bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin resistance is associated with skeletal muscle weakness in COPD
Authors: Wells Claire E , Polkey Michael I , Baker Emma H
Published: December 2015

Background and objective

Quadriceps weakness is seen across all GOLD stages of COPD and is associated with increased morbidity and mortality. As quadriceps weakness is only weakly associated with FEV1, mechanisms other than airflow obstruction are implicated. We tested the hypothesis that insulin resistance contributes to skeletal muscle weakness in people with stable COPD.

Methods

Fifty‐one COPD patients (no exacerbations preceding 6 weeks, no rehabilitation preceding 3 months) without known diabetes mellitus underwent assessment of skeletal muscle, including measurement of quadriceps maximal voluntary contraction (QMVC). Physical activity was measured for 7 days using a multisensory biaxial accelerometer armband. Insulin resistance (HOMA2 IR) was calculated from fasting blood glucose and insulin concentrations.

Results

QMVC was 30 ± 13 kg (74 ± 25% predicted) and 16 (31%) participants had quadriceps weakness. There was a negative univariate correlation between HOMA2 IR and QMVC (r = −0.446, P = 0.002). HOMA2 IR was greater in people with quadriceps weakness (1.59 ± 0.99) than in those without (1.11 ± 0.55, P = 0.032). On multivariate analysis, with age, sex, weight, BODE index and step count per day included in the model, a one‐unit increase in insulin resistance was associated with a 5.9 (2.0–9.8)‐kg decrease in QMVC (P = 0.004) and a 4.2 (1.3–14.3)‐fold increased risk of quadriceps weakness (P = 0.02).

Conclusion

Insulin resistance is associated with skeletal muscle weakness in COPD, independent of potential confounders. Further studies are required to explore underlying mechanisms and determine whether insulin‐sensitizing drugs could augment pulmonary rehabilitation in building skeletal muscle strength in COPD.
Liver Resident Macrophages (Kupffer Cells) Share Several Functional Antigens in Common with Endothelial Cells
Authors: Okada T. , Kimura A. , Kanki K. , Nakatani S. , Nagahara Y. , Hiraga M. , Watanabe Y.
Published: December 2015

The identification and specific functions of Kupffer cells (KCs), a liver resident macrophage subpopulation, are still unclear. We compared KCs with peritoneal macrophages using cDNA microarray analysis and found that these cells share some antigens with endothelial cells. KCs highly express VCAM‐1 and VEGF receptors (VEGF‐Rs) at transcriptional and protein levels. VCAM‐1 mediates the functional binding of KCs with lymphocytes and induces KC activation. Among the VEGF receptors, VEGF‐R2 and VEGF‐R3 were expressed on the KCs, while VEGF‐R1 was expressed on other tissue macrophage subsets. VEGF120, a ligand of both VEGF‐R1 and VEGF‐R2, transduced strong survival and chemotactic signals through the KCs, when compared to PIGF, a VEGF‐R1 ligand, indicating that VEGF‐R2 plays significant roles in regulating KC activities. Expression of the VEGF‐Rs was regulated by TLR4 signalling. These results suggest that the function of KCs is partly regulated by the common antigens shared with endothelial cells.
Penalized Weighted Least Squares to Small Area Estimation
Authors: Zhu Rong , Zou Guohua , Liang Hua , Zhu Lixing
Published: December 2015

In this paper, a penalized weighted least squares approach is proposed for small area estimation under the unit level model. The new method not only unifies the traditional empirical best linear unbiased prediction that does not take sampling design into account and the pseudo‐empirical best linear unbiased prediction that incorporates sampling weights but also has the desirable robustness property to model misspecification compared with existing methods. The empirical small area estimator is given, and the corresponding second‐order approximation to mean squared error estimator is derived. Numerical comparisons based on synthetic and real data sets show superior performance of the proposed method to currently available estimators in the literature.
Acute exercise stress promotes Ref1/Nrf2 signalling and increases mitochondrial antioxidant activity in skeletal muscle
Authors: Wang Ping , Li Chun Guang , Qi Zhengtang , Cui Di , Ding Shuzhe
Published: December 2015

New Findings

What is the central question of this study?

How does acute exercise affect the redox effector factor‐1 (Ref1) and nuclear factor erythroid 2‐related factor 2 (Nrf2) signalling and its association with mitochondrial H2O2 production and antioxidant capacity?

What is the main finding and its importance?

Ref1/Nrf2 signalling in skeletal muscles was activated by acute exercise, and this activation was correlated with increased mitochondrial H2O2 content and antioxidant capacity (reduced glutathione and manganese superoxide dismutase). The finding indicates that the oxidative stress induced by acute exercise in skeletal muscle mitochondria is associated with the upregulation of Ref1/Nrf2 signalling and enhancement of antioxidant defense pathways. This mechanism may play a role in preventing cellular oxidative stress resistance during acute exercise.

The molecular mechanism of exercise‐induced oxidative stress and adaptive activation of antioxidant responses in skeletal muscle has not been fully elucidated. This study aimed to investigate the effect of acute exercise on redox effector factor‐1 (Ref1) and nuclear factor erythroid 2‐related factor 2 (Nrf2) signalling and associations with mitochondrial H2O2 production and antioxidant mechanisms in skeletal muscles. Groups of male ICR/CD‐1 mice were subjected to an acute exercise bout of different durations (45, 90, 120 or 150 min). Muscle tissues (gastrocnemius and quadriceps femoris) were harvested after exercise to measure mitochondrial manganese superoxide dismutase (MnSOD) and copper–zinc superoxide dismutase (CuZnSOD) activities, reduced glutathione (GSH) content and expression of Ref1/Nrf2 genes and Ref1/Nrf2 proteins. The acute exercise increased oxidative stress and activated Ref1/Nrf2 signalling in a time‐dependent manner, with a linear correlation between the mitochondrial H2O2 content and Ref1/Nrf2 expressions. The GSH content and MnSOD activity were also significantly increased, but CuZnSOD activity was not significantly affected. The findings indicate that the H2O2 production induced by acute exercise in skeletal muscle mitochondria in the mouse is closely associated with upregulation of the Ref1/Nrf2 signalling pathway and enhancement of antioxidant defense components, including GSH and MnSOD. Activation of Ref1/Nrf2/antioxidant defense pathways may play a role in preventing cellular oxidative stress resistance during acute exercise.
Sine-wave and noise-vocoded sine-wave speech in a tone language: Acoustic details matter
Authors: Rosen Stuart , Hui Sze Ngar Catherine
Published: December 2015

Sine-wave speech (SWS) is a highly simplified version of speech consisting only of frequency- and amplitude-modulated sinusoids representing the formants. That listeners can successfully understand SWS has led to claims that speech perception must be based on abstract properties of the stimuli far removed from their specific acoustic form. Here it is shown, in bilingual Cantonese/English listeners, that performance with Cantonese SWS is improved by noise vocoding, with no effect on English SWS utterances. This manipulation preserves the abstract informational structure in the signals but changes its surface form. The differential effects of noise vocoding likely arise from the fact that Cantonese is a tonal language and hence more reliant on fundamental frequency (F0) contours for its intelligibility. SWS does not preserve tonal information from the original speech but does have false tonal information signalled by the lowest frequency sinusoid. Noise vocoding SWS appears to minimise the tonal percept, which thus interferes less in the perception of Cantonese. It has no effect in English, which is minimally reliant on F0 variations for intelligibility. Therefore it is not only the informational structure of a sound that is important but also how its acoustic detail interacts with the phonological structure of a given language.
Pacing Adjustments Associated With Familiarization: Heat Versus Temperate Environments
Authors: Schmit Cyril , Duffield Rob , Hausswirth Christophe , Coutts Aaron J. , Le Meur Yann
Published: December 2015

Purpose:

To describe the effect of the initial perceptual experience from heat familiarization on the pacing profile during a freepaced endurance time trial (TT) compared with temperate conditions.

Methods:

Two groups of well-trained triathletes performed two 20-km TTs in either hot (35°C and 50% relative humidity [RH], n = 12) or temperate (21°C and 50% RH, n = 22) conditions, after standardization of training for each group before both trials. To ensure no physiological acclimation differences between conditions, the TTs for both groups were separated by 11 ± 4 d.

Results:

Performance improvement in the heat (11 ± 24 W) from the 1st to 2nd trial appeared comparable to that in temperate conditions (8 ± 14 W, P = .67). However, the specific alteration in pacing profile in the heat was markedly different than temperate conditions, with a change from “positive” to an “even” pacing strategy.

Conclusions:

Altered perceptions of heat during heat familiarization, rather than physiological acclimatization per se, may mediate initial changes in pacing and TT performance in the heat. These results highlight the need for athletes without time for sufficient heat acclimatization to familiarize themselves with hot conditions to reduce the uncertainty from behavior-based outcomes that may impede performance.
Architecture of human mTOR complex 1
Authors: Aylett Christopher H. S. , Sauer Evelyn , Imseng Stefan , Boehringer Daniel , Hall Michael N. , Ban Nenad , Maier Timm
Published: December 2015

From sensing leucine to metabolic control

The mTORC1 protein kinase complex plays central roles in regulating cell growth and metabolism and is implicated in common human diseases such as diabetes and cancer. The level of the amino acid leucine tells an organism a lot about its physiological state, including how much food is available, how much insulin is going to be needed, and whether new muscle mass can be made (see the Perspective by Buel and Blenis). Wolfson
et al.
identified a biochemical sensor of leucine, Sestrin2, which connects the concentration of leucine to the control of organismal metabolism and growth. When leucine bound to Sestrin2, it was released from a complex with the mTORC1 regulatory factor GATOR2, activating the mTORC1 complex. Saxton
et al.
describe the crystal structure of Sestrin2 and show how it specifically detects leucine. Aylett
et al.
determined the structure of human mTORC1 by cryoelectron microscopy and the crystal structure of a regulatory subunit, Raptor. The results reveal the structural basis for the function and intricate regulation of this important enzyme, which is also a strategic drug target.

Science
, this issue p.
43
, p.
48
, p.
53
; see also p.
25
Genome Sequences of 11 Brucella abortus Isolates from Persistently Infected Italian Regions
Authors: Garofolo Giuliano , Foster Jeffrey T. , Drees Kevin , Zilli Katiuscia , Platone Ilenia , Ancora Massimo , Cammà Cesare , De Massis Fabrizio , Calistri Paolo , Di Giannatale Elisabetta
Published: December 2015

Bovine brucellosis, typically caused by
Brucella abortus
, has been eradicated from much of the developed world. However, the disease remains prevalent in southern Italy, persisting as a public and livestock health concern. We report here the whole-genome sequences of 11 isolates from cattle (
Bos taurus
) and water buffalo (
Bubalus bubalis
) that are representative of the current genetic diversity of
B. abortus
lineages circulating in Italy.
Permanent Draft Genome Sequence of
Frankia
sp. Strain ACN1
ag
, a Nitrogen-Fixing Actinobacterium Isolated from the Root Nodules of
Alnus glutinosa
Authors: Swanson Erik , Oshone Rediet , Simpson Stephen , Morris Krystalynne , Abebe-Akele Feseha , Thomas W. Kelley , Tisa Louis S.
Published: December 2015

Frankia
strain ACN1
ag
is a member of
Frankia
lineage Ia, which are able to re-infect plants of the
Betulaceae
and
Myricaceae
families. Here, we report a 7.5-Mbp draft genome sequence with a G+C content of 72.35% and 5,687 candidate protein-encoding genes.
Gallstone ileus of the sigmoid colon: an extremely rare cause of large bowel obstruction detected by multiplanar CT
Authors: Carlsson Tarryn , Gandhi Sanjay
Published: December 2015

Gallstone ileus of the sigmoid colon is an important, though extremely rare, cause of large bowel obstruction. The gallstone often enters the large bowel through a fistula formation between the gallbladder and colon, and impacts at a point of narrowing, causing large bowel obstruction. We describe the case of an 80-year-old woman who presented with features of bowel obstruction. Multiplanar abdominal CT demonstrated a cholecystocolonic fistula in exquisite detail. The scan also showed obstruction of the colon due to a large gallstone impacted just proximal to a stricture in the sigmoid. Owing to inflammatory adhesions and a stricture from extensive diverticular disease, the gallstone could not be retrieved. This frail and elderly woman was treated with a loop colostomy to relieve bowel obstruction. The patient made an uneventful recovery.
Difficult diagnosis: internal herniation of the terminal ileum through the foramen of Winslow into the lesser sac
Authors: Nazarian Scarlet , Clegg Daisy , Chang Sebastian , Kuriakose John
Published: December 2015

Herniation of the bowel through the foramen of Winslow is rare and accounts for 8% of all internal herniae. It typically presents clinically and biochemically as small bowel obstruction. It carries a high mortality as diagnosis is often delayed, despite bowel strangulation, as clinical signs are not typical and imaging may not be diagnostic. In the case presented here, a healthy 25-year-old man was admitted with sudden onset right-sided abdominal and back pain. He denied vomiting, and had opened his bowels. His bloods were normal and venous lactate <2; CT was not diagnostic. At laparotomy, he was found to have internal herniation of the terminal ileum through the foramen of Winslow, which was gangrenous and required resection. This paper discusses the difficulty in diagnosing internal herniation and poses the question as to whether we are too dependent on CT findings in the setting of an acute abdomen.
Aplasia of the lung in a neonate—the myth is explored
Authors: Aswathanarayana Iyer Venkatesh Harohalli , Charki Siddu , Shanthigrama Ramachandra Kumar
Published: December 2015

A term appropriate for gestational age baby boy was delivered by lower segment caesarean section. The baby was antenatally diagnosed with resolving cystic adenomatoid malformation. At birth, he developed respiratory distress requiring active resuscitation and later was diagnosed to have right lung aplasia, managed with respiratory support. He gradually improved and was discharged home on room air.
Angioleiomyoma of the larynx: beware the subglottic lesion
Authors: Hope Nicholas , Smith Caroline Patricia , McCluney Neil
Published: December 2015

Angioleiomyomas are a benign group of tumours rarely documented in the head and neck region. We present a case of a 47-year-old man attending the ear, nose and throat outpatient clinic, with a history of hoarseness over many years. Investigation revealed a left-sided subglottic lesion. He underwent microlaryngoscopy and biopsy, and the lesion was sent for histological analysis. Postoperatively, the patient began to expectorate fresh red blood that continued for several hours, requiring surgical intervention. Haemostatic control was achieved and a tracheostomy was sited for airway protection. Histopathology identified angioleiomyoma as the cause of his symptoms. Following multidisciplinary team discussion, this was managed with injection of bleomycin and subsequent surgical excision. This case is a reminder that subglottic lesions are often vascular in nature, and should be investigated with imaging and angiography prior to surgery, to avoid complications.
The assessment of Ki-67 as a prognostic marker in neuroendocrine tumours: a systematic review and meta-analysis
Authors: Richards-Taylor Sebastian , Ewings Sean M , Jaynes Eleanor , Tilley Charles , Ellis Sarah G , Armstrong Thomas , Pearce Neil , Cave Judith
Published: December 2015

Introduction

Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are classified according to tumour mitotic count or Ki-67 labelling index (LI).

Aim(s)

To systematically review articles reporting the prognosis of patients by Ki-67 LI and thereby improve the ability of clinicians to prognosticate for their patients.

Method

265 abstracts were identified relating Ki-67 and survival. After exclusion criteria were applied, 22 articles remained. Articles were excluded if they described non-human specimens, were non-English language, published prior to 2000, reported non-GEP NETs, reported subgroups selected by treatment modality or included <20 cases. Random-effects meta-analysis was used to combine studies to estimate survival proportions.

Results

Authors used varied methods in which to present 5-year survival, with often limited survival information. This reduced the number of studies that could be included in the meta-analysis. 5-year survival for patients with grade 1 and 2 GEP NETs were estimated to be 89% (95% CI 85% to 92%, m=12 studies, n=977 participants) and 70% (95% CI 62% to 79%, m=9, n=726), respectively. Using an alternative grade 1/2 boundary of 5%, 5-year survival rates for Ki-67≤5% and 5–20% were estimated as 89% (95% CI 84% to 94%, m=7, n=654) and 51% (95% CI 44% to 59%, m=4, n=183), respectively. For Ki-67>20%, 5-year survival was estimated to be 25% (95% CI 12% to 38%, m=10, n=208).

Conclusions

Standardisation of grade boundaries has allowed us to combine data from multiple studies and amass a body of evidence linking Ki-67 and survival.
Socioeconomic status, comorbidity and mortality in patients with type 2 diabetes mellitus in Scotland 2004–2011: a cohort study
Authors: Walker Jeremy , Halbesma Nynke , Lone Nazir , McAllister David , Weir Christopher J , Wild Sarah H
Published: December 2015

Background

Mortality in people with and without diabetes often exhibits marked social patterning, risk of death being greater in deprived groups. This may reflect deprivation-related differences in comorbid disease (conditions additional to diabetes itself). This study sought to determine whether the social patterning of mortality in a population with type 2 diabetes mellitus (T2DM) is explained by differential comorbidity.

Methods

Hospital records for 70 197 men and 56 451 women diagnosed with T2DM at 25 years of age and above in Scotland during the period 2004–2011 were used to construct comorbidity histories. Sex-specific logistic models were fitted to predict mortality at 1 year after diagnosis with T2DM, predicted initially by age and socioeconomic status (SES) then extended to incorporate in turn 5 representations of comorbidity (including the Charlson Index). The capacity of comorbidity to explain social mortality gradients was assessed by observing the change in regression coefficients for SES following the addition of comorbidity.

Results

After adjustment for age and Charlson Index, the OR for the contrast between the least deprived and most deprived quintiles of SES for men was 0.79 (95% CI 0.67 to 0.94). For women, the OR was 0.81 (0.67 to 0.97). Similar results were obtained for the 4 other comorbidity measures used.

Conclusions

The social patterning of mortality in people with T2DM is not fully explained by differing levels of comorbid disease additional to T2DM itself. Other dimensions of deprivation are implicated in the elevated death rates observed in deprived groups of people with T2DM.
Late cosmic acceleration in a vector-Gauss–Bonnet gravity model
Authors: Oliveros A. , Solis Enzo L. , Acero Mario A.
Published: December 2015

In this work, we study a general vector–tensor model of dark energy (DE) with a Gauss–Bonnet term coupled to a vector field and without explicit potential terms. Considering a spatially flat Friedmann–Robertson–Walker (FRW) type universe and a vector field without spatial components, the cosmological evolution is analyzed from the field equations of this model considering two sets of parameters. In this context, we have shown that it is possible to obtain an accelerated expansion phase of the universe since the equation state parameter [Formula: see text] satisfies the restriction [Formula: see text] (for suitable values of model parameters). Further, analytical expressions for the Hubble parameter [Formula: see text], equation state parameter [Formula: see text] and the invariant scalar [Formula: see text] are obtained. We also find that the square of the speed of sound is negative for all values of redshift, therefore, the model presented here shows a sign of instability under small perturbations. We finally perform an analysis using [Formula: see text] observational data and we find that for the free parameter [Formula: see text] in the interval [Formula: see text], at 99.73% C.L. (and fixing [Formula: see text] and [Formula: see text]), the model has a good fit to the data.
A review on the structure of cold-compressed graphite phase
Authors: Zhai Jinhui , Wan Ajun , Wu Wenbin
Published: December 2015

The room-temperature structural phase transition of graphite at elevated hydrostatic pressure has drawn considerable scientific interest for its fundamental importance in condensed matter physics and materials science over the past few decades. A pressure-induced phase transition has been demonstrated in previous experiments by the measurement of electrical resistance, optical spectrum, X-ray diffraction spectrum, inelastic X-ray scattering and Raman spectroscopy. However, the nature of the cold-compressed graphite phase has been puzzling the experts and pioneers in the field of high pressure research due to some inherent factors, until recently a monoclinic structure, i.e. [Formula: see text]-carbon, stands out from the other structure candidates and successfully accounts for the crystal structure of the cold-compressed graphite phase both in theory and experiment that eventually putting an end to this long-lasting controversial issue. This paper reviews the recent progress on the pressure-induced phase transitions of graphite at room temperature especially for the theoretical investigations. The review will focus on the recent proposed novel carbon allotropes as candidate structures of the cold-compressed graphite phase by using different crystal structure prediction methods. The history of structure determination of cold-compressed graphite phase is discussed.
Shadow of a dressed black hole and determination of spin and viewing angle
Authors: Yang Lingyun , Li Zilong
Published: December 2015

Shadows of black holes surrounded by an optically thin emitting medium have been extensively discussed in the literature. The Hioki–Maeda algorithm is a simple recipe to characterize the shape of these shadows and determine the parameters of the system. Here, we extend their idea to the case of a dressed black hole, namely a black hole surrounded by a geometrically thin and optically thick accretion disk. While the boundary of the shadow of black holes surrounded by an optically thin emitting medium corresponds to the apparent photon capture sphere, that of dressed black holes corresponds to the apparent image of the innermost stable circular orbit (ISCO). Even in this case, we can characterize the shape of the shadow and infer the black hole spin and viewing angle. The shape and the size of the shadow of a dressed black hole are strongly affected by the black hole spin and inclination angle. Despite that, it seems that we cannot extract any additional information from it. Here, we study the possibility of testing the Kerr metric. Even with the full knowledge of the boundary of the shadow, those of Kerr and non-Kerr black holes are very similar and it is eventually very difficult to distinguish the two cases.
BANKING NETWORKS AND LEVERAGE DEPENDENCE IN EMERGING COUNTRIES
Authors: APARICIO DIEGO , FRAIMAN DANIEL
Published: December 2015

We construct banking networks using bank-level balance sheet data from 2005 to 2010 from five emerging countries: Argentina, Brazil, Mexico, South Africa, and Taiwan. The network interaction is based on the leverage ratio dependence between each pair of banks within a same country. Despite leverage and accounting rules heterogeneity, the results are robust across countries. The leverage diversity produces financial networks with a modular structure characterized by one large bank community, some small ones, and isolated banks. However, these groups of banks merge together creating a financial network topology that converges to a unique large cluster at a relatively low leverage dependence level. Finally, we simulate the banking system through a model of corporate and interbank loans with credit shocks, where links between banks arise due to insufficient liquidity. The model yields leverage-based networks that are similar to the empirical ones. A model prediction for banks’ growth is presented and tested in the data.
Application of portable XRF to the direct analysis of till samples from various deposit types in Canada
Authors: Hall Gwendy E.M. , McClenaghan M. Beth , Pagé Lilianne
Published: December 2015

In this study, results by direct portable XRF (‘pXRF’) on unsieved till samples were compared with those by established laboratory methods (aqua regia or fusion ICP-MS and ICP-ES) on the <0.063-mm fraction to determine if the application of direct pXRF in the field would serve as an acceptable guide for immediate follow-up work. Four test sites in Canada were chosen: the Halfmile Lake Cu-Pb-Zn VMS deposit; the intrusion-hosted W-Mo Sisson deposit; a Pb-Zn Mississippi Valley–type (MVT) deposit in the Pine Point district; and the Triple B kimberlite. Unsieved till samples from the GSC archive collection were used for this study and included samples from background areas, immediately overlying, and at various distances down-ice of each deposit. Ziploc® and Whirl-Pak® bags that were used to contain the samples in the field were tested for their properties of X-ray attenuation and contamination.

In general, the performance of pXRF in the four test areas was very good where concentrations of elements of interest (indicator or pathfinder elements) were substantially above detection limits by this technique (in the low ppm range for many elements). The following elements, shown to be useful indicator elements (important constituents of the ore/commodity) or pathfinder elements (those associated with the commodity elements) by the established methodology, showed similar patterns by pXRF on the unsieved material: Zn, Cu, Pb, and As at Halfmile Lake; W, Mo, Cu, Zn, Pb, and As at the Sisson deposit; Zn, Pb, and Fe at Pine Point; and Ca, Sr, Cr, and Ni at Triple B. Pathfinder elements whose concentrations were too low for determination by pXRF include: Ag and Sb at Halfmile Lake; Ag and Cd at Sisson; Cd, S, and Se at Pine Point; and Co, Mg, P, U, and Th at Triple B. The high background for Bi by pXRF, equivalent to
c
. 50 ppm, and its noisy signal precluded its use at Halfmile Lake and Sisson. Elements which tended to show poor precision (three analyses each sample) by pXRF in some samples due to sample heterogeneity include Sn, V, and W. Mercury was erroneously reported for the majority of samples in the low ppm range by pXRF whereas its concentration in fact was in the low ppb range. Several Pb-, Zn- (
c
. 1% Pb, Zn) and Fe-rich (up to 16% Fe) samples demonstrated spectral interferences by: Pb on As, Th and Se; Zn on Cu; and Fe on Co.

Results for six till samples analysed in Ziploc® and Whirl-Pak® bags showed that Ziploc® absorbs fewer low-energy photons and hence is preferable for determining light elements such as Si, K and Ca.

Supplementary material:

Four data-sets are available at
http://www.geolsoc.org.uk/SUP18897
Late Triassic capitosaurian remains from Svalbard and the palaeobiogeographical context of Scandinavian Arctic temnospondyls
Authors: Kear Benjamin P. , Poropat Stephen F. , Bazzi Mohamad
Published: December 2015

The Norwegian Arctic Svalbard archipelago is famous for its prolific record of Early–Middle Triassic vertebrate fossils. These represent mainly marine amniotes, together with sharks, bony fishes and temnospondyl amphibians, the latter providing an important faunal correlate with coeval assemblages from the Danish autonomous region of Greenland. However, substantial biostratigraphical gaps exist in the Upper Triassic strata of Svalbard, which are marked by pronounced facies shifts from marine to deltaic systems and intermittent depositional hiatuses. These are accompanied by a dearth of documented vertebrate remains, a notable exception being the partial skull of the capitosaurian
Capitosaurus polaris
and a few isolated stereospondylian intercentra probably from the middle–late Carnian De Geerdalen Formation of Spitsbergen. Reassessment of this material, which incorporates the only undisputed capitosaurian fossil from Svalbard, indicates affinity with
Cyclotosaurus
, known elsewhere from the late Norian–early Rhaetian Fleming Fjord Formation of Greenland. The Scandinavian Arctic temnospondyls constituted components of sympatric assemblages that inhabited the Boreal margin of Pangaea throughout the Triassic.
Coprolites from the Late Triassic Kap Stewart Formation, Jameson Land, East Greenland: morphology, classification and prey inclusions
Authors: Hansen Bitten Bolvig , Milàn Jesper , Clemmensen Lars B. , Adolfssen Jan Schulz , Estrup Eliza Jarl , Klein Nicole , Mateus Octávio , Wings Oliver
Published: December 2015

A large collection of vertebrate coprolites from black lacustrine shales in the Late Triassic (Rhaetian–Sinemurian) Kap Stewart Formation, East Greenland is examined with regard to internal and external morphology, prey inclusions, and possible relationships to the contemporary vertebrate fauna. A number of the coprolites were mineralogically examined by X-ray diffraction (XRD), showing the primary mineral composition to be apatite, clay minerals, carbonates and, occasionally, quartz in the form of secondary mineral grains. The coprolite assemblage shows multiple sizes and morphotypes of coprolites, and different types of prey inclusions, demonstrating that the coprolite assemblage originates from a variety of different producers.

Supplementary material:

A description of the size, shape, structure, texture, contents and preservation of the 328 specimens is available at
https://doi.org/10.6084/m9.figshare.c.2134335
Reservoir architectures of interlava systems: a 3D photogrammetrical study of Eocene cliff sections, Faroe Islands
Authors: Vosgerau Henrik , Passey Simon R. , Svennevig Kristian , Strunck Max N. , Jolley David W.
Published: December 2015

Following the intra-volcanic Rosebank discovery in the Faroe–Shetland Basin, NE Atlantic, there has been a need to find suitable analogues to characterize reservoir architectures, connectivities and compartmentalization of interlava clastic beds. The Faroe Islands, situated
c.
160–190 km to the NW of this discovery, are an exposed remnant of the Palaeogene lava field host and the near-vertical cliff sections afford the opportunity to map lateral variations over many kilometres. This was achieved through 3D photogrammetry based on high-resolution digital photographs taken from a helicopter. The study focused on the Eocene Enni Formation, which is dominated by a mixture of simple and compound lava flows commonly separated by minor volcaniclastic beds, including the widespread Argir Beds. In general, the interlava beds are tabular shaped and <1 to
c.
6 m thick. Locally they thicken in depressions formed by the wedging out or differential erosion of underlying lava flow lobes. Connectivity may be caused by the wedging out of successive lava flows leading to the lateral merging of interlava beds or more rarely be hydraulically connected via conglomeratic fills of major channels. Lateral compartmentalization may be caused by the intersection of interlava beds by dykes, lava tubes, lava-filled channels or reverse faults.
Heat shock proteins and exercise adaptations. Our knowledge thus far and the road still ahead
Authors: Henstridge Darren C. , Febbraio Mark A. , Hargreaves Mark
Published: December 2015

By its very nature, exercise exerts a challenge to the body's cellular homeostatic mechanisms. This homeostatic challenge affects not only the contracting skeletal muscle but also a number of other organs and results over time in exercise-induced adaptations. Thus it is no surprise that heat shock proteins (HSPs), a group of ancient and highly conserved cytoprotective proteins critical in the maintenance of protein and cellular homeostasis, have been implicated in exercise/activity-induced adaptations. It has become evident that HSPs such as HSP72 are induced or activated with acute exercise or after chronic exercise training regimens. These observations have given scientists an insight into the protective mechanisms of these proteins and provided an opportunity to exploit their protective role to improve health and physical performance. Although our knowledge in this area of physiology has improved dramatically, many questions still remain unanswered. Further understanding of the role of HSPs in exercise physiology may prove beneficial for therapeutic targeting in diseased patient cohorts, exercise prescription for disease prevention, and training strategies for elite athletes.
Abstract A28: C-reactive protein as a predictive marker of response to sunitinib treatment in metastatic clear cell renal carcinoma
Authors: Pilskog Martin , Beisland Christian , Straume Oddbjørn
Published: December 2015

Background: Antiangiogenic treatment, is currently first line therapy in metastatic renal cell carcinoma (RCC). Due to high drug costs and potentially serious side effects there is an urgent need for clinically useful predictive markers. We conducted a single center phase II clinical trial with sunitinib treatment for metastatic RCC.

Study Design: Forty-five patients with metastatic or non-resectable clear cell RCC were included. Sunitinib was given in cycles of six weeks (four weeks of treatment, two weeks pause). Follow up was every six week. Primary endpoint was response rates (RECIST 1.1). Secondary endpoints were time to progression (TTP) and overall survival (OS). Toxicity and quality of life were recorded.

Results: Twenty five (55 %) cases showed clinical benefit with complete response (CR): 1, partial response (PR): 6, stable disease (SD)>6months: 18. Twelve patients showed progressive disease (PD). Eight patients stopped treatment or were still under treatment prior to the first radiologic evaluation, and were recorded as non-evaluable. The following parameters were recorded at baseline; gender, age, ECOG-, WHO- and Karnofsky's performance status, Heng- and Motzer prognostic criteria, blood pressure, hemoglobin, white blood count, neutrophil count, platelets, sodium, potassium, creatinine, corrected calcium, C-reactive protein(CRP), albumin, lactate dehydrogenase, thyroid-stimulating hormone, thyroid hormones and D dimer, body mass index, use of antihypertensive medication, location of metastasis and tumor load. Of these, CRP ≤ 10 mg/L at baseline (vs CRP > 10 mg/L), was significantly associated with objective response (CR+PR) (Fisher's Exact test, p=0,030). Good performance status showed a significant association with clinical benefit (Fisher's Exact test, p=0,049). Toxicity data and quality of life data will be presented.

Conclusion: Of the clinical markers under investigation, only CRP at baseline as well as performance status were found to be possible predictive markers of response to sunitinib in metastatic RCC. Our patient population is comparable to those in already reported studies and might be useful to further investigations of angiogenesis related predictive markers of response.

Citation Format: Martin Pilskog, Christian Beisland, Oddbjørn Straume. C-reactive protein as a predictive marker of response to sunitinib treatment in metastatic clear cell renal carcinoma. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr A28.
Abstract B13: Hematopoietic stem cell-derived cancer-associated fibroblasts are novel contributors to the pro-tumorigenic microenvironment
Authors: McDonald Lindsay T. , Laws Dayvia A. , Kelly Ryan R. , Xiong Ying , Motamarry Anjan , Patel Risha K. , Jones Jeffrey A. , Watson Patricia M. , Turner David P. , Watson Dennis K. , Soloff Adam C. , Findlay Victoria J. , LaRue Amanda C.
Published: December 2015

Targeting the tumor microenvironment is critical towards improving the effectiveness of current cancer therapeutics. Cancer-associated fibroblasts (CAFs) are one of the most abundant cell types of the tumor microenvironment, playing an important role in tumor progression and angiogenesis. Multiple origins for CAFs have been proposed including resident fibroblasts, adipocytes, and bone marrow. Our laboratory previously identified a novel hematopoietic stem cell (HSC) origin for CAFs; however, the functional roles of HSC-derived CAFs (HSC-CAFs) in tumor progression have not yet been examined. Thus, to test the hypothesis that HSC-CAFs promote tumor progression via contribution to extracellular matrix (ECM) and through paracrine production of pro-angiogenic factors, we developed a method to isolate HSC-CAFs. HSC-CAFs were profiled based on their expression of hematopoietic and fibroblastic markers in two murine tumor models, Lewis lung carcinoma (LLC) and E0771 breast cancer. Findings revealed HSC-CAF production of factors associated with both ECM deposition and remodeling. Functional in vivo studies showed that co-injection of HSC-CAFs with tumor cells resulted in increased tumor growth rate and significantly larger tumors than injection of tumor cells alone. Immunohistochemical studies revealed increased blood vessel density with co-injection, demonstrating a role for HSC-CAFs in tumor progression through promotion of tumor vascularization in vivo. Mechanistic in vitro studies indicated a role for HSC-CAF produced vascular endothelial growth factor (VEGF-A) and transforming growth factor-beta-1 (TGFβ-1) in endothelial tube formation and vascular patterning. These in vitro and in vivo findings suggest that HSC-CAFs are a critical component of the tumor microenvironment contributing to ECM production, ECM remodeling, and tumor vascularization. Given their role in multiple components of tumor progression, targeting the novel HSC-CAF may be a promising therapeutic strategy alone or in combination with existing anti-angiogenesis therapies.

Citation Format: Lindsay T. McDonald, Dayvia A. Laws, Ryan R. Kelly, Ying Xiong, Anjan Motamarry, Risha K. Patel, Jeffrey A. Jones, Patricia M. Watson, David P. Turner, Dennis K. Watson, Adam C. Soloff, Victoria J. Findlay, Amanda C. LaRue. Hematopoietic stem cell-derived cancer-associated fibroblasts are novel contributors to the pro-tumorigenic microenvironment. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr B13.
Abstract B20: Activin receptor-like kinase 1 complexes with endoglin in TGFß-mediated signaling in angiogenesis
Authors: Hawker James , Varacallo Patricia , Duffy Iain
Published: December 2015

Background: Activin Receptor-Like Kinase 1 (ALK1), a type I transforming growth factor (TGFß) family receptor, and endoglin, a type III receptor, are expressed in endothelial cells (EC) and involved in angiogenesis. Control of angiogenesis is critical in diseases such as cancer. Four ligands, TGFß, activin, bone morphogenetic protein 9 (BMP-9), and BMP-10, have been shown to bind ALK-1. Thus angiogenesis may be mediated by different combinations of ligands and receptors. Purpose: We investigated the role of TGFß and ALK-1 in tube formation. We also screened EC and also cancer cell lines for expression of various TGFß family receptors to begin to address which ligands and receptors are involved in angiogenesis and endothelial-tumor interactions,. Results: We also show that fibroblast growth factor 2 (FGF-2) + TGFß increase ALK-1 but not ALK 5 type I receptor expression in endothelial cells after tube formation. We show data that the type I receptor Activin-Like Kinase 1 and the co-receptor endoglin can signal in endothelial cells via the TGFß ligand. Antisense RNA that targets ALK 1 (and also ALK5) also disrupts tube formation. We further show that endogenous activin binds ALK 1 and can be displaced by exogenous TGFß. This suggests it may function to regulate control of ALK 1 activation. Further, ALK-1 and endoglin may also be involved in cell-cell interactions between endothelial and other cells. Thus we screened endothelial and cancer cells for TGFß family receptor expression by RT-PCR. Endothelial cells show similar expression of ALK-1, ALK-5, and endoglin and lower expression of BMP receptor II and TGFßRII. Cancer cells show much lower expression of type II receptors.

Citation Format: James Hawker, Patricia Varacallo, Iain Duffy. Activin receptor-like kinase 1 complexes with endoglin in TGFß-mediated signaling in angiogenesis. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr B20.
Abstract B27: Activin A induces vascular endothelial cell proliferation and angiogenesis in oral cancer
Authors: Oliveira Carine Ervolino de , Cervigne Nilva de Karla , Macedo Carolina Carneiro Souza , Leme Adriana Franco Paes , Graner Edgard , Coletta Ricardo Della
Published: December 2015

Solid tumors must develop direct and indirect ways to induce angiogenesis in order to continue progression and expansion. The expression of angiogenic factors in the tumor microenvironment is a complex process involving interactions among different cell types. Previous studies demonstrated activin A, a member of the TGF-β superfamily, participates in the development and progression of oral squamous cell carcinomas (OSCC) via regulation of the tumor microenvironment, but its effects in the modulation of angiogenesis are unknown. We examined whether activin A, recombinant or derivate from OSCC cells, promotes angiogenesis of the human umbilical vein endothelial cells (HUVECs). Activin A-treated cells increased tubulogenesis activity concomitantly with high cellular proliferation and low apoptosis. Conversely, follistatin, an activin A antagonist, and activin A knock down in HUVECs significantly inhibited proliferation, induced apoptosis and decreases tube formation. Similarly, conditioned media harvested from OSCC cells expressing high activin A levels increased the proliferative rate and the tubulogenic activity of HUVECs more than those obtained from OSCC cells expressing a shRNA to neutralize activin A expression. In conclusion, our results show that activin A derived from OSCC cells promotes endothelial cell proliferation and tumor angiogenesis, suggesting that activin A signaling could be an important target for tumor vascular disruption in oral cancer. Financial support: FAPESP #2013/19856-2 and #2013/01607-6.

Citation Format: Carine Ervolino de Oliveira, Nilva de Karla Cervigne, Carolina Carneiro Souza Macedo, Adriana Franco Paes Leme, Edgard Graner, Ricardo Della Coletta. Activin A induces vascular endothelial cell proliferation and angiogenesis in oral cancer. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr B27.
Abstract IA17: Influence on vessel shape of macrophage metabolism in the tumor hypoxic niche
Authors: Mazzone Massimiliano
Published: December 2015

Cancer typically has an inflammatory nature. Of all immune cells invading the tumor, the role of macrophages remains controversial because of their functionally distinct differentiation states. Classically activated (M1-like) macrophages and alternatively activated (M2-like) macrophages represent the two extremities of a continuum, in which the former are proinflammatory and tumoricidal, whereas the latter display pro-angiogenic and protumoral activities. This heterogeneity reflects the plasticity and versatility of these cells in response to microenvironmental signals. The tumor environment is constituted of cancer cells and stromal cells that coexist under different oxygen tensions and the influence of soluble factors. A plethora of (hypoxia-induced) cytokines and chemokines can define the macrophage phenotype and their positioning within the tumor. We have elucidated an elegant mechanism by which macrophages are recruited and retained in avascular hypoxic niches of the tumor, where they exert their immunosuppressive and pro-angiogenic activity. Hypoxia by itself indeed strongly affects macrophage function, as the cells are forced to adapt and alter their metabolism, which is accompanied by a drastic change in their transcriptome and proteome. We have found that the resultant metabolic changes drive macrophages towards a pro-angiogenic phenotype in an attempt to restore oxygenation. Soluble factors derived from the tumor exacerbate this macrophage shift by further enforcing this metabolic adaptation. As a consequence, tumor blood vessels are abnormal and dysfunctional, thus perpetuating hypoxia, which in turn fosters metastasis. By using genetic tools in mice, we show that inhibiting macrophage recruitment in hypoxic niches, or altering their metabolic and energetic state can break this feed-forward loop, resulting in normalized blood vessels and thus, strongly reducing metastatic dissemination.

Citation Format: Massimiliano Mazzone. Influence on vessel shape of macrophage metabolism in the tumor hypoxic niche. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr IA17.
The Pattern of Brain Amyloid Load in Posterior Cortical Atrophy Using 18F-AV45: Is Amyloid the Principal Actor in the Disease
Authors: Beaufils Emilie , Ribeiro Maria Joao , Vierron Emilie , Vercouillie Johnny , Dufour-Rainfray Diane , Cottier Jean-Philippe , Camus Vincent , Mondon Karl , Guilloteau Denis , Hommet Caroline
Published: December 2015

Background: Posterior cortical atrophy (PCA) is characterized by progressive higher-order visuoperceptual dysfunction and praxis declines. This syndrome is related to a number of underlying diseases, including, in most cases, Alzheimer's disease (AD). The aim of this study was to compare the amyloid load with 18F-AV45 positron emission tomography (PET) between PCA and AD subjects. Methods: We performed 18F-AV45 PET, cerebrospinal fluid (CSF) biomarker analysis and a neuropsychological assessment in 11 PCA patients and 12 AD patients. Results: The global and regional 18F-AV45 uptake was similar in the PCA and AD groups. No significant correlation was observed between global 18F-AV45 uptake and CSF biomarkers or between regional 18F-AV45 uptake and cognitive and affective symptoms. Conclusion: This 18F-AV45 PET amyloid imaging study showed no specific regional pattern of cortical 18F-AV45 binding in PCA patients. These results confirm that a distinct clinical phenotype in amnestic AD and PCA is not related to amyloid distribution.