Derivatives of dihydrostreptomycin

The work already carried out on the chemical modification of naturally occurring antibiotics is reviewed. The reasons for carrying out these modifications are discussed. Antibiotics which have been modified chemically in some way include the penicillins, the cephalosporins, the tetracyclines, griseofulvin and the aminoglycoside antibiotics including streptomycin itself. The value of these modifications varies from compound to compound, the most successful derivatives which have been prepared, to date, being the derivatives of penicillin. Compounds have been prepared which are more active, which are active orally and which are active against penicillinase producing micro-organisms. Derivatives of other antibiotics have, generally, been less successful, although valuable information about structure-action relationships has been obtained. The derivatives of dihydrostreptoraycin which are considered in this thesis are glycosides of dihyirostreptobiosamine, a disaccharide composed of dihydrostreptose linked glycosidically with N-methyl -L glucosamine. The methods available for glycoside synthesis, the Koenigs-Knorr, the Helferich and the Fischer syntheses, are reviewed. A modification of the Fischer synthesis was used for the preparation of the bensyl glycoside of dihydrostreptobiosamine, using methyl dihydrostreptoblosaminlde as starting material. No clear mechanism for this reaction has so far been postulated and therefore a series of reactions was carried out in order to elucidate the mechanism. A and B-methyl dihydrosterptobiosaminides were prepared and separated in the form of their acetates which were then used to prepare benzyl penta-acetyldihydrostreptobiosaminide by transglycosidation. The fact that the a-anomer was formed in both cases indicates that, every time, it is the more stable isomer which is formed. Direct benzyl alcoholysis of dihydrostreptomycin also gave a-benzyl penta-acetyldihydrostreptobiosaminide, confirming that theory. Methanolsys of a-benzyl-acetyldihydrosteptobiosaminide gave only the a-anomer of methyl penta-acetyldihdrostrantobiosaminide. There is some indication that the furanose ring of dihydrostraptose facilitates the reaction, in analogy with the Fisoher glycoside synthesis

Sixty Years of Fractal Projections

Sixty years ago, John Marstrand published a paper which, among other things, relates the Hausdorff dimension of a plane set to the dimensions of its orthogonal projections onto lines. For many years, the paper attracted very little attention. However, over the past 30 years, Marstrand's projection theorems have become the prototype for many results in fractal geometry with numerous variants and applications and they continue to motivate leading research.Comment: Submitted to proceedings of Fractals and Stochastics

Integrating Al with NiO nano honeycomb to realize an energetic material on silicon substrate

Nano energetic materials offer improved performance in energy release, ignition, and mechanical properties compared to their bulk or micro counterparts. In this study, the authors propose an approach to synthesize an Al/NiO based nano energetic material which is fully compatible with a microsystem. A two-dimensional NiO nano honeycomb is first realized by thermal oxidation of a Ni thin film deposited onto a silicon substrate by thermal evaporation. Then the NiO nano honeycomb is integrated with an Al that is deposited by thermal evaporation to realize an Al/NiO based nano energetic material. This approach has several advantages over previous investigations, such as lower ignition temperature, enhanced interfacial contact area, reduced impurities and Al oxidation, tailored dimensions, and easier integration into a microsystem to realize functional devices. The synthesized Al/NiO based nano energetic material is characterized by scanning electron microscopy, X-ray diffraction, differential thermal analysis, and differential scanning calorimetry

Fabrication of high quality plan-view TEM specimens using the focused ion beam

We describe a technique using a focused ion beam instrument to fabricate high quality plan-view specimens for transmission electron microscopy studies. The technique is simple, site-specific and is capable of fabricating multiple large, >100 μm2 electron transparent windows within epitaxially-grown thin films. A film of La0.67Sr0.33MnO3 is used to demonstrate the technique and its structural and functional properties are surveyed by high resolution imaging, electron spectroscopy, atomic force microscopy and Lorentz electron microscopy. The window is demonstrated to have good thickness uniformity and a low defect density that does not impair the film’s Curie temperature. The technique will enable the study of in–plane structural and functional properties of a variety of epitaxial thin film systems

Understanding the psychosocial experiences of adults with mild-moderate hearing loss: an application of Leventhal’s self-regulatory model

Objective: This study explored the psychosocial experiences of adults with hearing loss using the self-regulatory model as a theoretical framework. The primary components of the model, namely cognitive representations, emotional representations, and coping responses, were examined. Design: Individual semi-structured interviews were conducted. The data were analysed using an established thematic analysis procedure. Study sample: Twenty-five adults with mild-moderate hearing loss from the UK and nine hearing healthcare professionals from the UK, USA, and Canada were recruited via maximum variation sampling. Results: Cognitive representations: Most participants described their hearing loss as having negative connotations and consequences, although they were not particularly concerned about the progression or controllability/curability of the condition. Opinions differed regarding the benefits of understanding the causes of one’s hearing loss in detail. Emotional representations: negative emotions dominated, although some experienced positive emotions or muted emotions. Coping responses: engaged coping (e.g. hearing aids, communication tactics) and disengaged coping (e.g. withdrawal from situations, withdrawal within situations): both had perceived advantages and disadvantages. Conclusions: This novel application of the self-regulatory model demonstrates that it can be used to capture the key psychosocial experiences (i.e. perceptions, emotions, and coping responses) of adults with mild-moderate hearing loss within a single, unifying framework

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Determinants of Depressive Symptoms at 1 Year Following ICU Discharge in Survivors of $ 7 Days of Mechanical Ventilation : Results From the RECOVER Program, a Secondary Analysis of a Prospective Multicenter Cohort Study

Abstract : Background: Moderate to severe depressive symptoms occur in up to one-third of patients at 1 year following ICU discharge, negatively affecting patient outcomes. This study evaluated patient and caregiver factors associated with the development of these symptoms. Methods: This study used the Rehabilitation and Recovery in Patients after Critical Illness and Their Family Caregivers (RECOVER) Program (Phase 1) cohort of 391 patients from 10 medical/surgical university-affiliated ICUs across Canada. We determined the association between patient depressive symptoms (captured by using the Beck Depression Inventory II [BDI-II]), patient characteristics (age, sex, socioeconomic status, Charlson score, and ICU length of stay [LOS]), functional independence measure (FIM) motor subscale score, and caregiver characteristics (Caregiver Assistance Scale and Center for Epidemiologic Studies-Depression Scale) by using linear mixed models at time points 3, 6, and 12 months. Results: BDI-II data were available for 246 patients. Median age at ICU admission was 56 years (interquartile range, 45-65 years), 143 (58%) were male, and median ICU LOS was 19 days (interquartile range, 13-32 days). During the 12-month follow-up, 67 of 246 (27.2%) patients had a BDI-II score ≥ 20, indicating moderate to severe depressive symptoms. Mixed models showed worse depressive symptoms in patients with lower FIM motor subscale scores (1.1 BDI-II points per 10 FIM points), lower income status (by 3.7 BDI-II points; P = .007), and incomplete secondary education (by 3.8 BDI-II points; P = .009); a curvilinear relation with age (P = .001) was also reported, with highest BDI-II at ages 45 to 50 years. No associations were found between patient BDI-II and comorbidities (P = .92), sex (P = .25), ICU LOS (P = .51), or caregiver variables (Caregiver Assistance Scale [P = .28] and Center for Epidemiologic Studies Depression Scale [P = .74]). Conclusions: Increased functional dependence, lower income, and lower education are associated with increased severity of post-ICU depressive symptoms, whereas age has a curvilinear relation with symptom severity. Knowledge of risk factors may inform surveillance and targeted mental health follow-up. Early mobilization and rehabilitation aiming to improve function may serve to modify mood disorders

Regions of the genome that affect agronomic performance in two-row barley

Quantitative trait locus (QTL) main effects and QTL by environment (QTL × E) interactions for seven agronomic traits (grain yield, days to heading, days to maturity, plant height, lodging severity, kernel weight, and test weight) were investigated in a two-row barley (Hordeum vulgare L.) cross, Harrington/TR306. A 127-point base map was constructed from markers (mostly RFLP) scored in 146 random double-haploid (DH) lines from the Harrington/TR306 cross. Field experiments involving the two parents and 145 random DH lines were grown in 1992 and/or 1993 at 17 locations in North America. Analysis of QTL was based on simple and composite interval mapping. Primary QTL were declared at positions where both methods gave evidence for QTL. The number of primary QTL ranged from three to six per trait, collectively explaining 34 to 52% of the genetic variance. None of these primary QTL showed major effects, but many showed effects that were consistent across environments. The addition of secondary QTL gave models that explained 39 to 80% of the genetic variance. The QTL were dispersed throughout the barley genome and some were detected in regions where QTL have been found in previous studies. Eight chromosome regions contained pleiotropic loci and/or linked clusters of loci that affected multiple traits. One region on chromosome 7 affected all traits except days to heading. This study was an intensive effort to evaluate QTL in a narrow-base population grown in a large set of environments. The results reveal the types and distributions of QTL effects manipulated by plant breeders and provide opportunities for future testing of marker-assisted selection

Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study

A41 Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study In: Addiction Science & Clinical Practice 2017, 12(Suppl 1): A4