780 research outputs found
Hoeffding Tree Algorithms for Anomaly Detection in Streaming Datasets: A Survey
This survey aims to deliver an extensive and well-constructed overview of using machine learning for the problem of detecting anomalies in streaming datasets. The objective is to provide the effectiveness of using Hoeffding Trees as a machine learning algorithm solution for the problem of detecting anomalies in streaming cyber datasets. In this survey we categorize the existing research works of Hoeffding Trees which can be feasible for this type of study into the following: surveying distributed Hoeffding Trees, surveying ensembles of Hoeffding Trees and surveying existing techniques using Hoeffding Trees for anomaly detection. These categories are referred to as compositions within this paper and were selected based on their relation to streaming data and the flexibility of their techniques for use within different domains of streaming data. We discuss the relevance of how combining the techniques of the proposed research works within these compositions can be used to address the anomaly detection problem in streaming cyber datasets. The goal is to show how a combination of techniques from different compositions can solve a prominent problem, anomaly detection
Inhomogeneous d-wave superconducting state of a doped Mott insulator
Recent scanning tunneling microscope (STM) measurements discovered remarkable
electronic inhomogeneity, i.e. nano-scale spatial variations of the local
density of states (LDOS) and the superconducting energy gap, in the high-Tc
superconductor BSCCO. Based on the experimental findings we conjectured that
the inhomogeneity arises from variations in local oxygen doping level and may
be generic of doped Mott insulators which behave rather unconventionally in
screening the dopant ionic potentials at atomic scales comparable to the short
coherence length. Here, we provide theoretical support for this picture. We
study a doped Mott insulator within a generalized t-J model, where doping is
accompanied by ionic Coulomb potentials centered in the BiO plane. We calculate
the LDOS spectrum, the integrated LDOS, and the local superconducting gap, make
detailed comparisons to experiments, and find remarkable agreement with the
experimental data. We emphasize the unconventional screening in a doped Mott
insulator and show that nonlinear screening dominates at nano-meter scales
which is the origin of the electronic inhomogeneity. It leads to strong
inhomogeneous redistribution of the local hole density and promotes the notion
of a local doping concentration. We find that the inhomogeneity structure
manifests itself at all energy scales in the STM tunneling differential
conductance, and elucidate the similarity and the differences between the data
obtained in the constant tunneling current mode and the same data normalized to
reflect constant tip-to-sample distance. We also discuss the underdoped case
where nonlinear screening of the ionic potential turns the spatial electronic
structure into a percolative mixture of patches with smaller pairing gaps
embedded in a background with larger gaps to single particle excitations.Comment: 19 pages, final versio
Autophagy contributes to BMP type 2 receptor degradation and development of pulmonary arterial hypertension
Pulmonary arterial hypertension (PAH) is characterised by an increase in mean pulmonary arterial pressure which almost invariably leads to right heart failure and premature death. More than 70% of familial PAH and 20% of idiopathic PAH patients carry heterozygous mutations in the bone morphogenetic protein (BMP) type 2 receptor (BMPR2). However, the incomplete penetrance of BMPR2 mutations suggests that other genetic and environmental factors contribute to the disease. In the current study, we investigate the contribution of autophagy in the degradation of BMPR2 in pulmonary vascular cells. We demonstrate that endogenous BMPR2 is degraded through the lysosome in primary human pulmonary artery endothelial (PAECs) and smooth muscle cells (PASMCs): two cell types that play a key role in the pathology of the disease. By means of an elegant HaloTag system, we show that a block in lysosomal degradation leads to increased levels of BMPR2 at the plasma membrane. In addition, pharmacological or genetic manipulations of autophagy allow us to conclude that autophagy activation contributes to BMPR2 degradation. It has to be further investigated whether the role of autophagy in the degradation of BMPR2 is direct or through the modulation of the endocytic pathway. Interestingly, using an iPSC‐derived endothelial cell model, our findings indicate that BMPR2 heterozygosity alone is sufficient to cause an increased autophagic flux. Besides BMPR2 heterozygosity, pro‐inflammatory cytokines also contribute to an augmented autophagy in lung vascular cells. Furthermore, we demonstrate an increase in microtubule‐associated protein 1 light chain 3 beta (MAP1LC3B) levels in lung sections from PAH induced in rats. Accordingly, pulmonary microvascular endothelial cells (MVECs) from end‐stage idiopathic PAH patients present an elevated autophagic flux. Our findings support a model in which an increased autophagic flux in PAH patients contributes to a greater decrease in BMPR2 levels. Altogether, this study sheds light on the basic mechanisms of BMPR2 degradation and highlights a crucial role for autophagy in PAH. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland
Intermanifold similarities in partial photoionization cross sections of helium
Using the eigenchannel R-matrix method we calculate partial photoionization
cross sections from the ground state of the helium atom for incident photon
energies up to the N=9 manifold. The wide energy range covered by our
calculations permits a thorough investigation of general patterns in the cross
sections which were first discussed by Menzel and co-workers [Phys. Rev. A {\bf
54}, 2080 (1996)]. The existence of these patterns can easily be understood in
terms of propensity rules for autoionization. As the photon energy is increased
the regular patterns are locally interrupted by perturber states until they
fade out indicating the progressive break-down of the propensity rules and the
underlying approximate quantum numbers. We demonstrate that the destructive
influence of isolated perturbers can be compensated with an energy-dependent
quantum defect.Comment: 10 pages, 10 figures, replacement with some typos correcte
Humanized mice in studying efficacy and mechanisms of PD-1-targeted cancer immunotherapy.
Establishment of an in vivo small animal model of human tumor and human immune system interaction would enable preclinical investigations into the mechanisms underlying cancer immunotherapy. To this end, nonobese diabetic (NOD).Cg- PrkdcscidIL2rgtm1Wjl/Sz (null; NSG) mice were transplanted with human (h)CD34+ hematopoietic progenitor and stem cells, which leads to the development of human hematopoietic and immune systems [humanized NSG (HuNSG)]. HuNSG mice received human leukocyte antigen partially matched tumor implants from patient-derived xenografts [PDX; non-small cell lung cancer (NSCLC), sarcoma, bladder cancer, and triple-negative breast cancer (TNBC)] or from a TNBC cell line-derived xenograft (CDX). Tumor growth curves were similar in HuNSG compared with nonhuman immune-engrafted NSG mice. Treatment with pembrolizumab, which targets programmed cell death protein 1, produced significant growth inhibition in both CDX and PDX tumors in HuNSG but not in NSG mice. Finally, inhibition of tumor growth was dependent on hCD8+ T cells, as demonstrated by antibody-mediated depletion. Thus, tumor-bearing HuNSG mice may represent an important, new model for preclinical immunotherapy research.
FASEB J 2018 Mar; 32(3):1537-1549
The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III
The Sloan Digital Sky Survey (SDSS) started a new phase in August 2008, with
new instrumentation and new surveys focused on Galactic structure and chemical
evolution, measurements of the baryon oscillation feature in the clustering of
galaxies and the quasar Ly alpha forest, and a radial velocity search for
planets around ~8000 stars. This paper describes the first data release of
SDSS-III (and the eighth counting from the beginning of the SDSS). The release
includes five-band imaging of roughly 5200 deg^2 in the Southern Galactic Cap,
bringing the total footprint of the SDSS imaging to 14,555 deg^2, or over a
third of the Celestial Sphere. All the imaging data have been reprocessed with
an improved sky-subtraction algorithm and a final, self-consistent photometric
recalibration and flat-field determination. This release also includes all data
from the second phase of the Sloan Extension for Galactic Understanding and
Evolution (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars
at both high and low Galactic latitudes. All the more than half a million
stellar spectra obtained with the SDSS spectrograph have been reprocessed
through an improved stellar parameters pipeline, which has better determination
of metallicity for high metallicity stars.Comment: Astrophysical Journal Supplements, in press (minor updates from
submitted version
The Seventh Data Release of the Sloan Digital Sky Survey
This paper describes the Seventh Data Release of the Sloan Digital Sky Survey
(SDSS), marking the completion of the original goals of the SDSS and the end of
the phase known as SDSS-II. It includes 11663 deg^2 of imaging data, with most
of the roughly 2000 deg^2 increment over the previous data release lying in
regions of low Galactic latitude. The catalog contains five-band photometry for
357 million distinct objects. The survey also includes repeat photometry over
250 deg^2 along the Celestial Equator in the Southern Galactic Cap. A
coaddition of these data goes roughly two magnitudes fainter than the main
survey. The spectroscopy is now complete over a contiguous area of 7500 deg^2
in the Northern Galactic Cap, closing the gap that was present in previous data
releases. There are over 1.6 million spectra in total, including 930,000
galaxies, 120,000 quasars, and 460,000 stars. The data release includes
improved stellar photometry at low Galactic latitude. The astrometry has all
been recalibrated with the second version of the USNO CCD Astrograph Catalog
(UCAC-2), reducing the rms statistical errors at the bright end to 45
milli-arcseconds per coordinate. A systematic error in bright galaxy photometr
is less severe than previously reported for the majority of galaxies. Finally,
we describe a series of improvements to the spectroscopic reductions, including
better flat-fielding and improved wavelength calibration at the blue end,
better processing of objects with extremely strong narrow emission lines, and
an improved determination of stellar metallicities. (Abridged)Comment: 20 pages, 10 embedded figures. Accepted to ApJS after minor
correction
Quantum state preparation and macroscopic entanglement in gravitational-wave detectors
Long-baseline laser-interferometer gravitational-wave detectors are operating
at a factor of 10 (in amplitude) above the standard quantum limit (SQL) within
a broad frequency band. Such a low classical noise budget has already allowed
the creation of a controlled 2.7 kg macroscopic oscillator with an effective
eigenfrequency of 150 Hz and an occupation number of 200. This result, along
with the prospect for further improvements, heralds the new possibility of
experimentally probing macroscopic quantum mechanics (MQM) - quantum mechanical
behavior of objects in the realm of everyday experience - using
gravitational-wave detectors. In this paper, we provide the mathematical
foundation for the first step of a MQM experiment: the preparation of a
macroscopic test mass into a nearly minimum-Heisenberg-limited Gaussian quantum
state, which is possible if the interferometer's classical noise beats the SQL
in a broad frequency band. Our formalism, based on Wiener filtering, allows a
straightforward conversion from the classical noise budget of a laser
interferometer, in terms of noise spectra, into the strategy for quantum state
preparation, and the quality of the prepared state. Using this formalism, we
consider how Gaussian entanglement can be built among two macroscopic test
masses, and the performance of the planned Advanced LIGO interferometers in
quantum-state preparation
Searching for a Stochastic Background of Gravitational Waves with LIGO
The Laser Interferometer Gravitational-wave Observatory (LIGO) has performed
the fourth science run, S4, with significantly improved interferometer
sensitivities with respect to previous runs. Using data acquired during this
science run, we place a limit on the amplitude of a stochastic background of
gravitational waves. For a frequency independent spectrum, the new limit is
. This is currently the most sensitive
result in the frequency range 51-150 Hz, with a factor of 13 improvement over
the previous LIGO result. We discuss complementarity of the new result with
other constraints on a stochastic background of gravitational waves, and we
investigate implications of the new result for different models of this
background.Comment: 37 pages, 16 figure
Proteomics identifies neddylation as a potential therapy target in small intestinal neuroendocrine tumors.
Patients with small intestinal neuroendocrine tumors (SI-NETs) frequently develop spread disease; however, the underlying molecular mechanisms of disease progression are not known and effective preventive treatment strategies are lacking. Here, protein expression profiling was performed by HiRIEF-LC-MS in 14 primary SI-NETs from patients with and without liver metastases detected at the time of surgery and initial treatment. Among differentially expressed proteins, overexpression of the ubiquitin-like protein NEDD8 was identified in samples from patients with liver metastasis. Further, NEDD8 correlation analysis indicated co-expression with RBX1, a key component in cullin-RING ubiquitin ligases (CRLs). In vitro inhibition of neddylation with the therapeutic agent pevonedistat (MLN4924) resulted in a dramatic decrease of proliferation in SI-NET cell lines. Subsequent mass spectrometry-based proteomics analysis of pevonedistat effects and effects of the proteasome inhibitor bortezomib revealed stabilization of multiple targets of CRLs including p27, an established tumor suppressor in SI-NET. Silencing of NEDD8 and RBX1 using siRNA resulted in a stabilization of p27, suggesting that the cellular levels of NEDD8 and RBX1 affect CRL activity. Inhibition of CRL activity, by either NEDD8/RBX1 silencing or pevonedistat treatment of cells resulted in induction of apoptosis that could be partially rescued by siRNA-based silencing of p27. Differential expression of both p27 and NEDD8 was confirmed in a second cohort of SI-NET using immunohistochemistry. Collectively, these findings suggest a role for CRLs and the ubiquitin proteasome system in suppression of p27 in SI-NET, and inhibition of neddylation as a putative therapeutic strategy in SI-NET
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