70 research outputs found

    A Comparison of the Use of Binary Decision Trees and Neural Networks in Top Quark Detection

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    The use of neural networks for signal vs.~background discrimination in high-energy physics experiment has been investigated and has compared favorably with the efficiency of traditional kinematic cuts. Recent work in top quark identification produced a neural network that, for a given top quark mass, yielded a higher signal to background ratio in Monte Carlo simulation than a corresponding set of conventional cuts. In this article we discuss another pattern-recognition algorithm, the binary decision tree. We have applied a binary decision tree to top quark identification at the Tevatron and found it to be comparable in performance to the neural network. Furthermore, reservations about the "black box" nature of neural network discriminators do not apply to binary decision trees; a binary decision tree may be reduced to a set of kinematic cuts subject to conventional error analysis.Comment: 14pp. Plain TeX + mtexsis.tex (latter available through 'get mtexsis.tex'.) Two postscript files avail. by emai

    Concerted Phenotypic Flexibility of Avian Erythrocyte Size and Number in Response to Dietary Anthocyanin Supplementation

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    Background: Endurance flight impose substantial oxidative costs on the avian oxygen delivery system. In particular, the accumulation of irreversible damage in red blood cells can reduce the capacity of blood to transport oxygen and limit aerobic performance. Many songbirds consume large amounts of anthocyanin-rich fruit, which is hypothesized to reduce oxidative costs, enhance post-flight regeneration, and enable greater aerobic capacity. While their antioxidant benefits appear most straightforward, the effects of anthocyanins on blood composition remain so far unknown. We fed thirty hand-raised European starlings (Sturnus vulgaris) two semisynthetic diets (with or without anthocyanin supplement) and manipulated the extent of flight activity in a wind tunnel (daily flying or non-flying for over two weeks) to test for their interactive effects on functionally important haematological variables. Results: Supplemented birds had on average 15% more and 4% smaller red blood cells compared to non-supplemented individuals and these diet effects were independent of flight manipulation. Haemoglobin content was 7% higher in non-supplemented flying birds compared to non-flying birds, while similar haemoglobin content was observed among supplemented birds that were flown or not. Neither diet nor flight activity influenced haematocrit. Conclusion: The concerted adjustments suggest that supplementation generally improved antioxidant protection in blood, which could prevent the excess removal of cells from the bloodstream and may have several implications on the oxygen delivery system, including improved gas exchange and blood flow. The flexible haematological response to dietary anthocyanins may also suggest that free-ranging species preferentially consume anthocyanin-rich fruits for their natural blood doping, oxygen delivery-enhancement effects

    The Energy Savings-Oxidative Cost Trade- Off for Migratory Birds During Endurance Flight

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    Elite human and animal athletes must acquire the fuels necessary for extreme feats, but also contend with the oxidative damage associated with peak metabolic performance. Here, we show that a migratory bird with fuel stores composed of more omega-6 polyunsaturated fats (PUFA) expended 11% less energy during long-duration (6 hr) flights with no change in oxidative costs; however, this short-term energy savings came at the long-term cost of higher oxidative damage in the omega-6 PUFA-fed birds. Given that fatty acids are primary fuels, key signaling molecules, the building blocks of cell membranes, and that oxidative damage has long-term consequences for health and ageing, the energy savings-oxidative cost trade-off demonstrated here may be fundamentally important for a wide diversity of organisms on earth

    BRCA1/MAD2L1 deficiency disrupts the spindle assembly checkpoint to confer vinorelbine resistance in mesothelioma

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    Mesothelioma is a universally lethal cancer lacking effective therapy. The spindle poison vinorelbine exhibits clinical activity in the relapsed setting, and in preclinical models requires BRCA1 to initiate apoptosis. However, the mechanisms underlying this regulation and the clinical implications have not been explored. Here, we show that BRCA1 silencing abrogated vinorelbine-induced cell-cycle arrest, recruitment of BUBR1 to kinetochores, and apoptosis. BRCA1 silencing led to codepletion of MAD2L1 at the mRNA and protein levels consistent with its status as a transcriptional target of BRCA1. Silencing of MAD2L1 phenocopied BRCA1 and was sufficient to confer resistance to vinorelbine. This was recapitulated in cell lines selected for resistance to vinorelbine, which acquired loss of both BRCA1 and MAD2L1 expression. Following ex vivo vinorelbine in 20 primary tumor explants, apoptotic response rate was 59% in BRCA1/MAD2L1-positive explants compared with 0% in BRCA1/MAD2L1-negative explants. In 48 patients, BRCA1 and/or MAD2L1 loss of expression was not prognostic; however, in a subset of patients treated with vinorelbine, survival was shorter for patients lacking BRCA1/MAD2L1 expression compared with double-positive patients (5.9 vs. 36.7 months, P = 0.03). Our data implicate BRCA1/MAD2L1 loss as a putative predictive marker of resistance to vinorelbine in mesothelioma and warrant prospective clinical evaluation.Pathogenesis and treatment of chronic pulmonary disease

    The Feeding Biomechanics and Dietary Ecology of Paranthropus boisei

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    The African Plio‐Pleistocene hominins known as australopiths evolved derived craniodental features frequently interpreted as adaptations for feeding on either hard, or compliant/tough foods. Among australopiths, Paranthropus boisei is the most robust form, exhibiting traits traditionally hypothesized to produce high bite forces efficiently and strengthen the face against feeding stresses. However, recent mechanical analyses imply that P. boisei may not have been an efficient producer of bite force and that robust morphology in primates is not necessarily strong. Here we use an engineering method, finite element analysis, to show that the facial skeleton of P. boisei is structurally strong, exhibits a strain pattern different from that in chimpanzees (Pan troglodytes) and Australopithecus africanus, and efficiently produces high bite force. It has been suggested that P. boisei consumed a diet of compliant/tough foods like grass blades and sedge pith. However, the blunt occlusal topography of this and other species suggests that australopiths are adapted to consume hard foods, perhaps including grass and sedge seeds. A consideration of evolutionary trends in morphology relating to feeding mechanics suggests that food processing behaviors in gracile australopiths evidently were disrupted by environmental change, perhaps contributing to the eventual evolution of Homo and Paranthropus This is the peer reviewed version of the following article: Smith, A. L., Benazzi, S. , Ledogar, J. A., Tamvada, K. , Pryor Smith, L. C., Weber, G. W., Spencer, M. A., Lucas, P. W., Michael, S. , Shekeban, A. , Al‐Fadhalah, K. , Almusallam, A. S., Dechow, P. C., Grosse, I. R., Ross, C. F., Madden, R. H., Richmond, B. G., Wright, B. W., Wang, Q. , Byron, C. , Slice, D. E., Wood, S. , Dzialo, C. , Berthaume, M. A., van, Casteren, A. and Strait, D. S. (2015), The Feeding Biomechanics and Dietary Ecology of Paranthropus boisei, which has been published in final form at https://doi.org/10.1002/ar.23073. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Version

    Clonal architecture in mesothelioma is prognostic and shapes the tumour microenvironment.

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    Malignant Pleural Mesothelioma (MPM) is typically diagnosed 20-50 years after exposure to asbestos and evolves along an unknown evolutionary trajectory. To elucidate this path, we conducted multi-regional exome sequencing of 90 tumour samples from 22 MPMs acquired at surgery. Here we show that exomic intratumour heterogeneity varies widely across the cohort. Phylogenetic tree topology ranges from linear to highly branched, reflecting a steep gradient of genomic instability. Using transfer learning, we detect repeated evolution, resolving 5 clusters that are prognostic, with temporally ordered clonal drivers. BAP1/-3p21 and FBXW7/-chr4 events are always early clonal. In contrast, NF2/-22q events, leading to Hippo pathway inactivation are predominantly late clonal, positively selected, and when subclonal, exhibit parallel evolution indicating an evolutionary constraint. Very late somatic alteration of NF2/22q occurred in one patient 12 years after surgery. Clonal architecture and evolutionary clusters dictate MPM inflammation and immune evasion. These results reveal potentially drugable evolutionary bottlenecking in MPM, and an impact of clonal architecture on shaping the immune landscape, with potential to dictate the clinical response to immune checkpoint inhibition

    Improving the performance of the liquid argon TPC with tetra-methyl-germanium NUCLEAR INSTRUMENTS &METHODS IN PHYSICS RESEARCH by doping

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    Abstract In order to recover the charge lost by electron-ion recombination, we doped pure liquid argon with a photosensitive hydrocarbon, tetra-methyl-germanium (TMG). in the 3 ton ICARUS TPC. A charge increase of 25% to 220% was observed for different electric fields and for energy densities ranging from I .6 to 32 MeV/cm. The 3 ton liquid argon TPC has been in operation since May 1991 with pure liquid argon (LAr). In these three years we measured the basic parameters of the detector responses, such as the spatial resolution, the electron diffusion coefficient, the correlation of collected charge with electric field and energy density, by cosmic rays and external gamma ray sources [I]. In addition we have been continuously monitoring the stability of the liquid argon purity, the effectiveness of the recirculation system. and the reliabiIity of the electronics read-out. So far no degradation of any part of this detector has been found. As is well known, an ionizing particle in liquid argon will produce electron-ion pairs and excitons along the track. Depending on the ionization density and electric field, some of the pairs recombine and emit vacuum ultraviolet (VUV) photons with energy distribution peaked at 128 nm (9.7 eV). On the other hand, photon emission from excitons exhibits energy distribution peaking at the same energy (9.7 eV). With our data by minimum ionizing muons (mip), stopping muons and stopping protons, we have measured the coliected charge as a function of energy density 11.6 to 32 MeV/cm) and electric field (100 to 500 V/cm) in pure liquid argon. We found that the electron escape probability depends heavily on these two parameters. The percentage of free electron yield can vary from 70% to 14% at different energy densities and electric fields. This nonlinear detector response may degrade the particle identification capability of the liquid argon TPC. A possible solution to improve the linearity of the detector response is to introduce photosensitive dopants able to convert part of the scintillation light, either from electronion recombination or by direct excitation, into additional free electron-ion pairs, thus enhancing the linearity as a function of the deposited energy density and electric field. We chose TMG as photosensitive dopant because of the following advantages
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