832 research outputs found
Natural curvature for manifest T-duality
We reformulate the manifestly T-dual description of the massless sector of
the closed bosonic string, directly from the geometry associated with the (left
and right) affine Lie algebra of the coset space Poincare/Lorentz. This
construction initially doubles not only the (spacetime) coordinates for
translations but also those for Lorentz transformations (and their dual). As a
result, the Lorentz connection couples directly to the string (as does the
vielbein), rather than being introduced ad hoc to the covariant derivative as
previously. This not only reproduces the old definition of T-dual torsion, but
automatically gives a general, covariant definition of T-dual curvature (but
still with some undetermined connections).Comment: Minor changes in notations (see e.g. eq.(7), eq.(8)). Some typos
corrected: e.g factor "i" in equations (11) and (12). New references adde
Modulation of mammalian translation by a ribosome-associated tRNA half
Originally considered futile degradation products, tRNA-derived RNA fragments (tdRs) have been shown over the recent past to be crucial players in orchestrating various cellular functions. Unlike other small non-coding RNA (ncRNA) classes, tdRs possess a multifaceted functional repertoire ranging from regulating transcription, apoptosis, RNA interference, ribosome biogenesis to controlling translation efficiency. A subset of the latter tdRs has been shown to directly target the ribosome, the central molecular machine of protein biosynthesis. Here we describe the function of the mammalian tRNAPro 5ʹ half, a 35 residue long ncRNA associated with ribosomes and polysomes in several mammalian cell lines. Addition of tRNAPro halves to mammalian in vitro translation systems results in global translation inhibition and concomitantly causes the upregulation of a specific low molecular weight translational product. This tRNAPro 5ʹ half-dependent translation product consists of both RNA and amino acids. Transfection of the tRNAPro half into HeLa cells leads to the formation of the same product in vivo. The migration of this product in acidic gels, the insensitivity to copper sulphate treatment, the resistance to 3ʹ polyadenylation, and the association with 80S monosomes indicate that the accumulated product is peptidyl-tRNA. Our data thus suggest that binding of the tRNAPro 5ʹ half to the ribosome leads to ribosome stalling and to the formation of peptidyl-tRNA. Our findings revealed a so far unknown functional role of a tdR thus further enlarging the functional heterogeneity of this emerging class of ribo-regulators
Processing of the VP1/2A Junction Is Not Necessary for Production of Foot-and-Mouth Disease Virus Empty Capsids and Infectious Viruses: Characterization of “Self-Tagged” Particles
The foot-and-mouth disease virus (FMDV) capsid protein precursor, P1-2A, is cleaved by 3C(pro) to generate VP0, VP3, VP1, and the peptide 2A. The capsid proteins self-assemble into empty capsid particles or viruses which do not contain 2A. In a cell culture-adapted strain of FMDV (O1 Manisa [Lindholm]), three different amino acid substitutions (E83K, S134C, and K210E) were identified within the VP1 region of the P1-2A precursor compared to the field strain (wild type [wt]). Expression of the O1 Manisa P1-2A (wt or with the S134C substitution in VP1) plus 3C(pro), using a transient expression system, resulted in efficient capsid protein production and self-assembly of empty capsid particles. Removal of the 2A peptide from the capsid protein precursor had no effect on capsid protein processing or particle assembly. However, modification of E83K alone abrogated particle assembly with no apparent effect on protein processing. Interestingly, the K210E substitution, close to the VP1/2A junction, completely blocked processing by 3C(pro) at this cleavage site, but efficient assembly of “self-tagged” empty capsid particles, containing the uncleaved VP1-2A, was observed. These self-tagged particles behaved like the unmodified empty capsids in antigen enzyme-linked immunosorbent assays and integrin receptor binding assays. Furthermore, mutant viruses with uncleaved VP1-2A could be rescued in cells from full-length FMDV RNA transcripts encoding the K210E substitution in VP1. Thus, cleavage of the VP1/2A junction is not essential for virus viability. The production of such engineered self-tagged empty capsid particles may facilitate their purification for use as diagnostic reagents and vaccines
A RT-qPCR system using a degenerate probe for specific identification and differentiation of SARS-CoV-2 Omicron (B.1.1.529) variants of concern
Fast surveillance strategies are needed to control the spread of new emerging SARS-CoV-2 variants and gain time for evaluation of their pathogenic potential. This was essential for the Omicron variant (B.1.1.529) that replaced the Delta variant (B.1.617.2) and is currently the dominant SARS-CoV-2 variant circulating worldwide. RT-qPCR strategies complement whole genome sequencing, especially in resource lean countries, but mutations in the targeting primer and probe sequences of new emerging variants can lead to a failure of the existing RT-qPCRs. Here, we introduced an RT-qPCR platform for detecting the Delta- and the Omicron variant simultaneously using a degenerate probe targeting the key ΔH69/V70 mutation in the spike protein. By inclusion of the L452R mutation into the RT-qPCR platform, we could detect not only the Delta and the Omicron variants, but also the Omicron sub-lineages BA.1, BA.2 and BA.4/BA.5. The RT-qPCR platform was validated in small- and large-scale. It can easily be incorporated for continued monitoring of Omicron sub-lineages, and offers a fast adaption strategy of existing RT-qPCRs to detect new emerging SARS-CoV-2 variants using degenerate probes.</p
Binding and circular dichroism data on bilirubin-albumin in the presence of oleate and salicylate
The binding of equimolar amounts of bilirubin to human and bovine serum albumin in 0.1 phosphate buffer, pH 7.4, in the presence and absence of various concentrations of oleate or salicylate was studied by the use of an ultracentrifugal technique. The resultant data showed salicylate to be a poor competitor for the bilirubin binding sites; in the presence of a considerable excess of salicylate, only small amounts of bilirubin were liberated from the proteins. The dissociation of bilirubin from albumin by oleate was very dependent on the oleate concentration. No bilirubin was liberated from the proteins at oleate:albumin molar ratios below 5. All the bilirubin was liberated from the proteins at oleate:albumin molar ratios above 8.Marked changes in the absorption and circular dichroism spectra of the bilirubin-albumin solutions were observed on the addition of salicylate or oleate even under conditions in which little or no bilirubin was liberated from the proteins. While the binding characteristics and absorption spectra of the human and bovine albumin-bilirubin complexes in the presence and absence of oleate or salicylate were very similar, the Cotton effects generated by the addition of bilirubin to the human albumin were very different from those obtained with the bovine protein.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32702/1/0000069.pd
PaLM 2 Technical Report
We introduce PaLM 2, a new state-of-the-art language model that has better
multilingual and reasoning capabilities and is more compute-efficient than its
predecessor PaLM. PaLM 2 is a Transformer-based model trained using a mixture
of objectives. Through extensive evaluations on English and multilingual
language, and reasoning tasks, we demonstrate that PaLM 2 has significantly
improved quality on downstream tasks across different model sizes, while
simultaneously exhibiting faster and more efficient inference compared to PaLM.
This improved efficiency enables broader deployment while also allowing the
model to respond faster, for a more natural pace of interaction. PaLM 2
demonstrates robust reasoning capabilities exemplified by large improvements
over PaLM on BIG-Bench and other reasoning tasks. PaLM 2 exhibits stable
performance on a suite of responsible AI evaluations, and enables
inference-time control over toxicity without additional overhead or impact on
other capabilities. Overall, PaLM 2 achieves state-of-the-art performance
across a diverse set of tasks and capabilities.
When discussing the PaLM 2 family, it is important to distinguish between
pre-trained models (of various sizes), fine-tuned variants of these models, and
the user-facing products that use these models. In particular, user-facing
products typically include additional pre- and post-processing steps.
Additionally, the underlying models may evolve over time. Therefore, one should
not expect the performance of user-facing products to exactly match the results
reported in this report
Appropriate age range for introduction of complementary feeding into an infant’s diet
Peer reviewedPublisher PD
Measurement and interpretation of same-sign W boson pair production in association with two jets in pp collisions at s = 13 TeV with the ATLAS detector
This paper presents the measurement of fducial and diferential cross sections for both the inclusive and electroweak production of a same-sign W-boson pair in association with two jets (W±W±jj) using 139 fb−1 of proton-proton collision data recorded at a centre-of-mass energy of √s = 13 TeV by the ATLAS detector at the Large Hadron Collider. The analysis is performed by selecting two same-charge leptons, electron or muon, and at least two jets with large invariant mass and a large rapidity diference. The measured fducial cross sections for electroweak and inclusive W±W±jj production are 2.92 ± 0.22 (stat.) ± 0.19 (syst.)fb and 3.38±0.22 (stat.)±0.19 (syst.)fb, respectively, in agreement with Standard Model predictions. The measurements are used to constrain anomalous quartic gauge couplings by extracting 95% confdence level intervals on dimension-8 operators. A search for doubly charged Higgs bosons H±± that are produced in vector-boson fusion processes and decay into a same-sign W boson pair is performed. The largest deviation from the Standard Model occurs for an H±± mass near 450 GeV, with a global signifcance of 2.5 standard deviations
Studies of new Higgs boson interactions through nonresonant HH production in the b¯bγγ fnal state in pp collisions at √s = 13 TeV with the ATLAS detector
A search for nonresonant Higgs boson pair production in the b
¯bγγ fnal state
is performed using 140 fb−1 of proton-proton collisions at a centre-of-mass energy of 13 TeV
recorded by the ATLAS detector at the CERN Large Hadron Collider. This analysis supersedes
and expands upon the previous nonresonant ATLAS results in this fnal state based on the
same data sample. The analysis strategy is optimised to probe anomalous values not only of
the Higgs (H) boson self-coupling modifer κλ but also of the quartic HHV V (V = W, Z)
coupling modifer κ2V . No signifcant excess above the expected background from Standard
Model processes is observed. An observed upper limit µHH < 4.0 is set at 95% confdence
level on the Higgs boson pair production cross-section normalised to its Standard Model
prediction. The 95% confdence intervals for the coupling modifers are −1.4 < κλ < 6.9 and
−0.5 < κ2V < 2.7, assuming all other Higgs boson couplings except the one under study are
fxed to the Standard Model predictions. The results are interpreted in the Standard Model
efective feld theory and Higgs efective feld theory frameworks in terms of constraints on
the couplings of anomalous Higgs boson (self-)interactions
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