Computing optimal cocomo effort multiplier values and optimal casebase subsets using monte carlo methods

There have been many studies performed and techniques applied to solve the problem of estimating man-month effort for software projects. Despite all the effort expended to solving this problem the results achieved from the various techniques have not been embraced by the software community as very reliable or accurate. This thesis uses Monte Carlo methods to obtain optimal values for COCOMO effort multipliers which minimize the average of the absolute values of the relative errors (AARE) of man-month estimate for two industry supplied casebases. For example, when using three COCOMO cost drivers (complexity, language experience, application experience) and the COCOMO effort multiplier values, AARE values were 60% for casebase 1 and 53% for casebase 2; using Monte Carlo to obtain optimal effort multiplier values, AARE values were 34% for casebase 1 and 41% for casebase 2. By repeatedly removing the cases which contributed the greatest Absolute Relative Error, the Monte Carlo method was also used to determine optimal casebase subsets with AARE values of less than 10%. This latter approach identifies casebase cases for which the cost drivers may have been rated incorrectly or cases which are not rated consistently with respect to a subset of cases

Surface-Patterned Electrode Bioreactor for Electrical Stimulation

We present a microscale cell culture system with an interdigitated microarray of excimer-laser-ablated indium tin oxide electrodes for electrical stimulation of cultured cells. The system has been characterized in a range of geometeries and stimulation regimes via electrochemical impedance spectroscopy and used to culture primary cardiomyocytes and human adipose derived stem cells. Over 6 days of culture with electrical stimulation (2 ms duration, 1 Hz, 180 μm wide electrodes with 200 μm spacing), both cell types exhibited enhanced proliferation, elongation and alignment, and adipose derived stem cells exhibited higher numbers of Connexin-43-composed gap junctions

Neuronal Effects of Listening to Entrainment Music Versus Preferred Music in Patients With Chronic Cancer Pain as Measured via EEG and LORETA Imaging

Previous studies examining EEG and LORETA in patients with chronic pain discovered an overactivation of high theta (6–9 Hz) and low beta (12–16 Hz) power in central regions. MEG studies with healthy subjects correlating evoked nociception ratings and source localization described delta and gamma changes according to two music interventions. Using similar music conditions with chronic pain patients, we examined EEG in response to two different music interventions for pain. To study this process in-depth we conducted a mixed-methods case study approach, based on three clinical cases. Effectiveness of personalized music therapy improvisations (entrainment music – EM) versus preferred music on chronic pain was examined with 16 participants. Three patients were randomly selected for follow-up EEG sessions three months post-intervention, where they listened to recordings of the music from the interventions provided during the research. To test the difference of EM versus preferred music, recordings were presented in a block design: silence, their own composed EM (depicting both “pain” and “healing”), preferred (commercially available) music, and a non-participant’s EM as a control. Participants rated their pain before and after the EEG on a 1–10 scale. We conducted a detailed single case analysis to compare all conditions, as well as a group comparison of entrainment-healing condition versus preferred music condition. Power spectrum and according LORETA distributions focused on expected changes in delta, theta, beta, and gamma frequencies, particularly in sensory-motor and central regions. Intentional moment-by-moment attention on the sounds/music rather than on pain and decreased awareness of pain was experienced from one participant. Corresponding EEG analysis showed accompanying power changes in sensory-motor regions and LORETA projection pointed to insula-related changes during entrainment-pain music. LORETA also indicated involvement of visual-spatial, motor, and language/music improvisation processing in response to his personalized EM which may reflect active recollection of creating the EM. Group-wide analysis showed common brain responses to personalized entrainment-healing music in theta and low beta range in right pre- and post-central gyrus. We observed somatosensory changes consistent with processing pain during entrainment-healing music that were not seen during preferred music. These results may depict top–down neural processes associated with active coping for pain

Inflammation induces irreversible biophysical changes in isolated nucleus pulposus cells.

Intervertebral disc degeneration is accompanied by elevated levels of inflammatory cytokines that have been implicated in disease etiology and matrix degradation. While the effects of inflammatory stimulation on disc cell metabolism have been well-studied, their effects on cell biophysical properties have not been investigated. The hypothesis of this study is that inflammatory stimulation alters the biomechanical properties of isolated disc cells and volume responses to step osmotic loading. Cells from the nucleus pulposus (NP) of bovine discs were isolated and treated with either lipopolysaccharide (LPS), an inflammatory ligand, or with the recombinant cytokine TNF-α for 24 hours. We measured cellular volume regulation responses to osmotic loading either immediately after stimulation or after a 1 week recovery period from the inflammatory stimuli. Cells from each group were tested under step osmotic loading and the transient volume-response was captured via time-lapse microscopy. Volume-responses were analyzed using mixture theory framework to investigate two biomechanical properties of the cell, the intracellular water content and the hydraulic permeability. Intracellular water content did not vary between treatment groups, but hydraulic permeability increased significantly with inflammatory treatment. In the 1 week recovery group, hydraulic permeability remained elevated relative to the untreated recovery control. Cell radius was also significantly increased both after 24 hours of treatment and after 1 week recovery. A significant linear correlation was observed between hydraulic permeability and cell radius in untreated cells at 24 hours and at 1-week recovery, though not in the inflammatory stimulated groups at either time point. This loss of correlation between cell size and hydraulic permeability suggests that regulation of volume change is disrupted irreversibly due to inflammatory stimulation. Inflammatory treated cells exhibited altered F-actin cytoskeleton expression relative to untreated cells. We also found a significant decrease in the expression of aquaporin-1, the predominant water channel in disc NP cells, with inflammatory stimulation. To our knowledge, this is the first study providing evidence that inflammatory stimulation directly alters the mechanobiology of NP cells. The cellular biophysical changes observed in this study are coincident with documented changes in the extracellular matrix induced by inflammation, and may be important in disease etiology

Osmotic loading regime, representative volume-response curve, and equilibrium volume-concentration responses.

<p>(A) Osmolarity was applied in a step-wise fashion using decreasing concentrations of NaCl solutions. Each osmotic load was maintained for approximately 5 minutes to allow the cell volume change to reach equilibrium. (B) Representative time-dependent volume of an untreated cell. (C, D) Equilibrium volume (V), normalized by reference volume (V_r), is plotted as a function of applied external reference osmolarity (c_er) over current external osmolarity (c_e) for cells at (C) 24 hour and (D) 7-day recovery time points (n = 7–12 cells per group). The reference osmolarity and associated volume were taken at 333 mOsm/L equilibrium.</p

Cytoskeletal structure of rounded NP cells.

<p>Representative cytoskeletal staining of NP cells in each treatment group for (A–F) F-actin (red) and (G–L) β-tubulin (green), scale bar = 5 µm. Confocal z-stack images were acquired with 2 µm spacing throughout cell cross-sections, and images represent the slice acquired nearest the center of the cell (midplane).</p

Cell radius measured at 333 mOsm/L at (A) 24 hour and (B) 7-day recovery time points.

<p>Data shown is mean (▪), standard error (boxes), and 95% confidence intervals (whiskers; n = 52–127 cells per group). *p<0.03 vs. untreated or untreated recovery control.</p

Aquaporin-1 expression in NP cells.

<p>(A, B) Gene expression of aquaporin-1 at 24 hour or 7-day recovery time points. Expression levels are normalized to untreated time point control groups (*p<0.05 vs. control). (C) Representative immunoblot of Aqp-1 and (D, E) densitometry of Aqp-1 in NP cells at 24 hour or 7-day recovery time points, respectively. Expression levels are normalized to untreated time point control groups. *p<0.05 vs. time point control, ∧p = 0.07 vs. time point control. (F) Representative immunohistochemical (IHC) staining of Aqp-1 (green) and cell nuclei (blue, scale bars = 20 µm). (G, H) Quantification of Aqp-1 expression measured by IHC, normalized to time point untreated control group (*p<0.05 vs. time point control).</p

Regression analysis between and cell radius in each treatment group.

<p>Significant linear correlations were observed for cells in (A) untreated and (D) untreated recovery groups (p<0.05, indicated in red). No significant correlations were observed for cells from LPS or TNF-α at 24 hours (B, C) or at recovery time points (E, F). ‘R’ represents the regression coefficient for each group.</p

Intracellular water content determined by curve-fiting the volume-response curves at each osmolarity step.

<p>Mean ± standard deviation,</p><p>*p<0.05 vs. untreated or untreated recovery control;</p>†<p>p<0.05 vs. 466 to 333 mOsm/L step.</p