bluuebunny/crossref_metadata_2025_split huggingface dataset:
A constrained least‐squares approach to the automated quantitation of in vivo 1H magnetic resonance spectroscopy data
Authors: Wilson Martin , Reynolds Greg , Kauppinen Risto A. , Arvanitis Theodoros N. , Peet Andrew C. 
Published: September 2010

AbstractTotally Automatic Robust Quantitation in NMR (TARQUIN), a new method for the fully automatic analysis of short echo time in vivo 1H Magnetic resonance spectroscopy is presented. Analysis is performed in the time domain using non‐negative least squares, and a new method for applying soft constraints to signal amplitudes is used to improve fitting stability. Initial point truncation and Hankel singular value decomposition water removal are used to reduce baseline interference. Three methods were used to test performance. First, metabolite concentrations from six healthy volunteers at 3 T were compared with LCModel™. Second, a Monte‐Carlo simulation was performed and results were compared with LCModel™ to test the accuracy of the new method. Finally, the new algorithm was applied to 1956 spectra, acquired clinically at 1.5 T, to test robustness to noisy, abnormal, artifactual, and poorly shimmed spectra. Discrepancies of less than approximately 20% were found between the main metabolite concentrations determined by TARQUIN and LCModel™ from healthy volunteer data. The Monte‐Carlo simulation revealed that errors in metabolite concentration estimates were comparable with LCModel™. TARQUIN analyses were also found to be robust to clinical data of variable quality. In conclusion, TARQUIN has been shown to be an accurate and robust algorithm for the analysis of magnetic resonance spectroscopy data making it suitable for use in a clinical setting. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
More accurate estimation of diffusion tensor parameters using diffusion kurtosis imaging
Authors: Veraart Jelle , Poot Dirk H. J. , Van Hecke Wim , Blockx Ines , Van der Linden Annemie , Verhoye Marleen , Sijbers Jan 
Published: September 2010

AbstractWith diffusion tensor imaging, the diffusion of water molecules through brain structures is quantified by parameters, which are estimated assuming monoexponential diffusion‐weighted signal attenuation. The estimated diffusion parameters, however, depend on the diffusion weighting strength, the b‐value, which hampers the interpretation and comparison of various diffusion tensor imaging studies. In this study, a likelihood ratio test is used to show that the diffusion kurtosis imaging model provides a more accurate parameterization of both the Gaussian and non‐Gaussian diffusion component compared with diffusion tensor imaging. As a result, the diffusion kurtosis imaging model provides a b‐value‐independent estimation of the widely used diffusion tensor parameters as demonstrated with diffusion‐weighted rat data, which was acquired with eight different b‐values, uniformly distributed in a range of [0,2800 sec/mm2]. In addition, the diffusion parameter values are significantly increased in comparison to the values estimated with the diffusion tensor imaging model in all major rat brain structures. As incorrectly assuming additive Gaussian noise on the diffusion‐weighted data will result in an overestimated degree of non‐Gaussian diffusion and a b‐value‐dependent underestimation of diffusivity measures, a Rician noise model was used in this study. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.
In the ring with polycystic kidney disease—avoiding the knockout punch
Authors: Adam Julie , Pollard Patrick J 
Published: September 2010

AbstractAutosomal dominant polycystic kidney disease (PKD) is an inherited disease that results from mutations in either polycystin (PKD1) or polycystin 2 (PKD2), both of which are large, complex, and multifunctional proteins whose loss results in the development of numerous fluid‐filled cysts and fibrosis that compromise renal function. A number of spontaneous and engineered mouse models of PKD have provided some understanding of many aspects of cyst development, modifier genes, and mechanistic pathways, but fall short of reproducing the human disease accurately. Two recent papers in The Journal of Pathology set out new models using miRNA, or inducible and targeted recombination, that achieve partial or timed suppression of Pkd1. Instead of knocking out Pkd1 immediately, or completely, these more subtle approaches may help deliver more faithful models of this significant human renal disease. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Invited Commentary for Hassane S, Leonhard WN, van der Wal A, et al. Elevated TGFβ–Smad signalling in experimental Pkd1 models and human patients with polycystic kidney disease. J Pathol 2010; 222: 21–31. And for Wang E, Hsieh‐Li HM, Chiou YY, et al. Progressive renal distortion by multiple cysts in transgenic mice expressing artificial microRNAs against Pkd1. J Pathol 2010; 222: 238–248.
Genetically informed lung cancer medicine
Authors: Pao William , Iafrate A John , Su Zengliu 
Published: September 2010

AbstractKnowledge of tumour mutation status has become increasingly important for the prioritization of targeted therapies for cancer. We review here the major known ‘driver’ mutations with therapeutic relevance in non‐small cell lung cancer. We also discuss a variety of methods now being employed in molecular diagnostic laboratories to detect genetic alterations in lung tumours. A genetically‐informed approach to lung cancer medicine is rapidly becoming the standard of care worldwide and should lead to improved outcomes for patients. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Mutant K‐ras promotes carcinogen‐induced murine colorectal tumourigenesis, but does not alter tumour chromosome stability
Authors: Luo Feijun , Poulogiannis George , Ye Hongtao , Hamoudi Rifat , Zhang Wenyan , Dong Gehong , Arends Mark J 
Published: September 2010

AbstractK‐ras (KRAS) mutations are observed in around 40% of human colorectal adenomas and carcinomas. Previously, we developed and characterized a strain of transgenic mice with inducible intestinal epithelial expression of K‐ras$^{Val12}$ via a Cre/LoxP system. To evaluate the influence of mutant K‐ras on carcinogen‐induced colorectal tumourigenesis, we induced neoplastic alterations in the large intestines of wild‐type and K‐ras$^{Val12}$ mice using the colon‐selective carcinogen 1,2‐dimethylhydrazine (DMH), which has been widely used to induce colorectal tumours that are histopathologically similar to those observed in humans. K‐ras$^{Val12}$ expression significantly promoted DMH‐induced colorectal tumourigenesis: the average lifespan of the mice decreased from 38.52 ± 1.97 weeks for 40 control mice to 32.42 ± 2.17 weeks for 26 K‐ras$^{Val12}$ mice (mean ± SEM, p < 0.05) and the abundance of large intestinal tumours increased from 2.27 ± 0.15 per control mouse to 3.85 ± 0.20 in K‐ras$^{Val12}$ mice (mean ± SEM, p < 0.01). Adenomas from DMH‐treated K‐ras$^{Val12}$ mice showed significantly higher proportions of Ki‐67‐positive proliferating cells (10.9 ± 0.69%) compared with those from DMH‐treated wild‐type mice (7.77 ± 0.47%) (mean ± SEM, p < 0.01) and a mild increase in apoptotic nuclei staining for cleaved caspase‐3 (1.94 ± 0.21% compared with 1.15 ± 0.14%, mean ± SEM, p < 0.01). In the adenomas from DMH‐treated K‐ras$^{Val12}$ mice, K‐ras$^{Val12}$ transgene recombination and expression were confirmed, with immunohistochemical evidence of strong Erk/MapK and mild PI3K/Akt pathway activation compared with adenomas from DMH‐treated wild‐type mice. Microarray hybridization and clustering analysis demonstrated different expression profiles in adenomas from DMH‐treated wild‐type and DMH‐treated K‐ras$^{Val12}$ mice, indicating involvement of different molecular mechanisms including Erk/MapK and PI3K/Akt signalling in K‐ras$^{Val12}$‐expressing adenomas. Array‐comparative genomic hybridization analysis showed chromosome stability in both cohorts, with only a very few tiny alterations observed in one adenoma from a DMH‐treated K‐ras$^{Val12}$ mouse. Taken together, these data show that mutant K‐ras significantly promotes DMH‐induced colorectal tumourigenesis, resulting in distinct changes in cell signalling and proliferation, but does not alter chromosome stability in the tumours. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Signalling networks associated with urokinase‐type plasminogen activator (uPA) and its inhibitor PAI‐1 in breast cancer tissues: new insights from protein microarray analysis
Authors: Wolff Claudia , Malinowsky Katharina , Berg Daniela , Schragner Kerstin , Schuster Tibor , Walch Axel , Bronger Holger , Höfler Heinz , Becker Karl‐Friedrich 
Published: September 2010

AbstractThe urokinase‐type plasminogen activator (uPA) and the main uPA inhibitor PAI‐1 play important roles in cell migration and invasion in both physiological and pathological contexts. Both factors are clinically applicable predictive markers in node‐negative breast cancer patients that are used to stratify patients for adjuvant chemotherapy. In addition to their classical functions in plasmin regulation, both factors are key components in cancer‐related cell signalling. Such signalling cascades are well described in cell culture systems, but a better understanding of uPA‐ and PAI‐1‐associated signalling networks in clinical tissues is needed. We examined the expression of uPA, PAI‐1, and 21 signalling molecules in 201 primary breast cancer tissues using protein microarrays. Expression of uPA was significantly correlated with the expression of ERK and Stat3, while expression of PAI‐1 was correlated with the uPA receptor and Akt activation, presumably via integrin and HER‐receptor signalling. Analysis of uPA expression did not reveal any significant correlation with staging, grading or age of the patients. The PAI‐1 expression was correlated with nodal stage. Network monitoring for uPA and PAI‐1 in breast cancer reveals interactions with main signalling cascades and extends the findings from cell culture experiments. Our results reveal possible mechanisms underlying cancer development. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Cancer stem cells: problems for therapy?
Authors: Alison Malcolm R , Lim Susan ML , Nicholson Linda J 
Published: September 2010

AbstractMany, if not all, tumours contain a sub‐population of self‐renewing and expanding stem cells known as cancer stem cells (CSCs). The symmetric division of CSCs is one mechanism enabling expansion in their numbers as tumours grow, while epithelial–mesenchymal transition (EMT) is an increasingly recognized mechanism to generate further CSCs endowed with a more invasive and metastatic phenotype. Putative CSCs are prospectively isolated using methods based on either a surface marker or an intracellular enzyme activity and then assessed by a ‘sphere‐forming’ assay in non‐adherent culture and/or by their ability to initiate new tumour growth when xenotransplanted into immunocompromised mice—hence, these cells are often referred to as tumour‐propagating cells (TPCs). Cell sub‐populations enriched for tumour‐initiating ability have also been found in murine tumours, countering the argument that xenografting human cells merely select human cells with an ability to grow in mice. Cancer progression can be viewed as an evolutionary process that generates new/multiple clones with a fresh identity; this may be a major obstacle to successful cancer stem cell eradication if treatment targets only a single type of stem cell. In this review, we first briefly discuss evidence that cancer can originate from normal stem cells or closely related descendants. We then outline the attributes of CSCs and review studies in which they have been identified in various cancers. Finally, we discuss the implications of these findings for successful cancer therapies, concentrating on the self‐renewal pathways (Wnt, Notch, and Hedgehog), aldehyde dehydrogenase activity, EMT, miRNAs, and other epigenetic modifiers as potential targets for therapeutic manipulation. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
The positive predictive value of a hyperkalemia diagnosis in automated health care data
Authors: Raebel Marsha A. , Smith Michael L. , Saylor Gwyn , Wright Leslie A. , Cheetham Craig , Blanchette Christopher M. , Xu Stanley 
Published: September 2010

AbstractPurposeOur objectives were to determine performance of coded hyperkalemia diagnosis at identifying (1) clinically evident hyperkalemia and (2) serum potassium>6 mmol/L.MethodsThis retrospective observational study included 8722 patients with diabetes within an integrated healthcare system who newly initiated an angiotensin converting enzyme inhibitor, angiotensin receptor blocker, or spironolactone. The primary outcome was first hyperkalemia‐associated event (hospitalization, emergency department visit or death within 24 hours of coded diagnosis and/or potassium≥6 mmol/L) during the first year of therapy. Medical records were reviewed.ResultsAmong a random sample of 99 patients not coded as having hyperkalemia, none had hyperkalemia upon record review. Among all 64 patients identified as having hyperkalemia, all had hospitalization or emergency department visit associated with coded diagnosis or elevated potassium. Of 55 with coded diagnosis, 42 (PPV 76%) had clinically evident hyperkalemia; 32 (PPV 58%) had potassium≥6. Of 9 identified using only potassium≥6, 7 (PPV 78%) had clinically evident hyperkalemia.ConclusionsNearly one‐fourth of patients with coded diagnosis do not have clinically evident hyperkalemia and nearly one‐half do not have potassium≥6. Because both false positives and negatives occur with coded diagnoses, medical record validation of hyperkalemia‐associated outcomes is necessary. Copyright © 2010 John Wiley & Sons, Ltd.
Crystal structure analysis of Bacillus subtilis ferredoxin‐NADP+ oxidoreductase and the structural basis for its substrate selectivity
Authors: Komori Hirofumi , Seo Daisuke , Sakurai Takeshi , Higuchi Yoshiki 
Published: September 2010

AbstractBacillus subtilis yumC encodes a novel type of ferredoxin‐NADP+ oxidoreductase (FNR) with a primary sequence and oligomeric conformation distinct from those of previously known FNRs. In this study, the crystal structure of B. subtilis FNR (BsFNR) complexed with NADP+ has been determined. BsFNR features two distinct binding domains for FAD and NADPH in accordance with its structural similarity to Escherichia coli NADPH‐thioredoxin reductase (TdR) and TdR‐like protein from Thermus thermophilus HB8 (PDB code: 2ZBW). The deduced mode of NADP+ binding to the BsFNR molecule is nonproductive in that the nicotinamide and isoalloxazine rings are over 15 Å apart. A unique C‐terminal extension, not found in E. coli TdR but in TdR‐like protein from T. thermophilus HB8, covers the re‐face of the isoalloxazine moiety of FAD. In particular, Tyr50 in the FAD‐binding region and His324 in the C‐terminal extension stack on the si‐ and re‐faces of the isoalloxazine ring of FAD, respectively. Aromatic residues corresponding to Tyr50 and His324 are also found in the plastid‐type FNR superfamily of enzymes, and the residue corresponding to His324 has been reported to be responsible for nucleotide specificity. In contrast to the plastid‐type FNRs, replacement of His324 with Phe or Ser had little effect on the specificity or reactivity of BsFNR with NAD(P)H, whereas replacement of Arg190, which interacts with the 2′‐phosphate of NADP+, drastically decreased its affinity toward NADPH. This implies that BsFNR adopts the same nucleotide binding mode as the TdR enzyme family and that aromatic residue on the re‐face of FAD is hardly relevant to the nucleotide selectivity.
Tetrad selectivity in polarity‐driven switch peptides: the best turn is not always the best nucleation site
Authors: Gehenn Katja , Reed Jennifer 
Published: September 2010

AbstractIn some naturally occurring protein sequences, an abrupt, concerted refolding from β‐sheet to helical conformation occurs when the polarity of the surrounding medium drops below a critical level. This switch‐like behaviour was first observed on the HIV‐1 envelope glycoprotein gp120, where it plays a crucial role in the efficient binding of gp120 to the T‐cell receptor CD4. Previous work had shown that an N‐terminal amino acid tetrad LPCR and a Trp located 5–20 residues downstream to the tetrad are common motifs in polarity‐driven switch peptides. The LPCR tetrad governs the folding of the subsequent residues and acts as a helix initiation site, whereas the Trp is responsible for the cooperative character of the structural change due to multiple, simultaneous interactions of its quadrupole moment with several amino acid residues within the sequences. Here we identify and characterize new families of switch peptides that use different, turn‐probable tetrads (LPST and VPSR) as helix initiation sites at the N‐terminus. We have also been able to demonstrate that some tetrads with extremely high turn probability do not serve as helix initiation sites. Comparison of these with LPCR and the newly discovered tetrads LPST and VPSR has allowed a more comprehensive description of the physico‐chemical properties of helix‐inducing tetrads. The deeper understanding of the intrinsic properties of switch sequences allows the design of artificial polarity‐driven switches, applicable in engineering of, e.g. controllable binding sites in artificial proteins. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.
A case study on modeling and optimizing photolithography stage of semiconductor fabrication process
Authors: Kim Hyun‐Jin , Kim Kwang‐Jae , Kwak Doh‐Soon 
Published: September 2010

AbstractPhotolithography in the semiconductor fabrication process is the core stage that determines the quality of semiconductor chips. The fabrication process is a batch process that causes variation in the quality of chips; thus, uniformity has always been an important goal of the process. This research is a case study on optimizing the photolithography stage to improve uniformity and the target achievement of critical dimension, a quality measure of semiconductor chips. The case study finds the optimal setting of input variables in photolithography by applying multivariate normal linear modeling with operational data obtained by sampling during manufacturing. The predicted performance of the optimal setting is found to be close to the limit of improvement estimated based on the model. For practitioners, several issues that can be considered for better optimization are also provided. Copyright © 2010 John Wiley & Sons, Ltd.
Error propagation in normalization of stable isotope data: a Monte Carlo analysis
Authors: Skrzypek Grzegorz , Sadler Rohan , Paul Debajyoti 
Published: September 2010

AbstractA higher analytical precision of a stable isotope ratio mass spectrometer does not automatically guarantee accurate determination of the true isotope composition (δ‐value) of samples, since estimates of true δ‐values are obtained from the normalization of raw isotope data. We performed both Monte Carlo simulations and laboratory experiments to investigate aspects of error propagation during the normalization of carbon stable isotope data. We found that increasing both the number of different reference standards and the number of repetitions of each of these standards reduces the normalization error. A 50% reduction in the normalization error can be achieved over the two‐point normalization by either analyzing two standards four times each, or four standards two times each. If the true δ‐value of a sample is approximately known a priori, the normalization error may then be reduced through a targeted choice of locally optimal standards. However, the difference in improvement is minimal and, therefore, a more practical strategy is to use two or more standards covering the whole stable isotope scale. The selection of different sets of standards by different laboratories or for different batches of samples in the same laboratory may lead to significant differences in the normalized δ‐values of the same samples, leading to inconsistent results. Hence, the same set of standards should always be used for a particular element and a particular stable isotope analytical technique. Copyright © 2010 John Wiley & Sons, Ltd.
Marked difference in fragmentation between collision‐induced excitation and chemi‐excitation of keto esters produced from dioxetanes bearing a 4‐(benzothiazol‐2‐yl)‐3‐hydroxyphenyl moiety in negative‐mode matrix‐assisted laser desorption/ionization time‐of‐flight tandem mass spectrometry
Authors: Ijuin Hisako K. , Yamada Masaki , Ohashi Mamoru , Tanimura Masatoshi , Watanabe Nobuko , Matsumoto Masakatsu 
Published: September 2010

AbstractA dioxetane bearing a hydroxyphenyl group produces an unstable oxidoaryl anion by deprotonation which rapidly decomposes with accompanying emission of light effectively by the intramolecular charge‐transfer‐induced decomposition (CTID) mechanism. Although several mechanisms have been proposed to explain chemi‐excitation in CTID, strong experimental evidence is still lacking. In the course of our investigation to clarify the chemi‐excitation process, negative‐mode matrix‐assisted laser desorption/ionization time‐of‐flight collision‐induced dissociation tandem mass spectrometry (MALDI‐TOF‐CID‐MS/MS) was used to investigate the decomposition of bicyclic dioxetanes bearing a 4‐(benzothiazol‐2‐yl)‐3‐hydroxyphenyl moiety 1 and their related keto esters 2 in a gas phase. Dioxetanes 1 decomposed to give 2 in an electronically excited state, which underwent α‐cleavage of a ketone moiety, while authentic 2 (ground state) hardly showed fragmentation in MS1. On the other hand, 2 displayed fragment ions in CID‐MS/MS, though the fragmentation pattern was significantly different between 2a (R = tert‐butyl) and 2b–2d (R = isopropyl, ethyl and methyl, respectively): 2a exhibited mainly α‐cleavage of a ketone moiety, while 2b–2d showed β‐cleavage of the aromatic ester moiety. The marked difference in fragmentation between 2 (electronically excited state) produced directly from 1 and authentic 2 under CID was most likely due to the difference in the excitation processes: chemi‐excitation of 2 by CTID of 1 versus vibrational excitation of 2 induced by collision in MS/MS. Copyright © 2010 John Wiley & Sons, Ltd.
Role of the UV absorber as a matrix in matrix‐assisted laser desorption/ionization mass spectrometric analysis of a mixture of a UV absorber and a stabilizer
Authors: Im Song‐Hee , Choi Sung‐Seen 
Published: September 2010

AbstractA mixture of a UV absorber (Tinuvin 234 or Tinuvin 329) and a UV stabilizer (Tinuvin 770) was analyzed using matrix‐assisted laser desorption/ionization mass spectrometry (MALDI‐MS) without any matrix. Fragmentation patterns of the UV absorbers and stabilizer were also investigated. The mass spectra showed the [M+H]+ ions and some fragment ions. Tinuvin 234, Tinuvin 329, and Tinuvin 770 generated three (m/z 119, 370, 432), one (m/z 252), and two (m/z 124 and 140) fragment ions, repectively. These fragment ions can be used to identify the chemical structures of the UV absorbers and stabilizer. Since the UV absorber performed a role as the matrix, the ion abundance of the UV stabilizer was enhanced by mixing with the UV absorber. When organic materials extracted from polypropylene (PP) containing the UV absorber and stabilizer were directly analyzed using MALDI‐MS without any matrix, the protonated molecule of the UV stabilizer was detected in abundance but the product ions of the UV absorber were not observed. When 2,5‐dihydroxybenzoic acid was used as a matrix, the protonated molecule of the UV absorber was observed. Copyright © 2010 John Wiley & Sons, Ltd.