Exact Results and Holography of Wilson Loops in N=2 Superconformal (Quiver) Gauge Theories

Using localization, matrix model and saddle-point techniques, we determine exact behavior of circular Wilson loop in N=2 superconformal (quiver) gauge theories. Focusing at planar and large `t Hooft couling limits, we compare its asymptotic behavior with well-known exponential growth of Wilson loop in N=4 super Yang-Mills theory. For theory with gauge group SU(N) coupled to 2N fundamental hypermultiplets, we find that Wilson loop exhibits non-exponential growth -- at most, it can grow a power of `t Hooft coupling. For theory with gauge group SU(N) x SU(N) and bifundamental hypermultiplets, there are two Wilson loops associated with two gauge groups. We find Wilson loop in untwisted sector grows exponentially large as in N=4 super Yang-Mills theory. We then find Wilson loop in twisted sector exhibits non-analytic behavior with respect to difference of two `t Hooft coupling constants. By letting one gauge coupling constant hierarchically larger/smaller than the other, we show that Wilson loops in the second type theory interpolate to Wilson loop in the first type theory. We infer implications of these findings from holographic dual description in terms of minimal surface of dual string worldsheet. We suggest intuitive interpretation that in both type theories holographic dual background must involve string scale geometry even at planar and large `t Hooft coupling limit and that new results found in the gauge theory side are attributable to worldsheet instantons and infinite resummation therein. Our interpretation also indicate that holographic dual of these gauge theories is provided by certain non-critical string theories.Comment: 52 pages, 7 figures v2. more figures embedded v3. minor stylistic changes, v4. published versio

Revisiting Scalar and Pseudoscalar Couplings with Nucleons

Certain dark matter interactions with nuclei are mediated possibly by a scalar or pseudoscalar Higgs boson. The estimation of the corresponding cross sections requires a correct evaluation of the couplings between the scalar or pseudoscalar Higgs boson and the nucleons. Progress has been made in two aspects relevant to this study in the past few years. First, recent lattice calculations show that the strange-quark sigma term $\sigma_s$ and the strange-quark content in the nucleon are much smaller than what are expected previously. Second, lattice and model analyses imply sizable SU(3) breaking effects in the determination on the axial-vector coupling constant $g_A^8$ that in turn affect the extraction of the isosinglet coupling $g_A^0$ and the strange quark spin component $\Delta s$ from polarized deep inelastic scattering experiments. Based on these new developments, we re-evaluate the relevant nucleon matrix elements and compute the scalar and pseudoscalar couplings of the proton and neutron. We also find that the strange quark contribution in both types of couplings is smaller than previously thought.Comment: 17 pages, Sec. II is revised and the pion-nucleon sigma term extracted from the scattering data is discussed. Version to appear in JHE

Daily volume, intraday and overnight returns for volatility prediction: profitability or accuracy?

This article presents a comprehensive analysis of the relative ability of three information sets—daily trading volume, intraday returns and overnight returns—to predict equity volatility. We investigate the extent to which statistical accuracy of one-day-ahead forecasts translates into economic gains for technical traders. Various profitability criteria and utility-based switching fees indicate that the largest gains stem from combining historical daily returns with volume information. Using common statistical loss functions, the largest degree of predictive power is found instead in intraday returns. Our analysis thus reinforces the view that statistical significance does not have a direct mapping onto economic value. As a byproduct, we show that buying the stock when the forecasted volatility is extremely high appears largely profitable, suggesting a strong return-risk relationship in turbulent conditions

Behavior and Impact of Zirconium in the Soil–Plant System: Plant Uptake and Phytotoxicity

Because of the large number of sites they pollute, toxic metals that contaminate terrestrial ecosystems are increasingly of environmental and sanitary concern (Uzu et al. 2010, 2011; Shahid et al. 2011a, b, 2012a). Among such metals is zirconium (Zr), which has the atomic number 40 and is a transition metal that resembles titanium in physical and chemical properties (Zaccone et al. 2008). Zr is widely used in many chemical industry processes and in nuclear reactors (Sandoval et al. 2011; Kamal et al. 2011), owing to its useful properties like hardness, corrosion-resistance and permeable to neutrons (Mushtaq 2012). Hence, the recent increased use of Zr by industry, and the occurrence of the Chernobyl and Fukashima catastrophe have enhanced environmental levels in soil and waters (Yirchenko and Agapkina 1993; Mosulishvili et al. 1994 ; Kruglov et al. 1996)

GABAA receptors as molecular targets of general anesthetics: identification of binding sites provides clues to allosteric modulation

PurposeThe purpose of this review is to summarize current knowledge of detailed biochemical evidence for the role of γ-aminobutyric acid type A receptors (GABA(A)-Rs) in the mechanisms of general anesthesia.Principal findingsWith the knowledge that all general anesthetics positively modulate GABA(A)-R-mediated inhibitory transmission, site-directed mutagenesis comparing sequences of GABA(A)-R subunits of varying sensitivity led to identification of amino acid residues in the transmembrane domain that are critical for the drug actions in vitro. Using a photo incorporable analogue of the general anesthetic, R(+)etomidate, we identified two transmembrane amino acids that were affinity labelled in purified bovine brain GABA(A)-R. Homology protein structural modelling positions these two residues, αM1-11' and βM3-4', close to each other in a single type of intersubunit etomidate binding pocket at the β/α interface. This position would be appropriate for modulation of agonist channel gating. Overall, available information suggests that these two etomidate binding residues are allosterically coupled to sites of action of steroids, barbiturates, volatile agents, and propofol, but not alcohols. Residue α/βM2-15' is probably not a binding site but allosterically coupled to action of volatile agents, alcohols, and intravenous agents, and α/βM1-(-2') is coupled to action of intravenous agents.ConclusionsEstablishment of a coherent and consistent structural model of the GABA(A)-R lends support to the conclusion that general anesthetics can modulate function by binding to appropriate domains on the protein. Genetic engineering of mice with mutation in some of these GABA(A)-R residues are insensitive to general anesthetics in vivo, suggesting that further analysis of these domains could lead to development of more potent and specific drugs

Histone Deacetylase Inhibitors Downregulate Checkpoint Kinase 1 Expression to Induce Cell Death in Non-Small Cell Lung Cancer Cells

Background: Histone deacetylase inhibitors (HDACis) are promising anticancer drugs; however, the molecular mechanisms leading to HDACi-induced cell death have not been well understood and no clear mechanism of resistance has been elucidated to explain limited efficacy of HDACis in clinical trials. Methods and Findings: Here, we show that protein levels of checkpoint kinase 1 (Chk1), which has a major role in G2 cell cycle checkpoint regulation, was markedly reduced at the protein and transcriptional levels in lung cancer cells treated with pan-and selective HDACis LBH589, scriptaid, valproic acid, apicidin, and MS-275. In HDACi treated cells Chk1 function was impaired as determined by decreased inhibitory phosphorylation of cdc25c and its downstream target cdc2 and increased expression of cdc25A and phosphorylated histone H3, a marker of mitotic entry. In time course experiments, Chk1 downregulation occurred after HDACi treatment, preceding apoptosis. Ectopic expression of Chk1 overcame HDACiinduced cell death, and pretreating cells with the cdc2 inhibitor purvalanol A blocked entry into mitosis and prevented cell death by HDACis. Finally, pharmacological inhibition of Chk1 showed strong synergistic effect with LBH589 in lung cancer cells. Conclusions: These results define a pathway through which Chk1 inhibition can mediate HDACi-induced mitotic entry and cell death and suggest that Chk1 could be an early pharmacodynamic marker to assess HDACi efficacy in clinical samples

The DAC system and associations with multiple myeloma

Despite the clear progress achieved in recent years in the treatment of MM, most patients eventually relapse and therefore novel therapeutic options are still necessary for these patients. In this regard, several drugs that target specific mechanisms of the tumor cells are currently being explored in the preclinical and clinical setting. This manuscripts offers a review of the rationale and current status of the antimyeloma activity of one of the most relevant examples of these targeted drugs: deacetylase inhibitors (DACi). Several studies have demonstrated the prooncogenic activity of deacetylases (DACs) through the targeting not only of histones but also of non histone proteins relevant to tumor progression, such as p53, E2F family members, Bcl-6, Hsp90, HIF-1α or Nur77. This fact together with the DACs overexpression present in several tumors, has prompted the development of some DACi with potential antitumor effect. This situation is also evident in the case of MM as two mechanisms of DACi, the inhibition of the epigenetic inactivation of p53 and the blockade of the unfolded protein response, through the inhibition of the aggressome formation (by targeting DAC6) and the inactivation of the chaperone system (by acetylating HSP-90), provides the rationale for the exploration of the potential antimyeloma activity of these compounds. Several DACi with different chemical structure and different selectivity for targeting the DAC families have been tested in MM. Their preclinical activity in monotherapy has been quite exciting and has been described to be mediated by various mechanisms: the induction of apoptosis and cell cycle arrest mainly by the upregulation of p21; the interferece with the interaction between plasma cells and the microenvironment, by reducing the expression and signalling of several cytokines or by inhibiting angiogenesis. Finally they also have a role in protecting murine models from myeloma bone disease. Neverteless, the clinical activity in monotherapy of these drugs in relapsed/refractory MM patients has been very modest. This has prompted the development of combinations such as the one with bortezomib or lenalidomide and dexamethasone, which have already been taken into the clinics with positive preliminary results

LBH589, a deacetylase inhibitor, induces apoptosis in adult T-cell leukemia/lymphoma cells via activation of a novel RAIDD-caspase-2 pathway

Adult T-cell leukemia/lymphoma (ATLL), an aggressive neoplasm etiologically associated with human T-lymphotropic virus type-1 (HTLV-1), is resistant to treatment. In this study, we examined the effects of a new inhibitor of deacetylase enzymes, LBH589, on ATLL cells. LBH589 effectively induced apoptosis in ATLL-related cell lines and primary ATLL cells and reduced the size of tumors inoculated in SCID mice. Analyses, including with a DNA microarray, revealed that neither death receptors nor p53 pathways contributed to the apoptosis. Instead, LBH589 activated an intrinsic pathway through the activation of caspase-2. Furthermore, small interfering RNA experiments targeting caspase-2, caspase-9, RAIDD, p53-induced protein with a death domain (PIDD) and RIPK1 (RIP) indicated that activation of RAIDD is crucial and an event initiating this pathway. In addition, LBH589 caused a marked decrease in levels of factors involved in ATLL cell proliferation and invasion such as CCR4, IL-2R and HTLV-1 HBZ-SI, a spliced form of the HTLV-1 basic zipper factor HBZ. In conclusion, we showed that LBH589 is a strong inducer of apoptosis in ATLL cells and uncovered a novel apoptotic pathway initiated by activation of RAIDD

Computations of uncertainty mediate acute stress responses in humans

The effects of stress are frequently studied, yet its proximal causes remain unclear. Here we demonstrate that subjective estimates of uncertainty predict the dynamics of subjective and physiological stress responses. Subjects learned a probabilistic mapping between visual stimuli and electric shocks. Salivary cortisol confirmed that our stressor elicited changes in endocrine activity. Using a hierarchical Bayesian learning model, we quantified the relationship between the different forms of subjective task uncertainty and acute stress responses. Subjective stress, pupil diameter and skin conductance all tracked the evolution of irreducible uncertainty. We observed a coupling between emotional and somatic state, with subjective and physiological tuning to uncertainty tightly correlated. Furthermore, the uncertainty tuning of subjective and physiological stress predicted individual task performance, consistent with an adaptive role for stress in learning under uncertain threat. Our finding that stress responses are tuned to environmental uncertainty provides new insight into their generation and likely adaptive function. Copyright The Authors

The one loop MSbar static potential in the Gribov-Zwanziger Lagrangian

We compute the static potential in the Gribov-Zwanziger Lagrangian as a function of the Gribov mass, gamma, in the MSbar scheme in the Landau gauge at one loop. The usual gauge independent one loop perturbative static potential is recovered in the limit as gamma -> 0. By contrast the Gribov-Zwanziger static potential contains the term gamma^2/(p^2)^2. However, the linearly rising potential in coordinate space as a function of the radial variable r does not emerge due to a compensating behaviour as r -> infty. Though in the short distance limit a dipole behaviour is present. We also demonstrate enhancement in the propagator of the bosonic localizing Zwanziger ghost field when the one loop Gribov gap equation is satisfied. The explicit form of the one loop gap equation for the Gribov mass parameter is also computed in the MOM scheme and the zero momentum value of the renormalization group invariant effective coupling constant is shown to be the same value as that in the MSbar scheme.Comment: 54 latex pages, 6 figures, flaw in original Feynman rules corrected with updated two loop gap equation; new details added on derivation of propagators and their one loop corrections as well as bosonic ghost enhancemen