Guarding art galleries by guarding witnesses

Let P be a simple polygon. We de ne a witness set W to be a set of points su h that if any (prospective) guard set G guards W, then it is guaranteed that G guards P . We show that not all polygons admit a nite witness set. If a fi nite minimal witness set exists, then it cannot contain any witness in the interior of P ; all witnesses must lie on the boundary of P , and there an be at most one witness in the interior of any edge. We give an algorithm to compute a minimal witness set for P in O(n2 log n) time, if such a set exists, or to report the non-existence within the same time bounds. We also outline an algorithm that uses a witness set for P to test whether a (prospective) guard set sees all points in P

Targeting the Stress-Induced Protein NUPR1 to Treat Pancreatic Adenocarcinoma

Cancer cells activate stress-response mechanisms to adapt themselves to a variety of stressful conditions. Among these protective mechanisms, those controlled by the stress-induced nuclear protein 1 (NUPR1 ) belong to the most conserved ones. NUPR1 is an 82-residue-long, monomeric, basic and intrinsically disordered protein (IDP), which was found to be invariably overexpressed in some, if not all, cancer tissues. Remarkably, we and others have previously showed that genetic inactivation of the Nupr1 gene antagonizes the growth of pancreatic cancer as well as several other tumors. With the use of a multidisciplinary strategy by combining biophysical, biochemical, bioinformatic, and biological approaches, a trifluoperazine-derived compound, named ZZW-115, has been identified as an inhibitor of the NUPR1 functions. The anticancer activity of the ZZW-115 was first validated on a large panel of cancer cells. Furthermore, ZZW-115 produced a dose-dependent tumor regression of the tumor size in xenografted mice. Mechanistically, we have demonstrated that NUPR1 binds to several importins. Because ZZW-115 binds NUPR1 through the region around the amino acid Thr68, which is located into the nuclear location signal (NLS) region of the protein, we demonstrated that treatment with ZZW-115 inhibits completely the translocation of NUPR1 from the cytoplasm to the nucleus by competing with importins

Curvature effects on the surface thickness and tension at the free interface of 4^4He systems

The thickness $W$ and the surface energy $\sigma_A$ at the free interface of superfluid $^4$He are studied. Results of calculations carried out by using density functionals for cylindrical and spherical systems are presented in a unified way, including a comparison with the behavior of planar slabs. It is found that for large species $W$ is independent of the geometry. The obtained values of $W$ are compared with prior theoretical results and experimental data. Experimental data favor results evaluated by adopting finite range approaches. The behavior of $\sigma_A$ and $W \sigma_A$ exhibit overshoots similar to that found previously for the central density, the trend of these observables towards their asymptotic values is examined.Comment: 35 pages, TeX, 5 figures, definitive versio

Looking for magnetic monopoles at LHC with diphoton events

Magnetic monopoles have been a subject of interest since Dirac established the relation between the existence of monopoles and charge quantization. The intense experimental search carried thus far has not met with success. The Large Hadron Collider is reaching energies never achieved before allowing the search for exotic particles in the TeV mass range. In a continuing effort to discover these rare particles we propose here other ways to detect them. We study the observability of monopoles and monopolium, a monopole-antimonopole bound state, at the Large Hadron Collider in the $\gamma \gamma$ channel for monopole masses in the range 500-1000 GeV. We conclude that LHC is an ideal machine to discover monopoles with masses below 1 TeV at present running energies and with 5 fb$^{-1}$ of integrated luminosity.Comment: This manuscript contains information appeared in Looking for magnetic monopoles at LHC, arXiv:1104.0218 [hep-ph] and Monopolium detection at the LHC.,arXiv:1107.3684 [hep-ph] by the same authors, rewritten for joint publication in The European Physica Journal Plus. 26 pages, 22 figure

QED Effective Action at Finite Temperature: Two-Loop Dominance

We calculate the two-loop effective action of QED for arbitrary constant electromagnetic fields at finite temperature T in the limit of T much smaller than the electron mass. It is shown that in this regime the two-loop contribution always exceeds the influence of the one-loop part due to the thermal excitation of the internal photon. As an application, we study light propagation and photon splitting in the presence of a magnetic background field at low temperature. We furthermore discover a thermally induced contribution to pair production in electric fields.Comment: 34 pages, 4 figures, LaTe

ZZW-115-dependent inhibition of NUPR1 nuclear translocation sensitizes cancer cells to genotoxic agents

Establishing the interactome of the cancer-associated stress protein Nuclear Protein 1 (NUPR1), we found that it binds to several hundreds of proteins, including proteins involved in nuclear translocation, DNA repair, and key factors of the SUMO pathway. We demonstrated that the NUPR1 inhibitor ZZW-115, an organic synthetic molecule, competes with importins for the binding to the NLS region of NUPR1, thereby inhibiting its nuclear translocation. We hypothesized, and then proved, that inhibition of NUPR1 by ZZW-115 sensitizes cancer cells to DNA damage induced by several genotoxic agents. Strikingly, we found that treatment with ZZW-115 reduced SUMOylation of several proteins involved in DNA damage response (DDR). We further report that the presence of recombinant NUPR1 improved the SUMOylation in a cell-free system, indicating that NUPR1 directly stimulates the SUMOylation machinery. We propose that ZZW-115 sensitizes cancer cells to genotoxic agents by inhibiting the nuclear translocation of NUPR1 and thereby decreasing the SUMOylation-dependent functions of key proteins involved in the DDR

Carbapenem-resistant Citrobacter spp. isolated in Spain from 2013 to 2015 produced a variety of carbapenemases including VIM-1, OXA-48, KPC-2, NDM-1 and VIM-2

Objectives: There is little information about carbapenemase-producing (CP) Citrobacter spp.We studied the molecular epidemiology and microbiological features of CP Citrobacter spp. isolates collected in Spain (2013-15). Methods: In total, 119 isolates suspected of being CP by the EUCAST screening cut-off values were analysed. Carbapenemases and ESBLs were characterized using PCR and sequencing. The genetic relationship among Citrobacter freundii isolates was studied by PFGE. Results: Of the 119 isolates, 63 (52.9%) produced carbapenemases, of which 37 (58.7%) produced VIM-1, 20 (31.7%) produced OXA-48, 12 (19%) produced KPC-2, 2 (3.2%) produced NDM-1 and 1 (1.6%) produced VIM- 2; 9 C. freundii isolates co-produced VIM-1 plus OXA-48. Fourteen isolates (22.2%) also carried ESBLs: 8 CTX-M-9 plus SHV-12, 2 CTX-M-9, 2 SHV-12 and 2 CTX-M-15. Fifty-seven isolates (90.5%) were C. freundii, 4 (6.3%) were Citrobacter koseri, 1 (1.6%) was Citrobacter amalonaticus and 1 (1.6%) was Citrobacter braakii. By EUCAST breakpoints, eight (12.7%) of the CP isolates were susceptible to the four carbapenems tested. In the 53 CP C. freundii analysed by PFGE, a total of 44 different band patterns were observed. Four PFGE clusters were identified: cluster 1 included eight isolates co-producing VIM-1 and OXA-48; blaVIM-1 was carried in a class 1 integron (intI-blaVIM-1 - aacA4-dfrB1-aadA1-catB2-qacE¿1/sul1) and blaOXA-48 was carried in a Tn1999.2 transposon. Conclusions: We observed the clonal and polyclonal spread of CP Citrobacter spp. across several Spanish geographical areas. Four species of Citrobacter spp. produced up to five carbapenemase types, including coproduction of VIM-1 plus OXA-48. Some CP Citrobacter spp. isolates were susceptible to the four carbapenems tested, a finding with potential clinical implications

What pulmonologists think about the asthma–COPD overlap syndrome

Background: Some patients with COPD may share characteristics of asthma; this is the so-called asthma–COPD overlap syndrome (ACOS). There are no universally accepted criteria for ACOS, and most treatments for asthma and COPD have not been adequately tested in this population. Materials and methods: We performed a survey among pulmonology specialists in asthma and COPD aimed at collecting their opinions about ACOS and their attitudes in regard to some case scenarios of ACOS patients. The participants answered a structured questionnaire and attended a face-to-face meeting with the Metaplan methodology to discuss different aspects of ACOS. Results: A total of 26 pulmonologists with a mean age of 49.7 years participated in the survey (13 specialists in asthma and 13 in COPD). Among these, 84.6% recognized the existence of ACOS and stated that a mean of 12.6% of their patients might have this syndrome. In addition, 80.8% agreed that the diagnostic criteria for ACOS are not yet well defined. The most frequently mentioned characteristics of ACOS were a history of asthma (88.5%), significant smoking exposure (73.1%), and postbronchodilator forced expiratory volume in 1 second/forced vital capacity ,0.7 (69.2%). The most accepted diagnostic criteria were eosinophilia in sputum (80.8%), a very positive bronchodilator test (69.2%), and a history of asthma before 40 years of age (65.4%). Up to 96.2% agreed that first-line treatment for ACOS was the combination of a long-acting β2-agonist and inhaled steroid, with a long-acting antimuscarinic agent (triple therapy) for severe ACOS. Conclusion: Most Spanish specialists in asthma and COPD agree that ACOS exists, but the diagnostic criteria are not yet well defined. A previous history of asthma, smoking, and not fully reversible airflow limitation are considered the main characteristics of ACOS, with the most accepted first-line treatment being long-acting β2-agonist/inhaled corticosteroids

The upgrade of the ALICE TPC with GEMs and continuous readout

The upgrade of the ALICE TPC will allow the experiment to cope with the high interaction rates foreseen for the forthcoming Run 3 and Run 4 at the CERN LHC. In this article, we describe the design of new readout chambers and front-end electronics, which are driven by the goals of the experiment. Gas Electron Multiplier (GEM) detectors arranged in stacks containing four GEMs each, and continuous readout electronics based on the SAMPA chip, an ALICE development, are replacing the previous elements. The construction of these new elements, together with their associated quality control procedures, is explained in detail. Finally, the readout chamber and front-end electronics cards replacement, together with the commissioning of the detector prior to installation in the experimental cavern, are presented. After a nine-year period of R&D, construction, and assembly, the upgrade of the TPC was completed in 2020.publishedVersio