We study chimera baryons, fermion bound states composed of two (hyper)quarks transforming in the fundamental and one in the antisymmetric representation of a non-Abelian gauge group. While in QCD they coincide with ordinary baryons, in composite Higgs models (CHMs) with top partial compositeness, spin-1/2 chimera baryons serve as partners of the top quark and are responsible for its large mass. We perform non-perturbative lattice calculations of the low-lying spectrum of the chimera baryons, in a specific realization of CHMs based on a Sp(4) gauge theory. In the quenched approximation, we present the numerical results in the continuum and massless limits. Then, for dynamical fermions, we measure the spectrum and matrix elements by employing a newly developed spectral density analysis for several choices of the lattice parameters.
The kaon physics programme, long heralded as a cutting-edge frontier by the European Strategy for Particle Physics, continues to stand at the intersection of discovery and innovation in high-energy physics (HEP). With its unparalleled capacity to explore new physics at the multi-TeV scale, kaon research is poised to unveil phenomena that could reshape our understanding of the Universe. This document highlights the compelling physics case, with emphasis on exciting new opportunities for advancing kaon physics not only in Europe but also on a global stage. As an important player in the future of HEP, the kaon programme promises to drive transformative breakthroughs, inviting exploration at the forefront of scientific discovery.
Spectral densities encode non-perturbative information crucial in computing physical observables in strongly coupled field theories. Using lattice gauge theory data, we perform a systematic study to demonstrate the potential of recent technological advances in the reconstruction of spectral densities. We develop, maintain and make publicly available dedicated analysis code that can be used for broad classes of lattice theories. As a test case, we analyse the Sp(4) gauge theory coupled to an admixture of fermions transforming in the fundamental and two-index antisymmetric representations. We measure the masses of mesons in energy-smeared spectral densities, after optimising the smearing parameters for available lattice ensembles. We present a summary of the mesons mass spectrum in all the twelve (flavored) channels available, including also several excited states.
Spectral densities encode nonperturbative information that enters the calculation of a plethora of physical observables in strongly coupled field theories. Phenomenological applications encompass aspects of standard-model hadronic physics, observable at current colliders, as well as correlation functions characterizing new physics proposals, testable in future experiments. By making use of numerical data produced in a Sp(4) lattice gauge theory with matter transforming in an admixture of fundamental and 2-index antisymmetric representations of the gauge group, we perform a systematic study to demonstrate the effectiveness of recent technological progress in the reconstruction of spectral densities.To this purpose, we write and test new software packages that use energy-smeared spectral densities to analyze the mass spectrum of mesons. We assess the effectiveness of different smearing kernels and optimize the smearing parameters to the characteristics of available lattice ensembles. For concreteness, we analyze the Sp(4) lattice gauge theory with matter transforming in an admixture of fundamental and 2-index antisymmetric representations of the gauge group. We generate new ensembles for the theory in consideration, with lattices that have a longer extent in the time direction with respect to the spatial ones. We run our tests on these ensembles, obtaining new results about the spectrum of light mesons and their excitations. We make available our algorithm and software for the extraction of spectral densities, that can be applied to theories with other gauge groups, including the theory of strong interactions (QCD) governing hadronic physics in the standard model.
Supplementary Figure 1. Liver expansion and regression during pregnancy and weaning suggest weaning-induced liver involution. Supplementary Figure 2. Cycle of ECM remodeling in the rodent liver across reproductive stages. Supplementary Figure 3. ECM remodeling during weaning-induced liver involution occurs in the absence of overt fibrosis. Supplementary Figure 4. Weaning-induced liver involution in the mouse. Supplementary Figure 5. Myeloid cell populations increase in abundance and form foci during weaning-induced liver involution in rodents. Supplementary Figure 6. Detection of liver metastases using multi-color immunofluorescence. Supplementary Figure 7. Weaning-induced liver involution supports increased seeding but not outgrowth compared to nulliparous and regressed livers.
We compute the standard Euclidean window of the hadronic vacuum polarization using multiple independent blinded analyses. We improve the continuum and infinite-volume extrapolations of the dominant quark-connected light-quark isospin-symmetric contribution and address additional sub-leading systematic effects from sea-charm quarks and residual chiral-symmetry breaking from first principles. We find $a_\mu^{\rm W} = 235.56(65)(50) \times 10^{-10}$, which is in $3.8\sigma$ tension with the recently published dispersive result of Colangelo et al., $a_\mu^{\rm W} = 229.4(1.4) \times 10^{-10}$, and in agreement with other recent lattice determinations. We also provide a result for the standard short-distance window. The results reported here are unchanged compared to our presentation at the Edinburgh workshop of the g-2 Theory Initiative in 2022.
Semileptonic Bs -Key decays provide an alternative b-decay channel to determine the Cabibbo-Kobayashi-Maskawa (CKM) matrix element IVubI and to obtain a R-ratio to investigate lepton-flavor -universality violations. Results for the CKM matrix element may also shed light on the discrepancies seen between analyses of inclusive or exclusive decays. We calculate the decay form factors using lattice QCD with domain-wall light quarks and a relativistic b-quark. We analyze data at three lattice spacings with unitary pion masses down to 268 MeV. Our numerical results are interpolated/extrapolated to physical quark masses and to the continuum to obtain the vector and scalar form factors f+(q2) and f0(q2) with full error budgets at q2 values spanning the range accessible in our simulations. We provide a possible explanation of tensions found between results for the form factor from different lattice collaborations. Model-and truncation-independent z-parametrization fits following a recently proposed Bayesian-inference approach extend our results to the entire allowed kinematic range. Our results can be combined with experimental measurements of Bs -Ds and Bs -K semileptonic decays to determine IVubI = 3.8(6) x 10-3. The error is currently dominated by experiment. We compute differential branching fractions and two types of R ratios, the one commonly used as well as a variant better suited to test lepton -flavor universality.
We report the first calculation using physical light-quark masses of the electromagnetic form factor V(z) describing the long-distance contributions to the K+ -> pi+e+e- decay amplitude. The calculation is performed on a 2 + 1 flavor domain wall fermion ensemble with inverse lattice spacing a-1 = 1.730(4) GeV. We implement a Glashow-Iliopoulos-Maiani cancellation by extrapolating to the physical charm-quark mass from three below-charm masses. We obtain V(z = 0.013(2)) = -0.87(4.44), achieving a bound for the value. The large statistical error arises from stochastically estimated quark loops.
Semileptonic B_s → K ℓν decays provide an alternative b-decay channel to determine the CKM matrix element |V_ub|, and to obtain a R-ratio to investigate lepton-flavor-universality violations. Results for the CKM matrix element may also shed light on the discrepancies seen between analyses of inclusive or exclusive decays. We calculate the decay form factors using lattice QCD with domain-wall light quarks and a relativistic b-quark. We analyze data at three lattice spacings with unitary pion masses down to 268 MeV. Our numerical results are interpolated/extrapolated to physical quark masses and to the continuum to obtain the vector and scalar form factors f_+(q^2) and f_0(q^2) with full error budgets at q^2 values spanning the range accessible in our simulations. We provide a possible explanation of tensions found between results for the form factor from different lattice collaborations. Model- and truncation-independent z-parameterization fits following a recently proposed Bayesian-inference approach extend our results to the entire allowed kinematic range. Our results can be combined with experimental measurements of B_s → D_s and B_s→ K semileptonic decays to determine |V_ub|=3.8(6)× 10^-3. The error is currently dominated by experiment. We compute differential branching fractions and two types of R ratios, the one commonly used as well as a variant better suited to test lepton-flavor universality.
We report the first calculation using physical light-quark masses of the electromagnetic form factor $V(z)$ describing the long-distance contributions to the $K^+\to\pi^+\ell^+\ell^-$ decay amplitude. The calculation is performed on a 2+1 flavor domain wall fermion ensemble with inverse lattice spacing $a^{-1}=1.730(4)$GeV. We implement a Glashow-Iliopoulos-Maiani cancellation by extrapolating to the physical charm-quark mass from three below-charm masses. We obtain $V(z=0.013(2))=-0.87(4.44)$, achieving a bound for the value. The large statistical error arises from stochastically estimated quark loops.
Objective: There is a dire need for a heart valve that can grow with children. We fabricated tubes of biologically-engineered matrix that have been shown to regenerate and grow as a pulmonary artery replacement in lambs, and implemented a novel design for a valved conduit made from sewing three of these tubes together with degradable suture that confers valve growth potential. The study was to assess valve function and growth potential over a one-year period in the lamb model.Methods: Seven lambs were implanted with tri-tube valved conduits in sequential cohorts and compared to bioprosthetic conduits using longitudinal echocardiography and histological and mechanical characterization post-explantation.Results: Valves implanted in two lambs of the first cohort of four animals functioned with only mild regurgitation and systolic pressure drops <10 mmHg up to 52 weeks post-implantation, during which the valve diameter increased from 19 mm to a normal ~25 mm. In a second cohort of three animals, an additional tube was used to create a sleeve around the tri-tube valve to counteract faster root growth relative to the leaflets. Two valves exhibited only trivial-to-mild regurgitation at 52-weeks with similar diameter increase and systolic pressure drops of < 5 mm Hg. The same was true for the third animal until moderate regurgitation at 52 weeks correlating to hyper-increase of the valve diameter. In all explanted valves, the leaflets remained thin and pliable with only sparse, punctate microcalcification at most, and they contained interstitial cells and an endothelium progressing from the base of the leaflets.Conclusions: These results are demonstrably improved in terms of calcification and hemodynamic function compared to reported studies for clinically-used pediatric bioprosthetic valves tested in the same model. The results demonstrate the potential for long-term valve growth of this "off-the-shelf" tri-tube valved conduit in children.
Suppressive effects of extracellular matrix (ECM) upon various cancers have been reported. Glioblastoma multiforme has poor prognosis and new therapies are desired. This work investigated the effects of a saline-soluble fraction of urinary bladder ECM (ECM-SF) upon glioma cells. Viability at 24 hours in 1, 5, or 10 mg/mL ECM-SF-spiked media was evaluated in primary glioma cells (0319, 1015, 1119), glioma cell lines (A172, T98G, U87MG, C6), and brain cell lines (HCN-2, HMC3). Viability universally decreased at 5 and 10 mg/mL with U87MG, HCN-2, and HCM3 being least sensitive. Apoptosis in 0319 and 1119 cells was confirmed via NucView 488. Bi-weekly intravenous injection of ECM-SF (120 mg/kg) for 10 weeks in Sprague-Dawley rats did not affect weight, temperature, complete blood count, or multi-organ histology (N = 5). Intratumoral injection of ECM-SF (10 uL of 30 mg/mL) at weeks 2-4 post C6 inoculation in Wistar rats increased median survival from 24.5 to 51 days (hazard ratio for death 0.22) and decreased average tumor volume at time of death from 349 mm3 to 90 mm3 over 10 weeks (N = 6). Mass spectrometry identified 2,562 protein species in ECM-SF, parent ECM, and originating tissue. These results demonstrate the suppressive effects of ECM on glioma and warrant further study.
Congenital heart defects are the leading cause of right heart failure in pediatric patients. Implantation of c-kit+ cardiac-derived progenitor cells (CPCs) is being clinically evaluated to treat the failing right ventricle (RV), but faces limitations due to reduced transplant cell survival, low engraftment rates, and low retention. These limitations have been exacerbated due to the nature of cell delivery (narrow needles) and the non-optimal recipient microenvironment (reactive oxygen species (ROS)). Extracellular matrix (ECM) hydrogels derived from porcine left ventricular (LV) myocardium have emerged as a potential therapy to treat the ischemic LV and have shown promise as a vehicle to deliver cells to injured myocardium. However, no studies have evaluated the combination of an injectable biomaterial, such as an ECM hydrogel, in combination with cell therapy for treating RV failure. In this study we characterized LV and RV myocardial matrix (MM) hydrogels and performed in vitro evaluations of their potential to enhance CPC delivery, including resistance to forces experienced during injection and exposure to ROS, as well as their potential to enhance angiogenic paracrine signaling. While physical properties of the two hydrogels are similar, the decellularized LV and RV have distinct protein signatures. Both materials were equally effective in protecting CPCs against needle forces and ROS. CPCs encapsulated in either the LV MM or RV MM exhibited similar enhanced potential for angiogenic paracrine signaling when compared to CPCs in collagen. The RV MM without cells, however, likewise improved tube formation, suggesting it should also be evaluated as a potential standalone treatment.
Jonathan Flynn,a,b,∗ Ryan Hill,a,c,∗ Andreas Jüttner, Amarjit Soni, J Tobias Tsang f and Oliver Witzel Physics & Astronomy, University of Southampton, Southampton, SO17 1BJ, UK STAG Research Centre, University of Southampton, Southampton SO17 1BJ, UK DISCnet Centre for Doctoral Training, University of Southampton, Southampton SO17 1BJ, UK CERN TH Division, 1211 Genève 23, Switzerland Physics Department, Brookhaven National Laboratory, Upton, NY 11973, USA f CP3-Origins and IMADA, University of Southern Denmark, Campusvej 55, 5230 Odense M, Denmark Center for Particle Physics Siegen, Theoretische Physik 1, Naturwissenschaftlich-Technische Fakultät, Universität Siegen, 57068 Siegen, Germany E-mail: j.m.flynn@soton.ac.uk, r.c.hill@soton.ac.uk
While most bones fully self-heal, certain diseases require bone allograft to assist with fracture healing. Bone allografts offer promise as treatments for such fractures due to their osteogenic properties. However, current bone allografts made of decellularized bone extracellular matrix (ECM) have high failure rates, and thus grafts which improve fracture healing outcomes are needed. Understanding specific changes to the ECM proteome during normal fracture healing would enable the identification of key proteins that could be used enhance osteogenicity of bone allograft. Here, we performed a timeseries analysis of the fracture callus in mice to investigate proteomic and mineralization changes to the ECM at key stages of fracture healing. We found that changes to the ECM proteome largely coincide with the distinct phases of fracture healing. Basement membrane proteins (AGRN, COL4, LAMA), cartilage proteins (COL2A1, ACAN), and collagen crosslinking enzymes (LOXL, PLOD, ITIH) were initially upregulated, followed by bone specific proteoglycans and collagens (IBSP, COL1A1). Various tissue proteases (MMP2, 9, 13, 14; CTSK, CTSG, ELANE) were expressed at different levels throughout fracture healing. These changes coordinated with mineralization of the fracture callus, which increased steeply during the initial stages of healing. Interestingly the later timepoint was characterized by a response to wound healing and high expression of clotting factors (F2, 7, 9, 10). We identified ELANE and ITIH2 as tissue remodeling enzymes having no prior known involvement with fracture healing. This data can be further mined to identify regenerative proteins for enhanced bone graft design.
Lattice quantum chromodynamics has proven to be an indispensable method to determine nonperturbative strong contributions to weak decay processes. In this white paper for the Snowmass community planning process we highlight achievements and future avenues of research for lattice calculations of weak $b$ and $c$ quark decays, and point out how these calculations will help to address the anomalies currently in the spotlight of the particle physics community. With future increases in computational resources and algorithmic improvements, percent level (and below) lattice determinations will play a central role in constraining the standard model or identifying new physics.
As the native regenerative potential of adult cardiac tissue is limited post-injury, stimulating endogenous repair mechanisms in the mammalian myocardium is a potential goal of regenerative medicine therapeutics. Injection of myocardial matrix hydrogels into the heart post-myocardial infarction (MI) has demonstrated increased cardiac muscle and promotion of pathways associated with cardiac development, suggesting potential promotion of cardiomyocyte turnover. In this study, the myocardial matrix hydrogel was shown to have native capability as an effective reactive oxygen species scavenger and protect against oxidative stress induced cell cycle inhibition in vitro. Encapsulation of cardiomyocytes demonstrated an enhanced turnover in in vitro studies, and in vivo assessments of myocardial matrix hydrogel treatment post-MI showed increased thymidine analog uptake in cardiomyocyte nuclei compared to saline controls. Overall, this study provides evidence that properties of the myocardial matrix material provide a microenvironment mitigating oxidative damage and supportive of cardiomyocytes undergoing DNA synthesis, toward possible DNA repair or cell cycle activation. STATEMENT OF SIGNIFICANCE: Loss of adult mammalian cardiomyocyte turnover is influenced by shifts in oxidative damage, which represents a potential mechanism for improving restoration of cardiac muscle after myocardial infarction (MI). Injection of a myocardial matrix hydrogel into the heart post-MI previously demonstrated increased cardiac muscle and promotion of pathways associated with cardiac development, suggesting potential in promoting proliferation of cardiomyocytes. In this study, the myocardial matrix hydrogel was shown to protect cells from oxidative stress and increase proliferation in vitro. In a rat MI model, greater presence of tissue free thiol content spared from oxidative damage, lesser mitochondrial superoxide content, and increased thymidine analog uptake in cardiomyocytes was found in matrix injected animals compared to saline controls. Overall, this study provides evidence that properties of the myocardial matrix material provide a microenvironment supportive of cardiomyocytes undergoing DNA synthesis, toward possible DNA repair or cell cycle activation.