bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone regeneration by bioactive hybrid membrane containing FGF2 within rat calvarium
Authors: Hong Ki Seok , Kim Eun‐Cheol , Bang So‐Hee , Chung Chin‐Hyung , Lee Young Il , Hyun Jung Keun , Lee Hae‐Hyoung , Jang Jun‐Hyeog , Kim Tae‐Il , Kim Hae‐Won
Published: April 2010

This study examined the bone regeneration potential of a novel hybrid membrane consisting of collagen and nano‐bioactive glass (nBG) incorporating basic fibroblast growth factor (FGF2) for use in guided bone regeneration. nBG was added to a reconstitution of collagen at a concentration of 30%, and the hybrid was formulated into a thin membrane. FGF2 (50 μg/ml) was adsorbed to the hybrid membrane. This level of FGF2 was found to be the optimal concentration to stimulate osteoblastic differentiation in vitro. Three membrane groups, including pure collagen, collagen‐nBG hybrid and its combination with FGF2 were implanted within a rat calvarium defect (ϕ = 5 mm) for a period of 3 weeks. Histomorphometric analysis was carried out to evaluate the bone regeneration within the defect. The results showed that the defect in the collagen‐nBG‐FGF2 membrane was recovered almost completely, while partial recovery was observed in the other membrane groups (collagen and collagen‐BG). However, there was little defect recovery in the blank control. The new bone formation was as high as ∼60, ∼45, and ∼30% of the defect treated with the collagen‐nBG‐FGF2, collagen‐BG, and collagen, respectively, whilst only 4% of new bone was observed in the blank control. Overall, the nBG was shown to stimulate bone formation of the collagen membrane, and FGF2 synergistically accelerated the bone regeneration within a rat calvarium defect. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
Transitions towards either slow‐oxidative or fast‐glycolytic phenotype can be induced in the murine WTt myogenic cell line
Authors: Peltzer J. , Carpentier G. , Martelly I. , Courty J. , Keller A.
Published: April 2010

Contraction and energy metabolism are functions of skeletal muscles co‐regulated by still largely unknown signals. To help elucidating these interconnecting pathways, we are developing new cellular models that will allow to control the switch from a neonatal to an adult slow‐oxidative or fast‐glycolytic phenotype of myofibers, during in vitro differentiation. Thus, our purpose was to direct the differentiation of the newly characterized WTt clone, from a mixed towards either fast or slow phenotype, by modifying amounts of two transcription factors respectively involved in control of glycolytic and oxidative energy metabolism, namely HIF‐1α and PPARδ. Our data support the idea that HIF‐1α protein stabilization would favor expression of fast phenotypic markers, accompanied or not by a decreased expression of slow markers, depending on treatment conditions. Conversely, PPARδ over‐expression appears to enhance the slow‐oxidative phenotype of WTt myotubes. Furthermore, we have observed that expression of PGC‐1α, a coregulator of PPAR, is also modified in this cell line upon conditions that stabilize HIF‐1α protein. This observation points to the existence of a regulatory link between pathways controlled by the two transcription factors HIF‐1α and PPARδ. Therefore, these cells should be useful to analyze the balance between oxidative and glycolytic energy production as a function of phenotypic transitions occurring during myogenic maturation. The newly characterized murine WTt clone will be a good tool to investigate molecular mechanisms implicating HIF‐1α and PPARδ in the coordinated metabolic and contractile regulations involved in myogenesis. J. Cell. Biochem. 111: 82–93, 2010. © 2010 Wiley‐Liss, Inc.
HPV vaccines: State of the art
Authors: D'Andrilli Giuseppina , Bovicelli Alessandro , Giordano Antonio
Published: April 2010

Cervical cancer is one of the most common types of cancer in women worldwide and is frequent in relatively young women. In the last decades, its incidence has decreased following the implementation of screening programs, mainly in developed countries. Cervical screening programs, while successful if properly carried out, are difficult and expensive to implement, especially in developing countries. Advances in the understanding of the role of human papillomavirus (HPV) in the etiology of high‐grade cervical lesions and cervical cancer have led to the development and evaluation of two prophylactic HPV vaccines. Vaccination against the HPV, which is the major cause of cervical cancer, is a significant step forward. This review article provides a summary of the most recent studies related with the development and efficacy of the two HPV vaccines. J. Cell. Physiol. 224: 601–604, 2010. © 2010 Wiley‐Liss, Inc.
Navigating the nucleotide excision repair threshold
Authors: Liu Liren , Lee Jennifer , Zhou Pengbo
Published: April 2010

Nucleotide excision repair (NER) is the primary DNA repair pathway that removes helix‐distorting DNA strand damage induced by ultraviolet light irradiation or chemical carcinogens to ensure genome integrity. While the core NER proteins that carry out damage recognition, excision, and repair reactions have been identified and extensively characterized, and the NER pathway has been reconstituted in vitro, the regulatory pathways that govern the threshold levels of NER have not been fully elucidated. This mini‐review focuses on recently discovered transcriptional and post‐translational mechanisms that specify the capacity of NER, and suggests the potential implications of modulating NER activity in cancer prevention and therapeutic intervention. J. Cell. Physiol. 224: 585–589, 2010. © 2010 Wiley‐Liss, Inc.
Glucosamine promotes osteogenic differentiation of dental pulp stem cells through modulating the level of the transforming growth factor‐β type I receptor
Authors: Huang Chien‐Hsun , Tseng Wan‐Yu , Yao Chung‐Chen , Jeng Jiiang‐Huei , Young Tai‐Horng , Chen Yi‐Jane
Published: April 2010

Dental pulp stem cells (DPSCs) are clonogenic, self‐renewing, and multi‐potential DPSCs capable of differentiating into osteoblasts. In this study, primary cell cultures were obtained from human dental pulp tissue of developing third molars, and flow cytometry was used to sort the subpopulation of DPSCs with STRO‐1 and CD146 double‐positive expression (denoted “DPSCs”). It was noted that DPSCs exhibited superior clonogenic potential and osteogenic differentiation capability than the dental pulp cell subpopulation with STRO‐1 and CD146 double‐negative expression (denoted DPCs). Furthermore, a low concentration (0.005 mg/ml) of exogenous glucosamine (GlcN) was effective in promoting the early osteogenic differentiation of DPSCs through the transforming growth factor‐β receptor (TGF‐βr) type I and Smads signal pathways, which upregulated the Runt‐related transcription factor 2/core‐binding factor alpha1 (Runx2/Cbfa1) and alkaline phosphatase at both the mRNA and protein levels. In the presence of osteogenic supplements, GlcN‐treated DPSCs produced more mineralized‐matrix deposition than did the untreated groups. Taken together, this study demonstrates the capacity of GlcN to promote the osteogenic differentiation of human DPSCs, and the underlying mechanism involves a TGF‐βr‐dependent Smad signal pathway. J. Cell. Physiol. 225: 140–151, 2010. © 2010 Wiley‐Liss, Inc.
Role of TNF alpha and PLF in bone remodeling in a rat model of repetitive reaching and grasping
Authors: Rani Shobha , Barbe Mary F , Barr Ann E , Litivn Judith
Published: April 2010

We have previously developed a voluntary rat model of highly repetitive reaching that provides an opportunity to study effects of non‐weight bearing muscular loads on bone and mechanisms of naturally occurring inflammation on upper limb tissues in vivo. In this study, we investigated the relationship between inflammatory cytokines and matricellular proteins (Periostin‐like‐factor, PLF, and connective tissue growth factor, CTGF) using our model. We also examined the relationship between inflammatory cytokines, PLF and bone formation processes. Rats underwent initial training for 5 weeks, and then performed a high repetition high force (HRHF) task (12 reaches/min, 60% maximum grip force, 2 h/day, 3 days/week) for 6 weeks. We then examined the effect of training or task performance with or without treatment with a rat specific TNFα antibody on inflammatory cytokines, osteocalcin (a bone formation marker), PLF, CTGF, and behavioral indicators of pain or discomfort. The HRHF task decreased grip strength and induced forepaw mechanical hypersensitivity in both trained control and 6‐week HRHF animals. Two weeks of anti‐TNFα treatment improved grip strength in both groups, but did not ameliorate forepaw hypersensitivity. Moreover, anti‐TNFα treatment attenuated task‐induced increases in inflammatory cytokines (TNFα, IL‐1α, and MIP2 in serum; TNFα in forelimb bone and muscles) and serum osteocalcin in 6‐week HRHF animals. PLF levels in forelimb bones and flexor digitorum muscles increased significantly in 6‐week HRHF animals, increases attenuated by anti‐TNFα treatment. CTGF levels were unaffected by task performance or anti‐TNFα treatment in 6‐week HRHF muscles. In primary osteoblast cultures, TNFα, MIP2 and MIP3a treatment increased PLF levels in a dose dependent manner. Also in primary osteoblast cultures, increased PLF promoted proliferation and differentiation, the latter assessed by measuring Runx2, alkaline phosphatase (ALP) and osteocalcin mRNA levels; ALP activity; as well as calcium deposition and mineralization. Increased PLF also promoted cell adhesion in MC3T3‐E1 osteoblast‐like cell cultures. Thus, tissue loading in vivo resulted in increased TNFα, which increased PLF, which then induced anabolic bone formation, the latter results confirmed in vitro. J. Cell. Physiol. 225: 152–167, 2010. © 2010 Wiley‐Liss, Inc.
Analysis of CAPZA3 localization reveals temporally discrete events during the acrosome reaction
Authors: Sosnik Julian , Buffone Mariano G. , Visconti Pablo E.
Published: April 2010

In mammals, the starting point of development is the fusion between sperm and egg. It is well established that sperm fuse with the egg through the equatorial/post‐acrosomal region. Apart from this observation and the requirement of two proteins (CD9 in the egg and IZUMO1 in the sperm) very little is known about this fundamental process. Actin polymerization correlates with sperm capacitation in different mammalian species and it has been proposed that F‐actin breakdown is needed during the acrosome reaction. Recently, we have presented evidence that actin polymerization inhibitors block the movement of IZUMO1 that accompany the acrosome reaction. These results suggest that actin dynamics play a role in the observed changes in IZUMO1 localization. This finding is significant because IZUMO1 localization in acrosome‐intact sperm is not compatible with the known location of the initiation of the fusion between the sperm and the egg. To further understand the actin‐mediated changes in protein localization during the acrosome reaction, the distribution of the sperm‐specific plus‐end actin capping protein CAPZA3 was analyzed. Like IZUMO1, CAPZA3 shows a dynamic pattern of localization; however, these movements follow a different temporal pattern than the changes observed with IZUMO1. In addition, the actin polymerization inhibitor latrunculin A was unable to alter CAPZA3 movement. J. Cell. Physiol. 224: 575–580, 2010. © 2010 Wiley‐Liss, Inc.
Four‐dimensional transcatheter intra‐arterial perfusion MR imaging before and after uterine artery embolization in the rabbit VX2 tumor model
Authors: Chung Johnathan C. , Wang Dingxin , Lewandowski Robert J. , Tang Richard , Chrisman Howard B. , Vogelzang Robert L. , Woloschak Gayle E. , Larson Andrew C. , Omary Reed A. , Ryu Robert K.
Published: April 2010

Purpose:

To test the hypothesis that four‐dimensional (4D) transcatheter intra‐arterial perfusion (TRIP) MR imaging can measure uterine fibroid perfusion changes immediately before and after uterine artery embolization (UAE) in the rabbit VX2 tumor model.

Materials and Methods:

Eight VX2 uterine tumors were grown in six rabbits. After positioning a catheter within the uterine artery, we performed 4D TRIP‐MRI measurements with 3‐mL injections of 2.5% gadopentetate dimeglumine. We used a dynamic 3D spoiled‐gradient echo sequence with in vivo B1‐field correction for improved accuracy during perfusion quantification. We performed UAE using 1 mL of gelatin microspheres (2 × 106 particles; diameter 40–120 μm). Two regions‐of‐interest were drawn within each tumor upon perfusion maps. Functional embolic endpoints were reported as the mean percent reduction in fibroid tumor perfusion. Measurements before and after UAE were compared using paired t‐tests (α = 0.05).

Results:

VX2 uterine tumor perfusion decreased significantly from 27.1 at baseline to 7.09 after UAE (mL/min/100 mL of tissue, P < 0.0001). Overall perfusion reduction was 76.3% (95% confidence interval: 66.3–86.3%).

Conclusion:

Four‐dimensional TRIP MRI can objectively quantify uterine fibroid perfusion reductions during UAE in VX2 rabbits. This technique could be used clinically to potentially determine an optimal embolic endpoint with the long‐term goals of improving UAE success rates and minimizing procedure‐related ischemic pain. J. Magn. Reson. Imaging 2010;31:1137–1143. © 2010 Wiley‐Liss, Inc.
Whole‐heart coronary magnetic resonance angiography at 3.0T using short‐TR steady‐state free precession, vastly undersampled isotropic projection reconstruction
Authors: Xie Jingsi , Lai Peng , Bhat Himanshu , Li Debiao
Published: April 2010

Purpose

To evaluate the feasibility of improving 3.0T steady‐state free precession (SSFP) whole‐heart coronary magnetic resonance angiography (MRA) using short‐TR (repetition time) VIPR (vastly undersampled isotropic projection reconstruction).

Materials and Methods

SSFP is highly sensitive to field inhomogeneity. VIPR imaging uses nonselective radiofrequency pulses, allowing short TR and reduced banding artifacts, while achieving isotropic 3D resolution. Coronary artery imaging was performed in nine healthy volunteers using SSFP VIPR. TR was reduced to 3.0 msec with an isotropic spatial resolution of 1.3 × 1.3 × 1.3 mm3. Image quality, vessel sharpness, and lengths of major coronary arteries were measured. Comparison between SSFP using Cartesian trajectory and SSFP using VIPR trajectory was performed in all volunteers.

Results

Short‐TR SSFP VIPR resulted in whole‐heart images without any banding artifacts, leading to excellent coronary artery visualization. The average image quality score for VIPR‐SSFP was 3.12 ± 0.42 out of four while that for Cartesian SSFP was 0.92 ± 0.61. A significant improvement (P < 0.05) in image quality was shown by Wilcoxon comparison. The visualized coronary artery lengths for VIPR‐SSFP were: 10.13 ± 0.79 cm for the left anterior descending artery (LAD), 7.90 ± 0.91 cm for the left circumflex artery (LCX), 7.50 ± 1.65 cm for the right coronary artery (RCA), and 1.84 ± 0.23 cm for the left main artery (LM). The lengths statistics for Cartesian SSFP were 1.57 ± 2.02 cm, 1.54 ± 1.93 cm, 0.94 ± 1.17 cm, 0.46 ± 0.53 cm, respectively. The image sharpness was also increased from 0.61 ± 0.13 (mm−1) in Cartesian‐SSFP to 0.81 ± 0.11 (mm−1) in VIPR‐SSFP.

Conclusion

With VIPR trajectory the TR is substantially decreased, reducing the sensitivity of SSFP to field inhomogeneity and resulting in whole‐heart images without banding artifacts at 3.0T. Image quality improved significantly over Cartesian sampling. J. Magn. Reson. Imaging 2010; 31:1230–1235. © 2010 Wiley‐Liss, Inc.
Accuracy and repeatability of fourier velocity encoded M‐mode and two‐dimensional cine phase contrast for pulse wave velocity measurement in the descending aorta
Authors: Taviani Valentina , Patterson Andrew J. , Graves Martin J. , Hardy Christopher J. , Worters Pauline , Sutcliffe Michael P.F. , Gillard Jonathan H.
Published: April 2010

Purpose:

To assess the accuracy and repeatability of Fourier velocity encoded (FVE) M‐mode and two‐dimensional (2D) phase contrast with through‐plane velocity encoding (2D‐PC) for pulse wave velocity (PWV) evaluation in the descending aorta using five different analysis techniques.

Materials and Methods:

Accuracy experiments were conducted on a tubular human‐tissue‐mimicking phantom integrated into a flow simulator. The theoretical PWV value was derived from the Moens‐Korteweg equation after measurement of the tube elastic modulus by uniaxial tensile testing (PWV = 6.6 ± 0.7 m/s). Repeatability was assessed on 20 healthy volunteers undergoing three consecutive MR examinations.

Results:

FVE M‐mode PWV was more repeatable than 2D‐PC PWV independently of the analysis technique used. The early systolic fit (ESF) method, followed by the maximum of the first derivative (1st der.) method, was the most accurate (PWV = 6.8 ± 0.4 m/s and PWV = 7.0 ± 0.6 m/s, respectively) and repeatable (inter‐scan within‐subject variation δ = 0.096 and δ = 0.107, respectively) for FVE M‐mode. For 2D‐PC, the 1st der. method performed best in terms of accuracy (PWV = 6.8 ± 1.1 m/s), whereas the ESF algorithm was the most repeatable (δ = 0.386).

Conclusion:

FVE M‐mode allows rapid, accurate and repeatable central PWV evaluation when the ESF algorithm is used. 2D‐PC requires long scan times and can provide accurate although much less repeatable PWV measurements when the 1st der. method is used. J. Magn. Reson. Imaging 2010;31:1185–1194. © 2010 Wiley‐Liss, Inc.
Quantitative 4D transcatheter intraarterial perfusion MRI for monitoring chemoembolization of hepatocellular carcinoma
Authors: Wang Dingxin , Jin Brian , Lewandowski Robert J. , Ryu Robert K. , Sato Kent T. , Mulcahy Mary F. , Kulik Laura M. , Miller Frank H. , Salem Riad , Li Debiao , Omary Reed A. , Larson Andrew C.
Published: April 2010

Purpose:

To develop a fully quantitative 4D transcatheter intraarterial perfusion (TRIP) magnetic resonance imaging (MRI) technique and prospectively test the hypothesis that quantitative 4D TRIP‐MRI can be used clinically to monitor intraprocedural liver tumor perfusion reductions during transcatheter arterial chemoembolization (TACE).

Materials and Methods:

TACE was performed within an x‐ray digital subtraction angiography (DSA)‐MRI procedure suite in 16 patients with hepatocellular carcinoma. Quantitative 4D TRIP‐MRI with targeted radiofrequency field mapping and dynamic longitudinal relaxation rate mapping was used to monitor changes in tumor perfusion during TACE. First‐pass perfusion analysis was performed to produce intraprocedural blood flow (Fρ) maps. Mean liver tumor perfusions before and after TACE were compared with a paired t‐test (α = 0.05).

Results:

Perfusion reductions were successfully measured with quantitative 4D TRIP‐MRI in 22 separate tumors during 18 treatment sessions. Mean tumor perfusion Fρ decreased from 16.3 (95% confidence interval [CI]: 10.7–21.9) before TACE to 5.0 (95% CI: 3.5–6.5) (mL/min/100 mL) after TACE. Tumor perfusion reductions were statistically significant (P < 0.0005), with a mean absolute perfusion change of 11.4 (95% CI: 5.6–17.1) (mL/min/100 mL) and a mean percentage reduction of 61.0% (95% CI: 48.3%–73.6%).

Conclusion:

Quantitative 4D TRIP‐MRI can be successfully performed within clinical interventional settings to monitor intraprocedural changes in liver tumor perfusion during TACE. J. Magn. Reson. Imaging 2010;31:1106–1116. © 2010 Wiley‐Liss, Inc.
Preoperative detection of prostate cancer: A comparison with 11C‐choline PET, 18F‐fluorodeoxyglucose PET and MR imaging
Authors: Watanabe Haruo , Kanematsu Masayuki , Kondo Hiroshi , Kako Nobuo , Yamamoto Naoki , Yamada Toru , Goshima Satoshi , Hoshi Hiroaki , Bae Kyongtae T.
Published: April 2010

Purpose:

To compare 11C‐choline positron emission tomography (C‐PET), 18F‐fluorodeoxyglucose PET (FDG‐PET), and MR imaging in the preoperative detection of prostate cancer.

Materials and Methods:

C‐PET, FDG‐PET, and MR images were obtained in 43 consecutive patients with suspected prostate cancer, and prostate cancers were histopathologically confirmed in 26 patients. Unenhanced T1‐weighted, T2‐weighted, and gadolinium‐enhanced MR images were obtained. C‐PET and FDG‐PET were conducted 1.5 and 60 minutes after injection of 5.5 and 5.0 MBq/kg tracers, respectively. A nuclear and a genitourinary radiologist retrospectively reviewed PET and MR images at random, respectively, and assigned a confidence level for the presence of prostate cancer using a four‐point scale. Diagnostic performance was tested using the McNemar test and receiver operating characteristic curve analysis.

Results:

The sensitivity was greater (P < 0.05) with MR (88%) and C‐PET (73%) images than with FDG‐PET images (31%). The accuracy was greater (P < 0.05) with MR images (88%) than with C‐PET (67%) and FDG‐PET (53%) images. The area‐under‐curve value with MR (0.90) was greater than those with C‐PET (0.53) and FDG‐PET (0.54) images (P < 0.01).

Conclusion:

MR imaging should be primarily performed in the preoperative detection of prostate cancer. C‐PET and FDG‐PET did not improve the detection. J. Magn. Reson. Imaging 2010;31:1151–1156. © 2010 Wiley‐Liss, Inc.
Repeatability of T1‐quantification in dGEMRIC for three different acquisition techniques: Two‐dimensional inversion recovery, three‐dimensional look locker, and three‐dimensional variable flip angle
Authors: Siversson Carl , Tiderius Carl‐Johan , Neuman Paul , Dahlberg Leif , Svensson Jonas
Published: April 2010

Purpose:

To evaluate the repeatability of the dGEMRIC (delayed gadolinium enhanced MRI of cartilage) method in osteoarthritis‐prone knee joints for three different T1 quantification techniques: two‐dimensional inversion recovery (2D‐IR), three‐dimensional Look‐Locker (3D‐LL), and three‐dimensional variable flip angle (3D‐VFA).

Materials and Methods:

Nine subjects were examined twice, with a 2‐week interval, using all three measurement techniques. Four regions of interest were defined in the central medial and lateral femoral cartilage. The repeatability was evaluated for each measurement technique. For the 3D techniques, the variation between different slices was also evaluated.

Results:

Repeatability expressed by root‐mean‐square coefficient of variation (CVRMS) showed similar results for 2D‐IR and 3D‐LL (5.4–8.4%). For 3D‐VFA CVRMS was higher (9.3–15.2%). Intraclass correlation coefficient showed both 2D‐IR and 3D‐LL reliability to be moderate, while 3D‐VFA reliability was low. Inter‐slice CVRMS and ICC was of the same magnitude as the repeatability. No clear differences could be interpreted between the condyles.

Conclusion:

Both 2D‐IR and 3D‐LL perform well in generating repeatable dGEMRIC results, while 3D‐VFA results are somewhat inferior. Furthermore, repeatability results in this study are similar to previously published results for healthy subjects. Finally, the positioning of the analyzed images is crucial to generate reliable repeatability results. J. Magn. Reson. Imaging 2010;31:1203–1209. © 2010 Wiley‐Liss, Inc.
Optimal fast T2‐weighted magnetic resonance microscopy imaging of the eye and its clinical application
Authors: Tanitame Keizo , Sasaki Ko , Sone Takashi , Otani Keiko
Published: April 2010

Purpose:

To compare a half‐Fourier single‐shot rapid acquisition with relaxation enhancement (RARE) sequence with a balanced steady‐state free precession (b‐SSFP) sequence in the evaluation of the eye using magnetic resonance (MR) microscopy imaging and to clarify the usefulness of RARE microscopy imaging in evaluating nonoperative glaucoma patients and patients who have undergone surgery for glaucoma or cataract.

Materials and Methods:

One‐mm and 2‐mm slice thickness images of RARE sequence and b‐SSFP sequence using a 1.5 T MR unit and a 23‐mm microscopy coil were obtained in eight healthy volunteers. The signal‐to‐noise (S/N) ratio of aqueous humor in the anterior chamber was measured quantitatively and visualization of the anterior chamber anatomy was assessed qualitatively. Furthermore, we evaluated 21 glaucoma patients (including six postoperative patients) and four patients after cataract surgery with 2‐mm slice thickness RARE MRI.

Results:

The 2‐mm slice thickness RARE imaging had a significantly greater S/N ratio than the 1‐mm slice thickness RARE imaging (P < 0.05) and acquired the best image quality among the four types of images (P < 0.01). Additionally, 2‐mm slice thickness RARE microscopy imaging could depict anterior chamber anatomy of glaucoma eyes and eyes after cataract surgery.

Conclusion:

We believe that optimal fast T2‐weighted MR microimaging might become a useful ophthalmologic examination technique. J. Magn. Reson. Imaging 2010;31:1210–1214. ©2010 Wiley‐Liss, Inc.
The Quaternary of the British Isles: factors forcing environmental change
Authors: Rose James
Published: April 2010

This paper considers the processes that have controlled cool temperate latitude terrestrial environments over the last ca 3 Ma, with particular reference to the British Isles. A scheme is proposed that is based on the processes that act on the land over any given period of time and are the product of climate modulated by rock type (the resisting agent) and relief (determined by tectonics and antecedent relief‐forming factors). Climate is generalised in terms of the range and rates of climate change determined by orbital forcing. During precession cycles climate change was small and insolation levels were forced by chemically and biologically driven processes. The period of obliquity cycles is characterised by patterns of climate change in which physical processes became effective and high‐magnitude fluvial and slope processes were reinforced by periglaciation and glaciation in susceptible regions. Eccentricity cycles include climate extremes of longer duration, and glaciation and periglaciation were the major contributors to landscape change, sediment transfer and sediment mixing. These climate‐forced processes produce distinctive landform, sediment and soil assemblages characteristic of particular episodes of Quaternary time. The lags between the successive systems are identified. Copyright © 2010 John Wiley & Sons, Ltd.
Extent and timing of the Last Glacial Maximum (LGM) in Britain and Ireland: a review
Authors: Chiverrell Richard C. , Thomas Geoffrey S. P.
Published: April 2010

The Last Glacial Maximum (LGM) of Marine Isotope Stage (MIS) 2 is defined here as the period either of maximum global ice volume or in which major ice sheets reached their maximum extent. Both definitions lack clarity as there is no reason to suppose that maximum volumes or limits were reached simultaneously at either all ice sheets or around the margins of individual ice sheets. Here we review the traditional terrestrial limits of the BIIS (British‐Irish Ice Sheet), examine developments in understanding the offshore record, and attempt a redefinition of the extent and timing of the MIS 2 maximum. As a working chronological model the build‐up of the BIIS is assigned to after 35–32 ka, the maximum to the period 27–21 ka and a more limited readvance after 19 ka. As marginal oscillations, driven by ice sheet dynamics, appear to have characterised much of the advance, and especially the retreat of the BIIS, caution should be exercised in assigning climatic significance to the many identified ice limits or still‐stands. While much of the terrestrial limit in Britain remains relatively unaltered, significant revision is required offshore around Britain and Ireland, to portray an extensive ice advance to the shelf edge and a period when the BIIS was conjoined with the adjacent Fenno‐Scandinavian Ice Sheet. Although there appears to be a broad synchrony between the BIIS and other major ice sheets, local controls have produced some variation in the timing of advance to and retreat from maximum limits for particular ice streams or lobes, but much of the offshore limit remains very poorly age constrained. Consequently, a key objective in future research should be to improve and refine the chronological control for all portions of the maximum margin of the BIIS and its subsequent retreat stages. Copyright © 2010 John Wiley & Sons, Ltd.
The Quaternary of the British Isles and adjoining seas
Authors: Rose James , Coxon Peter
Published: April 2010

This Special Issue of the Journal of Quaternary Science contains a set of 13 papers based on presentations at the Annual Discussion Meeting of the Quaternary Research Association held in London in January 2008. This Special Issue is concerned with four main themes: long‐term landscape signatures, river landscapes and responses to climate change, glacial landscapes and Lateglacial landscapes. The papers include substantial new data on the terrestrial and offshore Quaternary of the British Isles and provide a benchmark for aspects of current thinking on this topic. This volume is published in parallel with other special issues based on the 2008 QRA Discussion Meeting. These consist of The Quaternary Geology of the British Isles edited by David Bridgland and Nick Golledge in the Proceedings of the Geologists' Association and Climate variability of the British Isles and surrounding seas edited by Dan Charman and Danny McCarroll in Quaternary Science Reviews. Copyright © 2010 John Wiley & Sons, Ltd.
Rapid and delayed death of cultured trabecular meshwork cells after selective laser trabeculoplasty
Authors: Wood John P.M. , Plunkett Malcolm , Previn Victor , Chidlow Glyn , Casson Robert J.
Published: April 2010

Background and Objective

Selective laser trabeculoplasty (SLT) is becoming increasingly employed to reduce elevated intraocular pressure in glaucoma patients. SLT is known to target the ocular trabecular meshwork (TM), but the exact response mechanisms to this treatment have not been clearly delineated. The aim of the present study, therefore, was to investigate the modes of death of cultured bovine TM cells subjected to SLT in vitro.

Materials and Methods

Bovine TM cell cultures were established, pigmented with exogenous melanin and irradiated with a Q‐switched, frequency doubled, Nd:YAG laser, at different energy settings (0.05–1.0 mJ). Influences on cells were determined for up to 10 days post‐treatment by trypan blue exclusion, terminal deoxynucleotidyl transferase dUTP nick‐end labeling (TUNEL) and by morphological assessment. Furthermore, homogeneous mixtures of pigmented and non‐pigmented TM cells were irradiated to ascertain selectivity of laser effects.

Results

At higher energy levels (1.0, 0.75 mJ), immediate loss of cells was detected at the irradiated site. Trypan blue exclusion analysis showed that necrotic cell death subsequently occurred up to 8 hours following irradiation, peaking at 60 minutes. This was followed by delayed cell death peripheral to the irradiated area which was characteristic of apoptosis and which peaked at 2–3 days post‐treatment. When mixed cultures were tested, laser treatment selectively killed pigmented cells at an energy level equivalent to the lower cell killing threshold in the initial studies (0.2 mJ) but at the higher laser energy of 0.35 mJ, all cells were non‐selectively killed.

Conclusions

SLT treatment killed pigmented TM cells in culture by a variety of processes (instant vaporization, rapid necrosis, delayed apoptosis), depending on the magnitude of the energy used and the distance from the center of the irradiated zone. These data may assist in the elucidation of the mechanism of action of the SLT procedure on TM cells in situ. Lasers Surg. Med. 42:326–337, 2010. © 2010 Wiley‐Liss, Inc.
Diffuse reflectance spectroscopy for optical soft tissue differentiation as remote feedback control for tissue‐specific laser surgery
Authors: Stelzle Florian , Tangermann‐Gerk Katja , Adler Werner , Zam Azhar , Schmidt Michael , Douplik Alexandre , Nkenke Emeka
Published: April 2010

Background and Objective

Laser surgery does not provide haptic feedback for operating layer‐by‐layer and thereby preserving vulnerable anatomical structures like nerve tissue or blood vessels. Diffuse reflectance spectra can facilitate remote optical tissue differentiation. It is the aim of the study to use this technique on soft tissue samples, to set a technological basis for a remote optical feedback system for tissue‐specific laser surgery.

Materials and Methods

Diffuse reflectance spectra (wavelength range: 350–650 nm) of ex vivo types of soft tissue (a total of 10,800 spectra) of the midfacial region of domestic pigs were remotely measured under reduced environmental light conditions and analyzed in order to differentiate between skin, mucosa, muscle, subcutaneous fat, and nerve tissue. We performed a principal components (PC) analysis (PCA) to reduce the number of variables. Linear discriminant analysis (LDA) was utilized for classification. For the tissue differentiation, we calculated the specificity and sensitivity by receiver operating characteristic (ROC) analysis and the area under curve (AUC).

Results

Six PCs were found to be adequate for tissue differentiation with diffuse reflectance spectra using LDA. All of the types of soft tissue could be differentiated with high specificity and sensitivity. Only the tissue pairs nervous tissue/fatty tissue and nervous tissue/mucosa showed a decline of differentiation due to bio‐structural similarity. However, both of these tissue pairs could still be differentiated with a specificity and sensitivity of more than 90%.

Conclusions

Analyzing diffuse reflectance spectroscopy with PCA and LDA allows for remote differentiation of biological tissue. Considering the limitations of the ex vivo conditions, the obtained results are promising and set a basis for the further development of a feedback system for tissue‐specific laser surgery. Lasers Surg. Med. 42:319–325, 2010. © 2010 Wiley‐Liss, Inc.
Protective effect of autophagy in laser‐induced glioma cell death in vitro
Authors: Krmpot Aleksandar J. , Janjetovic Kristina D. , Misirkic Maja S. , Vucicevic Ljubica M. , Pantelic Dejan V. , Vasiljevic Darko M. , Popadic Dusan M. , Jelenkovic Branislav M. , Trajkovic Vladimir S.
Published: April 2010

Background and Objective

Laser phototherapy could be potentially used for cancer treatment, but the mechanisms of laser‐induced cell death are not completely understood. Autophagy is the process in which the damaged cellular proteins and organelles are engulfed by and destroyed in acidified multiple‐membrane vesicles. The aim of the present study was to investigate the role of autophagy in laser‐induced tumor cell death in vitro.

Study Design/Materials and Methods

The monolayers of U251 human glioma tumor cells were exposed to 532 nm laser light from a single mode frequency‐doubled Nd‐YVO4 laser. A flattened Gaussian radial profile of laser beam (0.5–4 W) was used to uniformly illuminate entire colony of cells for various amounts of time (15–120 seconds) in the absence of cell culture medium. The cells were grown for 24 hours and the cell viability was determined by crystal violet or MTT assay. The presence of autophagy was assessed after 16 hours by fluorescence microscopy/flow cytometric analysis of acridine orange‐stained autophagolysosomes and Western blot analysis of the autophagosome‐associated LC3‐II protein. The concentration of the principal pro‐autophagic protein beclin‐1 was determined after 6 hours by cell‐based ELISA.

Results

The intracytoplasmic accumulation of autophagic vesicles, increase in LC3‐II and up‐regulation of beclin‐1 expression were clearly observed under irradiation conditions that caused approximately 50% cytotoxicity. Post‐irradiation addition of three different autophagy inhibitors (bafilomycin A1, chloroquine, or wortmannin) further increased the laser‐induced cytotoxicity, without affecting non‐irradiated cells.

Conclusions

These data indicate that beclin‐1‐dependent induction of autophagy can protect glioma cells from laser‐mediated cytotoxicity. Lasers Surg. Med. 42:338–347, 2010. © 2010 Wiley‐Liss, Inc.
Assessment of the return period of near‐PMP point and catchment rainfall for England and Wales
Authors: Collier Chris G. , Morris David G. , Jones David A.
Published: April 2010

The return periods of sub‐daily rainfall events approaching Probable Maximum Precipitation (PMP) have been estimated for point locations and catchment areas using the assumptions made in a previously published storm model. It has been assumed that PMP of around 12 h duration is the result of severe thunderstorms for catchments up to about 200 km2and of mesoscale convective systems (MCSs) for larger catchments. The analysis suggests return periods ranging from around 1 in 10 000 years for point locations to 1 in 500 000 years for large catchments, though these are very dependent on the assumptions. The results are compared with estimates from a number of other sources. Copyright © 2010 Royal Meteorological Society
Steering of aggregating magnetic microparticles using propulsion gradients coils in an MRI Scanner
Authors: Mathieu Jean‐Baptiste , Martel Sylvain
Published: April 2010

Upgraded gradient coils can effectively enhance the MRI steering of magnetic microparticles in a branching channel. Applications of this method include MRI targeting of magnetic embolization agents for oncologic therapy. A magnetic suspension of Fe3O4 magnetic particles was injected inside a y‐shaped microfluidic channel. Magnetic gradients of 0, 50, 100, 200, and 400 mT/m were applied to the magnetic particles perpendicularly to the flow by a custom‐built gradient coil inside a 1.5‐T MRI scanner. Measurement of the steering ratio was performed both by video analyses and quantification of the mass of the particles collected at each outlet of the microfluidic channel, using atomic absorption spectroscopy. Magnetic particles steering ratios of 0.99 and 0.75 were reached with 400 mT/m gradient amplitude and measured by video analyses and atomic absorption spectroscopy, respectively. Experimental data shows that the steering ratio increases with higher magnetic gradients. Moreover, theory suggests that larger particles (or aggregates), higher magnetizations, and lower flows can also be used to improve the steering ratio. The technological limitation of the approach is that an MRI gradient amplitude increase to a few hundred milliteslas per meter is needed. A simple analytical method based on magnetophoretic velocity predictions and geometric considerations is proposed for steering ratio calculation. Magn Reson Med 63:1336–1345, 2010. © 2010 Wiley‐Liss, Inc.
Quantitative two‐dimensional HRMAS 1H‐NMR spectroscopy‐based metabolite profiling of human cancer cell lines and response to chemotherapy
Authors: Bayet‐Robert Mathilde , Loiseau Dominique , Rio Pascale , Demidem Aicha , Barthomeuf Chantal , Stepien Georges , Morvan Daniel
Published: April 2010

NMR spectroscopy‐based metabolomics still needs development in quantification procedures. A method was designed for quantitative two‐dimensional high resolution magic angle spinning (HRMAS) proton‐NMR spectroscopy‐based metabolite profiling of intact cells. It uses referencing of metabolite‐related NMR signals to protein‐related NMR signals and yields straightforward and automatable metabolite profiling. The method enables exploitation of only two‐dimensionally visible metabolites and combination of one‐ and two‐dimensional spectra, thus providing an appreciable number of screened metabolites. With this procedure, 32 intracellular metabolites were attributed and quantified in human normal fibroblasts and tumor cells. The phenotype of several tumor cell lines (MCF7, PC3, 143B, and HepG2) was characterized by high levels of glutathione in cell lines with the higher proliferation rate, high levels of creatine, low levels of free amino acids, increased levels of phospholipid derivatives (mostly phosphocholine), and lower lactate content in cell lines with the higher proliferation rate. Other metabolites such as fatty acids differed widely among tumor cell lines. The response of tumor cell lines to chemotherapy also was evaluated by differential metabolite profiling, bringing insights into drug cytotoxicity and tumor cell adaptive mechanisms. The method may prove widely applicable to tumor cell phenotyping. Magn Reson Med 63:1172–1183, 2010. © 2010 Wiley‐Liss, Inc.
Quantitative evaluation of k‐space reordering schemes for compatible dual‐echo arteriovenography (CODEA)
Authors: Park Sung‐Hong , Shim Hackjoon , Moon Chan‐Hong , Kim Jung‐Hwan , Bae Kyongtae Ty
Published: April 2010

Compatible dual‐echo arteriovenography (CODEA) is a recently developed technique for simultaneous acquisition of time‐of‐flight MR angiogram (MRA) and blood oxygenation level–dependent MR venogram (MRV) using an echo‐specific k‐space reordering scheme. In this study, we evaluated and compared the image quality of CODEA MRA/MRV implemented with two different schemes of echo‐specific k‐space reordering: one along the 1st phase‐encode direction (one‐dimensional) only and the other along both phase‐encode directions (two‐dimensional). Our results showed that use of the two‐dimensional reordering scheme improved contrast‐to‐noise ratio of small arteries by ∼8%, although not statistically significant (P > 0.1). Contrast‐to‐noise ratio of the CODEA MRAs was better than that for the non‐CODEA dual‐echo MRA without k‐space reordering (contrast‐to‐noise ratio increased in large arteries by ∼10% and small arteries by ∼45%; P < 0.1). Contrast‐to‐noise ratio of the CODEA MRAs was comparable with that of the conventional single‐echo MRA for large arteries but reduced by ∼20% for small arteries. Contrast‐to‐noise ratio of veins on the CODEA MRVs was equivalent to that of the conventional single‐echo and the non‐CODEA dual‐echo MRVs. However, some veins in the CODEA MRVs showed stronger contrast than those in the single‐echo MRV in relation to the contrast of neighboring arterial signals. Magn Reson Med 63:1404–1410, 2010. © 2010 Wiley‐Liss, Inc.
Model‐based reconstruction for cardiac cine MRI without ECG or breath holding
Authors: Odille Freddy , Uribe Sergio , Batchelor Philip G. , Prieto Claudia , Schaeffter Tobias , Atkinson David
Published: April 2010

This paper describes an acquisition and reconstruction strategy for cardiac cine MRI that does not require the use of electrocardiogram or breath holding. The method has similarities with self‐gated techniques as information about cardiac and respiratory motion is derived from the imaging sequence itself; here, by acquiring the center k‐space line at the beginning of each segment of a balanced steady‐state free precession sequence. However, the reconstruction step is fundamentally different: a generalized reconstruction by inversion of coupled systems is used instead of conventional gating. By correcting for nonrigid cardiac and respiratory motion, generalized reconstruction by inversion of coupled systems (GRICS) uses all acquired data, whereas gating rejects data acquired in certain motion states. The method relies on the processing and analysis of the k‐space central line data: local information from a 32‐channel cardiac coil is used in order to automatically extract eigenmodes of both cardiac and respiratory motion. In the GRICS framework, these eigenmodes are used as driving signals of a motion model. The motion model is defined piecewise, so that each cardiac phase is reconstructed independently. Results from six healthy volunteers, with various slice orientations, show improved image quality compared to combined respiratory and cardiac gating. Magn Reson Med 63:1247–1257, 2010. © 2010 Wiley‐Liss, Inc.
Postprocessing correction for distortions in T2* decay caused by quadratic cross‐slice B0 inhomogeneity
Authors: Yang Xiangyu , Sammet Steffen , Schmalbrock Petra , Knopp Michael V.
Published: April 2010

Relaxometric measurement of the effective transverse relaxation rate R plays an important role in the quantitative evaluation of brain function, perfusion, and tissue iron content. However, accurate measurement of R is prone to macroscopic background field inhomogeneity. In clinical applications and systems, postprocessing correction techniques are more flexible in implementation than unsupported protocol or hardware modifications. The current postprocessing correction approach assumes the cross‐slice background field inhomogeneity can be approximated by a linear gradient and corrects for a sinc modulation function. The importance of the high‐order terms in background field inhomogeneity has increased with the fast development of high‐ and ultrahigh‐field scanners in recent years. In this study, we derived an analytical expression of the free induction decay signal modulation in the presence of a quadratic cross‐slice background field inhomogeneity. The proposed quadratic correction method was applied to phantom and volunteer studies and demonstrated to be superior to the classic monoexponential model, monoexponential‐plus‐constant model, and the linear sinc correction method in recovering background field inhomogeneity‐induced. R overestimations with visual inspection of R parametric maps and a statistical model selection technique. We also tabulated 7‐T T/R measurements of several human brain structures and MnCl2 solutions with various concentrations for fellow researchers' reference. Magn Reson Med 63:1258–1268, 2010. © 2010 Wiley‐Liss, Inc.
Phase‐sensitive, dual‐acquisition, single‐slab, 3D, turbo‐spin‐echo pulse sequence for simultaneous T2‐weighted and fluid‐attenuated whole‐brain imaging
Authors: Park Jaeseok , Park Suhyung , Yeop Kim Eung , Suh Jin‐Suck
Published: April 2010

Conventional T2‐weighted turbo/fast spin echo imaging is clinically accepted as the most sensitive method to detect brain lesions but generates a high signal intensity of cerebrospinal fluid (CSF), yielding diagnostic ambiguity for lesions close to CSF. Fluid‐attenuated inversion recovery can be an alternative, selectively eliminating CSF signals. However, a long time of inversion, which is required for CSF suppression, increases imaging time substantially and thereby limits spatial resolution. The purpose of this work is to develop a phase‐sensitive, dual‐acquisition, single‐slab, three‐dimensional, turbo/fast spin echo imaging, simultaneously achieving both conventional T2‐weighted and fluid‐attenuated inversion recovery–like high‐resolution whole‐brain images in a single pulse sequence, without an apparent increase of imaging time. Dual acquisition in each time of repetition is performed, wherein an in phase between CSF and brain tissues is achieved in the first acquisition, while an opposed phase, which is established by a sequence of a long refocusing pulse train with variable flip angles, a composite flip‐down restore pulse train, and a short time of delay, is attained in the second acquisition. A CSF‐suppressed image is then reconstructed by weighted averaging the in‐ and opposed‐phase images. Numerical simulations and in vivo experiments are performed, demonstrating that this single pulse sequence may replace both conventional T2‐weighted imaging and fluid‐attenuated inversion recovery. Magn Reson Med 63:1422–1430, 2010. © 2010 Wiley‐Liss, Inc.