Functional impairment following axonal injury

Following trauma or other neurological disorders, a series of events happen that cause axonal dysfunction or ultimately lead to axonal death. Computational modeling of the nervous system facilitates systematic study of the effects of each injury parameter on the output. The overall goal of this research was to develop a new method of simulating axon damage in a biophysical model and quantify the effects of structural damage on signal conduction. To achieve this, three objectives were addressed 1) quantify the effects of normal morphological variation and demyelination on axonal conduction characteristics, 2) develop a new computationally efficient method for modeling damage in axons, and 3) characterize the structure changes observed in human axons and quantify the relationship between these observed changes and axonal function. Biophysical computational models developed in NEURON were employed to characterize morphological changes in damaged axons and study the effects of some of the most common axonal injuries such as myelin damage and spheroid formation on signal propagation in axons with different calibers. To facilitate efficient computational simulation, a new approach for increasing geometrical resolution in NEURON was developed and assessed. To investigate the effects of axonal swelling on action potential conduction in myelinated axons, the morphological properties of axonal spheroids were characterized by analyzing a series of confocal images captured from post-mortem human brain samples of patients with MS and infarction. Our results indicate that subtle abnormalities in nodal, paranodal and juxtaparanodal regions may have sizable effects on action potential amplitude and velocity and more targeted treatments need to be developed that focus on these regions. In addition, the results of our histopathological and computational studies suggest that axons with different diameters may respond differently to injuries and diseases. Therefore, it is important to perform experimental injury models across a wide range of axons to get a more comprehensive understanding of the relationship between axonal morphological features, injury parameters and functional responses. We expect this research to lay the quantitative foundation for finding new potential functional markers of white matter tissue damage and provide further insights into how myelin damage and axonal spheroids may affect function

Proposing a rigorous empirical model for estimating the bubble point pressure in heterogeneous carbonate reservoirs

 Bubble point pressure is of great significance in reservoir engineering calculations affecting the success of reservoir simulation. For determining this valuable parameter, experimental tests are the most reliable techniques; however, these measurements are costly and time-consuming. So, it is crucial to propose an empirical model for estimating bubble point pressure. The existing correlations mainly have large errors and develop based on restricted database from a specific geographical location. As a result, development of an all-inclusive correlation is essential. In current article, gene expression programming (GEP) was used to create a generalized model for bubble point pressure estimation. To do this, an all-inclusive source of data was utilized for training and testing the model from the petroleum industry. Several statistical approaches including both illustration tools and diverse error functions were utilized to show the supremacy of the developed GEP model. Consequently, the recommended model is the most accurate as compared to the similar correlations in literature with the average absolute relative error (AARE = 11.41%) and determination coefficient (R2 = 0.96). Furthermore, the solution gas-oil ratio shows to be the most influencing variable on determining bubble point pressure according to sensitivity analysis. The results of contour map analysis demonstrate that most portions of the experimental region are predicted via the GEP equation with fewer errors as compared to two well-known literature correlations. Finally, the proposed GEP model can be of high prominence for accurate bubble point pressure estimation.Cited as: Rostami, A., Daneshi, A., Miri, R. Proposing a rigorous empirical model for estimating the bubble point pressure in heterogeneous carbonate reservoirs. Advances in Geo-Energy Research, 2020, 4(2): 126-134, doi: 10.26804/ager.2020.02.0

IAGNOSTIC VALUE OF MAGNETIC RESONANCE SPECTROSCOPY IN MORPHOMETRICAL ANALYSIS OF BASAL GANGLIA IN PATIENTS WITH IDIOPATHIC GENERALIZED EPILEPSY‏

Idiopathic generalized epilepsy (IGE) is a kind of epilepsy that has tonic-colonic characteristic and myocolonic tensions and its clinical symptom starts from the first 20 years of the life. Proton magnetic resonance spectroscopy (H1-MRS) technique applies as a noninvasive procedure to find metabolic disorders by evaluating brain metabolites. Purpose of this study was to determine efficacy of the MRS in thalamus imaging of patients with IGE. Applying H1-MRS (technique: PRESS-CSI], we evaluated thalamus images of 63 people (35 controls: 23 males, 12 females, ranging in age 19-46 years, average: 34.8±0.62 years) and 28 IGE patients (10 males, 18 females, ranging in age 20-49 years, average: 37.4±1.04 years). The data analyzed by SPSS (v.20]. Comparing the average NAA/Cr for the right thalamus, a significant reduction was seen between the control group and the IGE patients (p<0.0001]. Likewise, for the left thalamus, the NAA/Cr was significantly decreased when we compared it for the control group and the IGE patients (p<0.001). H1-MRS could be a suitable diagnostic technique to evaluate epilepsy in IGE patients. The possible alteration of neuronal pathways in the thalamo-cortical circuit seems to play a critical role in epileptogenesis of IGE

Obstructed and channelized viscoplastic flow in a Hele-Shaw cell

A theoretical study is presented of the flow of viscoplastic fluid through a Hele-Shaw cell that contains various kinds of obstructions. Circular and elliptical blockages of the cell are considered together with stepwise contractions or expansions in slot width, all within the simplifying approximation of a narrow gap. Specific attention is paid to the flow patterns that develop around the obstacles, particularly any stagnant plugged regions, and the asymptotic limits of relatively small or large yield stress. Periodic arrays of circular contractions or expansions are studied to explore the interference between obstructions. Finally, viscoplastic flow through a cell with randomly roughened walls is examined, and it is shown that constructive interference of local contractions and expansions leads to a pronounced channelization of the flow. An optimization algorithm based on minimization of the pressure drop is derived to construct the path of the channels in the limit of relatively large yield stress or, equivalently, relatively slow flow.D.R.H. is grateful to the Killam Foundation for a Postdoctoral Fellowship.This is the author accepted manuscript. The final version is available from Cambridge University Press via http://dx.doi.org/10.1017/jfm.2016.

Using Theory of Constraints in selecting product mix

Theory of Constraints suggests when the product was limited by bottleneck, the best strategy for selecting the product mix is based on the throughput - system performance- in terms of the desired constraint. This issue is not true for products which have been limited by a few quantities . Four realities, which are in opposition to the current thought in TOC literature, have been proved in this article. For instance, the mixed products include some things which have the product lowest margin and the lowest throughput ratio in a limited time and violate marginal and TOC approaches. Such formula constraints which caused by selected mixed products have been proved in this article

Sputtered Gallium Nitride Tunnel Junction Contacts

Gallium nitride LEDs produced for commercialization currently use indium tin oxide (ITO) as both a current spreading layer (CSL) and a contact to p-GaN. ITO is known to absorb wavelengths in the UV and visible light regions, the primary spectrum of GaN devices [20]. Tunnel junctions (TJ) have been proposed as an alternative p-contact and CSL which would transmit more light from the active region [20] while generating holes, from the electron tunneling, to reach the quantum wells of the LEDs for additional radiative recombination [18]-[21]. The fabrication process would also be simplified because the top layer of both the p- and n-contacts would be n-GaN and the metal contacts to both could be deposited at the same time. However, until now all GaN TJs have been deposited by MOCVD or MBE systems despite sputtering machines offering a lower cost and easier to use method of depositing GaN [12] [13]. This thesis explores the application of two sputtering techniques, the electron cyclotron resonance (ECR) and radio frequency (RF) magnetron, to the creation of TJs on blue GaN LEDs.Both sputtering methods utilized silicon doped n-GaN targets with the intention of depositing the n-GaN layer of the TJs. The films were examined for their transmissivity of 440 nm light as well as their resistivity. The ECR system was observed to produce GaN that lost around 5% of the emitted light when N2 in conjunction with argon was used in the sputtering gas. Substrate heating did not meaningfully affect the transmissive property of the deposited GaN. Despite the good optical quality, the GaN remained resistive. Secondary ion mass spectrometry (SIMS) of the n-GaN target found it contain many impurities. High amounts of carbon, hydrogen, oxygen, magnesium, and calcium among other elements were discovered to be within the target. This stopped the research to produce a tunnel junction with the ECR system, but with a cleaner target it could still be a viable option.The RF magnetron machine also relied upon nitrogen within the sputtering gas mixture to produce transparent GaN films. In general, the higher the rate of N2 the less absorption of the tested 440 nm light. Substrate heating did improve the transparency of the GaN when sputtered with the RF magnetron machine. For a gas mixture of 38:25 sccm of N2:Ar and a temperature of 800 ⁰C, the GaN layer absorbed less than one percent of the blue wavelength. Hall-effect measurements showed greater substrate heating also increased the carrier concentration with films reaching the high 1019 and low 1020 cm-3 ranges.During the course of this work the RF magnetron system was modified and the maximum substrate temperature was lowered to 650 ⁰C. Some previous films had been grown at 600 ⁰C and this temperature was kept for continuity, but a silicon target was co-sputtered with the n-GaN target to raise the carrier concentration of the GaN. Hall measurements of these samples presented them to have higher mobilities compared to the GaN sputtered with only the GaN target. Sputtering the silicon target at 35 W of power was determined to give the highest carrier concentration of 1.137x1018 cm-3.A tunnel junction was created utilizing the RF magnetron sputtering system on a UCSB blue LED structure deposited on a sapphire substrate with a MOCVD machine. Silicon was co-sputtered at 35 W and the nitrogen and substrate temperature were set to 38 sccm and 650 ⁰C, respectively, to create the n-GaN layer of the TJ. LEDs with an area of 0.1 mm2 were fabricated and required only two photolithography steps compared to the three steps necessary for ITO GaN LEDs. After a chlorine etch performed by a RIE machine to create the LED mesas, the MOCVD n-GaN around the mesas was noted to be rough in some areas of the wafer. When metal contacts were deposited on these areas, the metal did not stick to the n-GaN. Many LEDs were created in the smoother regions and were observed to emit blue light. These were tested for their current-voltage relationships and were found to have turn-on voltages of approximately 6.5 V with the least resistive devices reaching almost 5 mA at 10 V. These are the first reported GaN tunnel junctions deposited onto LEDs with a sputtering system

Estimation of Association Between a Longitudinal Marker and Interval-Censored Progression Times

In longitudinal studies, we observe the subjects who are likely to progress to a new state during the study time. For example, in clinical trials the stage of a progressing disease is recorded at each follow-up visit. The primary goal is to estimate the relationship between the attributes and the subject\u27s progression state. In such studies, some subjects complete all their follow-up visits and their progression state are observed without any missingness. However, others miss their follow-up visits and when they come back, they learn that they have progressed to a new state. In this case, not only are their progression states at each follow-up interval-censored, but their time-dependent covariates are incomplete. In such studies, the observations are missing at random (MAR). The event of interest, i.e., progression, may have several possible patterns. In some studies, we might be studying progression to only one new state. For example, we are interested in studying the attributes that affect an individual\u27s progression from being a non-smoker to a frequent smoker. Another example would be the patients who are believed to have high risk for developing diabetes, are monitored for advancing to type 2 diabetes. In other studies, the event of interest involves multiple stages. Examples of these studies include several stages of cancer, or different stages of smoking (nonsmoker, light smoker, intermittent smoker, heavy smoker, etc.). These states are chronological. The times of observation, i.e., follow-up interview visits, are pre-specified for these studies. At each time point, the attributes are measured and recorded. Since the study continues over time, it is common for some subjects to miss their follow-up visits. In this case not only the outcome (event of interest) is censored, but their time-dependent attributes are incomplete. In this case, both outcome and attributes need to be estimated for the missed visits. We are interested in studying the time-dependent covariates\u27 effect on the progression. Expectation-maximization (EM) algorithm is used for estimating the parameters. The variance-covariance matrix of the maximum likelihood estimator (MLE) is calculated using the missing information principles. Simulation studies revealed that the proposed method works well in terms of variance, bias, and power in the samples of moderate sizes. When we are estimating the association between longitudinal covariates and an event, we may run into the large number of attributes, which are explanatory but could be highly correlated. Using the usual maximum likelihood estimation method leads to inaccurate parameter estimates. Additionally, the estimators have large variance. Elliot, et al., [14] proposed Mixed Ridge Regression when the outcome of the process is continuous. This method applies ridge regression to a linear mixed effects longitudinal model. In our proposed model, the longitudinal outcome is binary. We apply ridge penalization (based on the L2 norm) to our model to get more accurate parameter estimates. Another important aspect in building a good predictive model is variable selection. Sometimes there are many attributes in a dataset. These attributes are not necessarily correlated. We are interested in choosing a smallest best subset of them for inference. We perform the variable selection by adding the LASSO penalization (based on the L1 norm) to the likelihood to be able to simultaneously choose the appropriate covariates and estimate the covariate effects. Lastly, the preliminary model is extended to the case when there are more than one progression states in the model. These progressions are chronological and assumed to be non-time-reversible. Missing pattern is more complex than that for one progression state case, but the rest of the procedures are pretty similar to those for one progression state case

Environmental Impact of Water Use in Life Cycle of Milk Production

Water has a key role in dairy industry and life cycle assessment (LCA) is one of the tools for environmental assessment of products &amp; processes. A cradle to gate assessment of market milk was performed by separating the system into three sub-systems: agronomy, animal farm and processing plant. Data were gathered from multiple sources e.g. published papers, questionnaire, national and international databases, and the processing plant. Throughout the study, ISO framework and IDF guideline on LCA were used. The functional unit for reporting results was one liter of pasteurized milk (2.5% fat) packaged in plastic pouch. Finally, to quantify and assess the environmental impacts from blue water consumption, parameters of a global water impacts assessment model were modified and used in this case study. In production of one FU, about 370 liters of water is needed mostly for feed production. Feed agriculture sub-system alone withdraws 97% of total. Throughout the market milk product chain, about 40 and 28% of total water withdrawal come from alfalfa and barley production mainly from irrigation. In production of one FU, modified model’s estimate for the impact on human health with the unit of disability-adjusted life years (DALY) was about 0.35*10-6, and its estimated value for the impact on ecosystem quality was 0.324 m2*y

Obstructed viscoplastic flow in a Hele–Shaw cell

Experiments are conducted exploring the flow of Carbopol past obstacles in a narrow slot and compared with predictions of a model based on the Herschel-Bulkley constitutive law and the conventional Hele-Shaw approximation. Although Carbopol is often assumed to be a relatively simple yield-stress fluid, the flow pattern around an obstacle markedly lacks the fore-aft symmetry expected theoretically. Such asymmetry has been observed previously for viscoplastic flows past obstacles in unconfined geometries, but the narrowness of the Hele-Shaw cell ensures that the stress state is very different, placing further constraints on the underlying origin. The asymmetry is robust, as demonstrated by varying the shape and number of the obstacles, the surfaces of the cell walls, and the steadiness of the flow rate. The results suggest that rheological hysteresis near the yield point may be the cause of the asymmetry