Activation of the epidermal growth factor receptor (EGFR) by a novel metalloprotease pathway

Neutrophil Elastase (NE) is a pro-inflammatory protease present at higher than normal levels in the lung during inflammatory disease. NE regulates IL-8 production from airway epithelial cells and can activate both EGFR and TLR4. TACE/ADAM17 has been reported to trans-activate EGFR in response to NE. Here, using 16HBE14o-human bronchial epithelial cells we demonstrate a new mechanism by which NE regulates both of these events. A high molecular weight soluble metalloprotease activity detectable only in supernatants from NE-treated cells by gelatin and casein zymography was confirmed to be meprin alpha by Western immunoblotting. In vitro studies demonstrated the ability of NE to activate meprin alpha, which in turn could release soluble TGFalpha and induce IL-8 production from 16HBE14o- cells. These effects were abrogated by actinonin, a specific meprin inhibitor. NE-induced IL-8 expression was also inhibited by meprin alpha siRNA. Immunoprecipitation studies detected EGFR/TLR4 complexes in NE-stimulated cells overexpressing these receptors. Confocal studies confirmed colocalization of EGFR and TLR4 in 16HBE14o- cells stimulated with meprin alpha. NFkappaB was also activated via MyD88 in these cells by meprin alpha. In bronchoalveolar lavage fluid from NE knock-out mice infected intra-tracheally with Pseudomonas aeruginosa meprin alpha was significantly decreased compared with control mice, and was significantly increased and correlated with NE activity, in bronchoalveolar lavage fluid from individuals with cystic fibrosis but not healthy controls. The data describe a previously unidentified lung metalloprotease meprin alpha, and its role in NE-induced EGFR and TLR4 activation and IL-8 production.

Geology of a Portion of the Bull Mountain Range Jefferson County, Montana

Work was first done on a known section, the south Boulder Section, in order to familiarize the student with the formations. Most of the area was mapped by plane table and telescopic alidade, general features being surveyed by automobile traverse and a pacing traverse.

High Temperature Superconductivity: Taming Serendipity

A century after the discovery of superconductivity, the design of new and more useful superconductors remains enigmatic. High-temperature super-conductors offer unique solutions to fundamental grid challenges of the 21st century and hold great promise in addressing global energy challenges in energy production, storage, and distribution. Traditionally guided by serendipity, researchers now endeavor to design new superconductors predictively. Advanced experimental techniques, such as point contact spectroscopy measurements, aid in identifying promising candidates.

A Study of the Physical Properties of Low Tin Solders

In 1947, out of the 100,000 long tons of tin con­sumed in the United States, 25,000 tons went into solder. Tin plate took 39,000 tons while babbit, bronze and coll­apsible tubes accounted for approximately 17,000 tons. Solder ranked second to tin plate and required more than the next three major uses combined.

Inverse relationship between fractionated electrograms and atrial fibrosis in persistent atrial fibrillation: combined magnetic resonance imaging and high-density mapping

OBJECTIVES This study sought to evaluate the relationship between fibrosis imaged by delayed-enhancement (DE) magnetic resonance imaging (MRI) and atrial electrograms (Egms) in persistent atrial fibrillation (AF). BACKGROUND Atrial fractionated Egms are strongly related to slow anisotropic conduction. Their relationship to atrial fibrosis has not yet been investigated. METHODS Atrial high-resolution MRI of 18 patients with persistent AF (11 long-lasting persistent AF) was registered with mapping geometry (NavX electro-anatomical system (version 8.0, St. Jude Medical, St. Paul, Minnesota)). DE areas were categorized as dense or patchy, depending on their DE content. Left atrial Egms during AF were acquired using a high-density, 20-pole catheter (514 ± 77 sites/map). Fractionation, organization/regularity, local mean cycle length (CL), and voltage were analyzed with regard to DE. RESULTS Patients with long-lasting persistent versus persistent AF had larger left atrial (LA) surface area (134 ± 38 cm(2) vs. 98 ± 9 cm(2), p = 0.02), a higher amount of atrial DE (70 ± 16 cm(2) vs. 49 ± 10 cm(2), p = 0.01), more complex fractionated atrial Egm (CFAE) extent (54 ± 16 cm(2) vs. 28 ± 15 cm(2), p = 0.02), and a shorter baseline AF CL (147 ± 10 ms vs. 182 ± 14 ms, p = 0.01). Continuous CFAE (CFEmean [NavX algorithm that quantifies Egm fractionation] <80 ms) occupied 38 ± 19% of total LA surface area. Dense DE was detected at the left posterior left atrium. In contrast, the right posterior left atrium contained predominantly patchy DE. Most CFAE (48 ± 14%) occurred at non-DE LA sites, followed by 41 ± 12% CFAE at patchy DE and 11 ± 6% at dense DE regions (p = 0.005 and p = 0.008, respectively); 19 ± 6% CFAE sites occurred at border zones of dense DE. Egms were less fractionated, with longer CL and lower voltage at dense DE versus non-DE regions: CFEmean: 97 ms versus 76 ms, p < 0.0001; local CL: 153 ms versus 143 ms, p < 0.0001; mean voltage: 0.63 mV versus 0.86 mV, p < 0.0001. CONCLUSIONS Atrial fibrosis as defined by DE MRI is associated with slower and more organized electrical activity but with lower voltage than healthy atrial areas. Ninety percent of continuous CFAE sites occur at non-DE and patchy DE LA sites. These findings are important when choosing the ablation strategy in persistent AF.

Testing for Measurement Equivalence in Surveys: Dimensions of Social Trust across Cultural Contexts

Our study evaluates the dimensionality and equivalence of social trust across cultural contexts, using new data from Switzerland and the World Values Survey 2005–2008. Whereas some scholars assert that trust should be regarded as a coherent concept, others claim that trust is better conceived of as a multidimensional concept. In contrast to the conventional dichotomy of the forms of social trust, we identify three distinct forms of trust, namely, particularized, generalized, and identity-based trust. Moreover, we dispute the view that respondents understand the wording of survey questions regarding social trust differently between different cultural contexts, which would imply that comparative research on trust is a pointless endeavor. Applying multiple-group confirmatory factor analysis to the various constructs of social trust, we conclude that one may study relationships among the three forms of trust and other theoretical constructs as well as compare latent means across cultural contexts. Our analyses therefore provide an optimistic outlook for future comparative analyses that investigate forms of social trust across cultural contexts.

Political Depolarization in German Public Opinion, 1980–2010

Little is known about political polarization in German public opinion. This article offers an issue-based perspective and explores trends of opinion polarization in Germany. Public opinion polarization is conceptualized and measured as alignment of attitudes. Data from the German General Social Survey (1980 to 2010) comprise attitudes towards manifold issues, which are classified into several dimensions. This study estimates multilevel models that reveal general and issue- as well as dimension-specific levels and trends in attitude alignment for both the whole German population and sub-groups. It finds that public opinion polarization has decreased over the last three decades in Germany. In particular, highly educated and more politically interested people have become less polarized over time. However, polarization seems to have increased in attitudes regarding gender issues. These findings provide interesting contrasts to existing research on the American public.

Persistence of biological traces in gun Barrels after fatal contact shots

Backspatter from wounds caused by contact shots against a biological target had before been shown to be propelled into firearms' barrels where they can persist and be retrieved from as relevant forensic evidence. Herein, that insight was applied to the investigation of a case of multiple familial homicide with a firearm. Samples of backspatter were collected from the firearm using DNA-free swabs. DNA was extracted from the swabs, and 16 STR systems were PCR-amplified to generate DNA profiles of all victims shot by the firearm. The quality of the resulting DNA profiles was sufficient to exclude the perpetrator as donor and to differentiate the three closely related victims thereby proving that all three victims had been shot by the same firearm from very close or contact distance. A key insight gained from this case was that not only a firearms' barrel inside but other inner surfaces may be charged with profilable DNA.

Anmerkungen zu den (spät)persischen Samaria-Bullen aus dem Wadi ed-Dalije. Hellenisches, Persisches und Lokaltraditionen im Grenzgebiet der Provinz Jehud

The present article deals exemplarily with the remarkable iconographic attestations connected with the Wadi ed-Daliye (WD) findings. The discussed bullae were attached to papyri which provide a clear dating of the hoard between 375-335 BCE. Considering style and convention the preserved motives are to be classified as Persian, Greek or Greco-Persian. A major goal of the following presentation is the contextualization of the very material; this is achieved by taking into account local parallels as well as relevant attestations of the dominant / “imperial” cultures of Persia and Greece. The correlation of motives with the (often more complex, more detailed or more contoured) examples stemming from the “source-cultures” follows a clear agenda: It is methodologically based on the approach that was employed by Silvia Schroer and Othmar Keel throughout the project „Die Ikonographie Palästinas/Israels und der Alte Orient (IPIAO). Eine Religionsgeschichte in Bildern” (2005, 23ff). The WD-findings demand a careful analysis since the influencing cultures behind the imagery are deeply rooted in the field of Greek mythology and iconography. Special attention has to be drawn to the bullae, as far as excavated, from a huge Punic temple archive of Carthago (Berges 1997 and 2002) as well as those from the archive of the satrap seat in Daskyleion in the Northwest of Asia Minor (Kaptan 2002), which are chronologically close (end 5th and 4th century BCE) to the WD-finds. Not each and every single motive and artifact of the WD-corpus comprising more than 120 items can be dealt with in detail throughout the following pages. We refer to the editio princeps by Leith (1990, 1997) respectively to the concerning chapter in Keel’s Corpus volume II (Keel 2010, 340-379). The article gives a brief history of research (2.), some basic remarks on the development of style (3.) and a selection of detail-studies (4.). A crosscheck with other relevant corpora of stamp-seals (5.) as well as a compressed synthesis (6.) are contributions in order to characterize and classify the unique iconographic assemblage. There are rather few references to the late Persian coins from Samaria (Meshorer/Qedar 1999), which have been impressed about contemporaneous with the WD-bullae (372-333 BCE), as there is an article by Patrick Wyssmann in this volume about that specific corpus. Through the perspective of the late Persian iconography, Samaria appears as a dazzling metropolis at the crossroads of Greek and Persian culture, which is far away from a strict and revolutionary religious orthodoxy