Safety and efficacy of helical tomotherapy following lung-sparing surgery in locally advanced malignant pleural mesothelioma.

PURPOSE: To assess the value of radiation therapy (RT) with helical tomotherapy (HT) in the management of locally advanced malignant pleural mesothelioma (MPM) receiving no or lung-sparing surgery. METHODS: Consecutive MPM cases not undergoing extrapleural pneumonectomy and receiving intensity-modulated (IM) HT were retrospectively evaluated for local control, distant control, progression-free survival (PFS), and overall survival (OS). Impact of age, systemic treatment, RT dose, and recurrence patterns was analyzed by univariate and multivariate analysis. As a secondary endpoint, reported toxicity was assessed. RESULTS: A total of 34 localized MPM cases undergoing IMHT were identified, of which follow-up data were available for 31 patients. Grade 3 side effects were experienced by 26.7% of patients and there were no grade 4 or 5 events observed. Median PFS was 19 months. Median OS was 20 months and the rates for 1­ and 2­year OS were 86.2 and 41.4%, respectively. OS was significantly superior for patients receiving adjuvant chemotherapy (p = 0.008). CONCLUSION: IMHT of locally advanced MPM after lung-sparing surgery is safe and feasible, resulting in satisfactory local control and survival. Adjuvant chemotherapy significantly improves OS. Randomized clinical trials incorporating modern RT techniques as a component of trimodal treatment are warranted to establish an evidence-based standard of care pattern for locally advanced MPM.

Characterization of phage vB_EcoS-EE09 infecting E. coli DSM613 Isolated from Wastewater Treatment Plant Effluent and Comparative Proteomics of the Infected and Non-Infected Host.

Phages influence microbial communities, can be applied in phage therapy, or may serve as bioindicators, e.g., in (waste)water management. We here characterized the Escherichia phage vB_EcoS-EE09 isolated from an urban wastewater treatment plant effluent. Phage vB_EcoS-EE09 belongs to the genus Dhillonvirus, class Caudoviricetes. It has an icosahedral capsid with a long non-contractile tail and a dsDNA genome with an approximate size of 44 kb and a 54.6% GC content. Phage vB_EcoS-EE09 infected 12 out of the 17 E. coli strains tested. We identified 16 structural phage proteins, including the major capsid protein, in cell-free lysates by protein mass spectrometry. Comparative proteomics of protein extracts of infected E. coli cells revealed that proteins involved in amino acid and protein metabolism were more abundant in infected compared to non-infected cells. Among the proteins involved in the stress response, 74% were less abundant in the infected cultures compared to the non-infected controls, with six proteins showing significant less abundance. Repressing the expression of these proteins may be a phage strategy to evade host defense mechanisms. Our results contribute to diversifying phage collections, identifying structural proteins to enable better reliability in annotating taxonomically related phage genomes, and understanding phage-host interactions at the protein level.

Screening the Thermotoga maritima genome for new wide-spectrum nucleoside and nucleotide kinases.

Enzymes from thermophilic organisms are interesting biocatalysts for a wide variety of applications in organic synthesis, biotechnology, and molecular biology. Next to an increased stability at elevated temperatures, they were described to show a wider substrate spectrum than their mesophilic counterparts. To identify thermostable biocatalysts for the synthesis of nucleotide analogs, we performed a database search on the carbohydrate and nucleotide metabolism of Thermotoga maritima. After expression and purification of 13 enzyme candidates involved in nucleotide synthesis, these enzymes were screened for their substrate scope. We found that the synthesis of 2'-deoxynucleoside 5'-monophosphates (dNMPs) and uridine 5'-monophosphate from nucleosides was catalyzed by the already known wide-spectrum thymidine kinase and the ribokinase. In contrast, no NMP-forming activity was detected for adenosine-specific kinase, uridine kinase, or nucleotidase. The NMP kinases (NMPKs) and the pyruvate-phosphate-dikinase of T. maritima exhibited a rather specific substrate spectrum for the phosphorylation of NMPs, while pyruvate kinase, acetate kinase, and three of the NMPKs showed a broad substrate scope with (2'-deoxy)nucleoside 5'-diphosphates as substrates. Based on these promising results, TmNMPKs were applied in enzymatic cascade reactions for nucleoside 5'-triphosphate synthesis using four modified pyrimidine nucleosides and four purine NMPs as substrates, and we determined that base- and sugar-modified substrates were accepted. In summary, besides the already reported TmTK, NMPKs of T. maritima were identified to be interesting enzyme candidates for the enzymatic production of modified nucleotides.

Evaluation of a document search engine in a clinical department system.

MorphoSaurus, a concept-based document search engine,was incorporated into an EHR system in order to support search across the whole corpus of patient discharge letters and other clinically relevant documents. A user survey showed a general satisfaction with the system and revealed novel usages for information stored in discharge letters.The retrieval system was also used to identify relevant documents for a five-year retrospective survey of suspicious syphilis cases in the department. This retrieval scenario was used to assess the performance of MorphoSaurus against a manually created gold standard. A substring search for the German words "syphilis" and"lues" was used as baseline. The system yielded a precision p = 20.1% and a recall r = 100%. The values for the substring "syphilis" were p = 65.5% and r = 47.5%, for"lues" p = 15.4% and r = 87.7%. The results support the use of the proposed recall-oriented search across EHR documents to acquire valid and complete data for epidemiology studies in hospital populations.

The dark spots of Arago.

We explore the diffraction and propagation of Laguerre- Gaussian beams of varying azimuthal index past a circular obstacle both experimentally and numerically. When the beam and obstacle centers are aligned the famous spot of Arago, which arises for zero azimuthal index, is replaced for non-zero azimuthal indices by a dark spot of Arago, a simple consequence of the conserved phase singularity at the beam center. We explore how the dark spot of Arago behaves as the beam and obstacle centers are progressively misaligned, and find that the central dark spot may break into several dark spots of Arago for higher incident azimuthal index beams.

White light propagation invariant beams.

Propagation invariant light fields such as Bessel light beams are of interest in a variety of current areas such as micromanipulation of atoms and mesoscopic particles, laser plasmas, and the study of optical angular momentum. Considering the optical fields as a superposition of conical waves, we discuss how the coherence properties of light play a key role in their formation. As an example, we show that Bessel beams can be created from temporally incoherent broadband light sources including a halogen bulb. By using a supercontinuum source we elucidate how the beam behaves as a function of bandwidth of the incident light field.