Simple transporter trafficking model for amphetamine-induced dopamine efflux

Amphetamine and its derivatives are important drugs of abuse causing both short-term excitatory and long-term addictive effects. The short-term excitatory effects are linked to amphetamine's ability to maintain high levels of dopamine (DA) outside the cell both by inhibiting DA reuptake after synaptic transmission and by enhancing the efflux of DA from the dopaminergic cells. The molecular mechanisms by which amphetamine elicits the efflux of DA and similar monoamines are still unclear. Recent literature data suggest that trafficking of the monoamine transporters is a phenomenon that underlies observed changes in amphetamine-induced monoamine reuptake and efflux. We develop an ordinary differential equation model incorporating the diverse mechanistic details behind amphetamine-induced DA efflux and demonstrate its utility in describing our experimental data. We also demonstrate an experimental method to track the time-varying concentration of membrane-bound transporter molecules from the DA efflux data. The good fit between our model and the experimental data supports the hypothesis that amphetamine-induced transporter trafficking is necessary to produce extended efflux of DA. This model can explain the relative significance of different processes associated with DA efflux at different times and at different concentration ranges of amphetamine and DA. Synapse 61:500–514, 2007. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56075/1/20390_ftp.pd

Functional Electric Stimulation Cycle Ergometry Training Effect on Lower Limb Muscles in Acute SCI Individuals

The purpose of this study was to compare three different intervals for a between sets rest period during a common isokinetic knee extension strength-testing protocol of twenty older Brazilian men (66.30 ± 3.92 yrs). The volunteers underwent unilateral knee extension (Biodex System 3) testing to determine their individual isokinetic peak torque at 60, 90, and 120° ·s-1. The contraction speeds and the rest periods between sets (30, 60 and 90 s) were randomly performed in three different days with a minimum rest period of 48 hours. Significant differences between and within sets were analyzed using a One Way Analysis of Variance (ANOVA) with repeated measures. Although, at angular velocity of 60°·s-1 produced a higher peak torque, there were no significant differences in peak torque among any of the rest periods. Likewise, there were no significant differences between mean peak torque among all resting periods (30, 60 and 90s) at angular velocities of 90 and 120°·s-1. The results showed that during a common isokinetic strength testing protocol a between set rest period of at least 30 s is sufficient for recovery before the next test set in older men

Why do Process Improvement Projects Fail in Organizations? A Review and Future Research Agenda

Purpose: The purpose of this article is to examine the Critical Failure Factors (CFFs) linked to various types of Process improvement (PI) projects such as Kaizen, Lean, Six Sigma, Lean Six Sigma and Agile. Proposing a mitigation framework accordingly is also an aim of this study. Design/ Methodology/ Approach: This research undertakes a systematic literature review of 49 articles that were relevant to the scope of our study and that were published in four prominent databases including Google Scholar, Scopus, Web of Science and EBSCO. Findings: Further analysis identifies 39 factors that contribute to the failure of PI projects. Among these factors, significant emphasis is placed on issues such as "resistance to cultural change," "insufficient support from top management," "inadequate training and education," "poor communication," and "lack of resources", as primary causes of PI project failures. To address and overcome the PI project failures, we propose a framework for failure mitigation based on change management models. We present future research directions that aim to enhance both the theoretical understanding and practical aspects of PI project failures. Practical Implications: Through this study researchers and project managers can benefit from well structured guidelines and invaluable insights that will help them identify and address potential failures, leading to successful implementation and sustainable improvements within organizations. Originality: This paper is the first study of its kind that examine the CFFs of five PI methodologies and introduces a novel approach derived from change management theory as a solution to minimize the risk associated with PI failure

Shear Lag Sutures: Improved Suture Repair through the use of Adhesives

Conventional surgical suture is mechanically limited by the ability of the suture to transfer load to tissue at suture anchor points. Sutures coated with adhesives can improve mechanical load transfer beyond the range of performance of existing suture methods, thereby strengthening orthopaedic repairs and decreasing the risk of failure. The mechanical properties of suitable adhesives were identified using a shear lag model. Examination of the design space for an optimal adhesive demonstrated requirements for strong adhesion and low stiffness to maximize strength. As a proof of concept, cyanoacrylate-coated sutures were used to perform a clinically relevant flexor digitorum profundus tendon repair in cadaver tissue. Even with this non-ideal adhesive, the maximum load resisted by repaired cadaveric canine flexor tendon increased by ∼ 17.0% compared to standard repairs without adhesive. To rapidly assess adhesive binding to tendon, we additionally developed a lap shear test method using bovine deep digital flexor tendons as the adherends. Further study is needed to develop a strongly adherent, compliant adhesive within the optimal design space described by the model

Body Mass Index Associations Between Mother and Offspring from Birth to Age 18: The Fels Longitudinal Study

Background: Parental obesity is a known determinant of childhood obesity. Previous research has shown a strong maternal influence on body mass index (BMI) during infancy and early childhood. Objectives: The purpose of this research was to investigate the BMI associations between mother and offspring from birth to age 18 years. Methods: Participants were selected from the Fels Longitudinal Study. The current study sample includes 427 (215 mother/son and 212 mother/daughter) mother/child pairs. These pairs are repeatedly measured at multiple age groups in children, resulting in a total of 6,263 (3,215 mother/son, 3,048 mother/daughter) observations for data analysis. Inclusion criteria were children with measured height and weight for BMI collected at ages 0 to 18 years and their mother with BMI data. Maternal influences of BMI on offspring BMI from birth to early adulthood were analyzed by Spearman correlations and linear regression analyses. Results: Mother/son BMI correlations became statistically significant (p ≤ 0.05) at age 5–6 years and were significant through puberty and into early adulthood at age 18 years. Mother/daughter correlations became significant at age 1.5 years and also continued through adolescence, puberty and early adulthood at age 18 years. Associations persisted after the study sample was grouped into life stages and adjusted for decade of birth and parity. Conclusions: The mother/daughter relationship was more strongly correlated than the mother/son relationship and also became statistically significant at an earlier age than boys

Stimulation of Myofibrillar Protein Synthesis in Hindlimb Suspended Rats by Resistance Exercise and Growth Hormone

The objective of this study was to determine the ability of a single bout of resistance exercise alone or in combination with recombinant human growth hormone (rhGH) to stimulate myofibrillar protein synthesis (Ks) in hindlimb suspended (HLS) adult female rats. Plantar flexor muscles were stimulated with resistance exercise, consisting of 10 repetitions of ladder climbing on a 1 m grid (85 deg.), carrying an additional 50% of their body weight attached to their tails. Saline or rhGH (1 mg/kg) was administered 30' prior to exercise, and Ks was determined with a constant infusion of H-3-Leucine at 15', 60', 180', and 360' following exercise. Three days of HLS depressed Ks is approx. equal to 65% and 30-40% in the soleus and gastrocnemius muscles, respectively (p is less than or equal to 0.05). Exercise increased soleus Ks in saline-treated rats 149% 60' following exercise (p less than or equal to 0.05), decaying to that of non-exercised animals during the next 5 hours. Relative to suspended, non-exercised rats rhGH + exercise increased soleus Ks 84%, 108%, and 72% at 15', 60' and 360' following exercise (p is less than or equal to 0.05). Gastrocnemius Ks was not significantly increased by exercise or the combination of rhGH and exercise up to 360' post-exercise. Results from this study indicate that resistance exercise stimulated Ks 60' post-exercise in the soleus of HLS rats, with no apparent effect of rhGH to enhance or prolong exercise-induced stimulation. Results suggests that exercise frequency may be important to maintenance of the slow-twitch soleus during non-weightbearing, but that the ability of resistance exercise to maintain myofibrillar protein content in the gastrocnemius of hindlimb suspended rats cannot be explained by acute stimulation of synthesis

Estimation of the Optimal Statistical Quality Control Sampling Time Intervals Using a Residual Risk Measure

Background: An open problem in clinical chemistry is the estimation of the optimal sampling time intervals for the application of statistical quality control (QC) procedures that are based on the measurement of control materials. This is a probabilistic risk assessment problem that requires reliability analysis of the analytical system, and the estimation of the risk caused by the measurement error. Methodology/Principal Findings: Assuming that the states of the analytical system are the reliability state, the maintenance state, the critical-failure modes and their combinations, we can define risk functions based on the mean time of the states, their measurement error and the medically acceptable measurement error. Consequently, a residual risk measure rr can be defined for each sampling time interval. The rr depends on the state probability vectors of the analytical system, the state transition probability matrices before and after each application of the QC procedure and the state mean time matrices. As optimal sampling time intervals can be defined those minimizing a QC related cost measure while the rr is acceptable. I developed an algorithm that estimates the rr for any QC sampling time interval of a QC procedure applied to analytical systems with an arbitrary number of critical-failure modes, assuming any failure time and measurement error probability density function for each mode. Furthermore, given the acceptable rr, it can estimate the optimal QC sampling time intervals

Recognition of Handwriting from Electromyography

Handwriting – one of the most important developments in human culture – is also a methodological tool in several scientific disciplines, most importantly handwriting recognition methods, graphology and medical diagnostics. Previous studies have relied largely on the analyses of handwritten traces or kinematic analysis of handwriting; whereas electromyographic (EMG) signals associated with handwriting have received little attention. Here we show for the first time, a method in which EMG signals generated by hand and forearm muscles during handwriting activity are reliably translated into both algorithm-generated handwriting traces and font characters using decoding algorithms. Our results demonstrate the feasibility of recreating handwriting solely from EMG signals – the finding that can be utilized in computer peripherals and myoelectric prosthetic devices. Moreover, this approach may provide a rapid and sensitive method for diagnosing a variety of neurogenerative diseases before other symptoms become clear