bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pb isotopic domains from the Indian Ocean sector of Antarctica: implications for past Antarctica–India connections
Authors: Flowerdew M. J. , Tyrrell S. , Boger S. D. , Fitzsimons I. C. W. , Harley S. L. , Mikhalsky E. V. , Vaughan A. P. M. 
Published: May 2013

Abstract
New feldspar lead isotope compositions of crystalline rocks from the Indian Ocean sector of East Antarctica, in conjunction with the review of data from elsewhere within the continent and from continents formerly adjacent within Gondwana, refine boundaries and evolutionary histories of terranes previously inferred from geological mapping and complementary isotope studies. Coastal Archaean Vestfold and Napier complexes have overlapping compositions and had Pb isotopes homogenized at 2.5 Ga sourced from or within already fractionated protoliths with high and variable U–Pb. Identical compositions from the Dharwar Craton of India support a correlation with these Antarctic terranes. The Proterozoic–Palaeozoic Rayner Complex and Prydz Belt yield more radiogenic compositions and are broadly similar and strongly suggest these units correlate with parts of the Eastern Ghats Belt of India. A strikingly different signature is evident from the inboard Ruker Complex, which yielded unradiogenic compositions. This complex is unlike any unit within India or Australia, suggesting that these rocks represent exposures of an Antarctic (Crohn) Craton. Compositions from the enigmatic Rauer Terrane are consistent with a shared early history with the Ruker Complex but with a different post-Archaean evolution.

Supplementary material:

Feldspar LA-ICP-MS Pb isotope data are available at
www.geolsoc.org.uk/SUP18622
Boron- and phosphate-rich rocks in the Larsemann Hills, Prydz Bay, East Antarctica: tectonic implications
Authors: Grew Edward S. , Carson Christopher J. , Christy Andrew G. , Boger Steven D. 
Published: May 2013

Abstract

Granulite-facies paragneisses enriched in boron and phosphorus are exposed over
c.
15×5 km
2
in the Larsemann Hills, Antarctica. The most widespread are biotite gneisses containing centimetre-sized prismatine crystals, but tourmaline metaquartzite and borosilicate gneisses are richest in B (676–19 700 µg/g or 0.22–6.34 wt%; B
2
O
3
). Chondrite-normalized rare-earth element (REE) patterns give two groups: (1) La
N
>150, Eu*/Eu<0.4, which comprises most apatite-bearing metaquartzite and metapelite, tourmaline metaquartzite, and Fe-rich rocks (up to 2.3 wt%; P
2
O
5
); (2) La
N
<150, Eu*/Eu > 0.4, which comprises most borosilicate and sodic leucogneisses (2.5–7.4wt%; Na
2
O). Enrichment in boron and phosphorus is attributed to premetamorphic hydrothermal alteration, either in a rifted, most likely marine basin or in a mud volcanic system located inboard of a
c.
1000 Ma continental arc that was active along the leading edge of the Indo-Antarctic craton. This margin developed before collision with the Australo-Antarctic craton (
c.
530 Ma) merged these rocks into Gondwana and sutured them into their present position in Antarctica. Rocks lithologically similar to those in the Larsemann Hills include prismatine-bearing granulites in the Windmill Islands, Wilkes Land, and tourmaline–quartz rocks, sodic gneisses and apatitic iron formation in the Willyama Supergroup, Broken Hill, Australia.
Future directions task group
Authors: Kaczmarczyk Lisa 
Published: May 2013

Just about a year ago, John Impagliazzo asked if I'd be willing to form a task group to put together a report on the future of this magazine. I suspect he asked me for a couple of reasons. First, because I've been involved with Inroads for several years in a variety of capacities. Second, because I'm ridiculously organized. Third, because I'm a sucker for interesting assignments. Fourth, because I'm rather fond of Inroads. Fifth, because I'm a sucker for interesting assignments.
What a wonderful group of people to work with. Mikey, Fran, Beth, Joe and I met every other week via Skype for half a year. John joined us when he was able. We formulated our recommendations, reformulated them, reformulated them some more, sent them out for feedback to the Associate Editors and the Editorial Advisory Board, revised them some more. Even though we never met in person, and in some cases had never met in person, everyone got along swimmingly; even when there were tough questions to address and differences of opinion. And get this: they wanted to keep on meeting even when we had completed our task! At one point, I received a plaintive email from John asking me if I could please offcially declare the task group: Dismissed. Sigh… (So we gathered at SIGCSE for a social hour and found out what we really looked like.)
If you are a reviewer for the magazine, you will no doubt have seen the new reviewer scorecard. The task group developed this scorecard to help you, and to help authors, have a better understanding of what sort of material Inroads is looking for. Still in pilot phase, we are working out the kinks but we sincerely hope it is helpful. If you have comments about the scorecard or any other part of the recommendations (which follow below) please let one of us know. That would provide us a reason to hold another Skype call.

Lisa Kaczmarczyk Task Group Chair
lisakacz@gmail.com
Neuropilin-2 Promotes Extravasation and Metastasis by Interacting with Endothelial α5 Integrin
Authors: Cao Ying , Hoeppner Luke H. , Bach Steven , E Guangqi , Guo Yan , Wang Enfeng , Wu Jianmin , Cowley Mark J. , Chang David K. , Waddell Nicola , Grimmond Sean M. , Biankin Andrew V. , Daly Roger J. , Zhang Xiaohui , Mukhopadhyay Debabrata 
Published: May 2013

Abstract
Metastasis, the leading cause of cancer death, requires tumor cell intravasation, migration through the bloodstream, arrest within capillaries, and extravasation to invade distant tissues. Few mechanistic details have been reported thus far regarding the extravasation process or re-entry of circulating tumor cells at metastatic sites. Here, we show that neuropilin-2 (NRP-2), a multifunctional nonkinase receptor for semaphorins, vascular endothelial growth factor (VEGF), and other growth factors, expressed on cancer cells interacts with α5 integrin on endothelial cells to mediate vascular extravasation and metastasis in zebrafish and murine xenograft models of clear cell renal cell carcinoma (RCC) and pancreatic adenocarcinoma. In tissue from patients with RCC, NRP-2 expression is positively correlated with tumor grade and is highest in metastatic tumors. In a prospectively acquired cohort of patients with pancreatic cancer, high NRP-2 expression cosegregated with poor prognosis. Through biochemical approaches as well as Atomic Force Microscopy (AFM), we describe a unique mechanism through which NRP-2 expressed on cancer cells interacts with α5 integrin on endothelial cells to mediate vascular adhesion and extravasation. Taken together, our studies reveal a clinically significant role of NRP-2 in cancer cell extravasation and promotion of metastasis. Cancer Res; 73(14); 4579–90. ©2013 AACR.
The Ubiquitin–CXCR4 Axis Plays an Important Role in Acute Lung Infection–Enhanced Lung Tumor Metastasis
Authors: Yan Libo , Cai Qingchun , Xu Yan 
Published: May 2013

Abstract
Purpose: Our goals were to test the effect of acute lung infection on tumor metastasis and to investigate the underlying mechanisms.
Experimental Design: We combined bacteria-induced and lipopolysaccharide (LPS)-induced acute lung injury/inflammation (ALI) mouse models with mouse metastatic models to study the effect of acute inflammation on lung metastasis in mice. The mechanisms were investigated in ex vivo, in vitro, and in vivo studies.
Results: Both bacteria- and LPS-induced ALI significantly enhanced lung metastasis of four tail vein–injected mouse tumor cell lines. Bacteria also enhanced lung metastasis when 4T1 cells were orthotopically injected. The bronchoalveolar lavage fluid (BALF) from LPS- or bacteria-injected mice stimulated migration of tumor cells. In vivo tracking of metastatic RM-9 cells showed that bacterial injection enhanced early dissemination of tumor cells to the lung. The majority of the BALF migratory activity could be blocked by AMD3100, a chemokine receptor 4 (CXCR4) inhibitor. All tested cell lines expressed CXCR4. The levels of extracellular ubiquitin, but not stromal cell–derived factor-1, in BALF were significantly increased by LPS. Ubiquitin was able to induce AMD3100-sensitive migration of tumor cells. Finally, the antibacterial agent amoxicillin and the CXCR4 inhibitor AMD3100 blocked the enhancement effect of bacterial infection on tumor metastasis.
Conclusions: Acute lung infection dramatically increased cancer cell homing to the lung and lung metastasis. This change may be due to an alteration of the lung microenvironment and preparation of a favorable metastatic “niche.” This effect was seen in multiple cancer types and thus may have broad applications for cancer patients in prevention and/or treatment of metastasis. Clin Cancer Res; 19(17); 4706–16. ©2013 AACR.
Adoptive Transfer of Tumor-Infiltrating Lymphocytes in Patients with Metastatic Melanoma: Intent-to-Treat Analysis and Efficacy after Failure to Prior Immunotherapies
Authors: Besser Michal J. , Shapira-Frommer Ronnie , Itzhaki Orit , Treves Avraham J. , Zippel Douglas B. , Levy Daphna , Kubi Adva , Shoshani Noa , Zikich Dragoslav , Ohayon Yaara , Ohayon Daniel , Shalmon Bruria , Markel Gal , Yerushalmi Ronit , Apter Sara , Ben-Nun Alon , Ben-Ami Eytan , Shimoni Avichai , Nagler Arnon , Schachter Jacob 
Published: May 2013

Abstract
Purpose: Adoptive cell transfer (ACT) using autologous tumor-infiltrating lymphocytes (TIL) was reported to yield objective responses in about 50% of metastatic patients with melanoma. Here, we present the intent-to-treat analysis of TIL ACT and analyze parameters predictive to response as well as the impact of other immunotherapies.
Experimental Design: Eighty patients with stage IV melanoma were enrolled, of which 57 were treated with unselected/young TIL and high-dose interleukin-2 (IL-2) following nonmyeloablative lymphodepleting conditioning.
Results: TIL cultures were established from 72 of 80 enrolled patients. Altogether 23 patients were withdrawn from the study mainly due to clinical deterioration during TIL preparation. The overall response rate and median survival was 29% and 9.8 months for enrolled patients and 40% and 15.2 months for treated patients. Five patients achieved complete and 18 partial remission. All complete responders are on unmaintained remission after a median follow-up of 28 months and the 3-year survival of responding patients was 78%. Multivariate analysis revealed blood lactate-dehydrogenase levels, gender, days of TIL in culture, and the total number of infused CD8+ cells as independent predictive markers for clinical outcome. Thirty-two patients received the CTLA-4-blocking antibody ipilimumab prior or post TIL infusion. Retrospective analysis revealed that nonresponders to ipilimumab or IL-2 based therapy had the same overall response rate to ACT as other patients receiving TIL. No additional toxicities to TIL therapy occurred following ipilimumab treatment.
Conclusion: Adoptive transfer of TIL can yield durable and complete responses in patients with refractory melanoma, even when other immunotherapies have failed. Clin Cancer Res; 19(17); 4792–800. ©2013 AACR.
Combined Targeting of mTOR and AKT Is an Effective Strategy for Basal-like Breast Cancer in Patient-Derived Xenograft Models
Authors: Xu Siguang , Li Shunqiang , Guo Zhanfang , Luo Jingqin , Ellis Matthew J. , Ma Cynthia X. 
Published: May 2013

Abstract
Basal-like breast cancer is an aggressive disease for which targeted therapies are lacking. Recent studies showed that basal-like breast cancer is frequently associated with an increased activity of the phosphatidylinositol 3-kinase (PI3K) pathway, which is critical for cell growth, survival, and angiogenesis. To investigate the therapeutic potential of PI3K pathway inhibition in the treatment of basal-like breast cancer, we evaluated the antitumor effect of the mTOR inhibitor MK-8669 and AKT inhibitor MK-2206 in WU-BC4 and WU-BC5, two patient-derived xenograft models of basal-like breast cancer. Both models showed high levels of AKT phosphorylation and loss of PTEN expression. We observed a synergistic effect of MK-8669 and MK-2206 on tumor growth and cell proliferation in vivo. In addition, MK-8669 and MK-2206 inhibited angiogenesis as determined by CD31 immunohistochemistry. Biomarker studies indicated that treatment with MK-2206 inhibited AKT activation induced by MK-8669. To evaluate the effect of loss of PTEN on tumor cell sensitivity to PI3K pathway inhibition, we knocked down PTEN in WU-BC3, a basal-like breast cancer cell line with intact PTEN. Compared with control (GFP) knockdown, PTEN knockdown led to a more dramatic reduction in cell proliferation and tumor growth inhibition in response to MK-8669 and MK-2206 both in vitro and in vivo. Furthermore, a synergistic effect of these two agents on tumor volume was observed in WU-BC3 with PTEN knockdown. Our results provide a preclinical rationale for future clinical investigation of this combination in basal-like breast cancer with loss of PTEN. Mol Cancer Ther; 12(8); 1665–75. ©2013 AACR.
Comparison of Echocardiographic and Cardiac Magnetic Resonance Imaging in Hypertrophic Cardiomyopathy Sarcomere Mutation Carriers Without Left Ventricular Hypertrophy
Authors: Valente Anne Marie , Lakdawala Neal K. , Powell Andrew J. , Evans Sarah P. , Cirino Allison L. , Orav E. John. , MacRae Calum A. , Colan Steven D. , Ho Carolyn Y. 
Published: May 2013

Background—
Left ventricular hypertrophy (LVH) typically manifests during or after adolescence in sarcomere mutation carriers at risk for developing hypertrophic cardiomyopathy. Guidelines recommend serial imaging of mutation carriers without LVH (G+/LVH−) to monitor for phenotypic evolution, but the optimal strategy is undefined. Compared with echocardiography (echo), cardiac MRI (CMR) offers improved endocardial visualization and potential to assess scar. However, the incremental advantage offered by CMR for early diagnosis of hypertrophic cardiomyopathy is unclear. Therefore, we systematically compared echo and CMR in G+/LVH− subjects.

Methods and Results—

A total of 40 sarcomere mutation carriers with normal echo wall thickness (<12 mm or
z
score <2.5 in children) underwent concurrent CMR. Mean age was 21.7±11.1 years, 55% were female. If left ventricular wall thickness seemed nonuniform, the size and location of relatively thickened segments were noted. Late gadolinium enhancement was assessed with CMR. Diagnostic agreement between echo and CMR was good (90%), although CMR measurements of left ventricular wall thickness were ≈19% lower than echo. Four subjects had mild hypertrophy (12.6–14 mm; ≤2 segments) appreciated by CMR but not echo. No subjects had late gadolinium enhancement. During median 35-month follow-up, 2 subjects developed overt hypertrophic cardiomyopathy, including 1 with mild LVH by CMR at baseline.

Conclusions—
Echo is unlikely to miss substantial LVH; however, CMR identified mild hypertrophy in ≈10% of mutation carriers with normal echo wall thickness. CMR may be a useful adjunct in hypertrophic cardiomyopathy family screening, particularly in higher risk situations, or if echocardiographic images are suboptimal or suggest borderline LVH.
Residual Ischemia After Revascularization in Multivessel Coronary Artery Disease
Authors: Arnold Jayanth R. , Karamitsos Theodoros D. , van Gaal William J. , Testa Luca , Francis Jane M. , Bhamra-Ariza Paul , Ali Ali , Selvanayagam Joseph B. , Westaby Steve , Sayeed Rana , Jerosch-Herold Michael , Neubauer Stefan , Banning Adrian P. 
Published: May 2013

Background—
Revascularization strategies for multivessel coronary artery disease include percutaneous coronary intervention and coronary artery bypass grafting. In this study, we compared the completeness of revascularization as assessed by coronary angiography and by quantitative serial perfusion imaging using cardiovascular magnetic resonance.

Methods and Results—

Patients with multivessel coronary disease were recruited into a randomized trial of treatment with either coronary artery bypass grafting or percutaneous coronary intervention. Angiographic disease burden was determined by the Bypass Angioplasty Revascularization Investigation (BARI) myocardial jeopardy index. Cardiovascular magnetic resonance first-pass perfusion imaging was performed before and 5 to 6 months after revascularization. Using model-independent deconvolution, hyperemic myocardial blood flow was evaluated, and ischemic burden was quantified. Sixty-seven patients completed follow-up (33 coronary artery bypass grafting and 34 percutaneous coronary intervention). The myocardial jeopardy index was 80.7±15.2% at baseline and 6.9±11.3% after revascularization (
P
<0.0001), with revascularization deemed complete in 62.7% of patients. Relative to cardiovascular magnetic resonance, angiographic assessment overestimated disease burden at baseline (80.7±15.2% versus 49.9±29.2% [
P
<0.0001]), but underestimated it postprocedure (6.9±11.3% versus 28.1±33.4% [
P
<0.0001]). Fewer patients achieved complete revascularization based on functional criteria than on angiographic assessment (38.8% versus 62.7%;
P
=0.015). After revascularization, hyperemic myocardial blood flow was significantly higher in segments supplied by arterial bypass grafts than those supplied by venous grafts (2.04±0.82 mL/min per gram versus 1.89±0.81 mL/min per gram, respectively;
P
=0.04).

Conclusions—
Angiographic assessment may overestimate disease burden before revascularization, and underestimate residual ischemia after revascularization. Functional data demonstrate that a significant burden of ischemia remains even after angiographically defined successful revascularization.

Clinical Trial Registration—

URL:
http://www.controlled-trials.com
. Unique identifier:ISRCTN25699844.
Serum Proprotein Convertase Subtilisin/Kexin Type 9 and Cell Surface Low-Density Lipoprotein Receptor
Authors: Tavori Hagai , Fan Daping , Blakemore John L. , Yancey Patricia G. , Ding Lei , Linton MacRae F. , Fazio Sergio 
Published: May 2013

Background—
Proprotein convertase subtilisin/kexin type 9 (PCSK9) modulates low-density lipoprotein (LDL) receptor (LDLR) degradation, thus influencing serum cholesterol levels. However, dysfunctional LDLR causes hypercholesterolemia without affecting PCSK9 clearance from the circulation.

Methods and Results—

To study the reciprocal effects of PCSK9 and LDLR and the resultant effects on serum cholesterol, we produced transgenic mice expressing human (h) PCSK9. Although hPCSK9 was expressed mainly in the kidney, LDLR degradation was more evident in the liver. Adrenal LDLR levels were not affected, likely because of the impaired PCSK9 retention in this tissue. In addition, hPCSK9 expression increased hepatic secretion of apolipoprotein B–containing lipoproteins in an LDLR-independent fashion. Expression of hPCSK9 raised serum murine PCSK9 levels by 4.3-fold in wild-type mice and not at all in LDLR
−/−
mice, in which murine PCSK9 levels were already 10-fold higher than in wild-type mice. In addition, LDLR
+/−
mice had a 2.7-fold elevation in murine PCSK9 levels and no elevation in cholesterol levels. Conversely, acute expression of human LDLR in transgenic mice caused a 70% decrease in serum murine PCSK9 levels. Turnover studies using physiological levels of hPCSK9 showed rapid clearance in wild-type mice (half-life, 5.2 minutes), faster clearance in human LDLR transgenics (2.9 minutes), and much slower clearance in LDLR
−/−
recipients (50.5 minutes). Supportive results were obtained with an in vitro system. Finally, up to 30% of serum hPCSK9 was associated with LDL regardless of LDLR expression.

Conclusions—
Our results support a scenario in which LDLR represents the main route of elimination of PCSK9 and a reciprocal regulation between these 2 proteins controls serum PCSK9 levels, hepatic LDLR expression, and serum LDL levels.
Top–Down Modulation from Inferior Frontal Junction to FEFs and Intraparietal Sulcus during Short-term Memory for Visual Features
Authors: Sneve Markus H. , Magnussen Svein , Alnæs Dag , Endestad Tor , D'Esposito Mark 
Published: May 2013

Abstract
Visual STM of simple features is achieved through interactions between retinotopic visual cortex and a set of frontal and parietal regions. In the present fMRI study, we investigated effective connectivity between central nodes in this network during the different task epochs of a modified delayed orientation discrimination task. Our univariate analyses demonstrate that the inferior frontal junction (IFJ) is preferentially involved in memory encoding, whereas activity in the putative FEFs and anterior intraparietal sulcus (aIPS) remains elevated throughout periods of memory maintenance. We have earlier reported, using the same task, that areas in visual cortex sustain information about task-relevant stimulus properties during delay intervals [Sneve, M. H., Alnæs, D., Endestad, T., Greenlee, M. W., & Magnussen, S. Visual short-term memory: Activity supporting encoding and maintenance in retinotopic visual cortex. Neuroimage, 63, 166–178, 2012]. To elucidate the temporal dynamics of the IFJ-FEF-aIPS-visual cortex network during memory operations, we estimated Granger causality effects between these regions with fMRI data representing memory encoding/maintenance as well as during memory retrieval. We also investigated a set of control conditions involving active processing of stimuli not associated with a memory task and passive viewing. In line with the developing understanding of IFJ as a region critical for control processes with a possible initiating role in visual STM operations, we observed influence from IFJ to FEF and aIPS during memory encoding. Furthermore, FEF predicted activity in a set of higher-order visual areas during memory retrieval, a finding consistent with its suggested role in top–down biasing of sensory cortex.
T'ain't What You Say, It's the Way That You Say It—Left Insula and Inferior Frontal Cortex Work in Interaction with Superior Temporal Regions to Control the Performance of Vocal Impersonations
Authors: McGettigan Carolyn , Eisner Frank , Agnew Zarinah K. , Manly Tom , Wisbey Duncan , Scott Sophie K. 
Published: May 2013

AbstractHistorically, the study of human identity perception has focused on faces, but the voice is also central to our expressions and experiences of identity [Belin, P., Fecteau, S., & Bedard, C. Thinking the voice: Neural correlates of voice perception. Trends in Cognitive Sciences, 8, 129–135, 2004]. Our voices are highly flexible and dynamic; talkers speak differently, depending on their health, emotional state, and the social setting, as well as extrinsic factors such as background noise. However, to date, there have been no studies of the neural correlates of identity modulation in speech production. In the current fMRI experiment, we measured the neural activity supporting controlled voice change in adult participants performing spoken impressions. We reveal that deliberate modulation of vocal identity recruits the left anterior insula and inferior frontal gyrus, supporting the planning of novel articulations. Bilateral sites in posterior superior temporal/inferior parietal cortex and a region in right middle/anterior STS showed greater responses during the emulation of specific vocal identities than for impressions of generic accents. Using functional connectivity analyses, we describe roles for these three sites in their interactions with the brain regions supporting speech planning and production. Our findings mark a significant step toward understanding the neural control of vocal identity, with wider implications for the cognitive control of voluntary motor acts.