The New Fat Higgs: Slimmer and More Attractive

In this paper we increase the MSSM tree level higgs mass bound to a value that is naturally larger than the LEP-II search constraint by adding to the superpotential a $\lambda S H_{u}H_{d}$ term, as in the NMSSM, and UV completing with new strong dynamics {\it before} $\lambda$ becomes non-perturbative. Unlike other models of this type the higgs fields remain elementary, alleviating the supersymmetric fine-tuning problem while maintaining unification in a natural way.Comment: 14 pages and 2 figures. Added references and updated argument about constraints from reheating temperatur

Targeting EGF-receptor(s) - STAT1 axis attenuates tumor growth and metastasis through downregulation of MUC4 mucin in human pancreatic cancer.

Transmembrane proteins MUC4, EGFR and HER2 are shown to be critical in invasion and metastasis of pancreatic cancer. Besides, we and others have demonstrated de novo expression of MUC4 in ~70-90% of pancreatic cancer patients and its stabilizing effects on HER2 downstream signaling in pancreatic cancer. Here, we found that use of canertinib or afatinib resulted in reduction of MUC4 and abrogation of in vitro and in vivo oncogenic functions of MUC4 in pancreatic cancer cells. Notably, silencing of EGFR family member in pancreatic cancer cells decreased MUC4 expression through reduced phospho-STAT1. Furthermore, canertinib and afatinib treatment also inhibited proliferation, migration and survival of pancreatic cancer cells by attenuation of signaling events including pERK1/2 (T202/Y204), cyclin D1, cyclin A, pFAK (Y925) and pAKT (Ser473). Using in vivo bioluminescent imaging, we demonstrated that canertinib treatment significantly reduced tumor burden (P=0.0164) and metastasis to various organs. Further, reduced expression of MUC4 and EGFR family members were confirmed in xenografts. Our results for the first time demonstrated the targeting of EGFR family members along with MUC4 by using pan-EGFR inhibitors. In conclusion, our studies will enhance the translational acquaintance of pan-EGFR inhibitors for combinational therapies to combat against lethal pancreatic cancer

Suppressed supersymmetry breaking terms in the Higgs sector

We study the little hierarchy between mass parameters in the Higgs sector and other SUSY breaking masses. This type of spectrum can relieve the fine-tuning problem in the MSSM Higgs sector. Our scenario can be realized by superconformal dynamics. The spectrum in our scenario has significant implications in other phenomenological aspects like the relic abundance of the lightest neutralino and relaxation of the unbounded-from-below constraints.Comment: 14 pages, late

Impaired expression of protein phosphatase 2A subunits enhances metastatic potential of human prostate cancer cells through activation of AKT pathway.

BACKGROUND: Protein phosphatase 2A (PP2A) is a dephosphorylating enzyme, loss of which can contribute to prostate cancer (PCa) pathogenesis. The aim of this study was to analyse the transcriptional and translational expression patterns of individual subunits of the PP2A holoenzyme during PCa progression. METHODS: Immunohistochemistry (IHC), western blot, and real-time PCR was performed on androgen-dependent (AD) and androgen-independent (AI) PCa cells, and benign and malignant prostate tissues for all the three PP2A (scaffold, regulatory, and catalytic) subunits. Mechanistic and functional studies were performed using various biochemical and cellular techniques. RESULTS: Through immunohistochemical analysis we observed significantly reduced levels of PP2A-A and -B\u27γ subunits (P CONCLUSION: We conclude that loss of expression of scaffold and regulatory subunits of PP2A is responsible for its altered function during PCa pathogenesis

PR55α Regulatory Subunit of PP2A Inhibits the MOB1/LATS Cascade and Activates YAP in Pancreatic Cancer Cells

PP2A holoenzyme complexes are responsible for the majority of Ser/Thr phosphatase activities in human cells. Each PP2A consists of a catalytic subunit (C), a scaffold subunit (A), and a regulatory subunit (B). While the A and C subunits each exists only in two highly conserved isoforms, a large number of B subunits share no homology, which determines PP2A substrate specificity and cellular localization. It is anticipated that different PP2A holoenzymes play distinct roles in cellular signaling networks, whereas PP2A has only generally been defined as a putative tumor suppressor, which is mostly based on the loss-of-function studies using pharmacological or biological inhibitors for the highly conserved A or C subunit of PP2A. Recent studies of specific pathways indicate that some PP2A complexes also possess tumor-promoting functions. We have previously reported an essential role of PR55α, a PP2A regulatory subunit, in the support of oncogenic phenotypes, including in vivo tumorigenicity/metastasis of pancreatic cancer cells. In this report, we have elucidated a novel role of PR55α-regulated PP2A in the activation of YAP oncoprotein, whose function is required for anchorage-independent growth during oncogenesis of solid tumors. Our data show two lines of YAP regulation by PR55α: (1) PR55α inhibits the MOB1-triggered autoactivation of LATS1/2 kinases, the core member of the Hippo pathway that inhibits YAP by inducing its proteasomal degradation and cytoplasmic retention and (2) PR55α directly interacts with and regulates YAP itself. Accordingly, PR55α is essential for YAP-promoted gene transcriptions, as well as for anchorage-independent growth, in which YAP plays a key role. In summary, current findings demonstrate a novel YAP activation mechanism based on the PR55α-regulated PP2A phosphatase

The MSSM fine tuning problem: a way out

As is well known, electroweak breaking in the MSSM requires substantial fine-tuning, mainly due to the smallness of the tree-level Higgs quartic coupling, lambda_tree. Hence the fine tuning is efficiently reduced in supersymmetric models with larger lambda_tree, as happens naturally when the breaking of SUSY occurs at a low scale (not far from the TeV). We show, in general and with specific examples, that a dramatic improvement of the fine tuning (so that there is virtually no fine-tuning) is indeed a very common feature of these scenarios for wide ranges of tan(beta) and the Higgs mass (which can be as large as several hundred GeV if desired, but this is not necessary). The supersymmetric flavour problems are also drastically improved due to the absence of RG cross-talk between soft mass parameters.Comment: 28 pages, 9 PS figures, LaTeX Published versio

Accelerated Design of Block Copolymers: An Unbiased Exploration Strategy via Fusion of Molecular Dynamics Simulations and Machine Learning

Star block copolymers (s-BCPs) have potential applications as novel surfactants or amphiphiles for emulsification, compatbilization, chemical transformations and separations. s-BCPs are star-shaped macromolecules comprised of linear chains of different chemical blocks (e.g., solvophilic and solvophobic blocks) that are covalently joined at one junction point. Various parameters of these macromolecules can be tuned to obtain desired surface properties, including the number of arms, composition of the arms, and the degree-of-polymerization of the blocks (or the length of the arm). This makes identification of the optimal s-BCP design highly non-trivial as the total number of plausible s-BCPs architectures is experimentally or computationally intractable. In this work, we use molecular dynamics (MD) simulations coupled with reinforcement learning based Monte Carlo tree search (MCTS) to identify s-BCPs designs that minimize the interfacial tension between polar and non-polar solvents. We first validate the MCTS approach for design of small- and medium-sized s-BCPs, and then use it to efficiently identify sequences of copolymer blocks for large-sized s-BCPs. The structural origins of interfacial tension in these systems are also identified using the configurations obtained from MD simulations. Chemical insights on the arrangement of copolymer blocks that promote lower interfacial tension were mined using machine learning (ML) techniques. Overall, this work provides an efficient approach to solve design problems via fusion of simulations and ML and provide important groundwork for future experimental investigation of s-BCPs sequences for various applications

Comparison of the CDC Backpack aspirator and the Prokopack aspirator for sampling indoor- and outdoor-resting mosquitoes in southern Tanzania.

BACKGROUND\ud \ud Resting mosquitoes can easily be collected using an aspirating device. The most commonly used mechanical aspirator is the CDC Backpack aspirator. Recently, a simple, and low-cost aspirator called the Prokopack has been devised and proved to have comparable performance. The following study evaluates the Prokopack aspirator compared to the CDC backpack aspirator when sampling resting mosquitoes in rural Tanzania.\ud \ud METHODS\ud \ud Mosquitoes were sampled in- and outdoors of 48 typical rural African households using both aspirators. The aspirators were rotated between collectors and households in a randomized, Latin Square design. Outdoor collections were performed using artificial resting places (large barrel and car tyre), underneath the outdoor kitchen (kibanda) roof and from a drop-net. Data were analysed with generalized linear models.\ud \ud RESULTS\ud \ud The number of mosquitoes collected using the CDC Backpack and the Prokopack aspirator were not significantly different both in- and outdoors (indoors p = 0.735; large barrel p = 0.867; car tyre p = 0.418; kibanda p = 0.519). The Prokopack was superior for sampling of drop-nets due to its smaller size. The number mosquitoes collected per technician was more consistent when using the Prokopack aspirator. The Prokopack was more user-friendly: technicians preferred using the it over the CDC backpack aspirator as it weighs considerably less, retains its charge for longer and is easier to manoeuvre.\ud \ud CONCLUSIONS\ud \ud The Prokopack proved in the field to be more advantageous than the CDC Backpack aspirator. It can be self assembled using simple, low-cost and easily attainable materials. This device is a useful tool for researchers or vector-control surveillance programs operating in rural Africa, as it is far simpler and quicker than traditional means of sampling resting mosquitoes. Further longitudinal evaluations of the Prokopack aspirator versus the gold standard pyrethrum spray catch for indoor resting catches are recommended

Efficient Probabilistic Computing with Stochastic Perovskite Nickelates

Probabilistic computing has emerged as a viable approach to solve hard optimization problems. Devices with inherent stochasticity can greatly simplify their implementation in electronic hardware. Here, we demonstrate intrinsic stochastic resistance switching controlled via electric fields in perovskite nickelates doped with hydrogen. The ability of hydrogen ions to reside in various metastable configurations in the lattice leads to a distribution of transport gaps. With experimentally characterized p-bits, a shared-synapse p-bit architecture demonstrates highly-parallelized and energy-efficient solutions to optimization problems such as integer factorization and Boolean-satisfiability. The results introduce perovskite nickelates as scalable potential candidates for probabilistic computing and showcase the potential of light-element dopants in next-generation correlated semiconductors

Phenomenology of the nMSSM from colliders to cosmology

Low energy supersymmetric models provide a solution to the hierarchy problem and also have the necessary ingredients to solve two of the most outstanding issues in cosmology: the origin of dark matter and baryonic matter. One of the most attractive features of this framework is that the relevant physical processes are related to interactions at the weak scale and therefore may be tested in collider experiments in the near future. This is true for the Minimal Supersymmetric Standard Model (MSSM) as well as for its extension with the addition of one singlet chiral superfield, the so-called nMSSM. It has been recently shown that within the nMSSM an elegant solution to both the problem of baryogenesis and dark matter may be found, that relies mostly on the mixing of the singlet sector with the Higgs sector of the theory. In this work we review the nMSSM model constraints from cosmology and present the associated collider phenomenology at the LHC and the ILC. We show that the ILC will efficiently probe the neutralino, chargino and Higgs sectors, allowing to confront cosmological observations with computations based on collider measurements. We also investigate the prospects for a direct detection of dark matter and the constraints imposed by the current bounds of the electron electric dipole moment in this model.Comment: 44 pp, 10 figures; Fig.9 replaced; discussion on CP violation extended and references added; few minor additions in text about details of the cut