Electroweak Baryogenesis, Electric Dipole Moments, and Higgs Diphoton Decays

We study the viability of electroweak baryogenesis in a two Higgs doublet model scenario augmented by vector-like, electroweakly interacting fermions. Considering a limited, but illustrative region of the model parameter space, we obtain the observed cosmic baryon asymmetry while satisfying present constraints from the non-observation of the permanent electric dipole moment (EDM) of the electron and the combined ATLAS and CMS result for the Higgs boson diphoton decay rate. The observation of a non-zero electron EDM in a next generation experiment and/or the observation of an excess (over the Standard Model) of Higgs to diphoton events with the 14 TeV LHC run or a future $e^+e^-$ collider would be consistent with generation of the observed baryon asymmetry in this scenario.Comment: 22 pages, 3 figure

Indirect Detection Imprint of a CP Violating Dark Sector

We introduce a simple scenario involving fermionic dark matter ($\chi$) and singlet scalar mediators that may account for the Galactic Center GeV $\gamma$-ray excess while satisfying present direct detection constraints. CP-violation in the scalar potential leads to mixing between the Standard Model Higgs boson and the scalar singlet, resulting in three scalars $h_{1,2,3}$ of indefinite CP-transformation properties. This mixing enables s-wave $\chi{\bar\chi}$ annihilation into di-scalar states, followed by decays into four fermion final states. The observed $\gamma$-ray spectrum can be fitted while respecting present direct detection bounds and Higgs boson properties for $m_{\chi} = 60 \sim 80$ GeV, and $m_{h_3} \sim m_{\chi}$. Searches for the Higgs exotic decay channel $h_1 \to h_3 h_3$ at the 14 TeV LHC should be able to further probe the parameter region favored by the $\gamma$-ray excess.Comment: 18 pages, 13 figures, 1 tabl

Skeletal muscle as an experimental model of choice to study tissue aging and rejuvenation.

Skeletal muscle is among the most age-sensitive tissues in mammal organisms. Significant changes in its resident stem cells (i.e., satellite cells, SCs), differentiated cells (i.e., myofibers), and extracellular matrix cause a decline in tissue homeostasis, function, and regenerative capacity. Based on the conservation of aging across tissues and taking advantage of the relatively well-characterization of the myofibers and associated SCs, skeletal muscle emerged as an experimental system to study the decline in function and maintenance of old tissues and to explore rejuvenation strategies. In this review, we summarize the approaches for understanding the aging process and for assaying the success of rejuvenation that use skeletal muscle as the experimental system of choice. We further discuss (and exemplify with studies of skeletal muscle) how conflicting results might be due to variations in the techniques of stem cell isolation, differences in the assays of functional rejuvenation, or deciding on the numbers of replicates and experimental cohorts

Higgs vacuum stability, neutrino mass, and dark matter

Recent results from ATLAS and CMS point to a narrow range for the Higgs mass: M_H∈(124,126)  GeV. Given this range, a case may be made for new physics beyond the Standard Model (SM) because of the resultant vacuum stability problem, i.e., the SM Higgs quartic coupling may run to negative values at a scale below the Planck scale. We study representative minimal extensions of the SM that can keep the SM Higgs vacuum stable to the Planck scale by introducing new scalar or fermion interactions at the TeV scale while solving other phenomenological problems. In particular, we consider the type-II seesaw model, which is introduced to explain the nonzero Majorana masses of the active neutrinos. Similarly, we observe that if the stability of the SM Higgs vacuum is ensured by the running of the gauge sector couplings, then one may require a series of new electroweak multiplets, the neutral component of which can be a cold dark matter candidate. Stability may also point to a new U(1) gauge symmetry, in which the SM Higgs carries a nonzero charge

Through-wall Phased Array Imaging of Small Surface-Breaking Cracks

Accurate and reliable measurements of small surface-breaking cracks are becoming increasingly important in safety-critical components such as in nuclear power plants, because of the desire for increased operational lifetimes. With great coverage and low cost, the use of imaging to find and size surface-breaking cracks with data from ultrasonic phased arrays is becoming more attractive. For the phased array imaging, both the array configuration and the technique used to generate the images from the measurements are key factors in the image quality and sizing accuracy. Thus, the selection of a proper imaging technique is essential to ensure accurate results for a specific situation of inspection. Additionally, a particular challenge in imaging surface-breaking cracks using through-wall measurement so see cracks at the remote wall (backwall) is that the reflection from the backwall is very strong, often masking the presence of the defect itself; this presents a particular challenge to the imaging algorithms used to reconstruct an image. In this study, the performance of three algorithms, the Total Focusing Method (TFM), the Half-Skip TFM (HSTFM) and the Factorisation Method (FM) will be compared for surface-breaking cracks. These three imaging algorithms will be used on simulated and experimental array data. Their performances will be compared in both the accuracy of sizing the defects and the quality of the images produced

A chemical genetic approach reveals distinct EphB signaling mechanisms during brain development.

EphB receptor tyrosine kinases control multiple steps in nervous system development. However, it remains unclear whether EphBs regulate these different developmental processes directly or indirectly. In addition, given that EphBs signal through multiple mechanisms, it has been challenging to define which signaling functions of EphBs regulate particular developmental events. To address these issues, we engineered triple knock-in mice in which the kinase activity of three neuronally expressed EphBs can be rapidly, reversibly and specifically blocked. We found that the tyrosine kinase activity of EphBs was required for axon guidance in vivo. In contrast, EphB-mediated synaptogenesis occurred normally when the kinase activity of EphBs was inhibited, suggesting that EphBs mediate synapse development by an EphB tyrosine kinase-independent mechanism. Taken together, our data indicate that EphBs control axon guidance and synaptogenesis by distinct mechanisms and provide a new mouse model for dissecting EphB function in development and disease

Rejuvenation of brain, liver and muscle by simultaneous pharmacological modulation of two signaling determinants, that change in opposite directions with age.

We hypothesize that altered intensities of a few morphogenic pathways account for most/all the phenotypes of aging. Investigating this has revealed a novel approach to rejuvenate multiple mammalian tissues by defined pharmacology. Specifically, we pursued the simultaneous youthful in vivo calibration of two determinants: TGF-beta which activates ALK5/pSmad 2,3 and goes up with age, and oxytocin (OT) which activates MAPK and diminishes with age. The dose of Alk5 inhibitor (Alk5i) was reduced by 10-fold and the duration of treatment was shortened (to minimize overt skewing of cell-signaling pathways), yet the positive outcomes were broadened, as compared with our previous studies. Alk5i plus OT quickly and robustly enhanced neurogenesis, reduced neuro-inflammation, improved cognitive performance, and rejuvenated livers and muscle in old mice. Interestingly, the combination also diminished the numbers of cells that express the CDK inhibitor and marker of senescence p16 in vivo. Summarily, simultaneously re-normalizing two pathways that change with age in opposite ways (up vs. down) synergistically reverses multiple symptoms of aging

Disruption of mesoderm formation during cardiac differentiation due to developmental exposure to 13-cis-retinoic acid.

13-cis-retinoic acid (isotretinoin, INN) is an oral pharmaceutical drug used for the treatment of skin acne, and is also a known teratogen. In this study, the molecular mechanisms underlying INN-induced developmental toxicity during early cardiac differentiation were investigated using both human induced pluripotent stem cells (hiPSCs) and human embryonic stem cells (hESCs). Pre-exposure of hiPSCs and hESCs to a sublethal concentration of INN did not influence cell proliferation and pluripotency. However, mesodermal differentiation was disrupted when INN was included in the medium during differentiation. Transcriptomic profiling by RNA-seq revealed that INN exposure leads to aberrant expression of genes involved in several signaling pathways that control early mesoderm differentiation, such as TGF-beta signaling. In addition, genome-wide chromatin accessibility profiling by ATAC-seq suggested that INN-exposure leads to enhanced DNA-binding of specific transcription factors (TFs), including HNF1B, SOX10 and NFIC, often in close spatial proximity to genes that are dysregulated in response to INN treatment. Altogether, these results identify potential molecular mechanisms underlying INN-induced perturbation during mesodermal differentiation in the context of cardiac development. This study further highlights the utility of human stem cells as an alternative system for investigating congenital diseases of newborns that arise as a result of maternal drug exposure during pregnancy