Search

Charged particle velocity-space diffusion in a prescribed one-dimensional turbulent electric field is investigated through numerical trajectories in phase-space and compared against quasi-linear theory (QL), including resonance broadening (RB). A Gaussian spectrum electric field of variable amplitude E is studied in conjunction with two plasma dispersion relations, namely, the Langmuir and ion-acoustic dispersion. A first parameter scan shows that RB effects become significant for a Kubo number K of a few percent. A Kubo number scan shows that diffusion increases as a power law of D∝K3∝E3/2 for large Kubo numbers. Moreover, at large Kubo numbers, transport processes include significant diffusion measured at velocities much higher than the resonant region, where QL and RB predict negligible diffusion. For times much larger than the trapped particle flight time τb and the autocorrelation time τ0, the velocity distribution departs from a Gaussian. Nevertheless, measurements show that the variance increases linearly in time, with a Hurst parameter of H∼0.5, where the diffusion scales as K5/2∝E5/4 and K3/2∝E3/4 for small and large Kubo number, respectively.

Magnetospheres are a ubiquitous feature of magnetized bodies embedded in a plasma flow. While large planetary magnetospheres have been studied for decades by spacecraft, ion-scale “mini” magnetospheres can provide a unique environment to study kinetic-scale, collisionless plasma physics in the laboratory to help validate models of larger systems. In this work, we present preliminary experiments of ion-scale magnetospheres performed on a unique high-repetition-rate platform developed for the Large Plasma Device at the University of California, Los Angeles. The experiments utilize a high-repetition-rate laser to drive a fast plasma flow into a pulsed dipole magnetic field embedded in a uniform magnetized background plasma. 2D maps of the magnetic field with high spatial and temporal resolution are measured with magnetic flux probes to examine the evolution of magnetosphere and current density structures for a range of dipole and upstream parameters. The results are further compared to 2D particle-in-cell simulations to identify key observational signatures of the kinetic-scale structures and dynamics of the laser-driven plasma. We find that distinct 2D kinetic-scale magnetopause and diamagnetic current structures are formed at higher dipole moments, and their locations are consistent with predictions based on pressure balances and energy conservation.

DUNE is a dual-site experiment for long-baseline neutrino oscillation studies, neutrino astrophysics and nucleon decay searches. ProtoDUNE Dual Phase (DP) is a 6  ×  6  ×  6 m 3 liquid argon time-projection-chamber (LArTPC) that recorded cosmic-muon data at the CERN Neutrino Platform in 2019-2020 as a prototype of the DUNE Far Detector. Charged particles propagating through the LArTPC produce ionization and scintillation light. The scintillation light signal in these detectors can provide the trigger for non-beam events. In addition, it adds precise timing capabilities and improves the calorimetry measurements. In ProtoDUNE-DP, scintillation and electroluminescence light produced by cosmic muons in the LArTPC is collected by photomultiplier tubes placed up to 7 m away from the ionizing track. In this paper, the ProtoDUNE-DP photon detection system performance is evaluated with a particular focus on the different wavelength shifters, such as PEN and TPB, and the use of Xe-doped LAr, considering its future use in giant LArTPCs. The scintillation light production and propagation processes are analyzed and a comparison of simulation to data is performed, improving understanding of the liquid argon properties.

The observation of 236 MeV muon neutrinos from kaon-decay-at-rest (KDAR) originating in the core of the Sun would provide a unique signature of dark matter annihilation. Since excellent angle and energy reconstruction are necessary to detect this monoenergetic, directional neutrino flux, DUNE with its vast volume and reconstruction capabilities, is a promising candidate for a KDAR neutrino search. In this work, we evaluate the proposed KDAR neutrino search strategies by realistically modeling both neutrino-nucleus interactions and the response of DUNE. We find that, although reconstruction of the neutrino energy and direction is difficult with current techniques in the relevant energy range, the superb energy resolution, angular resolution, and particle identification offered by DUNE can still permit great signal/background discrimination. Moreover, there are non-standard scenarios in which searches at DUNE for KDAR in the Sun can probe dark matter interactions.

The deep underground neutrino experiment (DUNE), a 40-kton underground liquid argon time projection chamber experiment, will be sensitive to the electron-neutrino flavor component of the burst of neutrinos expected from the next Galactic core-collapse supernova. Such an observation will bring unique insight into the astrophysics of core collapse as well as into the properties of neutrinos. The general capabilities of DUNE for neutrino detection in the relevant few- to few-tens-of-MeV neutrino energy range will be described. As an example, DUNE’s ability to constrain the νe spectral parameters of the neutrino burst will be considered.

Neutralizing agents against SARS-CoV-2 are urgently needed for the treatment and prophylaxis of COVID-19. Here, we present a strategy to rapidly identify and assemble synthetic human variable heavy (VH) domains toward neutralizing epitopes. We constructed a VH-phage library and targeted the angiotensin-converting enzyme 2 (ACE2) binding interface of the SARS-CoV-2 Spike receptor-binding domain (Spike-RBD). Using a masked selection approach, we identified VH binders to two non-overlapping epitopes and further assembled these into multivalent and bi-paratopic formats. These VH constructs showed increased affinity to Spike (up to 600-fold) and neutralization potency (up to 1,400-fold) on pseudotyped SARS-CoV-2 virus when compared to standalone VH domains. The most potent binder, a trivalent VH, neutralized authentic SARS-CoV-2 with a half-maximal inhibitory concentration (IC50) of 4.0 nM (180 ng ml-1). A cryo-EM structure of the trivalent VH bound to Spike shows each VH domain engaging an RBD at the ACE2 binding site, confirming our original design strategy.

The Deep Underground Neutrino Experiment (DUNE) will be a powerful tool for a variety of physics topics. The high-intensity proton beams provide a large neutrino flux, sampled by a near detector system consisting of a combination of capable precision detectors, and by the massive far detector system located deep underground. This configuration sets up DUNE as a machine for discovery, as it enables opportunities not only to perform precision neutrino measurements that may uncover deviations from the present three-flavor mixing paradigm, but also to discover new particles and unveil new interactions and symmetries beyond those predicted in the Standard Model (SM). Of the many potential beyond the Standard Model (BSM) topics DUNE will probe, this paper presents a selection of studies quantifying DUNE's sensitivities to sterile neutrino mixing, heavy neutral leptons, non-standard interactions, CPT symmetry violation, Lorentz invariance violation, neutrino trident production, dark matter from both beam induced and cosmogenic sources, baryon number violation, and other new physics topics that complement those at high-energy colliders and significantly extend the present reach.

We present a public catalog of transients from the Zwicky Transient Facility (ZTF) Bright Transient Survey, a magnitude-limited (m < 19 mag in either the g or r filter) survey for extragalactic transients in the ZTF public stream. We introduce cuts on survey coverage, sky visibility around peak light, and other properties unconnected to the nature of the transient, and show that the resulting statistical sample is spectroscopically 97% complete at -16 mag), 10% in red-sequence galaxies, and 1% in massive ellipticals. We find no significant difference in the luminosity or color distributions between the host galaxies of SNe Type II and SNe Type Ib/c, suggesting that line-driven wind stripping does not play a major role in the loss of the hydrogen envelope from their progenitors. Future large-scale classification efforts with ZTF and other wide-area surveys will provide highquality measurements of the rates, properties, and environments of all known types of optical transients and limits on the existence of theoretically predicted but as yet unobserved explosions.

The Deep Underground Neutrino Experiment is a next-generation neutrino oscillation experiment that aims to measure CP-violation in the neutrino sector as part of a wider physics program. A deep learning approach based on a convolutional neural network has been developed to provide highly efficient and pure selections of electron neutrino and muon neutrino charged-current interactions. The electron neutrino (antineutrino) selection efficiency peaks at 90% (94%) and exceeds 85% (90%) for reconstructed neutrino energies between 2-5 GeV. The muon neutrino (antineutrino) event selection is found to have a maximum efficiency of 96% (97%) and exceeds 90% (95%) efficiency for reconstructed neutrino energies above 2 GeV. When considering all electron neutrino and antineutrino interactions as signal, a selection purity of 90% is achieved. These event selections are critical to maximize the sensitivity of the experiment to CP-violating effects.

The sensitivity of the Deep Underground Neutrino Experiment (DUNE) to neutrino oscillation is determined, based on a full simulation, reconstruction, and event selection of the far detector and a full simulation and parameterized analysis of the near detector. Detailed uncertainties due to the flux prediction, neutrino interaction model, and detector effects are included. DUNE will resolve the neutrino mass ordering to a precision of 5σ, for all δCP values, after 2 years of running with the nominal detector design and beam configuration. It has the potential to observe charge-parity violation in the neutrino sector to a precision of 3σ (5σ) after an exposure of 5 (10) years, for 50% of all δCP values. It will also make precise measurements of other parameters governing long-baseline neutrino oscillation, and after an exposure of 15 years will achieve a similar sensitivity to sin 22 θ13 to current reactor experiments.

Somatic mutations that perturb Parkin ubiquitin ligase activity and the misregulation of iron homeostasis have both been linked to Parkinson's disease. Lactotransferrin (LTF) is a member of the family of transferrin iron binding proteins that regulate iron homeostasis, and increased levels of LTF and its receptor have been observed in neurodegenerative disorders like Parkinson's disease. Here, we report that Parkin binds to LTF and ubiquitylates LTF to influence iron homeostasis. Parkin-dependent ubiquitylation of LTF occurred most often on lysines (K) 182 and 649. Substitution of K182 or K649 with alanine (K182A or K649A, respectively) led to a decrease in the level of LTF ubiquitylation, and substitution at both sites led to a major decrease in the level of LTF ubiquitylation. Importantly, Parkin-mediated ubiquitylation of LTF was critical for regulating intracellular iron levels as overexpression of LTF ubiquitylation site point mutants (K649A or K182A/K649A) led to an increase in intracellular iron levels measured by ICP-MS/MS. Consistently, RNAi-mediated depletion of Parkin led to an increase in intracellular iron levels in contrast to overexpression of Parkin that led to a decrease in intracellular iron levels. Together, these results indicate that Parkin binds to and ubiquitylates LTF to regulate intracellular iron levels. These results expand our understanding of the cellular processes that are perturbed when Parkin activity is disrupted and more broadly the mechanisms that contribute to Parkinson's disease.

BackgroundEngineered vaccine proteins incorporating both antigen and adjuvant components are constructed with the aim of combining functions to induce effective protective immunity. Bacterial flagellin is a strong candidate for an engineered vaccine scaffold as it is known to provide adjuvant activity through its TLR5 and inflammasome activation. Moreover, polymerized flagellin filaments can elicit a more robust immunoglobulin response than monomeric flagellin, and the multimeric antigen form can also promote T cell-independent antibody responses. Here, we aim to produce and test a covalently stabilized polymerized flagellar filament, providing additional immune efficacy through stabilization of its polymeric filament structure, as well as stabilization for long-term storage.ResultsComputational modeling of monomer packing in flagellin filaments helped identify amino acids with proximity to neighboring flagella protofilaments. Paired cysteine substitutions were made at amino acids predicted to form inter-monomer disulfide cross-links, and these substitutions were capable of forming flagella when transfected into a flagellin-negative strain of Salmonella enterica subspecies Typhimurium. Interestingly, each paired substitution stabilized different helical conformational polymorphisms; the stabilized filaments lost the ability to transition between conformations, reducing bacterial motility. More importantly, the paired substitutions enabled extensive disulfide cross links and intra-filament multimer formation, and in one of the three variants, permitted filament stability in high acidic and temperature conditions where wild-type filaments would normally rapidly depolymerize. In addition, with regard to potential adjuvant activity, all crosslinked flagella filaments were able to induce wild-type levels of epithelial NF-κB in a cell reporter system. Finally, bacterial virulence was unimpaired in epithelial adherence and invasion, and the cysteine substitutions also appeared to increase bacterial resistance to oxidizing and reducing conditions.ConclusionsWe identified amino acid pairs, with cysteine substitutions, were able to form intermolecular disulfide bonds that stabilized the resulting flagellar filaments in detergent, hydrochloric acid, and high temperatures while retaining its immunostimulatory function. Flagellar filaments with disulfide-stabilized protofilaments introduce new possibilities for the application of flagella as a vaccine adjuvant. Specifically, increased stability and heat tolerance permits long-term storage in a range of temperature environments, as well as delivery under a range of clinical conditions.

Lytic polysaccharide monooxygenases (LPMOs) are redox-enzymes involved in biomass degradation. All characterized LPMOs possess an active site of two highly conserved histidine residues coordinating a copper ion (the histidine brace), which are essential for LPMO activity. However, some protein sequences that belong to the AA9 LPMO family display a natural N-terminal His to Arg substitution (Arg-AA9). These are found almost entirely in the phylogenetic fungal class Agaricomycetes, associated with wood decay, but no function has been demonstrated for any Arg-AA9. Through bioinformatics, transcriptomic, and proteomic analyses we present data, which suggest that Arg-AA9 proteins could have a hitherto unidentified role in fungal degradation of lignocellulosic biomass in conjunction with other secreted fungal enzymes. We present the first structure of an Arg-AA9, LsAA9B, a naturally occurring protein from Lentinus similis The LsAA9B structure reveals gross changes in the region equivalent to the canonical LPMO copper-binding site, whereas features implicated in carbohydrate binding in AA9 LPMOs have been maintained. We obtained a structure of LsAA9B with xylotetraose bound on the surface of the protein although with a considerably different binding mode compared with other AA9 complex structures. In addition, we have found indications of protein phosphorylation near the N-terminal Arg and the carbohydrate-binding site, for which the potential function is currently unknown. Our results are strong evidence that Arg-AA9s function markedly different from canonical AA9 LPMO, but nonetheless, may play a role in fungal conversion of lignocellulosic biomass.

Members of the New Kinase Family 3 (NKF3), PEAK1/SgK269 and Pragmin/SgK223 pseudokinases, have emerged as important regulators of cell motility and cancer progression. Here, we demonstrate that C19orf35 (PEAK3), a newly identified member of the NKF3 family, is a kinase-like protein evolutionarily conserved across mammals and birds and a regulator of cell motility. In contrast to its family members, which promote cell elongation when overexpressed in cells, PEAK3 overexpression does not have an elongating effect on cell shape but instead is associated with loss of actin filaments. Through an unbiased search for PEAK3 binding partners, we identified several regulators of cell motility, including the adaptor protein CrkII. We show that by binding to CrkII, PEAK3 prevents the formation of CrkII-dependent membrane ruffling. This function of PEAK3 is reliant upon its dimerization, which is mediated through a split helical dimerization domain conserved among all NKF3 family members. Disruption of the conserved DFG motif in the PEAK3 pseudokinase domain also interferes with its ability to dimerize and subsequently bind CrkII, suggesting that the conformation of the pseudokinase domain might play an important role in PEAK3 signaling. Hence, our data identify PEAK3 as an NKF3 family member with a unique role in cell motility driven by dimerization of its pseudokinase domain.

Aminoacyl-tRNA synthetases (ARSs) function to transfer amino acids to cognate tRNA molecules, which are required for protein translation. To date, biallelic mutations in 31 ARS genes are known to cause recessive, early-onset severe multi-organ diseases. VARS encodes the only known valine cytoplasmic-localized aminoacyl-tRNA synthetase. Here, we report seven patients from five unrelated families with five different biallelic missense variants in VARS. Subjects present with a range of global developmental delay, epileptic encephalopathy and primary or progressive microcephaly. Longitudinal assessment demonstrates progressive cortical atrophy and white matter volume loss. Variants map to the VARS tRNA binding domain and adjacent to the anticodon domain, and disrupt highly conserved residues. Patient primary cells show intact VARS protein but reduced enzymatic activity, suggesting partial loss of function. The implication of VARS in pediatric neurodegeneration broadens the spectrum of human diseases due to mutations in tRNA synthetase genes.

Enhancing the magnetoelectric coupling in a strain-mediated multiferroic composite structure plays a vital role in controlling magnetism by electric fields. An enhancement of magnetoelastic coupling between ferroelectric single crystal (011)-cut [Pb(Mg1/3Nb2/3)O3](1-x)-[PbTiO3]x (PMN-PT, x≈ 0.30) and ferromagnetic polycrystalline Ni thin film through an interposed benzocyclobutene polymer thin film is reported. A nearly twofold increase in sensitivity of remanent magnetization in the Ni thin film to an applied electric field is observed. This observation suggests a viable method of improving the magnetoelectric response in these composite multiferroic systems.

The functional and biological significance of the selected CASP12 targets are described by the authors of the structures. The crystallographers discuss the most interesting structural features of the target proteins and assess whether these features were correctly reproduced in the predictions submitted to the CASP12 experiment.

Germline mutations in the BRCA2 tumour suppressor are associated with both an increased lifetime risk of developing prostate cancer (PCa) and increased risk of aggressive disease. To understand this aggression, here we profile the genomes and methylomes of localized PCa from 14 carriers of deleterious germline BRCA2 mutations (BRCA2-mutant PCa). We show that BRCA2-mutant PCa harbour increased genomic instability and a mutational profile that more closely resembles metastastic than localized disease. BRCA2-mutant PCa shows genomic and epigenomic dysregulation of the MED12L/MED12 axis, which is frequently dysregulated in metastatic castration-resistant prostate cancer (mCRPC). This dysregulation is enriched in BRCA2-mutant PCa harbouring intraductal carcinoma (IDC). Microdissection and sequencing of IDC and juxtaposed adjacent non-IDC invasive carcinoma in 10 patients demonstrates a common ancestor to both histopathologies. Overall we show that localized castration-sensitive BRCA2-mutant tumours are uniquely aggressive, due to de novo aberration in genes usually associated with metastatic disease, justifying aggressive initial treatment.

Sortases function as cysteine transpeptidases that catalyze the covalent attachment of virulence-associated surface proteins into the cell wall peptidoglycan in Gram-positive bacteria. The substrate proteins targeted by sortase enzymes have a cell wall sorting signal (CWSS) located at the C-terminus. Up to date, it is still not well understood how sortases with structural resemblance among different classes and diverse species of bacteria achieve substrate specificity. In this study, we focus on elucidating the molecular basis for specific recognition of peptide substrate PPKTG by Clostridium difficile sortase B (Cd-SrtB). Combining structural studies, biochemical assays and molecular dynamics simulations, we have constructed a computational model of Cd-SrtBΔN26-PPKTG complex and have validated the model by site-directed mutagensis studies and fluorescence resonance energy transfer (FRET)-based assay. Furthermore, we have revealed that the fourth amino acid in the N-terminal direction from cleavage site of PPKTG forms specific interaction with Cd-SrtB and plays an essential role in configuring the peptide to allow more efficient substrate-specific cleavage by Cd-SrtB.

The Helicobacter pylori adhesin BabA binds mucosal ABO/Le(b) blood group (bg) carbohydrates. BabA facilitates bacterial attachment to gastric surfaces, increasing strain virulence and forming a recognized risk factor for peptic ulcers and gastric cancer. High sequence variation causes BabA functional diversity, but the underlying structural-molecular determinants are unknown. We generated X-ray structures of representative BabA isoforms that reveal a polymorphic, three-pronged Le(b) binding site. Two diversity loops, DL1 and DL2, provide adaptive control to binding affinity, notably ABO versus O bg preference. H. pylori strains can switch bg preference with single DL1 amino acid substitutions, and can coexpress functionally divergent BabA isoforms. The anchor point for receptor binding is the embrace of an ABO fucose residue by a disulfide-clasped loop, which is inactivated by reduction. Treatment with the redox-active pharmaceutic N-acetylcysteine lowers gastric mucosal neutrophil infiltration in H. pylori-infected Le(b)-expressing mice, providing perspectives on possible H. pylori eradication therapies.

Silyl-triflate-catalyzed (4+3) cycloadditions of epoxy enolsilanes with dienes provide a mild and chemoselective synthetic route to seven-membered carbocycles. Epoxy enolsilanes containing a terminal enolsilane and a single stereocenter undergo cycloaddition with almost complete conservation of enantiomeric purity, a finding that argues against the involvement of oxyallyl cation intermediates which have been previously proposed for these types of reactions. Reported are theoretical and experimental investigations of the cycloaddition mechanism. The major enantiomers of the cycloadducts are derived from S(N)2-like reactions of the silylated epoxide with the diene, in which stereospecific ring opening and formation of the two new C-C bonds occur in a single step. Calculations predict, and experiments confirm, that the observed small losses of enantiomeric purity are traced to a triflate-mediated double S(N)2 cycloaddition pathway.

Based on a sample of 500 million e+e-→cc¯ events recorded by the BABAR detector at c.m. energies of close to 10.6 GeV, we report on a study of the decay D0→π-e+νe. We measure the ratio of branching fractions, RD=B(D0→π-e+νe)/B(D0→K-π+)=0.0713±0.0017stat±0.0024syst, and use the present world average for B(D0→K-π+) to obtain B(D0→π-e+νe)=(2.770±0.068stat±0.092syst±0.037ext)×10-3 where the third error accounts for the uncertainty on the branching fraction for the reference channel. The measured dependence of the differential branching fraction on q2, the four-momentum transfer squared between the D and the π meson, is compared to various theoretical predictions for the hadronic form factor, f+,Dπ(q2), and the normalization |Vcd|×f+,Dπ(q2=0)=0.1374±0.0038stat±0.0022syst±0.0009ext. is extracted from a fit to data. Using the most recent LQCD prediction of f+,Dπ(q2=0)=0.666±0.029, we obtain |Vcd|=0.206±0.007exp±0.009LQCD. Assuming, instead, |Vcd|=|Vus|=0.2252±0.0009, we obtain f+,Dπ(q2=0)=0.610±0.020exp±0.005ext. The q2 dependence of f+,Dπ(q2) is compared to a variety of multipole parametrizations. This information is applied to B0→π-e+νe decays and, combined with an earlier B0→π-e+νe measurement by BABAR, is used to derive estimates of |Vub|.

We present Dalitz plot analyses for the decays of B mesons to D-D0K+ and D¯0D0K+. We report the observation of the Ds1∗(2700)+ resonance in these two channels and obtain measurements of the mass M(Ds1∗(2700)+)=2699-7+14MeV/c2 and of the width Γ(Ds1∗(2700)+)=127-19+24MeV, including statistical and systematic uncertainties. In addition, we observe an enhancement in the D0K+ invariant mass around 2350-2500MeV/c2 in both decays B0→D-D0K+ and B+→D¯0D0K+, which we are not able to interpret. The results are based on 429fb-1 of data containing 471×106BB¯ pairs collected at the (4S) resonance with the BABAR detector at the SLAC National Accelerator Laboratory.

We present Dalitz plot analyses for the decays of B mesons to D-D0K+ and D¯0D0K+. We report the observation of the Ds1∗(2700)+ resonance in these two channels and obtain measurements of the mass M(Ds1∗(2700)+)=2699-7+14MeV/c2 and of the width Γ(Ds1∗(2700)+)=127-19+24MeV, including statistical and systematic uncertainties. In addition, we observe an enhancement in the D0K+ invariant mass around 2350-2500MeV/c2 in both decays B0→D-D0K+ and B+→D¯0D0K+, which we are not able to interpret. The results are based on 429fb-1 of data containing 471×106BB¯ pairs collected at the (4S) resonance with the BABAR detector at the SLAC National Accelerator Laboratory.

Based on a sample of 500 million e+e-→cc¯ events recorded by the BABAR detector at c.m. energies of close to 10.6 GeV, we report on a study of the decay D0→π-e+νe. We measure the ratio of branching fractions, RD=B(D0→π-e+νe)/B(D0→K-π+)=0.0713±0.0017stat±0.0024syst, and use the present world average for B(D0→K-π+) to obtain B(D0→π-e+νe)=(2.770±0.068stat±0.092syst±0.037ext)×10-3 where the third error accounts for the uncertainty on the branching fraction for the reference channel. The measured dependence of the differential branching fraction on q2, the four-momentum transfer squared between the D and the π meson, is compared to various theoretical predictions for the hadronic form factor, f+,Dπ(q2), and the normalization |Vcd|×f+,Dπ(q2=0)=0.1374±0.0038stat±0.0022syst±0.0009ext. is extracted from a fit to data. Using the most recent LQCD prediction of f+,Dπ(q2=0)=0.666±0.029, we obtain |Vcd|=0.206±0.007exp±0.009LQCD. Assuming, instead, |Vcd|=|Vus|=0.2252±0.0009, we obtain f+,Dπ(q2=0)=0.610±0.020exp±0.005ext. The q2 dependence of f+,Dπ(q2) is compared to a variety of multipole parametrizations. This information is applied to B0→π-e+νe decays and, combined with an earlier B0→π-e+νe measurement by BABAR, is used to derive estimates of |Vub|.

We report the observation of the baryonic decay B¯0→Λc+p¯K-K+ using a data sample of 471×106 BB¯ pairs produced in e+e- annihilations at s=10.58GeV. This data sample was recorded with the BABAR detector at the PEP-II storage ring at SLAC. We find B(B¯0→Λc+p¯K-K+)=(2.5±0.4(stat)±0.2(syst)±0.6B(Λc+))×10-5, where the uncertainties are statistical, systematic, and due to the uncertainty of the Λc+→pK-π+ branching fraction, respectively. The result has a significance corresponding to 5.0 standard deviations, including all uncertainties. For the resonant decay B¯0→Λc+p¯φ, we determine the upper limit B(B¯0→Λc+p¯φ)

We report the observation of the baryonic decay B¯0→Λc+p¯K-K+ using a data sample of 471×106 BB¯ pairs produced in e+e- annihilations at s=10.58GeV. This data sample was recorded with the BABAR detector at the PEP-II storage ring at SLAC. We find B(B¯0→Λc+p¯K-K+)=(2.5±0.4(stat)±0.2(syst)±0.6B(Λc+))×10-5, where the uncertainties are statistical, systematic, and due to the uncertainty of the Λc+→pK-π+ branching fraction, respectively. The result has a significance corresponding to 5.0 standard deviations, including all uncertainties. For the resonant decay B¯0→Λc+p¯φ, we determine the upper limit B(B¯0→Λc+p¯φ)

We study the rare B meson decays B±,0→J/ψK+K-K±,0, B±,0→J/ψφK±,0, and search for B0→J/ψφ, using 469×106 BB¯ events collected at the γ(4S) resonance with the BABAR detector at the PEP-II e+e- asymmetric energy collider. We present new measurements of branching fractions and a study of the J/ψφ mass distribution in search of new charmonium-like states. In addition, we search for the decay B0→J/ψφ and find no evidence of a signal.

We study the rare B meson decays B±,0→J/ψK+K-K±,0, B±,0→J/ψφK±,0, and search for B0→J/ψφ, using 469×106 BB¯ events collected at the γ(4S) resonance with the BABAR detector at the PEP-II e+e- asymmetric energy collider. We present new measurements of branching fractions and a study of the J/ψφ mass distribution in search of new charmonium-like states. In addition, we search for the decay B0→J/ψφ and find no evidence of a signal.

We use (121±1) million Υ(3S) and (98±1) million Υ(2S) mesons recorded by the BABAR detector at the PEP-II e+e- collider at SLAC to perform a study of radiative transitions involving the χbJ(1P,2P) states in exclusive decays with μ+μ-γγ final states. We reconstruct twelve channels in four cascades using two complementary methods. In the first we identify both signal photon candidates in the electromagnetic calorimeter (EMC), employ a calorimeter timing-based technique to reduce backgrounds, and determine branching-ratio products and fine mass splittings. These results include the best observational significance yet for the χb0(2P)→γΥ(2S) and χb0(1P)→γΥ(1S) transitions. In the second method, we identify one photon candidate in the EMC and one which has converted into an e+e- pair due to interaction with detector material, and we measure absolute product branching fractions. This method is particularly useful for measuring Υ(3S)→γχb1,2(1P) decays. Additionally, we provide the most up-to-date derived branching fractions, matrix elements and mass splittings for χb transitions in the bottomonium system. Using a new technique, we also measure the two lowest-order spin-dependent coefficients in the nonrelativistic QCD Hamiltonian.

We report on a search in e+e- annihilations for new π0-like particles produced in association with a τ-lepton pair. These objects, with a similar mass and similar decay modes to π0 mesons, could provide an explanation for the non-asymptotic behavior of the pion-photon transition form factor observed by the BABAR Collaboration. No significant signal is observed, and limits on the production cross section at the level of 73 fb or 370 fb, depending on the model parameters, are determined at 90% confidence level. These upper limits lie below the cross section values needed to explain the BABAR form factor data.

We use (121±1) million Υ(3S) and (98±1) million Υ(2S) mesons recorded by the BABAR detector at the PEP-II e+e- collider at SLAC to perform a study of radiative transitions involving the χbJ(1P,2P) states in exclusive decays with μ+μ-γγ final states. We reconstruct twelve channels in four cascades using two complementary methods. In the first we identify both signal photon candidates in the electromagnetic calorimeter (EMC), employ a calorimeter timing-based technique to reduce backgrounds, and determine branching-ratio products and fine mass splittings. These results include the best observational significance yet for the χb0(2P)→γΥ(2S) and χb0(1P)→γΥ(1S) transitions. In the second method, we identify one photon candidate in the EMC and one which has converted into an e+e- pair due to interaction with detector material, and we measure absolute product branching fractions. This method is particularly useful for measuring Υ(3S)→γχb1,2(1P) decays. Additionally, we provide the most up-to-date derived branching fractions, matrix elements and mass splittings for χb transitions in the bottomonium system. Using a new technique, we also measure the two lowest-order spin-dependent coefficients in the nonrelativistic QCD Hamiltonian.

We measure the direct CP violation asymmetry, ACP, in B→Xsγ and the isospin difference of the asymmetry, ΔACP, using 429fb-1 of data collected at(4S) resonance with the BABAR detector at the PEP-II asymmetric-energy e+e- storage rings operating at the SLAC National Accelerator Laboratory. B mesons are reconstructed from ten charged B final states and six neutral B final states. We find ACP=+(1.7±1.9±1.0)%, which is in agreement with the Standard Model prediction and provides an improvement on the world average. Moreover, we report the first measurement of the difference between ACP for charged and neutral decay modes, ΔACP=+(5.0±3.9±1.5)%. Using the value of ΔACP, we also provide 68% and 90% confidence intervals on the imaginary part of the ratio of the Wilson coefficients corresponding to the chromomagnetic dipole and the electromagnetic dipole transitions.

We measure the direct CP violation asymmetry, ACP, in B→Xsγ and the isospin difference of the asymmetry, ΔACP, using 429fb-1 of data collected at(4S) resonance with the BABAR detector at the PEP-II asymmetric-energy e+e- storage rings operating at the SLAC National Accelerator Laboratory. B mesons are reconstructed from ten charged B final states and six neutral B final states. We find ACP=+(1.7±1.9±1.0)%, which is in agreement with the Standard Model prediction and provides an improvement on the world average. Moreover, we report the first measurement of the difference between ACP for charged and neutral decay modes, ΔACP=+(5.0±3.9±1.5)%. Using the value of ΔACP, we also provide 68% and 90% confidence intervals on the imaginary part of the ratio of the Wilson coefficients corresponding to the chromomagnetic dipole and the electromagnetic dipole transitions.

UnlabelledPairing high-throughput sequencing technologies with high-throughput mutagenesis enables genome-wide investigations of pathogenic organisms. Knowledge of the specific functions of protein domains encoded by the genome of the hepatitis C virus (HCV), a major human pathogen that contributes to liver disease worldwide, remains limited to insight from small-scale studies. To enhance the capabilities of HCV researchers, we have obtained a high-resolution functional map of the entire viral genome by combining transposon-based insertional mutagenesis with next-generation sequencing. We generated a library of 8,398 mutagenized HCV clones, each containing one 15-nucleotide sequence inserted at a unique genomic position. We passaged this library in hepatic cells, recovered virus pools, and simultaneously assayed the abundance of mutant viruses in each pool by next-generation sequencing. To illustrate the validity of the functional profile, we compared the genetic footprints of viral proteins with previously solved protein structures. Moreover, we show the utility of these genetic footprints in the identification of candidate regions for epitope tag insertion. In a second application, we screened the genetic footprints for phenotypes that reflected defects in later steps of the viral life cycle. We confirmed that viruses with insertions in a region of the nonstructural protein NS4B had a defect in infectivity while maintaining genome replication. Overall, our genome-wide HCV mutant library and the genetic footprints obtained by high-resolution profiling represent valuable new resources for the research community that can direct the attention of investigators toward unidentified roles of individual protein domains.ImportanceOur insertional mutagenesis library provides a resource that illustrates the effects of relatively small insertions on local protein structure and HCV viability. We have also generated complementary resources, including a website (http://hangfei.bol.ucla.edu) and a panel of epitope-tagged mutant viruses that should enhance the research capabilities of investigators studying HCV. Researchers can now detect epitope-tagged viral proteins by established antibodies, which will allow biochemical studies of HCV proteins for which antibodies are not readily available. Furthermore, researchers can now quickly look up genotype-phenotype relationships and base further mechanistic studies on the residue-by-residue information from the functional profile. More broadly, this approach offers a general strategy for the systematic functional characterization of viruses on the genome scale.

We analyze Mg II λλ2796, 2803 and Fe II λλ2586, 2600 absorption profiles in individual spectra of 105 galaxies at 0.3 < z < 1.4. The galaxies, drawn from redshift surveys of the GOODS fields and the Extended Groth Strip, sample the range in star formation rates (SFRs) occupied by the star-forming sequence with stellar masses log M ∗/M ≳ 9.6 down to SFR ≳ 2 M yr-1 at 0.3 < z < 0.7. Using the Doppler shifts of Mg II and Fe II absorption as tracers of cool gas kinematics, we detect large-scale winds in 66 ± 5% of the galaxies. Hubble Space Telescope Advanced Camera for Surveys imaging and our spectral analysis indicate that the outflow detection rate depends primarily on galaxy orientation: winds are detected in ∼89% of galaxies having inclinations (i) 50° (edge-on). Combined with the comparatively weak dependence of wind detection rate on intrinsic galaxy properties, this implies that biconical outflows are ubiquitous in normal, star-forming galaxies at z ∼ 0.5. We find that wind velocity is correlated with galaxy M ∗ at 3.4σ significance, while outflow equivalent width is correlated with SFR at 3.5σ significance, suggesting hosts with higher SFR launch more material and/or generate a larger velocity spread for the absorbing clouds. Assuming the gas is driven into halos with isothermal density profiles, the wind velocities (∼200-400 km s-1) permit escape from the halo potentials only for the lowest-M ∗ systems in the sample. However, the gas carries sufficient energy to reach distances ≳ 50 kpc, and may therefore be a viable source of material for the massive, cool circumgalactic medium around bright galaxies at z ∼ 0.

We present measurements of Collins asymmetries in the inclusive process e+e-→ππX, where π stands for charged pions, at a center-of-mass energy of 10.6 GeV. We use a data sample of 468fb-1 collected by the BABAR experiment at the PEP-II B factory at SLAC, and consider pairs of charged pions produced in opposite hemispheres of hadronic events. We observe clear asymmetries in the distributions of the azimuthal angles in two distinct reference frames. We study the dependence of the asymmetry on several kinematic variables, finding that it increases with increasing pion momentum and momentum transverse to the analysis axis, and with increasing angle between the thrust and beam axis.

Microvilli are membrane extensions on the apical surface of polarized epithelia, such as intestinal enterocytes and tubule and duct epithelia. One notable exception in mucosal epithelia is M cells, which are specialized for capturing luminal microbial particles; M cells display a unique apical membrane lacking microvilli. Based on studies of M cell uptake under different ionic conditions, we hypothesized that microvilli may augment the mucosal barrier by providing an increased surface charge density from the increased membrane surface and associated glycoproteins. Thus, electrostatic charges may repel microbes from epithelial cells bearing microvilli, while M cells are more susceptible to microbial adhesion. To test the role of microvilli in bacterial adhesion and uptake, we developed polarized intestinal epithelial cells with reduced microvilli ("microvillus-minus," or MVM) but retaining normal tight junctions. When tested for interactions with microbial particles in suspension, MVM cells showed greatly enhanced adhesion and uptake of particles compared to microvillus-positive cells. This preference showed a linear relationship to bacterial surface charge, suggesting that microvilli resist binding of microbes by using electrostatic repulsion. Moreover, this predicts that pathogen modification of electrostatic forces may contribute directly to virulence. Accordingly, the effacement effector protein Tir from enterohemorrhagic Escherichia coli O157:H7 expressed in epithelial cells induced a loss of microvilli with consequent enhanced microbial binding. These results provide a new context for microvillus function in the host-pathogen relationship, based on electrostatic interactions.

We present measurements of the inclusive production of antideuterons in e+e- annihilation into hadrons at ≈10.58GeV center-of-mass energy and in (1S,2S,3S) decays. The results are obtained using data collected by the BABAR detector at the PEP-II electron-positron collider. Assuming a fireball spectral shape for the emitted antideuteron momentum, we find B((1S)→d̄X)=(2. 81±0.49(stat)-0.24+0.20(syst))×10-5, B((2S)→d̄X)=(2. 64±0.11(stat)-0.21+0.26(syst))×10-5, B((3S)→d̄X)=(2. 33±0.15(stat)-0.28+0.31(syst))×10-5, and σ(e+e- →d̄X)=(9.63±0.41(stat)-1.01+1.17(syst)fb. © 2014 American Physical Society.

We study the processes γγ→K+K-η and γγ→K+K-π0 using a data sample of 519fb-1 recorded with the BABAR detector operating at the SLAC PEP-II asymmetric-energy e+e- collider at center-of-mass energies at and near the (nS) (n=2,3,4) resonances. We observe ηc→K+K-π0 and ηc→K+K-η decays, measure their relative branching fraction, and perform a Dalitz plot analysis for each decay. We observe the K0*(1430)→Kη decay and measure its branching fraction relative to the Kπ decay mode to be R(K0*(1430))=B(K0*(1430) →Kη)B(K0*(1430)→Kπ)=0.092±0.025-0.025+0.010. The ηc→K+K-η and K0*(1430)→Kη results correspond to the first observations of these channels. The data also show evidence for ηc(2S)→K+K-π0 and first evidence for ηc(2S)→K+K-η. © 2014 American Physical Society.

Evidence is presented for the baryonic B meson decay B̄0→ D0ΛΛ̄ based on a data sample of 471×106 BB̄ pairs collected with the BABAR detector at the PEP-II asymmetric e+e- collider located at the SLAC National Accelerator Laboratory. The branching fraction is determined to be B(B̄0→D0ΛΛ̄)=(9.8-2.6+2. 9±1.9)×10-6, corresponding to a significance of 3.4 standard deviations including additive systematic uncertainties. A search for the related baryonic B meson decay B̄0→D0Σ0Λ̄ with Σ0→Λγ is performed and an upper limit B(B̄0→D0Σ0Λ̄+B̄0→D0ΛΣ̄0)

We study the processes γγ→K+K-η and γγ→K+K-π0 using a data sample of 519fb-1 recorded with the BABAR detector operating at the SLAC PEP-II asymmetric-energy e+e- collider at center-of-mass energies at and near the (nS) (n=2,3,4) resonances. We observe ηc→K+K-π0 and ηc→K+K-η decays, measure their relative branching fraction, and perform a Dalitz plot analysis for each decay. We observe the K0*(1430)→Kη decay and measure its branching fraction relative to the Kπ decay mode to be R(K0*(1430))=B(K0*(1430) →Kη)B(K0*(1430)→Kπ)=0.092±0.025-0.025+0.010. The ηc→K+K-η and K0*(1430)→Kη results correspond to the first observations of these channels. The data also show evidence for ηc(2S)→K+K-π0 and first evidence for ηc(2S)→K+K-η. © 2014 American Physical Society.

We present measurements of the inclusive production of antideuterons in e+e- annihilation into hadrons at ≈10.58GeV center-of-mass energy and in (1S,2S,3S) decays. The results are obtained using data collected by the BABAR detector at the PEP-II electron-positron collider. Assuming a fireball spectral shape for the emitted antideuteron momentum, we find B((1S)→d̄X)=(2. 81±0.49(stat)-0.24+0.20(syst))×10-5, B((2S)→d̄X)=(2. 64±0.11(stat)-0.21+0.26(syst))×10-5, B((3S)→d̄X)=(2. 33±0.15(stat)-0.28+0.31(syst))×10-5, and σ(e+e- →d̄X)=(9.63±0.41(stat)-1.01+1.17(syst)fb. © 2014 American Physical Society.

We study the processes e+e-→KS0KL0γ, KS0KL0π+π-γ, KS0KS0π+π-γ, and KS0KS0K+K-γ, where the photon is radiated from the initial state, providing cross section measurements for the hadronic states over a continuum of center-of-mass energies. The results are based on 469fb-1 of data collected with the BABAR detector at SLAC. We observe the φ(1020) resonance in the KS0KL0 final state and measure the product of its electronic width and branching fraction with about 3% uncertainty. We present a measurement of the e+e-→KS0KL0 cross section in the energy range from 1.06 to 2.2 GeV and observe the production of a resonance at 1.67 GeV. We present the first measurements of the e+e-→KS0KL0π+π-, KS0KS0π+π-, and KS0KS0K+K- cross sections and study the intermediate resonance structures. We obtain the first observations of J/ψ decay to the KS0KL0π+π-, KS0KS0π+π-, and KS0KS0K+K- final states. © 2014 American Physical Society.

We study the processes e+e-→KS0KL0γ, KS0KL0π+π-γ, KS0KS0π+π-γ, and KS0KS0K+K-γ, where the photon is radiated from the initial state, providing cross section measurements for the hadronic states over a continuum of center-of-mass energies. The results are based on 469fb-1 of data collected with the BABAR detector at SLAC. We observe the φ(1020) resonance in the KS0KL0 final state and measure the product of its electronic width and branching fraction with about 3% uncertainty. We present a measurement of the e+e-→KS0KL0 cross section in the energy range from 1.06 to 2.2 GeV and observe the production of a resonance at 1.67 GeV. We present the first measurements of the e+e-→KS0KL0π+π-, KS0KS0π+π-, and KS0KS0K+K- cross sections and study the intermediate resonance structures. We obtain the first observations of J/ψ decay to the KS0KL0π+π-, KS0KS0π+π-, and KS0KS0K+K- final states. © 2014 American Physical Society.

We report a search for the decay B̄0→Λc+p̄pp̄. Using a data sample of 471×106 BB̄ pairs collected with the BABAR detector at the PEP-II2 storage ring at SLAC, we find no events and set an upper limit on the branching fraction B(B̄0→Λc+p̄pp̄) ×B(Λc+→pK-π+)0.050

We describe searches for B meson decays to the charmless vector-vector final states ωω and ωφ with 471×106BB̄ pairs produced in e+e- annihilation at s=10.58GeV using the BABAR detector at the PEP-II collider at the SLAC National Accelerator Laboratory. We measure the branching fraction B(B0→ωω)=(1.2±0.3-0.2+0.3)×10- 6, where the first uncertainty is statistical and the second is systematic, corresponding to a significance of 4.4 standard deviations. We also determine the upper limit B(B0→ωφ)