bluuebunny/crossref_metadata_2025 huggingface dataset:
Sciatic nerve transection triggers release and intercellular transfer of a genetically expressed macromolecular tracer in dorsal root ganglia
Authors: Bráz João M. , Ackerman Larry , Basbaum Allan I.
Published: April 2011

We recently developed a genetic transneuronal tracing approach that allows for the study of circuits that are altered by nerve injury. We generated transgenic (ZW‐X) mice in which expression of a transneuronal tracer, wheat germ agglutinin (WGA), is induced in primary sensory neurons, but only after transection of their peripheral axon. By following the transneuronal transport of the tracer into the central nervous system (CNS) we can label the circuits that are engaged by the WGA‐expressing damaged neurons. Here we used the ZW‐X mouse line to analyze dorsal root ganglia (DRG) for intraganglionic connections between injured sensory neurons and their neighboring “intact” neurons. Because neuropeptide Y (NPY) expression is strongly induced in DRG neurons after peripheral axotomy, we crossed the ZW‐X mouse line with a mouse that expresses Cre recombinase under the influence of the NPY promoter. As expected, sciatic nerve transection triggered WGA expression in NPY‐positive DRG neurons, most of which are of large diameter. As expected, double labeling for ATF‐3, a marker of cell bodies with damaged axons, showed that the tracer predominated in injured (i.e., axotomized) neurons. However, we also found the WGA tracer in DRG cell bodies of uninjured sensory neurons. Importantly, in the absence of nerve injury there was no intraganglionic transfer of WGA. Our results demonstrate that intraganglionic, cell‐to‐cell communication, via transfer of large molecules, occurs between the cell bodies of injured and neighboring noninjured primary afferent neurons. J. Comp. Neurol. 519:2648–2657, 2011. © 2011 Wiley‐Liss, Inc.
Sites of origin and developmental dynamics of the neurons in the core and shell regions of torus semicircularis in the chinese softshell turtle (Pelodiscus sinensis)
Authors: Xi Chao , Chen Qiong , Zeng Shao‐Ju , Lin Yu‐Tao , Huang Yu‐Fang , Liu Yu , Zhang Xin‐Wen , Zuo Ming‐Xue
Published: April 2011

To know the embryogenesis of the core and shell regions of the midbrain auditory nucleus, a single dose of [3H]‐thymidine was injected into the turtle embryos at peak stages of neurogenesis in the shell and core of the torus semicircularis. Following sequential survival times, labeled neurons and the dynamics of cell proliferation were examined. The expression of vimentin (VM), reelin, calbindin, parvalbumin, and substance P were also studied. The results showed that: 1) progenitor cells for the core and shell regions were generated in different sites of the ventricular zone; 2) the length of the cell cycle or S‐phase for the shell region were both longer than those for the core region (4.7 and 3.2 hours longer, respectively), suggesting that mitotic activity in the core region is higher than it is in the shell region; 3) the elongated cell bodies of the labeled core and shell cells had close apposition to VM fibers, suggesting that the migration of these cells is guided by VM fibers; 4) the germinal sites of the core and shell constructed by projecting the orientation of radial VM fibers back to the ventricular zone was consistent with those obtained by short and sequential survival [3H]‐thymidine radiography; and 5) the beginning of positive staining for parvalbumin in the core region was interposed between those for calbindin and substance P in the shell regions. This study contributes to the understanding of how auditory nuclei are organized and how their components developed and evolved. J. Comp. Neurol. 519:2677–2696, 2011. © 2011 Wiley‐Liss, Inc.
Adolescent binge alcohol exposure alters hippocampal progenitor cell proliferation in rats: Effects on cell cycle kinetics
Authors: McClain Justin A. , Hayes Dayna M. , Morris Stephanie A. , Nixon Kimberly
Published: April 2011

Binge alcohol exposure in adolescent rats potently inhibits adult hippocampal neurogenesis by altering neural progenitor cell (NPC) proliferation and survival; however, it is not clear whether alcohol results in an increase or decrease in net proliferation. Thus, the effects of alcohol on hippocampal NPC cell cycle phase distribution and kinetics were assessed in an adolescent rat model of an alcohol use disorder. Cell cycle distribution was measured using a combination of markers (Ki‐67, bromodeoxyuridine incorporation, and phosphohistone H3) to determine the proportion of NPCs within G1, S, and G2/M phases of the cell cycle. Cell cycle kinetics were calculated using a cumulative bromodeoxyuridine injection protocol to determine the effect of alcohol on cell cycle length and S‐phase duration. Binge alcohol exposure reduced the proportion of NPCs in S‐phase, but had no effect on G1 or G2/M phases, indicating that alcohol specifically targets S‐phase of the cell cycle. Cell cycle kinetics studies revealed that alcohol reduced NPC cell cycle duration by 36% and shortened S‐phase by 62%, suggesting that binge alcohol exposure accelerates progression through the cell cycle. This effect would be expected to increase NPC proliferation, which was supported by a slight, but significant increase in the number of Sox‐2+ NPCs residing in the hippocampal subgranular zone following binge alcohol exposure. These studies suggest the mechanism of alcohol inhibition of neurogenesis and also reveal the earliest evidence of the compensatory neurogenesis reaction that has been observed a week after binge alcohol exposure. J. Comp. Neurol. 519:2697–2710, 2011. © 2011 Wiley‐Liss, Inc.
Sexually dimorphic expression of hypothalamic estrogen receptors α and β and kiss1 in neonatal male and female rats
Authors: Cao Jinyan , Patisaul Heather B.
Published: April 2011

Release of gonadotropins in adult rodents is sex specific and dependent upon kisspeptin (Kiss1) neurons. This crucial pathway within the hypothalamic‐pituitary‐gonadal (HPG) axis is profoundly influenced by neonatal estrogens, which induce a male‐like phenotype. Classically, estrogen activity is mediated via the estrogen receptors α and β (ERα and ERβ), but the relative roles each plays in organizing the sex‐specific ontogeny of kisspeptin signaling pathways remain unresolved. Thus, the present study used in situ hybridization histochemistry (ISHH) to map the temporal and sexually dimorphic neonatal mRNA expression profiles of ERα, ERβ, and Kiss1 in the anterioventral periventricular nucleus (AVPV), medial preoptic area (MPOA), ventromedial nucleus (VMN), and arcuate nucleus (ARC), all regions critical for kisspeptin regulation of gonadotropin secretion. In general, females had higher levels of ERα, in all regions examined, a sex difference that persisted until postnatal day (PND) 19 except in the ARC. Males had significantly more ERβ expression in the AVPV at birth, but this sex difference was lost and then re‐emerged on PND 19, with females having more than males. VMN ERβ levels were higher in females until PND 19. Kiss1 was not detectable until PND 11 in the anterior hypothalamus, but expression levels were equivalent at birth in the ARC. By PND 2, ARC ERα and Kiss1 levels were abundant, sexually dimorphic (higher in females), and, respectively, showed a U‐ and a bell‐shaped pattern with age. Sex differences in ARC Kiss1 expression provide evidence that Kiss1 may play a role in the sexual dimorphic organization of the neonatal brain. These detailed profiles of neonatal Kiss1 and ERs mRNA levels will help elucidate the relative roles each plays in the sex‐specific, estrogen‐dependent organization of gonadotropin signaling pathways. J. Comp. Neurol. 519:2954–2977, 2011. © 2011 Wiley‐Liss, Inc.
Involvement of the drosophila taurine/aspartate transporter dEAAT2 in selective olfactory and gustatory perceptions
Authors: Besson M.T. , Sinakevitch I. , Melon C. , Iché‐Torres M. , Birman S.
Published: April 2011

Excitatory amino acid transporters (EAATs) are membrane proteins involved in the uptake of neurotransmitter amino acids in the nervous system. The Drosophila
dEAAT2 gene was previously described to encode a taurine/aspartate transporter. To analyze further the expression pattern and physiological function of this protein, we generated transgenic flies containing either the dEAAT2 promoter region fused to GAL4 (dEAAT2‐GAL4) or a transgene allowing expression of a dEAAT2::GFP fusion protein (UAS‐dEAAT2::GFP). We observed that dEAAT2‐GAL4 expresses green fluorescent protein (GFP) in neurons in central and peripheral structures of third‐instar larvae and adult flies. Labeled neurons were found in olfactory and gustatory pathways, in which dEAAT2::GFP was detected from the dendrites of the sensory neurons up to the first‐ and second‐order centers. dEAAT2‐GAL4 is also expressed in mechanosensory neurons. We found that a viable piggyBac insertion strain disrupts dEAAT2 expression. This mutant appears morphologically normal and presents no locomotor or phototaxis impairments; however, its brain taurine level is significantly reduced compared with that of wild‐type flies. The dEAAT2 mutant showed decreased avoidance behavior in the presence of high concentration of propionic acid compared with wild‐type flies, but no modification of the avoidance response to benzaldehyde. In gustatory tests, both mutant and control flies were normally attracted to sucrose; however, the dEAAT2 mutant presented a higher salt sensitivity, being repulsed by low and high salt concentrations. Therefore, we conclude that dEAAT2 does function as a taurine transporter in vivo and that this protein is physiologically required for the sensory perception of specific environmental molecules. J. Comp. Neurol. 519:2734–2757, 2011. © 2011 Wiley‐Liss, Inc.
Improved compensation in flow cytometry by multivariable optimization
Authors: Sugár István P. , González‐Lergier Joanna , Sealfon Stuart C.
Published: April 2011

Conventional compensation of flow cytometry (FMC) data of an N‐stained sample requires additional data sets, of N single‐stained control samples, to estimate the spillover coefficients. Single‐stained controls however are the least rigorous controls because any of the multi‐stained controls are closer to the N‐stained sample. In this article, a new, optimization based, compensation method has been developed that is able to use not only single‐ but also multi‐stained controls to improve estimates of the spillover coefficients. The method is demonstrated on a data set from five‐stained dentritic cells (DCs) with five single‐stained and eight multi‐stained controls. This approach is practical and leads to significant improvements in FCM compensation. © 2011 International Society for Advancement of Cytometry
Additional slides from residual ThinPrep Pap tests: Of potential diagnostic benefit in equivocal cases?
Authors: Grapsa D. , Ioakim‐Liossi A. , Stergiou E. , Petrakakou E. , Nicolopoulou‐Stamati P. , Patsouris E. , Athanassiadou P.
Published: April 2011

The aim of this study was to further evaluate the diagnostic significance of additional slides prepared from residual ThinPrep (TP) Pap Tests. Up to 10 repeat slides were prepared from 105 residual TP cervical samples. All additional slides were evaluated for the presence of diagnostic elements which were not found on the primary TP slide. After the evaluation of the repeat slides, an upgraded diagnosis was noted in 15 cases (14.3%). The reclassified cases included: three negative cases reclassified as two ASC‐US and as one LSIL, seven cases of ASC‐US reclassified as six LSIL and as one HSIL, and five cases of LSIL reclassified as HSIL. The highest rate (7/15 cases, 46.7%) of cases with an upgraded diagnosis was noted in the ASC‐US diagnostic category. Our results suggest that repeat processing of residual TP cervical samples may represent an adjunctive diagnostic tool for a more accurate classification of ASC‐US cases. Nevertheless, the practical value of this approach seems to be limited by its significant cost and its uncertain effectiveness. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.
FNA in diagnosis of orbital lesions causing proptosis in adults
Authors: Singhal Niti , Mundi Irneet Kaur , Handa Uma , Punia R. P. S. , Mohan Harsh
Published: April 2011

The orbit is affected by a wide range of pathologic lesions, for which a morphologic diagnosis is needed to allow adequate therapy. With increasing use of fine needle aspiration (FNA) in diagnostic pathology, the procedure has been applied for the diagnosis of space occupying lesions of the orbit. We present the cytomorphological diagnosis on orbital FNA in adult patients presenting with proptosis.

Records of seven adult patients who had presented with proptosis and had undergone orbital FNA were retrieved and analysed. FNA was performed from the palpable mass in six cases and under ultrasound guidance in one case. No complication during or after FNA was reported in any of the cases. Histopathological diagnosis was available in 5 cases.

Out of the 7 cases, 3 were non‐neoplastic (2 inflammatory lesions, 1 reactive lymphoid hyperplasia) and 4 were neoplastic (2 primary tumors and 2 secondary involvement). Both the primary tumors were non Hodgkin's lymphoma (NHL) B‐cell type. Metastases included one case of uterine sarcomatoid carcinoma and one case of secondary involvement by extension of olfactory neuroblastoma. In all the neoplastic cases, cytological diagnosis corresponded with the histopathological diagnosis.

It can be concluded that cause of proptosis among adults are different from those among children and include secondary malignancies. FNA is a simple and important preliminary diagnostic modality in the assessment of adult proptosis prior to any surgical intervention. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.
Role of DNA flow cytometry and immunocytochemical analysis in diagnosis of malignant effusions
Authors: Kundu Reetu , Handa Uma , Mohan Harsh
Published: April 2011

Body cavity fluid examination sometimes presents a diagnostic challenge in cytology practice. This study was undertaken to evaluate efficacy of cytomorphology, epithelial membrane antigen immunocytochemistry (EMA‐ICC) and DNA flow cytometry (FCM) in detection of malignant cells in effusions.

One hundred effusions (55 pleural, 44 ascitic, and 1 pericardial fluid) were studied by cytology, EMA, and FCM. There were 29 malignant and 71 benign cases. On cytology, 28 of 29 malignant cases were diagnosed. With no false positives, the sensitivity and specificity was 96.55% and 100% respectively. FCM detected aneuploidy in 85.71% of cytologically malignant and 4.17% of cytologically benign effusions. EMA was positive in 75% of cytologically malignant and 4.17% of cytologically benign cases. EMA had lower sensitivity than cytology; 75.86% versus 96.55%. Sensitivity and specificity of FCM was 86.21%, and 97.18% respectively. FCM had lower sensitivity than cytology; 86.21% versus 96.55%. Sensitivity increased to 100% (P < 0.05) when the combinations of cytology plus EMA or cytology plus ploidy were applied compared to cytology alone (96.55%). Also, the combination of cytology plus EMA had higher sensitivity than EMA alone (100% versus 75.86%, P < 0.05) and combined cytology plus ploidy had higher sensitivity than ploidy alone (100% versus 86.21%, P < 0.05).

The study demonstrates the usefulness of EMA‐ICC and DNA FCM as adjuncts to cytology to diagnose malignancy in effusions. FCM in combination with ICC can be further developed to reduce number of false‐negative cases on cytology and add objectivity to cytologically doubtful or equivocal cases. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.
A functional scaffold of CNS neurons for the vertebrates: The developing Xenopus laevis spinal cord
Authors: Roberts Alan , Li Wen‐Chang , Soffe Stephen R.
Published: April 2011

In young and developing amphibians and fish the spinal cord is functional but remarkably simple compared with the adult. Is the pattern of neurons and their connections common across at least these lower vertebrates? Does this basic pattern extend into the brainstem? Could the development of simple functioning neuronal networks depend on very basic rules of connectivity and act as pioneer networks providing a substrate for the development of more complex and subtle networks. In this review of the functional neuron classes in the Xenopus laevis tadpole spinal cord up to hatching, we will consider progress and difficulties in using anatomy, transcription factor expression, physiology, and activity to define spinal neuron types. Even here it is not straightforward and is rarely possible to bring all the different strands of evidence together. But, we think we have a rather complete picture of the hatchling tadpole spinal neuron types and can define clear roles for most of them in behavior. Our present knowledge about the hatchling Xenopus spinal cord should set up many of the problems to be unraveled in the future by more developmentally oriented research. © 2011 Wiley Periodicals, Inc. Develop Neurobiol 72: 575–584, 2012
Treatment with the TLR7 agonist R848 induces regulatory T‐cell‐mediated suppression of established asthma symptoms
Authors: Pham Van Linh , Bardel Emilie , Gregoire Sylvie , Vanoirbeek Jeroen , Schneider Elke , Dy Michel , Thieblemont Nathalie
Published: April 2011

The evolution of allergic asthma is tightly controlled by effector and regulatory cells, as well as cytokines such as IL‐10 and/or TGF‐β, and it is widely acknowledged that environmental exposure to allergens and infectious agents can influence these processes. In this context, the recognition of pathogen‐associated motifs, which trigger TLR activation pathways, plays a critical role with important consequences for disease progression and outcome. We addressed the question whether the TLR7 ligand resiquimod (R848), which has been shown to be protective in several experimental allergic asthma protocols, can also suppress typical asthma symptoms once the disease is established. To this end, we used an OVA‐induced experimental model of murine allergic asthma in which R848 was injected after a series of challenges with aerosolized OVA. We found that the treatment attenuated allergic symptoms through a mechanism that required Tregs, as assessed by the expansion of this population in the lungs of mice having received R848, and the loss of R848‐mediated suppression of allergic responses after in vivo Treg depletion. IL‐10 provided only a minor contribution to this suppressive effect that was largely mediated through a TGF‐β‐dependent pathway, a finding that opens new therapeutic opportunities for the pharmacological targeting of Tregs.
Recognition of yeast nucleic acids triggers a host‐protective type I interferon response
Authors: Biondo Carmelo , Signorino Giacomo , Costa Alessandro , Midiri Angelina , Gerace Elisabetta , Galbo Roberta , Bellantoni Antonella , Malara Antonio , Beninati Concetta , Teti Giuseppe , Mancuso Giuseppe
Published: April 2011

Although type I interferons (IFN‐α/β) have been traditionally associated with antiviral responses, their importance in host defense against bacterial pathogens is being increasingly appreciated. Little is known, however, about the occurrence and functional role of IFN‐α/β production in response to pathogenic yeasts. Here, we found that conventional DCs, but not macrophages nor plasmacytoid DCs, mounted IFN‐β responses after in vitro stimulation with Candida spp. or Saccharomyces cerevisiae. These responses absolutely required MyD88, a Toll‐like receptor (TLR) adaptor molecule, and were partially dependent on TLR9 and TLR7. Moreover, Candida DNA, as well as RNA, could recapitulate the IFN‐β response. After intravenous challenge with Candida albicans, most mice lacking the IFN‐α/β receptor died from their inability to control fungal growth, whereas all WT controls survived. These data suggest that recognition of yeast nucleic acids by TLR7 and TLR9 triggers a host‐protective IFN‐α/β response.
Shelf‐life prediction of perilla oil by considering the induction period of lipid oxidation
Authors: Shim Soo Dong , Lee Seung Ju
Published: April 2011

Kinetic models for the induction period (IP) of lipid oxidation were developed to predict the shelf‐life of perilla oil during storage. The degree of lipid oxidation was measured in terms of peroxide values (PV). The perilla oil was stored in the dark at various temperatures. The IP was measured at the intersection point of two linear lines and in terms of time and PV at the IP. The IP was expressed by an Arrhenius‐like relationship. Before and after the IP, the reaction followed pseudo‐zero‐order kinetics. The oxidation degrees according to storage times were computed by considering the variables, IP and reaction rate constants. The prediction model equation that was developed to determine shelf‐life is more accurate than in previous studies. Conclusively, considering the IP of lipid oxidation is essential for predicting the shelf‐life of perilla oil and is expected to be applicable to other vegetable oils.

Practical applications: In kinetic modeling for shelf‐life estimation in terms of lipid oxidation, induction period (IP) is rarely considered. Thus the estimation of peroxide values (PV) from such models might be inaccurate. The IP was observed in perilla oil oxidation and kinetic models involving the IP were developed. This work enables a better estimation of oxidation. Besides, a shelf‐life diagram of perilla oil has been constructed as a valuable tool for quality control in the food industry.
Determination of polyphenols, tocopherols, and antioxidant capacity in virgin argan oil (Argania spinosa, Skeels)
Authors: Marfil Rocío , Giménez Rafael , Martínez Olga , Bouzas Paula R. , Rufián‐Henares José A. , Mesías Marta , Cabrera‐Vique Carmen
Published: April 2011

This study establishes data on polyphenols, tocopherols, and antioxidant capacity (AC) of virgin argan oil. A total of 22 samples from Morocco were analyzed. Total polyphenol content ranged between 6.07 and 152.04 mg GAE/kg. Total tocopherols varied between 427.0 and 654.0 mg/kg, being γ‐tocopherol the major fraction (84.68%); α‐, β‐, and δ‐tocopherols represent 7.75, 0.33, and 7.29%, respectively. No influence of oil extraction method on total tocopherols was observed. The AC of argan virgin oils determined by the ABTS method in n‐hexane oils dilution ranged between 14.16 and 28.02 mmol Trolox/kg, and by the ABTS, DPPH, and FRAP methods in methanolic oil extracts between 2.31–14.15, 0.19–0.87, and 0.62–2.32 mmol Trolox/kg, respectively. A high correlation was found between ABTS and DPPH methods applied to a methanolic oil extract. Virgin argan oil presents a higher polyphenol and tocopherol content, and total AC than other edible vegetable oils.
Viscosity and rheological behavior of castor–canola mixture
Authors: Mirzayi Behruz , Heydari Amir , Noori Leyla , Arjomand Roghayye
Published: April 2011

In this work, the effects of shear rate on viscosity of selected pure food grade oils (castor and canola) are investigated. The rheological behavior of castor–canola oil mixture is also studied through modeling the experimental data. The effect of shear rate on the variation of viscosity was clearly observed. Interpretations of the results from rheological models indicate that these food grade oils belong to pseudo‐plastic category. The results also show that among the six used mixing rules, Grunberg–Nissan model seems very well fitted to the experimental data.
Neighbouring Formyl Group Assisted Oxidation of o‐Alkynylarenecarbaldehydes by an Iodine/Water System
Authors: Sakthivel Karuppusamy , Srinivasan Kannupal
Published: April 2011

The oxidation of o‐alkynylarenecarbaldehydes into tricarbonyl compounds by an iodine/water system is described. The reaction takes place via isochromenol intermediates formed by intramolecular assistance of the formyl group. The procedure was applied to various o‐alkynylarenecarbaldehydes to afford the corresponding products in good to excellent yields.
Building Heterocyclic Systems with RC(OR)2+ Carbocations in Recyclable Brønsted Acidic Ionic Liquids: Facile Synthesis of 1‐Substituted 1H‐1,2,3,4‐Tetrazoles, Benzazoles and Other Ring Systems with CH(OEt)3 and EtC(OEt)3 in [EtNH3][NO3] and [PMIM(SO3H)][OTf]
Authors: Aridoss Gopalakrishnan , Laali Kenneth K.
Published: April 2011

1‐Aryl/alkyl‐1H‐1,2,3,4‐tetrazoles can conveniently be synthesized in one‐pot reactions from the corresponding amines by reaction with TMSN3 and CH(OEt)3 using the readily available, recyclable, Brønsted acidic ionic liquids [EtNH3][NO3] IL‐1 and [PMIM(SO3 H)][OTf] IL‐2 under mild conditions in high yields. Based on comparative reactions, whereas both ILs are excellent promoters, reactions are completed with shorter reaction times and in higher yields with IL‐2. Among 24 examples provided, identical products were obtained via the two ILs, except in the case of 2‐aminobenzoic acid where tetrazole was formed with IL‐2 and 2‐ethylquinazolin‐4(3H)‐one was formed with IL‐1. By leaving out TMS‐N3 from the reaction, the in‐situ formed CH(OEt)2+ and EtC(OEt)2+ (via their corresponding orthoesters) react under sonication with o‐phenylenediamine bearing various substituents, o‐aminothiophenol and o‐aminophenol to form a wide array of benzazoles (benzimidazole, benzothiazole and benzoxazole) and quinazolin‐4(3H)‐one in high yields (18 examples). The two ILs reacted differently in reaction with 2‐aminobenzamide, whereas quinazolin‐4(3H)one was formed with IL‐2/CH(OEt)3, the “unexpected” N‐ethylquinazolin‐4(3H)one was isolated with IL‐1/CH(OEt)3. The latter was also formed from 2‐aminobenzoic acid in IL‐1/CH(OEt)3. Mechanistic implications are addressed. The reported protocols enable rapid assembly of a host of heterocyclic systems in high yields with the added advantage of recycling and re‐use of the ILs.
Algorithms for interface treatment and load computation in embedded boundary methods for fluid and fluid–structure interaction problems
Authors: Wang K. , Rallu A. , Gerbeau J.‐F. , Farhat C.
Published: April 2011

Embedded boundary methods for CFD (computational fluid dynamics) simplify a number of issues. These range from meshing the fluid domain, to designing and implementing Eulerian‐based algorithms for fluid–structure applications featuring large structural motions and/or deformations. Unfortunately, embedded boundary methods also complicate other issues such as the treatment of the wall boundary conditions in general, and fluid–structure transmission conditions in particular. This paper focuses on this aspect of the problem in the context of compressible flows, the finite volume method for the fluid, and the finite element method for the structure. First, it presents a numerical method for treating simultaneously the fluid pressure and velocity conditions on static and dynamic embedded interfaces. This method is based on the exact solution of local, one‐dimensional, fluid–structure Riemann problems. Next, it describes two consistent and conservative approaches for computing the flow‐induced loads on rigid and flexible embedded structures. The first approach reconstructs the interfaces within the CFD solver. The second one represents them as zero level sets, and works instead with surrogate fluid/structure interfaces. For example, the surrogate interfaces obtained simply by joining contiguous segments of the boundary surfaces of the fluid control volumes that are the closest to the zero level sets are explored in this work. All numerical algorithms presented in this paper are applicable with any embedding CFD mesh, whether it is structured or unstructured. Their performance is illustrated by their application to the solution of three‐dimensional fluid–structure interaction problems associated with the fields of aeronautics and underwater implosion. Copyright © 2011 John Wiley & Sons, Ltd.
Quantitative WD‐XRF calibration for small ceramic samples and their source material
Authors: De Vleeschouwer François , Renson Virginie , Claeys Philippe , Nys Karin , Bindler Richard
Published: April 2011

A wavelength‐dispersive X‐ray fluorescence (WD‐XRF) calibration is developed for small powdered samples (300mg) with the purpose of analyzing ceramic artifacts that might be available only in limited quantity. This is compared to a conventional calibration using a larger sample mass (2g). The comparison of elemental intensities obtained in both calibrations shows that the decrease in analyzed sample mass results in a linear decrease in measured intensity for the analyzed elements. This indicates that the small‐ and large‐sample calibrations are comparable. Moreover, the elemental contents of four ceramic sherds and two potential clay sources fall well within the range of the certified reference materials that are the basis of the calibration curves. The advantage with the analytical method presented here is that it is rapid and requires only a small amount of sample that can easily be re‐used for further analyses. This method has great potential in ceramic provenance studies. © 2011 Wiley Periodicals, Inc.
Factors predictive of severity of osteoradionecrosis of the mandible
Authors: Chopra Shamit , Kamdar Dev , Tulunay Ugur Ozlem E. , Chen George , Peshek Brian , Marunick Mark , Kim Harold , Lin Ho‐Sheng , Jacobs John
Published: April 2011

Background

An analysis of risk factors predictive of severe mandibular osteoradionecrosis (ORN) is needed to aid prophylaxis and management of this condition.

Methods

We retrospectively analyzed 46 patients diagnosed between June 2002 and March 2009: 93% had mandibular ORN, which was staged 0 to III (Store and Boysen). Patient, tumor, treatment‐related, and other variables were analyzed for association with mandibular ORN severity.

Results

Oral or oropharyngeal tumors comprised 85% of our primary tumors, 80% were stage IV, and 91% were squamous cell carcinomas. Most patients (87%) received 3‐dimensional (3D) conformal radiation therapy (RT), with 60 Gray (Gy) median dose; 28% and 72% received primary and adjuvant RT, respectively; 78% received chemotherapy, mostly concurrent (97%) and platinum‐based (96%). Median time to development of ORN was 7.5 months. White ethnicity and secondary infection correlated significantly with stage III mandibular ORN (p = .038, p = .0007, respectively). Advanced age, stage IV, RT dose, post‐RT, and lack of pre‐RT dental extractions appeared predictive of severe mandibular ORN.

Conclusions

The above‐cited factors are predictive of severity and can potentially guide prophylaxis and management. © 2011 Wiley Periodicals, Inc. Head Neck, 2011.
Effective treatment of 7,12‐dimethylbenz(a)anthracene–induced hamster buccal pouch precancerous lesions by topical photosan‐mediated photodynamic therapy
Authors: Chiang Chun‐Pin , Huang Wan‐Ting , Lee Jeng‐Woei , Hsu Yih‐Chih
Published: April 2011

Background

Previous studies found that topical photodynamic therapy (PDT) is very effective for human oral precancerous lesions.

Methods

This study evaluated whether topical photosan‐mediated PDT (topical photosan–PDT), using a 640‐nm light‐emitting diode (LED) light, is an effective treatment modality for hamster buccal pouch precancerous lesions. Fourteen 7,12‐dimethylbenz(a)anthracene (DMBA)–induced hamster buccal pouch precancerous lesions were treated with topical photosan–PDT using the 640‐nm LED light twice a week.

Results

All 14 of the precancerous lesions showed a complete histologically confirmed response to the lesions after an average of 3.79 (range, 3–5) PDT treatments. Normal and precancerous pouch mucosae in the other 4 hamsters received 17 or 19 treatments of topical photosan–PDT showed no cumulative side effects. No recurrence of the lesions was found in these 18 PDT‐treated hamsters after a follow‐up period of 50 weeks.

Conclusion

Our findings indicate that topical photosan–PDT is a very effective treatment modality for DMBA‐induced hamster buccal pouch precancerous lesions. © 2011 Wiley Periodicals, Inc. Head Neck, 2012.
A new apparatus for measuring total hemispherical emittance of surfaces at room temperature
Authors: Wakabayashi Hidenobu , Makino Toshiro
Published: April 2011

Radiation heat transfer is an important mode of heat transfer even in our life space at room temperature. Such radiation heat transfer is evaluated mostly by calculating the radiation energy exchange among surfaces in an enclosure. For this evaluation, knowledge of the hemispherical emittances of the constituent life surfaces is needed. However, there has not been a suitable technique for measuring the emittance of each surface in the life space at room temperature. In the present work we develop a new apparatus for measuring total hemispherical emittances of real surfaces at room temperature. The apparatus consists of a total radiation flux meter and a Peltier element cooler to cool the flux meter surface from the back, and measure the net total radiation flux from the specimen surface to the surrounding surfaces to determine the total hemispherical emittance of the specimen surface. This apparatus is effective to measure total hemispherical emittances of surfaces at room temperature on site. We apply the developed apparatus to measure the total hemispherical emittances of various surfaces in the life space, such as metals, human skin, cloth, floor mat, wood, glass, brick tile, stone, cement, plant leaves, etc., and demonstrate the feasibility of the apparatus. © 2011 Wiley Periodicals, Inc. Heat Trans Asian Res; Published online in Wiley Online Library (wileyonlinelibrary.com/journal/htj). DOI 10.1002/htj.20349
Circulating angiopoietin‐1 to angiopoietin‐2 ratio is an independent prognostic factor for survival in newly diagnosed patients with multiple myeloma who received therapy with novel antimyeloma agents
Authors: Terpos Evangelos , Anargyrou Konstantinos , Katodritou Eirini , Kastritis Efstathios , Papatheodorou Athanasios , Christoulas Dimitrios , Pouli Anastasia , Michalis Eurydiki , Delimpasi Sosana , Gkotzamanidou Maria , Nikitas Nikitas , Koumoustiotis Vasilios , Margaritis Dimitrios , Tsionos Konstantinos , Stefanoudaki Ekaterini , Meletis John , Zervas Konstantinos , Dimopoulos Meletios A. ,   on behalf of the Greek Myeloma Study Group, Greece
Published: April 2011

The circulating levels of several angiogenic cytokines [angiopoietin‐1 (Ang‐1), angiopoietin‐2 (Ang‐2), vascular endothelial growth factor (VEGF), angiogenin and basic fibroblast growth factor (bFGF)] were evaluated in 174 consecutive patients with newly diagnosed, symptomatic, multiple myeloma (MM). Circulating levels of Ang‐1/Ang‐2 were reduced in myeloma patients compared to controls, whereas VEGF and angiogenin levels were increased. Reduced angiopoietin‐1/angiopoietin‐2 ratio correlated with advanced disease features including international staging system (ISS)‐3 stage, renal impairment and extensive bone disease. Based on immunohistochemical results in 20 patients (10 with the higher and 10 with the lower values of circulating angiopoietin‐2) we found that angiopoietin‐2 is expressed by myeloma cells and correlates with increased microvessel density in subsets of patients. Furthermore, Ang‐1/Ang‐2 ratio correlated with survival. Patients with circulating Ang‐1/Ang‐2 below or equal to the median value (6.03) had a median survival of 26.3 months compared to 53 months of all others (p = 0.002). Interestingly, this was mainly observed in patients who received first‐line therapy with novel agent‐based regimens (65% of our patients). Furthermore, a subset of ISS‐3 patients with serum Ang‐1/Ang‐2 above the median value had favourable prognosis (median survival: 45 months versus 17 months of all others; p = 0.0001). The multivariate analysis revealed that low Ang‐1/Ang‐2 ratio could independently predict for inferior survival in our cohort of patients (relative risk (RR) 2.07, 95% CI 1.50–2.42; p < 0.001). These results highlight the role of angiopoietins pathway in the biology of MM and reveal novel targets for the development of antimyeloma agents.
Differential carcinogenicity of cigarette smoke in mice exposed either transplacentally, early in life or in adulthood
Authors: Balansky Roumen , Ganchev Gancho , Iltcheva Marietta , Nikolov Manasi , Steele Vernon E. , De Flora Silvio
Published: April 2011

Cigarette smoke (CS) plays a dominant role in the epidemiology of human cancer. However, it is difficult to reproduce its carcinogenicity in laboratory animals. Recently, we showed that CS becomes a potent carcinogen in mice when exposure starts soon after birth. In our study, we comparatively evaluated the carcinogenic response to mainstream CS in mice at different ages. Neonatal mice were exposed daily for 4 months to CS, starting within 12 hr after birth, and sacrificed at 8 months. Adult mice were exposed for the same time period (3–7 months) and sacrificed at 11 months. Other mice were exposed transplacentally or both transplacentally and early in life. A total of 351 neonatal mice and 80 adult Swiss H mice were used. With varying intensity depending on age, CS induced pulmonary emphysema, bronchial and alveolar epithelial hyperplasia, blood vessel proliferation and hemangiomas and microadenomas in lung as well as parenchymal degeneration of liver. Histopathological alterations of kidney were only observed in mice exposed to CS early in life. Lung adenomas and malignant tumors of various histopathological nature were detected in neonatally exposed mice but not in adults. Transplacental CS induced the formation of lung adenomas in the offspring 8 months after birth. Previous exposure during pregnancy attenuated CS‐related alveolar epithelial hyperplasia induced after birth. In conclusion, the carcinogenic response to CS varies depending on the developmental stage. The early postnatal life and the prenatal life are particularly at risk for the later development of CS‐related tumors.
Nuclear HER3 is associated with favorable overall survival in uveal melanoma
Authors: Trocmé Eric , Mougiakakos Dimitrios , Johansson C. Christian , All‐Eriksson Charlotta , Economou Mario A. , Larsson Olle , Seregard Stefan , Kiessling Rolf , Lin Yingbo
Published: April 2011

HER3 is a member of the epidermal growth factor receptor (EGFR) family and is expressed in several types of cancer. Both the cytoplasmic and nuclear appearances of the receptor have been reported. Here, we investigate the expression and subcellular distribution of HER3 in uveal melanoma (UM) cells and tissues and its potential impact on clinical outcome of patients. Paraffin‐embedded samples from 128 consecutive UM patients, enucleated without alternative treatment on UM diagnosis, were evaluated for HER3 using immunohistochemistry. Immunoreactivity was scored for frequency, intensity of positive cells, and subcellular distribution. The results were correlated with the established clinicopathological parameters using univariate and multivariate statistical analyses. HER3 expression was shown in 70% of the cases (89/128). This contrasts with the other EGFR family receptors (EGFR, HER2 and HER4) that are infrequently expressed in UM. Surprisingly, HER3 was found to be localized solely in the cell nuclei in 56 cases. The remaining 33 HER3 positive cases showed diffuse distribution (cytoplasmic ± nuclear). Nuclear HER3 was independently correlated with a more favorable overall survival (p = 0.043 and hazard ratio = 0.618) compared to cases with diffuse and/or no HER3. Nuclear localization of HER3 was also confirmed in fresh UM material and in UM cell lines. In conclusion, HER3 is frequently localized solely in the cell nuclei in UM and as such it predicts a more favorable overall survival.
In vivo pH in metabolic‐defective Ras‐transformed fibroblast tumors: Key role of the monocarboxylate transporter, MCT4, for inducing an alkaline intracellular pH
Authors: Chiche Johanna , Fur Yann Le , Vilmen Christophe , Frassineti Frédéric , Daniel Laurent , Halestrap Andrew P. , Cozzone Patrick J. , Pouysségur Jacques , Lutz Norbert W.
Published: April 2011

We present an investigation of tumor pH regulation, designed to support a new anticancer therapy concept that we had previously proposed. Our study uses a tumor model of ras‐transformed hamster fibroblasts, CCL39, xenografted in the thighs of nude mice. We demonstrate, for the first time, that genetic modifications of specific mechanisms of proton production and/or proton transport result in distinct, reproducible changes in intracellular and extracellular tumor pH that can be detected and quantified noninvasively in vivo, simultaneously with determinations of tumor energetic status and necrosis in the same experiment. The CCL39 variants used were deficient in the sodium/proton exchanger, NHE‐1, and/or in the monocarboxylate transporter, MCT4; further, variants were deficient in glycolysis or respiration. MCT4 expression markedly increased the gradient between intracellular and extracellular pH from 0.14 to 0.43 when compared to CCL39 wild‐type tumors not expressing MCT4. The other genetic modifications studied produced smaller but significant increases in intracellular and decreases in extracellular pH. In general, increased pH gradients were paralleled by increased tumor growth performance and diminished necrotic regions, and 50% of the CCL39 variant expressing neither MCT4 nor NHE‐1, but possessing full genetic capacity for glycolysis and oxidative phosphorylation, underwent regression before reaching a 1‐cm diameter. Except for CCL39 wild‐type tumors, no significant HIF‐1α expression was detected. Our in vivo results support a multipronged approach to tumor treatment based on minimizing intracellular pH by targeting several proton production and proton transport processes, among which the very efficient MCT4 proton/lactate co‐transport deserves particular attention.
Indocyanine green enhanced near‐infrared laser treatment of murine mammary carcinoma
Authors: Shafirstein Gal , Bäumler Wolfgang , Hennings Leah J. , Siegel Eric R. , Friedman Ran , Moreno Mauricio A. , Webber Jessica , Jackson Cassie , Griffin Robert J.
Published: April 2011

It is well accepted that near‐infrared (NIR) lasers are appropriate to ablate benign lesions and induce irreversible thermal injury in deeply seated blood vessels. At this wavelength, the laser light penetrates deep (3–5 mm) into the skin. However, many researchers have reported noticeable pain, extending from mild to severe, during and immediately after NIR laser treatment. Intravenous administration of an exogenous chromophore [indocyanine green (ICG), dye] can effectively convert NIR laser light into heat. In this approach, the presence of ICG has shown to enhance thermal injury of blood vessels in the treatment of healthy tissues. However, the effectiveness of thermal injury on the regression of cutaneous carcinomas during ICG/NIR laser therapy has not been assessed. The purpose of our study was to evaluate the potential benefit of using ICG/NIR laser therapy to regress superficial carcinoma with thermal injury. Two groups of A/J mice with subcutaneous mammary adenocarcinoma tumors (7–9 mm) were irradiated with a 808‐nm NIR laser preceded by tail vein injection of ICG dye or sterile saline. Histological evaluation of the subcutaneous tissue revealed minor thermal damage and necrosis in the laser/saline group and substantial damage (up to 100% necrosis) in the laser/ICG group. The laser/ICG‐treated group showed a steady reduction in tumor volume compared to the laser/saline group: 48% by day 5 (p = 0.045) and 69–70% by days 8, 9 and 10 (p values 0.0005 or less). The vascular‐targeted ICG–NIR laser therapy appears to have potential for treating superficial tumors.
CDKI‐71, a novel CDK9 inhibitor, is preferentially cytotoxic to cancer cells compared to flavopiridol
Authors: Liu Xiangrui , Shi Shenhua , Lam Frankie , Pepper Chris , Fischer Peter M. , Wang Shudong
Published: April 2011

Cancer cells appear to depend heavily on antiapoptotic proteins for survival and so targeted inhibition of these proteins has therapeutic potential. One innovative strategy is to inhibit the cyclin‐dependent kinases (CDKs) responsible for the regulation of RNA polymerase II (RNAPII). In our study, we investigated the detailed cellular mechanism of a novel small‐molecule CDK inhibitor (CDKI‐71) in cancer cell lines, primary leukemia cells, normal B ‐ & T‐ cells, and embryonic lung fibroblasts and compared the cellular and molecular responses to the clinical CDK inhibitor, flavopiridol. Like flavopiridol, CDKI‐71 displayed potent cytotoxicity and caspase‐dependent apoptosis induction that were closely associated with the inhibition of RNAPII phosphorylation at serine‐2. This was caused by effective targeting of cyclinT–CDK9 and resulted in the downstream inhibition of Mcl‐1. No correlation between apoptosis and inhibition of cell‐cycle CDKs 1 and 2 was observed. CDKI‐71 showed a 10‐fold increase in potency in tumor cell lines when compared to MRC‐5 human fibroblast cells. Significantly, CDKI‐71 also demonstrated potent anti‐chronic lymphocytic leukemia activity with minimal toxicity in normal B‐ and T‐cells. In contrast, flavopiridol showed little selectivity between cancer and normal cells. Here, we provide the first cell‐based evidence that flavopiridol induces DNA double‐strand breaks: a fact which may explain why flavopiridol has such a narrow therapeutic window in preclinical and clinical settings. Taken together, our data provide a rationale for the development of selective CDK inhibitors as therapeutic agents and CDKI‐71 represents a promising lead in this context.
Experience with high‐risk human papillomavirus testing on vaginal brush‐based self‐samples of non‐attendees of the cervical screening program
Authors: Gök Murat , van Kemenade Folkert J. , Heideman Daniëlle A.M. , Berkhof Johannes , Rozendaal Lawrence , Spruyt Johan W.M. , Beliën Jeroen A.M. , Babovic Milena , Snijders Peter J.F. , Meijer Chris J.L.M.
Published: April 2011

We evaluated the effect of offering brush‐based vaginal self‐sampling for high‐risk human papillomavirus (hrHPV) testing to non‐attendees of the cervical screening program on response rate, compliance to follow‐up and cervical intraepithelial neoplasia grade 2 or 3 (CIN2+/CIN3+) yield. In addition, concordance of hrHPV test results between physician‐taken cervical scrapes and vaginal self‐samples was determined. A total of 26,409 nonattending women were randomly assigned to receive a vaginal brush device for hrHPV testing by Hybrid Capture‐2® method (i.e., self‐sampling group, n = 26,145) or a reinvitation for regular cytology‐based screening (i.e., recall control group, n = 264). hrHPV‐positive self‐sampling responders were invited for a physician‐taken scrape for cytology and blinded hrHPV testing. If cytology was abnormal, women were referred for colposcopy. Response rate in the self‐sampling group was significantly increased compared to the recall control group (30.8% versus 6.5%; p < 0.001). The concordance rate between hrHPV detection in self‐samples and corresponding physician‐taken cervical scrape samples was 68.8%. Amongst women with CIN3+ and CIN2+, the concordance rates in hrHPV positivity between both samples were 95.5% and 93.8%, respectively. Adherence at baseline to cytology triage of hrHPV‐positive self‐sampling women (89.1%) and colposcopy referral of those with abnormal cytology (95.8%) was high. The CIN2+/CIN3+/carcinoma yields were 1.5%, 1.0% and 0.1%, respectively, in self‐sampling responders. In conclusion, offering hrHPV testing on self‐sampled vaginal material with a brush device to non‐attendees significantly increases the attendance to the regular screening program, yields hrHPV test results that are in very good concordance with those of physician‐taken scrapes in women with CIN2+/CIN3+, and is effective in detecting CIN2+/CIN3+.