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Papers by John Simon

Childhood acute myeloid leukemia in mice with severe combined immunodeficiency

Blood, 1994

Primary bone marrow blasts from 4 children with t(8;21) acute myeloid leukemia (AML), 6 children ... more Primary bone marrow blasts from 4 children with t(8;21) acute myeloid leukemia (AML), 6 children with inv(16) AML, and 2 children with t(9;11) AML were injected intravenously or transplanted under the kidney capsule of sublethally irradiated mice with severe combined immunodeficiency (SCID). Leukemic cells from all AML patients infiltrated the SCID mouse thymus, suggesting that the thymic microenvironment supports the survival and growth of human AML blasts. Blasts from 1 of 4 t(8;21) AML patients and 4 of 6 inv(16) AML patients caused histopathologically detectable disseminated leukemia. Blasts from the remaining patients produced disseminated occult leukemia that was only detected by polymerase chain reaction. Occurrence of histopathologically detectable disseminated leukemia was dependent on intravenous injection of leukemic cells; none of the mice challenged with an inoculum transplanted under the kidney capsule developed overt leukemia. No obvious association was noted between ...

Commentary: Climate change resiliency in remediation

Remediation Journal, 2018

The lead article in this issue of Remediation, titled "Resilient Remediation: Addressing Extreme ... more The lead article in this issue of Remediation, titled "Resilient Remediation: Addressing Extreme Weather and Climate Change, Creating Community Value" (Maco et al., 2018), addresses a critical issue facing the remediation industry-considering the effects of changing weather patterns in the design, optimization, and operation of remediation systems. The effect of climate change on remediation programs can take many forms, including warmer, wetter, or dryer weather affecting cover systems, reduced groundwater depths, and catastrophic weather events, such as floods, tornadoes, or hurricanes, damaging remediation systems. However, integrating climate change risks into remediation programs poses issues to the remediation community as most remediation professionals do not have the training and experience to evaluate climate risks, identify the associated vulnerabilities to contaminated sites, and design weather-resilient remediation systems.

Comprar 2008-2009 Basic And Clinical Science Course, Section 6: Pediatric Ophthalmology And Strabismus (American Academy Of Ophtalmology) | Simon John | 9781560558798 | American Academy of Ophthalmology

Http Www Libreriasaulamedica Com, 2008

Tienda online donde Comprar 2008-2009 Basic And Clinical Science Course, Section 6: Pediatric Oph... more

Probing the Spatial Dependence of the Emission Spectrum of Single Human Retinal Lipofuscin Granules Using Near-field Scanning Optical Microscopy¶

Photochemistry and Photobiology, 2001

The emission spectra of single lipofuscin granules are examined using spectrally resolved confoca... more The emission spectra of single lipofuscin granules are examined using spectrally resolved confocal microscopy and near-field scanning optical microscopy (NSOM). The emission spectrum varies among the granules examined revealing that individual granules are characterized by different distributions of fluorophores. The range of spectra observed is consistent with in vivo spectra of human retinal pigment epithelium cells. NSOM measurements reveal that the shape of the spectrum does not vary with position within the emissive regions of single lipofuscin granules. These results suggest that the relative distribution of fluorophores within the emissive regions of an individual granule is homogeneous on the spatial scale ϳ150 nm.

Protein-based molecular contrast optical coherence tomography

SPIE Proceedings, 2004

We describe a novel technique for contrast enhancement in optical coherence tomography (OCT) whic... more We describe a novel technique for contrast enhancement in optical coherence tomography (OCT) which uses optically switchable protein based chromophores. Photosensitive proteins, such as bacteriorhodopsin and phytochrome, are promising OCT molecular contrast agents by reason of their remarkably low transition activation intensities compatible with in vivo imaging, and their potential for use as genetically expressible markers for molecular imaging. This study details the use of a novel optical switch suppression scheme which uses the absorption change between the two state groups of phytochrome to extract concentration and distribution information of the contrast agent within a target sample.

Research in action: from AIDS to global health to impact. A symposium in recognition of the scientific contributions of Professor Joep Lange

Antiviral Therapy, 2015

On Tuesday 14 October 2014, 850 family members, friends, colleagues, prominent scientists and dig... more On Tuesday 14 October 2014, 850 family members, friends, colleagues, prominent scientists and dignitaries from all over the world gathered in Amsterdam to pay tribute to the lives and legacies of Joep Lange and Jacqueline van Tongeren. The remembrance was held at the Amsterdam Medical Centre (AMC) where Joep and Jacqueline met and worked together for many years. The day was organized by the AMC, the Amsterdam Institute for Global Health and Development (AIGHD) and PharmAccess Foundation. The latter two were both founded by Joep. A morning symposium titled ‘Research in action: from AIDS to global health to impact’ highlighted Joep's scientific legacy (Figure 1). During the remembrance in the afternoon, a range of speakers shared memories of Joep and Jacqueline. As was the case during their lives, the personal and the professional were closely intertwined throughout the day. As Prof Peter Piot said, Joep and Jacqueline shared a common perspective on life: ‘La folie suprême est de ...

Fever, Headache, and Myalgias after Deployment to the Philippines

Military Medicine, 2008

Classic dengue fever presents with a triad of fever, headache, and rash. A "saddleback" fever pat... more Classic dengue fever presents with a triad of fever, headache, and rash. A "saddleback" fever pattern, morbilliform rash with islets of sparing after apyrexia, and hematological/hepatic abnormalities are common findings. As the most common arbovirus infection, dengue is a significant health threat to deployed military forces worldwide. Preventive measures such as personal protective equipment and repellants should be employed by individuals and other preventive measures should be considered for units departing endemic areas. Due to the increased risk of severe or hemorrhagic syndromes in the case of reinfection, limiting redeployment of individuals who have been infected by dengue should be considered, and further research is needed in this area. Development of tetravalent or DNA-based vaccines should be a priority to improve health protection for deploying forces. *2D BN/1st Marines, 1st Marine Division (REIN),

Paris Letter

The Hudson Review, 1964

Review of vector-borne diseases in Hong Kong

Travel Medicine and Infectious Disease, 2011

The epidemiology of vector-borne diseases in Hong Kong has changed over the past decade but still... more The epidemiology of vector-borne diseases in Hong Kong has changed over the past decade but still poses a significant public health risk. We provided a comprehensive review of the epidemiological information and analysed the trends of major vector-borne diseases, including the vector situation in Hong Kong. The incidence of malaria has dropped dramatically in the past few decades and is now mainly an imported disease acquired from malaria endemic countries. Locally acquired dengue fever occurred in 2002 and 2003, and thereafter all cases were imported, mainly from Southeast Asia areas. Only a few local cases of Japanese encephalitis were reported in the past decade. In contrast, there is a notable increase in scrub typhus and spotted fever cases. The emergence of chikungunya fever in Asia and Indian Ocean countries also resulted in importation of human cases. Given the heavy traffic between this international city and other parts of the world, as well as the presence of vectors in this densely populated area, vigilance should be maintained against these infections. Comprehensive public health measures encompassing disease surveillance, vector surveillance and control measures with support from all sectors of the community are required to combat the old and newly emerging vector-borne diseases in Hong Kong.

Reproductive Ecology of the Maui Parrotbill

The Wilson Bulletin, 2000

The endangered Maui Parrotbill (Pseudonestor xanthophrys) is an excavating, insectivorous Hawaiia... more The endangered Maui Parrotbill (Pseudonestor xanthophrys) is an excavating, insectivorous Hawaiian honeycreeper endemic to the high elevation rain forests of east Maui, Hawaii. From March 1994 to June 1997, we studied various aspects of their breeding ecology. We color-banded 18 individuals, located and monitored 9 active nests, and took behavioral data during 440 hrs of nest observation. Both members of a pair maintained a year-round, all-purpose territory that included nest sites and food resources. Maui Parrotbill were monogamous within and between years; we found no evidence of polyandry, polygyny, or helpers at the nest. Nests were cup-shaped, composed mainly of lichen interlaced with small twigs, and positioned in the outer canopy forks of mature ohia (Metrosideros polymorpha) trees. Modal clutch size was one. Females performed most nest construction and all incubation and brooding; males provisioned females and assisted in feeding nestlings after their fourth day. Fledglings depended on parental care for 5-8 months, during which their bill strength increased and foraging skills improved. We calculated the overall nest success rate by the Mayfield Method as 0.42 for the 1995/1996 and 1996/1997 breeding seasons combined. Nest failure and fledgling disappearance coincided with events of high rainfall. Their breeding ecology most closely resembled the Akiapolaau (Hemignathus munroi), another excavating, insectivorous Hawaiian honeycreeper found on Hawaii Island. As with the Akiapolaau, the threat of extinction is persistent and results from both the constraints of inherent life history traits and artificial ecological changes. We advocate the protection and expansion of habitable forest areas and an ongoing program to monitor and mitigate the effects of invasive species.

Quantification of the Binding Properties of Cu2+ to the Amyloid Beta Peptide: Coordination Spheres for Human and Rat Peptides and Implication on Cu2+-Induced Aggregation

The Journal of Physical Chemistry B, 2010

There is no consensus on the coordinating ligands for Cu 2+ by A. However, the differences in pep... more There is no consensus on the coordinating ligands for Cu 2+ by A. However, the differences in peptide sequence between human and rat have been hypothesized to alter metal ion binding in a manner that alters Cu 2+-induced aggregation of A. Herein, we employ isothermal titration calorimetry (ITC), circular dichroism (CD), and electron paramagnetic resonance (EPR) spectroscopy to examine the Cu 2+ coordination spheres to human and rat A and an extensive set of A (16) mutants. EPR of the mutant peptides is consistent with a 3N1O binding geometry, like the native human peptide at pH 7.4. The thermodynamic data reveal an equilibrium between three coordination spheres, {NH

Polarization-Induced Hole Doping in Wide–Band-Gap Uniaxial Semiconductor Heterostructures

Science, 2009

Activating Stubborn Dopants Many applications of semiconductor light-emitting diodes and lasers, ... more Activating Stubborn Dopants Many applications of semiconductor light-emitting diodes and lasers, such as reading optical disks, benefit from shorter wavelengths, but this requires materials with larger energy gaps between their valance and conduction bands. The electronic conductivity of these materials often has to be increased by doping with impurity atoms. However, in nitride materials, such as GaN and AlGaN, hole doping with acceptor atoms such as Mg is ineffective at room temperature. Simon et al. (p. 60 ) grew a gradient of AlGaN on the surface of GaN and found that the polarization of the layer could field-ionize the acceptor dopants efficiently at room temperature. The heterostructure was used successfully in a light-emitting diode that emits in the ultraviolet.

$concentrations and conductivities. Holes in polarization-doped layers are resistant to freezeout at low temperatures, and their mobility and con- centration can be measured down to cryogenic temperatures. Fig. 3. Hall-effect temperature-dependent (A) hole concentration, (B) hole mobilities, and (C) hole concentration and mobility measured down toT =4 K. The polarization-doped graded AlGaN p-type layers show higher hole The mechanism of polarization-induced hole formation is illustrated schematically in Fig. 1. The total polarization (spontaneous plus piezo- electric) can be pictured as charge dipoles in every unit cell of the crystal (Fig. 1A). Because Al,Ga,_,.N (where x is the Al mole fraction) has higher polarization than GaN, the sheet-charge dipoles in unit cells of the AlGaN layer are of a higher magnitude than in GaN, so the dipole strength increases linearly with the composition. When the composition of the layer is graded with increasing Al mole fraction, the net unbalanced the [0001] direction) and compositional grading from GaN to AlGaN should result in mobile 3D hole slabs. The ability to do so without the intro- duction of Mg-acceptor dopants hinges on the propensity of the surface to act as a remote ac- ceptor state. The surface of III-V nitride semi- conductors freely provides mobile electrons, but not holes, and this difference has been attributed to the presence of deep-level traps that localize holes (/7). Lowering of defect and trap densities may enable dopant-free p-type carriers, but in- tentionally introducing Mg-acceptor dopant atoms in the N-face graded AlGaN layer serves as the necessary source of holes. This work demon- strates the ability to use the polarization charges bound polarization charge is negative (Fig. 1B), given by p,(z) =—-V - P(z) ~5 x 10! x (x49 — xd cm >, where x, and x2 are the Al compositions at the ends of the graded layer of thickness d (in centimeters). This bound charge creates a built-in electric field (Fig. 1C) and energy-band bending that would be greater than the band gap of the semiconductor layer if left uncompensated (Fig. 1D). To neutralize the bound, negative po- larization charge, holes are consequently field- ionized from the deep Mg-acceptor atoms and form a high-density mobile 3D hole gas. The concentration of the 3D hole gas should then exhibit a weak temperature dependence and resist freezeout at low temperatures. In addition, the in N-face [0001] layers to generate polarization- induced, p-type graded AlGaN slabs that are highly conductive.$

Spectroscopic and morphological studies of human retinal lipofuscin granules

Proceedings of the National Academy of Sciences, 2003

The emission properties of ocular lipofuscin granules isolated from human retinal pigment epithel... more The emission properties of ocular lipofuscin granules isolated from human retinal pigment epithelial cells are examined by using steady-state fluorescence spectroscopy and spectrally resolved confocal microscopy. The shape of the emission spectrum of a thick sample of lipofuscin granules dried on glass varies with excitation energy. The polarization of this emission is wavelength-dependent, exhibiting significant polarization near the excitation wavelength and becoming mostly depolarized over the majority of the emission spectrum. These results show that the yellow-emitting fluorophores [e.g., A2E (2-[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1 E ,3 E ,5 E ,7 E -octatetraenyl]-1-(2-hydroxyethyl)-4-[4-methyl-6-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1 E ,3 E ,5 E -hexatrienyl]-pyridinium)] are excited as a result of energy transfer within the granules and therefore are not the dominant blue-absorbing chromophores within lipofuscin granules. Atomic force microscopy images show li...

Polarization-Induced Zener Tunnel Junctions in Wide-Band-Gap Heterostructures

Physical Review Letters, 2009

The large electronic polarization in III-V nitrides allow for novel physics not possible in other... more The large electronic polarization in III-V nitrides allow for novel physics not possible in other semiconductor families. In this work, interband Zener tunneling in wide-bandgap GaN heterojunctions is demonstrated by using polarization-induced electric fields. The resulting tunnel diodes are more conductive under reverse bias, which has applications for zero-bias rectification and mm-wave imaging. Since interband tunneling is traditionally prohibitive in wide-bandgap semiconductors, these polarization-induced structures and their variants can enable a number of devices such as multijunction solar cells that can operate under elevated temperatures and high fields.

Quantification of Naturally Occurring Pyrrole Acids in Melanosomes

Photochemistry and Photobiology, 2008

Three naturally occurring pyrrole acids were found in Sepia, human black hair, and bovine choroid... more Three naturally occurring pyrrole acids were found in Sepia, human black hair, and bovine choroid and iris melanosomes using high-performance liquid chromatography and mass spectrometry-pyrrole-2,3-dicarboxylic acid (PDCA), pyrrole-2,3,5-tricarboxylic acid (PTCA) and pyrrole-2,3,4,5-tetracarboxylic acid (PTeCA). PDCA and PTCA are common markers quantified from oxidative degradation of eumelanins. Using standards, the amounts of naturally occurring PDCA and PTCA were determined and compared to those obtained following peroxide oxidation of the same samples. Because the naturally occurring acids are water soluble, these results indicate that care must be exercised when comparing PDCA and PTCA yields from the degradation analyses of melanins isolated and prepared by different methods. This work also establishes that PTeCA is a naturally occurring pyrrole acid in melanosomes.

The Origin of the Wavelength-Dependent Photoreactivity of Trans-Urocanic Acid

Photochemistry and Photobiology, 1998

Two-color, pulsed-laser photoacoustic calorimetry is used to distinguish between multiple rotarne... more Two-color, pulsed-laser photoacoustic calorimetry is used to distinguish between multiple rotarner or electronic state contributions to the absorption spectrum of the epidermal chromophore trans-urocanic acid. The data definitively show that the wavelength-dependent photochemistry of trans-urocanic acid results from the presence of two distinct, weakly coupled electronic states absorbing between 264 nm and 310 nm.

Physical and Chemical Characterization of Iris and Choroid Melanosomes Isolated from Newborn and Mature Cows

Photochemistry and Photobiology, 2005

Bovine iris and choroid melanosomes at two ages (<1 week and >2 years) were examined by inductive... more Bovine iris and choroid melanosomes at two ages (<1 week and >2 years) were examined by inductively coupled plasma mass spectrometry (ICP-MS), elemental analysis, infrared spectrometry (IR) and X-ray photoelectron spectrometry (XPS). When iris and choroid melanosomes at the same age were compared, the quantification of metal elements by ICP-MS revealed that choroid melanosomes had a higher binding capacity for the carboxylate-binding metal ions (e.g. Na+, K+, MgZ+, Ca" and Zn2+). Elemental analysis showed a higher O:N ratio in choroid melanosomes. Both observations suggested that choroid melanosomes have a higher content of carboxylate-containing monomer than iris melanosomes. IR spectrometric analysis showed a red shift (-8 cm-') of the absorption peak of aromatic C=C, C=N and C=O at-1630 cm-' in the IR spectrum of iris melanosomes relative to choroid melanosomes. Increased conjugation in the molecular structure of the pigment is proposed to contribute to this peak shift. It is also notable that although the elemental analysis showed different C, N and 0 contents in the two types of melanosomes, XPS showed almost the same elemental compositions on the surface of two types of iris and choroid melanosomes studied. When the melanosomes from the same tissues at different ages were compared, ICP-MS analysis suggested that the number of carboxylate groups in the melanosomes decreased with age. Both elemental analysis and XPS showed that C:N ratio decreased with age, which was proposed to be due to both a decrease in carboxylate groups in mature samples and to the fissure of phenol rings caused by age-associated oxidation. Such age-related oxidative damage diminishes conjugation and is manifested by blue shifts of absorption peaks for aromatic double bonds in the IR spectra of mature melanosomes. XPS TPosted on the website

Comparison of Structural and Chemical Properties of Black and Red Human Hair Melanosomes¶

Photochemistry and Photobiology, 2007

Melanosomes in black and red human hair are isolated and characterized by various chemical and ph... more Melanosomes in black and red human hair are isolated and characterized by various chemical and physical techniques. Different yields of 4-amino-hydroxyphenolanaline by HI hydrolysis (a marker for pheomelanin) and pyrrole-2,3,5tricarboxylic acid by KMn04/H+ oxidation (a marker for qPosted on the website on

Spectral triangulation molecular contrast optical coherence tomography with indocyanine green as the contrast agent

Optics Letters, 2004

We report a new molecular contrast optical coherence tomography (MCOCT) implementation that profi... more We report a new molecular contrast optical coherence tomography (MCOCT) implementation that profiles the contrast agent distribution in a sample by measuring the agent's spectral differential absorption. The method, spectra triangulation MCOCT, can effectively suppress contributions from spectrally dependent scatterings from the sample without a priori knowledge of the scattering properties. We demonstrate molecular imaging with this new MCOCT modality by mapping the distribution of indocyanine green, a FDA-approved infrared red dye, within a stage 54 Xenopus laevis.

The fabrication of large-area, free-standing GaN by a novel nanoetching process

Nanotechnology, 2010

A simple yet versatile nanoetching process in porosifying and &amp;amp;amp;amp;amp;amp;amp;am... more A simple yet versatile nanoetching process in porosifying and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;machining&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; GaN is reported in this work. By combining different porosifying conditions through potentiostatic modulation or embedding doping design, we are able to separate and lift off GaN layers over a macroscopic area (≥cm(2)). Strain relaxation and single crystallinity are confirmed by Raman and transmission electron microscopy, respectively. This method is expected to open up a new dimension in epitaxy, design and manufacture of GaN heterostructures and devices.

Childhood acute myeloid leukemia in mice with severe combined immunodeficiency

Blood, 1994

Primary bone marrow blasts from 4 children with t(8;21) acute myeloid leukemia (AML), 6 children ... more Primary bone marrow blasts from 4 children with t(8;21) acute myeloid leukemia (AML), 6 children with inv(16) AML, and 2 children with t(9;11) AML were injected intravenously or transplanted under the kidney capsule of sublethally irradiated mice with severe combined immunodeficiency (SCID). Leukemic cells from all AML patients infiltrated the SCID mouse thymus, suggesting that the thymic microenvironment supports the survival and growth of human AML blasts. Blasts from 1 of 4 t(8;21) AML patients and 4 of 6 inv(16) AML patients caused histopathologically detectable disseminated leukemia. Blasts from the remaining patients produced disseminated occult leukemia that was only detected by polymerase chain reaction. Occurrence of histopathologically detectable disseminated leukemia was dependent on intravenous injection of leukemic cells; none of the mice challenged with an inoculum transplanted under the kidney capsule developed overt leukemia. No obvious association was noted between ...

Commentary: Climate change resiliency in remediation

Remediation Journal, 2018

The lead article in this issue of Remediation, titled "Resilient Remediation: Addressing Extreme ... more The lead article in this issue of Remediation, titled "Resilient Remediation: Addressing Extreme Weather and Climate Change, Creating Community Value" (Maco et al., 2018), addresses a critical issue facing the remediation industry-considering the effects of changing weather patterns in the design, optimization, and operation of remediation systems. The effect of climate change on remediation programs can take many forms, including warmer, wetter, or dryer weather affecting cover systems, reduced groundwater depths, and catastrophic weather events, such as floods, tornadoes, or hurricanes, damaging remediation systems. However, integrating climate change risks into remediation programs poses issues to the remediation community as most remediation professionals do not have the training and experience to evaluate climate risks, identify the associated vulnerabilities to contaminated sites, and design weather-resilient remediation systems.

Comprar 2008-2009 Basic And Clinical Science Course, Section 6: Pediatric Ophthalmology And Strabismus (American Academy Of Ophtalmology) | Simon John | 9781560558798 | American Academy of Ophthalmology

Http Www Libreriasaulamedica Com, 2008

Tienda online donde Comprar 2008-2009 Basic And Clinical Science Course, Section 6: Pediatric Oph... more

Probing the Spatial Dependence of the Emission Spectrum of Single Human Retinal Lipofuscin Granules Using Near-field Scanning Optical Microscopy¶

Photochemistry and Photobiology, 2001

The emission spectra of single lipofuscin granules are examined using spectrally resolved confoca... more The emission spectra of single lipofuscin granules are examined using spectrally resolved confocal microscopy and near-field scanning optical microscopy (NSOM). The emission spectrum varies among the granules examined revealing that individual granules are characterized by different distributions of fluorophores. The range of spectra observed is consistent with in vivo spectra of human retinal pigment epithelium cells. NSOM measurements reveal that the shape of the spectrum does not vary with position within the emissive regions of single lipofuscin granules. These results suggest that the relative distribution of fluorophores within the emissive regions of an individual granule is homogeneous on the spatial scale ϳ150 nm.

Protein-based molecular contrast optical coherence tomography

SPIE Proceedings, 2004

We describe a novel technique for contrast enhancement in optical coherence tomography (OCT) whic... more We describe a novel technique for contrast enhancement in optical coherence tomography (OCT) which uses optically switchable protein based chromophores. Photosensitive proteins, such as bacteriorhodopsin and phytochrome, are promising OCT molecular contrast agents by reason of their remarkably low transition activation intensities compatible with in vivo imaging, and their potential for use as genetically expressible markers for molecular imaging. This study details the use of a novel optical switch suppression scheme which uses the absorption change between the two state groups of phytochrome to extract concentration and distribution information of the contrast agent within a target sample.

Research in action: from AIDS to global health to impact. A symposium in recognition of the scientific contributions of Professor Joep Lange

Antiviral Therapy, 2015

On Tuesday 14 October 2014, 850 family members, friends, colleagues, prominent scientists and dig... more On Tuesday 14 October 2014, 850 family members, friends, colleagues, prominent scientists and dignitaries from all over the world gathered in Amsterdam to pay tribute to the lives and legacies of Joep Lange and Jacqueline van Tongeren. The remembrance was held at the Amsterdam Medical Centre (AMC) where Joep and Jacqueline met and worked together for many years. The day was organized by the AMC, the Amsterdam Institute for Global Health and Development (AIGHD) and PharmAccess Foundation. The latter two were both founded by Joep. A morning symposium titled ‘Research in action: from AIDS to global health to impact’ highlighted Joep's scientific legacy (Figure 1). During the remembrance in the afternoon, a range of speakers shared memories of Joep and Jacqueline. As was the case during their lives, the personal and the professional were closely intertwined throughout the day. As Prof Peter Piot said, Joep and Jacqueline shared a common perspective on life: ‘La folie suprême est de ...

Fever, Headache, and Myalgias after Deployment to the Philippines

Military Medicine, 2008

Classic dengue fever presents with a triad of fever, headache, and rash. A "saddleback" fever pat... more Classic dengue fever presents with a triad of fever, headache, and rash. A "saddleback" fever pattern, morbilliform rash with islets of sparing after apyrexia, and hematological/hepatic abnormalities are common findings. As the most common arbovirus infection, dengue is a significant health threat to deployed military forces worldwide. Preventive measures such as personal protective equipment and repellants should be employed by individuals and other preventive measures should be considered for units departing endemic areas. Due to the increased risk of severe or hemorrhagic syndromes in the case of reinfection, limiting redeployment of individuals who have been infected by dengue should be considered, and further research is needed in this area. Development of tetravalent or DNA-based vaccines should be a priority to improve health protection for deploying forces. *2D BN/1st Marines, 1st Marine Division (REIN),

Paris Letter

The Hudson Review, 1964

Review of vector-borne diseases in Hong Kong

Travel Medicine and Infectious Disease, 2011

The epidemiology of vector-borne diseases in Hong Kong has changed over the past decade but still... more The epidemiology of vector-borne diseases in Hong Kong has changed over the past decade but still poses a significant public health risk. We provided a comprehensive review of the epidemiological information and analysed the trends of major vector-borne diseases, including the vector situation in Hong Kong. The incidence of malaria has dropped dramatically in the past few decades and is now mainly an imported disease acquired from malaria endemic countries. Locally acquired dengue fever occurred in 2002 and 2003, and thereafter all cases were imported, mainly from Southeast Asia areas. Only a few local cases of Japanese encephalitis were reported in the past decade. In contrast, there is a notable increase in scrub typhus and spotted fever cases. The emergence of chikungunya fever in Asia and Indian Ocean countries also resulted in importation of human cases. Given the heavy traffic between this international city and other parts of the world, as well as the presence of vectors in this densely populated area, vigilance should be maintained against these infections. Comprehensive public health measures encompassing disease surveillance, vector surveillance and control measures with support from all sectors of the community are required to combat the old and newly emerging vector-borne diseases in Hong Kong.

Reproductive Ecology of the Maui Parrotbill

The Wilson Bulletin, 2000

The endangered Maui Parrotbill (Pseudonestor xanthophrys) is an excavating, insectivorous Hawaiia... more The endangered Maui Parrotbill (Pseudonestor xanthophrys) is an excavating, insectivorous Hawaiian honeycreeper endemic to the high elevation rain forests of east Maui, Hawaii. From March 1994 to June 1997, we studied various aspects of their breeding ecology. We color-banded 18 individuals, located and monitored 9 active nests, and took behavioral data during 440 hrs of nest observation. Both members of a pair maintained a year-round, all-purpose territory that included nest sites and food resources. Maui Parrotbill were monogamous within and between years; we found no evidence of polyandry, polygyny, or helpers at the nest. Nests were cup-shaped, composed mainly of lichen interlaced with small twigs, and positioned in the outer canopy forks of mature ohia (Metrosideros polymorpha) trees. Modal clutch size was one. Females performed most nest construction and all incubation and brooding; males provisioned females and assisted in feeding nestlings after their fourth day. Fledglings depended on parental care for 5-8 months, during which their bill strength increased and foraging skills improved. We calculated the overall nest success rate by the Mayfield Method as 0.42 for the 1995/1996 and 1996/1997 breeding seasons combined. Nest failure and fledgling disappearance coincided with events of high rainfall. Their breeding ecology most closely resembled the Akiapolaau (Hemignathus munroi), another excavating, insectivorous Hawaiian honeycreeper found on Hawaii Island. As with the Akiapolaau, the threat of extinction is persistent and results from both the constraints of inherent life history traits and artificial ecological changes. We advocate the protection and expansion of habitable forest areas and an ongoing program to monitor and mitigate the effects of invasive species.

Quantification of the Binding Properties of Cu2+ to the Amyloid Beta Peptide: Coordination Spheres for Human and Rat Peptides and Implication on Cu2+-Induced Aggregation

The Journal of Physical Chemistry B, 2010

There is no consensus on the coordinating ligands for Cu 2+ by A. However, the differences in pep... more There is no consensus on the coordinating ligands for Cu 2+ by A. However, the differences in peptide sequence between human and rat have been hypothesized to alter metal ion binding in a manner that alters Cu 2+-induced aggregation of A. Herein, we employ isothermal titration calorimetry (ITC), circular dichroism (CD), and electron paramagnetic resonance (EPR) spectroscopy to examine the Cu 2+ coordination spheres to human and rat A and an extensive set of A (16) mutants. EPR of the mutant peptides is consistent with a 3N1O binding geometry, like the native human peptide at pH 7.4. The thermodynamic data reveal an equilibrium between three coordination spheres, {NH

Polarization-Induced Hole Doping in Wide–Band-Gap Uniaxial Semiconductor Heterostructures

Science, 2009

Activating Stubborn Dopants Many applications of semiconductor light-emitting diodes and lasers, ... more Activating Stubborn Dopants Many applications of semiconductor light-emitting diodes and lasers, such as reading optical disks, benefit from shorter wavelengths, but this requires materials with larger energy gaps between their valance and conduction bands. The electronic conductivity of these materials often has to be increased by doping with impurity atoms. However, in nitride materials, such as GaN and AlGaN, hole doping with acceptor atoms such as Mg is ineffective at room temperature. Simon et al. (p. 60 ) grew a gradient of AlGaN on the surface of GaN and found that the polarization of the layer could field-ionize the acceptor dopants efficiently at room temperature. The heterostructure was used successfully in a light-emitting diode that emits in the ultraviolet.

$concentrations and conductivities. Holes in polarization-doped layers are resistant to freezeout at low temperatures, and their mobility and con- centration can be measured down to cryogenic temperatures. Fig. 3. Hall-effect temperature-dependent (A) hole concentration, (B) hole mobilities, and (C) hole concentration and mobility measured down toT =4 K. The polarization-doped graded AlGaN p-type layers show higher hole The mechanism of polarization-induced hole formation is illustrated schematically in Fig. 1. The total polarization (spontaneous plus piezo- electric) can be pictured as charge dipoles in every unit cell of the crystal (Fig. 1A). Because Al,Ga,_,.N (where x is the Al mole fraction) has higher polarization than GaN, the sheet-charge dipoles in unit cells of the AlGaN layer are of a higher magnitude than in GaN, so the dipole strength increases linearly with the composition. When the composition of the layer is graded with increasing Al mole fraction, the net unbalanced the [0001] direction) and compositional grading from GaN to AlGaN should result in mobile 3D hole slabs. The ability to do so without the intro- duction of Mg-acceptor dopants hinges on the propensity of the surface to act as a remote ac- ceptor state. The surface of III-V nitride semi- conductors freely provides mobile electrons, but not holes, and this difference has been attributed to the presence of deep-level traps that localize holes (/7). Lowering of defect and trap densities may enable dopant-free p-type carriers, but in- tentionally introducing Mg-acceptor dopant atoms in the N-face graded AlGaN layer serves as the necessary source of holes. This work demon- strates the ability to use the polarization charges bound polarization charge is negative (Fig. 1B), given by p,(z) =—-V - P(z) ~5 x 10! x (x49 — xd cm >, where x, and x2 are the Al compositions at the ends of the graded layer of thickness d (in centimeters). This bound charge creates a built-in electric field (Fig. 1C) and energy-band bending that would be greater than the band gap of the semiconductor layer if left uncompensated (Fig. 1D). To neutralize the bound, negative po- larization charge, holes are consequently field- ionized from the deep Mg-acceptor atoms and form a high-density mobile 3D hole gas. The concentration of the 3D hole gas should then exhibit a weak temperature dependence and resist freezeout at low temperatures. In addition, the in N-face [0001] layers to generate polarization- induced, p-type graded AlGaN slabs that are highly conductive.$

Spectroscopic and morphological studies of human retinal lipofuscin granules

Proceedings of the National Academy of Sciences, 2003

The emission properties of ocular lipofuscin granules isolated from human retinal pigment epithel... more The emission properties of ocular lipofuscin granules isolated from human retinal pigment epithelial cells are examined by using steady-state fluorescence spectroscopy and spectrally resolved confocal microscopy. The shape of the emission spectrum of a thick sample of lipofuscin granules dried on glass varies with excitation energy. The polarization of this emission is wavelength-dependent, exhibiting significant polarization near the excitation wavelength and becoming mostly depolarized over the majority of the emission spectrum. These results show that the yellow-emitting fluorophores [e.g., A2E (2-[2,6-dimethyl-8-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1 E ,3 E ,5 E ,7 E -octatetraenyl]-1-(2-hydroxyethyl)-4-[4-methyl-6-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1 E ,3 E ,5 E -hexatrienyl]-pyridinium)] are excited as a result of energy transfer within the granules and therefore are not the dominant blue-absorbing chromophores within lipofuscin granules. Atomic force microscopy images show li...

Polarization-Induced Zener Tunnel Junctions in Wide-Band-Gap Heterostructures

Physical Review Letters, 2009

The large electronic polarization in III-V nitrides allow for novel physics not possible in other... more The large electronic polarization in III-V nitrides allow for novel physics not possible in other semiconductor families. In this work, interband Zener tunneling in wide-bandgap GaN heterojunctions is demonstrated by using polarization-induced electric fields. The resulting tunnel diodes are more conductive under reverse bias, which has applications for zero-bias rectification and mm-wave imaging. Since interband tunneling is traditionally prohibitive in wide-bandgap semiconductors, these polarization-induced structures and their variants can enable a number of devices such as multijunction solar cells that can operate under elevated temperatures and high fields.

Quantification of Naturally Occurring Pyrrole Acids in Melanosomes

Photochemistry and Photobiology, 2008

Three naturally occurring pyrrole acids were found in Sepia, human black hair, and bovine choroid... more Three naturally occurring pyrrole acids were found in Sepia, human black hair, and bovine choroid and iris melanosomes using high-performance liquid chromatography and mass spectrometry-pyrrole-2,3-dicarboxylic acid (PDCA), pyrrole-2,3,5-tricarboxylic acid (PTCA) and pyrrole-2,3,4,5-tetracarboxylic acid (PTeCA). PDCA and PTCA are common markers quantified from oxidative degradation of eumelanins. Using standards, the amounts of naturally occurring PDCA and PTCA were determined and compared to those obtained following peroxide oxidation of the same samples. Because the naturally occurring acids are water soluble, these results indicate that care must be exercised when comparing PDCA and PTCA yields from the degradation analyses of melanins isolated and prepared by different methods. This work also establishes that PTeCA is a naturally occurring pyrrole acid in melanosomes.

The Origin of the Wavelength-Dependent Photoreactivity of Trans-Urocanic Acid

Photochemistry and Photobiology, 1998

Two-color, pulsed-laser photoacoustic calorimetry is used to distinguish between multiple rotarne... more Two-color, pulsed-laser photoacoustic calorimetry is used to distinguish between multiple rotarner or electronic state contributions to the absorption spectrum of the epidermal chromophore trans-urocanic acid. The data definitively show that the wavelength-dependent photochemistry of trans-urocanic acid results from the presence of two distinct, weakly coupled electronic states absorbing between 264 nm and 310 nm.

Physical and Chemical Characterization of Iris and Choroid Melanosomes Isolated from Newborn and Mature Cows

Photochemistry and Photobiology, 2005

Bovine iris and choroid melanosomes at two ages (<1 week and >2 years) were examined by inductive... more Bovine iris and choroid melanosomes at two ages (<1 week and >2 years) were examined by inductively coupled plasma mass spectrometry (ICP-MS), elemental analysis, infrared spectrometry (IR) and X-ray photoelectron spectrometry (XPS). When iris and choroid melanosomes at the same age were compared, the quantification of metal elements by ICP-MS revealed that choroid melanosomes had a higher binding capacity for the carboxylate-binding metal ions (e.g. Na+, K+, MgZ+, Ca" and Zn2+). Elemental analysis showed a higher O:N ratio in choroid melanosomes. Both observations suggested that choroid melanosomes have a higher content of carboxylate-containing monomer than iris melanosomes. IR spectrometric analysis showed a red shift (-8 cm-') of the absorption peak of aromatic C=C, C=N and C=O at-1630 cm-' in the IR spectrum of iris melanosomes relative to choroid melanosomes. Increased conjugation in the molecular structure of the pigment is proposed to contribute to this peak shift. It is also notable that although the elemental analysis showed different C, N and 0 contents in the two types of melanosomes, XPS showed almost the same elemental compositions on the surface of two types of iris and choroid melanosomes studied. When the melanosomes from the same tissues at different ages were compared, ICP-MS analysis suggested that the number of carboxylate groups in the melanosomes decreased with age. Both elemental analysis and XPS showed that C:N ratio decreased with age, which was proposed to be due to both a decrease in carboxylate groups in mature samples and to the fissure of phenol rings caused by age-associated oxidation. Such age-related oxidative damage diminishes conjugation and is manifested by blue shifts of absorption peaks for aromatic double bonds in the IR spectra of mature melanosomes. XPS TPosted on the website

Comparison of Structural and Chemical Properties of Black and Red Human Hair Melanosomes¶

Photochemistry and Photobiology, 2007

Melanosomes in black and red human hair are isolated and characterized by various chemical and ph... more Melanosomes in black and red human hair are isolated and characterized by various chemical and physical techniques. Different yields of 4-amino-hydroxyphenolanaline by HI hydrolysis (a marker for pheomelanin) and pyrrole-2,3,5tricarboxylic acid by KMn04/H+ oxidation (a marker for qPosted on the website on

Spectral triangulation molecular contrast optical coherence tomography with indocyanine green as the contrast agent

Optics Letters, 2004

We report a new molecular contrast optical coherence tomography (MCOCT) implementation that profi... more We report a new molecular contrast optical coherence tomography (MCOCT) implementation that profiles the contrast agent distribution in a sample by measuring the agent's spectral differential absorption. The method, spectra triangulation MCOCT, can effectively suppress contributions from spectrally dependent scatterings from the sample without a priori knowledge of the scattering properties. We demonstrate molecular imaging with this new MCOCT modality by mapping the distribution of indocyanine green, a FDA-approved infrared red dye, within a stage 54 Xenopus laevis.

The fabrication of large-area, free-standing GaN by a novel nanoetching process

Nanotechnology, 2010

A simple yet versatile nanoetching process in porosifying and &amp;amp;amp;amp;amp;amp;amp;am... more A simple yet versatile nanoetching process in porosifying and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;machining&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; GaN is reported in this work. By combining different porosifying conditions through potentiostatic modulation or embedding doping design, we are able to separate and lift off GaN layers over a macroscopic area (≥cm(2)). Strain relaxation and single crystallinity are confirmed by Raman and transmission electron microscopy, respectively. This method is expected to open up a new dimension in epitaxy, design and manufacture of GaN heterostructures and devices.