bluuebunny/crossref_metadata_2025 huggingface dataset:
Fibrocystic disease of liver and pancreas; under‐recognized features of the X‐linked ciliopathy oral‐facial‐digital syndrome type 1 (OFD I)
Authors: Chetty‐John Shilpa , Piwnica‐Worms Katie , Bryant Joy , Bernardini Isa , Fischer Roxanne E. , Heller Theo , Gahl William A. , Gunay‐Aygun Meral
Published: September 2010

OFD I is an X‐linked dominant male‐lethal ciliopathy characterized by prominent external features including oral clefts, hamartomas or cysts of the tongue, and digital anomalies. Although these external features are easy to recognize and often lead to diagnosis in early childhood, visceral findings in OFD I, especially the fibrocystic liver and pancreas disease, are under‐recognized. In addition, while the occurrence of polycystic kidney disease (PKD) in OFD I is well known, few patients are evaluated and monitored for this complication. We report on two adult females diagnosed with OFD I in infancy, but not evaluated for visceral involvement. In adulthood, they were incidentally found to have severe hypertension and chronic renal insufficiency due to undiagnosed PKD. A pancreatic cystic lesion, also discovered incidentally, was thought to be malignant and led to consideration of major surgery. We present NIH evaluations, including documentation of OFD I mutations, extreme beading of the intrahepatic bile ducts, pancreatic cysts, and tabulate features of reported OFD I cases having hepatic, pancreatic, and renal cystic disease. Liver and pancreas are not routinely evaluated in OFD I patients. Increased awareness and lifelong monitoring of visceral complications, particularly involving the liver, pancreas, and kidney, are essential for timely and accurate treatment. Published 2010 Wiley‐Liss, Inc.
Immunohistochemical Localization of Cytokeratins in the Junctional Region of Ectoderm and Endoderm
Authors: Hosoya Akihiro , Kwak Sungwook , Kim Eun‐Jung , Lunny Declan Patrick , Birgitte Lane E. , Cho Sung‐Won , Jung Han‐Sung
Published: September 2010

Although tridermic species have two junctional regions of ectoderm and endoderm between their epidermis and digestive tract, we actually know little about these particular boundaries. Cytokeratins are the major intermediate filaments of epithelial cells and show a high degree of tissue specificity. Therefore, to characterize the epithelial cells in the junctional region of ectoderm and endoderm, we immunohistochemically examined the localization of cytokeratins 5, 7/17, 14, 18, Sox17, and alpha‐fetoprotein (AFP) in the oropharyngeal and anorectal regions during the mouse gastrulation process. At embryonic day (E) 9.5, cytokeratins 5, 7/17, 14, and 18 were detected in all epithelial cells of the oropharyngeal region. At E12.5, cytokeratin 5‐positive cells were not observed in the middle area of the oral cavity; however, the immunoreactivity was strong in the anterior and posterior areas. The immunoreaction of cytokeratins 18 was seen only in the middle and posterior areas of the oral mucosa. Cytokeratins 7/17 and 14 were localized in all areas of the oropharyngeal region. Sox17 and AFP, which are endodermal markers, were detected in the middle and posterior areas of the oral mucosa, but not in the anterior area. Moreover, this same localization pattern of cytokeratins also existed in the anorectal region of the E12.5 embryo, suggesting that the localization of cytokeratins and endodermal markers might give an implication for the boundary between ectoderm and endoderm. These results also suggest that these cytokeratins are useful molecules for monitoring the epithelial cell differentiation in the junctional region of the germ layers. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.
Ontogeny of the Kidney and Renal Developmental Markers in the Rhesus Monkey (Macaca Mulatta)
Authors: Batchelder Cynthia A. , Lee C. Chang I. , Martinez Michele L. , Tarantal Alice F.
Published: September 2010

Nonhuman primates share many developmental similarities with humans, thus they provide an important preclinical model for understanding the ontogeny of biomarkers of kidney development and assessing new cell‐based therapies to treat human disease. To identify morphological and developmental changes in protein and RNA expression patterns during nephrogenesis, immunohistochemistry and quantitative real‐time PCR were used to assess temporal and spatial expression of WT1, Pax2, Nestin, Synaptopodin, alpha‐smooth muscle actin (α‐SMA), CD31, vascular endothelial growth factor (VEGF), and Gremlin. Pax2 was expressed in the condensed mesenchyme surrounding the ureteric bud and in the early renal vesicle. WT1 and Nestin were diffusely expressed in the metanephric mesenchyme, and expression increased as the Pax2‐positive condensed mesenchyme differentiated. The inner cleft of the tail of the S‐shaped body contained the podocyte progenitors (visceral epithelium) that were shown to express Pax2, Nestin, and WT1 in the early second trimester. With maturation of the kidney, Pax2 expression diminished in these structures, but was retained in cells of the parietal epithelium, and as WT1 expression was upregulated. Mature podocytes expressing WT1, Nestin, and Synaptopodin were observed from the mid‐third trimester through adulthood. The developing glomerulus was positive for α‐SMA (vascular smooth muscle) and Gremlin (mesangial cells), CD31 (glomerular endothelium), and VEGF (endothelium), and showed loss of expression of these markers as glomerular maturation was completed. These data form the basis for understanding nephrogenesis in the rhesus monkey and will be useful in translational studies that focus on embryonic stem and other progenitor cell populations for renal tissue engineering and repair. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.
Genetic Models of Serotonin (5‐HT) Depletion: What do They Tell Us About the Developmental Role of 5‐HT?
Authors: Trowbridge Sara , Narboux‐Nême Nicolas , Gaspar Patricia
Published: September 2010

A large number of hyposerotonergic genetic models have been generated over the past few years. Serotonin (5‐HT) depletion has been obtained via targeting of genes involved in 5‐HT synthesis (Tph1 and Tph2), specification and determination of the 5‐HT phenotype during development (GATA3, Pet1, and Lmx1b), and 5‐HT storage or clearance (Vmat2 and SERT). Here we review these various models from a developmental perspective, beginning with a description of the sources of 5‐HT during development. We then summarize the neurological and behavioral alterations that have been observed in the genetic hyposerotonergic models. Although these models appear to have normal brain development and do not exhibit any gross morphological defects, problems in somatic growth and physiological functions have been observed. Abnormal adult behavior is also seen, although whether it results from depletion of 5‐HT during development or functional 5‐HT deficiencies in adult life remains unclear. Evidence from these hyposerotonergic models suggests that the developing brain may not need 5‐HT for the establishment of general organization and structure. However, central 5‐HT appears to be necessary for postnatal body growth, maturation of respiratory and vegetative control, and possibly for the development of normal adult behavior. Anat Rec, 2011. © 2011 Wiley‐Liss, Inc.
Hypersensitive‐Like Response to the Pore‐Former Peptaibol Alamethicin in Arabidopsis Thaliana
Authors: Rippa Sonia , Eid Marguerita , Formaggio Fernando , Toniolo Claudio , Béven Laure
Published: September 2010

In Arabidopsis thaliana cell cultures, the peptaibol alamethicin induced a form of active cell death that was associated with cell shrinkage and DNA fragmentation. The transfer of mature A. thaliana plants from a peptide‐free medium to a medium containing a moderate concentration of alamethicin caused the development of lesions in leaves after a few days. These lesions were characterized by cell death, deposition of callose, production of autofluorescent phenolic compounds, and transcription of defense genes, just like in the hypersensitive response to a pathogen attack. The induction of defense‐like responses in Arabidopsis by other membrane‐disrupting peptides was also evaluated. The peptides selected for comparison included the natural antimicrobial melittin and the peptaibol ampullosporin A, as well as synthetic analogues of the peptaibols cervinin and trichogin. The response amplitude in A. thaliana increased with the peptaibol's ability to permeabilize biological membranes through a pore‐forming mechanism and was strongly associated with their content in the helicogenic α‐aminoisobutyric acid residue.
Molecular typing of epithelial ovarian carcinomas using inflammatory markers
Authors: Ali‐Fehmi Rouba , Semaan Assaad , Sethi Sima , Arabi Haitham , Bandyopadhyay Sudeshna , Hussein Yaser R. , Diamond Michael P. , Saed Ghasan , Morris Robert T. , Munkarah Adnan R.
Published: September 2010

BACKGROUND:

Ovarian epithelial carcinomas have recently been classified as slow growing type I tumors and rapidly growing highly aggressive type II tumors. The present study sought to molecularly characterize type I and II tumors using known molecular markers.

METHODS:

Specimens from 213 patients with ovarian carcinoma were categorized as type I or type II, and evaluated by immunohistochemistry for the inflammatory markers glucose transporter protein‐1 (Glut‐1), inducible nitric oxide synthase (iNOS), cyclooxygenase‐1 (COX‐1), cyclooxygenase‐2 (COX‐2), and nuclear factor kappa B. Statistical analysis was performed to investigate whether these molecular markers could distinguish between type I and type II tumors. Kaplan‐Meier survival curves and COX regression analysis were used to determine the prognostic effect of these markers on survival in the 2 types of tumors.

RESULTS:

Overexpression of COX‐1, COX‐2, iNOS, and Glut‐1 was significantly higher in type II tumors (P < .05). Women with type II tumors had a poorer median survival (60 months) as compared with those with type I tumors (141 months) (P = .0001). Multivariate analysis revealed type II tumors, late stage, and age >60 years as significant predictors of poor survival. For type II tumors, median survival of patients with tumors overexpressing COX‐2 was 44 compared with 85 months for those with tumors with low COX‐2 expression (P = .029). Looking at both type I and II tumors, the number of markers simultaneously overexpressed in each tumor was a significant predictor of poor patient survival (P = .005).

CONCLUSIONS:

The present study demonstrates that the new proposed histologic classification of ovarian epithelial carcinomas correlates with a distinct expression of inflammatory pathway proteins. High expression of these markers may explain the different biologic behavior of these 2 tumor types and provide targets for therapy. Cancer 2011. © 2010 American Cancer Society.
Intraoperative frozen section analysis of sentinel lymph nodes in breast cancer patients
Authors: Liu Liang‐Chih , Lang Julie E. , Lu Ying , Roe Denise , Hwang Shelley E. , Ewing Cheryl A. , Esserman Laura J. , Morita Eugene , Treseler Patrick , Leong Stanley P.
Published: September 2010

BACKGROUND:

Accurate intraoperative pathologic examination of sentinel lymph nodes (SLNs) has been an important tool that can reduce the need for reoperations in patients with SLN‐positive breast cancer. The objective of the current study was to determine the accuracy of intraoperative frozen section (IFS) of SLNs during breast cancer surgery.

METHODS:

The authors retrospectively reviewed the records of 326 patients with breast cancer who underwent IF analysis of SLNs at a single institution. Then, they conducted a meta‐analysis that included 47 published studies of IFS of SLNs in patients with breast cancer.

RESULTS:

Hematoxylin and eosin (H&E) staining revealed metastasis in SLNs in 99 patients (30.4%), including 61 patients with macrometastasis (MAM) (>2 mm) (the MAM group) and 38 patients with micrometastasis (Mi) or isolated tumor cell (ITC) deposits (the Mi/ITC group). The overall sensitivity of the institutional series was 60.6% (60 of 99 patients), and overall specificity was 100% (227 of 227 true negatives). The sensitivity of IFS was significantly lower in the Mi/ITC group (28.9%) than in the MAM group (80.3%; P < .0001). According to the meta‐analysis of published studies and data from the author's institution (47 studies, for a total of 13,062 patients who underwent SLN dissection with IFS of SLNs), the mean sensitivity was 73%, and the mean specificity was 100%. The mean sensitivity was 94% for the MAM group and 40% for the Mi/ITC group.

CONCLUSIONS:

IFS of SLNs was more reliable for detecting MAM than for detecting Mi/ITC deposits. It lacked sufficient accuracy to rule out Mi/ITC deposits. Cancer 2011. © 2010 American Cancer Society.
NHC‐Mediated Chlorination of Unsymmetrical Ketenes: Catalysis and Asymmetry
Authors: Douglas James , Ling Kenneth B. , Concellón Carmen , Churchill Gwydion , Slawin Alexandra M. Z. , Smith Andrew D.
Published: September 2010

NHCs promote the efficient chlorination of unsymmetrical disubstituted ketenes with a range of chlorinating agents; chiral NHCs display promising levels of asymmetric induction in the chlorination process with up to 61 % ee observed using 2,3,4,5,6,6‐hexachlorocyclohexa‐2,4‐dienone.
The DNA damage response—Repair or despair?
Authors: Ljungman Mats
Published: September 2010

The term “the DNA damage response” (DDR) encompasses a sophisticated array of cellular initiatives set in motion as cells are exposed to DNA‐damaging events. It has been known for over half a century that all organisms have the ability to restore genomic integrity through DNA repair. More recent discoveries of signal transduction pathways linking DNA damage to cell cycle arrest and apoptosis have greatly expanded our views of how cells and tissues limit mutagenesis and tumorigenesis. DNA repair not only plays a pivotal role in suppressing mutagenesis but also in the reversal of signals inducing the stress response. If repair is faulty or the cell is overwhelmed by damage, chances are that the cell will despair and be removed by apoptosis. This final fate is determined by intricate cellular dosimeters that are yet to be fully understood. Here, key findings leading to our current view of DDR are discussed as well as potential areas of importance for future studies. Environ. Mol. Mutagen., 2010. © 2010 Wiley‐Liss, Inc.
A new computation model of fractured horizontal well coupling with reservoir
Authors: Lian P. Q. , Cheng L. S. , Cui J. Y.
Published: September 2010

Based on Green's functions and Newman's product principle, pressure drop formula was derived for considering simultaneous production of fractures and horizontal wellbore in unsteady state. A reservoir/fractured horizontal well coupling model is developed for finite conductivity condition that can be solved by the combination of quasi‐Newton method and PSO (Particle Swarm Optimization) algorithm. The solution of a practical example shows that lots of factors can affect the productivity of the fractured horizontal well. The number of the fractures has an optimizing range. Different fractures have different flow rates and the production in the central fracture is the lowest. The distribution of production rate in the wellbore has a wave‐like shape due to the influence of fractures. The closer fractures are the lower flow rate in well segments. Considering the horizontal wellbore production, the production rates in the fractures are asymmetric and the corresponding pressure drop curve is smoother. Copyright © 2010 John Wiley & Sons, Ltd.
Effect of collision‐partner selection schemes on the accuracy and efficiency of the direct simulation Monte Carlo method
Authors: Gallis M. A. , Torczynski J. R.
Published: September 2010

The effect of the collision‐partner selection scheme on the accuracy and the efficiency of the Direct Simulation Monte Carlo method is investigated. Several schemes that reduce the mean collision separation, including the fixed sub‐cell scheme, the transient adaptive sub‐cell scheme, and the virtual sub‐cell scheme, are evaluated. Additionally, a new scheme is proposed that limits the population from which collision partners are selected based on the distance traveled by a simulator and performs near‐neighbor collisions using this population. These collision‐partner selection schemes are assessed for Fourier flow (heat conduction between parallel plates) and a standard hypersonic benchmark problem (Mach 15.6 nitrogen flow over a 25–55° biconic). The new limited‐selection near‐neighbor scheme has superior performance compared to the other schemes for both flows and reduces both the spatial and temporal discretization errors relative to random‐selection and nearest‐neighbor collision‐partner selection schemes. Copyright © 2010 John Wiley & Sons, Ltd.
Sodium/myo-inositol cotransporter 1 and myo-inositol are essential for osteogenesis and bone formation
Authors: Dai Zhijie , Chung Sookja K , Miao Dengshun , Lau Kam S , Chan Alfred WH , Kung Annie WC
Published: September 2010

myo-Inositol (MI) plays an essential role in several important processes of cell physiology, is involved in the neural system, and provides an effective treatment for some psychiatric disorders. Its role in osteogenesis and bone formation nonetheless is unclear. Sodium/MI cotransporter 1 (SMIT1, the major cotransporter of MI) knockout (SMIT1−/−) mice with markedly reduced tissue MI levels were used to characterize the essential roles of MI and SMIT1 in osteogenesis. SMIT1−/− embryos had a dramatic delay in prenatal mineralization and died soon after birth owing to respiratory failure, but this could be rescued by maternal MI supplementation. The rescued SMIT1−/− mice had shorter limbs, decreased bone density, and abnormal bone architecture in adulthood. Deletion of SMIT1 resulted in retarded postnatal osteoblastic differentiation and bone formation in vivo and in vitro. Continuous MI supplementation partially restored the abnormal bone phenotypes in adult SMIT1−/− mice and strengthened bone structure in SMIT1+/+ mice. Although MI content was much lower in SMIT1−/− mesenchymal cells (MSCs), the I(1,4,5)P3 signaling pathway was excluded as the means by which SMIT1 and MI affected osteogenesis. PCR expression array revealed Fgf4, leptin, Sele, Selp, and Nos2 as novel target genes of SMIT1 and MI. SMIT1 was constitutively expressed in multipotential C3H10T1/2 and preosteoblastic MC3T3-E1 cells and could be upregulated during bone morphogenetic protein 2 (BMP-2)–induced osteogenesis. Collectively, this study demonstrated that deficiency in SMIT1 and MI has a detrimental impact on prenatal skeletal development and postnatal bone remodeling and confirmed their essential roles in osteogenesis, bone formation, and bone mineral density (BMD) determination. © 2011 American Society for Bone and Mineral Research.
Anticancer efficacy of Apo2L/TRAIL is retained in the presence of high and biologically active concentrations of osteoprotegerin in vivo
Authors: Zinonos Irene , Labrinidis Agatha , Lee Michelle , Liapis Vasilios , Hay Shelley , Ponomarev Vladimir , Diamond Peter , Findlay David M , Zannettino Andrew CW , Evdokiou Andreas
Published: September 2010

Osteoprotegerin (OPG) is a secreted member of the tumor necrosis factor (TNF) receptor superfamily that binds to the ligand for receptor activator of nuclear factor κB (RANKL) and inhibits bone resorption. OPG can also bind and inhibit the activity of the TNF-related apoptosis-inducing ligand (Apo2L/TRAIL), raising the possibility that the anticancer efficacy of soluble Apo2L/TRAIL may be abrogated in the bone microenvironment where OPG expression is high. In this study we used a murine model of breast cancer growth in bone to evaluate the efficacy of recombinant soluble Apo2L/TRAIL against intratibial tumors that were engineered to overexpress native full-length human OPG. In vitro, OPG-overexpressing breast cancer cells were protected from Apo2L/TRAIL-induced apoptosis, an effect that was reversed with the addition of soluble RANKL or neutralizing antibodies to OPG. In vivo, mice injected intratibially with cells containing the empty vector developed large osteolytic lesions. In contrast, OPG overexpression preserved the integrity of bone and prevented breast cancer–induced bone destruction. This effect was due primarily to the complete absence of osteoclasts in the tibias of mice inoculated with OPG-transfected cells, confirming the biologic activity of the transfected OPG in vivo. Despite the secretion of supraphysiologic levels of OPG, treatment with Apo2L/TRAIL resulted in strong growth inhibition of both empty vector and OPG-overexpressing intratibial tumors. While Apo2L/TRAIL-induced apoptosis may be abrogated in vitro by OPG overexpression, the in vivo anticancer efficacy of recombinant soluble Apo2L/TRAIL is retained in the bone microenvironment even in the presence of biologically active OPG at supraphysiologic concentrations. © 2011 American Society for Bone and Mineral Research.
CSF Aβ42 and tau in Parkinson's disease with cognitive impairment
Authors: Montine Thomas J. , Shi Min , Quinn Joseph F. , Peskind Elaine R. , Craft Suzanne , Ginghina Carmen , Chung Kathryn A. , Kim Hojoong , Galasko Douglas R. , Jankovic Joseph , Zabetian Cyrus P. , Leverenz James B. , Zhang Jing
Published: September 2010

We tested the hypothesis that the CSF biomarker signature associated with Alzheimer's disease (AD) is present in a subset of individuals with Parkinson's disease and Dementia (PD‐D) or with PD and Cognitive Impairment, Not Dementia (PD‐CIND). We quantified CSF Aβ42, total tau (T‐tau), and phospho‐tau (P181‐tau) using commercially available kits. Samples were from 345 individuals in seven groups (n): Controls ≤50 years (35), Controls >50 years (115), amnestic Mild Cognitive Impairment (aMCI) (24), AD (49), PD (49), PD‐CIND (62), and PD‐D (11). We observed expected changes in AD or aMCI compared with age‐matched or younger controls. CSF Aβ42 was reduced in PD‐CIND (P < 0.05) and PD‐D (P < 0.01), whereas average CSF T‐tau and P181‐tau were unchanged or decreased. One‐third of PD‐CIND and one‐half of PD‐D patients had the biomarker signature of AD. Abnormal metabolism of Aβ42 may be a common feature of PD‐CIND and PD‐D. © 2010 Movement Disorder Society
Cerebellar dysfunction in progressive supranuclear palsy: A transcranial magnetic stimulation study
Authors: Shirota Yuichiro , Hamada Masashi , Hanajima Ritsuko , Terao Yasuo , Matsumoto Hideyuki , Ohminami Shinya , Tsuji Shoji , Ugawa Yoshikazu
Published: September 2010

Progressive supranuclear palsy (PSP) rarely shows cerebellar signs and symptoms even though the cerebellar dentate nuclei are involved pathologically. This study evaluates cerebellar function using transcranial magnetic stimulation (TMS) to determine whether subclinical cerebellar involvement is present in PSP patients. We studied 11 patients with PSP, 11 patients with Parkinson's disease (PD), and 10 age‐matched controls. Patients were examined with their usual medications and in their relative on state. Motor evoked potentials (MEPs) were recorded from the hand muscle. Cerebellar function was evaluated using suppressive effects of TMS over the cerebellum on MEPs elicited by TMS over the contralateral motor cortex, which we call cerebellar inhibition (CBI). Interstimulus intervals (ISIs) of 4 to 8 ms were used, and the time course of CBI was analyzed. The CBI was reduced in PSP patients. By contrast, the CBI was normal in PD patients in their on state. Although the CBI in their off state should be examined in future studies, the results described herein suggest that Purkinje cells or the dentato–thalamo–cortical pathway assessed by CBI is involved in PSP. Our results are compatible with the pathological findings showing severe dentate nucleus degeneration in PSP patients. © 2010 Movement Disorder Society
Carbidopa/levodopa pharmacy errors in Parkinson's disease
Authors: Khadem Nasim R. , Nirenberg Melissa J.
Published: September 2010

Outpatient pharmacy errors are common, but little is known about their occurrence in Parkinson's disease (PD). We prospectively studied carbidopa/levodopa pharmacy errors in a cohort of PD outpatients. Over 1 year, pharmacy errors occurred in 8/73 (11%) subjects treated with this medication, producing adverse drug events (ADEs) in 7/8 (87.5%) and increased healthcare utilization in 6/8 (75%) cases. The most common errors were substitution of controlled‐release for immediate‐release carbidopa/levodopa 25/100 mg (5/8; 62.5%) or dispensation of the wrong carbidopa/levodopa dosage (2/8; 25%). All errors involved ongoing prescriptions, including three interpharmacy transfers. Three subjects (37.5%) questioned pharmacy staff about the change in appearance of the tablets, but the error was corrected in only 1/3 of these cases. Carbidopa/levodopa outpatient pharmacy errors are a common, preventable cause of morbidity and excessive healthcare utilization in PD. Education of healthcare providers, patients, and pharmacy staff is warranted to reduce these errors and associated ADEs. © 2010 Movement Disorder Society
Estimation of skeletal muscle energy metabolism in Machado‐Joseph disease using 31P‐MR spectroscopy
Authors: Yabe Ichiro , Tha Khin K. , Yokota Takashi , Sato Kazunori , Soma Hiroyuki , Takei Asako , Terae Satoshi , Okita Koichi , Sasaki Hidenao
Published: September 2010

The aim of this study was to determine if muscle energy metabolism, as measured by 31P‐magnetic resonance spectroscopy (MRS), is a metabolic marker for the efficacy of treatment of Machado‐Joseph disease (MJD). We obtained 31P‐MRS in the calf muscle of 8 male patients with MJD and 11 healthy men before, during, and after a 4 minute plantar flexion exercise in a supine position. The data showed that there was a significant difference between the groups in terms of the PCr/(Pi + PCr) ratio at rest (P = 0.03) and the maximum rate of mitochondrial ATP production (Vmax) (P < 0.01). In addition, Vmax was inversely correlated with the scale for the assessment and rating of ataxia score (r = −0.34, P = 0.04). The MJD group also showed a reduction in Vmax over the course of 2 years (P < 0.05). These data suggest that this noninvasive measurement of muscle energy metabolism may represent a surrogate marker for MJD. © 2010 Movement Disorder Society
Bone Metastases: Molecular Mechanisms and Novel Therapeutic Interventions
Authors: Papachristou Dionysios J. , Basdra Efthimia K. , Papavassiliou Athanasios G.
Published: September 2010

It has been long recognized that skeleton represents one of the most favored metastatic sites for common cancers like breast and prostate. During the last decade the molecular mechanisms that are responsible for the development of bone metastasis have been gradually illuminated. It appears that the bone microenvironment has a pivotal role in this process. Metastatic tumor cells interact with bone triggering a cascade of molecular events that produce osteolytic and/or osteoblastic phenomena. In this review, we summarize and discuss the most significant factors and signaling pathways implicated in bone colonization. Moreover, based on the recent literature and data, we foresee the need for designing novel agents that will efficiently disrupt these interactions among cancer cells and bone microenvironment, bringing hope for more effective treatments. © 2010 Wiley Periodicals, Inc. Med Res Rev, 32, No. 3, 611–636, 2012
High efficient n‐type back‐junction back‐contact silicon solar cells with screen‐printed Al‐alloyed emitter and effective emitter passivation study
Authors: Gong Chun , Singh Sukhvinder , Robbelein Jo , Posthuma Niels , Van Kerschaver Emmanuel , Poortmans Jef , Mertens Robert
Published: September 2010

N‐type back‐junction back‐contact (BJ–BC) silicon solar cells have been successfully introduced in industry by Sunpower with efficiencies up to 23.4% and are being investigated by several research groups. For such n‐type bulk Si solar cells, the formation of the p+ emitter is still an issue. A traditional method is boron diffusion, which needs high temperature processes to form the emitter and to remove the silicate glass boron skin. In recent years, people have shown excellent results on n‐type front contact rear junction cells with a screen‐printed Al‐alloyed emitter. In this work, we demonstrate the use of such emitters on n‐type BJ–BC silicon solar cells. Different pitch sizes and emitter fractions have been studied. Clear trends of the short‐circuit current densities have been observed. Light beam induced current technique is used to investigate this phenomenon. Different front surface field (FSF) profiles were applied to our cells. The shallower FSF with a lower surface doping concentration results in lower front surface recombination, which results in the best cell performance. Efficiencies of 19.1% under 1 Sun on BJ–BC solar cells with an aperture area of 2 cm × 2 cm have been achieved on n‐type FZ and CZ silicon wafers. Good short‐circuit current densities and fill factors have been obtained. Compared to the boron‐diffused emitter BJ–BC solar cells, relatively low open‐circuit voltages were obtained. Better quality emitter with more effective cleaning process steps and passivation layers have been developed, to result in a further increase in cell efficiency in the future work. Copyright © 2010 John Wiley & Sons, Ltd.
Solution structure and function of YndB, an AHSA1 protein fromBacillus subtilis
Authors: Stark Jaime L. , Mercier Kelly A. , Mueller Geoffrey A. , Acton Thomas B. , Xiao Rong , Montelione Gaetano T. , Powers Robert
Published: September 2010

The solution structure of theBacillus subtilisprotein YndB has been solved using NMR to investigate proposed biological functions. The YndB structure exhibits the helix‐grip fold, which consists of a β‐sheet with two small and one long α‐helix, forming a hydrophobic cavity that preferentially binds lipid‐like molecules. Sequence and structure comparisons with proteins from eukaryotes, prokaryotes, and archaea suggest that YndB is very similar to the eukaryote protein Aha1, which binds to the middle domain of Hsp90 and induces ATPase activity. On the basis of these similarities, YndB has been classified as a member of the activator of Hsp90 ATPase homolog 1‐like protein (AHSA1) family with a function that appears to be related to stress response. Anin silicoscreen of a compound library of ∼18,500 lipids was used to identify classes of lipids that preferentially bind YndB. Thein silicoscreen identified, in order of affinity, the chalcone/hydroxychalcone, flavanone, and flavone/flavonol classes of lipids, which was further verified by 2D1H‐15N HSQC NMR titration experiments withtrans‐chalcone, flavanone, flavone, and flavonol. All of these compounds are typically found in plants as precursors to various flavonoid antibiotics and signaling molecules. The sum of the data suggests an involvement of YndB with the stress response ofB. subtilisto chalcone‐like flavonoids released by plants due to a pathogen infection. The observed binding of chalcone‐like molecules by YndB is likely related to thesymbiotic relationship betweenB. subtilisand plants. Proteins 2010. © 2010 Wiley‐Liss, Inc.
Surface plasmon waveguide Schottky detectors operating near breakdown
Authors: Olivieri Anthony , Akbari Ali , Berini Pierre
Published: September 2010

Surface plasmon waveguide Schottky detectors were investigated experimentally at room temperature near junction breakdown. The detectors consist of an Au stripe on n‐Si forming a Schottky contact thereon and supporting strongly confined surface plasmons localised at the Au/Si interface. The detectors were excited by end‐fire coupling at λ0 = 1310 nm where the detection mechanism is the internal photoelectric effect. A ∼10× increase in responsivity was measured at strong reverse biases compared to no bias due to plasmon‐induced junction breakdown. A maximum responsivity of 2.35 mA/W is reported.

magnified image

Surface plasmon waveguide Schottky detector

(© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Quantifying suspended frazil ice using multi‐frequency underwater acoustic devices
Authors: Richard Martin , Morse Brian , Daly Steven F. , Emond Josée
Published: September 2010

An intensive frazil ice field sampling campaign was undertaken at the Port of Quebec on the St. Lawrence River from February–March 2009. Two underwater acoustic instruments set at different frequencies of 420 and 1228.8 kHz were used to detect frazil ice in the water column. In this paper, frequency inversion methods are presented and subsequently applied to the observations to estimate frazil ice characteristics and concentration. Using inversion methods, most of the detected ice crystals had estimated radii of 0.06–0.18 mm. This range compares favourably to the estimated value of 0.20 mm obtained by analysing the Rouse number related to the vertical distribution of the frazil crystals. The results were in contrast to a previous study of frazil ice at another site in the St. Lawrence, which reported radii tens of times larger . The tiny crystals observed here were of similar size to those observed in laboratories (e.g. 0.09 mm), suggesting that the particles formed locally. Frequency analyses were also used to estimate the volumetric suspended frazil concentration, which appeared to be on the order of 6 ppm. Based on evidence suggested by the data and the volume backscattering coefficient at the two frequencies, this study also presents the complex sequence of processes that occurs during a typical supercooling frazil event. This paper concludes with future directions for research using acoustic instrumentation for further understanding of frazil ice dynamics. Copyright © 2010 John Wiley & Sons, Ltd.
The structure and tribological properties of aluminum/carbon nanocomposite thin films synthesized by reactive magnetron sputtering
Authors: Zhou Shengguo , Wang Liping , Xue Qunji
Published: September 2010

Hydrogenated nanocomposite aluminum/carbon thin films (Al/a‐C:H) were fabricated on stainless steel and silicon wafer substrates via unbalanced reactive magnetron sputtering from an Al target in CH4/Ar plasma. The composition and structure of Al/a‐C:H films were investigated by high‐resolution transmission electron microscope (HRTEM), XPS and micro‐Raman spectroscopy. Nanoindenter, interferometer and ball‐on‐disc tribometer were carried out to evaluate the hardness, internal stress and tribological properties of Al/a‐C:H films. HRTEM observations confirmed that the metallic Al nanocrystallites were uniformly dispersed in the amorphous carbon matrix. XPS and Raman analyses indicated that the sp2 content increased with the increase of Al content in the films. Nanoindenter and interferometer tests exhibited that the uniform incorporation of Al nanocrystallites can diminish drastically the magnitude of internal stress with maintaining the higher hardness of as‐deposited films. Especially, the ball‐on‐disc tribometer measurements revealed that the nanocomposite film with 2.3 at.% Al content exhibited relatively better wear resistance and self‐lubrication performance with a friction coefficient of 0.06 and wear rate of 3.1 × 10−16 m3/ N·m under ambient air, which can be attributed to the relatively higher hardness, the formation of continuous graphitized transfer film on counterface and the reduced reaction of oxygen with carbon. Copyright © 2010 John Wiley & Sons, Ltd.
One‐step electrodeposition of amorphous carbon films containing WO3 with high conductivity and good wettability
Authors: Huang Deming , Wan Shanhong , Wang Liping , Xue Qunji
Published: September 2010

Tungsten trioxide‐incorporated hydrogenated amorphous carbon (WO3/a‐C:H) films have been fabricated on a single‐crystal silicon wafer by liquid phase electrodeposition using methanol as carbon source and tungsten carbonyl as incorporated reagent. The morphology, composition and structure of the films have been investigated by SEM, XPS, Raman scattering spectroscopy, Fourier transform infrared spectroscopy (FTIR) and Transmission electron microscope (TEM), respectively. The effects of WO3 incorporation on the electrical and wetting properties were studied in detail. The characterization results showed that tungsten trioxide nanocrystalline particles with diameters in the range of 10–20 nm were homogenously embedded in the amorphous carbon films. Also, the electrical conductivity and wetting ability of the films were strongly improved due to the contribution of the tungsten trioxide. Copyright © 2010 John Wiley & Sons, Ltd.
Oil Microsealing: A Robust Micro‐compartmentalization Method for On‐Chip Chemical and Biological Assays
Authors: Yamada Ayako , Barbaud Fanny , Cinque Lucia , Wang Li , Zeng Qian , Chen Yong , Baigl Damien
Published: September 2010

A simple and robust method to compartmentalize aqueous solutions into an array of independent microchambers is presented. The array of microchambers fabricated in poly(dimethylsiloxane) are filled with the sample solution through a microfluidic channel and then sealed with oil to isolate the microchambers from each other. A water reservoir close to the microchambers allows the maintainance and incubation of sub‐nanoliter solutions (e.g., at 37 °C) within the chambers for hours without any problem of evaporation. Once assembled, the device is self‐sustainable and can be used for different application purposes. As a demonstration, the device configuration is shown to be suitable for spatiotemporal control of the inner solution conditions by light stimulation through a photomask. This method was applied for the generation of regular EmGFP (emerald green fluorescent protein) expression arrays, selective photobleaching, photopatterning of calcium concentration, and cell culture in independent microchambers.
An information systems design product theory for the class of integrated requirements and release management systems
Authors: Käkölä Timo , Koivulahti‐Ojala Mervi , Liimatainen Jani
Published: September 2010

High‐tech companies conducting product development need to collect and analyze requirements effectively, plan and implement releases, and allocate requirements to appropriate releases. Requirements and release management are complicated because development activities typically are scattered across multiple sites, involve multiple partners in different countries, leverage various development methods and tools, and are realized through various organizational arrangements such as release projects in organizations structured around products and permanent release teams in organizations responsible for the long‐term development and maintenance of strategic software and hardware assets. Flexible, scalable, and secure groupware‐based support for the activities provides substantial payoffs. Yet, the extant literature provides little theoretical guidance for designing and using requirements and release management systems (RRMS) in multi‐site, multi‐partner environments. This article develops the meta‐requirements and a meta‐design of an Information Systems Design Product Theory for the class of RRMS based on a case study in a global company and a literature review. The theory is scalable to meet the needs of global companies but simple enough so that small and medium‐sized companies can also leverage it to implement requirements and release management solutions. Copyright © 2010 John Wiley & Sons, Ltd.
Business process modeling with continuous validation
Authors: Kühne Stefan , Kern Heiko , Gruhn Volker , Laue Ralf
Published: September 2010

In this article, we present the prototype of a modeling tool that applies graph‐based rules for identifying problems in business process models. The advantage of our approach is twofold. First, it is unnecessary to compute the complete state space of the model to find errors. Second, our technique can even be applied to incomplete business process models. Thus, the modeler can be supported by direct feedback during the model construction. This feedback not only reports problems, but also identifies their reasons and gives suggestions for improvement. Copyright © 2010 John Wiley & Sons, Ltd.
Shifts in the intensity of purifying selection: An analysis of genome-wide polymorphism data from two closely related yeast species
Authors: Elyashiv Eyal , Bullaughey Kevin , Sattath Shmuel , Rinott Yosef , Przeworski Molly , Sella Guy
Published: September 2010

How much does the intensity of purifying selection vary among populations and species? How uniform are the shifts in selective pressures across the genome? To address these questions, we took advantage of a recent, whole-genome polymorphism data set from two closely related species of yeast, Saccharomyces cerevisiae and S. paradoxus, paying close attention to the population structure within these species. We found that the average intensity of purifying selection on amino acid sites varies markedly among populations and between species. As expected in the presence of extensive weakly deleterious mutations, the effect of purifying selection is substantially weaker on single nucleotide polymorphisms (SNPs) segregating within populations than on SNPs fixed between population samples. Also in accordance with a Nearly Neutral model, the variation in the intensity of purifying selection across populations corresponds almost perfectly to simple measures of their effective size. As a first step toward understanding the processes generating these patterns, we sought to tease apart the relative importance of systematic, genome-wide changes in the efficacy of selection, such as those expected from demographic processes and of gene-specific changes, which may be expected after a shift in selective pressures. For that purpose, we developed a new model for the evolution of purifying selection between populations and inferred its parameters from the genome-wide data using a likelihood approach. We found that most, but not all changes seem to be explained by systematic shifts in the efficacy of selection. One population, the sake-derived strains of S. cerevisiae, however, also shows extensive gene-specific changes, plausibly associated with domestication. These findings have important implications for our understanding of purifying selection as well as for estimates of the rate of molecular adaptation in yeast and in other species.
Human mesenchymal stem cells inhibit metastasis of a hepatocellular carcinoma model using the MHCC97‐H cell line
Authors: Li Guo‐Cai , Ye Qing‐Hai , Xue Yu‐Hua , Sun Hai‐Jing , Zhou Hai‐Jun , Ren Ning , Jia Hu‐Liang , Shi Jiong , Wu Jin‐Cai , Dai Chun , Dong Qiong‐Zhu , Qin Lun‐Xiu
Published: September 2010

The effects of mesenchymal stem cells (MSC) on the growth and metastasis of human malignancies including hepatocellular carcinoma (HCC) are controversial, and the underlying mechanisms are not yet understood. The aim of this study was to explore the role of MSC in the progression of HCC. We investigated the effect of MSC on in vitro proliferation and invasion and in vivo tumor growth and pulmonary metastasis of MHCC97‐H HCC cells with a high metastatic potential. The mRNA and protein levels of transforming growth factor‐beta 1 (TGFβ1) and MMP, and their association with the effects of MSC on HCC cells were also evaluated. Co‐culture of MHCC97‐H cells with MSC conditioned medium significantly enhanced in vitro proliferation but inhibited invasiveness. Following MSC treatment of a nude mouse model bearing human HCC, the MSC were predominantly located in the HCC tissues. Compared with controls, MSC‐treated mice exhibited significantly larger tumors (3080.51 ± 1234.78 mm3vs 2223.75 ± 1000.60 mm3, P = 0.045), but decreased cellular numbers of lung metastases (49.75 ± 18.86 vs 227.22 ± 74.67, P = 0.046). Expression of TGFβ1 and MMP‐2 was significantly downregulated in the MSC‐treated HCC cells. TGFβ siRNA concurrently downregulated expression of TGFβ and MMP‐2 in HCC cells and blocked the MSC‐induced proliferation and invasiveness of MHCC97‐H cells. The MSC enhanced tumor growth but significantly inhibited the invasiveness and metastasis of HCC, possibly through downregulation of TGFβ1. These findings suggest that MSC could be useful in controlling metastatic recurrence of HCC. (Cancer Sci 2010; 101: 2546–2553)
Assessment of algorithms for predicting drug–drug interactions via inhibition mechanisms: comparison of dynamic and static models
Authors: Guest Eleanor J. , Rowland‐Yeo Karen , Rostami‐Hodjegan Amin , Tucker Geoffrey T. , Houston J. Brian , Galetin Aleksandra
Published: September 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The prediction of drug–drug interactions (DDIs) fromin vitrodata usually utilizes an average dosing interval estimate of inhibitor concentration in an equation‐basedstatic model.

• Simcyp®, a population‐based ADME simulator, is becoming widely used for the prediction of DDIs and has the ability to incorporate the time‐course of inhibitor concentration and hence generate a temporal profile of the inhibition process within adynamic model.

WHAT THIS PAPER ADDS

• Prediction of DDIs for 35 clinical studies incorporating a representative range of drug–drug interactions, with multiple studies across different inhibitors and victim drugs.

• Assessment of whether the inclusion of the time course of inhibition in the dynamic model improves prediction in comparison with the static model.

• Investigation of the impact of different inhibitor and victim drug parameters on DDI prediction accuracy including dosing time and the inclusion of active metabolites. Assessment of ability of the dynamic model to predict inter‐individual variability in the DDI magnitude.

AIMSStatic and dynamic models (incorporating the time course of the inhibitor) were assessed for their ability to predict drug–drug interactions (DDIs) using a population‐based ADME simulator (Simcyp®V8). The impact of active metabolites, dosing time and the ability to predict inter‐individual variability in DDI magnitude were investigated using the dynamic model.

METHODSThirty‐fivein vivoDDIs involving azole inhibitors and benzodiazepines were predicted using the static and dynamic model; both models were employed within Simcyp for consistency in parameters. Simulations comprised of 10 trials with matching population demographics and dosage regimen to thein vivostudies. Predictive utility of the static and dynamic model was assessed relative to the inhibitor or victim drug investigated.

RESULTSUse of the dynamic and static models resulted in comparable prediction success, with 71 and 77% of DDIs predicted within two‐fold, respectively. Over 40% of strong DDIs (>five‐fold AUC increase) were under‐predicted by both models. Incorporation of the itraconazole metabolite into the dynamic model resulted in increased prediction accuracy of strong DDIs (80% within two‐fold). Bias and imprecision in prediction of triazolam DDIs were higher in comparison with midazolam and alprazolam; >50% of triazolam DDIs were under‐predicted regardless of the model used. Predicted inter‐individual variability in the AUC ratio (coefficient of variation of 45%) was consistent with the observed variability (50%).

CONCLUSIONSHigh prediction accuracy was observed using both the Simcyp dynamic and static models. The differences observed with the dose staggering and the incorporation of active metabolite highlight the importance of these variables in DDI prediction.