3,871 research outputs found

    Spiral Morphology-Dependent Resonances in an Optical Fiber: Effects of Fiber Tilt and Focused Gaussian Beam Illumination

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    Spiral morphology-dependent resonances have been observed in a tilted optical fiber. The polarization-preserving and the cross-polarized elastic-scattering spectra for plane-wave illumination show that the wavelengths of the resonances are blueshifted quadratically as the fiber tilt angle increases. When a focused Gaussian beam illuminates the fiber at its edge, the resonances are blueshifted and broadened as the detector is offset from the scattering plane with the maximum scattering intensity. The blueshift with focused beam illumination is also a consequence of the spiral resonances. (C) 1998 Optical Society of America

    Repetitive Eccentric Muscle Contractions Increase Torque Unsteadiness in the Human Triceps Brachii

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    Torque steadiness and low-frequency fatigue (LFF) were examined in the human triceps brachii after concentric or eccentric fatigue protocols. Healthy young males (n = 17) performed either concentric or eccentric elbow extensor contractions until the eccentric maximal voluntary torque decreased to 75% of pre-fatigue for both (concentric and eccentric) protocols. The number of concentric contractions was greater than the number of eccentric contractions needed to induce the same 25% decrease in eccentric MVC torque (52.2 ± 2.9 vs. 41.5 ± 2.1 for the concentric and eccentric protocols, respectively, p \u3c .01). The extent of peripheral fatigue was 12% greater after the concentric compared to the eccentric protocol (twitch amplitude), whereas LFF (increase in double pulse torque/single pulse torque), was similar across protocols. Steadiness, or the ability for a subject to hold a submaximal isometric contraction, was 20% more inpaired during the Ecc protocol (p = .052). Similarly, the EMG activity required to hold the torque steady was nearly 20% greater after the eccentric compared to concentric protocol. These findings support that task dependent eccentric contractions preferentially alter CNS control during a precision based steadiness task

    Microlensing Characterization of Wide-Separation Planets

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    With their excellent photometric precision and dramatic increase in monitoring frequency, future microlensing survey experiments are expected to be sensitive to very short time-scale, isolated events caused by free-floating and wide-separation planets with mass as low as a few lunar masses. We estimate the probability of measuring the Einstein radius \theta_E for bound and free-floating planets. We carry out detailed simulations of the planetary events expected in next-generation surveys and estimate the resulting uncertainty in \theta_E for these events. We show that, for main-sequence sources and Jupiter-mass planets, the caustic structure of wide-separation planets with projected separations of < 20 AU substantially increases the probability of measuring the dimensionless source size and thus determining \theta_E compared to the case of unbound planets. In this limit where the source is much smaller than the caustic, the effective cross-section to measure \theta_E to 10% is ~25% larger than the full width of the caustic. Measurement of the lens parallax is possible for low-mass planetary events by combined observations from the ground and a satellite located in an L2 orbit; this would complete the mass measurements for such wide-separation planets. Finally, short-duration events caused by bound planets can be routinely distinguished from those caused by free-floating planets for planet-star separations < 20 AU from either the deviations due to the planetary caustic or (more often) the low-amplitude bump from the magnification due to the parent star.Comment: 10 pages including 7 figures. ApJ, in pres

    Defining the clinical genomic landscape for real-world precision oncology

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    Through the delivery of large international projects including ICGC and TCGA, knowledge of cancer genomics is reaching saturation point. Enabling this to improve patient outcomes now requires embedding comprehensive genomic profiling into routine oncology practice. Towards this goal, this study defined the biologically and clinically relevant genomic features of adult cancer through detailed curation and analysis of large genomic datasets, accumulated literature and biomarker-driven therapeutics in clinic and development. The characteristics and prevalence of these features were then interrogated in 2348 whole genome sequences, covering 21 solid tumour types, generated by the PCAWG project. This analysis highlights the predominant contribution of copy number alterations and identifies a critical role for disruptive structural variants in the inactivation of clinically important tumour suppressor genes, including PTEN and RB1, which are not currently captured by diagnostic assays. This study defines a set of essential genomic features for the characterisation of common adult cancers

    Center-surround vs. distance-independent lateral connectivity in the olfactory bulb

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    Lateral neuronal interactions are known to play important roles in sensory information processing. A center-on surround-off local circuit arrangement has been shown to play a role in mediating contrast enhancement in the visual, auditory, and somatosensory systems. The lateral connectivity and the influence of those connections have been less clear for the olfactory system. A critical question is whether the synaptic connections between the primary projection neurons, mitral and tufted (M/T) cells, and their main inhibitory interneurons, the granule cells (GCs), can support a center-surround motif. Here, we study this question by injecting a “center” in the glomerular layer of the olfactory bulb (OB) with a marker of synaptic connectivity, the pseudorabies virus (PRV), then examines the distribution of labeling in the “surround” of GCs. We use a novel method to score the degree to which the data fits a center-surround model vs. distance-independent connectivity. Data from 22 injections show that M/T cells generally form lateral connections with GCs in patterns that lie between the two extremes

    Exploiting the neoantigen landscape for immunotherapy of pancreatic ductal adenocarcinoma

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    Immunotherapy approaches for pancreatic ductal adenocarcinoma (PDAC) have met with limited success. It has been postulated that a low mutation load may lead to a paucity of T cells within the tumor microenvironment (TME). However, it is also possible that while neoantigens are present, an effective immune response cannot be generated due to an immune suppressive TME. To discern whether targetable neoantigens exist in PDAC, we performed a comprehensive study using genomic profiles of 221 PDAC cases extracted from public databases. Our findings reveal that: (a) nearly all PDAC samples harbor potentially targetable neoantigens; (b) T cells are present but generally show a reduced activation signature; and (c) markers of efficient antigen presentation are associated with a reduced signature of markers characterizing cytotoxic T cells. These findings suggest that despite the presence of tumor specific neoepitopes, T cell activation is actively suppressed in PDAC. Further, we identify iNOS as a potential mediator of immune suppression that might be actionable using pharmacological avenues

    AS-TRUST: A Trust Characterization Scheme for Autonomous Systems in BGP

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    Border Gateway Protocol (BGP) works by frequently exchanging updates which, disseminate reachability information (RI) about IP prefixes (i.e., address blocks) between Autonomous Systems (ASes) on the Internet. The current operation of BGP implicitly trusts the ASes to disseminate valid—accurate, stable and routing policy compliant — RI. This assumption is problematic as demonstrated by the recent documented instances of invalid RI dissemination. This paper presents AS-TRUST, a scheme which comprehensively characterizes the trustworthiness of ASes, with respect to disseminating valid RI. AS-TRUST quantifies trust using the notion of reputation. To compute reputation, AS-TRUST evaluates the past RI received for validity, based on a set of well-defined properties. It then classifies the resulting observations into multiple types of feedback. The feedback is used by a reputation function to compute a probabilistic view of AS trustworthiness. The contributions of the paper are: (1) a comprehensive trust characterization of ASes; (2) a set of well-defined properties for evaluating the validity of RI provided by ASes; and (3) a novel and theoretically sound reputation computation mechanism. Our implementation of AS-TRUST scheme using publicly available BGP traces demonstrates: the number of ASes involved in violating the BGP operational trust assumption is significant, dissemination of invalid RI is consistently present, and the proposed reputation mechanism is sensitive enough to capture even rare instances of an AS’ deviation from trustworthy behavior

    Can non‐invasive brain stimulation modulate peak alpha frequency in the human brain? A systematic review and meta‐analysis

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    Peak alpha frequency (PAF), the dominant oscillatory frequency within the alpha range (8–12 Hz), is associated with cognitive function and several neurological conditions, including chronic pain. Manipulating PAF could offer valuable insight into the relationship between PAF and various functions and conditions, potentially providing new treatment avenues. This systematic review aimed to comprehensively synthesise effects of non‐invasive brain stimulation (NIBS) on PAF speed. Relevant studies assessing PAF pre‐ and post‐NIBS in healthy adults were identified through systematic searches of electronic databases (Embase, PubMed, PsychINFO, Scopus, The Cochrane Library) and trial registers. The Cochrane risk‐of‐bias tool was employed for assessing study quality. Quantitative analysis was conducted through pairwise meta‐analysis when possible; otherwise, qualitative synthesis was performed. The review protocol was registered with PROSPERO (CRD42020190512) and the Open Science Framework (https://osf.io/2yaxz/). Eleven NIBS studies were included, all with a low risk‐of‐bias, comprising seven transcranial alternating current stimulation (tACS), three repetitive transcranial magnetic stimulation (rTMS), and one transcranial direct current stimulation (tDCS) study. Meta‐analysis of active tACS conditions (eight conditions from five studies) revealed no significant effects on PAF (mean difference [MD] = −0.12, 95% CI = −0.32 to 0.08, p = 0.24). Qualitative synthesis provided no evidence that tDCS altered PAF and moderate evidence for transient increases in PAF with 10 Hz rTMS. However, it is crucial to note that small sample sizes were used, there was substantial variation in stimulation protocols, and most studies did not specifically target PAF alteration. Further studies are needed to determine NIBS's potential for modulating PAF

    Intercomparison of Satellite-Derived Snow-Cover Maps

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    In anticipation of the launch of the Earth Observing System (EOS) Terra, and the PM-1 spacecraft in 1999 and 2000, respectively, efforts are ongoing to determine errors of satellite-derived snow-cover maps. EOS Moderate Resolution Imaging Spectroradiometer (MODIS) and Advanced Microwave Scanning Radiometer-E (AMSR-E) snow-cover products will be produced. For this study we compare snow maps covering the same study area acquired from different sensors using different snow- mapping algorithms. Four locations are studied: 1) southern Saskatchewan; 2) a part of New England (New Hampshire, Vermont and Massachusetts) and eastern New York; 3) central Idaho and western Montana; and 4) parts of North and South Dakota. Snow maps were produced using a prototype MODIS snow-mapping algorithm used on Landsat Thematic Mapper (TM) scenes of each study area at 30-m and when the TM data were degraded to 1 -km resolution. National Operational Hydrologic Remote Sensing Center (NOHRSC) 1 -km resolution snow maps were also used, as were snow maps derived from 1/2 deg. x 1/2 deg. resolution Special Sensor Microwave Imager (SSM/1) data. A land-cover map derived from the International Geosphere-Biosphere Program (IGBP) land-cover map of North America was also registered to the scenes. The TM, NOHRSC and SSM/I snow maps, and land-cover maps were compared digitally. In most cases, TM-derived maps show less snow cover than the NOHRSC and SSM/I maps because areas of incomplete snow cover in forests (e.g., tree canopies, branches and trunks) are seen in the TM data, but not in the coarser-resolution maps. The snow maps generally agree with respect to the spatial variability of the snow cover. The 30-m resolution TM data provide the most accurate snow maps, and are thus used as the baseline for comparison with the other maps. Comparisons show that the percent change in amount of snow cover relative to the 3 0-m resolution TM maps is lowest using the TM I -km resolution maps, ranging from 0 to 40%. The highest percent change (less than 100%) is found in the New England study area, probably due to the presence of patchy snow cover. A scene with patchy snow cover is more difficult to map accurately than is a scene with a well-defined snowline such as is found on the North and South Dakota scene where the percent change ranged from 0 to 40%. There are also some important differences in the amount of snow mapped using the two different SSM/I algorithms because they utilize different channels
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