bluuebunny/crossref_metadata_2025 huggingface dataset:
Locoregional treatment of primary breast cancer
Authors: Kaufmann Manfred , Morrow Monica , von Minckwitz Gunter , Harris Jay R.
Published: January 2010

Guidelines for the locoregional treatment of primary breast cancer were last published by the US National Institutes of Health in 1991. Since then, new surgical and radiotherapeutic techniques have been developed, clinical trials have provided new evidence, and intriguing long‐term effects have emerged from global metadatabases. A revision of these guidelines is therefore necessary and timely. To address this concern, in October 2008, a group of opinion leaders from Austria, Denmark, France, Germany, Italy, the Netherlands, the United Kingdom, and the United States who have worked and published in the field of locoregional treatment met and collectively prepared and approved the described set of recommendations for the use of surgery and radiotherapy in primary breast cancer outside of clinical trials. Cancer 2010. © 2010 American Cancer Society.
Axillary sentinel lymph node biopsy after neoadjuvant chemotherapy for carcinoma of the breast
Authors: Schwartz Gordon F. , Tannebaum Jonathan E. , Jernigan Amelia M. , Palazzo Juan P.
Published: January 2010

BACKGROUND:

The timing and accuracy of axillary sentinel lymph node biopsy (SLNB) in patients who are receiving neoadjuvant chemotherapy (NACT) for breast cancer are controversial. To examine the accuracy of SLNB after NACT, the authors performed SLNB after chemotherapy on all of patients who received NACT at their institution starting in January 1997.

METHODS:

Seventy‐nine women who underwent NACT between 1997 and 2008 comprised this study and were divided as follows: 4 women had stage I disease, 60 women had stage II disease, and 15 women had stage III disease, including 10 women who had multicentric disease. Thirty‐nine women (49.4%) had clinical evidence of axillary metastasis (N1‐N2) at the time of diagnosis. The regimen, the duration of treatment, and the number of cycles of NACT depended on clinical response. The choice of breast conservation therapy or mastectomy was based on the patient's response to treatment and patient preference. All patients underwent SLNB after NACT.

RESULTS:

Seventy‐three patients underwent breast conservation therapy, and 6 patients underwent mastectomy. Sentinel lymph nodes were identified in 98.7% of patients (in 1 patient, SLNB failed to capture 1 proven axillary metastasis), and 29 patients underwent full axillary lymph node dissection. Fourteen patients (17.7%) had no residual carcinoma (invasive or ductal carcinoma in situ) in their breast, 5 patients (6.3%) had residual ductal carcinoma in situ (only), and 60 patients (75.9%) had residual invasive carcinoma. One false‐negative SLNB was reported in the group of 23 patients who underwent full axillary dissection after a negative SLNB. No patient had a subsequent axillary recurrence.

CONCLUSIONS:

SLNB after NACT was feasible in virtually all patients and accurately selected patients who required complete level I and II axillary dissection. NACT frequently downstaged the axilla, converting patients with N1‐N2 lymph node status to N0 status and also avoiding full axillary dissection in these patients. Cancer 2010. © 2010 American Cancer Society.
Synthesis and Photophysical Properties of Substituted Tris(phenylbenzimidazolinato) IrIII Carbene Complexes as a Blue Phosphorescent Material
Authors: Tsuchiya Kazuyoshi , Yagai Shiki , Kitamura Akihide , Karatsu Takashi , Endo Kyoko , Mizukami Junji , Akiyama Seiji , Yabe Masayoshi
Published: January 2010

Substitution effects on the photoluminescence and electrochemical properties and the photochemical stability of tris(phenylbenzimidazolinato)IrIII complexes were investigated. Facial and meridional isomers of a series of complexes having the general structure of Ir(C C)3, where (C C) is (4‐R‐phenyl)benzimidazolinato (R = H, CF3, CN, OCH3), were prepared. They are abbreviated to Ir(pmb)3 (1), Ir(CF3pmb)3 (2), Ir(CNpmb)3 (3), and Ir(Opmb)3 (4), respectively. Electron‐donating or ‐withdrawing groups on the phenyl ring lead to both higher emission quantum yields and longer emission lifetimes compared to those of 1 in each mer and fac series. Particularly, the emission quantum yields were high in the cases of 2a, 3a, 3b, and 4a. No photochemical isomerization was observed in both fac‐ (a) and mer (b) isomers of Ir(pmb)3, Ir(CF3pmb)3, and Ir(CNpmb)3 on irradiation with a 313‐nm wavelength light from a 400 W mercury lamp for more than 20 h. All complexes excluding fac‐Ir(pmb)3 (1a) show excellent photochemical stability in degassed anhydrous thf solution. The locations of the HOMO and LUMO and the lowest excitation energy of these complexes were investigated by DFT and TD‐DFT calculations on fac‐ and mer‐Ir(Opmb)3 (4a and 4b). The HOMO is mainly localized over the Ir metal center and the phenyl moiety, and the LUMO mainly localized over the benzimidazole moiety. The calculated lowest excitation energies agree with the experimental values. The X‐ray single crystal structures obtained for fac‐Ir(CF3pmb)3 (2a) and mer‐Ir(Opmb)3 (4b) are also discussed.
Luminescence Properties of Redispersible Tb3+‐Doped GdPO4 Nanoparticles Prepared by an Ethylene Glycol Route
Authors: Yaiphaba Ningombam , Ningthoujam Raghumani Singh , Singh Nongmaithem Rajmuhon , Vatsa Rajesh Kumar
Published: January 2010

Nanoparticles of Tb3+‐doped GdPO4 (Tb3+ = 0, 2, 5, 7, 10, and 20 atom‐%) have been prepared at a relatively low temperature of 160 °C in ethylene glycol medium. The particles crystallize in a monoclinic structure with an average crystallite size of 30–50 nm. From the luminescence study of Tb3+‐doped GdPO4, the magnetic dipole transition (5D4 → 7F5) at 545 nm (green) was found to be more prominent than the electric dipole transition (5D4 → 7F6) at 484 nm (blue). Maximum luminescence intensity and lifetime was observed for 7 atom‐% Tb3+. Above 7 atom‐% Tb3+, a decrease in luminescence was observed. This has been attributed to a concentration‐quenching effect due to the cross‐relaxation among Tb3+ ions. The highest luminescence intensity of Tb3+ was observed after excitation at 274 nm (8S7/2 → 6I11/2 of Gd3+) among various excitation wavelengths (including f–f absorptions of Tb3+). This is due to an efficient transfer of energy from Gd3+ to Tb3+ that shows GdPO4 to be a potential host for Tb3+. These nanoparticles are found to be redispersible in water and ethanol and are incorporated into polyvinyl alcohol film homogeneously. This film showed bright green emission.
Hydrocarbon Oxygenation by Metal Nitrite Adducts: Theoretical Comparison with Ferryl‐Based Oxygenation Agents
Authors: Silaghi‐Dumitrescu Radu , Makarov Sergei V.
Published: January 2010

Metal nitrite adducts can, under certain conditions, insert one of their oxygen atoms into hydrocarbons. This reaction is to some extent reminiscent of the process whereby high‐valent ferryl (formally FeIV=O) species such as compound I in hemoproteins also insert an oxygen atom into hydrocarbons. Density functional theory (DFT) data are shown here, examining the oxygenation ability of ferrous and ferric nitrite adducts in octahedral coordination environments modeling those seen in hemoproteins where such adducts are well characterized. A comparison of these results with those obtained with similar methods on formal FeV–oxido models of hemoprotein compound I models relevant for such enzymes as cytochrome P450 and chloroperoxidase reveals a key role of the redox potential in dictating oxygenation ability, in good agreement with interpretations previously given by Green and co‐workers.
Syntheses and Physicochemical Properties of Low‐Melting Salts Based on VOF4– and MoOF5–, and the Molecular Geometries of the Dimeric (VOF4–)2 and Mo2O4F62– Anions
Authors: Kanatani Takatsugu , Matsumoto Kazuhiko , Hagiwara Rika
Published: January 2010

1‐Ethyl‐3‐methylimidazolium (EMIm+) and N‐butylpyridinium (BPy+) salts of the oxotetrafluorovanadate (VOF4–) and oxopentafluoromolybdate (MoOF5–) anions with low melting temperatures have been synthesized by the reactions of the corresponding fluorohydrogenate ionic liquids and metal oxide fluoride. Differential scanning calorimetry reveals that the melting points of EMImVOF4, BPyVOF4, and BPyMoOF5 are 348, 346, and 346 K, respectively, whereas the room‐temperature ionic liquid EMImMoOF5 only exhibits a glass transition at 190 K. Density, viscosity, and ionic conductivity of EMImMoOF5 are 1.76 g cm–1, 86 cP, and 5.1 mS cm–1 at 298 K, respectively. The cathode and anode limits of EMImMoOF5 are –0.3 and +1.4 V (vs. Ag+/Ag), respectively. The molecular geometries of the VOF4– and Mo2O4F62– anions have been determined by single‐crystal X‐ray diffraction, the latter being obtained by the hydrolysis of MoOF5–. The two VOF4– anions in EMImVOF4 interact with each other through two highly asymmetric V–F···V bridges with V–F and V···F distances of 1.8633(7) and 2.3786(7) Å, respectively. A dinuclear anion in (BPy)2Mo2O4F6 possesses two symmetric Mo–F–Mo bonds with Mo–F lengths of 2.1691(12) and 2.1829(11) Å.
A Straightforward Entry to 7‐Azabicyclo[2.2.1]heptane‐1‐carbonitriles in the Synthesis of Novel Epibatidine Analogues
Authors: Heugebaert Thomas , Van Hevele Joke , Couck Wouter , Bruggeman Vicky , Van der Jeught Sarah , Masschelein Kurt , Stevens Christian V.
Published: January 2010

This paper presents the synthesis of epibatidine analogues by a straightforward one‐pot method for the synthesis of 7‐azabicyclo[2.2.1]heptane‐1‐carbonitriles, starting from cyclohexanones bearing a leaving group at the 4‐position. In situ imine formation, followed by reversible cyanide addition, allows complete conversion of 4‐(mesyloxy)cyclohexanone to the bicyclic core. Elaboration of the introduced nitrile functionality and deprotection of the tertiary amine leads to five new epibatidine analogues.
Horner–Wadsworth–Emmons Reaction of Unprotected Sugars in Water or in the Absence of Any Solvent: One‐Step Access to C‐Glycoside Amphiphiles
Authors: Ranoux Adeline , Lemiègre Loïc , Benoit Maud , Guégan Jean‐Paul , Benvegnu Thierry
Published: January 2010

The synthesis of C‐glycosides in water or in the absence of any solvent from free sugars and β‐keto phosphonates is reported. The methodology permits a one‐step access to C‐glycoside amphiphiles in moderate‐to‐good yields. The selectivity (α/β and furanoside/pyranoside) is discussed and a process that leads to pure β‐C‐pyranosides is also described.
Sources and sediment yield from a rural catchment in humid temperate environment, northwest Spain
Authors: Rodríguez‐Blanco M. L. , Taboada‐Castro M. M. , Taboada‐Castro M. T.
Published: January 2010

A study was carried out on a rural catchment located in northwest Spain to examine the sediment yield from the catchment by measuring suspended sediments during rainfall events. Within the catchment regular surveys were conducted to obtain data on the suspended sediment sources. Important variations in sediment load were detected at event scale (0·3–21·0 Mg); some of these can be explained in terms of event size, antecedent conditions, rainfall distribution and soil surface erosion. To study the variables controlling suspended sediment yield during the events in the catchment, several event and pre‐event variables were calculated for all events. The sediment load is strongly influenced by discharge variables. During the events discharge–suspended sediments were also analysed. When the soil surface was unprotected, the formation of rills and ephemeral gullies on agricultural land at the catchment head was an important source of suspended sediments in the catchment. Copyright © 2010 John Wiley & Sons, Ltd.
Towards a protocol for laser scanning of rock surfaces
Authors: Schaefer Martin , Inkpen Robert
Published: January 2010

The precision of height measurements derived from laser scanning a weathered rock surface was analysed. Different registration methods for comparing surfaces to deduce weathering were assessed and the most precise was found to be the method that used registration shapes as control, located in different planes relative to the scanned surface. In addition, the different sources of error in scanning precision were assessed by varying factors such as scan distance, lens configuration, scan angle and the nature of the topography being scanned. From this analysis it was possible to suggest what the optimal scanning conditions were for this particular experimental set‐up. The procedures outlined for assessing errors in the precision of height measurements are transferable to other scanning studies. Copyright © 2010 John Wiley & Sons, Ltd.
Tracing sediment redistribution across a break in slope using rare earth elements
Authors: Michaelides Katerina , Ibraim Ioana , Nord Guillaume , Esteves Michel
Published: January 2010

Experimentally determined spatial patterns of soil redistribution across a break in slope derived using 10 rare earth element (REE) oxides as sediment tracers are presented. An erosion experiment was conducted using simulated rainfall within a laboratory slope model measuring 2·5 m wide by 6 m long with a gradient of 15° declining to 2°. Soil was tagged with multiple REE and placed in different locations over the slope and at the end of the experiment REE concentrations were measured in samples collected spatially. A new method was developed to quantify the erosion and deposition depths spatially, the relative source contributions to deposited sediment and the sediment transport distances. Particle‐size selectivity over an area of net deposition was also investigated, by combining downslope changes in particle‐size distributions with changes in sediment REE composition within a flow pathway. During the experiment, the surface morphology evolved through upslope propagation of rill headcuts, which gradually incised the different REE‐tagged zones and led to sediment deposition at the break in slope and the development of a fan extending over the shallow slope segment. The spatial patterns in REE concentrations, the derived erosion and deposition depths, the relative source contributions to deposition zones and the sediment transport distances, corroborate the morphological observations and demonstrate the potential of using REE for quantifying sediment transport processes. Copyright © 2010 John Wiley & Sons, Ltd.
Significance of AMS in multilayer systems in fold‐and‐thrust belts. A case study from the Eocene turbidites in the southern Pyrenees (Spain)
Authors: Anchuela Ó. Pueyo , Imaz A. Gil , Juan A. Pocoví
Published: January 2010

The anisotropy of magnetic susceptibility (AMS), and other magnetic fabric techniques have been tested in a multilayer system of Eocene turbidites from the Southern Pyrenees. The identified magnetic fabrics can be grouped into (1) fabrics related to layer parallel shortening (LPS) acquired in pre‐folding conditions, (2) fabrics related to cleavage development and (3) fabrics related to shear parallel to the thrust movement and intermediate cases. AMS depends on (i) the paramagnetic contribution to the susceptibility and (ii) on the position of sites in the fold‐thrust belt. The study of sites in the southern Pyrenees shows that the processes underwent by rocks and recorded by the different magnetic fabrics are independent from their lithology. The most paramagnetic samples show fabrics related to LPS and cleavage, whereas shear parallel to the thrust movement is observed in the most ferromagnetic ones. Measurement of other magnetic fabrics shows the presence of more than one magnetic fabric at site scale with independence of the AMS ellipsoid aspect ratio. The intersection lineation fabrics are interpreted as composite magnetic fabrics, developing a progression between LPS, intersection fabrics (from magnetic foliation parallel to bedding, to magnetic foliation parallel to cleavage) and magnetic axes switching from K1 parallel to the intersection lineation, to K1 parallel to the dip direction of cleavage or amplification direction. This change can be inferred from the transition from the outer (farther from the Axial Zone) to inner domains of the studied zone, consistent with the intensity of cleavage at outcrop scale. Copyright © 2010 John Wiley & Sons, Ltd.
Folding in orogens: a case study in the northern Iberian Variscan Belt
Authors: Bastida F. , Aller J. , Pulgar J. A. , Toimil N. C. , Fernández F. J. , Bobillo‐Ares N. C. , Menéndez C. O.
Published: January 2010

Folding during the Variscan deformation in NW Iberia has been analysed from the foreland to the hinterland of the orogen using several geometrical techniques complemented by the numerical simulation of kinematical folding mechanisms with the aid of a computer program (‘FoldModeler’). In the foreland, folds are related to thrusts; in the inner zones, folds can be attributed to three deformation phases.D1andD2involved deformation with horizontal foreland‐directed displacements.D1gave rise to closed or tight folds (F1) and cleavage (S1); development of large recumbentF1folds in the hinterland required a simple shear regime and a final coaxial strain component with sub‐vertical maximum shortening. Strain incompatibilities at deeper levels, together with high temperatures, favoured the concentration of ductile deformation in shear zones and development of mylonites duringD2. Local flow instabilities generatedF2folds that were passively amplified by a combination of simple shear, coaxial strain and area change.D3involved a change to a regime with dominant coaxial deformation and a sub‐horizontal maximum shortening; it gave rise to upright or steeply inclined folds (F3). Development ofD3structures was heterogeneous and depended on the previous dip of the bedding andS1, the presence or emplacement of granitoids, the stacking of thrust sheets or the previous development of large faults bringing into contact rocks with different competence.D3structures are mainly concentrated in metapelitic areas and appear distributed in bands on several scales. On a small scale, tectonic banding appears associated with small folds as a result of pressure‐solution processes. In areas with sub‐verticalS1, later sub‐horizontal kink bands were formed by a vertical compression. Copyright © 2010 John Wiley & Sons, Ltd.
The role of the superior temporal sulcus and the mirror neuron system in imitation
Authors: Molenberghs Pascal , Brander Christopher , Mattingley Jason B. , Cunnington Ross
Published: January 2010

It has been suggested that in humans the mirror neuron system provides a neural substrate for imitation behaviour, but the relative contributions of different brain regions to the imitation of manual actions is still a matter of debate. To investigate the role of the mirror neuron system in imitation we used fMRI to examine patterns of neural activity under four different conditions: passive observation of a pantomimed action (e.g., hammering a nail); (2) imitation of an observed action; (3) execution of an action in response to a word cue; and (4) self‐selected execution of an action. A network of cortical areas, including the left supramarginal gyrus, left superior parietal lobule, left dorsal premotor area and bilateral superior temporal sulcus (STS), was significantly active across all four conditions. Crucially, within this network the STS bilaterally was the only region in which activity was significantly greater for action imitation than for the passive observation and execution conditions. We suggest that the role of the STS in imitation is not merely to passively register observed biological motion, but rather to actively represent visuomotor correspondences between one's own actions and the actions of others. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.
“Brain‐reading” of perceived colors reveals a feature mixing mechanism underlying perceptual filling‐in in cortical area V1
Authors: Hsieh Po‐Jang , Tse Peter U.
Published: January 2010

Visual filling‐in occurs when a retinally stabilized object undergoes perceptual fading. As the term “filling‐in” implies, it is commonly believed that information about the apparently vanished object is lost and replaced solely by information arising from the surrounding background. Here we report multivoxel pattern analysis fMRI data that challenge this long‐held belief. When subjects view blue disks on a red background while fixating, the stimulus and background appear to turn a uniform purple upon perceptual fading, suggesting that a feature mixing mechanism may underlie color filling‐in. We find that ensemble fMRI signals in retinotopic visual areas reliably predict (i) which of three colors a subject reports seeing; (ii) whether a subject is in a perceptually filled‐in state or not; and (iii) furthermore, while subjects are in the perceptual state of filling‐in, the BOLD signal activation pattern in the sub‐areas of V1 corresponding to the location of the blue disks behaves as if subjects are in fact viewing a perceptually mixed color (purple), rather than the color of the disks (blue) or the color of the background (red). These results imply that the mechanism of filling‐in in stimuli in which figure and background surfaces are equated is a process of “feature mixing”, not “feature replacement”. These data indicate that feature mixing may involve cortical areas as early as V1. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.
Brain‐derived neurotrophic factor expression is increased in the hippocampus of 5‐HT2C receptor knockout mice
Authors: Hill Rachel A. , Murray Simon S. , Halley Paul G. , Binder Michele D. , Martin Sally J. , van den Buuse Maarten
Published: January 2010

Several studies have suggested a close interaction between serotonin (5‐HT) and BDNF; however, little is known of the specific relationship between BDNF and the 5‐HT2C receptor. Therefore, in this study we investigated BDNF expression in 5‐HT2C receptor knockout mice (5‐HT2CKO). We also assessed functional consequences of any changes in BDNF using a behavioral test battery. Western blot analysis demonstrated a significant 2.2‐fold increase in the expression of the mature form of BDNF in 5‐HT2CKO mice when compared with wild‐type controls (WT) in the hippocampus (P = 0.008), but not frontal cortex or striatum. No differences in the expression of the pro‐BDNF isoform were found, and the ratio of mature/pro BDNF was significantly increased in 5‐HT2CKO (P = 0.003). BDNF mRNA expression in the hippocampus was not different between the genotypes. Hence, increased mature BDNF levels in 5‐HT2CKO hippocampus are most likely due to increased extracellular cleavage rates of pro‐BDNF to its mature form. Protein expression of the BDNF receptor, tropomycin‐related receptor B (TrkB), was also unchanged in the hippocampus, frontal cortex and striatum. With repeated training in a 10‐day win‐shift radial arm maze task, 5‐HT2CKO and WT showed similar decreases of the number of working memory and reference memory errors. In addition, no genotype specific differences were observed for passive or active avoidance learning. 5‐HT2CKO showed modest locomotor hyperactivity but no differences in tests for anxiety, sensorimotor gating, or depressive‐like behaviors; however, in the tail suspension test 5‐HT2CKO showed significantly reduced climbing (P < 0.05). In conclusion, loss of 5‐HT2C receptor expression leads to a marked and selective increase in levels of the mature form of BDNF in the hippocampus. Despite this marked increase, 5‐HT2CKO show only subtle behavioral changes. © 2010 Wiley‐Liss, Inc.
Endogenous nociceptin/orphanin‐fq in the dorsal hippocampus facilitates despair‐related behavior
Authors: Goeldner Celia , Reiss David , Kieffer Brigitte L. , Ouagazzal Abdel‐Mouttalib
Published: January 2010

Nociceptin/orphanin‐FQ (N/OFQ) peptide and its receptor (NOP: N/OFQ opioid peptide receptor) are highly expressed in the hippocampus, but their functional role remains poorly understood. We recently showed that hippocampal N/OFQ inhibits learning and memory abilities in mice. Here, we investigated whether the endogenous peptide also regulated emotional responses at the level of the hippocampus. Bilateral infusions of the selective NOP receptor antagonist, UFP‐101 (1–3 nmol/side), into the dorsal hippocampus produced antidepressant‐like effects in the mouse forced swim and tail suspension tests comparable with those obtained with the prototypical antidepressant, fluoxetine (10–30 mg/kg, intraperitoneal). In the light‐dark test, neither UFP‐101 (1–3 nmol/side) nor N/OFQ peptide (1–3 nmol/side) modified anxiety measures when injected at behaviorally active doses in the dorsal hippocampus. These findings show a clear dissociation in the involvement of hippocampal N/OFQ system in anxiety‐ and despair‐related behaviors. We conclude that the dorsal hippocampus is a brain region in which there is an important N/OFQ modulation of mnemonic processes and adaptive emotional responses associated to despair states. © 2010 Wiley‐Liss, Inc.
Overexpression of the oncogenic signal transducer Gab2 occurs early in breast cancer development
Authors: Fleuren Emmy D.G. , O'Toole Sandra , Millar Ewan K. , McNeil Catriona , Lopez‐Knowles Elena , Boulghourjian Alice , Croucher David R. , Schramek Daniel , Brummer Tilman , Penninger Josef M. , Sutherland Robert L. , Daly Roger J.
Published: January 2010

Gab2, a docking‐type signaling protein with demonstrated oncogenic potential, is overexpressed in breast cancer, but its prognostic significance and role in disease evolution remain unclear. Immunohistochemical detection of Gab2 in a large cohort of primary human breast cancers of known outcome revealed that while Gab2 expression was positively correlated with increased tumor grade, it did not correlate with disease recurrence or breast cancer‐related death in the total cohort or in patients stratified according to lymph node, estrogen receptor (ER) or HER2 status. Interestingly, analysis of a “progression series” that included premalignant and preinvasive breast lesions as well as samples of metastatic disease revealed that Gab2 expression was significantly enhanced in the earliest lesion examined, usual ductal hyperplasia, with a further increase detected in ductal carcinoma in situ (DCIS). Furthermore, expression was less in invasive cancers and lymph node metastases than in DCIS, but still higher than in normal breast. These findings indicate that while Gab2 expression is not prognostic in breast cancer, its role in early disease evolution warrants further analysis, as Gab2 and its effectors may provide targets for novel strategies aimed at preventing breast cancer development.
New implementations of MRCI in semiempirical frameworks
Authors: Lei Yibo , Suo Bingbing , Dou Yusheng , Wang Yubin , Wen Zhenyi
Published: January 2010

Multireference configuration interaction with single and double excitations (MRCISD) as well as its analytic CI gradients has been implemented in the semiempirical framework. The hole‐particle symmetry and a mixed driven model for computing coupling coefficients have been used in the new code that allows us to perform MRCI and gradient calculations with higher efficiency and less storage requirements. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
Calculation of chemical reaction energies using the AM05 density functional
Authors: Muller Richard P. , Mattsson Ann E. , Janssen Curtis L.
Published: January 2010

We present results that compare the accuracy of the AM05 density functional (Armiento and Mattsson, Phys Rev B 2005, 72, 085108; Mattsson et al., J Chem Phys 2008, 128, 084714) to a set of chemical reaction energies. The reactions were generated from the singlet species in the well‐known G2 test suite (Curtiss et al., J Chem Phys 1991; Curtiss et al., J Chem Phys 1997; 106, 1063). Our results show that, in general, the AM05 functional performs nearly as well as the other “pure” density functionals, but none of these perform as well as the hybrid B3LYP functional. These results are nonetheless encouraging because the AM05 functional arises from very simple assumptions, and does not require the calculation of the Hartree‐Fock exchange integrals. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
Flexible protein‐protein docking based on Best‐First search algorithm
Authors: Noy Efrat , Goldblum Amiram
Published: January 2010

We developed a new high resolution protein‐protein docking method based on Best‐First search algorithm that loosely imitates protein‐protein associations. The method operates in two stages: first, we perform a rigid search on the unbound proteins. Second, we search alternately on rigid and flexible degrees of freedom starting from multiple configurations from the rigid search. Both stages use heuristics added to the energy function, which causes the proteins to rapidly approach each other and remain adjacent, while optimizing on the energy. The method deals with backbone flexibility explicitly by searching over ensembles of conformations generated before docking. We ran the rigid docking stage on 66 complexes and grouped the results into four classes according to evaluation criteria used in Critical Assessment of Predicted Interactions (CAPRI; “high,” “medium,” “acceptable,” and “incorrect”). Our method found medium binding conformations for 26% of the complexes and acceptable for additional 44% among the top 10 configurations. Considering all the configurations, we found medium binding conformations for 55% of the complexes and acceptable for additional 39% of the complexes. Introducing side‐chains flexibility in the second stage improves the best found binding conformation but harms the ranking. However, introducing side‐chains and backbone flexibility improve both the best found binding conformation and the best found conformation in the top 10. Our approach is a basis for incorporating multiple flexible motions into protein‐protein docking and is of interest even with the current use of a simple energy function. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
The choice of internal coordinates in complex chemical systems
Authors: Németh Károly , Challacombe Matt , Van Veenendaal Michel
Published: January 2010

This article presents several considerations for the appropriate choice of internal coordinates in various complex chemical systems. The appropriate and black box recognition of internal coordinates is of fundamental importance for the extension of internal coordinate algorithms to all fields where previously Cartesian coordinates were the preferred means of geometry manipulations. Such fields range from local and global geometry optimizations to molecular dynamics as applied to a wide variety of chemical systems. We present a robust algorithm that is capable to quickly determine the appropriate choice of internal coordinates in a wide range of atomic arrangements. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010
Prolidase activity and oxidative status in patients with thalassemia major
Authors: Cakmak Alpay , Soker Murat , Koc Ahmet , Aksoy Nurten
Published: January 2010

Aim: Prolidase is a specific imidodipeptidase involved in collagen degradation. The increase in the enzyme activity is believed to be correlated with the increased intensity of collagen degradation. The study aimed to evaluate the relationship between prolidase activity and oxidative status in patients with thalassemia major. Methods: Comparison was made between 87 patients diagnosed with thalassemia major and 33 healthy children of similar age and gender. Mean age of the subjects was 7.5±4.3 years in the group of patients with thalassemia major and 8.9±3.1 years in the control group. Serum prolidase activity was measured spectrophotometrically. Oxidative status was determined using total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI) measurement. Results: Prolidase activity was significantly increased in patients with thalassemia major (53.7±8.7 U/l) compared to the control group (49.2±7.2 U/l, P<0.001). TOS was significantly increased in the patient group (5.31±3.14 mmol H2O2 equiv./l) compared to the control group (3.49±2.98 μmol H2O2 equiv./l) and the OSI was also significantly increased in the patient group (3.86±3.28 arbitrary unit) compared to the control group (2.53±2.70 arbitrary unit) (P<0.0001 and P<0.001, respectively), while there were no significant differences between the patient (1.61±0.30 μmol Trolox equiv./l) and control (1.64±0.33 μmol Trolox equiv./l) groups with respect to TAC. Conclusion: Significant increases in prolidase activity in patients with thalassemia major may constitute a key parameter in demonstrating a disorder of the collagen metabolism. J. Clin. Lab. Anal. 24:6–11, 2010. © 2010 Wiley‐Liss, Inc.
Correlates of NT‐proBNP concentration in patients with essential hypertension in absence of congestive heart failure
Authors: Toda Keizo , Sato Yukihito , Hara Tomoko , Hijiya Kenro , Kaneko Ryutaro , Okada Tatuo , Takatsu Yoshiki , Fujiwara Hisayoshi , Iwasaki Toshiaki
Published: January 2010

Background: N‐terminal proBNP (NT‐proBNP) is widely used as a diagnostic biomarker and for the risk stratification of patients with heart failure (HF). Its role in the evaluation of patients with essential hypertension (EHT) is less clear. We examined the relationship between NT‐proBNP concentrations and various clinical characteristics in hypertensive patients without HF. Methods: This study included 186 consecutive patients with EHT and no history of HF, ischemic heart disease, or atrial fibrillation. Single and multiple variable regression analyses were performed in search of clinical correlates of NT‐proBNP concentrations. Results: In patients with EHT, median serum concentration of NT‐proBNP was 73 pg/ml, and interquartile range (IQR) was 40–128 pg/ml. NT‐proBNP was significantly higher (P<0.001) in women (87 pg/ml; IQR 55–137 pg/ml) than in men (52 pg/ml; IQR 24–115 pg/ml). Age (r=0.371, P<0.001), precordial QRS voltage (r=0.223, P<0.001), hemoglobin (Hgb) concentration, (r=−0.208, P=0.023) and estimated glomerular filtration rate (r=−0.139, P=0.044) were correlated with log‐transformed NT‐proBNP by multiple variable analysis. In men, age (r=0.453, P<0.001) and QRS voltage (r=0.283, P=0.004), and in women age (r=0.299, P=0.006), QRS voltage (r=0.212, P=0.019), Hgb (r=−0.182, P=0.049), and estimated glomerular filtration rate (r=−0.272, P=0.009) were correlated with serum concentrations of NT‐proBNP. Conclusions: Age, gender, Hgb, left ventricular hypertrophy and renal function were correlated with NT‐proBNP in patients with EHT. J. Clin. Lab. Anal. 24:12–16, 2010. © 2010 Wiley‐Liss, Inc.
Characterization of group A rotavirus infections in adolescents and adults from Pune, India: 1993–1996 and 2004–2007
Authors: Tatte Vaishali S. , Gentsch Jon R. , Chitambar Shobha D.
Published: January 2010

A total of 1,591 fecal specimens were collected in 1993–1996 and 2004–2007 from adolescents and adults with acute gastroenteritis in Pune, India for detection and characterization of rotavirus. At the two time points, group A rotavirus was detected in 8.6% and 16.2% of the adolescents and 5.2% and 17.2% of the adults, respectively. Reverse transcription‐PCR with consensus primers followed by multiplex genotyping PCR detected common strains G1P[8], G2P[4], G3P[8], and G4P[8] in a total of 53.1% of the samples from 1993 to 1996, while the only prevalent strain identified in 2004–2007 was G2P[4] (23.5% of total). Uncommon rotavirus strains (G1P[4], G2P[8] G9P[6]/P[4]) increased from 7.8% (1993–1996) to 41.2% (2004–2007), while the prevalence of mixed rotavirus infections was high (39%/35%) at both time points. Mixed infections detected by multiplex PCR were confirmed by sequencing two or more individual genotype‐specific PCR products of the VP7 and VP4 genes from the same sample. Phylogenetic analysis of the sequences showed circulation of a heterogeneous rotavirus strain population comprising genotypes G1 (lineages I and IIb), G2 (lineages I and IIb), G4 (lineage Ia), P[4] (lineages P[4]‐5 and P[4]‐1), P[8] (lineages P[8]‐II and P[8]‐III), and P[6] (M37‐like lineage). The VP6 gene sequences of the nontypeable strains were most homologous to animal strains. This study documents the molecular epidemiology of rotavirus strains in adolescents and adults in India, and suggests that it may be important to monitor these strains over time for the potential impact on rotavirus vaccines under development for use in the Indian population. J. Med. Virol. 82:519–527, 2010. © 2010 Wiley‐Liss, Inc.
A new panel of NS1 antibodies for easy detection and titration of influenza A virus
Authors: Tan Zhihao , Akerstrom Sara , Wee Boon Yu , Lal Sunil K. , Mirazimi Ali , Tan Yee‐Joo
Published: January 2010

The non‐structural protein NS1 of the influenza A virus is a good target for the development of diagnostic assays. In this study, three NS1 monoclonal antibodies (mAbs) were generated by using recombinant NS1 protein of H5N1 virus and found to bind both the native and denatured forms of NS1. Two of the mAbs, 6A4 and 2H6, bind NS1 of three different strains of influenza A virus, namely H1N1, H3N2, and H5N1. Epitope mapping revealed that residues 42–53 of H5N1 NS1 are essential for the interaction with both mAbs. Between the three strains, there is only one amino acid difference in this domain, which is consistent with the observed cross‐reactivities. On the other hand, mAb 1G1 binds to residues 206–215 of H5N1 NS1 and does not bind NS1 of H1N1 or H3N2. Furthermore, all three mAbs detected NS1 proteins expressed in virus infected MDCK cells and indirect immunofluorescence staining with mAbs 6A4 and 2H6 provided an alternative method for viral titer determination. Quantifying the numbers of fluorescent foci units yielded viral titers for three different isolates of H5N1 virus that are highly comparable to that obtained by observing cytopathic effect induced by virus infection. Importantly, this alternative method yields results at 1 day post‐infection while the conventional method using cytopathic effect yields results at 3 days post‐infection. The results showed that this new panel of NS1 antibodies can detect NS1 protein expressed during viral infection and can be used for fast and easy titration of influenza A virus. J. Med. Virol. 82:467–475, 2010. © 2010 Wiley‐Liss, Inc.
Genotypic and clinicopathological characterization of Kaposi's sarcoma‐associated herpesvirus infection in Japan
Authors: Kanno Takayuki , Sato Yuko , Nakamura Tomoyuki , Sakamoto Kouta , Sata Tetsutaro , Katano Harutaka
Published: January 2010

Kaposi's sarcoma‐associated herpesvirus (KSHV) is related causally to Kaposi's sarcoma, primary effusion lymphoma, and a subset of cases of multicentric Castleman's disease. As the numbers of acquired immunodeficiency syndrome (AIDS) patients have increased, KSHV‐associated diseases have also increased in Japan. Sporadic cases of classic Kaposi's sarcoma have also been reported in Japan. In the present study, the clinicopathological characteristics of 75 samples, comprising 68 cases of Kaposi's sarcoma, 5 cases of primary effusion lymphoma, and 5 cases of multicentric Castleman's disease were investigated. All of these cases were positive for KSHV by immunohistochemistry or PCR analysis. All fifty‐two of the AIDS‐associated Kaposi's sarcoma cases were males, whereas 7 of the 13 non‐AIDS‐associated Kaposi's sarcoma cases were females. The mean age of patients with AIDS‐associated Kaposi's sarcoma or primary effusion lymphoma was 46 years, whereas the mean age of patients with non‐AIDS‐associated Kaposi's sarcoma or primary effusion lymphoma was 71.8 and 97.5, respectively. KSHV genotypes were determined based on the sequence of variable region 1 in the K1 gene. Genotypes A and C of KSHV were detected in both AIDS‐ and non‐AIDS‐associated Kaposi's sarcoma. Genotype A was detected more frequently in AIDS‐associated cases than non‐AIDS‐associated cases, suggesting that genotype C is broadly distributed in Japan, and genotype A spreads among AIDS patients. Genotype D was detected only in non‐AIDS‐associated Kaposi's sarcoma. These data confirmed the difference between AIDS‐ and non‐AIDS‐associated KSHV diseases with regard to age of onset, gender, and genotypes in Japan. J. Med. Virol. 82:400–406, 2010. © 2010 Wiley‐Liss, Inc.
Association of candidate susceptible loci with chronic infection with hepatitis B virus in a Chinese population
Authors: Chen Ding‐Qiang , Zeng Yong , Zhou Jie , Yang Ling , Jiang Shibo , Huang Jian‐Dong , Lu Liwei , Zheng Bo‐Jian
Published: January 2010

A number of genetic loci have been proposed to be associated with persistent hepatitis B virus (HBV) infection. This study aimed to evaluate the association and interaction of susceptible genes with HBV persistence in a Chinese population. A total of 17 polymorphisms in 9 candidate genes were studied in 361 Chinese chronic hepatitis B patients and 304 patients who recovered spontaneously. Distributions of susceptible polymorphisms were examined in healthy Chinese and Caucasian populations. Gene–gene interactions were tested by the multifactor dimensionality reduction (MDR) method. The TNF −308 G/G genotype and G allele, IL‐10RB codon 47 A allele, and MCP‐1 −2518 G/G genotype and G allele were more frequent in patients than controls (P < 0.01, after multiple corrections Pc < 0.05), while the frequencies of TNF −308 A/G genotype and IL‐10 −592 A/A genotype were significantly higher in controls than in the patient group (Pc < 0.05). The frequencies of the risk allele MCP‐1 −2518 G and CTLA4 6230 G were much higher in Chinese than in the Caucasian groups (P < 0.001). An interaction between CCR5 −2459, TNFA −863, IL‐10RB codon 47, and MCP‐1 −2518 was detected by MDR (P = 0.001). The results indicate that genetic determinants may affect the outcome of HBV infection in both independent and synergic manners. J. Med. Virol. 82:371–378, 2010. © 2010 Wiley‐Liss, Inc.
Immunohistochemical expression of HER1, HER3, and HER4 in HER2‐positive breast cancer patients treated with trastuzumab‐containing neoadjuvant chemotherapy
Authors: Yonemori Kan , Tsuta Koji , Shimizu Chikako , Hatanaka Yutaka , Hirakawa Akihiro , Ono Makiko , Kouno Tsutomu , Katsumata Noriyuki , Ando Masashi , Tamura Kenji , Hasegawa Tadashi , Kinoshita Takayuki , Fujiwara Yasuhiro
Published: January 2010

Background and Objectives

The aim of the present study was to examine the association between the expression of human epidermal receptor (HER) 1, HER3, and HER4 and pathologic complete response (pCR) in HER2‐positive patients treated with trastuzumab‐containing neo‐adjuvant chemotherapy.

Methods

Immunohistochemical analyses of HER1, HER3, and HER4 were performed using tumor specimens obtained from patients treated with trastuzumab‐containing neoadjuvant chemotherapy. The staining intensity of each biomarker was evaluated, and the correlations between the immunohistochemical profiles and pCR were examined.

Results

The present study included 44 patients with HER2‐positive breast cancer treated with trastuzumab‐containing neo‐adjuvant chemotherapy. Seventeen patients achieved a pCR. The expressions of HER1, HER3, and HER4 were observed in 18.2%, 27.3%, and 18.2% of the specimens, respectively. A marginally significant negative correlation between the expression of HER1 and pCR was observed, irrespective of the expression of HER3 and HER4, whereas the expressions of HER3 and HER4 were not significantly correlated with pCR.

Conclusion

The expression of HER1 might be an independently negative predictor of pCR in HER2‐positive breast cancer patients treated with trastuzumab‐containing neoadjuvant chemotherapy. J. Surg. Oncol. 2010; 101:222–227. © 2010 Wiley‐Liss, Inc.
Development, validation, and implementation of capillary gel electrophoresis as a replacement for SDS‐PAGE for purity analysis of IgG2 mAbs
Authors: Lacher Nathan A. , Roberts Rachel K. , He Yan , Cargill Holly , Kearns Katrina M. , Holovics Heidi , Ruesch Margaret N.
Published: January 2010

Capillary gel electrophoresis (CGE) methods with UV detection were developed for reduced and non‐reduced mAb analysis. These methods can be used to evaluate mAb purity, offering more reproducible quantitation compared with that of traditional SDS‐PAGE methods. These CGE methods have been utilized as platform technology for bioprocess development, formulation development, mAb characterization, drug substance/drug product release testing as well as a required methodology for stability testing. We have found these CGE methods to be applicable across a platform of mAbs in preclinical and clinical development, with the majority of mAbs requiring no modification to the method conditions. This methodology has been ICH validated and transferred to several supporting organizations. The data presented herein describes the development of CGE methodology, platform application to mAb purity analysis, ICH validation, reliability metrics, and considerations on technology enhancement for improved performance and throughput.
Differences in porous characteristics of styrenic monoliths prepared by controlled thermal polymerization in molds of varying dimensions
Authors: Byström Emil , Viklund Camilla , Irgum Knut
Published: January 2010

Nitroxide‐mediated polymerization was used as a model system for preparing styrenic monolithic materials with significant mesopore contents in different mold formats, with the aim of assessing the validity of pore characterization of capillary monoliths by analysis of parallel bulk polymerized precursor solution. Capillary monoliths were prepared in 250 μm id fused silica tubes (quadruplicate samples, in total 17 m), and the batch polymerizations were carried out in parallel in 100 μL microvials and regular 2 mL glass vials, both in quintuplicate. The monoliths recovered from the molds were characterized for their meso‐ and macroporous properties by nitrogen sorptiometry (three repeated runs on each sample), followed by a single analysis by mercury intrusion porosimetry. A total of 14 monolith samples were thus analyzed. A Grubbs' test identified one regular vial sample as an outlier in the sorptiometric surface area measurements, and data from this sample were consequently excluded from the pore size calculations, which are based on the same nitrogen sorption data, and also from the mercury intrusion data set. The remaining data were subjected to single factor analyses of variance analyses to test if the porous properties of the capillary monoliths were different from those of the bulk monoliths prepared in parallel. Significant differences were found between all three formats both in their meso‐ and macroporous properties. When the dimension was shrunk from conventional vial to capillary size, the specific surface area decreased from 52.2±4.7 to 34.6±1.7 m2/g. This decrease in specific surface area was accompanied by a significant shift in median diameter of the through‐pores, from 310±3.9 to 544±13 nm. None of these differences were obvious from the scanning electron micrographs that were acquired for each sample type. The common practice of determining the mesopore characteristics from analysis of samples prepared by parallel bulk polymerization and looking for changes in the macropore structure by visual assessment of SEMs are therefore both rather questionable, at least for monoliths of the kind used in this study.
Dental evidence of congenital syphilis in a 19th century cemetery from the mid‐hudson valley
Authors: Nystrom K. C.
Published: January 2010

The purpose of this communication is to provide a description of a pattern of enamel defects that are consistent with a diagnosis of congenital syphilis. While there is an abundance of literature documenting the skeletal manifestations of congenital syphilis, the description, and particularly the depiction, of the dental stigmata associated with this disease are rare in the paleopathological literature. This report describes enamel defects in the unerupted permanent dentition of two subadults recovered from a historic cemetery in Newburgh, New York. Copyright © 2010 John Wiley & Sons, Ltd.