Asymptotic symmetries of projectively compact order one Einstein manifolds.

We show that the boundary of a projectively compact Einstein manifold of dimension [Formula: see text] can be extended by a line bundle naturally constructed from the projective compactification. This extended boundary is such that its automorphisms can be identified with asymptotic symmetries of the compactification. The construction is motivated by the investigation of a new curved orbit decomposition for a [Formula: see text] dimensional manifold which we prove results in a line bundle over projectively compact order one Einstein manifolds.

How should communities be meaningfully engaged (if at all) when setting priorities for biomedical research? Perspectives from the biomedical research community.

Background: There is now rising consensus that community engagement is ethically and scientifically essential for all types of health research. Yet debate continues about the moral aims, methods and appropriate timing in the research cycle for community engagement to occur, and whether the answer should vary between different types of health research. Co-design and collaborative partnership approaches that involve engagement during priority-setting, for example, are common in many forms of applied health research but are not regular practice in biomedical research.

Standardised data on initiatives-STARDIT: Beta version.

Background And Objective: There is currently no standardised way to share information across disciplines about initiatives, including fields such as health, environment, basic science, manufacturing, media and international development. All problems, including complex global problems such as air pollution and pandemics require reliable data sharing between disciplines in order to respond effectively. Current reporting methods also lack information about the ways in which different people and organisations are involved in initiatives, making it difficult to collate and appraise data about the most effective ways to involve different people.

Assessing knowledge, attitudes and beliefs of nurses about LGBTQ older adults using a documentary video.

Background: Statistics reveal that lesbian, gay, bisexual, transgender, and queer (LGBTQ) older adults experience health disparities and barriers to accessing healthcare because of discrimination and fear of disclosing sexual orientation. Nurses receive limited education on LGBTQ health issues and even less information specifically about LGBTQ older adults. This study exposed novice nurses to the documentary, Gen Silent, which details LGBTQ older adult experiences.

Decaprenylphosphoryl-β-d-ribose Oxidase Inhibitors: Expeditious Reconstruction of Suboptimal Hits into a Series with Potent in Vivo Activity.

Decaprenylphosphoryl-β-d-ribose 2'-epimerase (DprE1) is an essential enzyme in and has recently been studied as a potential drug target, with inhibitors progressing to clinical studies. Here we describe the identification of a novel series of morpholino-pyrimidine DprE1 inhibitors. These were derived from a phenotypic high-throughput screening (HTS) hit with suboptimal physicochemical properties.

Identification and Optimization of Novel Small c-Abl Kinase Activators Using Fragment and HTS Methodologies.

Abelson kinase (c-Abl) is a ubiquitously expressed, nonreceptor tyrosine kinase which plays a key role in cell differentiation and survival. It was hypothesized that transient activation of c-Abl kinase via displacement of the N-terminal autoinhibitory "myristoyl latch", may lead to an increased hematopoietic stem cell differentiation. This would increase the numbers of circulating neutrophils and so be an effective treatment for chemotherapy-induced neutropenia.

Structurally Diverse Mitochondrial Branched Chain Aminotransferase (BCATm) Leads with Varying Binding Modes Identified by Fragment Screening.

Inhibitors of mitochondrial branched chain aminotransferase (BCATm), identified using fragment screening, are described. This was carried out using a combination of STD-NMR, thermal melt (Tm), and biochemical assays to identify compounds that bound to BCATm, which were subsequently progressed to X-ray crystallography, where a number of exemplars showed significant diversity in their binding modes. The hits identified were supplemented by searching and screening of additional analogues, which enabled the gathering of further X-ray data where the original hits had not produced liganded structures.

The Discovery of in Vivo Active Mitochondrial Branched-Chain Aminotransferase (BCATm) Inhibitors by Hybridizing Fragment and HTS Hits.

The hybridization of hits, identified by complementary fragment and high throughput screens, enabled the discovery of the first series of potent inhibitors of mitochondrial branched-chain aminotransferase (BCATm) based on a 2-benzylamino-pyrazolo[1,5-a]pyrimidinone-3-carbonitrile template. Structure-guided growth enabled rapid optimization of potency with maintenance of ligand efficiency, while the focus on physicochemical properties delivered compounds with excellent pharmacokinetic exposure that enabled a proof of concept experiment in mice. Oral administration of 2-((4-chloro-2,6-difluorobenzyl)amino)-7-oxo-5-propyl-4,7-dihydropyrazolo[1,5-a]pyrimidine-3-carbonitrile 61 significantly raised the circulating levels of the branched-chain amino acids leucine, isoleucine, and valine in this acute study.

Structure-guided optimization of small molecule c-Abl activators.

c-Abl kinase is maintained in its normal inactive state in the cell through an assembled, compact conformation. We describe two chemical series that bind to the myristoyl site of the c-Abl kinase domain and stimulate c-Abl activation. We hypothesize that these molecules activate c-Abl either by blocking the C-terminal helix from adopting a bent conformation that is critical for the formation of the autoinhibited conformation or by simply providing no stabilizing interactions to the bent conformation of this helix.

The characterization of a novel V1b antagonist lead series.

The SAR around a V1b antagonist HTS hit 3 was explored to produce a series of thiazole sulfonamides as a lead series with selectivity over the related V1 and oxytocin receptors.

Acute retinal necrosis post intravitreal injection of triamcinolone acetonide.

Although few data exist on the complication of intravitreal injection of triamcinolone acetonide (IVTA) in human eyes, it is generally thought to be well-tolerated. The commonest reported adverse events are raised intraocular pressure and progression of cataract. Acute retinal necrosis, as far as the authors are aware, has not been reported to be associated with IVTA in the literature before.

Determination of the transcript profile of human endometrium.

The response of the human endometrium to the ovarian hormones, estrogen and progesterone, has been the focus of decades of research. In order to understand this critical aspect of endometrial physiology, we undertook a genome-wide analysis of transcript abundance and changes in transcript level between normal endometrium in the proliferative and secretory phases of the menstrual cycle. A high-density, oligonucleotide gene array, comprising 60 000 gene targets, was used to define the gene expression profile of proliferative and secretory phase endometrium.

Loss of vision caused by expansion of intraocular perfluoropropane (C(3)F(8)) gas during nitrous oxide anesthesia.

Purpose: To report visual loss associated with nitrous oxide anesthesia in patients with intraocular perfluoropropane (C(3)F(8)) gas.

Design: Observational case series.

Methods: Three patients are described who lost vision in the eye with intraocular gas after subsequent nitrous oxide general anesthesia.

Relationship of adipose tissue cholesteryl ester transfer protein (CETP) mRNA to plasma concentrations of CETP in man.

Adipose tissue is an important site of cholesteryl ester transfer protein (CETP) synthesis and CETP plays a local role in adipocyte cholesteryl ester accumulation from high density lipoproteins (HDL). Human adipose tissue maintained in organ culture secretes CETP, but it is not known to what extent adipose tissue CETP contributes to the plasma pool of CETP in man. Aging is associated with changes in adipose tissue composition and function, including impaired adipocyte triglyceride lipolysis.

Sunglasses: are they necessary in Christchurch?

Concern over potential eye injury from sunlight prompted this study to see if the levels of sunlight in Christchurch posed a particular risk to our population's eyes, whether the populace was aware of any risk and whether effective sunglasses were freely available to the public. While there has been a 4% to 9% increase in UV radiation since 1969 due to global ozone depletion, no firm evidence was found that focal ozone depletion was a particular problem in New Zealand. Christchurch residents were poorly informed about the ocular hazards of sunlight.

The in vitro effect of hypotensive agents on the affinity of haemoglobin for oxygen.

The effect of nitroglycerine, sodium nitroprusside, trimetaphan, pentolinium, labetalol and propranolol on the affinity of haemoglobin for oxygen was studied in vitro. Only pentolinium had a significant effect, increasing the binding of oxygen by haemoglobin. The significance of these results is discussed.

Selective reactions in the analytical characterisation of steroids by gas chromatography-mass spectrometry.

The analytical characterization, by GC-MS, of individual compounds in mixtures of steroids, such as occur frequently in biological extracts, is difficult because of the close similarities in structure and properties of many components. The improved separating power of capillary (open-tubular) columns alleviates the problem, but does not solve it fully: for example, the coincidence of retention times of two different compounds may still be virtually complete. Comparative analyses on two distinctively different phases afford one valuable application of selectivity, but may not always be feasible when costly columns are required.