First Measurement of R(X_{τ/ℓ}) as an Inclusive Test of the b→cτν Anomaly.

We measure the tau-to-light-lepton ratio of inclusive B-meson branching fractions R(X_{τ/ℓ})≡B(B→Xτν)/B(B→Xℓν), where ℓ indicates an electron or muon, and thereby test the universality of charged-current weak interactions. We select events that have one fully reconstructed B meson and a charged lepton candidate from 189 fb^{-1} of electron-positron collision data collected with the Belle II detector. We find R(X_{τ/ℓ})=0.228±0.016(stat)±0.036(syst), in agreement with standard-model expectations. This is the first direct measurement of R(X_{τ/ℓ}).

Measurement of the Λ_{c}

An absolute measurement of the Λ_{c}^{+} lifetime is reported using Λ_{c}^{+}→pK^{-}π^{+} decays in events reconstructed from data collected by the Belle II experiment at the SuperKEKB asymmetric-energy electron-positron collider. The total integrated luminosity of the data sample, which was collected at center-of-mass energies at or near the ϒ(4S) resonance, is 207.2 fb^{-1}. The result, τ(Λ_{c}^{+})=203.20±0.89±0.77 fs, where the first uncertainty is statistical and the second systematic, is the most precise measurement to date and is consistent with previous determinations.

Search for a Dark Photon and an Invisible Dark Higgs Boson in µ

The dark photon A^{'} and the dark Higgs boson h^{'} are hypothetical particles predicted in many dark sector models. We search for the simultaneous production of A^{'} and h^{'} in the dark Higgsstrahlung process e^{+}e^{-}→A^{'}h^{'} with A^{'}→µ^{+}µ^{-} and h^{'} invisible in electron-positron collisions at a center-of-mass energy of 10.58 GeV in data collected by the Belle II experiment in 2019. With an integrated luminosity of 8.34 fb^{-1}, we observe no evidence for signal. We obtain exclusion limits at 90% Bayesian credibility in the range of 1.7-5.0 fb on the cross section and in the range of 1.7×10^{-8}-200×10^{-8} on the effective coupling ϵ^{2}×α_{D} for the A^{'} mass in the range of 4.0 GeV/c^{2}

Test of Light-Lepton Universality in the Rates of Inclusive Semileptonic B-Meson Decays at Belle II.

We present the first measurement of the ratio of branching fractions of inclusive semileptonic B-meson decays, R(X_{e/µ})=B(B→Xeν)/B(B→Xµν), a precision test of electron-muon universality, using data corresponding to 189 fb^{-1} from electron-positron collisions collected with the Belle II detector. In events where the partner B meson is fully reconstructed, we use fits to the lepton momentum spectra above 1.3 GeV/c to obtain R(X_{e/µ})=1.007±0.009(stat)±0.019(syst), which is the most precise lepton-universality test of its kind and agrees with the standard-model expectation.

Search for Lepton-Flavor-Violating τ Decays to a Lepton and an Invisible Boson at Belle II.

We search for lepton-flavor-violating τ^{-}→e^{-}α and τ^{-}→µ^{-}α decays, where α is an invisible spin-0 boson. The search uses electron-positron collisions at 10.58 GeV center-of-mass energy with an integrated luminosity of 62.8 fb^{-1}, produced by the SuperKEKB collider and collected with the Belle II detector. We search for an excess in the lepton-energy spectrum of the known τ^{-}→e^{-}ν[over ¯]_{e}ν_{τ} and τ^{-}→µ^{-}ν[over ¯]_{µ}ν_{τ} decays. We report 95% confidence-level upper limits on the branching-fraction ratio B(τ^{-}→e^{-}α)/B(τ^{-}→e^{-}ν[over ¯]_{e}ν_{τ}) in the range (1.1-9.7)×10^{-3} and on B(τ^{-}→µ^{-}α)/B(τ^{-}→µ^{-}ν[over ¯]_{µ}ν_{τ}) in the range (0.7-12.2)×10^{-3} for α masses between 0 and 1.6 GeV/c^{2}. These results provide the most stringent bounds on invisible boson production from τ decays.

Precise Measurement of the D_{s}

We measure the lifetime of the D_{s}^{+} meson using a data sample of 207 fb^{-1} collected by the Belle II experiment running at the SuperKEKB asymmetric-energy e^{+}e^{-} collider. The lifetime is determined by fitting the decay-time distribution of a sample of 116×10^{3} D_{s}^{+}→ϕπ^{+} decays. Our result is τ_{D_{s}^{+}}=(499.5±1.7±0.9) fs, where the first uncertainty is statistical and the second is systematic. This result is significantly more precise than previous measurements.

Tests of Light-Lepton Universality in Angular Asymmetries of B

We present the first comprehensive tests of the universality of the light leptons in the angular distributions of semileptonic B^{0}-meson decays to charged spin-1 charmed mesons. We measure five angular-asymmetry observables as functions of the decay recoil that are sensitive to lepton-universality-violating contributions. We use events where one neutral B is fully reconstructed in ϒ(4S)→BB[over ¯] decays in data corresponding to 189 fb^{-1} integrated luminosity from electron-positron collisions collected with the Belle II detector. We find no significant deviation from the standard model expectations.

Measurement of CP Violation in B

We report a measurement of the CP-violating parameters C and S in B^{0}→K_{S}^{0}π^{0} decays at Belle II using a sample of 387×10^{6} BB[over ¯] events recorded in e^{+}e^{-} collisions at a center-of-mass energy corresponding to the ϒ(4S) resonance. These parameters are determined by fitting the proper decay-time distribution of a sample of 415 signal events. We obtain C=-0.04_{-0.15}^{+0.14}±0.05 and S=0.75_{-0.23}^{+0.20}±0.04, where the first uncertainties are statistical and the second are systematic.

Search for a τ

We report the first search for a nonstandard-model resonance decaying into τ pairs in e^{+}e^{-}→µ^{+}µ^{-}τ^{+}τ^{-} events in the 3.6-10 GeV/c^{2} mass range. We use a 62.8 fb^{-1} sample of e^{+}e^{-} collisions collected at a center-of-mass energy of 10.58 GeV by the Belle II experiment at the SuperKEKB collider. The analysis probes three different models predicting a spin-1 particle coupling only to the heavier lepton families, a Higgs-like spin-0 particle that couples preferentially to charged leptons (leptophilic scalar), and an axionlike particle, respectively. We observe no evidence for a signal and set exclusion limits at 90% confidence level on the product of cross section and branching fraction into τ pairs, ranging from 0.7 to 24 fb, and on the couplings of these processes. We obtain world-leading constraints on the couplings for the leptophilic scalar model for masses above 6.5 GeV/c^{2} and for the axionlike particle model over the entire mass range.

Search for an Invisible Z

The L_{µ}-L_{τ} extension of the standard model predicts the existence of a lepton-flavor-universality-violating Z^{'} boson that couples only to the heavier lepton families. We search for such a Z^{'} through its invisible decay in the process e^{+}e^{-}→µ^{+}µ^{-}Z^{'}. We use a sample of electron-positron collisions at a center-of-mass energy of 10.58 GeV collected by the Belle II experiment in 2019-2020, corresponding to an integrated luminosity of 79.7 fb^{-1}. We find no excess over the expected standard-model background. We set 90%-confidence-level upper limits on the cross section for this process as well as on the coupling of the model, which ranges from 3×10^{-3} at low Z^{'} masses to 1 at Z^{'} masses of 8 GeV/c^{2}.

Search for B

A search for the flavor-changing neutral-current decay B^{+}→K^{+}νν[over ¯] is performed at the Belle II experiment at the SuperKEKB asymmetric energy electron-positron collider. The data sample corresponds to an integrated luminosity of 63 fb^{-1} collected at the ϒ(4S) resonance and a sample of 9 fb^{-1} collected at an energy 60 MeV below the resonance. Because the measurable decay signature involves only a single charged kaon, a novel measurement approach is used that exploits not only the properties of the B^{+}→K^{+}νν[over ¯] decay, but also the inclusive properties of the other B meson in the ϒ(4S)→BB[over ¯] event, to suppress the background from other B meson decays and light-quark pair production. This inclusive tagging approach offers a higher signal efficiency compared to previous searches. No significant signal is observed. An upper limit on the branching fraction of B^{+}→K^{+}νν[over ¯] of 4.1×10^{-5} is set at the 90% confidence level.

Precise Measurement of the D

We report a measurement of the D^{0} and D^{+} lifetimes using D^{0}→K^{-}π^{+} and D^{+}→K^{-}π^{+}π^{+} decays reconstructed in e^{+}e^{-}→cc[over ¯] data recorded by the Belle II experiment at the SuperKEKB asymmetric-energy e^{+}e^{-} collider. The data, collected at center-of-mass energies at or near the ϒ(4S) resonance, correspond to an integrated luminosity of 72 fb^{-1}. The results, τ(D^{0})=410.5±1.1(stat)±0.8(syst) fs and τ(D^{+})=1030.4±4.7(stat)±3.1(syst) fs, are the most precise to date and are consistent with previous determinations.

Genomic evaluation of regional dairy cattle breeds in single-breed and multibreed contexts.

An important prerequisite for high prediction accuracy in genomic prediction is the availability of a large training population, which allows accurate marker effect estimation. This requirement is not fulfilled in case of regional breeds with a limited number of breeding animals. We assessed the efficiency of the current French routine genomic evaluation procedure in four regional breeds (Abondance, Tarentaise, French Simmental and Vosgienne) as well as the potential benefits when the training populations consisting of males and females of these breeds are merged to form a multibreed training population. Genomic evaluation was 5-11% more accurate than a pedigree-based BLUP in three of the four breeds, while the numerically smallest breed showed a < 1% increase in accuracy. Multibreed genomic evaluation was beneficial for two breeds (Abondance and French Simmental) with maximum gains of 5 and 8% in correlation coefficients between yield deviations and genomic estimated breeding values, when compared to the single-breed genomic evaluation results. Inflation of genomic evaluation of young candidates was also reduced. Our results indicate that genomic selection can be effective in regional breeds as well. Here, we provide empirical evidence proving that genetic distance between breeds is only one of the factors affecting the efficiency of multibreed genomic evaluation.

Genetic tools to improve reproduction traits in dairy cattle.

Fertility is a major concern in the dairy cattle industry and has been the subject of numerous studies over the past 20 years. Surprisingly, most of these studies focused on rough female phenotypes and, despite their important role in reproductive success, male- and embryo-related traits have been poorly investigated. In recent years, the rapid and important evolution of technologies in genetic research has led to the development of genomic selection. The generalisation of this method in combination with the achievements of the AI industry have led to the constitution of large databases of genotyping and sequencing data, as well as refined phenotypes and pedigree records. These resources offer unprecedented opportunities in terms of fundamental and applied research. Here we present five such examples with a focus on reproduction-related traits: (1) detection of quantitative trait loci (QTL) for male fertility and semen quality traits; (2) detection of QTL for refined phenotypes associated with female fertility; (3) identification of recessive embryonic lethal mutations by depletion of homozygous haplotypes; (4) identification of recessive embryonic lethal mutations by mining whole-genome sequencing data; and (5) the contribution of high-density single nucleotide polymorphism chips, whole-genome sequencing and imputation to increasing the power of QTL detection methods and to the identification of causal variants.

HIV-1 Nef associated PAK and PI3-kinases stimulate Akt-independent Bad-phosphorylation to induce anti-apoptotic signals.

A highly conserved signaling property of Nef proteins encoded by human or simian immunodeficiency virus is the binding and activation of a PAK kinase whose function is unclear. Here we show that Nef-mediated p21-activated kinase (PAK) activation involves phosphatidylinositol 3-kinase, which acts upstream of PAK and is bound and activated by Nef similar to the manner of Polyoma virus middle T antigen. The Nef-associated phosphatidylinositol-3-PAK complex phosphorylated the pro-apoptotic Bad protein without involving the protein kinase B-Akt kinase, which is generally believed to inactivate Bad by serine phosphorylation. Consequently, Nef, but not a Nef mutant incapable of activating PAK, blocked apoptosis in T cells induced by serum starvation or HIV replication. Nef anti-apoptotic effects are likely a crucial mechanism for viral replication in the host and thus in AIDS pathogenesis.

Rare occurrence of classical Hodgkin's disease as a T cell lymphoma.

Recent work identified Hodgkin and Reed-Sternberg (H/RS) cells in classical Hodgkin's disease (cHD) as clonal progeny of mature B cells. Therefore, it is generally assumed that cHD homogenously represents a B cell lymphoma. In a subset of cHD, however, H/RS cells expressing T cell-associated proteins may be candidates for alternative lineage derivation. Single H/RS cells with cytotoxic T cell phenotype were micromanipulated from three cases of cHD and analyzed by single cell polymerase chain reaction for immunoglobulin heavy (IgH) and light chain (IgL) gene rearrangements, T cell receptor (TCR)-beta gene rearrangements, and germline configuration of the IgH and TCR-beta loci. H/RS cells from two cases of cHD harbored clonal, somatically mutated Ig gene rearrangements, whereas TCR-beta loci were in germline configuration. In contrast, H/RS cells from an additional case harbored clonal TCR-beta variable/diversity/joining (VDJ) and DJ gene rearrangements, whereas the IgH locus was in germline configuration on both alleles. Thus, in two cases of cHD with H/RS cells expressing cytotoxic T cell molecules, the tumor cells are derived from mature B cells that aberrantly express T cell markers. In a third case, however, H/RS cells were derived from a T cell, demonstrating that cHD can also occur as a T cell lymphoma.

Induction of Fas ligand expression by HIV involves the interaction of Nef with the T cell receptor zeta chain.

During HIV/SIV infection, there is widespread programmed cell death in infected and, perhaps more importantly, uninfected cells. Much of this apoptosis is mediated by Fas-Fas ligand (FasL) interactions. Previously we demonstrated in macaques that induction of FasL expression and apoptotic cell death of both CD4(+) and CD8(+) T cells by SIV is dependent on a functional nef gene. However, the molecular mechanism whereby HIV-1 induces the expression of FasL remained poorly understood. Here we report a direct association of HIV-1 Nef with the zeta chain of the T cell receptor (TCR) complex and the requirement of both proteins for HIV-mediated upregulation of FasL. Expression of FasL through Nef depended upon the integrity of the immunoreceptor tyrosine-based activation motifs (ITAMs) of the TCR zeta chain. Conformation for the importance of zeta for Nef-mediated signaling in T cells came from an independent finding. A single ITAM motif of zeta but not CD3epsilon was both required and sufficient to promote activation and binding of the Nef-associated kinase (NAK/p62). Our data imply that Nef can form a signaling complex with the TCR, which bypasses the requirement of antigen to initiate T cell activation and subsequently upregulation of FasL expression. Thus, our study may provide critical insights into the molecular mechanism whereby the HIV-1 accessory protein Nef contributes to the pathogenesis of HIV.

Prostate Cancer Nodal Staging: Using Deep Learning to Predict 68Ga-PSMA-Positivity from CT Imaging Alone.

Lymphatic spread determines treatment decisions in prostate cancer (PCa) patients. 68Ga-PSMA-PET/CT can be performed, although cost remains high and availability is limited. Therefore, computed tomography (CT) continues to be the most used modality for PCa staging. We assessed if convolutional neural networks (CNNs) can be trained to determine 68Ga-PSMA-PET/CT-lymph node status from CT alone. In 549 patients with 68Ga-PSMA PET/CT imaging, 2616 lymph nodes were segmented. Using PET as a reference standard, three CNNs were trained. Training sets balanced for infiltration status, lymph node location and additionally, masked images, were used for training. CNNs were evaluated using a separate test set and performance was compared to radiologists' assessments and random forest classifiers. Heatmaps maps were used to identify the performance determining image regions. The CNNs performed with an Area-Under-the-Curve of 0.95 (status balanced) and 0.86 (location balanced, masked), compared to an AUC of 0.81 of experienced radiologists. Interestingly, CNNs used anatomical surroundings to increase their performance, "learning" the infiltration probabilities of anatomical locations. In conclusion, CNNs have the potential to build a well performing CT-based biomarker for lymph node metastases in PCa, with different types of class balancing strongly affecting CNN performance.

Contribution of promoter to tissue-specific expression of the mouse immunoglobulin kappa gene.

The immunoglobulin kappa (kappa) gene promoter was activated by a "neutral" enhancer derived from Harvey murine sarcoma virus (HaMuSV) in immunoglobulin-producing myeloma cells, regardless of the enhancer's orientation or position in the vector. In one fibroblast line (3T3) the immunoglobulin kappa gene promoter was completely inactive when linked to the HaMuSV enhancer, whereas in mouse L cells, promoter activity was observed only with the HaMuSV enhancer in tandem with the immunoglobulin kappa gene promoter. The differential behavior of the gene promoter, when activated by a neutral enhancer in these three murine cell lines, suggests that promoter sequences contribute to the tissue-specific expression of this gene.

Vaccination with a synthetic zona pellucida peptide produces long-term contraception in female mice.

The zona pellucida surrounding mouse oocytes is an extracellular matrix composed of three sulfated glycoproteins, ZP1, ZP2, and ZP3. It has been demonstrated that a monoclonal antibody to ZP3 injected into female mice inhibits fertilization by binding to the zona pellucida and blocking sperm penetration. A complementary DNA encoding ZP3 was randomly cleaved and 200- to 1000-base pair fragments were cloned into the expression vector lambda gt11. This epitope library was screened with the aforementioned contraceptive antibody, and the positive clones were used to map the seven-amino acid epitope recognized by the antibody. Female mice were immunized with a synthetic peptide containing this B cell epitope coupled to a carrier protein to provide helper T cell epitopes. The resultant circulating antibodies to ZP3 bound to the zona pellucida of immunized animals and produced long-lasting contraception. The lack of ovarian histopathology or cellular cytotoxicity among the immunized animals may be because of the absence of zona pellucida T cell epitopes in this vaccine.