42 research outputs found
Frequency domain diffuse optical tomography with a single source and detector via high- speed hypocycloid scanning
Diffuse Optical Imaging (DOI) relies on the fact that near infrared light (600-1000 nm) is strongly scattered in biological tissue, and weakly absorbed by tissue chromophores such as blood, fat, water, and melanin. In frequency domain DOI, intensity modulated light is introduced into the tissue and the observed absorption and phase changes enable absolute concentrations of these chromophores to be calculated. These concentrations provide valuable insight into tissue metabolic activity that have proven useful for a variety of clinical outcomes from exercise physiology to predicting tumor response to treatment.
Diffuse Optical Tomography (DOT) is an extension of DOI that allows three dimensional reconstruction of tissue chromophore concentrations. Typically, DOT requires a large number (~10-100) of light sources and detectors to collect the data necessary for 3D reconstruction. In these systems, each source and detector pair probes a specific volume of tissue and an algorithm is used to reconstruct tissue chromophore concentration within each voxel. However, the use of large numbers of fibers results in imaging systems that are large, expensive, unwieldy, and often anatomically specific (i.e. systems are constructed for breast measurements and cannot be easily used on other anatomical locations). In this poster I will present a new method for DOT that uses a single source and detector fiber in a potentially hand-held format that is able to probe a large volume of tissue using rapid scanning of each fiber in a hypocycloid pattern.
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Human serine racemase structure/activity relationship studies provide mechanistic insight and point to position 84 as a hot spot for \u3ci\u3eβ\u3c/i\u3e-elimination function
There is currently great interest in human serine racemase, the enzyme responsible for producing the NMDA co-agonist D-serine. Reported correlation of D-serine levels with disorders including Alzheimer’s disease, ALS, and ischemic brain damage (elevated D-serine) and schizophrenia (reduced D-serine) has further piqued this interest. Reported here is a structure/activity relationship study of position Ser84, the putative re-face base. In the most extreme case of functional reprogramming, the S84D mutant displays a dramatic reversal of β-elimination substrate specificity in favor of L-serine over the normally preferred L-serine-O-sulfate (~1200-fold change in kcat/Km ratios) and L (L-THA; ~5000-fold change in kcat/Km ratios) alternative substrates. On the other hand, the S84T (which performs L-Ser racemization activity), S84A (good kcat but high Km for L-THA elimination), and S84N mutants (nearly WT efficiency for L-Ser elimination) displayed intermediate activity, all showing a preference for the anionic substrates, but generally attenuated compared with the native enzyme. Inhibition studies with L-erythro-β-hydroxyaspartate follow this trend, with both WT serine racemase and the S84N mutant being competitively inhibited, with Ki = 31 ± 1.5 μM and 1.5 ± 0.1mM, respectively, and the S84D being inert to inhibition. Computational modeling pointed to a key role for residue Arg-135 in binding and properly positioning the L-THA and L-serine-O-sulfate substrates and the L-erythro-β-hydroxyaspartate inhibitor. Examination of available sequence data suggests that Arg-135 may have originated for L-THA-like-β-elimination function in earlier evolutionary variants, and examination of available structural data suggests that a Ser84-H2O-Lys114 hydrogen-bonding network in human serine racemase lowers the pKa of the Ser84 re-face base
Deep \u3cem\u3eChandra\u3c/em\u3e, \u3cem\u3eHST\u3c/em\u3e-Cos, and MegaCam Observations of the Phoenix Cluster: Extreme Star Formation and AGN Feedback on Hundred Kiloparsec Scales
We present new ultraviolet, optical, and X-ray data on the Phoenix galaxy cluster (SPT-CLJ2344-4243). Deep optical imaging reveals previously undetected filaments of star formation, extending to radii of ~50–100 kpc in multiple directions. Combined UV-optical spectroscopy of the central galaxy reveals a massive (2 x 109 M⊙), young (~4.5 Myr) population of stars, consistent with a time-averaged star formation rate of 610 ± 50 M⊙ yr−1. We report a strong detection of O ᴠɪ λλ1032,1038, which appears to originate primarily in shock-heated gas, but may contain a substantial contribution (\u3e1000 M⊙ yr−1) from the cooling intracluster medium (ICM). We confirm the presence of deep X-ray cavities in the inner ~10 kpc, which are among the most extreme examples of radio-mode feedback detected to date, implying jet powers of 2–7 x 1045 erg s−1. We provide evidence that the active galactic nucleus inflating these cavities may have only recently transitioned from quasar-mode to radio-mode, and may currently be insufficient to completely offset cooling. A model-subtracted residual X-ray image reveals evidence for prior episodes of strong radio-mode feedback at radii of ~100 kpc, with extended ghost cavities indicating a prior epoch of feedback roughly 100 Myr ago. This residual image also exhibits significant asymmetry in the inner ~200 kpc (0.15R500), reminiscent of infalling cool clouds, either due to minor mergers or fragmentation of the cooling ICM. Taken together, these data reveal a rapidly evolving cool core which is rich with structure (both spatially and in temperature), is subject to a variety of highly energetic processes, and yet is cooling rapidly and forming stars along thin, narrow filaments
Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.
BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500
Mechanisms of Hearing Loss after Blast Injury to the Ear
Given the frequent use of improvised explosive devices (IEDs) around the world, the study of traumatic blast injuries is of
increasing interest. The ear is the most common organ affected by blast injury because it is the bodyメs most sensitive
pressure transducer. We fabricated a blast chamber to re-create blast profiles similar to that of IEDs and used it to develop a
reproducible mouse model to study blast-induced hearing loss. The tympanic membrane was perforated in all mice after
blast exposure and found to heal spontaneously. Micro-computed tomography demonstrated no evidence for middle ear or
otic capsule injuries; however, the healed tympanic membrane was thickened. Auditory brainstem response and distortion
product otoacoustic emission threshold shifts were found to be correlated with blast intensity. As well, these threshold
shifts were larger than those found in control mice that underwent surgical perforation of their tympanic membranes,
indicating cochlear trauma. Histological studies one week and three months after the blast demonstrated no disruption or
damage to the intra-cochlear membranes. However, there was loss of outer hair cells (OHCs) within the basal turn of the
cochlea and decreased spiral ganglion neurons (SGNs) and afferent nerve synapses. Using our mouse model that
recapitulates human IED exposure, our results identify that the mechanisms underlying blast-induced hearing loss does not
include gross membranous rupture as is commonly believed. Instead, there is both OHC and SGN loss that produce auditory
dysfunction
Galaxy Clusters Discovered via the Sunyaev-Zel'dovich Effect in the 2500-square-degree SPT-SZ survey
We present a catalog of galaxy clusters selected via their Sunyaev-Zel'dovich (SZ) effect signature from 2500 deg2 of South Pole Telescope (SPT) data. This work represents the complete sample of clusters detected at high significance in the 2500 deg2 SPT-SZ survey, which was completed in 2011. A total of 677 (409) cluster candidates are identified above a signal-to-noise threshold of ξ = 4.5 (5.0). Ground- and space-based optical and near-infrared (NIR) imaging confirms overdensities of similarly colored galaxies in the direction of 516 (or 76%) of the ξ > 4.5 candidates and 387 (or 95%) of the ξ > 5 candidates; the measured purity is consistent with expectations from simulations. Of these confirmed clusters, 415 were first identified in SPT data, including 251 new discoveries reported in this work. We estimate photometric redshifts for all candidates with identified optical and/or NIR counterparts; we additionally report redshifts derived from spectroscopic observations for 141 of these systems. The mass threshold of the catalog is roughly independent of redshift above z ~ 0.25 leading to a sample of massive clusters that extends to high redshift. The median mass of the sample is M 500c(ρcrit) , the median redshift is z med = 0.55, and the highest-redshift systems are at z > 1.4. The combination of large redshift extent, clean selection, and high typical mass makes this cluster sample of particular interest for cosmological analyses and studies of cluster formation and evolution.Physic
Human serine racemase structure/activity relationship studies provide mechanistic insight and point to position 84 as a hot spot for \u3ci\u3eβ\u3c/i\u3e-elimination function
There is currently great interest in human serine racemase, the enzyme responsible for producing the NMDA co-agonist D-serine. Reported correlation of D-serine levels with disorders including Alzheimer’s disease, ALS, and ischemic brain damage (elevated D-serine) and schizophrenia (reduced D-serine) has further piqued this interest. Reported here is a structure/activity relationship study of position Ser84, the putative re-face base. In the most extreme case of functional reprogramming, the S84D mutant displays a dramatic reversal of β-elimination substrate specificity in favor of L-serine over the normally preferred L-serine-O-sulfate (~1200-fold change in kcat/Km ratios) and L (L-THA; ~5000-fold change in kcat/Km ratios) alternative substrates. On the other hand, the S84T (which performs L-Ser racemization activity), S84A (good kcat but high Km for L-THA elimination), and S84N mutants (nearly WT efficiency for L-Ser elimination) displayed intermediate activity, all showing a preference for the anionic substrates, but generally attenuated compared with the native enzyme. Inhibition studies with L-erythro-β-hydroxyaspartate follow this trend, with both WT serine racemase and the S84N mutant being competitively inhibited, with Ki = 31 ± 1.5 μM and 1.5 ± 0.1mM, respectively, and the S84D being inert to inhibition. Computational modeling pointed to a key role for residue Arg-135 in binding and properly positioning the L-THA and L-serine-O-sulfate substrates and the L-erythro-β-hydroxyaspartate inhibitor. Examination of available sequence data suggests that Arg-135 may have originated for L-THA-like-β-elimination function in earlier evolutionary variants, and examination of available structural data suggests that a Ser84-H2O-Lys114 hydrogen-bonding network in human serine racemase lowers the pKa of the Ser84 re-face base
Data from: Stomatopods detect and assess achromatic cues in contests
Conspicuous, colorful displays are often used by animals to communicate within and between species. Previously, researchers have manipulated specific components of color signals (i.e., hue, total reflectance, and/or chroma) using paints, photographs, videos, or filters. However, these manipulations may not adequately mimic the spectrum of color signals outside the range of human perception. Thus, these methods are inappropriate for organisms with unconventional visual systems, such as stomatopods (mantis shrimp). Here, we describe a novel application of a femtosecond laser to increase total reflectance of the stomatopod meral spot, a distinct area on the raptorial appendage used in territorial contests. Ultrafast lasers provide a programmable way to precisely manipulate patch total reflectance of live stomatopods without causing collateral damage. We tested how experimentally increasing meral spot reflectance impacted receiver behavior during territorial contests. Contests in which receiver stomatopods faced an opponent with a lightened meral spot were shorter and receivers showed increased rates of agonistic behaviors. This result suggests that lighter meral spots indicate lower fighting ability; thus, receivers are more willing to engage in a contest. This research provides the first demonstration that stomatopods can detect and assess achromatic variation in contests. Furthermore, we demonstrate that ultrafast lasers provide a powerful tool to investigate achromatic signaling, particularly for organisms whose size, aquatic habitat, or visual system otherwise prevent realistic alterations to color signals (e.g., butterflies, jumping spiders, or decapod crustaceans). This study advances our knowledge about stomatopod visual communication and offers a valuable tool for future research