bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigations on the pattern recognition molecule M-ficolin: quantitative aspects of bacterial binding and leukocyte association
Authors: Kjaer Troels R , Hansen Annette G , Sørensen Uffe B S , Nielsen Ole , Thiel Steffen , Jensenius Jens C 
Published: July 2011

ABSTRACTM-ficolin is a PRM of the innate immune system, found in serum and associated with leukocytes. We used the soluble form to study specificity toward Gram-positive bacteria and characterized and quantified cell-associated M-ficolin. The binding of M-ficolin to capsulated and noncapsulated strains of Streptococcus agalactiae (GBS) and Staphylococcus aureus was investigated. We did not observe binding of M-ficolin to any of 13 serotypes of S. aureus. Dose-dependent binding of M-ficolin was demonstrated for all of the capsulated GBS strains. The binding was abolished by prior treatment of the bacteria with sialidase, indicating that sialic acid is the ligand for M-ficolin on these bacteria. GlcNAc could inhibit the binding, suggesting that M-ficolin binds via its FBG. M-ficolin was found associated with the complement-activating enzyme in serum, and M-ficolin bound to GBS mediated activation of the complement system. M-ficolin expression on leukocytes was evaluated by flow cytometry with anti-M-ficolin mAb. Total M-ficolin of different leukocytes was quantified in detergent extracts. Monocytes and granulocytes showed similar M-ficolin surface expression, 1.1 × 105 and 0.7 × 105 M-ficolin molecules/cell, respectively. The total M-ficolin content of the cells was 1.5 × 106 molecules/monocyte and approximately one-third of this for granulocytes. Lymphocytes contained &lt;1.5% of the amount estimated for monocytes, and none was revealed on the surface of lymphocytes by flow cytometry. Immunohistochemical analysis of the distribution of M-ficolin in 25 tissues revealed staining of only granulocytes and monocytes. Reported M-ficolin expression by type II pneumocytes could not be verified. We demonstrate the specific binding of M-ficolin to sialic acids in the capsule of GBS and give quantitative aspects of the cell-associated M-ficolin.
Heterogeneous Distribution of EGFR Mutations Is Extremely Rare in Lung Adenocarcinoma
Authors: Yatabe Yasushi , Matsuo Keitaro , Mitsudomi Tetsuya 
Published: July 2011

Purpose Some studies have shown that epidermal growth factor receptor (EGFR) mutations can be heterogeneously distributed in individual tumors. In this study, we re-evaluated the distribution of EGFR mutations within tumors. Patients and Methods We used multiple approaches, including an analysis of simultaneous dual hot spot mutations, a trans-sectional analysis of individual lung adenocarcinomas, and comparisons of the mutation patterns between primary and metastatic sites and between primary and recurrent tumors. Results None of the 862 tumors harboring an EGFR mutation showed simultaneous dual hot spot mutations, although identical EGFR mutations were found throughout individual tumors in a trans-sectional analysis involving 50 tumors divided into three parts and five lung adenocarcinomas divided into 100 parts. In addition, no discordant mutation patterns were detected among 77 paired primary and metastatic site samples or among 54 primary and recurrent tumor pairs. Conclusion All of these results suggest that the heterogeneous distribution of EGFR mutations is extremely rare. However, it is possible that pseudoheterogeneity occurs because of a combination of mutant allele–specific imbalance and heterogeneously distributed EGFR amplification, especially when a less sensitive method is used for detection. Specifically, when EGFR amplification occurs, the mutant allele is amplified, and this amplification is involved in invasive growth. Accordingly, invasive growth area significantly over-represents the mutation signal. In contrast, weak EGFR mutation signals in the area without EGFR amplification may not reach the threshold of detection because of the mixture with normal cells. Such unbalanced mutation signals might lead to pseudoheterogeneity.
Mantle Cell Lymphoma International Prognostic Index but Not Pretransplantation Induction Regimen Predicts Survival for Patients With Mantle-Cell Lymphoma Receiving High-Dose Therapy and Autologous Stem-Cell Transplantation
Authors: Budde Lihua E. , Guthrie Katherine A. , Till Brian G. , Press Oliver W. , Chauncey Thomas R. , Pagel John M. , Petersdorf Steven H. , Bensinger William I. , Holmberg Leona A. , Shustov Andrei R. , Green Damian J. , Maloney David G. , Gopal Ajay K. 
Published: July 2011

Purpose High-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) are frequently used in an attempt to improve outcome in patients with mantle-cell lymphoma (MCL); however, the importance of intensive induction regimens before transplantation is unknown. Patients and Methods To address this question, we evaluated baseline characteristics, time to treatment, induction regimen, disease status at the time of transplantation, and MIPI score at diagnosis and their associations with survival in 118 consecutive patients with MCL who received HDT and ASCT at our centers. Results The MIPI was independently associated with survival after transplantation in all 118 patients (hazard ratio [HR], 3.5; P < .001) and in the 85 patients who underwent ASCT as initial consolidation (HR, 7.2; P < .001). Overall survival rates were 93%, 60%, and 32% at 2.5 years from ASCT for all patients with low-, intermediate-, and high-risk MIPI, respectively. Low-risk MIPI scores were more common in the intensive induction group than the standard induction group in all patients (64% v 46%, respectively; P = .03) and in the initial consolidation group (66% v 45%, respectively; P = .03). After adjustment for the MIPI, an intensive induction regimen was not associated with improved survival after transplantation in all patients (HR, 0.5; P = .10), the initial consolidation group (HR, 1.1; P = .86), or patients ≤ 60 years old (HR, 0.6; P = .50). Observation of more than 3 months before initiating therapy did not yield inferior survival (HR, 2.1; P = .12) after adjustment for the MIPI in patients receiving ASCT. Conclusion An intensive induction regimen before HDT and ASCT was not associated with improved survival after adjusting for differences in MIPI scores at diagnosis.
The zebrafish embryo as a tool for screening and characterizing pleurocidin host-defense peptides as anti-cancer agents
Authors: Morash Michael G. , Douglas Susan E. , Robotham Anna , Ridley Christina M. , Gallant Jeffrey W. , Soanes Kelly H. 
Published: July 2011

SUMMARY
The emergence of multidrug-resistant cancers and the lack of targeted therapies for many cancers underscore an unmet need for new therapeutics with novel modes of action towards cancer cells. Host-defense peptides often exhibit selective cytotoxicity towards cancer cells and show potential as anti-cancer therapeutics. Here, we screen 26 naturally occurring variants of the peptide pleurocidin for cytotoxic and anti-cancer activities, and investigate the underlying mechanism of action. Cytotoxicities were assessed in vitro using cell-based assays and in vivo using zebrafish embryos. Morphological changes were assessed by both transmission and scanning electron microscopy, and functional assays were performed on zebrafish embryos to investigate the mechanism of cell death. A total of 14 peptides were virtually inactive against HL60 human leukemia cells, whereas 12 caused &gt;50% death at ≤32 μg/ml. Morphological changes characteristic of oncosis were evident by electron microscopy after only 1 minute of treatment with 32 μg/ml of variant NRC-03. Only two peptides were hemolytic. Four peptides showed no toxicity towards zebrafish embryos at the highest concentration tested (25 μM; ∼64 μg/ml) and one peptide was highly toxic, killing 4-hour-post-fertilization (hpf) embryos immediately after exposure to 1 μM peptide. Four other peptides killed embryos after 24 hours of exposure at 1 μM. Most peptides caused mortality at one or more developmental stages only after continuous exposure (24 hours) with higher lethal doses (≥5 μM). Pleurocidin NRC-03 bound to embryos and induced the release of superoxide, caused an increase in the number of TUNEL-positive nuclei, and caused membrane damage and the loss of embryonic epithelial integrity, marked by the exclusion of cells from the outer epithelium and the appearance of F-actin within the circumferential cells of the repair site. Our results indicate that specific pleurocidin variants are attractive cancer-selective agents that selectively induce cell death in target cells but leave non-target cells such as erythrocytes and non-transformed cells unaffected.
A high level of liver-specific expression of oncogenic KrasV12 drives robust liver tumorigenesis in transgenic zebrafish
Authors: Nguyen Anh Tuan , Emelyanov Alexander , Koh Chor Hui Vivien , Spitsbergen Jan M. , Lam Siew Hong , Mathavan Sinnakaruppan , Parinov Serguei , Gong Zhiyuan 
Published: July 2011

SUMMARY
Human liver cancer is one of the deadliest cancers worldwide, with hepatocellular carcinoma (HCC) being the most common type. Aberrant Ras signaling has been implicated in the development and progression of human HCC, but a complete understanding of the molecular mechanisms of this protein in hepatocarcinogenesis remains elusive. In this study, a stable in vivo liver cancer model using transgenic zebrafish was generated to elucidate Ras-driven tumorigenesis in HCC. Using the liver-specific fabp10 (fatty acid binding protein 10) promoter, we overexpressed oncogenic krasV12 specifically in the transgenic zebrafish liver. Only a high level of krasV12 expression initiated liver tumorigenesis, which progressed from hyperplasia to benign and malignant tumors with activation of the Ras-Raf-MEK-ERK and Wnt–β-catenin pathways. Histological diagnosis of zebrafish tumors identified HCC as the main lesion. The tumors were invasive and transplantable, indicating malignancy of these HCC cells. Oncogenic krasV12 was also found to trigger p53-dependent senescence as a tumor suppressive barrier in the pre-neoplastic stage. Microarray analysis of zebrafish liver hyperplasia and HCC uncovered the deregulation of several stage-specific and common biological processes and signaling pathways responsible for krasV12-driven liver tumorigenesis that recapitulated the molecular hallmarks of human liver cancer. Cross-species comparisons of cancer transcriptomes further defined a HCC-specific gene signature as well as a liver cancer progression gene signature that are evolutionarily conserved between human and zebrafish. Collectively, our study presents a comprehensive portrait of molecular mechanisms during progressive Ras-induced HCC. These observations indicate the validity of our transgenic zebrafish to model human liver cancer, and this model might act as a useful platform for drug screening and identifying new therapeutic targets.
The Seven Station Series
Authors: Gray Vincent 
Published: July 2011

Historical evidence shows that the mean temperatures in the main cities in New Zealand have not changed significantly since records began in the 1860s1–4. Recently, the New Zealand Institute for Water and Air Research11, after a thorough Review, has presented a revised temperature anomaly chart for the average temperatures of seven of the major urban centres in New Zealand which shows that there has been an increasing temperature trend of 0.91°C per century since 1909. This paper analyses the Review and concludes that the results are compatible with the historic view of no significant change since records began. Although the trends found are explained by natural causes their statistical significance is very low because of the unsuitability of the “neighbour station” comparison used, and the inaccuracy of the measured and processed temperature measurements.
Distribution of Training Volume and Intensity of Elite Male and Female Track and Marathon Runners
Authors: Enoksen Eystein , Tjelta Asle Rønning , Tjelta Leif Inge 
Published: July 2011

The aim of this study was to compare training volume and the distribution of training intensity of six of the best long-distance runners in Norway from the last decade. Three international-level long-distance runners (two males and one female) and three marathon runners (one male and two females) were included. The runners' training diaries for one of the seasons they competed in an international championship were analysed. The reported running volume (km/week) was used to estimate the distribution of training at the prescribed intensity zones in representative weeks in the preparation period and in the competition season. During the preparation period (November - February) the marathon runners ran an average of 186.6 ± 25.7 km/week and the track runners 161 ± 11 km/week. For all runners, 80 ± 5% of the weekly training distance (km/week) in this period was continuous running with a heart rate (HR) between 65–82% of maximum. The remaining 20% of total training volume (km/week) was performed at intensities near and above the anaerobic threshold (82–92% of HRmax). This was done in three to five weekly interval sessions or continuous running sessions. All athletes ran 11 – 13 sessions per week. The training volume (km/week) in the pre-competition period and the competition season did not differ much from the volume in the preparation period. The track runners increased the amount of high-intensity training at specific race pace in the pre-competition period (March and April), and in the track competition season (May - September).
Another Tragic Parenteral Nutrition Compounding Error: Change in Anzemet Indication: Teva's Lansoprazole Orally Disentegrating Tablet Clogs Tubes: Lawyers Weigh in on Consistent Use of Smart Pump Libraries
Authors: Cohen Michael R. , Smetzer Judy L. 
Published: July 2011

These medication errors have occurred in health care facilities at least once. They will happen again—perhaps where you work. Through education and alertness of personnel and procedural safeguards, they can be avoided. You should consider publishing accounts of errors in your newsletters and/or presenting them at your inservice training programs. Your assistance is required to continue this feature. The reports described here were received through the Institute for Safe Medication Practices (ISMP) Medication Errors Reporting Program. Any reports published by ISMP will be anonymous. Comments are also invited; the writers' names will be published if desired. ISMP may be contacted at the address shown below. Errors, close calls, or hazardous conditions may be reported directly to ISMP through the ISMP Web site ( www.ismp.org ), by calling 800-FAIL-SAFE, or via e-mail at ismpinfo@ismp.org . ISMP guarantees the confidentiality and security of the information received and respects reporters' wishes as to the level of detail included in publications.
Busulfan and Metronidazole: An Often Forgotten but Significant Drug Interaction
Authors: Gulbis Alison M , Culotta Kirk S , Jones Roy B , Andersson Borje S 
Published: July 2011

Objective: To report the case of a clinically significant drug interaction between intravenous busulfan and oral metronidazole observed through busulfan therapeutic drug monitoring (TDM). Case Summary: A 7-year-old boy with a history of myelodysplasia that progressed to acute myeloid leukemia received busulfan with therapeutic drug monitoring (TDM), clofarabine, and thiotepa as a pretransplant conditioning regimen for a cord blood transplant. The patient received metronidazole the day after a busulfan test dose of 0.5 mg/kg was administered. On the day of the first busulfan therapeutic dose, TDM was performed and the clearance of busulfan was significantly decreased by 46%. After 2 doses of busulfan therapy, the course area under the curve was exceeded, requiring discontinuation of busulfan. Metronidazole is not known to affect glutathione or the glutathione S-transferase AI (GSTA1) enzyme system or cytochrome P450 (CYP) 3A4. Discussion: Busulfan is a bifunctional alkylating agent widely used in pretransplant conditioning regimens in patients undergoing stem cell transplantation for hematologic malignancies. Busulfan metabolism is best described by hepatic conjugation to glutathione by GSTA1, although some CYP-dependent pathways have been described. Currently there is 1 publication describing the drug interaction between oral busulfan and oral metronidazole, in which concomitant use of metronidazole resulted in higher busulfan trough concentrations and higher risk of veno-occlusive disease. Our case represents a possible drug interaction based on the Horn Drug Interaction Probability Scale. Conclusions: Though the mechanistic basis for this interaction is unknown, the risks and benefits of using metronidazole during and in close proximity to busulfan should be carefully considered and therapeutic alternatives to metronidazole should be used when appropriate.
Prothrombin Complex Concentrate for Critical Bleeding
Authors: Patanwala Asad E , Acquisto Nicole M , Erstad Brian L 
Published: July 2011

Objective: To review the evidence supporting the use of prothrombin complex concentrate (PCC) as a hemostatic agent in individuals without hemophilia. Data Sources: Articles were identified through a search of Ovid/MEDLINE (up to April 2011) and Cochrane Central Register of Controlled Trials (up to April 2011). The search terms used were prothrombin complex concentrate, hemorrhage, and bleeding. Study Selection and Data Extraction: The search was limited to comparative studies. Bibliographies of retrieved articles were reviewed to obtain additional articles. The intent of the search was to identify original research comparing PCC to fresh frozen plasma (FFP) or recombinant factor VIIa for the management of bleeding in patients without hemophilia. Data Synthesis: PCCs are recommended as an alternative to FFP and recombinant factor VIIa for the treatment of serious or life-threatening bleeding related to vitamin K antagonist therapy. Studies in this setting have shown that PCCs are safe and effective and provide prompt reduction of international normalized ratio (INR) compared to FFP. However, most trials are uncontrolled, and the primary outcomes in these studies have been INR reduction rather than hemostatic effect. Other common off-label uses include coagulopathy due to hepatic failure and traumatic hemorrhage; however, there is insufficient evidence to support use of PCC in these settings. Advantages of PCC include the low drug volume required compared to FFP. The use of PCC may be associated with thromboembolic complications. Conclusions: PCC is a safe and effective alternative to FFP and provides rapid reversal of INR in patients on vitamin K antagonist therapy. These agents may be advantageous compared to FFP in patients with volume restrictions. Comparative trials are needed to compare the various PCC products, FPP, and recombinant factor VIIa with regard to clinically significant outcomes such as hemostatic effect.
Electron beam modification of space durable polymeric nano-adhesive bonding of ultra-high temperature resistant polymer
Authors: Bhatnagar Nitu , Pyngrope Davidson , Pradhan Rajiv , Jha Sangeeta , Bhowmik Shantanu , Poulis Hans , Bui Van Tam , Bonin Hughes 
Published: July 2011

Abstract
This investigation highlights fabrication of ultra-high temperature resistant polymers such as polybenzimidazole (PBI) by high-performance nano-adhesive. High-performance nano-adhesive is prepared by dispersing carbon nano-fibers into ultra-high temperature resistant epoxy adhesive. Prior to fabrication of PBI, the surface of PBI is ultrasonically cleaned by acetone and then modified by atmospheric pressure plasma with 30, 60 and 90 s of exposure and low-pressure plasma with 30, 60, 120, 240 and 480 s of exposure. Surface characterization of the unmodified and modified PBI sheets is carried out by contact angle measurements and surface energy of the polymer is estimated. It is observed that the polar component of surface energy leading to total surface energy of the polymer increases significantly when exposed to atmospheric pressure plasma. Tensile lap shear strength of adhesive bonded PBI reveals that atmospheric pressure plasma is more useful than low-pressure plasma in terms of adhesive bond strength of PBI and increases further when fabricated by nano-carbon fibers dispersed epoxy adhesive. The nano-adhesive bonded PBI sheets are post-cured by electron beam radiation under the SLOWPOKE-2 nuclear reactor. Post curing under electron beam radiation further increases the adhesive bond strength considerably.
Hippocampal synaptic plasticity in Alzheimer’s disease: what have we learned so far from transgenic models?
Authors: Marchetti Cristina , Marie Hélène 
Published: July 2011

AbstractTransgenic (Tg) mouse models of Alzheimer’s disease (AD) are used to investigate mechanisms underlying disease pathology and identify therapeutic strategies. Most Tg AD models, which at least partly recapitulate the AD phenotype, are based on insertion of one or more human mutations (identified in Familial AD) into the mouse genome, with the notable exception of the anti-NGF mouse, which is based on the cholinergic unbalance hypothesis. It has recently emerged that impaired hippocampal synaptic function is an early detectable pathological alteration, well before the advanced stage of amyloid plaque accumulation and general cell death. Nevertheless, electrophysiological studies performed on different Tg models or on the same model by different research groups have yielded contrasting results. We therefore summarized data from original research papers studying hippocampal synaptic function using electrophysiology, to review what we have learned so far. We analyzed results obtained using the following Tg models: (1) single/multiple APP mutations; (2) single presenilin (PS) mutations; (3) APPxPS1 mutations; (4) APPxPS1xtau mutations (3xTg); and (5) anti-NGF expressing (AD11) mice. We observed that the majority of papers focus on excitatory basic transmission and long-term potentiation, while few studies evaluate inhibitory transmission and long-term depression. We searched for common synaptic alterations in the various models that might underlie the memory deficits observed in these mice. We also considered experimental variables that could explain differences in the reported results and briefly discuss successful rescue strategies. These analyses should prove useful for future design of electrophysiology experiments to assess hippocampal function in AD mouse models.
V = Land Intuitive Plausibility in set Theory. A Case Study
Authors: Arrigoni Tatiana 
Published: July 2011

AbstractWhat counts as an intuitively plausible set theoretic content (notion, axiom or theorem) has been a matter of much debate in contemporary philosophy of mathematics. In this paper I develop a critical appraisal of the issue. I analyze first R. B. Jensen's positions on the epistemic status of theaxiom of constructibility. I then formulate and discuss a view of intuitiveness in set theory that assumes it to hinge basically on mathematicalsuccess. At the same time, I present accounts of set theoretic axioms and theorems formulated in non-strictly mathematical terms, e.g., by appealing to theiterative conceptof set and/or to overall methodological principles, likeunifyandmaximize, and investigate the relation of the latter to success in mathematics.