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Search Results: 1 - 10 of 14082 matches for " Sarah Young "
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Aminoglycosides: Molecular Insights on the Recognition of RNA and Aminoglycoside Mimics
Maruthi Chittapragada, Sarah Roberts and Young Wan Ham
Perspectives in Medicinal Chemistry , 2012,
Abstract: RNA is increasingly recognized for its significant functions in biological systems and has recently become an important molecular target for therapeutics development. Aminoglycosides, a large class of clinically significant antibiotics, exert their biological functions by binding to prokaryotic ribosomal RNA (rRNA) and interfering with protein translation, resulting in bacterial cell death. They are also known to bind to viral mRNAs such as HIV-1 RRE and TAR. Consequently, aminoglycosides are accepted as the single most important model in understanding the principles that govern small molecule-RNA recognition, which is essential for the development of novel antibacterial, antiviral or even anti-oncogenic agents. This review outlines the chemical structures and mechanisms of molecular recognition and antibacterial activity of aminoglycosides and various aminoglycoside mimics that have recently been devised to improve biological efficacy, binding affinity and selectivity, or to circumvent bacterial resistance.
Aminoglycosides: Molecular Insights on the Recognition of RNA and Aminoglycoside Mimics
Maruthi Chittapragada,Sarah Roberts,Young Wan Ham
Perspectives in Medicinal Chemistry , 2009,
Abstract: RNA is increasingly recognized for its significant functions in biological systems and has recently become an important molecular target for therapeutics development. Aminoglycosides, a large class of clinically significant antibiotics, exert their biological functions by binding to prokaryotic ribosomal RNA (rRNA) and interfering with protein translation, resulting in bacterial cell death. They are also known to bind to viral mRNAs such as HIV-1 RRE and TAR. Consequently, aminoglycosides are accepted as the single most important model in understanding the principles that govern small molecule-RNA recognition, which is essential for the development of novel antibacterial, antiviral or even anti-oncogenic agents. This review outlines the chemical structures and mechanisms of molecular recognition and antibacterial activity of aminoglycosides and various aminoglycoside mimics that have recently been devised to improve biological efficacy, binding affinity and selectivity, or to circumvent bacterial resistance.
The 2014 March 29 X-flare: sub-arcsecond resolution observations of Fe XXI 1354.1
Peter Young,Hui Tian,Sarah Jaeggli
Physics , 2014, DOI: 10.1088/0004-637X/799/2/218
Abstract: The Interface Region Imaging Spectrometer (IRIS) is the first solar instrument to observe $\sim 10$ MK plasma at subarcsecond spatial resolution through imaging spectroscopy of the Fe XXI $\lambda$1354.1 forbidden line. IRIS observations of the X1 class flare that occurred on 2014 March 29 at 17:48 UT reveal Fe XXI emission from both the flare ribbons and the post-flare loop arcade. Fe XXI appears at all of the chromospheric ribbon sites, although typically with a delay of one raster (75 seconds) and sometimes offset by up to 1$^{\prime\prime}$. 100--200 km s$^{-1}$ blue-shifts are found at the brightest ribbons, suggesting hot plasma upflow into the corona. The Fe XXI ribbon emission is compact with a spatial extent of $< 2^{\prime\prime}$, and can extend beyond the chromospheric ribbon locations. Examples are found of both decreasing and increasing blue-shift in the direction away from the ribbon locations, and blue-shifts were present for at least 6 minutes after the flare peak. The post-flare loop arcade, seen in Atmospheric Imaging Assembly (AIA) 131 \AA\ filtergram images that are dominated by Fe XXI, exhibited bright loop-tops with an asymmetric intensity distribution. The sizes of the loop-tops are resolved by IRIS at $\ge 1^{\prime\prime}$, and line widths in the loop-tops are not broader than in the loop-legs suggesting the loop-tops are not sites of enhanced turbulence. Line-of-sight speeds in the loop arcade are typically $<10$ km s$^{-1}$, and mean non-thermal motions fall from 43 km s$^{-1}$ at the flare peak to 26 km s$^{-1}$ six minutes later. If the average velocity in the loop arcade is assumed to be at rest, then it implies a new reference wavelength for the Fe XXI line of $1354.106\pm 0.023$ \AA.
Myth and Momentum: A Critique of Environmental Impact Assessments  [PDF]
Andrew J. Wright, Sarah J. Dolman, Michael Jasny, E. C. M. Parsons, Doris Schiedek, Sharon B. Young
Journal of Environmental Protection (JEP) , 2013, DOI: 10.4236/jep.2013.48A2009
Abstract:

Environmental Impact Assessments (EIAs) are designed to evaluate all reasonably foreseeable environmental consequences of human activities. Appropriate governmental scientists traditionally produced EIAs for management agencies in many countries. However, many EIAs are now contracted out, often to the lowest bidder without due consideration of expertise. Others suffer from limited agency resources. Consequently, many EIAs have become insufficiently researched documents that draw heavily from previous EIAs while being rushed to completion to meet legislative deadlines or avoid delaying projects. Habitual treatment of topics often ignores recent scientific literature, perpetuating previous misconceptions and analytical flaws. Common problems in EIAs discussing wildlife include: a focus on lethal takes, with little consideration of non-lethal impacts or habitat degradation; a general dismissal of the possibility that non-significant (to the resource) impacts can, when combined, become significant; and the assumption that behavioral habituation in animals represents an end of impact. Incentive to break the cycle is somewhat lacking in this now often commercially competitive environment, where contracts are increasingly awarded by industry, generating potential conflict of interest. We believe investment in thorough, impartially written, scientifically-based and up-to-date EIAs is important for appropriately representing and managing ecosystems and their resources and avoiding potentially expensive litigation.

Plantagora: Modeling Whole Genome Sequencing and Assembly of Plant Genomes
Roger Barthelson,Adam J. McFarlin,Steven D. Rounsley,Sarah Young
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0028436
Abstract: Genomics studies are being revolutionized by the next generation sequencing technologies, which have made whole genome sequencing much more accessible to the average researcher. Whole genome sequencing with the new technologies is a developing art that, despite the large volumes of data that can be produced, may still fail to provide a clear and thorough map of a genome. The Plantagora project was conceived to address specifically the gap between having the technical tools for genome sequencing and knowing precisely the best way to use them.
Synthetic Polymer Scaffolds for Stem Cell Transplantation in Retinal Tissue Engineering
Jing Yao,Sarah L. Tao,Michael J. Young
Polymers , 2011, DOI: 10.3390/polym3020899
Abstract: Age-related macular degeneration and retinitis pigmentosa are two leading causes of irreversible blindness characterized by photoreceptor loss. Cell transplantation may be one of the most promising approaches of retinal repair. However, several problems hinder the success of retinal regeneration, including cell delivery and survival, limited cell integration and incomplete cell differentiation. Recent studies show that polymer scaffolds can address these three problems. This article reviews the current literature on synthetic polymer scaffolds used for stem cell transplantation, especially retinal progenitor cells. The advantages and disadvantages of different polymer scaffolds, the role of different surface modifications on cell attachment and differentiation, and controlled drug delivery are discussed. The development of material and surface modification techniques is vital in making cell transplantation a clinical success.
Removal of a below knee plaster cast worn for 28 months: a case report
Helen Ingoe, Sarah Eastwood, David W Elson, Claire F Young
Journal of Medical Case Reports , 2011, DOI: 10.1186/1752-1947-5-74
Abstract: The cast was removed from the leg of a 45-year-old Caucasian woman. Significant muscle atrophy and dense skin scales were present but the underlying skin surface was relatively healthy with only small pitted 1-2 mm ulcers. No pathogenic organisms were cultured from this environment.It seems likely that skin can tolerate cast immobilization for prolonged duration.Extremity casts are frequently applied for routine immobilization for many acute fractures. The period of immobilization varies according to the patient and the fracture. For example, a non-operatively treated tibial fracture is rarely immobilized for longer than six months. Total contact casting has been used in the treatment of Charcot's neuropathy for periods of up to one year [1]. We report a case of a below knee cast removal after 28 months.When she was 40 years old, a Caucasian woman underwent bunion surgery for pain whilst ambulating. The wounds healed without complication but she went on to develop mechanical allodynia, intermittent swelling and a bluish discoloration of the foot, consistent with a diagnosis of type 1 complex regional pain syndrome. She received many different treatments for continued pain over the subsequent years. Drug therapies using pregabalin, strong opiates and epidural analgesia were not fully successful and she was offered a below knee cast as a temporizing measure. There was no pre-existing psychiatric diagnosis but the patient developed a psychological dependence upon this cast. She was reluctant to have it removed, believing that her pain remained inadequately treated. She failed to attend several appointments at the pain clinic. When she did return, the anesthetists asked for orthopaedic assistance to remove her cast. By this point she was 45 years old and had spent the previous 28 months in the same below knee cast. She was no longer taking regular analgesia but was unable to tolerate anyone touching her leg and therefore received a general anesthetic to facilitate the c
The Transition from Primary siRNAs to Amplified Secondary siRNAs That Regulate Chalcone Synthase During Development of Glycine max Seed Coats
Young B. Cho, Sarah I. Jones, Lila Vodkin
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0076954
Abstract: The I locus is a 27-kb inverted repeat cluster of chalcone synthase genes CHS1-3-4 that mediates siRNA down-regulation of CHS7 and CHS8 target mRNAs during seed development leading to yellow seed coats lacking anthocyanin pigments. Here, we report small RNA sequencing of ten stages of seed development from a few days post fertilization through maturity, revealing the amplification from primary to secondary short interfering RNAs (siRNAs) occurring during development. The young seed populations had a higher proportion of siRNAs representing the CHS1-3-4 gene family members, consistent with this region as the origin of the primary siRNAs. More intriguingly, the very young seed had a higher proportion of 22-nt CHS siRNAs than did the mid-maturation seed. We infer that the primary CHS siRNAs increase during development to levels sufficient to trigger amplification of secondary CHS siRNAs from the CHS7/8 target mRNAs, enabling the total levels of 21-nt CHS siRNAs to rise dramatically. Further, we demonstrate that the soybean system exhibits tissue-specific CHS siRNA production because primary CHS siRNA levels are not sufficient to trigger secondary amplification in tissues other than the seed coat.
An Enhanced Heterologous Virus-Like Particle for Human Papillomavirus Type 16 Tumour Immunotherapy
Khairunadwa Jemon, Vivienne Young, Michelle Wilson, Sara McKee, Vernon Ward, Margaret Baird, Sarah Young, Merilyn Hibma
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0066866
Abstract: Cervical cancer is caused by high-risk, cancer-causing human papillomaviruses (HPV) and is the second highest cause of cancer deaths in women globally. The majority of cervical cancers express well-characterized HPV oncogenes, which are potential targets for immunotherapeutic vaccination. Here we develop a rabbit haemorrhagic disease virus (RHDV) virus-like particle (VLP)-based vaccine designed for immunotherapy against HPV16 positive tumours. An RHDV-VLP, modified to contain the universal helper T cell epitope PADRE and decorated with an MHC I-restricted peptide (aa 48–57) from the HPV16 E6, was tested for its immunotherapeutic efficacy against the TC-1 HPV16 E6 and E7-expressing tumour in mice. The E6-RHDV-VLP-PADRE was administered therapeutically for the treatment of a pre-existing TC-1 tumour and was delivered with antibodies either to deplete regulatory T cells (anti-CD25) or to block T cell suppression mediated through CTLA-4. As a result, the tumour burden was reduced by around 50% and the median survival time of mice to the humane endpoint was almost doubled the compared to controls. The incorporation of PADRE into the RHDV-VLP was necessary for an E6-specific enhancement of the anti-tumour response and the co-administration of the immune modifying antibodies contributed to the overall efficacy of the immunotherapy. The E6-RHDV-VLP-PADRE shows immunotherapeutic efficacy, prolonging survival for HPV tumour-bearing mice. This was enhanced by the systemic administration of immune-modifying antibodies that are commercially available for use in humans. There is potential to further modify these particles for even greater efficacy in the path to development of an immunotherapeutic treatment for HPV precancerous and cancer stages.
Beta Agonist Lung Injury TrIal-2 (BALTI-2) trial protocol: A randomised, double-blind, placebo-controlled of intravenous infusion of salbutamol in the acute respiratory distress syndrome
Gavin D Perkins, Simon Gates, Sarah E Lamb, Chris McCabe, Duncan Young, Fang Gao
Trials , 2011, DOI: 10.1186/1745-6215-12-113
Abstract: Patients fulfilling the American-European Consensus Conference Definition of ARDS will be randomised in a 1:1 ratio to receive an IV infusion either of salbutamol (15 μg kg ideal body weight-1 hr-1) or placebo (0.9% sodium chloride solution), for a maximum of seven days. Allocation to randomised groups will use minimisation to ensure balance with respect to hospital of recruitment, age group (<64, 65-84, >85 years) and PaO2/FiO2 ratio (≤6.7, 6.8- 13.2, ≥13.3 kPa). Data will be recorded by participating ICUs until hospital discharge, and all surviving patients will be followed up by post at six and twelve months post randomisation. The primary outcome is mortality at 28 days after randomisation; secondary outcomes are mortality in ICU, mortality in hospital, number of ventilator-free days, number of organ failure-free days, mortality at twelve months post-randomisation, quality of life at six and twelve months, length of stay in ICU, length of stay in hospital, adverse effects (tachycardia, arrhythmia or other side effects sufficient to stop treatment drug). 1,334 patients will be recruited from about fifty ICUs in the UK. An economic evaluation will be conducted alongside the trial.Current Controlled Trials ISRCTN38366450.The acute respiratory distress syndrome (ARDS) is a condition characterised by a failure of pulmonary oxygen exchange due to increased alveolar-capillary permeability and resultant lung oedema [1]. It can be caused by primary lung conditions such as aspiration, pneumonia, or can arise as a complication of non-pulmonary conditions such as severe sepsis. ARDS is defined by the 1994 American-European Consensus Conference [2] as the acute onset of hypoxaemia (PaO2:FiO2 ratio of < 200mm Hg), bilateral infiltrates on a chest radiograph in the absence of cardiogenic causes of pulmonary oedema.ARDS is common, The ALIVE study reported 13.3% of patients who require mechanical ventilation have ARDS [3]. Intensive Care Unit (ICU) mortality is estimated at 41-4
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