bluuebunny/crossref_metadata_2025 huggingface dataset:
Qualities of sessile serrated adenoma/polyp/lesion and its borderline variant in the context of synchronous colorectal carcinoma
Authors: Mohammadi Mahin , Kristensen Michael Holmsgaard , Nielsen Hans Jørgen , Bonde Jesper Hansen , Holck Susanne
Published: July 2012

Aims

Although much data have accumulated on sessile serrated adenoma/polyp/lesion (SSA/P/L) in general, its characteristics in specified contexts are less well elucidated. This lack of knowledge is even more conspicuous concerning its borderline counterpart, referred to as BSSA/P/L. The previous histological observations of the authors on SSA/P/L and BSSA/P/L in general are here extended to encompass attributes of these polyps in the context of synchronous colorectal carcinoma (SCRC), with a focus on the place of BSSA/P/L in the spectrum of non-dysplastic serrated polyps.

Methods

219 SSA/P/Ls, 206 BSSA/P/Ls and 170 hyperplastic polyps (HPs) were examined for SCRC. Demographics, polyp details (size, site, BRAF(V600E)) and advanced synchronous conventional adenomas were recorded.

Results

SCRC was present in 12.3% of SSA/P/Ls, 7.1% of HPs (p=0.09) and 8.3% of BSSA/P/Ls. Patients' ages were comparable. Gender distribution of SSA/P/L and BSSA/P/L was equal, which differed, albeit insignificantly, from a male predominance of HPs. More SSA/P/Ls and BSSA/P/Ls than HPs exceeded 4 mm (p≤0.0001). A proximal site characterised SSA/P/L compared with BBSA/P/L and HP (p<0.0001).BRAFmutation was more prevalent in SSA/P/Ls and BSSA/P/Ls, which further coexisted with advanced synchronous conventional adenomas less commonly than HPs.

Conclusions

BSSA/P/L was like SSA/P/L in most respects. The lower SCRC prevalence of BSSA/P/L could fit the idea of BSSA/P/L as a precursor to SSA/P/L, a notion that deserves attention when formulating guidelines for CRC screening.
Dynamics of bovine herpesvirus type 1 infection in Estonian dairy herds with and without a control programme
Authors: Raaperi K. , Aleksejev A. , Orro T. , Viltrop A.
Published: July 2012

Bovine herpesvirus type 1 (BHV‐1) is an important bovine pathogen, exacerbating poor health and the productivity of cattle. The aims of this study were to detect the efficacy of vaccination programmes in lowering the seroprevalence of BHV‐1 gE within the dairy herd and to follow the dynamics of the infection in non‐vaccinated herds with uninfected heifers. A two‐year longitudinal study was carried out on seven herds that were vaccinated, and in five herds with uninfected heifers without applying a control programme. After the start of the vaccination programme, calves born remained free from the virus. However, in one herd, 7 per cent (95 per cent CI 2 to 18) of these animals showed antibodies to BHV‐1 two years after the first vaccination. A decline in BHV‐1 antibody prevalence was found in vaccinating herds. Among the five herds not under the control programme, one experienced active virus spread, although one herd experienced self‐clearance of the virus. In the herds with high BHV‐1 prevalence, vaccinating all cattle from three months of age twice a year with a commercial inactivated marker vaccine efficiently protected offspring from becoming infected, and lowered the prevalence of BHV‐1 within the herd. A small proportion of herds may experience self‐clearance of the virus.
First detection of ‘CandidatusMycoplasma haemolamae’ infection in alpacas in England
Authors: Crosse P. , Ayling R. , Whitehead C. , Szladovits B. , English K. , Bradley D. , Solano‐Gallego L.
Published: July 2012

This is the first report of detection ofCandidatusMycoplasma haemolamae in alpacas in England. The primary case occurred in a three year‐old male alpaca in the south‐east of England which presented with a history of progressive weight loss, lethargy, swelling of the scrotum and pale mucous membranes. Blood smear examination revealed a moderate, regenerative anaemia, with numerous small basophilic coccoid structures consistent withCandidatusM haemolamae. To confirm the presence ofCandidatusM haemolamae, a portion of the 16S rDNA gene was amplified and analysed by denaturing gradient gel electrophoresis (DGGE). 16S rDNA gene sequencing showed a 99.8 per cent homology withCandidatusM haemolamae sequences deposited in GenBank. Subsequently, a cross‐sectional study was carried out to investigate the presence of Candidatus M haemolamae infection in the alpaca herd from which the primary case was detected (n=131). Blood smear examinations and PCR with DGGE were used and compared with a species‐specific PCR. The prevalence of infection when PCR positive results were combined was 29 per cent. A substantial agreement between the PCR/DGGE and the species‐specific PCR was found (κ=0.86). A significant association was also found between age and infection (P=0.04) while no significant association was found with sex or origin.
STATIC AND DYNAMIC STABILITY ANALYSIS OF A FUNCTIONALLY GRADED TIMOSHENKO BEAM
Authors: MOHANTY S. C. , DASH R. R. , ROUT T.
Published: July 2012

This article presents the evaluation of static and dynamic behavior of functionally graded ordinary (FGO) beam and functionally graded sandwich (FGSW) beam for pined–pined end condition. The variation of material properties along the thickness is assumed to follow exponential and power law. A finite element method is used assuming first order shear deformation theory for the analysis. The element chosen is different from the conventional elements as the shape functions of the element are obtained from the exact solution of the static part of governing differential equation derived according to Hamilton's principle. Moreover, the shape functions depend on length, cross-section and material properties which ensure better accuracy of the solution. The effect of power law index on critical buckling load and natural frequencies of FGO beam is investigated. The critical buckling load of FGO beam with steel-rich bottom increases with power law index whereas the trend reverses for beam with Al-rich bottom. The first three natural frequencies of FGO beam are found to decrease to a minimum value and then increase as the power law index increases from one. The dynamic stability of FGO beam with steel-rich bottom is found to be more than that of beam with Al-rich bottom. An FGSW beam with alumina as bottom skin, steel top skin, and mixture of alumina and steel as core is chosen for analysis. The critical buckling load of FGSW beam increases with the increase of core thickness for variation of material properties in core as per power law with index more than one, whereas it decreases with the increase of core thickness for variation of material properties in core as per exponential law. The first three natural frequencies of the FGSW beam increase with the increase of FGM core for both the types of property distributions. The dynamic stability of the FGSW beam is enhanced as the thickness of the FGM core is increased.
A STABILIZED PARTICLE METHOD FOR LARGE DEFORMATION DYNAMIC ANALYSIS OF STRUCTURES
Authors: OSTAD H. , MOHAMMADI S.
Published: July 2012

The property of free movement of particles allows for most meshless particle methods to be efficiently used for simulation of solid problems involving large deformation as it removes the necessity of remeshing, which is one of the time-consuming parts of the traditional finite element method based on an updated Lagrangian formulation. One of the main sources of instabilities in meshfree particle methods, which approximate the strong form of partial differential equations, is the existence of extra high frequency vibrations. They are induced into the solution due to the use of truncated Taylor series expansions. The cumulative effect of the extra vibrations makes the solution to be polluted by zero energy modes and tensile instabilities. In this paper, the CSPM particle method is used to solve elastodynamic large deformation problems based on an updated Lagrangian procedure. A field smoothing approach, recently proposed for reduction of instabilities that rise from excessive high frequency vibrations, is further extended to large deformation problems. Also, the phenomenon of particles penetration can be prevented without the requirement of any additional artificial damping forces. Another major advantage of the new approach is its generality which allows for its implementation into other particle methods and its application for solving other physical problems. A variety of large deformation problems are solved by the proposed approach and the results are compared with other available results.
DISORDER INDUCED BCS-BEC CROSSOVER
Authors: KHAN AYAN
Published: July 2012

Of late, the study of BCS-BEC crossover in the presence of weak random impurity is an interesting issue. In this proceedings we study the effect of this disorder which is included through the Nozières and Smith-Rink theory of superconducting fluctuations. In the weak regime, the random potential leaves an effect on the superconducting order parameter but it spares the chemical potential. Here we present the exact behavior of the mean field quantities as a function of the disorder by self-consistently solving the coupled equations.
QUANTIZED INTRINSICALLY LOCALIZED MODES: LOCALIZATION THROUGH INTERACTION
Authors: RISEBOROUGH PETER S.
Published: July 2012

We have calculated the lowest energy quantized spectra of Intrinsically Localized Modes (ILMs) for the Fermi-Pasta-Ulam lattices. The quantized ILM spectra are composed of resonances in the two-phonon continuum and branches of infinitely long-lived excitations that are bound states formed from even numbers of phonons. For quartic anharmonicity and one atom per unit cell, the calculated ILMs are consistent with the results of previous calculations using the number conserving approximation. However, by contrast the ILM spectrum of the lattice with cubic interactions couples resonantly with the single-phonon spectrum and cannot be calculated within a number conserving approximation. Furthermore we argue that, by introducing a sufficiently strong cubic non-linearity, the quantized ILMs can be observed directly through the single-phonon inelastic neutron scattering spectrum. We compare our theoretical predictions with the recent experimental observation of breathers in NaI by Manley et al.
"RARE" FLUCTUATION EFFECTS IN THE ANDERSON MODEL OF LOCALIZATION
Authors: BHATT R.N. , JOHRI S.
Published: July 2012

We discuss the role of rare fluctuation effects in quantum condensed matter systems. In particular, we present recent numerical results of the effect of resonant states in Anderson's original model of electron localization. We find that such resonances give rise to anomalous behavior of eigenstates not just far in the Lifshitz tail, but rather for a substantial fraction of eigenstates, especially for intermediate disorder. The anomalous behavior includes non-analyticity in various properties as a characteristic. The effect of dimensionality on the singularity, which is present in all dimensions, is described, and the behavior for bounded and unbounded disorder is contrasted.
Palaeomagnetism and
40
Ar/
39
Ar dating from Lower Jurassic rocks in Gastre, central Patagonia: further data to explore tectonomagmatic events associated with the break-up of Gondwana
Authors: Zaffarana Claudia Beatriz , Somoza Rubén
Published: July 2012

New
40
Ar/
39
Ar data indicate ages of
c
. 185 Ma for the Lonco Trapial volcanic field in Gastre, north–central Patagonia, implying that this andesitic unit is roughly coeval with the Marifil silicic province that crops out in the eastern part of northern Patagonia. These volcanic fields are therefore roughly coeval with the Karoo–Ferrar large igneous province, further contributing to the huge, 185–180 Ma magmatic outpouring in southern Gondwana. The comparison of palaeomagnetic results from the unit with Early Jurassic reference palaeopoles suggests that Gastre records a small, anticlockwise finite rotation with respect to stable South America. This contrasts sharply with the large clockwise rotation recorded by roughly coeval dolerites from the Falkland/Malvinas Islands, and argues against a direct relationship between the rotation of the islands and the tectonic activity in Gastre. The results support previous suggestions that the Gastre Fault System is not the locus of major strike-slip displacement activity in the Jurassic as some workers have suggested. Taken as a whole, palaeomagnetic data from Patagonia suggest a more complex than previously thought pattern of distributed and variable deformation during the early stages of Gondwana breakup. The crustal block boundaries in the region remain cryptic.

Supplementary material:

40
Ar/
39
Ar analytical procedures and expanded data are available at
http://www.geolsoc.org.uk/SUP18522
.
Late Palaeozoic architecture and evolution of the southwestern Barents Sea: insights from a new generation of aeromagnetic data
Authors: Gernigon Laurent , Brönner Marco
Published: July 2012

A new generation of aeromagnetic surveys highlights the Caledonian basement grain and pre-Permian basin architecture of the southwestern Barents Sea. This configuration involved several Caledonian thrust sheets that reactivated and controlled the post-Caledonian rift development of the southwestern Barents Sea during Late Palaeozoic time. Contrary to previous geological models, we consider that the sub-Permian basins and underlying basement grain have a dominantly NNW–SSE orientation in most of the southwestern Barents Sea. Moreover, we do not see magnetic evidence that could support a major NE–SW or NNE–SSW regional axis that has commonly been proposed for the Late Palaeozoic rift system and inherited Caledonian structural grain in the Barents Sea.

Supplementary material:

An outline of the new magnetic profiles acquired during the BASAR project and an outline of the vintage magnetic profiles available before the BASAR project are available at
www.geolsoc.org.uk/SUP18524
.
Overexpression of the SK3 channel alters vascular remodeling during pregnancy, leading to fetal demise
Authors: Rada Cara C. , Pierce Stephanie L. , Nuno Daniel W. , Zimmerman Kathy , Lamping Kathryn G. , Bowdler Noelle C. , Weiss Robert M. , England Sarah K.
Published: July 2012

The maternal cardiovascular system undergoes hemodynamic changes during pregnancy via angiogenesis and vasodilation to ensure adequate perfusion of the placenta. Improper vascularization at the maternal-fetal interface can cause pregnancy complications and poor fetal outcomes. Recent evidence indicates that small conductance Ca2+-activated K+ channel subtype 3 (SK3) contributes to vascular remodeling during pregnancy, and we hypothesized that abnormal SK3 channel expression would alter the ability of the maternal cardiovascular system to adapt to pregnancy demands and lead to poor fetal outcomes. We investigated this hypothesis using transgenic Kcnn3tm1Jpad/Kcnn3tm1Jpad (SK3T/T) mice that overexpress the channel. Isolated pressurized uterine arteries from nonpregnant transgenic SK3T/T mice had larger basal diameters and decreased agonist-induced constriction than those from their wild-type counterparts; however, non-receptor-mediated depolarization remained intact. In addition to vascular changes, heart rates and ejection fraction were increased, whereas end systolic volume was reduced in SK3T/T mice compared with their wild-type littermates. Uterine sonography of the fetuses on pregnancy day 14 showed a significant decrease in fetal size in SK3T/T compared with wild-type mice; thus, SK3T/T mice displayed an intrauterine growth-restricted phenotype. The SK3T/T mice showed decreased placental thicknesses and higher incidence of fetal loss, losing over half of their complement of pups by midgestation. These results establish that the SK3 channel contributes to both maternal and fetal outcomes during pregnancy and point to the importance of SK3 channel regulation in maintaining a healthy pregnancy.
Two-Step Galileo E1 CBOC Tracking Algorithm: When Reliability and Robustness Are Keys!
Authors: Jovanovic Aleksandar , Mongrédien Cécile , Tawk Youssef , Botteron Cyril , Farine Pierre-André
Published: July 2012

The majority of 3G mobile phones have an integrated GPS chip enabling them to calculate a navigation solution. But to deliver continuous and accurate location information, the satellite tracking process has to be stable and reliable. This is still challenging, for example, in heavy multipath and non-line of sight (NLOS) environments. New families of Galileo and GPS navigation signals, such as Alternate Binary Offset Carrier (AltBOC), Composite Binary Offset Carrier (CBOC), and Time-Multiplex Binary Offset Carrier (TMBOC), will bring potential improvements in the pseudorange calculation, including more signal power, better multipath mitigation capabilities, and overall more robust navigation. However, GNSS signal tracking strategies have to be more advanced in order to profit from the enhanced properties of the new signals.In this paper, a tracking algorithm designed for Galileo E1 CBOC signal that consists of two steps, coarse and fine, with different tracking parameters in each step, is presented and analyzed with respect to tracking accuracy, sensitivity and robustness. The aim of this paper is therefore to provide a full theoretical analysis of the proposed two-step tracking algorithm for Galileo E1 CBOC signals, as well as to confirm the results through simulations as well as using real Galileo satellite data.
Astrocytes and Developmental Plasticity in Fragile X
Authors: Cheng Connie , Sourial Mary , Doering Laurie C.
Published: July 2012

A growing body of research indicates a pivotal role for astrocytes at the developing synapse. In particular, astrocytes are dynamically involved in governing synapse structure, function, and plasticity. In the postnatal brain, their appearance at synapses coincides with periods of developmental plasticity when neural circuits are refined and established. Alterations in the partnership between astrocytes and neurons have now emerged as important mechanisms that underlie neuropathology. With overall synaptic function standing as a prominent link to the expression of the disease phenotype in a number of neurodevelopmental disorders and knowing that astrocytes influence synapse development and function, this paper highlights the current knowledge of astrocyte biology with a focus on their involvement in fragile X syndrome.
Global Asymptotic Stability of a Predator‐Prey Model with Modified Leslie‐Gower and Holling‐Type II Schemes
Authors: Yu Shengbin
Published: July 2012

We study the predator‐prey model proposed by Aziz‐Alaoui and Okiye (Appl. Math. Lett. 16 (2003) 1069–1075) First, the structure of equilibria and their linearized stability is investigated. Then, we provide two sufficient conditions on the global asymptotic stability of a positive equilibrium by employing the Fluctuation Lemma and Lyapunov direct method, respectively. The obtained results not only improve but also supplement existing ones.
Etiopathogenetic Mechanisms of Pulmonary Hypertension in Sleep-Related Breathing Disorders
Authors: Adegunsoye Ayodeji , Ramachandran Siva
Published: July 2012

Obstructive sleep apnea syndrome is a common disorder with significant health consequences and is on the rise in consonance with the obesity pandemic. In view of the association between sleep-disordered breathing and pulmonary hypertension as depicted by multiple studies, current clinical practice guidelines categorize obstructive sleep apnea as a risk factor for pulmonary hypertension and recommend an assessment for sleep disordered breathing in evaluating patients with pulmonary hypertension. The dysregulatory mechanisms associated with hypoxemic episodes observed in sleep related breathing disorders contribute to the onset of pulmonary hypertension and identification of these potentially treatable factors might help in the reduction of overall cardiovascular mortality.
Effect of Atypical Antipsychotics on Fetal Growth: Is the Placenta Involved?
Authors: Raha Sandeep , Taylor Valerie H. , Holloway Alison C.
Published: July 2012

There is currently considerable uncertainty regarding prescribing practices for pregnant women with severe and persistent psychiatric disorders. The physician and the mother have to balance the risks of untreated psychiatric illness against the potential fetal toxicity associated with pharmacological exposure. This is especially true for women taking atypical antipsychotics. Although these drugs have limited evidence for teratological risk, there are reports of altered fetal growth, both increased and decreased, with maternal atypical antipsychotic use. These effects may be mediated through changes in the maternal metabolism which in turn impacts placental function. However, the presence of receptors targeted by atypical antipsychotics in cell lineages present in the placenta suggests that these drugs can also have direct effects on placental function and development. The signaling pathways involved in linking the effects of atypical antipsychotics to placental dysfunction, ultimately resulting in altered fetal growth, remain elusive. This paper focuses on some possible pathways which may link atypical antipsychotics to placental dysfunction.
In VitroandIn VivoGenotoxicity Assessment ofAristolochia manshuriensisKom.
Authors: Hwang Youn-Hwan , Kim Taesoo , Cho Won-Kyung , Yang Hye Jin , Kwak Dong Hoon , Ha Hyunil , Song Kwang Hoon , Ma Jin Yeul
Published: July 2012

Arisolochiae speciesplants containing aristolochic acids I and II (AA I and AA II) are well known to cause aristolochic acid nephropathy (AAN). Recently, there are various approaches to use AAs-containing herbs after the removal of their toxic factors. However, there is little information about genotoxicity ofArisolochiae manshuriensisKom. (AMK)per se. To obtain safety information for AMK, its genotoxicity was evaluated in accordance with OECD guideline. To evaluate genotoxicity of AMK, we tested bacterial reverse mutation assay, chromosomal aberration test, and micronucleus test. Here, we also determined the amounts of AA I and II in AMK (2.85 ± 0.08 and 0.50 ± 0.02 mg/g extract, resp.). In bacterial reverse mutation assay, AMK dose-dependently increased revertant colony numbers in TA98, TA100 and TA1537 regardless of metabolic activation. AMK increased the incidence of chromosomal aberration in Chinese hamster ovary-K1 cells, but there was no statistically significant difference. The incidences of micronucleus in bone marrow erythrocyte were significantly increased in mice after oral administration of AMK (5000 mg/kg), comparing with those of vehicle group (P<0.05). The results of three standard tests suggest that the genotoxicity of AMK is directly related to the AAs contents in AMK.
Elimination of the Actin-Binding Domain in Kelch-Like 1 Protein Induces T-Type Calcium Channel Modulation Only in the Presence of Action Potential Waveforms
Authors: Aromolaran Kelly A. , Benzow Kelly A. , Cribbs Leanne L. , Koob Michael D. , Piedras-Rentería Erika S.
Published: July 2012

The Kelch-like 1 protein (KLHL1) is a neuronal actin-binding protein that modulates calcium channel function. It increases the current density of Cav3.2 (α1H) calcium channels via direct interaction with α1H and actin-F, resulting in biophysical changes in Cav3.2 currents and an increase in recycling endosomal activity with subsequent increased α1H channel number at the plasma membrane. Interestingly, removal of the actin-binding Kelch motif (ΔKelch) prevents the increase in Cav3.2 current density seen with wild-type KLHL1 when tested with normal square pulse protocols but does not preclude the effect when tested using action potential waveforms (AP).
Here, we dissected the kinetic properties of the AP waveform that confer the mutant Kelch the ability to interact with Cav3.2 and induce an increase in calcium influx. We modified the action potential waveform by altering the slopes of repolarization and/or recovery from hyperpolarization or by changing the duration of the depolarization plateau or the hyperpolarization phase and tested the modulation of Cav3.2 by the mutant ΔKelch. Our results show that the recovery phase from hyperpolarization phase determines the conformational changes that allow the α1H subunit to properly interact with mutant KLHL1 lacking its actin-binding Kelch domains, leading to increased Ca influx.
Toxicity of Aqueous Fullerene nC60 to Activated Sludge: Nitrification Inhibition and Microtox Test
Authors: Yang Yongkui , Nakada Norihide , Nakajima Ryoji , Wang Chao , Tanaka Hiroaki
Published: July 2012

The increasing production and use of fullerene nanomaterials raised their exposure potential to the activated sludge during biological wastewater treatment process. In this study, the toxicity of aqueous nanoscaled C60 (nC60) to activated sludge was investigated using nitrification inhibition and Microtox test. The test solutions of nC60 were prepared using two methods: long stirring (Stir/nC60) and toluene exchange (Tol/nC60). The nC60 aggregation in test medium was also evaluated for toxicity assessment. The results showed that the nC60 aggregation behaved differently in two test mediums during the incubation periods. The nC60 toxicity was greatly influenced by the preparation method. Stir/nC60 presented no significant toxicity to both the nitrification sludge and bioluminescent bacteria at the maximum concentration studied. In contrast, the EC20 of Tol/nC60 was obtained to be 4.89 mg/L (3 h) for the nitrification inhibition and 3.44 mg/L (30 min) for Microtox test, respectively.
Treatment of Inverted Nipple with Subareolar Abscess: Usefulness of High-Resolution MRI for Preoperative Evaluation
Authors: Enomoto Sayaka , Matsuzaki Kyoichi
Published: July 2012

Background. Inverted nipples with subareolar abscesses can recur due to insufficient resection. It is important to provide reliable curative treatment after determination of the extent of resection by preoperative imaging evaluation. Methods. Ten patients were treated for inverted nipples with subareolar abscess. Sonography and high-resolution MRI were used as preoperative imaging modalities. The endpoints of preoperative imaging evaluation were defined as the identification of the abscess site, isolated fistula site, and extent of inflammation. Results. In all patients, sonography confirmed the presence of abscesses but their locations could not be identified. Sonography could not confirm the presence of isolated fistula or inflammation. In contrast, high-resolution MRI not only confirmed the presence of abscesses but also revealed their positional relationships with the nipples. In addition, high-resolution MRI confirmed the presence of isolated fistulas and inflammation as well as revealed their positional relationships with the nipples. In all patients, no recurrence was observed, and satisfactory surgical results were obtained. Conclusion. High-resolution MRI is useful in determination of the extent of resection of subareolar abscess associated with inverted nipple.
Impact of Oxidative Stress in Fetal Programming
Authors: Thompson Loren P. , Al-Hasan Yazan
Published: July 2012

Intrauterine stress induces increased risk of adult disease through fetal programming mechanisms. Oxidative stress can be generated by several conditions, such as, prenatal hypoxia, maternal under- and overnutrition, and excessive glucocorticoid exposure. The role of oxidant molecules as signaling factors in fetal programming via epigenetic mechanisms is discussed. By linking oxidative stress with dysregulation of specific target genes, we may be able to develop therapeutic strategies that protect against organ dysfunction in the programmed offspring.
Pilot Study of the Delivery of Microcollimated Pars Plana External Beam Radiation in Porcine Eyes: 270-Day Analysis
Authors: Singh Rishi P. , Shusterman E. Mark , Moshfeghi Darius , Danis Ronald , Gertner Michael
Published: July 2012

Objective. To determine the dose response and toxicity threshold of micro-collimated X-rays delivered to porcine maculae by a stereotactic radiosurgical system after 270 days.Methods. Twelve eyes of six Yucatan mini-swine were randomized to receive up to 90 Gy to the retina, using an office-based trans-pars plana delivery system. To determine the safety profile of this radiation delivery, ophthalmic examination, fundus photography, fluorescein angiography (FA), and spectral domain optical coherence tomography (SD-OCT) were obtained at multiple time points up to 270 days post treatment.Results. No abnormalities were noted on external examination. Cataracts were noted in 4 of 12 eyes. Dose and time-dependent changes were noted on fundus examination, FA, ICG and SD-OCT. No significant abnormalities were seen in the control, 16 Gy or 24 Gy groups using any modality. Histopathology revealed a dose response effect with no discernable lesions in the 16 Gy group.Conclusion. The X-ray delivery system precisely targets the porcine retina in vivo with little effect on surrounding structures. No ophthalmic or intracranial adverse effects were noted at clinically relevant doses at 270 days following radiation delivery.
Different Origins of the Fractionation of Platinum-Group Elements in Raobazhai and Bixiling Mafic-Ultramafic Rocks from the Dabie Orogen, Central China
Authors: Liu Qing , Hou Quanlin , Xie Liewen , Li Hui , Ni Shanqin , Wu Yudong
Published: July 2012

Concentrations of the platinum group elements (PGEs), including Ir, Ru, Rh, Pt, and Pd, have been determined for both Raobazhai and Bixiling mafic-ultramafic rocks from the Dabie Orogen by fire assay method. Geochemical compositions suggest that the Raobazhai mafic-ultramafic rocks represent mantle residues after variable degrees of partial melting. They show consistent PGE patterns, in which the IPGEs (i.e., Ir and Ru) are strongly enriched over the PPGEs (i.e., Pt and Pd). Both REE and PGE data of the Raobazhai mafic-ultramafic rocks suggest that they have interacted with slab-derived melts during subduction and/or exhumation. The Bixiling ultramafic rocks were produced through fractional crystallization and cumulation from magmas, which led to the fractionated PGE patterns. During fractional crystallization, Pd is in nonsulfide phases, whereas both Ir and Ru must be compatible in some mantle phases. We suggest that the PGE budgets of the ultramafic rocks could be fractionated by interaction with slab-derived melts and fractional crystallization processes.
Ki-67 Antigen Overexpression Is Associated with the Metaplasia-Adenocarcinoma Sequence in Barrett's Esophagus
Authors: Volkweis Bernardo Silveira , Gurski Richard Ricachenevsky , Meurer Luise , Pretto Guilherme Gonçalves , Mazzini Guilherme da Silva , Edelweiss Maria Isabel
Published: July 2012

Introduction. The objective of this study was to evaluate Ki-67 antigen expression in patients with Barrett’s esophagus and esophageal adenocarcinoma and to assess its correlation with the metaplasia-esophageal adenocarcinoma progression.Methods. Using immunohistochemistry we evaluated the Ki-67 index in patients with Barrett’s esophagus, esophageal adenocarcinoma, and controls. We included patients with endoscopically visible columnar mucosa of the distal esophagus (whose biopsies revealed specialized intestinal-type metaplasia), patients with esophageal and esophagogastric tumors types I and II, and patients with histologically normal gastric mucosa (control).Results. In the 57 patients studied there were no statistically significant differences between the groups with respect to age or race. Patients with cancer were predominantly men. The Ki-67 index averaged10±4% in patients with normal gastric mucosa (n=17),21±15% in patients with Barrett’s esophagus (n=21), and38±16% in patients with cancer (n=19). Ki-67 expression was significantly different between all groups (P<0.05). There was a strong linear correlation between Ki-67 expression and the metaplasia-adenocarcinoma sequence (P<0.01). In patients with cancer, Ki-67 was not associated with clinical or surgical staging.Conclusions. Ki-67 antigen has increased expression along the metaplasia-adenocarcinoma sequence. There is a strong linear correlation between Ki-67 proliferative activity and Barrett’s carcinogenesis.
In SilicoModelling of Tumour Margin Diffusion and Infiltration: Review of Current Status
Authors: Moghaddasi Fatemeh Leyla , Bezak Eva , Marcu Loredana
Published: July 2012

As a result of advanced treatment techniques, requiring precise target definitions, a need for more accurate delineation of the Clinical Target Volume (CTV) has arisen. Mathematical modelling is found to be a powerful tool to provide fairly accurate predictions for the Microscopic Extension (ME) of a tumour to be incorporated in a CTV. In general terms, biomathematical models based on a sequence of observations or development of a hypothesis assume some links between biological mechanisms involved in cancer development and progression to provide quantitative or qualitative measures of tumour behaviour as well as tumour response to treatment. Generally, two approaches are taken: deterministic and stochastic modelling. In this paper, recent mathematical models, including deterministic and stochastic methods, are reviewed and critically compared. It is concluded that stochastic models are more promising to provide a realistic description of cancer tumour behaviour due to being intrinsically probabilistic as well as discrete, which enables incorporation of patient-specific biomedical data such as tumour heterogeneity and anatomical boundaries.
Transcriptional Regulation of thep53Tumor Suppressor Gene in S-Phase of the Cell-Cycle and the Cellular Response to DNA Damage
Authors: Reisman David , Takahashi Paula , Polson Amanda , Boggs Kristy
Published: July 2012

Thep53tumor suppressor induces the transcription of genes that negatively regulate progression of the cell cycle in response to DNA damage or other cellular stressors and thus participates in maintaining genome stability. Numerous studies have demonstrated thatp53transcription is activated before or during early S-phase in cells progressing from G0/G1into S-phase through the combined action of two DNA-binding factors RBP-Jκand C/EBPβ-2. Here, we review evidence that this induction occurs to provide availablep53mRNA in order to prepare the cell for DNA damage in S-phase, this ensuring a rapid response to DNA damage before exiting this stage of the cell cycle.
Reactive Chemical Vapor Deposition Method as New Approach for Obtaining Electroluminescent Thin Film Materials
Authors: Utochnikova Valentina V. , Kotova Oxana V. , Vaschenko Andrey A. , Lepnev Leonid S. , Vitukhnovsky Alexei G. , Kuzmina Natalia P.
Published: July 2012

The new reactive chemical vapor deposition (RCVD) method has been proposed for thin film deposition of luminescent nonvolatile lanthanide aromatic carboxylates. This method is based on metathesis reaction between the vapors of volatile lanthanide dipivaloylmethanate (Ln(dpm)3) and carboxylic acid (HCarb orH2Carb′) and was successfully used in case of HCarb. Advantages of the method were demonstrated on example of terbium benzoate (Tb(bz)3) ando-phenoxybenzoate thin films, and Tb(bz)3thin films were successfully examined in the OLED with the following structure glass/ITO/PEDOT:PSS/TPD/Tb(bz)3/Ca/Al. Electroluminescence spectra of Tb(bz)3showed only typical luminescent bands, originated from transitions of the terbium ion. Method peculiarities for deposition of compounds of dibasic acids H2Carb′ are established on example of terbium and europium terephtalates and europium 2,6-naphtalenedicarboxylate.
Glioblastoma Presenting with Steroid-Induced Pseudoregression of Contrast Enhancement on Magnetic Resonance Imaging
Authors: Mazur Marcus D. , Nguyen Vinh , Fults Daniel W.
Published: July 2012

Corticosteroid-induced reduction in contrast enhancement on radiographic imaging is most commonly associated with lymphoma but has been reported in other entities, including glioma. This finding may represent a diagnostic dilemma. Concern that steroid-induced cytotoxicity obscures histological diagnosis of suspected lymphoma may lead to postponement of a biopsy. If glioma is not considered in the differential diagnosis, reduction in tumor contrast enhancement may be misinterpreted as disease regression rather than a transient radiographic change. We report a case of a patient with an enhancing right temporoparietal mass adjacent to the atrium of the lateral ventricle. After treatment with dexamethasone was started, the mass exhibited marked reduction in contrast enhancement, with symptom improvement. The clinical course suggested lymphoma, and surgery was not performed. Subsequent screening for extra-axial lymphoma was negative. Two weeks later, the patient developed worsening symptoms, and repeat T1-weighted imaging showed interval increase in size and enhancement. The findings suggested a possible diagnosis of malignant glioma. The patient underwent a stereotactic-guided craniotomy for excision of the right temporoparietal mass lesion. Final histological diagnosis was glioblastoma multiforme, World Health Organization grade IV.
NECOP Propagation Experiment: Rain-Rate Distributions Observations and Prediction Model Comparisons
Authors: Ojo J. S. , Falodun S. E.
Published: July 2012

Empirical distribution functions for one-minute average rain-rate values were compiled for three station year of observations at Nigeria environmental and climatic observatory (NECOP) propagation experiment terminal sites. The empirical distribution functions were compared with cumulative distribution functions generated using four different rain-rate distribution models. It is found that although each of the models shows similar qualitative features at lower exceedance of time, the characteristic at higher time percentages shows quantitative difference from the experimental data except the improved version of Moupfouma model. The results further show that the rainfall rate and the microwave propagation characteristics in this region are out of accord with International Telecommunication Union predictions. This information is vital for predicting rain fading cumulative probability distributions over this region.
Placental Amino Acids Transport in Intrauterine Growth Restriction
Authors: Avagliano Laura , Garò Chiara , Marconi Anna Maria
Published: July 2012

The placenta represents a key organ for fetal growth as it acts as an interface between mother and fetus, regulating the fetal-maternal exchange of nutrients, gases, and waste products. During pregnancy, amino acids represent one of the major nutrients for fetal life, and both maternal and fetal concentrations are significantly different in pregnancies with intrauterine growth restriction when compared to uncomplicated pregnancies. The transport of amino acids across the placenta is a complex process that includes the influx of neutral, anionic, and cationic amino acids across the microvilluos plasma membrane of the syncytiotrophoblast, the passage through the cytoplasm of the trophoblasts, and the transfer outside the trophoblasts across the basal membrane into the fetal circulation. In this paper, we review the transport mechanisms of amino acids across the placenta in normal pregnancies and in pregnancies complicated by intrauterine growth restriction.
A Phase I Dose-Escalation Trial of Trastuzumab and Alvespimycin Hydrochloride (KOS-1022; 17 DMAG) in the Treatment of Advanced Solid Tumors
Authors: Jhaveri Komal , Miller Kathy , Rosen Lee , Schneider Bryan , Chap Linnea , Hannah Alison , Zhong Ziyang , Ma Weining , Hudis Clifford , Modi Shanu
Published: July 2012

Purpose: We conducted a phase I dose-escalation study to define the maximum tolerated dose (MTD), pharmacokinetics (PK), and pharmacodynamics of alvespimycin (17-DMAG), a heat shock protein 90 (Hsp90) inhibitor, given in combination with trastuzumab.

Experimental Design: Patients were treated with trastuzumab followed by intravenous alvespimycin on a weekly schedule. Hsp90 client proteins were measured at baseline and serially in peripheral blood lymphocytes (PBL) during cycle 1. Patients with advanced solid tumors progressing on standard therapy were eligible.

Results: Twenty-eight patients (25, breast; 3, ovarian) were enrolled onto three dose cohorts: 60 (n = 9), 80 (n = 13), and 100 mg/m2 (n = 6). Dose-limiting toxicities (DLT) were: grade III left ventricular systolic dysfunction presenting as congestive heart failure in 1 patient (100 mg/m2), and reversible grade III keratitis in two patients (80 mg/m2). Drug-related grade III toxicity included one episode each of fatigue, diarrhea, myalgia, and back pain. Common mild to moderate toxicities included diarrhea, fatigue, myalgia, arthralgia, nausea, blurry vision, headache, back pain, and dry eyes. There was one partial response and seven cases of stable disease (range, 4–10 months), all in HER2+ MBC. In addition, an ovarian cancer patient had complete resolution of ascites and pleural effusion that lasted 24.8 months. There was no change in PK upon weekly dosing. Hsp70 effect continued to increase across four weeks and was most pronounced at 80 and 100 mg/m2.

Conclusion: The combination of alvespimycin and trastuzumab is safe and tolerable at MTD. Antitumor activity was seen in patients with refractory HER2+ MBC and ovarian cancer. The recommended dose of alvespimycin for further study in this combination is 80 mg/m2 weekly. Clin Cancer Res; 18(18); 5090–8. ©2012 AACR.
Peptidomimetic Src/Pretubulin Inhibitor KX-01 Alone and in Combination with Paclitaxel Suppresses Growth, Metastasis in Human ER/PR/HER2-Negative Tumor Xenografts
Authors: Anbalagan Muralidharan , Ali Alaa , Jones Ryan K. , Marsden Carolyn G. , Sheng Mei , Carrier Latonya , Bu Yahao , Hangauer David , Rowan Brian G.
Published: July 2012

Src kinase is elevated in breast tumors that are ER/PR negative and do not overexpress HER2, but clinical trials with Src inhibitors have shown little activity. The present study evaluated preclinical efficacy of a novel peptidomimetic compound, KX-01 (KX2-391), that exhibits dual action as an Src and pretubulin inhibitor. KX-01 was evaluated as a single-agent and in combination with paclitaxel in MDA-MB-231, MDA-MB-157, and MDA-MB-468 human ER/PR/HER2-negative breast cancer cells. Treatments were evaluated by growth/apoptosis, isobologram analysis, migration/invasion assays, tumor xenograft volume, metastasis, and measurement of Src, focal adhesion kinase (FAK), microtubules, Ki67, and microvessel density. KX-01 inhibited cell growth in vitro and in combination with paclitaxel resulted in synergistic growth inhibition. KX-01 resulted in a dose-dependent inhibition of MDA-MB-231 and MDA-MB-157 tumor xenografts (1 and 5 mg/kg, twice daily). KX-01 inhibited activity of Src and downstream mediator FAK in tumors that was coincident with reduced proliferation and angiogenesis and increased apoptosis. KX01 also resulted in microtubule disruption in tumors. Combination of KX-01 with paclitaxel resulted in significant regression of MDA-MB-231 tumors and reduced metastasis to mouse lung and liver. KX-01 is a potently active Src/pretubulin inhibitor that inhibits breast tumor growth and metastasis. As ER/PR/HER2-negative patients are candidates for paclitaxel therapy, combination with KX-01 may potentiate antitumor efficacy in management of this aggressive breast cancer subtype. Mol Cancer Ther; 11(9); 1936–47. ©2012 AACR.
Pioglitazone, a PPARγ Agonist, Suppresses CYP19 Transcription: Evidence for Involvement of 15-Hydroxyprostaglandin Dehydrogenase and BRCA1
Authors: Subbaramaiah Kotha , Howe Louise R. , Zhou Xi Kathy , Yang Peiying , Hudis Clifford A. , Kopelovich Levy , Dannenberg Andrew J.
Published: July 2012

Estrogen synthesis is catalyzed by cytochrome P450 aromatase, which is encoded by the CYP19 gene. In obese postmenopausal women, increased aromatase activity in white adipose tissue is believed to contribute to hormone-dependent breast cancer. Prostaglandin E2 (PGE2) stimulates the cAMP→protein kinase A (PKA) pathway leading to increased CYP19 transcription and elevated aromatase activity in inflamed white adipose tissue. 15-hydroxyprostaglandin dehydrogenase (15-PGDH) plays a major role in the catabolism of PGE2. Here, we investigated the mechanism by which pioglitazone, a ligand of the nuclear receptor PPARγ suppressed aromatase expression. Treatment of human preadipocytes with pioglitazone suppressed Snail, a repressive transcription factor, resulting in elevated levels of 15-PGDH and reduced levels of PGE2 in the culture medium. Pioglitazone also inhibited cAMP→PKA signaling leading to reduced interaction between phosphorylated cAMP responsive element–binding protein, p300, and CYP19 I.3/II promoter. BRCA1, a repressor of CYP19 transcription, was induced by pioglitazone. Consistent with these in vitro findings, treatment of mice with pioglitazone activated PPARγ, induced 15-PGDH and BRCA1 while suppressing aromatase levels in the mammary gland. Collectively, these results indicate that the activation of PPARγ induces BRCA1 and suppresses the PGE2→cAMP→PKA axis leading to reduced levels of aromatase. PPARγ agonists may have a role in reducing the risk of hormone-dependent breast cancer in obese postmenopausal women. Cancer Prev Res; 5(10); 1183–94. ©2012 AACR.
Selective Activation of Oxygen-Deprived Tumor-Infiltrating Lymphocytes through Local Intratumoral Delivery of CD137 Monoclonal Antibodies
Authors: Melief Cornelis J.M.
Published: July 2012

Summary: Hypoxia-inducing transcription factor-1α (HIF-1α) in hypoxic tumors induces the TNF receptor family member CD137 on tumor-infiltrating lymphocytes. This can be exploited for intratumoral low-dose injection of effective systemic immunotherapy with agonist CD137-specific monoclonal antibodies that induce circulation of systemic tumor-specific effector T cells capable of eradicating distant metastases. Cancer Discov; 2(7); 586–7. ©2012 AACR.

Commentary on Palazón et al., p. 608.
Association between Thigh Muscle Development and the Metabolic Syndrome in Adults
Authors: Londoño Francisco J. , Calderón Juan C. , Gallo Jaime
Published: July 2012

Background: Previous research has demonstrated an association between the metabolic syndrome (MS) and muscle mass; however, no studies have shown any relationship with a particular segment of the body, which would be more useful in clinical settings. Aims: To investigate the association between muscle development of different segments of the body and presence of the MS in adults. Methods: We used fractionation of body mass to calculate the development of muscle mass and correlated this with presence of the MS in a cross-sectional study in adults. Results: The mean age and body mass index were 42.7 ± 6.6 years and 25.3 ± 3.7 kg/m2, respectively. 23.1% of adults suffered from the MS. After adjusting for multiple variables, the Z score of both thigh and chest muscle girths were significantly associated with the MS. There were significant differences between adults with or without the MS in the Z score of thigh [–0.686; 95% confidence interval (95% CI) –1.020 to –0.351], mid-thigh (–0.566; 95% CI –0.931 to –0.200) and chest (0.611; 95% CI 0.260–0.962) girths. Conclusions: There is an association between muscle development and the MS; moreover, muscle thigh perimeter was larger in those without the MS. The use of muscle development of the thigh as an indicator of cardiovascular health-related metabolic alterations is proposed.