559 research outputs found
An environmental equalizer for underwater acoustic communications Tested at Hydralab III
It is known that small changes in source and receiver locations can cause significant changes in underwater acoustic channel impulse responses. At HYDRALAB III an underwater acoustic experiment was conducted to show that a source depth-shift causes a frequency-shift in the channel impulse response and that such behavior can be used to implement an environmental-based equalizer for underwater communications that compensates for the performance loss due to the source depth-shift
YAP and β-catenin co-operate to drive oncogenesis in basal breast cancer
Targeting cancer stem cells (CSCs) can serve as an effective approach toward limiting resistance to therapies and the development of metastases in many forms of cancer. While basal breast cancers encompass cells with CSC features, rational therapies remain poorly established. Here, we show that receptor tyrosine kinase Met signalling promotes the activity of the Hippo component YAP in basal breast cancer. Further analysis revealed enhanced YAP activity within the CSC population. Using both genetic and pharmaceutical approaches, we show that interfering with YAP activity delays basal cancer formation, prevents luminal to basal trans-differentiation and reduces CSC survival. Gene expression analysis of YAP knock-out mammary glands revealed a strong decrease in β-catenin target genes in basal breast cancer, suggesting that YAP is required for nuclear β-catenin activity. Mechanistically, we find that nuclear YAP interacts and overlaps with β-catenin and TEAD4 at common gene regulatory elements. Analysis of proteomic data from primary breast cancer patients identified a significant upregulation of the YAP activity signature in basal compared to other breast cancers, suggesting that YAP activity is limited to basal types. Our findings demonstrate that in basal breast cancers, β-catenin activity is dependent on YAP signalling and controls the CSC program. These findings suggest that targeting the YAP/TEAD4/β-catenin complex offers a potential therapeutic strategy for eradicating CSCs in basal (triple-negative) breast cancers
Unitary Differential Space-Time-Frequency Codes for MB-OFDM UWB Wireless Communications
Self-consistent Green's function approaches
We present the fundamental techniques and working equations of many-body
Green's function theory for calculating ground state properties and the
spectral strength. Green's function methods closely relate to other polynomial
scaling approaches discussed in chapters 8 and 10. However, here we aim
directly at a global view of the many-fermion structure. We derive the working
equations for calculating many-body propagators, using both the Algebraic
Diagrammatic Construction technique and the self-consistent formalism at finite
temperature. Their implementation is discussed, as well as the inclusion of
three-nucleon interactions. The self-consistency feature is essential to
guarantee thermodynamic consistency. The pairing and neutron matter models
introduced in previous chapters are solved and compared with the other methods
in this book.Comment: 58 pages, 14 figures, Submitted to Lect. Notes Phys., "An advanced
course in computational nuclear physics: Bridging the scales from quarks to
neutron stars", M. Hjorth-Jensen, M. P. Lombardo, U. van Kolck, Editor
Comparison of Zn_{1-x}Mn_xTe/ZnTe multiple-quantum wells and quantum dots by below-bandgap photomodulated reflectivity
Large-area high density patterns of quantum dots with a diameter of 200 nm
have been prepared from a series of four Zn_{0.93}Mn_{0.07}Te/ZnTe multiple
quantum well structures of different well width (4 nm, 6 nm, 8 nm and 10 nm) by
electron beam lithography followed by Ar+ ion beam etching. Below-bandgap
photomodulated reflectivity spectra of the quantum dot samples and the parent
heterostructures were then recorded at 10 K and the spectra were fitted to
extract the linewidths and the energy positions of the excitonic transitions in
each sample. The fitted results are compared to calculations of the transition
energies in which the different strain states in the samples are taken into
account. We show that the main effect of the nanofabrication process is a
change in the strain state of the quantum dot samples compared to the parent
heterostructures. The quantum dot pillars turn out to be freestanding, whereas
the heterostructures are in a good approximation strained to the ZnTe lattice
constant. The lateral size of the dots is such that extra confinement effects
are not expected or observed.Comment: 23 pages, LaTeX2e (amsmath, epsfig), 7 EPS figure
Prediction of huge X-ray Faraday rotation at the Gd N_4,5 threshold
X-ray absorption spectra in a wide energy range around the 4d-4f excitation
threshold of Gd were recorded by total electron yield from in-plane magnetized
Gd metal films. Matching the experimental spectra to tabulated absorption data
reveals unprecedented short light absorption lengths down to 3 nm. The
associated real parts of the refractive index for circularly polarized light
propagating parallel or antiparallel to the Gd magnetization, determined
through the Kramers-Kronig transformation, correspond to a magneto-optical
Faraday rotation of 0.7 degrees per atomic layer. This finding shall allow the
study of magnetic structure and magnetization dynamics of lanthanide elements
in nanosize systems and dilute alloys.Comment: 4 pages, 2 figures, final version resubmitted to Phys. Rev. B, Brief
Reports. Minor change
Review of biorthogonal coupled cluster representations for electronic excitation
Single reference coupled-cluster (CC) methods for electronic excitation are
based on a biorthogonal representation (bCC) of the (shifted) Hamiltonian in
terms of excited CC states, also referred to as correlated excited (CE) states,
and an associated set of states biorthogonal to the CE states, the latter being
essentially configuration interaction (CI) configurations. The bCC
representation generates a non-hermitian secular matrix, the eigenvalues
representing excitation energies, while the corresponding spectral intensities
are to be derived from both the left and right eigenvectors. Using the
perspective of the bCC representation, a systematic and comprehensive analysis
of the excited-state CC methods is given, extending and generalizing previous
such studies. Here, the essential topics are the truncation error
characteristics and the separability properties, the latter being crucial for
designing size-consistent approximation schemes. Based on the general order
relations for the bCC secular matrix and the (left and right) eigenvector
matrices, formulas for the perturbation-theoretical (PT) order of the
truncation errors (TEO) are derived for energies, transition moments, and
property matrix elements of arbitrary excitation classes and truncation levels.
In the analysis of the separability properties of the transition moments, the
decisive role of the so-called dual ground state is revealed. Due to the use of
CE states the bCC approach can be compared to so-called intermediate state
representation (ISR) methods based exclusively on suitably orthonormalized CE
states. As the present analysis shows, the bCC approach has decisive advantages
over the conventional CI treatment, but also distinctly weaker TEO and
separability properties in comparison with a full (and hermitian) ISR method
Deconstructing sarcomeric structure-function relations in titin-BioID knock-in mice
Proximity proteomics has greatly advanced the analysis of native protein complexes and subcellular structures in culture, but has not been amenable to study development and disease in vivo. Here, we have generated a knock-in mouse with the biotin ligase (BioID) inserted at titin's Z-disc region to identify protein networks that connect the sarcomere to signal transduction and metabolism. Our census of the sarcomeric proteome from neonatal to adult heart and quadriceps reveals how perinatal signaling, protein homeostasis and the shift to adult energy metabolism shape the properties of striated muscle cells. Mapping biotinylation sites to sarcomere structures refines our understanding of myofilament dynamics and supports the hypothesis that myosin filaments penetrate Z-discs to dampen contraction. Extending this proof of concept study to BioID fusion proteins generated with Crispr/CAS9 in animal models recapitulating human pathology will facilitate the future analysis of molecular machines and signaling hubs in physiological, pharmacological, and disease context
A CRISPR/Cas9-mediated screen identifies determinants of early plasma cell differentiation
INTRODUCTION: The differentiation of B cells into antibody-secreting plasma cells depends on cell division-coupled, epigenetic and other cellular processes that are incompletely understood. METHODS: We have developed a CRISPR/Cas9-based screen that models an early stage of T cell-dependent plasma cell differentiation and measures B cell survival or proliferation versus the formation of CD138+ plasmablasts. Here, we refined and extended this screen to more than 500 candidate genes that are highly expressed in plasma cells. RESULTS: Among known genes whose deletion preferentially or mostly affected plasmablast formation were the transcription factors Prdm1 (BLIMP1), Irf4 and Pou2af1 (OBF-1), and the Ern1 gene encoding IRE1a, while deletion of XBP1, the transcriptional master regulator that specifies the expansion of the secretory program in plasma cells, had no effect. Defective plasmablast formation caused by Ern1 deletion could not be rescued by the active, spliced form of XBP1 whose processing is dependent on and downstream of IRE1a, suggesting that in early plasma cell differentiation IRE1a acts independently of XBP1. Moreover, we newly identified several genes involved in NF-kB signaling (Nfkbia), vesicle trafficking (Arf4, Preb) and epigenetic regulators that form part of the NuRD complex (Hdac1, Mta2, Mbd2) to be required for plasmablast formation. Deletion of ARF4, a small GTPase required for COPI vesicle formation, impaired plasmablast formation and blocked antibody secretion. After Hdac1 deletion plasmablast differentiation was consistently reduced by about 50%, while deletion of the closely related Hdac2 gene had no effect. Hdac1 knock-out led to strongly perturbed protein expression of antagonistic transcription factors that govern plasma cell versus B cell identity (by decreasing IRF4 and BLIMP1 and increasing BACH2 and PAX5). DISCUSSION: Taken together, our results highlight specific and non-redundant roles for Ern1, Arf4 and Hdac1 in the early steps of plasma cell differentiation
- …