5,138 research outputs found
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Bio-inspired canopies for the reduction of roughness noise
This work takes inspiration from the structure of the down covering the flight feathers of larger species of owls, which contributes to their ability to fly almost silently at frequencies above 1.6 kHz. Microscope photographs of the down show that it consists of hairs that form a structure similar to that of a forest. The hairs initially rise almost perpendicular to the feather surface but then bend over in the flow direction to form a canopy with an open area ratio of about 70 percent. Experiments have been performed to examine the noise radiated by a large open area ratio canopy suspended above a surface. The canopy is found to dramatically reduce pressure fluctuations on the underlying surface. While the canopy can produce its own sound, particularly at high frequencies, the reduction in surface pressure fluctuations can reduce the noise scattered from an underlying rough surface at lower frequencies. A theoretical model is developed which characterizes the mechanism of surface pressure reduction as a result of the mixing layer instability of flow over forest canopies.Office of Naval Research (Grant IDs: N00014-13-1-0244, N00014-14-1-0242
XMMSL2 J144605.0+685735: a slow tidal disruption event
Aims. We investigate the evolution of X-ray selected tidal disruption events.
Methods. New events are found in near real-time data from XMM-Newton slews, and are monitored by multi-wavelength facilities.
Results. In August 2016, X-ray emission was detected from the galaxy XMMSL2 J144605.0+685735 (also known as 2MASX 14460522+6857311), that was 20 times higher than an upper limit from 25 years earlier. The X-ray flux was flat for ∼100 days and then fell by a factor of 100 over the following 500 days. The UV flux was stable for the first 400 days before fading by a magnitude, while the optical (U,B,V) bands were roughly constant for 850 days. Optically, the galaxy appears to be quiescent, at a distance of 127 ± 4 Mpc (z = 0.029 ± 0.001) with a spectrum consisting of a young stellar population of 1–5 Gyr in age, an older population, and a total stellar mass of ∼6 × 109 M⊙. The bolometric luminosity peaked at Lbol ∼ 1043 ergs s−1 with an X-ray spectrum that may be modelled by a power law of Γ ∼ 2.6 or Comptonisation of a low-temperature thermal component by thermal electrons. We consider a tidal disruption event to be the most likely cause of the flare. Radio emission was absent in this event down to < 10 μJy, which limits the total energy of a hypothetical off-axis jet to E <  5 × 1050 ergs. The independent behaviour of the optical, UV, and X-ray light curves challenges models where the UV emission is produced by reprocessing of thermal nuclear emission or by stream-stream collisions. We suggest that the observed UV emission may have been produced from a truncated accretion disc and the X-rays from Compton upscattering of these disc photons
Diffusion in a Random Velocity Field: Spectral Properties of a Non-Hermitian Fokker-Planck Operator
We study spectral properties of the Fokker-Planck operator that describes
particles diffusing in a quenched random velocity field. This random operator
is non-Hermitian and has eigenvalues occupying a finite area in the complex
plane. We calculate the eigenvalue density and averaged one-particle Green's
function, for weak disorder and dimension d>2. We relate our results to the
time-evolution of particle density, and compare them with numerical
simulations.Comment: 4 pages, 2 figure
Negative and positive selection of antigen-specific cytotoxic T lymphocytes affected by the α3 domain of MHC I molecules
THE α1 and α2 domains of major histocompatibility complex (MHC) class I molecules function in the binding and presentation of foreign peptides to the T-cell antigen receptor and control both negative and positive selection of the T-cell repertoire. Although the α3 domain of class I is not involved in peptide binding, it does interact with the T-cell accessory molecule, CDS. CDS is important in the selection of T cells as anti-CDS antibody injected into perinatal mice interfers with this process. We previously used a hybrid class I molecule with the α1/α2 domains from L^d and the α3 domain from Q7^b and showed that this molecule binds an L^d-restricted peptide but does not interact with CD8-dependent cytotoxic T lymphocytes. Expression of this molecule in transgenic mice fails to negatively select a subpopulation of anti-L^d cytotoxic T lymphocytes. In addition, positive selection of virus-specific L^d-restricted cytotoxic T lymphocytes does not occur. We conclude that besides the α1/α2 domains of class I, the α3 domain plays an important part in both positive and negative selection of antigen-specific cells
Is soft breaking of BRST symmetry consistent?
A definition of soft breaking of BRST symmetry in the field-antifield
formalism is proposed, valid for general gauge theories and arbitrary gauge
fixing. The Ward identities for the generating functionals of Green's functions
are derived, and their gauge dependence is investigated. We discuss the
Gribov-Zwanziger action for the one-parameter family of R_xi gauges. It is
argued that gauge theories with a soft breaking of BRST symmetry are
inconsistent.Comment: 1+16 pages; v2: example of section 5 changed to R_xi gauges; v3:
small corrections to section 5, one reference added, published versio
Primary liver cancer in the UK: Incidence, incidence-based mortality, and survival by subtype, sex, and nation
Background & Aims: The incidence of primary liver cancer (PLC) is increasing in Western Europe. To understand trends over time and the current burden in the UK, a detailed analysis of the epidemiology of PLC and its subtypes was conducted. Methods: Data on PLCs diagnosed during 1997-2017 were obtained from population-based, nationwide registries in the UK. European age-standardised incidence (ASR) and incidence-based mortality rates (ASMR) per 100,000 person-years were calculated overall and by sex and UK-nation. Annual percentage change in rates was estimated using Joinpoint regression. One-, 2-, and 5-year age-standardised net survival was estimated. Results: A total of 82,024 PLCs were diagnosed. Both hepatocellular carcinoma (HCC) incidence and mortality rates trebled (ASR 1.8-5.5 per 100,000, ASMR 1.3-4.0). The rate of increase appeared to plateau around 2014/2015. Scottish men consistently had the highest HCC incidence rates. PLC survival increased, driven by a substantial increase in the proportion that are HCC (as prognosis is better than other PLCs) and in HCC survival (change in 1-year survival 24-47%). Intrahepatic cholangiocarcinoma was the most common PLC in women and 1-year survival improved from 22.6% to 30.5%. Conclusions: PLC incidence has been increasing rapidly but, as most risk factors are modifiable, it is largely a preventable cancer. This rate of increase has slowed in recent years, possibly attributable to effective treatment for hepatitis C. As other risk factors such as obesity and diabetes remain prevalent in the UK, it is unlikely the considerable burden of this disease will abate. While improvements in survival have been made, over half of patients are not alive after 1 year, therefore further progress in prevention, early detection, and treatment innovation are needed. Lay summary: Many more people are getting liver cancer, particularly the subtype hepatocellular carcinoma, than 20 years ago. Men in Scotland are most likely to get liver cancer and to die from it. Survival after liver cancer diagnosis is getting longer but still less than half are alive after 1 year
Tunable magnetic exchange interactions in manganese-doped inverted core/shell ZnSe/CdSe nanocrystals
Magnetic doping of semiconductor nanostructures is actively pursued for
applications in magnetic memory and spin-based electronics. Central to these
efforts is a drive to control the interaction strength between carriers
(electrons and holes) and the embedded magnetic atoms. In this respect,
colloidal nanocrystal heterostructures provide great flexibility via
growth-controlled `engineering' of electron and hole wavefunctions within
individual nanocrystals. Here we demonstrate a widely tunable magnetic sp-d
exchange interaction between electron-hole excitations (excitons) and
paramagnetic manganese ions using `inverted' core-shell nanocrystals composed
of Mn-doped ZnSe cores overcoated with undoped shells of narrower-gap CdSe.
Magnetic circular dichroism studies reveal giant Zeeman spin splittings of the
band-edge exciton that, surprisingly, are tunable in both magnitude and sign.
Effective exciton g-factors are controllably tuned from -200 to +30 solely by
increasing the CdSe shell thickness, demonstrating that strong quantum
confinement and wavefunction engineering in heterostructured nanocrystal
materials can be utilized to manipulate carrier-Mn wavefunction overlap and the
sp-d exchange parameters themselves.Comment: To appear in Nature Materials; 18 pages, 4 figures + Supp. Inf
Establishing the precise evolutionary history of a gene improves prediction of disease-causing missense mutations
PURPOSE: Predicting the phenotypic effects of mutations has become an important application in clinical genetic diagnostics. Computational tools evaluate the behavior of the variant over evolutionary time and assume that variations seen during the course of evolution are probably benign in humans. However, current tools do not take into account orthologous/paralogous relationships. Paralogs have dramatically different roles in Mendelian diseases. For example, whereas inactivating mutations in the NPC1 gene cause the neurodegenerative disorder Niemann-Pick C, inactivating mutations in its paralog NPC1L1 are not disease-causing and, moreover, are implicated in protection from coronary heart disease. METHODS: We identified major events in NPC1 evolution and revealed and compared orthologs and paralogs of the human NPC1 gene through phylogenetic and protein sequence analyses. We predicted whether an amino acid substitution affects protein function by reducing the organism’s fitness. RESULTS: Removing the paralogs and distant homologs improved the overall performance of categorizing disease-causing and benign amino acid substitutions. CONCLUSION: The results show that a thorough evolutionary analysis followed by identification of orthologs improves the accuracy in predicting disease-causing missense mutations. We anticipate that this approach will be used as a reference in the interpretation of variants in other genetic diseases as well. Genet Med 18 10, 1029–1036
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Bioinspired trailing-edge noise control
Strategies for trailing edge noise control have been inspired by the downy canopy that covers the surface of exposed flight feathers of many owl species. Previous wind tunnel measurements demonstrate that canopies of similar characteristics can reduce pressure fluctuations on the underlying surface by as much as 30dB, and significantly attenuate roughness noise generated by that surface. In the present work, surface treatments are designed to replicate the effects of the canopy in a form suitable for application to an airfoil. These treatments are installed directly upstream of the trailing edge to modify the boundary layer turbulence prior to acoustic scattering by the edge. Over 20 variants of these designs have been tested by performing aeroacoustic wind tunnel measurements on a tripped DU96-W180 airfoil at chord Reynolds numbers of up to 3 million. Compared to the unmodified airfoil, the treatments provided up to 10dB of broadband attenuation of trailing edge noise. The effectiveness of the treatment is not highly dependent on a particular geometry, but there appears to be strong potential for optimization. The surface treatments remain effective over an angle of attack range that extends over 9 degrees from zero lift. Aerodynamic impact of the treatment appears minimal.Office of Naval Research (Grant IDs: N00014-13-1-0244, N00014-14-1-0242, N62909-12-1-7116 (NICOP)), College of Engineering at Virginia Tech, AVEC Incorporate
Evidence for Two Modes of Synergistic Induction of Apoptosis by Mapatumumab and Oxaliplatin in Combination with Hyperthermia in Human Colon Cancer Cells
Colorectal cancer is the third leading cause of cancer-related mortality in the world-- the main cause of death from colorectal cancer is hepatic metastases, which can be treated with isolated hepatic perfusion (IHP). Searching for the most clinically relevant approaches for treating colorectal metastatic disease by isolated hepatic perfusion (IHP), we developed the application of oxaliplatin concomitantly with hyperthermia and humanized death receptor 4 (DR4) antibody mapatumumab (Mapa), and investigated the molecular mechanisms of this multimodality treatment in human colon cancer cell lines CX-1 and HCT116 as well as human colon cancer stem cells Tu-12, Tu-21 and Tu-22. We showed here, in this study, that the synergistic effect of the multimodality treatment-induced apoptosis was caspase dependent and activated death signaling via both the extrinsic apoptotic pathway and the intrinsic pathway. Death signaling was activated by c-Jun N-terminal kinase (JNK) signaling which led to Bcl-xL phosphorylation at serine 62, decreasing the anti-apoptotic activity of Bcl-xL, which contributed to the intrinsic pathway. The downregulation of cellular FLICE inhibitory protein long isoform (c-FLIPL) in the extrinsic pathway was accomplished through ubiquitination at lysine residue (K) 195 and protein synthesis inhibition. Overexpression of c-FLIPL mutant (K195R) and Bcl-xL mutant (S62A) completely abrogated the synergistic effect. The successful outcome of this study supports the application of multimodality strategy to patients with colorectal hepatic metastases who fail to respond to standard chemoradiotherapy that predominantly targets the mitochondrial apoptotic pathway. © 2013 Song et al
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