Publications by authors named "Thomas Frost"

Glycoprotein C (gC), one of ∼12 HSV-1 envelope glycoproteins, carries out several important functions during infection, including the enhancement of virion attachment by binding to host cell heparan sulfate proteoglycans (HSPG). Here we report that gC can also enhance the release of cell-free progeny virions at the end of the infectious cycle. This activity was observed in multiple cellular contexts including Vero cells and immortalized human keratinocytes.

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BackgroundMerkel cell carcinoma (MCC) is an aggressive neuroendocrine (NE) skin cancer caused by severe UV-induced mutations or expression of Merkel cell polyomavirus (MCPyV) large and small T antigens (LT and ST). Despite deep genetic differences between MCPyV-positive and -negative subtypes, current clinical diagnostic markers are indistinguishable, and the expression profile of MCC tumors is, to our knowledge, unexplored.MethodsHere, we leveraged bulk and single-cell RNA-Seq of patient-derived tumor biopsies and cell lines to explore the underlying transcriptional environment of MCC.

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Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the skin with 2 etiologies. Merkel cell polyomavirus (MCPyV) integration is present in about 80% of all MCC. Virus-positive MCC (MCCP) tumors have few somatic mutations and usually express WT p53 (TP53).

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Article Synopsis
  • Cancers like Merkel cell carcinoma (MCC) can evade the immune system by disrupting HLA class I antigen presentation, which is crucial for immune detection.
  • Researchers generated cell lines from MCC patients and found that certain genes responsible for HLA-I presentation were suppressed.
  • They identified two main regulators of HLA-I loss: MYCL and the PRC1.1 complex, with a focus on USP7 as a potential target for drug development to enhance HLA-I expression in MCC.
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Merkel cell carcinoma (MCC) is an aggressive malignancy with neuroendocrine (NE) features, limited treatment options, and a lack of druggable targets. There is no reported involvement of the MUC1-C oncogenic protein in MCC progression. We show here that MUC1-C is broadly expressed in MCCs and at higher levels in Merkel cell polyomavirus (MCPyV)-positive (MCCP) relative to MCPyV-negative (MCCN) tumors.

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Polyomaviruses (PyV) are ubiquitous pathogens that can cause devastating human diseases. Due to the small size of their genomes, PyV utilize complex patterns of RNA splicing to maximize their coding capacity. Despite the importance of PyV to human disease, their transcriptome architecture is poorly characterized.

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Polycomb repressive complex 2 has a critical role in the maintenance of bivalent promoters and is often perturbed in cancer, including neuroendocrine tumors. In this study, we investigated the susceptibility of Merkel cell carcinoma (MCC), a neuroendocrine carcinoma of the skin, to inhibitors of the Polycomb repressive complex 2 catalytic subunit EZH2. We show that a subset of MCC cell lines is sensitive to EZH2 inhibitor-induced cell viability loss.

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Epstein-Barr virus (EBV) is associated with multiple human malignancies. To evade immune detection, EBV switches between latent and lytic programs. How viral latency is maintained in tumors or in memory B cells, the reservoir for lifelong EBV infection, remains incompletely understood.

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We present monolithically integrated multi-channel coherent L-band transmitter (Tx) and receiver (Rx) photonic integrated circuits (PICs) on InP substrates. The L-band PICs are able to provide post-forward error correction (FEC), error-free operation for dual-polarization (DP) 16-QAM coherent transmission at 33 Gbaud. These transceivers operate at 200 Gbps per channel and support 1.

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Epstein-Barr virus (EBV) is a gamma-herpesvirus that establishes lifelong infection in the majority of people worldwide. EBV uses epigenetic reprogramming to switch between multiple latency states in order to colonize the memory B-cell compartment and to then periodically undergo lytic reactivation upon plasma cell differentiation. This review focuses on recent advances in the understanding of epigenetic mechanisms that EBV uses to control its lifecycle and to subvert the growth and survival pathways that underly EBV-driven B-cell differentiation versus B-cell growth transformation, a hallmark of the first human tumor virus.

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The Gram-negative bovine pathogen Moraxella bovis is a causative agent of Infectious bovine keratoconjunctivitis, 'pink-eye' that affects cattle. Here we report that strain L183/2 has the same capsular polysaccharide (CPS) of unsulfated chondroitin, as does strain Mb25, whereas strain Epp63 does not express CPS. NMR analysis of the oligosaccharides (OS) derived from the lipooligosaccharides (LOS) in these three strains by NMR has shown that strain Mb25 and Epp63 have the same OS structure with a terminal N-acetylgalactosamine ((1S)-GalaNAc) residue →4,6-linked.

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Oncolytic viruses, including herpes simplex viruses (HSVs), are a new class of cancer therapeutic engineered to infect and kill cancer cells while sparing normal tissue. To ensure that oncolytic HSV (oHSV) is safe in the brain, all oHSVs in clinical trial for glioma lack the γ34.5 genes responsible for neurovirulence.

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A spin-polarized laser offers inherent control of the output circular polarization. We have investigated the output polarization characteristics of a bulk GaN-based microcavity polariton diode laser at room temperature with electrical injection of spin-polarized electrons via a FeCo/MgO spin injector. Polariton laser operation with a spin-polarized current is characterized by a threshold of ∼69  A/cm^{2} in the light-current characteristics, a significant reduction of the electroluminescence linewidth and blueshift of the emission peak.

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Background: The growing burden of non-communicable diseases (NCDs) presented new challenges for medical humanitarian aid and little was known about primary health care approaches for these diseases in humanitarian response. We aimed to evaluate Médecins Sans Frontières (MSF's) use of total CVD risk based prevention strategies amongst Syrian refugees in northern Jordan to identify opportunities to improve total CVD risk based guidance for humanitarian settings.

Methods: We evaluated CVD risk assessment and management in two outpatient NCD clinics in the Irbid governorate of Jordan using a mixed methods design with qualitative and quantitative strands of equal priority, integrated during data collection and interpretation.

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We present a detailed study of the effects of dangling bond passivation and the comparison of different sulfide passivation processes on the properties of InGaN/GaN quantum-disk (Qdisk)-in-nanowire based light emitting diodes (NW-LEDs). Our results demonstrated the first organic sulfide passivation process for nitride nanowires (NWs). The results from Raman spectroscopy, photoluminescence (PL) measurements, and X-ray photoelectron spectroscopy (XPS) showed that octadecylthiol (ODT) effectively passivated the surface states, and altered the surface dynamic charge, and thereby recovered the band-edge emission.

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Complex refractive indices of In(x)Ga(1-x)N epitaxial layers have been determined from analysis of data obtained by spectroscopic ellipsometry. The measurements were made in the wavelength range of 400-1687 nm. The samples were grown by plasma-assisted molecular beam epitaxy on (001) silicon substrate and are of the wurtzite crystalline form.

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Use of large bandgap materials together with electrical injection makes the polariton laser an attractive low-power coherent light source for medical and biomedical applications or short distance plastic fiber communication at short wavelengths (violet and ultra-violet), where a conventional laser is difficult to realize. The dynamic properties of a polariton laser have not been investigated experimentally. We have measured, for the first time, the small signal modulation characteristics of a GaN-based electrically pumped polariton laser operating at room temperature.

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We present a physical model for recently demonstrated high indium content self-assembled In0.4Ga0.6N/GaN quantum dot (QD)-based ridge-waveguide lasers emitting at red wavelengths.

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Background: Efforts to measure quality of care do not capture the unique aspects of ambulatory oncology settings. To retain nurses, ensure a safe practice environment, and encourage behaviors that support high-quality care, there is a need to identify factors associated with job satisfaction and turnover with measures that reflect the ambulatory setting.

Objective: The objective of this study was to examine the patterns and correlates of the work environment for nurses and nurse practitioners working in a National Cancer Institute-designated Comprehensive Cancer Center.

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InGaN/GaN disk-in-nanowire heterostructures on silicon substrates have emerged as important gain media for the realization of visible light sources. The nature of quantum confinement in the disks is largely unknown. From the unique nature of the measured temperature dependence of the radiative lifetime and direct transmission electron microscopy, it is evident that such self-organized islands (disks) behave as quantum dots.

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Room temperature electrically pumped inversionless polariton lasing is observed from a bulk GaN-based microcavity diode. The low nonlinear threshold for polariton lasing occurs at 169 A/cm(2) in the light-current characteristics, accompanied by a collapse of the emission linewidth and small blueshift of the emission peak. Measurement of angle-resolved luminescence, polariton condensation and occupation in momentum space, and output spatial coherence and polarization have also been made.

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A silicon-based laser, preferably electrically pumped, has long been a scientific and engineering goal. We demonstrate here, for the first time, an edge-emitting InGaN/GaN disk-in-nanowire array electrically pumped laser emitting in the green (λ = 533 nm) on (001) silicon substrate. The devices display excellent dc and dynamic characteristics with values of threshold current density, differential gain, T0 and small signal modulation bandwidth equal to 1.

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When an individual facing intractable pain is given an estimate of a few months to live, does hastening death become a viable and legitimate alternative for willing patients? Has the time come for physicians to do away with the traditional notion of healthcare as maintaining or improving physical and mental health, and instead accept their own limitations by facilitating death when requested? The Universities of Oxford and Cambridge held the 2013 Varsity Medical Debate on the motion "This House Would Legalise Assisted Dying". This article summarises the key arguments developed over the course of the debate. We will explore how assisted dying can affect both the patient and doctor; the nature of consent and limits of autonomy; the effects on society; the viability of a proposed model; and, perhaps most importantly, the potential need for the practice within our current medico-legal framework.

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