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Muscle design constraints preclude simultaneous specialization of the vertebrate locomotor system for explosive and economical force generation. The resulting performance trade-off between power and economy has been attributed primarily to individual differences in muscle fiber type composition. While certainly crucial for performance specialization, fiber type likely interacts with muscle architectural parameters, such as fascicle length, to produce this trade-off. Longer fascicles composed of more serial sarcomeres can achieve faster shortening velocities, allowing for greater power production. Long fascicles likely reduce economy, however, because more energy-consuming contractile units are activated for a given force production. We hypothesized that longer fascicles are associated with both increased power production and locomotor cost. In 11 power-trained and 13 endurance-trained recreational athletes, we measured (1) muscle fascicle length via ultrasound in the gastrocnemius lateralis, gastrocnemius medialis and vastus lateralis, (2) maximal power during cycling and countermovement jumps, and (3) running cost of transport. We estimated muscle fiber type non-invasively based on the pedaling rate at which maximal cycling power occurred. As predicted, longer gastrocnemius muscle fascicles were correlated with greater lower-body power production and cost of transport. Multiple regression analyses revealed that variability in maximal power was explained by fiber type (46% for cycling, 24% for jumping) and average fascicle length (20% for cycling, 13% for jumping), while average fascicle length accounted for 15% of the variation in cost of transport. These results suggest that, at least for certain muscles, fascicle length plays an important role in the power versus economy performance trade-off.
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Músculo Esquelético , Corrida , Fenômenos Biomecânicos , Humanos , Contração Muscular , Músculo Esquelético/diagnóstico por imagem , Músculo Quadríceps , UltrassonografiaRESUMO
Heterogeneous metal oxide catalysts are widely studied for the aerobic oxidations of C1-C4 alkanes to form olefins and oxygenates. In this review, we outline the properties of supported metal oxides, mixed-metal oxides, and zeolites and detail their most common applications as catalysts for partial oxidations of light alkanes. By doing this we establish similarities between different classes of metal oxides and identify common themes in reaction mechanisms and research strategies for catalyst improvement. For example, almost all partial alkane oxidations, regardless of the metal oxide, follow Mars-van Krevelen reaction kinetics, which utilize lattice oxygen atoms to reoxidize the reduced metal centers while the gaseous O2 reactant replenishes these lattice oxygen vacancies. Many of the most-promising metal oxide catalysts include V5+ surface species as a necessary constituent to convert the alkane. Transformations involving sequential oxidation steps (i.e., propane to acrylic acid) require specific reaction sites for each oxidation step and benefit from site isolation provided by spectator species. These themes, and others, are discussed in the text.
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Boron-containing materials, and in particular boron nitride, have recently been identified as highly selective catalysts for the oxidative dehydrogenation of alkanes such as propane. To date, no mechanism exists that can explain both the unprecedented selectivity, the observed surface oxyfunctionalization, and the peculiar kinetic features of this reaction. We combine catalytic activity measurements with quantum chemical calculations to put forward a bold new hypothesis. We argue that the remarkable product distribution can be rationalized by a combination of surface-mediated formation of radicals over metastable sites, and their sequential propagation in the gas phase. Based on known radical propagation steps, we quantitatively describe the oxygen pressure-dependent relative formation of the main product propylene and by-product ethylene. Free radical intermediates most likely differentiate this catalytic system from less selective vanadium-based catalysts.
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Boron-containing materials have recently been identified as highly selective catalysts for the oxidative dehydrogenation (ODH) of alkanes to olefins. It has previously been demonstrated by several spectroscopic characterization techniques that the surface of these boron-containing ODH catalysts oxidize and hydrolyze under reaction conditions, forming an amorphous B2 (OH)x O(3-x/2) (x=0-6) layer. Yet, the precise nature of the active site(s) remains elusive. In this Communication, we provide a detailed characterization of zeolite MCM-22 isomorphously substituted with boron (B-MWW). Using 11 B solid-state NMR spectroscopy, we show that the majority of boron species in B-MWW exist as isolated BO3 units, fully incorporated into the zeolite framework. However, this material shows no catalytic activity for ODH of propane to propene. The catalytic inactivity of B-MWW for ODH of propane falsifies the hypothesis that site-isolated BO3 units are the active site in boron-based catalysts. This observation is at odds with other traditionally studied catalysts like vanadium-based catalysts and provides an important piece of the mechanistic puzzle.
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Hexagonal boron nitride (h-BN) and boron nitride nanotubes (BNNT) were recently reported as highly selective catalysts for the oxidative dehydrogenation (ODH) of alkanes to olefins in the gas phase. Previous studies revealed a substantial increase in surface oxygen content after exposure to ODH conditions (heating to ca. 500 °C under a flow of alkane and oxygen); however, the complexity of these materials has thus far precluded an in-depth understanding of the oxygenated surface species. In this contribution, we combine advanced NMR spectroscopy experiments with scanning electron microscopy and soft X-ray absorption spectroscopy to characterize the molecular structure of the oxygen functionalized phase that arises on h-BN and BNNT following catalytic testing for ODH of propane. The pristine BN materials are readily oxidized and hydrolyzed under ODH reaction conditions to yield a phase consisting of three-coordinate boron sites with variable numbers of hydroxyl and bridging oxide groups which is denoted B(OH) xO3- x (where x = 0-3). Evidence for this robust oxide phase revises previous literature hypotheses of hydroxylated BN edges as the active component on h-BN.
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Light olefins such as ethylene and propylene form the foundation of the modern chemical industry, with yearly production volumes well into the hundreds of millions of metric tons. Currently, these light olefins are mainly produced via energy-intensive steam cracking. Alternatively, oxidative dehydrogenation (ODH) of light alkanes to produce olefins allows for lower operation temperatures and extended catalyst lifetimes, potentially leading to valuable process efficiencies. The potential benefits of this route have led to significant research interest due to the wide availability of natural gas from shale deposits. Advances in this area have still not yielded catalysts that are sufficiently selective to olefins for industrial implementation, and ODH still remains a holy grail of selective alkane oxidation research. The main challenge in selective oxidation lies in preventing the overoxidation of the desired product, such as propylene during propane oxidation, to CO and CO2. Research into selective heterogeneous catalysts for the oxidative dehydrogenation of propane has led to the extensive use of vanadium oxide-based catalysts, and studies on the surface mechanism involved have been used to improve the catalytic activity of the material. Despite decades of research, however, selectivity toward propylene has not proven satisfactory at industrially relevant conversions. It is imperative for new catalytic systems that minimize product overoxidation to be developed for future applications of oxidative dehydrogenation processes. While rational catalyst design has been successful in developing homogeneous catalyst systems, its practical use in heterogeneous catalyst development remains modest. The complexity of surfaces with a variety of terminations and bulk structures, let alone their modification by the chemical potential of a reaction mixture, makes heterogeneous catalyst discovery serendipitous in many cases. The catalyst family presented in this Account is no exception. The importance of catalysis research lies in exploring the science behind serendipity. In this Account, we will first present our initial discovery of boron nitride (BN) as an unexpected catalyst for the oxidative dehydrogenation of light alkanes. Beyond its surprising activity, BN also drew interest due to its low selectivity to carbon oxides. This observation made BN distinct from previously studied metal oxide catalysts for selective alkane oxidation. We narrowed down its unique reactivity to the oxygen functionalization of the catalyst surface, particularly the formation of B-O species as probed by various spectroscopic techniques. In investigating the critical role of each of the structural elements during ODH, we discovered that not only BN but an entire class of boron-containing compounds are active and selective for the formation of propylene from propane. All these materials form a complex oxidized surface with a distribution of BO x surface sites. This discovery opens the doors to a new field of boron-based oxidation chemistry that currently has more questions than answers. We aim to make this Account a starting point for the research community to explore these new materials to understand their surface mechanisms and the surface species that offer a unique selectivity toward olefinic products. Effective use of these materials may lead to novel processes for efficient use of abundant light alkane resources by oxidation chemistry.
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In this paper, we study dynamic stability during running, focusing on the effects of speed, and the use of a leg prosthesis. We compute and compare the maximal Lyapunov exponents of kinematic time-series data from subjects with and without unilateral transtibial amputations running at a wide range of speeds. We find that the dynamics of the affected leg with the running-specific prosthesis are less stable than the dynamics of the unaffected leg and also less stable than the biological legs of the non-amputee runners. Surprisingly, we find that the center-of-mass dynamics of runners with two intact biological legs are slightly less stable than those of runners with amputations. Our results suggest that while leg asymmetries may be associated with instability, runners may compensate for this effect by increased control of their center-of-mass dynamics.
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BACKGROUND: Numerous rehabilitation protocols exist for postoperative rotator cuff repairs. Because the goal of early rehabilitation is to prevent postoperative adhesions while protecting the repaired tendons, it would be advantageous to know which range-of-motion exercises allow the rotator cuff to remain the most passive in a painful, guarded, postsurgical shoulder. METHODS: Twenty-six subjects who had undergone subacromial decompression, distal clavicle resection, or a combination of both procedures volunteered to participate within the first 4 days after surgery. Fine-wire electrodes were inserted into the subject's supraspinatus (SS) and infraspinatus (IS). Muscle activity was recorded at resting baseline (BL) and during 14 exercises that have been found in the passive phase of rotator cuff protocols and tested in healthy subjects. Each exercise was compared with BL activity as well as with other exercises in the same movement group. RESULTS: The SS remained as passive as BL during therapist- and self-assisted external rotation, therapist-assisted elevation, pendulums, and isometric internal rotation and adduction. The IS was activated greater than BL for all 14 exercises studied. CONCLUSION: Of the 14 exercises studied, 6 allowed the SS and 0 allowed the IS to remain as passive as quiet-stance BL in postsurgical subacromial decompression/distal clavicle resection patients.
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Terapia por Exercício/métodos , Manguito Rotador/fisiologia , Manguito Rotador/cirurgia , Eletromiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , ReabilitaçãoRESUMO
Locomotor respiratory coupling patterns in humans have been assessed on the basis of the interaction between different physiological and motor subsystems; these interactions have implications for movement economy. A complex and dynamical systems framework may provide more insight than entrainment into the variability and adaptability of these rhythms and their coupling. The purpose of this study was to investigate the relationship between steady state locomotor-respiratory coordination dynamics and oxygen consumption [Formula: see text] of the movement by varying walking stride frequency from preferred. Twelve male participants walked on a treadmill at a self-selected speed. Stride frequency was varied from -20 to +20% of preferred stride frequency (PSF) while respiratory airflow, gas exchange variables, and stride kinematics were recorded. Discrete relative phase and return map techniques were used to evaluate the strength, stability, and variability of both frequency and phase couplings. Analysis of [Formula: see text] during steady-state walking showed a U-shaped response (P = 0.002) with a minimum at PSF and PSF - 10%. Locomotor-respiratory frequency coupling strength was not greater (P = 0.375) at PSF than any other stride frequency condition. The dominant coupling across all conditions was 2:1 with greater occurrences at the lower stride frequencies. Variability in coupling was the greatest during PSF, indicating an exploration of coupling strategies to search for the coupling frequency strategy with the least oxygen consumption. Contrary to the belief that increased strength of frequency coupling would decrease oxygen consumption; these results conclude that it is the increased variability of frequency coupling that results in lower oxygen consumption.
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Marcha/fisiologia , Locomoção/fisiologia , Consumo de Oxigênio/fisiologia , Respiração , Caminhada/fisiologia , Adaptação Fisiológica/fisiologia , Adulto , Relógios Biológicos/fisiologia , Fenômenos Biomecânicos/fisiologia , Teste de Esforço , Humanos , Masculino , Adulto JovemRESUMO
Running-specific prostheses (RSP) emulate the spring-like behaviour of biological limbs during human running, but little research has examined the mechanical means by which amputees achieve top speeds. To better understand the biomechanical effects of RSP during sprinting, we measured ground reaction forces (GRF) and stride kinematics of elite unilateral trans-tibial amputee sprinters across a range of speeds including top speed. Unilateral amputees are ideal subjects because each amputee's affected leg (AL) can be compared with their unaffected leg (UL). We found that stance average vertical GRF were approximately 9 per cent less for the AL compared with the UL across a range of speeds including top speed (p < 0.0001). In contrast, leg swing times were not significantly different between legs at any speed (p = 0.32). Additionally, AL and UL leg swing times were similar to those reported for non-amputee sprinters. We infer that RSP impair force generation and thus probably limit top speed. Some elite unilateral trans-tibial amputee sprinters appear to have learned or trained to compensate for AL force impairment by swinging both legs rapidly.
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Amputados , Membros Artificiais , Corrida/fisiologia , Análise de Variância , Fenômenos Biomecânicos , HumanosRESUMO
In recent years, hexagonal boron nitride (hBN) has emerged as an unexpected catalyst for the oxidative dehydrogenation of alkanes. Here, the versatility of hBN was extended to alkane oxidative cracking chemistry by investigating the production of ethylene and propylene from n-butane. Cracking selectivity was primarily controlled by the ratio of n-butane to O2 within the reactant feed. Under O2 -lean conditions, increasing temperature led to increased selectivity to ethylene and propylene and decreased selectivity to COx . In addition to surface-mediated chemistry, homogeneous gas-phase reactions likely contributed to the observed product distribution, and a reaction mechanism was proposed based on these observations. The catalyst showed good stability under oxidative cracking conditions for 100â h time-on-stream while maintaining high selectivity to ethylene and propylene.
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Boron-based heterogenous catalysts, such as hexagonal boron nitride (h-BN) as well as supported boron oxides, are highly selective catalysts for the oxidative dehydrogenation (ODH) of light alkanes to olefins. Previous catalytic measurements and molecular characterization of boron-based catalysts by 11B solid-state NMR spectroscopy and other techniques suggests that oxidized/hydrolyzed boron clusters are the catalytically active sites for ODH. However, 11B solid-state NMR spectroscopy often suffers from limited resolution because boron-11 is an I = 3/2 half-integer quadrupolar nucleus. Here, ultra-high magnetic field (B 0 = 35.2 T) is used to enhance the resolution of 11B solid-state NMR spectra and unambiguously determine the local structure and connectivity of boron species in h-BN nanotubes used as a ODH catalyst (spent h-BNNT), boron substituted MCM-22 zeolite [B-MWW] and silica supported boron oxide [B/SiO2] before and after use as an ODH catalyst. One-dimensional direct excitation 11B NMR spectra recorded at B 0 = 35.2 T are near isotropic in nature, allowing for the easy identification of all boron species. Two-dimensional 1H-11B heteronuclear correlation NMR spectra aid in the identification of boron species with B-OH functionality. Most importantly, 2D 11B dipolar double-quantum single-quantum homonuclear correlation NMR experiments were used to unambiguously probe boron-boron connectivity within all heterogeneous catalysts. These experiments are practically infeasible at lower, more conventional magnetic fields due to a lack of resolution and reduced NMR sensitivity. The detailed molecular structures determined for the amorphous oxidized/hydrolyzed boron layers on these heterogenous catalysts will aid in the future development of next generation ODH catalysts.
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Nm23-H1 suppresses metastasis, as well as in vitro cell motility, invasion and anchorage independent growth, in a variety of cancer models. Eight human homologs of Nm23 have been identified that share 26-88% identity with the prototype Nm23-H1. Here, we examine the potential of its homologs, -H2, DR-, -H4 and -H5, to inhibit in vitro correlates of metastasis in two highly metastatic human cell lines, MDA-MB-435 and MDA-MB-231. The metastatic cells were transfected with mammalian expression constructs containing the genes encoding for Nm23-H1, -H2, DR-, -H4 and -H5 and the resultant transfectants were analyzed by Boyden chamber motility and soft agar colonization assays. Nm23-H1 suppressed motility by 3.3- and 1.5-fold in MDA-MB-435 and MDA-MB-231 cells, respectively and inhibited anchorage independent growth in soft agar by 2.9- and 1.9-fold, respectively. None of the -H1 homologs were capable of suppressing motility in MDA-MB-435 cells, but in MDA-MB-231 cells, -H2 inhibited motility by 3-fold upon overexpression. When anchorage independent growth was assessed, -H2, -H4 and -H5 suppressed growth from 1.2- to 2.0-fold in both cell lines. Given their ability to suppress anchorage independent growth, Nm23-H1 homologs -H2, -H4 and -H5 may have some capacity to suppress metastasis. Motility suppression appears to be cell context dependent, but sequence disparities between -H1/H2 and the other family members may reveal regions critical for this inhibitory phenotype. Similarly, sequence differences between DR-Nm23 and its homologs may be important for anchorage independent growth suppression.
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Movimento Celular/fisiologia , Nucleosídeo NM23 Difosfato Quinases/fisiologia , Metástase Neoplásica/genética , Sequência de Aminoácidos , Linhagem Celular Tumoral , Feminino , Humanos , Dados de Sequência Molecular , Nucleosídeo NM23 Difosfato Quinases/genética , Homologia de Sequência de Aminoácidos , TransfecçãoRESUMO
Platelet rich plasma (PRP) has recently been investigated for use in tissue regeneration studies that seek to utilize the numerous growth factors released from platelet alpha-granules. This study examined gene expression patterns, DNA, and collagen content of equine flexor digitorum superficialis tendon (SDFT) explants cultured in media consisting of PRP and other blood products. Blood and bone marrow aspirate (BMA) were collected from horses and processed to obtain plasma, PRP, and platelet poor plasma (PPP). IGF-I, TGF-beta1, and PDGF-BB were quantified in all blood products using ELISA. Tendons were cultured in explant fashion with blood, plasma, PRP, PPP, or BMA at concentrations of 100%, 50%, or 10% in serum-free DMEM with amino acids. Quantitative RT-PCR for expression of collagen type I (COL1A1), collagen type III (COL3A1), cartilage oligomeric matrix protein (COMP), decorin, matrix metalloproteinase-3 (MMP-3), and matrix metalloproteinase-13 (MMP-13) was performed as were DNA and total soluble collagen assays. TGF-beta1 and PDGF-BB concentrations were higher in PRP compared to all other blood products tested. Tendons cultured in 100% PRP showed enhanced gene expression of the matrix molecules COL1A1, COL3A1, and COMP with no concomitant increase in the catabolic molecules MMP-3 and MMP-13. These findings support in vivo investigation of PRP as an autogenous, patient-side treatment for tendonitis.
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Regulação da Expressão Gênica/fisiologia , Metabolismo/fisiologia , Plasma Rico em Plaquetas , Tendões/metabolismo , Animais , Becaplermina , Colágeno/genética , Colágeno/metabolismo , DNA/genética , DNA/metabolismo , Relação Dose-Resposta a Droga , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Glicoproteínas/genética , Glicoproteínas/metabolismo , Cavalos , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Proteínas Matrilinas , Metabolismo/genética , Fator de Crescimento Derivado de Plaquetas/genética , Fator de Crescimento Derivado de Plaquetas/metabolismo , Plasma Rico em Plaquetas/fisiologia , Proteínas Proto-Oncogênicas c-sis , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Tendinopatia/tratamento farmacológico , Técnicas de Cultura de Tecidos , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismoRESUMO
PURPOSE: To determine differences in bone geometry, estimates of bone strength, muscle size and bone strength relative to load, in women runners with and without a history of stress fracture. METHODS: We recruited 32 competitive distance runners aged 18-35, with (SFX, n=16) or without (NSFX, n=16) a history of stress fracture for this case-control study. Peripheral quantitative computed tomography (pQCT) was used to assess volumetric bone mineral density (vBMD, mg/mm3), total (ToA) and cortical (CtA) bone areas (mm2), and estimated compressive bone strength (bone strength index; BSI, mg/mm4) at the distal tibia. ToA, CtA, cortical vBMD, and estimated strength (section modulus; Zp, mm3 and strength strain index; SSIp, mm3) were measured at six cortical sites along the tibia. Mean active peak vertical (pkZ) ground reaction forces (GRFs), assessed from a fatigue run on an instrumented treadmill, were used in conjunction with pQCT measurements to estimate bone strength relative to load (mm2/N∗kg-1) at all cortical sites. RESULTS: SSIp and Zp were 9-11% lower in the SFX group at mid-shaft of the tibia, while ToA and vBMD did not differ between groups at any measurement site. The SFX group had 11-17% lower bone strength relative to mean pkZ GRFs (p<0.05). CONCLUSION: These findings indicate that estimated bone strength at the mid-tibia and mean pkZ GRFs are lower in runners with a history of stress fracture. Bone strength relative to load is also lower in this same region suggesting that strength deficits in the middle 1/3 of the tibia and altered gait biomechanics may predispose an individual to stress fracture.
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Osso e Ossos/patologia , Osso e Ossos/fisiopatologia , Fraturas de Estresse/patologia , Fraturas de Estresse/fisiopatologia , Corrida/fisiologia , Adulto , Fenômenos Biomecânicos , Estudos de Casos e Controles , Demografia , Feminino , Humanos , Tíbia/patologia , Tíbia/fisiopatologiaRESUMO
This study examined the effects of speed and leg prostheses on mediolateral (ML) foot placement and its variability in sprinters with and without transtibial amputations. We hypothesized that ML foot placement variability would: 1. increase with running speed up to maximum speed and 2. be symmetrical between the legs of non-amputee sprinters but asymmetrically greater for the affected leg of sprinters with a unilateral transtibial amputation. We measured the midline of the body (kinematic data) and center of pressure (kinetic data) in the ML direction while 12 non-amputee sprinters and 7 Paralympic sprinters with transtibial amputations (6 unilateral, 1 bilateral) ran across a range of speeds up to maximum speed on a high-speed force measuring treadmill. We quantified ML foot placement relative to the body's midline and its variability. We interpret our results with respect to a hypothesized relation between ML foot placement variability and lateral balance. We infer that greater ML foot placement variability indicates greater challenges with maintaining lateral balance. In non-amputee sprinters, ML foot placement variability for each leg increased substantially and symmetrically across speed. In sprinters with a unilateral amputation, ML foot placement variability for the affected and unaffected leg also increased substantially, but was asymmetric across speeds. In general, ML foot placement variability for sprinters with a unilateral amputation was within the range observed in non-amputee sprinters. For the sprinter with bilateral amputations, both affected legs exhibited the greatest increase in ML foot placement variability with speed. Overall, we find that maintaining lateral balance becomes increasingly challenging at faster speeds up to maximum speed but was equally challenging for sprinters with and without a unilateral transtibial amputation. Finally, when compared to all other sprinters in our subject pool, maintaining lateral balance appears to be the most challenging for the Paralympic sprinter with bilateral transtibial amputations.
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Amputados , Membros Artificiais , Marcha/fisiologia , Corrida/fisiologia , Fenômenos Biomecânicos/fisiologia , Humanos , Perna (Membro)/fisiologiaRESUMO
Running-specific prostheses (RSF) are designed to replicate the spring-like nature of biological legs (bioL) during running. However, it is not clear how these devices affect whole leg stiffness characteristics or running dynamics over a range of speeds. We used a simple spring-mass model to examine running mechanics across a range of speeds, in unilateral and bilateral transtibial amputees and performance-matched controls. We found significant differences between the affected leg (AL) of unilateral amputees and both ALs of bilateral amputees compared with the bioL of non-amputees for nearly every variable measured. Leg stiffness remained constant or increased with speed in bioL, but decreased with speed in legs with RSPs. The decrease in leg stiffness in legs with RSPs was mainly owing to a combination of lower peak ground reaction forces and increased leg compression with increasing speeds. Leg stiffness is an important parameter affecting contact time and the force exerted on the ground. It is likely that the fixed stiffness of the prosthesis coupled with differences in the limb posture required to run with the prosthesis limits the ability to modulate whole leg stiffness and the ability to apply high vertical ground reaction forces during sprinting.
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Amputados , Membros Artificiais , Força Compressiva , Corrida , Adulto , Fenômenos Biomecânicos , Feminino , Humanos , MasculinoRESUMO
Nm23-H1 transcriptionally down-regulates expression of the lysophosphatidic acid receptor EDG2 and this down-regulation is critical for Nm23-H1-mediated motility suppression in vitro. We investigated the effect of altered EDG2 expression on Nm23-H1-mediated metastasis suppression in vivo. Clonal MDA-MB-435-derived tumor cell lines transfected with Nm23-H1 together with either a vector control or EDG2 had similar anchorage-dependent and anchorage-independent growth rates in vitro. However, a 45- and 300-fold inhibition of motility and invasion (P < 0.0001), respectively, was observed in Nm23-H1/vector lines, whereas coexpression of EDG2 restored activity to levels observed in the parental line. Using fluorescently labeled cells and ex vivo microscopy, the capacity of these cells to adhere, arrest, extravasate, and survive in the murine lung over a 24-h time course was measured. Only 5% of Nm23-H1/vector-transfected cells were retained in the murine lung 6 h following tail vein injection; coexpression of EDG2 enhanced retention 8- to 13-fold (P < 0.01). In a spontaneous metastasis assay, the primary tumor size of Nm23-H1/vector and Nm23-H1/EDG2 clones was not significantly different. However, restoration of EDG2 expression augmented the incidence of pulmonary metastasis from 51.9% to 90.4% (P = 2.4 x 10(-5)), comparable with parental MDA-MB-435 cells. To determine the relevance of this model system to human breast cancer, a cohort of breast carcinomas was stained for Nm23-H1 and EDG2 and a statistically significant inverse correlation between these two proteins was revealed (r = -0.73; P = 0.004). The data indicate that Nm23-H1 down-regulation of EDG2 is functionally important to suppression of tumor metastasis.
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Neoplasias da Mama/genética , Nucleosídeo NM23 Difosfato Quinases/metabolismo , Metástase Neoplásica/prevenção & controle , Receptores de Ácidos Lisofosfatídicos/antagonistas & inibidores , Receptores de Ácidos Lisofosfatídicos/genética , Neoplasias da Mama/patologia , Divisão Celular , Linhagem Celular Tumoral , Movimento Celular , Sobrevivência Celular , Humanos , Imuno-Histoquímica , Invasividade Neoplásica/prevenção & controle , TransfecçãoRESUMO
It has been suggested that stronger coupling between locomotory and breathing rhythms may occur as a result of training in the particular movement pattern and also may reduce the perceived workload or metabolic cost of the movement. Research findings on human locomotor-respiratory coordination are equivocal, due in part to the fact that assessment techniques range in sensitivity to important aspects of coordination (e.g. temporal ordering of patterns, half-integer couplings and changes in frequency and phase coupling). An additional aspect that has not received much attention is the adaptability of this coordination to changes in task constraints. The current study investigated the effect of running training on the locomotor-respiratory coordination and the adaptive strategies observed across a wide range of walking and running speeds. Locomotor-respiratory coordination was evaluated by the strength and variability of both frequency and phase coupling patterns that subjects displayed within and across the speed conditions. Male subjects (five runners, five non-runners) locomoted at seven different treadmill speeds. Group results indicated no differences between runners and non-runners with respect to breathing parameters, stride parameters, as well as the strength and variability of the coupling at each speed. Individual results, however, showed that grouping subjects masks large individual differences and strategies across speeds. Coupling strategies indicated that runners show more stable dominant couplings across locomotory speeds than non-runners do. These findings suggest that running training does not change the strength of locomotor-respiratory coupling but rather how these systems adapt to changing speeds.