Collapse of an Instanton

We construct a two parameter family of collapsing solutions to the 4+1 Yang-Mills equations and derive the dynamical law of the collapse. Our arguments indicate that this family of solutions is stable. The latter fact is also supported by numerical simulations.Comment: 17 pages, 1 figur

Novel Combination Strategies to Enhance Immune Checkpoint Inhibition in Cancer Immunotherapy: A Narrative Review

Programmed cell death protein-1 (PD-1) is an immune checkpoint receptor that induces and maintains tolerance of T cells, invariant natural killer T (iNKT) cells, and natural killer (NK) cells, among other lymphocytes. Immune checkpoint inhibition by PD-1 blockade restores the lymphocytic immunostimulatory phenotype and has been successful in the treatment of various malignancies. However, while immune checkpoint blockade has been shown to provide robust antitumor treatment outcomes, its overall response rate remains low in a significant portion of cancer patients. An essential unmet need in cancer therapy is the development of novel pharmacologic strategies designed to lower rates of resistance associated with immune checkpoint blockade. Therefore, efforts that seek to enhance the efficacy of PD-1 inhibition possess profound immunotherapeutic potential. Here, three promising combination strategies that harness the antitumor effects of immune checkpoint inhibitors (ICIs) together with non-ICI antitumor therapeutic agents are reviewed. These agents include (1) ABX196, a potent inducer of iNKT cells, (2) chimeric antigen receptor (CAR)-T cell therapy, and (3) NK cell therapy. A comprehensive literature search was conducted using the PubMed and ClinicalTrials.gov databases for scientific articles and active trials, respectively, pertaining to immune checkpoint inhibition, iNKT cells, CAR-T cells, and NK cell immunotherapy. Preliminary clinical and preclinical data suggest that these combination treatment regimens greatly suppress tumor growth and may serve as innovative methods to enhance and optimize anticancer immunotherapy

The Role of Wnt and R-spondin in the Stomach During Health and Disease

The Wnt signaling pathway is one of the most prominent developmental signals. In addition to its functions in development, there is emerging evidence that it is also crucial for various organ functions in adult organisms, where Wnt signaling controls tissue stem cell behavior, proliferation and differentiation. Deregulation of Wnt signaling is involved in various pathological conditions and has been linked to malignant tissue transformation in different organ systems. The study of the Wnt signaling pathway has revealed a complex regulatory network that tightly balances the quality and strength of Wnt signaling in tissues. In this context, R-spondins are secreted proteins that stabilize Wnt receptors and enhance Wnt signaling. In this review we focus on new insights into the regulatory function of Wnt and R-spondin signaling in the stomach. In addition to its function in the healthy state, we highlight the connection between Wnt signaling and infection with Helicobacter pylori (H. pylori), a pathogen that colonizes the stomach and is the main risk factor for gastric cancer. In addition to experimental data that link Wnt signaling to carcinogenesis, we discuss that Wnt signaling is affected in a substantial proportion of patients with gastric cancer, and provide examples for potential clinical implications for altered Wnt signaling in gastric cancer

Defence and adaptation mechanisms of the intestinal epithelium upon infection

The intestinal epithelium is a monolayer of polarized columnar cells that act as a border between the host and its environment and are the first line of defence against the luminal microbes. In addition to providing a physical barrier, the epithelium possesses a multitude of active mechanisms to fight invading pathogens and regulate the composition and spatial distribution of commensals. The different epithelial cell types have unique functions in this context, and crosstalk with the immune system further modulates their intricate antimicrobial responses. The epithelium is organized into clonal crypt units with a high cellular turnover that is driven by stem cells located at the base. There is increasing evidence that this anatomical organization, the stem cell turnover, and the lineage determination processes are essential for barrier maintenance. These processes can be modulated by microbes directly or by the immune responses to enteric pathogens, resulting in a rapid and efficient adaptation of the epithelium to environmental perturbations, injuries, and infections. Here we discuss the complex host-microbial interactions that shape the mucosa and how the epithelium maintains and re-establishes homeostasis after infection

Completeness of the Coulomb scattering wave functions

Completeness of the eigenfunctions of a self-adjoint Hamiltonian, which is the basic ingredient of quantum mechanics, plays an important role in nuclear reaction and nuclear structure theory. However, until now, there was no a formal proof of the completeness of the eigenfunctions of the two-body Hamiltonian with the Coulomb interaction. Here we present the first formal proof of the completeness of the two-body Coulomb scattering wave functions for repulsive unscreened Coulomb potential. To prove the completeness we use the Newton's method [R. Newton, J. Math Phys., 1, 319 (1960)]. The proof allows us to claim that the eigenfunctions of the two-body Hamiltonian with the potential given by the sum of the repulsive Coulomb plus short-range (nuclear) potentials also form a complete set. It also allows one to extend the Berggren's approach of modification of the complete set of the eigenfunctions by including the resonances for charged particles. We also demonstrate that the resonant Gamow functions with the Coulomb tail can be regularized using Zel'dovich's regularization method.Comment: 12 pages and 1 figur

Biomarkers of Tuberculosis Severity and Treatment Effect: A Directed Screen of 70 Host Markers in a Randomized Clinical Trial.

More efficacious treatment regimens are needed for tuberculosis, however, drug development is impeded by a lack of reliable biomarkers of disease severity and of treatment effect. We conducted a directed screen of host biomarkers in participants enrolled in a tuberculosis clinical trial to address this need. Serum samples from 319 protocol-correct, culture-confirmed pulmonary tuberculosis patients treated under direct observation as part of an international, phase 2 trial were screened for 70 markers of infection, inflammation, and metabolism. Biomarker assays were specifically developed for this study and quantified using a novel, multiplexed electrochemiluminescence assay. We evaluated the association of biomarkers with baseline characteristics, as well as with detailed microbiologic data, using Bonferroni-adjusted, linear regression models. Across numerous analyses, seven proteins, SAA1, PCT, IL-1β, IL-6, CRP, PTX-3 and MMP-8, showed recurring strong associations with markers of baseline disease severity, smear grade and cavitation; were strongly modulated by tuberculosis treatment; and had responses that were greater for patients who culture-converted at 8weeks. With treatment, all proteins decreased, except for osteocalcin, MCP-1 and MCP-4, which significantly increased. Several previously reported putative tuberculosis-associated biomarkers (HOMX1, neopterin, and cathelicidin) were not significantly associated with treatment response. In conclusion, across a geographically diverse and large population of tuberculosis patients enrolled in a clinical trial, several previously reported putative biomarkers were not significantly associated with treatment response, however, seven proteins had recurring strong associations with baseline radiographic and microbiologic measures of disease severity, as well as with early treatment response, deserving additional study

Local energy decay of massive Dirac fields in the 5D Myers-Perry metric

We consider massive Dirac fields evolving in the exterior region of a 5-dimensional Myers-Perry black hole and study their propagation properties. Our main result states that the local energy of such fields decays in a weak sense at late times. We obtain this result in two steps: first, using the separability of the Dirac equation, we prove the absence of a pure point spectrum for the corresponding Dirac operator; second, using a new form of the equation adapted to the local rotations of the black hole, we show by a Mourre theory argument that the spectrum is absolutely continuous. This leads directly to our main result.Comment: 40 page

THE ACCUSED IS ENTERING THE COURTROOM: THE LIVE-TWEETING OF A MURDER TRIAL.

© 2017 Informa UK Limited, trading as Taylor & Francis GroupThe use of social media is now widely accepted within journalism as an outlet for news information. Live tweeting of unfolding events is standard practice. In March 2014, Oscar Pistorius went on trial in the Gauteng High Court for murder. Hundreds of journalists present began live-tweeting coverage, an unprecedented combination of international interest, permission to use technology and access which resulted in massive streams of consciousness reports of events as they unfolded. Based on a corpus of Twitter feeds of twenty-four journalists covering the trial, this study analyses the content and strategies of these feeds in order to present an understanding of how microblogging is used as a live reporting tool. This study shows the development of standardised language and strategies in reporting on Twitter, concluding that journalists adopt a narrow range of approaches, with no significant variation in terms of gender, location, or medium. This is in contrast to earlier studies in the field (Awad, 2006, Hedman, 2015; Kothari, 2010; Lariscy, Avery, Sweetser, & Howes, 2009 Lasorsa, 2012; Lasorsa, Lewis, & Holton, 2011; Sigal, 1999, Vis, 2013).Peer reviewe