusion, support is provided for the dual processor model, and for pre-SMA involvement in the initiation of motor chunks. Copyright © 2014 Elsevier Ltd. All rights reserved.

Orbital atherectomy as an adjunct to debulk difficult calcified lesions prior to mesenteric artery stenting.

PubMed

Manunga, Jesse M; Oderich, Gustavo S

2012-08-01

To describe a technique in which percutaneous orbital atherectomy is used to debulk heavily calcified superior mesenteric artery (SMA) occlusions as an adjunct in patients undergoing angioplasty and stenting. The technique is demonstrated in a 62-year-old woman with a replaced right hepatic artery originating from an SMA occluded by densely calcified lesions. Via a left transbrachial approach, a 7-F MPA guide catheter was used to engage the ostium of the SMA, which was crossed using a catheter and guidewire. The calcified lesion was debulked using the 2-mm Diamondback 360° orbital atherectomy system. The wire was exchanged for a 0.014-inch filter wire and 0.018-inch guidewire. Using a 2-guidewire technique, the SMA was stented with a self-expanding stent for the distal lesion that crossed side branches and a balloon-expandable stent at the ostium. A 0.014-inch guidewire was placed into the replaced hepatic artery through a cell of the self-expanding stent, followed by deployment of a small balloon-expandable stent to address the residual lesion. The use of orbital atherectomy to debulk occluded and heavily calcified SMA lesions may optimize the technical results with angioplasty and stenting.

Exploiting NiTi shape memory alloy films in design of tunable high frequency microcantilever resonators

NASA Astrophysics Data System (ADS)

Stachiv, I.; Sittner, P.; Olejnicek, J.; Landa, M.; Heller, L.

2017-11-01

Shape memory alloy (SMA) films are very attractive materials for microactuators because of their high energy density. However, all currently developed SMA actuators utilize martensitic transformation activated by periodically generated heating and cooling; therefore, they have a slow actuation speed, just a few Hz, which restricts their use in most of the nanotechnology applications such as high frequency microcantilever based physical and chemical sensors, atomic force microscopes, or RF filters. Here, we design tunable high frequency SMA microcantilevers for nanotechnology applications. They consist of a phase transforming NiTi SMA film sputtered on the common elastic substrate material; in our case, it is a single-crystal silicon. The reversible tuning of microcantilever resonant frequencies is then realized by intentionally changing the Young's modulus and the interlayer stress of the NiTi film by temperature, while the elastic substrate guarantees the high frequency actuation (up to hundreds of kHz) of the microcantilever. The experimental results qualitatively agree with predictions obtained from the dedicated model based on the continuum mechanics theory and a phase characteristic of NiTi. The present design of SMA microcantilevers expands the capability of current micro-/nanomechanical resonators by enabling tunability of several consecutive resonant frequencies.

Selection and stopping in voluntary action: A meta-analysis and combined fMRI study☆

PubMed Central

Rae, Charlotte L.; Hughes, Laura E.; Weaver, Chelan; Anderson, Michael C.; Rowe, James B.

2014-01-01

Voluntary action control requires selection of appropriate responses and stopping of inappropriate responses. Selection and stopping are often investigated separately, but they appear to recruit similar brain regions, including the pre-supplementary motor area (preSMA) and inferior frontal gyrus. We therefore examined the evidence for overlap of selection and stopping using two approaches: a meta-analysis of existing studies of selection and stopping, and a novel within-subject fMRI study in which action selection and a stop signal task were combined factorially. The novel fMRI study also permitted us to investigate hypotheses regarding a common mechanism for selection and stopping. The preSMA was identified by both methods as common to selection and stopping. However, stopping a selected action did not recruit preSMA more than stopping a specified action, nor did stop signal reaction times differ significantly across the two conditions. These findings suggest that the preSMA supports both action selection and stopping, but the two processes may not require access to a common inhibition mechanism. Instead, the preSMA might represent information about potential actions that is used in both action selection and stopping in order to resolve conflict between competing available responses. PMID:24128740

Fabricating Composite-Material Structures Containing SMA Ribbons

NASA Technical Reports Server (NTRS)

Turner, Travis L.; Cano, Roberto J.; Lach, Cynthia L.

2003-01-01

An improved method of designing and fabricating laminated composite-material (matrix/fiber) structures containing embedded shape-memory-alloy (SMA) actuators has been devised. Structures made by this method have repeatable, predictable properties, and fabrication processes can readily be automated. Such structures, denoted as shape-memory-alloy hybrid composite (SMAHC) structures, have been investigated for their potential to satisfy requirements to control the shapes or thermoelastic responses of themselves or of other structures into which they might be incorporated, or to control noise and vibrations. Much of the prior work on SMAHC structures has involved the use SMA wires embedded within matrices or within sleeves through parent structures. The disadvantages of using SMA wires as the embedded actuators include (1) complexity of fabrication procedures because of the relatively large numbers of actuators usually needed; (2) sensitivity to actuator/ matrix interface flaws because voids can be of significant size, relative to wires; (3) relatively high rates of breakage of actuators during curing of matrix materials because of sensitivity to stress concentrations at mechanical restraints; and (4) difficulty of achieving desirable overall volume fractions of SMA wires when trying to optimize the integration of the wires by placing them in selected layers only.

The supplementary motor area in motor and perceptual time processing: fMRI studies.

PubMed

Macar, Françoise; Coull, Jennifer; Vidal, Franck

2006-06-01

The neural bases of timing mechanisms in the second-to-minute range are currently investigated using multidisciplinary approaches. This paper documents the involvement of the supplementary motor area (SMA) in the encoding of target durations by reporting convergent fMRI data from motor and perceptual timing tasks. Event-related fMRI was used in two temporal procedures, involving (1) the production of an accurate interval as compared to an accurate force, and (2) a dual-task of time and colour discrimination with parametric manipulation of the level of attention attributed to each parameter. The first study revealed greater activation of the SMA proper in skilful control of time compared to force. The second showed that increasing attentional allocation to time increased activity in a cortico-striatal network including the pre-SMA (in contrast with the occipital cortex for increasing attention to colour). Further, the SMA proper was sensitive to the attentional modulation cued prior to the time processing period. Taken together, these data and related literature suggest that the SMA plays a key role in time processing as part of the striato-cortical pathway previously identified by animal studies, human neuropsychology and neuroimaging.

Theta burst magnetic stimulation over the pre-supplementary motor area improves motor inhibition.

PubMed

Obeso, Ignacio; Wilkinson, Leonora; Teo, James T; Talelli, Penelope; Rothwell, John C; Jahanshahi, Marjan

Stopping an ongoing motor response or resolving conflict induced by conflicting stimuli are associated with activation of a right-lateralized network of inferior frontal gyrus (IFG), pre-supplementary motor area (pre-SMA) and subthalamic nucleus (STN). However, the roles of the right IFG and pre-SMA in stopping a movement and in conflict resolution remain unclear. We used continuous theta burst stimulation (cTBS) to examine the involvement of the right IFG and pre-SMA in inhibition and conflict resolution using the conditional stop signal task. We measured stop signal reaction time (SSRT, measure of reactive inhibition), response delay effect (RDE, measure of proactive action restraint) and conflict induced slowing (CIS, measure of conflict resolution). Stimulation over the pre-SMA resulted in significantly shorter SSRTs (improved inhibition) compared to sham cTBS. This effect was not observed for CIS, RDE, or any other measures. cTBS over the right IFG had no effect on SSRT, CIS, RDE or on any other measure. The improvement of SSRT with cTBS over the pre-SMA suggests its critical contribution to stopping ongoing movements. Copyright © 2017 Elsevier Inc. All rights reserved.

Fabrication of TiNi/CFRP smart composite using cold drawn TiNi wires

NASA Astrophysics Data System (ADS)

Xu, Ya; Otsuka, Kazuhiro; Toyama, Nobuyuki; Yoshida, Hitoshi; Jang, Byung-Koog; Nagai, Hideki; Oishi, Ryutaro; Kishi, Teruo

2002-07-01

In recent years, pre-strained TiNi shape memory alloys (SMA) have been used for fabricating smart structure with carbon fibers reinforced plastics (CFRP) in order to suppress microscopic mechanical damages. However, since the cure temperature of CFRP is higher than the reverse transformation temperatures of TiNi SMA, special fixture jigs have to be used for keeping the pre-strain during fabrication, which restricted its practical application. In order to overcome this difficulty, we developed a new method to fabricate SMA/CFRP smart composites without using special fixture jigs by controlling the transformation temperatures of SMA during fabrication. This method consists of using heavily cold-worked wires to increase the reverse transformation temperatures, and of using flash electrical heating of the wires after fabrication in order to decrease the reverse transformation temperatures to a lower temperature range again without damaging the epoxy resin around SMA wires. By choosing proper cold-working rate and composition of TiNi alloys, the reverse transformation temperatures were well controlled, and the TiNi/CFRP hybrid smart composite was fabricated without using special fixture jigs. The damage suppressing effect of cold drawn wires embedded in CFRP was confirmed.

Shape memory alloy wires turn composites into smart structures: II. Manufacturing and properties

NASA Astrophysics Data System (ADS)

Michaud, Veronique J.; Schrooten, Jan; Parlinska, Magdelena; Gotthardt, Rolf; Bidaux, Jacques-Eric

2002-07-01

The manufacturing route and resulting properties of adaptive composites are presented in the second part of this European project report. Manufacturing was performed using a specially designed frame to pre-strain the SMA wires, embed them into Kevlar-epoxy prepregs, and maintain them during the curing process in an autoclave. Composite compounds were then tested for strain response, recovery stress response in a clamped-clamped configuration, as well as vibrational response. Through the understanding of the transformational behavior of constrained SMA wires, interesting and unique functional properties of SMA composites could be measured, explained and modeled. Large recovery stresses and as a consequence, a change in vibrational response in a clamped- clamped condition, or a reversible shape change in a free standing condition, could be generated by the SMA composites in a controllable way. These properties were dependent on composite design aspects and exhibited a reproducible and stable behavior, provided that the properties of the matrix, of the wires and the processing route were carefully optimized. In conclusion, the achievements of this effort in areas such as thermomechanics, transformational and vibrational behavior and durability of SMA based composites provide a first step towards a reliable materials design, and potentially an industrial application.

Overview of engineering activities at the SMA

NASA Astrophysics Data System (ADS)

Christensen, R. D.; Kubo, D. Y.; Rao, Ramprasad

2008-07-01

The Submillmeter Array (SMA) consists of 8 6-meter telescopes on the summit of Mauna Kea. The array has been designed to operate from the summit of Mauna Kea and from 3 remote facilities: Hilo, Hawaii, Cambridge, Massachusetts and Taipei, Taiwan. The SMA provides high-resolution scientific observations in most of the major atmospheric windows from 180 to 700 GHz. Each telescope can house up to 8 receivers in a single cryostat and can operate with one or two receiver bands simultaneously. The array being a fully operational observatory, the demand for science time is extremely high. As a result specific time frames have been set-aside during both the day and night for engineering activities. This ensures that the proper amount of time can be spent on maintaining existing equipment or upgrading the system to provide high quality scientific output during nighttime observations. This paper describes the methods employed at the SMA to optimize engineering development of the telescopes and systems such that the time available for scientific observations is not compromised. It will also examine some of the tools used to monitor the SMA during engineering and science observations both at the site and remote facilities.

[Observation on alpha-SMA during Erigeron Breviscapus (Vant) Hand-Mazz obstructs the evolution of carcinogenesis of golden hamster cheek pouch].

PubMed

Zhou, C T; Zhang, S L; Ding, R Y; Hua, L; Zhong, W J

2000-06-01

To observe dynamically that Erigeron Breviscapus (Vant) Hand-Mazz (HEr) affects the expression of alpha-smooth muscle actin (alpha-SMA). To discuss the probable mechanism of obstructing leukoplakia carcinogenesis of this medicine. 120 golden hamsters were randomly divided into model group (48), HEr group (48) and control group (6). HEr was applied to obstruct the evolution of carcinogenesis of golden hamster cheek pouch. Immunohistochemistry was used to detect the expression level of alpha-SMA with cheek pouch specimen that besmears DMBA in 4-9 weeks. Results were compared with model group. Vessel density dyed with alpha-SMA continuously of HEr group was 65.76 significantly higher than that of model group 42.12 (P<0.001). High classification cases in HEr group were much more than model group when cases were divided into five groups as follow: 100%, 50%, 20%, 10%, 3% (P<0.01). HEr can raise the expression level of alpha-SMA exactly during the evolution of leukoplakia carcinogenesis of golden hamster, which shows that this medicine obstructs carcinogenesis by keeping the normal physiological function of vascular myoepithelial cell and integrity of vascular basement membrane.

Spinal muscular atrophy type II (intermediary) and III (Kugelberg-Welander). Evolution of 50 patients with physiotherapy and hydrotherapy in a swimming pool.

PubMed

Cunha, M C; Oliveira, A S; Labronici, R H; Gabbai, A A

1996-09-01

We added hydrotherapy to 50 patients with spinal muscular atrophy (SMA) who were being treated with individual conventional physiotherapy. Hydrotherapy performed at an approximate temperature of 30 degrees Celsius, twice a week, for thirty minutes in children and forty-five minutes in adults during a 2-year period. The outcome derived from this combined modality of treatment was rated according to physiotherapeutic evaluations, the MMT (Manual Muscular Test), and the Barthel Ladder. Patients were reevaluated at 2-month intervals. After two years of ongoing treatment, we were able to observe that the deformities in hip, knee and foot were progressive in all SMA Type II patients, and in some Type III. Muscle strength stabilized in most SMA Type III patients, and improved in some. MMT was not done in SMA Type II. In all patients we were able to detect an improvement in the Barthel Ladder scale. This study suggests that a measurable improvement in the quality of daily living may be obtained in patients with SMA Types II and III subjected to conventional physiotherapy when associated with hydrotherapy.

Control of Thermal Deflection, Panel Flutter and Acoustic Fatigue at Elevated Temperatures Using Shape Memory Alloys

NASA Technical Reports Server (NTRS)

Mei, Chuh; Huang, Jen-Kuang

1996-01-01

The High Speed Civil Transport (HSCT) will have to be designed to withstand high aerodynamic load at supersonic speeds (panel flutter) and high acoustic load (acoustic or sonic fatigue) due to fluctuating boundary layer or jet engine acoustic pressure. The thermal deflection of the skin panels will also alter the vehicle's configuration, thus it may affect the aerodynamic characteristics of the vehicle and lead to poor performance. Shape memory alloys (SMA) have an unique ability to recover large strains completely when the alloy is heated above the characteristic transformation (austenite finish T(sub f)) temperature. The recovery stress and elastic modulus are both temperature dependent, and the recovery stress also depends on the initial strain. An innovative concept is to utilize the recovery stress by embedding the initially strained SMA wire in a graphite/epoxy composite laminated panel. The SMA wires are thus restrained and large inplane forces are induced in the panel at elevated temeperatures. By embedding SMA in composite panel, the panel becomes much stiffer at elevated temperatures. That is because the large tensile inplane forces induced in the panel from the SMA recovery stress. A stiffer panel would certainly yield smaller dynamic responses.

A Mutation in the Vesicle-Trafficking Protein VAPB Causes Late-Onset Spinal Muscular Atrophy and Amyotrophic Lateral Sclerosis

PubMed Central

Nishimura, Agnes L.; Mitne-Neto, Miguel; Silva, Helga C. A.; Richieri-Costa, Antônio; Middleton, Susan; Cascio, Duilio; Kok, Fernando; Oliveira, João R. M.; Gillingwater, Tom; Webb, Jeanette; Skehel, Paul; Zatz, Mayana

2004-01-01

Motor neuron diseases (MNDs) are a group of neurodegenerative disorders with involvement of upper and/or lower motor neurons, such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), progressive bulbar palsy, and primary lateral sclerosis. Recently, we have mapped a new locus for an atypical form of ALS/MND (atypical amyotrophic lateral sclerosis [ALS8]) at 20q13.3 in a large white Brazilian family. Here, we report the finding of a novel missense mutation in the vesicle-associated membrane protein/synaptobrevin-associated membrane protein B (VAPB) gene in patients from this family. Subsequently, the same mutation was identified in patients from six additional kindreds but with different clinical courses, such as ALS8, late-onset SMA, and typical severe ALS with rapid progression. Although it was not possible to link all these families, haplotype analysis suggests a founder effect. Members of the vesicle-associated proteins are intracellular membrane proteins that can associate with microtubules and that have been shown to have a function in membrane transport. These data suggest that clinically variable MNDs may be caused by a dysfunction in intracellular membrane trafficking. PMID:15372378

Measuring cortical motor hemodynamics during assisted stepping - An fNIRS feasibility study of using a walker.

PubMed

de Lima-Pardini, Andrea Cristina; Zimeo Morais, Guilherme A; Balardin, Joana Bisol; Coelho, Daniel Boari; Azzi, Nametala Maia; Teixeira, Luis Augusto; Sato, João Ricardo

2017-07-01

Walkers are commonly prescribed worldwide to individuals unable to walk independently. Walker usage leads to improved postural control and voluntary movement during step. In the present study, we aimed to provide a concept-proof on the feasibility of an event-related protocol integrating the analyses of biomechanical variables of step initiation and functional near-infrared spectroscopy (fNIRS) to measure activation of the supplementary motor area (SMA) while using a walker. Healthy young participants were tested while stepping with versus without the use of the walker. Behavioral analysis showed that anticipatory postural adjustments (APA) decreased when supporting the body weight on the walker. Delta (without-with) of activation magnitude of the muscle tibialis anterior was positively correlated to the delta of deoxyhemoglobin concentration changes in the SMA. The novelty of this study is the development of a protocol to assess brain function together with biomechanical analysis during the use of a walker. The method sheds light to the potential utility of combining fNIRS and biomechanical assessment during assistive step initiation, which can represent a new opportunity to study populations with mobility deficits. Copyright © 2017 Elsevier B.V. All rights reserved.

Power systems and requirements for the integration of smart structures into aircraft

NASA Astrophysics Data System (ADS)

Lockyer, Allen J.; Martin, Christopher A.; Lindner, Douglas K.; Walia, Paramjit S.

2002-07-01

Electrical power distribution for recently developed smart actuators becomes an important air-vehicle challenge if projected smart actuation benefits are to be met. Among the items under development are variable shape inlets and control surfaces that utilize shape memory alloys (SMA); full span, chord-wise and span-wise contouring trailing control surfaces that use SMA or piezoelectric materials for actuation; and other strain-based actuators for buffet load alleviation, flutter suppression and flow control. At first glance, such technologies afford overall vehicle performance improvement, however, integration system impacts have yet to be determined or quantified. Power systems to support smart structures initiatives are the focus of the current paper. The paper has been organized into five main topics for further discussion: (1) air-vehicle power system architectures - standard and advanced distribution concepts for actuators, (2) smart wing actuator power requirements and results - highlighting wind tunnel power measurements from shape memory alloy and piezoelectric ultrasonic motor actuated control surfaces and different dynamic pressure and angle of attack; (3) vehicle electromagnetic effects (EME) issues, (4) power supply design considerations for smart actuators - featuring the aircraft power and actuator interface, and (5) summary and conclusions.

Network Modeling for Functional Magnetic Resonance Imaging (fMRI) Signals during Ultra-Fast Speech Comprehension in Late-Blind Listeners

PubMed Central

Dietrich, Susanne; Hertrich, Ingo; Ackermann, Hermann

2015-01-01

In many functional magnetic resonance imaging (fMRI) studies blind humans were found to show cross-modal reorganization engaging the visual system in non-visual tasks. For example, blind people can manage to understand (synthetic) spoken language at very high speaking rates up to ca. 20 syllables/s (syl/s). FMRI data showed that hemodynamic activation within right-hemispheric primary visual cortex (V1), bilateral pulvinar (Pv), and left-hemispheric supplementary motor area (pre-SMA) covaried with their capability of ultra-fast speech (16 syllables/s) comprehension. It has been suggested that right V1 plays an important role with respect to the perception of ultra-fast speech features, particularly the detection of syllable onsets. Furthermore, left pre-SMA seems to be an interface between these syllabic representations and the frontal speech processing and working memory network. So far, little is known about the networks linking V1 to Pv, auditory cortex (A1), and (mesio-) frontal areas. Dynamic causal modeling (DCM) was applied to investigate (i) the input structure from A1 and Pv toward right V1 and (ii) output from right V1 and A1 to left pre-SMA. As concerns the input Pv was significantly connected to V1, in addition to A1, in blind participants, but not in sighted controls. Regarding the output V1 was significantly connected to pre-SMA in blind individuals, and the strength of V1-SMA connectivity correlated with the performance of ultra-fast speech comprehension. By contrast, in sighted controls, not understanding ultra-fast speech, pre-SMA did neither receive input from A1 nor V1. Taken together, right V1 might facilitate the “parsing” of the ultra-fast speech stream in blind subjects by receiving subcortical auditory input via the Pv (= secondary visual pathway) and transmitting this information toward contralateral pre-SMA. PMID:26148062

Candidate Proteins, Metabolites and Transcripts in the Biomarkers for Spinal Muscular Atrophy (BforSMA) Clinical Study

PubMed Central

Finkel, Richard S.; Crawford, Thomas O.; Swoboda, Kathryn J.; Kaufmann, Petra; Juhasz, Peter; Li, Xiaohong; Guo, Yu; Li, Rebecca H.; Trachtenberg, Felicia; Forrest, Suzanne J.; Kobayashi, Dione T.; Chen, Karen S.; Joyce, Cynthia L.; Plasterer, Thomas

2012-01-01

Background Spinal Muscular Atrophy (SMA) is a neurodegenerative motor neuron disorder resulting from a homozygous mutation of the survival of motor neuron 1 (SMN1) gene. The gene product, SMN protein, functions in RNA biosynthesis in all tissues. In humans, a nearly identical gene, SMN2, rescues an otherwise lethal phenotype by producing a small amount of full-length SMN protein. SMN2 copy number inversely correlates with disease severity. Identifying other novel biomarkers could inform clinical trial design and identify novel therapeutic targets. Objective: To identify novel candidate biomarkers associated with disease severity in SMA using unbiased proteomic, metabolomic and transcriptomic approaches. Materials and Methods: A cross-sectional single evaluation was performed in 108 children with genetically confirmed SMA, aged 2–12 years, manifesting a broad range of disease severity and selected to distinguish factors associated with SMA type and present functional ability independent of age. Blood and urine specimens from these and 22 age-matched healthy controls were interrogated using proteomic, metabolomic and transcriptomic discovery platforms. Analyte associations were evaluated against a primary measure of disease severity, the Modified Hammersmith Functional Motor Scale (MHFMS) and to a number of secondary clinical measures. Results A total of 200 candidate biomarkers correlate with MHFMS scores: 97 plasma proteins, 59 plasma metabolites (9 amino acids, 10 free fatty acids, 12 lipids and 28 GC/MS metabolites) and 44 urine metabolites. No transcripts correlated with MHFMS. Discussion In this cross-sectional study, “BforSMA” (Biomarkers for SMA), candidate protein and metabolite markers were identified. No transcript biomarker candidates were identified. Additional mining of this rich dataset may yield important insights into relevant SMA-related pathophysiology and biological network associations. Additional prospective studies are needed to confirm these findings, demonstrate sensitivity to change with disease progression, and assess potential impact on clinical trial design. Trial Registry Clinicaltrials.gov NCT00756821. PMID:22558154

A Novel Morpholino Oligomer Targeting ISS-N1 Improves Rescue of Severe Spinal Muscular Atrophy Transgenic Mice

PubMed Central

Janghra, Narinder; Mitrpant, Chalermchai; Dickinson, Rachel L.; Anthony, Karen; Price, Loren; Eperon, Ian C.; Wilton, Stephen D.; Morgan, Jennifer

2013-01-01

Abstract In the search for the most efficacious antisense oligonucleotides (AOs) aimed at inducing SMN2 exon 7 inclusion, we systematically assessed three AOs, PMO25 (−10, −34), PMO18 (−10, −27), and PMO20 (−10, −29), complementary to the SMN2 intron 7 splicing silencer (ISS-N1). PMO25 was the most efficacious in augmenting exon 7 inclusion in vitro in spinal muscular atrophy (SMA) patient fibroblasts and in vitro splicing assays. PMO25 and PMO18 were compared further in a mouse model of severe SMA. After a single intracerebroventricular (ICV) injection in neonatal mice, PMO25 increased the life span of severe SMA mice up to 30-fold, with average survival greater by 3-fold compared with PMO18 at a dose of 20 μg/g and 2-fold at 40 μg/g. Exon 7 inclusion was increased in the CNS but not in peripheral tissues. Systemic delivery of PMO25 at birth achieved a similar outcome and produced increased exon 7 inclusion both in the CNS and peripherally. Systemic administration of a 10-μg/g concentration of PMO25 conjugated to an octaguanidine dendrimer (VMO25) increased the life span only 2-fold in neonatal type I SMA mice, although it prevented tail necrosis in mild SMA mice. Higher doses and ICV injection of VMO25 were associated with toxicity. We conclude that (1) the 25-mer AO is more efficient than the 18-mer and 20-mer in modifying SMN2 splicing in vitro; (2) it is more efficient in prolonging survival in SMA mice; and (3) naked Morpholino oligomers are more efficient and safer than the Vivo-Morpholino and have potential for future SMA clinical applications. PMID:23339722

Haplotype of non-synonymous mutations within IL-23R is associated with susceptibility to severe malaria anemia in a P. falciparum holoendemic transmission area of Kenya.

PubMed

Munde, Elly O; Raballah, Evans; Okeyo, Winnie A; Ong'echa, John M; Perkins, Douglas J; Ouma, Collins

2017-04-20

Improved understanding of the molecular mechanisms involved in pediatric severe malarial anemia (SMA) pathogenesis is a crucial step in the design of novel therapeutics. Identification of host genetic susceptibility factors in immune regulatory genes offers an important tool for deciphering malaria pathogenesis. The IL-23/IL-17 immune pathway is important for both immunity and erythropoiesis via its effects through IL-23 receptors (IL-23R). However, the impact of IL-23R variants on SMA has not been fully elucidated. Since variation within the coding region of IL-23R may influence the pathogenesis of SMA, the association between IL-23R rs1884444 (G/T), rs7530511 (C/T), and SMA (Hb < 6.0 g/dL) was examined in children (n = 369, aged 6-36 months) with P. falciparum malaria in a holoendemic P. falciparum transmission area. Logistic regression analysis, controlling for confounding factor of anemia, revealed that individual genotypes of IL-23R rs1884444 (G/T) [GT; OR = 1.34, 95% CI = 0.78-2.31, P = 0.304 and TT; OR = 2.02, 95% CI = 0.53-7.74, P = 0.286] and IL-23R rs7530511 (C/T) [CT; OR = 2.6, 95% CI = 0.59-11.86, P = 0.202 and TT; OR = 1.66, 95% CI = 0.84-3.27, P = 0.142] were not associated with susceptibility to SMA. However, carriage of IL-23R rs1884444T/rs7530511T (TT) haplotype, consisting of both mutant alleles, was associated with increased susceptibility to SMA (OR = 1.12, 95% CI = 1.07-4.19, P = 0.030). Results presented here demonstrate that a haplotype of non-synonymous IL-23R variants increase susceptibility to SMA in children of a holoendemic P. falciparum transmission area.

Bereitschaftspotential as an indicator of movement preparation in supplementary motor area and motor cortex.

PubMed

Deecke, L

1987-01-01

Topographical studies in humans of the Bereitschaftspotential (BP, or readiness potential, as averaged from the electroencephalogram) and the Bereitschaftsmagnetfeld (BM, or readiness magnetic field, as averaged from the magnetoencephalogram) revealed a widespread distribution of motor preparation over both hemispheres even before unilateral movement. This indicates the existence of several generators responsible for the BP, including generators in the ipsilateral hemisphere, which is in agreement with measurements of regional cerebral blood flow or regional cerebral energy metabolism. Nevertheless, two principal generators seem to prevail: (1) An early generator, starting its activity 1s or more before the motor act, with its maximum at the vertex. For this and other reasons, early BP generation probably stems from cortical tissue representing or including the supplementary motor area (SMA). (2) A later generator, starting its activity about 0.5s before the onset of movement and biased towards the contralateral hemisphere (contralateral preponderance of negativity, CPN). For unilateral finger movements the CPN succeeds the BP's initial bilateral symmetry in the later preparation period. Thus, this lateralized BP component probably stems from the primary motor area, MI (area 4, hand representation). While regional cerebral blood flow or regional cerebral energy metabolism show that the SMA is active in conjunction with motor acts, these data do not permit the conclusion that SMA activity precedes motor acts. This can only be shown by the Bereitschaftspotential, which proves that SMA activity occurs before the onset of movement and, what is more, before the onset of MI activity. This important order of events (first SMA, then MI activation) has been elucidated by our BP studies. It gives the SMA an important functional role: the initiation of voluntary movement. The recording of movement-related potentials associated with manual hand-tracking and motor learning points to the SMA and frontal cortex having an important role in these functions.

Network Modeling for Functional Magnetic Resonance Imaging (fMRI) Signals during Ultra-Fast Speech Comprehension in Late-Blind Listeners.

PubMed

Dietrich, Susanne; Hertrich, Ingo; Ackermann, Hermann

2015-01-01

In many functional magnetic resonance imaging (fMRI) studies blind humans were found to show cross-modal reorganization engaging the visual system in non-visual tasks. For example, blind people can manage to understand (synthetic) spoken language at very high speaking rates up to ca. 20 syllables/s (syl/s). FMRI data showed that hemodynamic activation within right-hemispheric primary visual cortex (V1), bilateral pulvinar (Pv), and left-hemispheric supplementary motor area (pre-SMA) covaried with their capability of ultra-fast speech (16 syllables/s) comprehension. It has been suggested that right V1 plays an important role with respect to the perception of ultra-fast speech features, particularly the detection of syllable onsets. Furthermore, left pre-SMA seems to be an interface between these syllabic representations and the frontal speech processing and working memory network. So far, little is known about the networks linking V1 to Pv, auditory cortex (A1), and (mesio-) frontal areas. Dynamic causal modeling (DCM) was applied to investigate (i) the input structure from A1 and Pv toward right V1 and (ii) output from right V1 and A1 to left pre-SMA. As concerns the input Pv was significantly connected to V1, in addition to A1, in blind participants, but not in sighted controls. Regarding the output V1 was significantly connected to pre-SMA in blind individuals, and the strength of V1-SMA connectivity correlated with the performance of ultra-fast speech comprehension. By contrast, in sighted controls, not understanding ultra-fast speech, pre-SMA did neither receive input from A1 nor V1. Taken together, right V1 might facilitate the "parsing" of the ultra-fast speech stream in blind subjects by receiving subcortical auditory input via the Pv (= secondary visual pathway) and transmitting this information toward contralateral pre-SMA.

Laparoscopic pancreatoduodenectomy with superior mesenteric artery-first approach and pancreatogastrostomy assisted by mini-laparotomy.

PubMed

Zimmitti, Giuseppe; Manzoni, Alberto; Addeo, Pietro; Garatti, Marco; Zaniboni, Alberto; Bachellier, Philippe; Rosso, Edoardo

2016-04-01

Laparoscopic pancreatoduodenectomy (LPD) is a complex procedure. Critical steps are achieving a negative retroperitoneal margin and re-establishing pancreatoenteric continuity minimizing postoperative pancreatic leak risk. Aiming at increasing the rate of R0 resection during pancreatoduodenectomy, many experienced teams have recommended the superior mesenteric artery (SMA)-first approach, consisting in early identification of the SMA at its origin, with further resection guided by SMA anatomic course. We describe our technique of LPD with SMA-first approach and pancreatogastrostomy assisted by mini-laparotomy. The video concerns a 77-year-old man undergoing our variant of LPD for a 2.5-cm pancreatic head mass. After kocherization, the SMA is identified above the left renocaval confluence and dissected-free from the surrounding tissue. Dissection of the posterior pancreatic aspect exposes the confluence between splenic vein, superior mesenteric vein (SMV), and portal vein. Following duodenal section, the common hepatic artery is dissected and the gastroduodenal artery sectioned at the origin. The first jejunal loop is divided, skeletonized, and passed behind the superior mesenteric vessel. Following pancreatic transection, the uncinate process is dissected from the SMV and the SMA is cleared from retroportal tissue rejoining the previously dissected plain. Laparoscopic choledocojejunostomy is followed by a mini-laparotomy-assisted pancreatogastrostomy, performed as previously described, and a terminolateral gastrojejeunostomy. Twelve patients underwent our variant of LPD (July 2013-May 2015). Female/male ratio was 3:1, median age 65 years (range 57-79), median operation duration 590 min (580-690), intraoperative blood loss 150 cl (100-250). R0 resection rate was 100 %, and the median number of resected lymph nodes was 24 (22-28). Postoperative complications were grade II in two patients and IIIa in one. Median postoperative length of stay was 16 days (14-21). LPD with SMA-first approach with pancreatogastrostomy assisted by a mini-laparotomy well combines the benefits of laparoscopy with low risk of postoperative complications and high rate of curative resection.

Types of SMA (Spinal Muscular Atrophy)

MedlinePlus

... Funding Opportunities Research Conference Recruit for Clinical Trials Research Publications Spinraza Support & Care For Newly Diagnosed Care Packages Information Packets Equipment Pool Living With SMA Medical Issues Palliative Breathing Orthopedics Nutrition Equipment Daily Life At School At Home ...

Calcium phosphate coating of nickel-titanium shape-memory alloys. Coating procedure and adherence of leukocytes and platelets.

PubMed

Choi, Jongsik; Bogdanski, Denise; Köller, Manfred; Esenwein, Stefan A; Müller, Dietmar; Muhr, Gert; Epple, Matthias

2003-09-01

Nickel-titanium shape-memory alloys (NiTi-SMA) were coated with calcium phosphate by dipping in oversaturated calcium phosphate solution. The layer thickness (typically 5-20 micrometer) can be varied by choice of the immersion time. The porous nature of the layer of microcrystals makes it mechanically stable enough to withstand both the shape-memory transition upon cooling and heating and also strong bending of the material (superelastic effect). This layer may improve the biocompatibility of NiTi-SMA, particulary for osteosynthetic devices by creating a more physiological surface and by restricting a potential nickel release. The adherence of human leukocytes (peripheral blood mononuclear cells and polymorphonuclear neutrophil granulocytes) and platelets to the calcium phosphate layer was analyzed in vitro. In comparison to non-coated NiTi-SMA, leukocytes and platelets showed a significantly increased adhesion to the coated NiTi-SMA.

Successful Use of Orbital Atherectomy as an Adjunct in Treating Extensively Calcified Mesenteric Artery Lesions.

PubMed

Richard, Michele; Krol, Emilia; Dietzek, Alan

2016-10-01

To describe the use of orbital technique of atherectomy as an adjunct to successful angioplasty and stent placement of the superior mesenteric artery (SMA). The technique is demonstrated in a 68-year-old man with critical SMA stenosis. The SMA was cannulated with 0.014-in wire, but the lesion was highly stenotic and densely calcified and prevented the passage of even the smallest 1.5-mm balloon. Orbital atherectomy was thus performed with a 1.25-mm CSI crown. Balloon angioplasty was then possible with a 4 mm × 2 cm balloon followed by placement of a 7 mm × 22 mm balloon-mounted stent. The use of atherectomy as an adjunct to angioplasty and stenting in extensive, calcified SMA lesions supports the value of this technique to avoid a much larger and morbid open procedure. Published by Elsevier Inc.

Bi-Metallic Composite Structures With Designed Internal Residual Stress Field

NASA Technical Reports Server (NTRS)

Brice, Craig A.

2014-01-01

Shape memory alloys (SMA) have a unique ability to recover small amounts of plastic strain through a temperature induced phase change. For these materials, mechanical displacement can be accomplished by heating the structure to induce a phase change, through which some of the plastic strain previously introduced to the structure can be reversed. This paper introduces a concept whereby an SMA phase is incorporated into a conventional alloy matrix in a co-continuous reticulated arrangement forming a bi-metallic composite structure. Through memory activation of the mechanically constrained SMA phase, a controlled residual stress field is developed in the interior of the structure. The presented experimental data show that the memory activation of the SMA composite component significantly changes the residual stress distribution in the overall structure. Designing the structural arrangement of the two phases to produce a controlled residual stress field could be used to create structures that have much improved durability and damage tolerance properties.

Development of SMA Actuated Morphing Airfoil for Wind Turbine Load Alleviation

NASA Astrophysics Data System (ADS)

Karakalas, A.; Machairas, T.; Solomou, A.; Riziotis, V.; Saravanos, D.

Wind turbine rotor upscaling has entered a range of rotor diameters where the blade structure cannot sustain the increased aerodynamic loads without novel load alleviation concepts. Research on load alleviation using morphing blade sections is presented. Antagonistic shape memory alloy (SMA) actuators are implemented to deflect the section trailing edge (TE) to target shapes and target time-series relating TE movement with changes in lift coefficient. Challenges encountered by the complex thermomechanical response of morphing section and the enhancement of SMA transient response to achieve frequencies meaningful for aerodynamic load alleviation are addressed. Using a recently developed finite element for SMA actuators [1], actuator configurations are considered for fast cooling and heating cycles. Numerical results quantify the attained ranges of TE angle movement, the moving time period and the developed stresses. Estimations of the attained variations of lift coefficient vs. time are also presented to assess the performance of the morphing section.

A manipulator arm for zero-g simulations

NASA Technical Reports Server (NTRS)

Brodie, S. B.; Grant, C.; Lazar, J. J.

1975-01-01

A 12-ft counterbalanced Slave Manipulator Arm (SMA) was designed and fabricated to be used for resolving the questions of operational applications, capabilities, and limitations for such remote manned systems as the Payload Deployment and Retrieval Mechanism (PDRM) for the shuttle, the Free-Flying Teleoperator System, the Advanced Space Tug, and Planetary Rovers. As a developmental tool for the shuttle manipulator system (or PDRM), the SMA represents an approximate one-quarter scale working model for simulating and demonstrating payload handling, docking assistance, and satellite servicing. For the Free-Flying Teleoperator System and the Advanced Tug, the SMA provides a near full-scale developmental tool for satellite servicing, docking, and deployment/retrieval procedures, techniques, and support equipment requirements. For the Planetary Rovers, it provides an oversize developmental tool for sample handling and soil mechanics investigations. The design of the SMA was based on concepts developed for a 40-ft NASA technology arm to be used for zero-g shuttle manipulator simulations.

Design and performance of a shape memory alloy-reinforced composite aerodynamic profile

NASA Astrophysics Data System (ADS)

Simpson, J. C.; Boller, C.

2008-04-01

Based on a shape memory alloy (SMA)-reinforced composite developed separately, the applicability of the composite has been demonstrated through realization of a realistically scaled aerodynamic profile of around 0.5 m span by 0.5 m root chord whose skins had been made from this composite. The design, manufacturing and assembly of the profile are described. The curved skins were manufactured with two layers of SMA wires integrated into the layup of aramid fibre prepregs. All SMA wires were connected such that they can be operated as individual sets of wires and at low voltages, similar to the conditions for electrical energy generation in a real aircraft. The profile was then mounted on a vibration test rig and excited by a shaker at its tip which allowed the dynamic performance of the profile to be validated under internal actuation conditions generated through the SMA wires.

Finite element simulation of adaptive aerospace structures with SMA actuators

NASA Astrophysics Data System (ADS)

Frautschi, Jason; Seelecke, Stefan

2003-07-01

The particular demands of aerospace engineering have spawned many of the developments in the field of adaptive structures. Shape memory alloys are particularly attractive as actuators in these types of structures due to their large strains, high specific work output and potential for structural integration. However, the requisite extensive physical testing has slowed development of potential applications and highlighted the need for a simulation tool for feasibility studies. In this paper we present an implementation of an extended version of the M'ller-Achenbach SMA model into a commercial finite element code suitable for such studies. Interaction between the SMA model and the solution algorithm for the global FE equations is thoroughly investigated with respect to the effect of tolerances and time step size on convergence, computational cost and accuracy. Finally, a simulation of a SMA-actuated flexible trailing edge of an aircraft wing modeled with beam elements is presented.

Design and demonstration of a fish robot actuated by a SMA-driven actuation system

NASA Astrophysics Data System (ADS)

Le, Chan H.; Nguyen, Quang S.; Park, Hoon C.

2010-04-01

This paper presents a concept of a fish robot actuated by an SMA-based actuator. The bending-type actuator system is composed of a 0.1mm diameter SMA wire and a 0.5mm thick glass/epoxy strip. The SMA wire is installed to the bent composite strip. The actuator can produce about 200gf of blocking force and 3.5mm displacement at the center of the glass/epoxy strip. The bending motion of the actuator is converted into the tail-beat motion of a fish robot through a linkage system. The fish robot is evaluated by measuring the tail-beat angle, swimming speed and thrust produced by the fish robot. The tail-beat angle is about 20° and the maximum swimming speed is about 1.6cm/s. The measured thrust is about 0.4gf when the fish robot is operated at 0.9Hz.

Early functional impairment of sensory-motor connectivity in a mouse model of spinal muscular atrophy

PubMed Central

Mentis, George Z.; Blivis, Dvir; Liu, Wenfang; Drobac, Estelle; Crowder, Melissa E.; Kong, Lingling; Alvarez, Francisco J.; Sumner, Charlotte J.; O'Donovan, Michael J.

2011-01-01

SUMMARY To define alterations of neuronal connectivity that occur during motor neuron degeneration, we characterized the function and structure of spinal circuitry in spinal muscular atrophy (SMA) model mice. SMA motor neurons show reduced proprioceptive reflexes that correlate with decreased number and function of synapses on motor neuron somata and proximal dendrites. These abnormalities occur at an early stage of disease in motor neurons innervating proximal hindlimb muscles and medial motor neurons innervating axial muscles, but only at end-stage disease in motor neurons innervating distal hindlimb muscles. Motor neuron loss follows afferent synapse loss with the same temporal and topographical pattern. Trichostatin A, which improves motor behavior and survival of SMA mice, partially restores spinal reflexes illustrating the reversibility of these synaptic defects. De-afferentation of motor neurons is an early event in SMA and may be a primary cause of motor dysfunction that is amenable to therapeutic intervention. PMID:21315257

Structural Covariance of the Prefrontal-Amygdala Pathways Associated with Heart Rate Variability

PubMed Central

Wei, Luqing; Chen, Hong; Wu, Guo-Rong

2018-01-01

The neurovisceral integration model has shown a key role of the amygdala in neural circuits underlying heart rate variability (HRV) modulation, and suggested that reciprocal connections from amygdala to brain regions centered on the central autonomic network (CAN) are associated with HRV. To provide neuroanatomical evidence for these theoretical perspectives, the current study used covariance analysis of MRI-based gray matter volume (GMV) to map structural covariance network of the amygdala, and then determined whether the interregional structural correlations related to individual differences in HRV. The results showed that covariance patterns of the amygdala encompassed large portions of cortical (e.g., prefrontal, cingulate, and insula) and subcortical (e.g., striatum, hippocampus, and midbrain) regions, lending evidence from structural covariance analysis to the notion that the amygdala was a pivotal node in neural pathways for HRV modulation. Importantly, participants with higher resting HRV showed increased covariance of amygdala to dorsal medial prefrontal cortex and anterior cingulate cortex (dmPFC/dACC) extending into adjacent medial motor regions [i.e., pre-supplementary motor area (pre-SMA)/SMA], demonstrating structural covariance of the prefrontal-amygdala pathways implicated in HRV, and also implying that resting HRV may reflect the function of neural circuits underlying cognitive regulation of emotion as well as facilitation of adaptive behaviors to emotion. Our results, thus, provide anatomical substrates for the neurovisceral integration model that resting HRV may index an integrative neural network which effectively organizes emotional, cognitive, physiological and behavioral responses in the service of goal-directed behavior and adaptability. PMID:29545744

Design and fabrication of a three-finger prosthetic hand using SMA muscle wires

NASA Astrophysics Data System (ADS)

Simone, Filomena; York, Alexander; Seelecke, Stefan

2015-03-01

Bio-inspired hand-like gripper systems based on shape memory alloy (SMA) wire actuation have the potential to enable a number of useful applications in, e.g., the biomedical field or industrial assembly systems. The inherent high energy density makes SMA solutions a natural choice for systems with lightweight, low noise and high force requirements, such as hand prostheses or robotic systems in a human/machine environment. The focus of this research is the development, design and realization of a SMA-actuated prosthetic hand prototype with three fingers. The use of thin wires (100 μm diameter) allows for high cooling rates and therefore fast movement of each finger. Grouping several small wires mechanically in parallel allows for high force actuation. To save space and to allow for a direct transmission of the motion to each finger, the SMA wires are attached directly within each finger, across each phalanx. In this way, the contraction of the wires will allow the movement of the fingers without the use of any additional gears. Within each finger, two different bundles of wires are mounted: protagonist ones that create bending movement and the antagonist ones that enable stretching of each phalanx. The resistance change in the SMA wires is measured during actuation, which allows for monitoring of the wire stroke and potentially the gripping force without the use of additional sensors. The hand is built with modern 3D-printing technologies and its performance while grasping objects of different size and shape is experimentally investigated illustrating the usefulness of the actuator concept.

Effectiveness of prediabetes nutrition shared medical appointments: prevention of diabetes.

PubMed

Cole, Renee E; Boyer, Kathleen M; Spanbauer, Sean M; Sprague, Denise; Bingham, Mona

2013-01-01

The purpose of this study is to evaluate the effectiveness of a nutrition-based shared medical appointment (SMA) intervention in the treatment of prediabetes compared to the individualized counseling standard of care. A randomized controlled trial design comparing health outcomes in patients with prediabetes attending either an individualized counseling (control group) or three 90-minute nutrition SMA (intervention group) sessions. Demographic, anthropometric (weight and body mass index), clinical (blood pressure), and biochemical (lipid profile, fasting blood sugar, glycated hemoglobin, albumin-to-creatinine ratio) measures were obtained from all participants at baseline, at 3 months, and at 1 year. Ninety-four participants were randomized into the 2 study groups with a 69% completion rate at 1 year (n = 34 SMA, n = 31 control). The average participant was Caucasian (64%), male (54%), 58.3 ± 9.6 years, had a BMI of 30.8 ± 4.9 kg/m(2) (obese), and fasting blood glucose of 109 ± 9.5 mg/dL. The SMA and control participants lost a mean of 6.6 pounds and 3.6 pound, respectively; neither group met the 5% modest weight loss expected. The SMA and control group experienced a mean drop in fasting blood glucose of 6 mg/dL. As demands on health care providers continue to rise, finding innovative ways to manage the patient load while providing quality health care is increasingly important. SMA health outcomes were equivalent to individual counseling outcomes, while increasing the provider's productivity by treating 6 to 8 people with prediabetes in 90 minutes compared to 1 patient in 60 minutes.

Small Molecule Suppressors of Drosophila Kinesin Deficiency Rescue Motor Axon Development in a Zebrafish Model of Spinal Muscular Atrophy

PubMed Central

Gassman, Andrew; Hao, Le T.; Bhoite, Leena; Bradford, Chad L.; Chien, Chi-Bin; Beattie, Christine E.; Manfredi, John P.

2013-01-01

Proximal spinal muscular atrophy (SMA) is the most common inherited motor neuropathy and the leading hereditary cause of infant mortality. Currently there is no effective treatment for the disease, reflecting a need for pharmacologic interventions that restore performance of dysfunctional motor neurons or suppress the consequences of their dysfunction. In a series of assays relevant to motor neuron biology, we explored the activities of a collection of tetrahydroindoles that were reported to alter the metabolism of amyloid precursor protein (APP). In Drosophila larvae the compounds suppressed aberrant larval locomotion due to mutations in the Khc and Klc genes, which respectively encode the heavy and light chains of kinesin-1. A representative compound of this class also suppressed the appearance of axonal swellings (alternatively termed axonal spheroids or neuritic beads) in the segmental nerves of the kinesin-deficient Drosophila larvae. Given the importance of kinesin-dependent transport for extension and maintenance of axons and their growth cones, three members of the class were tested for neurotrophic effects on isolated rat spinal motor neurons. Each compound stimulated neurite outgrowth. In addition, consistent with SMA being an axonopathy of motor neurons, the three axonotrophic compounds rescued motor axon development in a zebrafish model of SMA. The results introduce a collection of small molecules as pharmacologic suppressors of SMA-associated phenotypes and nominate specific members of the collection for development as candidate SMA therapeutics. More generally, the results reinforce the perception of SMA as an axonopathy and suggest novel approaches to treating the disease. PMID:24023935

Anatomical variations in the origins of the celiac axis and the superior mesenteric artery: MDCT angiographic findings and their probable embryological mechanisms.

PubMed

Wang, Yi; Cheng, Cheng; Wang, Lu; Li, Ran; Chen, Jin-hua; Gong, Shui-gen

2014-08-01

To identify the spectrum and prevalence of anatomical variations in the origin of the celiac axis (CA), the superior mesenteric artery (SMA) and their major branches by using multidetector computed tomographic (MDCT) angiography. A retrospective evaluation was carried out on 1,500 abdominal MDCT angiography images. The aortic origins of the CA, the SMA and their major branch patterns were investigated. Normal aortic origins of CA and SMA were noted in 1,347 (89.8%) patients. Seven types of CA and SMA origin variants were identified in 153 (10.2%) patients. The three most common variations were hepatomesenteric trunk (67 patients, 4.47%), celiomesenteric trunk (CMT) (51 patients, 3.4%) and splenomesenteric trunk (18 patients, 1.2%). An evaluation of CMT was classified as long (34 patients, 66.7%) or short (17 patients, 33.3%) subtypes, compared with the length of the common trunk. Further CMT classification was based on the origin of the left gastric artery: subtype I, 26 patients (53.1%); subtype II, 5 patients (10.2%); subtype III, 15 patients (30.6%); subtype IV, 3 patients (6.1%). Dislocation interruption, incomplete interruption and persistence of the longitudinal anastomosis could be the embryological mechanisms of the variant origins of the CA, the SMA and their major branches. • Aortic origins of CA, SMA and their major branches were investigated. • Celiomesenteric trunk includes several different subtypes and configurations. • Probable embryological mechanisms of origin variants in these observed arteries were discussed. • Origin variants in these observed arteries have wide-ranging health implications.

Design and quasi-static characterization of SMASH (SMA stabilizing handgrip)

NASA Astrophysics Data System (ADS)

Pathak, Anupam; Brei, Diann; Luntz, Jonathan; LaVigna, Chris; Kwatny, Harry

2007-04-01

Due to physiologically induced body tremors, there is a need for active stabilization in many hand-held devices such as surgical tools, optical equipment (cameras), manufacturing tools, and small arms weapons. While active stabilization has been achieved with electromagnetic and piezoceramics actuators for cameras and surgical equipment, the hostile environment along with larger loads introduced by manufacturing and battlefield environments make these approaches unsuitable. Shape Memory Alloy (SMA) actuators are capable of alleviating these limitations with their large force/stroke generation, smaller size, lower weight, and increased ruggedness. This paper presents the actuator design and quasi-static characterization of a SMA Stabilizing Handgrip (SMASH). SMASH is an antagonistically SMA actuated two degree-of-freedom stabilizer for disturbances in the elevation and azimuth directions. The design of the SMASH for a given application is challenging because of the difficulty in accurately modeling systems loads such as friction and unknown shakedown SMA material behavior (which is dependent upon the system loads). Thus, an iterative empirical design process is introduced that provides a method to estimate system loads, a SMA shakedown procedure using the system loads to reduce material creep, and a final selection and prediction for the full SMASH system performance. As means to demonstrate this process, a SMASH was designed, built and experimentally characterized for the extreme case study of small arms stabilization for a US Army M16 rifle. This study successfully demonstrated the new SMASH technology along with the unique design procedure that can be applied to small arms along with a variety of other hand-held devices.

Effect of transcranial direct current stimulation (tDCS) during complex whole body motor skill learning.

PubMed

Kaminski, Elisabeth; Hoff, Maike; Sehm, Bernhard; Taubert, Marco; Conde, Virginia; Steele, Christopher J; Villringer, Arno; Ragert, Patrick

2013-09-27

The aim of the study was to investigate tDCS effects on motor skill learning in a complex whole body dynamic balance task (DBT). We hypothesized that tDCS over the supplementary motor area (SMA), a region that is known to be involved in the control of multi-joint whole body movements, will result in polarity specific changes in DBT learning. In a randomized sham-controlled, double-blinded parallel design, we applied 20 min of tDCS over the supplementary motor area (SMA) and prefrontal cortex (PFC) while subjects performed a DBT. Anodal tDCS over SMA with the cathode placed over contralateral PFC impaired motor skill learning of the DBT compared to sham. This effect was still present on the second day of training. Reversing the polarity (cathode over SMA, anode over PFC) did not affect motor skill learning neither on the first nor on the second day of training. To better disentangle whether the impaired motor skill learning was due to a modulation of SMA or PFC, we performed an additional control experiment. Here, we applied anodal tDCS over SMA together with a larger and presumably more ineffective electrode (cathode) over PFC. Interestingly this alternative tDCS electrode setup did not affect the outcome of DBT learning. Our results provide novel evidence that a modulation of the (right) PFC seems to impair complex multi-joint motor skill learning. Hence, future studies should take the positioning of both tDCS electrodes into account when investigating complex motor skill learning. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Cortical and subcortical interactions during action reprogramming and their related white matter pathways

PubMed Central

Neubert, Franz-Xaver; Mars, Rogier B.; Buch, Ethan R.; Olivier, Etienne; Rushworth, Matthew F. S.

2010-01-01

The right inferior frontal gyrus (rIFG) and the presupplementary motor area (pre-SMA) have been identified with cognitive control—the top-down influence on other brain areas when nonroutine behavior is required. It has been argued that they “inhibit” habitual motor responses when environmental changes mean a different response should be made. However, whether such “inhibition” can be equated with inhibitory physiological interactions has been unclear, as has the areas’ relationship with each other and the anatomical routes by which they influence movement execution. Paired-pulse transcranial magnetic stimulation (ppTMS) was applied over rIFG and primary motor cortex (M1) or over pre-SMA and M1 to measure their interactions, at a subsecond scale, during either inhibition and reprogramming of actions or during routine action selection. Distinct patterns of functional interaction between pre-SMA and M1 and between rIFG and M1 were found that were specific to action reprogramming trials; at a physiological level, direct influences of pre-SMA and rIFG on M1 were predominantly facilitatory and inhibitory, respectively. In a subsequent experiment, it was shown that the rIFG's inhibitory influence was dependent on pre-SMA. A third experiment showed that pre-SMA and rIFG influenced M1 at two time scales. By regressing white matter fractional anisotropy from diffusion-weighted magnetic resonance images against TMS-measured functional connectivity, it was shown that short-latency (6 ms) and longer latency (12 ms) influences were mediated by cortico-cortical and subcortical pathways, respectively, with the latter passing close to the subthalamic nucleus. PMID:20622155

Resting-State Hyperperfusion of the Supplementary Motor Area in Catatonia

PubMed Central

Schäppi, Lea; Federspiel, Andrea; Bohlhalter, Stephan; Wiest, Roland; Strik, Werner; Stegmayer, Katharina

2017-01-01

Abstract Catatonia is a psychomotor syndrome that not only frequently occurs in the context of schizophrenia but also in other conditions. The neural correlates of catatonia remain unclear due to small-sized studies. We therefore compared resting-state cerebral blood flow (rCBF) and gray matter (GM) density between schizophrenia patients with current catatonia and without catatonia and healthy controls. We included 42 schizophrenia patients and 41 controls. Catatonia was currently present in 15 patients (scoring >2 items on the Bush Francis Catatonia Rating Scale screening). Patients did not differ in antipsychotic medication or positive symptoms. We acquired whole-brain rCBF using arterial spin labeling and GM density. We compared whole-brain perfusion and GM density over all and between the groups using 1-way ANCOVAs (F and T tests). We found a group effect (F test) of rCBF within bilateral supplementary motor area (SMA), anterior cingulate cortex, dorsolateral prefrontal cortex, left interior parietal lobe, and cerebellum. T tests indicated 1 cluster (SMA) to be specific to catatonia. Moreover, catatonia of excited and retarded types differed in SMA perfusion. Furthermore, increased catatonia severity was associated with higher perfusion in SMA. Finally, catatonia patients had a distinct pattern of GM density reduction compared to controls with prominent GM loss in frontal and insular cortices. SMA resting-state hyperperfusion is a marker of current catatonia in schizophrenia. This is highly compatible with a dysregulated motor system in catatonia, particularly affecting premotor areas. Moreover, SMA perfusion was differentially altered in retarded and excited catatonia subtypes, arguing for distinct pathobiology. PMID:27729486

Cortical and subcortical interactions during action reprogramming and their related white matter pathways.

PubMed

Neubert, Franz-Xaver; Mars, Rogier B; Buch, Ethan R; Olivier, Etienne; Rushworth, Matthew F S

2010-07-27

The right inferior frontal gyrus (rIFG) and the presupplementary motor area (pre-SMA) have been identified with cognitive control-the top-down influence on other brain areas when nonroutine behavior is required. It has been argued that they "inhibit" habitual motor responses when environmental changes mean a different response should be made. However, whether such "inhibition" can be equated with inhibitory physiological interactions has been unclear, as has the areas' relationship with each other and the anatomical routes by which they influence movement execution. Paired-pulse transcranial magnetic stimulation (ppTMS) was applied over rIFG and primary motor cortex (M1) or over pre-SMA and M1 to measure their interactions, at a subsecond scale, during either inhibition and reprogramming of actions or during routine action selection. Distinct patterns of functional interaction between pre-SMA and M1 and between rIFG and M1 were found that were specific to action reprogramming trials; at a physiological level, direct influences of pre-SMA and rIFG on M1 were predominantly facilitatory and inhibitory, respectively. In a subsequent experiment, it was shown that the rIFG's inhibitory influence was dependent on pre-SMA. A third experiment showed that pre-SMA and rIFG influenced M1 at two time scales. By regressing white matter fractional anisotropy from diffusion-weighted magnetic resonance images against TMS-measured functional connectivity, it was shown that short-latency (6 ms) and longer latency (12 ms) influences were mediated by cortico-cortical and subcortical pathways, respectively, with the latter passing close to the subthalamic nucleus.

An Evaluation on the Smart Composite Damaged by Thermal Shock

NASA Astrophysics Data System (ADS)

Lee, Jin Kyung; Lee, Sang Pill; Park, Young Chul; Lee, Joon Hyun

A shape memory alloy (SMA) as part of some products and system has been used to keep their shape at any specified temperature. By using this characteristic of the shape memory alloy it can be solved the problem of the residual stress by difference of coefficients of thermal expansion between reinforcement and matrix within composite. In this study, TiNi/Al6061 shape memory alloy composite was fabricated through hot press method, and the optimal fabrication condition was created. The bonding effect of the matrix and the reinforcement within the SMA composite was strengthened by cold rolling. The SMA composite can be applied as the part of airplane and vessel, and used under tough condition of repetitive thermal shock cycles of high and low temperatures. Therefore, the thermal shock test was performed for the SMA composite, and mechanical properties were evaluated. The tensile strength of the SMA composite showed a slight decline with the thermal shock cycles. In addition, acoustic emission (AE) technique was used to quantify the microscopic damage behavior of cold rolled TiNi/Al6061 shape memory alloy composite that underwent thermal shock cycles. The damage degree on the specimen that underwent thermal shock cycles was discussed. Actually AE parameters such as AE event, count and energy was analyzed, and these parameters was useful to evaluate the damage behavior and degree of the SMA composite. The waveform of the signal caused by debonding was pulse type, and showed the frequency range of 160 kHz, however, the signal by the fiber fracture showed the pulse type of high magnitude and frequency range of 220 kH.

Morphological Characteristics of Motor Neurons Do Not Determine Their Relative Susceptibility to Degeneration in a Mouse Model of Severe Spinal Muscular Atrophy

PubMed Central

Mutsaers, Chantal A.; Thomson, Derek; Hamilton, Gillian; Parson, Simon H.; Gillingwater, Thomas H.

2012-01-01

Spinal muscular atrophy (SMA) is a leading genetic cause of infant mortality, resulting primarily from the degeneration and loss of lower motor neurons. Studies using mouse models of SMA have revealed widespread heterogeneity in the susceptibility of individual motor neurons to neurodegeneration, but the underlying reasons remain unclear. Data from related motor neuron diseases, such as amyotrophic lateral sclerosis (ALS), suggest that morphological properties of motor neurons may regulate susceptibility: in ALS larger motor units innervating fast-twitch muscles degenerate first. We therefore set out to determine whether intrinsic morphological characteristics of motor neurons influenced their relative vulnerability to SMA. Motor neuron vulnerability was mapped across 10 muscle groups in SMA mice. Neither the position of the muscle in the body, nor the fibre type of the muscle innervated, influenced susceptibility. Morphological properties of vulnerable and disease-resistant motor neurons were then determined from single motor units reconstructed in Thy.1-YFP-H mice. None of the parameters we investigated in healthy young adult mice – including motor unit size, motor unit arbor length, branching patterns, motor endplate size, developmental pruning and numbers of terminal Schwann cells at neuromuscular junctions - correlated with vulnerability. We conclude that morphological characteristics of motor neurons are not a major determinant of disease-susceptibility in SMA, in stark contrast to related forms of motor neuron disease such as ALS. This suggests that subtle molecular differences between motor neurons, or extrinsic factors arising from other cell types, are more likely to determine relative susceptibility in SMA. PMID:23285108

Latrunculin B and substratum stiffness regulate corneal fibroblast to myofibroblast transformation.

PubMed

Thomasy, Sara M; Raghunathan, Vijay Krishna; Miyagi, Hidetaka; Evashenk, Alexander T; Sermeno, Jasmyne C; Tripp, Geneva K; Morgan, Joshua T; Murphy, Christopher J

2018-05-01

The transformation of keratocytes and fibroblasts to myofibroblasts is important to corneal wound healing as well as formation of stromal haze. The purpose of this study was to determine the effect of latrunculin B, an actin cytoskeleton disruptor in conjunction with a fundamental biophysical cue, substrate stiffness, on myofibroblast transformation in vitro and in vivo. Rabbit corneal fibroblasts were cultured on substrates of differing compliance (1.5, 22, and 71 kPa) and tissue culture plastic (TCP; > 1 GPa) in media containing 0 or 10 ng/ml TGFβ1 for 72 h. Cells were treated with 0.4 μM Lat-B or DMSO for 30 min every 24 h for 72 h. RNA was collected from cells and expression of alpha-smooth muscle actin (α-SMA), keratocan, and ALDH1A1 determined using qPCR; immunocytochemistry was used to assess α-SMA protein expression. A rabbit phototherapeutic keratectomy (PTK) model was used to assess the impact of 0.1% Lat-B (n = 3) or 25% DMSO (vehicle control, n = 3) on corneal wound healing by assessment of epithelial wound size with fluorescein stain and semi-quantitative stromal haze scoring by an observer masked to treatment group as well as Fourier-domain optical coherence tomography (FD-OCT) at set time points. Statistical analysis was completed using one-way or two-way analysis of variance. Treatment with Lat-B versus DMSO resulted in significantly less αSMA mRNA (P ≤ 0.007) for RCF cells grown on 22 and 71 kPa substrates as well as TCP without or with TGFβ1, and significantly decreased α-SMA protein expression in RCFs cultured on the intermediate (22 kPa) stiffness in the absence (P = 0.028) or presence (P = 0.018) of TGFβ1. Treatment with Lat-B versus DMSO but did not significantly alter expression of keratocan or ALDH1A1 mRNA in RCFs (P > 0.05) in the absence or presence of TGFβ1, but RCFs grown on stiff hydrogels (71 kPa) had significantly more keratocan mRNA expression versus the 22 kPa hydrogel or TCP (P < 0.001) without TGFβ1. Administration of topical Lat-B BID was well tolerated by rabbits post-PTK but did not significantly alter epithelial wound closure, stromal haze score, stromal haze thickness as measured by FD-OCT in comparison to DMSO-treated rabbits. When corneal stromal cells are cultured on substrates possessing biologically relevant substratum stiffnesses, Lat-B modulates mRNA and protein expression of α-SMA and thus modulates myofibroblast transformation. At a dose and dose-frequency that reduced IOP in human glaucoma patients, Lat-B treatment did not substantially impact corneal epithelial or stromal wound healing in a rabbit PTK model. While a significant impact on wound healing was observed at the concentration and dose frequency reported here was not found, encouraging in vitro data support further investigations of topically applied Lat-B to determine if this compound can reduce stromal fibrosis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Heterogeneous alleles comprising G6PD deficiency trait in West Africa exert contrasting effects on two major clinical presentations of severe malaria.

PubMed

Shah, Shivang S; Rockett, Kirk A; Jallow, Muminatou; Sisay-Joof, Fatou; Bojang, Kalifa A; Pinder, Margaret; Jeffreys, Anna; Craik, Rachel; Hubbart, Christina; Wellems, Thomas E; Kwiatkowski, Dominic P

2016-01-07

Glucose-6-phosphate dehydrogenase (G6PD) deficiency exhibits considerable allelic heterogeneity which manifests with variable biochemical and clinical penetrance. It has long been thought that G6PD deficiency confers partial protection against severe malaria, however prior genetic association studies have disagreed with regard to the strength and specificity of a protective effect, which might reflect differences in the host genetic background, environmental influences, or in the specific clinical phenotypes considered. A case-control association study of severe malaria was conducted in The Gambia, a region in West Africa where there is considerable allelic heterogeneity underlying expression of G6PD deficiency trait, evaluating the three major nonsynonymous polymorphisms known to be associated with enzyme deficiency (A968G, T542A, and C202T) in a cohort of 3836 controls and 2379 severe malaria cases. Each deficiency allele exhibited a similar trend toward protection against severe malaria overall (15-26% reduced risk); however, in stratifying severe malaria to two of its constituent clinical subphenotypes, severe malarial anaemia (SMA) and cerebral malaria (CM), the three deficiency alleles exhibited trends of opposing effect, with risk conferred to SMA and protection with respect to CM. To assess the overall effect of G6PD deficiency trait, deficiency alleles found across all three loci were pooled. G6PD deficiency trait was found to be significantly associated with protection from severe malaria overall (OR 0.83 [0.75-0.92], P = 0.0006), but this was limited to CM (OR 0.73 [0.61-0.87], P = 0.0005), with a trend toward increased risk for SMA, especially in fully-deficient individuals (OR 1.43 [0.99-2.08], P = 0.056). Sex-stratified testing largely comported with these results, with evidence suggesting that protection by G6PD deficiency trait is conferred to both males and females, though susceptibility to SMA may be restricted to fully-deficient male hemizygotes. In a part of Africa where multiple alleles contribute to expression of G6PD deficiency trait, these findings clarify and extend previous work done in populations where a single variant predominates, and taken together suggest a causal role for G6PD deficiency trait itself with respect to severe malaria, with opposing effects seen on two major clinical subphenotypes.

Evaluating Georgia DOT's compaction requirements for stone matrix asphalt mixes.

DOT National Transportation Integrated Search

2006-06-01

This study determined a compactive effort for Stone Mastic Asphalt (SMA) mixes with the Superpave gyratory compactor (SGC) that would match a 50-blow Marshall compactive effort using aggregates and mix designs common in Georgia. SMA mix designs were ...

Development of a Meso-Scale SMA-Based Torsion Actuator for Image-Guided Procedures.

PubMed

Sheng, Jun; Gandhi, Dheeraj; Gullapalli, Rao; Simard, J Marc; Desai, Jaydev P

2017-02-01

This paper presents the design, modeling, and control of a meso-scale torsion actuator based on shape memory alloy (SMA) for image-guided surgical procedures. Developing a miniature torsion actuator is challenging, but it opens the possibility of significantly enhancing the robot agility and maneuverability. The proposed torsion actuator is bi-directionally actuated by a pair of antagonistic SMA torsion springs through alternate Joule heating and natural cooling. The torsion actuator is integrated into a surgical robot prototype to demonstrate its working performance in the humid environment under C-Arm CT image guidance.

Successful Recanalization of Acute Superior Mesenteric Artery Thromboembolic Occlusion by a Combination of Intraarterial Thrombolysis and Mechanical Thrombectomy with a Carotid Filter

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

Zelenak, Kamil, E-mail: zelenak@unm.sk; Sinak, Igor; Janik, Jan

2013-06-15

Acute superior mesenteric artery (SMA) occlusion is a life-threatening disease, and acute intestinal ischemia develops from the sudden decrease in perfusion to the intestines. The key to saving the patient's life is early diagnosis, and prompt revascularization of the SMA can prevent intestinal infarction and decrease the risk of bowel segment necrosis. Computed tomographic angiography may be useful for rapid diagnosis. We report recanalization of an SMA occlusion in an 80-year-old man with a combination of intraarterial thrombolysis and mechanical thrombectomy with a carotid filter.

Development of a Meso-Scale SMA-Based Torsion Actuator for Image-Guided Procedures

PubMed Central

Sheng, Jun; Gandhi, Dheeraj; Gullapalli, Rao; Simard, J. Marc; Desai, Jaydev P.

2016-01-01

This paper presents the design, modeling, and control of a meso-scale torsion actuator based on shape memory alloy (SMA) for image-guided surgical procedures. Developing a miniature torsion actuator is challenging, but it opens the possibility of significantly enhancing the robot agility and maneuverability. The proposed torsion actuator is bi-directionally actuated by a pair of antagonistic SMA torsion springs through alternate Joule heating and natural cooling. The torsion actuator is integrated into a surgical robot prototype to demonstrate its working performance in the humid environment under C-Arm CT image guidance. PMID:28210189

Study on reinforced concrete beams strengthened using shape memory alloy wires in combination with carbon-fiber-reinforced polymer plates

NASA Astrophysics Data System (ADS)

Li, Hui; Liu, Zhi-qiang; Ou, Jin-ping

2007-12-01

It has been proven that carbon-fiber-reinforced polymer (CFRP) sheets or plates are capable of improving the strength of reinforced concrete (RC) structures. However, residual deformation of RC structures in service reduces the effect of CFRP strengthening. SMA can be applied to potentially decrease residual deformation and even close concrete cracks because of its recovery forces imposed on the concrete when heated. Therefore, a method of a RC structure strengthened by CFRP plates in combination with SMA wires is proposed in this paper. The strengthening effect of this method is investigated through experiments and numerical study based on the nonlinear finite element software ABAQUS in simple RC beams. Parametric analysis and assessment of damage by defining a damage index are carried out. The results indicate that recovery forces of SMA wires can decrease deflections and even close cracks in the concrete. The recovery rate of deflection of the beam increases with increasing the ratio of SMA wires. The specimen strengthened with CFRP plates has a relatively large stiffness and smaller damage index value when the residual deformation of the beam is first reduced by activation of the SMA wires. The effectiveness of this strengthening method for RC beams is verified by experimental and numerical results.

High levels of maternally transferred mercury disrupt magnetic responses of snapping turtle hatchlings (Chelydra serpentina).

PubMed

Landler, Lukas; Painter, Michael S; Coe, Brittney Hopkins; Youmans, Paul W; Hopkins, William A; Phillips, John B

2017-09-01

The Earth's magnetic field is involved in spatial behaviours ranging from long-distance migration to non-goal directed behaviours, such as spontaneous magnetic alignment (SMA). Mercury is a harmful pollutant most often generated from anthropogenic sources that can bio-accumulate in animal tissue over a lifetime. We compared SMA of hatchling snapping turtles from mothers captured at reference (i.e., low mercury) and mercury contaminated sites. Reference turtles showed radio frequency-dependent SMA along the north-south axis, consistent with previous studies of SMA, while turtles with high levels of maternally inherited mercury failed to show consistent magnetic alignment. In contrast, there was no difference between reference and mercury exposed turtles on standard performance measures. The magnetic field plays an important role in animal orientation behaviour and may also help to integrate spatial information from a variety of sensory modalities. As a consequence, mercury may compromise the performance of turtles in a wide variety of spatial tasks. Future research is needed to determine the threshold for mercury effects on snapping turtles, whether mercury exposure compromises spatial behaviour of adult turtles, and whether mercury has a direct effect on the magnetoreception mechanism(s) that mediate SMA or a more general effect on the nervous system. Copyright © 2017 Elsevier Ltd. All rights reserved.

A new full-field digital mammography system with and without the use of an advanced post-processing algorithm: comparison of image quality and diagnostic performance.

PubMed

Ahn, Hye Shin; Kim, Sun Mi; Jang, Mijung; Yun, Bo La; Kim, Bohyoung; Ko, Eun Sook; Han, Boo-Kyung; Chang, Jung Min; Yi, Ann; Cho, Nariya; Moon, Woo Kyung; Choi, Hye Young

2014-01-01

To compare new full-field digital mammography (FFDM) with and without use of an advanced post-processing algorithm to improve image quality, lesion detection, diagnostic performance, and priority rank. During a 22-month period, we prospectively enrolled 100 cases of specimen FFDM mammography (Brestige®), which was performed alone or in combination with a post-processing algorithm developed by the manufacturer: group A (SMA), specimen mammography without application of "Mammogram enhancement ver. 2.0"; group B (SMB), specimen mammography with application of "Mammogram enhancement ver. 2.0". Two sets of specimen mammographies were randomly reviewed by five experienced radiologists. Image quality, lesion detection, diagnostic performance, and priority rank with regard to image preference were evaluated. Three aspects of image quality (overall quality, contrast, and noise) of the SMB were significantly superior to those of SMA (p < 0.05). SMB was significantly superior to SMA for visualizing calcifications (p < 0.05). Diagnostic performance, as evaluated by cancer score, was similar between SMA and SMB. SMB was preferred to SMA by four of the five reviewers. The post-processing algorithm may improve image quality with better image preference in FFDM than without use of the software.

Reduced Performance During a Sentence Repetition Task by Continuous Theta-Burst Magnetic Stimulation of the Pre-supplementary Motor Area.

PubMed

Dietrich, Susanne; Hertrich, Ingo; Müller-Dahlhaus, Florian; Ackermann, Hermann; Belardinelli, Paolo; Desideri, Debora; Seibold, Verena C; Ziemann, Ulf

2018-01-01

The pre-supplementary motor area (pre-SMA) is engaged in speech comprehension under difficult circumstances such as poor acoustic signal quality or time-critical conditions. Previous studies found that left pre-SMA is activated when subjects listen to accelerated speech. Here, the functional role of pre-SMA was tested for accelerated speech comprehension by inducing a transient "virtual lesion" using continuous theta-burst stimulation (cTBS). Participants were tested (1) prior to (pre-baseline), (2) 10 min after (test condition for the cTBS effect), and (3) 60 min after stimulation (post-baseline) using a sentence repetition task (formant-synthesized at rates of 8, 10, 12, 14, and 16 syllables/s). Speech comprehension was quantified by the percentage of correctly reproduced speech material. For high speech rates, subjects showed decreased performance after cTBS of pre-SMA. Regarding the error pattern, the number of incorrect words without any semantic or phonological similarity to the target context increased, while related words decreased. Thus, the transient impairment of pre-SMA seems to affect its inhibitory function that normally eliminates erroneous speech material prior to speaking or, in case of perception, prior to encoding into a semantically/pragmatically meaningful message.

Structural energy dissipation in extreme loading events using shape memory alloys

NASA Astrophysics Data System (ADS)

Angioni, Stefano L.

It is well known that composite materials have a poor resistance to the damage caused by the impact of foreign objects on their outer surface. There are various methods for improving the impact damage tolerance of composite materials, such as: fibre toughening, matrix toughening, interface toughening, through the thickness reinforcements and selective interlayers and hybrids. Hybrid composites with improved impact resistance would be particularly useful in military and commercial civil applications. Hybridizing composites using shape memory alloys (SMAs) is one solution since SMA materials can absorb the energy of impact through superelastic deformation or recovery stress reducing the effects of the impact on the composite structure. The SMA material may be embedded in the hybrid composites (SMAHC) in many different forms and also the characteristics of the fibre reinforcements may vary, such as SMA wires in unidirectional laminates or SMA foils in unidirectional laminates only to cite two examples. Recently SMA fibres have been embedded in 2-D woven composites. As part of this work, the existing theoretical models for woven composites have been extended to the case of woven SMAHC using a multiscale methodology in order to predict the mechanical properties and failure behaviour of SMAHC plates. Also several parts of the model have been coded in MATLAB and validated against results extracted from the literature, showing good correlation..

Abnormal mural cell recruitment in lymphatic capillaries: a common pathological feature in chronic lymphedematous skin?

PubMed

Yu, Zi-You; Sun, Di; Luo, Yi; Liu, Ning-Fei

2016-10-01

This study aimed to explore the structural and functional characteristics of dermal lymphatic capillaries in patients with chronic LE, specifically focused on the mural cells that are associated with skin lymphatics. Forty-four patients (30 primary LE and 14 secondary LE) and eight healthy controls were enrolled in this study. Genetic analysis of the FOXC2 was performed in 18 patients with primary LE. Full-thickness skin was excised and immunohistologically stained for podoplanin and α-SMA. The proportions of α-SMA + Lv (α-SMA + Lv%) were calculated. Lymphatic vascular function was assessed by indocyanine green lymphography. Analysis of FOXC2 revealed two mutations in two patients with LDs. Histologically, thirty-nine patients exhibited increased α-SMA + mural cell coverage of lymphatic capillaries. The α-SMA + Lv% values in the superficial and deep dermis in patients with primary and secondary LE were significantly higher than in the control group. Compared with imaging findings in healthy limbs, in which the collecting lymphatics were clearly visualized, lymphedematous extremities all exhibited dermal backflow. Abnormal recruitment of mural cells in dermal lymphatic capillaries is a common pathological event in chronic LE, and may play a role in disease evolution. © 2016 John Wiley & Sons Ltd.

Endovascular Management of Acute Embolic Occlusion of the Superior Mesenteric Artery: A 12-Year Single-Centre Experience

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

Raupach, J., E-mail: janraupach@seznam.cz; Lojik, M., E-mail: miroslav.lojik@fnhk.cz; Chovanec, V., E-mail: chovanec.v@seznam.cz

2016-02-15

PurposeRetrospective evaluation of 12-year experience with endovascular management of acute mesenteric ischemia (AMI) due to embolic occlusion of the superior mesenteric artery (SMA).Materials and methodsFrom 2003 to 2014, we analysed the in-hospital mortality of 37 patients with acute mesenteric embolism who underwent primary endovascular therapy with subsequent on-demand laparotomy. Transcatheter embolus aspiration was used in all 37 patients (19 women, 18 men, median age 76 years) with embolic occlusion of the SMA. Adjunctive local thrombolysis (n = 2) and stenting (n = 2) were also utilised.ResultsWe achieved complete recanalization of the SMA stem in 91.9 %. One patient was successfully treated by surgical embolectomy due tomore » a failed endovascular approach. Subsequent exploratory laparotomy was performed in 73.0 % (n = 27), and necrotic bowel resection in 40.5 %. The total in-hospital mortality was 27.0 %.ConclusionPrimary endovascular therapy for acute embolic SMA occlusion with on-demand laparotomy is a recommended algorithm used in our centre to treat SMA occlusion. This combined approach for the treatment of AMI is associated with in-hospital mortality rate of 27.0 %.« less

Regulation of Survival Motor Neuron Protein by the Nuclear Factor-Kappa B Pathway in Mouse Spinal Cord Motoneurons.

PubMed

Arumugam, Saravanan; Mincheva-Tasheva, Stefka; Periyakaruppiah, Ambika; de la Fuente, Sandra; Soler, Rosa M; Garcera, Ana

2018-06-01

Survival motor neuron (SMN) protein deficiency causes the genetic neuromuscular disorder spinal muscular atrophy (SMA), characterized by spinal cord motoneuron degeneration. Since SMN protein level is critical to disease onset and severity, analysis of the mechanisms involved in SMN stability is one of the central goals of SMA research. Here, we describe the role of several members of the NF-κB pathway in regulating SMN in motoneurons. NF-κB is one of the main regulators of motoneuron survival and pharmacological inhibition of NF-κB pathway activity also induces mouse survival motor neuron (Smn) protein decrease. Using a lentiviral-based shRNA approach to reduce the expression of several members of NF-κB pathway, we observed that IKK and RelA knockdown caused Smn reduction in mouse-cultured motoneurons whereas IKK or RelB knockdown did not. Moreover, isolated motoneurons obtained from the severe SMA mouse model showed reduced protein levels of several NF-κB members and RelA phosphorylation. We describe the alteration of NF-κB pathway in SMA cells. In the context of recent studies suggesting regulation of altered intracellular pathways as a future pharmacological treatment of SMA, we propose the NF-κB pathway as a candidate in this new therapeutic approach.

Celecoxib increases SMN and survival in a severe spinal muscular atrophy mouse model via p38 pathway activation.

PubMed

Farooq, Faraz; Abadía-Molina, Francisco; MacKenzie, Duncan; Hadwen, Jeremiah; Shamim, Fahad; O'Reilly, Sean; Holcik, Martin; MacKenzie, Alex

2013-09-01

The loss of functional Survival Motor Neuron (SMN) protein due to mutations or deletion in the SMN1 gene causes autosomal recessive neurodegenerative spinal muscle atrophy (SMA). A potential treatment strategy for SMA is to upregulate the amount of SMN protein originating from the highly homologous SMN2 gene, compensating in part for the absence of the functional SMN1 gene. We have previously shown that in vitro activation of the p38 pathway stabilizes and increases SMN mRNA levels leading to increased SMN protein levels. In this report, we explore the impact of the p38 activating, FDA-approved, blood brain barrier permeating compound celecoxib on SMN levels in vitro and in a mouse model of SMA. We demonstrate a significant induction of SMN protein levels in human and mouse neuronal cells upon treatment with celecoxib. We show that activation of the p38 pathway by low doses celecoxib increases SMN protein in a HuR protein-dependent manner. Furthermore, celecoxib treatment induces SMN expression in brain and spinal cord samples of wild-type mice in vivo. Critically, celecoxib treatment increased SMN levels, improved motor function and enhanced survival in a severe SMA mouse model. Our results identify low dose celecoxib as a potential new member of the SMA therapeutic armamentarium.

Reduced Performance During a Sentence Repetition Task by Continuous Theta-Burst Magnetic Stimulation of the Pre-supplementary Motor Area

PubMed Central

Dietrich, Susanne; Hertrich, Ingo; Müller-Dahlhaus, Florian; Ackermann, Hermann; Belardinelli, Paolo; Desideri, Debora; Seibold, Verena C.; Ziemann, Ulf

2018-01-01

The pre-supplementary motor area (pre-SMA) is engaged in speech comprehension under difficult circumstances such as poor acoustic signal quality or time-critical conditions. Previous studies found that left pre-SMA is activated when subjects listen to accelerated speech. Here, the functional role of pre-SMA was tested for accelerated speech comprehension by inducing a transient “virtual lesion” using continuous theta-burst stimulation (cTBS). Participants were tested (1) prior to (pre-baseline), (2) 10 min after (test condition for the cTBS effect), and (3) 60 min after stimulation (post-baseline) using a sentence repetition task (formant-synthesized at rates of 8, 10, 12, 14, and 16 syllables/s). Speech comprehension was quantified by the percentage of correctly reproduced speech material. For high speech rates, subjects showed decreased performance after cTBS of pre-SMA. Regarding the error pattern, the number of incorrect words without any semantic or phonological similarity to the target context increased, while related words decreased. Thus, the transient impairment of pre-SMA seems to affect its inhibitory function that normally eliminates erroneous speech material prior to speaking or, in case of perception, prior to encoding into a semantically/pragmatically meaningful message. PMID:29896086

Long-term exercise-specific neuroprotection in spinal muscular atrophy-like mice.

PubMed

Chali, Farah; Desseille, Céline; Houdebine, Léo; Benoit, Evelyne; Rouquet, Thaïs; Bariohay, Bruno; Lopes, Philippe; Branchu, Julien; Della Gaspera, Bruno; Pariset, Claude; Chanoine, Christophe; Charbonnier, Frédéric; Biondi, Olivier

2016-04-01

The real impact of physical exercise parameters, i.e. intensity, type of contraction and solicited energetic metabolism, on neuroprotection in the specific context of neurodegeneration remains poorly explored. In this study behavioural, biochemical and cellular analyses were conducted to compare the effects of two different long-term exercise protocols, high intensity swimming and low intensity running, on motor units of a type 3 spinal muscular atrophy (SMA)-like mouse model. Our data revealed a preferential SMA-induced death of intermediate and fast motor neurons which was limited by the swimming protocol only, suggesting a close relationship between neuron-specific protection and their activation levels by specific exercise. The exercise-induced neuroprotection was independent of SMN protein expression and associated with specific metabolic and behavioural adaptations with notably a swimming-induced reduction of muscle fatigability. Our results provide new insight into the motor units' adaptations to different physical exercise parameters and will contribute to the design of new active physiotherapy protocols for patient care. Spinal muscular atrophy (SMA) is a group of autosomal recessive neurodegenerative diseases differing in their clinical outcome, characterized by the specific loss of spinal motor neurons, caused by insufficient level of expression of the protein survival of motor neuron (SMN). No cure is at present available for SMA. While physical exercise might represent a promising approach for alleviating SMA symptoms, the lack of data dealing with the effects of different exercise types on diseased motor units still precludes the use of active physiotherapy in SMA patients. In the present study, we have evaluated the efficiency of two long-term physical exercise paradigms, based on either high intensity swimming or low intensity running, in alleviating SMA symptoms in a mild type 3 SMA-like mouse model. We found that 10 months' physical training induced significant benefits in terms of resistance to muscle damage, energetic metabolism, muscle fatigue and motor behaviour. Both exercise types significantly enhanced motor neuron survival, independently of SMN expression, leading to the maintenance of neuromuscular junctions and skeletal muscle phenotypes, particularly in the soleus, plantaris and tibialis of trained mice. Most importantly, both exercises significantly improved neuromuscular excitability properties. Further, all these training-induced benefits were quantitatively and qualitatively related to the specific characteristics of each exercise, suggesting that the related neuroprotection is strongly dependent on the specific activation of some motor neuron subpopulations. Taken together, the present data show significant long-term exercise benefits in type 3 SMA-like mice providing important clues for designing rehabilitation programmes in patients. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Micro-Ball-Lens Optical Switch Driven by SMA Actuator

NASA Technical Reports Server (NTRS)

Yang, Eui-Hyeok

2003-01-01

The figure is a simplified cross section of a microscopic optical switch that was partially developed at the time of reporting the information for this article. In a fully developed version, light would be coupled from an input optical fiber to one of two side-by-side output optical fibers. The optical connection between the input and the selected output fiber would be made via a microscopic ball lens. Switching of the optical connection from one output fiber to another would be effected by using a pair of thin-film shape-memory-alloy (SMA) actuators to toggle the lens between two resting switch positions. There are many optical switches some made of macroscopic parts by conventional fabrication techniques and some that are microfabricated and, hence, belong to the class of microelectromechanical systems (MEMS). Conventionally fabricated optical switches tend to be expensive. MEMS switches can be mass-produced at relatively low cost, but their attractiveness has been diminished by the fact that, heretofore, MEMS switches have usually been found to exhibit high insertion losses. The present switch is intended to serve as a prototype of low-loss MEMS switches. In addition, this is the first reported SMA-based optical switch. The optical fibers would be held in V grooves in a silicon frame. The lens would have a diameter of 1 m; it would be held by, and positioned between, the SMA actuators, which would be made of thin films of TiNi alloy. Although the SMA actuators are depicted here as having simple shapes for the sake of clarity of illustration, the real actuators would have complex, partly net-like shapes. With the exception of the lens and the optical fibers, the SMA actuators and other components of the switch would be made by microfabrication techniques. The components would be assembled into a sandwich structure to complete the fabrication of the switch. To effect switching, an electric current would be passed through one of the SMA actuators to heat it above its transition temperature, thereby causing it to deform to a different "remembered" shape. The two SMA actuators would be stiff enough that once switching had taken place and the electrical current was turned off, the lens would remain latched in the most recently selected position. In a test, the partially developed switch exhibited an insertion loss of only -1.9 dB and a switching contrast of 70 dB. One the basis of prior research on SMA actuators and assuming a lens displacement of 125 m between extreme positions, it has been estimated that the fully developed switch would be capable of operating at a frequency as high as 10 Hz.

Research notes : SMA, stone matrix resists ruts.

DOT National Transportation Integrated Search

2003-08-01

The first Oregon Department of Transportation SMA placement was part of a pilot project constructed on Interstate 5 (I-5) in 1996. : Four asphalt mixes were placed over a 3-mile section of concrete to evaluate the use of asphalt overlays for repair o...

A performance baseline for stone matrix asphalt.

DOT National Transportation Integrated Search

2005-01-01

In 2003, Virginia launched an expanded commitment to stone matrix asphalt (SMA). By the end of 2004, contracts that encompassed nearly 400,000 tons of SMA had been awarded and most of the material produced and placed. During this 2-year timeframe, mo...

Spinal muscular atrophy type I and the dual role of viruses: An interview with Professor Basil T. Darras, Professor of Neurology (Pediatrics) at Harvard Medical School

PubMed Central

Mammas, Ioannis N.; Spandidos, Demetrios A.

2018-01-01

According to Professor Basil T. Darras, Professor of Neurology (Pediatrics) at Harvard Medical School and Director of the Spinal Muscular Atrophy (SMA) Program at Boston Children's Hospital in Boston (MA, USA), the diagnosis of SMA type I is clinical and is based on detailed general physical and neurological examinations. SMA type I remains the most common genetic disease resulting in death in infancy and is really devastating for the child, the parents, as well as the medical professionals with the privilege of caring for patients with SMA and their parents. The proposed management options include: i) no respiratory support; ii) non-invasive ventilation; and iii) tracheotomy with mechanical ventilation. Deciding, which option is the best, is indeed a very personal decision. The optimal clinical care should be extremely mindful of parents' wishes and management goals with regard to the quality of life. Since the end of 2016 in the USA, and recently in Europe, there exists the possibility of accessing a novel treatment drug for SMA, namely Nusinersen. This antisense oligonucleotide is administered intrathecally and increases the production of the fully functional SMN protein, thus improving motor function, the quality of life and survival. Among the ongoing clinical trials, oral treatment with RG7916, a small molecule SMN2 splicing modifier, appears to be really promising. Gene therapy using viral vectors is expected to offer an ‘one and done’ therapy and possibly a cure, if administered early in life, before any symptoms appear. It is really interesting that viruses, which at the moment are the cause of death of children with SMA, if genetically modified, may be used for their treatment. PMID:29556256

Social/economic costs and health-related quality of life in patients with spinal muscular atrophy (SMA) in Spain.

PubMed

López-Bastida, Julio; Peña-Longobardo, Luz María; Aranda-Reneo, Isaac; Tizzano, Eduardo; Sefton, Mark; Oliva-Moreno, Juan

2017-08-18

The aim of this study was to determine the economic burden and health-related quality of life (HRQOL) of patients with Spinal Muscular Atrophy (SMA) and their caregivers in Spain. This was a cross-sectional and retrospective study of patients diagnosed with SMA in Spain. We adopted a bottom up, prevalence approach design to study patients with SMA. The patient's caregivers completed an anonymous questionnaire regarding their socio-demographic characteristics, use of healthcare services and non-healthcare services. Costs were estimated from a societal perspective (including healthcare costs and non-healthcare costs), and health-related quality of life (HRQOL) was assessed using the EQ-5D questionnaire. The main caregivers also answered a questionnaire on their characteristics and on their HRQOL. A total of 81 caregivers of patients with different subtypes of SMA completed the questionnaire. Based on the reference unitary prices for 2014, the average annual costs per patient were € 33,721. Direct healthcare costs were € 10,882 (representing around 32.3% of the total cost) and the direct non-healthcare costs were € 22,839 (67.7% of the total cost). The mean EQ-5D social tariff score for patients was 0.16, and the mean score of the EQ-5D visual analogue scale was 54. The mean EQ-5D social tariff score for caregivers was 0.49 and their mean score on the EQ-5D visual analogue scale was 69. The results highlight the burden that SMA has in terms of costs and decreased HRQOL, not only for patients but also for their caregivers. In particular, the substantial social/economic burden is mostly attributable to the high direct non-healthcare costs.

Thermomechanical Characterization and Modeling of Superelastic Shape Memory Alloy Beams and Frames

NASA Astrophysics Data System (ADS)

Watkins, Ryan

Of existing applications, the majority of shape memory alloy (SMA) devices consist of beam (orthodontic wire, eye glasses frames, catheter guide wires) and framed structures (cardiovascular stents, vena cava filters). Although uniaxial tension data is often sufficient to model basic beam behavior (which has been the main focus of the research community), the tension-compression asymmetry and complex phase transformation behavior of SMAs suggests more information is necessary to properly model higher complexity states of loading. In this work, SMA beams are experimentally characterized under general loading conditions (including tension, compression, pure bending, and buckling); furthermore, a model is developed with respect to general beam deformation based on the relevant phenomena observed in the experimental characterization. Stress induced phase transformation within superelastic SMA beams is shown to depend on not only the loading mode, but also kinematic constraints imposed by beam geometry (such as beam cross-section and length). In the cases of tension and pure bending, the structural behavior is unstable and corresponds to phase transformation localization and propagation. This unstable behavior is the result of a local level up--down--up stress/strain response in tension, which is measured here using a novel composite-based experimental technique. In addition to unstable phase transformation, intriguing post-buckling straightening is observed in short SMA columns during monotonic loading (termed unbuckling here). Based on this phenomenological understanding of SMA beam behavior, a trilinear based material law is developed in the context of a Shanley column model and is found to capture many of the relevant features of column buckling, including the experimentally observed unbuckling behavior. Due to the success of this model, it is generalized within the context of beam theory and, in conjunction with Bloch wave stability analysis, is used to model and design SMA honeycombs.

Orthopedic Management of Scoliosis by Garches Brace and Spinal Fusion in SMA Type 2 Children.

PubMed

Catteruccia, Michela; Vuillerot, Carole; Vaugier, Isabelle; Leclair, Danielle; Azzi, Viviane; Viollet, Louis; Estournet, Brigitte; Bertini, Enrico; Quijano-Roy, Susana

2015-11-21

Scoliosis is the most debilitating issue in SMA type 2 patients. No evidence confirms the efficacy of Garches braces (GB) to delay definitive spinal fusion. Compare orthopedic and pulmonary outcomes in children with SMA type 2 function to management. We carried out a monocentric retrospective study on 29 SMA type 2 children who had spinal fusion between 1999 and 2009. Patients were divided in 3 groups: group 1-French patients (12 children) with a preventive use of GB; group 2-French patients (10 children) with use of GB after the beginning of the scoliosis curve; and group 3-Italian patients (7 children) with use of GB after the beginning of the scoliosis curve referred to our centre to perform orthopedic preoperative management. Mean preoperative and postoperative Cobb angle were significantly lower in the group 1 of proactively braced than in group 2 or 3 (Anova p = 0.03; Kruskal Wallis test p = 0.05). Better surgical results were observed in patients with a minor preoperative Cobb angle (r = 0.92 p <  0.0001). Fewer patients in the group 1 proactively braced required trunk casts and/or halo traction and an additional anterior fusion in comparison with patients in the group 2 and 3. Moreover, major complications tend to be less in the group 1 proactively braced. No significant differences were found between groups in pulmonary outcome measures. A proactive orthotic management may improve orthopedic outcome in SMA type 2. Further prospective studies comparing SMA management are needed to confirm these results. Therapeutic Level III. See Instructions to Authors on jbjs.org for a complete description of levels of evidence (Retrospective comparative study).

Dynamic aftereffects in supplementary motor network following inhibitory transcranial magnetic stimulation protocols.

PubMed

Ji, Gong-Jun; Yu, Fengqiong; Liao, Wei; Wang, Kai

2017-04-01

The supplementary motor area (SMA) is a key node of the motor network. Inhibitory repetitive transcranial magnetic stimulation (rTMS) of the SMA can potentially improve movement disorders. However, the aftereffects of inhibitory rTMS on brain function remain largely unknown. Using a single-blind, crossover within-subject design, we investigated the role of aftereffects with two inhibitory rTMS protocols [1800 pulses of either 1-Hz repetitive stimulation or continuous theta burst stimulation (cTBS)] on the left SMA. A total of 19 healthy volunteers participated in the rTMS sessions on 2 separate days. Firstly, short-term aftereffects were estimated at three levels (functional connectivity, local activity, and network properties) by comparing the resting-state functional magnetic resonance imaging datasets (9min) acquired before and after each rTMS session. Local activity and network properties were not significantly altered by either protocol. Functional connectivity within the SMA network was increased (in the left paracentral gyrus) by 1-Hz stimulation and decreased (in the left inferior frontal gyrus and SMA/middle cingulate cortex) by cTBS. The subsequent three-way analysis of variance (site×time×protocol) did not show a significant interaction effect or "protocol" main effect, suggesting that the two protocols share an underlying mechanism. Secondly, sliding-window analysis was used to evaluate the dynamic features of aftereffects in the ~29min after the end of stimulation. Aftereffects were maintained for a maximum of 9.8 and 6.6min after the 1-Hz and cTBS protocols, respectively. In summary, this study revealed topographical and temporal aftereffects in the SMA network following inhibitory rTMS protocols, providing valuable information for their application in future neuroscience and clinical studies. Copyright © 2017 Elsevier Inc. All rights reserved.

The craniosacral progression of muscle development influences the emergence of neuromuscular junction alterations in a severe murine model for spinal muscular atrophy.

PubMed

Voigt, Tilman; Neve, Anuja; Schümperli, Daniel

2014-06-01

As 4-day-old mice of the severe spinal muscular atrophy (SMA) model (dying at 5-8 days) display pronounced neuromuscular changes in the diaphragm but not the soleus muscle, we wanted to gain more insight into the relationship between muscle development and the emergence of pathological changes and additionally to analyse intercostal muscles which are affected in human SMA. Structures of muscle fibres and neuromuscular junctions (NMJs) of the diaphragm, intercostal and calf muscles of prenatal (E21) and postnatal (P0 and P4) healthy and SMA mice were analysed by light and transmission electron microscopy. NMJ innervation was studied by whole mount immunofluorescence in diaphragms of P4 mice. During this period, the investigated muscles still show a significant neck-to-tail developmental gradient. The diaphragm and calf muscles are most and least advanced, respectively, with respect to muscle fibre fusion and differentiation. The number and depth of subsynaptic folds increases, and perisynaptic Schwann cells (PSCs) acquire a basal lamina on their outer surface. Subsynaptic folds are connected to an extensive network of tubules and beaded caveolae, reminiscent of the T system in adult muscle. Interestingly, intercostal muscles from P4 SMA mice show weaker pathological involvement (that is, vacuolization of PSCs and perineurial cells) than those previously described by us for the diaphragm, whereas calf muscles show no pathological changes. SMA-related alterations appear to occur only when the muscles have reached a certain developmental maturity. Moreover, glial cells, in particular PSCs, play an important role in SMA pathogenesis. © 2013 British Neuropathological Society.

SMN blood levels in a Porcine Model of Spinal Muscular Atrophy

PubMed Central

Iyer, Chitra; Wang, Xueqian; Renusch, Samantha R.; Duque, Sandra I.; Wehr, Allison M.; Mo, Xiaokui-Molly; McGovern, Vicki L.; Arnold, W. David; Burghes, Arthur H.M.; Kolb, Stephen J.

2017-01-01

Spinal Muscular Atrophy (SMA) is an autosomal recessive motor neuron disease that results in loss of spinal motor neurons, muscular weakness and, in severe cases, respiratory failure and death. SMA is caused by a deletion or mutation of the SMN1 gene and retention of the SMN2 gene that leads to low SMN expression levels. The measurement of SMN mRNA levels in peripheral blood samples has been used in SMA clinical studies as a pharmacodynamic biomarker for response to therapies designed to increase SMN levels. We recently developed a postnatal porcine model of SMA by the viral delivery of a short-hairpin RNA (shRNA) targeting porcine pSMN. scAAV9-mediated knockdown of pSMN mRNA at postnatal day 5 reliably resulted in denervation, weakness and motor neuron and ventral root axon loss that began 3–4 weeks after viral delivery, and this phenotype could be ameliorated by subsequent viral delivery of human SMN (hSMN). To determine if the effect of modulating SMN levels using gene therapy can be measured in blood, we measured expression of pSMN mRNA and hSMN mRNA by quantitative droplet digital PCR (ddPCR). We found that the endogenous expression of pSMN mRNA in blood increases in the first month of life. However, there were no significant differences in blood levels of pSMN mRNA after knock-down or of human SMN mRNA after gene therapy. Our results, obtained in a large animal model of SMA that is similar in size and anatomy to human infants, suggest that measurement of SMN mRNA levels in blood may not be informative in SMA clinical trials involving intrathecal delivery of SMN-modulating therapies. PMID:28269795

mRNA trans-splicing in gene therapy for genetic diseases.

PubMed

Berger, Adeline; Maire, Séverine; Gaillard, Marie-Claude; Sahel, José-Alain; Hantraye, Philippe; Bemelmans, Alexis-Pierre

2016-07-01

Spliceosome-mediated RNA trans-splicing, or SMaRT, is a promising strategy to design innovative gene therapy solutions for currently intractable genetic diseases. SMaRT relies on the correction of mutations at the post-transcriptional level by modifying the mRNA sequence. To achieve this, an exogenous RNA is introduced into the target cell, usually by means of gene transfer, to induce a splice event in trans between the exogenous RNA and the target endogenous pre-mRNA. This produces a chimeric mRNA composed partly of exons of the latter, and partly of exons of the former, encoding a sequence free of mutations. The principal challenge of SMaRT technology is to achieve a reaction as complete as possible, i.e., resulting in 100% repairing of the endogenous mRNA target. The proof of concept of SMaRT feasibility has already been established in several models of genetic diseases caused by recessive mutations. In such cases, in fact, the repair of only a portion of the mutant mRNA pool may be sufficient to obtain a significant therapeutic effect. However in the case of dominant mutations, the target cell must be freed from the majority of mutant mRNA copies, requiring a highly efficient trans-splicing reaction. This likely explains why only a few examples of SMaRT approaches targeting dominant mutations are reported in the literature. In this review, we explain in details the mechanism of trans-splicing, review the different strategies that are under evaluation to lead to efficient trans-splicing, and discuss the advantages and limitations of SMaRT. WIREs RNA 2016, 7:487-498. doi: 10.1002/wrna.1347 For further resources related to this article, please visit the WIREs website. © 2016 The Authors. WIREs RNA published by Wiley Periodicals, Inc.

Resting-State Hyperperfusion of the Supplementary Motor Area in Catatonia.

PubMed

Walther, Sebastian; Schäppi, Lea; Federspiel, Andrea; Bohlhalter, Stephan; Wiest, Roland; Strik, Werner; Stegmayer, Katharina

2017-09-01

Catatonia is a psychomotor syndrome that not only frequently occurs in the context of schizophrenia but also in other conditions. The neural correlates of catatonia remain unclear due to small-sized studies. We therefore compared resting-state cerebral blood flow (rCBF) and gray matter (GM) density between schizophrenia patients with current catatonia and without catatonia and healthy controls. We included 42 schizophrenia patients and 41 controls. Catatonia was currently present in 15 patients (scoring >2 items on the Bush Francis Catatonia Rating Scale screening). Patients did not differ in antipsychotic medication or positive symptoms. We acquired whole-brain rCBF using arterial spin labeling and GM density. We compared whole-brain perfusion and GM density over all and between the groups using 1-way ANCOVAs (F and T tests). We found a group effect (F test) of rCBF within bilateral supplementary motor area (SMA), anterior cingulate cortex, dorsolateral prefrontal cortex, left interior parietal lobe, and cerebellum. T tests indicated 1 cluster (SMA) to be specific to catatonia. Moreover, catatonia of excited and retarded types differed in SMA perfusion. Furthermore, increased catatonia severity was associated with higher perfusion in SMA. Finally, catatonia patients had a distinct pattern of GM density reduction compared to controls with prominent GM loss in frontal and insular cortices. SMA resting-state hyperperfusion is a marker of current catatonia in schizophrenia. This is highly compatible with a dysregulated motor system in catatonia, particularly affecting premotor areas. Moreover, SMA perfusion was differentially altered in retarded and excited catatonia subtypes, arguing for distinct pathobiology. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

An fMRI study of finger tapping in children and adults.

PubMed

Turesky, Ted K; Olulade, Olumide A; Luetje, Megan M; Eden, Guinevere F

2018-04-02

Functional brain imaging studies have characterized the neural bases of voluntary movement for finger tapping in adults, but equivalent information for children is lacking. When contrasted to adults, one would expect children to have relatively greater activation, reflecting compensation for an underdeveloped motor system combined with less experience in the execution of voluntary movement. To test this hypothesis, we acquired functional magnetic resonance imaging (fMRI) data on 17 healthy right-handed children (7.48 ± 0.66 years) and 15 adults (24.9 ± 2.9 years) while they performed an irregularly paced finger-tapping task in response to a visual cue (left- and right-hand examined separately). Whole-brain within-group analyses revealed that finger tapping in either age group and for either hand activated contralateral SM1, SMA, ipsilateral anterior cerebellum, and occipital cortices. We used an ANOVA factorial design to test for main effects of Age Group (children vs adults), Hand (left vs. right), and their interactions. For main effects of Age Group, children showed relatively greater activity in left SM1 (extending into bilateral SMA), and, surprisingly, adults exhibited relatively greater activity in right pre-SMA/SMA (extending into left pre-SMA/SMA), right lateral globus pallidus, left putamen, and right anterior cerebellum. The interaction of Age Group × Hand revealed that while both groups activated right SM1 during left finger tapping and exhibited signal decreases (i.e., below fixation baseline) during right finger tapping, both these responses were attenuated in children relative to adults. These data provide an important foundation by which to study children with motor disorders. © 2018 Wiley Periodicals, Inc.

Spinal muscular atrophy type I and the dual role of viruses: An interview with Professor Basil T. Darras, Professor of Neurology (Pediatrics) at Harvard Medical School.

PubMed

Mammas, Ioannis N; Spandidos, Demetrios A

2018-04-01

According to Professor Basil T. Darras, Professor of Neurology (Pediatrics) at Harvard Medical School and Director of the Spinal Muscular Atrophy (SMA) Program at Boston Children's Hospital in Boston (MA, USA), the diagnosis of SMA type I is clinical and is based on detailed general physical and neurological examinations. SMA type I remains the most common genetic disease resulting in death in infancy and is really devastating for the child, the parents, as well as the medical professionals with the privilege of caring for patients with SMA and their parents. The proposed management options include: i) no respiratory support; ii) non-invasive ventilation; and iii) tracheotomy with mechanical ventilation. Deciding, which option is the best, is indeed a very personal decision. The optimal clinical care should be extremely mindful of parents' wishes and management goals with regard to the quality of life. Since the end of 2016 in the USA, and recently in Europe, there exists the possibility of accessing a novel treatment drug for SMA, namely Nusinersen. This antisense oligonucleotide is administered intrathecally and increases the production of the fully functional SMN protein, thus improving motor function, the quality of life and survival. Among the ongoing clinical trials, oral treatment with RG7916, a small molecule SMN2 splicing modifier, appears to be really promising. Gene therapy using viral vectors is expected to offer an 'one and done' therapy and possibly a cure, if administered early in life, before any symptoms appear. It is really interesting that viruses, which at the moment are the cause of death of children with SMA, if genetically modified, may be used for their treatment.

Antisense Oligonucleotides for the Treatment of Spinal Muscular Atrophy

PubMed Central

Porensky, Paul N.

2013-01-01

Abstract Spinal muscular atrophy (SMA) is an autosomal recessive disease affecting ∼1 in 10,000 live births. The most striking component is the loss of α-motor neurons in the ventral horn of the spinal cord, resulting in progressive paralysis and eventually premature death. There is no current treatment paradigm other than supportive care, though the past 15 years has seen a striking advancement in understanding of both SMA genetics and molecular mechanisms. A variety of disease-modifying interventions are rapidly bridging the translational gap from the laboratory to clinical trials, including the application of antisense oligonucleotide (ASO) therapy for the correction of aberrant RNA splicing characteristic of SMA. Survival motor neuron (SMN) is a ubiquitously expressed 38-kD protein. Humans have two genes that produce SMN, SMN1 and SMN2, the former of which is deleted or nonfunctional in the majority of patients with SMA. These two genes are nearly identical with one exception, a C to T transition (C6T) within exon 7 of SMN2. C6T disrupts a modulator of splicing, leading to the exclusion of exon 7 from ∼90% of the mRNA transcript. The resultant truncated Δ7SMN protein does not oligomerize efficiently and is rapidly degraded. SMA can therefore be considered a disease of too little SMN protein. A number of cis-acting splice modifiers have been identified in the region of exon 7, the steric block of which enhances the retention of the exon and a resultant full-length mRNA sequence. ASOs targeted to these splice motifs have shown impressive phenotype rescue in multiple SMA mouse models. PMID:23544870

Learning about Spinal Muscular Atrophy

MedlinePlus

... causes the disorder. Top of page NHGRI Clinical Research on Spinal Muscular Atrophy Currently, NHGRI is not conducting studies on SMA. The National Institutes of Health is conducting clinical trials identified as enrolling individuals with SMA: Quantitative Analysis of SMN1 and SMN2 Gene Based on ...

Development of a Mixture Design Procedure for Stone Matrix Asphalt

DOT National Transportation Integrated Search

1997-03-01

Stone Matrix Asphalt (SMA) has been used successfully in Europe for over 20 : years to provide better rutting resistance and to resist studded tire wear. : Since 1991, the use of SMA has increased steadily in the United States. At : present, some sta...

Microstructural characteristics and biocompatibility of a Type-B carbonated hydroxyapatite coating deposited on NiTi shape memory alloy.

PubMed

Chu, Chenglin; Hu, T; Yin, L H; Pu, Y P; Dong, Y S; Lin, P H; Chung, C Y; Yeung, K W K; Chu, P K

2009-01-01

Microstructural characteristics and biocompatibility of a Type-B carbonated hydroxyapatite (HA) coating prepared on NiTi SMA by biomimetic deposition were characterized using XRD, SEM, XPS, FTIR and in vitro studies including hemolysis test, MTT cytotoxicity test and fibroblasts cytocompatibility test. It is found CO(3)(2-) groups were present as substitution of PO(4)(3-) anions in HA crystal lattice due to Type-B carbonate. The growth of Type-B carbonated HA coating in SBF containing HCO(3)(-) ions is stable during all periods of biomimetic deposition. The carbonated HA coating has better blood compatibility than the chemically-polished NiTi SMA. There was a good cell adhesion to this HA coating surface and cell proliferation in the vicinity of the coating was better than that for the chemically-polished NiTi SMA. Thus biomimetic deposition of this carbonated HA coating is a promising way to improve the biocompatibility of NiTi SMA for implant applications.

Heuristics for connectivity-based brain parcellation of SMA/pre-SMA through force-directed graph layout.

PubMed

Crippa, Alessandro; Cerliani, Leonardo; Nanetti, Luca; Roerdink, Jos B T M

2011-02-01

We propose the use of force-directed graph layout as an explorative tool for connectivity-based brain parcellation studies. The method can be used as a heuristic to find the number of clusters intrinsically present in the data (if any) and to investigate their organisation. It provides an intuitive representation of the structure of the data and facilitates interactive exploration of properties of single seed voxels as well as relations among (groups of) voxels. We validate the method on synthetic data sets and we investigate the changes in connectivity in the supplementary motor cortex, a brain region whose parcellation has been previously investigated via connectivity studies. This region is supposed to present two easily distinguishable connectivity patterns, putatively denoted by SMA (supplementary motor area) and pre-SMA. Our method provides insights with respect to the connectivity patterns of the premotor cortex. These present a substantial variation among subjects, and their subdivision into two well-separated clusters is not always straightforward. Copyright © 2010 Elsevier Inc. All rights reserved.

Inhibition of Apoptosis Blocks Human Motor Neuron Cell Death in a Stem Cell Model of Spinal Muscular Atrophy

PubMed Central

Heins, Brittany M.; McGivern, Jered V.; Ornelas, Loren; Svendsen, Clive N.

2012-01-01

Spinal muscular atrophy (SMA) is a genetic disorder caused by a deletion of the survival motor neuron 1 gene leading to motor neuron loss, muscle atrophy, paralysis, and death. We show here that induced pluripotent stem cell (iPSC) lines generated from two Type I SMA subjects–one produced with lentiviral constructs and the second using a virus-free plasmid–based approach–recapitulate the disease phenotype and generate significantly fewer motor neurons at later developmental time periods in culture compared to two separate control subject iPSC lines. During motor neuron development, both SMA lines showed an increase in Fas ligand-mediated apoptosis and increased caspase-8 and-3 activation. Importantly, this could be mitigated by addition of either a Fas blocking antibody or a caspase-3 inhibitor. Together, these data further validate this human stem cell model of SMA, suggesting that specific inhibitors of apoptotic pathways may be beneficial for patients. PMID:22723941

Development and Characterization of High Performance Shape Memory Alloy Coatings for Structural Aerospace Applications.

PubMed

Exarchos, Dimitrios A; Dalla, Panagiota T; Tragazikis, Ilias K; Dassios, Konstantinos G; Zafeiropoulos, Nikolaos E; Karabela, Maria M; De Crescenzo, Carmen; Karatza, Despina; Musmarra, Dino; Chianese, Simeone; Matikas, Theodore E

2018-05-18

This paper presents an innovative approach, which enables control of the mechanical properties of metallic components by external stimuli to improve the mechanical behavior of aluminum structures in aeronautical applications. The approach is based on the exploitation of the shape memory effect of novel Shape Memory Alloy (SMA) coatings deposited on metallic structural components, for the purpose of relaxing the stress of underlying structures by simple heating at field-feasible temperatures, therefore enhancing their structural integrity and increasing their stiffness and rigidity while allowing them to withstand expected loading conditions safely. Numerical analysis provided an insight in the expected response of the SMA coating and of the SMA-coated element, while the dependence of alloy composition and heat treatment on the experienced shape memory effect were investigated experimentally. A two-phase process is proposed for deposition of the SMA coating in an order that induces beneficial stress relaxation to the underlying structure through the shape memory effect.

MOSFET Switching Circuit Protects Shape Memory Alloy Actuators

NASA Technical Reports Server (NTRS)

Gummin, Mark A.

2011-01-01

A small-footprint, full surface-mount-component printed circuit board employs MOSFET (metal-oxide-semiconductor field-effect transistor) power switches to switch high currents from any input power supply from 3 to 30 V. High-force shape memory alloy (SMA) actuators generally require high current (up to 9 A at 28 V) to actuate. SMA wires (the driving element of the actuators) can be quickly overheated if power is not removed at the end of stroke, which can damage the wires. The new analog driver prevents overheating of the SMA wires in an actuator by momentarily removing power when the end limit switch is closed, thereby allowing complex control schemes to be adopted without concern for overheating. Either an integral pushbutton or microprocessor-controlled gate or control line inputs switch current to the actuator until the end switch line goes from logic high to logic low state. Power is then momentarily removed (switched off by the MOSFET). The analog driver is suited to use with nearly any SMA actuator.

Shape Memory Alloy Actuator Design: CASMART Collaborative Best Practices

NASA Technical Reports Server (NTRS)

Benafan, Othmane; Brown, Jeff; Calkins, F. Tad; Kumar, Parikshith; Stebner, Aaron; Turner, Travis; Vaidyanathan, Raj; Webster, John; Young, Marcus L.

2011-01-01

Upon examination of shape memory alloy (SMA) actuation designs, there are many considerations and methodologies that are common to them all. A goal of CASMART's design working group is to compile the collective experiences of CASMART's member organizations into a single medium that engineers can then use to make the best decisions regarding SMA system design. In this paper, a review of recent work toward this goal is presented, spanning a wide range of design aspects including evaluation, properties, testing, modeling, alloy selection, fabrication, actuator processing, design optimization, controls, and system integration. We have documented each aspect, based on our collective experiences, so that the design engineer may access the tools and information needed to successfully design and develop SMA systems. Through comparison of several case studies, it is shown that there is not an obvious single, linear route a designer can adopt to navigate the path of concept to product. SMA engineering aspects will have different priorities and emphasis for different applications.

Creation of smart composites using an embroidery machine

NASA Astrophysics Data System (ADS)

Torii, Nobuhiro; Oka, Kosuke; Ikeda, Tadashige

2016-04-01

A smart composite with functional fibers and reinforcement fibers optimally placed with an embroidery machine was created. Fiber orientation affects mechanical properties of composite laminates significantly. Accordingly, if the fibers can be placed along a desired curved path, fiber reinforced plastic (FRP) structures can be designed more lightly and more sophisticatedly. To this end a tailored fiber placement method using the embroidery machine have been studied. To add functions to the FRP structures, shape memory alloy (SMA) wires were placed as functional fibers. First, for a certain purpose the paths of the reinforcement fibers and the SMA wires were simultaneously optimized in analysis. Next, the reinforcement fibers and tubes with the SMA wires were placed on fabrics by using the embroidery machine and this fabric was impregnated with resin by using the vacuum assisted resin transfer molding method. This smart composite was activated by applying voltage to the SMA wires. Fundamental properties of the smart composite were examined and the feasibility of the proposed creation method was shown.

Revised upper limb module for spinal muscular atrophy: Development of a new module.

PubMed

Mazzone, Elena S; Mayhew, Anna; Montes, Jacqueline; Ramsey, Danielle; Fanelli, Lavinia; Young, Sally Dunaway; Salazar, Rachel; De Sanctis, Roberto; Pasternak, Amy; Glanzman, Allan; Coratti, Giorgia; Civitello, Matthew; Forcina, Nicola; Gee, Richard; Duong, Tina; Pane, Marika; Scoto, Mariacristina; Pera, Maria Carmela; Messina, Sonia; Tennekoon, Gihan; Day, John W; Darras, Basil T; De Vivo, Darryl C; Finkel, Richard; Muntoni, Francesco; Mercuri, Eugenio

2017-06-01

There is a growing need for a robust clinical measure to assess upper limb motor function in spinal muscular atrophy (SMA), as the available scales lack sensitivity at the extremes of the clinical spectrum. We report the development of the Revised Upper Limb Module (RULM), an assessment specifically designed for upper limb function in SMA patients. An international panel with specific neuromuscular expertise performed a thorough review of scales currently available to assess upper limb function in SMA. This review facilitated a revision of the existing upper limb function scales to make a more robust clinical scale. Multiple revisions of the scale included statistical analysis and captured clinically relevant changes to fulfill requirements by regulators and advocacy groups. The resulting RULM scale shows good reliability and validity, making it a suitable tool to assess upper extremity function in the SMA population for multi-center clinical research. Muscle Nerve 55: 869-874, 2017. © 2016 Wiley Periodicals, Inc.

Molecular, genetic and stem cell-mediated therapeutic strategies for spinal muscular atrophy (SMA).

PubMed

Zanetta, Chiara; Riboldi, Giulietta; Nizzardo, Monica; Simone, Chiara; Faravelli, Irene; Bresolin, Nereo; Comi, Giacomo P; Corti, Stefania

2014-02-01

Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease. It is the first genetic cause of infant mortality. It is caused by mutations in the survival motor neuron 1 (SMN1) gene, leading to the reduction of SMN protein. The most striking component is the loss of alpha motor neurons in the ventral horn of the spinal cord, resulting in progressive paralysis and eventually premature death. There is no current treatment other than supportive care, although the past decade has seen a striking advancement in understanding of both SMA genetics and molecular mechanisms. A variety of disease modifying interventions are rapidly bridging the translational gap from the laboratory to clinical trials. In this review, we would like to outline the most interesting therapeutic strategies that are currently developing, which are represented by molecular, gene and stem cell-mediated approaches for the treatment of SMA. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Design of two-way reversible bending actuator based on a shape memory alloy/shape memory polymer composite

NASA Astrophysics Data System (ADS)

Taya, Minoru; Liang, Yuanchang; Namli, Onur C.; Tamagawa, Hirohisa; Howie, Tucker

2013-10-01

The design of a reversible bending actuator based on a SMA/SMP composite is presented. The SMA/SMP composite is made of SMA NiTi wires with a bent ‘U’-shape in the austenite phase embedded in an epoxy SMP matrix which has a memorized flat shape. The bending motion is caused by heating the composite above TAf to activate the NiTi recovery. Upon cooling, the softening from the austenite to R-phase transformation results in a relaxation of the composite towards its original flat shape. In the three-point bending measurement the composite was able to exhibit a reversible deflection of 1.3 mm on a support with a 10 mm span. In addition, a material model for predicting the composite’s deflection is presented and predicts the experimental results reasonably well. The model also estimates the in-plane internal force and the degree of the SMA phase transformation.

Development and Characterization of High Performance Shape Memory Alloy Coatings for Structural Aerospace Applications

PubMed Central

Exarchos, Dimitrios A.; Dalla, Panagiota T.; Tragazikis, Ilias K.; Zafeiropoulos, Nikolaos E.; Karabela, Maria M.; De Crescenzo, Carmen; Karatza, Despina; Matikas, Theodore E.

2018-01-01

This paper presents an innovative approach, which enables control of the mechanical properties of metallic components by external stimuli to improve the mechanical behavior of aluminum structures in aeronautical applications. The approach is based on the exploitation of the shape memory effect of novel Shape Memory Alloy (SMA) coatings deposited on metallic structural components, for the purpose of relaxing the stress of underlying structures by simple heating at field-feasible temperatures, therefore enhancing their structural integrity and increasing their stiffness and rigidity while allowing them to withstand expected loading conditions safely. Numerical analysis provided an insight in the expected response of the SMA coating and of the SMA-coated element, while the dependence of alloy composition and heat treatment on the experienced shape memory effect were investigated experimentally. A two-phase process is proposed for deposition of the SMA coating in an order that induces beneficial stress relaxation to the underlying structure through the shape memory effect. PMID:29783626

Is Spinal Muscular Atrophy a disease of the motor neurons only: pathogenesis and therapeutic implications?

PubMed Central

Simone, Chiara; Ramirez, Agnese; Bucchia, Monica; Rinchetti, Paola; Rideout, Hardy; Papadimitriou, Dimitra; Re, Diane B.; Corti, Stefania

2016-01-01

Spinal Muscular Atrophy (SMA) is a genetic neurological disease that causes infant mortality; no effective therapies are currently available. SMA is due to homozygous mutations and/or deletions in the Survival Motor Neuron 1 (SMN1) gene and subsequent reduction of the SMN protein, leading to the death of motor neurons. However, there is increasing evidence that in addition to motor neurons, other cell types are contributing to SMA pathology. In this review, we will discuss the involvement of non-motor neuronal cells, located both inside and outside the central nervous system, in disease onset and progression. These contribution of non-motor neuronal cells to disease pathogenesis has important therapeutic implications: in fact, even if SMN restoration in motor neurons is needed, it has been shown that optimal phenotypic amelioration in animal models of SMA requires a more widespread SMN correction. It will be crucial to take this evidence into account before clinical translation of the novel therapeutic approaches that are currently under development. PMID:26681261

Enhancement of SMN protein levels in a mouse model of spinal muscular atrophy using novel drug-like compounds

PubMed Central

Cherry, Jonathan J; Osman, Erkan Y; Evans, Matthew C; Choi, Sungwoon; Xing, Xuechao; Cuny, Gregory D; Glicksman, Marcie A; Lorson, Christian L; Androphy, Elliot J

2013-01-01

Spinal muscular atrophy (SMA) is a neurodegenerative disease that causes progressive muscle weakness, which primarily targets proximal muscles. About 95% of SMA cases are caused by the loss of both copies of the SMN1 gene. SMN2 is a nearly identical copy of SMN1, which expresses much less functional SMN protein. SMN2 is unable to fully compensate for the loss of SMN1 in motor neurons but does provide an excellent target for therapeutic intervention. Increased expression of functional full-length SMN protein from the endogenous SMN2 gene should lessen disease severity. We have developed and implemented a new high-throughput screening assay to identify small molecules that increase the expression of full-length SMN from a SMN2 reporter gene. Here, we characterize two novel compounds that increased SMN protein levels in both reporter cells and SMA fibroblasts and show that one increases lifespan, motor function, and SMN protein levels in a severe mouse model of SMA. PMID:23740718

Semantic memory retrieval circuit: role of pre-SMA, caudate, and thalamus.

PubMed

Hart, John; Maguire, Mandy J; Motes, Michael; Mudar, Raksha Anand; Chiang, Hsueh-Sheng; Womack, Kyle B; Kraut, Michael A

2013-07-01

We propose that pre-supplementary motor area (pre-SMA)-thalamic interactions govern processes fundamental to semantic retrieval of an integrated object memory. At the onset of semantic retrieval, pre-SMA initiates electrical interactions between multiple cortical regions associated with semantic memory subsystems encodings as indexed by an increase in theta-band EEG power. This starts between 100-150 ms after stimulus presentation and is sustained throughout the task. We posit that this activity represents initiation of the object memory search, which continues in searching for an object memory. When the correct memory is retrieved, there is a high beta-band EEG power increase, which reflects communication between pre-SMA and thalamus, designates the end of the search process and resultant in object retrieval from multiple semantic memory subsystems. This high beta signal is also detected in cortical regions. This circuit is modulated by the caudate nuclei to facilitate correct and suppress incorrect target memories. Copyright © 2012 Elsevier Inc. All rights reserved.

Design of automatic rotor blades folding system using NiTi shape memory alloy actuator

NASA Astrophysics Data System (ADS)

Ali, M. I. F.; Abdullah, E. J.

2016-10-01

This present paper will study the requirements for development of a new Automatic Rotor Blades Folding (ARBF) system that could possibly solve the availability, compatibility and complexity issue of upgrading a manual to a fully automatic rotor blades folding system of a helicopter. As a subject matter, the Royal Malaysian Navy Super Lynx Mk 100 was chosen as the baseline model. The aim of the study was to propose a design of SMART ARBF's Shape Memory Alloy (SMA) actuator and proof of operating concept using a developed scale down prototype model. The performance target for the full folding sequence is less than ten minutes. Further analysis on design requirements was carried out, which consisted of three main phases. Phase 1 was studying the SMA behavior on the Nickel Titanium (NiTi) SMA wire and spring (extension type). Technical values like activation requirement, contraction length, and stroke- power and stroke-temperature relationship were gathered. Phase 2 was the development of the prototype where the proposed design of stepped-retractable SMA actuator was introduced. A complete model of the SMART ARBF system that consisted of a base, a main rotor hub, four main rotor blades, four SMA actuators and also electrical wiring connections was fabricated and assembled. Phase 3 was test and analysis whereby a PINENG-PN968s-10000mAh Power Bank's 5 volts, which was reduced to 2.5 volts using LM2596 Step-Down Converter, powered and activated the NiTi spring inside each actuator. The bias spring (compression type), which functions to protract and push the blades to spread position, will compress together with the retraction of actuators and pull the blades to the folding position. Once the power was removed and SMA spring deactivated, the bias spring stiffness will extend the SMA spring and casing and push the blades back to spread position. The timing for the whole revolution was recorded. Based on the experimental analysis, the recorded timing for folding sequence is 2.5 minutes in average and therefore met the required criteria.

Higher-order Brain Areas Associated with Real-time Functional MRI Neurofeedback Training of the Somato-motor Cortex.

PubMed

Auer, Tibor; Dewiputri, Wan Ilma; Frahm, Jens; Schweizer, Renate

2018-05-15

Neurofeedback (NFB) allows subjects to learn self-regulation of neuronal brain activation based on information about the ongoing activation. The implementation of real-time functional magnetic resonance imaging (rt-fMRI) for NFB training now facilitates the investigation into underlying processes. Our study involved 16 control and 16 training right-handed subjects, the latter performing an extensive rt-fMRI NFB training using motor imagery. A previous analysis focused on the targeted primary somato-motor cortex (SMC). The present study extends the analysis to the supplementary motor area (SMA), the next higher brain area within the hierarchy of the motor system. We also examined transfer-related functional connectivity using a whole-volume psycho-physiological interaction (PPI) analysis to reveal brain areas associated with learning. The ROI analysis of the pre- and post-training fMRI data for motor imagery without NFB (transfer) resulted in a significant training-specific increase in the SMA. It could also be shown that the contralateral SMA exhibited a larger increase than the ipsilateral SMA in the training and the transfer runs, and that the right-hand training elicited a larger increase in the transfer runs than the left-hand training. The PPI analysis revealed a training-specific increase in transfer-related functional connectivity between the left SMA and frontal areas as well as the anterior midcingulate cortex (aMCC) for right- and left-hand trainings. Moreover, the transfer success was related with training-specific increase in functional connectivity between the left SMA and the target area SMC. Our study demonstrates that NFB training increases functional connectivity with non-targeted brain areas. These are associated with the training strategy (i.e., SMA) as well as with learning the NFB skill (i.e., aMCC and frontal areas). This detailed description of both the system to be trained and the areas involved in learning can provide valuable information for further optimization of NFB trainings. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Validation of a new device to measure postsurgical scar adherence.

PubMed

Ferriero, Giorgio; Vercelli, Stefano; Salgovic, Ludovit; Stissi, Valeria; Sartorio, Francesco

2010-05-01

Scarring after surgery can lead to a wide range of disorders. At present, the degree of scar adhesion is assessed manually and by ordinal scales. This article describes a new device (the Adheremeter) to measure scar adhesion and assesses its validity, reliability, and sensitivity to change. This was a reliability and validity study. The study was conducted at the Scientific Institute of Veruno. Two independent raters, a physical therapist and a physical therapist student, used the Adheremeter to measure scar mobility and contralateral normal skin in a sample of 25 patients with adherent postsurgical scars before (T1) and after (T2) physical therapy. Two indexes of scar mobility, the adherence's surface mobility index (SM(A)) and the adherence severity index (AS), were calculated. Their correlation with the Vancouver Scar Scale (VSS) and its pliability subscale (PL-VSS) was assessed for the validity analysis. Both the SM(A) and the AS showed good-to-excellent intrarater reliability (intraclass correlation coefficient [ICC]=.96) and interrater reliability (SM(A): ICC=.97 and .99; AS: ICC=.87 and .87, respectively, at T1 and T2), correlated moderately with the VSS and PL-VSS only at T1 (r(s)=-.58 to -.66), and were able to detect changes (physical therapist/physical therapist student): z score=-4.09/-3.88 for the SM(A) and -4.32/-4.24 for the AS; effect size=0.6/0.4 for the SM(A) and 1.4/1.2 for the AS; standard error of measurement=4.59/4.79 mm(2) for the SM(A) and 0.05/0.06 for the AS; and minimum detectable change=12.68/13.23 mm(2) for the SM(A) and 0.14/0.17 for the AS. The measurement is based on the rater's evaluation of force to stretch the skin and on the patient's judgment of comfort. The Adheremeter showed a good level of reliability, validity, and sensitivity to change. Further studies are needed to confirm these results in larger cohorts and to assess the device's validity for other types of scars.

Fibrocyte migration, differentiation and apoptosis during the corneal wound healing response to injury.

PubMed

Lassance, Luciana; Marino, Gustavo K; Medeiros, Carla S; Thangavadivel, Shanmugapriya; Wilson, Steven E

2018-05-01

The aim of this study was to determine whether bone marrow-derived fibrocytes migrate into the cornea after stromal scar-producing injury and differentiate into alpha-smooth muscle actin (αSMA) + myofibroblasts. Chimeric mice expressing green fluorescent protein (GFP) bone marrow cells had fibrosis (haze)-generating irregular phototherapeutic keratectomy (PTK). Multiplex immunohistochemistry (IHC) for GFP and fibrocyte markers (CD34, CD45, and vimentin) was used to detect fibrocyte infiltration into the corneal stroma and the development of GFP+ αSMA+ myofibroblasts. IHC for activated caspase-3, GFP and CD45 was used to detect fibrocyte and other hematopoietic cells undergoing apoptosis. Moderate haze developed in PTK-treated mouse corneas at 14 days after surgery and worsened, and persisted, at 21 days after surgery. GFP+ CD34+ CD45+ fibrocytes, likely in addition to other CD34+ and/or CD45+ hematopoietic and stem/progenitor cells, infiltrated the cornea and were present in the stroma in high numbers by one day after PTK. The fibrocytes and other bone marrow-derived cells progressively decreased at four days and seven days after surgery. At four days after PTK, 5% of the GFP+ cells expressed activated caspase-3. At 14 days after PTK, more than 50% of GFP+ CD45+ cells were also αSMA+ myofibroblasts. At 21 days after PTK, few GFP+ αSMA+ cells persisted in the stroma and more than 95% of those remaining expressed activated caspase-3, indicating they were undergoing apoptosis. GFP+ CD45+ SMA+ cells that developed from 4 to 21 days after irregular PTK were likely developed from fibrocytes. After irregular PTK in the strain of C57BL/6-C57/BL/6-Tg(UBC-GFP)30Scha/J chimeric mice, however, more than 95% of fibrocytes and other hematopoietic cells underwent apoptosis prior to the development of mature αSMA+ myofibroblasts. Most GFP+ CD45+ αSMA+ myofibroblasts that did develop subsequently underwent apoptosis-likely due to epithelial basement membrane regeneration and deprivation of epithelium-derived TGFβ requisite for myofibroblast survival. Copyright © 2018 Elsevier Ltd. All rights reserved.

Design and experimental characterization of flexure activated by SMA wires for microassembly operations

NASA Astrophysics Data System (ADS)

Flores, Abiud; Ahuett, Horacio; Song, Gangbing

2006-03-01

Compliant mechanisms have a wide range of application in microassembly, micromanipulation and microsurgery. This article presents a low cost Flexure-Stage actuated by two SMA-wires that produces displacement in one direction in a range from 0 to 10 μm. The Flexure-Stage acts as a mechanical transform by reducing and changing the direction of the SMA actuator output displacement. The Flexure-Stage system has its application in microassembly operation and was built at cost of US$ 35 cost. The design methodology of a flexure-stage from concept design through FEA modeling and finally to construction and characterization is presented in this paper.

Ocean observations with EOS/MODIS: Algorithm Development and Post Launch Studies

NASA Technical Reports Server (NTRS)

Gordon, Howard R.

1998-01-01

Significant accomplishments made during the present reporting period: (1) We expanded our "spectral-matching" algorithm (SMA), for identifying the presence of absorbing aerosols and simultaneously performing atmospheric correction and derivation of the ocean's bio-optical parameters, to the point where it could be added as a subroutine to the MODIS water-leaving radiance algorithm; (2) A modification to the SMA that does not require detailed aerosol models has been developed. This is important as the requirement for realistic aerosol models has been a weakness of the SMA; and (3) We successfully acquired micro pulse lidar data in a Saharan dust outbreak during ACE-2 in the Canary Islands.

Development of an artificial urethral valve using SMA actuators

NASA Astrophysics Data System (ADS)

Chonan, S.; Jiang, Z. W.; Tani, J.; Orikasa, S.; Tanahashi, Y.; Takagi, T.; Tanaka, M.; Tanikawa, J.

1997-08-01

The development of an artificial urethral valve for the treatment of urinary incontinence which occurs frequently in the aged is described. The prototype urethral valve is assembled in hand-drum form with four thin shape memory alloy (SMA) (nickel - titanium alloy) plates of 0.3 mm thickness. The shape memory effect in two directions is used to replace the urinary canal sphincter muscles and to control the canal opening and closing functions. The characteristic of the SMA is to assume the shape of a circular arc at normal temperatures and a flat shape at higher temperatures. Experiments have been conducted using a canine bladder and urinary canal.

Administrative Record Index for SMA 4 - Former Chemical Plant and SMA 5 - Former Pig Iron Foundry

EPA Pesticide Factsheets

The Administrative Record Index lists the documents, data and other technical information that the EPA - Region 4 considered in preparing the Statement of Basis for the Former Chemical Plant and the Former Pig Iron Foundry at ERP Compliant Coke.

Performance of Stone Matrix Asphalt (SMA) Mixtures in the United States

DOT National Transportation Integrated Search

1997-01-01

Stone Matrix Asphalt (SMA) mixtures have been used in the United States since 1991. The traffic rate has been high on many of these pavements resulting in a significant amount of traffic during a short period of time. In 1994 the Federal Highway Admi...

Study of a reinforced concrete beam strengthened using a combination of SMA wire and CFRP plate

NASA Astrophysics Data System (ADS)

Liu, Zhi-qiang; Li, Hui

2006-03-01

Traditional methods used for strengthening of reinforced concrete (RC) structures, such as bonding of steel plates, suffer from inherent disadvantages. In recent years, strengthening of RC structures using carbon fiber reinforced polymer (CFRP) plates has attracted considerable attentions around the world. Most existing research on CFRP plate bonding for flexural strengthening of RC beams has been carried out for the strength enhancement. However, little research is focused on effect of residual deformations on the strengthening. The residual deformations have an important effect on the strengthening by CFRP plates. There exists a very significant challenge how the residual deformations are reduced. Shape memory alloy (SMA) has showed outstanding functional properties as an actuator. It is a possibility that SMA can be used to reduce the residual deformation and make cracks of concrete close by imposing the recovery forces on the concrete in the tensile zone. It is only an emergency damage repair since the SMA wires need to be heated continuously. So, an innovative method of a RC beam strengthened by CFRP plates in combination with SMA wires was first investigated experimentally in this paper. In addition, the nonlinear finite element software of ABAQUS was employed to further simulate the behavior of RC beams strengthened through the new strengthening method. It can be found that this is an excellent and effective strengthening method.

Shared medical appointments: improving access, outcomes, and satisfaction for patients with chronic cardiac diseases.

PubMed

Bartley, Kelly Bauer; Haney, Rebecca

2010-01-01

Improving access to care, health outcomes, and patient satisfaction are primary objectives for healthcare practices. This article outlines benefits, concerns, and possible challenges of shared medical appointments (SMAs) for patients and providers. The SMA model was designed to support providers' demanding schedules by allowing patients with the same chronic condition to be seen in a group setting. By concentrating on patient education and disease management, interactive meetings provide an opportunity for patients to share both successes and struggles with others experiencing similar challenges. Studies demonstrated that SMAs improved patient access, enhanced outcomes, and promoted patient satisfaction. This article describes the potential benefits of SMAs for patients with chronic heart disease, which consumes a large number of healthcare dollars related to hospital admissions, acute exacerbations, and symptom management. Education for self-management of chronic disease can become repetitive and time consuming. The SMA model introduces a fresh and unique style of healthcare visits, allowing providers to devote more time and attention to patients and improve productivity. The SMA model provides an outstanding method for nurse practitioners to demonstrate their role as a primary care provider, by leading patients in group discussions and evaluating their current health status. Patient selection, preparation, and facilitation of an SMA are discussed to demonstrate the complementary nature of an SMA approach in a healthcare practice.

Effect of caffeine on superior mesenteric artery blood flow velocities in preterm neonates.

PubMed

Abdel Wahed, Mohamed A; Issa, Hanan M; Khafagy, Soha M; Abdel Raouf, Shaimaa M

2017-09-22

To investigate the effect of caffeine infusion on superior mesenteric artery (SMA) blood flow velocities (BFV) in preterm infants. Prospective observational study on 38 preterm neonates 28-33 +6 weeks gestation, who developed apnea on their first day of life, and caffeine citrate infusion was initiated at a loading dose of 20 mg/kg, followed by a maintenance dose of 5-10 mg/kg/day. Duplex ultrasound measurements of SMA BFV were recorded: peak systolic velocity (PSV), end diastolic velocity (EDV) and resistive index (RI), at 15 min before, 1-, 2- and 6-h after caffeine loading dose, and 2 h after two maintenance doses. There was a significant reduction in PSV 1-h (p = .008), a significant decrease in EDV 1- and 2-h (p = .000 and p = .005, respectively) and a significant increase in RI 1- and 2-h (p = .003 and p = .005, respectively) following caffeine loading dose, as compared to values before caffeine infusion. No significant effect of caffeine maintenance doses on SMA BFV was observed (p > .05). Blood flow in SMA is significantly reduced after caffeine citrate infusion at a loading dose of 20 mg/kg. This effect continues for at least 2 h. Meanwhile, SMA BFV seems not affected by maintenance doses.

Malaria, Moderate to Severe Anaemia, and Malarial Anaemia in Children at Presentation to Hospital in the Mount Cameroon Area: A Cross-Sectional Study

PubMed Central

Taiwe, Germain Sotoing

2016-01-01

Background. Malaria remains a major killer of children in Sub-Saharan Africa, while anaemia is a public health problem with significant morbidity and mortality. Examining the factors associated with moderate to severe anaemia (MdSA) and malarial anaemia as well as the haematological characteristics is essential. Methodology. Children (1–14 years) at presentation at the Regional Hospital Annex-Buea were examined clinically and blood samples were collected for malaria parasite detection and full blood count evaluation. Results. Plasmodium falciparum, anaemia, and malarial anaemia occurred in 33.8%, 62.0%, and 23.6% of the 216 children, respectively. Anaemia prevalence was significantly higher in malaria parasite positive children and those with fever than their respective counterparts. MdSA and moderate to severe malarial anaemia (MdSMA) were detected in 38.0% and 15.3% of the participants, respectively. The prevalence of MdSA was significantly higher in children whose household head had no formal education, resided in the lowland, or was febrile, while MdSMA was significantly higher in febrile children only. Children with MdSMA had significantly lower mean white blood cell, lymphocyte, and platelet counts while the mean granulocyte count was significantly higher. Conclusion. Being febrile was the only predictor of both MdSA and MdSMA. More haematological insult occurred in children with MdSMA compared to MdSA. PMID:27895939

Parenterally administrable nano-micelles of 3,4-difluorobenzylidene curcumin for treating pancreatic cancer.

PubMed

Kesharwani, Prashant; Banerjee, Sanjeev; Padhye, Subhash; Sarkar, Fazlul H; Iyer, Arun K

2015-08-01

Pancreatic cancer remains one of the most devastating diseases in terms of patient mortality rates for which current treatment options are very limited. 3,4-Difluorobenzylidene curcumin (CDF) is a nontoxic analog of curcumin (CMN) developed in our laboratory, which exhibits extended circulation half-life, while maintaining high anticancer activity and improved pancreas specific accumulation in vivo, compared with CMN. CDF however has poor aqueous solubility and its dose escalation for systemic administration remains challenging. We have engineered self-assembling nano-micelles of amphiphilic styrene-maleic acid copolymer (SMA) with CDF by non-covalent hydrophobic interactions. The SMA-CDF nano-micelles were characterized for size, charge, drug loading, release, serum stability, and in vitro anticancer activity. The SMA-CDF nano-micelles exhibited tunable CDF loading from 5 to 15% with excellent aqueous solubility, stability, favorable hemocompatibility and sustained drug release characteristics. The outcome of cytotoxicity testing of SMA-CDF nano-micelles on MiaPaCa-2 and AsPC-1 pancreatic cancer cell lines revealed pronounced antitumor response due to efficient intracellular trafficking of the drug loaded nano-micelles. Additionally, the nano-micelles are administrable via the systemic route for future in vivo studies and clinical translation. The currently developed SMA based nano-micelles thus portend to be a versatile carrier for dose escalation and targeted delivery of CDF, with enhanced therapeutic margin and safety. Copyright © 2015 Elsevier B.V. All rights reserved.

Severe neuromuscular denervation of clinically relevant muscles in a mouse model of spinal muscular atrophy

PubMed Central

Ling, Karen K. Y.; Gibbs, Rebecca M.; Feng, Zhihua; Ko, Chien-Ping

2012-01-01

Spinal muscular atrophy (SMA), a motoneuron disease caused by a deficiency of the survival of motor neuron (SMN) protein, is characterized by motoneuron loss and muscle weakness. It remains unclear whether widespread loss of neuromuscular junctions (NMJs) is involved in SMA pathogenesis. We undertook a systematic examination of NMJ innervation patterns in >20 muscles in the SMNΔ7 SMA mouse model. We found that severe denervation (<50% fully innervated endplates) occurs selectively in many vulnerable axial muscles and several appendicular muscles at the disease end stage. Since these vulnerable muscles were located throughout the body and were comprised of varying muscle fiber types, it is unlikely that muscle location or fiber type determines susceptibility to denervation. Furthermore, we found a similar extent of neurofilament accumulation at NMJs in both vulnerable and resistant muscles before the onset of denervation, suggesting that neurofilament accumulation does not predict subsequent NMJ denervation. Since vulnerable muscles were initially innervated, but later denervated, loss of innervation in SMA may be attributed to defects in synapse maintenance. Finally, we found that denervation was amendable by trichostatin A (TSA) treatment, which increased innervation in clinically relevant muscles in TSA-treated SMNΔ7 mice. Our findings suggest that neuromuscular denervation in vulnerable muscles is a widespread pathology in SMA, and can serve as a preparation for elucidating the biological basis of synapse loss, and for evaluating therapeutic efficacy. PMID:21968514

Implementation of a diabetes self-management education program in primary care for adults using shared medical appointments.

PubMed

Sanchez, Iris

2011-01-01

The purpose of this study was to implement diabetes self-management education in primary care using the Chronic Care Model and shared medical appointments (SMA) to provide evidence-based interventions to improve process and measure outcomes. A quality improvement project using the Plan-Do-Check-Act cycle was implemented in a primary care setting in South Texas to provide diabetes self-management education for adults. Biological measures were evaluated in 70 patients at initiation of the project and thereafter based on current practice guidelines. The results of the project were consistent with the literature regarding the benefits, sustainability, and viability of SMA. As compared with that in studies presented in the literature, the patient population who participated in SMA had similar outcomes regarding improvement in A1C, self-management skills, and satisfaction. SMA are an innovative system redesign concept with the potential to provide comprehensive and coordinated care for patients with multiple and chronic health conditions while still being an efficient, effective, financially viable, and sustainable program. As the incidence and prevalence of diabetes increase, innovative models of care can meet the growing demand for access and utilization of diabetes self-management education programs. Programs focusing on chronic conditions to improve outcomes can be replicated by health care providers in primary care settings. SMA can increase revenue and productivity, improve disease management, and increase provider and patient satisfaction.

Phenotypic and genotypic studies of ALS cases in ALS-SMA families.

PubMed

Corcia, Philippe; Vourc'h, Patrick; Blasco, Helene; Couratier, Philippe; Dangoumau, Audrey; Bellance, Remi; Desnuelle, Claude; Viader, Fausto; Pautot, Vivien; Millecamps, Stephanie; Bakkouche, Salah; Salachas, FranÇois; Andres, Christian R; Meininger, Vincent; Camu, William

2018-08-01

Amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are the most frequent motor neuron disorders in adulthood and infancy, respectively. There is a growing literature supporting common pathophysiological patterns between those disorders. One important clinical issue for that is the co-occurrence of both diseases within a family. To collect families in which ALS and SMA patients co-exist and describe the phenotype and the genotype of ALS patients. Nine families with co-occurrence of SMA and ALS have been gathered over the last 15 years. Epidemiological, phenotype and genetic status were collected. Out of the nine families, six corresponded to the criteria of familial ALS (FALS). Clinical data were available for 11 patients out of the 15 ALS cases. Mean age of onset was 58.5 years, site of onset was lower limbs in nine cases (81.8%), median duration was 22 months. Four ALS patients carried a mutation: three mutations in SOD1 gene (G147N in two cases and one with E121G) and one repeat expansion in the C9ORF72 gene. Three patients had abnormal SMN1 copy numbers. While the high proportion of familial history of ALS cases in these ALS-SMA pedigrees could have suggested that these familial clusters of the two most frequent MND rely on a genetic background, we failed to exclude that this occurred by chance.

Styrene-maleic acid-copolymer conjugated zinc protoporphyrin as a candidate drug for tumor-targeted therapy and imaging.

PubMed

Fang, Jun; Tsukigawa, Kenji; Liao, Long; Yin, Hongzhuan; Eguchi, Kanami; Maeda, Hiroshi

2016-01-01

Previous studies indicated the potential of zinc protoporphyrin (ZnPP) as an antitumor agent targeting to the tumor survival factor heme oxygenase-1, and/or for photodynamic therapy (PDT). In this study, to achieve tumor-targeted delivery, styrene-maleic acid-copolymer conjugated ZnPP (SMA-ZnPP) was synthesized via amide bond, which showed good water solubility, having ZnPP loading of 15%. More importantly, it forms micelles in aqueous solution with a mean particle size of 111.6 nm, whereas it has an apparent Mw of 65 kDa. This micelle formation was not detracted by serum albumin, suggesting it is stable in circulation. Further SMA-ZnPP conjugate will behave as an albumin complex in blood with much larger size (235 kDa) by virtue of the albumin binding property of SMA. Consequently, SMA-ZnPP conjugate exhibited prolonged circulating retention and preferential tumor accumulation by taking advantage of enhanced permeability and retention (EPR) effect. Clear tumor imaging was thus achieved by detecting the fluorescence of ZnPP. In addition, the cytotoxicity and PDT effect of SMA-ZnPP conjugate was confirmed in human cervical cancer HeLa cells. Light irradiation remarkably increased the cytotoxicity (IC50, from 33 to 5 μM). These findings may provide new options and knowledge for developing ZnPP based anticancer theranostic drugs.

The Spatial-Kinematic Structure of the Region of Massive Star Formation S255N on Various Scales

NASA Astrophysics Data System (ADS)

Zemlyanukha, P. M.; Zinchenko, I. I.; Salii, S. V.; Ryabukhina, O. L.; Liu, S.-Y.

2018-05-01

The results of a detailed analysis of SMA, VLA, and IRAM observations of the region of massive star formation S255N in CO(2-1), N2H+(3-2), NH3(1, 1), C18O(2-1) and some other lines is presented. Combining interferometer and single-dish data has enabled a more detailed investigation of the gas kinematics in the moleclar core on various spatial scales. There are no signs of rotation or isotropic compression on the scale of the region as whole. The largest fragments of gas (≈0.3 pc) are located near the boundary of the regions of ionized hydrogen S255 and S257. Some smaller-scale fragments are associated with protostellar clumps. The kinetic temperatures of these fragments lie in the range 10-80 K. A circumstellar torus with inner radius R in ≈ 8000 AU and outer radius R out ≈ 12 000 AU has been detected around the clump SMA1. The rotation profile indicates the existence of a central object with mass ≈8.5/ sin2( i) M ⊙. SMA1 is resolved into two clumps, SMA1-NE and SMA1-SE, whose temperatures are≈150Kand≈25 K, respectively. To all appearances, the torus is involved in the accretion of surrounding gas onto the two protostellar clumps.

Prophylactic and therapeutic treatment with a synthetic analogue of a parasitic worm product prevents experimental arthritis and inhibits IL-1β production via NRF2-mediated counter-regulation of the inflammasome.

PubMed

Rzepecka, Justyna; Pineda, Miguel A; Al-Riyami, Lamyaa; Rodgers, David T; Huggan, Judith K; Lumb, Felicity E; Khalaf, Abedawn I; Meakin, Paul J; Corbet, Marlene; Ashford, Michael L; Suckling, Colin J; Harnett, Margaret M; Harnett, William

2015-06-01

Rheumatoid arthritis (RA) remains a debilitating autoimmune condition as many patients are refractory to existing conventional and biologic therapies, and hence successful development of novel treatments remains a critical requirement. Towards this, we now describe a synthetic drug-like small molecule analogue, SMA-12b, of an immunomodulatory parasitic worm product, ES-62, which acts both prophylactically and therapeutically against collagen-induced arthritis (CIA) in mice. Mechanistic analysis revealed that SMA-12b modifies the expression of a number of inflammatory response genes, particularly those associated with the inflammasome in mouse bone marrow-derived macrophages and indeed IL-1β was the most down-regulated gene. Consistent with this, IL-1β was significantly reduced in the joints of mice with CIA treated with SMA-12b. SMA-12b also increased the expression of a number of genes associated with anti-oxidant responses that are controlled by the transcription factor NRF2 and critically, was unable to inhibit expression of IL-1β by macrophages derived from the bone marrow of NRF2(-/-) mice. Collectively, these data suggest that SMA-12b could provide the basis of an entirely novel approach to fulfilling the urgent need for new treatments for RA. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

A Perturbed MicroRNA Expression Pattern Characterizes Embryonic Neural Stem Cells Derived from a Severe Mouse Model of Spinal Muscular Atrophy (SMA)

PubMed Central

Luchetti, Andrea; Ciafrè, Silvia Anna; Murdocca, Michela; Malgieri, Arianna; Masotti, Andrea; Sanchez, Massimo; Farace, Maria Giulia; Novelli, Giuseppe; Sangiuolo, Federica

2015-01-01

Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder and the leading genetic cause of death in infants. Despite the disease-causing gene, survival motor neuron (SMN1), encodes a ubiquitous protein, SMN1 deficiency preferentially affects spinal motor neurons (MNs), leaving the basis of this selective cell damage still unexplained. As neural stem cells (NSCs) are multipotent self-renewing cells that can differentiate into neurons, they represent an in vitro model for elucidating the pathogenetic mechanism of neurodegenerative diseases such as SMA. Here we characterize for the first time neural stem cells (NSCs) derived from embryonic spinal cords of a severe SMNΔ7 SMA mouse model. SMNΔ7 NSCs behave as their wild type (WT) counterparts, when we consider neurosphere formation ability and the expression levels of specific regional and self-renewal markers. However, they show a perturbed cell cycle phase distribution and an increased proliferation rate compared to wild type cells. Moreover, SMNΔ7 NSCs are characterized by the differential expression of a limited number of miRNAs, among which miR-335-5p and miR-100-5p, reduced in SMNΔ7 NSCs compared to WT cells. We suggest that such miRNAs may be related to the proliferation differences characterizing SMNΔ7 NSCs, and may be potentially involved in the molecular mechanisms of SMA. PMID:26258776

A Perturbed MicroRNA Expression Pattern Characterizes Embryonic Neural Stem Cells Derived from a Severe Mouse Model of Spinal Muscular Atrophy (SMA).

PubMed

Luchetti, Andrea; Ciafrè, Silvia Anna; Murdocca, Michela; Malgieri, Arianna; Masotti, Andrea; Sanchez, Massimo; Farace, Maria Giulia; Novelli, Giuseppe; Sangiuolo, Federica

2015-08-06

Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder and the leading genetic cause of death in infants. Despite the disease-causing gene, survival motor neuron (SMN1), encodes a ubiquitous protein, SMN1 deficiency preferentially affects spinal motor neurons (MNs), leaving the basis of this selective cell damage still unexplained. As neural stem cells (NSCs) are multipotent self-renewing cells that can differentiate into neurons, they represent an in vitro model for elucidating the pathogenetic mechanism of neurodegenerative diseases such as SMA. Here we characterize for the first time neural stem cells (NSCs) derived from embryonic spinal cords of a severe SMNΔ7 SMA mouse model. SMNΔ7 NSCs behave as their wild type (WT) counterparts, when we consider neurosphere formation ability and the expression levels of specific regional and self-renewal markers. However, they show a perturbed cell cycle phase distribution and an increased proliferation rate compared to wild type cells. Moreover, SMNΔ7 NSCs are characterized by the differential expression of a limited number of miRNAs, among which miR-335-5p and miR-100-5p, reduced in SMNΔ7 NSCs compared to WT cells. We suggest that such miRNAs may be related to the proliferation differences characterizing SMNΔ7 NSCs, and may be potentially involved in the molecular mechanisms of SMA.

Analysis of hybrid electric/thermofluidic inputs for wet shape memory alloy actuators

NASA Astrophysics Data System (ADS)

Flemming, Leslie; Mascaro, Stephen

2013-01-01

A wet shape memory alloy (SMA) actuator is characterized by an SMA wire embedded within a compliant fluid-filled tube. Heating and cooling of the SMA wire produces a linear contraction and extension of the wire. Thermal energy can be transferred to and from the wire using combinations of resistive heating and free/forced convection. This paper analyzes the speed and efficiency of a simulated wet SMA actuator using a variety of control strategies involving different combinations of electrical and thermofluidic inputs. A computational fluid dynamics (CFD) model is used in conjunction with a temperature-strain model of the SMA wire to simulate the thermal response of the wire and compute strains, contraction/extension times and efficiency. The simulations produce cycle rates of up to 5 Hz for electrical heating and fluidic cooling, and up to 2 Hz for fluidic heating and cooling. The simulated results demonstrate efficiencies up to 0.5% for electric heating and up to 0.2% for fluidic heating. Using both electric and fluidic inputs concurrently improves the speed and efficiency of the actuator and allows for the actuator to remain contracted without continually delivering energy to the actuator, because of the thermal capacitance of the hot fluid. The characterized speeds and efficiencies are key requirements for implementing broader research efforts involving the intelligent control of electric and thermofluidic networks to optimize the speed and efficiency of wet actuator arrays.

Predictors and outcomes of superior mesenteric artery syndrome in patients with constipation: a prospective, nested case-control study.

PubMed

Xu, Lin; Yu, Wen-Kui; Lin, Zhi-Liang; Jiang, Jun; Feng, Xiao-Bo; Li, Ning

2014-10-01

Superior mesenteric artery (SMA) syndrome may occur in patients with constipation, whereas the association between these two distinct diseases has not been confirmed yet. We investigated the incidence, risk factors and treatment strategy associated with SMA syndrome in constipated patients. We conducted a prospective nested case-control study from a 9-year hospitalization cohort (n=973). Cases were matched to controls 1:4 on factors of age and gender. Cases developed SMA syndrome in long term follow-up (n=26) and controls did not (n=104). Independent risk factors were identified by using univariate analysis and conditional logistic regression analysis. Enteral nutritional support was applied in all cases and its curative effect was evaluated by retrospective analysis. The incidence of SMA syndrome was 2.67%. The risk factors under scrutiny were body mass index (BMI)≤18 (odds ratio (OR) 2.89, 95% CI 1.14 to 9.31) and abnormal colon transit time (OR 3.57, 95% CI 1.36 to 9.35). Twenty-two patients recovered after treatment of nutritional support, and the success rate of conservative treatment was 84.6%. BMI≤18 and prolonged colon transit time both were risk factors associated with SMA syndrome in constipated patients. Enteral nutritional support should be adopted as the first-line treatment for this condition.

Stress recovery and cyclic behaviour of an Fe-Mn-Si shape memory alloy after multiple thermal activation

NASA Astrophysics Data System (ADS)

Hosseini, E.; Ghafoori, E.; Leinenbach, C.; Motavalli, M.; Holdsworth, S. R.

2018-02-01

The stress recovery and cyclic deformation behaviour of Fe-17Mn-5Si-10Cr-4Ni-1(V,C) shape memory alloy (Fe-SMA) strips, which are often used for pre-stressed strengthening of structural members, were studied. The evolution of recovery stress under different constraint conditions was studied. The results showed that the magnitude of the tensile stress in the Fe-SMA member during thermal activation can have a signification effect on the final recovery stress. The higher the tensile load in the Fe-SMA (e.g., caused by dead load or thermal expansion of parent structure during heating phase), the lower the final recovery stress. Furthermore, this study investigated the cyclic behaviour of the activated SMA followed by a second thermal activation. Although the magnitude of the recovery stress decreased during the cyclic loading, the second thermal activation could retrieve a significant part of the relaxed recovery stress. This observation suggests that the relaxation of recovery stress during cyclic loading is due to a reversible phase transformation-induced deformation (i.e., forward austenite-to-martensite transformation) rather than an irreversible dislocation-induced plasticity. Retrieval of the relaxed recovery stress by the reactivation process has important practical implications as the prestressing loss in pre-stressed civil structures can be simply recovered by reheating of the Fe-SMA elements.