bluuebunny/crossref_metadata_2025 huggingface dataset:
An Efficient Route to Nanostructured Tungsten Oxide Films with Improved Electrochromic Properties
Authors: Wu Wei‐Ting , Liao Wen‐Pin , Chen Jen‐Sue , Wu Jih‐Jen
Published: September 2010

An effective chemical route to nanostructured tungsten oxide films derived from a peroxopolytungstic acid (PTA)/thiourea precursor solution is demonstrated. The conventional procedure of preparing the precursor needs more than 24 h for well‐mixing and refluxing the PTA‐based solution, while the thiourea‐assisted approach takes less than 1 h to prepare the precursor solution because the excess hydrogen peroxide can be efficiently eliminated by oxidation of thiourea. With the precursor solution, tungsten oxide films are deposited by spin coating followed by high temperature annealing. The film annealed at 400 °C possesses a porous nanostructure of nanocrystalline tungsten oxide embedded in an amorphous tungsten oxide matrix, which arises from the gaseous species released through decomposition of thiourea oxides during annealing. The 400 °C‐annealed, thiourea‐assisted tungsten oxide film exhibits electrochromic (EC) properties superior to those of the film prepared without thiourea, including large transmittance modulation and coloration efficiency, fast response time and adequate reliability. When increasing the annealing temperature to 450 °C, the thiourea‐assisted tungsten oxide film is also porous but well‐crystallized and shows inferior EC properties. Electrochemical impedance spectroscopy analysis indicates that, in addition to the porous structure, a fast charge‐transport rate within the solid portion of the 400 °C‐annealed nanostructured film plays a crucial role in enhancing EC performances of the thiourea‐assisted tungsten oxide film.
Long‐term follow‐up of monoclonal B‐cell lymphocytosis detected in environmental health studies
Authors: Marti Gerald E. , Shim Youn K. , Albitar Maher , Middleton Dan , Abbasi Fatima , Anderson Ayana , Vogt Robert F.
Published: September 2010

Background:

Four individuals in whom Monoclonal B cell Lymphocytosis (MBL) had been previously detected were evaluated for the fourth time after 15–18 years since initial testing. All four were environmental health study participants without hematologic malignancies who had elevated absolute B cell counts at initial testing.

Methods:

The current laboratory evaluation included complete blood counts, lymphocyte immunophenotypes, immunoglobulin heavy‐chain variable (IGHV) gene mutation status, and serum tests for monoclonal immunoglobulins and free light chains. Results from this evaluation were compared with those from the three previous evaluations. Clinical status was assessed by reviewing medical records.

Results:

B‐cell clones with phenotypic characteristics of the original MBL clone were detected in three of the four individuals. Since the last evaluation in 2003, one participant who had a clinical diagnosis of Waldenstrom's Macroglobulinemia had developed a diffuse large cell lymphoma and was treated. Another participant continued to show a decline in lymphocyte and B cell counts, reaching clinical lymphocytopenia and B cell lymphopenia. The MBL clone was still detectable. The remaining two participants had stable blood counts and MBL phenotypes. Neither had been diagnosed with a hematologic malignancy. However, molecular analysis revealed clonal changes in both: one showed a marked decline in the percentage of somatically‐mutated B cells, and the other showed a clonal transition from IGHV3‐13 to IGHV4‐34.

Conclusions:

A diversity of clonal evolution was observed in these MBL cases. These observations suggest that long‐term follow‐up studies using standardized MBL subcategories are essential to understanding B‐cell pathobiology and optimizing clinical management. Published 2010 Wiley‐Liss, Inc.
Chronic lymphocytic leukaemia (CLL) and CLL‐type monoclonal B‐cell lymphocytosis (MBL) show differential expression of molecules involved in lymphoid tissue homing
Authors: Rawstron Andy C. , Shingles Jane , de Tute Ruth , Bennett Fiona , Jack Andrew S. , Hillmen Peter
Published: September 2010

Introduction:

The aim of this study was to screen for cell surface markers that could discriminate CLL‐type MBL from CLL or identify CLL cases likely to have stable disease.

Methods:

Six color flow cytometry was performed on CLL‐type MBL (n = 94) and CLL (n = 387) at diagnosis or relapse; 39 cases had poor‐risk chromosomal abnormalities (17p and/or 11q deletion). Expression of 30 markers was analysed: CCR6, CD10, CD103, CD11c, CD138, CD200, CD22, CD23, CD24, CD25, CD27, CD31, CD38, CD39, CD43, CD49d, CD5, CD52, CD62L, CD63, CD79b, CD81, CD86, CD95, CXCR5, HLADR, IgD, IgG, IgM, LAIR1.

Results:

There was no difference in expression between CLL‐type MBL and CLL for the majority of markers. Differential expression was observed for several markers, mainly between MBL and CLL cases with adverse‐risk chromosomal abnormalities. These differences included lower expression of CD38 (9.4‐fold lower, P = 0.007) and CD49d (3.2‐fold lower, P = 0.008) and higher expression of LAIR‐1 (3.7‐fold higher, P = 0.003), CXCR5 (1.25‐fold higher, P = 0.002), and CCR6 (1.9‐fold higher P < 0.001) on CLL‐type MBL compared to CLL with adverse chromosomal abnormalities. CD62L (L‐selectin) which mediates lymphocyte adhesion to endothelial venules of lymphoid tissue, was expressed at a significantly different level between CLL‐type MBL and both CLL sub‐groups, with 1.3‐fold lower (P = 0.04) expression levels on the MBL cases. However, there was broad overlap in expression levels.

Conclusions:

CLL‐type MBL is phenotypically identical to CLL for a very broad range of markers. Differential expression is predominantly related to known prognostic markers and proteins involved in homing to lymphoid tissue. © 2010 International Clinical Cytometry Society
Prevalence of monoclonal B‐cell lymphocytosis: A systematic review
Authors: Shim Youn K. , Middleton Dannie C. , Caporaso Neil E. , Rachel Jane M. , Landgren Ola , Abbasi Fatima , Raveche Elizabeth S. , Rawstron Andy C. , Orfao Alberto , Marti Gerald E. , Vogt Robert F.
Published: September 2010

Background:

Individuals with monoclonal B‐cell lymphocytosis (MBL) have been identified in clinic outpatients, in unaffected relatives of patients with chronic lymphocytic leukemia (CLL), and in general populations. MBL and its relationship with CLL have been actively investigated over the last decade. This report systematically reviews the prevalence of MBL in the context of the populations studied and the evolution of laboratory methods used to define MBL.

Methods:

To identify published studies that have assessed the prevalence of MBL, we systematically searched the MEDLINE® databases and consulted with members of the International MBL Study Group. We reviewed the 10 articles that were identified by this process. We abstracted information on study populations, laboratory tests, criteria for designating MBL, and the reported frequencies.

Results:

Three of the ten studies were published in 2009, three between 2007 and 2008, and four between 2002 and 2004. Reported prevalences varied widely, ranging from 0.12 to 18.2%. This variability was clearly associated with both the laboratory methods and the populations studied. MBL was more common among older individuals and kindred of persons with CLL. The most common MBL subtype was CLL‐like MBL.

Conclusions:

Large population‐based studies of MBL that employ standardized laboratory methods with a consensus case definition are needed to assess prevalence and establish risk factors. These studies should include prospective follow‐up of MBL cases to determine the relationship between MBL and CLL. Data from original studies should be reported in sufficient detail to allow future synthesis of information from multiple studies, such as meta‐analysis. Published 2010 Wiley‐Liss, Inc.
Monoclonal B cell lymphocytosis in hepatitis C virus infected individuals
Authors: Fazi Claudia , Dagklis Antonis , Cottini Francesca , Scarfò Lydia , Bertilaccio Maria Teresa Sabrina , Finazzi Renato , Memoli Massimo , Ghia Paolo
Published: September 2010

Background:

Monoclonal B cell lymphocytosis (MBL) is a preclinical condition characterized by an expansion of clonal B cells in the absence of B lymphocytosis (BALC < 5 × 109/L) in the peripheral blood, without clinical signs, suggestive of a lymphoproliferative disorder. B cell clonal expansions are also associated with hepatitis C virus (HCV) infection and they can evolve into lymphoproliferative disorders such as mixed cryoglobulinemia and non‐Hodgkin lymphomas (NHL). The relationship between MBL and HCV infection has not been established yet.

Methods:

By five‐colour flow cytometry, we analyzed 123 HCV positive subjects with diagnosis of chronic hepatitis (94) or cirrhosis (29); 16 of those with cirrhosis had a diagnosis of hepatocellular carcinoma.

Results:

MBL were identified in 35/123 (28.5%), at significantly higher frequency than in the general population. Sixteen/thirty‐five were atypical‐chronic lymphocytic leukemia (CLL) MBL (CD5+, CD20bright), 13/35 were CLL‐like MBL (CD5bright, CD20dim), and 6/35 were CD5− MBL. Twenty‐four/ninety‐four (25.5%) patients affected by chronic hepatitis had MBL, whereas 11/29 (37.9%) patients with cirrhosis showed a B cell clone. A biased usage of IGHVgenes similar to HCV‐associated NHL was evident.

Conclusions:

All three types of MBL can be identified in HCV‐infected individuals at a higher frequency than in the general population, and their presence appears to correlate with a more advanced disease stage. The phenotypic heterogeneity is reminiscent of the diversity of NHL arising in the context of HCV infection. The persistence of HCV may be responsible for the dysregulation of the immune system and in particular of the B cell compartment. © 2010 International Clinical Cytometry Society
Commentary: Comparison of current flow cytometry methods for monoclonal B cell lymphocytosis detection
Authors: Nieto Wendy G. , Almeida Julia , Teodosio Cristina , Abbasi Fatima , Allgood Sallie D. , Connors Fiona , Rachel Jane M. , Ghia Paolo , Lanasa Mark C. , Rawstron Andy C. , Orfao Alberto , Caporaso Neil E. , Hanson Curt A. , Shim Youn K. , Vogt Robert F. , Marti Gerald E.
Published: September 2010

Monoclonal B cell lymphocytosis (MBL) is now recognized as the B‐lymphocyte analogue of a monoclonal gammopathy of unknown significance. MBL can be the precursor of chronic lymphocytic leukemia or associated with non‐Hodgkin's lymphoma. It may be associated with an autoimmune abnormality or be related to aging (immunosenescence). The combination of available new fluorochrome‐conjugated monoclonal antibody reagents, multilaser instrumentation, and improved software tools have led to a new level of multicolor analysis of MBL. Presently, several centers, including the University of Salamanca (Spain), Duke University (Durham, NC), Mayo Clinic (Rochester, MN), and the National Cancer Institute (Bethesda, MD) in conjunction with the Genetics and Epidemiology of Familial chronic lymphocytic leukemia Consortium, the Food and Drug Administration (Bethesda, MD), and the Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry (Atlanta, GA) in collaboration with Saint Luke's Hospital (Kansas City, MO), the Università Vita‐Salute San Raffaele in Milan (Italy), and Leeds Teaching Hospital (UK) are all actively conducting studies on MBL. This commentary is an updated summary of the current methods used in these centers. It is important to note the diversity of use in reagents, instruments, and methods of analysis. Despite this diversity, there is a consensus in what constitutes the diagnosis of MBL and its subtypes. There is also an emerging consensus on what the next investigative steps should be. Published 2010 Wiley‐Liss, Inc.
T‐cell‐specific deletion of STIM1 and STIM2 protects mice from EAE by impairing the effector functions of Th1 and Th17 cells
Authors: Ma Jian , McCarl Christie‐Ann , Khalil Sara , Lüthy Kevin , Feske Stefan
Published: September 2010

T‐cell function is dependent on store‐operated Ca2+ influx that is activated by the stromal interaction molecules (STIM) 1 and 2. We show that mice with T‐cell‐specific deletion of STIM1 or STIM2 are protected from EAE, a mouse model of multiple sclerosis (MS). While STIM1‐ and STIM2‐deficient T cells could be successfully primed by autoantigen, they failed to produce the proinflammatory cytokines IL‐17 and IFN‐γ. STIM1‐deficient T cells showed reduced expression of IL‐23R, required for Th17 cell homeostasis, and had impaired chemokine‐dependent T‐cell migration caused by a lack of chemokine‐induced Ca2+ influx. Autoantigen‐specific STIM1‐ or STIM2‐deficient T cells failed to expand and accumulate in the CNS and lymph nodes following adoptive transfer to passively induce EAE, suggesting that autoantigen‐specific restimulation or homeostasis of STIM1‐ and STIM2‐deficient T cells are impaired. Combined deletion of both STIM1 and STIM2, previously shown to impair Treg development and function, completely protected mice from EAE. This indicates that, in the absence of Ca2+ influx, autoreactive T cells are severely dysfunctional rendering Treg dispensable for the prevention of CNS inflammation. Our findings demonstrate that both STIM1 and STIM2 are critical for T‐cell function and autoimmunity in vivo.
Abiotic, residual and functional components of landforms
Authors: Corenblit Dov , Steiger Johannes , Delmotte Sébastien
Published: September 2010

The concept of functional ecogeomorphology developed originally from the study of fluvial systems represents an insightful framework for describing landforms as structures adjusting to external physical forces, and also as functional components contributing to the complex play of interactions and reciprocal adjustments between biotic and abiotic elements of ecosystems. In this commentary we propose to extend the model of functional ecogeomorphology by classifying landforms in three fundamental components: abiotic, residual and functional. The various possible combinations of these three components are presented and discussed in the scope of evolutionary geomorphology. Copyright © 2010 John Wiley & Sons, Ltd.
The release of cytokines by macrophages is not affected by myelin ingestion
Authors: Glim J. E. , Vereyken E. J. F. , Heijnen D. A. M. , Vallejo J. J. GarcÍa , Dijkstra C. D.
Published: September 2010

Macrophages play an important role in demyelination in multiple sclerosis (MS). Activated macrophages ingest myelin particles, thereby acquiring a foamy appearance. Foamy macrophages in MS lesions were described as being anti‐inflammatory. Therefore, these cells might play a role in modulating the inflammatory state of an active lesion. Here, we investigated the mechanism by which myelin uptake leads to skewing of macrophages toward an anti‐inflammatory phenotype. Macrophages were incubated with myelin, leading to the development of foamy macrophages. Afterwards, the cells were stimulated with the TLR‐4 ligand lipopolysaccharide (LPS), and cytokine production was determined. Interestingly, foamy macrophages appeared to have a reduced cytokine secretion and were LPS insensitive only when generated with one of the myelin preparations. The factor responsible for the different outcomes between different myelin batches turned out to be LPS. We demonstrated that LPS contamination induced insensitivity to LPS in foamy macrophages. On the contrary, foamy macrophages generated in the presence of LPS‐free myelin were able to secrete cytokines upon activation. To conclude, myelin‐laden macrophages were not LPS insensitive, indicating that they had not acquired an anti‐inflammatory phenotype. © 2010 Wiley‐Liss, Inc.
A proteome map of axoglial specializations isolated and purified from human central nervous system
Authors: Dhaunchak Ajit S. , Huang Jeffrey K. , De Faria Omar , Roth Alejandro D. , Pedraza Liliana , Antel Jack P. , Bar‐Or Amit , Colman David R.
Published: September 2010

Compact myelin, the paranode, and the juxtaparanode are discrete domains that are formed on myelinated axons. In humans, neurological disorders associated with loss of myelin, including Multiple Sclerosis, often also result in disassembly of the node of Ranvier. Despite the importance of these domains in the proper functioning of the CNS, their molecular composition and assembly mechanism remains largely unknown. We therefore performed a large‐scale proteomics MudPIT screen for the identification of proteins in human myelin and axogliasomal fractions. We identified over 1,000 proteins in these fractions. Since even minor perturbations in neuron‐glial interactions can uncouple the glial support of axons, the proteome map presented here can be used as a reference library for “myelin health” and disease states, including white matter disorders such as leukodystrophies and multiple sclerosis. © 2010 Wiley‐Liss, Inc.
Pathological adaptive responses of Schwann cells to endoplasmic reticulum stress in bortezomib‐induced peripheral neuropathy
Authors: Shin Yoon Kyung , Jang So Young , Lee Hyun Kyoung , Jung Junyang , Suh Duk Joon , Seo Su‐Yeong , Park Hwan Tae
Published: September 2010

Bortezomib, a proteasome inhibitor, has been considered as a promising anticancer drug in the treatment of recurrent multiple myeloma and some solid tumors. The bortezomib‐induced peripheral neuropathy (BIPN) is a prominent cause of dose‐limiting toxicities after bortezomib treatment. In this study, we found that BIPN in a mouse model is characterized by acute but transient endoplasmic reticulum (ER) damages to Schwann cells. These damaged Schwann cells exhibit abnormal outcomes from healing processes such as the myelination of Remak bundles. A morphometric analysis of polymyelinated Remak bundles revealed that the pathological myelination was not related to the axonal parameters that regulate the normal myelination process during development. In addition, demyelinating macrophages were focally infiltrated within endoneurium of the sciatic nerve. To identify the mechanism underlying these pathologies, we applied a gene microarray analysis to bortezomib‐treated primary Schwann cells and verified the changes of several gene expression in bortezomib‐treated sciatic nerves. The analysis showed that bortezomib‐induced ER stress was accompanied by the activation of several protective molecular chaperones and the down‐regulation of myelin gene expression. ER stress inducers such as thapsigargin and bredelfin A also suppressed the mRNA expression of myelin gene P0 at transcriptional levels. In addition, the expression of chemokines such as the macrophage chemoattractants Ccl3 and Cxcl2 was significantly increased in Schwann cells in response to bortezomib and ER stress inducers. Taken together, these observations suggest that the pathological adaptive responses of Schwann cells to bortezomib‐induced ER stress may, in part, participate in the development of BIPN. © 2010 Wiley‐Liss, Inc.
Numerically modelling groundwater in an arid area with ANN‐generated dynamic boundary conditions
Authors: Huo Zailin , Feng Shaoyuan , Kang Shaozhong , Mao Xiaomin , Wang Fengxin
Published: September 2010

Groundwater is sensitive to the climate change and agricultural activities in arid and semi‐arid areas. Over the past several decades, human activities, such as groundwater extraction for irrigation, have resulted in aquifer overdraft and disrupted the natural equilibrium in these areas. Regional groundwater simulation is important to determine appropriate groundwater management policies, and numerical simulation has become the most popular method. However, most groundwater models were developed with static boundary conditions. In this research, the Minqin oasis, an arid region located in northwest China, was selected as the study area. An artificial neural network (ANN) was developed to simulate effects of weather conditions, agricultural activities and surface water on groundwater level in a dynamic boundary of the domain. Subsequently, a groundwater numerical model, named ANN‐FEFLOW model, was developed, with a dynamic boundary condition defined by the ANN model. The verifying results showed that the model has higher precision, with a root mean square error (RMSE) of 0·71 m, relative error (RE) of 17·96% and R2 of 0·84 relative to the great groundwater change. Furthermore, the groundwater model has higher precision than the conventional groundwater model with static boundary condition, particularly in the area near the dynamic boundary. This study demonstrated that dynamic boundaries can improve the precision of the regional groundwater model in an arid area and that ANN can provide higher accuracy prediction capability for groundwater levels with dynamic boundary. Copyright © 2010 John Wiley & Sons, Ltd.
MT119, a new planar‐structured compound, targets the colchicine site of tubulin arresting mitosis and inhibiting tumor cell proliferation
Authors: Zhang Zhixiang , Meng Tao , Yang Na , Wang Wei , Xiong Bing , Chen Yi , Ma Lanping , Shen Jingkang , Miao Ze‐Hong , Ding Jian
Published: September 2010

Microtubule‐targeted drugs are now indispensable for the therapy of various cancer types worldwide. In this article, we report MT119 [6‐[2‐(4‐methoxyphenyl) ‐ethyl]‐9‐[(pyridine‐3‐ylmethyl)amino]pyrido[2′,1′:2,3]imida‐zo[4,5‐c]isoquinolin‐5(6H)‐one] as a new microtubule‐targeted agent. MT119 inhibited tubulin polymerization significantly both in tumor cells and in cell‐free systems, which was followed by the disruption of mitotic spindle assembly. Surface plasmon resonance‐based analyses showed that MT119 bound to purified tubulin directly, with theKDvalue of 10.6 μM. The binding of MT119 in turn caused tubulin conformational changes as evidenced by the quenched tryptophan fluorescence, the reduction of the bis‐ANS reactivity and the decreased DTNB‐sulfhydryl reaction rate. Competitive binding assays further revealed that MT119 bound to tubulin at its colchicine site. Consequently, by inhibiting tubulin polymerization, MT119 arrested different tumor cells at mitotic phase, which contributed to its potent antitumor activityin vitro.MT119 was also similarly cytotoxic to vincristine‐, adriamycin‐ or mitoxantrone‐resistant cancer cells and to their corresponding parental cells. Together, these data indicate that MT119 represents a new class of colchicine‐site‐targeted inhibitors against tubulin polymerization, which might be a promising starting point for future cancer therapeutics.
A nation‐wide study comparing sporadic and familial adenomatous polyposis‐related desmoid‐type fibromatoses
Authors: Nieuwenhuis Marry H. , Casparie Mariel , Mathus‐Vliegen Lisbeth M.H. , Dekkers Olaf M. , Hogendoorn Pancras C.W. , Vasen Hans F.A.
Published: September 2010

Desmoid‐type fibromatoses are neoplasms of fibroblastic origin, occurring sporadically or associated with familial adenomatous polyposis (FAP) coli. By comparing sporadic and FAP‐associated desmoid‐type fibromatoses, we tried to identify clinical characteristics, which may indicate FAP. Histopathology data of all Dutch patients with desmoid‐type fibromatoses diagnosed between 1999 and 2009 were retrieved from PALGA, the nation‐wide network and registry of histopathology in the Netherlands. For calculation of incidence rates, person‐years from the general matched population were used. Based on polyp counts in pathological records, the cohort was divided into a FAP group and a non‐FAP group. Patient‐ and tumor characteristics were compared between the two groups. A total number of 519 patients older than 10 years with a confirmed diagnosis of desmoid‐type fibromatoses were included. Thirty‐nine (7.5%) desmoid patients were documented of having FAP. The incidences of sporadic and FAP‐related desmoid‐type fibromatoses were 3.42 and 2,784 per million person‐years, respectively. The majority of FAP patients developed desmoid‐type fibromatoses after the diagnosis of FAP. Having FAP was associated with male gender [odds ratio (OR) 2.0, p = 0.034], desmoid diagnosis at an earlier age (mean 36 vs. 42 years, p = 0.031), and desmoid localization intra‐abdominally (OR 18.9, p ≤ 0.001) or in the abdominal wall (OR 4.8, p ≤ 0.001), compared to extra‐abdominal desmoid localization. In conclusion, patients with desmoid‐type fibromatoses are at risk of underlying FAP. Especially cases with desmoid localization intra‐abdominal or in the abdominal wall, and all patients younger than 60 years, have a substantial increased risk and should be referred for colonoscopy.
CXCR4 peptide antagonist inhibits primary breast tumor growth, metastasis and enhances the efficacy of anti‐VEGF treatment or docetaxel in a transgenic mouse model
Authors: Hassan Saima , Buchanan Marguerite , Jahan Kaushar , Aguilar‐Mahecha Adriana , Gaboury Louis , Muller William J. , Alsawafi Yaqoob , Mourskaia Anna A. , Siegel Peter M. , Salvucci Ombretta , Basik Mark
Published: September 2010

CXCR4 is a chemokine receptor implicated in the homing of cancer cells to target metastatic organs, which overexpress its ligand, stromal cell‐derived factor (SDF)‐1. To determine the efficacy of targeting CXCR4 on primary tumor growth and metastasis, we used a peptide inhibitor of CXCR4, CTCE‐9908, that was administered in a clinically relevant approach using a transgenic breast cancer mouse model. We first performed a dosing experiment of CTCE‐9908 in the PyMT mouse model, testing 25, 50 and 100 mg/kg versus the scrambled peptide in groups of 8–16 mice. We then combined CTCE‐9908 with docetaxel or DC101 (an anti‐VEGFR2 monoclonal antibody). We found that increasing doses of CTCE‐9908 alone slowed the rate of tumor growth, with a 45% inhibition of primary tumor growth at 3.5 weeks of treatment with 50 mg/kg of CTCE‐9908 (p = 0.005). Expression levels of VEGF were also found to be reduced by 42% with CTCE‐9908 (p = 0.01). In combination with docetaxel, CTCE‐9908 administration decreased tumor volume by 38% (p = 0.02), an effect that was greater than that observed with docetaxel alone. In combination with DC101, CTCE‐9908 also demonstrated an enhanced effect compared to DC101 alone, with a 37% decrease in primary tumor volume (p = 0.01) and a 75% reduction in distant metastasis (p = 0.009). In combination with docetaxel or an anti‐angiogenic agent, the anti‐tumor and anti‐metastatic effects of CTCE‐9908 were markedly enhanced, suggesting potentially new effective combinatorial therapeutic strategies in the treatment of breast cancer, which include targeting the SDF‐1/CXCR4 ligand/receptor pair.
Increased efficacy of doxorubicin delivered in multifunctional microparticles for mesothelioma therapy
Authors: Hillegass Jedd M. , Blumen Steven R. , Cheng Kai , MacPherson Maximilian B. , Alexeeva Vlada , Lathrop Sherrill A. , Beuschel Stacie L. , Steinbacher Jeremy L. , Butnor Kelly J. , Ramos‐Niño Maria E. , Shukla Arti , James Ted A. , Weiss Daniel J. , Taatjes Douglas J. , Pass Harvey I. , Carbone Michele , Landry Christopher C. , Mossman Brooke T.
Published: September 2010

New and effective treatment strategies are desperately needed for malignant mesothelioma (MM), an aggressive cancer with a poor prognosis. We have shown previously that acid‐prepared mesoporous microspheres (APMS) are nontoxic after intrapleural or intraperitoneal (IP) administration to rodents. The purpose here was to evaluate the utility of APMS in delivering chemotherapeutic drugs to human MM cells in vitro and in two mouse xenograft models of MM. Uptake and release of doxorubicin (DOX) alone or loaded in APMS (APMS‐DOX) were evaluated in MM cells. MM cell death and gene expression linked to DNA damage/repair were also measured in vitro. In two severe combined immunodeficient mouse xenograft models, mice received saline, APMS, DOX or APMS‐DOX injected directly into subcutaneous (SC) MM tumors or injected IP after development of human MMs peritoneally. Other mice received DOX intravenously (IV) via tail vein injections. In comparison to DOX alone, APMS‐DOX enhanced intracellular uptake of DOX, MM death and expression of GADD34 and TP73. In the SC MM model, 3× weekly SC injections of APMS‐DOX or DOX alone significantly inhibited tumor volumes, and systemic DOX administration was lethal. In mice developing IP MMs, significant (p < 0.05) inhibition of mesenteric tumor numbers, weight and volume was achieved using IP administration of APMS‐DOX at one‐third the DOX concentration required after IP injections of DOX alone. These results suggest APMS are efficacious for the localized delivery of lower effective DOX concentrations in MM and represent a novel means of treating intracavitary tumors.
Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia: Testing a device as an adjunct to colposcopy
Authors: Cantor Scott B. , Yamal Jose‐Miguel , Guillaud Martial , Cox Dennis D. , Atkinson E. Neely , Benedet John L. , Miller Dianne , Ehlen Thomas , Matisic Jasenka , van Niekerk Dirk , Bertrand Monique , Milbourne Andrea , Rhodes Helen , Malpica Anais , Staerkel Gregg , Nader‐Eftekhari Shahla , Adler‐Storthz Karen , Scheurer Michael E. , Basen‐Engquist Karen , Shinn Eileen , West Loyd A. , Vlastos Anne‐Therese , Tao Xia , Beck J. Robert , MacAulay Calum , Follen Michele
Published: September 2010

Testing emerging technologies involves the evaluation of biologic plausibility, technical efficacy, clinical effectiveness, patient satisfaction, and cost‐effectiveness. The objective of this study was to select an effective classification algorithm for optical spectroscopy as an adjunct to colposcopy and obtain preliminary estimates of its accuracy for the detection of CIN 2 or worse. We recruited 1,000 patients from screening and prevention clinics and 850 patients from colposcopy clinics at two comprehensive cancer centers and a community hospital. Optical spectroscopy was performed, and 4,864 biopsies were obtained from the sites measured, including abnormal and normal colposcopic areas. The gold standard was the histologic report of biopsies, read 2 to 3 times by histopathologists blinded to the cytologic, histopathologic, and spectroscopic results. We calculated sensitivities, specificities, receiver operating characteristic (ROC) curves, and areas under the ROC curves. We identified a cutpoint for an algorithm based on optical spectroscopy that yielded an estimated sensitivity of 1.00 [95% confidence interval (CI) = 0.92–1.00] and an estimated specificity of 0.71 [95% CI = 0.62–0.79] in a combined screening and diagnostic population. The positive and negative predictive values were 0.58 and 1.00, respectively. The area under the ROC curve was 0.85 (95% CI = 0.81–0.89). The per‐patient and per‐site performance were similar in the diagnostic and poorer in the screening settings. Like colposcopy, the device performs best in a diagnostic population. Alternative statistical approaches demonstrate that the analysis is robust and that spectroscopy works as well as or slightly better than colposcopy for the detection of CIN 2 to cancer.
Differential regulation by fucoidan of IFN‐γ‐induced NO production in glial cells and macrophages
Authors: Do Hang , Kang Nam‐Sung , Pyo Suhkneung , Billiar Timothy R. , Sohn Eun‐Hwa
Published: September 2010

Fucoidan has shown numerous biological actions; however, the molecular bases of these actions have being issued. We examined the effect of fucoidan on NO production induced by IFN‐γ and the molecular mechanisms underlying these effects in two types of cells including glia (C6, BV‐2) and macrophages (RAW264.7, peritoneal primary cells). Fucoidan affected IFN‐γ‐induced NO and/or iNOS expression both in macrophages and glial cells but in a contrast way. Our data showed that in C6 glioma cells both JAK/STAT and p38 signaling positively regulated IFN‐γ‐induced iNOS, which were inhibited by fucoidan. In contrast, in RAW264.7 cells JAK/STAT is a positive regulator whereas p38 is a negative regulator of NO/iNOS production. In RAW264.7 cells, fucoidan enhanced p38 activation and induced TNF‐α production. We also confirmed the dual regulation of p38 in BV‐2 microglia and primary peritoneal macrophages. From these results, we suggest that fucoidan affects not only IFN‐γ‐induced NO/iNOS production differently in brain and peritoneal macrophages due to the different roles of p38 but the effects on TNF‐α production in the two cell types. These novel observations including selective and cell‐type specific effects of fucoidan on IFN‐γ‐mediated signaling and iNOS expression raise the possibility that it alters the sensitivity of cells to the p38 activation. J. Cell. Biochem. 111: 1337–1345, 2010. © 2010 Wiley‐Liss, Inc.
Prohibitin is a cholesterol‐sensitive regulator of cell cycle transit
Authors: Dong Pei , Flores Jessica , Pelton Kristine , Solomon Keith R.
Published: September 2010

Cholesterol is essential in establishing most functional animal cell membranes; cells cannot grow or proliferate in the absence of sufficient cholesterol. Consequently, almost every cell, tissue, and animal tightly regulates cholesterol homeostasis, including complex mechanisms of synthesis, transport, uptake, and disposition of cholesterol molecules. We hypothesize that cellular recognition of cholesterol insufficiency causes cell cycle arrest in order to avoid a catastrophic failure in membrane synthesis. Here, we demonstrate using unbiased proteomics and standard biochemistry that cholesterol insufficiency causes upregulation of prohibitin, an inhibitor of cell cycle progression, through activation of a cholesterol‐responsive promoter element. We also demonstrate that prohibitin protects cells from apoptosis caused by cholesterol insufficiency. This is the first study tying cholesterol homeostasis to a specific cell cycle regulator that inhibits apoptosis. J. Cell. Biochem. 111: 1367–1374, 2010. © 2010 Wiley‐Liss, Inc.
Expression of homeobox genes in oral squamous cell carcinoma cell lines treated with all‐trans retinoic acid
Authors: Acquafreda Thais , Nunes Fabio Daumas , Soprano Dianne Robert , Soprano Kenneth J.
Published: September 2010

Oral squamous cell carcinoma (OSCC) may arise from potentially malignant oral lesions. All‐trans retinoic acid (atRA), which plays a role in cell growth and differentiation, has been studied as a possible chemotherapeutic agent in the prevention of this progression. While the mechanism by which atRA suppresses cell growth has not been completely elucidated, it is known that homeobox genes are atRA targets. To determine if these genes are involved in the atRA‐mediated OSCC growth inhibition, PCR array was performed to evaluate the expression of 84 homeobox genes in atRA‐sensitive SCC‐25 cells compared to atRA‐resistant SCC‐9 cells following 7 days with atRA treatment. Results showed that the expression of 8 homeobox genes was downregulated and expression of 4 was upregulated in SCC‐25 cells but not in SCC‐9 cells. Gene expression levels were confirmed for seven of these genes by RT‐qPCR. Expression of three genes that showed threefold downregulation was evaluated in SCC‐25 cells treated with atRA for 3, 5, and 7 days. Three different patterns of atRA‐dependent gene expression were observed. ALX1 showed downregulation only on day 7. DLX3 showed reduced expression on day 3 and further reduced on day 7. TLX1 showed downregulation only on days 5 and 7. Clearly the expression of homeobox genes is modulated by atRA in OSCC cell lines. However, the time course of this modulation suggests that these genes are not direct targets of atRA mediating OSCC growth suppression. Instead they appear to act as downstream effectors of atRA signaling. J. Cell. Biochem. 111: 1437–1444, 2010. © 2010 Wiley‐Liss, Inc.
A soft‐cache strategy for pathologist's navigation in virtual microscopy
Authors: Gómez Francisco , Marín Diana , Romero Eduardo
Published: September 2010

Navigation through large microscopical images demands special characteristics like flexibility to access image data and progressive recovery or relevant information, i.e., several qualities, magnifications, and random accesses to any desired Window of Interest in the Virtual Slide (VS). Nowadays there exist systems that allow such interaction, but with a certain delay, which is dependent on the application. It has been shown that caching or prefetching policies can speed up interaction with these systems. This article presents an optimal soft‐cache strategy, which improves the navigation times in virtual microscopy. The entire method includes an optimal soft‐cache strategy and a dynamical probabilistic model of a pathologist's navigation. This strategy was implemented as a Client‐Server application, using the JPEG2000‐JPIP standard and evaluated using different navigation patterns, namely, four different pathologists exploring 10 VS, stained with different dyes. The present approach was compared with a conventional soft‐cache method and the cache performance improved, in average, in about a 10%. Microsc. Res. Tech., 2011. © 2010 Wiley‐Liss, Inc.
Gold nanoparticles and quantum dots for bioimaging
Authors: Hutter Eliza , Maysinger Dusica
Published: September 2010

Nanoparticles are the latest tool acquired by the science of bioimaging, serving primarily as new contrast agents, sensors, or signal enhancing agents in established and developing imaging techniques. This review focuses on the unique properties of two classes of nanoparticles: gold nanoparticles (GNP) and quantum dots, and how these properties are benefiting cellular and in vivo imaging. We discuss the surface plasmon resonance of GNP and its implications for various imaging techniques of biological relevance. Furthermore, the key properties of quantum dots are reviewed, and their use alone or in combination with traditional fluorescent dyes for biological imaging are described. The underlying principles of these techniques are provided, along with some representative examples. Microsc. Res. Tech., 2011. © 2010 Wiley‐Liss, Inc.
Synthesis and crystal structure of novel [1,2,4]oxadiazolo[5,4‐d][1,5]benzothiozepine derivatives containing pyrazole moiety
Authors: Zhou Ying‐Lei , Shen Song‐Wei , Liu Fang‐Ming
Published: September 2010

A series of new substituted‐[1,2,4]oxadiazolo[5,4‐d][1,5]benzothiazepine derivatives containing pyrazole ring 4/4′ was synthesized by substituted‐pyrazolo[1,5]benzothiazepines 2/2′ and substituted‐benzohydroximinoyl chlorides 3 through the 1,3‐dipolar cycloaddition reaction in the presence of Et3N at room temperature, and characterized by MS, IR, 1H NMR and elemental analyses. In addition, the structure of 4′l was determined by X‐ray crystallography. J. Heterocyclic Chem., 2011.
New succinyl‐spaced pyrazoles: Regioselective synthesis of 1,4‐bis[5‐(trichloromethyl)‐1H‐pyrazol‐1‐yl]butane‐1,4‐diones
Authors: Bonacorso Helio G. , Cechinel Cleber A. , Paim Gisele R. , Martins Marcos A. P. , Zanatta Nilo , Flores Alex F. C.
Published: September 2010

The facile and convenient access by a conventional procedure in ethanol as solvent to a new series of succinyl‐spaced pyrazoles including 1,4‐bis[5‐(trichloromethyl)‐5‐hydroxy‐4,5‐dihydro‐1H‐pyrazol‐1‐yl]butane‐1,4‐diones (64–82%) and the respective dehydrated derivatives as 1,4‐bis[5‐(trichloromethyl)‐1H‐pyrazol‐1‐yl]butane‐1,4‐diones in 57–82% yields, from the regioselective cyclocondensation reactions of 4‐substituted 4‐methoxy‐1,1,1‐trichloroalk‐3‐en‐2‐ones with succinic acid dihydrazide, where the 4‐substituents are Me, Ph, 4‐FC6H4, 4‐ClC6H4, 4‐NO2C6H4, 2‐furyl, and 2‐thienyl, is reported. J. Heterocyclic Chem., 2011.
Synthesis and fungicidal activity of novel 1,3‐disubstituted 1H‐diazirine derivatives
Authors: Eliazyan Karine A. , Avetisyan Frunze V. , Jivanshiryan Tamara L. , Pivazyan Vergush A. , Ghazaryan Emma A. , Shahbazyan Lusya V. , Harutyunyan Siranush V. , Yengoyan Aleksandr P.
Published: September 2010

A convenient method for synthesis of novel 1‐[pyrimidinyl], 1‐[1,3,5‐triazin‐2‐carbonyl], and 1‐[thiazol‐5‐carbonyl] derivatives of 3‐thioxo‐diaziridine1,3,5, and7from corresponding hydrazides, CS2, and KOH is elaborated. The highest reaction yield was observed when these initial reagents were taken in molar ratio of 1:1.7:2.0, respectively. By alkylation of compounds1,3,5, and7that proceeds exclusively at sulfur atom, the 3‐sulfanyl derivatives of 1‐[pyrimidinyl]‐, 1‐[1,3,5‐triazin‐2‐carbonyl]‐, and 1‐[thiazol‐5‐carbonyl]‐diazirines2,4,6, and8were formed. The structures of synthesized compounds were confirmed by proton and carbon nuclear magnetic resonance (NMR), mass spectra (MS), and elemental analysis. The fungicidal activities of S‐substituted derivatives were studied. Data of preliminary biological tests testify that these compounds can be of interest in search for new fungicides. J. Heterocyclic Chem., (2010).
A facile, one‐pot, green synthesis of polysubstituted 4H‐pyrans via piperidine‐catalyzed three‐component condensation in aqueous medium
Authors: Lu Guo‐Ping , Cai Chun
Published: September 2010

An efficient, one‐pot method was described for the synthesis of various polysubstituted 4H‐pyrans via piperidine catalyzed three‐component condensation in aqueous medium. The reaction could be promoted effectively by adding sodium dodecyl sulfate to aqueous medium. J. Heterocyclic Chem., (2010).
Comparison of systemic and otic administration of ofloxacin
Authors: Koulich Elena , Roland Peter S. , Pawlowski Karen S.
Published: September 2010

Objectives:

To assess the feasibility of delivering ofloxacin across the intact tympanic membrane; to compare middle ear bioavailability of ofloxacin after otic and systemic administrations; to determine distribution of otically delivered ofloxacin to other tissues.

Study Design:

A prospective, controlled animal study.

Methods:

Rats underwent surgery wherein the middle ear cavity was opened and filled with saline. An equivalent amount of ofloxacin was delivered intraperitoneally or into the external ear canal. Saline within the middle ear was sampled and completely replaced in 15‐minute intervals for 3 hours. Blood was collected twice after the initial application of ofloxacin for high‐performance liquid chromatography (HPLC). Animals were sacrificed 3 hours after the initial addition of ofloxacin; the temporal bones were harvested for histological analysis; urine and colon mucosa were collected for HPLC analysis.

Results:

Both systemic and otic applications led to a comparable accumulation of ofloxacin in the middle ear over the 3‐hour period after the initial administration. The pharmacokinetics of ofloxacin penetration into the middle ear was sporadic and subject‐dependent. Both methods of administration led to drug accumulation in blood serum, urine, and colonic mucosa.

Conclusions:

Topical application of ofloxacin to the intact tympanic membrane allows for drug penetration into the middle ear space. Similar middle ear ofloxacin levels could be achieved with systemic and topic applications, but drug concentrations were inconsistent. The accumulation of ofloxacin in other tissues suggests applications designed to be ototopical may also result in systemic absorption. Laryngoscope, 2010
Agricultural land conversion drivers: A comparison between less developed, developing and developed countries
Authors: Azadi H. , Ho P. , Hasfiati L.
Published: September 2010

This study examines the level of intensity, trend and the main drivers of agricultural land conversion (ALC) worldwide. Considering the World Bank classification and using a stratified random sampling, 94 countries were selected in three different groups: less developing, developing and developed countries. Data were obtained from two databases; Nation Master and Earth Trends for the period of 1961–2003. The empirical results revealed some differences in the level of intensity and the trend of ALC among the groups. Agricultural land loss was more intensified in developing countries experiencing rapid economic growth and a transition in their economic structure. The results also showed that there is a positive correlation between ALC and productivity, capital–labour ratio and urban population. Urban population was identified as the main driver affecting ALC in all the countries. Furthermore, although urbanization process exists in all the groups, the developed countries are more successful in managing urban development and ALC. Considering the increasing trend of ALC in the future and its socio‐economic and environmental impacts, this study concluded that governments' intervention in land policies is needed to preserve agricultural lands. Copyright © 2010 John Wiley & Sons, Ltd.
Utility of uncalibrated femoral stroke volume variation as a predictor of fluid responsiveness during the anhepatic phase of liver transplantation
Authors: Shin Young Hee , Ko Justin Sangwook , Gwak Mi Sook , Kim Gaab Soo , Lee Jong Hwan , Lee Suk-Koo
Published: September 2010

We evaluated the value of the stroke volume variation (SVV) calculated with the Vigileo monitor, which recently has been increasingly advocated for fluid management, as a predictor of fluid responsiveness during the anhepatic phase of liver transplantation (LT). We also compared SVV to the central venous pressure (CVP) and pulmonary arterial occlusion pressure (PAOP) in patients. Thirty-three adult recipients scheduled for elective living donor LT were enrolled in this study. Twenty minutes after the start of the anhepatic phase, the CVP, PAOP, approximate inferior vena caval pressure, femoral SVV, and cardiac output values were measured before and 12 minutes after fluid loading. Fluid loading was performed with a 6% hydroxyethyl starch solution (10 mL/kg). The responders were defined as patients whose cardiac index increased ≥15% after fluid loading. Receiver operating characteristic (ROC) analysis showed that only femoral SVV (area under the curve = 0.894, P = 0.0001) could be used to predict fluid responsiveness during the anhepatic phase of LT. The area under the ROC curve for femoral SVV was 0.894 (P = 0.0001), and it was significantly larger than those for CVP (area under the curve = 0.576, P = 0.004) and PAOP (area under the curve = 0.670, P = 0.021). Femoral SVV >8% identified the responders with a sensitivity of 89% and a specificity of 80%. Our results suggest that femoral SVV derived with the Vigileo monitor would be useful for fluid management during the anhepatic phase in LT recipients. Liver Transpl 17:53-59, 2011. © 2011 AASLD.
Multi‐objective optimization for channel allocation in mobile computing using NSGA‐II
Authors: Vidyarthi Deo , Khanbary Lutfi
Published: September 2010

Efficient channel allocation to mobile hosts aims to minimize the number of blocked hosts and is of utmost importance in a mobile computing network. Also, to achieve highly reliable data transmission, wireless mobile networks require efficient and reliable link connectivity regardless of terminal mobility, and thus reliable traffic performance. A mobile network consists of mobile nodes, base stations, links, etc. that are often prone to failure. The multi‐objective optimization problem (MOP), does not offer one best solution with respect to all the objectives. The aim is to determine the trade‐off surface, which is a set of non‐dominated solution points known as Pareto‐optimal. The two objectives addressed in this paper are to minimize the number of blocked hosts while maximizing the reliability of the data transmission. A multi‐objective optimization is carried out to optimize both objectives simultaneously. The elitist NSGA‐II (non‐dominated sorting genetic algorithm) has been used as an evolutionary optimization technique to solve this problem. A population of efficient solutions results when the termination condition is satisfied. Also the Pareto‐optimal fronts obtained provide a wide range of trade‐off operating conditions from which an appropriate operating point may be selected by the decision maker. The experimental results are presented and analyzed for overall evaluation of the performance of the proposed work. Further, comparison of the results with the two recent earlier models reveals that the proposed work performs better in serving mobile hosts as it caters to two objectives simultaneously. Copyright © 2010 John Wiley & Sons, Ltd.