Engineering tyrosine-based electron flow pathways in proteins: The case of aplysia myoglobin

Tyrosine residues can act as redox cofactors that provide an electron transfer ("hole-hopping") route that enhances the rate of ferryl heme iron reduction by externally added reductants, for example, ascorbate. Aplysia fasciata myoglobin, having no naturally occurring tyrosines but 15 phenylalanines that can be selectively mutated to tyrosine residues, provides an ideal protein with which to study such through-protein electron transfer pathways and ways to manipulate them. Two surface exposed phenylalanines that are close to the heme have been mutated to tyrosines (F42Y, F98Y). In both of these, the rate of ferryl heme reduction increased by up to 3 orders of magnitude. This result cannot be explained in terms of distance or redox potential change between donor and acceptor but indicates that tyrosines, by virtue of their ability to form radicals, act as redox cofactors in a new pathway. The mechanism is discussed in terms of the Marcus theory and the specific protonation/deprotonation states of the oxoferryl iron and tyrosine. Tyrosine radicals have been observed and quantified by EPR spectroscopy in both mutants, consistent with the proposed mechanism. The location of each radical is unambiguous and allows us to validate theoretical methods that assign radical location on the basis of EPR hyperfine structure. Mutation to tyrosine decreases the lipid peroxidase activity of this myoglobin in the presence of low concentrations of reductant, and the possibility of decreasing the intrinsic toxicity of hemoglobin by introduction of these pathways is discussed. © 2012 American Chemical Society

Supersonic jet mixing enhancement by delta-tabs

The results of a continuing investigation of the effect of vortex generators, in the form of small tabs at the nozzle exit, on the evolution of a jet are reported. Primarily, tabs of triangular shape are considered, and the effect is studied up to an equivalent jet Mach number of 1.8. By changing the orientation of the tab with respect to the nozzle exit plane, streamwise vortex pairs of opposite sign were generated. This resulted in either an outward election of jet core fluid into the ambient or an inward indentation of the mixing layer into the core of the jet. A triangular shaped tab with its apex leaning downstream, referred to as a delta tab, was found to be the most effective in influencing the jet evolution. Two delta tabs, spaced 180 degrees apart, completely bifurcated the jet. Four delta tabs increased jet mixing substantially, more than by various other methods tried previously; the mass flux at fourteen jet diameters downstream from the nozzle increased by about 50 percent over that for the no tab case. The tabs were found to be effective in jets with laminar or turbulent boundary layers as well as in jets with low or high core turbulence intensities

Effect of tabs on the evolution of an axisymmetric jet

The effect of vortex generators, in the form of small tabs at the nozzle exit, on the evolution of an axisymmetric jet was investigated experimentally over a jet Mach number range of 0.34 to 1.81. The effects of one, two, and four tabs were studied in comparison with the corresponding case without a tab. Each tab introduced an indentation in the shear layer, apparently through the action of streamwise vortices which appeared to be of the trailing vortex type originating from the tips of the tab rather that of the necklace vortex type originating from the base of the tab. The resultant effect of two tabs, placed at diametrically opposite locations, was to essentially bifurcate the jet. The influence of the tabs was essentially the same at subsonic and supersonic conditions indicating that compressibility has little to do with the effect

Activity Recognition and Prediction in Real Homes

In this paper, we present work in progress on activity recognition and prediction in real homes using either binary sensor data or depth video data. We present our field trial and set-up for collecting and storing the data, our methods, and our current results. We compare the accuracy of predicting the next binary sensor event using probabilistic methods and Long Short-Term Memory (LSTM) networks, include the time information to improve prediction accuracy, as well as predict both the next sensor event and its mean time of occurrence using one LSTM model. We investigate transfer learning between apartments and show that it is possible to pre-train the model with data from other apartments and achieve good accuracy in a new apartment straight away. In addition, we present preliminary results from activity recognition using low-resolution depth video data from seven apartments, and classify four activities - no movement, standing up, sitting down, and TV interaction - by using a relatively simple processing method where we apply an Infinite Impulse Response (IIR) filter to extract movements from the frames prior to feeding them to a convolutional LSTM network for the classification.Comment: 12 pages, Symposium of the Norwegian AI Society NAIS 201

Reduced risk of clinical malaria in children infected with multiple clones of Plasmodium falciparum in a highly endemic area: a prospective community study

A prospective community study in a highly malaria endemic area of Papua New Guinea found that infection with multiple Plasmodium falciparum genotypes was an indicator of lowered risk of subsequent clinical attack. The results suggest that concurrent or very recent infections provide protection from superinfecting parasites. The finding of an association between reduced risk of clinical malaria and infection with parasites of merozoite surface protein 1 (MSP-1) type RO33 or MSP-2 type 3D7 further suggests that the concomitant immunity is, at least in part, a consequence of a response to these major merozoite surface protein

Changes in auditory perceptions and cortex resulting from hearing recovery after extended congenital unilateral hearing loss

Monaural hearing induces auditory system reorganization. Imbalanced input also degrades time-intensity cues for sound localization and signal segregation for listening in noise. While there have been studies of bilateral auditory deprivation and later hearing restoration (e.g. cochlear implants), less is known about unilateral auditory deprivation and subsequent hearing improvement. We investigated effects of long-term congenital unilateral hearing loss on localization, speech understanding, and cortical organization following hearing recovery. Hearing in the congenitally affected ear of a 41 year old female improved significantly after stapedotomy and reconstruction. Pre-operative hearing threshold levels showed unilateral, mixed, moderately-severe to profound hearing loss. The contralateral ear had hearing threshold levels within normal limits. Testing was completed prior to, and three and nine months after surgery. Measurements were of sound localization with intensity-roved stimuli and speech recognition in various noise conditions. We also evoked magnetic resonance signals with monaural stimulation to the unaffected ear. Activation magnitudes were determined in core, belt, and parabelt auditory cortex regions via an interrupted single event design. Hearing improvement following 40 years of congenital unilateral hearing loss resulted in substantially improved sound localization and speech recognition in noise. Auditory cortex also reorganized. Contralateral auditory cortex responses were increased after hearing recovery and the extent of activated cortex was bilateral, including a greater portion of the posterior superior temporal plane. Thus, prolonged predominant monaural stimulation did not prevent auditory system changes consequent to restored binaural hearing. Results support future research of unilateral auditory deprivation effects and plasticity, with consideration for length of deprivation, age at hearing correction, degree and type of hearing loss

Redox and Peroxidase Activities of the Hemoglobin Superfamily: Relevance to Health and Disease

Significance: Erythrocyte hemoglobin (Hb) and myocyte myoglobin, although primarily oxygen-carrying proteins, have the capacity to do redox chemistry. Such redox activity in the wider family of globins now appears to have important associations with the mechanisms of cell stress response. In turn, an understanding of such mechanisms in vivo may have a potential in the understanding of cancer therapy resistance and neurodegenerative disorders such as Alzheimer’s. Recent Advances: There has been an enhanced understanding of the redox chemistry of the globin superfamily in recent years, leading to advances in development of Hb-based blood substitutes and in hypotheses relating to specific disease mechanisms. Neuroglobin (Ngb) and cytoglobin (Cygb) have been linked to cell protection mechanisms against hypoxia and oxidative stress, with implications in the onset and progression of neurodegenerative diseases for Ngb and cancer for Cygb. Critical Issues: Despite advances in the understanding of redox chemistry of globins, the physiological roles of many of these proteins still remain ambiguous at best. Confusion over potential physiological roles may relate to multifunctional roles for globins, which may be modulated by surface-exposed cysteine pairs in some globins. Such roles may be critical in deciphering the relationships of these globins in human diseases. Future Directions: Further studies are required to connect the considerable knowledge on the mechanisms of globin redox chemistry in vitro with the physiological and pathological roles of globins in vivo. In doing so, new therapies for neurodegenerative disorders and cancer therapy resistance may be targeted

Perceptions About Women in Science and Engineering History

This study investigated college students\u27 perceptions about the contributions of women to the history of science, technology, engineering and mathematics (STEM) (N = 1,147). Students were asked to write down as many famous or historically important scientists, inventors or engineers they could think of. After one minute, they were instructed to write down as many famous or historically important women scientists, inventors or engineers they could think of. For the first question, 95% of the responses referred to male scientists, inventors or engineers. For the second question, respondents named on average less than one woman (M=.86), and those named were more often from non-STEM fields (e.g., Rosa Parks) than actual scientists, inventors or engineers. Additionally, while respondents named a total of 279 distinct men, they named only 35 distinct women. Students in STEM fields could name significantly more male scientists, inventors or engineers than non-STEM students, but could not name significantly more women. The implications of these results are discussed, along with suggestions for educators on how to integrate the contributions of women in STEM into the classroom