bluuebunny/crossref_metadata_2025_split huggingface dataset:
MS2PIP: a tool for MS/MS peak intensity prediction
Authors: Degroeve Sven , Martens Lennart 
Published: September 2013

Abstract
Motivation: Tandem mass spectrometry provides the means to match mass spectrometry signal observations with the chemical entities that generated them. The technology produces signal spectra that contain information about the chemical dissociation pattern of a peptide that was forced to fragment using methods like collision-induced dissociation. The ability to predict these MS2 signals and to understand this fragmentation process is important for sensitive high-throughput proteomics research.
Results: We present a new tool called MS2PIP for predicting the intensity of the most important fragment ion signal peaks from a peptide sequence. MS2PIP pre-processes a large dataset with confident peptide-to-spectrum matches to facilitate data-driven model induction using a random forest regression learning algorithm. The intensity predictions of MS2PIP were evaluated on several independent evaluation sets and found to correlate significantly better with the observed fragment-ion intensities as compared with the current state-of-the-art PeptideART tool.
Availability: MS2PIP code is available for both training and predicting at http://compomics.com/.
Contact: sven.degroeve@UGent.be
Supplementary information: Supplementary data are available at Bioinformatics online.
Optimized atomic statistical potentials: assessment of protein interfaces and loops
Authors: Dong Guang Qiang , Fan Hao , Schneidman-Duhovny Dina , Webb Ben , Sali Andrej 
Published: September 2013

AbstractMotivation: Statistical potentials have been widely used for modeling whole proteins and their parts (e.g. sidechains and loops) as well as interactions between proteins, nucleic acids and small molecules. Here, we formulate the statistical potentials entirely within a statistical framework, avoiding questionable statistical mechanical assumptions and approximations, including a definition of the reference state.Results: We derive a general Bayesian framework for inferring statistically optimized atomic potentials (SOAP) in which the reference state is replaced with data-driven ‘recovery’ functions. Moreover, we restrain the relative orientation between two covalent bonds instead of a simple distance between two atoms, in an effort to capture orientation-dependent interactions such as hydrogen bonds. To demonstrate this general approach, we computed statistical potentials for protein–protein docking (SOAP-PP) and loop modeling (SOAP-Loop). For docking, a near-native model is within the top 10 scoring models in 40% of the PatchDock benchmark cases, compared with 23 and 27% for the state-of-the-art ZDOCK and FireDock scoring functions, respectively. Similarly, for modeling 12-residue loops in the PLOP benchmark, the average main-chain root mean square deviation of the best scored conformations by SOAP-Loop is 1.5 Å, close to the average root mean square deviation of the best sampled conformations (1.2 Å) and significantly better than that selected by Rosetta (2.1 Å), DFIRE (2.3 Å), DOPE (2.5 Å) and PLOP scoring functions (3.0 Å). Our Bayesian framework may also result in more accurate statistical potentials for additional modeling applications, thus affording better leverage of the experimentally determined protein structures.Availability and implementation: SOAP-PP and SOAP-Loop are available as part of MODELLER (http://salilab.org/modeller).Contact: sali@salilab.orgSupplementary information: Supplementary data are available at Bioinformatics online.
A super‐resolution ultrasound method for brain vascular mapping
Authors: OˈReilly Meaghan A. , Hynynen Kullervo 
Published: October 2013

Purpose:High‐resolution vascular imaging has not been achieved in the brain due to limitations of current clinical imaging modalities. The authors present a method for transcranial ultrasound imaging of single micrometer‐size bubbles within a tube phantom.Methods:Emissions from single bubbles within a tube phantom were mapped through anex vivo human skull using a sparse hemispherical receiver array and a passive beamforming algorithm. Noninvasive phase and amplitude correction techniques were applied to compensate for the aberrating effects of the skull bone. The positions of the individual bubbles were estimated beyond the diffraction limit of ultrasound to produce a super‐resolution image of the tube phantom, which was compared with microcomputed tomography (micro‐CT).Results:The resulting super‐resolution ultrasound image is comparable to results obtained via the micro‐CT for small tissue specimen imaging.Conclusions:This method provides superior resolution to deep‐tissue contrast ultrasound and has the potential to be extended to provide complete vascular network imaging in the brain.
Novel Secreted Antigens of Mycobacterium paratuberculosis as Serodiagnostic Biomarkers for Johne's Disease in Cattle
Authors: Facciuolo Antonio , Kelton David F. , Mutharia Lucy M. 
Published: October 2013

ABSTRACT

Johne's disease is a chronic gastroenteritis of cattle caused by
Mycobacterium avium
subsp.
paratuberculosis
that afflicts 40% of dairy herds worldwide.
M. avium
subsp.
paratuberculosis
-infected cattle can remain asymptomatic for years while transmitting the pathogen via fecal contamination and milk. Current serodiagnosis with enzyme-linked immunosorbent assays (ELISAs) fails to detect asymptomatic
M. avium
subsp.
paratuberculosis
-infected cattle due to the use of poorly defined antigens and knowledge gaps in our understanding of
M. avium
subsp.
paratuberculosis
components eliciting pathogen-specific immune responses. We set out to (i) define a subset of proteins that contain putative antigenic targets and (ii) screen these antigen pools for immunogens relevant in detecting infection. To accomplish our first objective, we captured and resolved
M. avium
subsp.
paratuberculosis
-secreted proteins using a 2-step fractionation method and reverse-phase liquid chromatography to identify 162 unique proteins, of which 66 had not been previously observed in
M. avium
subsp.
paratuberculosis
culture filtrates. Subsequent screening of
M. avium
subsp.
paratuberculosis
-secreted proteins showed four antigens, of which one or more reacted on immunoblotting with individual serum samples from 35
M. avium
subsp.
paratuberculosis
-infected cows. Moreover, these novel antigens reacted with sera from 6 low
M. avium
subsp.
paratuberculosis
shedders and 3 fecal-culture-positive cows labeled as ELISA seronegative. The specificity of these antigens was demonstrated using negative-control sera from uninfected calves (
n
= 5) and uninfected cows (
n
= 5), which did not react to any of these antigens in immunoblotting. As three of the four antigens are novel, their characterization and incorporation into an ELISA-based format will aid in detecting asymptomatic cattle in early or subclinical stages of disease.
Multicenter Evaluation of the Verigene Clostridium difficile Nucleic Acid Assay
Authors: Carroll Karen C. , Buchan Blake W. , Tan Sokha , Stamper Paul D. , Riebe Katherine M. , Pancholi Preeti , Kelly Cheryl , Rao Arundhati , Fader Robert , Cavagnolo Robert , Watson Wendy , Goering Richard V. , Trevino Ernest A. , Weissfeld Alice S. , Ledeboer Nathan A. 
Published: October 2013

ABSTRACT

The Verigene
Clostridium difficile
Nucleic Acid test (Verigene CDF test) (Nanosphere, Northbrook, IL) is a multiplex qualitative PCR assay that utilizes a nanoparticle-based array hybridization method to detect
C. difficile
tcdA
and
tcdB
in fecal specimens. In addition, the assay detects binary toxin gene sequences and the single base pair deletion at nucleotide 117 (Δ 117) in
tcdC
to provide a presumptive identification of the epidemic strain 027/NAP1/BI (referred to here as ribotype 027). This study compared the Verigene CDF test with anaerobic direct and enriched toxigenic culture on stool specimens from symptomatic patients among five geographically diverse laboratories within the United States. The Verigene CDF test was performed according to the manufacturer's instructions, and the reference methods performed by a central laboratory included direct culture onto cycloserine cefoxitin fructose agar (CCFA) and enriched culture using cycloserine cefoxitin mannitol broth with taurocholate and lysozyme. Recovered isolates were identified as
C. difficile
using gas liquid chromatography and were tested for toxin using a cell culture cytotoxicity neutralization assay. Strains belonging to ribotype 027 were determined by PCR ribotyping and bidirectional sequencing for Δ 117 in
tcdC
. A total of 1,875 specimens were evaluable. Of these, 275 specimens (14.7%) were culture positive by either direct or enriched culture methods. Compared to direct culture alone, the overall sensitivity, specificity, positive predictive value, and negative predictive value for the Verigene CDF test were 98.7%, 87.5%, 42%, and 99.9%, respectively. Compared to combined direct and enriched culture results, the sensitivity, specificity, positive predictive value, and negative predictive values of the Verigene CDF test were 90.9%, 92.5%, 67.6%, and 98.3%, respectively. Of the 250 concordantly culture-positive specimens, 59 (23.6%) were flagged as “hypervirulent”; 53 were confirmed as ribotype 027, and all 59 possessed Δ 117 in
tcdC
. Time to results was approximately 2.5 h per specimen. The Verigene CDF test is a novel nucleic acid microarray that reliably detects both
C. difficile
toxins A and B in unformed stool specimens and appears to adequately identify ribotype 027 isolates.
Superior Sensitivity and Decreased Time to Detection with the Bactec Peds Plus/F System Compared to the BacT/Alert Pediatric FAN Blood Culture System
Authors: Sullivan K. V. , Turner N. N. , Lancaster D. P. , Shah A. R. , Chandler L. J. , Friedman D. F. , Blecker-Shelly D. L. 
Published: October 2013

ABSTRACT

Here, we compare the sensitivities and times to detection (TTD) of BacT/Alert Pediatric FAN (PF) and Bactec Peds Plus blood culture bottles. Test bottles were inoculated with 2 ml of banked whole blood, 1-ml aliquots of antibiotic suspension, and organisms diluted to simulate a bacteremia level of 10 to 100 CFU/ml. The control bottles were inoculated with 3 ml of banked blood and organism suspensions only. The organism-drug combinations were
Staphylococcus epidermidis
and vancomycin, methicillin-resistant
Staphylococcus aureus
and vancomycin,
Streptococcus pneumoniae
, vancomycin, and ceftriaxone,
Streptococcus agalactiae
, ampicillin, and cefotaxime,
Escherichia coli
, cefotaxime, and cefepime,
Pseudomonas aeruginosa
, piperacillin-tazobactam, cefepime, and gentamicin,
Neisseria meningitidis
and ceftriaxone, and
Haemophilus influenzae
and ceftriaxone. The control and test bottle combinations were tested in duplicate. The bottles were incubated for 5 days; 32 control and 104 test bottles were incubated. Overall, the bacterial recovery rates for the PF and Peds Plus bottles were 37% and 62%, 94% and 100% in the controls, 19% and 50% in the test bottles, and 33% and 92% in the bottles with vancomycin, respectively. No bacteria were recovered from the bottles with
S. pneumoniae
,
S. agalactiae
,
E. coli
,
N. meningitidis
, or
H. influenzae
in combination with cefotaxime or ceftriaxone. The Peds Plus system detected
P. aeruginosa
in bottles with cefepime and piperacillin-tazobactam, but the PF system recovered bacteria only in bottles with trough levels of piperacillin-tazobactam. The mean TTD were shorter in the Peds Plus system controls (14.2 versus 18.0 h;
P
= 0.001) and the test bottles (14.3 versus 17.8 h;
P
= 0.008) than in the PF bottles. Overall, we demonstrated superior sensitivity, TTD, and antibiotic neutralization in the Bactec Peds Plus system compared to those in the Pediatric FAN system.
Emergence of an Oseltamivir-Resistant Influenza A/H3N2 Virus in an Elderly Patient Receiving a Suboptimal Dose of Antiviral Prophylaxis
Authors: Roussy Jean-François , Abed Yacine , Bouhy Xavier , Boivin Guy 
Published: October 2013

ABSTRACTWe report the emergence of an influenza virus A/H3N2-E119V neuraminidase variant from an elderly patient with renal dysfunction who received a suboptimal dose of oseltamivir prophylaxis. In neuraminidase inhibition assays, the E119V variant showed a 413-fold increase in the 50% inhibitory oseltamivir concentration and grew at titers comparable to those of the wild typein vitro.
Therapeutic Vaccination against the Rhesus Lymphocryptovirus EBNA-1 Homologue, rhEBNA-1, Elicits T Cell Responses to Novel Epitopes in Rhesus Macaques
Authors: Silveira Eduardo L. V. , Fogg Mark H. , Leskowitz Rachel M. , Ertl Hildegund C. , Wiseman Roger W. , O'Connor David H. , Lieberman Paul , Wang Fred , Villinger Francois 
Published: October 2013

ABSTRACTEpstein-Barr virus (EBV) is a vaccine/immunotherapy target due to its association with several human malignancies. EBNA-1 is an EBV protein consistently expressed in all EBV-associated cancers. Herein, EBNA-1-specific T cell epitopes were evaluated after AdC–rhEBNA-1 immunizations in chronically lymphocryptovirus-infected rhesus macaques, an EBV infection model. Preexisting rhEBNA-1-specific responses were augmented in 4/12 animals, and new epitopes were recognized in 5/12 animals after vaccinations. This study demonstrated that EBNA-1-specific T cells can be expanded by vaccination.
Highly Divergent Strains of Porcine Reproductive and Respiratory Syndrome Virus Incorporate Multiple Isoforms of Nonstructural Protein 2 into Virions
Authors: Kappes Matthew A. , Miller Cathy L. , Faaberg Kay S. 
Published: October 2013

ABSTRACT

Viral structural proteins form the critical intermediary between viral infection cycles within and between hosts, function to initiate entry, participate in immediate early viral replication steps, and are major targets for the host adaptive immune response. We report the identification of nonstructural protein 2 (nsp2) as a novel structural component of the porcine reproductive and respiratory syndrome virus (PRRSV) particle. A set of custom α-nsp2 antibodies targeting conserved epitopes within four distinct regions of nsp2 (the PLP2 protease domain [OTU], the hypervariable domain [HV], the putative transmembrane domain [TM], and the C-terminal region [C]) were obtained commercially and validated in PRRSV-infected cells. Highly purified cell-free virions of several PRRSV strains were isolated through multiple rounds of differential density gradient centrifugation and analyzed by immunoelectron microscopy (IEM) and Western blot assays using the α-nsp2 antibodies. Purified viral preparations were found to contain pleomorphic, predominantly spherical virions of uniform size (57.9 nm ± 8.1 nm diameter;
n
= 50), consistent with the expected size of PRRSV particles. Analysis by IEM indicated the presence of nsp2 associated with the viral particle of diverse strains of PRRSV. Western blot analysis confirmed the presence of nsp2 in purified viral samples and revealed that multiple nsp2 isoforms were associated with the virion. Finally, a recombinant PRRSV genome containing a
myc
-tagged nsp2 was used to generate purified virus, and these particles were also shown to harbor
myc
-tagged nsp2 isoforms. Together, these data identify nsp2 as a virion-associated structural PRRSV protein and reveal that nsp2 exists in or on viral particles as multiple isoforms.
Haemagglutinin and nucleoprotein replicon particle vaccination of swine protects against the pandemic H1N1 2009 virus
Authors: Vander Veen R. L. , Mogler M. A. , Russell B. J. , Loynachan A. T. , Harris D. L. H. , Kamrud K. I. 
Published: September 2013

The recent emergence of the pandemic H1N1 (pH1N1) and H3N2 variant influenza A viruses (IAV) in 2009 and 2011–2012, respectively, highlight the zoonotic potential of influenza viruses and the need for vaccines capable of eliciting heterosubtypic protection. In these studies, single‐cycle, propagation‐defective replicon particle (RP) vaccines expressing IAV haemagglutinin (HA) and nucleoprotein (NP) genes were constructed and efficacy was evaluated in homologous and heterologous pig challenge studies with the pH1N1 2009 influenza virus (A/California/04/2009). Homologous HA RP vaccination eliminated virus shedding and decreased pulmonary pathology in pigs following pH1N1 2009 challenge. An RP vaccine expressing an H3N2‐derived NP gene was able to decrease nasal shedding and viral load following heterosubtypic pH1N1 2009 challenge in pigs. These studies indicate that although homologous vaccination of swine remains the most effective means of preventing IAV infection, other vaccine alternatives do offer a level of heterosubtypic protection, and should continue to be evaluated for their ability to provide broader protection.
Childhood Height and Birth Weight in Relation to Future Prostate Cancer Risk: A Cohort Study Based on the Copenhagen School Health Records Register
Authors: Cook Michael B. , Gamborg Michael , Aarestrup Julie , Sørensen Thorkild I.A. , Baker Jennifer L. 
Published: October 2013

Abstract
Background: Adult height has been positively associated with prostate cancer risk. However, the exposure window of importance is currently unknown and assessments of height during earlier growth periods are scarce. In addition, the association between birth weight and prostate cancer remains undetermined. We assessed these relationships in a cohort of the Copenhagen School Health Records Register (CSHRR).
Methods: The CSHRR comprises 372,636 school children. For boys born between the 1930s and 1969, birth weight and annual childhood heights—measured between ages 7 and 13 years—were analyzed in relation to prostate cancer risk. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI).
Results: There were 125,211 males for analysis, 2,987 of who were subsequently diagnosed with prostate cancer during 2.57 million person-years of follow-up. Height z-score was significantly associated with prostate cancer risk at all ages (HRs, 1.13 to 1.14). Height at age 13 years was more important than height change (P = 0.024) and height at age 7 years (P = 0.024), when estimates from mutually adjusted models were compared. Adjustment of birth weight did not alter the estimates. Birth weight was not associated with prostate cancer risk.
Conclusions: The association between childhood height and prostate cancer risk was driven by height at age 13 years.
Impact: Our findings implicate late childhood, adolescence, and adulthood growth periods as containing the exposure window(s) of interest that underlies the association between height and prostate cancer. The causal factor may not be singular given the complexity of both human growth and carcinogenesis. Cancer Epidemiol Biomarkers Prev; 22(12); 2232–40. ©2013 AACR.
A New Reading of an Early Medieval Riddle
Authors: Chan Timothy Wai Keung 
Published: September 2013

In the history of Chinese literary riddles, one work marks an aesthetic milestone and yet still causes uncertainty with regard to its context, syntactical structure, and meaning. Composed sometime between the mid-second to early fourth centuries in southeastern China, this riddle is a “postscript” to a stele inscription that relates how a fourteen-year-old Maiden Cao 曹娥 (d. 143) sacrificed her life by jumping into a river to search for the body of her drowned father. The “question” and “answer” of the riddle have been deciphered and construed in early sources, but are only treated there as a self-descriptive comment, without a larger context. After a brief survey of different kinds of riddle texts, this essay applies current theories about riddle composition to the text in question, also making use of relevant but overlooked historical and geographical information. A new reading of the riddle is ventured, in which it is seen to epitomize in enigmatically refined language the tragic act of Ms. Cao. Une œuvre marque un jalon dans l’histoire des charades littéraires tout en continuant d’être source d’incertitudes quant à son contexte, sa structure syntactique et sa signification. Composée entre le milieu du second et le début du quatrième siècle dans le Sud-Est de la Chine, cette charade sert de post-scriptum à une inscription sur stèle relatant comment la jeune Cao (morte en 143), âgée de 14 ans, sacrifia sa vie en se précipitant dans une rivière à la recherche du corps de son père noyé. La “question” et la “réponse” de la charade ont été déchiffrées et analysées dans des sources anciennes, mais seulement sous la forme de com­mentaires autonomes, sans faire appel au contexte. Ayant brièvement passé en revue les différents types de charades, le présent essai applique au texte en question les théories actuelles sur la composition des charades, tout en faisant appel à des données historiques et géographiques jusqu’à présent négligées. Une nouvelle lecture de la charade est proposée, à travers laquelle on voit que le texte illustre à la perfection, et dans une langue aussi raffinée qu’énigmatique, l’acte tragique de la jeune Cao.
Making Sense of the Master
Authors: Lee Sukhee 
Published: September 2013

Zhu Xi’s Neo-Confucianism contained the seeds of a tension with the spreading localist tendencies of the Southern Song. How, then, did it make its way into the minds of local elites? By examining the thought of Wang Bo (1197-1274), this article shows the ways in which Zhu Xi’s Neo-Confucianism was interpreted in and reconciled with local contexts—how it was “localized.” First, Wang understood Zhu Xi’s major texts with the literary and historical sensitivity of Wuzhou scholarship, eventually challenging their ultimate authority through using his own local tradition. Second, he called into question the viability of Zhu’s local economic activism, thus speaking for the general economic interests of non-official, local elites like himself. Wang Bo’s “localized” Neo-Confucianism may have been a significant lapse from Zhu’s doctrine, but it was precisely such lapses that expanded its scope, making it possible for many more thinkers at the time to embrace it. Le néo-confucianisme de Zhu Xi contenait en germe une tension avec les tendances localistes qui se répandaient sous les Song du Sud. Comment dès lors ­parvint-il à s’imposer aux esprits parmi les élites locales? En examinant la pensée de Wang Bo (1197-1274), cet article met en évidence les différentes façons dont le néo-confucianisme de Zhu Xi a été interprété dans des contextes locaux et ­comment il a pu être réconcilié avec eux — comment il a été “localisé”. Pour com­mencer, Wang, qui comprenait les principaux textes de Zhu Xi à travers la sensibilité littéraire et historique de l’école de Wuzhou, finit par en contester l’autorité ultime en se basant sur sa propre tradition locale. Il mit par ailleurs en doute la viabilité des formes d’activisme économique local préconisées par Zhu Xi, en quoi il parlait au nom des intérêts économiques généraux de l’élite locale non bureaucratique dont il était un représentant. Si le néo-confucianisme “local” de Wang Bo a pu s’écarter significativement de la doctrine de Zhu Xi, ce sont précisément de tels écarts qui ont élargi la portée de celle-ci, permettant à l’époque à un nombre beaucoup plus grand de penseurs d’y adhérer.