Smallpox Models as Policy Tools1

Interactions between policymakers and mathematical modelers can improve biodefense strategies

MOVPE growth for GaAs-Based Photonic Crystal Surface Emitting Lasers

Photonic crystal surface emitting lasers (PCSELs) have emerged recently as class of laser diode that are of great commercial interest, offering high-power, single-mode surface emission across a wide range of wavelengths. The optical and electrical characteristics of PCSELs are intrinsically linked to the nanoscale structure of the two-dimensional photonic crystal (PC) grating layer that is embedded within the device structure by metalorganic vapour phase epitaxy (MOVPE) regrowth. In this regard, an understanding of, and the ability to influence, the formation of crystallographic voids within the PC during epitaxial regrowth is one of the key aspects for achieving optimised designs and device performance. This thesis presents a number of studies related to the application of MOVPE in the fabrication of GaAs-based PCSELs, with a particular focus on epitaxial regrowth and the engineering of voids. The mechanism of void formation and the factors dictating the extent of grating infill are investigated by electron microscopy-based structural analysis of regrown PC structures and correlated with device results. Initially, AlAs/GaAs PCSELs are presented for which the morphology of the initial PC grating pits has been modified by controlling the degree of mass-transport of material during the pre growth temperature ramp within the MOVPE reactor. It is shown that void formation is the result of low adatom surface mobility and selfshadowing effects which drive rapid lateral growth of the upper pit surface. The growth kinetics associated with the crystal planes of the underlying grating pits are shown to greatly impact the size and shape of the voids, with vastly different geometries observed in each of the devices. Following this, the role of adatom mobility in driving grating infill is demonstrated in PC structures for which the composition of the regrowth material is varied. It is shown that void formation is favoured when aluminium-containing layers are used, for which the inherent adatom mobility is low, and that complete grating infill is promoted in the case of higher mobility GaAs. Analysis of the threedimensional void shape in AlAs- and AlGaAs-regrown structures reveals that natural asymmetries emerge in the shape of voids even when symmetric, circular grating pits are used, owing to the differing polarities and growth kinetics of high-Miller index crystal planes in III-V materials. It is shown that the in-plane asymmetry of void shape can be greatly enhance by the use of (311)B orientated substrates, and that voids in these PCs display an additional out-of-plane asymmetry compared to those in the conventional (100) orientated structures. In addition to the PC regrowth studies described above, an initial investigation into the use selective area growth (SAG) as a method for realising multicolour PCSEL arrays is presented. It is shown that the growth rate enhancement and wavelength tuning associated with SAG is effective for InGaAs/GaAs multi-quantum well structures deposited in masked growth windows with dimensions up to 300 x 300 μm2. For selected features, it is shown that large areas of material with uniform emission wavelengths up to 100 x 100 μm2 in size can be achieved, being appropriate for the fabrication of monolithically integrated devices in the future

The identification of mitochondrial DNA variants in glioblastoma multiforme

Background: Mitochondrial DNA (mtDNA) encodes key proteins of the electron transfer chain (ETC), which produces ATP through oxidative phosphorylation (OXPHOS) and is essential for cells to perform specialised functions. Tumor-initiating cells use aerobic glycolysis, a combination of glycolysis and low levels of OXPHOS, to promote rapid cell proliferation and tumor growth. Glioblastoma multiforme (GBM) is an aggressively malignant brain tumor and mitochondria have been proposed to play a vital role in GBM tumorigenesis. Results: Using next generation sequencing and high resolution melt analysis, we identified a large number of mtDNA variants within coding and non-coding regions of GBM cell lines and predicted their disease-causing potential through in silico modeling. The frequency of variants was greatest in the D-loop and origin of light strand replication in non-coding regions. ND6 was the most susceptible coding gene to mutation whilst ND4 had the highest frequency of mutation. Both genes encode subunits of complex I of the ETC. These variants were not detected in unaffected brain samples and many have not been previously reported. Depletion of HSR-GBM1 cells to varying degrees of their mtDNA followed by transplantation into immunedeficient mice resulted in the repopulation of the same variants during tumorigenesis. Likewise, de novo variants identified in other GBM cell lines were also incorporated. Nevertheless, ND4 and ND6 were still the most affected genes. We confirmed the presence of these variants in high grade gliomas. Conclusions: These novel variants contribute to GBM by rendering the ETC. partially dysfunctional. This restricts metabolism to anaerobic glycolysis and promotes cell proliferation

The complex transcriptional landscape of the anucleate human platelet.

BACKGROUND: Human blood platelets are essential to maintaining normal hemostasis, and platelet dysfunction often causes bleeding or thrombosis. Estimates of genome-wide platelet RNA expression using microarrays have provided insights to the platelet transcriptome but were limited by the number of known transcripts. The goal of this effort was to deep-sequence RNA from leukocyte-depleted platelets to capture the complex profile of all expressed transcripts. RESULTS: From each of four healthy individuals we generated long RNA (≥40 nucleotides) profiles from total and ribosomal-RNA depleted RNA preparations, as well as short RNA (\u3c40 \u3enucleotides) profiles. Analysis of ~1 billion reads revealed that coding and non-coding platelet transcripts span a very wide dynamic range (≥16 PCR cycles beyond β-actin), a result we validated through qRT-PCR on many dozens of platelet messenger RNAs. Surprisingly, ribosomal-RNA depletion significantly and adversely affected estimates of the relative abundance of transcripts. Of the known protein-coding loci, ~9,500 are present in human platelets. We observed a strong correlation between mRNAs identified by RNA-seq and microarray for well-expressed mRNAs, but RNASeq identified many more transcripts of lower abundance and permitted discovery of novel transcripts. CONCLUSIONS: Our analyses revealed diverse classes of non-coding RNAs, including: pervasive antisense transcripts to protein-coding loci; numerous, previously unreported and abundant microRNAs; retrotransposons; and thousands of novel un-annotated long and short intronic transcripts, an intriguing finding considering the anucleate nature of platelets. The data are available through a local mirror of the UCSC genome browser and can be accessed at: http://cm.jefferson.edu/platelets_2012/

1.5 {\mu}m Epitaxially Regrown Photonic Crystal Surface Emitting Laser Diode

We present an InP-based epitaxially regrown photonic crystal surface emitting laser diode, lasing in quasi- CW conditions at 1523nm.Comment: 4 pages, 5 figures, journal submission for revie

Small signal modulation of photonic crystal surface emitting lasers

We report the small-signal characterization of a PCSEL device, extracting damping factors and modulation efficiencies, and demonstrating -3 dB modulation bandwidths of up to 4.26 GHz. Based on modelling we show that, by reducing the device width and improving the active region design for high-speed modulation, direct modulation frequencies in excess of 50 GHz are achievable

Epitaxially regrown quantum dot photonic crystal surface emitting lasers

Quantum dot-based epitaxially regrown photonic crystal surface emitting lasers are demonstrated at room temperature. The GaAs-based devices, which are monolithically integrated on the same wafer, exhibit ground state lasing at ∼1230 nm and excited state lasing at ∼1140 nm with threshold current densities of 0.69 and 1.05 kA/cm2, respectively

Scaling Up ART Adherence Clubs in the Public Sector Health System in the Western Cape, South Africa: a Study of the Institutionalisation of a Pilot Innovation

In 2011, a decision was made to scale up a pilot innovation involving ‘adherence clubs’ as a form of differentiated care for HIV positive people in the public sector antiretroviral therapy programme in the Western Cape Province of South Africa. In 2016 we were involved in the qualitative aspect of an evaluation of the adherence club model, the overall objective of which was to assess the health outcomes for patients accessing clubs through epidemiological analysis, and to conduct a health systems analysis to evaluate how the model of care performed at scale. In this paper we adopt a complex adaptive systems lens to analyse planned organisational change through intervention in a state health system. We explore the challenges associated with taking to scale a pilot that began as a relatively simple innovation by a non-governmental organisation

Prioritizing Emerging Zoonoses in The Netherlands

Background: To support the development of early warning and surveillance systems of emerging zoonoses, we present a general method to prioritize pathogens using a quantitative, stochastic multi-criteria model, parameterized for the Netherlands. Methodology/Principal Findings: A risk score was based on seven criteria, reflecting assessments of the epidemiology and impact of these pathogens on society. Criteria were weighed, based on the preferences of a panel of judges with a background in infectious disease control. Conclusions/Significance: Pathogens with the highest risk for the Netherlands included pathogens in the livestock reservoir with a high actual human disease burden (e.g. Campylobacter spp., Toxoplasma gondii, Coxiella burnetii) or a low current but higher historic burden (e.g. Mycobacterium bovis), rare zoonotic pathogens in domestic animals with severe disease manifestations in humans (e.g. BSE prion, Capnocytophaga canimorsus) as well as arthropod-borne and wildlife associated pathogens which may pose a severe risk in future (e.g. Japanese encephalitis virus and West-Nile virus). These agents are key targets for development of early warning and surveillance.Infrastructures, Systems and ServicesTechnology, Policy and Managemen