Genomic mining for complex disease traits with “random chemistry”

Our rapidly growing knowledge regarding genetic variation in the human genome offers great potential for understanding the genetic etiology of disease. This, in turn, could revolutionize detection, treatment, and in some cases prevention of disease. While genes for most of the rare monogenic diseases have already been discovered, most common diseases are complex traits, resulting from multiple gene–gene and gene-environment interactions. Detecting epistatic genetic interactions that predispose for disease is an important, but computationally daunting, task currently facing bioinformaticists. Here, we propose a new evolutionary approach that attempts to hill-climb from large sets of candidate epistatic genetic features to smaller sets, inspired by Kauffman’s “random chemistry” approach to detecting small auto-catalytic sets of molecules from within large sets. Although the algorithm is conceptually straightforward, its success hinges upon the creation of a fitness function able to discriminate large sets that contain subsets of interacting genetic features from those that don’t. Here, we employ an approximate and noisy fitness function based on the ReliefF data mining algorithm. We establish proof-of-concept using synthetic data sets, where individual features have no marginal effects. We show that the resulting algorithm can successfully detect epistatic pairs from up to 1,000 candidate single nucleotide polymorphisms in time that is linear in the size of the initial set, although success rate degrades as heritability declines. Research continues into seeking a more accurate fitness approximator for large sets and other algorithmic improvements that will enable us to extend the approach to larger data sets and to lower heritabilities.     

The who and the what of usage of two cancer online communities

The explosion of use of Internet-based communication for health requires attention to the ways survivors of specific diseases and those close to them participate in using resources. This research focuses on two cancer groups – breast and prostate – and how they use WebMD asynchronous bulletin boards. Four hundred and eighty two messages were coded for communicator (survivors, spouses, others) and content of messages. Most common communicators were survivors, but the two groups differed in percentages of communicator. Of four main categories of content – medical/treatment, intimacy/sexuality, emotional expression, and support – most common were support and medical/treatment. The groups differed significantly on those four categories, with breast cancer more support-dominated and prostate more medical/treatment-dominated and more intimacy/sexuality messages. There were no group differences in emotional-toned vs. social support seeking vs. providing support, or positive vs. negative emotions expressed. Generally, there was considerable commonality, and the differences found primarily supported gender-specific notions of communication and need.     

Further explorations of perceptual speed abilities in the context of assessment methods, cognitive abilities, and individual differences during skill acquisition.

Measures of perceptual speed ability have been shown to be an important part of assessment batteries for predicting performance on tasks and jobs that require a high level of speed and accuracy. However, traditional measures of perceptual speed ability sometimes have limited cost-effectiveness because of the requirements for administration and scoring of paper-and-pencil tests. There have also been concerns about the validity of previous computer approaches to administering perceptual speed tests (e.g., see Mead & Drasgow, 1993). The authors developed two sets of computerized perceptual speed tests, with touch-sensitive monitors, that were designed to parallel several paper-and-pencil tests. The reliability and validity of the tests were explored across three empirical studies (N = 167, 160, and 117, respectively). The final study included two criterion tasks with 4.67 and 10 hours of time-on-task practice, respectively. Results indicated that these new measures provide both high levels of reliability and substantial validity for performance on the two skill-learning tasks. Implications for research and application for computerized perceptual speed tests are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Individual differences in entrainment of mood to the weekly calendar.

This study addressed two questions: Do daily fluctuations in mood exhibit a 7-day (circaseptum) cycle, and are there reliable individual differences in how entrained peoples' moods are to such a weekly cycle? Spectral analysis of daily mood over 84 occasions revealed a strong weekly rhythm in the temporal organization of mood in a sample of 74 undergraduates. A sine wave with a period of 7 days accounted for 40% of the variance in the daily mood data. Individual differences were also found in how entrained subjects' moods were to this weekly rhythm. We predicted that extraverts (compared with introverts) should be less entrained to a weekly cycle. Results suggest that the novelty- and sensation-seeking behavior of extraverts most likely serves to lessen the cyclical predictability of their day-to-day moods. The origin and psychological meaning of the 7-day week are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Quantification of 3-D field effects during 2-D microwave imaging

Two-dimensional (2-D) approaches to microwave imaging have dominated the research landscape primarily due to the moderate levels of measurement data, data-acquisition time, and computational costs required. Three-dimensional (3-D) approaches have been investigated in simulation, phantom, and animal experiments. While 3-D approaches are certainly important in terms of the potential to improve image quality, their associated costs are significant at this time. In addition, benchmarks are needed to evaluate these new generation systems as more 3-D methods begin to appear. In this paper, we present a systematic series of experiments which assess the capability of our 2-D system to image classical 3-D geometries. We demonstrate where current methods suffer from 3-D effects but also identify situations where they remain quite useful. Comparisons between reconstructions utilizing phantom measurements and simulated 3-D data are also shown to validate the results. These findings suggest that for certain biomedical applications, 2-D approaches remain quite attractive.     

Edge Computing Platform with Efficient Migration Scheme for 5G/6G Networks

Next-generation cellular networks are expected to provide users with innovative gigabits and terabits per second speeds and achieve ultra-high reliability, availability, and ultra-low latency. The requirements of such networks are the main challenges that can be handled using a range of recent technologies, including multi-access edge computing (MEC), artificial intelligence (AI), millimeter-wave communications (mmWave), and software-defined networking. Many aspects and design challenges associated with the MEC-based 5G/6G networks should be solved to ensure the required quality of service (QoS). This article considers developing a complex MEC structure for fifth and sixth-generation (5G/6G) cellular networks. Furthermore, we propose a seamless migration technique for complex edge computing structures. The developed migration scheme enables services to adapt to the required load on the radio channels. The proposed algorithm is analyzed for various use cases, and a test bench has been developed to emulate the operator’s infrastructure. The obtained results are introduced and discussed.     

A technique for measuring bronchial mucociliary clearance in unsedated dogs

An unsedated dog model of bronchial mucociliary clearance was developed using radioaerosol techniques. A neutralized, concentrated, monodisperse iron oxide aerosol (5–6 μm MMAD) radiotagged with technetium-99m was delivered to the dog via a face mask. Retained activity was measured while the dog was restrained in front of a gamma camera. Measurements were made for 2–3 h post-inhalation and again at 24 h. Three beagle dogs, each studied four times, demonstrated mean percents for 2 h particle retention within the whole lung of 76 ± 13, 92 ± 7 and 89 ± 4, within the bronchial airways of 48 ± 27, 84 ± 15 and 73 ± 10, and mean 24 h particle retentions of 47 ± 18, 65 ± 11 and 57 ± 9, respectively. The unsedated beagle dog provides a potential model for study of the effects of drugs, disease and inhaled pollutants on mucociliary transport.     

Chemical Synthesis of A Pore‐Forming Antimicrobial Protein,Caenopore‐5, by Using Native Chemical Ligation at a Glu‐Cys Site

The 2014 report from the World Health Organization (WHO) on antimicrobial resistance revealed an alarming rise in antibiotic resistance all around the world. Unlike classical antibiotics, with the exception of a few species, no acquired resistance towards antimicrobial peptides (AMPs) has been reported. Therefore, AMPs represent leads for the development of novel antibiotics. Caenopore‐5 is constitutively expressed in the intestine of the nematode Caenorhabditis elegans and is a pore‐forming AMP. The protein (82 amino acids) was successfully synthesised by using Boc solid‐phase peptide synthesis and native chemical ligation. No γ‐linked by‐product was observed despite the use of a C‐terminal Glu‐thioester. The folding of the synthetic protein was confirmed by ¹H NMR spectroscopy and circular dichroism and compared with data recorded for recombinant caenopore‐5. The permeabilisation activities of the protein and of shortened analogues were evaluated.     

Atom Probe Tomography of Zinc Oxide Nanowires

Wide-bandgap zinc oxide (ZnO) semiconductors and nanowires have become important materials for electronic and photonic device applications. In this work, we report the growth of well-aligned single-crystal ZnO nanowire arrays on sapphire substrates by chemical vapor deposition and the development of atom probe tomography, an emerging nanoscale characterization method capable of providing deeper insight into the three-dimensional distribution of atoms and impurities within its structure. Using a metal-catalyst-free approach, the influence of the growth parameters on the orientation and density of the nanowires were studied. The resulting ZnO nanowires were determined to be single crystalline, with diameter on the order of 50 nm to 150 nm and length that could be controlled between 0.5 μm to 20 μm. Their density was on the order of high 10⁸ cm⁻² to low 10⁹ cm⁻². In addition to routine characterizations using scanning and transmission electron microscopy, x-ray diffraction, photoluminescence, and Raman spectroscopy, we developed the atom probe tomography technique for ZnO nanowires, comparing the voltage pulse and laser pulse modes. In-depth analysis of the data was carried out to determine the accurate chemical composition of the nanowires and reveal the incorporation of nitrogen impurities. The current–voltage characteristics of individual nanowires were measured to determine their electrical properties.