25,077 research outputs found

    The minor groove-binding agent ELB-21 forms multiple interstrand and intrastrand covalent cross-links with duplex DNA and displays potent bactericidal activity against methicillin-resistant Staphylococcus aureus

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    Objectives The antistaphylococcal pyrrolobenzodiazepine dimer ELB-21 forms multiple adducts with duplex DNA through covalent interactions with appropriately spaced guanine residues; it is now known to form interstrand and intrastrand adducts with oligonucleotide sequences of variable length. We determined the DNA sequence preferences of ELB-21 in relation to its capacity to exert a bactericidal effect by damaging DNA.Methods Formation of adducts by ELB-21 and 12- to 14-mer DNA duplexes was investigated using ion-pair reversed phase liquid chromatography and mass spectrometry. Drug-induced changes in gene expression were measured in prophage-free Staphylococcus aureus RN4220 by microarray analysis.Results ELB-21 preferentially formed intrastrand adducts with guanines separated by three nucleotide base pairs. Interstrand and intrastrand adducts were formed with duplexes both longer and shorter than the preferred target sequences. ELB-21 elicited rapid bactericidal effects against prophage-carrying and prophage-free S. aureus strains; cell lysis occurred following activation and release of resident prophages. Killing appeared to be due to irreparable damage to bacterial DNA and susceptibility to ELB-21 was governed by the capacity of staphylococci to repair DNA lesions through induction of the SOS DNA damage response mediated by the RecA-LexA pathway.Conclusions The data support the contention that ELB-21 arrests DNA replication, eliciting formation of ssDNA-RecA filaments that inactivate LexA, the SOS repressor, and phage repressors such as Cl, resulting in activation of the DNA damage response and de-repression of resident prophages. Above the MIC threshold, DNA repair is ineffective

    Jack Alive / Martin Dead : The Location of the "Author" in Jack London\u27s Martin Eden

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    This essay is an attempt to read Martin Eden, Jack Londonʼs autobiographical novel, in terms of the inextricable relationship between the author and the protagonist. Critics have often taken the unbalanced plot and the lack of ironic distance between narrator and character in Martin Eden as the technical weakness of London, but this paper argues that the achievement of this novel owes a great deal to the attachment of London to Martin. The unbalanced structure is a necessary product of the severe struggle of the author to kill his romantic alter ego. // Martin, who aspires to win Ruth Morse, tries to cross class boundaries by making a career of a writer. Even after realizing the emptiness of Ruth, who turns out to be nothing but a typical figure of the bourgeoisie, he somehow persists in loving her. The notion underlying here is that, for Martin, love, career and art are fundamentally inseparable. He objects to the aestheteʼs view of Brissenden on account of his separation of art from career. Martinʼs identity and life consist only in the triunity of love/career/art; the alternative is the repudiation of life. Thus, the unnatural delay of his disappointment in love can be regarded as Londonʼs strategy to set the suicide of Martin as the necessary consequence of the story. // By finishing the story and killing Martin, London finally detaches himself from Martin, reconstructs his self, and, unlike Martin, survives as a professional writer. In this sense, Martin Eden is a story about “writerʼs self-reconstruction.

    Robert Martin Tiffin's Mystery Man Newspaper Articles

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    Advertiser-Tribune newspaper clippings featuring a story about Robert Martin (written by Nancy Kleinhenz), a local author from Tiffin (Ohio) who wrote under the pseudonym of Lee Roberts, and two of his short stories. Martin wrote mystery novels in his spare time, creating more than 22 mystery novels. For more information about Robert Martin and a list of books go to http://www.mysteryfile.com/RMartin/JBennett.html

    Ruptured posterior circulation aneurysms: epidemiology, patterns of care, and outcomes from the Swiss SOS national registry

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    Background The treatment of ruptured posterior circulation aneurysms remains challenging despite progresses in the endovascular and neurosurgical techniques. Objective To provide epidemiological characterization of subjects presenting with ruptured posterior circulation aneurysms in Switzerland and thereby assessing the treatment patterns and neurological outcomes. Methods This is a retrospective analysis of the Swiss SOS registry for patients with aneurysmal subarachnoid hemorrhage. Patients were divided in 3 groups (upper, lower, and middle third) according to aneurysm location. Clinical, radiological, and treatment-related variables were identified and their impact on the neurological outcome was determined. Results From 2009 to 2014, we included 264 patients with ruptured posterior circulation aneurysms. Endovascular occlusion was the most common treatment in all 3 groups (72% in the upper third, 68% in the middle third, and 58.8% in the lower third). Surgical treatment was performed in 11.3%. Favorable outcome (mRS ≤ 3) was found in 56% at discharge and 65.7% at 1 year. No significant difference in the neurological outcome were found among the three groups, in terms of mRS at discharge (p = 0.20) and at 1 year (p = 0.18). High WFNS grade, high Fisher grade at presentation, and rebleeding before aneurysm occlusion (p = 0.001) were all correlated with the risk of unfavorable neurological outcome (or death) at discharge and at 1 year. Conclusions In this study, endovascular occlusion was the principal treatment, with a favorable outcome for two-thirds of patients at discharge and at long term. These results are similar to high volume neurovascular centers worldwide, reflecting the importance of centralized care at specialized neurovascular centers

    Experiences Using Large Scale Video Walls for Distance Education

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    We describe our experiences building and using the Rutgers Videowall, a low-cost telepresence system that has been used teaching 15 courses and colloquia. By relaxing typical spatial telepresence features, such as background continuity, we greatly reduced costs and gained flexibility in the rooms it could be deployed in. The lower costs and room flexibility enabled academic departments to use the wall, in contrast to traditional telepresence systems which remained inaccessible. We found that the Videowall’s spatial distortions did not have a significant impact on useability, as our initial survey results show that students had an overall positive experience.Technical report DCS-tr-72

    Hans Martin Schwarz Collection 1934 - 1938

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    This collection contains clippings of articles by Hans Martin Schwarz (1917, Hamburg – 2006, New York, better known as Martin Ebon), published between 1934 and 1938 in German-Jewish newspapers on a wide variety of subjects such as sports, emigration, the political situation in Germany, and religious attitudes of the young. It also contains reviews of his books "Einer wie Du und Ich" and "Heiteres, Besinnliches, Nachdenkliches."digitizedHans Martin Schwarz (1917, Hamburg – 2006, New York, better known as Martin Ebon), was a journalist and author. In Germany during the 1930s, he published in a variety of German-Jewish periodicals, primarily the Israelitisches Familienblatt. After immigrating to the United States in 1938, he changed his name to Martin Ebon, and published dozens of books in the areas of world affairs and parapsychology.Processe

    Interview with Father James Martin

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    In May 2011, the Ignatian Faculty Scholars at Regis University conducted a Skype interview with Father James Martin, S. J., author of The Jesuit Guide to Almost Everything. The Scholars had used Father Martin’s book as a text for their year of study, which focused on Ignatian Spirituality, the Ignatian Pedagogical Paradigm, and teaching and learning at a Jesuit university. The interview was transcribed and is printed below. Father Martin reflects on the book, and responds to questions about the book itself, about finding God in all learners, and about the Church

    Ruptured PICA aneurysms: presentation and treatment outcomes compared to other posterior circulation aneurysms. A Swiss SOS study

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    BACKGROUND AND PURPOSE: Aneurysms of the posterior inferior cerebellar artery (PICA) are relatively uncommon and evidence is sparse about patients presenting with ruptured PICA aneurysms. We performed an analysis of the Swiss SOS national registry to describe clinical presentation, treatment pattern, and neurological outcome of patients with ruptured PICA aneurysms compared with other ruptured posterior circulation (PC) aneurysms. METHODS: This was a retrospective analysis of anonymized data from the Swiss SOS registry (Swiss Study on Aneurysmal Subarachnoid Hemorrhage; 2009-2014). Patients with ruptured PC aneurysms were subdivided into a PICA and non-PICA group. Clinical, radiological, and treatment-related variables were identified, and their impact on the neurological outcome was determined in terms of modified Rankin score at discharge and at 1 year of follow-up for the two groups. RESULTS: Data from 1864 aneurysmal subarachnoid hemorrhage patients were reviewed. There were 264 patients with a ruptured PC aneurysm. Seventy-four PICA aneurysms represented 28% of the series; clinical and radiological characteristics at admission were comparable between the PICA and non-PICA group. Surgical treatment was accomplished in 28% of patients in the PICA group and in the 4.8% of patients in the non-PICA group. No statistically significant difference was found between the two groups in terms of complications after treatment. Hydrocephalus requiring definitive shunt was needed in 21.6% of PICA patients (p = 0.6); cranial nerve deficit was present in average a quarter of the patients in both PICA and non-PICA group with no statistical difference (p = 0.3). A more favorable outcome (66.2%) was reported in the PICA group at discharge (p < 0.05) but this difference faded over time with a similar neurological outcome at 1-year follow-up (p = 0.09) between both PICA and non-PICA group. The Kaplan-Meyer estimation showed no significant difference in the mortality rate between both groups (p = 0.08). CONCLUSIONS: In the present study, patients with ruptured PICA aneurysms had a favorable neurological outcome in more than two thirds of cases, similar to patients with other ruptured PC aneurysms. Surgical treatment remains a valid option in a third of cases with ruptured PICA aneurysms

    UV- and MMS-induced mutagenesis of lambdaO(am)8 phage under nonpermissive conditions for phage DNA replication.

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    Mutagenesis in Escherichia coli, a subject of many years of study is considered to be related to DNA replication. DNA lesions nonrepaired by the error-free nucleotide excision repair (NER), base excision repair (BER) and recombination repair (RR), stop replication at the fork. Reinitiation needs translesion synthesis (TLS) by DNA polymerase V (UmuC), which in the presence of accessory proteins, UmuD', RecA and ssDNA-binding protein (SSB), has an ability to bypass the lesion with high mutagenicity. This enables reinitiation and extension of DNA replication by DNA polymerase III (Pol III). We studied UV- and MMS-induced mutagenesis of lambdaO(am)8 phage in E. coli 594 sup+ host, unable to replicate the phage DNA, as a possible model for mutagenesis induced in nondividing cells (e.g. somatic cells). We show that in E. coli 594 sup+ cells UV- and MMS-induced mutagenesis of lambdaO(am)8 phage may occur. This mutagenic process requires both the UmuD' and C proteins, albeit a high level of UmuD' and low level of UmuC seem to be necessary and sufficient. We compared UV-induced mutagenesis of lambdaO(am)8 in nonpermissive (594 sup+) and permissive (C600 supE) conditions for phage DNA replication. It appeared that while the mutagenesis of lambdaO(am)8 in 594 sup+ requires the UmuD' and C proteins, which can not be replaced by other SOS-inducible protein(s), in C600 supE their functions may be replaced by other inducible protein(s), possibly DNA polymerase IV (DinB). Mutations induced under nonpermissive conditions for phage DNA replication are resistant to mismatch repair (MMR), while among those induced under permissive conditions, only about 40% are resistant
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