Glioblastoma Extracellular Vesicle-Specific Peptides Inhibit EV-Induced Neuronal Cytotoxicity

WHO Grade 4 IDH-wild type astrocytoma (GBM) is the deadliest brain tumor with a poor prognosis. Meningioma (MMA) is a more common “benign” central nervous system tumor but with significant recurrence rates. There is an urgent need for brain tumor biomarkers for early diagnosis and effective treatment options. Extracellular vesicles (EVs) are tiny membrane-enclosed vesicles that play essential functions in cell-to-cell communications among tumor cells. We aimed to identify epitopes of brain tumor EVs by phage peptide libraries. EVs from GBM plasma, MMA plasma, or brain tumor cell lines were used to screen phage-displayed random peptide libraries to identify high-affinity peptides. We purified EVs from three GBM plasma pools (23 patients), one MMA pool (10 patients), and four brain tumor cell lines. We identified a total of 21 high-affinity phage peptides (12 unique) specific to brain tumor EVs. The peptides shared high sequence homologies among those selected by the same EVs. Dose–response ELISA demonstrated that phage peptides were specific to brain tumor EVs compared to controls. Peptide affinity purification identified unique brain tumor EV subpopulations. Significantly, GBM EV peptides inhibit brain tumor EV-induced complement-dependent cytotoxicity (necrosis) in neurons. We conclude that phage display technology could identify specific peptides to isolate and characterize tumor EVs.     

Stability of a hierarchical clustering

Clustering algorithms have the annoying habit of finding clusters even when the data are generated randomly. Verifying that potential clusterings are real in some objective sense is receiving more attention as the number of new clustering algorithms and their applications grow. We consider one aspect of this question and study the stability of a hierarchical structure with a variation on a measure of stability proposed in the literature.^(1,2)Our measure of stability is appropriate for proximity matrices whose entries are on an ordinal scale. We randomly split the data set, cluster the two halves, and compare the two hierarchical clusterings with the clustering achieved on the entire data set. Two stability statistics, based on the Goodman-Kruskal rank correlation coefficient, are defined. The distributions of these statistics are estimated with Monte Carlo techniques for two clustering methods (single-link and complete-link) and under two conditions (randomly selected proximity matrices and proximity matrices with good hierarchical structure). The stability measures are applied to some real data sets.     

Iron Mobilization from Ferritin in Yeast Cell Lysate and Physiological Implications

Most in vitro iron mobilization studies from ferritin have been performed in aqueous buffered solutions using a variety of reducing substances. The kinetics of iron mobilization from ferritin in a medium that resembles the complex milieu of cells could dramatically differ from those in aqueous solutions, and to our knowledge, no such studies have been performed. Here, we have studied the kinetics of iron release from ferritin in fresh yeast cell lysates and examined the effect of cellular metabolites on this process. Our results show that iron release from ferritin in buffer is extremely slow compared to cell lysate under identical experimental conditions, suggesting that certain cellular metabolites present in yeast cell lysate facilitate the reductive release of ferric iron from the ferritin core. Using filtration membranes with different molecular weight cut-offs (3, 10, 30, 50, and 100 kDa), we demonstrate that a cellular component >50 kDa is implicated in the reductive release of iron. When the cell lysate was washed three times with buffer, or when NADPH was omitted from the solution, a dramatic decrease in iron mobilization rates was observed. The addition of physiological concentrations of free flavins, such as FMN, FAD, and riboflavin showed about a two-fold increase in the amount of released iron. Notably, all iron release kinetics occurred while the solution oxygen level was still high. Altogether, our results indicate that in addition to ferritin proteolysis, there exists an auxiliary iron reductive mechanism that involves long-range electron transfer reactions facilitated by the ferritin shell. The physiological implications of such iron reductive mechanisms are discussed.     

Investigation of HgCdTe p-n device structures grown by liquid-phase epitaxy

The microstructure of p-n device structures grown by liquid-phase epitaxy (LPE) on CdZnTe substrates has been evaluated using transmission electron microscopy (TEM). The devices consisted of thick (∼21-μm) n-type layers and thin (∼1.6-μm) p-type layers, with final CdTe (∼0.5 μm) passivation layers. Initial observations revealed small defects, both within the n-type layer (doped with 8×10¹⁴/cm³ of In) and also within the p-type layer but at a much reduced level. These defects were not visible, however, in cross-sectional samples prepared by ion milling with the sample held at liquid nitrogen temperature. Only isolated growth defects were observed in samples having low indium doping levels (2×10¹⁴/cm³). The CdTe passivation layers were generally columnar and polycrystalline, and interfaces with the p-type HgCdTe layers were uneven. No obvious structural changes were apparent in the region of the CdTe/HgCdTe interfaces as a result of annealing at 250°C.     

Optimising the design of a piston-ring pack using DoE methods

This paper shows how design of experiments can be used with a ring-pack simulation program to optimise the design of a piston-ring assembly. Ten factors are varied—six describing the ring profile, three ring tensions, and the lubricant viscosity. Statistical analysis shows that there are some significant interactions between some of the factors—an issue that should be considered when performing test-bed measurements on engines. It is shown that an improved design can be achieved that reduces ring losses by 57% whilst reducing upward oil flow by 39%. This could lead to a 7% improvement in fuel economy provided there are no deleterious effects in other parts of the engine.     

ODAM: An optimized distributed association rule mining algorithm

Association rule mining is an active data mining research area. However, most ARM algorithms cater to a centralized environment. In contrast to previous ARM algorithms, we have developed a distributed algorithm, called optimized distributed association mining, for geographically distributed data sets. ODAM generates support counts of candidate itemsets quicker than the other DARM algorithms and reduces the size of average transactions, data sets, and message exchanges.     

A 1-THz superconducting hot-electron-bolometer receiver for astronomical observations

In this paper, we describe a superconducting hot-electron-bolometer mixer receiver developed to operate in atmospheric windows between 800-1300 GHz. The receiver uses a waveguide mixer element made of 3-4-nm-thick NbN film deposited over crystalline quartz. This mixer yields double-sideband receiver noise temperatures of 1000 K at around 1.0 THz, and 1600 K at 1.26 THz, at an IF of 3.0 GHz. The receiver was successfully tested in the laboratory using a gas cell as a spectral line test source. It is now in use on the Smithsonian Astrophysical Observatory terahertz test telescope in northern Chile.     

Field survey of clinical mastitis in low somatic cell count herds

Nine commercial dairy herds, each with low herd milk somatic cell counts, were monitored for 1 yr to determine prevalence of intramammary infections and rates of clinical mastitis. Staphylococcus species was the bacterial group most frequently isolated from quarters at calving and at drying off. Environmental streptococci and coliform intramammary infections totaled less than 6% of quarters at both calving and at drying off. Staphylococcus aureus were isolated from less than 1% of quarters and Streptococcus agalactiae from 0% of quarters at both calving and drying off. A total of 646 clinical cases of mastitis were diagnosed in 548 quarters of 406 cows. Mean rate of clinical mastitis among herds was .457 clinical cases/305 cow-days. Rates of clinical mastitis ranged among herds from .273 to .748 clinical cases/305 cow-days. Coliforms and bacteriologically negative and environmental streptococci accounted for 82.3% of clinical cases. Rates of clinical mastitis and severity of clinical signs differed among herds, seasons of the year, parity groups, and stages of lactation. Rates of clinical mastitis were highest during summer, in first lactation cows, and during the first 7 d of lactation.