105110^{51} Ergs: The Evolution of Shell Supernova Remnants

This paper reports on a workshop hosted by the University of Minnesota, March 23-26, 1997. It addressed fundamental dynamical issues associated with the evolution of shell supernova remnants and the relationships between supernova remnants and their environments. The workshop considered, in addition to classical shell SNRs, dynamical issues involving X-ray filled composite remnants and pulsar driven shells, such as that in the Crab Nebula. Approximately 75 participants with wide ranging interests attended the workshop. An even larger community helped through extensive on-line debates prior to the meeting. Each of the several sessions, organized mostly around chronological labels, also addressed some underlying, general physical themes: How are SNR dynamics and structures modified by the character of the CSM and the ISM and vice versa? How are magnetic fields generated in SNRs and how do magnetic fields influence SNRs? Where and how are cosmic-rays (electrons and ions) produced in SNRs and how does their presence influence or reveal SNR dynamics? How does SNR blast energy partition into various components over time and what controls conversion between components? In lieu of a proceedings volume, we present here a synopsis of the workshop in the form of brief summaries of the workshop sessions. The sharpest impressions from the workshop were the crucial and under-appreciated roles that environments have on SNR appearance and dynamics and the critical need for broad-based studies to understand these beautiful, but enigmatic objects. \\Comment: 54 pages text, no figures, Latex (aasms4.sty). submitted to the PAS

Autophagy in periodontitis patients and gingival fibroblasts: unraveling the link between chronic diseases and inflammation

Authors are indebted with Ms Monica Glebocki for extensive editing of the manuscriptBackground: Periodontitis, the most prevalent chronic inflammatory disease, has been related to cardiovascular diseases. Autophagy provides a mechanism for the turnover of cellular organelles and proteins through a lysosome-dependent degradation pathway. The aim of this research was to study the role of autophagy in peripheral blood mononuclear cells from patients with periodontitis and gingival fibroblasts treated with a lipopolysaccharide of Porphyromonas gingivalis. Autophagy-dependent mechanisms have been proposed in the pathogenesis of inflammatory disorders and in other diseases related to periodontitis, such as cardiovascular disease and diabetes. Thus it is important to study the role of autophagy in the pathophysiology of periodontitis. Methods: Peripheral blood mononuclear cells from patients with periodontitis (n = 38) and without periodontitis (n = 20) were used to study autophagy. To investigate the mechanism of autophagy, we evaluated the influence of a lipopolysaccharide from P. gingivalis in human gingival fibroblasts, and autophagy was monitored morphologically and biochemically. Autophagosomes were observed by immunofluorescence and electron microscopy. Results: We found increased levels of autophagy gene expression and high levels of mitochondrial reactive oxygen species production in peripheral blood mononuclear cells from patients with periodontitis compared with controls. A significantly positive correlation between both was observed. In human gingival fibroblasts treated with lipopolysaccharide from P. gingivalis, there was an increase of protein and transcript of autophagy-related protein 12 (ATG12) and microtubule-associated protein 1 light chain 3 alpha LC3. A reduction of mitochondrial reactive oxygen species induced a decrease in autophagy whereas inhibition of autophagy in infected cells increased apoptosis, showing the protective role of autophagy. Conclusion: Results from the present study suggest that autophagy is an important and shared mechanism in other conditions related to inflammation or alterations of the immune system, such as periodontiti

More Than 1,001 Problems with Protein Domain Databases: Transmembrane Regions, Signal Peptides and the Issue of Sequence Homology

Large-scale genome sequencing gained general importance for life science because functional annotation of otherwise experimentally uncharacterized sequences is made possible by the theory of biomolecular sequence homology. Historically, the paradigm of similarity of protein sequences implying common structure, function and ancestry was generalized based on studies of globular domains. Having the same fold imposes strict conditions over the packing in the hydrophobic core requiring similarity of hydrophobic patterns. The implications of sequence similarity among non-globular protein segments have not been studied to the same extent; nevertheless, homology considerations are silently extended for them. This appears especially detrimental in the case of transmembrane helices (TMs) and signal peptides (SPs) where sequence similarity is necessarily a consequence of physical requirements rather than common ancestry. Thus, matching of SPs/TMs creates the illusion of matching hydrophobic cores. Therefore, inclusion of SPs/TMs into domain models can give rise to wrong annotations. More than 1001 domains among the 10,340 models of Pfam release 23 and 18 domains of SMART version 6 (out of 809) contain SP/TM regions. As expected, fragment-mode HMM searches generate promiscuous hits limited to solely the SP/TM part among clearly unrelated proteins. More worryingly, we show explicit examples that the scores of clearly false-positive hits, even in global-mode searches, can be elevated into the significance range just by matching the hydrophobic runs. In the PIR iProClass database v3.74 using conservative criteria, we find that at least between 2.1% and 13.6% of its annotated Pfam hits appear unjustified for a set of validated domain models. Thus, false-positive domain hits enforced by SP/TM regions can lead to dramatic annotation errors where the hit has nothing in common with the problematic domain model except the SP/TM region itself. We suggest a workflow of flagging problematic hits arising from SP/TM-containing models for critical reconsideration by annotation users

Transient Global Aphasia with Hemiparesis Following Cerebral Angiography : Relationship to Blood Brain Barrier Disruption

Temporary disruption of the blood-brain barrier (BBB) after cerebral angiography is presumably caused by nonionic radiographic contrast medium (CM). We hereby report a case of 58-year-old woman who developed decreased mentality, global aphasia and aggravated right hemiparesis after cerebral angiography. Brain CT examination demonstrated gyriform enhancement throughout the left cerebral cortex and thalamus. MR diffusion did not reveal acute infarction. MR angiography did not show any stenosis, spasm or occlusion at the major cerebral vessels. Follow-up CT scan after 1 day did not show any gyriform enhancement. Worsened neurologic signs and symptoms were improved completely after 7 days. In the present study, disruption of the BBB with contrast medium after angiography seems to be the causative factor of transient neurologic deterioration

Prospective evaluation of the partially covered nitinol \u201cComVi\u201d stent for malignant non hilar biliary obstruction

Background: Biliary partially covered self-expandable metal stents (PC-SEMS) offer prolonged relief of symptoms of biliary obstruction but may induce complications including pancreatitis, cholecystitis and migration. Aims: To assess efficacy and safety of the ComVi partially covered self-expandable metal stents as primary palliative treatment of distal malignant biliary obstruction. Methods: Seventy patients (mean age 69.2 years) with distal malignant biliary strictures were prospectively included and underwent endoscopic retrograde cholangio-pancreatography and partially covered self-expandable metal stents placement. Follow-up was done for 12 months. self-expandable metal stents patency, survival and complication-rate after partially covered self-expandable metal stents placement were evaluated. Results: Overall median survival time was 190 days (30\u2013856). Forty-four patients (62.8%) died after median 175.5 days (30\u2013614) without signs of stent dysfunction; 37 patients (52.8%) were alive after 6 months without signs of self-expandable metal stents occlusion. Survival rapidly dropped between 8 and 12 months after treatment. Survival was not influenced by sex (P = 0.1) or type of neoplasia (P = 0.178). Median survival was longer (254 days [44\u2013836]) in patients who underwent chemotherapy (P < 0.0001). Partially covered self-expandable metal stents occlusion had 24 (35.7%) patients 154 days (35\u2013485) after treatment. Median survival after re-treatment was 66 days (13\u2013597). Cholecystitis occurred in one patient (1.7%). Conclusions: The ComVi partially covered self-expandable metal stents is effective for palliation of biliary obstruction secondary to distal malignant biliary strictures. Self-expandable metal stents patency during follow-up is satisfactory without significant complications