The mixed metric dimension of flower snarks and wheels

New graph invariant, which is called mixed metric dimension, has been recently introduced. In this paper, exact results of mixed metric dimension on two special classes of graphs are found: flower snarks $J_n$ and wheels $W_n$. It is proved that mixed metric dimension for $J_5$ is equal to 5, while for higher dimensions it is constant and equal to 4. For $W_n$, its mixed metric dimension is not constant, but it is equal to $n$ when $n\geq 4$, while it is equal to 4, for $n=3$

Boiling and Condensation in Two-Phase System Transients with Water Hammer

Water hammer in two-phase systems, induced by direct steam condensation on subcooled water or by separation of subcooled water column, results in the most intensive pipeline pressure surges. Amplitudes of pressure spikes along the course of these dangerous transients strongly depend on the condensation and evaporation rates. The present paper provides a literature overview of thermal-hydraulic models for the prediction of water hammer phenomenon in two-phase systems, together with an original mechanistic approach for the prediction of phase transition rates, based on the shape and size of vapor-liquid interfacial area and the phase transition potential expressed through vapor and liquid phase temperature difference. Available water hammer experimental conditions were numerically simulated with the new modeling approach. Driving parameters of boiling and condensation rates at the steam-water interfaces are evaluated, and a good agreement is shown between numerical results and experimental data of bulk two-phase flow parameters during water hammer transients

Dissection des voies de signalisation contrôlant l'inflammation lors d'infections bactériennes à Gram négatif : le rôle de ALPK1, TIFA et TRAF6 lors d'une infection à Shigella flexneri

Epithelial cells represent the first line of defense against pathogens and play an active role in innate immunity. Via local secretion of cytokines, they are able to orchestrate the immune response against invading pathogens. The activation of both intracellular and extracellular pathogen recognition receptors leads to a complex signaling cascade, resulting in the activation of the transcription factor nuclear factor kB(NF-kB)and the subsequent production of pro-inflammatory cytokines. However, the molecular mechanisms governing this process have not been fully elucidated. The Gram-negative bacterium Shigella flexneriis an important human pathogen and the causative agent of bacillary dysentery. This disease is characterized by acute inflammation of the colon resulting in the destruction of the intestinal tissue and, in severe cases, death. S. flexneri can invade and replicate within colonic epithelial cells. Following detection of the bacteria, both infected and uninfected bystander cells initiate inflammatory signaling pathways, which result in massive interleukin-8 (IL-8) production by the latter. Using S. flexneri as a model of infection, we have identified a novel signaling pathway, which is central to the activation of NF-kB and the subsequent production of IL-8 during Gram-negative bacterial infections. Following the cytosolic detection of bacteria, the protein TRAF-interacting factor with forkhead-associated domain (TIFA) forms oligomers, a process dependent on its threonine at position 9 and theforkhead-associated domain. These oligomers interact withTNF receptor associated factor (TRAF)6, leading to its oligomerization and the subsequent activation of NF-kB. In addition, we show that oligomerization of TIFA is dependent on the kinase alpha-kinase(ALPK)1 and that this pathway is activated in response to the detection of the bacterial metabolite heptose-1, 7-bisphosphate (HBP). These observations could be extended to the enteroinvasive pathogen Salmonella typhimurium as well as the extracellular bacteria Neisseria meningitidis. Our results therefore demonstrate the central role of the ALPK1-TIFA-TRAF6 signaling pathway in response to HBP of both intracellular and extracellular Gram-negative bacterial pathogens, and offer a better understanding of the molecular mechanisms governing the epithelial cell immune response to pathogenic bacteria.Les cellules épithéliales constituent la première ligne de défense face à l’infection et jouent un rôle actif dans l'immunité innée. Par la sécrétion locale de cytokines, ces cellules sont capables d'orchestrer la réponse immunitaire contre les pathogènes invasifs. L'activation des récepteurs de reconnaissance de pathogènes, qu’ils soient intracellulaires ou extracellulaires, conduit à une cascade de signalisation complexe. Cette dernière entraîne l'activation du facteur de transcription NF-kB ainsi que la production ultérieure de cytokines pro-inflammatoires. Cependant, les mécanismes moléculaires qui gouvernent ce processus n'ont pas été entièrement élucidés. La bactérie à Gram négatif Shigella flexneri est un pathogène humain majeur à l’origine de la dysenterie bacillaire. Cette maladie se caractérise par une inflammation aiguë du colon qui peut entraîner la destruction du tissu intestinal et même dans les cas les plus graves, la mort. En effet, S. flexneri peut envahir les cellules épithéliales du colon et se répliquer dans leur cytoplasme. Après la détection de bactéries intracellulaires, les cellules infectées et non infectées déclenchent des voies de signalisation inflammatoire, ce qui entraîne une production massive d'interleukine-8. En utilisant S. flexneri comme modèle d'infection, nous avons identifié une nouvelle voie de signalisation qui joue un rôle central dans l'activation de NF-kB et la production d'IL-8 qui en résulte lors des infections bactériennes à Gram négatif. Après la détection cytosolique des bactéries, les protéines TIFA forment des oligomères à travers un processus dépendant de leur thréonine en position 9, ainsi que de leur domaine « Forkhead-associated ». D’une part, ces oligomères interagissent avec TRAF6, ce qui conduit à l’oligomérisation de cette dernière et à l'activation subséquente de NF-kB. D'autre part, nous montrons que l'oligomérisation de TIFA dépend de la kinase ALPK1 et que cette voie est activée en réponse au métabolite bactérien heptose-1, 7-bisphosphate. Ces observations pourraient être étendues au pathogène entéro-invasif Salmonella typhimurium ainsi qu'à la bactérie extracellulaire Neisseria meningitidis. Nos résultats démontrent donc le rôle central de la voie de signalisation ALPK1-TIFA-TRAF6 en réponse aux pathogènes bactériens à Gram négatif intracellulaires et extracellulaires. Ainsi, ces travaux contribuent à une meilleure compréhension des mécanismes moléculaires régissant la réponse immunitaire des cellules épithéliales aux bactéries pathogènes

When Law Doesnt Rule: State Capture of the Judiciary, Prosecution, Police in Serbia

The study When the Law Doesn't Rule, by the Open Society European Policy Institute, Transparency Serbia, and the Centre of Investigative Journalism of Serbia, identifies seven ways in which political control is being exerted over the judiciary, prosecution, and police in Serbia, and how systemic weaknesses in the exercise of the rule of law are being exploited. These include limited accountability of judges and prosecutors for ineffectiveness; the appointment of public prosecutors and court presidents on political grounds; an inordinate amount of discretion allowed to law enforcement when making investigation and prosecution decisions; inappropriate and partial briefing of the media; the misuse and manipulation of statistics; direct political influence on law enforcement; and deliberately dysfunctional criminal investigations in politically sensitive cases.The report illustrates these seven administrative and systemic weaknesses through 12 case studies

Diagnostic Value of Non-invasive Scoring Systems in the Prediction of Esophageal Varices in Patients with Liver Cirrhosis—Single Center Experience

Background and Objectives: Upper endoscopy is considered the gold standard for screening and diagnosis of esophageal varices (EV). Non-invasive methods for predicting EV have become a research hotspot in recent years. The aim of this study was to assess the role of non-invasive scores in predicting the presence of EV in patients with liver cirrhosis, and to determine the value of these scores in predicting the outcome of patients with cirrhosis presenting with acute variceal bleeding. Materials and Methods: A total of 386 patients with liver cirrhosis were included. The model for end-stage liver disease (MELD), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AST/ALT), AST to platelet ratio index (APRI), fibrosis-4-index (FIB-4), fibrosis index (FI), King’s Score, albumin-bilirubin (ALBI) score, and platelet-albumin-bilirubin (PALBI) score were calculated. The discriminatory capacities of the examined scores in predicting the presence of esophageal varices were tested using receiver operating characteristic (ROC) curves. Results: The ROC curve analysis showed (area under the curve) AUC values of ALBI and PALBI of 0.603, and 0.606, respectively, for the prediction of EV. APRI, MELD, PALBI, King’s, FIB-4, and ALBI scores showed statistically significant correlation with EV bleeding (p Conclusions: ALBI and PALBI scores had modest diagnostic accuracy of EVs in liver cirrhosis. APRI and MELD can be used as a reference index for the EV bleeding, and MELD score is best associated with short-term outcome in cirrhotic patients

ALPK1 controls TIFA/TRAF6-dependent innate immunity against heptose-1,7-bisphosphate of gram-negative bacteria

<div><p>During infection by invasive bacteria, epithelial cells contribute to innate immunity via the local secretion of inflammatory cytokines. These are directly produced by infected cells or by uninfected bystanders via connexin-dependent cell-cell communication. However, the cellular pathways underlying this process remain largely unknown. Here we perform a genome-wide RNA interference screen and identify TIFA and TRAF6 as central players of <i>Shigella flexneri</i> and <i>Salmonella typhimurium</i>-induced interleukin-8 expression. We show that threonine 9 and the forkhead-associated domain of TIFA are necessary for the oligomerization of TIFA in both infected and bystander cells. Subsequently, this process triggers TRAF6 oligomerization and NF-κB activation. We demonstrate that TIFA/TRAF6-dependent cytokine expression is induced by the bacterial metabolite heptose-1,7-bisphosphate (HBP). In addition, we identify alpha-kinase 1 (ALPK1) as the critical kinase responsible for TIFA oligomerization and IL-8 expression in response to infection with <i>S</i>. <i>flexneri</i> and <i>S</i>. <i>typhimurium</i> but also to <i>Neisseria meningitidis</i>. Altogether, these results clearly show that ALPK1 is a master regulator of innate immunity against both invasive and extracellular gram-negative bacteria.</p></div

Residue T9, the FHA domain and residue E178 of TIFA are necessary for IL-8 expression.

<p><b>A)</b> Schematic representation of wild-type TIFA and the T9, RKN and E178A TIFA mutants. <b>B</b>) Only wild-type TIFA rescues IL-8 expression after siRNA-mediated depletion of TIFA. HeLa cells were transfected for 72 hours with TIFA-targeting siRNA. 24 hours prior infection, cells were transfected with empty vector, wild-type or mutated TIFA cDNA constructs. All TIFA cDNA constructs are TIFA siRNA-resistant. Cells were infected with <i>S</i>. <i>flexneri</i> Δ<i>virG</i> (green) for 3.5 hours. After fixation, cells were stained for F-actin (grey), DNA (blue) and IL-8 (red). Scale bars, 20 μm. <b>C</b>) Quantification of IL-8 as shown in B. Data correspond to the mean +/- SD of 3 independent experiments, p***<0.0005, ns: non-significant p>0.05.</p