The effects of rapid stretch injury on rat neocortical cultures

Several key biological mechanisms of traumatic injury to axons have been elucidated using in vitro stretch injury models. These models, however, are based on the experimentation of single cultures keeping productivity slow. Indeed, low yield has hindered important and well founded investigations requiring high throughput methods such as proteomic analyses. To meet this need, a multi-well high throughput injury device is engineered to accelerate and accommodate the next generation of traumatic brain injury research. This modular system stretch-injures neuronal cultures in either a 24-well culture plate format or six individual wells simultaneously. Custom software control allows the user to accurately program the pressure pulse parameters to achieve the desired substrate deformation and injury parameters. Classically, in vitro research in TBI has shown increases in [Ca2+]i levels following injury. The Ca2+ sensitive fluorescent dye, Fluo-4AM, is used to observe the effects of strain rate on the changes in [Ca2+]i levels following injury. Neuronal cultures are injured at three strain levels: 20%, 40% and 60% strain. At each of these strain levels, two strain rates are applied; 30s-1 (slow) and 70s-1 (rapid). At each strain level, the data show that neurons injured at 70s-1 experience larger maximum F/F0 and longer sustained Ca2+ fluorescence than neurons injured at 30s-1. It is also shown that at high strain rates TTx no longer blocks increases in [Ca2+]i levels after injury. Traumatic injury to the brain is known to cause dysfunction in surviving neurons. The effects of simulated traumatic injury of rat neocortical neurons cultures are investigated. These neurons are subjected to a stretch injury of 60% strain over 20 ms using a custom in vitro injury device. Spontaneous and stimulated electrical properties are measured 20-60 minutes after stretch using current and voltage clamp techniques. The same measurements are performed in non-stretched neurons. All neurons display TTX-inhibitable action potentials when basal membrane potential was set at -60 mV, and many display bursting behavior in response to depolarizing current injection. No differences in resting membrane potential (-40 ± 1 mV [n=20]) or input resistance (1.0 ± 0.1 GΩ [n=20]) are observed in injured and non-injured neurons. Interestingly, stretch injury reduces the frequency of spontaneous action potentials (33 ± 6 min-1 [ n=13] and 11 ± 3 min-1 [n=16] in non-injured and injured neurons, respectively) and decreases spontaneous bursting activity by almost 90%. ADP50 and action potential amplitude are unchanged. However, A D P90 is significantly prolonged in injured neurons and characterized by a less pronounced action potential after-hyperpolarization. These data are consistent with an alteration in kinetics of K+ currents in injured neurons. Since spontaneous action potentials are blocked by 20 µM bicuculline and 3 mM kyneuri nic acid, the frequency of subthreshold depolarizations is measured to estimate overall neuronal network activity. The frequency of spontaneous subthreshold depolarizations is not significantly different in injured and non-injured neurons. These data show that spontaneous electrical signaling is acutely altered and suggest that action potential initiation is reduced by in vitro stretch in neuronal cell cultures

Inventory control of spare parts using a Bayesian approach: a case study

This paper presents a case study of applying a Bayesian approach to forecast demand and subsequently determine the appropriate parameter S of an (S-1,S) inventory system for controlling spare parts of electronic equipment. First, the problem and the current policy are described. Then, the basic elements of the Bayesian approach are introduced and the procedure for calculating the appropriate parameter S is illustrated. Finally, we present the results of applying the Bayesian approach in an innovative way to determine the stock levels of three types of circuit packs at several locations. According to the proposed method, a lower base stock than the one currently used is sufficient to achieve the desired service level.inventory control;spare parts;case study;Bayesian analysis

Holographic Wilsonian Renormalization and Chiral Phase Transitions

We explore the role of a holographic Wilsonian cut-off in simple probe brane models with chiral symmetry breaking/restoration phase transitions. The Wilsonian cut-off allows us to define supergravity solutions for off-shell configurations and hence to define a potential for the chiral condensate. We pay particular attention to the need for configurations whose action we are comparing to have the same IR and UV boundary conditions. We exhibit new first and second order phase transitions with changing cut-off. We derive the effective potential for the condensate including mean field and BKT type continuous transitions.Comment: 14 pages, 16 figures, v2: Added references, corrected typos, v3: minor corrections, the version to appear in PR

Inventory control of spare parts using a Bayesian approach: a case study

This paper presents a case study of applying a Bayesian approach to forecast demand and subsequently determine the appropriate parameter S of an (S-1,S) inventory system for controlling spare parts of electronic equipment. First, the problem and the current policy are described. Then, the basic elements of the Bayesian approach are introduced and the procedure for calculating the appropriate parameter S is illustrated. Finally, we present the results of applying the Bayesian approach in an innovative way to determine the stock levels of three types of circuit packs at several locations. According to the proposed method, a lower base stock than the one currently used is sufficient to achieve the desired service level

Phase diagram of the D3/D5 system in a magnetic field and a BKT transition

We study the full temperature and chemical potential dependence of the D3/D5 2+1 dimensional theory in the presence of a magnetic field. The theory displays separate transitions associated with chiral symmetry breaking and melting of the bound states. We display the phase diagram which has areas with first and second order transitions meeting at two critical points similar to that of the D3/D7 system. In addition there is the recently reported BKT transition at zero temperature leading to distinct structure at low temperatures.Comment: 5 pages, 3 figures, V2: references adde

Magnetic Field Induced Quantum Criticality via new Asymptotically AdS_5 Solutions

Using analytical methods, we derive and extend previously obtained numerical results on the low temperature properties of holographic duals to four-dimensional gauge theories at finite density in a nonzero magnetic field. We find a new asymptotically AdS_5 solution representing the system at zero temperature. This solution has vanishing entropy density, and the charge density in the bulk is carried entirely by fluxes. The dimensionless magnetic field to charge density ratio for these solutions is bounded from below, with a quantum critical point appearing at the lower bound. Using matched asymptotic expansions, we extract the low temperature thermodynamics of the system. Above the critical magnetic field, the low temperature entropy density takes a simple form, linear in the temperature, and with a specific heat coefficient diverging at the critical point. At the critical magnetic field, we derive the scaling law s ~ T^{1/3} inferred previously from numerical analysis. We also compute the full scaling function describing the region near the critical point, and identify the dynamical critical exponent: z=3. These solutions are expected to holographically represent boundary theories in which strongly interacting fermions are filling up a Fermi sea. They are fully top-down constructions in which both the bulk and boundary theories have well known embeddings in string theory.Comment: 50 page

The Baryonic Phase in Holographic Descriptions of the QCD Phase Diagram

We study holographic models of the QCD temperature-chemical potential phase diagram based on the D3/D7 system with chiral symmetry breaking. The baryonic phase may be included through linked D5-D7 systems. In a previous analysis of a model with a running gauge coupling a baryonic phase was shown to exist to arbitrarily large chemical potential. Here we explore this phase in a more generic phenomenological setting with a step function dilaton profile. The change in dilaton generates a linear confining $\bar{q}q$ potential and opposes the screening effect of temperature. We show that the persistence of the baryonic phase depends on the step size and that QCD-like phase diagrams can be described. The baryonic phase's existence is qualitatively linked to the existence of confinement in Wilson loop computations in the background.Comment: 21 pages, 7 figure

Towards a Holographic Model of the QCD Phase Diagram

We describe the temperature-chemical potential phase diagrams of holographic models of a range of strongly coupled gauge theories that display chiral symmetry breaking/restoration transitions. The models are based on the D3/probe-D7 system but with a phenomenologically chosen running coupling/dilaton profile. We realize chiral phase transitions with either temperature or density that are first or second order by changing the dilaton profile. Although the models are only caricatures of QCD they show that holographic models can capture many aspects of the QCD phase diagram and hint at the dependence on the running coupling.Comment: 11 pages, 9 figures, v2: minor corrections, Invited contribution to an AdS/CFT edition of Journal of Physics

Fluid percussion injury device for the precise control of injury parameters

BackgroundInjury to the brain can occur from a variety of physical insults and the degree of disability can greatly vary from person to person. It is likely that injury outcome is related to the biomechanical parameters of the traumatic event such as magnitude, direction and speed of the forces acting on the head.New methodTo model variations in the biomechanical injury parameters, a voice coil driven fluid percussion injury (FPI) system was designed and built to generate fluid percussion waveforms with adjustable rise times, peak pressures, and durations. Using this system, pathophysiological outcomes in the rat were investigated and compared to animals injured with the same biomechanical parameters using the pendulum based FPI system.Results in comparison with existing methodsImmediate post-injury behavior shows similar rates of seizures and mortality in adolescent rats and similar righting times, toe pinch responses and mortality rates in adult rats. Interestingly, post injury mortality in adult rats was sensitive to changes in injury rate. Fluoro-Jade labeling of degenerating neurons in the hilus and CA2-3 hippocampus were consistent between injuries produced with the voice coil and pendulum operated systems. Granule cell population spike amplitude to afferent activation, a measure of dentate network excitability, also showed consistent enhancement 1 week after injury using either system.ConclusionsOverall our results suggest that this new FPI device produces injury outcomes consistent with the commonly used pendulum FPI system and has the added capability to investigate pathophysiology associated with varying rates and durations of injury

Holographic descriptions of chiral phase transitions

Quantum Chromodynamics (QCD) poses a challenge in calculating physical phenomena in low energy scales due to its strongly coupled character. The tools available for understanding this region of QCD are limited. One such tool is gauge/gravity duality which promises to attack strongly coupled related phenomena, at least in a qualitative level, by using the conjectured equivalence between string theory and some classes of quantum field theories (gauge/gravity duality). In this thesis strongly coupled 3+1d and 2+1d field theories are explored by using D3/D7 and D3/D5 brane systems respectively. These theories exhibit some QCD-like characteristics like chiral symmetry breaking and confinement. The main focus of the following chapters is understanding chiral phase transitions in those theories and constructing their phase diagrams in finite temperature and chemical potential. Chiral symmetry breaking is induced in these holographic brane setups by turning on a background magnetic field or by choosing an appropriate running dilaton profile. The phase diagrams for each field theory considered are mapped, giving a rich structure of first, second and BKT holographic transitions. Some successful attempts where made to reproduce the standard QCD phase diagram, in the running dilaton scenario. Also, in the running dilaton case wrapped D5 branes where used to introduce holographic baryons. The baryonic phase, for some range of the parameter space, participates in the phase diagram and it is found in the regime expected from QCD. Finally, chiral phase transitions with energy scale where explored as well as their holographic effective potentials for various D3/D7 and D3/D5 systems