Form factors of descendant operators: Free field construction and reflection relations

The free field representation for form factors in the sinh-Gordon model and the sine-Gordon model in the breather sector is modified to describe the form factors of descendant operators, which are obtained from the exponential ones, \e^{\i\alpha\phi}, by means of the action of the Heisenberg algebra associated to the field $\phi(x)$. As a check of the validity of the construction we count the numbers of operators defined by the form factors at each level in each chiral sector. Another check is related to the so called reflection relations, which identify in the breather sector the descendants of the exponential fields \e^{\i\alpha\phi} and \e^{\i(2\alpha_0-\alpha)\phi} for generic values of $\alpha$. We prove the operators defined by the obtained families of form factors to satisfy such reflection relations. A generalization of the construction for form factors to the kink sector is also proposed.Comment: 29 pages; v2: minor corrections, some references added; v3: minor corrections; v4,v5: misprints corrected; v6: minor mistake correcte

Fusion products, Kostka polynomials, and fermionic characters of su(r+1)_k

Using a form factor approach, we define and compute the character of the fusion product of rectangular representations of \hat{su}(r+1). This character decomposes into a sum of characters of irreducible representations, but with q-dependent coefficients. We identify these coefficients as (generalized) Kostka polynomials. Using this result, we obtain a formula for the characters of arbitrary integrable highest-weight representations of \hat{su}(r+1) in terms of the fermionic characters of the rectangular highest weight representations.Comment: 21 pages; minor changes, typos correcte

Conical Defects in Higher Spin Theories

We study conical defect geometries in the SL(N) Chern-Simons formulation of higher spin gauge theories in AdS_3. We argue that (for N\geq 4) there are special values of the deficit angle for which these geometries are actually smooth configurations of the underlying theory. We also exhibit a gauge in which these geometries can be viewed as wormholes interpolating between two distinct asymptotically AdS_3 spacetimes. Remarkably, the spectrum of smooth SL(N,C) solutions, after an appropriate analytic continuation, exactly matches that of the so-called "light primaries" in the minimal model W_N CFTs at finite N. This gives a candidate bulk interpretation of the latter states in the holographic duality proposed in [1].Comment: 38 page

The HEARTS partner forum—supporting implementation of HEARTS to treat and control hypertension

Cardiovascular diseases (CVD), principally ischemic heart disease (IHD) and stroke, are the leading causes of death (18. 6 million deaths annually) and disability (393 million disability-adjusted life-years lost annually), worldwide. High blood pressure is the most important preventable risk factor for CVD and deaths, worldwide (10.8 million deaths annually). In 2016, the World Health Organization (WHO) and the United States Centers for Disease Control (CDC) launched the Global Hearts initiative to support governments in their quest to prevent and control CVD. HEARTS is the core technical package of the initiative and takes a public health approach to treating hypertension and other CVD risk factors at the primary health care level. The HEARTS Partner Forum, led by WHO, brings together the following 11 partner organizations: American Heart Association (AHA), Center for Chronic Disease Control (CCDC), International Society of Hypertension (ISH), International Society of Nephrology (ISN), Pan American Health Organization (PAHO), Resolve to Save Lives (RTSL), US CDC, World Hypertension League (WHL), World Heart Federation (WHF) and World Stroke Organization (WSO). The partners support countries in their implementation of the HEARTS technical package in various ways, including providing technical expertise, catalytic funding, capacity building and evidence generation and dissemination. HEARTS has demonstrated the feasibility and acceptability of a public health approach, with more than seven million people already on treatment for hypertension using a simple, algorithmic HEARTS approach. Additionally, HEARTS has demonstrated the feasibility of using hypertension as a pathfinder to universal health coverage and should be a key intervention of all basic benefit packages. The partner forum continues to find ways to expand support and reinvigorate enthusiasm and attention on preventing CVD. Proposed future HEARTS Partner Forum activities are related to more concrete information sharing between partners and among countries, expanded areas of partner synergy, support for implementation, capacity building, and advocacy with country ministries of health, professional societies, academy and civil societies organizations. Advancing toward the shared goals of the HEARTS partners will require a more formal, structured approach to the forum and include goals, targets and published reports. In this way, the HEARTS Partner Forum will mirror successful global partnerships on communicable diseases and assist countries in reducing CVD mortality and achieving global sustainable development goals (SDGs)

Primary gliosarcoma: key clinical and pathologic distinctions from glioblastoma with implications as a unique oncologic entity

This report presents the historical experience, clinical presentation, treatment, prognosis, and pathogenesis of gliosarcoma described to date in the English literature. PubMed query of term “gliosarcoma” was performed, followed by a rigorous review of cited literature. Articles selected for analysis included: (1) case reports of gliosarcoma, (2) review articles of gliosarcoma, and (3) studies of the pathogenesis or genetics of gliosarcoma in humans. Our review identified 219 cases of gliosarcoma in 34 reports and eight articles addressing the pathogenesis. Survival in larger series ranged 4–11.5 months. Features unique to gliosarcoma compared to glioblastoma (GBM) include their temporal lobe predilection, potential to appear similar to a meningioma at surgery, repeated reports of extracranial metastases, and infrequency of EGFR mutations. Published experience is limited to small case series, and the pathogenesis remains unclear. Clinical and pathologic characteristics distinct from GBM suggest that they may warrant specific treatment, separate from conventional GBM therapy

Endogenous DOPA inhibits melanoma through suppression of CHRM1 signaling

Melanoma risk is 30 times higher in people with lightly pigmented skin versus darkly pigmented skin. Using primary human melanocytes representing the full human skin pigment continuum and preclinical melanoma models, we show that cell-intrinsic differences between dark and light melanocytes regulate melanocyte proliferative capacity and susceptibility to malignant transformation, independent of melanin and ultraviolet exposure. These differences result from dihydroxyphenylalanine (DOPA), a melanin precursor synthesized at higher levels in melanocytes from darkly pigmented skin. We used both high-throughput pharmacologic and genetic in vivo CRISPR screens to determine that DOPA limits melanocyte and melanoma cell proliferation by inhibiting the muscarinic acetylcholine receptor M1 (CHRM1) signaling. Pharmacologic CHRM1 antagonism in melanoma leads to depletion of c-Myc and FOXM1, both of which are proliferation drivers associated with aggressive melanoma. In preclinical mouse melanoma models, pharmacologic inhibition of CHRM1 or FOXM1 inhibited tumor growth. CHRM1 and FOXM1 may be new therapeutic targets for melanoma

The Circadian Clock Protein Timeless Regulates Phagocytosis of Bacteria in Drosophila

Survival of bacterial infection is the result of complex host-pathogen interactions. An often-overlooked aspect of these interactions is the circadian state of the host. Previously, we demonstrated that Drosophila mutants lacking the circadian regulatory proteins Timeless (Tim) and Period (Per) are sensitive to infection by S. pneumoniae. Sensitivity to infection can be mediated either by changes in resistance (control of microbial load) or tolerance (endurance of the pathogenic effects of infection). Here we show that Tim regulates resistance against both S. pneumoniae and S. marcescens. We set out to characterize and identify the underlying mechanism of resistance that is circadian-regulated. Using S. pneumoniae, we found that resistance oscillates daily in adult wild-type flies and that these oscillations are absent in Tim mutants. Drosophila have at least three main resistance mechanisms to kill high levels of bacteria in their hemolymph: melanization, antimicrobial peptides, and phagocytosis. We found that melanization is not circadian-regulated. We further found that basal levels of AMP gene expression exhibit time-of-day oscillations but that these are Tim-independent; moreover, infection-induced AMP gene expression is not circadian-regulated. We then show that phagocytosis is circadian-regulated. Wild-type flies exhibit up-regulated phagocytic activity at night; Tim mutants have normal phagocytic activity during the day but lack this night-time peak. Tim appears to regulate an upstream event in phagocytosis, such as bacterial recognition or activation of phagocytic hemocytes. Interestingly, inhibition of phagocytosis in wild type flies results in survival kinetics similar to Tim mutants after infection with S. pneumoniae. Taken together, these results suggest that loss of circadian oscillation of a specific immune function (phagocytosis) can have significant effects on long-term survival of infection

Alcohol consumption and the risk of morbidity and mortality for different stroke types - a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Observational studies have suggested a complex relationship between alcohol consumption and stroke, dependent on sex, type of stroke and outcome (morbidity vs. mortality). We undertook a systematic review and a meta-analysis of studies assessing the association between levels of average alcohol consumption and relative risks of ischemic and hemorrhagic strokes separately by sex and outcome. This meta-analysis is the first to explicitly separate morbidity and mortality of alcohol-attributable stroke and thus has implications for public health and prevention.</p> <p>Methods</p> <p>Using Medical Subject Headings (alcohol drinking, ethanol, cerebrovascular accident, cerebrovascular disorders, and intracranial embolism and thrombosis and the key word stroke), a literature search of MEDLINE, EMBASE, CINAHL, CABS, WHOlist, SIGLE, ETOH, and Web of Science databases between 1980 to June 2009 was performed followed by manual searches of bibliographies of key retrieved articles. From twenty-six observational studies (cohort or case-control) with ischemic or hemorrhagic strokes the relative risk or odds ratios or hazard ratios of stroke associated with alcohol consumption were reported; alcohol consumption was quantified; and life time abstention (manually estimated where data for current abstainers were given) was used as the reference group. Two reviewers independently extracted the information on study design, participant characteristics, level of alcohol consumption, stroke outcome, control for potential confounding factors, risk estimates and key criteria of study quality using a standardized protocol.</p> <p>Results</p> <p>The dose-response relationship for hemorrhagic stroke had monotonically increasing risk for increasing consumption, whereas ischemic stroke showed a curvilinear relationship, with a protective effect of alcohol for low to moderate consumption, and increased risk for higher exposure. For more than 3 drinks on average/day, in general women had higher risks than men, and the risks for mortality were higher compared to the risks for morbidity.</p> <p>Conclusions</p> <p>These results indicate that heavy alcohol consumption increases the relative risk of any stroke while light or moderate alcohol consumption may be protective against ischemic stroke. Preventive measures that should be initiated are discussed.</p

Dysregulation of Cell Polarity Proteins Synergize with Oncogenes or the Microenvironment to Induce Invasive Behavior in Epithelial Cells

Changes in expression and localization of proteins that regulate cell and tissue polarity are frequently observed in carcinoma. However, the mechanisms by which changes in cell polarity proteins regulate carcinoma progression are not well understood. Here, we report that loss of polarity protein expression in epithelial cells primes them for cooperation with oncogenes or changes in tissue microenvironment to promote invasive behavior. Activation of ErbB2 in cells lacking the polarity regulators Scribble, Dlg1 or AF-6, induced invasive properties. This cooperation required the ability of ErbB2 to regulate the Par6/aPKC polarity complex. Inhibition of the ErbB2-Par6 pathway was sufficient to block ErbB2-induced invasion suggesting that two polarity hits may be needed for ErbB2 to promote invasion. Interestingly, in the absence of ErbB2 activation, either a combined loss of two polarity proteins, or exposure of cells lacking one polarity protein to cytokines IL-6 or TNFα induced invasive behavior in epithelial cells. We observed the invasive behavior only when cells were plated on a stiff matrix (Matrigel/Collagen-1) and not when plated on a soft matrix (Matrigel alone). Cells lacking two polarity proteins upregulated expression of EGFR and activated Akt. Inhibition of Akt activity blocked the invasive behavior identifying a mechanism by which loss of polarity promotes invasion of epithelial cells. Thus, we demonstrate that loss of polarity proteins confers phenotypic plasticity to epithelial cells such that they display normal behavior under normal culture conditions but display aggressive behavior in response to activation of oncogenes or exposure to cytokines

Prolyl-4-hydroxylase Α subunit 2 (P4HA2) expression is a predictor of poor outcome in breast ductal carcinoma in situ (DCIS)

© 2018, Cancer Research UK. Background: Extracellular matrix (ECM) plays a crucial role in tumour behaviour. Prolyl-4-hydroxlase-A2 (P4HA2) is a key enzyme in ECM remodelling. This study aims to evaluate the prognostic significance of P4HA2 in breast ductal carcinoma in situ (DCIS). Methods: P4HA2 expression was assessed immunohistochemically in malignant cells and surrounding stroma of a large DCIS cohort comprising 481 pure DCIS and 196 mixed DCIS and invasive carcinomas. Outcome analysis was evaluated using local recurrence free interval (LRFI). Results: High P4HA2 expression was detected in malignant cells of half of pure DCIS whereas its expression in stroma was seen in 25% of cases. Higher P4HA2 expression was observed in mixed DCIS cases compared to pure DCIS both in tumour cells and in stroma. High P4HA2 was associated with features of high risk DCIS including younger age, higher grade, comedo necrosis, triple negative and HER2-positive phenotypes. Interaction between P4HA2 and radiotherapy was also observed regarding the outcome. High P4HA2 expression was an independent prognostic factor in predicting shorter LRFI. Conclusion: P4HA2 plays a role in DCIS progression and can potentially be used to predict DCIS outcome. Incorporation of P4HA2 with other clinicopathological parameters could refine DCIS risk stratification that can potentially guide management decisions