bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the incidence of pancreatic abnormalities between high risk and control patients: Prospective pilot study with 3 tesla MR imaging
Authors: Shin Sang Soo , Armao Diane M. , Burke Lauren M.B. , Kim Hong Jin , Skrzynia Cecile , Otey Carol A. , Semelka Richard C.
Published: April 2011

Purpose:

To compare the incidence of pancreatic abnormalities detected by MR imaging between high‐risk patients and control patients.

Materials and Methods:

Forty‐one consecutive patients who had two or more first‐degree relatives with pancreatic cancer and who were asymptomatic with no clinical evidence of pancreatic cancer were prospectively included in this study. A control group was obtained by reviewing consecutive patients undergoing 3Tesla (T) MRI examinations for nonpancreatic indications. On MR imaging, the presence of pancreatic abnormalities were evaluated in consensus by two radiologists who were blinded to clinical history. Pancreatic abnormalities were categorized as developmental abnormalities, mass‐type lesions, inflammatory disease, and others.

Results:

Overall, the incidence of pancreatic abnormalities was greater in the high‐risk group than in the control group, but not statistically significant (P = 0.244). In the high‐risk group, a total of 16 patients (39%) were diagnosed with pancreatic abnormalities, whereas in the control group, 11 patients (25%) were diagnosed with pancreatic abnormalities. Regarding mass‐type lesions, there was a significant difference in incidence between the high‐risk group, with a total of seven patients (17%), and the control group, with one patient (2%) (P = 0.028). There were no cases of imaging diagnosis of pancreatic cancer or tissue evaluation by surgical pathology in either group.

Conclusion:

Our prospective pilot study demonstrated a higher incidence of mass‐type lesions in patients at increased risk for pancreatic cancer. J. Magn. Reson. Imaging 2011;33:1080–1085. © 2011 Wiley‐Liss, Inc.
Comparison of intravascular and extracellular contrast media for absolute quantification of myocardial rest‐perfusion using high‐resolution MRI
Authors: Ritter Christian O. , Wilke Aline , Wichmann Tobias , Beer Meinrad , Hahn Dietbert , Köstler Herbert
Published: April 2011

Purpose:

To use the contrast agent gadofosveset for absolute quantification of myocardial perfusion and compare it with gadobenate dimeglumine (Gd‐BOPTA) using a high‐resolution generalized autocalibrating partially parallel acquisition (GRAPPA) sequence.

Materials and Methods:

Ten healthy volunteers were examined twice at two different dates with a first‐pass perfusion examination at rest using prebolus technique. We used a 1.5 T scanner and a 32 channel heart‐array coil with a steady‐state free precession (SSFP) true fast imaging with steady state precession (trueFISP) GRAPPA sequence (acceleration‐factor 3). Manual delineation of the myocardial contours was performed and absolute quantification was performed after baseline and contamination correction. At the first appointment, 1cc/4cc of the extracellular contrast agent Gd‐BOPTA were administered, on the second date, 1cc/4cc of the blood pool contrast agent (CA) gadofosveset. At each date the examination was repeated after a 15‐minute time interval.

Results:

Using gadofosveset perfusion the value (in cc/g/min) at rest was 0.66 ± 0.25 (mean ± standard deviation) for the first, and 0.55 ± 0.24 for the second CA application; for Gd‐BOPTA it was 0.62 ± 0.25 and 0.45 ± 0.23. No significant difference was found between the acquired perfusion values. The apparent mean residence time in the myocardium was 23 seconds for gadofosveset and 19.5 seconds for Gd‐BOPTA. Neither signal‐to‐noise ratio (SNR) nor subjectively rated image contrast showed a significant difference.

Conclusion:

The application of gadofosveset for an absolute quantification of myocardial perfusion is possible. Yet the acquired perfusion values show no significant differences to those determined with Gd‐BOPTA, maintained the same SNR and comparable perfusion values, and did not picture the expected concentration time‐course for an intravasal CA in the first pass. J. Magn. Reson. Imaging 2011;33:1047–1051. © 2011 Wiley‐Liss, Inc.
Accelerated noncontrast‐enhanced pulmonary vein MRA with distributed compressed sensing
Authors: Akçakaya Mehmet , Hu Peng , Chuang Michael L. , Hauser Thomas H. , Ngo Long H. , Manning Warren J. , Tarokh Vahid , Nezafat Reza
Published: April 2011

Purpose:

To investigate the efficacy of distributed compressed sensing (CS) to accelerate free‐breathing, electrocardiogram (ECG)‐triggered noncontrast pulmonary vein (PV) magnetic resonance angiography (MRA).

Materials and Methods:

Fully sampled ECG‐triggered noncontrast PV MRA, using a spatially selective slab inversion preparation sequence, was acquired on seven healthy adult subjects (27 ± 17 years, range: 19–65 years, 4 women). The k‐space data were retrospectively randomly undersampled by factors of 2, 4, 6, 8, and 10 and then reconstructed using distributed CS and coil‐by‐coil CS methods. The reconstructed images were evaluated by two blinded readers in consensus for assessment of major PV branches as well as the presence of artifacts in left atrium (LA) and elsewhere. Diameters of right inferior and right superior PV branches were measured. Additionally, mean square errors (MSE) of the reconstructions were calculated.

Results:

Both CS methods resulted in image quality scores similar to the fully sampled reference images at undersampling factors up to 6‐fold for distributed CS and 4‐fold for coil‐by‐coil CS reconstructions. There was no difference in the presence of artifacts in LA and freedom from important artifacts elsewhere between the two techniques up to undersampling factors of 10 compared to the fully sampled reconstruction. For the PV diameters, no systematic variation between the reference and the reconstructions were observed for either technique. There were no significant differences in MSE between the two methods when compared at a given rate, but the difference was significant when compared across all rates.

Conclusion:

The sparsity of noncontrast PV MRA and the joint sparsity of different coil images allow imaging at high undersampling factors (up to 6‐fold) when distributed CS is used. J. Magn. Reson. Imaging 2011;33:1248–1255. © 2011 Wiley‐Liss, Inc.
Endorectal MRI after radiation therapy: Questioning the sextant analysis
Authors: Kumbhani Shilpa R. , Coakley Fergus V. , McCulloch Charles E. , Wang Z. Jane , Kurhanewicz John , Roach Mack , Westphalen Antonio C.
Published: April 2011

Purpose:

To evaluate whether the information gained by three coregistration systems (sextant, hemi‐prostate, and whole gland) differs significantly, suggesting that one approach should be routinely favored over the others. Despite its known limitations, sextant is the generally accepted standard for magnetic resonance imaging (MRI) and biopsy coregistration; nevertheless, depending on the magnitude of localization errors, other options may be adequate.

Materials and Methods:

Institutional Review Board approval was obtained and the study was Health Insurance Portability and Accountability Act (HIPAA)‐compliant. We identified 70 patients who underwent 1.5 T endorectal MRI of the prostate between 1999 and 2008 after external beam radiotherapy for prostate cancer. A single reader reviewed all T2‐weighted images for the presence or absence of tumor. The performance of each approach was quantified using receiver operating characteristic (ROC) curve analysis. Transrectal ultrasound‐guided sextant biopsies were used as a standard of reference.

Results:

The areas under the ROC curve indicating accuracy for each MRI approach were 0.63 (sextant), 0.68 (hemi‐prostate), and 0.71 (whole gland). There was no statistically significant difference among these approaches.

Conclusion:

As expected, the point estimate was higher for the whole‐gland approach, but not significantly. Reliable assessment of locally recurrent prostate cancer after external beam radiotherapy by endorectal MRI may be made using a sextant, hemi‐prostate, or whole gland approach. The option for one or another approach should not be solely based on estimations of imaging accuracy, but on the purpose of the procedure. J. Magn. Reson. Imaging 2011;33:1086–1090. © 2011 Wiley‐Liss, Inc.
Motion correction in diffusion‐weighted MRI of the breast at 3T
Authors: Arlinghaus Lori R. , Welch E. Brian , Chakravarthy A. Bapsi , Xu Lei , Farley Jaime S. , Abramson Vandana G. , Grau Ana M. , Kelley Mark C. , Mayer Ingrid A. , Means‐Powell Julie A. , Meszoely Ingrid M. , Gore John C. , Yankeelov Thomas E.
Published: April 2011

Purpose:

To provide a quantitative assessment of motion and distortion correction of diffusion‐weighted images (DWIs) of the breast and to evaluate the effects of registration on the mean apparent diffusion coefficient (mADC).

Materials and Methods:

Eight datasets from four patients with breast cancer and eight datasets from six healthy controls were acquired on a 3T scanner. A 3D affine registration was used to align each set of images and principal component analysis was used to assess the results. Variance in tumor ADC measurements, tumor mADC values, and voxel‐wise tumor mADC values were compared before and after registration for each patient.

Results:

Image registration significantly (P = 0.008) improved image alignment for both groups and significantly (P < 0.001) reduced the variance across individual tumor ADC measurements. While misalignment led to potential under‐ and overestimation of mADC values for individual voxels, average tumor mADC values did not significantly change (P > 0.09) after registration.

Conclusion:

3D affine registration improved the alignment of DWIs of the breast and reduced the variance between ADC measurements. Although the reduced variance did not significantly change tumor region‐of‐interest measures of mADC, it may have a significant impact on voxel‐based analyses. J. Magn. Reson. Imaging 2011;33:1063–1070. © 2011 Wiley‐Liss, Inc.
Phosphorylation status of heat shock protein 27 influences neurite growth in adult dorsal root ganglion sensory neurons in vitro
Authors: Williams Kristy L. , Mearow Karen M.
Published: April 2011

The small heat shock protein Hsp27 influences neurite growth, potentially via phosphorylation‐dependent interactions of Hsp27 with actin. To investigate the contribution of Hsp27 phosphorylation to neurite growth in adult DRG neurons, we employed hamster Hsp27 cDNA constructs (in pIRES‐EGFP) with mutations in the phosphorylation sites, either mimicking constitutively phosphorylated Hsp27 (with substitution of serines 15 and/or 90 by glutamate) or preventing phosphorylation at the site (serines 15/90 replaced by alanine). Five mutant constructs were employed in this study in addition to wild‐type hamster Hsp27; siRNA directed against the rat Hsp27 was used to depress endogenous Hsp27. Neurite growth was assessed in EGFP‐expressing cells following immunocytochemistry and tracing of neurite growth. Hsp27 staining and phalloidin labelling were used to examine Hsp27 and actin colocalization in neurons and growth cones. Overall, our results demonstrate that the role that Hsp27 plays in neurite growth can be affected by phosphorylation, oligomerization, or a combination of both. Hsp27 constructs that are able to dimerize and/or form large oligomers [WT, Hsp27‐AA, Hsp27‐AE, Hsp27−Δ(5–23)] rescued siRNA‐depressed neurite growth, whereas Hsp27 mutants that do not form dimers or oligomers (Hsp27‐EE and Hsp27‐EA) were unable to rescue the effect of the siRNA. The phalloidin labelling qualitatively showed a higher level of localization of actin with the Hsp27‐AA compared with the other constructs. Although phosphorylation appears to be important in growth, the ability of Hsp27 to exist in both phospho‐ and nonphospho‐ states is likely key to its role in regulating cytoskeletal elements involved in neurite growth. © 2011 Wiley‐Liss, Inc.
Optimizing the location of weather monitoring stations using estimation uncertainty
Authors: Amorim Ana M. T. , Gonçalves Alexandre B. , Nunes Luís Miguel , Sousa António Jorge
Published: April 2011

In this article, we address the problem of planning a network of weather monitoring stations observing average air temperature (AAT). Assuming the network planning scenario as a location problem, an optimization model and an operative methodology are proposed. The model uses the geostatistical uncertainty of estimation and the indicator formalism to consider in the location process a variable demand surface, depending on the spatial arrangement of the stations. This surface is also used to express a spatial representativeness value for each element in the network. It is then possible to locate such a network using optimization techniques, such as the used methods of simulated annealing (SA) and construction heuristics. This new approach was applied in the optimization of the Portuguese network of weather stations monitoring the AAT variable. In this case study, scenarios of reduction in the number of stations were generated and analysed: the uncertainty of estimation was computed, interpreted and applied to model the varying demand surface that is used in the optimization process. Along with the determination of spatial representativeness value of individual stations, SA was used to detect redundancies on the existing network and establish the base for its expansion. Using a greedy algorithm, a new network for monitoring average temperature in the selected study area is proposed and its effectiveness is compared with the current distribution of stations. For this proposed network distribution maps of the uncertainty of estimation and the temperature distribution were created. Copyright © 2011 Royal Meteorological Society
Effects of cuvette surface material on ammonia‐, nitrous oxide‐, carbon dioxide‐, and methane‐concentration measurements
Authors: Predotova Martina , Kretschmann Roland , Gebauer Jens , Buerkert Andreas
Published: April 2011

Closed‐chamber systems are commonly used to determine gaseous C and N emissions from agricultural soils. We investigated the effects of eight cuvette surfaces on two standard gas concentrations of NH3, N2O, CO2, and CH4 under laboratory conditions. Cuvette surface materials differentially affected gas adhesion or recovery as a function of the type and the concentration of the gases. Given the strong effects on results of gas measurements in closed‐chamber systems, both the type and the concentration of the measured gases need to be considered in selecting cuvette surface materials.
Morbidity, mortality, and pathological response in patients with gastric cancer preoperatively treated with chemotherapy or chemoradiotherapy
Authors: Valenti V. , Hernandez‐Lizoaín J.L. , Beorlegui M.C. , Diaz‐Gozalez J.A. , Regueira F.M. , Rodriguez J.J. , Viudez A. , Sola I. , Cienfuegos J.A.
Published: April 2011

Background

Significant tumor downstaging has been achieved in patients with localized gastric adenocarcinoma by preoperative chemoradiotherapy (ChRT) or induction chemotherapy (Ch). However the influence of ChRT and Ch on postoperative outcomes has not yet been clarified, with very few studies examining this issue. We retrospectively analyzed the efficacy in terms of pathological response and early postoperative complications of two protocols of preoperative ChRT and Ch for locally advanced gastric cancer.

Methods

Between 2000 and 2008, 72 patients with operable locally advanced gastric cancer (cT3‐4/N+) were treated with preoperative treatment: 1—patients receiving induction Ch or 2—neoadjuvant Ch followed by concurrent ChRT. Postoperative histopathological regression and surgical complications were investigated including variables related to patients, surgical variables, preoperative treatment, and tumor.

Results

There were no differences in the incidence of complications between the ChRT and Ch groups (30.9% vs. 33.3%). The most frequent complications were nonspecific surgical complications (pneumonia [12.5%] and infection from intravenous catheters [9.7%]). Risk factors for complications were high‐body mass index (BMI > 25 kg/m2) and extension of surgery to the pancreas and spleen. A major pathological response was observed in 33.3% of patients, being more frequent in the ChRT group (47.6% vs. 13.3%; χ2, P = 0.0024).

Conclusions

Preoperative treatment with Ch or ChRT for locally advanced gastric cancer can be performed safely with an acceptable operative morbidity and low operative mortality rate with careful consideration of the added risk associated with BMI and surgical resection of the pancreas and spleen. Ch and ChRT is feasible and effective in terms of pathological response and R0 resection. J. Surg. Oncol. 2011;104:124–129. © 2011 Wiley‐Liss, Inc.
Pediatric liver transplantation for primary sclerosing cholangitis
Authors: Miloh Tamir , Anand Ravinder , Yin Wendy , Vos Miriam , Kerkar Nanda , Alonso Estella
Published: April 2011

Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease in children. The aim of this study was to determine the characteristics and outcomes of children with PSC who were listed for liver transplantation (LT). Children who underwent transplantation for PSC according to the Studies of Pediatric Liver Transplantation (SPLIT) registry were compared to age-matched children with chronic liver disease who underwent transplantation for other indications. Seventy-nine patients (2.6% of the SPLIT cohort) required LT for PSC. The mean duration of the post-LT follow-up was 36.6 ± 32.7 months. Ulcerative colitis and Crohn's disease were diagnosed before LT in 46.0% and 3.3% of the patients, respectively, and inflammatory bowel disease (IBD) was diagnosed after LT in another 9.8%. The mean age at LT was 12.6 ± 3.9 years, and the mean waiting time was 10.2 ± 12.9 months. The mean z scores for height and weight at LT were significantly lower for the PSC group versus the non-PSC group. For the PSC group, the 1- and 5-year patient survival rates were 98.7% and 86.6%, respectively, and the 1- and 5-year graft survival rates were 93.0% and 76.1%, respectively. Intrahepatic biliary strictures in the first 6 months post-LT and cholangitis in the first 30 days post-LT were more common in the PSC group versus the non-PSC group (3.8% versus 0.8% for intrahepatic biliary strictures, P = 0.03, and 5.1% versus 1.1% for cholangitis, P = 0.01). Recurrent PSC was diagnosed in 9.8% of the patients at a mean of 18.7 ± 13.8 months after LT. IBD was associated with an increased risk of death (log-rank P = 0.01) and recurrent PSC (P = 0.02). Five years post-LT, the mean aspartate aminotransferase level was 60 ± 45 IU/L, and the mean gamma-glutamyltransferase level was 209 ± 302 IU/L; both levels were significantly higher than the levels for non-PSC patients. In conclusion, children with PSC had patient and graft survival rates equaling those of age-matched children who underwent transplantation for other indications. IBD was associated with worse outcomes. Recurrence was observed in 9.8%, and the PSC patients had higher mean liver enzyme levels 5 years post-LT. Liver Transpl 17:925–933, 2011. © 2011 AASLD.
Covalent Growth Factor Immobilization Strategies for Tissue Repair and Regeneration
Authors: Masters Kristyn S.
Published: April 2011

Growth factors play a critical role in regulating processes involved in cellular differentiation and tissue regeneration, and are therefore considered essential elements in many tissue engineering strategies. The covalent immobilization of growth factors to biomaterial matrices addresses many of the challenges associated with delivering freely‐diffusible growth factors and has thus emerged as a promising method of achieving localized and sustained growth factor delivery. This Feature Article discusses methods that have been used to immobilize growth factors to substrates, followed by an overview of several tissue repair and regeneration applications in which immobilized growth factors have been used.

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Towards the Sustainable Production of Higher‐Molecular‐Weight Polyglycerol
Authors: Salehpour Somaieh , Dubé Marc A.
Published: April 2011

The step‐growth polymerization of glycerol to relatively high molecular weight polyglycerol is investigated. Glycerol is a renewable material that can be derived from the transesterification of vegetable oils to biodiesel. Several soluble catalysts and their reaction mechanisms are compared and their effect on polymer molecular weight and microstructure is measured. High‐molecular‐weight PG with multimodal molecular weight distributions is observed using GPC, and partial branching is identified using 13C NMR spectroscopy. Theoretical models are used to predict the gel point and to calculate monomer functionality.

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Dose escalation of intravenous irinotecan using oral cefpodoxime: A phase I study in pediatric patients with refractory solid tumors
Authors: McGregor Lisa M. , Stewart Clinton F. , Crews Kristine R. , Tagen Michael , Wozniak Amy , Wu Jianrong , McCarville M. Beth , Navid Fariba , Santana Victor M. , Houghton Peter J. , Furman Wayne L. , Rodriguez‐Galindo Carlos
Published: April 2011

Background

Administration of an oral cephalosporin allowed advancement of the dosage of oral irinotecan. This study investigates whether administration of an oral cephalosporin increases the maximum tolerated dose (MTD) of intravenous irinotecan.

Procedure

Irinotecan was administered intravenously on Days 1–5 and Days 8–12 of a 21‐day cycle with continuous oral cefpodoxime starting 2 days prior to irinotecan. Cohorts of 3–6 pediatric patients with refractory solid tumors were enrolled at 4 dosage levels, starting at the single‐agent irinotecan MTD of 20 mg/m2/dose.

Results

The 17 evaluable patients received 39 courses of therapy. None of the patients treated with 20 mg/m2/dose experienced dose‐limiting toxicity (DLT). One of six patients treated at 30 mg/m2/dose experienced dose‐limiting neutropenia. Two of three patients treated with 45 mg/m2/dose and two of five treated with 40 mg/m2/dose experienced dose‐limiting diarrhea, with associated dehydration and anorexia. Two unconfirmed partial responses were observed after one course in a patient with Ewing sarcoma and one with paraganglioma. A child with refractory neuroblastoma had disease stabilization through 12 courses of therapy. Median (range) systemic exposure to SN‐38 at the MTD (30 mg/m2/dose) was 67 ng‐h/mL (36 to 111 ng‐h/mL).

Conclusions

The MTD of intravenous irinotecan administered on a protracted schedule was increased by 50% from 20 to 30 mg/m2/dose with the addition of oral cefpodoxime. The most prominent DLT remained diarrhea. High interpatient variability in irinotecan pharmacokinetics was observed; however, SN‐38 exposure at the MTD was greater than most reported exposures with the 20 mg/m2 dosage. Pediatr Blood Cancer 2012; 58: 372–379. © 2011 Wiley Periodicals, Inc.
Time‐to‐antibiotic administration as a quality of care measure in children with febrile neutropenia: A survey of pediatric oncology centers
Authors: McCavit Timothy L. , Winick Naomi
Published: April 2011

Time‐to‐antibiotic administration (TTA) has been suggested as a quality‐of‐care (QOC) measure for pediatric oncology patients with febrile neutropenia (FN). Unknown, however, is to what extent pediatric oncology centers utilize TTA. Therefore, we designed and administered an electronic survey (68% response rate) of programs in the Children's Oncology Group to assess TTA utilization. Nearly half of respondents track TTA. Most reported using a benchmark of less than 60 min from arrival. TTA is a commonly used QOC measure for pediatric FN despite an absence of studies establishing its validity and a lack of data supporting its impact on outcomes of FN. Pediatr Blood Cancer 2012; 58: 303–305. © 2011 Wiley Periodicals, Inc.
Morphology of Titanium Nanocluster Films Prepared by Gas Aggregation Cluster Source
Authors: Drábik Martin , Choukourov Andrei , Artemenko Anna , Kousal Jaroslav , Polonskyi Oleksandr , Solař Pavel , Kylián Ondřej , Matoušek Jindřich , Pešička Josef , Matolínová Iva , Slavínská Danka , Biederman Hynek
Published: April 2011

Titanium nanocluster films were prepared using a gas aggregation cluster source based on a planar magnetron following a Haberland concept and using Ar as a working gas. The films were deposited in dependence on the argon pressure inside the cluster source and on the magnetron current. Prior to the analysis, deposited metal nanocluster films were allowed to oxidize in air at room temperature. Selected nanocluster films were annealed in air at 420 °C. The films were studied by TEM, SEM, and AFM in order to describe their morphology and topography. Crystal structure of the nanoclusters was estimated from electron diffraction patterns by SAD analysis. Chemical composition of the film surface was determined by XPS. Special attention was paid to describing the changes in the nanocluster films connected with ageing.

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A database of reaction monitoring mass spectrometry assays for elucidating therapeutic response in cancer
Authors: Remily‐Wood Elizabeth R. , Liu Richard Z. , Xiang Yun , Chen Yi , Thomas C. Eric , Rajyaguru Neal , Kaufman Laura M. , Ochoa Joana E. , Hazlehurst Lori , Pinilla‐Ibarz Javier , Lancet Jeffrey , Zhang Guolin , Haura Eric , Shibata David , Yeatman Timothy , Smalley Keiran S. M. , Dalton William S. , Huang Emina , Scott Ed , Bloom Gregory C. , Eschrich Steven A. , Koomen John M.
Published: April 2011

Purpose: The Quantitative Assay Database (QuAD), http://proteome.moffitt.org/QUAD/, facilitates widespread implementation of quantitative mass spectrometry in cancer biology and clinical research through sharing of methods and reagents for monitoring protein expression and modification.

Experimental design: Liquid chromatography coupled to multiple reaction monitoring (LC‐MRM) mass spectrometry assays are developed using SDS‐PAGE fractionated lysates from cancer cell lines. Pathway maps created using GeneGO Metacore provide the biological relationships between proteins and illustrate concepts for multiplexed analysis; each protein can be selected to examine assay development at the protein and peptide levels.

Results: The coupling of SDS‐PAGE and multiple reaction monitoring mass spectrometry screening has been used to detect 876 peptides from 218 cancer‐related proteins in model systems including colon, lung, melanoma, leukemias, and myeloma, which has led to the development of 95 quantitative assays including stable‐isotope‐labeled peptide standards. Methods are published online and peptide standards are made available to the research community. Protein expression measurements for heat shock proteins, including a comparison with ELISA and monitoring response to the HSP90 inhibitor, 17‐(dimethylaminoethylamino)‐17‐demethoxygeldanamycin (17‐DMAG), are used to illustrate the components of the QuAD and its potential utility.

Conclusions and Clinical Relevance: This resource enables quantitative assessment of protein components of signaling pathways and biological processes and holds promise for systematic investigation of treatment responses in cancer.
Utility of formalin‐fixed, paraffin‐embedded liver biopsy specimens for global proteomic analysis in nonalcoholic steatohepatitis
Authors: Bell Lauren N. , Saxena Romil , Mattar Samer G. , You Jinsam , Wang Mu , Chalasani Naga
Published: April 2011

Purpose: To compare the proteomic profiles of formalin‐fixed, paraffin‐embedded (FFPE) liver biopsy material and matched frozen liver tissue from patients with nonalcoholic steatohepatitis (NASH).

Experimental design: A label‐free mass spectrometry‐based approach was used to profile global protein expression in FFPE and frozen liver biopsy specimens from five patients with NASH.

Results: Eight hundred and sixty proteins were identified with >75% confidence: 225 common proteins were identified in both the FFPE and frozen tissues, and an additional 142 and 493 proteins were identified in the FFPE and frozen tissues, respectively. Functional analyses revealed a general, nonspecific reduction in the number of proteins identified in FFPE tissue compared with frozen tissue. No bias toward proteins located in any specific subcellular compartments or implicated in any particular biological functions was observed. The relative abundance of several proteins with functions relating to the pathogenesis of NASH (peroxiredoxin‐1, fatty acid binding protein 1, fatty acid synthase, vimentin, catalase, and glutathione S‐transferase A1) was similar in FFPE and frozen liver tissues.

Conclusions and clinical relevance: FFPE liver biopsy material from NASH patients can be used for global proteomic analysis and biomarker identification studies, although a universal reduction in the number of identified proteins compared with frozen tissue is likely.
De novo protein structure prediction by dynamic fragment assembly and conformational space annealing
Authors: Lee Juyong , Lee Jinhyuk , Sasaki Takeshi N. , Sasai Masaki , Seok Chaok , Lee Jooyoung
Published: April 2011

Ab initio protein structure prediction is a challenging problem that requires both an accurate energetic representation of a protein structure and an efficient conformational sampling method for successful protein modeling. In this article, we present an ab initio structure prediction method which combines a recently suggested novel way of fragment assembly, dynamic fragment assembly (DFA) and conformational space annealing (CSA) algorithm. In DFA, model structures are scored by continuous functions constructed based on short‐ and long‐range structural restraint information from a fragment library. Here, DFA is represented by the full‐atom model by CHARMM with the addition of the empirical potential of DFIRE. The relative contributions between various energy terms are optimized using linear programming. The conformational sampling was carried out with CSA algorithm, which can find low energy conformations more efficiently than simulated annealing used in the existing DFA study. The newly introduced DFA energy function and CSA sampling algorithm are implemented into CHARMM. Test results on 30 small single‐domain proteins and 13 template‐free modeling targets of the 8th Critical Assessment of protein Structure Prediction show that the current method provides comparable and complementary prediction results to existing top methods. Proteins 2011; © 2011 Wiley‐Liss, Inc.
Crystal structure of the novel PaiA N‐acetyltransferase from Thermoplasma acidophilum involved in the negative control of sporulation and degradative enzyme production
Authors: Filippova E.V. , Shuvalova L. , Minasov G. , Kiryukhina O. , Zhang Y. , Clancy S. , Radhakrishnan I. , Joachimiak A. , Anderson W.F.
Published: April 2011

GCN5‐related N‐acetyltransferases (GNATs) are the most widely distributed acetyltransferase systems among all three domains of life. GNATs appear to be involved in several key processes, including microbial antibiotic resistance, compacting eukaryotic DNA, controlling gene expression, and protein synthesis. Here, we report the crystal structure of a putative GNAT Ta0374 from Thermoplasma acidophilum, a hyperacidophilic bacterium, that has been determined in an apo‐form, in complex with its natural ligand (acetyl coenzyme A), and in complex with a product of reaction (coenzyme A) obtained by cocrystallization with spermidine. Sequence and structural analysis reveals that Ta0374 belongs to a novel protein family, PaiA, involved in the negative control of sporulation and degradative enzyme production. The crystal structure of Ta0374 confirms that it binds acetyl coenzyme A in a way similar to other GNATs and is capable of acetylating spermidine. Based on structural and docking analysis, it is expected that Glu53 and Tyr93 are key residues for recognizing spermidine. Additionally, we find that the purification His‐Tag in the apo‐form structure of Ta0374 prevents binding of acetyl coenzyme A in the crystal, though not in solution, and affects a chain‐flip rotation of “motif A” which is the most conserved sequence among canonical acetyltransferases. Proteins 2011; © 2011 Wiley‐Liss, Inc.
FISH HABITAT OPTIMIZATION TO PRIORITIZE RIVER RESTORATION DECISIONS
Authors: Null S. E. , Lund J. R.
Published: April 2011

This paper examines and ranks restoration alternatives for improving fish habitat by evaluating tradeoffs between fish production and restoration costs. Optimization modelling is used to maximize out‐migrating coho salmon (Oncorhynchus kisutch) from a natal stream and is applied as a case study in California's Shasta River. Restoration activities that alter flow and water temperature conditions are the decision variables in the model and include relocating a major diversion, increasing riparian shading, increasing instream flow, restoring a cool‐water spring and removing a dam. A budget constraint limits total restoration expenditures. This approach combines simple fish population modelling with flow and water quality modelling to explore management strategies and aid decision making. Previous fish habitat optimization research typically uses single restoration strategies, usually by altering reservoir releases or modifying outlet structures. Our method enlarges the solution space to more accurately represent extensive and integrated solutions to fish habitat problems. Results indicate that restoration alternatives can be prioritized by fish habitat improvement and restoration cost. For the Shasta River case study, considerable habitat restoration investments were required before fish productivity increased substantially. This exercise illustrates the potential of ecological optimization for highlighting promising restoration approaches and dismissing poor alternatives. Copyright © 2011 John Wiley & Sons, Ltd.
Strontium Enhances Osteogenic Differentiation of Mesenchymal Stem Cells and In Vivo Bone Formation by Activating Wnt/Catenin Signaling
Authors: Yang Fan , Yang Dazhi , Tu Jie , Zheng Qixin , Cai Lintao , Wang Liping
Published: April 2011

Strontium ranelate is a newly approved drug that can reduce the risk of vertebral fracture, which is attributed to its dual function in increasing the bone formation and decreasing the bone resorption. Strontium-containing hydroxyapatite was also demonstrated to stimulate the osteoblast activity and inhibit the osteoclast activity. However, the molecular mechanisms of strontium underlying such beneficial effects were still not fully understood. In this study, we investigated the effects of strontium on the osteogenic differentiation of human mesenchymal stem cells (MSCs) and its related mechanism; its osteogenic potential was also evaluated using a calvarial defect model in rats. We found that strontium could enhance the osteogenic differentiation of the MSCs, with upregulated extracellular matrix (ECM) gene expression and activated Wnt/β-catenin pathway. After transplanting the collagen-strontium-substituted hydroxyapatite scaffold into the bone defect region, histology and computed tomography scanning revealed that in vivo bone formation was significantly enhanced; the quantity of mature and remodeled bone substantially increased and ECM accumulated. Interestingly, strontium induced an increase of β-catenin expression in newly formed bone area. In this study, we showed for the first time that strontium could stimulate the β-catenin expression in vitro and in vivo, which might contribute to the enhanced osteogenic differentiation of MSCs and in vivo bone formation.
Concise Review: Transplantation of Human Hematopoietic Cells for Extracellular Matrix Protein Deficiency in Epidermolysis Bullosa
Authors: Tolar Jakub , Blazar Bruce R. , Wagner John E.
Published: April 2011

The skin is constantly exposed to environmental insults and requires effective repair processes to maintain its protective function. Wound healing is severely compromised in people with congenital absence of structural proteins of the skin, such as in dystrophic epidermolysis bullosa, a severe congenital mechanobullous disorder caused by mutations in collagen type VII. Remarkably, stem cell transplantation can ameliorate deficiency of this skin-specific structural protein in both animal models and in children with the disorder. Healthy donor cells from the hematopoietic graft migrate to the injured skin; simultaneously, there is an increase in the production of collagen type VII, increased skin integrity, and reduced tendency to blister formation. How hematogenous stem cells from bone marrow and cord blood can alter skin architecture and wound healing in a robust, clinically meaningful way is unclear. We review the data and the resulting hypotheses that have a potential to illuminate the mechanisms for these effects. Further modifications in the use of stem cell transplantation as a durable source of extracellular matrix proteins may make this regenerative medicine approach effective in other cutaneous and extracutaneous conditions.
Concise Review: Contribution of Cancer Stem Cells to Neovascularization
Authors: Ping Yi-Fang , Bian Xiu-Wu
Published: April 2011

Cancer stem cells (CSCs), a special subpopulation of tumor cells, are considered as tumor initiating cells. More recently, these cells have also been identified as initiators of tumor neovascularization. A better understanding of the contribution of CSCs to neovascularization should elucidate the mechanisms of cancer initiation and progression as well as establish new concepts for cancer diagnosis and treatment. In this review, we discuss the evidence for the roles of CSCs in tumor vascularization, including production of proangiogenic factors, transdifferentiation into vascular mural cells such as endothelial and smooth muscle-like cells, and formation of nonendothelium-lined vasculogenic mimicry. In addition, the potential therapeutic significance of targeting CSCs is envisaged.
Toll-Like Receptor-3-Activated Human Mesenchymal Stromal Cells Significantly Prolong the Survival and Function of Neutrophils
Authors: Cassatella Marco A. , Mosna Federico , Micheletti Alessandra , Lisi Veronica , Tamassia Nicola , Cont Caterina , Calzetti Federica , Pelletier Martin , Pizzolo Giovanni , Krampera Mauro
Published: April 2011

Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are stromal precursors endowed with extensive immunomodulative properties. In this study, we aimed to assess whether Toll-like receptor-3 (TLR3)- and TLR4-activated BM-MSC influence human neutrophil (PMN) responses under coculture conditions. We show that TLR3 triggering by polyinosinic:polycytidylic acid dramatically amplifies, in a more significant manner than TLR4 triggering by lipopolysaccharide, the antiapoptotic effects that resting BM-MSC constitutively exert on PMN under coculture conditions, preserving a significant fraction of viable and functional PMN up to 72 hours. In addition, TLR3- and TLR4-activated BM-MSC enhance respiratory burst ability and CD11b expression by PMN. The coculture in the absence of cell contact and the incubation of PMN in supernatants harvested from TLR3- and TLR4-activated BM-MSC yield comparable results in terms of increased survival and immunophenotypic changes, thus suggesting the involvement of endogenous soluble factors. Neutralizing experiments reveal that the biological effects exerted on PMN by TLR3-activated BM-MSC are mediated by the combined action of interleukin 6, interferon-β (IFN-β), and granulocyte macrophage colony-stimulating factor (GM-CSF), while those exerted by TLR4-activated BM-MSC mostly depend on GM-CSF. MSC isolated from thymus, spleen, and subcutaneous adipose tissue behaves similarly. Finally, the effects exerted by TLR3- or TLR4-stimulated BM-MSC on PMN are conserved even after the previous priming of BM-MSC with IFN-γ and tumor necrosis factor-α. Our data highlight a novel mechanism by which MSC sustain and amplify the functions of PMN in response to TLR3- and TLR4-triggering and may consequently contribute to inflammatory disorders.
Thread algebra for poly-threading
Authors: Bergstra J. A. , Middelburg C. A.
Published: April 2011

It is a fact of life that sequential programs are often fragmented. Consequently, fragmented program behaviours are frequently found. We consider this phenomenon in the setting of thread algebra. We extend basic thread algebra with poly-threading, the barest mechanism for sequencing of threads that are taken for program fragment behaviours. This mechanism is the counterpart of program overlaying at the level of program behaviours. We relate the resulting theory to the process theory known as ACP and use it to describe analytic execution architectures suited for fragmented programs. We also consider the case where the steps of fragmented program behaviours are interleaved in the ways of non-distributed and distributed multi-threading.
Retrospective Comparison of Clinical Outcomes between Endovenous Laser and Saphenous Vein‐sparing Surgery for Treatment of Varicose Veins
Authors: Chan Chih‐Yang , Chen Tzu‐Chun , Hsieh Yung‐Kun , Huang Jih‐Hsin
Published: April 2011

Background

The purpose of the present study was to compare management of varicose veins by endovenous laser ablation (EVL) and a vein‐sparing procedure (CHIVA: Conservatrice et Hémodynamique de l’Insuffisance Veineuse en Ambulatoire) for management of varicose veins.

Methods

Data from 82 consecutive patients with great saphenous vein (GSV) reflux and primary varicose veins presenting to the vascular clinic at the Far Eastern Memorial Hospital between June and December 2005 were reviewed. Of these, 74 who met the inclusion criteria were included in this study. CHIVA was performed by a double division of the refluxing saphenous vein (i.e., proximal and distal ligation), and EVL was performed using 10–14 W beginning approximately 4 cm below the saphenofemoral junction to the level of the knee. Phlebectomy for significant branch varicose veins on the leg was routinely performed in all patients. Outcome measures included postoperative thrombophlebitis, bruising, pain, assessment of ultrasonographic and clinical symptoms (measured by the Venous Clinical Severity Score [VCSS]) and comparison of quality of life survey scores obtained preoperatively and postoperatively (measured by the Aberdeen Varicose Veins Score [AVVQ] and RAND‐36). Patients were examined one week post‐procedurally and again at 1, 3, 6, and 12 months.

Results

Endovenous laser ablation and CHIVA were performed on 54 and 20 patients, respectively. The EVL patients had significantly higher pain scores and bruising than the CHIVA group (p < 0.001). The VCSS of varicose, edema, pigmentation, and inflammation were significantly reduced after both EVL and CHIVA; however, patients treated by EVL had significantly more pain postoperatively than those treated by CHIVA (p = 0.003). Twenty‐two of 54 (40.7%) and 3 of 17 (17.6%) patients in the EVL and CHIVA groups, respectively, required sclerotherapy for residual varicosities (p = 0.026). Both groups benefited significantly from surgery in disease‐specific perceptions.

Conclusions

The CHIVA patients had less pain postoperatively and a significantly higher sclerotherapy‐free period compared to patients in the EVL group. Further follow‐up studies to compare long‐term results of various approaches to surgically managing varicose veins are needed.
A new synaptic player leading to autism risk: Met receptor tyrosine kinase
Authors: Judson Matthew C. , Eagleson Kathie L. , Levitt Pat
Published: April 2011

The validity for assigning disorder risk to an autism spectrum disorder (ASD) candidate gene comes from convergent genetic, clinical, and developmental neurobiology data. Here, we review these lines of evidence from multiple human genetic studies, and non-human primate and mouse experiments that support the conclusion that the MET receptor tyrosine kinase (RTK) functions to influence synapse development in circuits relevant to certain core behavioral domains of ASD. There is association of both common functional alleles and rare copy number variants that impact levels of MET expression in the human cortex. The timing of Met expression is linked to axon terminal outgrowth and synaptogenesis in the developing rodent and primate forebrain, and both in vitro and in vivo studies implicate this RTK in dendritic branching, spine maturation, and excitatory connectivity in the neocortex. This impact can occur in a cell-nonautonomous fashion, emphasizing the unique role that Met plays in specific circuits relevant to ASD.
Subsurface Structure Derived from Detailed Gravity and Magnetic Investigations along the Pala-Maneri Traverse of the Main Central Thrust, NW Himalaya
Authors: Seshunarayana T. , Prasad B. Rajendra , Prasad A.S.S.S.R.S. , Mysaiah D.
Published: April 2011

A detailed, integrated gravity and magnetic study across the Main Central Thrust (MCT) along the Pala- Maneri traverse in Uttaranchal, NW Himalaya was carried out. The gravity data was acquired using a CG-3 gravity meter with an accuracy of 0.005 mGal, while magnetic data was acquired using a proton precession magnetometer with a station interval of 20 m. Data was collected along a 11.7 km, NE–SW traverse from Pala to Maneri along the proposed route of a hydroelectric headrace tunnel. The measured variation in the gravity field was approximately 70 mGal, with two prominent highs recorded at distances of 0.5 km, 7.5 km and lows at 3.0 km, 10.5 km from Maneri. The gravity highs can be attributed to presence of high-density rocks along the thrust planes. The sharp gravity low recorded at 10.5 km distance possibly indicates a sympathetic fault of the MCT that is highly saturated with fluids (water). The broad gravity low between 2.5 km and 4.0 km distance is likely to represent the gravity signature of the MCT itself. The measured variation in the magnetic field was approximately 285 nT. The associated gravity and magnetic signatures located several faults along the traverse including presence of the MCT at Kumaltigad.
Paleobiogeography, Paleoecology and Paleoenvironmental Significance of the Cambrian Trilobites from the Zanskar Region (Zanskar-Spiti-Kinnaur Basin), Northwest Himalaya
Authors: Singh Birendra P.
Published: April 2011

In present study the newly recorded latest Middle Cambrian trilobite fauna from the Cambrian succession of the Zanskar region of Zanskar-Spiti-Kinnaur Basin (Tethyan Himalaya) is analyzed critically to assess relationships with other Cambrian faunal elements of equatorial peri-Gondwanaland. The identification of genus Neoanomocarella, Parablackwelderia, Kunmingaspis, Fuchouia, Damesella and Dorypyge from the Cambrian of the Zanskar region and their comparison with those of South China and Australia is significant. It constitutes the basis for assessing the paleobiogeographic affinities during the Cambrian. The latest Middle Cambrian trilobite fauna from Zanskar shows proximity of Indian margin with that of southwest China “outboard” micro-continent. The recovery of analogous Middle Cambrian species i.e., Dorypyge perconvexlis, Fuchouia bulba, Fuchouia cf. oratolimba, Parablackwelderia sp. and Damesella sp. from the Zanskar region (Tethyan Himalaya) suggests a contiguous close proximity with south China and Australia during the latest Middle Cambrian, which supports the model of Meert and Van der Voo (1997) for assembly of Gondwanaland. The presence of Kunmingaspis in Zanskar and similar reports from northwestern Yunnan-Tibetan region, northern Henan, central and southeastern Hubei, north China, western Xinjiang and Yangtze platform reveal a close affinity between the Indian margin and the Yangtze platform during the Middle Cambrian. The trilobite fauna indicates the deeper shelf-shallow slope environment of deposition under fluctuating conditions of relative sea-level. The faunal elements of the Lejopyge acantha and Proagnostus bulbus zones indicate that the sea inundated the northern margin of Zanskar region during the latest Middle Cambrian time (Teta transgression) which is synchronous with globally recognized eustatic events during Lejopyge laevigata Zone.