Development of micro immunosensors to study genomic and proteomic biomarkers related to cancer and Alzheimer's disease

A report from the National Institutes of Health defines a disease biomarker as a “characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.” Early diagnosis is a crucial factor for incurable disease such as cancer and Alzheimer’s disease (AD). During the last decade researchers have discovered that biochemical changes caused by a disease can be detected considerably earlier as compared to physical manifestations/symptoms. In this dissertation electrochemical detection was utilized as the detection strategy as it offers high sensitivity/specificity, ease of operation, and capability of miniaturization and multiplexed detection. Electrochemical detection of biological analytes is an established field, and has matured at a rapid pace during the last 50 years and adapted itself to advances in micro/nanofabrication procedures. Carbon fiber microelectrodes were utilized as the platform sensor due to their high signal to noise ratio, ease and low-cost of fabrication, biocompatibility, and active carbon surface which allows conjugation with biorecognition moieties. This dissertation specifically focuses on the detection of 3 extensively validated biomarkers for cancer and AD. Firstly, vascular endothelial growth factor (VEGF) a cancer biomarker was detected using a one-step, reagentless immunosensing strategy. The immunosensing strategy allowed a rapid and sensitive means of VEGF detection with a detection limit of about 38 pg/mL with a linear dynamic range of 0–100 pg/mL. Direct detection of AD-related biomarker amyloid beta (Aβ) was achieved by exploiting its inherent electroactivity. The quantification of the ratio of Aβ1-40/42 (or Aβ ratio) has been established as a reliable test to diagnose AD through human clinical trials. Triple barrel carbon fiber microelectrodes were used to simultaneously detect Aβ1-40 and Aβ1-42 in cerebrospinal fluid from rats within a detection range of 100nM to 1.2μM and 400nM to 1μM respectively. In addition, the release of DNA damage/repair biomarker 8-hydroxydeoxyguanine (8-OHdG) under the influence of reactive oxidative stress from single lung endothelial cell was monitored using an activated carbon fiber microelectrode. The sensor was used to test the influence of nicotine, which is one of the most biologically active chemicals present in cigarette smoke and smokeless tobacco.

The Creation and Evaluation of Novel Canine Training Aids for Cocaine Using Molecularly Encapsulated Sol-Gel Polymers and an Investigation of Canine Field Accuracy

Biological detectors, such as canines, are valuable tools used for the rapid identification of illicit materials. However, recent increased scrutiny over the reliability, field accuracy, and the capabilities of each detection canine is currently being evaluated in the legal system. For example, the Supreme Court case, State of Florida v. Harris, discussed the need for continuous monitoring of canine abilities, thresholds, and search capabilities. As a result, the fallibility of canines for detection was brought to light, as well as a need for further research and understanding of canine detection. This study is two-fold, as it looks to not only create new training aids for canines that can be manipulated for dissipation control, but also investigates canine field accuracy to objects with similar odors to illicit materials. It was the goal of this research to improve upon current canine training aid mimics. Sol-gel polymer training aids, imprinted with the active odor of cocaine, were developed. This novel training aid improved upon the longevity of currently existing training aids, while also provided a way to manipulate the polymer network to alter the dissipation rate of the imprinted active odors. The manipulation of the polymer network could allow handlers to control the abundance of odors presented to their canines, familiarizing themselves to their canine’s capabilities and thresholds, thereby increasing the canines’ strength in court. The field accuracy of detection canines was recently called into question during the Supreme Court case, State of Florida v. Jardines, where it was argued that if cocaine’s active odor, methyl benzoate, was found to be produced by the popular landscaping flower, snapdragons, canines will false alert to said flowers. Therefore, snapdragon flowers were grown and tested both in the laboratory and in the field to determine the odors produced by snapdragon flowers; the persistence of these odors once flowers have been cut; and whether detection canines will alert to both growing and cut flowers during a blind search scenario. Results revealed that although methyl benzoate is produced by snapdragon flowers, certified narcotics detection canines can distinguish cocaine’s odor profile from that of snapdragon flowers and will not alert.

The application of a novel, cell permeable activity-based probe for the detection of cysteine cathepsins.

Cysteine cathepsins, such as cathepsin S (CTSS), are implicated in the pathology of a wide range of diseases and are of potential utility as diagnostic and prognostic biomarkers. In previous work, we demonstrated the potency and efficiency of a biotinylated diazomethylketone (DMK)-based activity-based probe (ABP), biotin-PEG-LVG-DMK, for disclosure of recombinant CTSS and CTSS in cell lysates. However, the limited cell permeability of both the biotin and spacer groups restricted detection of CTSS to cell lysates. The synthesis and characterisation of a cell permeable ABP to report on intracellular CTSS activity is reported. The ABP, Z-PraVG-DMK, a modified peptidyl diazomethylketone, was based on the N-terminus of human cystatin motif (Leu-Val-Gly). The leucine residue was substituted for the alkyne-bearing proparcylglycine to facilitate conjugation of an azide-tagged reporter group using click chemistry, following irreversible inhibition of CTSS. When incubated with viable Human Embryonic Kidney 293 cells, Z-PraVG-DMK permitted disclosure of CTSS activity following cell lysis and rhodamine azide conjugation, by employing standard click chemistry protocols. Furthermore, the fluorescent tag facilitated direct detection of CTSS using in-gel fluorescent scanning, obviating the necessity for downstream biotin-streptavidin conjugation and detection procedures.

A survey of intrusion detection system technologies

This paper provides an overview of IDS types and how they work as well as configuration considerations and issues that affect them. Advanced methods of increasing the performance of an IDS are explored such as specification based IDS for protecting Supervisory Control And Data Acquisition (SCADA) and Cloud networks. Also by providing a review of varied studies ranging from issues in configuration and specific problems to custom techniques and cutting edge studies a reference can be provided to others interested in learning about and developing IDS solutions. Intrusion Detection is an area of much required study to provide solutions to satisfy evolving services and networks and systems that support them. This paper aims to be a reference for IDS technologies other researchers and developers interested in the field of intrusion detection.

A Mobile High Sensitivity On-field Organophosphorous Compounds Detecting System for IoT Based Food Safety Tracking

Food safety has always been a social issue that draws great public attention. With the rapid development of wireless communication technologies and intelligent devices, more and more Internet of Things (IoT) systems are applied in the food safety tracking field. However, connection between things and information system is usually established by pre-storing information of things into RFID Tag, which is inapplicable for on-field food safety detection. Therefore, considering pesticide residue is one of the severe threaten to food safety, a new portable, high-sensitivity, low-power, on-field organophosphorus (OP) compounds detection system is proposed in this thesis to realize the on-field food safety detection. The system is designed based on optical detection method by using a customized photo-detection sensor. A Micro Controller Unit (MCU) and a Bluetooth Low Energy (BLE) module are used to quantize and transmit detection result. An Android Application (APP) is also developed for the system to processing and display detection result as well as control the detection process. Besides, a quartzose sample container and black system box are also designed and made for the system demonstration. Several optimizations are made in wireless communication, circuit layout, Android APP and industrial design to realize the mobility, low power and intelligence.

The creation and evaluation of novel canine training aids for cocaine using molecularly encapsulated sol-gel polymers and an investigation of canine field accuracy

Biological detectors, such as canines, are valuable tools used for the rapid identification of illicit materials. However, recent increased scrutiny over the reliability, field accuracy, and the capabilities of each detection canine is currently being evaluated in the legal system. For example, the Supreme Court case, State of Florida v. Harris, discussed the need for continuous monitoring of canine abilities, thresholds, and search capabilities. As a result, the fallibility of canines for detection was brought to light, as well as a need for further research and understanding of canine detection. This study is two-fold, as it looks to not only create new training aids for canines that can be manipulated for dissipation control, but also investigates canine field accuracy to objects with similar odors to illicit materials. ^ It was the goal of this research to improve upon current canine training aid mimics. Sol-gel polymer training aids, imprinted with the active odor of cocaine, were developed. This novel training aid improved upon the longevity of currently existing training aids, while also provided a way to manipulate the polymer network to alter the dissipation rate of the imprinted active odors. The manipulation of the polymer network could allow handlers to control the abundance of odors presented to their canines, familiarizing themselves to their canine’s capabilities and thresholds, thereby increasing the canines’ strength in court.^ The field accuracy of detection canines was recently called into question during the Supreme Court case, State of Florida v. Jardines, where it was argued that if cocaine’s active odor, methyl benzoate, was found to be produced by the popular landscaping flower, snapdragons, canines will false alert to said flowers. Therefore, snapdragon flowers were grown and tested both in the laboratory and in the field to determine the odors produced by snapdragon flowers; the persistence of these odors once flowers have been cut; and whether detection canines will alert to both growing and cut flowers during a blind search scenario. Results revealed that although methyl benzoate is produced by snapdragon flowers, certified narcotics detection canines can distinguish cocaine’s odor profile from that of snapdragon flowers and will not alert.^

A fiber Bragg grating sensor system for train axle counting

Railway signaling facilitates two main functions, namely, train detection and train control, in order to maintain safe separations among the trains. Track circuits are the most commonly used train detection means with the simple open/close circuit principles; and subsequent adoption of axle counters further allows the detection of trains under adverse track conditions. However, with electrification and power electronics traction drive systems, aggravated by the electromagnetic interference in the vicinity of the signaling system, railway engineers often find unstable or even faulty operations of track circuits and axle counting systems, which inevitably jeopardizes the safe operation of trains. A new means of train detection, which is completely free from electromagnetic interference, is therefore required for the modern railway signaling system. This paper presents a novel optical fiber sensor signaling system. The sensor operation, field setup, axle detection solution set, and test results of an installation in a trial system on a busy suburban railway line are given.

Light stop in the MSSM after LHC Run 1

The discovery of a Higgs boson with a mass of 126 GeV at the LHC when combined with the non-observation of new physics both in direct and indirect searches imposes strong constraints on supersymmetric models and in particular on the top squark sector. The experiments for direct detection of dark matter have provided with yet more constraints on the neutralino LSP mass and its interactions. After imposing limits from the Higgs, flavour and dark matter sectors, we examine the feasibility for a light stop in the context of the pMSSM, in light of current results for stop and other SUSY searches at the LHC. We only require that the neutralino dark matter explains a fraction of the cosmologically measured dark matter abundance. We find that a stop with mass below similar to 500 GeV is still allowed. We further study various probes of the light stop scenario that could be performed at the LHC Run-II either through direct searches for the light and heavy stop, or SUSY searches not currently available in simplified model results. Moreover we study the characteristics of heavy Higgs for the points in the parameter space allowed by all the available constraints and illustrate the region with large cross sections to fermionic or electroweakino channels. Finally we show that nearly all scenarios with a small stop-LSP mass difference will be tested by Xenon1T provided the NLSP is a chargino, thus probing a region hard to access at the LHC.

Properties of amorphous carbon-silicon alloys deposited by a high plasma density source

The addition of silicon to hydrogenated amorphous carbon can have the advantageous effect of lowering the compressive stress, improving the thermal stability of its hydrogen, and maintaining a low friction coefficient up to high humidity. Most experiments to date have been on hydrogenated amorphous carbon-silicon alloys (a-C1-xSix:H) deposited by rf plasma enhanced chemical vapor deposition. This method gives alloys with sizeable hydrogen content and only moderate hardness. Here we use a high plasma density source known as the electron cyclotron wave resonance source to prepare films with higher sp3 content and lower hydrogen content. The composition and bonding in the alloys is determined by x-ray photoelectron spectroscopy, Rutherford backscattering, elastic recoil detection analysis, visible and ultraviolet (UV) Raman spectroscopy, infrared spectroscopy, and x-ray reflectivity. We find that it is possible to produce relatively hard, low stress, low friction, almost humidity insensitive a-C1-xSix:H alloys with a good optical transparency and a band gap well over 2.5 eV. The friction behavior and friction mechanism of these alloys are studied and compared with that of a-C:H, ta-C:H, and ta-C. We show how UV Raman spectroscopy allows the direct detection of Si-C, Si-Hx, and C-Hx vibrations, not seen in visible Raman spectra. © 2001 American Institute of Physics.

Entwicklung einer einfachen und schnellen Analysenmethode für Kohlenmonoxid in Fisch und Durchführung orientierender Untersuchungen

Treatment with gases containing CO, misleadingly called “tasteless smoke” or “clear smoke”, prior to freezing of fish like tuna, tilapia and swordfish (to name only a few of these species that are characterised by an intensive coloration of flesh) stabilise the fresh red colour of muscle also after thawing and suggest consumers non-existing freshness. In the European Union, carbon monoxide is excluded from being a permitted additive and therefore this handling is not allowed. Notwithstanding of the clear legal position, producers and traders are trying to establish CO treated fish on the market. In the case of taking legal measures the food control laboratories have to provide evidence that fish has been treated by CO and therefore a respective method is necessary. The method of determination of carbon monoxide in fish flesh presently applied requires considerable material and mechanistic effort to detect CO by GC after catalytic transformation into methane. The aim of our work was a direct detection of CO using suitable sensor technology. Mechanistic requirements and results of preliminary investigations to detect carbon monoxide in fish flesh will be described.

Baryon number violation beyond the standard model

This thesis describes simple extensions of the standard model with new sources of baryon number violation but no proton decay. The motivation for constructing such theories comes from the shortcomings of the standard model to explain the generation of baryon asymmetry in the universe, and from the absence of experimental evidence for proton decay. However, lack of any direct evidence for baryon number violation in general puts strong bounds on the naturalness of some of those models and favors theories with suppressed baryon number violation below the TeV scale. The initial part of the thesis concentrates on investigating models containing new scalars responsible for baryon number breaking. A model with new color sextet scalars is analyzed in more detail. Apart from generating cosmological baryon number, it gives nontrivial predictions for the neutron-antineutron oscillations, the electric dipole moment of the neutron, and neutral meson mixing. The second model discussed in the thesis contains a new scalar leptoquark. Although this model predicts mainly lepton flavor violation and a nonzero electric dipole moment of the electron, it includes, in its original form, baryon number violating nonrenormalizable dimension-five operators triggering proton decay. Imposing an appropriate discrete symmetry forbids such operators. Finally, a supersymmetric model with gauged baryon and lepton numbers is proposed. It provides a natural explanation for proton stability and predicts lepton number violating processes below the supersymmetry breaking scale, which can be tested at the Large Hadron Collider. The dark matter candidate in this model carries baryon number and can be searched for in direct detection experiments as well. The thesis is completed by constructing and briefly discussing a minimal extension of the standard model with gauged baryon, lepton, and flavor symmetries.

Lock Acquisition and Sensitivity Analysis of Advanced LIGO Interferometers

Laser interferometer gravitational wave observatory (LIGO) consists of two complex large-scale laser interferometers designed for direct detection of gravitational waves from distant astrophysical sources in the frequency range 10Hz - 5kHz. Direct detection of space-time ripples will support Einstein's general theory of relativity and provide invaluable information and new insight into physics of the Universe.

Initial phase of LIGO started in 2002, and since then data was collected during six science runs. Instrument sensitivity was improving from run to run due to the effort of commissioning team. Initial LIGO has reached designed sensitivity during the last science run, which ended in October 2010.

In parallel with commissioning and data analysis with the initial detector, LIGO group worked on research and development of the next generation detectors. Major instrument upgrade from initial to advanced LIGO started in 2010 and lasted till 2014.

This thesis describes results of commissioning work done at LIGO Livingston site from 2013 until 2015 in parallel with and after the installation of the instrument. This thesis also discusses new techniques and tools developed at the 40m prototype including adaptive filtering, estimation of quantization noise in digital filters and design of isolation kits for ground seismometers.

The first part of this thesis is devoted to the description of methods for bringing interferometer to the linear regime when collection of data becomes possible. States of longitudinal and angular controls of interferometer degrees of freedom during lock acquisition process and in low noise configuration are discussed in details.

Once interferometer is locked and transitioned to low noise regime, instrument produces astrophysics data that should be calibrated to units of meters or strain. The second part of this thesis describes online calibration technique set up in both observatories to monitor the quality of the collected data in real time. Sensitivity analysis was done to understand and eliminate noise sources of the instrument.

Coupling of noise sources to gravitational wave channel can be reduced if robust feedforward and optimal feedback control loops are implemented. The last part of this thesis describes static and adaptive feedforward noise cancellation techniques applied to Advanced LIGO interferometers and tested at the 40m prototype. Applications of optimal time domain feedback control techniques and estimators to aLIGO control loops are also discussed.

Commissioning work is still ongoing at the sites. First science run of advanced LIGO is planned for September 2015 and will last for 3-4 months. This run will be followed by a set of small instrument upgrades that will be installed on a time scale of few months. Second science run will start in spring 2016 and last for about 6 months. Since current sensitivity of advanced LIGO is already more than factor of 3 higher compared to initial detectors and keeps improving on a monthly basis, upcoming science runs have a good chance for the first direct detection of gravitational waves.

Noise Cancellation for Gravitational Wave Detectors

The LIGO gravitational wave detectors are on the brink of making the first direct detections of gravi- tational waves. Noise cancellation techniques are described, in order to simplify the commissioning of these detectors as well as significantly improve their sensitivity to astrophysical sources. Future upgrades to the ground based detectors will require further cancellation of Newtonian gravitational noise in order to make the transition from detectors striving to make the first direct detection of gravitational waves, to observatories extracting physics from many, many detections. Techniques for this noise cancellation are described, as well as the work remaining in this realm.

车载直接探测多普勒测风激光雷达光学鉴频器

基于建立的车载直接探测激光雷达系统，对接收光学鉴频器进行了研究。针对边界层、对流层和平流层不同的气溶胶和大气分子浓度以及风速动态范围，同时采用直接探测的两种主要技术。利用多光束菲索（Fizeau）干涉仪（MFI）和阵列光电倍增管（PMT），接收气溶胶散射信号，获得边界层风速。采用双法布里-珀罗（Fabry-Perot）干涉仪（DFP）和光电倍增管探测器，分析分子散射信号，得到对流层风场。使用实际的激光雷达系统参数和大气模型参数，对两个鉴频器进行了优化设计，分析了它们的风速测量灵敏度和精度。多光束菲索干涉仪

光谱稳定性对直接探测多普勒测风激光雷达的影响研究

The wind error of the double-edge technique Doppler lidar due to the instability of injection-seeding solid laser and the drift of interferometer s spectrum was analyzed. Corresponding numerical simulation indicated that if the wind error of 1 m/s was achieved, the unsuccessful injection-seeding pulses should be less than 0.06% in integration time of 5 min. (30000 pulses). In the respect of spectrum drift of the interferometer, double temperature control systems were used and the accuracy of minus or plus 0.002°C was obtained, corresponding to the wind error of minus or plus 0.226 m/s. Monitoring of buildup time of the injection-seeding laser and temperature of the interferometer was significantly to improve the invertion accuracy of wind error by rejecting the data with frequency jumping and drifting. Researches of injection-seeding and spectrum stability of the interferometer were practical for the development of double-edge wind lidar.}