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Papers by David Abraham

MRS Proceedings, 2000

In this paper we describe improved methods of fabrication for an oxide channel field effect trans... more In this paper we describe improved methods of fabrication for an oxide channel field effect transistor (OxFET) similar in architecture to a conventional FET. We demonstrate that a substrate treatment consisting of a low power oxygen ashing followed by annealing yields a strontium (A-site) terminated surface in single-crystal strontium titanate (STO). This surface termination of the substrate results in pulsed laser deposited cuprate-channel films of improved quality.

Extended Abstracts of the 2010 International Conference on Solid State Devices and Materials, 2010

Medical Dosimetry, 2000

The use of total-body irradiation (TBI) for the purpose of bone marrow transplant is an establish... more The use of total-body irradiation (TBI) for the purpose of bone marrow transplant is an established procedure at many institutions. In our institution, the TBI monitor unit (MU) calculation starts with the calibration done at the same conditions of the treatment source-axis distance (SAD) ‫؍‬ 350 cm for the field size of 40 ؋ 40 cm at a depth of 10 cm). The dose rate in the central axis of the beam at this distance is measured in cGy/MU. A tissue phantom ratio table obtained in the condition of treatment together with off-axis factors is used in the MU calculation for each particular patient. The treatment is done with the patient lying on his/her back and the beam is delivered using right-to-left lateral beams. Due to different thickness' of the patient, a lead compensator is built to compensate for the different parts of the body. Eighteen or 10-MV x-ray photons are used in the TBI treatment, and a 1-cm-thick lucite plate is placed near the patient to increase the dose to the surface. In vivo dosimetry using diodes is done to verify the calculations. The Rando-Phantom™ was computedtomography scanned from the head to the abdomen with 1-cm-thick slices covering 70 cm of the phantom. This simulated the TBI treatment and correlated the calculations done by the ADAC treatment planning system to film measurements at the pelvis and lung levels. These results agreed within 5% of the measured dose. The use of the upper arms to reduce the dose to the lungs and optimization of dose using special compensators has been studied using the treatment planning system. Use of the multileaf collimator to compensate the dose received by the patient has been explored in this paper.

The human saphenous vein (SV) suffers trauma during harvesting for CABG which reflects on the gra... more The human saphenous vein (SV) suffers trauma during harvesting for CABG which reflects on the graft patency (Souza 1996, Souza et al. 2006, Dashwood and Loesch 2007). Commonly used harvesting procedures involve stripping the pedicle of connective tissue from the vein followed by the distension to overcome venospasm (Souza 1996). Such procedures cause structural damage of the vein vascular smooth muscle cells (VSMC) and rapid expression of immunoreactive iNOS (Loesch et al. 2006). Here, we used standard protocols of immunolabelling for confocal and electron microscopy (EM) and Western blot analysis to study the co-expression of iNOS and ET-1 in medial VSMC of SV harvested in patients undergoing CABG. Objectives: To study the effects of harvesting techniques on the expression of iNOS and ET-1 in the tunica media of SV used as grafts in ten patients undergoing CABG. These patients received both SV grafts harvested conventionally and SV grafts harvested using the ‘no-touch’ technique (S...

International Journal for Parasitology, 2014

Vaccination of Mongolian gerbils with Brugia malayi cysteine protease inhibitor-2 in which the am... more Vaccination of Mongolian gerbils with Brugia malayi cysteine protease inhibitor-2 in which the amino acid Asn66 was mutated to Lys66 (Bm-CPI-2M) resulted in reduced parasite numbers of 48.6% and 48.0 % at 42 and 90 days p.i. with B. malayi L3s. Fertility of female worms was also affected at 90 days p.i. In vitro killing of L3s observed in the presence of gerbil peritoneal exudate cells and anti-Bm-CPI-2M sera suggests antibody-dependent cell-mediated cytotoxicity as a putative protective mechanism. These observations suggest that Bm-CPI-2M is a promising prophylactic and anti-fecundity vaccine candidate.

Physical Review B, 1987

Images of the (0001) surface of graphite observed in the scanning-tunneling microscope (STM) show... more Images of the (0001) surface of graphite observed in the scanning-tunneling microscope (STM) show a strong asymmetry in the tunneling current between neighboring carbon atoms in the hexagonal ring. The magnitude of this asymmetry is seen to be almost independent of the polarity and to decrease slightly with increasing amplitude of the bias voltage for voltages below 1 V. A theory is developed that explains this anomaly as a purely electronic effect, arising from the symmetry of the states scanned by the STM, which dominates over the topography of graphite. The predicted trends for the bias-voltage dependence of the asymmetry are confirmed experimentally. (b) (c). , ' FICJ. l. (a) Observed and (b) and (c) calculated STM current densities j(x,y, z =const) for a bias voltage V=Q. I V. In (c), calculated results of (b) have been Fourier analyzed and filtered to mimic the experimental conditions. On the grey scale, white corresponds to large current densities.

International Journal for Parasitology, 2014

Human onchocerciasis is a neglected tropical disease caused by Onchocerca volvulus and an importa... more Human onchocerciasis is a neglected tropical disease caused by Onchocerca volvulus and an important cause of blindness and chronic disability in the developing world. Although mass drug administration of ivermectin has had a profound effect on control of the disease, additional tools are critically needed including the need for a vaccine against onchocerciasis. The objectives of the present study were to: (i) select antigens with known vaccine pedigrees as components of a vaccine; (ii) produce the selected vaccine antigens under controlled conditions, using two expression systems and in one laboratory and (iii) evaluate their vaccine efficacy using a single immunisation protocol in mice. In addition, we tested the hypothesis that joining protective antigens as a fusion protein or in combination, into a multivalent vaccine, would improve the ability of the vaccine to induce protective immunity. Out of eight vaccine candidates tested in this study, Ov-103, Ov-RAL-2 and Ov-CPI-2M were shown to reproducibly induce protective immunity when administered individually, as fusion proteins or in combination. Although there was no increase in the level of protective immunity induced by combining the antigens into one vaccine, these antigens remain strong candidates for inclusion in a vaccine to control onchocerciasis in humans.

Vascular Pharmacology, 2006

International Journal of Biochemistry, 1988

Abstract 1. 1. The intracellular distribution of α- d -mannosidase in homogenates of murine liver... more Abstract 1. 1. The intracellular distribution of α- d -mannosidase in homogenates of murine liver and spleen was investigated by differential and gradient density centrifugation. 2. 2. In both tissues an enzyme with a neutral pH optimum was found in the cytosol together with an α- d -mannosidase with optimal activity between pH 5.5 and 6.0 which was also partially membrane-bound. 3. 3. In liver the acidic α- d -mannosidase was obtained almost entirely in a particulate form distributed equally between a heterogeneous low density region and heavy density lysosomes. 4. 4. The lysosomal form of the liver enzyme was purified to electrophoretic homogeneity and shown to be a glycoprotein composed of four identical subunits of molecular weight 65 kDa. 5. 5. Antibody raised against the purified liver α- d -mannosidase immunoprecipitated a polypeptide from spleen which had the same molecular size. This acidic enzyme was the predominant type of α- d -mannosidase in spleen, but in contrast to liver, it was obtained mainly in a cytosoluble form, the remaining activity being present in the heterogenous light density compartment. 6. 6. Although both tissues contain the same molecular form of the acidic α- d -mannosidase, in murine spleen this enzyme does not appear to be associated with stable heavy density lysosomes.

Springer Seminars in Immunopathology, 2000

PLoS Neglected Tropical Diseases, 2011

Background: Differences between noninfective first-stage (L1) and infective third-stage (L3i) lar... more Background: Differences between noninfective first-stage (L1) and infective third-stage (L3i) larvae of parasitic nematode Strongyloides stercoralis at the molecular level are relatively uncharacterized. DNA microarrays were developed and utilized for this purpose. Methods and Findings: Oligonucleotide hybridization probes for the array were designed to bind 3,571 putative mRNA transcripts predicted by analysis of 11,335 expressed sequence tags (ESTs) obtained as part of the Nematode EST project. RNA obtained from S. stercoralis L3i and L1 was co-hybridized to each array after labeling the individual samples with different fluorescent tags. Bioinformatic predictions of gene function were developed using a novel cDNA Annotation System software. We identified 935 differentially expressed genes (469 L3i-biased; 466 L1-biased) having twofold expression differences or greater and microarray signals with a p value,0.01. Based on a functional analysis, L1 larvae have a larger number of genes putatively involved in transcription (p = 0.004), and L3i larvae have biased expression of putative heat shock proteins (such as hsp-90). Genes with products known to be immunoreactive in S. stercoralis-infected humans (such as SsIR and NIE) had L3i biased expression. Abundantly expressed L3i contigs of interest included S. stercoralis orthologs of cytochrome oxidase ucr 2.1 and hsp-90, which may be potential chemotherapeutic targets. The S. stercoralis ortholog of fatty acid and retinol binding protein-1, successfully used in a vaccine against Ancylostoma ceylanicum, was identified among the 25 most highly expressed L3i genes. The sperm-containing glycoprotein domain, utilized in a vaccine against the nematode Cooperia punctata, was exclusively found in L3i biased genes and may be a valuable S. stercoralis target of interest. Conclusions: A new DNA microarray tool for the examination of S. stercoralis biology has been developed and provides new and valuable insights regarding differences between infective and noninfective S. stercoralis larvae. Potential therapeutic and vaccine targets were identified for further study.

Parasite Immunology, 2002

The objective of this study was to examine the role of B cells in primary and challenge infection... more The objective of this study was to examine the role of B cells in primary and challenge infections of larval Strongyloides stercoralis in mice. Two strains of B-cell deficient mice were used in these studies, µ MT mice that lack all B cells and Xid mice that lack B-1 cells. Primary immune responses in µ MT mice were sufficient to eliminate all parasites within 1 week after infection. Immunized µ MT and Xid mice, however, were unable to kill challenge parasites at 24 h post infection, the time that they were eliminated in immunized wild-type mice. This was despite having a significant increase in interleukin-5 secreting cells and high numbers of eosinophils in the microenvironment of the challenge larvae. In addition, immunized Xid mice did not generate parasite-specific immunoglobulin (Ig)M but did develop a weak IgG response compared to wild-type mice. These results demonstrate a dichotomy in the requirement of B cells in immunity to S. stercoralis. B cells are not required in the primary response, yet they are required in the secondary immune response. B-1 cells are required for the secondary immune response and their role appears to be the production of IgM and not as a source of immunoregulatory molecules.

Journal of the Optical Society of America B, 1997

We address the propagation properties of short, noisy pulses in the spectral vicinity of the zero... more We address the propagation properties of short, noisy pulses in the spectral vicinity of the zero-dispersion wavelength of single-mode fibers. We present a numerical propagation model that includes amplitude fluctuations by introducing a Gaussian statistical distribution of the peak powers. Experiments that use as a source a figure-eight-shaped fiber laser terminated by various types and lengths of dispersion-shifted fiber confirm the calculated propagation properties. We demonstrate the dependence on mean peak power, on noise, and on fiber length of the spectral and temporal evolutions of the propagating pulses.

Microbes and Infection, 2011

Neutrophil recruitment via CXCR2 is required for innate and adaptive protective immunity to the l... more Neutrophil recruitment via CXCR2 is required for innate and adaptive protective immunity to the larvae of Strongyloides stercoralis in mice. The goal of the present study was to determine the mechanism of CXCR2-mediated neutrophil recruitment to S. stercoralis. Mice deficient in the receptor for IL-17A and IL-17F, upstream mediators of CXCR2 ligand production, were infected with S. stercoralis larvae; there was no difference in larval survival, neutrophil recruitment, or production of CXCR2 ligands compared with wild type mice. In vivo and in vitro stimulation of neutrophils with S. stercoralis soluble extract resulted in significant neutrophil recruitment. In vitro assays demonstrated that the recruitment functioned through both chemokinesis and chemotaxis, was specific for CXCR2, and was a G protein coupled response involving tyrosine kinase and PI3K. Finally, neutrophil stimulation with S. stercoralis soluble extract induced release of the CXCR2 ligands MIP-2 and KC from neutrophils, thereby potentially enhancing neutrophil recruitment.

Matrix Biology, 2008

Most tissue cells need to anchor to a 'solid' for viability, and over the last decade it has beco... more Most tissue cells need to anchor to a 'solid' for viability, and over the last decade it has become increasingly clear that the physical 'elasticity' of that solid-like matrix is literally 'felt' by cells. In fact, matrix elasticity as an insoluble cue now appears to synergize with the effects of soluble factors [1]. We will show that Mesenchymal Stem Cells (MSCs) specify lineage and commit to phenotypes with extreme sensitivity to the elasticity typical of tissues [2]. In serum only media, soft matrices that mimic brain appear neurogenic, stiffer matrices that mimic muscle are myogenic, and comparatively rigid matrices that mimic collagenous 'osteoid' prove osteogenic. Inhibition of myosin II blocks all lineage specification, indicating that the cell pulls on matrix through adhesions. In addition to the work with stem cells, studies of isolated, beating cardiomyocytes on elastic matrices demonstrate the sensitivity of cell differentiation: cardiomyocytes stop beating most rapidly on matrices as rigid as an infarct scarand this is shown to be about as hard as osteoid. The results predict that an infarct scar not only opposes cardiogenesis through de-differentiation but would tend to promote osteogenesis, which appears consistent with recent observations in mouse [3]. The results have also motivated development of a proteomic-scale method to identify mechano-responsive protein structures [4].

Matrix Biology, 2004

An enhancer region in the type I collagen alpha 2 chain (pro-Col1a2) promoter has been previously... more An enhancer region in the type I collagen alpha 2 chain (pro-Col1a2) promoter has been previously identified approximately y17 kb away from the transcription start site. This upstream region termed the far-upstream-enhancer contains three DNAse I hypersensitive sites and has been shown to be conserved between mouse and human genes. In this study, we used transgenic mice harbouring the complete promotor sequence of the pro-Col1a2 gene up to y17 kb to examine the role of this enhancer in the expression and regulation of the collagen gene during development and in adult tissues pre and post injury. By careful histological mapping of the collagen type I endogenous gene distribution with that of the transgene driven by the mouse far upstream enhancer, we are able to show that in early days of collagen expression, E8.5-9.5, the endogenous gene preceded transgene expression. However, by E11.5 the overall pattern becomes synchronous with a few exceptions. In adult tissue, both endogenous and transgene expression are attenuated and both are reactivated in parallel in various organs by physical injury or fibrogenic cytokine injection. These findings suggest that the enhancer is central to the activation of the collagen type I and that mice harbouring this enhanceryreporter provide a useful model to follow collagen gene transcription activity and for investigating cellular activity in tissue fibrosis.

Journal of Vascular Surgery, 2011

Journal of Vascular Surgery, 2013

Journal of Micro/Nanolithography, MEMS, and MOEMS, 2006

Antireflective (AR) coating on waveguides with high refractive index is imperative to minimize in... more Antireflective (AR) coating on waveguides with high refractive index is imperative to minimize insertion losses. In fabricating silicon, rectangular, suspended waveguides on silicon-on-insulator (SOI) wafers, a single Si3N4 layer is deposited on the waveguide walls. For the purpose of applying an optimum layer, we develop an integrated micromechanical gauge to determine the coating width by measuring the induced stress in the silicon. Gauges at different sites on a wafer produce results with a standard deviation of about 0.5%. The insertion loss due to the waveguides is measured directly by coupling a laser beam at 1550 nm from a single-mode fiber to the waveguide, then to another fiber and a detector. Tests are run on six wafers and two types of devices: a waveguide with two facets and a waveguide with a gap, presenting four facets. The optimal silicon-nitride thickness is found at 200 nm, featuring a fiber-waveguide-fiber insertion loss of about 1 dB for a two-facet device and 1.7 dB for a four-facet device.

Journal of Leukocyte Biology, 2007

The heterotrimeric guanine nucleotidebinding protein G␣i2 is involved in regulation of immune res... more The heterotrimeric guanine nucleotidebinding protein G␣i2 is involved in regulation of immune responses against microbial and nonmicrobial stimuli. G␣i2 ؊/؊ mice have a selectively impaired IgM response consistent with a disorder in B cell development yet have augmented T cell effector function associated with increased production of IFN-␥ and IL-4. The goal of the present study was to determine if a deficiency in the G␣i2 protein in mice would affect the protective immune response against Strongyloides stercoralis, which is IL-4-, IL-5-, and IgM-dependent. G␣i2 ؊/؊ and wild-type mice were immunized and challenged with S. stercoralis larvae and analyzed for protective immune responses against infection. G␣i2 ؊/؊ mice failed to kill the larvae in the challenge infection as compared with wild-type mice, despite developing an antigen-specific Th2 response, characterized by increased IL-4, IL-5, IgM, and IgG. Transfer of serum collected from immunized G␣i2 ؊/؊ mice to naïve, wild-type mice conferred passive, protective immunity against S. stercoralis infection, thus confirming the development of a protective antibody response in G␣i2 ؊/؊ mice. Differential cell analyses and myeloperoxidase assays for quantification of neutrophils showed a significantly reduced recruitment of neutrophils into the microenvironment of the parasites in immunized G␣i2 ؊/؊ mice. However, cell transfer studies demonstrated that neutrophils from G␣i2 ؊/؊ mice are competent in killing larvae. These data demonstrate that G␣i2 signaling events are not required for the development of the protective immune responses against S. stercoralis; however, G␣i2 is essential for the recruitment of neutrophils required for host-dependent killing of larvae.

MRS Proceedings, 2000

In this paper we describe improved methods of fabrication for an oxide channel field effect trans... more In this paper we describe improved methods of fabrication for an oxide channel field effect transistor (OxFET) similar in architecture to a conventional FET. We demonstrate that a substrate treatment consisting of a low power oxygen ashing followed by annealing yields a strontium (A-site) terminated surface in single-crystal strontium titanate (STO). This surface termination of the substrate results in pulsed laser deposited cuprate-channel films of improved quality.

Extended Abstracts of the 2010 International Conference on Solid State Devices and Materials, 2010

Medical Dosimetry, 2000

The use of total-body irradiation (TBI) for the purpose of bone marrow transplant is an establish... more The use of total-body irradiation (TBI) for the purpose of bone marrow transplant is an established procedure at many institutions. In our institution, the TBI monitor unit (MU) calculation starts with the calibration done at the same conditions of the treatment source-axis distance (SAD) ‫؍‬ 350 cm for the field size of 40 ؋ 40 cm at a depth of 10 cm). The dose rate in the central axis of the beam at this distance is measured in cGy/MU. A tissue phantom ratio table obtained in the condition of treatment together with off-axis factors is used in the MU calculation for each particular patient. The treatment is done with the patient lying on his/her back and the beam is delivered using right-to-left lateral beams. Due to different thickness' of the patient, a lead compensator is built to compensate for the different parts of the body. Eighteen or 10-MV x-ray photons are used in the TBI treatment, and a 1-cm-thick lucite plate is placed near the patient to increase the dose to the surface. In vivo dosimetry using diodes is done to verify the calculations. The Rando-Phantom™ was computedtomography scanned from the head to the abdomen with 1-cm-thick slices covering 70 cm of the phantom. This simulated the TBI treatment and correlated the calculations done by the ADAC treatment planning system to film measurements at the pelvis and lung levels. These results agreed within 5% of the measured dose. The use of the upper arms to reduce the dose to the lungs and optimization of dose using special compensators has been studied using the treatment planning system. Use of the multileaf collimator to compensate the dose received by the patient has been explored in this paper.

The human saphenous vein (SV) suffers trauma during harvesting for CABG which reflects on the gra... more The human saphenous vein (SV) suffers trauma during harvesting for CABG which reflects on the graft patency (Souza 1996, Souza et al. 2006, Dashwood and Loesch 2007). Commonly used harvesting procedures involve stripping the pedicle of connective tissue from the vein followed by the distension to overcome venospasm (Souza 1996). Such procedures cause structural damage of the vein vascular smooth muscle cells (VSMC) and rapid expression of immunoreactive iNOS (Loesch et al. 2006). Here, we used standard protocols of immunolabelling for confocal and electron microscopy (EM) and Western blot analysis to study the co-expression of iNOS and ET-1 in medial VSMC of SV harvested in patients undergoing CABG. Objectives: To study the effects of harvesting techniques on the expression of iNOS and ET-1 in the tunica media of SV used as grafts in ten patients undergoing CABG. These patients received both SV grafts harvested conventionally and SV grafts harvested using the ‘no-touch’ technique (S...

International Journal for Parasitology, 2014

Vaccination of Mongolian gerbils with Brugia malayi cysteine protease inhibitor-2 in which the am... more Vaccination of Mongolian gerbils with Brugia malayi cysteine protease inhibitor-2 in which the amino acid Asn66 was mutated to Lys66 (Bm-CPI-2M) resulted in reduced parasite numbers of 48.6% and 48.0 % at 42 and 90 days p.i. with B. malayi L3s. Fertility of female worms was also affected at 90 days p.i. In vitro killing of L3s observed in the presence of gerbil peritoneal exudate cells and anti-Bm-CPI-2M sera suggests antibody-dependent cell-mediated cytotoxicity as a putative protective mechanism. These observations suggest that Bm-CPI-2M is a promising prophylactic and anti-fecundity vaccine candidate.

Physical Review B, 1987

Images of the (0001) surface of graphite observed in the scanning-tunneling microscope (STM) show... more Images of the (0001) surface of graphite observed in the scanning-tunneling microscope (STM) show a strong asymmetry in the tunneling current between neighboring carbon atoms in the hexagonal ring. The magnitude of this asymmetry is seen to be almost independent of the polarity and to decrease slightly with increasing amplitude of the bias voltage for voltages below 1 V. A theory is developed that explains this anomaly as a purely electronic effect, arising from the symmetry of the states scanned by the STM, which dominates over the topography of graphite. The predicted trends for the bias-voltage dependence of the asymmetry are confirmed experimentally. (b) (c). , ' FICJ. l. (a) Observed and (b) and (c) calculated STM current densities j(x,y, z =const) for a bias voltage V=Q. I V. In (c), calculated results of (b) have been Fourier analyzed and filtered to mimic the experimental conditions. On the grey scale, white corresponds to large current densities.

International Journal for Parasitology, 2014

Human onchocerciasis is a neglected tropical disease caused by Onchocerca volvulus and an importa... more Human onchocerciasis is a neglected tropical disease caused by Onchocerca volvulus and an important cause of blindness and chronic disability in the developing world. Although mass drug administration of ivermectin has had a profound effect on control of the disease, additional tools are critically needed including the need for a vaccine against onchocerciasis. The objectives of the present study were to: (i) select antigens with known vaccine pedigrees as components of a vaccine; (ii) produce the selected vaccine antigens under controlled conditions, using two expression systems and in one laboratory and (iii) evaluate their vaccine efficacy using a single immunisation protocol in mice. In addition, we tested the hypothesis that joining protective antigens as a fusion protein or in combination, into a multivalent vaccine, would improve the ability of the vaccine to induce protective immunity. Out of eight vaccine candidates tested in this study, Ov-103, Ov-RAL-2 and Ov-CPI-2M were shown to reproducibly induce protective immunity when administered individually, as fusion proteins or in combination. Although there was no increase in the level of protective immunity induced by combining the antigens into one vaccine, these antigens remain strong candidates for inclusion in a vaccine to control onchocerciasis in humans.

Vascular Pharmacology, 2006

International Journal of Biochemistry, 1988

Abstract 1. 1. The intracellular distribution of α- d -mannosidase in homogenates of murine liver... more Abstract 1. 1. The intracellular distribution of α- d -mannosidase in homogenates of murine liver and spleen was investigated by differential and gradient density centrifugation. 2. 2. In both tissues an enzyme with a neutral pH optimum was found in the cytosol together with an α- d -mannosidase with optimal activity between pH 5.5 and 6.0 which was also partially membrane-bound. 3. 3. In liver the acidic α- d -mannosidase was obtained almost entirely in a particulate form distributed equally between a heterogeneous low density region and heavy density lysosomes. 4. 4. The lysosomal form of the liver enzyme was purified to electrophoretic homogeneity and shown to be a glycoprotein composed of four identical subunits of molecular weight 65 kDa. 5. 5. Antibody raised against the purified liver α- d -mannosidase immunoprecipitated a polypeptide from spleen which had the same molecular size. This acidic enzyme was the predominant type of α- d -mannosidase in spleen, but in contrast to liver, it was obtained mainly in a cytosoluble form, the remaining activity being present in the heterogenous light density compartment. 6. 6. Although both tissues contain the same molecular form of the acidic α- d -mannosidase, in murine spleen this enzyme does not appear to be associated with stable heavy density lysosomes.

Springer Seminars in Immunopathology, 2000

PLoS Neglected Tropical Diseases, 2011

Background: Differences between noninfective first-stage (L1) and infective third-stage (L3i) lar... more Background: Differences between noninfective first-stage (L1) and infective third-stage (L3i) larvae of parasitic nematode Strongyloides stercoralis at the molecular level are relatively uncharacterized. DNA microarrays were developed and utilized for this purpose. Methods and Findings: Oligonucleotide hybridization probes for the array were designed to bind 3,571 putative mRNA transcripts predicted by analysis of 11,335 expressed sequence tags (ESTs) obtained as part of the Nematode EST project. RNA obtained from S. stercoralis L3i and L1 was co-hybridized to each array after labeling the individual samples with different fluorescent tags. Bioinformatic predictions of gene function were developed using a novel cDNA Annotation System software. We identified 935 differentially expressed genes (469 L3i-biased; 466 L1-biased) having twofold expression differences or greater and microarray signals with a p value,0.01. Based on a functional analysis, L1 larvae have a larger number of genes putatively involved in transcription (p = 0.004), and L3i larvae have biased expression of putative heat shock proteins (such as hsp-90). Genes with products known to be immunoreactive in S. stercoralis-infected humans (such as SsIR and NIE) had L3i biased expression. Abundantly expressed L3i contigs of interest included S. stercoralis orthologs of cytochrome oxidase ucr 2.1 and hsp-90, which may be potential chemotherapeutic targets. The S. stercoralis ortholog of fatty acid and retinol binding protein-1, successfully used in a vaccine against Ancylostoma ceylanicum, was identified among the 25 most highly expressed L3i genes. The sperm-containing glycoprotein domain, utilized in a vaccine against the nematode Cooperia punctata, was exclusively found in L3i biased genes and may be a valuable S. stercoralis target of interest. Conclusions: A new DNA microarray tool for the examination of S. stercoralis biology has been developed and provides new and valuable insights regarding differences between infective and noninfective S. stercoralis larvae. Potential therapeutic and vaccine targets were identified for further study.

Parasite Immunology, 2002

The objective of this study was to examine the role of B cells in primary and challenge infection... more The objective of this study was to examine the role of B cells in primary and challenge infections of larval Strongyloides stercoralis in mice. Two strains of B-cell deficient mice were used in these studies, µ MT mice that lack all B cells and Xid mice that lack B-1 cells. Primary immune responses in µ MT mice were sufficient to eliminate all parasites within 1 week after infection. Immunized µ MT and Xid mice, however, were unable to kill challenge parasites at 24 h post infection, the time that they were eliminated in immunized wild-type mice. This was despite having a significant increase in interleukin-5 secreting cells and high numbers of eosinophils in the microenvironment of the challenge larvae. In addition, immunized Xid mice did not generate parasite-specific immunoglobulin (Ig)M but did develop a weak IgG response compared to wild-type mice. These results demonstrate a dichotomy in the requirement of B cells in immunity to S. stercoralis. B cells are not required in the primary response, yet they are required in the secondary immune response. B-1 cells are required for the secondary immune response and their role appears to be the production of IgM and not as a source of immunoregulatory molecules.

Journal of the Optical Society of America B, 1997

We address the propagation properties of short, noisy pulses in the spectral vicinity of the zero... more We address the propagation properties of short, noisy pulses in the spectral vicinity of the zero-dispersion wavelength of single-mode fibers. We present a numerical propagation model that includes amplitude fluctuations by introducing a Gaussian statistical distribution of the peak powers. Experiments that use as a source a figure-eight-shaped fiber laser terminated by various types and lengths of dispersion-shifted fiber confirm the calculated propagation properties. We demonstrate the dependence on mean peak power, on noise, and on fiber length of the spectral and temporal evolutions of the propagating pulses.

Microbes and Infection, 2011

Neutrophil recruitment via CXCR2 is required for innate and adaptive protective immunity to the l... more Neutrophil recruitment via CXCR2 is required for innate and adaptive protective immunity to the larvae of Strongyloides stercoralis in mice. The goal of the present study was to determine the mechanism of CXCR2-mediated neutrophil recruitment to S. stercoralis. Mice deficient in the receptor for IL-17A and IL-17F, upstream mediators of CXCR2 ligand production, were infected with S. stercoralis larvae; there was no difference in larval survival, neutrophil recruitment, or production of CXCR2 ligands compared with wild type mice. In vivo and in vitro stimulation of neutrophils with S. stercoralis soluble extract resulted in significant neutrophil recruitment. In vitro assays demonstrated that the recruitment functioned through both chemokinesis and chemotaxis, was specific for CXCR2, and was a G protein coupled response involving tyrosine kinase and PI3K. Finally, neutrophil stimulation with S. stercoralis soluble extract induced release of the CXCR2 ligands MIP-2 and KC from neutrophils, thereby potentially enhancing neutrophil recruitment.

Matrix Biology, 2008

Most tissue cells need to anchor to a 'solid' for viability, and over the last decade it has beco... more Most tissue cells need to anchor to a 'solid' for viability, and over the last decade it has become increasingly clear that the physical 'elasticity' of that solid-like matrix is literally 'felt' by cells. In fact, matrix elasticity as an insoluble cue now appears to synergize with the effects of soluble factors [1]. We will show that Mesenchymal Stem Cells (MSCs) specify lineage and commit to phenotypes with extreme sensitivity to the elasticity typical of tissues [2]. In serum only media, soft matrices that mimic brain appear neurogenic, stiffer matrices that mimic muscle are myogenic, and comparatively rigid matrices that mimic collagenous 'osteoid' prove osteogenic. Inhibition of myosin II blocks all lineage specification, indicating that the cell pulls on matrix through adhesions. In addition to the work with stem cells, studies of isolated, beating cardiomyocytes on elastic matrices demonstrate the sensitivity of cell differentiation: cardiomyocytes stop beating most rapidly on matrices as rigid as an infarct scarand this is shown to be about as hard as osteoid. The results predict that an infarct scar not only opposes cardiogenesis through de-differentiation but would tend to promote osteogenesis, which appears consistent with recent observations in mouse [3]. The results have also motivated development of a proteomic-scale method to identify mechano-responsive protein structures [4].

Matrix Biology, 2004

An enhancer region in the type I collagen alpha 2 chain (pro-Col1a2) promoter has been previously... more An enhancer region in the type I collagen alpha 2 chain (pro-Col1a2) promoter has been previously identified approximately y17 kb away from the transcription start site. This upstream region termed the far-upstream-enhancer contains three DNAse I hypersensitive sites and has been shown to be conserved between mouse and human genes. In this study, we used transgenic mice harbouring the complete promotor sequence of the pro-Col1a2 gene up to y17 kb to examine the role of this enhancer in the expression and regulation of the collagen gene during development and in adult tissues pre and post injury. By careful histological mapping of the collagen type I endogenous gene distribution with that of the transgene driven by the mouse far upstream enhancer, we are able to show that in early days of collagen expression, E8.5-9.5, the endogenous gene preceded transgene expression. However, by E11.5 the overall pattern becomes synchronous with a few exceptions. In adult tissue, both endogenous and transgene expression are attenuated and both are reactivated in parallel in various organs by physical injury or fibrogenic cytokine injection. These findings suggest that the enhancer is central to the activation of the collagen type I and that mice harbouring this enhanceryreporter provide a useful model to follow collagen gene transcription activity and for investigating cellular activity in tissue fibrosis.

Journal of Vascular Surgery, 2011

Journal of Vascular Surgery, 2013

Journal of Micro/Nanolithography, MEMS, and MOEMS, 2006

Antireflective (AR) coating on waveguides with high refractive index is imperative to minimize in... more Antireflective (AR) coating on waveguides with high refractive index is imperative to minimize insertion losses. In fabricating silicon, rectangular, suspended waveguides on silicon-on-insulator (SOI) wafers, a single Si3N4 layer is deposited on the waveguide walls. For the purpose of applying an optimum layer, we develop an integrated micromechanical gauge to determine the coating width by measuring the induced stress in the silicon. Gauges at different sites on a wafer produce results with a standard deviation of about 0.5%. The insertion loss due to the waveguides is measured directly by coupling a laser beam at 1550 nm from a single-mode fiber to the waveguide, then to another fiber and a detector. Tests are run on six wafers and two types of devices: a waveguide with two facets and a waveguide with a gap, presenting four facets. The optimal silicon-nitride thickness is found at 200 nm, featuring a fiber-waveguide-fiber insertion loss of about 1 dB for a two-facet device and 1.7 dB for a four-facet device.

Journal of Leukocyte Biology, 2007

The heterotrimeric guanine nucleotidebinding protein G␣i2 is involved in regulation of immune res... more The heterotrimeric guanine nucleotidebinding protein G␣i2 is involved in regulation of immune responses against microbial and nonmicrobial stimuli. G␣i2 ؊/؊ mice have a selectively impaired IgM response consistent with a disorder in B cell development yet have augmented T cell effector function associated with increased production of IFN-␥ and IL-4. The goal of the present study was to determine if a deficiency in the G␣i2 protein in mice would affect the protective immune response against Strongyloides stercoralis, which is IL-4-, IL-5-, and IgM-dependent. G␣i2 ؊/؊ and wild-type mice were immunized and challenged with S. stercoralis larvae and analyzed for protective immune responses against infection. G␣i2 ؊/؊ mice failed to kill the larvae in the challenge infection as compared with wild-type mice, despite developing an antigen-specific Th2 response, characterized by increased IL-4, IL-5, IgM, and IgG. Transfer of serum collected from immunized G␣i2 ؊/؊ mice to naïve, wild-type mice conferred passive, protective immunity against S. stercoralis infection, thus confirming the development of a protective antibody response in G␣i2 ؊/؊ mice. Differential cell analyses and myeloperoxidase assays for quantification of neutrophils showed a significantly reduced recruitment of neutrophils into the microenvironment of the parasites in immunized G␣i2 ؊/؊ mice. However, cell transfer studies demonstrated that neutrophils from G␣i2 ؊/؊ mice are competent in killing larvae. These data demonstrate that G␣i2 signaling events are not required for the development of the protective immune responses against S. stercoralis; however, G␣i2 is essential for the recruitment of neutrophils required for host-dependent killing of larvae.