pinecone/core-2020-05-10-deduplication huggingface dataset:
Unanchored K48-Linked Polyubiquitin Synthesized by the E3-Ubiquitin Ligase TRIM6 Stimulates the Interferon-IKKε Kinase-Mediated Antiviral Response

SummaryType I interferons (IFN-I) are essential antiviral cytokines produced upon microbial infection. IFN-I elicits this activity through the upregulation of hundreds of IFN-I-stimulated genes (ISGs). The full breadth of ISG induction demands activation of a number of cellular factors including the IκB kinase epsilon (IKKε). However, the mechanism of IKKε activation upon IFN receptor signaling has remained elusive. Here we show that TRIM6, a member of the E3-ubiquitin ligase tripartite motif (TRIM) family of proteins, interacted with IKKε and promoted induction of IKKε-dependent ISGs. TRIM6 and the E2-ubiquitin conjugase UbE2K cooperated in the synthesis of unanchored K48-linked polyubiquitin chains, which activated IKKε for subsequent STAT1 phosphorylation. Our work attributes a previously unrecognized activating role of K48-linked unanchored polyubiquitin chains in kinase activation and identifies the UbE2K-TRIM6-ubiquitin axis as critical for IFN signaling and antiviral response
A robust, fine pitch probe card

AbstractA new type of probe card is described which consists of inclined nickel cantilevers formed on top of a three dimensional PDMS layer. A prototype card has been built with an in-line pitch of 23 μm. The presence of a PDMS layer beneath the cantilevers creates mechanically robust probes. The probes can apply up to 100 mN contact force and be deflected up to 40 μm without damage. Typical contact resistances of less than 5 Ω against gold and 15 Ω against copper are reported. The leakage current between adjacent probes is less than 1 nA measured at 100 V
Modeling of Noisy Spindle Dynamics Reveals Separable Contributions to Achieving Correct Orientation

AbstractThe mechanisms by which the mammalian mitotic spindle is guided to a predefined orientation through microtubule-cortex interactions have recently received considerable interest, but there has been no dynamic model that describes spindle movements toward the preferred axis in human cells. Here, we develop a dynamic model based on stochastic activity of cues anisotropically positioned around the cortex of the mitotic cell and we show that the mitotic spindle does not reach equilibrium before chromosome segregation. Our model successfully captures the characteristic experimental behavior of noisy spindle rotation dynamics in human epithelial cells, including a weak underlying bias in the direction of rotation, suppression of motion close to the alignment axis, and the effect of the aspect ratio of the interphase cell shape in defining the final alignment axis. We predict that the force exerted per cue has a value that minimizes the deviation of the spindle from the predefined axis. The model has allowed us to systematically explore the parameter space around experimentally relevant configurations, and predict the mechanistic function of a number of established regulators of spindle orientation, highlighting how physical modeling of a noisy system can lead to functional biological understanding. We provide key insights into measurable parameters in live cells that can help distinguish between mechanisms of microtubule and cortical-cue interactions that jointly control the final orientation of the spindle
B-cell reconstitution after lentiviral vector–mediated gene therapy in patients with Wiskott-Aldrich syndrome

BackgroundWiskott-Aldrich syndrome (WAS) is a severe X-linked immunodeficiency characterized by microthrombocytopenia, eczema, recurrent infections, and susceptibility to autoimmunity and lymphomas. Hematopoietic stem cell transplantation is the treatment of choice; however, administration of WAS gene–corrected autologous hematopoietic stem cells has been demonstrated as a feasible alternative therapeutic approach.ObjectiveBecause B-cell homeostasis is perturbed in patients with WAS and restoration of immune competence is one of the main therapeutic goals, we have evaluated reconstitution of the B-cell compartment in 4 patients who received autologous hematopoietic stem cells transduced with lentiviral vector after a reduced-intensity conditioning regimen combined with anti-CD20 administration.MethodsWe evaluated B-cell counts, B-cell subset distribution, B cell–activating factor and immunoglobulin levels, and autoantibody production before and after gene therapy (GT). WAS gene transfer in B cells was assessed by measuring vector copy numbers and expression of Wiskott-Aldrich syndrome protein.ResultsAfter lentiviral vector-mediated GT, the number of transduced B cells progressively increased in the peripheral blood of all patients. Lentiviral vector-transduced progenitor cells were able to repopulate the B-cell compartment with a normal distribution of B-cell subsets both in bone marrow and the periphery, showing a WAS protein expression profile similar to that of healthy donors. In addition, after GT, we observed a normalized frequency of autoimmune-associated CD19+CD21−CD35− and CD21low B cells and a reduction in B cell–activating factor levels. Immunoglobulin serum levels and autoantibody production improved in all treated patients.ConclusionsWe provide evidence that lentiviral vector-mediated GT induces transgene expression in the B-cell compartment, resulting in ameliorated B-cell development and functionality and contributing to immunologic improvement in patients with WAS
Gauge link structure in quark–quark correlators in hard processes

AbstractDistribution functions in hard processes can be described by quark–quark correlators, nonlocal matrix elements of quark fields. Color gauge invariance requires inclusion of appropriate gauge links in these correlators. For transverse momentum dependent distribution functions, in particular important for describing T-odd effects in hard processes, we find that new link structures containing loops can appear in Abelian and non-Abelian theories. In transverse moments, e.g., measured in azimuthal asymmetries, these loops may enhance the contribution of gluonic poles. Some explicit results for the link structure are given in high-energy leptoproduction and hadron–hadron scattering
Search for a heavy narrow resonance decaying to eμ, eτ, or μτ with the ATLAS detector in s=7 TeV pp collisions at the LHC

AbstractThis Letter presents the results of a search for a heavy particle decaying into an e±μ∓, e±τ∓, or μ±τ∓ final state in pp collisions at s=7 TeV. The data were recorded with the ATLAS detector at the LHC during 2011 and correspond to an integrated luminosity of 4.6 fb−1. No significant excess above the Standard Model expectation is observed, and exclusions at 95% confidence level are placed on the cross section times branching ratio for the production of an R-parity-violating supersymmetric tau sneutrino. For a sneutrino mass of 500 (2000) GeV, the observed limits on the production cross section times branching ratio are 3.2 (1.4) fb, 42 (17) fb, and 40 (18) fb for the eμ, eτ, and μτ modes, respectively. These results considerably extend constraints from Tevatron experiments
Posterior Cingulate Cortex Integrates the Senses of Self-Location and Body Ownership

SummaryThe senses of owning a body and being localized somewhere in space are two key components of human self-consciousness. Despite a wealth of neurophysiological and neuroimaging research on the representations of the spatial environment in the parietal and medial temporal cortices, the relationship between body ownership and self-location remains unexplored. To investigate this relationship, we used a multisensory out-of-body illusion to manipulate healthy participants’ perceived self-location, head direction, and sense of body ownership during high-resolution fMRI. Activity patterns in the hippocampus and the posterior cingulate, retrosplenial, and intraparietal cortices reflected the sense of self-location, whereas the sense of body ownership was associated with premotor-intraparietal activity. The functional interplay between these two sets of areas was mediated by the posterior cingulate cortex. These results extend our understanding of the role of the posterior parietal and medial temporal cortices in spatial cognition by demonstrating that these areas not only are important for ecological behaviors, such as navigation and perspective taking, but also support the perceptual representation of the bodily self in space. Our results further suggest that the posterior cingulate cortex has a key role in integrating the neural representations of self-location and body ownership
Measurement of masses and widths of excited charm mesons D2∗ and evidence for broad states

AbstractUsing data from the FOCUS experiment we analyze the D+π− and D0π+ invariant mass distributions. We measure the D2∗0 mass MD2∗0=(2464.5±1.1±1.9)MeV/c2 and width ΓD2∗0=(38.7±5.3±2.9)MeV/c2, and the D2∗+ mass MD2∗+=(2467.6±1.5±0.76)MeV/c2 and width ΓD2∗+=(34.1±6.5±4.2)MeV/c2. We find evidence for broad structures over background in both the neutral and charged final state. If each is interpreted as evidence for a single L=1, jq=1/2 excited charm meson resonance, the masses and widths are M1/20=(2407±21±35)MeV/c2, Γ1/20=(240±55±59)MeV/c2, and M1/2+=(2403±14±35)MeV/c2, Γ1/2+=(283±24±34)MeV/c2, respectively
GABA-mediated changes in inter-hemispheric beta frequency activity in early-stage Parkinson’s disease

AbstractIn Parkinson’s disease (PD), elevated beta (15–35Hz) power in subcortical motor networks is widely believed to promote aspects of PD symptomatology, moreover, a reduction in beta power and coherence accompanies symptomatic improvement following effective treatment with l-DOPA. Previous studies have reported symptomatic improvements that correlate with changes in cortical network activity following GABAA receptor modulation. In this study we have used whole-head magnetoencephalography to characterize neuronal network activity, at rest and during visually cued finger abductions, in unilaterally symptomatic PD and age-matched control participants. Recordings were then repeated following administration of sub-sedative doses of the hypnotic drug zolpidem (0.05mg/kg), which binds to the benzodiazepine site of the GABAA receptor. A beamforming based ‘virtual electrode’ approach was used to reconstruct oscillatory power in the primary motor cortex (M1), contralateral and ipsilateral to symptom presentation in PD patients or dominant hand in control participants. In PD patients, contralateral M1 showed significantly greater beta power than ipsilateral M1. Following zolpidem administration contralateral beta power was significantly reduced while ipsilateral beta power was significantly increased resulting in a hemispheric power ratio that approached parity. Furthermore, there was highly significant correlation between hemispheric beta power ratio and Unified Parkinson’s Disease Rating Scale (UPDRS). The changes in contralateral and ipsilateral beta power were reflected in pre-movement beta desynchronization and the late post-movement beta rebound. However, the absolute level of movement-related beta desynchronization was not altered. These results show that low-dose zolpidem not only reduces contralateral beta but also increases ipsilateral beta, while rebalancing the dynamic range of M1 network oscillations between the two hemispheres. These changes appear to underlie the symptomatic improvements afforded by low-dose zolpidem
On the minimization of XML Schemas and tree automata for unranked trees

AbstractAutomata for unranked trees form a foundation for XML Schemas, querying and pattern languages. We study the problem of efficiently minimizing such automata. First, we study unranked tree automata that are standard in database theory, assuming bottom-up determinism and that horizontal recursion is represented by deterministic finite automata. We show that minimal automata in that class are not unique and that minimization is np-complete. Second, we study more recent automata classes that do allow for polynomial time minimization. Among those, we show that bottom-up deterministic stepwise tree automata yield the most succinct representations. Third, we investigate abstractions of XML schema languages. In particular, we show that the class of one-pass preorder typeable schemas allows for polynomial time minimization and unique minimal models
Interaction between soluble Aβ-(1–40) monomer and Aβ-(1–42) fibrils probed by paramagnetic relaxation enhancement

AbstractThe most common isoforms of amyloid-β (Aβ) proteins are composed of 40 or 42 amino acid residues. While Aβ-(1–40) is the predominant species, Aβ-(1–42) is more fibrillogenic and neurotoxic, suggesting that Aβ-(1–42) plays a critical role in the initiation of amyloid fibril formation. We investigated the mechanisms by which soluble Aβ-(1–40) associates with preformed Aβ-(1–42) seeds. A paramagnetic relaxation enhancement analysis showed that the Aβ-(1–40) monomer and Aβ-(1–42) seed interact via their C-terminal region in a parallel fashion, and the N-terminal part does not to contribute to the interaction.Structured summary of protein interactionsA beta-(1–40) and A beta-(1–42) bind by fluorescence technology (View interaction)A beta-(1–42) and A beta-(1–40) bind by nuclear magnetic resonance (View interaction
The eruptive history and magmatic evolution of Aluto volcano: new insights into silicic peralkaline volcanism in the Ethiopian rift

AbstractThe silicic peralkaline volcanoes of the East African Rift are some of the least studied volcanoes on Earth. Here we bring together new constraints from fieldwork, remote sensing, geochronology and geochemistry to present the first detailed account of the eruptive history of Aluto, a restless silicic volcano located in a densely populated section of the Main Ethiopian Rift. Prior to the growth of the Aluto volcanic complex (before 500ka) the region was characterized by a significant period of fault development and mafic fissure eruptions. The earliest volcanism at Aluto built up a trachytic complex over 8km in diameter. Aluto then underwent large-volume ignimbrite eruptions at 316±19ka and 306±12ka developing a~42km2 collapse structure. After a hiatus of ~250ka, a phase of post-caldera volcanism initiated at 55±19ka and the most recent eruption of Aluto has a radiocarbon age of 0.40±0.05cal. ka BP. During this post-caldera phase highly-evolved peralkaline rhyolite lavas, ignimbrites and pumice fall deposits have erupted from vents across the complex. Geochemical modelling is consistent with rhyolite genesis from protracted fractionation (>80%) of basalt that is compositionally similar to rift-related basalts found east of the complex. Based on the style and volume of recent eruptions we suggest that silicic eruptions occur at an average rate of 1 per 1000years, and that future eruptions of Aluto will involve explosive emplacement of localised pumice cones and effusive obsidian coulees of volumes in the range 1–100×106m3
Study of CP violation in D→VV decay at BES-III

AbstractIn this Letter, we intend to study the problem of CP violation in D meson by D→VV decay mode in which the T violating triple-product correlation is examined. That would undoubtedly be another excellent probe of New Physics beyond Standard Model. For the neutral D, we focus on direct CP violation without considering D0–D¯0 oscillation. Experimentally, by a full angular analysis one may obtain such CP violating signals, and particularly it is worth mentioning that the upcoming large D data samples at BES-III in Beijing will provide a great opportunity to perform it
Jet (de)coherence in Pb–Pb collisions at the LHC

AbstractWe study the modifications of jets created in heavy-ion collisions at LHC energies. The inherent hierarchy of scales governing the jet evolution allows to distinguish a leading jet structure, which interacts coherently with the medium as a single color charge, from softer sub-structures that will be sensitive to effects of color decoherence. We argue how this separation comes about and show that this picture is consistent with experimental data on reconstructed jets at the LHC, providing a quantitative description simultaneously of the jet nuclear modification factor, the missing energy in di-jet events and the modification of the fragmentation functions. In particular, we demonstrate that effects due to color decoherence are manifest in the excess of soft particles measured in fragmentation functions in Pb–Pb compared to proton–proton collisions
A conditional transgenic mouse line for targeted expression of the stem cell marker LGR5

AbstractLGR5 is a known marker of embryonic and adult stem cells in several tissues. In a mouse model, Lgr5+ cells have shown tumour-initiating properties, while in human cancers, such as basal cell carcinoma and colon cancer, LGR5 expression levels are increased: however, the effect of increased LGR5 expression is not fully understood. To study the effects of elevated LGR5 expression levels we generated a novel tetracycline-responsive, conditional transgenic mouse line expressing human LGR5, designated TRELGR5. In this transgenic line, LGR5 expression can be induced in any tissue depending on the expression pattern of the chosen transcriptional regulator. For the current study, we used transgenic mice with a tetracycline-regulated transcriptional transactivator linked to the bovine keratin 5 promoter (K5tTA) to drive expression of LGR5 in the epidermis. As expected, expression of human LGR5 was induced in the skin of double transgenic mice (K5tTA;TRELGR5). Inducing LGR5 expression during embryogenesis and early development resulted in macroscopically and microscopically detectable phenotypic changes, including kink tail, sparse fur coat and enlarged sebaceous glands. The fur and sebaceous gland phenotypes were reversible upon discontinued expression of transgenic LGR5, but this was not observed for the kink tail phenotype. There were no apparent phenotypic changes if LGR5 expression was induced at three weeks of age. The results demonstrate that increased expression of LGR5 during embryogenesis and the neonatal period alter skin development and homeostasis
Glacial history of sub-Antarctic South Georgia based on the submarine geomorphology of its fjords

AbstractWe present multibeam swath bathymetric surveys of the major fjords surrounding the sub-Antarctic island of South Georgia to characterise the glacial geomorphology and to identify the relative timings and extent of past glacial advance and retreat. Bathymetry data revealed a range of glacial features including terminal, retreat and truncated moraines, deep (distal) outer and shallow (proximal) inner basins and cross shelf troughs. These provide evidence of glacial advance and retreat through several glacial cycles. A near consistent pattern of large scale submarine geomorphological features was observed in the different fjords suggesting a similar response of margins of the island ice cap to past climate forcing. A relative chronology based on the relationships between the submarine features with their radiocarbon and cosmogenic isotope dated terrestrial counterparts suggests that widely observed inner basin moraines date from the last major glacial advance or Last Glacial Maximum, while deep basin moraines may date from an earlier (pre-LGM) more extensive glaciation, which we speculate corresponds to MIS6. On the sides of the deep basins a series of truncated moraines show ice advance positions from preceding glacial periods. The cross shelf troughs, and mid-trough moraines are interpreted as the product of much more extensive glaciations that predate the fjord geomorphology mapped here, thus possibly older than MIS6. This hypothesis would suggest that South Georgia followed a glacial history similar to that of central Patagonia (46°S) where a series of Pleistocene glaciations (of MIS 20 and younger) extended beyond LGM limits, with the most extensive glacial advance occurring at c. 1.1 Ma
Problematic aspects of Kaluza–Klein excitations in multidimensional models with Einstein internal spaces

AbstractWe consider Kaluza–Klein (KK) models where internal spaces are compact Einstein spaces. These spaces are stabilized by background matter (e.g., monopole form-fields). We perturb this background by a compact matter source (e.g., the system of gravitating masses) with the zero pressure in the external/our space and an arbitrary pressure in the internal space. We show that the Einstein equations are compatible only if the matter source is smeared over the internal space and perturbed metric components do not depend on coordinates of extra dimensions. The latter means the absence of KK modes corresponding to the metric fluctuations. Maybe, the absence of KK particles in LHC experiments is explained by such mechanism
Phosphorylation and DNA Binding of HJURP Determine Its Centromeric Recruitment and Function in CenH3CENP-A Loading

SummaryCentromeres, epigenetically defined by the presence of the histone H3 variant CenH3, are essential for ensuring proper chromosome segregation. In mammals, centromeric CenH3CENP-A deposition requires its dedicated chaperone HJURP and occurs during telophase/early G1. We find that the cell-cycle-dependent recruitment of HJURP to centromeres depends on its timely phosphorylation controlled via cyclin-dependent kinases. A nonphosphorylatable HJURP mutant localizes prematurely to centromeres in S and G2 phase. This unregulated targeting causes a premature loading of CenH3CENP-A at centromeres, and cell-cycle delays ensue. Once recruited to centromeres, HJURP functions to promote CenH3CENP-A deposition by a mechanism involving a unique DNA-binding domain. With our findings, we propose a model wherein (1) the phosphorylation state of HJURP controls its centromeric recruitment in a cell-cycle-dependent manner, and (2) HJURP binding to DNA is a mechanistic determinant in CenH3CENP-A loading
Ambitwistors, oscillators and massless fields on AdS5

AbstractPositive energy unitary irreducible representations of SU(2,2) can be constructed with the aid of bosonic oscillators in (anti)fundamental representation of SU(2)L×SU(2)R that are closely related to Penrose twistors. Starting with the correspondence between the doubleton representations, homogeneous functions on projective twistor space and on-shell generalized Weyl curvature SL(2,C) spinors and their low-spin counterparts, we study in the similar way the correspondence between the massless representations, homogeneous functions on ambitwistor space and, via the Penrose transform, with the gauge fields on Minkowski boundary of AdS5. The possibilities of reconstructing massless fields on AdS5 and some applications are also discussed