INVESTIGATIONS INTO THE FATIGUE-RELATED REDUCTION IN TORQUE, SHORTENING VELOCITY, AND JOINT RANGE OF MOTION IN HUMANS

Studies in humans and animals have derived much understanding of neuromuscular function from isometric (static) contractions. In comparison, fewer studies have evaluated dynamic contractions, which are relevant to everyday movements and activities of daily living. The primary purpose of this thesis was to investigate and compare the contributing factors to fatigue during different voluntary contraction tasks. The interpolated twitch technique is commonly used to assess voluntary activation, but with changes in muscle length, musculotendinous slackness can diminish the amplitude of electrically-evoked twitches used to calculate voluntary activation. This might result in erroneous measurements of voluntary activation. Chapter 2 describes an experiment in which at the short muscle lengths, when voluntary activation is 80% or lower, actual activation will be underestimated. Maximum voluntary isometric contraction (MVC) torque is often used to assess overall neuromuscular function, and any activity-induced decline in MVC torque is indicative of fatigue. However, a reduction in shortening velocity is also an important feature of fatigue. Results from Chapter 3 indicate that shortening velocity was an important and perhaps more sensitive measure of fatigue following both isometric and dynamic contraction tasks than MVC torque per se. These findings are further supported in Chapter 4, in which, following comparable repetitive shortening contraction tasks in two different muscles, shortening velocity was reduced to a greater extent at task failure but was restored more rapidly than MVC torque. Shortening contractions are also characterized by a fatigue-related reduction in joint range of motion (ROM) and it was suggested that the reduction in ROM might be due to length-dependent alterations in torque or contractile slowing with fatigue. Results iii presented in Chapter 5, suggest that length-dependent alterations in torque or contractile slowing cannot explain the fatigue-related reduction in dorsiflexion ROM. Thus, in addition to fatigue-related reductions in torque, decreases in shortening velocity and joint range of motion are important indicators of a fatigue-induced impairment in muscle shortening capacity

High temperature dilute acid pretreatment of coastal Bermuda grass for enzymatic hydrolysis

Dilute sulfuric acid was used to pretreat coastal Bermuda grass at high temperature prior to enzymatic hydrolysis. After both pretreatment and enzymatic hydrolysis processes, the highest yield of total sugars (combined xylose and glucose) was 97% of the theoretical value. The prehydrolyzate liquor was analyzed for inhibitory compounds (furfural, hydroxymethylfurfural (HMF)) in order to assess potential risk for inhibition during the following fermentation. Accounting for the formation of the inhibitory compounds, a pretreatment with 1.2% acid at 140 °C for 30 min with a total sugar yield of 94% of the theoretical value may be more favorable for fermentation. From this study, it can be concluded that dilute sulfuric acid pretreatment can be successfully applied to coastal Bermuda grass to achieve high yields of monomeric glucose and xylose with acceptable levels of inhibitory compound formation

Intramuscular Contributions to Low-Frequency Force Potentiation Induced by a High-Frequency Conditioning Stimulation.

Electrically-evoked low-frequency (submaximal) force is increased immediately following high-frequency stimulation in human skeletal muscle. Although central mechanisms have been suggested to be the major cause of this low-frequency force potentiation, intramuscular factors might contribute. Thus, we hypothesized that two intramuscular Ca(2+)-dependent mechanisms can contribute to the low-frequency force potentiation: increased sarcoplasmic reticulum Ca(2+) release and increased myofibrillar Ca(2+) sensitivity. Experiments in humans were performed on the plantar flexor muscles at a shortened, intermediate, and long muscle length and electrically evoked contractile force and membrane excitability (i.e., M-wave amplitude) were recorded during a stimulation protocol. Low-frequency force potentiation was assessed by stimulating with a low-frequency tetanus (25 Hz, 2 s duration), followed by a high-frequency tetanus (100 Hz, 2 s duration), and finally followed by another low-frequency (25 Hz, 2 s duration) tetanus. Similar stimulation protocols were performed on intact mouse single fibers from flexor digitorum brevis muscle, whereby force and myoplasmic free [Ca(2+)] ([Ca(2+)]i) were assessed. Our data show a low-frequency force potentiation that was not muscle length-dependent in human muscle and it was not accompanied by any increase in M-wave amplitude. A length-independent low-frequency force potentiation could be replicated in mouse single fibers, supporting an intramuscular mechanism. We show that at physiological temperature (31°C) this low-frequency force potentiation in mouse fibers corresponded with an increase in sarcoplasmic reticulum (SR) Ca(2+) release. When mimicking the slower contractile properties of human muscle by cooling mouse single fibers to 18°C, the low-frequency force potentiation was accompanied by minimally increased SR Ca(2+) release and hence it could be explained by increased myofibrillar Ca(2+) sensitivity. Finally, introducing a brief 200 ms pause between the high- and low-frequency tetanus in human and mouse muscle revealed that the low-frequency force potentiation is abolished, arguing that increased myofibrillar Ca(2+) sensitivity is the main intramuscular mechanism underlying the low-frequency force potentiation in humans

Exacerbation of glycoprotein VI-dependent platelet responses in a rhesus monkey model of type 1 diabetes

Thrombosis is a life-threatening complication of diabetes. Platelet reactivity is crucial to thrombus formation, particularly in arterial vessels and in thrombotic complications causing myocardial infarction or ischaemic stroke, but diabetic patients often respond poorly to current antiplatelet medication. In this study, we used a nonhuman primate model of Type 1 diabetes to measure early downstream signalling events following engagement of the major platelet collagen receptor, glycoprotein (GP)VI. Diabetic monkeys were given enough insulin to maintain their blood glucose levels either at ~8 mM (well-controlled diabetes) or ~15 mM (poorly controlled diabetes). Flow cytometric analysis was used to measure platelet reactive oxygen species (ROS) generation, calcium mobilisation, receptor surface expression, and immature platelet fraction. We observed exacerbated intracellular ROS and calcium flux associated with engagement of GPVI in monkeys with poorly controlled diabetes. GPVI surface levels did not differ between healthy monkeys or the two diabetic groups. Treatment of platelets with the specific Syk inhibitor BAY61-3606 inhibited GPVI-dependent ROS and, importantly, reduced ROS generation in the poorly controlled diabetes group to that observed in healthy monkeys. These data indicate that glycaemic control is important in reducing GPVI-dependent platelet hyperreactivity and point to a potential antithrombotic therapeutic benefit of Syk inhibition in hyperglycaemic diabete

SiGe-On-Insulator (SGOI): Two Structures for CMOS Application

Two SiGe-on-insulator (SGOI) structures for CMOS application are presented: surface-channel strained-Si on SGOI (SSOI) and dual-channel SGOI structures. Comparisons between two structures are made from both device performance and CMOS process point of view. We have demonstrated both structures on SGOI, and have fabricated n-MOSFET’s and p-MOSFET’s on those two structures respectively. Device characteristics are presented. The devices show enhancement on both electron and hole mobilities.Singapore-MIT Alliance (SMA

Collective Intelligence for Control of Distributed Dynamical Systems

We consider the El Farol bar problem, also known as the minority game (W. B. Arthur, ``The American Economic Review'', 84(2): 406--411 (1994), D. Challet and Y.C. Zhang, ``Physica A'', 256:514 (1998)). We view it as an instance of the general problem of how to configure the nodal elements of a distributed dynamical system so that they do not ``work at cross purposes'', in that their collective dynamics avoids frustration and thereby achieves a provided global goal. We summarize a mathematical theory for such configuration applicable when (as in the bar problem) the global goal can be expressed as minimizing a global energy function and the nodes can be expressed as minimizers of local free energy functions. We show that a system designed with that theory performs nearly optimally for the bar problem.Comment: 8 page

Perceived Versus Performance Fatigability in Patients With Rheumatoid Arthritis

Rheumatoid arthritis (RA) is a chronic, inflammatory disease that affects 1% of the general population. Fatigue is a common complaint of patients with RA, however their perceived fatigue may be more exacerbated than objective measures of fatigue may indicate. The assessment of fatigue is made complex due to inconsistent and vague terms used to define fatigue, and the task dependence of fatigability. Fatigue is defined as a state of exhaustion and decreased strength, while fatigability indicates an individual’s susceptibility to fatigue. In order to offer some clarity to the manifestation of fatigue in clinical populations, in this review we outline that fatigue should be described with subsections that are related to the symptom, such as: perceived fatigability and performance fatigability. Where perceived fatigability indicates the subjective state of the individual and thus involves the individual’s subjective measure of fatigue, performance fatigability would be measured through clinical and laboratory-based assessments that quantify the functional decline in performance. This review describes RA and the various neuromuscular changes associated with the disease that can lead to alterations in both perceived and performance fatigue. From there, we discuss fatigue and RA, how fatigue can be assessed, effects of exercise interventions on RA symptoms and fatigue, and recommendations for future studies investigating subjective and objective measures of fatigability