Soil Liquefaction Seismic Risk Analysis Based on Post 1979 Earthquake Observations in Montenegro

The scale and consequences of soil liquefaction during April 15, 1979 Montenegro earthquake rose a problem of explanation of this phenomena and assessment of the ground behaviour during future earthquakes. The analysis, the details and results presented in this paper is divided into two parts: The first part comprises soil liquefaction during Aprill5 1979 earthquake including the analysis of both geotechnical conditions and excitation potential inducing them. In order to realise the scale and the properties of the phenomenon, distribution of the locations with manifestations likely to have been induced by soil liquefaction, as observed on the ground surface and on civil engineering structures, has been given and described. To identify the presence of conditions inducing soil liquefaction the geotechnical soil properties for several typical locations have been analysed. Analysis of the characteristic ground surface horizontal acceleration records obtained by the earthquake from the aspect of their potential to cause liquefaction have been also carried out. To determine the liquefaction potential of the considered earthquake detailed analysis of typical geotechnical model of a site have been performed. In the second part is presented the seismic risk analysis background for soil liquefaction aimed at explanation of the essential problems concerning the evaluation of geotechnical media comprising of loose sand under the effect of future earthquakes. At the same time, the complexity of the problems which have to be dealt with during the seismic risk investigations has been pointed out concerning the necessity of investigation in this sense. It is necessary to make some assumptions and simplifications for solving sane of these problems. Applying the results of the analysis from the first part as well as the assumptions and simplifications, an assesment of the seismic risk for soil liquefaction analysed in details in the first part applying one of the possible methodologies, has been carried out

A STUDY OF SUBCLINICAL MASTITIS IN TWO HERDS, ONE MANAGED ORGANICALLY, THE OTHER CONVENTIONALLY, AND THE EFFECT OF DIFFERENT MANAGEMENT STRATEGIES

Mastitis in two herds managed as a comparison between organic and conventional dairy farming systems was monitored for 9 years utilising regular bacterial culture of milk samples, individual and bulk somatic cell counts and observation by farm staff. The most important isolates in pure cultures were coagulase-negative staphylococci, Staphylococcus aureus, Streptococcus uberis, and Bacillus spp. Positive cultures were generally not associated with subclinical mastitis. The objective was to develop strategies for the control of mastitis in organic cows without the use of antibiotics. Within a set of key control measures, two management strategies were trialled, one of which reduced the prevalence of subclinical mastitis to very low levels

The ability of four strains of Streptococcus uberis to induce clinical mastitis after intramammary inoculation in lactating cows

AIM: To compare the ability of four strains of Streptococcus uberis at two doses to induce clinical mastitis in lactating dairy cows after intramammary inoculation in order to evaluate their usefulness for future experimental infection models. MATERIALS AND METHODS: Four field strains of Streptococcus uberis (26LB, S418, and S523 and SR115) were obtained from cows with clinical mastitis in the Wairarapa and Waikato regions of New Zealand. Twenty-four crossbred lactating cows, with no history of mastitis and absence of major pathogens following culture of milk samples, were randomly allocated to four groups (one per strain) of six cows. Each cow was infused (Day 0) in one quarter with approximately 104 cfu and in the contralateral quarter with approximately 106 cfu of the same strain. The other two quarters remained unchallenged. All four quarters were then inspected for signs of clinical mastitis, by palpation and observation of the foremilk, twice daily from Days 0–9, and composite milk samples were collected from Days 0–8 for analysis of somatic cell counts (SCC). Quarters were treated with penicillin when clinical mastitis was observed. Duplicate milk samples were collected and cultured on presentation of each clinical case and on Day 4 from challenged quarters with no clinical signs. RESULTS: Clinical mastitis was diagnosed in 26/48 (54%) challenged quarters. Challenge with strain S418 resulted in more cases of mastitis (12/12 quarters) than strains SR115 (7/12), 26LB (6/12) or S523 (1/12), and the mean interval from challenge to first diagnosis of mastitis was shorter for S418 than the other strains (p<0.001). The proportion of quarters from which S. uberis could be isolated after challenge was less for strain 26LB (1/6) than SR115 (6/7) (p<0.05), and SCC following challenge was lower for strain S523 than the other strains (p<0.05). CONCLUSIONS: There were significant differences between the strains in the proportion of quarters developing clinical mastitis, the interval to mastitis onset, SCC following challenge and the proportion of clinical cases from which S. uberis could be isolated. These results illustrate the difference in the ability of S. uberis strains to cause mastitis and the severity of the infections caused. CLINICAL RELEVANCE: Experimental challenge models can be used to compare infectivity and pathogenicity of different strains of mastitis-causing bacteria, the efficacy of pharmaceutical products and host-responses in a cost-effective manner.S Notcovich, G deNicolo, NB Williamson, A Grinberg, N Lopez-Villalobos, KR Petrovsk

ATP Release from Dying Autophagic Cells and Their Phagocytosis Are Crucial for Inflammasome Activation in Macrophages

Pathogen-activated and damage-associated molecular patterns activate the inflammasome in macrophages. We report that mouse macrophages release IL-1β while co-incubated with pro-B (Ba/F3) cells dying, as a result of IL-3 withdrawal, by apoptosis with autophagy, but not when they are co-incubated with living, apoptotic, necrotic or necrostatin-1 treated cells. NALP3-deficient macrophages display reduced IL-1β secretion, which is also inhibited in macrophages deficient in caspase-1 or pre-treated with its inhibitor. This finding demonstrates that the inflammasome is activated during phagocytosis of dying autophagic cells. We show that activation of NALP3 depends on phagocytosis of dying cells, ATP release through pannexin-1 channels of dying autophagic cells, P2X7 purinergic receptor activation, and on consequent potassium efflux. Dying autophagic Ba/F3 cells injected intraperitoneally in mice recruit neutrophils and thereby induce acute inflammation. These findings demonstrate that NALP3 performs key upstream functions in inflammasome activation in mouse macrophages engulfing dying autophagic cells, and that these functions lead to pro-inflammatory responses

Cigarette smoke-exposed neutrophils die unconventionally but are rapidly phagocytosed by macrophages

Pulmonary accumulation of neutrophils is typical for active smokers who are also predisposed to multiple inflammatory and infectious lung diseases. We show that human neutrophil exposure to cigarette smoke extract (CSE) leads to an atypical cell death sharing features of apoptosis, autophagy and necrosis. Accumulation of tar-like substances in autophagosomes is also apparent. Before detection of established cell death markers, CSE-treated neutrophils are effectively recognized and non-phlogistically phagocytosed by monocyte-derived macrophages. Blockade of LOX-1 and scavenger receptor A, but not MARCO or CD36, as well as pre-incubation with oxLDL, inhibited phagocytosis, suggesting that oxLDL-like structures are major phagocytosis signals. Specific lipid (β-carotene and quercetin), but not aqueous, antioxidants increased the pro-phagocytic effects of CSE. In contrast to non-phlogistic phagocytosis, degranulation of secondary granules, as monitored by lactoferrin release, was apparent on CSE exposure, which is likely to promote pulmonary inflammation and tissue degradation. Furthermore, CSE-exposed neutrophils exhibited a compromised ability to ingest the respiratory pathogen, Staphylococcus aureus, which likely contributes to bacterial persistence in the lungs of smokers and is likely to promote further pulmonary recruitment of neutrophils. These data provide mechanistic insight into the lack of accumulation of apoptotic neutrophil populations in the lungs of smokers and their increased susceptibility to degradative pulmonary diseases and bacterial infections

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Whole-exome sequencing in undiagnosed genetic diseases: interpreting 119 trios

Purpose: Despite the recognized clinical value of exome-based diagnostics, methods for comprehensive genomic interpretation remain immature. Diagnoses are based on known or presumed pathogenic variants in genes already associated with a similar phenotype. Here, we extend this paradigm by evaluating novel bioinformatics approaches to aid identification of new gene–disease associations. Methods: We analyzed 119 trios to identify both diagnostic genotypes in known genes and candidate genotypes in novel genes. We considered qualifying genotypes based on their population frequency and in silico predicted effects we also characterized the patterns of genotypes enriched among this collection of patients. Results: We obtained a genetic diagnosis for 29 (24%) of our patients. We showed that patients carried an excess of damaging de novo mutations in intolerant genes, particularly those shown to be essential in mice (P = 3.4 × 10−8). This enrichment is only partially explained by mutations found in known disease-causing genes. Conclusion: This work indicates that the application of appropriate bioinformatics analyses to clinical sequence data can also help implicate novel disease genes and suggest expanded phenotypes for known disease genes. These analyses further suggest that some cases resolved by whole-exome sequencing will have direct therapeutic implications

Systems genetics identifies Sestrin 3 as a regulator of a proconvulsant gene network in human epileptic hippocampus

Gene-regulatory network analysis is a powerful approach to elucidate the molecular processes and pathways underlying complex disease. Here we employ systems genetics approaches to characterize the genetic regulation of pathophysiological pathways in human temporal lobe epilepsy (TLE). Using surgically acquired hippocampi from 129 TLE patients, we identify a gene-regulatory network genetically associated with epilepsy that contains a specialized, highly expressed transcriptional module encoding proconvulsive cytokines and Toll-like receptor signalling genes. RNA sequencing analysis in a mouse model of TLE using 100 epileptic and 100 control hippocampi shows the proconvulsive module is preserved across-species, specific to the epileptic hippocampus and upregulated in chronic epilepsy. In the TLE patients, we map the trans-acting genetic control of this proconvulsive module to Sestrin 3 (SESN3), and demonstrate that SESN3 positively regulates the module in macrophages, microglia and neurons. Morpholino-mediated Sesn3 knockdown in zebrafish confirms the regulation of the transcriptional module, and attenuates chemically induced behavioural seizures in vivo