bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ratcheting Studies on Type 304LN Stainless Steel Elbows subjected to
Combined Internal Pressure and In-Plane Bending Moment
Authors: Vishnuvardhan S. , Raghava G. , Gandhi P. , Saravanan M. , Pukazhendhi D. M. , Goyal Sumit , Gupta Suneel K. , Bhasin Vivek , Vaze K. K. 
Published: July 2012

Abstract
“Ratcheting” is a phenomenon which leads to reduction in fatigue life of a structural component by loss of ductility due to cycle by cycle accumulation of plastic strain. Ratcheting occurs in a structure subjected to a combination of steady/sustained and cyclic loads such that the material response is in inelastic region. Ratcheting studies were carried out on Type 304LN stainless steel elbows, subjected to steady internal pressure and cyclic bending. The elbows filled with water were pressurized between 27.6 MPa and 39.2 MPa. Cyclic bending load, under opening and closing moments, was applied on the elbows at ambient temperature. Number of cycles corresponding to occurrence of a through-wall crack was recorded. Crack was observed in the bent portion at one of the crown locations in all the four specimens. Maximum strain was observed at the intrados and crown locations of the elbows. The ratcheting strain increased with number of cycles at crown and intrados locations. However, the strain accumulation rate decreased with number of cycles. Strain was observed to be minimum at the extrados location and the same stabilized toward the end of the tests. The specimens have failed by occurrence of through-wall axial crack accompanied by simultaneous ballooning. The ballooning was found to be varying from 3.8% to 5.8% with respect to the original circumference in the bent portion. The reduction in thickness was found to be around 12%–15%.
High performance lung nodule detection schemes in CT using local and global information
Authors: Guo Wei , Li Qiang 
Published: July 2012

Purpose:A key issue in current computer‐aided diagnostic (CAD) schemes for nodule detection in CT is the large number of false positives, because current schemes use only global three‐dimensional (3D) information to detect nodules and discard useful local two‐dimensional (2D) information. Thus, the authors integrated local and global information to markedly improve the performance levels of CAD schemes.Methods:Our database was obtained from the standard CT lung nodule database created by the Lung Image Database Consortium (LIDC). It consisted of 85 CT scans with 111 nodules of 3 mm or larger in diameter. The 111 nodules were confirmed by at least two of the four radiologists participated in the LIDC. Twenty‐six nodules were missed by two of the four radiologists and were thus very difficult to detect. The authors developed five CAD schemes for nodule detection in CT using global 3D information (3D scheme), local 2D information (2D scheme), and both local and global information (2D + 3D scheme, 2D − 3D scheme, and 3D − 2D scheme). The 3D scheme, which was developed previously, used only global 3D information and discarded local 2D information, as other CAD schemes did. The 2D scheme used a uniform viewpoint reformation technique to decompose a 3D nodule candidate into a set of 2D reformatted images generated from representative viewpoints, and selected and used “effective” 2D reformatted images to remove false positives. The 2D + 3D scheme, 2D − 3D scheme, and 3D − 2D scheme used complementary local and global information in different ways to further improve the performance of lung nodule detection. The authors employed a leave‐one‐scan‐out testing method for evaluation of the performance levels of the five CAD schemes.Results:At the sensitivities of 85%, 80%, and 75%, the existing 3D scheme reported 17.3, 7.4, and 2.8 false positives per scan, respectively; the 2D scheme improved the detection performance and reduced the numbers of false positives to 7.6, 2.5, and 1.3 per scan; the 2D + 3D scheme further reduced those to 2.7, 1.9, and 0.6 per scan; the 2D − 3D scheme reduced those to 7.6, 2.1, and 0.8 per scan; and the 3D − 2D scheme reduced those to 17.3, 1.6, and 1.0 per scan.Conclusions:The local 2D information appears to be more useful than the global 3D information for nodule detection, particularly, when it is integrated with 3D information.
Pharmacokinetics of Amphotericin B Colloidal Dispersion in Critically Ill Patients with Cholestatic Liver Disease
Authors: Weiler Stefan , Überlacher Elisabeth , Schöfmann Julia , Stienecke Eva , Dunzendorfer Stefan , Joannidis Michael , Bellmann Romuald 
Published: July 2012

ABSTRACT
The pharmacokinetics of lipid-bound and liberated amphotericin B (AMB) was assessed in 11 critically ill patients with cholestatic liver disease (CSLD) and in 9 subjects with normal liver function treated with AMB colloidal dispersion (ABCD). Exposure to lipid-bound AMB was higher in patients with CSLD. Levels of liberated AMB were elevated by CSLD only after the first dose, whereas its pharmacokinetics was unaffected at steady state. The standard dosage of ABCD is probably adequate for patients with CSLD.
Inhibition of Human Respiratory Syncytial Virus Infectivity by a Dendrimeric Heparan Sulfate-Binding Peptide
Authors: Donalisio Manuela , Rusnati Marco , Cagno Valeria , Civra Andrea , Bugatti Antonella , Giuliani Andrea , Pirri Giovanna , Volante Marco , Papotti Mauro , Landolfo Santo , Lembo David 
Published: July 2012

ABSTRACT

Respiratory syncytial virus (RSV) interacts with cell surface heparan sulfate proteoglycans (HSPGs) to initiate infection. The interaction of RSV with HSPGs thus presents an attractive target for the development of novel inhibitors of RSV infection. In the present study, a minilibrary of linear, dimeric, and dendrimeric peptides containing clusters of basic amino acids was screened with the aim of identifying peptides able to bind HSPGs and thus block RSV attachment and infectivity. Of the compounds identified, the dendrimer SB105-A10 was the most potent inhibitor of RSV infectivity, with 50% inhibitory concentrations (IC
50
s) of 0.35 μM and 0.25 μM measured in Hep-2 and A549 cells, respectively. SB105-A10 was found to bind to both cell types via HSPGs, suggesting that its antiviral activity is indeed exerted by competing with RSV for binding to cell surface HSPGs. SB105-A10 prevented RSV infection when added before the viral inoculum, in line with its proposed HSPG-binding mechanism of action; moreover, antiviral activity was also exhibited when SB105-A10 was added postinfection, as it was able to reduce the cell-to-cell spread of the virus. The antiviral potential of SB105-A10 was further assessed using human-derived tracheal/bronchial epithelial cells cultured to form a pseudostratified, highly differentiated model of the epithelial tissue of the human respiratory tract. SB105-A10 strongly reduced RSV infectivity in this model and exhibited no signs of cytotoxicity or proinflammatory effects. Together, these features render SB105-A10 an attractive candidate for further development as a RSV inhibitor to be administered by aerosol delivery.
Evaluation of an Oral Suspension of VP20621, Spores of Nontoxigenic Clostridium difficile Strain M3, in Healthy Subjects
Authors: Villano Stephen A. , Seiberling Michael , Tatarowicz Walter , Monnot-Chase Elizabeth , Gerding Dale N. 
Published: July 2012

ABSTRACT

VP20621, spores of nontoxigenic
Clostridium difficile
(NTCD) strain M3, is protective against challenge with toxigenic strains in hamsters. Human administration and colonization may prevent primary
C. difficile
infection (CDI) or recurrent CDI. Healthy adult subjects 18 to 45 years old or ≥60 years old received single or multiple doses of an oral suspension of VP20621 (10
4
, 10
6
, or 10
8
spores) or placebo. Group 4 (≥60 years old) received oral vancomycin for 5 days, followed by 14 days of VP20621 or placebo. Subjects were monitored for safety and followed through day 28. Stool was cultured for
C. difficile
before, during, and after VP20621 administration. Isolates were tested for toxin by enzyme immunoassay, and VP20621 was confirmed by molecular typing. After single escalating doses, no subjects had
C. difficile
-positive stool cultures. VP20621 was found in the stool of all subjects given 10
8
spores twice a day. Following vancomycin administration, VP20621 was detected in the stool of all subjects given 10
4
, 10
6
, or 10
8
spores daily beginning on day 2 to 6. Recovered isolates were toxin negative and confirmed to be VP20621. There were no serious adverse events, and no subjects prematurely discontinued study drugs. Following vancomycin administration, 2 placebo subjects became colonized with toxigenic
C. difficile
and 3 placebo subjects became colonized with VP20621. Persistent colonization with VP20621 was detected in stools on days 21 to 28 in 44% of subjects. VP20621 was well tolerated and able to colonize the gastrointestinal tracts of subjects pretreated with vancomycin. Further study of VP20621 to prevent CDI in patients is warranted.
Linezolid Is Superior to Vancomycin in Experimental Pneumonia Caused by Superantigen-Producing Staphylococcus aureus in HLA Class II Transgenic Mice
Authors: Karau Melissa J. , Tilahun Ashenafi Y. , Schmidt Suzannah M. , Clark Chad R. , Patel Robin , Rajagopalan Govindarajan 
Published: July 2012

ABSTRACT

Superantigens (SAg), the potent activators of the immune system, are important determinants of
Staphylococcus aureus
virulence and pathogenicity. Superior response to SAg in human leukocyte antigen (HLA)-DR3 transgenic mice rendered them more susceptible than C57BL/6 mice to pneumonia caused by SAg-producing strains of
S. aureus
. Linezolid, a bacterial protein synthesis inhibitor, was superior to vancomycin in inhibiting SAg production by
S. aureus
in vitro
and conferred greater protection from pneumonia caused by SAg-producing staphylococci.
Identification of Small Molecules That Antagonize Diguanylate Cyclase Enzymes To Inhibit Biofilm Formation
Authors: Sambanthamoorthy Karthik , Sloup Rudolph E. , Parashar Vijay , Smith Joshua M. , Kim Eric E. , Semmelhack Martin F. , Neiditch Matthew B. , Waters Christopher M. 
Published: July 2012

ABSTRACT

Bacterial biofilm formation is responsible for numerous chronic infections, causing a severe health burden. Many of these infections cannot be resolved, as bacteria in biofilms are resistant to the host's immune defenses and antibiotic therapy. New strategies to treat biofilm-based infections are critically needed. Cyclic di-GMP (c-di-GMP) is a widely conserved second-messenger signal essential for biofilm formation. As this signaling system is found only in bacteria, it is an attractive target for the development of new antibiofilm interventions. Here, we describe the results of a high-throughput screen to identify small-molecule inhibitors of diguanylate cyclase (DGC) enzymes that synthesize c-di-GMP. We report seven small molecules that antagonize these enzymes and inhibit biofilm formation by
Vibrio cholerae
. Moreover, two of these compounds significantly reduce the total concentration of c-di-GMP in
V. cholerae
, one of which also inhibits biofilm formation by
Pseudomonas aeruginosa
in a continuous-flow system. These molecules represent the first compounds described that are able to inhibit DGC activity to prevent biofilm formation.
Vaccine-Induced Th17 Cells Are Maintained Long-Term Postvaccination as a Distinct and Phenotypically Stable Memory Subset
Authors: Lindenstrøm Thomas , Woodworth Joshua , Dietrich Jes , Aagaard Claus , Andersen Peter , Agger Else Marie 
Published: July 2012

ABSTRACTTh17 cells are increasingly being recognized as an important T helper subset for immune-mediated protection, especially against pathogens at mucosal ports of entry. In several cases, it would thus be highly relevant to induce Th17 memory by vaccination. Th17 cells are reported to exhibit high plasticity and may not stably maintain their differentiation program once induced, questioning the possibility of inducing durable Th17 memory. Accordingly, there is no consensus as to whether Th17 memory can be established unless influenced by continuous Th17 polarizing conditions. We have previously reported (T. Lindenstrøm, et al., J. Immunol. 182:8047–8055, 2009) that the cationic liposome adjuvant CAF01 can prime both Th1 and Th17 responses and promote robust, long-lived Th1 memory. Here, we demonstrate that subunit vaccination in mice with CAF01 leads to establishment of bona fide Th17 memory cells. Accordingly, Th17 memory cells exhibited lineage stability by retaining both phenotypic and functional properties for nearly 2 years. Antigen-specific, long-term Th17 memory cells were found to be mobilized from lung-draining lymph nodes to the lung following an aerosol challenge byMycobacterium tuberculosisnearly 2 years after their induction and proliferated at levels comparable to those of Th1 memory cells. During the infection, the vaccine-induced Th17 memory cells expanded in the lungs and adapted Th1 characteristics, implying that they represent a metastable population which exhibits plasticity when exposed to prolonged Th1 polarizing, inflammatory conditions such as those found in theM. tuberculosis-infected lung. In the absence of overt inflammation, however, stable bona fide Th17 memory can indeed be induced by parenteral immunization.
Activation of Host Mitogen-Activated Protein Kinases by Secreted Legionella pneumophila Effectors That Inhibit Host Protein Translation
Authors: Fontana Mary F. , Shin Sunny , Vance Russell E. 
Published: July 2012

ABSTRACT

Studies of innate immunity in metazoans have largely focused on detection of microbial molecules by host pattern recognition receptors (PRRs). A complementary mode of innate immune recognition, based on detection of pathogen-encoded activities, has long been recognized in plants, where it is termed effector-triggered immunity; however, little is known about the possibility of effector-triggered immunity in metazoans.
Legionella pneumophila
is an intracellular bacterial pathogen that causes Legionnaires' disease, an inflammatory pneumonia. We recently demonstrated that macrophages infected with
L. pneumophila
exhibit mitogen-activated protein (MAP) kinase (MAPK) activation that is independent of known PRRs but dependent on a functional bacterial secretion system. Here, we show that five secreted
L. pneumophila
effectors are responsible for the activation of host MAP kinases. These five effectors inhibit host translation, and their activity is required for host MAPK activation. We demonstrate that MAPK activation by these effectors shapes the host transcriptional response to
L. pneumophila
. Furthermore, we find that uninfected macrophages treated with two different translation inhibitors exhibit activation of MAP kinases and upregulation of target genes, indicating that translation inhibition alone is sufficient to elicit this response in macrophages. MAP kinase pathways are crucial in many aspects of the immune response, including inflammation and cell motility. Our results demonstrate that this important host pathway can be activated in response to a pathogen-encoded activity, adding to an emerging body of evidence in support of this novel mode of innate immune detection in metazoans.
Markers of B-Cell Activation in Relation to Risk of Non-Hodgkin Lymphoma
Authors: De Roos Anneclaire J. , Mirick Dana K. , Edlefsen Kerstin L. , LaCroix Andrea Z. , Kopecky Kenneth J. , Madeleine Margaret M. , Magpantay Larry , Martínez-Maza Otoniel 
Published: July 2012

AbstractB-cell activation biomarkers have been associated with increased risk of non-Hodgkin lymphoma (NHL) in HIV-infected populations. However, whether a similar association may exist in general populations has not been established. We conducted a case-control study within the Women's Health Initiative Observational Study cohort to measure the B-cell activation biomarkers sCD23, sCD27, sCD30, sCD44, and CXCL13 in serum samples collected an average of 6 years before NHL diagnosis in 491 cases and 491 controls. Using logistic regression to estimate odds ratios, we observed strong associations between NHL and markers for all B-cell NHL and for major subtypes. Women with marker levels in the highest-versus-lowest quartile categories of CD23, CD27, CD30, or CXCL13 were at 2.8- to 5.5-fold increased risk of B-NHL. In addition, there were significant trends of risk with increasing levels of these markers present. Associations were strongest for cases with shortest lag times between blood draw and diagnosis (&lt;3 years). However, there were also significant associations for cases with the longest prediagnostic lag (9 to 13 years). Taken together, our findings indicate a prominent role for B-cell activation among postmenopausal women in the etiology of B-cell NHL and/or in processes reflective of early disease development as early as 9 years before diagnosis. Cancer Res; 72(18); 4733–43. ©2012 AACR.
Failure Rates in the Hepatocellular Carcinoma Surveillance Process
Authors: Singal Amit G. , Yopp Adam C. , Gupta Samir , Skinner Celette Sugg , Halm Ethan A. , Okolo Eucharia , Nehra Mahendra , Lee William M. , Marrero Jorge A. , Tiro Jasmin A. 
Published: July 2012

Abstract
Hepatocellular carcinoma (HCC) surveillance is underutilized among patients with cirrhosis. Understanding which steps in the surveillance process are not being conducted is essential for designing effective interventions to improve surveillance rates. The aim of our study was to characterize reasons for failure in the HCC surveillance process among a cohort of cirrhotic patients with HCC. We conducted a retrospective cohort study of cirrhotic patients diagnosed with HCC at a large urban safety-net hospital between 2005 and 2011. Patients were characterized by receipt of HCC surveillance over a two-year period before HCC diagnosis. Among patients without HCC surveillance, we classified reasons for failure into four categories: failure to recognize liver disease, failure to recognize cirrhosis, failure to order surveillance, and failure to complete surveillance despite orders. Univariate and multivariate analyses were conducted to identify predictors of failures. We identified 178 patients with HCC, of whom 20% had undergone surveillance. There were multiple points of failure—20% had unrecognized liver disease, 19% had unrecognized cirrhosis, 38% lacked surveillance orders, and 3% failed to complete surveillance despite orders. Surveillance was more likely among patients seen by hepatologists [OR, 6.11; 95% confidence interval (CI), 2.5–14.8] and less likely in those with alcohol abuse (OR, 0.14; 95% CI, 0.03–0.65). Although a retrospective analysis in a safety-net hospital, our data suggest that only one in five patients received surveillance before HCC diagnosis. There are multiple points of failure in the surveillance process, with the most common being failure to order surveillance in patients with known cirrhosis. Future interventions must target multiple failure points in the surveillance process to be highly effective. Cancer Prev Res; 5(9); 1124–30. ©2012 AACR.
Neurodevelopmental Outcomes in Children With Congenital Heart Disease: Evaluation and Management
Authors: Marino Bradley S. , Lipkin Paul H. , Newburger Jane W. , Peacock Georgina , Gerdes Marsha , Gaynor J. William , Mussatto Kathleen A. , Uzark Karen , Goldberg Caren S. , Johnson Walter H. , Li Jennifer , Smith Sabrina E. , Bellinger David C. , Mahle William T. 
Published: July 2012

Background—
The goal of this statement was to review the available literature on surveillance, screening, evaluation, and management strategies and put forward a scientific statement that would comprehensively review the literature and create recommendations to optimize neurodevelopmental outcome in the pediatric congenital heart disease (CHD) population.

Methods and Results—
A writing group appointed by the American Heart Association and American Academy of Pediatrics reviewed the available literature addressing developmental disorder and disability and developmental delay in the CHD population, with specific attention given to surveillance, screening, evaluation, and management strategies. MEDLINE and Google Scholar database searches from 1966 to 2011 were performed for English-language articles cross-referencing CHD with pertinent search terms. The reference lists of identified articles were also searched. The American College of Cardiology/American Heart Association classification of recommendations and levels of evidence for practice guidelines were used. A management algorithm was devised that stratified children with CHD on the basis of established risk factors. For those deemed to be at high risk for developmental disorder or disabilities or for developmental delay, formal, periodic developmental and medical evaluations are recommended. A CHD algorithm for surveillance, screening, evaluation, reevaluation, and management of developmental disorder or disability has been constructed to serve as a supplement to the 2006 American Academy of Pediatrics statement on developmental surveillance and screening. The proposed algorithm is designed to be carried out within the context of the medical home. This scientific statement is meant for medical providers within the medical home who care for patients with CHD.

Conclusions—
Children with CHD are at increased risk of developmental disorder or disabilities or developmental delay. Periodic developmental surveillance, screening, evaluation, and reevaluation throughout childhood may enhance identification of significant deficits, allowing for appropriate therapies and education to enhance later academic, behavioral, psychosocial, and adaptive functioning.
The Contribution of Primary and Secondary Somatosensory Cortices to the Representation of Body Parts and Body Sides: An fMRI Adaptation Study
Authors: Tamè Luigi , Braun Christoph , Lingnau Angelika , Schwarzbach Jens , Demarchi Gianpaolo , Li Hegner Yiwen , Farnè Alessandro , Pavani Francesco 
Published: July 2012

AbstractAlthough the somatosensory homunculus is a classically used description of the way somatosensory inputs are processed in the brain, the actual contributions of primary (SI) and secondary (SII) somatosensory cortices to the spatial coding of touch remain poorly understood. We studied adaptation of the fMRI BOLD response in the somatosensory cortex by delivering pairs of vibrotactile stimuli to the finger tips of the index and middle fingers. The first stimulus (adaptor) was delivered either to the index or to the middle finger of the right or left hand, and the second stimulus (test) was always administered to the left index finger. The overall BOLD response evoked by the stimulation was primarily contralateral in SI and was more bilateral in SII. However, our fMRI adaptation approach also revealed that both somatosensory cortices were sensitive to ipsilateral as well as to contralateral inputs. SI and SII adapted more after subsequent stimulation of homologous as compared with nonhomologous fingers, showing a distinction between different fingers. Most importantly, for both somatosensory cortices, this finger-specific adaptation occurred irrespective of whether the tactile stimulus was delivered to the same or to different hands. This result implies integration of contralateral and ipsilateral somatosensory inputs in SI as well as in SII. Our findings suggest that SI is more than a simple relay for sensory information and that both SI and SII contribute to the spatial coding of touch by discriminating between body parts (fingers) and by integrating the somatosensory input from the two sides of the body (hands).