bluuebunny/crossref_metadata_2025 huggingface dataset:
Sol–Gel Combustion‐Derived CoCuMnOx Spinels as Pigment for Spectrally Selective Paints
Authors: Geng Qing‐Fen , Zhao Xin , Gao Xiang‐Hu , Liu Gang
Published: November 2010

In this work, sol–gel combustion synthesis of spinel CoCuMnOx was reported. X‐ray diffraction (XRD) and Fourier transformation infrared spectroscopy (FTIR) techniques were used to study the reaction processes. The as‐synthesized spinel CoCuMnOx was further characterized by XRD, X‐ray photoelectron spectroscopy, and field‐emission scanning electron microscopy. The CoCuMnOx powders with a deep black hue were then used as solar energy‐absorbing additive to make a novel kind of spectrally selective paint coatings. The solar absorptance (αs) and the thermal emittance (ɛT) of the coatings were determined from the corresponding diffuse reflectance spectra in the 0.3–20 μm range. The optimum selective sample exhibited values of αs=0.928 and ɛ100=0.198. Besides ideal optical properties, the coatings also show excellent long‐term stability, which is confirmed by results of accelerated tests established by IEA‐SHC Task X, indicating that they could be a good alternative to the materials present today in the market.
Melatonin modulates neuroinflammation and oxidative stress in experimental diabetic neuropathy: effects on NF‐κB and Nrf2 cascades
Authors: Negi Geeta , Kumar Ashutosh , Sharma Shyam S.
Published: November 2010

Abstract:  Melatonin exhibits an array of biological activities, including antioxidant and anti‐inflammatory actions. Diabetic neuropathy is one of the complications of diabetes with a prevalence rate of 50–60%. We have previously reported the protective effect of melatonin in experimental diabetic neuropathy. In this study, we investigated the role of nuclear factor‐kappa B (NF‐κB) and nuclear erythroid 2‐related factor 2 (Nrf2) in melatonin‐mediated protection against streptozotocin‐induced diabetic neuropathy. Melatonin at doses of 3 and 10 mg/kg was administered daily in seventh and eighth week after diabetes induction. Motor nerve conduction velocity and nerve blood flow were improved in melatonin‐treated animals. Melatonin also reduced the elevated expression of NF‐κB, IκB‐α, and phosphorylated IκB‐α. Further, melatonin treatment also reduced the elevated levels of proinflammatory cytokines (TNF‐α and IL‐6), iNOS and COX‐2 in sciatic nerves of animals. The capacity of melatonin to modulate Nrf2 pathway was associated with increased heme oxygenase‐1 (HO‐1) expression, which strengthens antioxidant defense. This fact was also established by decreased DNA fragmentation (because inhibition of excessive oxidant‐induced DNA damage) in the sciatic nerve of melatonin‐treated animals. The results of this study suggest that melatonin modulates neuroinflammation by decreasing NF‐κB activation cascade and oxidative stress by increasing Nrf2 expression, which might be responsible at least in part, for its neuroprotective effect in diabetic neuropathy.
Statistical-noise effect on autocorrelation function of line-edge and line-width roughness
Authors: Hiraiwa Atsushi , Nishida Akio
Published: November 2010

Accurate characterization of line-edge roughness (LER) and line-width roughness (LWR) is essential to cope with the growing challenge of device variability in large-scale integrations. The accuracy is affected markedly by statistical noise, which is caused by the finiteness of a number of samples. The statistical noise produces random oscillatory fluctuations of autocorrelation function (ACF) of LER/LWR. These fluctuations are obstacles to estimating LWR statistics by comparing experimental and theoretical ACFs. Using the Monte Carlo (MC) method to prepare pseudoexperimental ACFs (MC-ACFs), the authors found that an error η of the estimates is minimized in the case when a ratio of a fitting-window size to a correlation length is 0.3 or smaller, being less affected by the statistical noise. η under a fixed sampling interval is determined by the total number Nall of width data used to obtain the MC-ACF. This comes from the fact that the MC-ACF is obtained after averaging approximately for Nall times. The authors also investigated the case when LWR consisted of two components that had different correlation lengths. They confirmed that η of both components increase with a decrease in their occupancies in the entire LWR. This, together with a large correlation length, makes it difficult to accurately characterize the longer-correlation component, which is mostly minor (small occupancy) in actual cases. This difficulty is also an obstacle to estimating the shorter-correlation component, because the statistics of the former are mostly the prerequisites for analyzing the latter. These facts make a stark contrast to a power-spectral-density (PSD) fitting method, where at least the shorter-correlation component is estimated with almost the same accuracy as in the case of a single component. Based on these results, the authors propose to investigate PSDs, rather than ACFs, in the case of multicomponent LWR.
Mammalian Endothermy Optimally Restricts Fungi and Metabolic Costs
Authors: Bergman Aviv , Casadevall Arturo
Published: November 2010

Endothermy and homeothermy are mammalian characteristics whose evolutionary origins are poorly understood. Given that fungal species rapidly lose their capacity for growth above ambient temperatures, we have proposed that mammalian endothermy enhances fitness by creating exclusionary thermal zones that protect against fungal disease. According to this view, the relative paucity of invasive fungal diseases in immunologically intact mammals relative to other infectious diseases would reflect an inability of most fungal species to establish themselves in a mammalian host. In this study, that hypothesis was tested by modeling the fitness increase with temperature versus its metabolic costs. We analyzed the tradeoff involved between the costs of the excess metabolic rates required to maintain a body temperature and the benefit gained by creating a thermal exclusion zone that protects against environmental microbes such as fungi. The result yields an optimum at 36.7°C, which closely approximates mammalian body temperatures. This calculation is consistent with and supportive of the notion that an intrinsic thermally based resistance against fungal diseases could have contributed to the success of mammals in the Tertiary relative to that of other vertebrates.

IMPORTANCE
Mammals are characterized by both maintaining and closely regulating high body temperatures, processes that are known as endothermy and homeothermy, respectively. The mammalian lifestyle is energy intensive and costly. The evolutionary mechanisms responsible for the emergence and success of these mammalian characteristics are not understood. This work suggests that high mammalian temperatures represent optima in the tradeoff between metabolic costs and the increased fitness that comes with resistance to fungal diseases.
BORDER-COLLISION BIFURCATIONS IN 1D PIECEWISE-LINEAR MAPS AND LEONOV'S APPROACH
Authors: GARDINI LAURA , TRAMONTANA FABIO , AVRUTIN VIKTOR , SCHANZ MICHAEL
Published: November 2010

50 years ago (1959) in a series of publications by Leonov, a detailed analytical study of the nested period adding bifurcation structure occurring in piecewise-linear discontinuous 1D maps was presented. The results obtained by Leonov are barely known, although they allow the analytical calculation of border-collision bifurcation subspaces in an elegant and much more efficient way than it is usually done. In this work we recall Leonov's approach and explain why it works. Furthermore, we slightly improve the approach by avoiding an unnecessary coordinate transformation, and also demonstrate that the approach can be used not only for the calculation of border-collision bifurcation curves.
PREPARATION AND CHARACTERISTICS OF FUNCTIONALIZED MULTIWALLED CARBON NANOTUBES IN POLYIMIDE MIXED MATRIX MEMBRANE
Authors: SANIP S. M. , ISMAIL A. F. , GOH P. S. , NG B. C. , ABDULLAH M. S. , SOGA T. , TANEMURA M. , YASUHIKO H.
Published: November 2010

The functionalization of multiwalled carbon nanotubes (MWNTs) with β cyclodextrin (β-CD) is described. The functionalization using β-CD treatment is an environmentally friendly and nondestructive method to modify carbon nanotubes. It was observed that the degree of functionalization increases with increasing ratios of β-CD as seen from the Raman analysis. The Raman spectra also indicated that the nanotubes walls were not damaged. The presence of functional groups associated with β-CD on the functionalized MWNTs indicated that the cyclodextrin groups were found to be adsorbed at the surface of the nanotubes walls. Mixed matrix membrane (MMM) was prepared by a phase inversion process. Enhanced selectivity and permeability for CO2over CH4was observed for MMM prepared using functionalized MWNTs.
PREPARATION AND CHARACTERIZATION OF ELECTRIC ZAO NANOPARTICLES
Authors: SHI HAO-WEI , XIE HONG-ZHEN , LIU JIN-KU , WANG YAN
Published: November 2010

The white good dispersion zinc aluminium oxide (ZAO) nanoparticles were efficiently prepared by solid phase synthesis method. The morphologies, structures, photoelectricity of the ZAO nanoparticles and the thermochemistry behavior of the precursor were analyzed by TEM, XRD, UV-vis and TG, etc. The phytotoxicity properties of the ZAO nanoparticles were researched for the first time. The results show that the ZAO nanoparticles have a strong inhibition of seed germination and root growth. The biological toxicity of ZAO nanoparticle reduces along with the enlargement of nanoparticle size.
SYNTHESIS AND PHOTOLUMINESCENCE PROPERTIES OF ZnSe-CORE/SnO2-SHELL NANORODS
Authors: JIN CHANGHYUN , KIM HYUNSOO , BAEK KYUNGJOON , LEE CHONGMU
Published: November 2010

ZnSe -core/ SnO2 -shell nanorods have been prepared by using a two-step process comprising the thermal evaporation of ZnSe powders and the atomic layer deposition of SnO2 . ZnSe nanorods have been grown by the thermal evaporation of ZnSe powders on gold-coated Al2O3 (0001) substrates. The ZnSe -core/ SnO2 -shell nanorods were 0.1–0.2 μm in diameter and up to a few tens of micrometers in length. Transmission electron microscopy and X-ray diffraction analysis results indicate that the cores and shells are single crystal zinc blende-type ZnSe and polycrystalline simple orthorhombic-type SnO2 , respectively. Photoluminescence measurements show that the ZnSe -core/ SnO2 -shell nanorods have a strong orange emission band centered at around 650 nm. The orange emission of the ZnSe nanorods is enhanced in intensity by coating them with SnO2 and further enhanced by annealing them. A reducing atmosphere is more efficient in enhancing the orange emission than an oxidative atmosphere. The highest emission intensity is obtained for the shell layer thickness corresponding to 1500 ALD cycles. The orange emission enhancement by annealing is mainly attributed to the formation of Sn interstitials in the ZnSe cores during the annealing process.
The characteristics of rare earth elements in bulk precipitation, throughfall, foliage and lichens in the Lesní potok catchment and its vicinity, Czech Republic
Authors: Špičková Jitka , Navrátil Tomáš , Rohovec Jan , Mihaljevič Martin , Kubínová Petra , Minařík Luděk , Skřivan Petr
Published: November 2010

A comparison of rare earth elements' (REE) atmospheric signatures in various ecosystem compartments was carried out in the vicinity of the Lesní potok catchment (LP), Czech Republic. REE signatures were investigated from 2004 to 2006 in rainwater, throughfall, tree foliage (
Picea abies
,
Fagus sylvatica
) and lichens (
Hypogymnia physodes
) for selected elements (Al, Ca, Fe, K, Mg, Mn, Na, P, S, Si). REE concentrations increased in the following sequences: bulk precipitation < beech throughfall < spruce throughfall and spruce needles < beech leaves ≪ lichens.

The crustal origin of REEs in bulk precipitation was confirmed by its high correlation with lithogenic elements, by the seasonal variation in REE concentrations and by comparison of REE distribution patterns of the upper continental crust, local granites and soil. Enrichment factors calculated in relation to bulk precipitation and normalized to Na enabled elimination of the influence of dry deposition and wash-out. Higher REE concentrations in throughfall were then identified to be the result of the wash-out of dry deposition, while REEs were found to bioaccumulate in vegetation, although at a much smaller rate than the essential elements K, Mn, P, Mg and Ca.

Supplementary material:
various REE and major ions concentrations are available at http://www.geolsoc.org.uk/SUP18437.
Role of the adipocyte-specific NF-κB activity in the regulation of IP-10 and T cell migration
Authors: Krinninger Patricia , Brunner Cornelia , Ruiz Pedro A. , Schneider Elisabeth , Marx Nikolaus , Foryst-Ludwig Anna , Kintscher Ulrich , Haller Dirk , Laumen Helmut , Hauner Hans
Published: November 2010

Infiltration of immune cells into adipose tissue plays a central role in the pathophysiology of obesity-associated low-grade inflammation. The aim of this study was to analyze the role of adipocyte NF-κB signaling in the regulation of the chemokine/adipokine interferon-γ-induced protein 10 kDa (IP-10) and adipocyte-mediated T cell migration. Therefore, the regulation of IP-10 was investigated in adipose tissue of male C57BL/6J mice, primary human and 3T3-L1 preadipocytes/adipocytes. To specifically block the NF-κB pathway, 3T3-L1 cells stably overexpressing a transdominant mutant of IκBα were generated, and the chemical NF-κB inhibitor Bay117082 was used. Adipocyte-mediated T cell migration was assessed by a migration assay. It could be shown that IP-10 expression was higher in mature adipocytes compared with preadipocytes. Induced IP-10 expression and secretion were completely blocked by an NF-κB inhibitor in 3T3-L1 and primary human adipocytes. Stable overexpression of a transdominant mutant of IκBα in 3T3-L1 adipocytes led to an inhibition of basal and stimulated IP-10 expression and secretion. T cell migration was induced by 3T3-L1 adipocyte-conditioned medium, and both basal and induced T cell migration was strongly inhibited by stable overexpression of a transdominant IκBα mutant. In addition, with the use of an anti-IP-10 antibody, a significant decrease of adipocyte-induced T cell migration was shown. In conclusion, in this study, we could demonstrate that the NF-κB pathway is essential for the regulation of IP-10 in 3T3-L1 and primary human adipocytes. Adipocytes rather than preadipocytes contribute to NF-κB-dependent IP-10 expression and secretion. Furthermore, NF-κB-dependent factors and especially IP-10 represent novel signals from adipocytes to induce T cell migration.
Regulation of adiponectin production by insulin: interactions with tumor necrosis factor-α and interleukin-6
Authors: Hajri Tahar , Tao Huan , Wattacheril Julia , Marks-Shulman Pamela , Abumrad Naji N.
Published: November 2010

Obesity is often associated with insulin resistance, low-grade systemic inflammation, and reduced plasma adiponectin. Inflammation is also increased in adipose tissue, but it is not clear whether the reductions of adiponectin levels are related to dysregulation of insulin activity and/or increased proinflammatory mediators. In this study, we investigated the interactions of insulin, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in the regulation of adiponectin production using in vivo and in vitro approaches. Plasma adiponectin and parameters of insulin resistance and inflammation were assessed in a cohort of lean and obese insulin-resistant subjects. In addition, the effect of insulin was examined in vivo using the hyperinsulinemic-euglycemic clamp, and in adipose tissue (AT) cultures. Compared with lean subjects, the levels of total adiponectin, and especially the high-molecular-weight (HMW) isomer, were abnormally low in obese insulin-resistant subjects. The hyperinsulinemic clamp data confirmed the insulin-resistant state in the obese patients and showed that insulin infusion significantly increased the plasma adiponectin in lean but not obese subjects ( P < 0.01). Similarly, insulin increased total adiponectin release from AT explants of lean and not obese subjects. Moreover, expression and secretion of TNF-α and IL-6 increased significantly in AT of obese subjects and were negatively associated with expression and secretion of adiponectin. In 3T3-L1 and human adipocyte cultures, insulin strongly enhanced adiponectin expression (2-fold) and secretion (3-fold). TNF-α, and not IL-6, strongly opposed the stimulatory effects of insulin. Intriguingly, the inhibitory effect of TNF-α was especially directed toward the HMW isomer of adiponectin. In conclusion, these studies show that insulin upregulates adiponectin expression and release, and that TNF-α opposes the stimulatory effects of insulin. A combination of insulin resistance and increased TNF-α production could explain the decline of adiponectin levels and alterations of isomer composition in plasma of obese insulin-resistant subjects.
Transaldolase exchange and its effects on measurements of gluconeogenesis in humans
Authors: Basu Rita , Barosa Cristina , Basu Ananda , Pattan Vishwanath , Saad Ahmed , Jones John , Rizza Robert
Published: November 2010

The deuterated water method is used extensively to measure gluconeogenesis in humans. This method assumes negligible exchange of the lower three carbons of fructose 6-phsophate via transaldolase exchange since this exchange will result in enrichment of carbon 5 of glucose in the absence of net gluconeogenesis. The present studies tested this assumption.2H2O and acetaminophen were ingested and [1-13C]acetate infused in 11 nondiabetic subjects after a 16-h fast. Plasma and urinary glucuronide enrichments were measured using nuclear magnetic resonance spectroscopy before and during a 0.35 mU·kg FFM−1·min−1insulin infusion. Rates of endogenous glucose production measured with [3-3H]- and [6,6-2H2]glucose did not differ either before (14.0 ± 0.7 vs. 13.8 ± 0.7 μmol·kg−1·min−1) or during the clamp (10.4 ± 0.9 vs. 10.9 ± 0.7 μmol·kg−1·min−1), consistent with equilibration and quantitative removal of tritium during triose isomerase exchange. Plasma [3-13C] glucose-to-[4-13C]glucose and urinary [3-13C] glucuronide-to-[4-13C]glucuronide ratios were <1.0 ( P < 0.001) in all subjects both before (0.66 ± 0.04 and 0.60 ± 0.04) and during (059 ± 0.05 and 0.56 ± 0.06) the insulin infusion, respectively, indicating that ∼35–45% of the labeling of the 5th carbon of glucose by deuterium was due to transaldolase exchange rather than gluconeogenesis. When corrected for transaldolase exchange, rates of gluconeogenesis were lower ( P < 0.001) and glycogenolysis higher ( P < 0.001) than uncorrected rates both before and during the insulin infusion. In conclusion, assuming negligible dilution by glycerol and near-complete triose isomerase equilibration, these data provide strong experimental evidence that transaldolase exchange occurs in humans, resulting in an overestimate of gluconeogenesis and an underestimate of glycogenolysis when measured with the2H2O method. Use of appropriate13C tracers provides a means of correcting for transaldolase exchange.
Glucose homeostasis in rainbow trout fed a high-carbohydrate diet: metformin and insulin interact in a tissue-dependent manner
Authors: Polakof S. , Moon T. W. , Aguirre P. , Skiba-Cassy S. , Panserat S.
Published: November 2010

Carnivorous fish species such as the rainbow trout ( Oncorhynchus mykiss ) are considered to be “glucose intolerant” because of the prolonged hyperglycemia experienced after intake of a carbohydrate-enriched meal. In the present study, we use this species to study glucose homeostasis in fish chronically infused with the hypoglycemic agents, insulin, and metformin, and fed with a high proportion of carbohydrates (30%). We analyzed liver, skeletal muscle, and white adipose tissue (WAT), which are insulin- and metformin-specific targets at both the biochemical and molecular levels. Trout infused with the combination of insulin and metformin can effectively utilize dietary glucose at the liver, resulting in lowered glycemia, increased insulin sensitivity, and glucose storage capacity, combined with reduced glucose output. However, in both WAT and skeletal muscle, we observed decreased insulin sensitivity with the combined insulin + metformin treatment, resulting in the absence of changes at the metabolic level in the skeletal muscle and an increased potential for glucose uptake and storage in the WAT. Thus, the poor utilization by rainbow trout of a diet with a high proportion of carbohydrate can at least be partially improved by a combined treatment with insulin and metformin, and the glucose intolerance observed in this species could be, in part, due to some of the downstream components of the insulin and metformin signaling pathways. However, the predominant effects of metformin treatment on the action of insulin in these three tissues thought to be involved in glucose homeostasis remain exclusive in this species.
Enhancement of renin and prorenin receptor in collecting duct of Cyp1a1-Ren2 rats may contribute to development and progression of malignant hypertension
Authors: Prieto Minolfa C. , Williams Dustyn E. , Liu Liu , Kavanagh Kimberly L. , Mullins John J. , Mitchell Kenneth D.
Published: November 2010

To determine whether in the transgenic rat model [TGR(Cyp1a1Ren2)] with inducible ANG II-dependent malignant hypertension changes in the activation of intrarenal renin-angiotensin system may contribute to the pathogenesis of hypertension, we examined the gene expression of angiotensinogen (AGT) in renal cortical tissues and renin and prorenin receptor [(P)RR] in the collecting duct (CD) of the kidneys from Cyp1a1Ren2 rats ( n = 6) fed a normal diet containing 0.3% indole-3-carbinol (I3C) for 10 days and noninduced rats maintained on a normal diet (0.6% NaCl diet; n = 6). Rats induced with I3C developed malignant hypertension and exhibited alterations in the expression of renin and (P)RR expressed by the CD cells. In the renal medullary tissues of the Cyp1a1Ren2 transgenic rats with malignant hypertension, renin protein levels in CD cells were associated with maintained renin content and lack of suppression of the endogenous Ren1c gene expression. Furthermore, these tissues exhibited increased levels of (P)RR transcript, as well as of the protein levels of the soluble form of this receptor, the s(P)RR. Intriguingly, although previous findings demonstrated that urinary AGT excretion is augmented in Cyp1a1Ren2 transgenic rats with malignant hypertension, in the present study we did not find changes in the gene expression of AGT in renal cortical tissues of these rats. The data suggest that upregulation of renin and the s(P)RR in the CD, especially in the renal medullary tissues of Cyp1a1Ren2 transgenic rats with malignant hypertension, along with the previously demonstrated increased availability of AGT in the urine of these rats, may constitute a leading mechanism to explain elevated formation of kidney ANG II levels in this model of ANG II-dependent hypertension.
Sequential Activation of Motor Cortical Neurons Contributes to Intralimb Coordination During Reaching in the Cat by Modulating Muscle Synergies
Authors: Yakovenko Sergiy , Krouchev Nedialko , Drew Trevor
Published: November 2010

We examined the contribution of the motor cortex to the control of intralimb coordination during reaching in the standing cat. We recorded the activity of 151 pyramidal tract neurons (PTNs) in the forelimb representation of three cats during a task in which the cat reached forward from a standing position to press a lever. We simultaneously recorded the activity of muscles in the contralateral forelimb acting around each of the major joints. Cell activity was recorded with and without the presence of an obstacle requiring a modification of limb trajectory. The majority of the PTNs (134/151, 89%) modulated their discharge activity at some period of the reach while 84/151 (56%) exhibited a significant peak or trough of activity as the limb was transported from its initial position to the lever. These phasic changes of activity were distributed sequentially throughout the transport phase. A cluster analysis of muscle activity in two of the cats showed the presence of five muscle synergies during this transport period. One of the synergies was related to the lift of the paw from the support surface, two to flexion of the limb and dorsiflexion of the paw, one to preparation for contact with the lever, and one to the transport of the entire limb forward; a sixth synergy was activated during the lever press. An analysis of the phase of cell activity with respect to the phase of activity of muscles selected to represent each of these synergies showed that different populations of PTNs were activated sequentially and coincidentally with each synergy. We suggest that this sequential activation of populations of PTNs is compatible with a contribution to the initiation and modulation of functionally distinct groups of synergistic muscles and ultimately serves to ensure the appropriate multiarticular, intralimb coordination of the limb during reaching.
Hepatocyte Nuclear Factor-4α Promotes Gut Neoplasia in Mice and Protects against the Production of Reactive Oxygen Species
Authors: Darsigny Mathieu , Babeu Jean-Philippe , Seidman Ernest G. , Gendron Fernand-Pierre , Levy Emile , Carrier Julie , Perreault Nathalie , Boudreau François
Published: November 2010

Hepatocyte nuclear factor-4α (Hnf4α) is a transcription factor that controls epithelial cell polarity and morphogenesis. Hnf4α conditional deletion during postnatal development has minor effects on intestinal epithelium integrity but promotes activation of the Wnt/β-catenin pathway without causing tumorigenesis. Here, we show that Hnf4α does not act as a tumor-suppressor gene but is crucial in promoting gut tumorigenesis in mice. Polyp multiplicity in ApcMin mice lacking Hnf4α is suppressed compared with littermate ApcMin controls. Analysis of microarray gene expression profiles from mice lacking Hnf4α in the intestinal epithelium identifies novel functions of this transcription factor in targeting oxidoreductase-related genes involved in the regulation of reactive oxygen species (ROS) levels. This role is supported with the demonstration that HNF4α is functionally involved in the protection against spontaneous and 5-fluorouracil chemotherapy-induced production of ROS in colorectal cancer cell lines. Analysis of a colorectal cancer patient cohort establishes that HNF4α is significantly upregulated compared with adjacent normal epithelial resections. Several genes involved in ROS neutralization are also induced in correlation with HNF4A expression. Altogether, the findings point to the nuclear receptor HNF4α as a potential therapeutic target to eradicate aberrant epithelial cell resistance to ROS production during intestinal tumorigenesis. Cancer Res; 70(22); 9423–33. ©2010 AACR.
Mammalian Target of Rapamycin–Dependent Acinar Cell Neoplasia after Inactivation of Apc and Pten in the Mouse Salivary Gland: Implications for Human Acinic Cell Carcinoma
Authors: Diegel Cassandra R. , Cho Kathleen R. , El-Naggar Adel K. , Williams Bart O. , Lindvall Charlotta
Published: November 2010

Cross-talk between the canonical Wnt and mammalian target of rapamycin (mTOR) signaling pathways occurs at multiple levels in the cell and likely contributes to the oncogenic effects of these pathways in human cancer. To gain more insight into the interplay between Wnt and mTOR signaling in salivary gland tumorigenesis, we developed a mouse model in which both pathways are constitutively activated by the conditional inactivation of the Apc and Pten tumor suppressor genes. Loss of either Apc or Pten alone did not cause tumor development. However, deletion of both genes resulted in the formation of salivary gland tumors with 100% penetrance and short latency that showed a remarkable morphologic similarity to human acinic cell carcinoma. Treatment of tumor-bearing mice using the mTOR inhibitor rapamycin led to complete regression of tumors, indicating that tumor growth was dependent on continued mTOR signaling. Importantly, we found that human salivary gland acinic cell carcinomas also express markers of activated mTOR signaling. Together, these results suggest that aberrant activation of mTOR signaling plays a pivotal role in acinar cell neoplasia of the salivary gland. Because rapamycin analogues are approved for treating other types of human malignancies, our findings suggest that rapamycin therapy should be evaluated for treating patients with salivary gland acinic cell carcinoma. Cancer Res; 70(22); 9143–52. ©2010 AACR.
High-Throughput Characterization of 10 New Minor Histocompatibility Antigens by Whole Genome Association Scanning
Authors: Van Bergen Cornelis A.M. , Rutten Caroline E. , Van Der Meijden Edith D. , Van Luxemburg-Heijs Simone A.P. , Lurvink Ellie G.A. , Houwing-Duistermaat Jeanine J. , Kester Michel G.D. , Mulder Arend , Willemze Roel , Falkenburg J.H. Frederik , Griffioen Marieke
Published: November 2010

Patients with malignant diseases can be effectively treated with allogeneic hematopoietic stem cell transplantation (allo-SCT). Polymorphic peptides presented in HLA molecules, the so-called minor histocompatibility antigens (MiHA), play a crucial role in antitumor immunity as targets for alloreactive donor T cells. Identification of multiple MiHAs is essential to understand and manipulate the development of clinical responses after allo-SCT. In this study, CD8+ T-cell clones were isolated from leukemia patients who entered complete remission after allo-SCT, and MiHA-specific T-cell clones were efficiently selected for analysis of recognition of a panel of EBV-transformed B cells positive for the HLA restriction elements of the selected T-cell clones. One million single nucleotide polymorphisms (SNP) were determined in the panel cell lines and investigated for matching with the T-cell recognition data by whole genome association scanning (WGAs). Significant association with 12 genomic regions was found, and detailed analysis of genes located within these genomic regions revealed SNP disparities encoding polymorphic peptides in 10 cases. Differential recognition of patient-type, but not donor-type, peptides validated the identification of these MiHAs. Using tetramers, distinct populations of MiHA-specific CD8+ T cells were detected, demonstrating that our WGAs strategy allows high-throughput discovery of relevant targets in antitumor immunity after allo-SCT. Cancer Res; 70(22); 9073–83. ©2010 AACR.
A Sense of Urgency: Evaluating the Link between Clinical Trial Development Time and the Accrual Performance of Cancer Therapy Evaluation Program (NCI-CTEP) Sponsored Studies
Authors: Cheng Steven K. , Dietrich Mary S. , Dilts David M.
Published: November 2010

Purpose: Postactivation barriers to oncology clinical trial accruals are well documented; however, potential barriers prior to trial opening are not. We investigate one such barrier: trial development time.

Experimental Design: National Cancer Institute Cancer Therapy Evaluation Program (CTEP)–sponsored trials for all therapeutic, nonpediatric phase I, I/II, II, and III studies activated between 2000 and 2004 were investigated for an 8-year period (n = 419). Successful trials were those achieving 100% of minimum accrual goal. Time to open a study was the calendar time from initial CTEP submission to trial activation. Multivariate logistic regression analysis was used to calculate unadjusted and adjusted odds ratios (OR), controlling for study phase and size of expected accruals.

Results: Among the CTEP-approved oncology trials, 37.9% (n = 221) failed to attain the minimum accrual goals, with 70.8% (n = 14) of phase III trials resulting in poor accrual. A total of 16,474 patients (42.5% of accruals) accrued to those studies were unable to achieve the projected minimum accrual goal. Trials requiring less than 12 months of development were significantly more likely to achieve accrual goals (OR, 2.15; 95% confidence interval, 1.29-3.57, P = 0.003) than trials with the median development times of 12 to 18 months. Trials requiring a development time of greater than 24 months were significantly less likely to achieve accrual goals (OR, 0.40; 95% confidence interval, 0.20-0.78; P = 0.011) than trials with the median development time.

Conclusions: A large percentage of oncology clinical trials do not achieve minimum projected accruals. Trial development time appears to be one important predictor of the likelihood of successfully achieving the minimum accrual goals. Clin Cancer Res; 16(22); 5557–63. ©2010 AACR.
Atu027 Prevents Pulmonary Metastasis in Experimental and Spontaneous Mouse Metastasis Models
Authors: Santel Ansgar , Aleku Manuela , Röder Nadine , Möpert Kristin , Durieux Birgit , Janke Oliver , Keil Oliver , Endruschat Jens , Dames Sibylle , Lange Christian , Eisermann Mona , Löffler Kathrin , Fechtner Melanie , Fisch Gerald , Vank Christiane , Schaeper Ute , Giese Klaus , Kaufmann Jörg
Published: November 2010

Purpose: Atu027, a novel RNA interference therapeutic, has been shown to inhibit lymph node metastasis in orthotopic prostate cancer mouse models. The aim of this study is to elucidate the pharmacologic activity of Atu027 in inhibiting hematogenous metastasis to the target organ lung in four different preclinical mouse models.

Experimental Design: Atu027 compared with vehicle or control small interfering RNA lipoplexes was tested in two experimental lung metastasis models (Lewis lung carcinoma, B16V) and spontaneous metastasis mouse models (MDA-MB-435, MDA-MB-231, mammary fat pad). Different dosing schedules (repeated low volume tail vein injections) were applied to obtain insight into effective Atu027 treatment. Primary tumor growth and lung metastasis were measured, and tissues were analyzed by immunohistochemistry and histology. In vitro studies in human umbilical vein endothelial cells were carried out to provide an insight into molecular changes on depletion of PKN3, in support of efficacy results.

Results: Intravenous administration of Atu027 prevents pulmonary metastasis. In particular, formation of spontaneous lung metastasis was significantly inhibited in animals with large tumor grafts as well as in mice with resected primary mammary fat pad tumors. In addition, we provide evidence that an increase in VE-cadherin protein levels as a downstream result of PKN3 target gene inhibition may change endothelial function, resulting in reduced colonization and micrometastasis formation.

Conclusion: Atu027 can be considered as a potent drug for preventing lung metastasis formation, which might be suitable for preventing hematogenous metastasis in addition to standard cancer therapy. Clin Cancer Res; 16(22); 5469–80. ©2010 AACR.
Adamantyl-Substituted Retinoid-Related Molecules Induce Apoptosis in Human Acute Myelogenous Leukemia Cells
Authors: Farhana Lulu , Dawson Marcia I. , Xia Zebin , Aboukameel Amro , Xu Liping , Liu Gang , Das Jayanta K. , Hatfield James , Levi Edi , Mohammad Ramzi , Fontana Joseph A.
Published: November 2010

The adamantyl-substituted retinoid-related (ARR) compounds 3-Cl-AHPC and AHP3 induce apoptosis in vitro and in vivo in a newly established human acute myelogenous leukemia (AML) cell line, FFMA-AML, and in the established TF(v-SRC) AML cell line. FFMA-AML and TF(v-SRC) cells displayed resistance to apoptosis mediated by the standard retinoids (including trans-retinoic acid, 9-cis-retinoic acid, and the synthetic retinoid TTNPB) but showed sensitivity to apoptosis mediated by 3-Cl-AHPC– and AHP3 in vitro and in vivo as documented by poly(ADP-ribose) polymerase (PARP) cleavage and apoptosis terminal deoxyribonucleotidyl transferase–mediated dUTP nick end labeling assay. 3-Cl-AHPC or AHP3 exposure in vitro resulted in decreased expression of the antiapoptotic proteins (cellular inhibitor of apoptosis 1, X-linked inhibitor of apoptosis protein) and phospho-Bad and activated the NF-κB canonical pathway. A significant prolongation of survival was observed both in nonobese diabetic severe combined immunodeficient mice carrying FFMA-AML cells and treated with either 3-Cl-AHPC or AHP3 and in severe combined immunodeficient mice carrying TF(v-SRC) cells and treated with AHP3. We have previously shown that ARRs bind to the orphan nuclear receptor small heterodimer partner (SHP) and that the expression of SHP is required for ARR-mediated apoptosis. Induced loss of SHP in these AML cells blocked 3-Cl-AHPC– and AHP3-mediated induction of apoptosis. These results support the further development of 3-Cl-AHPC and AHP3 as potential therapeutic agents in the treatment of AML patients. Mol Cancer Ther; 9(11); 2903–13. ©2010 AACR.
Treatment Efficacy/Safety and Prognostic Factors in Patients with Advanced Biliary Tract Cancer Receiving Gemcitabine Monotherapy: An Analysis of 100 Cases
Authors: Suzuki Eiichiro , Furuse Junji , Ikeda Masafumi , Okusaka Takuji , Nakachi Kohei , Mitsunaga Shuichi , Ueno Hideki , Morizane Chigusa , Kondo Shunsuke , Shimizu Satoshi , Kojima Yasushi , Hagihara Atsushi
Published: November 2010

Aim: The purpose of this study was to elucidate the treatment efficacy and safety of gemcitabine monotherapy, and to identify prognostic factors in patients with advanced biliary tract cancer receiving this therapy. Method: The data of 100 patients with advanced biliary tract cancer who were treated with gemcitabine as first-line chemotherapy were reviewed retrospectively. Results: One patient showed complete response (1.0%) and 6 patients showed partial response (6.0%), yielding an overall response rate of 7.0%. The main grade 3/4 toxicities were neutropenia and leukopenia. The median survival, 1-year survival rate and progression-free survival were 7.3 months, 21.6% and 3.1 months, respectively. Multivariate analysis identified a performance status of 0–1, serum C-reactive protein level of <3.0 mg/dl, serum carcinoembryonic antigen level of <10 ng/ml and serum albumin level of ≧3.5 g/dl as factors independently associated with a favorable prognosis. Conclusions: Gemcitabine monotherapy showed modest efficacy with manageable toxicity in patients with biliary tract cancer. These results could be useful as reference data for optimizing treatment strategies and planning future clinical trials in patients with advanced biliary tract cancer.
Bile Changes after Liver Surgery: Experimental and Clinical Lessons for Future Applications
Authors: Gravante Gianpiero , Knowles Timothy , Ong Seok Ling , Al-Taan Omer , Metcalfe Matthew , Dennison Ashley R. , Lloyd David M.
Published: November 2010

Introduction: The aim of this review is to summarize the available evidence for changes in bile composition following liver surgery and assess their use in predicting post-operative complications. Materials and Methods: A literature search was undertaken for all studies focusing on bile composition, bile volume and analysis. Articles were selected from MEDLINE, Embase and the Cochrane Central Register of Controlled Trials databases up to May 2009. Results: Low values of pre-operative bilirubin diglucuronide predict reduced post-operative liver function and the occurrence of jaundice. Low concentrations of hepatocyte growth factor and interleukin-6 in bile following surgery are associated with the subsequent development of liver failure and are probably surrogate markers for situations where the resultant hepatic regeneration is inadequate. Conclusions: Analysis of the composition and quality of bile is probably underused as a tool for the pre-operative screening and early post-operative monitoring of patients at high risk of developing liver failure following major hepatobiliary procedures.
Predictors of Timing and Patterns of Recurrence after Curative Resection for Gastric Cancer
Authors: Eom Bang Wool , Yoon Hongman , Ryu Keun Won , Lee Jun Ho , Cho Soo Jeong , Lee Jong Yeul , Kim Chan Gyoo , Choi Il Ju , Lee Jong Seok , Kook Myung Cherl , Park Sook Ryun , Nam Byung-Ho , Kim Young-Woo
Published: November 2010

Aims: The aim of the study was to characterize recurrence patterns and identify predictors of recurrence after curative resection. Methods: Of 2,786 patients that underwent curative resection for gastric cancer from 2001 to 2006 at the Korean National Cancer Center, 439 (15.8%) experienced recurrence. Patterns of recurrence, clinicopathological characteristics, and therapeutic modalities were compared between 251 patients who had recurrence within 1 year (the early recurrence group) and 188 patients who had recurrence after more than a year (the late recurrence group). Multivariate analysis was performed to identify independent factors associated with the timing of recurrence. Results: In the early recurrence group, the most common pattern was hematogenous metastasis, and in the late recurrence group, the most common pattern was locoregional and peritoneal recurrence. The early recurrence group was characterized by a larger tumor, frequent lymph node (LN) metastasis, and venous, and perineural invasion. Multivariate analysis showed that LN metastasis and venous invasion were independent predictors of early recurrence. Median survival after recurrence was significantly shorter in the early recurrence group (p < 0.001). Conclusion: Hematogeneous metastasis was more common in the early recurrence group and LN metastasis and venous invasion were independent predictors of the timing of recurrence.
Liver X Receptor Agonist Methyl-3β-Hydroxy-5α,6α-Epoxycholanate Attenuates Atherosclerosis in Apolipoprotein E Knockout Mice without Increasing Plasma Triglyceride
Authors: Yan Wei , Zhang Tongxin , Cheng Jun , Zhou Xiangdong , Qu Xiaolong , Hu Houyuan
Published: November 2010

Background: Liver X receptors (LXRs) promote macrophage reverse cholesterol transport and cholesterol excretion from the body. The synthetic LXR ligands T0901317 and GW3965 were shown to significantly inhibit atherosclerosis in mice and to increase the expression of ATP-binding cassette transporter A1 (ABCA1) in the atherosclerotic lesions. However, these compounds increase plasma and hepatic triglyceride (TG) levels in mice. Methyl-3β-hydroxy-5α,6α-epoxycholanate (MHEC), synthesized from hyodeoxycholic acid, functions as an LXR agonist, but its role in atherogenesis and lipid metabolism remained to be elucidated. Methods: THP-1-derived macrophages were cultured in the medium con- taining various concentrations of MHEC or T0901317 (0–10 µmol/l) for 24 h. Reverse transcription polymerase chain reaction was used to quantify LXRα, LXRβ and ABCA1 mRNA levels in macrophages. Additionally, MHEC or T0901317 was orally administered at 10 mg/kg daily for 6 weeks in apolipoprotein E knockout (apoE–/–) mice fed a high-cholesterol diet. Plasma lipids were determined enzymatically. The area of and ABCA1 expression in the aortic atherosclerotic lesions were measured by oil red O staining and immunohistochemistry, respectively. Results: Both MHEC and T0901317 equally stimulated LXRα and ABCA1 mRNA expression in a dose-dependent manner in THP-1-derived macrophages, but they did not induce LXRβ mRNA expression significantly. The plasma levels of total cholesterol, TG and high-density lipoprotein cholesterol were significantly higher in T0901317-treated mice than in the vehicle-treated control group. Interestingly, MHEC treatment dramatically increased plasma high-density lipoprotein cholesterol without altering plasma levels of total cholesterol and TG. Both MHEC and T0901317 equally inhibited the development of atherosclerotic lesions in apoE–/– mice. The expression of ABCA1, a cholesterol efflux transporter, was greatly induced by the two LXR agonists in the artery wall. Conclusions: MHEC is a novel LXR agonist and it inhibits atherosclerosis in apoE–/– mice without raising blood TG. Thus, MHEC relative to T0901317 may be a better therapeutic LXR agonist for the treatment of atherosclerosis.
The Marginal as Central: Al-Jadid and the Development of a Palestinian Public Sphere, 1953–1970
Authors: Nassar Maha
Published: November 2010

This article argues that throughout the 1950s and 1960s the communist-sponsored Arabic literary journal al-Jadid played a central role in creating a Palestinian-Arab counterpublic within Israel by challenging Zionist discourses and championing Arab and Palestinian causes. As a result, when Palestinian writers, activists and intellectuals in Israel were reconnected with Palestinians outside Israel after the 1967 War, they played a vital role in the development of a broader Palestinian public sphere that emphasized perseverance, ties to the land, and resistance to Zionist hegemony. rough content analysis of over 140 issues of al-Jadid published between 1953 and 1967, this article demonstrates al-Jadid's signifi cant role in communicating politically subversive discourses to an increasingly literate public living under military rule, as well as its part in the social circulation of these discourses in the region following the 1967 War. In doing so, it sheds new light on the nexus of media, literature and nationalism in the Palestinian context.
Kafah and the Non-Profit Globalization of Palestinian Media
Authors: Sienkiewicz Matt
Published: November 2010

This article provides a close analysis of the Ma'an Network's made-for-television film, Kafah, placing it within the context of major debates in the field of Palestinian media scholarship. It argues that Kafah challenges many historical limitations that scholars have attributed to media in the Palestinian territories and introduces new and potentially problematic power dynamics. As an international co-production between Western NGOs and Palestinian producers intended to impact Palestinian culture and media, Kafah exists both as a tool of local expression and as a means of foreign influence. The article attempts to identify the true balance of power driving the film's content through close textual analyses, reviews of internal documents and interviews with the film's creators and funding partners. Ultimately, it claims that while both internal and external pressures exert strong influence over the possibilities for the project, the producers are nonetheless able to express their own ideas and make a noteworthy contribution to the Palestinian mediated public sphere.
The Production and Interpretation of Anaphora and Ellipsis
Authors: Zeevat Henk
Published: November 2010

The paper tries to apply a psychological theory of language production and interpretation to the linguistic description of pronouns. The claim is that this is possible and helpful and that a full theory of the use and interpretation of pronouns is possible from this perspective, i.e.one that can both predict when pronouns are used and what is their antecedent. In particular, the theory should be able to explain the properties of pronoun resolution, pronoun selection in natural language generation and the grammaticalisation processes that lead to pronouns. The psychological theory proposed is motivated as an account of parity: the probable identity between the speaker intention and the hearer interpretation. It has four components: a minimal account of legal forms for a given input, speaker self-monitoring for a prioritised set of features, cue-based understanding and filtering by production. A good form for an intention is legal and marks the most prioritised features best, a good interpretation meets the production filter and is most strongly cued by the signal. Descriptively, the main component of self-monitoring for pronouns is an extension of the referential hierarchy (Gundel et al., 1993). Recency, frequency and relevance are effects of cue-based interpretation and central to pronoun resolution. The role of syntax is limited to the agreement features and subclassification of pronouns. The aim of the paper is not to contribute to pronoun resolution or generation but to explore the descriptive potential of a psychologically inspired account of parity in linguistic communication, with of course the hope that the understanding of pronouns benefits from this exercise.