Interference lithography for optical devices and coatings

Interference lithography can create large-area, defect-free nanostructures with unique optical properties. In this thesis, interference lithography will be utilized to create photonic crystals for functional devices or coatings. For instance, typical lithographic processing techniques were used to create 1, 2 and 3 dimensional photonic crystals in SU8 photoresist. These structures were in-filled with birefringent liquid crystal to make active devices, and the orientation of the liquid crystal directors within the SU8 matrix was studied. Most of this thesis will be focused on utilizing polymerization induced phase separation as a single-step method for fabrication by interference lithography. For example, layered polymer/nanoparticle composites have been created through the one-step two-beam interference lithographic exposure of a dispersion of 25 and 50 nm silica particles within a photopolymerizable mixture at a wavelength of 532 nm. In the areas of constructive interference, the monomer begins to polymerize via a free-radical process and concurrently the nanoparticles move into the regions of destructive interference. The holographic exposure of the particles within the monomer resin offers a single-step method to anisotropically structure the nanoconstituents within a composite. A one-step holographic exposure was also used to fabricate self- healing coatings that use water from the environment to catalyze polymerization. Polymerization induced phase separation was used to sequester an isocyanate monomer within an acrylate matrix. Due to the periodic modulation of the index of refraction between the monomer and polymer, the coating can reflect a desired wavelength, allowing for tunable coloration. When the coating is scratched, polymerization of the liquid isocyanate is catalyzed by moisture in air; if the indices of the two polymers are matched, the coatings turn transparent after healing. Interference lithography offers a method of creating multifunctional self-healing coatings that readout when damage has occurred.

Modeling the distribution of crossovers and interference with mice DNA data

Chiasma and crossover are two related biological processes of great importance in the understanding genetic variation. The study of these processes is straightforward in organisms where all products of meiosis are recovered and can be observed. This is not the case in mammals. Our understanding of these processes depends on our ability to model them. In this study I describe the biological processes that underline chiasma and crossover as well as the two main inference problems associated with these processes: i) in mammals we only recover one of the four products of meiosis and, ii) in general, we do not observe where the crossovers actually happen, but we find an interval containing type-2 censored information. NPML estimate was proposed and used in this work and used to compare chromosome length and chromosome expansion through the crosses.

Experimental Modeling of Twin-Screw Extrusion Processes to Predict Properties of Extruded Composites

Twin-screw extrusion is used to compound fillers into a polymer matrix in order to improve the properties of the final product. The resultant properties of the composite are determined by the operating conditions used during extrusion processing. Changes in the operating conditions affect the physics of the melt flow, inducing unique composite properties. In the following work, the Residence Stress Distribution methodology has been applied to model both the stress behavior and the property response of a twin-screw compounding process as a function of the operating conditions. The compounding of a pigment into a polymer melt has been investigated to determine the effect of stress on the degree of mixing, which will affect the properties of the composite. In addition, the pharmaceutical properties resulting from the compounding of an active pharmaceutical ingredient are modeled as a function of the operating conditions, indicating the physical behavior inducing the property responses.

Toward an effective strategy in glioblastoma treatment. Part II: RNA interference as a promising way to sensitize glioblastomas to temozolomide.

International audience

Reverse flow and supersonic interference.

"AFOSR TN-58-625. ASTIA doc. no. AD 162 155."

Shifting development in mid-childhood: the influence of between-task interference

Performance on the task-switching paradigm is greatly affected by the amount of conflict between tasks. Compared to adults, children appear to be particularly influenced by this conflict, suggesting that the ability to resolve interference between tasks improves with age. We used the task-switching paradigm to investigate how this ability develops in mid-childhood. Experiment 1 compared 5- to 8-year-olds’ and 9- to 11-year-olds’ ability to switch between decisions about the colour of an object and its shape. The 5- to 8-year-olds were slower to switch task and experienced more interference from the irrelevant task than the 9-to 11-year-olds, suggesting a developmental improvement in resolving conflict between tasks during mid-childhood. Experiment 2 explored this further, examining the influence of stimulus and response interference at different ages. This was done by separating the colour and shape dimensions of the stimulus and reducing overlap between responses. The results supported the development of conflict resolution in task-switching during mid-childhood. They also revealed that a complex interplay of factors, including the tasks used and previous experience with the task, affected children’s shifting performance.

Investigation of the functional roles of host cell proteins involved in Coronavirus infection using highly specific and scalable RNA interference (RNAi) approach

Since its identification in the 1990s, the RNA interference (RNAi) pathway has proven extremely useful in elucidating the function of proteins in the context of cells and even whole organisms. In particular, this sequence-specific and powerful loss-of-function approach has greatly simplified the study of the role of host cell factors implicated in the life cycle of viruses. Here, we detail the RNAi method we have developed and used to specifically knock down the expression of ezrin, an actin binding protein that was identified by yeast two-hybrid screening to interact with the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) spike (S) protein. This method was used to study the role of ezrin, specifically during the entry stage of SARS-CoV infection.

Radio Frequency Superconducting Quantum Interference Device Meta-atoms and Metamaterials: Experiment, Theory, and Analysis

Metamamterials are 1D, 2D or 3D arrays of articial atoms. The articial atoms, called "meta-atoms", can be any component with tailorable electromagnetic properties, such as resonators, LC circuits, nano particles, and so on. By designing the properties of individual meta-atoms and the interaction created by putting them in a lattice, one can create a metamaterial with intriguing properties not found in nature. My Ph. D. work examines the meta-atoms based on radio frequency superconducting quantum interference devices (rf-SQUIDs); their tunability with dc magnetic field, rf magnetic field, and temperature are studied. The rf-SQUIDs are superconducting split ring resonators in which the usual capacitance is supplemented with a Josephson junction, which introduces strong nonlinearity in the rf properties. At relatively low rf magnetic field, a magnetic field tunability of the resonant frequency of up to 80 THz/Gauss by dc magnetic field is observed, and a total frequency tunability of 100% is achieved. The macroscopic quantum superconducting metamaterial also shows manipulative self-induced broadband transparency due to a qualitatively novel nonlinear mechanism that is different from conventional electromagnetically induced transparency (EIT) or its classical analogs. A near complete disappearance of resonant absorption under a range of applied rf flux is observed experimentally and explained theoretically. The transparency comes from the intrinsic bi-stability and can be tuned on/ off easily by altering rf and dc magnetic fields, temperature and history. Hysteretic in situ 100% tunability of transparency paves the way for auto-cloaking metamaterials, intensity dependent filters, and fast-tunable power limiters. An rf-SQUID metamaterial is shown to have qualitatively the same behavior as a single rf-SQUID with regards to dc flux, rf flux and temperature tuning. The two-tone response of self-resonant rf-SQUID meta-atoms and metamaterials is then studied here via intermodulation (IM) measurement over a broad range of tone frequencies and tone powers. A sharp onset followed by a surprising strongly suppressed IM region near the resonance is observed. This behavior can be understood employing methods in nonlinear dynamics; the sharp onset, and the gap of IM, are due to sudden state jumps during a beat of the two-tone sum input signal. The theory predicts that the IM can be manipulated with tone power, center frequency, frequency difference between the two tones, and temperature. This quantitative understanding potentially allows for the design of rf-SQUID metamaterials with either very low or very high IM response.

Fitness cost and interference of Arm/Rmt aminoglycoside resistance with the RsmF housekeeping methyltransferases

Arm/Rmt methyltransferases have emerged recently in pathogenic bacteria as enzymes that confer high-level resistance to 4,6-disubstituted aminoglycosides through methylation of the G1405 residue in the 16S rRNA (like ArmA and RmtA to -E). In prokaryotes, nucleotide methylations are the most common type of rRNA modification, and they are introduced posttranscriptionally by a variety of site-specific housekeeping enzymes to optimize ribosomal function. Here we show that while the aminoglycoside resistance methyltransferase RmtC methylates G1405, it impedes methylation of the housekeeping methyltransferase RsmF at position C1407, a nucleotide that, like G1405, forms part of the aminoglycoside binding pocket of the 16S rRNA. To understand the origin and consequences of this phenomenon, we constructed a series of in-frame knockout and knock-in mutants of Escherichia coli, corresponding to the genotypes rsmF(+), ΔrsmF, rsmF(+) rmtC(+), and ΔrsmF rmtC(+). When analyzed for the antimicrobial resistance pattern, the ΔrsmF bacteria had a decreased susceptibility to aminoglycosides, including 4,6- and 4,5-deoxystreptamine aminoglycosides, showing that the housekeeping methylation at C1407 is involved in intrinsic aminoglycoside susceptibility in E. coli. Competition experiments between the isogenic E. coli strains showed that, contrary to expectation, acquisition of rmtC does not entail a fitness cost for the bacterium. Finally, matrix-assisted laser desorption ionization (MALDI) mass spectrometry allowed us to determine that RmtC methylates the G1405 residue not only in presence but also in the absence of aminoglycoside antibiotics. Thus, the coupling between housekeeping and acquired methyltransferases subverts the methylation architecture of the 16S rRNA but elicits Arm/Rmt methyltransferases to be selected and retained, posing an important threat to the usefulness of aminoglycosides worldwide.

Convergent evolution of PICIs-mediated phage interference

Staphylococcal pathogenicity islands (SaPIs), the prototype members of the family of phage inducible chromosomal islands (PICIs), are extremely mobile phage satellites, which are transferred between bacterial hosts after their induction by a helper phage. The intimate relationship between SaPIs and their helper phages is one of the most studied examples of virus satellite interactions in prokaryotic cells. SaPIs encode and disseminate virulence and fitness factors, representing a driving force for bacterial adaptation and pathogenesis. Many SaPIs encode a conserved morphogenetic operon, including a core set of genes whose function allows them to parasitize and exploit the phage life cycle. One of the central mechanisms of this molecular piracy is the specific packaging of the SaPI genomes into reduced sized capsid structures derived from phage proteins. Pac phages were classically thought to be the only phages involved in the mobilisation of phage-mediated virulence genes, including the transfer of SaPIs within related and non-related bacteria. This study presents the involvement of S. aureus cos phages in the intra- and intergeneric transfer of cos SaPIs for the first time. A novel example of molecular parasitism is shown, by which this newly characterised group of cos SaPIs uses two distinct and complementary mechanisms to take over the helper phage packaging machinery for their own reproduction. SaPIbov5, the prototype of the cos SaPIs, does not encode the characteristic morphogenetic operon found in pac SaPIs. However, cos SaPIs features both pac and cos phage cleavage sequences in their genome, ensuring SaPI packaging in small- and full-sized phage particles, depending on the helper phage. Moreover, cos-site packaging in S. aureus was shown to require the activity of a phage HNH nuclease. The HNH protein functions together with the large terminase subunit, triggering cleavage and melting of the cos-site sequence. In addition, a novel piracy strategy, severely interfering with the helper phage reproduction, was identified in cos SaPIs and characterised. This mechanism of piracy depends on the cos SaPI-encoded ccm gene, which encodes a capsid protein involved in the formation of small phage particles, modifying the assembling process via a scaffolding mechanism. This strategy resembles the ones described for pac SaPIs and represents a remarkable example of convergent evolution. A further convergent mechanism of capsid size-reduction was identified and characterised for the Enterococcus faecalis EfCIV583 pathogenicity island, another member of the PICI family. In this case, the self-encoded CpmE conducts this molecular piracy through a putative scaffolding function. Similar to cos SaPIs, EfCIV583 carries the helper phage cleavage sequence in its genome enabling its mobilisation by the phage terminase complex. The results presented in this thesis show how two examples of non-related members of the PICI family follow the same evolutionary convergent strategy to interfere with their helper phage. These findings could indicate that the described strategies might be widespread among PICIs and implicate a significant impact of PICIs mediated-virulence gene transfer in bacterial evolution and the emergence of pathogenic bacteria.

Congenital thoracic vertebral malformations in brachycephalic “screw-tailed” dog breeds: Validation of a human classification scheme and a method of Cobb angle measurement in the assessment of vertebral column deformity

Congenital vertebral malformations are common in brachycephalic “screw-tailed” dog breeds such as French bulldogs, English bulldogs, Boston terriers, and Pugs. Those vertebral malformations disrupt the normal vertebral column anatomy and biomechanics, potentially leading to deformity of the vertebral column and subsequent neurological dysfunction. The initial aim of this work was to study and determine whether the congenital vertebral malformations identified in those breeds could be translated in a radiographic classification scheme used in humans to give an improved classification, with clear and well-defined terminology, with the expectation that this would facilitate future study and clinical management in the veterinary field. Therefore, two observers who were blinded to the neurologic status of the dogs classified each vertebral malformation based on the human classification scheme of McMaster and were able to translate them successfully into a new classification scheme for veterinary use. The following aim was to assess the nature and the impact of vertebral column deformity engendered by those congenital vertebral malformations in the target breeds. As no gold standard exists in veterinary medicine for the calculation of the degree of deformity, it was elected to adapt the human equivalent, termed the Cobb angle, as a potential standard reference tool for use in veterinary practice. For the validation of the Cobb angle measurement method, a computerised semi-automatic technique was used and assessed by multiple independent observers. They observed not only that Kyphosis was the most common vertebral column deformity but also that patients with such deformity were found to be more likely to suffer from neurological deficits, more especially if their Cobb angle was above 35 degrees.

Study of the Electromagnetic Interference Generated by Wireless Power Transfer Systems

This paper presents a study related with measuring of radio frequency emissions. The purpose is to determine the level of interference generated by wireless power transfer equipment in a specific frequency range, and to compare those levels to the existing standards. The technology of wireless power transfer, especially for electric vehicles batteries charging, is rapidly developing in the recent years. An increasing use of this technology in industrial and consumer electronic products has raised concerns about the possible unfavorable health-effects onto the human being. Another concern is raised from the high intensity fields produced by wireless power transfer systems which will generate highly undesired influence on other electrical and electronic equipment. As a protection against the potential health effects, the governments imposed limits on the occupational and general public exposure to the radio frequencies. These limitations are set out in national and international safety guidelines, standards and regulations. The measurement and evaluation of the human exposure to electromagnetic fields are essential to guarantee occupational and general public safety.

Radiographic outcomes over time after endoscopic anterior scoliosis correction

A prospective, consecutive series of 106 patients receiving endoscopic anterior scoliosis correction. The aim was to analyse changes in radiographic parameters and rib hump in the two years following surgery. Endoscopic anterior scoliosis correction is a level sparing approach, therefore it is important to assess the amount of decompensation which occurs after surgery. All patients received a single anterior rod and vertebral body screws using a standard compression technique. Cleared disc spaces were packed with either mulched femoral head allograft or rib head/iliac crest autograft. Radiographic parameters (major, instrumented, minor Cobb, T5-T12 kyphosis) and rib hump were measured at 2,6,12 and 24 months after surgery. Paired t-tests and Wilcoxon signed ranks tests were used to assess the statistical significant of changes between adjacent time intervals.----- Results: Mean loss of major curve correction from 2 to 24 months after surgery was 4 degrees. Mean loss of rib hump correction was 1.4 degrees. Mean sagittal kyphosis increased from 27 degrees at 2 months to 30.6 degrees at 24 months. Rod fractures and screw-related complications resulted in several degrees less correction than patients without complications, but overall there was no clinically significant decompensation following complications. The study concluded that there are small changes in deformity measures after endoscopic anterior scoliosis surgery, which are statistically significant but not clinically significant.

Low-complexity estimation of CFO and frequency independent I/Q mismatch for OFDM systems

CFO and I/Q mismatch could cause significant performance degradation to OFDM systems. Their estimation and compensation are generally difficult as they are entangled in the received signal. In this paper, we propose some low-complexity estimation and compensation schemes in the receiver, which are robust to various CFO and I/Q mismatch values although the performance is slightly degraded for very small CFO. These schemes consist of three steps: forming a cosine estimator free of I/Q mismatch interference, estimating I/Q mismatch using the estimated cosine value, and forming a sine estimator using samples after I/Q mismatch compensation. These estimators are based on the perception that an estimate of cosine serves much better as the basis for I/Q mismatch estimation than the estimate of CFO derived from the cosine function. Simulation results show that the proposed schemes can improve system performance significantly, and they are robust to CFO and I/Q mismatch.