bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conjugation of Polysaccharide 6B from Streptococcus pneumoniae with Pneumococcal Surface Protein A: PspA Conformation and Its Effect on the Immune Response
Authors: Perciani Catia T. , Barazzone Giovana C. , Goulart Cibelly , Carvalho Eneas , Cabrera-Crespo Joaquin , Gonçalves Viviane M. , Leite Luciana C. C. , Tanizaki Martha M. 
Published: April 2013

ABSTRACTDespite the substantial beneficial effects of incorporating the 7-valent pneumococcal conjugate vaccine (PCV7) into immunization programs, serotype replacement has been observed after its widespread use. As there are many serotypes currently documented, the use of a conjugate vaccine relying on protective pneumococcal proteins as active carriers is a promising alternative to expand PCV coverage. In this study, capsular polysaccharide serotype 6B (PS6B) and recombinant pneumococcal surface protein A (rPspA), a well-known protective antigen fromStreptococcus pneumoniae, were covalently attached by two conjugation methods. The conjugation methodology developed by our laboratory, employing 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) as an activating agent through carboxamide formation, was compared with reductive amination, a classical methodology. DMT-MM-mediated conjugation was shown to be more efficient in coupling PS6B to rPspA clade 1 (rPspA1): 55.0% of PS6B was in the conjugate fraction, whereas 24% was observed in the conjugate fraction with reductive amination. The influence of the conjugation process on the rPspA1 structure was assessed by circular dichroism. According to our results, both conjugation processes reduced the alpha-helical content of rPspA; reduction was more pronounced when the reaction between the polysaccharide capsule and rPspA1 was promoted between the carboxyl groups than the amine groups (46% and 13%, respectively). Regarding the immune response, both conjugates induced functional anti-rPspA1 and anti-PS6B antibodies. These results suggest that the secondary structure of PspA1, as well as its reactive groups (amine or carboxyl) involved in the linkage to PS6B, may not play an important role in eliciting a protective immune response to the antigens.
Clostridium difficile Ribotype Diversity at Six Health Care Institutions in the United States
Authors: Waslawski Sheila , Lo Eugene S. , Ewing Sarah A. , Young Vincent B. , Aronoff David M. , Sharp Susan E. , Novak-Weekley Susan M. , Crist Arthur E. , Dunne W. Michael , Hoppe-Bauer Joan , Johnson Michelle , Brecher Stephen M. , Newton Duane W. , Walk Seth T. 
Published: April 2013

ABSTRACT

Capillary-based PCR ribotyping was used to quantify the presence/absence and relative abundance of 98
Clostridium difficile
ribotypes from clinical cases of disease at health care institutions in six states of the United States. Regionally important ribotypes were identified, and institutions in close proximity did not necessarily share more ribotype diversity than institutions that were farther apart.
Detection of New Delhi Metallo-β-Lactamase (Encoded by
bla
NDM-1
) in Acinetobacter schindleri during Routine Surveillance
Authors: McGann Patrick , Milillo Michael , Clifford Robert J. , Snesrud Erik , Stevenson Lindsay , Backlund Michael G. , Viscount Helen B. , Quintero Reyes , Kwak Yoon I. , Zapor Michael J. , Waterman Paige E. , Lesho Emil P. 
Published: April 2013

ABSTRACT

A carbapenem-resistant
Alcaligenes faecalis
strain was isolated from a surveillance swab of a service member injured in Afghanistan. The isolate was positive for
bla
NDM
by real-time PCR. Species identification was reevaluated on three identification systems but was inconclusive. Genome sequencing indicated that the closest relative was
Acinetobacter schindleri
and that
bla
NDM-1
was carried on a plasmid that shared >99% identity with one identified in an
Acinetobacter lwoffii
isolate. The isolate also carried a novel chromosomally encoded class D oxacillinase.
Identification and Characterization of a Peptide Affinity Reagent for Detection of Noroviruses in Clinical Samples
Authors: Rogers Jennifer D. , Ajami Nadim J. , Fryszczyn Bartlomiej G. , Estes Mary K. , Atmar Robert L. , Palzkill Timothy 
Published: April 2013

ABSTRACT
Norovirus (NoV) is the most common agent of nonbacterial epidemic gastroenteritis and is estimated to cause 21 million cases of the disease in the United States annually. The antigen enzyme-linked immunosorbent assays (ELISAs) currently available for NoV diagnosis detect only certain strains and are approved for use in the United States only in epidemics where NoV is suspected. There is a clear need for simpler, more rapid, and more reliable diagnostic tools for the detection of NoV. In this study, phage display technology was used to screen a library of phage displaying random 12-mer peptides for those that bind to Norwalk virus virus-like particles (NV VLPs). Three phage clones displaying unique peptides were identified, and both the peptide-displaying phages and the peptides were confirmed to bind specifically to NV VLPs. The peptide displayed on phage clone NV-N-R5-1 was determined to bind to the protruding domain of the VP1 capsid protein. This phage also bound to NV VLPs seeded into NoV-negative stool with a limit of detection of 1.56 ng NV VLP. This value was comparable to monoclonal antibody (MAb) 3912, which is currently used in commercially available assays. Furthermore, the NV-N-R5-1 phage exhibited high specificity by detecting NV only in previously characterized NV-positive stool samples in contrast to no detection in NV-negative stool samples. These data demonstrate that the further development of NV-N-R5-1 phage as a diagnostic reagent is possible and might offer several distinct advantages over antibodies, such as decreases in the time and cost of production and ease of isolating phage against other epidemic strains currently circulating as well as those that are emerging.
Analysis of the Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrum of Staphylococcus aureus Identifies Mutations That Allow Differentiation of the Main Clonal Lineages
Authors: Josten Michaele , Reif Marion , Szekat Christiane , Al-Sabti Nahed , Roemer Terry , Sparbier Katrin , Kostrzewa Markus , Rohde Holger , Sahl Hans-Georg , Bierbaum Gabriele 
Published: April 2013

ABSTRACT

Nosocomial infections involving epidemic methicillin-resistant
Staphylococcus aureus
(MRSA) strains are a serious problem in many countries. In order to analyze outbreaks, the infectious isolates have to be typed; however, most molecular methods are expensive or labor-intensive. Here, we evaluated matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) of cell extracts for the molecular characterization of
S. aureus
strains. The peak patterns of 401 MRSA and methicillin-susceptible
S. aureus
(MSSA) strains, including clinical and laboratory strains, were analyzed. Database searches indicated the peptides that were represented by the corresponding peaks in the spectra. The identities of the peptides were confirmed by the sequencing of mutants, the expression of antisense RNA fragments that resulted in the knockdown of the peptide of interest and the concomitant loss of the signal, or tandem MALDI-TOF MS (MALDI-TOF/TOF MS). It was shown that the signals derive mainly from stress proteins and ribosomal proteins. Peak shifts that differentiate the main
S. aureus
clonal complexes CC5, CC22, CC8, CC45, CC30, and CC1 correlate to point mutations in the respective genes. Retrospective typing of an MRSA outbreak showed that it is possible to differentiate unrelated MSSA, MRSA, and borderline resistant
S. aureus
(BORSA) strains isolated from health care workers. In conclusion, this method allows for the detection of the epidemic lineages of
S. aureus
during species identification by MALDI-TOF MS analysis.
Septic Arthritis and Concern for Osteomyelitis in a Child with Rat Bite Fever
Authors: Flannery Dustin D. , Akinboyo Ibukunoluwa , Ty Jennifer M. , Averill Lauren W. , Freedman Abigail 
Published: April 2013

ABSTRACT

Rat bite fever is a rare infection usually caused by
Streptobacillus moniliformis
. A case of septic arthritis and possible osteomyelitis as sequelae of rat bite fever in a pediatric patient is described.
Detection of non-
jejuni
and -coli Campylobacter Species from Stool Specimens with an Immunochromatographic Antigen Detection Assay
Authors: Couturier Brianne A. , Couturier Marc Roger , Kalp Kim J. , Fisher Mark A. 
Published: April 2013

ABSTRACT

The STAT! Campy immunochromatographic assay for
Campylobacter
antigen was compared to culture for 500 clinical stool specimens. Antigen was detected in six culture-negative, PCR-positive specimens.
C. upsaliensis
, a pathogenic species that is traditionally difficult to recover in routine stool cultures, was detected in two of these culture-negative specimens. This study provides evidence that antigen testing may cross-react with at least one additional non-
jejuni
and -
coli Campylobacter
species that may be missed by routine culture for campylobacteriosis.
Microbiological Diagnosis of Severe Diarrhea in Kidney Transplant Recipients by Use of Multiplex PCR Assays
Authors: Coste Jean-François , Vuiblet Vincent , Moustapha Betoul , Bouin Alexis , Lavaud Sylvie , Toupance Olivier , de Rougemont Alexis , Benejat Lucie , Megraud Francis , Wolak-Thierry Aurore , Villena Isabelle , Chemla Cathy , Le Magrex Elisabeth , de Champs Christophe , Andreoletti Laurent , Rieu Philippe , Leveque Nicolas 
Published: April 2013

ABSTRACT

Diarrhea is a frequent complication after kidney transplantation, ascribed to adverse effects of the immunosuppressive therapy in case of negative microbiological examination of the stools. The aim of this study was to improve the microbiological diagnosis by implementing molecular tests. Fifty-four severe diarrhea events that occurred in 49 adult kidney transplant recipients from September 2010 to November 2011 were investigated. One or several enteric pathogens were detected in 13 (23%) stool samples using classical microbiological methods versus 39 (72%) for the seven commercially available multiplex PCR assays used retrospectively (
P
= 0.006). Interestingly, molecular diagnosis identified 15 multiple infections compared to none using classical techniques. The primary pathogens detected were enteropathogenic
Escherichia coli
(EPEC) (
n
= 15; 38%),
Campylobacter
spp. (
n
= 15; 38%), and
Norovirus
(
n
= 14; 36%). Specificities for
Campylobacter
and
Norovirus
infection diagnosis were 75 and 100%, respectively, by comparison to reference methods. Based on molecular findings, a cyclosporine-mycophenolate mofetil combination was identified as a risk factor for developing
Norovirus
-induced diarrhea.
Norovirus
infections were also responsible for higher weight loss than all the other causes of diarrhea. In samples from asymptomatic immunocompromised and immunocompetent patients, EPEC but not
Norovirus
and
Campylobacter
infections were detected at a frequency similar to that observed in symptomatic kidney transplant recipients. In conclusion, molecular tools significantly improved the detection of single and multiple enteric infections by comparison to classical techniques and could quickly become the key element in the management of severe acute diarrhea in transplant recipients.
HIV-1 Vpu Does Not Degrade Interferon Regulatory Factor 3
Authors: Hotter Dominik , Kirchhoff Frank , Sauter Daniel 
Published: April 2013

ABSTRACT
It has been reported that HIV-1 Vpu mediates the degradation of interferon regulatory factor 3 (IRF-3) to avoid innate immune sensing. Here, we show that Vpu does not deplete IRF-3 from transfected cell lines or HIV-1-infected primary cells. Furthermore, the Vpu-dependent suppression of beta interferon expression described in previous studies could be ascribed to inhibition of NF-κB activation. Thus, Vpu suppresses innate immune activation through inhibition of NF-κB rather than degradation of IRF-3.
Genome-Wide Analysis of Host mRNA Translation during Hepatitis C Virus Infection
Authors: Colman Hélène , Le Berre-Scoul Catherine , Hernandez Céline , Pierredon Sandra , Bihouée Audrey , Houlgatte Rémi , Vagner Stephan , Rosenberg Arielle R. , Féray Cyrille 
Published: April 2013

ABSTRACT
In the model of Huh-7.5.1 hepatocyte cells infected by the JFH1 hepatitis C virus (HCV) strain, transcriptomic and proteomic studies have revealed modulations of pathways governing mainly apoptosis and cell cycling. Differences between transcriptomic and proteomic studies pointed to regulations occurring at the posttranscriptional level, including the control of mRNA translation. In this study, we investigated at the genome-wide level the translational regulation occurring during HCV infection. Sucrose gradient ultracentrifugation followed by microarray analysis was used to identify translationally regulated mRNAs (mRNAs associated with ribosomes) from JFH1-infected and uninfected Huh-7.5.1 cells. Translationally regulated mRNAs were found to correspond to genes enriched in specific pathways, including vesicular transport and posttranscriptional regulation. Interestingly, the strongest translational regulation was found for mRNAs encoding proteins involved in pre-mRNA splicing, mRNA translation, and protein folding. Strikingly, these pathways were not previously identified, through transcriptomic studies, as being modulated following HCV infection. Importantly, the observed changes in host mRNA translation were directly due to HCV replication rather than to HCV entry, since they were not observed in JFH1-infected Huh-7.5.1 cells treated with a potent HCV NS3 protease inhibitor. Overall, this study highlights the need to consider, beyond transcriptomic or proteomic studies, the modulation of host mRNA translation as an important aspect of HCV infection.
Coal deposits in Colombia
Authors: Suescún-Gomez Dario 
Published: April 2013

Colombian coal deposits range in age from Maestrichtian-Paleocene in the Sabana de Bogotá and Boyacá basins to middle Oligocene in the Amagá-Titiribí basin in Antioquia. On the basis of age alone, these coal beds should be of lignitic rank, but because of the intense Andean tectonism (especially during Pliocene time) the rank has been increased to bituminous coal with high to medium volatile-matter content. In some areas, as a result of thermometa-morphic action by the intrusion of porphyritic andesite, the coal beds have been transformed to meta-anthracite. Chemical analyses of the best known coal deposits show a large range in rank.
The main basins studied are Amagá-Titiribí (middle Oligo-cene), Santander (Paleocene-Oligocene), Valle del Cauca (Eocene), Cerrejón and Jagua de Ibirico (Paleocene), and Boyacá-Sabana de Bogotá (Maestrichtian-Paleocene).
Evaluations made in Colombia in 1968 were 5 billion metric tons of exploitable coal, of which 5 percent is measured coal, 15 percent is indicated coal, and 80 percent is inferred coal. There are some basins yet to be explored and evaluated; when this is accomplished, total coal resources in Columbia may be as much as 10 billion metric tons.
Main coal regions of Mexico
Authors: Ojeda-Rivera Jesús 
Published: April 2013

Most of the coal in Mexico is concentrated in three widely separated regions
Coahuila on the northeast, Sonora on the northwest, and Oaxaca on the south-southeast. In the Coahuila region, bituminous coking coals are present in Upper Cretaceous rocks. The Sonora region contains deposits of Upper Triassic anthracitic coal, altered by probable thermal metamorphism. The Oaxaca region contains anthracitic and some bituminous coking coal in Lower(?) to Middle Jurassic sequences.
Through 1973, only the coal deposits of the Coahuila region had been developed commercially. The coals of the Sonora and Oaxaca regions are undeveloped because of unfavorable geo-economic conditions and lack of exploration. Through 1973, the Coahuila region had yielded about 110 million metric tons of coal, most of which was used to produce coke. Present production is 4,250,000 metric tons per year. The largest mines include one underground mine (Sabinas no. 2) and one openpit mine (La Florida), which produce 40,000 metric tons per month.
Only reconnaissance-geologic investigations, complemented locally by a few limited drilling projects, have been made in the Sonora and Oaxaca regions. Exploration has been more extensive in the Coahuila region. There are many totally unexplored areas with potential coal resources.
The estimated resources in the Sabinas area of the Coahuila region total 1,781 million metric tons classed as reserves in situ, and 1,180 million metric tons classed as potential but not commercially important at present. North of the Sabinas area, in the Río Escondido basin, the estimated resources total 120 million metric tons classed as measured.
In the Sonora region the estimated resources total 11 million metric tons classed as reserves in situ for the Santa Clara coalfield and 4 million metric tons classed as measured, 9 million metric tons classed as inferred, and 18 million metric tons classed as possible for the San Marcial district.
In the Mixtepec and Tezoatlán coal fields of the Oaxaca region, the estimated resources total 24 million metric tons classed as inferred and 26 million metric tons classed as possible.
Utilization of lignite in the United States
Authors: Scollon T. Reed , Sheridan Eugene T. 
Published: April 2013

The remote location of most United States lignite deposits with respect to major markets and the relatively low calorific value of lignite have prevented, until recently, any significant growth in demand. Unprecedented demands for electric power and recent innovations in its transmission now enable lignite to share with other coals in this growth market. This is particularly true as oil and natural gas resources in the United States decrease and become more difficult to find. Whereas the total reported shipments of lignite had fluctuated between 2.9 and 4.4 million short tons in the decade before 1968, shipments by 1975 had increased significantly to about 19.8 million short tons. The 1975 figure, however, reflects the production of Texas, which was not included in the data for 1956–1968.
In 1975, approximately 4.2 million short tons of U.S. lignite was consumed annually in markets other than electricity—for example, in residential, commercial, and industrial establishments and as a raw material for producing barbeque briquettes, montan wax, and activated char. Although not economically feasible at this time, processes have been developed in which lignite also can be used for the production of chemicals, high-Btu gases, liquid fuels, fertilizers, specialty carbons, and as a reductant for preparation of taconite pellets.
Reserves of lignite are adequate to meet substantial increases in demand, and the costs of recovering the reserves are among the lowest in the United States compared to the costs of recovering reserves of other types of energy. In the immediate future, additional demand for lignite will depend essentially on its increased use to generate electric power. In the long range, nuclear power may limit increases in demand for lignite for power generation. Growth in the utilization of lignite may then depend on the development of the new markets or new products from lignite, such as synthetic fuels. The present United States oil and natural gas shortage also will increase the demand for lignite.
EMD 1214063 and EMD 1204831 Constitute a New Class of Potent and Highly Selective c-Met Inhibitors
Authors: Bladt Friedhelm , Faden Bettina , Friese-Hamim Manja , Knuehl Christine , Wilm Claudia , Fittschen Claus , Grädler Ulrich , Meyring Michael , Dorsch Dieter , Jaehrling Frank , Pehl Ulrich , Stieber Frank , Schadt Oliver , Blaukat Andree 
Published: April 2013

Abstract
Purpose: The mesenchymal–epithelial transition factor (c-Met) receptor, also known as hepatocyte growth factor receptor (HGFR), controls morphogenesis, a process that is physiologically required for embryonic development and tissue repair. Aberrant c-Met activation is associated with a variety of human malignancies including cancers of the lung, kidney, stomach, liver, and brain. In this study, we investigated the properties of two novel compounds developed to selectively inhibit the c-Met receptor in antitumor therapeutic interventions.
Experimental Design: The pharmacologic properties, c-Met inhibitory activity, and antitumor effects of EMD 1214063 and EMD 1204831 were investigated in vitro and in vivo, using human cancer cell lines and mouse xenograft models.
Results: EMD 1214063 and EMD 1204831 selectively suppressed the c-Met receptor tyrosine kinase activity. Their inhibitory activity was potent [inhibitory 50% concentration (IC50), 3 nmol/L and 9 nmol/L, respectively] and highly selective, when compared with their effect on a panel of 242 human kinases. Both EMD 1214063 and EMD 1204831 inhibited c-Met phosphorylation and downstream signaling in a dose-dependent fashion, but differed in the duration of their inhibitory activity. In murine xenograft models, both compounds induced regression of human tumors, regardless of whether c-Met activation was HGF dependent or independent. Both drugs were well tolerated and induced no substantial weight loss after more than 3 weeks of treatment.
Conclusions: Our results indicate selective c-Met inhibition by EMD 1214063 and EMD 1204831 and strongly support clinical testing of these compounds in the context of molecularly targeted anticancer strategies. Clin Cancer Res; 19(11); 2941–51. ©2013 AACR.
Reevaluating the Accelerated Approval Process for Oncology Drugs
Authors: Wilson Wyndham H. , Schenkein David P. , Jernigan Cheryl L. , Woodcock Janet , Schilsky Richard L. 
Published: April 2013

Abstract
For a new therapy to qualify for the accelerated approval pathway, it must treat a serious disease for which there is “unmet medical need”—defined as providing a therapy where none exists or providing a therapy that may be potentially superior to existing therapy. The increasing number of available therapies, coupled with the lack of accepted endpoints considered “reasonably likely to predict clinical benefit” and the lack of clarity early in development about circumstances in which a new product will qualify for accelerated approval, is pushing developers to pursue accelerated approval in heavily pretreated patients to fulfill an unmet need. To optimize the accelerated approval pathway, we propose here a reevaluation of what constitutes “unmet medical need” and “available therapy” in oncology. We also discuss ways for new endpoints to become qualified for use in supporting accelerated approval, and propose a structured process for pursuing accelerated approval. Clin Cancer Res; 19(11); 2804–9. ©2013 AACR.