Quantitative measurements in 3-dimensional datasets of mouse lymph nodes resolve organ-wide functional dependencies

Deep tissue imaging has become state of the art in biology, but now the problem is to quantify spatial information in a global, organ-wide context. Although access to the raw data is no longer a limitation, the computational tools to extract biologically useful information out of these large data sets is still catching up. In many cases, to understand the mechanism behind a biological process, where molecules or cells interact with each other, it is mandatory to know their mutual positions. We illustrate this principle here with the immune system. Although the general functions of lymph nodes as immune sentinels are well described, many cellular and molecular details governing the interactions of lymphocytes and dendritic cells remain unclear to date and prevent an in-depth mechanistic understanding of the immune system. We imaged ex vivo lymph nodes isolated from both wild-type and transgenic mice lacking key factors for dendritic cell positioning and used software written in MATLAB to determine the spatial distances between the dendritic cells and the internal high endothelial vascular network. This allowed us to quantify the spatial localization of the dendritic cells in the lymph node, which is a critical parameter determining the effectiveness of an adaptive immune response.

Molecular investigation of lymph nodes in colon cancer patients using one-step nucleic acid amplification (OSNA): a new road to better staging?

A new diagnostic system, called one-step nucleic acid amplification (OSNA), has recently been designed to detect cytokeratin 19 mRNA as a surrogate for lymph node metastases. The objective of this prospective investigation was to compare the performance of OSNA with both standard hematoxylin and eosin (H&E) analysis and intensive histopathology in the detection of colon cancer lymph node metastases.

Characterization of retinal damage in the episcleral vein cauterization rat glaucoma model

Episcleral vein cauterization (EVC) is used in rats to generate a glaucoma model with high intraocular pressure (IOP). The long-term retinal damage in this glaucoma model, however, has not been accurately quantified. We report the location and amount of retinal ganglion cell (RGC) damage caused by (EVC) induced IOP elevation in two rat strains. IOP was raised in one eye of Wistar (N = 5) and Brown-Norway(B-N)(N = 7) rats by EVC and monitored monthly until IOP in contralateral eyes equalized at 5 months post-surgery. Animals were maintained for 3.5-4.5 additional months. B-N rats (N = 7) that had no EVC served as controls for this strain. Scotopic flash ERGs were recorded at baseline and just prior to euthanasia. Automated counts of all retrogradely labeled RGCs in retinal flat-mounts were determined and compared between contralateral eyes. RGC density maps were constructed and RGC size distribution was determined. Oscillatory potentials in the group of eyes which had elevated IOP were decreased at the time of euthanasia, when IOP had returned to normal. The group of normal B-N rats had similar RGC counts between contralateral eyes. In the experimental group the mean number of RGCs was not significantly different between control and experimental eyes, but 1 of 5 Wistar and 2 of 7 B-N experimental eyes had at least 30% fewer RGCs than contralateral control eyes. Total retinal area in B-N experimental eyes was higher compared to contralateral eyes. Cumulative IOP exposure of the experimental eyes was modestly correlated with RGC loss while oscillatory potentials appeared to be inversely related to RGC loss. In retinas with extensive (> 30% RGC loss) but not complete damage, smaller cells were preserved better than larger ones. The above results indicate that RGC loss in both Wistar and B-N strains is variable after a prolonged elevation of IOP via EVC. Such variability despite equivalent IOP levels and ERG abnormalities, suggests unknown factors that can protect IOP-stressed RGCs. Identification and enhancement of such factors could prove useful for glaucoma therapy.

Use of straight and curved 3-dimensional titanium miniplates for fracture fixation at the mandibular angle

PURPOSE: The aim of this follow-up study was to evaluate the clinical usefulness of a new type of 3-dimensional (3D) miniplate for open reduction and monocortical fixation of mandibular angle fractures. PATIENTS AND METHODS: In 20 consecutive patients, noncomminuted mandibular angle fractures were treated with open reduction and fixation using a 2 mm 3D miniplate system in a transoral approach. All patients were systematically monitored until 6 months postoperatively. Among the outcome parameters recorded were infection, hardware failure, wound dehiscence, and sensory disturbance of the inferior alveolar nerve. RESULTS: The mean operation time from incision to wound closure was 65 minutes. Two patients had a mucosal wound dehiscence with no consequences. None developed an infection requiring a plate removal. All but 2 patients had normal sensory function 3 months after surgery. Plate fracture occurred in one patient in whom a preceding surgical removal of the third molar had been the reason for the mandibular fracture. In the absence of clinical symptoms, the patient declined plate removal. On final follow-up, fracture healing was considered clinically complete in all patients. CONCLUSIONS: The 3D plating system described here is suitable for fixation of simple mandibular angle fractures and is an easy-to-use alternative to conventional miniplates. The system may be contraindicated in patients in whom insufficient interfragmentary bone contact causes minor stability of the fracture.

Dynamic modeling of active regeneration in catalyzed and non-catalyzed diesel particulate filters

Particulate matter (PM) emissions standards set by the US Environmental Protection Agency (EPA) have become increasingly stringent over the years. The EPA regulation for PM in heavy duty diesel engines has been reduced to 0.01 g/bhp-hr for the year 2010. Heavy duty diesel engines make use of an aftertreatment filtration device, the Diesel Particulate Filter (DPF). DPFs are highly efficient in filtering PM (known as soot) and are an integral part of 2010 heavy duty diesel aftertreatment system. PM is accumulated in the DPF as the exhaust gas flows through it. This PM needs to be removed by oxidation periodically for the efficient functioning of the filter. This oxidation process is also known as regeneration. There are 2 types of regeneration processes, namely active regeneration (oxidation of PM by external means) and passive oxidation (oxidation of PM by internal means). Active regeneration occurs typically in high temperature regions, about 500 - 600 °C, which is much higher than normal diesel exhaust temperatures. Thus, the exhaust temperature has to be raised with the help of external devices like a Diesel Oxidation Catalyst (DOC) or a fuel burner. The O2 oxidizes PM producing CO2 as oxidation product. In passive oxidation, one way of regeneration is by the use of NO2. NO2 oxidizes the PM producing NO and CO2 as oxidation products. The passive oxidation process occurs at lower temperatures (200 - 400 °C) in comparison to the active regeneration temperatures. Generally, DPF substrate walls are washcoated with catalyst material to speed up the rate of PM oxidation. The catalyst washcoat is observed to increase the rate of PM oxidation. The goal of this research is to develop a simple mathematical model to simulate the PM depletion during the active regeneration process in a DPF (catalyzed and non-catalyzed). A simple, zero-dimensional kinetic model was developed in MATLAB. Experimental data required for calibration was obtained by active regeneration experiments performed on PM loaded mini DPFs in an automated flow reactor. The DPFs were loaded with PM from the exhaust of a commercial heavy duty diesel engine. The model was calibrated to the data obtained from active regeneration experiments. Numerical gradient based optimization techniques were used to estimate the kinetic parameters of the model.

Optical hysteresis of ridge waveguide magnetic garnet films and cavities in two-dimensional magneto-photonic crystal slabs

Magnetic iron garnets as well as magnetic photonic crystals are of great interests in magneto-optic applications such as isolators, current captors, circulators, TE-TM mode conversion, wavelength accordable filters, optical sensors and switches, all of which provide a promising platform for future integrated optical circuits. In the present work, two topics are studied based on magnetic iron garnet films. In the first part, the characteristics of the magnetization are investigated for ridge waveguides fabricated on (100) oriented iron garnet thin films. The magnetic response in magneto-optic waveguides patterned on epitaxial magnetic garnet films depends on the crystallographic orientation of the waveguides and the magnetic anisotropy of the material. These can be studied by polarization rotation hysteresis loops, which are related to the component of magnetization parallel to the light propagation direction and the linear birefringence. Polarization rotation hysteresis loops for low birefringence waveguides with different orientations are experimentally investigated. Asymmetric stepped curves are obtained from waveguides along, due to the large magnetocrystalline anisotropy in the plane. A model based on the free energy density is developed to demonstrate the motion of the magnetization and can be used in the design of magneto-optic devices. The second part of this thesis focuses on the design and fabrication of high-Q cavities in two-dimensional magneto-photonic crystal slabs. The device consists of a layer of silicon and a layer of iron garnet thin film. Triangular lattice elliptical air holes are patterned in the slab. The fundamental TM band gap overlaps with the first-order TE band gap from 0374~0.431(a/λ) showing that both TE and TM polarization light can be confined in the photonic crystals. A nanocavity is designed to obtain both TE and TM defect modes in the band gaps. Additional work is needed to overlap the TE and TM defect modes and obtain a high-Q cavity so as to develop miniaturized Faraday rotators.

Development of system separation strategy using synchrophasor data

In the current market system, power systems are operated at higher loads for economic reasons. Power system stability becomes a genuine concern in such operating conditions. In case of failure of any larger component, the system may become stressed. These events may start cascading failures, which may lead to blackouts. One of the main reasons of the major recorded blackout events has been the unavailability of system-wide information. Synchrophasor technology has the capability to provide system-wide real time information. Phasor Measurement Units (PMUs) are the basic building block of this technology, which provide the Global Positioning System (GPS) time-stamped voltage and current phasor values along with the frequency. It is being assumed that synchrophasor data of all the buses is available and thus the whole system is fully observable. This information can be used to initiate islanding or system separation to avoid blackouts. A system separation strategy using synchrophasor data has been developed to answer the three main aspects of system separation: (1) When to separate: One class support machines (OC-SVM) is primarily used for the anomaly detection. Here OC-SVM was used to detect wide area instability. OC-SVM has been tested on different stable and unstable cases and it is found that OC-SVM has the capability to detect the wide area instability and thus is capable to answer the question of “when the system should be separated”. (2) Where to separate: The agglomerative clustering technique was used to find the groups of coherent buses. The lines connecting different groups of coherent buses form the separation surface. The rate of change of the bus voltage phase angles has been used as the input to this technique. This technique has the potential to exactly identify the lines to be tripped for the system separation. (3) What to do after separation: Load shedding was performed approximately equal to the sum of power flows along the candidate system separation lines should be initiated before tripping these lines. Therefore it is recommended that load shedding should be initiated before tripping the lines for system separation.

Driver Safety in Far-side and Far-oblique Crashes: A Study of Patrol Vehicles in the United States of America

The dissertation titled "Driver Safety in Far-side and Far-oblique Crashes" presents a novel approach to assessing vehicle cockpit safety by integrating Human Factors and Applied Mechanics. The methodology of this approach is aimed at improving safety in compact mobile workspaces such as patrol vehicle cockpits. A statistical analysis performed using Michigan state's traffic crash data to assess various contributing factors that affect the risk of severe driver injuries showed that the risk was greater for unrestrained drivers (OR=3.38, p<0.0001) and for incidents involving front and far-side crashes without seatbelts (OR=8.0 and 23.0 respectively, p<0.005). Statistics also showed that near-side and far-side crashes pose similar threat to driver injury severity. A Human Factor survey was conducted to assess various Human-Machine/Human-Computer Interaction aspects in patrol vehicle cockpits. Results showed that tasks requiring manual operation, especially the usage of laptop, would require more attention and potentially cause more distraction. A vehicle survey conducted to evaluate ergonomics-related issues revealed that some of the equipment was in airbag deployment zones. In addition, experiments were conducted to assess the effects on driver distraction caused by changing the position of in-car accessories. A driving simulator study was conducted to mimic HMI/HCI in a patrol vehicle cockpit (20 subjects, average driving experience = 5.35 years, s.d. = 1.8). It was found that the mounting locations of manual tasks did not result in a significant change in response times. Visual displays resulted in response times less than 1.5sec. It can also be concluded that the manual task was equally distracting regardless of mounting positions (average response time was 15 secs). Average speeds and lane deviations did not show any significant results. Data from 13 full-scale sled tests conducted to simulate far-side impacts at 70 PDOF and 40 PDOF was used to analyze head injuries and HIC/AIS values. It was found that accelerations generated by the vehicle deceleration alone were high enough to cause AIS 3 - AIS 6 injuries. Pretensioners could mitigated injuries only in 40 PDOF (oblique) impacts but are useless in 70 PDOF impacts. Seat belts were ineffective in protecting the driver's head from injuries. Head would come in contact with the laptop during a far-oblique (40 PDOF) crash and far-side door for an angle-type crash (70 PDOF). Finite Element analysis head-laptop impact interaction showed that the contact velocity was the most crucial factor in causing a severe (and potentially fatal) head injury. Results indicate that no equipment may be mounted in driver trajectory envelopes. A very narrow band of space is left in patrol vehicles for installation of manual-task equipment to be both safe and ergonomic. In case of a contact, the material stiffness and damping properties play a very significant role in determining the injury outcome. Future work may be done on improving the interiors' material properties to better absorb and dissipate kinetic energy of the head. The design of seat belts and pretensioners may also be seen as an essential aspect to be further improved.