bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of a poly(ADP‐ribose) polymerase‐1 inhibitor against esophageal squamous cell carcinoma cell lines
Authors: Nasuno Tomomitsu , Mimaki Sachiyo , Okamoto Makito , Esumi Hiroyasu , Tsuchihara Katsuya 
Published: November 2013

Effective molecular target drugs that improve therapeutic efficacy with fewer adverse effects for esophageal cancer are highly anticipated. Poly(ADP‐ribose) polymerase (PARP) inhibitors have been proposed as low‐toxicity agents to treat double strand break (DSB)‐repair defective tumors. Several findings imply the potential relevance of DSB repair defects in the tumorigenesis of esophageal squamous cell carcinoma (ESCC). We evaluated the effect of a PARP Inhibitor (AZD2281) on the TE‐series ESCC cell lines. Of these eight cell lines, the clonogenic survival of one (TE‐6) was reduced by AZD2281 to the level of DSB repair‐defective Capan‐1 and HCC1937 cells. AZD2281‐induced DNA damage was implied by increases in γ‐H2AX and cell cycle arrest at G2/M phase. The impairment of DSB repair in TE‐6 cells was suggested by a sustained increase in γ‐H2AX levels and the tail moment calculated from a neutral comet assay after X‐ray irradiation. Because the formation of nuclear DSB repair protein foci was impaired in TE‐6 cells, whole‐exome sequencing of these cells was performed to explore the gene mutations that might be responsible. A novel mutation in RNF8, an E3 ligase targeting γ‐H2AX was identified. Consistent with this, polyubiquitination of γ‐H2AX after irradiation was impaired in TE‐6 cells. Thus, AZD2281 induced growth retardation of the DSB repair‐impaired TE‐6 cells. Interestingly, a strong correlation between basal expression levels of γ‐H2AX and sensitivity to AZD2281was observed in the TE‐series cells (R2 = 0.5345). Because the assessment of basal DSB status could serve as a biomarker for selecting PARP inhibitor‐tractable tumors, further investigation is warranted.
Accuracy of Quantitative Computed Tomography Bone Mineral Density Measurements in Mandibles: A Cadaveric Study
Authors: Miguel‐Sánchez Alfonso , Vilaplana‐Vivo Jaime , Vilaplana‐Vivo Carlos , Vilaplana‐Gómez Juan Ángel , Camacho‐Alonso Fabio 
Published: November 2013

AbstractPurposeThe aim was to investigate the accuracy of quantitative computed tomography bone mineral density (BMD) measurements in mandibles, comparing measured BMD with calibrated BMD.Materials and MethodsSeventy mandibles from adult cadavers were used. Twenty tomographic cuts were made in each mandible. In each tomographic cut, a region of interest was located, and the bone density was measured in Hounsfield unit (HU). A polymethyl methacrylate phantom containing four inserts of different predetermined densities (hydroxyapatite 100, 200, 500, and 700 mg/cm3) was used to calculate calibrated bone density. Correlation between measured and calibrated bone densities was calculated.ResultsMean total correlation between measured and calibrated BMD in the 20 sagittal tomography cuts showed almost perfect positive correlation (r = 0.998, p < .001). However, when average BMD measurements in HU were compared, the measured total BMD (in the 20 sagittal tomography cuts studied) was 54.99 ± 421.59, whereas the total calibrated BMD was 49.28 ± 364.95, with statistically significant difference (p = .001).ConclusionsThere are discrepancies between measured and calibrated BMD; in this sense, a calibrated bone phantom with a predetermined mineral density should be used to determine the exact BMD before dental implants surgery.
Loss of melanocytes in hypopigmented mycosis fungoides: a study of 18 patients
Authors: Furlan Fabricio C. , de Paula Pereira Bruna A. , da Silva Luiz F. , Sanches José A. 
Published: November 2013

BackgroundHypopigmentation in hypopigmented mycosis fungoides (MF) is thought to result from the action of CD8+ cells on melanocytes. Here, we investigated the immunophenotype and melanocytic markers in hypopigmented MF lesions.MethodsSpecimens of hypopigmented lesions and normal skin from 18 patients with hypopigmented MF and specimens of non‐hypopigmented lesions from 8 patients with classic/conventional MF were subjected to neoplastic immunophenotyping and melanocyte immunostaining with Melan‐A, tyrosinase, stem cell factor receptor (CD117) and microphthalmia‐associated transcription factor (MiTF).ResultsThe CD8+ immunophenotype was more common in hypopigmented MF lesions (14/18) than in conventional MF lesions (1/8, p = 0.0033). There was a main effect of specimen type (hypopigmented MF lesion, hypopigmented MF normal skin, conventional MF lesion) on the number of melanocytes stained with Melan‐A (median number/mm basal membrane, 1.97 vs. 4.77 vs. 5.42, respectively, p = 0.0046), tyrosinase (2.19 vs. 4.02 vs. 5.26, p = 0.0114), CD117 (4.29 vs. 7.81 vs. 5.45, p = 0.0064), and MiTF (2.75 vs. 4.43 vs. 4.98, p = 0.005).ConclusionsThese results confirm previous findings of fewer melanocytes and CD117‐positive melanocytes in hypopigmented MF and showed reduced MiTF identification, which is crucial for the function and survival of melanocytes. Thus cytotoxic CD8+ cell action may determine CD117/MiTF dysfunction, causing hypopigmentation.
Regulation of Na+/K+‐ATPase by neuron‐specific transcription factor Sp4: implication in the tight coupling of energy production, neuronal activity and energy consumption in neurons
Authors: Johar Kaid , Priya Anusha , Wong‐Riley Margaret T. T. 
Published: November 2013

AbstractA major source of energy demand in neurons is the Na+/K+‐ATPase pump that restores the ionic gradient across the plasma membrane subsequent to depolarizing neuronal activity. The energy comes primarily from mitochondrial oxidative metabolism, of which cytochrome c oxidase (COX) is a key enzyme. Recently, we found that all 13 subunits of COX are regulated by specificity (Sp) factors, and that the neuron‐specific Sp4, but not Sp1 or Sp3, regulates the expression of key glutamatergic receptor subunits as well. The present study sought to test our hypothesis that Sp4 also regulates Na+/K+‐ATPase subunit genes in neurons. By means of multiple approaches, including in silico analysis, electrophoretic mobility shift and supershift assays, chromatin immunoprecipitation, promoter mutational analysis, over‐expression, and RNA interference studies, we found that Sp4, with minor contributions from Sp1 and Sp3, functionally regulate the Atp1a1, Atp1a3, and Atp1b1 subunit genes of Na+/K+‐ATPase in neurons. Transcripts of all three genes were up‐regulated by depolarizing KCl stimulation and down‐regulated by the impulse blocker tetrodotoxin (TTX), indicating that their expression was activity‐dependent. Silencing of Sp4 blocked the up‐regulation of these genes induced by KCl, whereas over‐expression of Sp4 rescued them from TTX‐induced suppression. The effect of silencing or over‐expressing Sp4 on primary neurons was much greater than those of Sp1 or Sp3. The binding sites of Sp factors on these genes are conserved among mice, rats and humans. Thus, Sp4 plays an important role in the transcriptional coupling of energy generation and energy consumption in neurons.
Pathophysiology of epileptic encephalopathies
Authors: Lado Fred A. , Rubboli Guido , Capovilla Pippo , Avanzini Giuliano , Moshé Solomon L. 
Published: November 2013

SummaryThe application of metabolic imaging and genetic analysis, and now the development of appropriate animal models, has generated critical insights into the pathogenesis of epileptic encephalopathies. In this article we present ideas intended to move from the lesions associated with epileptic encephalopathies toward understanding the effects of these lesions on the functioning of the brain, specifically of the cortex. We argue that the effects of focal lesions may be magnified through the interaction between cortical and subcortical structures, and that disruption of subcortical arousal centers that regulate cortex early in life may lead to alterations of intracortical synapses that affect a critical period of cognitive development. Impairment of interneuronal function globally through the action of a genetic lesion similarly causes widespread cortical dysfunction manifesting as increased delta slow waves on electroencephalography (EEG) and as developmental delay or arrest clinically. Finally, prolonged focal epileptic activity during sleep (as occurring in the syndrome of continuous spike‐wave in slow sleep, or CSWSS) might interfere with local slow wave activity at the site of the epileptic focus, thereby impairing the neural processes and, possibly, the local plastic changes associated with learning and other cognitive functions. Seizures may certainly add to these pathologic processes, but they are likely not necessary for the development of the cognitive pathology. Nevertheless, although seizures may be either a consequence or symptom of the underlying lesion, their effective treatment can improve outcomes as both clinical and experimental studies may suggest. Understanding their substrates may lead to novel, effective treatments for all aspects of the epileptic encephalopathy phenotype.
Progress in a replicated selection for elevated blood ethanol concentrations in HDID mice
Authors: Crabbe J. C. , Metten P. , Belknap J. K. , Spence S. E. , Cameron A. J. , Schlumbohm J. P. , Huang L. C. , Barkley‐Levenson A. M. , Ford M. M. , Phillips T. J. 
Published: November 2013

AbstractDrinking in the dark (DID) is a limited access ethanol‐drinking phenotype in mice. High Drinking in the Dark (HDID‐1) mice have been bred for 27 selected generations (S27) for elevated blood ethanol concentrations (BECs) after a 4‐h period of access to 20% ethanol. A second replicate line (HDID‐2) was started later from the same founder population and is currently in S20. An initial report of response to selection in HDID‐1 was published after S11. This article reports genetic and behavioral characteristics of both lines in comparison with the HS controls. Heritability is low in both replicates (h2 = 0.09) but the lines have shown 4–5 fold increases in BEC since S0; 80% of HDID‐1 and 60% of HDID‐2 mice reach BECs greater than 1.0 mg/ml. Several hours after a DID test, HDID mice show mild signs of withdrawal. Although not considered during selection, intake of ethanol (g/kg) during the DID test increased by approximately 80% in HDID‐1 and 60% in HDID‐2. Common genetic influences were more important than environmental influences in determining the similarity between BEC and intake for HDID mice. Analysis of the partitioning of intake showed that 60% of intake is concentrated in the last 2 h of the 4 h session. However, this has not changed during selection. Hourly BECs during the DID test reach peak levels after 3 or 4 h of drinking. HDID mice do not differ from HS mice in their rate of elimination of an acute dose of alcohol.
Vagrancy fails to predict colonization of oceanic islands
Authors: Lees Alexander C. , Gilroy James J. 
Published: November 2013

AbstractAimTheories of island biogeography typically predict a close link between patterns of immigration and the dynamics of colonization and extinction on islands, but relatively little is known of the immigration process owing to the difficulty of observing immigration directly. We assess the relationship between propagule immigration and colonization success using records of out‐of‐range ‘vagrant’ animals compiled by amateur and professional biologists.LocationA global sample of 66 oceanic islands and archipelagos.MethodsWe compiled a database of landbird records from each archipelago including occasional visitors (vagrants) and colonizers (defined as non‐endemic species with breeding populations on islands). Using a database of species traits for all the world's passerine and near‐passerine birds (migratory status and range size), we compared the characteristics of vagrants and colonizers and assessed how island characteristics influenced vagrant and colonizer communities.ResultsWe show that variation in the propensity for vagrancy to oceanic islands world‐wide is a surprisingly poor predictor of colonization success across species on a global scale. Colonization success is positively related to global range size, and is higher for migrants than residents (particularly on higher‐latitude islands). Species richness of vagrant communities increases with the area and local isolation of island groups, and decreases with isolation from continents and latitude. Colonizer species richness increases with island area and decreases with isolation and latitude, and is little influenced by vagrant species richness.Main conclusionsContrary to expectations, we find that the capacity for trans‐oceanic dispersal may not be a key determinant of oceanic island colonization amongst landbirds.
At a loss for birds: insularity increases asymmetry in seed‐dispersal networks
Authors: Schleuning Matthias , Böhning‐Gaese Katrin , Dehling D. Matthias , Burns Kevin C. 
Published: November 2013

AbstractAimThe decline of species richness with insularity is a well‐known pattern in ecology and biogeography. Despite recent progress, our understanding of the effects of insularity on other components of biodiversity, e.g. the diversity of species interactions, is still poorly developed. In this study, we investigated the effect of insularity on the structure of seed‐dispersal networks on a global scale.LocationWorld‐wide.MethodsWe compiled a large dataset of seed‐dispersal networks (n = 28). We (1) compared the diversity (interaction evenness, complementary specialization) and asymmetry (web asymmetry, interaction strength asymmetry) of interactions between island and mainland networks, and (2) tested the effects of island area and isolation on the four network metrics.ResultsNeither measure of interaction diversity differed between islands and the mainland. In contrast, island networks were more asymmetric than mainland networks, due to a paucity of animal frugivores, especially birds. Both measures of network asymmetries were closely associated with island isolation, but were unrelated to island area. Patterns were consistent in analyses with and without non‐native plant and animal species.Main conclusionsBecause of the highly asymmetric structure of seed‐dispersal networks on islands, plant species on islands are highly dependent on particular animal species. These asymmetries probably arise from low rates of colonization and high rates of human‐caused extinction of frugivorous animals on isolated islands. Although interaction evenness and specialization were similar between islands and the mainland, additional work is needed to test whether high asymmetries will make island networks more vulnerable to future change and functional collapse.
Structure, Mechanisms of Reaction, and Strength of an Alkali‐Activated Blast‐Furnace Slag
Authors: Burciaga‐Díaz Oswaldo , Escalante‐García José Iván 
Published: November 2013

This research examines the chemical activation of blast‐furnace slag pastes with alkaline solutions by means of various characterization techniques. Pastes were activated using sodium silicate solutions with modulus (Ms) of 0, 1, 1.5, 2, and Na2O at 5%, 10%, and 15%. Compressive strengths of up to 108 MPa were achieved for Ms = 1–1.5 after 720 d of curing at 20°C. The addition of Na2O > 10% resulted in the formation of hydrotalcite and carbonated pastes with low compressive strength. X‐ray diffraction, microanalysis of outer products (OP), and nuclear magnetic resonance (NMR) results showed that the main reaction products in the activated cements with Ms = 1 and 5%Na2O had an average ratio Ca/Si = 0.71–0.9 and consisted of a mixture of two kinds of C–S–H; one similar to a 9 Å tobermorite‐type calcium silicate hydrate (Ca5Si6O16(OH)2 and other amorphous related to a cross‐linked structure of C–N–(A)–S–H gel. Both were intermixed with hydrotalcite and cross‐linked structures of silica gel.
Flexural Strength by Fractography in Modern Brittle Materials
Authors: Dugnani Roberto , Zednik Ricardo 
Published: November 2013

Thin components made from advanced brittle glasses or ceramics are becoming increasingly important due to the widespread adoption of portable consumer products as well as other modern electronic and medical devices. The strength of these brittle materials is traditionally estimated from empirical relationships relating the stress at failure to characteristic lengths derived from the fracture surface's topography. One example is Orr's relationship, σf∙Rm1/2 = Am, which correlates the material strength, σf, to the radius of the “mirror‐mist boundary region,”Rm, through the empirical constant,Am. Although various studies have shown that, for flexural fractures (failed in bending),Amdepends on the specimen's geometry, this effect has been generally neglected by arguing that the magnitude ofAmis almost constant for thicker specimens. However, we show that this argument cannot be applied to thin geometries, and that by not accounting for the thickness of the sample, the flexural strength will be grossly underestimated. In this work, we introduce an expression based on an iterative fracture mechanics algorithm which yields more accurate estimates of flexural strength for thin brittle components in bending. The accuracy of the model is validated both through flexural strength tests on glass and by comparing our predictions to an extensive literature survey of experimental results.
Dielectric Properties of Ba0.8Ca0.2TiO3–Bi(Mg0.5,Ti0.5)O3–NaNbO3 Ceramics
Authors: Zeb Aurang , Milne Steven J. 
Published: November 2013

Ceramics in the system 0.45Ba0.8Ca0.2TiO3–(0.55−x)Bi(Mg0.5Ti0.5)O3–xNaNbO3, x = 0–0.02 were fabricated by a conventional solid‐state reaction route. X‐ray powder diffraction indicated cubic or pseudocubic symmetry for all samples. The parent 0.45Ba0.8Ca0.2TiO3–0.55Bi(Mg0.5Ti0.5)O3 composition is a relaxor dielectric with a near‐stable temperature coefficient of relative permittivity, εr = 950 ± 10% across the temperature range 80°C–600°C. Incorporation of NaNbO3 at x = 0.2 extends the lower working temperature to ≤25°C, with εr = 575% ± 15% from temperatures ≤25°C to >400°C, and tan δ < 0.025 from 25°C to 400°C. Values of dc resistivity ranged from ~109 Ω·m at 250°C to ~106 Ω·m at 500°C. The properties suggest that this material may be of interest for high‐temperature capacitor applications.
The Lowered Dielectric Loss and Grain‐Boundary Effects in La‐doped Y2/3Cu3Ti4O12 Ceramics
Authors: Liang Pengfei , Chao Xiaolian , Wang Fang , Liu Zhanqing , Yang Zupei 
Published: November 2013

The effects of La concentration on the electrical conductivity and electric modulus of Y2/3−xLaxCu3Ti4O12 ceramics (0.00 ≦ x ≦ 0.20) were investigated in detail. Proper amount of La substitution in Y2/3−xLaxCu3Ti4O12 ceramics made the dielectric loss decreased. When x = 0.10, Y2/3−0.10La0.10Cu3Ti4O12 ceramics exhibited the highest grain‐boundary resistance (0.893 MΩ) and the lowest dielectric loss (about 0.025 at 1 kHz), meanwhile the samples exhibited a relatively high dielectric constant above 6000 over a wide frequency range from 40 Hz to 1 MHz. The decreased dielectric loss was attributed to the enhanced grain‐boundary resistance. With the increase in La concentration, the dielectric relaxation behaviors correlated with the grain‐boundary effects were significantly enhanced. By La doping, the activation energies for the conduction in grain boundaries were slightly depressed, and the activation energies for the relaxation process in grain boundaries were slightly changed. Based on the activation values, it can be concluded that the doubly ionized oxygen vacancies had substantial contribution to the conduction and relaxation behaviors in grain boundaries.
Silencing of the cell cycle checkpoint gene 14‐3‐3σ in basal cell carcinomas correlates with reduced expression of IKK‐α
Authors: Molin S. C. , Grgic M. , Ruzicka T. , Herzinger T. 
Published: November 2013

AbstractBackground14‐3‐3σ is down‐regulated in a large proportion of basal cell carcinomas (BCC). IkappaB kinase α (IKK‐α), one of the two catalytic subunits of the IKK complex involved in NF‐kappaB‐activation, also functions as a modulator of epidermal development and differentiation. Down‐regulation of IKK‐α causes hyperplasia and promotes skin cancer. IKK‐α has been found to regulate the expression of 14‐3‐3σ by shielding its promoter from hypermethylation and thereby preventing its silencing in mouse keratinocytes.ObjectivesTo evaluate the potential role of IKK‐α in the silencing of 14‐3‐3σ in basal cell carcinoma.Materials and methodsExpression of 14‐3‐3σ and IKK‐α was studied by immunohistochemistry in 33 sporadic BCCs and 26 BCCs from patients with basal cell nevus syndrome (BCNS).ResultsMarked reduction or absence of 14‐3‐3σ was found in 24 (92%) BCCs from BCNS patients, and in 29 (88%) sporadic BCCs. Marked reduction or absence of IKK‐α was found in 22 (85%) BCCs from patients with BCNS, and in 27 (82%) sporadic BCCs. Expression levels for 14‐3‐3σ and IKK‐α correlated positively in 92% of BCCs from BCNS patients, and in 85% of sporadic BCCs.ConclusionsOur findings suggest that down‐regulation of IKK‐α is required for 14‐3‐3σ promoter methylation and silencing in the pathogenesis of BCC. Besides, our observation that 14‐3‐3σ silencing is also frequently found in BCC from patients with BCNS suggests a possible link between the sonic hedgehog/patched and 14‐3‐3σ/IKK‐α pathways.
Evaluation of alpha‐fetoprotein in detecting hepatocellular carcinoma recurrence after radiofrequency ablation
Authors: Siripongsakun Surachate , Wei Sindy H , Lin Stephanie , Chen Jeffrey , Raman Steven S , Sayre James , Tong Myron J , Lu David S 
Published: November 2013

AbstractBackground and AimThe performance of alpha‐fetoprotein (AFP) in the detection of hepatocellular carcinoma (HCC) recurrence after radiofrequency ablation was analyzed.MethodsOne hundred and forty‐six solitary HCC lesions treated by radiofrequency ablation were evaluated. Using the AFP cutoff level at ≥ 20 ng/mL, tumors were categorized into AFP or non‐AFP‐producing HCC. Factors associated with true and false interpretations for cancer recurrence including analysis of elevated alanine aminotransferase (ALT) were evaluated. The performance of AFP using different cutoff levels adjusted for abnormal ALT was compared.ResultsOf 146 HCCs, 103 demonstrated no HCC recurrence while 43 had local recurrence. In non‐recurrence HCC cases, increased AFP levels (false positive) were associated with concomitant ALT elevations, while those with normal AFP (true negative) had correspondingly normal ALT values (P < 0.001). The AFP false positive rate in cases of elevated ALT was significantly higher than those with normal ALT levels (31.9% vs 5.4%, P = 0.001). Among all positive AFP tests, those with false positive values (non‐recurrence) had a significantly lower AFP level than the true positive (recurrence) HCC cases (39.8 ng/mL vs 372 ng/mL, P < 0.001).At the 20 ng/mL cutoff level, the sensitivities of AFP for detecting recurrence in non‐AFP‐producing HCC and AFP‐producing HCC were 12.0%, and 72.2%, respectively. Using a modified AFP criteria of ≥ 100 ng/mL for cases where ALT ≥ 40 U/L, the sensitivity and specificity in AFP‐producing tumors increased from 72.2% and 56% to 100% and 85%, respectively.ConclusionSerum AFP is a useful test in the detection of HCC recurrence in AFP‐producing HCC. The performance in AFP‐producing HCC was significantly improved after adjusting for elevation of serum ALT.