bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Lower Palaeozoic palaeogeographical evolution of the northeastern and eastern peri-Gondwanan margin from Turkey to New Zealand
Authors: Torsvik Trond H. , Cocks L. Robin M. 
Published: December 2009

Abstract
In Lower Palaeozoic times, Gondwana was by far the largest tectonic entity, stretching from the South Pole to north of the Equator, and is termed a superterrane. We consider the northeastern sector of the Gondwanan and peri-Gondwanan margin, from Turkey through the Middle East, the north of the Indian subcontinent, southern China and SE Asia, to Australia and New Zealand. There was progressive tectonic activity along some of its margins during the period, with areas such as southeastern Australia undergoing enlargement through the accretion of island arcs as that part of Gondwana rotated. However, most of the area, from the Taurides of Turkey to at least east of India, represented a passive margin for the whole of the Lower Palaeozoic. Other adjacent areas, such as the Pontides of Turkey and Annamia (Indochina), were separate from the main Gondwanan craton as independent terranes. The quality and quantity of available data on Lower Palaeozoic rocks and faunas varies enormously over different parts of this substantial area, and there are few or no detailed palaeomagnetic data available for most of it. Some workers have considered the string of terranes from Armorica to the Malaysia Peninsula as having left Gondwana together in the late Cambrian as a Hun superterrane, leaving a widening Palaeotethys Ocean between it and Gondwana. However, we consider that the Palaeotethys opened no earlier than in late Silurian time (with Armorica and other terranes to its north), and that the Hun superterrane was not a cohesive unity. Other researchers vary in presenting many substantial Central Asian and Far Eastern terranes, including North China, South China, Tarim, Annamia and others, as integral parts of core Gondwana and not leaving it until Devonian and later times. We conclude that North China, Tarim and Annamia, among others, were probably not attached to core Gondwana in the Lower Palaeozoic, that South China was close to Gondwana (but not an integral part of it), and that Sibumasu was probably part of Gondwana. We try to reconcile the very varied published geological data and opinions, and present new palaeogeographical maps for that sector of Gondwana and surrounding areas for the Cambrian (500 Ma), Ordovician (480 Ma) and Silurian (425 Ma).
Avalonia: a long-lived terrane in the Lower Palaeozoic?
Authors: Cocks L. R. M. , Fortey R. A. 
Published: December 2009

Abstract
Avalonia was undoubtedly an independent terrane throughout the Ordovician, merging with Baltica at about Ordovician–Silurian boundary times (443 Ma). We consider it to have been internally unified throughout the Lower Palaeozoic, and not the two independent ‘East’ and ‘West’ Avalonian terranes of some authors. In the early Ordovician its faunas were certainly Gondwanan. However, its earlier history is controversial: we discuss whether Avalonia split off from Gondwana in the early Ordovician, or whether it left Gondwana in the late Neoproterozoic. We conclude that the varied basement terranes underlying Avalonia were aggregated to the margin of Gondwana before 650 Ma. Some substantial transform movements occurred along the Gondwanan margin between 610 and 530 Ma, but the Avalonian area remained part of core Gondwana until about the end of the Cambrian (490 Ma), when the rift–drift initiation of the opening Rheic Ocean between Gondwana and Avalonia began.
Ordovician life around the Celtic fringes: diversifications, extinctions and migrations of brachiopod and trilobite faunas at middle latitudes
Authors: Harper David A. T. , Owen Alan W. , Bruton David L. 
Published: December 2009

Abstract
During the early to mid-Ordovician, marine life experienced an unprecedented rise in diversity at the species, genus and family levels that firmly installed the suspension-feeding benthos as the main component of the Palaeozoic fauna. The earlier Ordovician was characterized by a wide dispersal of the continents together with a high frequency of microcontinents and volcanic arcs. Magmatic and tectonic activity was intense, climates were warm and sea levels were high. Central to the entire diversification is the role of gamma (inter-provincial) diversity and by implication the spread of the continents and frequency of island arcs and microcontinents. A disparate group of continental fragments and island arcs loosely assigned to the Celtic province contained distinctive shelly faunas that formed a testable biogeographical unit. The Celtic faunas are characterized by a large number of endemic brachiopod taxa, some cosmopolitan forms, and taxa at the beginning or end of their stratigraphical ranges. The associated trilobite faunas are composed largely of wide-ranging genera, a few genera at the start of their stratigraphical range and some recently evolved taxa extending their geographical range. The Celtic province helped provide a burst of gamma diversity during the early stages of the Ordovician Radiation whereas the timing and position of the archipelagos associated with the Celtic province may have provided a mechanism for the diachroneity associated with the diversification.
A survey of attack and defense techniques for reputation systems
Authors: Hoffman Kevin , Zage David , Nita-Rotaru Cristina 
Published: December 2009

Reputation systems provide mechanisms to produce a metric encapsulating reputation for a given domain for each identity within the system. These systems seek to generate an accurate assessment in the face of various factors including but not limited to unprecedented community size and potentially adversarial environments.We focus on attacks and defense mechanisms in reputation systems. We present an analysis framework that allows for the general decomposition of existing reputation systems. We classify attacks against reputation systems by identifying which system components and design choices are the targets of attacks. We survey defense mechanisms employed by existing reputation systems. Finally, we analyze several landmark systems in the peer-to-peer domain, characterizing their individual strengths and weaknesses. Our work contributes to understanding (1) which design components of reputation systems are most vulnerable, (2) what are the most appropriate defense mechanisms and (3) how these defense mechanisms can be integrated into existing or future reputation systems to make them resilient to attacks.
Encoding information flow in AURA (abstract only)
Authors: Jia Limin , Zdancewic Steve 
Published: December 2009

Two of the main ways to protect security-sensitive resources in computer systems are to enforce access-control policies and information-flow policies. In this paper, we show how to enforce information-flow policies in AURA, which is a programming language for access control. When augmented with this mechanism for enforcing information-flow polices, AURA can further improve the security of reference monitors that implement access control.
We show how to encode security types and lattices of security labels using AURA's existing constructs for authorization logic. We prove a noninterference theorem for this encoding. We also investigate how to use expressive access-control policies specified in authorization logic as the policies for information declassification.
Catch me if you can
Authors: Askarov Aslan , Sabelfeld Andrei 
Published: December 2009

Program errors are a source of information leaks. Tracking these leaks is hard because error propagation breaks out of program structure. Programming languages often feature exception constructs to provide some structure to error handling: for example, the try...catch blocks in Java and Caml. Mainstream information-flow security compilers such as Jif and FlowCaml enforce rigid rules for exceptions in order to prevent leaks via public side effects of computation whose reachability depends on exceptions.
This paper presents a general and permissive alternative to the rigid solution: the programmer is offered a choice for each type of error/exception whether to handle it or not. The security mechanism ensures that, in the former case, it is never handled and, in the latter case, it is always handled with the mainstream restrictions. This mechanism extends naturally to a language with procedures and output, where we show the soundness of the mechanism with respect to termination-insensitive noninterference.
Measuring channel capacity to distinguish undue influence (abstract only)
Authors: Newsome James , McCamant Stephen , Song Dawn 
Published: December 2009

The channel capacity of a program is a quantitative measure of the amount of control that the inputs to a program have over its outputs. Because it corresponds to worst-case assumptions about the probability distribution over those inputs, it is particularly appropriate for security applications where the inputs are under the control of an adversary. We introduce a family of complementary techniques for measuring channel capacity automatically using a decision procedure (SAT or #SAT solver), which give either exact or narrow probabilistic bounds.
We then apply these techniques to the problem of analyzing false positives produced by dynamic taint analysis used to detect control-flow hijacking in commodity software. Dynamic taint analysis is based on the principle that an attacker should not be able to control values such as function pointers and return addresses, but it uses a simple binary approximation of control that commonly leads to both false positive and false negative errors. Based on channel capacity, we propose a more refined quantitative measure of influence, which can effectively distinguish between true attacks and false positives. We use a practical implementation of our influence measuring techniques, integrated with a dynamic taint analysis operating on x86 binaries, to classify tainting warnings produced by vulnerable network servers, such as those attacked by the Blaster and SQL Slammer worms. Influence measurement correctly distinguishes real attacks from tainting false positives, a task that would otherwise need to be done manually.
Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer
Authors: Hammerman Peter S. , Jänne Pasi A. , Johnson Bruce E. 
Published: December 2009

AbstractGefitinib and erlotinib are ATP competitive inhibitors of the epidermal growth factor receptor (EGFR) tyrosine kinase and are approved around the world for the treatment of patients with non-small cell lung cancer (NSCLC). Somatic mutations in the EGFR are found in 10 to 40% of patients with NSCLC. Patients with sensitizing somatic mutations of EGFR treated with gefitinib or erlotinib have an initial clinical response of 60 to 80%, approximately twice as high as the responses associated with the administration of conventional platinum-based chemotherapy. However, the efficacy of EGFR tyrosine kinase inhibitors (TKI) is limited by either primary (de novo) or acquired resistance after therapy and investigations to define the mechanisms of resistance are active areas of ongoing preclinical and clinical studies. Primary resistance is typically caused by other somatic mutations in genes such as KRAS, which also have an impact on the EGFR signaling pathway or by mutations in the EGFR gene that are not associated with sensitivity to EGFR-TKIs. Two established mechanisms of acquired resistance are caused by additional mutations in the EGFR gene acquired during the course of treatment that change the protein-coding sequence or by amplification of another oncogene signaling pathway driven by the MET oncogene. This review focuses on characterized mechanisms of resistance to the EGFR TKIs and efforts to overcome the problem of resistance aimed at improving the therapy of patients with NSCLC. (Clin Cancer Res 2009;15(24):7502–9)
Vascular Endothelial Growth Factor Receptor-1 Is Synthetic Lethal to Aberrant β-Catenin Activation in Colon Cancer
Authors: Naik Snehal , Dothager Robin S. , Marasa Jayne , Lewis Cory L. , Piwnica-Worms David 
Published: December 2009

Abstract
Purpose: The Wnt/β-catenin (β-cat) signaling cascade is a key regulator of development, and dysregulation of Wnt/β-cat contributes to selected cancers, such as colorectal, breast, and hepatocellular carcinoma, through abnormal activation of Wnt target genes. To identify novel modulators of the Wnt/β-cat pathway that may emerge as therapeutic targets, we did an unbiased high-throughput RNA interference screen.
Experimental Design: A synthetic oligonucleotide small interfering RNA library targeting 691 known and predicted human kinases was screened in Wnt3a-stimulated human cells in a live cell luciferase assay for modulation of Wnt/β-cat–dependent transcription. Follow-up studies of a selected high-confidence “hit” were conducted.
Results: A robust quartile-based statistical analysis and secondary screen yielded several kinases worthy of further investigation, including Cdc2L1, Lmtk3, Pank2, ErbB3, and, of note, vascular endothelial growth factor receptor (VEGFR)1/Flt1, a receptor tyrosine kinase (TK) with putative weak kinase activity conventionally believed to be a negative regulator of angiogenesis. A series of loss-of-function, genetic null, and VEGFR TK inhibitor assays further revealed that VEGFR1 is a positive regulator of Wnt signaling that functions in a glycogen synthase kinase-3β (GSK3β)–independent manner as a potential synthetic lethal target in Wnt/β-cat–addicted colon carcinoma cells.
Conclusions: This unanticipated non-endothelial link between VEGFR1 TK activity and Wnt/β-cat signaling may refine our understanding of aberrant Wnt signaling in colon carcinoma and points to new combinatorial therapeutics targeted to the tumor cell compartment, rather than angiogenesis, in the context of colon cancer. (Clin Cancer Res 2009;15(24):7529–37)
Hyaluronan-CD44 Interactions in Cancer: Paradoxes and Possibilities
Authors: Toole Bryan P. 
Published: December 2009

Abstract
Hyaluronan is a prominent component of the micro-environment in most malignant tumors and can be prognostic for tumor progression. Extensive experimental evidence in animal models implicates hyaluronan interactions in tumor growth and metastasis, but it is also evident that a balance of synthesis and turnover by hyaluronidases is critical. CD44, a major hyaluronan receptor, is commonly but not uniformly associated with malignancy, and is frequently used as a marker for cancer stem cells in human carcinomas. Multivalent interactions of hyaluronan with CD44 collaborate in driving numerous tumor-promoting signaling pathways and transporter activities. It is widely accepted that hyaluronan-CD44 interactions are crucial in both malignancy and resistance to therapy, but major challenges for future research in the field are the mechanism of activation of hyaluronan-CD44 signaling in cancer cells, the relative importance of variant forms of CD44 and other hyaluronan receptors, e.g., Rhamm, in different tumor contexts, and the role of stromal versus tumor cell production and turnover of hyaluronan. Despite these caveats, it is clear that hyaluronan-CD44 interactions are an important target for translation into the clinic. Among the approaches that show promise are antibodies and vaccines to specific variants of CD44 that are uniquely expressed at critical stages of progression of a particular cancer, hyaluronidase-mediated reduction of barriers to drug access, and small hyaluronan oligosaccharides that attenuate constitutive hyaluronan-receptor signaling and enhance chemosensitivity. In addition, hyaluronan is being used to tag drugs and delivery vehicles for targeting of anticancer agents to CD44-expressing tumor cells. (Clin Cancer Res 2009;15(24):7462–8)
A Phase I Clinical Trial of CHT-25 a 131I-Labeled Chimeric Anti-CD25 Antibody Showing Efficacy in Patients with Refractory Lymphoma
Authors: Dancey Gairin , Violet John , Malaroda Alessandra , Green Alan J. , Sharma Surinder K. , Francis Roslyn , Othman Shokri , Parker Sweta , Buscombe John , Griffin Natalie , Chan Pei-San , Malhotra Anmol , Woodward Nicholas , Ramsay Alan , Ross Philip , Lister T. Andrew , Amlot Peter , Begent Richard , McNamara Christopher 
Published: December 2009

AbstractPurpose: There is a need for new treatments for Hodgkin and T-cell lymphoma due to the development of drug resistance in a proportion of patients. This phase I study of radioimmunotherapy used CHT-25, a chimeric antibody to the α-chain of the interleukin-2 receptor, CD25, conjugated to iodine-131 (131I) in patients with refractory CD25-positive lymphomas.Experimental Design: Fifteen patients were treated (Hodgkin lymphoma, 12; angioimmunoblastic T-cell lymphoma, 1; adult T-cell leukemia/lymphoma, 2). Tumor was monitored by computed tomography and in all but two patients by 18F-fluorodeoxyglucose positron emission tomography.Results: There were no grade 3 or 4 infusion reactions. At the maximum tolerated dose of 1,200 MBq/m2, the major side effect was delayed myelotoxicity with the nadir for platelets at 38 days and for neutrophils at 53 days. One patient treated with 2,960 MBq/m2 developed prolonged grade 4 neutropenia and thrombocytopenia and died of Pneumocystis jiroveci pneumonia. Nonhematologic toxicity was mild. Single photon emission computer tomography imaging showed tumor-specific uptake and retention of 131I and no excessive retention in normal organs. Of nine patients receiving ≥1,200 MBq/m2, six responded (three complete response and three partial response); one of six patients with administered radioactivity of ≤740 MBq/m2 had a complete response.Conclusions: CHT-25 is well tolerated with 1,200 MBq/m2 administered radioactivity and shows clinical activity in patients who are refractory to conventional therapies. Phase II studies are justified to determine efficacy and toxicity in a broader range of clinical scenarios. (Clin Cancer Res 2009;15(24):7701–10)
Inhibition of Vascular Endothelial Growth Factor Receptor-1/Wnt/β-catenin Crosstalk Leads to Tumor Cell Death
Authors: Zeitlin Benjamin D. , Ellis Lee M. , Nör Jacques E. 
Published: December 2009

Abstract
Two genes are considered synthetic lethal if mutation of either alone allows cell viability, whereas simultaneous mutation leads to cell death. A synthetic lethal screen unveiled the dependency of Wnt/β-catenin-addicted colorectal cancer cells on vascular endothelial growth factor receptor-1 kinase activity and suggested a novel therapeutic approach for this malignancy. (Clin Cancer Res 2009;15(24):7453–5)
Impacts of Historic Climate Variability on Seasonal Soil Frost in the Midwestern United States
Authors: Sinha Tushar , Cherkauer Keith A. , Mishra Vimal 
Published: December 2009

Abstract
The present study examines the effects of historic climate variability on cold-season processes, including soil temperature, frost depth, and the number of frost days and freeze–thaw cycles. Considering the importance of spatial and temporal variability in cold-season processes, the study was conducted in the midwestern United States using both observations and model simulations. Model simulations used the Variable Infiltration Capacity (VIC) land surface model (LSM) to reconstruct and to analyze changes in the long-term (i.e., 1917–2006) means of soil frost variables. The VIC model was calibrated using observed streamflow records and near-surface soil temperatures and then evaluated for streamflow, soil temperature, frost depth, and soil moisture before its application at the regional scale. Soil frost indicators—such as the number of frost days and freeze–thaw cycles—were determined from observed records and were tested for the presence of significant trends. Overall trends in extreme and mean seasonal soil temperature from 1967 onward indicated a warming of soil temperatures at a depth of 10 cm—specifically in northwest Indiana, north-central Illinois, and southeast Minnesota—leading to a reduction in the number of soil frost days. Model simulations indicated that by the late-century period (1977–2006), soil frost duration decreased by as much as 36 days compared to the midcentury period (1947–76). Spatial averages for the study area in warm years indicated shallower frost penetration by 15 cm and greater soil temperatures by about 3°C at 10-cm soil depth than in the cold years.
A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment)
Authors: Passamonti Francesco , Cervantes Francisco , Vannucchi Alessandro Maria , Morra Enrica , Rumi Elisa , Pereira Arturo , Guglielmelli Paola , Pungolino Ester , Caramella Marianna , Maffioli Margherita , Pascutto Cristiana , Lazzarino Mario , Cazzola Mario , Tefferi Ayalew 
Published: December 2009

Abstract
Age older than 65 years, hemoglobin level lower than 100 g/L (10 g/dL), white blood cell count greater than 25 × 109/L, peripheral blood blasts 1% or higher, and constitutional symptoms have been shown to predict poor survival in primary myelofibrosis (PMF) at diagnosis. To investigate whether the acquisition of these factors during follow-up predicts survival, we studied 525 PMF patients regularly followed. All 5 variables had a significant impact on survival when analyzed as time-dependent covariates in a multivariate Cox proportional hazard model and were included in 2 separate models, 1 for all patients (Dynamic International Prognostic Scoring System [DIPSS]) and 1 for patients younger than 65 years (age-adjusted DIPSS). Risk factors were assigned score values based on hazard ratios (HRs). Risk categories were low, intermediate-1, intermediate-2, and high in both models. Survival was estimated by the HR. When shifting to the next risk category, the HR was 4.13 for low risk, 4.61 for intermediate-1, and 2.54 for intermediate-2 according to DIPSS; 3.97 for low risk, 2.84 for intermediate-1, and 1.81 for intermediate-2 according to the age-adjusted DIPSS. The novelty of these models is the prognostic assessment of patients with PMF anytime during their clinical course, which may be useful for treatment decision-making.
EEVD motif of heat shock cognate protein 70 contributes to bacterial uptake by trophoblast giant cells
Authors: Watanabe Kenta , Tachibana Masato , Kim Suk , Watarai Masahisa 
Published: December 2009

Abstract

Background
The uptake of abortion-inducing pathogens by trophoblast giant (TG) cells is a key event in infectious abortion. However, little is known about phagocytic functions of TG cells against the pathogens. Here we show that heat shock cognate protein 70 (Hsc70) contributes to bacterial uptake by TG cells and the EEVD motif of Hsc70 plays an important role in this.

Methods

Brucella abortus and Listeria monocytogenes were used as the bacterial antigen in this study. Recombinant proteins containing tetratricopeptide repeat (TPR) domains were constructed and confirmation of the binding capacity to Hsc70 was assessed by ELISA. The recombinant TPR proteins were used for investigation of the effect of TPR proteins on bacterial uptake by TG cells and on pregnancy in mice.

Results
The monoclonal antibody that inhibits bacterial uptake by TG cells reacted with the EEVD motif of Hsc70. Bacterial TPR proteins bound to the C-terminal of Hsc70 through its EEVD motif and this binding inhibited bacterial uptake by TG cells. Infectious abortion was also prevented by blocking the EEVD motif of Hsc70.

Conclusions
Our results demonstrate that surface located Hsc70 on TG cells mediates the uptake of pathogenic bacteria and proteins containing the TPR domain inhibit the function of Hsc70 by binding to its EEVD motif. These molecules may be useful in the development of methods for preventing infectious abortion.