bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced epidermal dose caused by localized electron contamination from lead cutouts used in kilovoltage radiotherapy
Authors: Lye J. E. , Butler D. J. , Webb D. V.
Published: July 2010

Purpose:

To investigate and quantify electron contamination from the lead cutouts used in kilovoltage x‐ray radiotherapy.

Methods:

The lead cutouts were modeled with the Monte Carlo EGSnrc user codes DOSXYZnrc and DOSRZnrc for x‐ray beams ranging from 50 to. The results from the model were confirmed with Gafchromic film measurements. The model and measurements investigated the dose distribution with and without gladwrap™ shielding under the lead, and dose distributions with round, square, and serrated edge cutouts.

Results:

Large dose enhancement near the edges of the lead was observed due to electron contamination. At the epidermal/dermal border, there is double the dose at the edge of the lead compared to the central dose due to electron contamination for a beam and three times the dose for a beam. gladwrap™ shielding effectively removes the contaminant dose enhancement using ten and four layers for 300 and beams, respectively.

Conclusions:

The contaminant dose enhancement is undesirable as it could cause unnecessary erythema and hyperpigmentation at the border of the treated and untreated skin and lead to a poorer cosmetic outcome. The contamination is easily removed by gladwrap™ shielding placed under or around the lead cutout.
A novel solid‐angle tomosynthesis (SAT) scanning scheme
Authors: Zhang Jin , Yu Cedric
Published: July 2010

Purpose:

Digital tomosynthesis (DTS) recently gained extensive research interests in both diagnostic and radiation therapy fields. Conventional DTS images are generated by scanning an x‐ray source and flat‐panel detector pair on opposite sides of an object, with the scanning trajectory on a one‐dimensional curve. A novel tomosynthesis method named solid‐angle tomosynthesis (SAT) is proposed, where the x‐ray source scans on an arbitrary shaped two‐dimensional surface.

Methods:

An iterative algorithm in the form of total variation regulated expectation maximization is developed for SAT image reconstruction. The feasibility and effectiveness of SAT is corroborated by computer simulation studies using three‐dimensional (3D) numerical phantoms including a 3D Shepp–Logan phantom and a volumetric CT image set of a human breast.

Results:

SAT is able to cover more space in Fourier domain more uniformly than conventional DTS. Greater coverage and more isotropy in the frequency domain translate to fewer artifacts and more accurately restored features in the in‐plane reconstruction.

Conclusions:

Comparing with conventional DTS, SAT allows cone‐shaped x‐ray beams to project from more solid angles, thus provides more coverage in the spatial‐frequency domain, resulting in better quality of reconstructed image.
Adaptive learning for relevance feedback: Application to digital mammography
Authors: Oh Jung Hun , Yang Yongyi , El Naqa Issam
Published: July 2010

Purpose:

With the rapid growing volume of images in medical databases, development of efficient image retrieval systems to retrieve relevant or similar images to a query image has become an active research area. Despite many efforts to improve the performance of techniques for accurate image retrieval, its success in biomedicine thus far has been quite limited. This article presents an adaptive content‐based image retrieval (CBIR) system for improving the performance of image retrieval in mammographic databases.

Methods:

In this work, the authors propose a new relevance feedback approach based on incremental learning with support vector machine (SVM) regression. Also, the authors present a new local perturbation method to further improve the performance of the proposed relevance feedback system. The approaches enable efficient online learning by adapting the current trained model to changes prompted by the user's relevance feedback, avoiding the burden of retraining the CBIR system. To demonstrate the proposed image retrieval system, the authors used two mammogram data sets: A set of 76 mammograms scored based on geometrical similarity and a larger set of 200 mammograms scored by expert radiologists based on pathological findings.

Results:

The experimental results show that the proposed relevance feedback strategy improves the retrieval precision for both data sets while achieving high efficiency compared to offline SVM. For the data set of 200 mammograms, the authors obtained an average precision of 0.48 and an area under the precision‐recall curve of 0.79. In addition, using the same database, the authors achieved a high pathology matching rate greater than 80% between the query and the top retrieved images after relevance feedback.

Conclusions:

Using mammographic databases, the results demonstrate that the proposed approach is more accurate than the model without using relevance feedback not only in image retrieval but also in pathology matching while maintaining its effectiveness for online relevance feedback applications.
Balancing dose and image registration accuracy for cone beam tomosynthesis (CBTS) for breast patient setupa)
Authors: Winey B. A. , Zygmanski P. , Cormack R. A. , Lyatskaya Y.
Published: July 2010

Purpose:

To balance dose reduction and image registration accuracy in breast setup imaging. In particular, the authors demonstrate the relationship between scan angle and dose delivery for cone beam tomosynthesis (CBTS) when employed for setup verification of breast cancer patients with surgical clips.

Methods:

The dose measurements were performed in a female torso phantom for varying scan angles of CBTS. Setup accuracy was measured using three registration methods: Clip centroid localization accuracy and the accuracy of two semiautomatic registration algorithms. The dose to the organs outside of the ipsilateral breast and registration accuracy information were compared to determine the optimal scan angle for CBTS for breast patient setup verification. Isocenter positions at the center of the patient and at the breast‐chest wall interface were considered.

Results:

Image registration accuracy was within 1 mm for the CBTS scan angles above 20° for some scenarios and as large as 80° for the worst case, depending on the imaged breast and registration algorithm. Registration accuracy was highest based on clip centroid localization. For left and right breast imaging with the isocenter at the chest wall, the dose to the contralateral side of the patient was very low for all scan angles considered. For central isocenter location, the optimal scan angles were 30°–50° for the left breast imaging and 40°–50° for the right breast imaging, with the difference due to the geometric asymmetry of the current clinical imaging system.

Conclusions:

The optimal scan angles for CBTS imaging were found to be between 10° and 50°, depending on the isocenter location and ipsilateral breast. Use of the isocenter at the breast‐chest wall locations always resulted in greater accuracy of image registration at smaller angles (10°–20°) and at lower doses to the contralateral organs. For chest wall isocenters, doses delivered to organs outside of the target breast were much smaller than the scattered and leakage doses of the treatment beams. The complete volumetric information of all clips in the region of interest, combined with the small dose to the contralateral organs and the small scan angle, could result in an advantage for small angle CBTS with off center isocenters over simple orthogonal pairs.
Segmenting CT prostate images using population and patient‐specific statistics for radiotherapy
Authors: Feng Qianjin , Foskey Mark , Chen Wufan , Shen Dinggang
Published: July 2010

Purpose:

In the segmentation of sequential treatment‐time CT prostate images acquired in image‐guided radiotherapy, accurately capturing the intrapatient variation of the patient under therapy is more important than capturing interpatient variation. However, using the traditional deformable‐model‐based segmentation methods, it is difficult to capture intrapatient variation when the number of samples from the same patient is limited. This article presents a new deformable model, designed specifically for segmenting sequential CT images of the prostate, which leverages both population and patient‐specific statistics to accurately capture the intrapatient variation of the patient under therapy.

Methods:

The novelty of the proposed method is twofold:First, a weighted combination of gradient and probability distribution function (PDF) features is used to build the appearance model to guide model deformation. The strengths of each feature type are emphasized by dynamically adjusting the weight between the profile‐based gradient features and the local‐region‐based PDF features during the optimization process. An additional novel aspect of the gradient‐based features is that, to alleviate the effect of feature inconsistency in the regions of gas and bone adjacent to the prostate, the optimal profile length at each landmark is calculated by statistically investigating the intensity profile in the training set. The resulting gradient‐PDF combined feature produces more accurate and robust segmentations than general gradient features. Second, an online learning mechanism is used to build shape and appearance statistics for accurately capturing intrapatient variation.

Results:

The performance of the proposed method was evaluated on 306 images of the 24 patients. Compared to traditional gradient features, the proposed gradient‐PDF combination features brought 5.2% increment in the success ratio of segmentation (from 94.1% to 99.3%). To evaluate the effectiveness of online learning mechanism, the authors carried out a comparison between partial online update strategy and full online update strategy. Using the full online update strategy, the mean DSC was improved from 86.6% to 89.3% with 2.8% gain. On the basis of full online update strategy, the manual modification before online update strategy was introduced and tested, the best performance was obtained; here, the mean DSC and the mean ASD achieved 92.4% and 1.47 mm, respectively.

Conclusions:

The proposed prostate segmentation method provided accurate and robust segmentation results for CT images even under the situation where the samples of patient under radiotherapy were limited. A conclusion that the proposed method is suitable for clinical application can be drawn.
The diagnostic capability of x‐ray scattering parameters for the characterization of breast cancer
Authors: Elshemey Wael M. , Desouky Omar S. , Fekry Mostafa M. , Talaat Sahar M. , Elsayed Anwar A.
Published: July 2010

Purpose: The evaluation of the diagnostic capability of easy to measure x‐ray scattering profile characterization parameters for the detection of breast cancer in excised samples. The selected parameters are the full width at half maximum (FWHM) and area under the x‐ray scattering profile of breast tissue in addition to the ratio of scattering intensities at to that at (corresponding to scattering from soft and adipose tissues, respectively).

Methods: A histopathologist is asked to classify 36 excised breast tissue samples into healthy or malignant. A conventional x‐ray diffractometer is used to acquire the scattering profiles of the investigated samples. The values of three profile characterization parameters are calculated and the diagnostic capability of each is evaluated by determining the optimal cutoffs of scatter diagrams, calculating the diagnostic indices, and plotting the receiver operating characteristic (ROC) curves.

Results: At the calculated optimal cutoff for each of the examined parameters, the sensitivity ranged from 78% (for area under curve) up to 94% (for FWHM), the specificity ranged from 94% [for and area under curve] up to 100% (for FWHM), and the diagnostic accuracy ranged from 86% (for area under curve) up to 97% (for FWHM). The area under the ROC curves is greater than 0.95 for all of the investigated parameters, reflecting a highly accurate diagnostic performance.

Conclusions: The discussed tests offered a means to quantitatively evaluate the performance of the suggested breast tissue x‐ray scattering characterization parameters. The performance results are promising, indicating that the evaluated parameters would be considered a tool for fast, on spot probing of breast cancer in excised tissue samples.
Thermoacoustic molecular tomography with magnetic nanoparticle contrast agents for targeted tumor detection
Authors: Nie Liming , Ou Zhongmin , Yang Sihua , Xing Da
Published: July 2010

Purpose:

The primary feasibility steps of demonstrating the ability of microwave‐induced thermoacoustic (TA) in phantoms have been previously reported. However, none were shown to target a diseased site in living subjects in thermoacoustic tomography (TAT) field so far. To determine the expressions of oncogenic surface molecules, it is quite necessary to image tumor lesions and acquire pathogenic status on them via TAT.

Methods:

Compared to biological tissues, iron oxide nanoparticles have a much higher microwave absorbance./polyaniline (PANI) nanoparticles were prepared via polymerization of aniline in the superparamagnetic fluids. Then /PANI was conjugated to folic acid (FA), which can bind specifically to the surface of the folate receptor used as a tumor marker. /PANI targeted tumor was irradiated by pulsed microwave at 6 GHz for thermoacoustic detection and imaging.

Results:

The effect of the/PANI superparamagnetic nanoparticles for enhancing TAT images was successfully investigated in ex vivo human blood and in vivo mouse tail. Intravenous administration of the targeted nanoparticles to mice bearing tumors showed fivefold greater thermoacoustic signal and much longer elimination time than that of mice injected with nontargeted nanoparticles in the tumor. The specific targeting ability of /PANI to tumor was also verified on fluorescence microscopy.

Conclusions:

Fabricated iron oxide nanoparticles conjugated with tumor ligands for targeted TAT tumor detection at the molecular level was reported for the first time. The results indicate that thermoacoustic molecular imaging with functionalized iron oxide nanoparticles may contribute to targeted and functional early cancer imaging. Also, the modified iron oxide nanoparticles combined with suitable tumor markers may also be used as novel nanomaterials for targeted and guided cancer thermal therapy.
Quantum Oscillations and Hall Anomaly of Surface States in the Topological Insulator Bi
2
Te
3
Authors: Qu Dong-Xia , Hor Y. S. , Xiong Jun , Cava R. J. , Ong N. P.
Published: July 2010

Carrier Mobility in Topological Insulators

In addition to an energy gap, which is a characteristic of all band insulators, the electronic structure of the recently discovered three-dimensional topological insulators Bi
2
Te
3
and Bi
2
Se
3
contains a surface state with a Dirac-like dispersion. This state is predicted to be associated with high carrier mobility. However, the transport properties of the surface state are obscured by the bulk material and challenging to measure.

Qu
et al.

(p.
821
, published online 29 July) produced crystals of Bi
2
Te
3
with the Fermi energy lying in the bulk gap and detected quantum oscillations whose magnetic field dependence reveals that they come from a two-dimensional Fermi surface. An anomaly in the Hall conductance originating from the surface state was also observed. The two measurements independently yield mutually consistent high electron mobilities.
Land-Level Changes Produced by the
M
w
8.8 2010 Chilean Earthquake
Authors: Farías Marcelo , Vargas Gabriel , Tassara Andrés , Carretier Sébastien , Baize Stéphane , Melnick Daniel , Bataille Klaus
Published: July 2010

The 2010
M
w
8.8 Chilean earthquake ruptured ~500 kilometers and vertically displaced over 3 meters.
Spontaneous bacterial peritonitis due toListeria monocytogenes: importance of enrichment culture
Authors: Jayasinghe Saroj , Connor Martin , Donaldson Shona , Austin Hannah , Foster Adele
Published: July 2010

A case ofListeria monocytogenesinduced spontaneous bacterial peritonitis (SBP) is reported in a patient with primary biliary cirrhosis. It is an indolent illness and may not show a neutrophil reaction in peritoneal fluid. Enrichment broth was required to isolateL monocytogenesin the patient. This is not routinely used in the UK and therefore isolates may be missed.L monocytogenesremains sensitive to ampicillin, penicillin and gentamicin, but is resistant to cephalosporin antibiotics. The rising incidence of listeriosis in the population suggests that the incidence of SBP fromL monocytogenesis likely to increase.
Surface bacteriology of venous leg ulcers and healing outcome
Authors: Moore Keith , Hall Val , Paull Alan , Morris Trefor , Brown Sarah , McCulloch Dorothy , Richardson Mark C , Harding Keith G
Published: July 2010

Aim

Bacteria can be cultured from all venous leg ulcers (VLUs) regardless of healing status, and the significance of a positive swab result in non-clinically infected ulcers is unknown. The aim of this study was to characterise the bacteriological flora of VLUs by routine culture to determine whether the data generated had prognostic value.

Methods

The ulcers of 178 patients were sampled weekly for 12 weeks and healing outcome monitored while the limb was treated with graduated compression. Wound bacteriology was assessed using culture methodology standardised to ensure data reproducibility.

Results

153 individual bacterial species were identified. The species most frequently found wereStaphylococcus aureus(64.3% of assessments),Corynebacterium striatum(60.6%),Pseudomonas aeruginosa(32.6%),Helcococcus kunzii(22.0%),Finegoldia magna(21.4%) andProteus mirabilis(16.1%). No single species or the presence of anaerobes and increasing diversity of bacterial species, previously thought to be predictive of impaired healing, was shown to be associated with healing outcome. The presence ofC striatumwas associated with healing outcome but not after adjusting for the known prognostic factors of wound area and duration.

Conclusion

Routine bacteriological culture analysis of the VLU wound surface may be used to identify diverse flora in all ulcers. However, the data generated are of no additional value as a prognostic indicator of healing outcome. The presence ofC striatummay represent colonisation of non-healing VLU by normal skin flora.
Are Australian smokers interested in using low-nitrosamine smokeless tobacco for harm reduction?
Authors: Gartner C E , Jimenez-Soto E V , Borland R , O'Connor R J , Hall W D
Published: July 2010

Aims

To determine (1) whether Australian smokers are aware of low-nitrosamine smokeless tobacco (LNSLT) products and (2) whether they would be interested in using LNSLT either as a long-term substitute for smoking or as an aid to quitting, if these products were to become legally available.

Methods

401 daily smokers were recruited by a market research company to complete an internet questionnaire about their smoking history, knowledge of smokeless tobacco and intentions to purchase LNSLT under different scenarios.

Findings

Just under half (48%) indicated they were willing to buy an LNSLT product. Predictors of an interest in purchasing LNSLT were low income, poorer health, prior SLT use, belief that SLT is less harmful than cigarettes, switching to a lower tar cigarette in the past year, ever using nicotine replacement therapy products for quitting or other reasons, having made a failed cessation attempt in the previous year and not planning to quit smoking. Analysis of quitting and LNSLT purchasing intentions under different scenarios suggest that making LNSLT available at a much lower cost than smoked cigarettes while increasing taxes on cigarettes could provide a greater reduction in the number of smokers than the same tax increase alone. These results support further examination of the potential for LNSLT to reduce smoking-related harm in Australia.
PSEUDO-FINSLERIAN SPACE–TIMES AND MULTIREFRINGENCE
Authors: SKÁKALA JOZEF , VISSER MATT
Published: July 2010

Ongoing searches for a quantum theory of gravity have repeatedly led to the suggestion that space–time might ultimately be anisotropic (Finsler-like) and/or exhibit multirefringence (multiple signal cones). Multiple (and even anisotropic) signal cones can be easily dealt with in a unified manner, by writing down a single Fresnel equation to simultaneously encode all signal cones in an even-handed manner. Once one gets off the signal cone and attempts to construct a full multirefringent space–time metric the situation becomes more problematic. In the multirefringent case we shall report a significant no-go result: in multirefringent models there is no simple or compelling way to construct any unifying notion of pseudo-Finsler space–time metric, different from a monorefringenent model, where the signal cone structure plus a conformal factor completely specifies the full pseudo-Riemannian metric.

To throw some light on this situation we use an analog model where both anisotropy and multirefringence occur simultaneously: biaxial birefringent crystal. But the significance of our results extends beyond the optical framework in which (purely for pedagogical reasons) we are working, and has implications for any attempt at introducing multirefringence and intrinsic anisotropies to any model of quantum gravity that has a low energy manifold-like limit.
OSCILLATORY PHASE OF NONCLASSICAL THERMAL INFLATON IN FRW UNIVERSE
Authors: VENKATARATNAM K. K. , SURESH P. K.
Published: July 2010

A minimally coupled nonclassical homogeneous scalar field is examined in the flat FRW universe in the semiclassical theory of gravity. Particle production in thermal coherent and squeezed states is studied for the flat FRW universe, in the oscillatory phase of the inflaton. Solutions for the semiclassical Friedmann equations are obtained in the thermal nonclassical states. Validity of the semiclassical theory is examined in the thermal coherent and squeezed states in the oscillatory phase of inflaton. Particle creation can be enhanced due to thermal and quantum effects. Quantum fluctuations of the inflaton in thermal coherent and squeezed state formalisms are also studied. Classical gravity differ from semiclassical gravity in the thermal coherent state only by an amplitude factor.
SYNTHESIS FOR NANOFLOWER AND ROD OF ZnO BY A SURFACTANT FREE AND LOW TEMPERATURE METHOD
Authors: HAN BYUNG SUN , UHM YOUNG RANG , RHEE CHANG KYU
Published: July 2010

ZnO with 2D flower-like and 1D rod shape were obtained from simple and rapid hydrolysis of Zn nanopowder. The Zn nanopowders were incorporated into distilled water with acetic acid and then the solution was stirred at 60°C for 8 h. The nanoflower-like and rod shape were formed without any surfactant. It seems that the acetic acid played a role of controlling PH and etching the oxide layer on the surface of metal nanopowders to enhance rapid reaction with distilled water. X-ray diffraction patterns for all samples exhibited that the resultant precipitates were completely transformed to ZnO powder. It is clearly observed that the morphological changes of ZnO with reaction time in aqueous solution follows chestnut bur → flower → tetrahedron → rod sequences during the hydrolysis reaction.
SiC-NANOPARTICLE DISPERSED COMPOSITE SOLDER BUMPS FABRICATED BY ELECTROPLATING
Authors: SHIN YUE-SEON , KO YOUNG-KI , KIM JUN-KI , YOO SEHOON , LEE CHANG-WOO
Published: July 2010

SiC -mixed Sn–58Bi composite solder bumps were successfully fabricated via an electroplating process. For the composite solder bump fabrication, ultrasonically dispersed SiC nanoparticles were added to the plating solutions. DSC analysis indicated that the melting temperature of SiC -mixed Sn–58Bi solders was the same as that of the non-mixed Sn–58Bi . Shear strengths of Sn–58Bi+SiC solder bumps were 6% higher than that of non-mixed solder bumps. The thicknesses of intermetallic compound were almost the same for both Sn–58Bi and Sn–58Bi+SiC samples. The Sn–58Bi+SiC composite solder bumps had finer lamellar structures than non-mixed Sn–58Bi . From the fracture surface analysis, fracture occurred at solder bump matrix, not at joint interface. Therefore, the addition of the SiC nanoparticles in the Sn–58Bi solders decreased the grain sizes, which increased the shear strengths.
GRAPHITE REINFORCED Fe–Al–X COMPOSITES FOR SLIDE BEARING APPLICATIONS
Authors: KO SE-HYUN , LEE WONSIK , JANG JIN MAN , KIM IL-HO , SHIN SEONG-GUN
Published: July 2010

The Fe–Al–X(Cu, Ni, Ti) composites reinforced with graphite particles were fabricated employing the powder metallurgy process for slide bearing applications. In all samples, graphite particles of 6 wt.% were added. Elemental powders were mixed to specific compositions with a powder lubricant, and then the mixed powders were compacted at 500 MPa. The green compacts were heated to 450°C to remove the lubricant and sintered at 1200°C for 1 h. The sintering was conducted in vacuum. The sintering of binary Fe–Al –graphite system showed low density and growth in dimension. Complex addition of Cu , Ni and Ti improved the sinterability of green compacts due to occurrence of partial liquid phases. Hardness of sintered samples strongly depended on dimensional change during sintering. The samples of high hardness showed better wear resistance properties.
FABRICATION OF POROUSTi- ANDW-COMPACTS BY ELECTRO-DISCHARGE-SINTERING PROCESS
Authors: SONG GI-AN , SHIN JI-SEON , KANG TAE-JU , CHOI HAN SHIN , LEE JIN KYU , LEE MIN HA , KIM TAEK SOO , LEE WON HEE , KIM KI BUEM
Published: July 2010

A single pulse of 0.57–1.1 kJ/0.3 g-spherical Ti -powder in size range of 30–70 μm, using a constant 450 μF capacitor, was applied to produce fully porous Ti - and W -compacts by electro-discharge sintering. Microstructure examination and hardness measurement of the porous Ti -compacts revealed that more stable necks formed with increasing electrical input energy up to 1.1 kJ. On the contrary, W -compacts using rectangular W -powders in size range of 5–15 μm are composed of solid region with micropore and porous layer with weak particle bonding indicating heterogeneous structure. These results suggest that the powder morphology plays a crucial role to control the porous microstructure.
THEORETICAL STUDY ON OXYGEN–OXYGEN HOMOLYTIC BOND DISSOCIATION ENTHALPIES OF PEROXIDES
Authors: ZOU CHUN-SEN , LIU JING
Published: July 2010

Seven theoretical methods (B3LYP, B3P86, X3LYP, BMK, MP2, CBS-QB3, G3B3) were employed to calculate oxygen–oxygen homolytic bond dissociation enthalpies of 13 peroxides. Comparison of the performances of these methods with the available experimental data showed that ROBMK method is suitable and economical for calculating O–O homolytic bond dissociation enthalpies of peroxides. Then ROBMK method was used to calculate O–O homolytic bond dissociation enthalpies of a series of peroxides. Meanwhile, the α-substituent effect and Hammett relationship were also discussed.
SUPPLEMENTING THE PBSA APPROACH WITH QUANTUM MECHANICS TO STUDY THE BINDING BETWEEN CDK2 ANDN2-SUBSTITUTEDO6-CYCLOHEXYLMETHOXYGUANINE INHIBITORS
Authors: SHI JUYING , LU ZHUAN , ZHANG QIANLING , WANG MINGLIANG , WONG CHUNG F. , LIU JIANHONG
Published: July 2010

Because classical Poisson–Boltzman Surface Area (PBSA) model does not allow re-polarization of charges and does not account for charge transfer when a ligand binds to a protein, we have examined a hybrid approach in which we describe the protein–ligand interface by quantum mechanics and the rest of the system with the classical PBSA model. We found this approach to rank order the binding of five N2-substituted O6-cyclohexylmethoxyguanine inhibitors to CDK2 (cyclin-dependent kinase 2) properly. The calculated binding free energy correlated well with experimental Log(IC50) with a correlation coefficient of 0.94. A regression fit between experimental Log(IC50) and calculated binding free energy yielded a root-mean-square error of 0.48 when Log(IC50) spanned a range over three units. In addition, we observed charge transfer between the ligand and the protein at the interface — an effect not accounted for by the classical PBSA model. We also found that the direct interactions between the protein and the ligands provided the dominant factor to distinguish the binding affinity of the five ligands studied here. This hybrid approach can better prioritize derivatives of lead compounds for synthesis and biological evaluation.
VIBRATIONAL SPECTROSCOPIC INVESTIGATION AND CONFORMATIONAL ANALYSIS OF 1-PENTYLAMINE: A COMPARATIVE DENSITY FUNCTIONAL STUDY
Authors: ALVER ÖZGÜR , PARLAK CEMAL
Published: July 2010

The possible stable conformers of 1-pentylamine (1-pa) molecule were experimentally and theoretically studied by FT-IR and Raman spectroscopy in the region of 4000–400 cm-1. The optimized geometric structures concerning the minimum on the potential energy surface were investigated by Becke-3–Lee–Yang–Parr (B3LYP) density functional method together with 6-31G(d) basis set. Based on the energy calculations, 10 possible rotamers of 1-pa (TT, TG, GT, GT1, GG1, GG2, GG3, GG4, GG5 and GG6; T and G denote trans and gauge, respectively) were proposed. Optimized energies of the possible conformers were obtained in the gas phase and within the chloroform, carbon tetrachloride, methanol and water solvent environments all of which have different polarities. Comparison between the experimental and theoretical results based on the correlation graphics and mean absolute error calculations presented in this study indicates that density functional B3LYP method is able to provide satisfactory results for predicting vibrational wavenumbers and TT isomer is the most stable form of 1-pa molecule.
CALCULATION OFHO2DENSITY OF STATES ON THREE POTENTIAL ENERGY SURFACES
Authors: ZHANG H. , SMITH S. C.
Published: July 2010

Density of states (DOS) in both bound and unimolecular dissociation regime for HO2system have been calculated quantum mechanically by Lanczos homogeneous filter diagonalization (LHFD) method. Three potential energy surfaces are explored and the results are contrasted for the total angular momentum J = 0 density of states. While two ab initio potential energy surfaces (PESs) (TU PES, J Chem Phys, 115:3621 and XXZLG PES, J Chem Phys122:244) produce the DOSs which are in fairly good agreement, the semi-empirical double many-body expansion (DMBE) IV PES (J Phys Chem94:8073) generates the much higher DOSs in higher energy range. The quantum mechanical DOSs are also compared with Troe et al.'s results from harmonic density, semiclassical density and their early density of states on the same TU ab initio surface.
Tauroursodeoxycholic acid reduces endoplasmic reticulum stress, trypsin activation, and acinar cell apoptosis while increasing secretion in rat pancreatic acini
Authors: Malo A. , Krüger B. , Seyhun E. , Schäfer C. , Hoffmann R. T. , Göke B. , Kubisch C. H.
Published: July 2010

Endoplasmic reticulum (ER) stress leads to accumulation of un- or misfolded proteins inside the ER and initiates the unfolded protein response (UPR). Several UPR components are physiologically involved in pancreatic development and are pathophysiologically activated during acute pancreatitis. However, the exact role of ER stress in exocrine pancreatic acini is mainly unclear. The present study examined the effects of tauroursodeoxycholic acid (TUDCA), a known ER chaperone, on acinar function and UPR components. Isolated rat pancreatic acini were stimulated by increasing concentrations of cholecystokinin (CCK-8) with or without preincubation of TUDCA. UPR components were analyzed, including chaperone binding protein (BiP), protein kinase-like ER kinase (PERK), X-box binding protein (XBP)-1, c-Jun NH2-terminal kinase (JNK), CCAAT/enhancer binding protein homologues protein (CHOP), caspase 3 activation, and apoptosis. In addition, TUDCA effects were measured on amylase secretion, calcium signaling, trypsin, and cathepsin B activation. TUDCA preincubation led to a significant increase in amylase secretion after CCK-8 stimulation, a 50% reduction of intracellular trypsin activation, and reduced cathepsin B activity, although the effects for cathepsin B were not statistical significant. Furthermore, TUDCA prevented the CCK-8-induced BiP upregulation, diminished PERK and JNK phosphorylation, and prohibited the expression of CHOP, caspase 3 activation and apoptosis. XBP-1 splicing was not altered. ER stress response mechanisms are activated in pancreatic inflammation. Chemical chaperones enhance enzyme secretion of pancreatic acini, reduce ER stress responses, and attenuate ER stress-associated apoptosis. These data hint new perspectives for an employment of chemical chaperones in the therapy of acute pancreatitis.
Measuring FMD in the brachial artery: how important is QRS gating?
Authors: Kizhakekuttu Tinoy J. , Gutterman David D. , Phillips Shane A. , Jurva Jason W. , Arthur Emily I. L. , Das Emon , Widlansky Michael E.
Published: July 2010

Recommendations for the measurement of brachial flow-mediated dilation (FMD) typically suggest images be obtained at identical times in the cardiac cycle, usually end diastole (QRS complex onset). This recommendation presumes that inter-individual differences in arterial compliance are minimized. However, published evidence is conflicting. Furthermore, ECG gating is not available on many ultrasound systems; it requires an expensive software upgrade or increased image processing time. We tested whether analysis of images acquired with QRS gating or with the more simplified method of image averaging would yield similar results. We analyzed FMD and nitroglycerin-mediated dilation (NMD) in 29 adults with type 2 diabetes mellitus and in 31 older adults and 12 young adults without diabetes, yielding a range of brachial artery distensibility. FMD and NMD were measured using recommended QRS-gated brachial artery diameter measurements and, alternatively, the average brachial diameters over the entire R-R interval. We found strong agreement between both methods for FMD and NMD (intraclass correlation coefficients = 0.88–0.99). Measuring FMD and NMD using average diameter measurements significantly reduced post-image-processing time (658.9 ± 71.6 vs. 1,024.1 ± 167.6 s for QRS-gated analysis, P < 0.001). FMD and NMD measurements based on average diameter measurements can be performed without reducing accuracy. This finding may allow for simplification of FMD measurement and aid in the development of FMD as a potentially useful clinical tool.
Lung structure phenotype variation in inbred mouse strains revealed through in vivo micro-CT imaging
Authors: Thiesse Jacqueline , Namati Eman , Sieren Jessica C. , Smith Amanda R. , Reinhardt Joseph M. , Hoffman Eric A. , McLennan Geoffrey
Published: July 2010

Within pulmonary research, the development of mouse models has provided insight into disease development, progression, and treatment. Structural phenotypes of the lung in healthy inbred mouse strains are necessary for comparison to disease models. To date, progress in the assessment of lung function in these small animals using whole lung function tests has been made. However, assessment of in vivo lung structure of inbred mouse strains has yet to be well defined. Therefore, the link between the structure and function phenotypes is still unclear. With advancements in small animal imaging it is now possible to investigate lung structures such as the central and peripheral airways, whole lung, and lobar volumes of mice in vivo, through the use of micro-CT imaging. In this study, we performed in vivo micro-CT imaging of the C57BL/6, A/J, and BALB/c mouse strains using the intermittent iso-pressure breath hold (IIBH) technique. The resulting high-resolution images were used to extract lung structure phenotypes. The three-dimensional lobar structures and airways were defined and a meaningful mouse airway nomenclature was developed. In addition, using these techniques we have uncovered significant differences in the airway structures between inbred mouse strains in vivo.
Emotional and Psychological Distress of Persons Involved in the Care of Patients with Alzheimer Disease Predicts Falls and Fractures in Their Care Recipients
Authors: Maggio Dario , Ercolani Sara , Andreani Sonia , Ruggiero Carmelinda , Mariani Elena , Mangialasche Francesca , Palmari Nicola , Mecocci Patrizia
Published: July 2010

Background/Aims: Elderly patients with dementia have a higher risk of falls and fractures as compared to cognitively intact elderly subjects. To investigate whether psychological distress of the caregiver might predispose older persons with Alzheimer disease (AD) to falls and fractures, we performed a prospective cohort study. Methods: A consecutive series of 110 subjects with dementia underwent baseline and follow-up clinical and functional evaluations. The burden of the caregivers was recorded at baseline. Any intervening fall or fracture was ascertained at the 1-year follow-up. Results: The caregiver burden was significantly higher in persons involved in the care of patients with AD who subsequently fell. In a multivariate regression model, the caregiver burden score predicted falls and fractures. Conclusion: Part of the increased risk of falls and fractures in AD might be due to the distress of caregivers, a factor potentially amenable to treatment.
Physical and Physiological Effects on Otoacoustic Emissions in Hypobaric Hypoxia
Authors: Ide Rika , Harada Tatsuhiko , Kanzaki Sho , Saito Hideyuki , Hoshikawa Masako , Kawahara Takashi , Ogawa Kaoru
Published: July 2010

Tinnitus and dizziness are symptoms of acute mountain sickness. We investigated the mechanism by which high altitude (i.e. hypobaric hypoxia) affects inner ear function by measuring transient evoked otoacoustic emissions (TEOAE) and distortion product otoacoustic emissions (DPOAE) under conditions of normobaric normoxia (1,013 hPa; 760 mm Hg) and hypobaric hypoxia (540 hPa; 405 mm Hg). The possibility that air pressure effects on the eustachian tube impacted our findings was excluded by the use of tympanograms. The nonphysiological effects of hypobaric hypoxia on TEOAE and DPOAE were also assessed using an ear simulator. Under conditions of hypobaric hypoxia, both TEOAE and DPOAE levels were reduced. The amount of reduction that occurred was approximately 4 dB in the total echo power and signal-to-noise ratio of the TEOAE, and in the 2f1 – f2 element level of the DPOAE. Stimulus levels that were measured using an ear simulator were also reduced by approximately 4 dB under conditions of hypobaric hypoxia. These results do not indicate that stimulus levels affected TEOAE and DPOAE levels because these levels were actually only slightly affected by changes in the stimulus level. Instead, this reduction was likely due to the nonphysiological hypobaric effects of the sound pressure emitted from the tympanic membrane. We conclude that the impact of hypobaric hypoxia on cochlear function was negligible up to pressures of 540 hPa.
Dabigatran: An Oral Novel Potent Reversible Nonpeptide Inhibitor of Thrombin
Authors: Eisert Wolfgang G. , Hauel Norbert , Stangier Joachim , Wienen Wolfgang , Clemens Andreas , van Ryn Joanne
Published: July 2010

Dabigatran is a highly selective, reversible, and potent thrombin inhibitor and is orally available as the prodrug, dabigatran etexilate. It has shown antithrombotic efficacy in animal models of thrombosis, with a rapid onset of action and predictable pharmacodynamic response. Peak plasma concentrations of dabigatran occur 1 to 2 hours after ingestion of the prodrug. The terminal half-life of dabigatran is 12 to 14 hours in elderly volunteers. Dabigatran is not metabolized by cytochrome P450 isoenzymes and does not interact with food. Dabigatran has a low potential for drug-drug interactions and is predominantly renally excreted. Dabigatran etexilate as chronic therapy effectively prevents the recurrence of venous thromboembolism and cardioembolic stroke. For the first time, it has been demonstrated clinically that there may be an effective and safe alternative to warfarin.
Plasma γ-Glutamyltransferase, Cysteinyl-Glycine, and Oxidized Low-Density Lipoprotein
Authors: Drogan Dagmar , Weikert Cornelia , Dierkes Jutta , Klipstein-Grobusch Kerstin , Buijsse Brian , Möhlig Matthias , Pfeiffer Andreas F. H. , Pischon Tobias , Spranger Joachim , Boeing Heiner
Published: July 2010

Objective—

To investigate the interrelation between plasma γ-glutamyltransferase (GGT) activity, cysteinyl-glycine (Cys-Gly) (ie, a thiol originating from GGT-mediated cleavage of glutathione), and oxidized low-density lipoprotein (oxLDL) with regard to myocardial infarction (MI) risk in a prospective study.

Methods and Results—

Incident cases of MI were identified among European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam participants without prior MI during 6.0 years of follow-up. Baseline levels of Cys-Gly and oxLDL and GGT activity in plasma were measured in a case-cohort study comprising 837 subjects without incident MI and 116 subjects with incident MI. The relation of GGT, Cys-Gly and oxLDL to MI risk was assessed using Cox proportional hazards regression analysis. After adjustment for established risk factors, hazard ratios associated with a 1-SD unit increase in the log-transformed biomarker were 1.63 (95% CI, 1.30 to 2.05) for GGT, 1.36 (95% CI, 1.07 to 1.72) for Cys-Gly, and 1.37 (95% CI, 1.00 to 1.86) for oxLDL. Cys-Gly and oxLDL accounted for 2.3% of the relation between GGT and MI risk.

Conclusion—

The positive association between GGT activity and MI risk appears to be independent of circulating Cys-Gly and oxLDL levels. With Cys-Gly, we found a potential new predictor of MI risk whose impact needs to be further elucidated.
Smooth Muscle Cell–Specific Insulin-Like Growth Factor-1 Overexpression in
Apoe
−/−
Mice Does Not Alter Atherosclerotic Plaque Burden but Increases Features of Plaque Stability
Authors: Shai Shaw-Yung , Sukhanov Sergiy , Higashi Yusuke , Vaughn Charlotte , Kelly James , Delafontaine Patrice
Published: July 2010

Objective—

Growth factors may play a permissive role in atherosclerosis initiation and progression, in part via their promotion of vascular smooth muscle cell (VSMC) accumulation in plaques. However, unstable human plaques often have a relative paucity of VSMC, which has been suggested to contribute to plaque rupture and erosion and to clinical events. Insulin-like growth factor-1 (IGF-1) is an endocrine and autocrine/paracrine growth factor that is a mitogen for VSMC, but when infused into
Apoe
−/−
mice it paradoxically reduces atherosclerosis burden.

Methods and Results—

To determine the effect of stimulation of VSMC growth on atherosclerotic plaque development and to understand mechanisms of IGF-1’s atheroprotective effect, we assessed atherosclerotic plaques in mice overexpressing IGF-1 in smooth muscle cells (SMC) under the control of the α-smooth muscle actin promoter, after backcrossing to the
Apoe
−/−
background (SMP8/
Apoe
−/−
). Compared with
Apoe
−/−
mice, these SMP8/
Apoe
−/−
mice developed a comparable plaque burden after 12 weeks on a Western diet, suggesting that the ability of increased circulating IGF-1 to reduce plaque burden was mediated in large part via non-SMC target cells. However, advanced plaques in SMP8/
Apoe
−/−
mice displayed several features of plaque stability, including increased fibrous cap area, α-smooth muscle actin–positive SMC and collagen content, and reduced necrotic cores.

Conclusion—

These findings indicate that stimulation of VSMC IGF-1 signaling does not alter total atherosclerotic plaque burden and may improve atherosclerotic plaque stability.
Synergistic Induction of Mitogen-Activated Protein Kinase Phosphatase-1 by Thrombin and Epidermal Growth Factor Requires Vascular Endothelial Growth Factor Receptor-2
Authors: Chandrasekharan Unni M. , Waitkus Matthew , Kinney Corttrell M. , Walters-Stewart Alicia , DiCorleto Paul E.
Published: July 2010

Objective—

To determine the molecular mechanism underlying the synergistic response of mitogen-activated protein kinase phosphatase-1 (MKP-1), which is induced by thrombin and epidermal growth factor (EGF).

Methods and Results—

MKP-1 induction by thrombin (approximately 6-fold) was synergistically increased (approximately 18-fold) by cotreatment with EGF in cultured endothelial cells. EGF alone did not induce MKP-1 substantially (<2-fold). The synergistic induction of MKP-1 was not mediated by matrix metalloproteinases. The EGF receptor kinase inhibitor AG1478 blocked approximately 70% of MKP-1 induction by thrombin plus EGF (from 18- to 6-fold) but not the response to thrombin alone. An extracellular signal–regulated kinase (ERK)–dependent protease-activated receptor-1 (PAR-1) signal was required for the thrombin alone effect; an ERK-independent PAR-1 signal was necessary for the approximately 12-fold MKP-1 induction by thrombin plus EGF. VEGF induction of MKP-1 was also approximately 12-fold and c-Jun N-terminal kinase (JNK) dependent. Inhibitors of extracellular signal–regulated kinase and JNK activation blocked thrombin plus EGF-induced MKP-1 completely. Furthermore, VEGF receptor 2 depletion blocked the synergistic response without affecting the induction of MKP-1 by thrombin alone.

Conclusion—

We have identified a novel signaling interaction between protease-activated receptor-1 and EGF receptor that is mediated by VEGF receptor 2 and results in synergistic MKP-1 induction.
Receptor Activator of Nuclear Factor κB Ligand Is a Novel Inducer of Tissue Factor in Macrophages
Authors: Kim Jihye , Min Jeong-Ki , Park Jeong Ae , Doh Hyun-Ju , Choi Yeon-Sook , Rho Jaerang , Kim Young-Myeong , Kwon Young-Guen
Published: July 2010

Rationale:

Although recent studies have suggested a role for the receptor activator of nuclear factor κB ligand (RANKL) in the late stages of atherosclerosis (eg, plaque destabilization and rupture), the underlying mechanisms and subsequent events are unclear.

Objective:

Because blood clotting is common after plaque rupture, we hypothesized that RANKL influenced tissue factor (TF) expression and activity to initiate the coagulation cascade.

Methods and Results:

RANKL increased the TF mRNA level and procoagulant activity in macrophages, as determined by semiquantitative reverse transcription polymerase chain reaction (semiquantitative RT-PCR) and a chromogenic assay. TF promoter analysis revealed that AP-1 and Egr-1 are responsible for RANKL-induced TF transcription. In addition, RANKL increased phosphorylation of c-Jun NH
2
-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK)1/2. RANKL-induced TF expression was attenuated by JNK- and MEK1-specific inhibitors and by small interfering RNA knockdown of c-Jun and Egr-1.

Conclusion:

Our results indicate that RANKL induces TF in macrophages mainly through the cooperative action of AP-1 and Egr-1 via JNK and ERK1/2 pathways. These findings provide strong mechanistic support for the role of RANKL in the thrombogenicity of atherosclerotic plaques.