bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized Pilot Trial of Eight Weeks of Bedaquiline (TMC207) Treatment for Multidrug-Resistant Tuberculosis: Long-Term Outcome, Tolerability, and Effect on Emergence of Drug Resistance
Authors: Diacon A. H. , Donald P. R. , Pym A. , Grobusch M. , Patientia R. F. , Mahanyele R. , Bantubani N. , Narasimooloo R. , De Marez T. , van Heeswijk R. , Lounis N. , Meyvisch P. , Andries K. , McNeeley D. F.
Published: March 2012

The 2-year follow-up results for a randomized placebo-controlled study of 47 patients with multidrug-resistant pulmonary tuberculosis treated with either the new diarylquinoline TMC207, recently renamed bedaquiline, or placebo, added to the first 8 weeks of a background regimen, are presented. Bedaquiline significantly reduced the time to culture conversion over 24 weeks (hazard ratio, 2.253; 95% confidence interval, 1.08 to 4.71;
P
= 0.031). With the exception of nausea reported in 26% of patients receiving bedaquiline and none receiving placebo, adverse events occurred at similar frequencies in both groups of patients: bilateral hearing impairment, extremity pain, acne, and noncardiac chest pain occurred in 13 and 21%, 17 and 13%, 9 and 17%, and 4 and 17% of patients, respectively, receiving bedaquiline or placebo. Excluding resistance to ethambutol and ethionamide, only one patient receiving bedaquiline acquired resistance to companion drugs, but five patients receiving placebo (4.8% versus 21.7%;
P
= 0.18) acquired resistance to companion drugs, and resistance to ofloxacin was acquired in four patients receiving placebo and none receiving bedaquiline (0% versus 22%; 0 = 0.066). In all, 23 patients (49%), including 13 receiving placebo (54%) and 10 receiving bedaquiline (44%), discontinued the study prior to its completion, 12 during the first 24 weeks of treatment. Eight subjects were withdrawn for noncompliance or default, and seven withdrew consent, citing the rigorous program of investigations for safety and pharmacokinetic monitoring. Bedaquiline may contribute to the management of multidrug-resistant tuberculosis by effecting more rapid sputum culture negativity and by preventing acquired resistance to companion drugs.
Empirical Use of Ciprofloxacin for Acute Uncomplicated Pyelonephritis Caused by Escherichia coli in Communities Where the Prevalence of Fluoroquinolone Resistance Is High
Authors: Jeon Jae Hyun , Kim Kyuseok , Han Woong Dae , Song Sang Hoon , Park Kyoung Un , Rhee Joong Eui , Song Kyoung-Ho , Park Wan Beom , Kim Eu Suk , Park Sang Won , Kim Nam Joong , Oh Myoung-don , Kim Hong Bin
Published: March 2012

There is little information about the effectiveness of ciprofloxacin in regions where ciprofloxacin-resistant
Escherichia coli
is prevalent. This study was conducted to evaluate whether ciprofloxacin is effective as the initial empirical antibiotic for treatment of uncomplicated acute pyelonephritis (APN) due to ciprofloxacin-resistant
E. coli
. A total of 255 women with clinical diagnoses of uncomplicated APN due to
E. coli
were enrolled in the emergency department between March 2005 and December 2008. All enrolled patients were initially treated with ciprofloxacin. Patients were followed up 4 to 7 days after the start of therapy and 14 to 21 days after its completion. At the first follow-up visit, ciprofloxacin was changed to the appropriate antibiotic when necessary, depending on the antibiotic susceptibility results. Not only improvement of symptoms and signs but also microbiologic eradication was assessed at each visit. Fifteen percent (39/255) of the
E. coli
isolates were resistant to ciprofloxacin. There was no statistically significant difference between the clinical cure rates of the ciprofloxacin-susceptible group and the ciprofloxacin-resistant group at the first follow-up (87.0% versus 76.9%,
P
= 0.135) or the second follow-up (98.6% versus 94.9%,
P
= 0.177). However, there was a lower microbiologic cure rate in the ciprofloxacin-resistant group than in the ciprofloxacin-susceptible group (92.4% versus 41.7%,
P
= 0.000) at the first follow-up visit. No complications occurred in the ciprofloxacin-resistant group during the follow-up period. Our findings indicate that ciprofloxacin is an appropriate choice for empirical therapy of uncomplicated APN and has no serious adverse outcomes, if it is tailored appropriately, even for women infected with ciprofloxacin-resistant
E. coli
.
Activity of a Novel Cyclic Lipopeptide, CB-183,315, against Resistant Clostridium difficile and Other Gram-Positive Aerobic and Anaerobic Intestinal Pathogens
Authors: Snydman D. R. , Jacobus N. V. , McDermott L. A.
Published: March 2012

We evaluated the activity of CB-183,315 against
Clostridium difficile
, including strains that are resistant to fluoroquinolones and metronidazole and with elevated MICs to vancomycin as well as other Gram-positive intestinal pathogens. The MICs of CB-183,315 against all
C. difficile
isolates were ≤1 μg/ml. CB-183,315 had greater activity than vancomycin and metronidazole against
C. difficile
isolates and was more active than the comparators against vancomycin-resistant enterococcus (VRE). CB-183,315 also had excellent activity against methicillin-resistant
Staphylococcus aureus
(MRSA), other
Clostridium
spp., and
Peptostreptococcus
spp.
Effects of Dimerization on the Structure and Biological Activity of Antimicrobial Peptide Ctx-Ha
Authors: Lorenzón E. N. , Cespedes G. F. , Vicente E. F. , Nogueira L. G. , Bauab T. M. , Castro M. S. , Cilli E. M.
Published: March 2012

It is well known that cationic antimicrobial peptides (cAMPs) are potential microbicidal agents for the increasing problem of antimicrobial resistance. However, the physicochemical properties of each peptide need to be optimized for clinical use. To evaluate the effects of dimerization on the structure and biological activity of the antimicrobial peptide Ctx-Ha, we have synthesized the monomeric and three dimeric (Lys-branched) forms of the Ctx-Ha peptide by solid-phase peptide synthesis using a combination of 9-fluorenylmethyloxycarbonyl (Fmoc) and
t
-butoxycarbonyl (Boc) chemical approaches. The antimicrobial activity assay showed that dimerization decreases the ability of the peptide to inhibit growth of bacteria or fungi; however, the dimeric analogs displayed a higher level of bactericidal activity. In addition, a dramatic increase (50 times) in hemolytic activity was achieved with these analogs. Permeabilization studies showed that the rate of carboxyfluorescein release was higher for the dimeric peptides than for the monomeric peptide, especially in vesicles that contained sphingomyelin. Despite different biological activities, the secondary structure and pore diameter were not significantly altered by dimerization. In contrast to the case for other dimeric cAMPs, we have shown that dimerization selectively decreases the antimicrobial activity of this peptide and increases the hemolytic activity. The results also show that the interaction between dimeric peptides and the cell wall could be responsible for the decrease of the antimicrobial activity of these peptides.
Effects of Antibiotics on Shiga Toxin 2 Production and Bacteriophage Induction by Epidemic Escherichia coli O104:H4 Strain
Authors: Bielaszewska Martina , Idelevich Evgeny A. , Zhang Wenlan , Bauwens Andreas , Schaumburg Frieder , Mellmann Alexander , Peters Georg , Karch Helge
Published: March 2012

The role of antibiotics in treatment of enterohemorrhagic
Escherichia coli
(EHEC) infections is controversial because of concerns about triggering hemolytic-uremic syndrome (HUS) by increasing Shiga toxin (Stx) production. During the recent large EHEC O104:H4 outbreak, antibiotic therapy was indicated for some patients. We tested a diverse panel of antibiotics to which the outbreak strain is susceptible to interrogate the effects of subinhibitory antibiotic concentrations on induction of
stx
2
-harboring bacteriophages,
stx
2
transcription, and Stx2 production in this emerging pathogen. Ciprofloxacin significantly increased
stx
2
-harboring phage induction and Stx2 production in outbreak isolates (
P
values of <0.001 to <0.05), while fosfomycin, gentamicin, and kanamycin insignificantly influenced them (
P
> 0.1) and chloramphenicol, meropenem, azithromycin, rifaximin, and tigecycline significantly decreased them (
P
≤ 0.05). Ciprofloxacin and chloramphenicol significantly upregulated and downregulated
stx
2
transcription, respectively (
P
< 0.01); the other antibiotics had insignificant effects (
P
> 0.1). Meropenem, azithromycin, and rifaximin, which were used for necessary therapeutic or prophylactic interventions during the EHEC O104:H4 outbreak, as well as tigecycline, neither induced
stx
2
-harboring phages nor increased
stx
2
transcription or Stx2 production in the outbreak strain. These antibiotics might represent therapeutic options for patients with EHEC O104:H4 infection if antibiotic treatment is inevitable. We await further analysis of the epidemic to determine if usage of these agents was associated with an altered risk of developing HUS.
Effect of HIV-1 Infection and Sex on the Cellular Pharmacology of the Antiretroviral Drugs Zidovudine and Lamivudine
Authors: Rower Joseph E. , Meditz Amie , Gardner Edward M. , Lichtenstein Kenneth , Predhomme Julie , Bushman Lane R. , Klein Brandon , Zheng Jia-Hua , MaWhinney Samantha , Anderson Peter L.
Published: March 2012

The cellular pharmacology of zidovudine (ZDV) and lamivudine (3TC)
in vivo
is not completely understood. This prospective longitudinal study investigated the relationship between HIV-1 serostatus, sex, race, and time on therapy with intracellular and plasma ZDV and 3TC concentrations. Of 20 HIV-seronegative and 23 HIV-seropositive volunteers enrolled, 16 (8 women) and 21 (5 women) completed all 12 study days, respectively. Volunteers began ZDV-3TC therapy (plus a third active drug in HIV-seropositive volunteers), and steady-state concentrations (
C
ss
) were determined after days 1, 3, 7, and 12. A repeated-measures mixed model was utilized. HIV-seronegative status was associated with 22% (95% confidence interval [CI], 0%, 50%) and 37% (15%, 67%) higher
C
ss
estimates compared to those of HIV-seropositive individuals for intracellular ZDV-TP and 3TC-TP levels, respectively. African-Americans had 36% (8%, 72%) higher ZDV-TP estimates than non-African-Americans. Sex was not associated with ZDV-TP or 3TC-TP (
P
> 0.19). Women had 36% (4%, 78%) higher plasma ZDV, but the effect was lessened when normalized by lean body weight (5% [−19%, 38%];
P
= 0.68). Plasma 3TC was 19% (0%, 41%) higher in HIV-seropositive volunteers and 22% (0%, 48%) higher in African American volunteers, but these effects were not significant when corrected for creatinine clearance (7% [−9%, 20%] and −5% [−26%, 12%] for HIV serostatus and race, respectively;
P
> 0.35). These results suggest that HIV-seropositive status decreases and African American race elevates the cellular triphosphates of ZDV and 3TC. This information extends knowledge of ZDV and 3TC cellular pharmacology
in vivo
and provides new leads for future cellular pharmacology studies aimed at optimizing HIV prevention/treatment with these agents.
The Vibrio parahaemolyticus ToxRS Regulator Is Required for Stress Tolerance and Colonization in a Novel Orogastric Streptomycin-Induced Adult Murine Model
Authors: Whitaker W. Brian , Parent Michelle A. , Boyd Aoife , Richards Gary P. , Boyd E. Fidelma
Published: March 2012

Vibrio parahaemolyticus
, a marine bacterium, is the causative agent of gastroenteritis associated with the consumption of seafood. It contains a homologue of the
toxRS
operon that in
V. cholerae
is the key regulator of virulence gene expression. We examined a nonpolar mutation in
toxRS
to determine the role of these genes in
V. parahaemolyticus
RIMD2210633, an O3:K6 isolate, and showed that compared to the wild type, Δ
toxRS
was significantly more sensitive to acid, bile salts, and sodium dodecyl sulfate stresses. We demonstrated that ToxRS is a positive regulator of
ompU
expression, and that the complementation of Δ
toxRS
with
ompU
restores stress tolerance. Furthermore, we showed that ToxRS also regulates type III secretion system genes in chromosome I via the regulation of the
leuO
homologue VP0350. We examined the effect of Δ
toxRS in vivo
using a new orogastric adult murine model of colonization. We demonstrated that streptomycin-treated adult C57BL/6 mice experienced prolonged intestinal colonization along the entire intestinal tract by the streptomycin-resistant
V. parahaemolyticus
. In contrast, no colonization occurred in non-streptomycin-treated mice. A competition assay between the Δ
toxRS
and wild-type
V. parahaemolyticus
strains marked with the β-galactosidase gene
lacZ
demonstrated that the Δ
toxRS
strain was defective in colonization compared to the wild-type strain. This defect was rescued by ectopically expressing
ompU
. Thus, the defect in stress tolerance and colonization in Δ
toxRS
is solely due to OmpU. To our knowledge, the orogastric adult murine model reported here is the first showing sustained intestinal colonization by
V. parahaemolyticus
.
Density-dependent regulation of year-class strength in age-0 juvenile striped bass (Morone saxatilis)
Authors: Martino E.J. , Houde E.D.
Published: March 2012

Abundance of age-0 striped bass ( Morone saxatilis ) exhibits 50-fold variability in Chesapeake Bay. Processes that act to reduce and thus regulate this variability were investigated. The potential for density-dependent regulation of growth and mortality in the early juvenile stage and its causes were investigated. Data from multiple seine and trawl surveys in upper Chesapeake Bay and tributaries were analyzed to construct growth and mortality indices having a high degree of spatial and temporal resolution. Age-0 mean lengths in September were inversely related to density, ranging from 67.8 mm in 1994, when mean density was 0.036·m–2, to 104.5 mm in 1992, when mean density was 0.003·m–2. Except for the Potomac River, evidence for density-dependent growth was consistent across subpopulations. Bioenergetics modeling indicated that prey consumption was limiting except in low-abundance years. Mortality increased with respect to abundance and also was density-dependent. The significant interaction between age-0 juvenile length in September and subsequent winter temperature on mortality indicated that density-dependent growth leads to size-selective overwinter mortality. A statistical model including age-0 abundances, age-0 lengths, and winter temperature explained a substantial fraction of variability and the mechanisms for regulation of striped bass recruitment.
Landscape heterogeneity influences carbon dioxide production in a young boreal reservoir
Authors: Brothers Soren M. , del Giorgio Paul A. , Teodoru Cristian R. , Prairie Yves T.
Published: March 2012

Surface carbon dioxide (CO2) emissions exhibit a high degree of spatial heterogeneity in the young boreal Eastmain-1 hydroelectric reservoir, located in northern Quebec, Canada. Estimates of the individual components of net CO2 production within the reservoir (benthic respiration, water column respiration, and primary production) furthermore provide a link between the heterogeneity in surface CO2 emissions and the flooded landscapes below. Specifically, the preflood carbon stock and soil–sediment respiration rates of flooded landscapes were found to influence benthic CO2 production, the rate of decline of hypolimnetic dissolved organic carbon (DOC), and the estimated rate at which flooded landscapes release DOC, further influencing water column respiration rates. Estimates of the individual components of net CO2 production in Eastmain-1 are supported by a positive relationship (t test, r2 = 0.64, P < 0.01) between measured surface CO2 emissions (mean ± SE = 1540 ± 145.4 mg C·m–2·day–1) and independently derived estimates of total net CO2 production (mean ± SE = 1230 ± 162.4 mg C·m–2·day–1). Our findings emphasize the utility of fundamental landscape characterization prior to construction in predicting reservoir greenhouse gas emissions.
Silicon and silicon oxide surface modification using thiamine-catalyzed benzoin condensations
Authors: Hoop Kelly A. , Kennedy David C. , Mishki Trevor , Lopinski Gregory P. , Pezacki John Paul
Published: March 2012

The benzoin condensation that involves the umpolung coupling of two aldehyde groups has been applied to the formation of functionalized silicon and silicon oxide surfaces using thiamine and other N-heterocyclic carbene (NHC) catalysis in water. This bioorthogonal conjugation of an aldehyde to a modified silicon or silicon oxide surface has been monitored and characterized using X-ray photoelectron spectroscopy and IR spectroscopy. NHC catalysis was found to be efficient in water mediating full conversion of the aldehyde functionalized silicon oxide surfaces at the interface.
Cell surface properties of two differently virulent strains of Acinetobacter baumannii isolated from a patient
Authors: Kempf Marie , Eveillard Matthieu , Deshayes Caroline , Ghamrawi Sarah , Lefrançois Corinne , Georgeault Sonia , Bastiat Guillaume , Seifert Harald , Joly-Guillou Marie-Laure
Published: March 2012

The aim of this study was to unravel, by focusing on cell surface properties, the underlying virulence factors contributing to the difference in the pathogenicity observed in two Acinetobacter baumannii strains isolated from the same patient. The two strains were phenotypically different: (i) a mucoid strain (AB-M), highly virulent in a mouse model of pneumonia, and (ii) a nonmucoid strain (AB-NM), moderately virulent in the same model. The study of the cell surface properties included the microbial adhesion to solvents method, the measurement of the electrophoretic mobility of bacteria, the analysis of biofilm formation by calcofluor white staining, the adherence to silicone catheters, and scanning electron microscopy. The AB-NM strain was more hydrophobic, more adherent to silicone catheters, and produced more biofilm than the AB-M strain. Scanning electron microscopy showed bacterial cells with a rough surface and the formation of large cell clusters for AB-NM whereas the AB-M strain had a smooth surface and formed only a few cell clusters. Contrary to the results of most previous studies, cell surface properties were not correlated to the virulence described in our experimental model, indicating that mechanisms other than adherence may be involved in the expression of A. baumannii virulence.
Structure of bacterial communities in diverse freshwater habitats
Authors: Aizenberg-Gershtein Yana , Vaizel-Ohayon Dalit , Halpern Malka
Published: March 2012

The structures and dynamics of bacterial communities from raw source water, groundwater, and drinking water before and after filtration were studied in four seasons of a year, with culture-independent methods. Genomic DNA from water samples was analyzed by the polymerase chain reaction – denaturing gradient gel electrophoresis system and by cloning of the 16S rRNA gene. Water samples exhibited complex denaturing gradient gel electrophoresis genetic profiles composed of many bands, corresponding to a great variety of bacterial taxa. The bacterial communities of different seasons from the four sampling sites clustered into two major groups: (i) water before and after filtration, and (ii) source water and groundwater. Phylogenetic analyses of the clones from the autumn sampling revealed 13 phyla, 19 classes, and 155 operational taxonomic units. Of the clones, 66% showed less than 97% similarities to known bacterial species. Representatives of the phyla Proteobacteria, Bacteroidetes, and Actinobacteria were found at all four sampling sites. Species belonging to the phylum Firmicutes were an important component of the microbial community in filtered water. Representatives of Enterobacteriaceae were not detected, indicating the absence of fecal pollution in the drinking water. Differences were found in the bacterial populations that were sampled from the same sites in different seasons. Each water habitat had a unique bacterial profile. Drinking water harbors diverse and dynamic microbial communities, part of which may be active and resilient to chlorine disinfection. This study provides, for the first time, basic data for uncultivable drinking water bacteria in Israel.
Genetic variability in arbuscular mycorrhizal fungi compatibility supports the selection of durum wheat genotypes for enhancing soil ecological services and cropping systems in Canada
Authors: Singh A.K. , Hamel C. , DePauw R.M. , Knox R.E.
Published: March 2012

Crop nutrient- and water-use efficiency could be improved by using crop varieties highly compatible with arbuscular mycorrhizal fungi (AMF). Two greenhouse experiments demonstrated the presence of genetic variability for this trait in modern durum wheat ( Triticum turgidum L. var. durum Desf.) germplasm. Among the five cultivars tested, ‘AC Morse’ had consistently low levels of AM root colonization and DT710 had consistently high levels of AM root colonization, whereas ‘Commander’, which had the highest colonization levels under low soil fertility conditions, developed poor colonization levels under medium fertility level. The presence of genetic variability in durum wheat compatibility with AMF was further evidenced by significant genotype × inoculation interaction effects in grain and straw biomass production; grain P, straw P, and straw K concentrations under medium soil fertility level; and straw K and grain Fe concentrations at low soil fertility. Mycorrhizal dependency was an undesirable trait of ‘Mongibello’, which showed poor growth and nutrient balance in the absence of AMF. An AMF-mediated reduction in grain Cd under low soil fertility indicated that breeding durum wheat for compatibility with AMF could help reduce grain Cd concentration in durum wheat. Durum wheat genotypes should be selected for compatibility with AMF rather than for mycorrhizal dependency.
Method for the validation of intraspecific crosses ofSaccharomyces cerevisiaestrains by minisatellite analysis
Authors: Boveri Silvio , Rainieri Sandra , Pulvirenti Andrea
Published: March 2012

The crossing of Saccharomyces strains by spore conjugation is one of the ways to obtain new starter cultures for the fermentation industry. One of the major difficulties of this practice is the identification of the newly formed hybrids. In this work we describe an effective molecular method for the validation of Saccharomyces intraspecific crosses. The method described is based in the hypothesis that hybrids constructed by spore conjugation contain the sum of the genomes of both parental strains. As a consequence, the conjugation of spores of two yeasts showing different genomic fingerprinting profiles will result in a hybrid culture that will show the sum of both profiles. We demonstrated that the detection of polymorphism in two genes containing minisatellite-like sequences, either SED1 or AGA1, is suitable for this purpose. Using this strategy we were able to validate 15 crosses out of 162 hybridization attempts.
Fisher Scientific Award Lecture — The capsular polysaccharides of Group BStreptococcusandStreptococcus suisdifferently modulate bacterial interactions with dendritic cells1This article is based on an Award Lecture by Dr. Mariela Segura at the 61st Annual Meeting of the Canadian Society of Microbiologists in St. John’s, Newfoundland, on 23 June 2011. Dr. Segura was the recipient of the 2011 Fisher Scientific Award, a national award sponsored by Fisher Scientific to recognize excellence in microbiology research.
Authors: Segura Mariela
Published: March 2012

Infections with encapsulated bacteria cause serious clinical problems. Besides being poorly immunogenic, the bacterial capsular polysaccharide (CPS) cloaks antigenic proteins, allowing bacterial evasion of the host immune system. Despite the clinical significance of bacterial CPS and its suggested role in the pathogenesis of the infection, the mechanisms underlying innate and, critically, adaptive immune responses to encapsulated bacteria have not been fully elucidated. As such, we became interested in studying the CPS of two similar, but unique, streptococcal species: Group B Streptococcus (GBS) and Streptococcus suis . Both streptococci are well encapsulated, some capsular types are more virulent than others, and they can cause severe meningitis and septicemia. For both pathogens, the CPS is considered the major virulence factor. Finally, these two streptococci are the sole Gram-positive bacteria possessing sialic acid in their capsules. GBS type III is a leading cause of neonatal invasive infections. Streptococcus suis type 2 is an important swine and emerging zoonotic pathogen in humans. We recently characterized the S. suis type 2 CPS. It shares common structural elements with GBS, but sialic acid is α2,6-linked to galactose rather than α2,3-linked. Differential sialic acid expression by pathogens might result in modulation of immune cell activation and, consequently, may affect the immuno-pathogenesis of these bacterial infections. Here, we review and compare the interactions of these two sialylated encapsulated bacteria with dendritic cells, known as the most potent antigen-presenting cells linking innate and adaptive immunity. We further address differences between dendritic cells and professional phagocytes, such as macrophages and neutrophils, in their interplay with these encapsulated pathogens. Elucidation of the molecular and cellular basis of the impact of CPS composition on bacterial interactions with immune cells is critical for mechanistic understanding of anti-CPS responses. Knowledge generated will help to advance the development of novel, more effective anti-CPS vaccines and improved immunotherapies.
A THEOREM OF SOLÉR, THE THEORY OF SYMMETRY AND QUANTUM MECHANICS
Authors: CASSINELLI GIANNI , LAHTI PEKKA
Published: March 2012

A classical problem in axiomatic quantum mechanics is deducing a Hilbert space realization for a quantum logic that admits a vector space coordinatization of the Piron–McLaren type. Our aim is to show how a theorem of M. Solér [Characterization of Hilbert spaces by orthomodular spaces, Comm. Algebra23 (1995) 219–243.] can be used to get a (partial) solution of this problem. We first derive a generalization of the Wigner theorem on symmetry transformations that holds already in the Piron–McLaren frame. Then we investigate which conditions on the quantum logic allow the use of Solér's theorem in order to obtain a Hilbert space solution for the coordinatization problem.
Experimental investigation of CO
2
breakthrough and flow mechanisms in shale
Authors: Skurtveit Elin , Aker Eyvind , Soldal Magnus , Angeli Matthieu , Wang Zhong
Published: March 2012

Supercritical CO
2
breakthrough and flow mechanisms in shale have been investigated in laboratory experiments using a high pressure flow cell and cylindrical samples of shale from the Draupne formation in the North Sea. The main objective is to study the basic mechanisms involved in the breakthrough process and define the controlling parameters for supercritical CO
2
flow in a low permeable shale.

Experimental testing provides new insight into the CO
2
breakthrough process through simultaneous measurements of deformation and ultrasonic velocities in the sample. A marked sample dilation associated with the CO
2
breakthrough is identified accompanied with a pronounced drop in ultrasonic velocities. X-ray images of the sample using a high resolution 3D computer tomography (CT) scanner provide information on macroscopic fracture distribution inside the sample before and after testing.

The CO
2
breakthrough pressure for the Draupne material seems to depend on confining pressure and effective pressure rather than pore pressure difference across the sample. After breakthrough the effective CO
2
permeability was found to follow a simple model for permeability in fractured rock. The drop in ultrasonic velocity was associated with mechanical changes and possible micro fracturing inside the sample. Based on our observations we conclude that pressure-induced opening of micro-fractures during the breakthrough process is an important mechanism for flow in addition to capillary displacement. Our findings may have important consequences for later testing and estimation of CO
2
breakthrough pressure and flow in shale.
RENAR
Authors: Zaghouani Wajdi
Published: March 2012

Named entity recognition has served many natural language processing tasks such as information retrieval, machine translation, and question answering systems. Many researchers have addressed the name identification issue in a variety of languages and recently some research efforts have started to focus on named entity recognition for the Arabic language. We present a working Arabic information extraction (IE) system that is used to analyze large volumes of news texts every day to extract the named entity (NE) types person, organization, location, date, and number, as well as quotations (direct reported speech) by and about people. The named entity recognition (NER) system was not developed for Arabic, but instead a multilingual NER system was adapted to also cover Arabic. The Semitic language Arabic substantially differs from the Indo-European and Finno-Ugric languages currently covered. This article thus describes what Arabic language-specific resources had to be developed and what changes needed to be made to the rule set in order to be applicable to the Arabic language. The achieved evaluation results are generally satisfactory, but could be improved for certain entity types.
The S2E Platform
Authors: Chipounov Vitaly , Kuznetsov Volodymyr , Candea George
Published: March 2012

This article presents S
2
E, a platform for analyzing the properties and behavior of software systems, along with its use in developing tools for comprehensive performance profiling, reverse engineering of proprietary software, and automated testing of kernel-mode and user-mode binaries. Conceptually, S
2
E is an automated path explorer with modular path analyzers: the explorer uses a symbolic execution engine to drive the target system down all execution paths of interest, while analyzers measure and/or check properties of each such path. S
2
E users can either combine existing analyzers to build custom analysis tools, or they can directly use S
2
E’s APIs.

S
2
E’s strength is the ability to scale to large systems, such as a full Windows stack, using two new ideas:
selective symbolic execution
, a way to automatically minimize the amount of code that has to be executed symbolically given a target analysis, and
execution consistency models
, a way to make principled performance/accuracy trade-offs during analysis. These techniques give S
2
E three key abilities: to simultaneously analyze entire families of execution paths instead of just one execution at a time; to perform the analyses in-vivo within a real software stack---user programs, libraries, kernel, drivers, etc.---instead of using abstract models of these layers; and to operate directly on binaries, thus being able to analyze even proprietary software.
A mass spectrometric investigation on some 5‐substituted adamantan‐2‐ones
Authors: Martínez Roberto , Cetina Raúl , Jiménez Federico , Velasco Luis , Pérez Javier
Published: March 2012

The mass spectrometric behavior of a series of 5‐substituted adamantan‐2‐ones has been studied in different ionization conditions (Electron Ionization and Fast Atom Bombardment), with the aid of linked scan experiments.
Combination of capillary GC, GC/MS and 13C‐NMR for the characterization of the rhizome oil of Piper betle L. (Piperaceae) from Vietnam
Authors: Thanh Lê , Dũng Nguyên Xuân , Bighelliand Ange , Casanova Joseph , Leclercq Piet A.
Published: March 2012

The essential oil from the rhizomes of Piper betle L. (betel), collected around Hue, was obtained in 0.20% yield. The oil was examined by a combination of capillary GC and GC/MS. 13C‐NMR studies confirmed the structure assignments proposed by retention data and mass spectra of the components with a content higher than 1%. In some instances the structure elucidation based on GC and GC/MS data had to be corrected. More than forty constituents were found of which the major ones were α‐cadinol (26.2%), δ‐cadinene (11.7%), and about equal amounts of T‐cadinol and T‐muurolol (unseparated, together 20.7%). This study clearly illustrates the advantage of complementary identification techniques.
1H and 13C NMR study of perdeuterated pyrazoles
Authors: Jimeno María Luisa , Jagerovic Nadine , Elguero José , Junk Thomas , Catallo W. James
Published: March 2012

The 1H and 13C chemical shifts as well as the 1H–2H and 2H–13C coupling constants of perdeuterated 3,5‐dimethylpyrazole and 3,5‐diphenylpyrazole have been measured and the values compared with those of the unlabelled compounds.
Application of artificial intelligence in organic chemistry. Part XIX*. Pattern recognition and structural determination of flavonoids using 13C‒NMR spectra
Authors: Emerenciano Vicente de P. , Melo Lilian D. , Rodrigues Gilberto do V. , Gastmans Jean P.
Published: March 2012

This essay describes another improvement to the expert system named SISTEMAT. The purpose of such improvement is to help chemists who work with natural products to figure out chemical structures. SISTEMAT uses Nuclear Magnetic Resonance (NMR) 13C data to ensemble compatible substructures according to related spectra. The system also is able to suggest a list of probable carbon skeletons. Those will work as models to structure generating programs, reducing the combinatorial explosion problem. This is the first essay from our research group which shows our system applications to aromatic compounds. A database with 700 NMR 13C spectra of flavonoids obtained from the literature was used. We applied heuristic SISTEMAT in order to discover ranges of chemical shifts that characterise several skeleton types. The diversity of flavonoid structures is due to several oxidation patterns at rings A and B. This phenomenon causes a great complexity in the absorptions at the aromatic region. Heuristic SISTEMAT was able to discover more accurate rules that differentiate specific patterns of oxidation for some skeleton types. The performance of the software was checked against a higher complex structure of a dimeric flavonoid recently isolated. The system gives only two possibilities of skeleton types (among 70 others). Both substructures found by the program showed correct linkages between carbons 2 and 7″ and 4 and 8″ of the monomers.
Electron impact mass spectrometry of some thienopyrimidone derivatives
Authors: de Oliveira Renata C. , Freitas Antonio C. C. , de Lima José G.
Published: March 2012

The electron impact mass spectra of some previously synthesized thienopyrimidones have been recorded and the identity of various ions in the mass spectra established.
2D 1H and 13C NMR studies of the adducts obtained by cyclostereoselective oligomerization of α,β‒unsaturated arylidenketones promoted by 6 amino‒1,3‒dimethyl uracil
Authors: Díaz E. , Barrios H. , Gúzman A. , Corona D. , Díaz R. , Fuentes A. , Jankowski C. K.
Published: March 2012

The reaction of the 6‒amino‒1,3‒dimethyl uracil with the arylidenketones 1–4, enabled us to obtain adducts whose structures result from nucleophilic attack and self condensation, yielding with monomeric, dimeric or trimeric derivatives obtained with moderate (40–50%) yields. The reaction was induced by the uracil derivative and the role of this reagent was that of a nucleophile and oligomerization promoter. The structures obtained in this study were mainly elucidated with 1D and 2D high resolution NMR experiments.
Structural studies of pyoverdins with cyclopeptidic substructures by electrospray ionization and collision induced fragmentation 1,2
Authors: Fuchs Regine , Budzikiewicz Herbert
Published: March 2012

By collision induced fragmentation of the [M+2H]2+‒ions of pyoverdins with a partially cyclic peptide structure the nature of the amino acids present and their sequence can be determined. The results obtained with pyoverdins of known structure could be used for structure proposals for new representatives.
Gas‒phase reactions of NO+ with Glu and γ‒Glu–Met
Authors: Wincel H. , Fokkens R. H. , Nibbering N. M. M.
Published: March 2012

The reactivity of the nitrosonium ion, NO+, with the amino acid Glu and the dipeptide γ‒Glu–Met in the gas phase has been investigated using the combination of chemical ionisation mass spectrometry and MS/MS. It is shown that NO+ reacts efficiently with both Glu and Glu–Met leading to the formation of the nitroso‒group containing ions at m/z 159 and 288.

The formation of m/z 159, (GluNO‒18)+, is rationalized by a mechanism involving an electrophilic attack of NO+ upon the carbonyl oxygen atom of one of the carboxylic groups of Glu and the N‒terminal carboxylic group of Glu–Met leading to the neutral losses of H2O and Met, respectively. The unimolecular decompositions of the metastable and collisionally activated m/z 159 ions lead primarily to the elimination of the neutral species HNO (major) and the (Glu‒18) residue (minor). The formation of the m/z 288 ions can be described by a mechanistic scheme which involves the ion‒molecule interaction of m/z 159 with Glu and Glu–Met and subsequent losses of H2O and Met, respectively. Unimolecular and collisionally activated dissociations of m/z 288 suggest the formation of the proton‒bridged ion‒neutral complex [(GluNO‒18)···H+···(Glu‒18)].
Proton transfer equilibria, temperature and substituent effects on hydrogen bonded complexes between chloranilic acid and anilines
Authors: Gohar Gamal A. , Habeeb Moustafa M.
Published: March 2012

The proton transfer equilibrium constants (KPT) for 1 : 1 complex formation between Chloranilic Acid (CA) and a series of p‐ and m‒substituted anilines have been measured in 1,4‐dioxane spectrophotometrically. The results supported the concept of amine‐solvent hydrogen bond formation (short range solvation effect). Beside, this effect, the KPT values were apparently affected by the electron donation power of the aniline ring substituent, which was transmitted to the interaction center via resonance and inductive effects. Linear relationships between KPT and σ‐Hammett substituent constants, or pK values for m and p anilines,were obtained verifying the above conclusions. The solute‐solvent hydrogen bond formation might increase the reactivity of the aniline nitrogen than would the inductive effect of the alkyl group, in case of CA‐N‐alkyl aniline complexes. The thermodynamic parameters for the proton transfer complex formation were estimated and it was indicated that the solvent–aniline hydrogen bond formation was preferred in the case of p‐substituted aniline complexes more than in the case of the corresponding m‒isomer. It has been found that the proton transfer process was enthalpy and entropy controlled.
Spectroscopic characterization of insulin and small molecule ligand binding to the insulin receptor
Authors: Schlein Morten , Ludvigsen Svend , Olsen Helle B. , Dunn Michael F. , Kaarsholm Niels C.
Published: March 2012

We have applied spectroscopic techniques to study two kinds of ligand binding to the insulin receptor. First, a fluorescently labelled insulin analogue is used to characterize the mechanism of reversible 1 :1 complex formation with a fragment of the insulin receptor ectodomain. The receptor induced fluorescence enhancement of the labelled insulin analogue provides the basis for stopped flow kinetic experiments. The kinetic data are consistent with a bimolecular binding event followed by a conformational change. This emphasizes the importance of insulin induced conformational changes in the activation of the insulin receptor. Second, the binding of fluorescein derivatives to the insulin receptor is studied. These small molecule ligands displace insulin from its receptor with micromolar affinity. The binding is verified by transferred NOESY NMR experiments. Their chromophoric properties are used to measure the affinity by UV‐vis and fluorescence difference spectroscopies and the resulting Kd values are similar to those observed in the displacement receptor binding assay. However, these experiments and a stoichiometry determination indicate multiple binding sites, of which one overlaps with the insulin binding site. These two examples illustrate how spectroscopy complements biochemical receptor binding assays and provides information on ligand–insulin receptor interactions in the absence of three dimensional structures.
Dynamic aspect of bacteriorhodopsin as viewed from 13C NMR: Conformational elucidation, surface dynamics and information transfer from the surface to inner residues
Authors: Saitô H. , Kawaminami R. , Tanio M. , Arakawa T. , Yamaguchi S. , Tuzi S.
Published: March 2012

We demonstrate here how dynamic as well as conformational features of bacteriorhodopsin (bR) in purple membrane (PM) as a typical membrane protein are revealed by extensive 13C NMR studies on [3‐13C]‐, [2‐13C]‐, [1‐13C]Ala or [1‐13C]Val‐labeled bR and a variety of site‐directed mutants. A number of 13C NMR peaks were well‐resolved for [3‒13C]Ala‒ and [1‐13C]Val‐bR under the condition of fully hydrated PM at ambient temperature and assigned to individual amino‐acid residues, initially by regio‐specific manner with reference to the data of the conformation‐dependent displacements of peaks from model polypeptides and subsequently by site‐specific manner with reference to the specifically reduced peak‐intensities of site‐directed mutant as compared with those of wild type. It is noticeable that the revealed bR structure at ambient temperature by 13C NMR is not static as anticipated from the data of diffraction studies at cryo‐temperature but is dynamically heterogeneous undergoing motional fluctuations with various frequencies (102–108 Hz) depending upon the domains of interest. We further applied this approach to reveal how charged state of surface residues, especially at the side‐chain of exracellular Glu residues (Glu 194 and 204), could be transmitted to the inner part of the helices such as Ala 53, 84, and 215 to alter their local conformations of transmembrane helices near at the Schiff base through side‐chain interactions. We also analyzed how information of the protonation at Asp 85 from helix C is initially transmitted to helices B (Val 49) and G (Val 213) though modified helix‒helix interactions through the side‐chains of Arg 82.
Muscle oxygenation and ATP turnover when blood flow is impaired by vascular disease
Authors: Kemp Graham J. , Roberts Neil , Bimson William E. , Bakran Ali , Frostick Simon P.
Published: March 2012

In exercising muscle, creatine kinase ensures that mismatch between ATP supply and ATP use results in net phosphocreatine (PCr) splitting. This, inter alia, makes 31P magnetic resonance spectroscopy a useful tool for studying muscle ‘energy metabolism’ noninvasively in vivo. We combined this with near–infrared spectroscopy (NIRS) to study ATP synthesis and oxygenation in calf muscle of normal subjects and patients with peripheral vascular disease. Experimental and clinical details and basic data have been published elsewhere (G.J. Kemp et al., Journal of Vascular Surgery 34 (2001), 1103–10); we here propose an analysis of interactions between metabolic ‘error signals’ and cellular PO2 (estimated from NIRS changes, provisionally assumed to reflect deoxymyoglobin). Post–exercise PCr recovery is monoexponential, and the linear relationship between PCr resynthesis rate (= oxidative ATP synthesis) and the perturbation in PCr (conceptually the simplest error signal) is consistent with negative feedback. In patients the inferred ‘mitochondrial capacity’ (= oxidative ATP synthesis at ‘zero’ PCr) is decreased by 53±6%, leading to reduced oxidative ATP contribution in exercise, because of increased deoxygenation. Increased PCr perturbation partially outweighs cellular hypoxia, but as low cellular PO2 is required for capillary–mitochondrion O2 diffusion, rate–signal relationships may overstate maximum oxidative ATP synthesis rate.
Ibuprofen against Aspirin – you first, please! Thanks go ahead…
Authors: Jankowski Christopher K. , Leclair Gaëtan
Published: March 2012

Aspirin (ASA) and Ibuprofen (IBU), two common NSAIDs, seem to exert a mutual interference on the blood platelet aggregation level. We wish to clarify this controversy on the basis of crystallographic data and molecular modelling.
Peptide and protein analysis with mass spectrometry
Authors: Trauger Sunia A. , Webb William , Siuzdak Gary
Published: March 2012

Mass spectrometry (MS) is rapidly becoming a fundamental tool for biologists and biochemists in their efforts to characterize cellular function. Recent advancements in MS technology and front‐end methodologies, along with the completion of the human genome have greatly popularized its use by researchers for protein identification and characterization. This paper is a general overview of how mass spectrometry is being used for the analysis of peptides and proteins, focusing on its application to molecular weight determination. Sample preparatory and cleanup techniques used in our laboratory for protein and peptide analysis are provided, along with a discussion of data interpretation. The utility of mass spectrometry for protein and peptide analyses lies in its ability to provide highly accurate molecular weight information on intact molecules. The ability to generate such accurate information can be extremely useful for protein identification and characterization. For example, a protein can often be unambiguously identified by the accurate mass analysis of its constituent peptides produced by either chemical or enzymatic treatment of the sample. Furthermore, protein identification can also be facilitated by analysis of the protein′s proteolytic peptide fragments in the gas phase; fragment ions generated inside the mass spectrometer via collision‐induced dissociation (CID) to yield information about the primary structure and modifications. This overview describes how electrospray ionization (ESI) and matrix‒assisted laser desorption/ionization (MALDI) mass spectrometry is being used for peptide and protein characterization focusing on its application to molecular weight determination.
Study of surfactant—liposome interactions at sublytic level by means of a surface probe
Authors: Cócera M. , López O. , Estelrich J. , Parra J. L. , de la Maza A.
Published: March 2012

The incorporation of the sodium lauryl ether sulfate (SLES) on phosphatidylcholine (PC) liposomes has been studied with time using the fluorescent probe 2‐(p‐toluidinyl)‐naphthalene‐6‐sodium sulfonate (TNS). This probe reports changes on the surface potential of PC liposomes by effect of the anionic surfactant adsorption. The addition of small SLES amounts promoted an abrupt fall in the fluorescence intensity (F.I.) and this fall was already detected 10 secs after mixing. Only slight changes with time were observed in the F.I. of SLES—liposome‐probe systems. These results indicate a fast and almost complete incorporation of SLES on the liposome surface. The surfactant/lipid molar ratios (Re) and the surfactant partition coefficients bilayer/aqueous phase (K) were determined from the linear dependence between lipid and surfactant concentrations obtained for a fixed number of surfactant molecules on the liposome surface. The Re values indicated that the highest SLES ability to adsorb on the surface occurs at the initial adsorption moments. The K values indicated that the affinity of the surfactant by the liposomes decreased after about 7500 surfactant molecules were adsorbed on the bilayer. This fact is probably caused by the increase of electrostatic repulsion between surfactant monomers in the bulk solution and the bound surfactant. The aforementioned linear dependence obtained from the data for a given number of SLES molecules on the bilayer and the range of SLES concentrations used (below/above its critical micelle concentration, CMC) suggest an adsorption mechanism regardless of the surfactant concentration: a monomeric adsorption of SLES is always assumed in both above/below surfactant CMC. In comparison with the higher adsorption reported for the analogous sodium dodecyl sulfate, the ethylene oxide moles in SLES could hinder its incorporation on PC liposomes. Thus, this study of sublytic interactions allows to follow the incorporation of surfactants on the lipid bilayers and to compare the effect of different surfactants on the membranes before the lysis.