A Simple Electronic Speckle Pattern Interferometry System using Holographic Optical Elements

The aim of the work reported in this thesis is to develop a simple electronic speckle pattern interferometry (ESPI) system by combining holographic optical element technology with speckly interferometry. A holographic optical element is used in an ESPI system instead of the lenses, mirrors, beam splitters and beam combiners which are usually required in a conventional system. The final ESPI system consists only of a single holographic element, laser and CCD camera. Many currently available systems are complicated and consist of expensive optics that can be difficult to align. Even the simplest require several conventional optical elements to manipulate the laser light and provide the necessary object and reference beams. In this thesis holographic optical element technology is combined with speckle interferometry in order to make a simple, compact and low cost ESPI system. A compact ESPI system is built by incorporating a single holographic optical element, which generates a specked reference beam and combines this with the object wavefront as it approaches the camera. In addition, a dual interferometer was constructed with a facility to test an object using both ESPI and holographic interferometry. In this way the advantages of high quality interference fringes in holographic interferometry, speed and convencience of ESPI can be exploited. Firstly, the use of a self developing holographic recording material allowed live holographic interferometry to be carried out, and viewed with a CCD camera. It was then shown that the recorded hologram could be used, with no further adjustment, to provide a speckle reference beam to the camera, so that ESPI could be performed in the same optical set up. The out of plane deformation of the object was studied with the two techniques in one interferometer and results were presented. The self developing acrylamide based photopolymer used was a holographic recording material formulated and prepared at the Centre for Industrial and Engineering Optics (IEO). Initially, silver halide emulsions (including the HP series silver halide emulsions produced in the Central Laboratory for Optical Storage and Processing of Information, Bulgarian Academy of Sciences, Sofia, Bulgaria) were used to fabricate some of the holographic optical elements because they allowed the recording of reflection format HOEs essential to the compact final ESPI system design. However, as improved formulations of IEO’s own photopolymer became available, reflection holographic optical elements were also recorded in the photopolymer. Full field displacement maps of object deformations were obtained by implementing phase shifting techniques using a laser diode in which the drive current was modulated to produce a path length change by varying the wavelength. The final compact ESPI system using a reflection holographic optical element was also used to study vibration mode patterns. Amplitude and phase of the modes were mapped using phase shifting techniques and the results were presented. For the first time, reflection holographic optical elements recorded in acrylamide based photopolymer material were used in a single optical element interferometer. This system was also used to study the vibration mode pattern of the object

SOLUBILITY AND DISSOLUTION ENHANCEMENT OF IVACAFTOR TABLETS BY USING SOLID DISPERSION TECHNIQUE OF HOT-MELT EXTRUSION - A DESIGN OF EXPERIMENTAL APPROACH

Objective: The objective was to improve the solubility and dissolution of ivacaftor tablets by using solid dispersion (SD) technique.Methods: Ivacaftor is practically insoluble (<0.001 mg/mL) over pH value of 3.0–7.5 due to low solubility, and it shows poor bioavailability after oral administration. Therefore, SDs of Ivacaftor were prepared by SD technique of hot-melt extrusion (HME) by adding different polymers such as Soluplus, Hypromellose 5 cps, and Copovidone with surfactants sodium lauryl sulfate, poloxamer, and polysorbate 80 to enhance its solubility.Results: After the analysis of Fourier-transform infrared spectrometry, X-ray diffraction, and differential scanning calorimetry of SDs by HME shows a converted in crystalline structure form to an amorphous structure form of Ivacaftor. The results show that the formulation of Ivacaftor SDs by HMT has enhanced the solubility and dissolution of Ivacaftor.Conclusion: In the present study, the SDs of the poorly soluble drug substance Ivacaftor were successfully prepared using HME. The in vitro dissolution test shows a significant increase in dissolution rate of SDs prepared by HME (95%) in formulation FHM8 compared with plain Ivacaftor (9%) within 30 min

SOLID DISPERSION - A NOVEL APPROACH FOR BIOAVAILABILITY ENHANCEMENT OF POORLY WATER-SOLUBLE DRUGS IN SOLID ORAL DOSAGE FORMS

Enhancement of the bioavailability of poorly water-soluble drugs is a challenging task in drug development. Currently 40% of new chemical entities are discovered as poorly water-soluble drugs. Solid dispersion is one of the best technology for improving solubility, dissolution rate, and bioavailability. Solid dispersion techniques are more useful for enhancing drug solubility for a combination of drug and inert carrier to improve wettability, reduced particle size, and converting amorphous particles. This article reviews various advantages, methods of solid dispersions, carriers used in solid dispersion, characterization, and marketed products

A Compact Electronic Speckle Pattern Interferometry System using a Photopolymer Reflection Holographic Optical Element

A simple and compact electronic speckle pattern interferometry system using a reflection holographic optical element is presented. The reflection holographic optical element is recorded on an acrylamide based photopolymer formulated and prepared at the Centre for Industrial & Engineering Optics. Light intensity of 40mW/cm2 with an exposure time of 60 seconds was used in fabricating the holographic optical element. The vibration mode patterns of a 4 cm diameter thin circular sheet of brass metal attached to a 4 cm diameter paper cone loud speaker are presented

Maternal Risk Factors Associated with Hypospadias

AbstractIntroduction: Epidemiological studies have elucidated maternal and fetal factors that are associated with an increased risk of hypospadias .This study examined the association of hypospadias risk with several maternal reproductive and demographic characteristics: age, parity, body mass index (BMI), nausea and vomiting of pregnancy, fertility treatments , education and diet .Materials and Methods: Mothers of children with hypospadias were invited to participate in this case control study. Participating mothers completed a self administered questionnaire or a social worker administered/assisted questionnaire. Mothers of age matched children without hypospadias acted as controls and they too similarly completed the same questionnaire.Results: The risk factors associated with hypospadias were maternal age, primiparity , previous fertility treatment and nausea and vomiting of pregnancy .Conclusions: Increased maternal age, primiparity and previous fertility treatments in mothers are associated with an increased risk of hypospadias in male offsprings.Keywords: Hypospadias, Maternal age, Parity, Fertility, Maternal education, Nausea and vomitin

The N-Terminal Domain of Y-Box Binding Protein-1 Induces Cell Cycle Arrest in G2/M Phase by Binding to Cyclin D1

Y-box binding protein YB-1 is a multifunctional protein involved in cell proliferation, regulation of transcription and translation. Our previous study indicated that disruption of one allele of Chk-YB-1b gene in DT-40 cells resulted in major defects in the cell cycle. The abnormalities seen in heterozygous mutants could be attributed to a dominant negative effect exerted by the disrupted YB-1 allele product. To test this hypothesis the N-terminal sequence of the YB-1 was fused with the third helix of antennapedia and the green fluorescent protein. These purified fusion proteins were introduced into rat hepatoma cells and their effect on cell proliferation was studied. Results indicate that the N-terminal 77 amino acid domain of the YB-1 protein induced the cells to arrest in G2/M phase of the cell cycle and undergo apoptosis. Additional deletion analysis indicated that as few as 26 amino acids of the N-terminus of YB-1 can cause these phenotypic changes. We further demonstrated that this N-terminal 77 amino acid domain of YB-1 sequesters cyclin D1 in the cytoplasm of cells at G2/M phase of cell cycle. We conclude that the N-terminal domain of YB-1 plays a major role in cell cycle progression through G2/M phase of cell cycle

Torsional Strength and Stiffness of a Passenger Car Coupling System

Between September 2019 and June 2022, the Federal Railroad Administration (FRA) sponsored a research team from Sharma & Associates to model and test the torsional strength of a passenger car coupling system to understand the performance of coupling systems in train accidents and to enhance current specifications. The team designed a test fixture to apply a controlled torque to a complete coupling system comprising a coupler, yoke, draft gear, and draft sill, and developed a Finite Element (FE) model of the test fixture to assess its structural integrity and to predict the applied torque necessary for failure. The team identified two modes of failure, draft sill failure and coupler shank failure. The mode of failure was found to depend on the degree of constraint provided by the draft sill. Researchers found the results of full-scale testing agreed reasonably well with those measured in the FE model tests. Classical overturning calculations indicated that an applied torsional moment of 297 kip-ft, the lowest measured torsional capacity of the tested coupling system, would likely rollover a single rail car. Such an applied torsional moment will likely be near or beyond the yield capacity of modern car structures and would need to be evaluated on a case-by-case basis in possible future work

Macrocyclic colibactin induces DNA double-strand breaks via copper-mediated oxidative cleavage.

Colibactin is an assumed human gut bacterial genotoxin, whose biosynthesis is linked to the clb genomic island that has a widespread distribution in pathogenic and commensal human enterobacteria. Colibactin-producing gut microbes promote colon tumour formation and enhance the progression of colorectal cancer via cellular senescence and death induced by DNA double-strand breaks (DSBs); however, the chemical basis that contributes to the pathogenesis at the molecular level has not been fully characterized. Here, we report the discovery of colibactin-645, a macrocyclic colibactin metabolite that recapitulates the previously assumed genotoxicity and cytotoxicity. Colibactin-645 shows strong DNA DSB activity in vitro and in human cell cultures via a unique copper-mediated oxidative mechanism. We also delineate a complete biosynthetic model for colibactin-645, which highlights a unique fate of the aminomalonate-building monomer in forming the C-terminal 5-hydroxy-4-oxazolecarboxylic acid moiety through the activities of both the polyketide synthase ClbO and the amidase ClbL. This work thus provides a molecular basis for colibactin's DNA DSB activity and facilitates further mechanistic study of colibactin-related colorectal cancer incidence and prevention

Selection of RNA aptamers that bind HIV-1 LTR DNA duplexes: strand invaders

RNA that can specifically bind to double-stranded DNA is of interest because it might be used as a means to regulate transcription of the target genes. To explore possible interactions between RNA and duplex DNA, we selected for RNA aptamers that can bind to the long terminal repeats (LTRs) of human immunodeficiency virus type 1 DNA. The selected aptamers were classified into four major groups based on the consensus sequences, which were found to locate in the non-stem regions of the predicted RNA secondary structures, consistent with roles in target binding. Analysis of the aptamer consensus sequences suggested that the conserved segments could form duplexes via Watson–Crick base-pairing with preferred sequences in one strand of the DNA, assuming the aptamer invaded the duplex. The aptamer binding sites on the LTR were experimentally determined to be located preferentially at these sites near the termini of double-stranded target DNA, despite selection schemes that were designed to minimize preferences for termini. The results presented here show that aptamer RNAs can be selected in vitro that strand-invade at preferred DNA duplex sequences to form stable complexes