Identification of hydroxyapatite spherules provides new insight into subretinal pigment epithelial deposit formation in the aging eye.

Accumulation of protein- and lipid-containing deposits external to the retinal pigment epithelium (RPE) is common in the aging eye, and has long been viewed as the hallmark of age-related macular degeneration (AMD). The cause for the accumulation and retention of molecules in the sub-RPE space, however, remains an enigma. Here, we present fluorescence microscopy and X-ray diffraction evidence for the formation of small (0.5-20 μm in diameter), hollow, hydroxyapatite (HAP) spherules in Bruch's membrane in human eyes. These spherules are distinct in form, placement, and staining from the well-known calcification of the elastin layer of the aging Bruch's membrane. Secondary ion mass spectrometry (SIMS) imaging confirmed the presence of calcium phosphate in the spherules and identified cholesterol enrichment in their core. Using HAP-selective fluorescent dyes, we show that all types of sub-RPE deposits in the macula, as well as in the periphery, contain numerous HAP spherules. Immunohistochemical labeling for proteins characteristic of sub-RPE deposits, such as complement factor H, vitronectin, and amyloid beta, revealed that HAP spherules were coated with these proteins. HAP spherules were also found outside the sub-RPE deposits, ready to bind proteins at the RPE/choroid interface. Based on these results, we propose a novel mechanism for the growth, and possibly even the formation, of sub-RPE deposits, namely, that the deposit growth and formation begin with the deposition of insoluble HAP shells around naturally occurring, cholesterol-containing extracellular lipid droplets at the RPE/choroid interface; proteins and lipids then attach to these shells, initiating or supporting the growth of sub-RPE deposits

The case for cyber foraging

In this paper, we propose cyber foraging: a mechanism to augment the computational and storage capabilities of mobile devices. Cyber foraging uses opportunistically discovered servers in the environment to improve the performance of interactive applications and distributed file systems on mobile clients. We show how the performance of distributed file systems can be improved by staging data at these servers even though the servers are not trusted. We also show how the performance of interactive applications can be improved via remote execution. Finally, we present VERSUDS: a virtual interface to heteregeneous service discovery protocols that can be used to discover these servers

A New Type of Electron Nuclear-Spin Interaction from Resistively Detected NMR in the Fractional Quantum Hall Effect Regime

Two dimensional electron gases in narrow GaAs quantum wells show huge longitudinal resistance (HLR) values at certain fractional filling factors. Applying an RF field with frequencies corresponding to the nuclear spin splittings of {69}Ga, {71}Ga and {75}As leads to a substantial decreases of the HLR establishing a novel type of resistively detected NMR. These resonances are split into four sub lines each. Neither the number of sub lines nor the size of the splitting can be explained by established interaction mechanisms.Comment: 4 pages, 3 figure

Towards Truly “Global” Near Infrared Calibrations for Protein and Neutral Detergent Fibre in Dried Ground Forages

Over the past five years, Foss and DeLaval have sponsored the activities of a group of forage analysts with the aim of developing global Near Infrared (NIR) calibrations for parameters that are important in ruminant nutrition. The approach adopted has been based on the amalgamation of historical databases from centres worldwide and calibrations for protein and neutral detergent fibre (NDF) in dried ground forages have been developed based on databases that currently comprise approximately 30,000 records. Protein and NDF, while not the most important parameters in ruminant nutrition, were chosen for the initial calibration development exercise because of the amount of data available and because the methodologies adopted by different laboratories worldwide were relatively uniform. The aim was to create calibrations that would work for any forage type in any area of the world. Over the past two years, several trials have been carried out worldwide comparing the performance of global calibrations with the performance of locally developed calibrations for indigenous forages and based on reference values from local laboratories

Safety and activity of varlilumab, a novel and first-in-class agonist anti-CD27 antibody, for hematologic malignancies.

CD27, a costimulatory molecule on T cells, induces intracellular signals mediating cellular activation, proliferation, effector function, and cell survival on binding to its ligand, CD70. Varlilumab, a novel, first-in-class, agonist immunoglobulin G1 anti-CD27 antibody, mediates antitumor immunity and direct killing of CD27+ tumor cells in animal models. This first-in-human, dose-escalation, and expansion study evaluated varlilumab in patients with hematologic malignancies. Primary objectives were to assess safety and the maximum tolerated and optimal biologic doses of varlilumab. Secondary objectives were to evaluate pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity. In a 3 + 3 dose-escalation design, 30 patients with B-cell (n = 25) or T-cell (n = 5) malignancies received varlilumab (0.1, 0.3, 1, 3, or 10 mg/kg IV) as a single dose with a 28-day observation period, followed by weekly dosing (4 doses per cycle, up to 5 cycles, depending on tumor response). In an expansion cohort, 4 additional patients with Hodgkin lymphoma received varlilumab at 0.3 mg/kg every 3 weeks (4 doses per cycle, up to 5 cycles). No dose-limiting toxicities were observed. Treatment-related adverse events, generally grade 1 to 2, included fatigue, decreased appetite, anemia, diarrhea, and headache. Exposure was linear and dose-proportional across dose groups and resulted in increases in proinflammatory cytokines and soluble CD27. One patient with stage IV Hodgkin lymphoma experienced a complete response and remained in remission at \u3e33 months with no further anticancer therapy. These data support further investigation of varlilumab for hematologic malignancies, particularly in combination approaches targeting nonredundant immune regulating pathways. This trial was registered at www.clinicaltrials.gov as #NCT01460134

1972 Research Progress Reports, Fruit and Vegetable Processing and Food Technology

Evaluation of tomato cultivars / W. A. Gould, James Black, Louise Howiler, Shirley Perryman, and Stanley Z. Berry -- Effects of food additives on the quality of canned tomatoes / Wilbur A. Gould, John Mount, Jacquelyn Gould, Louise Howiler, and James Black -- Effect of storage temperature on shelf life of ascorbic acid fortified tomato juice / Gerald A. Pope and Wilbur A. Gould -- Survey of waste disposal practices of Ohio tomato processors / J. R. Geisman -- Evaluation of snap bean varieties for processing / Wilbur A. Gould, Jacquelyn Gould and Roberta Topits -- The effect of variety, size, and fermentation temperature on the quality attributes of cucumber pickles / Gary Flinn and Wilbur A. Gould -- Progress report on frozen corn-on-the-cob / James W. Swinehart and Wilbur A. Gould -- Progress report on cabbage lipids / Andrew C. Peng -- Effect of soybean flour on quality and protein content in the manufacture of doughnuts / Mohamed I. Mahmoud and Wilbur A. Goul

Exploratory Biomarker Analysis In The Ph 3 Echelon‐1 Study: Worse Outcome With Abvd In Patients With Elevated Baseline Levels Of Scd30 And Tarc

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149507/1/hon99_2630.pd

Zinc intake, status and indices of cognitive function in adults and children: a systematic review and meta-analysis

In developing countries, deficiencies of micronutrients are thought to have a major impact on child development; however, a consensus on the specific relationship between dietary zinc intake and cognitive function remains elusive. The aim of this systematic review was to examine the relationship between zinc intake, status and indices of cognitive function in children and adults. A systematic literature search was conducted using EMBASE, MEDLINE and Cochrane Library databases from inception to March 2014. Included studies were those that supplied zinc as supplements or measured dietary zinc intake. A meta-analysis of the extracted data was performed where sufficient data were available. Of all of the potentially relevant papers, 18 studies met the inclusion criteria, 12 of which were randomised controlled trials (RCTs; 11 in children and 1 in adults) and 6 were observational studies (2 in children and 4 in adults). Nine of the 18 studies reported a positive association between zinc intake or status with one or more measure of cognitive function. Meta-analysis of data from the adult’s studies was not possible because of limited number of studies. A meta-analysis of data from the six RCTs conducted in children revealed that there was no significant overall effect of zinc intake on any indices of cognitive function: intelligence, standard mean difference of <0.001 (95% confidence interval (CI) –0.12, 0.13) P=0.95; executive function, standard mean difference of 0.08 (95% CI, –0.06, 022) P=0.26; and motor skills standard mean difference of 0.11 (95% CI –0.17, 0.39) P=0.43. Heterogeneity in the study designs was a major limitation, hence only a small number (n=6) of studies could be included in the meta-analyses. Meta-analysis failed to show a significant effect of zinc supplementation on cognitive functioning in children though, taken as a whole, there were some small indicators of improvement on aspects of executive function and motor development following supplementation but high-quality RCTs are necessary to investigate this further