bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of near‐infrared fluorescent deoxyglucose probes with different dyes for tumor diagnosis in vivo
Authors: Guo Jing , Du Changli , Shan Lingling , Zhu Hongyan , Xue Bing , Qian Zhiyu , Achilefu Samuel , Gu Yueqing
Published: April 2012

Glucose plays a central role in the cellular energy metabolism. Malignant tumors exhibit an elevated rate of glycolysis over normal tissues. In this study, two near‐infrared fluorescent dyes, Cypate and ICG‐Der‐02, with different water solubility, were conjugated to 2‐amino‐2‐deoxy‐d‐glucose (2DG) to form Cypate‐2DG and ICG‐Der‐02‐2DG, respectively, for NIR fluorescent imaging of tumors in nude mice. The clear routes and tumor targeting abilities of the two NIR fluorescent 2DG probes were compared. Results showed that ICG‐Der‐02‐2DG with higher hydrophilicity was cleared faster by kidneys than the more lipophilic Cypate‐2DG. Cypate‐2DG had slower but stronger tumor targeting ability compared with ICG‐Der‐02‐2DG. To investigate the correlation between the targeting ability of the probe and the glucose transporter (GLUT1) expression levels of cancer cells, the accumulation of Cypate‐2DG in tumors was assessed in MCF‐7/estradiol, U87MG, MCF‐7 and MDA‐MB‐435 tumor xenografts, which express different levels of GLUT1. The results show that both Cypate‐2DG and ICG‐Der‐02‐2DG possess tumor targeting ability on all the tumors examined, with a proportional correlation to GLUT1 expression. The findings demonstrate the broad applicability of these molecular probes for optical imaging of tumors and glucose‐related pathologies. Copyright © 2012 John Wiley & Sons, Ltd.
Electron paramagnetic resonance as a sensitive tool to assess the iron oxide content in cells for MRI cell labeling studies
Authors: Danhier P. , De Preter G. , Boutry S. , Mahieu I. , Leveque P. , Magat J. , Haufroid V. , Sonveaux P. , Bouzin C. , Feron O. , Muller R. N. , Jordan B. F. , Gallez B.
Published: April 2012

MRI cell tracking is a promising technique to track various cell types (stem cells, tumor cells, etc.) in living animals. Usually, cells are incubated with iron oxides (T2 contrast agent) in order to take up the particles before being injected in vivo. Iron oxide quantification is important in such studies for validating the labeling protocols and assessing the dilution of the particles with cell proliferation. We here propose to implement electron paramagnetic resonance (EPR) as a very sensitive method to quantify iron oxide concentration in cells. Iron oxide particles exhibit a unique EPR spectrum, which directly reflects the number of particles in a sample. In order to compare EPR with existing methods (Perls's Prussian blue reaction, ICP‐MS and fluorimetry), we labeled tumor cells (melanoma and renal adenocarcinoma cell lines) and fibroblasts with fluorescent iron oxide particles, and determined the limits of detection of the different techniques. We show that EPR is a very sensitive technique and is specific for iron oxide quantification as measurements are not affected by endogenous iron. As a consequence, EPR is well adapted to perform ex vivo analysis of tissues after cell tracking experiments in order to confirm MRI results. Copyright © 2012 John Wiley & Sons, Ltd.
Imaging of Her2‐targeted magnetic nanoparticles for breast cancer detection: comparison of SQUID‐detected magnetic relaxometry and MRI
Authors: Adolphi Natalie L. , Butler Kimberly S. , Lovato Debbie M. , Tessier T. E. , Trujillo Jason E. , Hathaway Helen J. , Fegan Danielle L. , Monson Todd C. , Stevens Tyler E. , Huber Dale L. , Ramu Jaivijay , Milne Michelle L. , Altobelli Stephen A. , Bryant Howard C. , Larson Richard S. , Flynn Edward R.
Published: April 2012

Both magnetic relaxometry and magnetic resonance imaging (MRI) can be used to detect and locate targeted magnetic nanoparticles, noninvasively and without ionizing radiation. Magnetic relaxometry offers advantages in terms of its specificity (only nanoparticles are detected) and the linear dependence of the relaxometry signal on the number of nanoparticles present. In this study, detection of single‐core iron oxide nanoparticles by superconducting quantum interference device (SQUID)‐detected magnetic relaxometry and standard 4.7 T MRI are compared. The nanoparticles were conjugated to a Her2 monoclonal antibody and targeted to Her2‐expressing MCF7/Her2‐18 (breast cancer cells); binding of the nanoparticles to the cells was assessed by magnetic relaxometry and iron assay. The same nanoparticle‐labeled cells, serially diluted, were used to assess the detection limits and MR relaxivities. The detection limit of magnetic relaxometry was 125 000 nanoparticle‐labeled cells at 3 cm from the SQUID sensors. T2‐weighted MRI yielded a detection limit of 15 600 cells in a 150 µl volume, with r1 = 1.1 mm−1 s−1 and r2 = 166 mm−1 s−1. Her2‐targeted nanoparticles were directly injected into xenograft MCF7/Her2‐18 tumors in nude mice, and magnetic relaxometry imaging and 4.7 T MRI were performed, enabling direct comparison of the two techniques. Co‐registration of relaxometry images and MRI of mice resulted in good agreement. A method for obtaining accurate quantification of microgram quantities of iron in the tumors and liver by relaxometry was also demonstrated. These results demonstrate the potential of SQUID‐detected magnetic relaxometry imaging for the specific detection of breast cancer and the monitoring of magnetic nanoparticle‐based therapies. Copyright © 2012 John Wiley & Sons, Ltd.
Impact of H‐aggregation on activatable MMP‐2‐specific probes for optical imaging
Authors: Lebel Réjean , Bonin Marc‐André , Zriba Riadh , Radulska Adrianna , Neugebauer Witold , Lepage Martin
Published: April 2012

In order to target and image MMP‐2 activity using optical imaging, we developed a panel of new MMP‐2 probes based on Cy5 and QSY21 as fluorophore/quencher FRET partners, separated by various MMP‐2 specific peptide substrates. We compared these probes for their specificity against other MMPs, their rate of activation by MMP‐2 and their initial quenching. Copyright © 2012 John Wiley & Sons, Ltd.
Prolonged in vivo circulation time by zwitterionic modification of magnetite nanoparticles for blood pool contrast agents
Authors: Xiao Wangchuan , Lin Jiang , Li Mingli , Ma Yongjie , Chen Yuxin , Zhang Chunfu , Li Dan , Gu Hongchen
Published: April 2012

Long circulation time is critical for blood pool contrast agents used in high‐resolution magnetic resonance angiography. For iron oxide particle contrast agents, size and surface properties significantly influence their in vivo performance. We developed a novel long‐circulating blood pool contrast agent by introducing zwitterionic structure onto the particle surface. Zwitterionic structure was fabricated by 3‐(diethylamino)propylamine (DEAPA) grafted onto the surface of ployacrylic acid coated magnetite nanoparticles via EDC/NHS [N‐(3‐dimethylaminopropyl)‐N′‐ethylcarbo‐diimide hydrochloride/N‐hydroxysuccinimide] coupling chemistry. Zwitterionic particles demonstrated five times lower macrophage cell uptake than the original particles and low cell toxicity. Magnetic resonance angiography indicated that zwitterionic nanoparticles had much longer in vivo circulation time than the original particles and were an ideal candidate for blood pool contrast agent. We suppose that zwitterionic modification by DEAPA and EDC/NHS can be used generally for coating nanoparticles with carboxyl surface and to prolong their circulating time. Copyright © 2012 John Wiley & Sons, Ltd.
Phase 2 trial of maintenance bevacizumab alone after bevacizumab plus pemetrexed and carboplatin in advanced, nonsquamous nonsmall cell lung cancer
Authors: Stevenson James P. , Langer Corey J. , Somer Robert A. , Evans Tracey L. , Rajagopalan Kumar , Krieger Kimberly , Jacobs‐Small Mona , Dyanick Nikolas , Milcarek Barry , Coakley Susan , Walker Suzanne , Eaby‐Sandy Beth , Hageboutros Alexandre
Published: April 2012

BACKGROUND:

The authors performed a phase 2 study of bevacizumab plus pemetrexed and carboplatin followed by maintenance bevacizumab in patients with advanced, nonsquamous nonsmall cell lung cancer.

METHODS:

Previously untreated patients with advanced, nonsquamous nonsmall cell lung cancer and an Eastern Cooperative Oncology Group performance status of 0 or 1 received bevacizumab 15 mg/kg, pemetrexed 500 mg/m2 and carboplatin at an area under the concentration‐time curve of 6 intravenously on day 1 every 21 days. Responding or stable patients who completed 6 cycles then received bevacizumab maintenance every 21 days until disease progression.

RESULTS:

In total, 43 patients (40 who were evaluable for response) were entered on the study. Treatment‐related grade 3/4 toxicities were low and included febrile neutropenia (2%), neutropenia (28%), anemia (18%), thrombocytopenia (11%), hypertension (7%), epistaxis (5%), venous thrombosis (8%), dyspnea (7%), rectovaginal fistula (2.3%), infusion reaction (2%), and cerebrovascular event (2%). One patient died from complications of venous thromboembolism and cerebrovascular accident after Cycle 2. Minimal clinically significant toxicity occurred during maintenance bevacizumab. Two complete responses (5%) were observed, and 17 patients (42%) had a partial response. Fifteen patients (38%) displayed disease stability. The overall disease control rate was 85%. At a median follow‐up of 15.8 months, the median progression‐free survival was 7.1 months (95% confidence interval, 5.9‐8.3 months), and the median overall survival was 17.1 months (95% confidence interval, 8.8‐25.5 months).

CONCLUSIONS:

Combined bevacizumab, pemetrexed, and carboplatin followed by maintenance bevacizumab was well tolerated and displayed remarkable activity in patients with previously untreated, advanced, nonsquamous nonsmall cell lung cancer. Cancer 2012. © 2012 American Cancer Society.
Impact of diagnosis and treatment of clinically localized prostate cancer on health‐related quality of life for older Americans
Authors: Reeve Bryce B. , Stover Angela M. , Jensen Roxanne E. , Chen Ronald C. , Taylor Kathryn L. , Clauser Steven B. , Collins Sean P. , Potosky Arnold L.
Published: April 2012

BACKGROUND:

Few studies have measured longitudinal changes in health‐related quality of life (HRQOL) among patients with prostate cancer starting before their cancer diagnosis or have provided simultaneous comparisons with a matched noncancer cohort. In the current study, the authors addressed these gaps by providing unique estimates of the effects of a cancer diagnosis on HRQOL accounting for the confounding effects of ageing and comorbidity.

METHODS:

Data from the Surveillance, Epidemiology, and End Results registry were linked with Medicare Health Outcomes Survey (MHOS) data. Eligible patients (n = 445) were Medicare beneficiaries aged ≥65 years from 1998 to 2003 whose first prostate cancer diagnosis occurred between their baseline and follow‐up MHOS. By using propensity score matching, 2225 participants without cancer were identified from the MHOS data. Analysis of covariance models were used to estimate changes in HRQOL as assessed with the Medical Outcomes Study Short Form‐36 survey and the activities of daily living scale.

RESULTS:

Before diagnosis, patients with prostate cancer reported HRQOL similar to that of men without cancer. After diagnosis, men with prostate cancer experienced significant decrements in physical, mental, and social aspects of their lives relative to controls, especially within the first 6 months after diagnosis. For men who were surveyed beyond 1 year after diagnosis, HRQOL was similar to that for controls. However, an increased risk for major depressive disorder was observed among men who received either conservative management or external beam radiation.

CONCLUSIONS:

The current findings illustrated the time‐sensitive nature of decline in HRQOL after a cancer diagnosis and enhanced understanding of the impact of prostate cancer diagnosis and treatment on physical, mental, and social well being among older men. Cancer 2012. © 2012 American Cancer Society.
Clinicopathologic features, patterns of recurrence, and survival among women with triple‐negative breast cancer in the National Comprehensive Cancer Network
Authors: Lin Nancy U. , Vanderplas Ann , Hughes Melissa E. , Theriault Richard L. , Edge Stephen B. , Wong Yu‐Ning , Blayney Douglas W. , Niland Joyce C. , Winer Eric P. , Weeks Jane C.
Published: April 2012

BACKGROUND:

The objective of this study was to describe clinicopathologic features, patterns of recurrence, and survival according to breast cancer subtype with a focus on triple‐negative tumors.

METHODS:

In total, 15,204 women were evaluated who presented to National Comprehensive Cancer Network centers with stage I through III breast cancer between January 2000 and December 2006. Tumors were classified as positive for estrogen receptor (ER) and/or progesterone receptor (PR) (hormone receptor [HR]‐positive) and negative for human epidermal growth factor receptor 2 (HER2); positive for HER2 and any ER or PR status (HER2‐positive); or negative for ER, PR, and HER2 (triple‐negative).

RESULTS:

Subtype distribution was triple‐negative in 17% of women (n = 2569), HER2‐positive in 17% of women (n = 2602), and HR‐positive/HER2‐negative in 66% of women (n = 10,033). The triple‐negative subtype was more frequent in African Americans compared with Caucasians (adjusted odds ratio, 1.98; P < .0001). Premenopausal women, but not postmenopausal women, with high body mass index had an increased likelihood of having the triple‐negative subtype (P = .02). Women with triple‐negative cancers were less likely to present on the basis of an abnormal screening mammogram (29% vs 48%; P < .0001) and were more likely to present with higher tumor classification, but they were less likely to have lymph node involvement. Relative to HR‐positive/HER2‐negative tumors, triple‐negative tumors were associated with a greater risk of brain or lung metastases; and women with triple‐negative tumors had worse breast cancer‐specific and overall survival, even after adjusting for age, disease stage, race, tumor grade, and receipt of adjuvant chemotherapy (overall survival: adjusted hazard ratio, 2.72; 95% confidence interval, 2.39‐3.10; P < .0001). The difference in the risk of death by subtype was most dramatic within the first 2 years after diagnosis (overall survival for 0‐2 years: OR, 6.10; 95% confidence interval, 4.81‐7.74).

CONCLUSIONS:

Triple‐negative tumors were associated with unique risk factors and worse outcomes compared with HR‐positive/HER2‐negative tumors. Cancer 2012. © 2012 American Cancer Society.
The long‐term outcome of treated high‐risk nonmuscle‐invasive bladder cancer
Authors: Thomas Francis , Rosario Derek J. , Rubin Naomi , Goepel John R. , Abbod Maysam F. , Catto James W. F.
Published: April 2012

BACKGROUND:

The treatment of high‐risk nonmuscle‐invasive bladder cancer (NMIBC) is difficult given its unpredictable natural history and patient comorbidities. Because current case series are mostly limited in size, the authors report the outcomes from a large, single‐center series.

METHODS:

The authors reviewed all patients with primary, high‐risk NMIBC at their institution from 1994 to 2010. Outcomes were matched with clinicopathologic data. Patients who had muscle invasion within 6 months or had insufficient follow‐up (<6 months) were excluded. Correlations were analyzed using multivariable Cox regression and log‐rank analysis (2‐sided; P < .05).

RESULTS:

In total, 712 patients (median age, 73.7 years) were included. Progression to muscle invasion occurred in 110 patients (15.8%; 95% confidence interval [CI], 13%‐18.3%) at a median of 17.2 months (interquartile range, 8.9‐35.8 months), including 26.5% (95% CI, 22.2%‐31.3%) of the 366 patients who had >5 years follow‐up. Progression was associated with age (hazard ratio [HR], 1.04; P = .007), dysplastic urothelium (HR, 1.6; P = .003), urothelial cell carcinoma variants (HR, 3.2; P = .001), and recurrence (HR, 18.3; P < .001). Disease‐specific mortality occurred in 134 patients (18.8%; 95% CI, 16.1%‐21.9%) at a median of 28 months (interquartile range, 15‐45 months), including 28.7% (95% CI, 24.5%‐33.3%) of those who had 5 years of follow‐up. Disease‐specific mortality was associated with age (HR, 1.1; P < .001), stage (HR, 1.7; P = .003), dysplasia (HR, 1.3; P = .05), and progression (HR, 5.2; P < .001). Neither progression nor disease‐specific mortality were associated with the receipt of bacillus Calmette‐Guerin (P > .6).

CONCLUSIONS:

Within a program of conservative treatment, progression of high‐risk NMIBC was associated with a poor prognosis. Surveillance and bacillus Calmette‐Guerin were ineffective in altering the natural history of this disease. The authors concluded that the time has come to rethink the paradigm of management of this disease. Cancer 2012. © 2012 American Cancer Society.
Exact location of consensus and consistency colors in the osa‐ucs for the italian language
Authors: Paggetti Giulia , Menegaz Gloria
Published: April 2012

In a previous work, the authors reported on the results of a color naming experiment performed on native Italian speakers regarding the location of focal colors and centroids in the Uniform Color Scales of the Optical Society of America color system. That work was aiming at comparing such data with those previously obtained by Boynton and Olson (B&O) accounting for the differences in the paradigm and the language. The number of consistency and consensus colors in the different lightness plans was also reported but no information was provided on their placement. Though, such information is very important for any subsequent modeling stage. The objective of this article is to fill such a gap and share such data with the scientific community to provide a reference database for future investigation. Three different datasets were considered: the extended OSA (E‐OSA), the reduced OSA (R‐OSA), and the B&O's (B&O) sets of reference colors. Results show a good overlap among the locations of the consensus colors in the {L, j, g} color model between B&O and the subset of E‐OSA colors overlapping with the B&O 424 colors (R‐OSA), as well as a strong agreement on consistency. Furthermore, a close proximity among the centroids of homologue regions for the majority of the classes was found. © 2012 Wiley Periodicals, Inc. Col Res Appl, 38, 437–447, 2013
The effect of hue on the perception of blackness using munsell samples
Authors: Haslup J. Reid Clonts , Shamey Renzo , Hinks David
Published: April 2012

Although black is an important color, the perception of black objects has not been systematically examined. The purpose of this work was to determine the influence of hue on the perception of preferred blackness. A set of 20 glossy low chroma Munsell sheets were purchased comprising a complete hue circle with a value and chroma of two and one, respectively (L* = 19.3–20.75, and C* = 3.66–6.58). The Munsell samples were divided into two interleaved groups: (5R, 5YR, 5Y, 5GY, 5G, 5BG, 5B, 5PB, 5P, and 5RP) and (10R, 10YR, 10Y, 10GY, 10G, 10BG, 10B, 10PB, 10P, and 10RP). Fifty color‐normal observers force‐ranked the two sets of 10 samples from “most like black” to “least like black.” Observers then assessed a set of six samples that represented the three samples from each set of 10 that the observer chose to be “most like black.” The 50 observers were found to have fairly good autoconcordance and concordance values. In repeat experiments observers agreed with themselves in 81% of the pairwise decisions, and they agreed with the grand mean rank 76% of the time. The blue–green samples (with Munsell hue notations 10G, 5BG, and 10BG) were most selected (and were considered blackest), followed by green, blue, and purple–blue. The samples selected the fewest times by any observer as being most black were the red samples. The grand mean rankings demonstrate that greenish to bluish blacks are perceived by the observers as “blacker” than yellowish and reddish blacks. © 2012 Wiley Periodicals, Inc. Col Res Appl, 38, 423–428, 2013
Conformational Distributions of N‐Acetyl‐L‐cysteine in Aqueous Solutions: A Combined Implicit and Explicit Solvation Treatment of VA and VCD Spectra
Authors: Poopari Mohammad Reza , Dezhahang Zahra , Yang Guochun , Xu Yunjie
Published: April 2012

The conformational distributions of N‐acetyl‐L‐cysteine (NALC) in aqueous solutions at several representative pH values are investigated using vibrational absorption (VA), UV/Vis, and vibrational circular dichroism (VCD) spectroscopy, together with DFT and molecular dynamics (MD) simulations. The experimental VA and UV/Vis spectra of NALC in water are obtained under strongly acid, neutral, and strongly basic conditions, as well as the VCD spectrum at pH 7 in D2O. Extensive searches are carried out to locate the most stable conformers of the protonated, neutral, deprotonated, and doubly deprotonated NALC species at the B3LYP/6‐311++G(d,p) level. The inclusion of the polarizable continuum model (PCM) modifies the geometries and the relative stabilities of the conformers noticeably. The simulated PCM VA spectra show significantly better agreement with the experimental data than the gas‐phase ones, thus allowing assignment of the conformational distributions and dominant species under each experimental condition. To further properly account for the discrepancies noted between the experimental and simulated VCD spectra, PCM and the explicit solvent model are utilized. MD simulations are used to aid the modelling of the NALC–(water)N clusters. The geometry optimization, harmonic frequency calculations, and VA and VCD intensities are computed for the NALC–(water)3,4 clusters at the B3LYP/6‐311++G(d,p) level without and with the PCM. The inclusion of both explicit and implicit solvation models at the same time provides a decisively better agreement between theory and experiment and therefore conclusive information about the conformational distributions of NALC in water and hydrogen‐bonding interactions between NALC and water molecules.
The association studies of ADIPOQ with type 2 diabetes mellitus in Chinese populations
Authors: Li Yiping , Yang Ying , Shi Li , Li Xianli , Zhang Ying , Yao Yufeng
Published: April 2012

Adiponectin, which is secreted by the white adipose tissue, plays an important role in type 2 diabetes mellitus (T2DM) and its complications. Since 2002, many investigators explored the association between ADIPOQ single nucleotide polymorphisms and T2DM in different ethnic populations from different regions. In China, the results of numerous studies of the association between ADIPOQ and T2DM were not consistent, which may be caused by population‐specific effects or environmental effects. This review describes the association between ADIPOQ and T2DM, the metabolic characteristics and the complications of T2DM in Chinese populations. Copyright © 2012 John Wiley & Sons, Ltd.
Simulated effect of soil depth and bedrock topography on near‐surface hydrologic response and slope stability
Authors: Lanni Cristiano , McDonnell Jeff , Hopp Luisa , Rigon Riccardo
Published: April 2012

This paper explores the effect of hillslope hydrological behavior on slope stability in the context of transient subsurface saturation development and landslide triggering. We perform a series of virtual experiments to address how subsurface topography affects the location and spatial pattern of slip surface development and pore pressure dynamics. We use a 3D Darcy–Richards equation solver (Hydrus 3‐D) combined with a cellular automata slope stability model to simulate the spatial propagation of the destabilized area. Our results showed that the soil–bedrock interface and in particular, bedrock depressions, played a key role in pore pressure dynamics, acting as an impedance for the downslope drainage of perched water. Filling and spilling of depressions in the bedrock surface microtopography induced localized zones of increased pressure head such that the development of pore‐pressure fields—not predictable by surface topography—lead to rapid landslide propagation. Our work suggests that landslide models should consider the subsurface topography in order to include a connectivity component in the mathematical description of hydrological processes operating at the hillslope scale. Copyright © 2012 John Wiley & Sons, Ltd.
Outcomes of squamous cell cancer of the oral tongue managed at the princess margaret hospital
Authors: Goldstein David P. , Bachar Gideon Y. , Lea Jane , Shrime Mark G. , Patel Rajan S. , Gullane Patrick J. , Brown Dale H. , Gilbert Ralph W. , Kim John , Waldron Jonathan , Perez–Ordonez Bayardo , Davis Aileen M. , Cheng Lu , Xu Wei , Irish Jonathan C.
Published: April 2012

Background

The purpose of this study was to analyze the outcomes and treatment in patients with squamous cell carcinoma (SCC) of the oral tongue, as well as validate previously reported predictors of survival.

Methods

We retrospectively reviewed 259 patients treated with curative intent between 1994 and 2004. Kaplan–Meier estimates, log‐rank test, and Cox regression models were used for statistical analysis.

Results

Two hundred fifty‐nine patients were managed with surgery; 67 patients (25%) received adjuvant radiotherapy. Mean follow‐up was 60 months. The 5‐year local and regional control rates were 78% and 69.4%, respectively. The 5‐year overall, disease‐specific, and recurrence‐free survival rates were 69%, 70.9%, and 53%, respectively. The only significant predictor of both overall survival (OS) and disease‐free survival (DFS) on multivariable analysis was pathologic N classification.

Conclusion

Treatment of early tongue SCC effectively achieves local control and DFS. Nodal disease remains to be 1 of the most important prognostic factors in terms of recurrence and survival. © 2012 Wiley Periodicals, Inc. Head Neck, 2013
Hematopoietic chimerism in liver transplantation patients and hematopoietic stem/progenitor cells in adult human liver
Authors: Wang Xiao Qi , Lo Chung Mau , Chen Lin , Cheung Cindy K.Y. , Yang Zhen Fan , Chen Yong Xiong , Ng Michael N. , Yu Wan Ching , Ming Xiaoyan , Zhang Wu , Ho David W.Y. , Chan See Ching , Fan Sheung Tat
Published: April 2012

Liver transplantation (LT) is a cure for many liver diseases. Blood chimerism of donor origin can develop after LT, which raises the possibility of the existence of hematopoietic stem/progenitor cells (HSPCs) in the liver. We characterized the blood chimerism in a large cohort of 249 LT patients and analyzed putative HSPCs in adult human livers. The overall incidence of chimerism was 6.43%, of which 11.11% was among short-term (1 day to 6 months) and 3.77% was among long-term (6 months to 8 years) LT patients. Hematopoietic Lin−CD34+CD38−CD90+ populations have been demonstrated to generate long-term lymphomyeloid grafts in transplantations. In human adult livers, we detected Lin−CD34+CD38−CD90+ populations accounting for 0.03% ± 0.017% of the total single liver cells and for 0.05% ± 0.012% of CD45+ liver cells. Both Lin−CD34+ and Lin−CD45+ liver cells, from extensively perfused human liver grafts, were capable of forming hematopoietic myeloid-lineage and erythroid-lineage methylcellulose colonies. More importantly, Lin−CD45+ or CD45+ liver cells could be engrafted into hematopoietic cells in an immunodeficient mouse model. These results are the first evidence of the presence of putative HSPC populations in the adult human liver, where the liver is a good ectopic niche. The discovery of the existence of HSPCs in the adult liver have implications for the understanding of extramarrow hematopoiesis, liver regeneration, mechanisms of tolerance in organ transplantation, and

de novo

cancer recurrence in LT patients.

Conclusion

: The human adult liver contains a small population of HSPCs. In LT patients, there are two types of chimerisms: transient chimerism, resulting from mature leucocytes, and long-term chimerism, derived from putative HSPCs in the liver graft. (Hepatology 2012)
Molecular Alignment Induced by Ultrashort Laser Pulses and Its Impact on Molecular Motion
Authors: Fleischer Sharly , Khodorkovsky Yuri , Gershnabel Erez , Prior Yehiam , Averbukh Ilya Sh.
Published: April 2012

Spectroscopy aims at extracting information about matter through its interaction with light. However, when performed on gas and liquid phases as well as solid phases lacking long‐range order, the extracted spectroscopic features are in fact averaged over the molecular isotropic angular distributions. The reason is that light–matter processes depend on the angle between the transitional molecular dipole and the polarization of the light interacting with it. This understanding gave birth to the constantly expanding field of “laser‐induced molecular alignment”. In this paper, we attempt to guide the readers through our involvement (both experimental and theoretical) in this field in the last few years. We start with the basic phenomenon of molecular alignment induced by a single pulse, continue with selective alignment of close molecular species and unidirectional molecular rotation induced by two time‐delayed pulses, and lead up to novel schemes for manipulating the spatial distributions of molecular samples through rotationally controlled scattering off inhomogeneous fields and surfaces.
Quantum Control Landscape for a Λ‐atom in the Vicinity of Second‐Order Traps
Authors: Pechen Alexander N. , Tannor David J.
Published: April 2012

We show that the second‐order traps in the control landscape for a three‐level Λ‐system found in our previous work (Phys. Rev. Lett.2011,106, 120402) are not local maxima: there exist directions in the space of controls in which the objective grows. The growth of the objective is slow — at best 4th order for weak variations of the control. This implies that simple gradient methods would be problematic in the vicinity of second‐order traps, where more sophisticated algorithms that exploit the higher order derivative information are necessary to climb up the control landscape efficiently. The theory is supported by a numerical investigation of the landscape in the vicinity of theε(t)=0 second‐order trap, performed using the GRAPE and BFGS algorithms.
Toxic effects of microcystin‐LR on the HepG2 cell line under hypoxic and normoxic conditions
Authors: Zhang Xin , Xie Ping , Zhang Xuezhen , Zhou Wenshan , Zhao Sujuan , Zhao Yanyan , Cai Yan
Published: April 2012

Microcystins (MCs) are highly liver‐specific and evidenced as a liver tumor promoter. Oxidative stress is one of the most important toxicity mechanisms of MCs, which is tightly related to oxygen concentration. The effects of MCs on animals and cell lines in normoxia and the mechanisms have been well studied, but such effects in different oxygen conditions were still unclear. The aim of the present study was to explore the cellular response of the human hepatocellular carcinoma cell line (HepG2) to MC‐LR exposure under hypoxic (1% O2) and normoxic (21% O2) conditions. We examined cell viability, mitochondrial membrane potential (MMP), superoxide dismutase (SOD) activity and gene expression posttoxin exposure. Cell viability was increased by MC‐LR in normoxia although decreased in hypoxia. MC‐LR markedly induced MMP loss under hypoxic condition but only slightly MMP loss under normoxic condition. SOD activity was significantly induced by MC‐LR in hypoxia, indicating prolonged oxidative stress. Inhibitory apoptosis protein (c‐IAP2) was significantly up‐regulated by MC‐LR under normoxic condition, suggesting that c‐IAP2 played an important role in the promotion of cell proliferation by MC‐LR. These results indicate that MC‐LR promotes cell proliferation under normoxic condition whereas induces cell apoptosis under hypoxic condition. Copyright © 2012 John Wiley & Sons, Ltd.
Cellular signal transduction can be induced by TRAIL conjugated to microcapsules
Authors: Wheatley Margaret A. , Cochran Michael C. , Eisenbrey John R. , Oum Kelleny L.
Published: April 2012

The extracellular agent tumor necrosis factor‐related apoptosis‐inducing ligand (TRAIL) can induce apoptosis in tumor cells but spare normal cells. Ligation of TRAIL to a nanoparticle would serve to facilitate targeting to an extravascular site. Polymeric ultrasound contrast agents (UCA) (microencapsulated gas bubbles) can be tracked by ultrasound imaging, and fragmented into nanoparticles by focused ultrasound. This tumor‐targeted delivery system has been shown to deliver more efficiently than solid nanoparticles. Additionally, small molecule inhibitors such as bortezomib, shown to sensitize TRAIL‐resistant cells, could be co‐administered within these UCA. In this pilot study, TRAIL was conjugated to UCA while preserving the agent's sensitivity to ultrasound. Human cancer cell lines, OVCAR‐3 and A2058, were bathed with the TRAIL‐UCA with and without the addition of bortezomib. Apoptosis was quantified using flow cytometry. OVCAR‐3 treated with TRAIL‐UCA exhibit significant (p < 0.05) apoptotosis compared to unmodified UCA, equal to positive controls, but no synergistic effect when combined with bortezomib. A2058 cells treated with TRAIL‐UCA also exhibited significant apoptosis (p < 0.01) compared to unmodified UCA, similar to positive controls and bortezomib significantly increased apoptosis in combination with TRAIL‐UCA. We conclude that TRAIL‐ligated UCA show exciting potential as a new therapy. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A 100A: 2602–2611, 2012.
Pteros: Fast and easy to use open‐source C++ library for molecular analysis
Authors: Yesylevskyy Semen O.
Published: April 2012

An open‐source Pteros library for molecular modeling and analysis of molecular dynamics trajectories for C++ programming language is introduced. Pteros provides a number of routine analysis operations ranging from reading and writing trajectory files and geometry transformations to structural alignment and computation of nonbonded interaction energies. The library features asynchronous trajectory reading and parallel execution of several analysis routines, which greatly simplifies development of computationally intensive trajectory analysis algorithms. Pteros programming interface is very simple and intuitive while the source code is well documented and easily extendible. Pteros is available for free under open‐source Artistic License from http://sourceforge.net/projects/pteros/. © 2012 Wiley Periodicals, Inc.
DFT study of the mechanism of hydroamination of ethylene with ammonia catalyzed by diplatinum(II) complexes: Inner‐ or outer‐sphere?
Authors: Kefalidis Christos E. , Tsipis Constantinos A.
Published: April 2012

A detailed analysis of the reaction profiles of the hydroamination reaction between ethylene and ammonia catalyzed by the diplatinum(II) [{Pt(NH2)(μ‐H)(PPh3)}2] complex is presented herein using density functional theory computational techniques. The coordinatively unsaturated 14e T‐shaped [Pt(NH2)(PPh3)H] species resulted from the dissociation of the diplatinum [{Pt(NH2)(μ‐H)(PPh3)}2] precatalyst are identified as the active catalytic species. All possible reaction pathways that constitute the entire catalytic cycle have exhaustively been investigated. Overall, the rate‐determining step of all catalytic cycles constructed was found to be the oxidative addition of ammonia that leads to the regeneration of the catalyst. According to the energy span model, the outer‐sphere mechanism for the hydroamination of ethylene with ammonia catalyzed by the diplatinum complexes is favored over the inner‐sphere one, whereas TOF values are in favor of the inner‐sphere mechanism. © 2012 Wiley Periodicals, Inc.
Embryonic Development and Gene Expression of Porcine SCNTEmbryos Treated With Sodium Butyrate
Authors: LIU LIMEI , LIU YING , GAO FEI , SONG GUANGQI , WEN JIANG , GUAN JIYU , YIN YUPENG , MA XIN , TANG BO , LI ZIYI
Published: April 2012

Incomplete epigenetic modification is one of important reasons of inefficient reprogramming of the donor cell nuclei in ooplasm after somatic cell nuclear transfer (SCNT). It may also underlie the observed reduced viability of cloned embryos. Sodium butyrate (NaBu) is a natural histone deacetylase inhibitor that is produced in the intestine. In the current study, we evaluated the effects of NaBu on preimplantation development, histone acetylation, and gene expression in porcine SCNT embryos. Our results showed that the blastocyst rate (24.88 ± 2.09) of cloned embryos treated with 1.0 mM NaBu for 12 hr after activation was significantly higher (P < 0.05) than that of untreated cloned embryos (13.15 ± 3.07). In addition, treated embryos displayed a global acetylated histone H3 at lysine 14 profile similar to that of in vitro fertilized (IVF) embryos during preimplantation development. Lower levels of Oct4 and Bcl‐2, but higher levels of Hdac1, in SCNT embryos at the two‐cell and blastocyst stages were observed, compared with those in the IVF counterparts. The four‐cell embryos showed no differences in the levels of these genes among IVF embryos or SCNT embryos treated with or without NaBu; however, the levels of Dnmt3b were significantly different. NaBu‐treated SCNT embryos showed similar levels of Oct4, Bcl‐2, and Dnmt3b as in IVF blastocysts. These results indicated that NaBu treatment in SCNT embryos alters their histone acetylation pattern to provide beneficial effects on in vitro developmental competence and gene expression. J. Exp. Zool. (Mol. Dev. Evol.) 318:224–234, 2012. © 2012 Wiley Periodicals, Inc.
Development and evaluation of TWIST Dixon for dynamic contrast‐enhanced (DCE) MRI with improved acquisition efficiency and fat suppression
Authors: Le Yuan , Kroeker Randall , Kipfer Hal D. , Lin Chen
Published: April 2012

Purpose:

To develop a new pulse sequence called time‐resolved angiography with stochastic trajectories (TWIST) Dixon for dynamic contrast enhanced magnetic resonance imaging (DCE‐MRI).

Materials and Methods:

The method combines dual‐echo Dixon to generate separated water and fat images with a k‐space view‐sharing scheme developed for 3D TWIST. The performance of TWIST Dixon was compared with a volume interpolated breathhold examination (VIBE) sequence paired with spectrally selective adiabatic inversion Recovery (SPAIR) and quick fat‐sat (QFS) fat‐suppression techniques at 3.0T using quantitative measurements of fat‐suppression accuracy and signal‐to‐noise ratio (SNR) efficiency, as well as qualitative breast image evaluations.

Results:

The water fraction of a uniform phantom was calculated from the following images: 0.66 ± 0.03 for TWIST Dixon; 0.56 ± 0.23 for VIBE‐SPAIR, and 0.53 ± 0.14 for VIBE‐QFS, while the reference value is 0.70 measured by spectroscopy. For phantoms with contrast (Gd‐BOPTA) concentration ranging from 0–6 mM, TWIST Dixon also provides consistently higher SNR efficiency (3.2–18.9) compared with VIBE‐SPAIR (2.8–16.8) and VIBE‐QFS (2.4–12.5). Breast images acquired with TWIST Dixon at 3.0T show more robust and uniform fat suppression and superior overall image quality compared with VIBE‐SPAIR.

Conclusion:

The results from phantom and volunteer evaluation suggest that TWIST Dixon outperforms conventional methods in almost every aspect and it is a promising method for DCE‐MRI and contrast‐enhanced perfusion MRI, especially at higher field strength where fat suppression is challenging. J. Magn. Reson. Imaging 2012;36:483–491. © 2012 Wiley Periodicals, Inc.
Optimized inversion‐prepared gradient echo imaging
Authors: Kir Albert , McMillan Alan
Published: April 2012

Purpose:

To implement a method using an extended phase graph (EPG)‐based simulation to optimize inversion‐prepared gradient echo sequences with respect to signal and contrast within the shortest acquisition time.

Materials and Methods:

A critical issue in rapid gradient‐echo imaging is the effect of residual transverse magnetization between consecutive data acquisition windows. Various spoiling schemes have been proposed to mitigate this problem, and while spoiling is often considered to be perfect, imaging can be more truthfully described using the EPG. An EPG‐based simulation is used to analyze and predict the image signal and contrast to serve as a basis for sequence optimization.

Results:

Fourteen biological phantom experiments and five brain imaging experiments on each of five healthy volunteers was performed to validate and verify the accuracy of the EPG‐based simulation. In addition, two experiments on an in‐cranial cadaver brain were performed to show the ability of the proposed method for improving overall image quality.

Conclusion:

From the experiment results, it is demonstrated that optimization of 3D magnetization‐prepared rapid gradient‐echo imaging sequences can be performed with an EPG‐based simulation to manipulate the sequence parameters for generating images with highly specific signal and contrast characteristics for quantitative T1‐weighted human brain imaging. J. Magn. Reson. Imaging 2012;36:748–755. © 2012 Wiley Periodicals, Inc.
Least square support vector and multi‐linear regression for statistically downscaling general circulation model outputs to catchment streamflows
Authors: Sachindra D. A. , Huang F. , Barton A. , Perera B. J. C.
Published: April 2012

This study employed least square support vector machine regression (LS‐SVM‐R) and multi‐linear regression (MLR) for statistically downscaling monthly general circulation model (GCM) outputs directly to monthly catchment streamflows. The scope of the study was limited to calibration and validation of the downscaling models. The methodology was demonstrated by its application to a streamflow site in the Grampian water supply system in northwestern Victoria, Australia. Probable predictors for the study were selected from the National Center for Environmental Prediction/National Center for Atmospheric Research (NCEP/NCAR) reanalysis data set based on the past literature and hydrology. Probable variables that displayed the best significant correlations, consistently with the streamflows over the entire period of the study (1950–2010) and under three 20‐year time slices (1950–1969, 1970–1989 and 1990–2010) were selected as potential predictors. To better capture seasonal variations of streamflows, downscaling models were developed for each calendar month. The standardized potential predictors were introduced to the LS‐SVM‐R and MLR models, starting from the best correlated three and then, others one by one, based on their correlations with the streamflows, until the model performance in validation was maximized. This stepwise model development enabled the identification of the optimum number of potential variables for each month. The model calibration was performed over the period 1950–1989 and validation was done for 1990–2010. LS‐SVM‐R model parameter optimization was achieved using simplex algorithm and leave‐one‐out cross‐validation. The MLR models were optimized by minimizing the sum of squared errors. In both modelling techniques, validation was performed as an independent simulation. In calibration, LS‐SVM‐R and MLR models displayed equally good performances with a trend of under‐predicting high flows. During validation, LS‐SVM‐R outperformed MLR, though both techniques over‐predicted most of the streamflows. It was concluded that LS‐SVM‐R is a better technique for statistically downscaling GCM outputs to streamflows than MLR, but still MLR is a potential technique for the same task. Copyright © 2012 Royal Meteorological Society
Observed air/soil temperature trends in open land and understory of a subtropical mountain forest, SW China
Authors: You Guangyong , Zhang Yiping , Schaefer Douglas , Sha Liqing , Liu Yuhong , Gong Hede , Tan Zhenghong , Lu Zhiyun , Wu Chuansheng , Xie Youneng
Published: April 2012

This study seeks a further understanding on climate trends in a subtropical mountain forest, SW China. Air (Ta) and soil temperature (Ts), both in open land (1983–2010) and under a forest canopy (1986–2010), were investigated. Short‐term radiation components were also measured simultaneously both in open land and understory to explore the relationships of microclimatic variables. Correlations of Ta and Ts with sunshine hours (St) and wind speed (Ws) were also analysed as driving factors of the temperature trends.

The results showed that (1) Understory radiation components were greatly reduced by the forest canopy, showing a strong effect of forest canopy on microclimatic variables. Ts_0 in open land was significantly correlated with solar radiation. Wind speed had significant influences on differences between Ta and Ts_0, between open land Ts_0 and understory Ts_0. The long‐term data showed that Ts_0 under forest canopy were closely coupled with Ta in open land. (2) Ta had a larger increase than Ts_0 in open land, and temperature increases in winter were greater than in other seasons. Soil temperature at depths under forest canopy had nearly twice the increases of those on open land; we attributed this to the higher relative increase of Ws over St. (3) A slope change in 1998 was detected in the Ts_0 and Ta difference (Ts_0 − Ta) series, suggesting different response of Ts_0 and Ta since that year. Deceleration of St and stability of Ws may have been factors.

This study improves our understanding of warming in a nature reserve where anthropogenic influences are absent. Further studies are needed for the biological and biochemical implications on subtropical mountain forest. Copyright © 2012 Royal Meteorological Society
Lamb weather types derived from reanalysis products
Authors: Jones P. D. , Harpham C. , Briffa K. R.
Published: April 2012

Weather typing, based on surface pressure charts, has been one of the principal means of analysis in synoptic climatology. Here, we summarize the history of manual and automated schemes, in the northwest European context, illustrating how the approaches can take advantage of the extended reanalysis products that have recently become available. The British Isles and the associated Lamb weather types (LWTs) are the focus of this study, but the approach can be applied to any mid‐to‐high latitude region to provide series back to 1871. However, caution is advised in the use of the approach where the quality and quantity of input data into the extended reanalysis are known to be temporally and spatially variable and/or poor in early years. This study intercompares the use of automated schemes with operational analyses, reanalyses and earlier manually derived LWTs. Copyright © 2012 Royal Meteorological Society
Label‐free imaging of polymeric nanomedicines using coherent anti‐stokes Raman scattering microscopy
Authors: Garrett N. L. , Lalatsa A. , Begley D. , Mihoreanu L. , Uchegbu I. F. , Schätzlein A. G. , Moger J.
Published: April 2012

Nanoparticulate drug delivery is known to greatly improve the efficacy of pharmaceuticals and has found a wide range of applications with different administration methods including oral, intravenous, transcutaneous and ocular routes. However, the mechanisms by which these nanoparticles travel through, interact with, and modify tissues and how this relates to the improved drug performance are still unclear. These are critical questions that need to be answered to optimise the properties of future pharmaceuticals, dose rates and frequencies, and reduce potential side effects. Our ability to answer these questions is greatly hindered by the fact that there is currently no imaging modality available to directly visualise such small particles and the structure and function of the surrounding tissue, without the aid of contrast agents or highly invasive methods. Current imaging modalities derive image contrast of the nanoparticles and/or the surrounding tissues by means of external labels. We present coherent antistokes Raman scattering microscopy as a novel tool for imaging nanoparticle drug carriers against a background of biological tissues and cells. Copyright © 2012 John Wiley & Sons, Ltd.