14-3-3ζ Suppresses RANKL Signaling by Destabilizing TRAF6.

Macrophages are essential regulators of inflammation and bone loss. RANKL, a pro-inflammatory cytokine, is responsible for macrophage differentiation to osteoclasts and bone loss. We recently showed that 14-3-3ζ-knockout (YwhazKO) rats exhibit increased bone loss in the inflammatory arthritis model. 14-3-3ζ is a cytosolic adaptor protein that actively participates in many signaling transductions. However, the role of 14-3-3ζ in RANKL signaling or bone remodeling is unknown. We investigated how 14-3-3ζ affects osteoclast activity by evaluating its role in RANKL signaling. We utilized 14-3-3ζ-deficient primary bone marrow-derived macrophages (BMDMs) obtained from wildtype (Wt) and YwhazKO animals, and RAW cells generated using CRISPR-Cas9. Our results showed that 14-3-3ζ-deficient macrophages, upon RANKL stimulation, have bigger and stronger TRAP-positive multinucleated cells and increased bone resorption activity. The presence of 14-3-3ζ suppressed RANKL-induced MAPK and AKT phosphorylation, transcription factors (NFATC1 and p65) nuclear translocation, and subsequently, gene induction (Rank, Acp5, and Ctsk). Mechanistically, 14-3-3ζ interacts with TRAF6, an essential component of the RANKL receptor complex. Upon RANKL stimulation, 14-3-3ζ-TRAF6 interaction was increased, while RANK-TRAF6 interaction was decreased. Importantly, 14-3-3ζ supported TRAF6 ubiquitination and degradation by the proteasomal pathway, thus dampening the downstream RANKL signaling. Together, we show that 14-3-3ζ regulates TRAF6 levels to suppress inflammatory RANKL signaling and osteoclast activity. To the best of our knowledge, this is the first report on 14-3-3ζ regulation of RANKL signaling and osteoclast activation.

Observation of Seven Astrophysical Tau Neutrino Candidates with IceCube.

We report on a measurement of astrophysical tau neutrinos with 9.7 yr of IceCube data. Using convolutional neural networks trained on images derived from simulated events, seven candidate ν_{τ} events were found with visible energies ranging from roughly 20 TeV to 1 PeV and a median expected parent ν_{τ} energy of about 200 TeV. Considering backgrounds from astrophysical and atmospheric neutrinos, and muons from π^{±}/K^{±} decays in atmospheric air showers, we obtain a total estimated background of about 0.5 events, dominated by non-ν_{τ} astrophysical neutrinos. Thus, we rule out the absence of astrophysical ν_{τ} at the 5σ level. The measured astrophysical ν_{τ} flux is consistent with expectations based on previously published IceCube astrophysical neutrino flux measurements and neutrino oscillations.

Achieving Energy Efficiency and Impact of SAR in a WBAN Through Optimal Placement of the Relay Node.

Wireless Body Area Network (WBAN) is an emerging and promising specialized area in Wireless networks that deals with crucial health-related datasets. Unlike other wireless networks, as this type of network deals with medical facts, losing it is fatal. WBAN is a highly constrained network. Reducing energy consumption and enhancing lifetime are the two most important challenges of WBANs. One way to achieve these is by deploying relay nodes optimally in WBANs. Generally, a relay node is placed at the midpoint of the line joining the source and the destination (D) nodes. We show that such simplistic deployment of the relay nodes is not the optimal deployment, which can hamper the overall lifetime of WBANs. In this paper, we have investigated the best location to deploy a relay node on a human body. We assume that an adaptive decode and forward relay node (R) can move linearly between the source (S) and the destination (D) nodes. Moreover, the assumption is that a relay node can be deployed linearly and that the body part of a human is a flat surface and hard. We have investigated the most energy-efficient data payload size based on the optimally placed relay location. The impact of such a deployment on different system parameters, such as distance (d), payload (L), modulation scheme, specific absorption rate, and an end to end outage (O) are examined as well. It is observed that in every aspect optimal deployment of the relay node performs an important role to enhance the lifetime of wireless body area networks. Sometimes linear relay deployment is very difficult to implement, especially on the different body parts of the human body. To address these issues, we have examined the optimal region for the relay node based on a 3D non-linear system model. The paper provides guidance for both linear and non-linear relay deployment along with the optimal data payload size under various circumstances and also considered the impact of specific absorption rates on the human body.

Evidence for Nonlinear Gluon Effects in QCD and Their Mass Number Dependence at STAR.

The STAR Collaboration reports measurements of back-to-back azimuthal correlations of di-π^{0}s produced at forward pseudorapidities (2.6<η<4.0) in p+p, p+Al, and p+Au collisions at a center-of-mass energy of 200 GeV. We observe a clear suppression of the correlated yields of back-to-back π^{0} pairs in p+Al and p+Au collisions compared to the p+p data. The observed suppression of back-to-back pairs as a function of transverse momentum suggests nonlinear gluon dynamics arising at high parton densities. The larger suppression found in p+Au relative to p+Al collisions exhibits a dependence of the saturation scale Q_{s}^{2} on the mass number A. A linear scaling of the suppression with A^{1/3} is observed with a slope of -0.09±0.01.

Experimental demonstration of optical stochastic cooling.

Particle accelerators and storage rings have been transformative instruments of discovery, and, for many applications, innovations in particle-beam cooling have been a principal driver of that success1. Stochastic cooling (SC), one of the most important conceptual and technological advances in this area2-6, cools a beam through granular sampling and correction of its phase-space structure, thus bearing resemblance to a 'Maxwell's demon'. The extension of SC from the microwave regime up to optical frequencies and bandwidths has long been pursued, as it could increase the achievable cooling rates by three to four orders of magnitude and provide a powerful tool for future accelerators. First proposed nearly 30 years ago, optical stochastic cooling (OSC) replaces the conventional microwave elements of SC with optical-frequency analogues and is, in principle, compatible with any species of charged-particle beam7,8. Here we describe a demonstration of OSC in a proof-of-principle experiment at the Fermi National Accelerator Laboratory's Integrable Optics Test Accelerator9,10. The experiment used 100-MeV electrons and a non-amplified configuration of OSC with a radiation wavelength of 950 nm, and achieved strong, simultaneous cooling of the beam in all degrees of freedom. This realization of SC at optical frequencies serves as a foundation for more advanced experiments with high-gain optical amplification, and advances opportunities for future operational OSC systems with potential benefit to a broad user community in the accelerator-based sciences.

Fermi surface of the chiral topological semimetal PtGa.

PtGa is a topological semimetal with giant spin-split Fermi arcs. Here, we report on angular-dependent de Haas-van Alphen (dHvA) measurements combined with band-structure calculations to elucidate the details of the bulk Fermi surface of PtGa. The strong spin-orbit coupling leads to eight bands crossing the Fermi energy that form a multitude of Fermi surfaces with closed extremal orbits and results in very rich dHvA spectra. The large number of experimentally observed dHvA frequencies make the assignment to the equally large number of calculated dHvA orbits challenging. Nevertheless, we find consistency between experiment and calculations verifying the topological character with maximal Chern number of the spin-split Fermi surface.

Measurements of Proton High-Order Cumulants in sqrt[s_{NN}]=3 GeV Au+Au Collisions and Implications for the QCD Critical Point.

We report cumulants of the proton multiplicity distribution from dedicated fixed-target Au+Au collisions at sqrt[s_{NN}]=3.0 GeV, measured by the STAR experiment in the kinematic acceptance of rapidity (y) and transverse momentum (p_{T}) within -0.5

Measurements of _{Λ}

We report precision measurements of hypernuclei _{Λ}^{3}H and _{Λ}^{4}H lifetimes obtained from Au+Au collisions at sqrt[s_{NN}]=3.0 GeV and 7.2 GeV collected by the STAR experiment at the Relativistic Heavy Ion Collider, and the first measurement of _{Λ}^{3}H and _{Λ}^{4}H midrapidity yields in Au+Au collisions at sqrt[s_{NN}]=3.0 GeV. _{Λ}^{3}H and _{Λ}^{4}H, being the two simplest bound states composed of hyperons and nucleons, are cornerstones in the field of hypernuclear physics. Their lifetimes are measured to be 221±15(stat)±19(syst) ps for _{Λ}^{3}H and 218±6(stat)±13(syst) ps for _{Λ}^{4}H. The p_{T}-integrated yields of _{Λ}^{3}H and _{Λ}^{4}H are presented in different centrality and rapidity intervals. It is observed that the shape of the rapidity distribution of _{Λ}^{4}H is different for 0%-10% and 10%-50% centrality collisions. Thermal model calculations, using the canonical ensemble for strangeness, describes the _{Λ}^{3}H yield well, while underestimating the _{Λ}^{4}H yield. Transport models, combining baryonic mean-field and coalescence (jam) or utilizing dynamical cluster formation via baryonic interactions (phqmd) for light nuclei and hypernuclei production, approximately describe the measured _{Λ}^{3}H and _{Λ}^{4}H yields. Our measurements provide means to precisely assess our understanding of the fundamental baryonic interactions with strange quarks, which can impact our understanding of more complicated systems involving hyperons, such as the interior of neutron stars or exotic hypernuclei.

Probing the Gluonic Structure of the Deuteron with J/ψ Photoproduction in d+Au Ultraperipheral Collisions.

Understanding gluon density distributions and how they are modified in nuclei are among the most important goals in nuclear physics. In recent years, diffractive vector meson production measured in ultraperipheral collisions (UPCs) at heavy-ion colliders has provided a new tool for probing the gluon density. In this Letter, we report the first measurement of J/ψ photoproduction off the deuteron in UPCs at the center-of-mass energy sqrt[s_{NN}]=200 GeV in d+Au collisions. The differential cross section as a function of momentum transfer -t is measured. In addition, data with a neutron tagged in the deuteron-going zero-degree calorimeter is investigated for the first time, which is found to be consistent with the expectation of incoherent diffractive scattering at low momentum transfer. Theoretical predictions based on the color glass condensate saturation model and the leading twist approximation nuclear shadowing model are compared with the data quantitatively. A better agreement with the saturation model has been observed. With the current measurement, the results are found to be directly sensitive to the gluon density distribution of the deuteron and the deuteron breakup process, which provides insights into the nuclear gluonic structure.

Search for the Chiral Magnetic Effect via Charge-Dependent Azimuthal Correlations Relative to Spectator and Participant Planes in Au+Au Collisions at sqrt[s_{NN}]=200 GeV.

The chiral magnetic effect (CME) refers to charge separation along a strong magnetic field due to imbalanced chirality of quarks in local parity and charge-parity violating domains in quantum chromodynamics. The experimental measurement of the charge separation is made difficult by the presence of a major background from elliptic azimuthal anisotropy. This background and the CME signal have different sensitivities to the spectator and participant planes, and could thus be determined by measurements with respect to these planes. We report such measurements in Au+Au collisions at a nucleon-nucleon center-of-mass energy of 200 GeV at the Relativistic Heavy-Ion Collider. It is found that the charge separation, with the flow background removed, is consistent with zero in peripheral (large impact parameter) collisions. Some indication of finite CME signals is seen in midcentral (intermediate impact parameter) collisions. Significant residual background effects may, however, still be present.

Selective, Ultra-Sensitive, and Rapid Detection of Serotonin by Optimized ZnO Nanorod FET Biosensor.

BACKGROUND: Fluctuation in serotonin (5-HT) level is an essential manifestation of several neurological disorders. In view of such importance, it is necessary to monitor the levels of 5-HT with good sensitivity, selectivity, affordability and low response time. Zinc oxide (ZnO) based field effect transistors (FET) with attributes like minimized noise levels and large on-off ratio are regarded as emerging high performance biosensor platforms. However, their response is significantly non-linear and there has been no appreciable endeavor for improving the non-linearity. METHOD: In this paper, we have introduced embedded gate electrode encompassing the channel of the FET which improves the uniformity in electric field line distribution through the electrolyte and proportionately enhances the capture of target biomolecule at ultra-low concentrations, thereby increasing the linearity. Further, we have incorporated the optimized parameters of ZnO nanorods reported previously, for rapid and selective detection of 5-HT. RESULTS: It has been observed that the fabricated ZnO FET biosensor lowers the detection limit down to 0.1fM which is at least one order of magnitude lower than the existing reports. The sensor also has wide linear range from 0.1fM to 1nM with a detection time of about 20 minutes. CONCLUSION: The proposed zinc oxide nanorod-based sensor can be used as an excellent tool for future diagnosis of neurological disorders.

Expression profile, transcriptional and post-transcriptional regulation of genes involved in hydrogen sulphide metabolism connecting the balance between development and stress adaptation in plants: a data-mining bioinformatics approach.

Recent research focused on novel aspects of sulphur and sulphur-containing molecules in fundamental plant processes has highlighted the importance of these compounds. Currently, the focus has shifted to the efficacy of hydrogen sulphide (H2 S) as signalling compounds that regulate different development and stress mitigation in plants. Accordingly, we used an in silico approach to study the differential expression patterns of H2 S metabolic genes at different growth/development stages and their tissue-specific expression patterns under a range of abiotic stresses. Moreover, to understand the multilevel regulation of genes involved in H2 S metabolism, we performed computation-based promoter analysis, alternative splice variant analysis, prediction of putative miRNA targets and co-expression network analysis. Gene expression analysis suggests that H2 S biosynthesis is highly influenced by developmental and stress stimuli. The functional annotation of promoter structures reveales a wide range of plant hormone and stress responsive cis-regulatory elements (CREs) that regulate H2 S metabolism. Co-expression analysis suggested that genes involved in H2 S metabolism are also associated with different metabolic processes. In this data-mining study, the primary focus was to understand the genetic architecture governing pathways of H2 S metabolism in different cell compartments under various developmental and stress signalling cascades. The present study will help to understand the genetic architecture of H2 S metabolism via cysteine metabolism and the functional roles of these genes in development and stress tolerance mechanisms.

Collision-System and Beam-Energy Dependence of Anisotropic Flow Fluctuations.

Elliptic flow measurements from two-, four-, and six-particle correlations are used to investigate flow fluctuations in collisions of U+U at sqrt[s_{NN}]=193 GeV, Cu+Au at sqrt[s_{NN}]=200 GeV and Au+Au spanning the range sqrt[s_{NN}]=11.5-200 GeV. The measurements show a strong dependence of the flow fluctuations on collision centrality, a modest dependence on system size, and very little if any, dependence on particle species and beam energy. The results, when compared to similar LHC measurements, viscous hydrodynamic calculations, and trento model eccentricities, indicate that initial-state-driven fluctuations predominate the flow fluctuations generated in the collisions studied.

Erratum: Azimuthal Anisotropy of K_{S}

This corrects the article DOI: 10.1103/PhysRevLett.89.132301.

Erratum: Azimuthal Anisotropy at the Relativistic Heavy Ion Collider: The First and Fourth Harmonics [Phys. Rev. Lett. 92, 062301 (2004)].

This corrects the article DOI: 10.1103/PhysRevLett.92.062301.

Measurement of the Sixth-Order Cumulant of Net-Proton Multiplicity Distributions in Au+Au Collisions at sqrt[s_{NN}]=27, 54.4, and 200 GeV at RHIC.

According to first-principle lattice QCD calculations, the transition from quark-gluon plasma to hadronic matter is a smooth crossover in the region µ_{B}≤T_{c}. In this range the ratio, C_{6}/C_{2}, of net-baryon distributions are predicted to be negative. In this Letter, we report the first measurement of the midrapidity net-proton C_{6}/C_{2} from 27, 54.4, and 200 GeV Au+Au collisions at the Relativistic Heavy Ion Collider (RHIC). The dependence on collision centrality and kinematic acceptance in (p_{T}, y) are analyzed. While for 27 and 54.4 GeV collisions the C_{6}/C_{2} values are close to zero within uncertainties, it is observed that for 200 GeV collisions, the C_{6}/C_{2} ratio becomes progressively negative from peripheral to central collisions. Transport model calculations without critical dynamics predict mostly positive values except for the most central collisions within uncertainties. These observations seem to favor a smooth crossover in the high-energy nuclear collisions at top RHIC energy.

Intestinal microbiota and vaccine efficacy in children from resource poor settings - potential impact for the usefulness of probiotics?

Developing countries continue to contribute significantly to the global burden of childhood mortality due to infectious diseases. Infections leading to diseases like diarrhoea, pneumonia and meningitis account for millions of deaths annually. Most of these diseases are preventable by vaccination and therefore global vaccination rates have risen substantially with clear benefits. But paradoxically, the vaccines have demonstrated lower immunogenicity in developing countries as compared to their industrialised counterparts. Malnutrition in resource poor settings along with repeated polymicrobial infections at early age are some of the reasons for the differences in vaccine efficacy in different settings. Recent studies indicate that the gastrointestinal microbiota possibly influences maturation of immune system as well as vaccine efficacy. In this review we discuss evidences from in vitro, animal and human studies showing that probiotics can positively modulate gut microbiota composition and exert immunomodulatory effects on the host. We also discuss how they should be evaluated for their ability to improve vaccine performance especially in low resource settings.

Observation of giant spin-split Fermi-arc with maximal Chern number in the chiral topological semimetal PtGa.

Non-symmorphic chiral topological crystals host exotic multifold fermions, and their associated Fermi arcs helically wrap around and expand throughout the Brillouin zone between the high-symmetry center and surface-corner momenta. However, Fermi-arc splitting and realization of the theoretically proposed maximal Chern number rely heavily on the spin-orbit coupling (SOC) strength. In the present work, we investigate the topological states of a new chiral crystal, PtGa, which has the strongest SOC among all chiral crystals reported to date. With a comprehensive investigation using high-resolution angle-resolved photoemission spectroscopy, quantum-oscillation measurements, and state-of-the-art ab initio calculations, we report a giant SOC-induced splitting of both Fermi arcs and bulk states. Consequently, this study experimentally confirms the realization of a maximal Chern number equal to ±4 in multifold fermionic systems, thereby providing a platform to observe large-quantized photogalvanic currents in optical experiments.

Influence of family history on risk of second primary cancers and survival in patients with squamous cell skin cancer.

BACKGROUND: Patients with squamous cell skin cancer (SCC) have an excellent prognosis but second primary cancers (SPCs) weaken survival prospects. Family history is a known risk factor for cancer but whether it is a risk factor for SPC in patients with SCC is not known. OBJECTIVES: To quantify the risk of family history on SPCs in patients with SCC and estimate survival probabilities of patients with SPCs depending on family history. METHODS: With 13 945 histologically verified SCCs, relative risks (RRs) were estimated for family history using a generalized regression model. For survival analysis, hazard ratios (HRs) were assessed using a multivariable Cox proportional-hazards model. RESULTS: Family history of invasive SCC increased risk of second invasive SCC [RR = 42·92, 95% confidence interval (CI) 33·69-50·32] compared with risk without family history (RR 19·12, 95% CI 17·88-21·08). Family history of any nonskin cancer in invasive SCC increased risk of the same cancers to be diagnosed as SPC (RRFH = 1·48, 95% CI 1·35-1·61 vs. RRno FH = 1·40, 95% CI 1·32-1·48); significant increases were observed for seven different nonskin cancers. Most results were replicated for in situ SCC. SPC was deleterious for survival irrespective of family history; HR for patients with SPC was 4·28 (95% CI 3·83-4·72) vs. those without SPC (1·04). CONCLUSIONS: Family history of nonskin cancer was associated with approximately a doubling of risk for SPCs in patients with SCC. SPC increases the death rate in patients with SCC 3-4 times, irrespective of family history. Taking family history into account at SCC diagnosis may help prevention or early detection of SPCs. What's already known about this topic? Second primary cancers (SPCs) are frequently diagnosed in patients with invasive and in situ squamous cell carcinoma (SCC); some epidemiological studies suggest a link to immune dysfunction. Family history of cancer is a risk factor for practically all first primary cancers but whether it also influences risk of SPCs in patients with SCC is not known. The possible influence of family history on survival in patients with SCC remains to be established. Linked Comment: Youlden and Baade. Br J Dermatol 2020; 183:414-415.

First Observation of the Directed Flow of D

We report the first measurement of rapidity-odd directed flow (v_{1}) for D^{0} and D^{0}[over ¯] mesons at midrapidity (|y|<0.8) in Au+Au collisions at sqrt[s_{NN}]=200 GeV using the STAR detector at the Relativistic Heavy Ion Collider. In 10-80% Au+Au collisions, the slope of the v_{1} rapidity dependence (dv_{1}/dy), averaged over D^{0} and D^{0}[over ¯] mesons, is -0.080±0.017(stat)±0.016(syst) for transverse momentum p_{T} above 1.5 GeV/c. The absolute value of D^{0} meson dv_{1}/dy is about 25 times larger than that for charged kaons, with 3.4σ significance. These data give a unique insight into the initial tilt of the produced matter, and offer constraints on the geometric and transport parameters of the hot QCD medium created in relativistic heavy-ion collisions.