Modeling of experimentally observed topological defects inside bulk polycrystals

A rigorous methodology is developed for computing elastic fields generated by experimentally observed defect structures within grains in a polycrystal that has undergone tensile extension. An example application is made using a near-field High Energy X-ray Diffraction Microscope measurement of a zirconium sample that underwent $13.6\%$ tensile extension from an initially well-annealed state. (Sub)grain boundary features are identified with apparent disclination line defects in them. The elastic fields of these features identified from the experiment are calculated

A study of stress gradients in a titanium alloy

A study of the stress gradient developed in a Ti-7AL sample is examined using the technique of High-Energy Diffraction Microscopy. The experiment is conducted at beamline 1-ID of the Advanced Photon Source of Argonne National Laboratory, using high-resolution monochromator. A map of grain orientation in the cross-section of the sample is determined through use of a near-field technique. The near-field study is complemented by analysis using data from a far-field detector to develop lattice strain on a grain-by-grain basis. A state of bending with superposed tension is revealed through correlation of the near-field grain map with the far-field center of mass result. A comparison of “macro” stress and the “grain scale” stresses is featured. An assessment is given on the benefits and limitations of using the high-resolution monochromator in the strain analysis of far-field detector images

Manifestations of hypertensive encephalopathy in cats

Objectives Hypertensive encephalopathy in cats is an important entity but is underestimated in clinical practice. This could be explained, in part, by non-specific clinical signs. The objective of this study was to characterise the clinical manifestations of hypertensive encephalopathy in cats. Methods Cats with systemic hypertension (SHT) recognised by routine screening, associated with underlying predisposing disease or a clinical presentation suggestive of SHT (neurological or non-neurological), were prospectively enrolled over a 2-year period. Confirmation of SHT was based on at least two sets of measurements of systolic blood pressure >160 mmHg by Doppler sphygmomanometry. Results Fifty-six hypertensive cats with a median age of 16.5 years were identified; 31 had neurological signs. In 16/31 cats, neurological abnormalities were the primary complaint. The other 15 cats were first presented to the medicine or ophthalmology service, and neurological disease was recognised based on the cat’s history. The most common neurological signs were ataxia, various manifestations of seizures and altered behaviour. Individual cats also showed paresis, pleurothotonus, cervical ventroflexion, stupor and facial nerve paralysis. In 28/30 cats, retinal lesions were detected. Of these 28 cats, six presented with a primary complaint of visual deficits, and neurological signs were not the primary complaint; nine presented with non-specific medical issues, without suspicion of SHT-induced organ damage; in 13 cats, neurological issues were the primary complaint and fundic abnormalities were detected subsequently. Conclusions and relevance SHT is common in older cats and the brain is an important target organ; however, neurological deficits are commonly ignored in cats with SHT. Gait abnormalities, (partial) seizures and even mild behavioural changes should prompt clinicians to consider the presence of SHT. A fundic examination in cats with suspected hypertensive encephalopathy is a sensitive test to support the diagnosis

Spirulina is an effective dietary source of zeaxanthin to humans

Zeaxanthin is a predominant xanthophyll in human eyes and may reduce the risk of cataracts and age-related macular degeneration. Spirulina is an algal food that contains a high concentration of zeaxanthin. In order to determine the zeaxanthin bioavailability of spirulina for dietary supplementation in humans, spirulina was grown in nutrient solution with 2H2O for carotenoid labelling. Single servings of 2H-labelled spirulina (4·0-5·0g) containing 2·6-3·7mg zeaxanthin were consumed by fourteen healthy male volunteers (four Americans and ten Chinese) with 12g dietary fat. Blood samples were collected over a 45d period. The serum concentrations of total zeaxanthin were measured using HPLC, and the enrichment of labelled zeaxanthin was determined using LC-atmospheric pressure chemical ionisation-MS (LC-APCI-MS). The results showed that intrinsically labelled spirulina zeaxanthin in the circulation was detected at levels as low as 10% of the total zeaxanthin for up to 45d after intake of the algae. A single dose of spirulina can increase mean serum zeaxanthin concentration in humans from 0·06 to 0·15μmol/l, as shown in our study involving American and Chinese volunteers. The average 15 d area under the serum zeaxanthin response curve to the single dose of spirulina was 293nmol×d/μmol (range 254-335) in American subjects, and 197nmol×d/μmol (range 154-285) in Chinese subjects. It is concluded that the relative bioavailability of spirulina zeaxanthin can be studied with high sensitivity and specificity using 2H labelling and LC-APCI-MS methodology. Spirulina can serve as a rich source of dietary zeaxanthin in human

The novel BET inhibitor UM-002 reduces glioblastoma cell proliferation and invasion

Bromodomain and extraterminal domain (BET) proteins have emerged as therapeutic targets in multiple cancers, including the most common primary adult brain tumor glioblastoma (GBM). Although several BET inhibitors have entered clinical trials, few are brain penetrant. We have generated UM-002, a novel brain penetrant BET inhibitor that reduces GBM cell proliferation in vitro and in a human cerebral brain organoid model. Since UM-002 is more potent than other BET inhibitors, it could potentially be developed for GBM treatment. Furthermore, UM-002 treatment reduces the expression of cell-cycle related genes in vivo and reduces the expression of invasion related genes within the non-proliferative cells present in tumors as measured by single cell RNA-sequencing. These studies suggest that BET inhibition alters the transcriptional landscape of GBM tumors, which has implications for designing combination therapies. Importantly, they also provide an integrated dataset that combines in vitro and ex vivo studies with in vivo single-cell RNA-sequencing to characterize a novel BET inhibitor in GBM

Grain boundary migration in polycrystalline α\alpha-Fe

High energy x-ray diffraction microscopy was used to image the microstructure of $\alpha$-Fe before and after a 600 $^\circ$C anneal. These data were used to determine the areas, curvatures, energies, and velocities of approximately 40,000 grain boundaries. The measured grain boundary properties depend on the five macroscopic grain boundary parameters. The velocities are not correlated with the product of the mean boundary curvature and grain boundary energy, usually assumed to be the driving force. Boundary migration is made up of area changes (lateral motion) and translation (normal motion) and both contribute to the total migration. Through the lateral motion component of the migration, low energy boundaries tend to expand in area while high energy boundaries shrink, reducing the average energy through grain boundary replacement. The driving force for this process is not related to curvature and might disrupt the expected curvature-velocity relationship.Comment: 33 pages, double spaced, accepted for publication in Acta Materiali

Decreased Expression Of apM1 in Omental and Subcutaneous Adipose Tissue of Humans With Type 2 Diabetes

We have screened a subtracted cDNA library in order to identify differentially expressed genes in omental adipose tissue of human patients with Type 2 diabetes. One clone (#1738) showed a marked reduction in omental adipose tissue from patients with Type 2 diabetes. Sequencing and BLAST analysis revealed clone #1738 was the adipocyte-specific secreted protein gene apM1 (synonyms ACRP30, AdipoQ, GBP28). Consistent with the murine orthologue, apM1 mRNA was expressed in cultured human adipocytes and not in preadipocytes. Using RT-PCR we confirmed that apM1 mRNA levels were significantly reduced in omental adipose tissue of obese patients with Type 2 diabetes compared with lean and obese normoglycemic subjects. Although less pronounced, apM1 mRNA levels were reduced in subcutaneous adipose tissue of Type 2 diabetic patients. Whereas the biological function of apM1 is presently unknown, the tissue specific expression, structural similarities to TNFα and the dysregulated expression observed in obese Type 2 diabetic patients suggest that this factor may play a role in the pathogenesis of insulin resistance and Type 2 diabetes