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.     

Mass Spectrometry-Based Disulfide Mapping of Lysyl Oxidase-like 2

Lysyl oxidase-like 2 (LOXL2) catalyzes the oxidative deamination of peptidyl lysines and hydroxylysines to promote extracellular matrix remodeling. Aberrant activity of LOXL2 has been associated with organ fibrosis and tumor metastasis. The lysine tyrosylquinone (LTQ) cofactor is derived from Lys653 and Tyr689 in the amine oxidase domain via post-translational modification. Based on the similarity in hydrodynamic radius and radius of gyration, we recently proposed that the overall structures of the mature LOXL2 (containing LTQ) and the precursor LOXL2 (no LTQ) are very similar. In this study, we conducted a mass spectrometry-based disulfide mapping analysis of recombinant LOXL2 in three forms: a full-length LOXL2 (fl-LOXL2) containing a nearly stoichiometric amount of LTQ, Δ1-2SRCR-LOXL2 (SRCR1 and SRCR2 are truncated) in the precursor form, and Δ1-3SRCR-LOXL2 (SRCR1, SRCR2, SRCR3 are truncated) in a mixture of the precursor and the mature forms. We detected a set of five disulfide bonds that is conserved in both the precursor and the mature recombinant LOXL2s. In addition, we detected a set of four alternative disulfide bonds in low abundance that is not associated with the mature LOXL2. These results suggest that the major set of five disulfide bonds is retained post-LTQ formation.     

Factors facilitating or impeding older adults’ creative contributions in the collaborative design of a novel DTV-based application

This article describes some of the challenges of supporting older adults’ creative input to the design of an (as yet) undefined digital television application. Focusing on commonly used brainstorming and paper prototyping techniques, constructive insights are gathered from users with limited experience of interactive technology. Encouraging older participants to move beyond what they are familiar with, the research reports on how fragmented conceptual knowledge of familiar technologies can either facilitate or impede the creative development of new ideas. This includes bias or contradictory ideas that can emerge in the elicitation process. As reported, other factors, such as the self-perception of inadequate drawing skills, demonstrate further barriers for some older adults to articulate their visions and aspirations for suitably designed technology.     

Thanks, but I'm used to better: A relative rank model of gratitude.

We argue that more help does not necessarily lead to more gratitude. Rather, gratitude depends on how a given instance of help compares with the help that a person is used to receiving. Participants read vignettes detailing an event in which 11 different friends either lent them varying amounts of money or spent varying amounts of time providing help. The amount of gratitude elicited by a given amount of help (e.g., a loan of ￡36 [about $56] or 49 min help) differed substantially depending on how this amount ranked among the help they were getting from their other friends. Comparison across four experimental conditions suggested that these judgments operated via the same general cognitive mechanisms used to judge other social events and psychophysical stimuli (as outlined by range frequency theory). Although more help does lead to more gratitude, people appear to be sensitive to how that help compares with what others are providing, and experienced gratitude depends on these relative judgments. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

The research productivity of academic psychologists: assessment,trends, and best practice recommendations

Research productivity affects the careers of academic psychologists. Unfortunately, there is a surprising lack of consensus on productivity’s meaning, measurement, and how to compare the productivity of one academic psychologist to another. In the present study, we review academic productivity research within psychology, and using a sample of 673 psychologists, compute six indexes of productivity. Most productivity metrics (publication count, citation count, or some combination of the two) were substantially interrelated and one (Integrated Research Productivity Index) was independent from years in the field. Female psychologists were equally as productive as male psychologists after accounting for years in the field, and pre-tenure psychologists showed steeper change-over-time productivity slopes than post-tenure psychologists. Based on these findings, we provide recommendations for the use and measurement of academic research productivity.     

Electrical impedance spectroscopy of the human prostate

Tissue electrical impedance is a function of its architecture and has been used to differentiate normal and cancer tissues in a variety of organs including breast, cervix, skin, and bladder. This paper investigates the possibility of differentiating normal and malignant prostate tissue using bioimpedance spectra. A probe was designed to measure impedance spectra over the range of 10 kHz to 1 MHz. The probe was fully characterized using discrete loads and saline solutions of different concentrations. Impedance spectra of five ex vivo prostates were measured in the operating room immediately following radical prostatectomy. Wilcoxon signed-rank tests were used to compare the normal and malignant findings. The impedance probe had a signal-to-noise ratio (SNR) > 84 dB across the entire spectrum and measured a tissue volume of approximately 46 mm(3). At 10 kHz, prostate conductivity (or) ranged from 0.232 S/m to 0.310 S/m for tumor and from 0.238 S/m to 0.901 S/m for normal tissue. At 1 MHz the ranges were 0.301 S/m to 0.488 S/m for tumor and 0.337 S/m to 1.149 S/m for normal. Prostate permittivity (epsilonr) ranged from 6.64 x10(4) to 1.25 x 10(5) for tumor and from 9.08 x 10(4) to 4.49 x 10(5) for normal tissues at 10 kHz. And, at 1 MHz the er ranges were 9.23 x 10(2) to 1.88 x 10(3) for tumor and 1.16 x 10(3) to 2.18 x 10(3) for normal tissue. Both sigma and epsilonr of tumor tissue were found to be significantly lower than that of normal tissue (P < 0.0001). Conductivity and permittivity are both higher in normal prostate tissues than they are in malignant tissue making them suitable parameters for tissue differentiation. This is in agreement with trends observed in other tissues reported in much of the literature. Expanded studies are needed to further validate this finding and to explore the biological mechanism responsible for generating the results.     

Statistical Tolerance Analysis for Assured Analog Test Coverage

Increasing numbers of analog components in today's systems necessitate system level test composition methods that utilize on-chip capabilities rather than solely relying on costly DFT approaches. We outline a tolerance analysis methodology for test signal propagation to be utilized in hierarchical test generation for analog circuits. A detailed justification of this proposed novel tolerance analysis methodology is undertaken by comparing our results with detailed SPICE Monte-Carlo simulation data on several combinations of analog modules. The results of our experiments confirm the high accuracy and efficiency of the proposed tolerance analysis methodology.     

Self‐Compensation in Transparent Conducting F‐Doped SnO2

The factors limiting the conductivity of fluorine‐doped tin dioxide (FTO) produced via atmospheric pressure chemical vapor deposition are investigated. Modeling of the transport properties indicates that the measured Hall effect mobilities are far below the theoretical ionized impurity scattering limit. Significant compensation of donors by acceptors is present with a compensation ratio of 0.5, indicating that for every two donors there is approximately one acceptor. Hybrid density functional theory calculations of defect and impurity formation energies indicate the most probable acceptor‐type defects. The fluorine interstitial defect has the lowest formation energy in the degenerate regime of FTO. Fluorine interstitials act as singly charged acceptors at the high Fermi levels corresponding to degenerately n‐type films. X‐ray photoemission spectroscopy of the fluorine impurities is consistent with the presence of substitutional F_O donors and interstitial F_i in a roughly 2:1 ratio in agreement with the compensation ratio indicated by the transport modeling. Quantitative analysis through Hall effect, X‐ray photoemission spectroscopy, and calibrated secondary ion mass spectrometry further supports the presence of compensating fluorine‐related defects.