Frequency shift keying in vortex-based spin torque oscillators

Vortex-based spin-torque oscillators can be made from extended spin valves connected to an electrical nanocontact. We study the implementation of frequency shift keying modulation in these oscillators. Upon a square modulation of the current in the 10 MHz range, the vortex frequency follows the current command, with easy identification of the two swapping frequencies in the spectral measurements. The frequency distribution of the output power can be accounted for by convolution transformations of the dc current vortex waveform, and the current modulation. Modeling indicates that the frequency transitions are phase coherent and last less than 25 ns. Complementing the multi-octave tunability and first-class agility, the capability of frequency shift keying modulation is an additional milestone for the implementation of vortex-based oscillators in RF circuit.Comment: 6 pages, 5 figure

Phase Coherent Precessional Magnetization Reversal in Micro-scopic Spin Valve Elements

We study the precessional switching of the magnetization in microscopic spin valve cells induced by ultra short in-plane hard axis magnetic field pulses. Stable and highly efficient switching is monitored following pulses as short as 140 ps with energies down to 15 pJ. Multiple application of identical pulses reversibly toggles the cell's magnetization be-tween the two easy directions. Variations of pulse duration and amplitude reveal alter-nating regimes of switching and non-switching corresponding to transitions from in-phase to out-of-phase excitations of the magnetic precession by the field pulse. In the low field limit damping becomes predominant and a relaxational reversal is found allowing switching by hard axis fields below the in-plane anisotropy field threshold.Comment: 17 pages, 4 figure

Structure and regulation of mammalian S-adenosylmethionine decarboxylase

In order to understand the structure and regulation of S-adenosylmethionine decarboxylase, cDNA clones encoding this enzyme have been isolated from rat prostate and human fibroblast cDNA libraries. The authenticity of the cDNAs was verified by: (a) transfecting the Chinese hamster ovary cells with the human cDNA in the pcD vector which resulted in a transient 10-20-fold increase in S-adenosylmethionine decarboxylase activity in recipient cells; and (b) translating the mRNA formed by transcription of the cDNA insert in a reticulocyte lysate and recording an increase in S-adenosylmethionine decarboxylase activity. The amino acid sequences deduced from the cDNAs indicate that the human proenzyme for this protein contains 334 amino acids and has a molecular weight of 38,331 whereas the rat proenzyme contains 333 amino acid residues. The human and rat enzymes are very similar having only 11 amino acid differences and the cDNAs are also closely related showing over 90% homology in the 1617-nucleotide overlap which was sequenced. A further indication of the highly conserved nature of mammalian S-adenosylmethionine decarboxylases is that the amino acid sequences deduced from the human and the rat cDNAs contained peptide sequences identical to those previously reported for the purified bovine enzyme. In vitro transcription/translation experiments showed that the proenzyme is converted to two polypeptides of molecular weights about 32,000 and 6,000 in a processing reaction which generates the prosthetic pyruvate group and that the final enzyme contains both polypeptides. Two forms of S-adenosylmethionine decarboxylase mRNA (2.1 and about 3.4-3.6 kilobases) are present in human and rodent tissues and may originate from the utilization of two different polyadenylation signals. Southern blots of rat genomic DNA indicated that the S-adenosylmethionine decarboxylase gene belongs to a multigene family. Depletion of cellular polyamines by inhibitors or ornithine decarboxylase or the aminopropyltransferases led to an increase in the content of S-adenosylmethionine decarboxylase protein and mRNA, but the elevation in the mRNA was not sufficient to account for all of the change in the enzyme level, particularly in cells in which spermine was depleted

Hypopigmentation and Maternal-Zygotic Embryonic Lethality Caused by a Hypomorphic Mbtps1 Mutation in Mice

The site 1 protease, encoded by Mbtps1, mediates the initial cleavage of site 2 protease substrates, including sterol regulatory element binding proteins and CREB/ATF transcription factors. We demonstrate that a hypomorphic mutation of Mbtps1 called woodrat (wrt) caused hypocholesterolemia, as well as progressive hypopigmentation of the coat, that appears to be mechanistically unrelated. Hypopigmentation was rescued by transgenic expression of wild-type Mbtps1, and reciprocal grafting studies showed that normal pigmentation depended upon both cell-intrinsic or paracrine factors, as well as factors that act systemically, both of which are lacking in wrt homozygotes. Mbtps1 exhibited a maternal-zygotic effect characterized by fully penetrant embryonic lethality of maternal-zygotic wrt mutant offspring and partial embryonic lethality (~40%) of zygotic wrt mutant offspring. Mbtps1 is one of two maternal-zygotic effect genes identified in mammals to date. It functions nonredundantly in pigmentation and embryogenesis

Ultrafast terahertz detectors based on 3D meta-atoms

In this contribution, we demonstrate ultrafast sub-wavelength (λ/10) THz QWIP detectors based on a 3D split-ring geometry recently developed in our team [3]. The key idea is to exploit a miniaturized loop RF antenna as a coupler element to efficiently feed THz radiation (λ=100-200 μm) into an ultra-sub-wavelength (λ/25) QWIP active core (active volume ~20 μm3), as depicted in Fig. 1(a). The LC resonance of the device has been set by carefully selecting both the capacitor and inductor sizes in order to match the GaAs/AlGaAs QWIP response band (detection peak at ~3 THz) [4]

Ultrafast terahertz detectors based on three-dimensional meta-atoms

Terahertz (THz) and sub-THz frequency emitter and detector technologies are receiving increasing attention, underpinned by emerging applications in ultra-fast THz physics, frequency-combs technology and pulsed laser development in this relatively unexplored region of the electromagnetic spectrum. In particular, semiconductor-based ultrafast THz receivers are required for compact, ultrafast spectroscopy and communication systems, and to date, quantum-well infrared photodetectors (QWIPs) have proved to be an excellent technology to address this, given their intrinsic picosecond-range response. However, with research focused on diffraction-limited QWIP structures ( /2), RC constants cannot be reduced indefinitely, and detection speeds are bound to eventually meet an upper limit. The key to an ultra-fast response with no intrinsic upper limit even at tens of gigahertz (GHz) is an aggressive reduction in device size, below the diffraction limit. Here we demonstrate sub-wavelength ( /10) THz QWIP detectors based on a 3D split-ring geometry, yielding ultra-fast operation at a wavelength of around 100 μm. Each sensing meta-atom pixel features a suspended loop antenna that feeds THz radiation in the ∼20  μm³ active volume ( eff~3×10‾⁴( /2)³). Arrays of detectors as well as single-pixel detectors have been implemented with this new architecture, with the latter exhibiting ultra-low dark currents below the nA level. This extremely small resonator architecture leads to measured optical response speeds—on arrays of 300 devices—of up to ∼3  GHz and an expected device operation of up to tens of GHz, based on the measured parameters on single devices and arrays

Nuclear expression of FLT1 and its ligand PGF in FUS-DDIT3 carrying myxoid liposarcomas suggests the existence of an intracrine signaling loop

<p>Abstract</p> <p>Background</p> <p>The FUS-DDIT3 fusion oncogene encodes an abnormal transcription factor that has a causative role in the development of myxoid/round-cell liposarcomas (MLS/RCLS). We have previously identified <it>FLT1 </it>(<it>VEGFR1</it>) as a candidate downstream target gene of FUS-DDIT3. The aim of this study was to investigate expression of FLT1 and its ligands in MLS cells.</p> <p>Methods</p> <p>HT1080 human fibrosarcoma cells were transiently transfected with <it>FUS-DDIT3</it>-GFP variant constructs and FLT1 expression was measured by quantitative real-time PCR. In addition, <it>FLT1</it>, <it>PGF, VEGFA and VEGFB </it>expression was measured in MLS/RCLS cell lines, MLS/RCLS tumors and in normal adiopocytes. We analyzed nine cases of MLS/RCLS and one cell line xenografted in mice for FLT1 protein expression using immunohistochemistry. MLS/RCLS cell lines were also analyzed for FLT1 by immunofluorescence and western blot. MLS/RCLS cell lines were additionally treated with FLT1 tyrosine kinase inhibitors and assayed for alterations in proliferation rate.</p> <p>Results</p> <p><it>FLT1 </it>expression was dramatically increased in transfected cells stably expressing FUS-DDIT3 and present at high levels in cell lines derived from MLS. The FLT1 protein showed a strong nuclear expression in cells of MLS tissue as well as in cultured MLS cells, which was confirmed by cellular fractionation. Tissue array analysis showed a nuclear expression of the FLT1 protein also in several other tumor and normal cell types including normal adipocytes. The FLT1 ligand coding gene <it>PGF </it>was highly expressed in cultured MLS cells compared to normal adipocytes while the other ligand genes <it>VEGFA </it>and <it>VEGFB </it>were expressed to lower levels. A more heterogeneous expression pattern of these genes were observed in tumor samples. No changes in proliferation rate of MLS cells were detected at concentrations for which the kinase inhibitors have shown specific inhibition of FLT1.</p> <p>Conclusions</p> <p>Our results imply that <it>FLT1 </it>is induced as an indirect downstream effect of FUS-DDIT3 expression in MLS. This could be a consequence of the ability of FUS-DDIT3 to hijack parts of normal adipose tissue development and reprogram primary cells to a liposarcoma-like phenotype. The findings of nuclear FLT1 protein and expression of corresponding ligands in MLS and normal tissues may have implications for tissue homeostasis and tumor development through auto- or intracrine signaling.</p

Identification of DNA-Damage DNA-Binding Protein 1 as a Conditional Essential Factor for Cytomegalovirus Replication in Interferon-γ-Stimulated Cells

The mouse cytomegaloviral (MCMV) protein pM27 represents an indispensable factor for viral fitness in vivo selectively, antagonizing signal transducer and activator of transcription 2 (STAT2)-mediated interferon signal transduction. We wished to explore by which molecular mechanism pM27 accomplishes this effect. We demonstrate that pM27 is essential and sufficient to curtail the protein half-life of STAT2 molecules. Pharmacologic inhibition of the proteasome restored STAT2 amounts, leading to poly-ubiquitin-conjugated STAT2 forms. PM27 was found in complexes with an essential host ubiquitin ligase complex adaptor protein, DNA-damage DNA-binding protein (DDB) 1. Truncation mutants of pM27 showed a strict correlation between DDB1 interaction and their ability to degrade STAT2. SiRNA-mediated knock-down of DDB1 restored STAT2 in the presence of pM27 and strongly impaired viral replication in interferon conditioned cells, thus phenocopying the growth attenuation of M27-deficient virus. In a constructive process, pM27 recruits DDB1 to exploit ubiquitin ligase complexes catalyzing the obstruction of the STAT2-dependent antiviral state of cells to permit viral replication

Dendritic Cell Subtypes from Lymph Nodes and Blood Show Contrasted Gene Expression Programs upon Bluetongue Virus Infection

Chantier qualité GAHuman and animal hemorrhagic viruses initially target dendritic cells (DCs). It has been proposed, but not documented, that both plasmacytoid DCs (pDCs) and conventional DCs (cDCs) may participate in the cytokine storm encountered in these infections. In order to evaluate the contribution of DCs in hemorrhagic virus pathogenesis, we performed a genome-wide expression analysis during infection by Bluetongue virus (BTV), a double-stranded RNA virus that induces hemorrhagic fever in sheep and initially infects cDCs. Both pDCs and cDCs accumulated in regional lymph nodes and spleen during BTV infection. The gene response profiles were performed at the onset of the disease and markedly differed with the DC subtypes and their lymphoid organ location. An integrative knowledge-based analysis revealed that blood pDCs displayed a gene signature related to activation of systemic inflammation and permeability of vasculature. In contrast, the gene profile of pDCs and cDCs in lymph nodes was oriented to inhibition of inflammation, whereas spleen cDCs did not show a clear functional orientation. These analyses indicate that tissue location and DC subtype affect the functional gene expression program induced by BTV and suggest the involvement of blood pDCs in the inflammation and plasma leakage/hemorrhage during BTV infection in the real natural host of the virus. These findings open the avenue to target DCs for therapeutic interventions in viral hemorrhagic diseases

Broken replication forks trigger heritable DNA breaks in the terminus of a circular chromosome

<p><u>(A) Circular map of the <i>E</i>. <i>coli</i> chromosome</u>: <i>oriC</i>, <i>dif</i> and <i>terD</i> to <i>terB</i> sites are indicated. Numbers refer to the chromosome coordinates (in kb) of MG1655. (<u>B) Linear map of the terminus region:</u> chromosome coordinates are shown increasing from left to right, as in the marker frequency panels (see Figure 1C for example), therefore in the opposite direction to the circular map. In addition to <i>dif</i> and <i>ter</i> sites, the positions of the <i>parS</i>_pMT1 sites used for microscopy experiments are indicated. (<u>C) MFA analysis of terminus DNA loss in the <i>recB</i> mutant</u>: sequence read frequencies of exponential phase cells normalized to the total number of reads were calculated for each strain. Ratios of normalized reads in isogenic wild-type and <i>recB</i> mutant are plotted against chromosomal coordinates (in kb). The profile ratio of the terminus region is enlarged and the profile of the corresponding entire chromosomes is shown in inset. Original normalized profiles used to calculate ratios are shown in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1007256#pgen.1007256.s005" target="_blank">S1 Fig</a>. The position of <i>dif</i> is indicated by a red arrow. The <i>ter</i> sites that arrest clockwise forks (<i>terC</i>, <i>terB</i>, green arrow) and counter-clockwise forks (<i>terA</i>, <i>terD</i>, blue arrow) are shown. <u>(D) Schematic representation of focus loss in the <i>recB</i> mutant:</u> Time-lapse microscopy experiments showed that loss of a focus in the <i>recB</i> mutant occurs concomitantly with cell division in one of two daughter cells, and that the cell that keeps the focus then generates a focus-less cell at each generation. The percentage of initial events was calculated as the percentage of cell divisions that generate a focus-less cell, not counting the following generations. In this schematic representation, two initial events occurred (generations #2 and #7) out of 9 generations, and focus loss at generation #2 is heritable. Panels shown in this figure were previously published in [<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1007256#pgen.1007256.ref019" target="_blank">19</a>] and are reproduced here to introduce the phenomenon.</p