University General - Research Publications
Now showing items 1-12 of 87
Structural comparison of allogeneic and syngeneic T cell receptor-peptide-major histocompatibility complex complexes: A buried alloreactive mutation subtly alters peptide presentation substantially increasing V-beta interactions
(ROCKEFELLER UNIV PRESS, 2002-05-06)
The crystal structures of the 2C/H-2K(bm3)-dEV8 allogeneic complex at 2.4 A and H-2K(bm3)-dEV8 at 2.15 A, when compared with their syngeneic counterparts, elucidate structural changes that induce an alloresponse. The Asp77Ser mutation that imbues H-2K(bm3)-dEV8 with its alloreactive properties is located beneath the peptide and does not directly contact the T cell receptor (TCR). However, the buried mutation induces local rearrangement of the peptide itself to preserve hydrogen bonding interactions between the peptide and the alpha(1) 77 residue. The COOH terminus of the peptide main chain is tugged toward the alpha(1)-helix such that its presentation to the TCR is altered. These changes increase the stability of the allogeneic peptide-major histocompatibility complex (pMHC) complex and increase complementarity in the TCR-pMHC interface, placing greater emphasis on recognition of the pMHC by the TCR beta-chain, evinced by an increase in shape complementarity, buried surface area, and number of TCR-pMHC contacting residues. A nearly fourfold increase in the number of beta-chain-pMHC contacts is accompanied by a concomitant 64% increase in beta-chain-pMHC shape complementarity. Thus, the allogeneic mutation causes the same peptide to be presented differently, temporally and spatially, by the allogeneic and syngeneic MHCs.
Direct fabrication of 3D graphene on nanoporous anodic alumina by plasma-enhanced chemical vapor deposition
(NATURE PUBLISHING GROUP, 2016-01-25)
High surface area electrode materials are of interest for a wide range of potential applications such as super-capacitors and electrochemical cells. This paper describes a fabrication method of three-dimensional (3D) graphene conformally coated on nanoporous insulating substrate with uniform nanopore size. 3D graphene films were formed by controlled graphitization of diamond-like amorphous carbon precursor films, deposited by plasma-enhanced chemical vapour deposition (PECVD). Plasma-assisted graphitization was found to produce better quality graphene than a simple thermal graphitization process. The resulting 3D graphene/amorphous carbon/alumina structure has a very high surface area, good electrical conductivity and exhibits excellent chemically stability, providing a good material platform for electrochemical applications. Consequently very large electrochemical capacitance values, as high as 2.1 mF for a sample of 10 mm(3), were achieved. The electrochemical capacitance of the material exhibits a dependence on bias voltage, a phenomenon observed by other groups when studying graphene quantum capacitance. The plasma-assisted graphitization, which dominates the graphitization process, is analyzed and discussed in detail.
Modest Declines in Proteome Quality Impair Hematopoietic Stem Cell Self-Renewal
Low protein synthesis is a feature of somatic stem cells that promotes regeneration in multiple tissues. Modest increases in protein synthesis impair stem cell function, but the mechanisms by which this occurs are largely unknown. We determine that low protein synthesis within hematopoietic stem cells (HSCs) is associated with elevated proteome quality in vivo. HSCs contain less misfolded and unfolded proteins than myeloid progenitors. Increases in protein synthesis cause HSCs to accumulate misfolded and unfolded proteins. To test how proteome quality affects HSCs, we examine Aarssti/sti mice that harbor a tRNA editing defect that increases amino acid misincorporation. Aarssti/sti mice exhibit reduced HSC numbers, increased proliferation, and diminished serial reconstituting activity. Misfolded proteins overwhelm the proteasome within Aarssti/sti HSCs, which is associated with increased c-Myc abundance. Deletion of one Myc allele partially rescues serial reconstitution defects in Aarssti/sti HSCs. Thus, HSCs are dependent on low protein synthesis to maintain proteostasis, which promotes their self-renewal.
Supervised exercise delivered via telehealth in real time to manage chronic conditions in adults: a protocol for a scoping review to inform future research in stroke survivors
(BMJ PUBLISHING GROUP, 2019-06-01)
INTRODUCTION: Increasing physical activity reduces secondary stroke risk factors, but many stroke survivors have low levels of physical activity. Supervised exercise delivered via telehealth has the potential to overcome barriers to increased physical activity in stroke survivors. Our scoping review will examine the emerging field of supervised exercise delivered via telehealth to map the available evidence in relation to its efficacy, acceptability, safety and feasibility in chronic conditions to inform future research into its ability to increase physical activity. METHODS AND ANALYSIS: The methodological framework of Arksey and O'Malley will be applied to our scoping review. A systematic search of Medline, CINAHL, Scopus, Cochrane, Pedro and Embase; hand searching of pertinent studies' reference lists; and consultation with experts in the field will identify relevant papers. Studies involving participants with a chronic condition who undertake supervised exercise delivered by a health professional via telehealth targeted at improving secondary stroke risk factors or involving lower limb weight-bearing exercise will be included. Study selection and critical appraisal of individual studies will be carried out independently by two authors with discrepancies resolved by a third author. Quantitative and qualitative data will be charted using a standardised form. Results will be tabulated and narratively summarised to highlight findings relevant to the review's research questions and to inform recommendations for future research. ETHICS AND DISSEMINATION: Our review will significantly contribute to the knowledge base of exercise and rehabilitation delivered via telehealth and its application in chronic conditions, including stroke. Findings will be relevant to researchers, healthcare workers and policy-makers and will be disseminated through publication and presentations. Only secondary deidentified data will be included, therefore ethics approval will not be sought. This protocol is not registered as PROSPERO currently excludes scoping reviews.
Generalized Method of Images and Reflective Color Generation from Ultrathin Multipole Resonators
(AMER CHEMICAL SOC, 2018-06-01)
The multipole expansion has found limited applicability for optical dielectric resonators in inhomogeneous environment, such as on the surface of substrates. Here, we generalize the method of images to multipole analysis for light scattering by dielectric nanoparticles on conductive substrates. We present examples illustrating the physical insight provided by our method, including selection rules governing the excitation of the multipoles. We propose and experimentally demonstrate a new mechanism to generate high resolution surface color. The dielectric resonators employed are very thin (less than 50 nm), i.e., similar in thickness to the plasmonic resonators that are currently being investigated for structural color. The generalized method of images opens up new prospects for design and analysis of metasurfaces and optical dielectric resonators.
Controlling the Light Absorption in a Photodetector Via Nanowire Waveguide Resonances for Multispectral and Color Imaging
(IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC, 2018-11-01)
The responsivity spectrum of a photodetector is one of its key specifications. It ultimately originates from the combination of the absorption spectrum of the photosensitive region and the internal quantum efficiency. Many applications of photodetectors would benefit from an improved ability to tailor the responsivity spectrum. This is particularly true for color and multispectral imaging. The absorption spectrum of a bulk (unstructured) semiconductor is fixed however, being determined by its complex refractive index. Here, we review recent work that demonstrates that the absorption spectrum of a photodetector can be controlled via waveguide resonances in semiconductor nanowires. We discuss the physical interpretation for this phenomenon. We review work in which p-i-n photodiodes were incorporated into vertically oriented silicon nanowires, and then used for color imaging. We review work in which tandem-style photodetectors were demonstrated, with a p-i-n silicon nanowire photodiode formed above an n-i-p planar silicon photodiode. We review work in which narrowband photodetection across the visible-to-infrared was demonstrated using germanium nanowires. Finally, we describe related work in which silicon nanowires have been explored for other applications, namely solar cells.
Vertical Ge-Si Nanowires with Suspended Graphene Top Contacts as Dynamically Tunable Multispectral Photodetectors
(AMER CHEMICAL SOC, 2019-03-20)
Numerous applications would be enabled by pixels for multispectral imaging whose spectral responses can be dynamically tuned and that can be potentially manufactured at low cost. Here, we show such a capability, by experimentally demonstrating arrays of vertically oriented germanium–silicon heterojunction nanowires with graphene top contacts. Our devices present opportunities for multispectral imaging because their responsivity spectra can be tailored by choice of nanowire radius for enhanced absorption at certain wavelengths across the visible to short-wave infrared. Importantly, these responsivity spectra can also be dynamically tuned by bias voltage. We demonstrate this experimentally by tuning the responsivity peak of a single pixel across the visible region by varying the bias voltage and by showing that this would allow red/green/blue channels to be reconstructed. This opens the exciting prospect of a single pixel that can resolve color (i.e., replacing the three red/green/blue pixels of traditional approaches) or even resolve several bands for multispectral imaging.
From rehabilitation to recovery: protocol for a randomised controlled trial evaluating a goal-based intervention to reduce depression and facilitate participation post-stroke
BACKGROUND: There is much discourse in healthcare about the importance of client-centred rehabilitation, however in the realm of community-based therapy post-stroke there has been little investigation into the efficacy of goal-directed practice that reflects patients' valued activities. In addition, the effect of active involvement of carers in such a rehabilitation process and their subsequent contribution to functional and emotional recovery post-stroke is unclear. In community based rehabilitation, interventions based on patients' perceived needs may be more likely to alter such outcomes. In this paper, we describe the methodology of a randomised controlled trial of an integrated approach to facilitating patient goal achievement in the first year post-stroke. The effectiveness of this intervention in reducing the severity of post-stroke depression, improving participation status and health-related quality of life is examined. The impact on carers is also examined. METHODS/DESIGN: Patients (and their primary carers, if available) are randomly allocated to an intervention or control arm of the study. The intervention is multimodal and aims to screen for adverse stroke sequelae and address ways to enhance participation in patient-valued activities. Intervention methods include: telephone contacts, written information provision, home visitation, and contact with treating health professionals, with further relevant health service referrals as required. The control involves treatment as usual, as determined by inpatient and community rehabilitation treating teams. Formal blinded assessments are conducted at discharge from inpatient rehabilitation, and at six and twelve months post-stroke. The primary outcome is depression. Secondary outcome measures include participation and activity status, health-related quality of life, and self-efficacy. DISCUSSION: The results of this trial will assist with the development of a model for community-based rehabilitation management for stroke patients and their carers, with emphasis on goal-directed practice to enhance home and community participation status. Facilitation of participation in valued activities may be effective in reducing the incidence or severity of post-stroke depression, as well as enhancing the individual's perception of their health-related quality of life. The engagement of carers in the rehabilitation process will enable review of the influence of the broader social context on recovery. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12608000042347.
Azithromycin Versus Doxycycline for the Treatment of Genital Chlamydia Infection: A Meta-analysis of Randomized Controlled Trials
(OXFORD UNIV PRESS INC, 2014-07-15)
BACKGROUND: There has been recent debate questioning the efficacy of azithromycin for the treatment of urogenital chlamydia infection. We conducted a meta-analysis to compare the efficacy of 1 g azithromycin with 100 mg doxycycline twice daily (7 days) for the treatment of urogenital chlamydia infection. METHODS: Medline, PubMed, Embase, Cochrane Controlled Trials Register, Cochrane reviews, and Cumulative Index to Nursing and Allied Health Literature were searched until 31 December 2013. Randomized controlled trials comparing azithromycin with doxycycline for the treatment of genital chlamydia with evaluation of microbiological cure within 3 months of treatment were included. Sex, diagnostic test, follow-up time, attrition, patient symptomatic status, and microbiological cure were extracted. The primary outcome was the difference in efficacy at final follow-up. Study bias was quantitatively and qualitatively summarized. RESULTS: Twenty-three studies were included evaluating 1147 and 912 patients for azithromycin and doxycycline, respectively. We found a pooled efficacy difference in favor of doxycycline of 1.5% (95% confidence interval [CI], -.1% to 3.1%; I(2) = 1.9%; P = .435; random effects) to 2.6% (95% CI, .5%-4.7%; fixed effects). Subgroup analyses showed that the fixed effects pooled efficacy difference for symptomatic men was 7.4% (95% CI, 2.0%-12.9%), and the random effects was 5.5% (95% CI, -1.4% to 12.4%). CONCLUSIONS: There may be a small increased efficacy of up to 3% for doxycycline compared with azithromycin for the treatment of urogenital chlamydia and about 7% increased efficacy for doxycycline for the treatment of symptomatic urethral infection in men. However, the quality of the evidence varies considerably, with few double-blind placebo-controlled trials conducted. Given increasing concern about potential azithromycin failure, further well-designed and statistically powered double-blind, placebo-controlled trials are needed.
The efficacy of azithromycin and doxycycline for the treatment of rectal chlamydia infection: a systematic review and meta-analysis
(OXFORD UNIV PRESS, 2015-05-01)
BACKGROUND: There are increasing concerns about treatment failure following treatment for rectal chlamydia with 1 g of azithromycin. A systematic review and meta-analysis was conducted to investigate the efficacy of 1 g of azithromycin as a single dose or 100 mg of doxycycline twice daily for 7 days for the treatment of rectal chlamydia. METHODS: Medline, Embase, PubMed, Cochrane Controlled Trials Register, Australia New Zealand Clinical Trial Register and ClinicalTrials.gov were searched to the end of April 2014. Studies using 1 g of azithromycin or 7 days of doxycycline for the treatment of rectal chlamydia were eligible. Gender, diagnostic test, serovar, symptomatic status, other sexually transmitted infections, follow-up time, attrition and microbial cure were extracted. Meta-analysis was used to calculate pooled (i) azithromycin and doxycycline efficacy and (ii) efficacy difference. RESULTS: All eight included studies were observational. The random-effects pooled efficacy for azithromycin (based on eight studies) was 82.9% (95% CI 76.0%-89.8%; I(2) = 71.0%; P < 0.01) and for doxycycline (based on five studies) was 99.6% (95% CI 98.6%-100%; I(2) = 0%; P = 0.571), resulting in a random-effects pooled efficacy difference (based on five studies) of 19.9% (95% CI 11.4%-28.3%; I(2) = 48.5%; P = 0.101) in favour of doxycycline. CONCLUSIONS: The efficacy of single-dose azithromycin may be considerably lower than 1 week of doxycycline for treating rectal chlamydia. However, the available evidence is very poor. Robust randomized controlled trials are urgently required.
The Efficacy of Azithromycin for the Treatment of Genital Mycoplasma genitalium: A Systematic Review and Meta-analysis
(OXFORD UNIV PRESS INC, 2015-11-01)
BACKGROUND: Mycoplasma genitalium (MG) is associated with nongonococcal urethritis in men and cervicitis in women. Current guidelines recommend treatment with 1 gram of azithromycin; however, treatment failure has increasingly been reported. This meta-analysis estimates treatment efficacy following treatment with 1 gram of azithromycin. METHODS: Electronic databases were searched for articles published to the end of February 2015 using the following search terms: (Mycoplasma genitalium) AND (azithromycin OR zithromax OR [treatment efficacy]). Studies were included if they were English language, had participants aged ≥12 years diagnosed with urogenital MG, and had microbial cure measured within 12 months of treatment. Treatment efficacy was measured as microbial cure at last follow-up after treatment. RESULTS: A total of 21 studies, including 1490 participants, fulfilled the inclusion criteria. Most studies were observational, with only 5 controlled trials identified. The random-effects pooled microbial cure was 77.2% (95% confidence interval [CI], 71.1%-83.4%; I(2) = 80.8%, P < .01). For the 12 studies conducted prior to 2009, pooled microbial cure was 85.3% (CI, 82.3%-88.3%; I(2) = 19.7%, P = .25); for the 9 studies conducted since the beginning of 2009, pooled microbial cure was 67.0% (CI, 57.0%-76.9%; I(2) = 80.9%, P < .01). CONCLUSIONS: The efficacy of a single dose of 1 gram of azithromycin for the treatment of urogenital MG has decreased to approach 60%. Even though most of the available evidence is based on observational studies that have considerable variability in sample size and timing of microbial cure, this low efficacy is of considerable concern. It is vital that new treatment options for MG are investigated.
Higher organism load associated with failure of azithromycin to treat rectal chlamydia
(CAMBRIDGE UNIV PRESS, 2016-09-01)
Repeat rectal chlamydia infection is common in men who have sex with men (MSM) following treatment with 1 g azithromycin. This study describes the association between organism load and repeat rectal chlamydia infection, genovar distribution, and efficacy of azithromycin in asymptomatic MSM. Stored rectal chlamydia-positive samples from MSM were analysed for organism load and genotyped to assist differentiation between reinfection and treatment failure. Included men had follow-up tests within 100 days of index infection. Lymphogranuloma venereum and proctitis diagnosed symptomatically were excluded. Factors associated with repeat infection, treatment failure and reinfection were investigated. In total, 227 MSM were included - 64 with repeat infections [28·2%, 95% confidence interval (CI) 22·4-34·5]. Repeat positivity was associated with increased pre-treatment organism load [odds ratio (OR) 1·7, 95% CI 1·4-2·2]. Of 64 repeat infections, 29 (12·8%, 95% CI 8·7-17·8) were treatment failures and 35 (15·4%, 95% CI 11·0-20·8) were reinfections, 11 (17·2%, 95% CI 8·9-28·7) of which were definite reinfections. Treatment failure and reinfection were both associated with increased load (OR 2·0, 95% CI 1·4-2·7 and 1·6, 95% CI 1·2-2·2, respectively). The most prevalent genovars were G, D and J. Treatment efficacy for 1 g azithromycin was 83·6% (95% CI 77·2-88·8). Repeat positivity was associated with high pre-treatment organism load. Randomized controlled trials are urgently needed to evaluate azithromycin's efficacy and whether extended doses can overcome rectal infections with high organism load.