INFOS: spectrum fitting software for NMR analysis

Software for fitting of NMR spectra in MATLAB is presented. Spectra are fitted in the frequency domain, using Fourier transformed lineshapes, which are derived using the experimental acquisition and processing parameters. This yields more accurate fits compared to common fitting methods that use Lorentzian or Gaussian functions. Furthermore, a very time-efficient algorithm for calculating and fitting spectra has been developed. The software also performs initial peak picking, followed by subsequent fitting and refinement of the peak list, by iteratively adding and removing peaks to improve the overall fit. Estimation of error on fitting parameters is performed using a Monte-Carlo approach. Many fitting options allow the software to be flexible enough for a wide array of applications, while still being straightforward to set up with minimal user input.     

Phrasal Paraphrase Based Question Reformulation for Archived Question Retrieval

Lexical gap in cQA search, resulted by the variability of languages, has been recognized as an important and widespread phenomenon. To address the problem, this paper presents a question reformulation scheme to enhance the question retrieval model by fully exploring the intelligence of paraphrase in phrase-level. It compensates for the existing paraphrasing research in a suitable granularity, which either falls into fine-grained lexical-level or coarse-grained sentence-level. Given a question in natural language, our scheme first detects the involved key-phrases by jointly integrating the corpus-dependent knowledge and question-aware cues. Next, it automatically extracts the paraphrases for each identified key-phrase utilizing multiple online translation engines, and then selects the most relevant reformulations from a large group of question rewrites, which is formed by full permutation and combination of the generated paraphrases. Extensive evaluations on a real world data set demonstrate that our model is able to characterize the complex questions and achieves promising performance as compared to the state-of-the-art methods.     

Module-based construction of plasmids for chromosomal integration of the fission yeast Schizosaccharomyces pombe

Integration of an external gene into a fission yeast chromosome is useful to investigate the effect of the gene product. An easy way to knock-in a gene construct is use of an integration plasmid, which can be targeted and inserted to a chromosome through homologous recombination. Despite the advantage of integration, construction of integration plasmids is energy- and time-consuming, because there is no systematic library of integration plasmids with various promoters, fluorescent protein tags, terminators and selection markers; therefore, researchers are often forced to make appropriate ones through multiple rounds of cloning procedures. Here, we establish materials and methods to easily construct integration plasmids. We introduce a convenient cloning system based on Golden Gate DNA shuffling, which enables the connection of multiple DNA fragments at once: any kind of promoters and terminators, the gene of interest, in combination with any fluorescent protein tag genes and any selection markers. Each of those DNA fragments, called a ‘module’, can be tandemly ligated in the order we desire in a single reaction, which yields a circular plasmid in a one-step manner. The resulting plasmids can be integrated through standard methods for transformation. Thus, these materials and methods help easy construction of knock-in strains, and this will further increase the value of fission yeast as a model organism.     

Percutaneous closure of a patent foramen ovale after cryptogenic stroke

A patent foramen ovale is a common intracardiac finding that is located between the left and right atrium. It can cause right-to-left shunting and has a high prevalence in patients who suffer a cryptogenic stroke. Earlier trials did not show superiority of percutaneous patent foramen ovale closure with standard medical therapy over standard medical therapy alone in the treatment of cryptogenic stroke. Interestingly, several meta-analyses show positive results regarding closure, suggesting underpowering of the individual trials. Recently, two large prospective trials and one long-term follow-up study showed benefit of percutaneous closure over standard medical therapy in treatment of cryptogenic stroke. A larger right-to-left shunt or the presence of an atrial septal aneurysm were predictors for a recurrent event. Therefore, percutaneous patent foramen ovale closure after cryptogenic stroke should be recommended over antiplatelet therapy alone in patients younger than 55 years of age with a high-risk patent foramen ovale.     

Fickean and Non-Fickean Water Desorption During Vacuum Drying of <Emphasis Type="Italic">L. bulgaricus</Emphasis>

The recovery of Lactobacillus bulgaricus was studied in correlation to the kinetics of cell drying. When bacteria were dehydrated at 30 °C, either in the presence or the absence of sucrose, the drying kinetics corresponds to a Fickean diffusion in correspondence with a short lag time. In contrast, when the bacteria were dehydrated at 70 °C in the absence of sugar, the kinetics corresponds to an anomalous diffusion, and the lag time is four to five times higher than that at 30 °C. However, when drying at 70 °C was carried out in the presence of sucrose, drying kinetics turned into a Fickean process parallel to a substantial decrease in the lag time. The pattern of water desorption was correlated with the critical water activity. When the drying kinetics corresponds to a Fickean diffusion, the lag time started to increase at 0.7 water activity, but when the cells were dried at 70 °C, the damage started at 0.5 water activity. This observation indicates that the drying rate affects the pattern of water desorption, and it can change the value of critical water activity. These results put into relevance that the cell recovery is due to the drying history and that the recovery increase produced by sucrose can be related to the maintenance of kinetic barriers for water desorption.     

Structural characterization and dynamics of globotetraosylceramide in vascular endothelial cells under TNF-α stimulation

In several vascular inflammatory reactions (i.e. immunity and thrombosis) inflammatory mediators lead to the activation of vascular endothelial cells (EC). To date, a number of functional molecules induced on the surface of activated-EC have been identified. We report here that Globotetraosylceramide (Gb4), a glycosphingolipid expressed in EC, is a novel inducible molecule on EC activated by TNF-α. The cell surface expression of Gb4 is increased in a time-dependent manner under TNF-α stimulation, which shows distinct expression kinetics of major proteins induced by TNF-α on EC. MALDI-TOF-MS analysis revealed that the enhanced Gb4 predominantly contains C24:0 fatty acid in the ceramide moiety. Isolated caveolae/lipid raft-enriched detergent insoluble membrane domains in activated-EC predominantly contain this molecular species of Gb4. Gb4 containing C16:0 fatty acid in the ceramide moiety, which is known to constitute the major species of Gb4 in plasma, is also found as a major molecular species in EC. These observations indicate that Gb4, especially with very long fatty acid, is enhanced in EC during its inflammatory reaction, and suggest the potential utility of Gb4 as a biomarker for monitoring inflammation status of EC involving its related diseases.     

Multimeric bivalent immunogens from recombinant tetanus toxin H<Subscript>C</Subscript> fragment,synthetic hexasaccharides,and a glycopeptide adjuvant

Using recombinant tetanus toxin H_C fragment (rTT-H_C) as carrier, we prepared multimeric bivalent immunogens featuring the synthetic hexasaccharide fragment of O-PS of Vibrio cholerae O:1, serotype Ogawa, in combination with either the synthetic hexasaccharide fragment of O-PS of Vibrio cholerae O:1, serotype Inaba, or a synthetic disaccharide tetrapeptide peptidoglycan fragment as adjuvant. The conjugation reaction was effected by squaric acid chemistry and monitored in virtually real time by SELDI-TOF MS. In this way, we could prepare well-defined immunogens with predictable carbohydrate–carrier ratio, whose molecular mass and the amount of each saccharide attached could be independently determined. The ability to prepare such neoglycoconjugates opens unprecedented possibilities for preparation of conjugate vaccines for bacterial diseases from synthetic carbohydrates.