bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct TRAIL Resistance Mechanisms Can Be Overcome by Proteasome Inhibition but not Generally by Synergizing Agents
Authors: Menke Christina , Bin Lianghua , Thorburn Jacqueline , Behbakht Kian , Ford Heide L. , Thorburn Andrew 
Published: March 2011

Abstract
One impediment to the use of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-targeted agents as antitumor drugs is the evolution of resistance, a common problem in cancer. On the contrary, many different kinds of drugs synergize with TRAIL in TRAIL-sensitive tumor cells, raising the question whether one can overcome resistance with the same drugs producing synergy. This is an important question, because recent clinical trials suggest that combination treatments with cytotoxic drugs and TRAIL receptor-targeted agents do not provide additional benefit compared with cytotoxic agents on their own. Such results might be expected if drug combinations that synergize in sensitive tumor cells but cannot overcome TRAIL resistance are used in patients whose tumors were not selected for retention of TRAIL sensitivity. We tested this idea by creating isogenic tumor cells with acquired TRAIL resistance or defined mechanisms of resistance that occur in human tumors and then comparing them to the TRAIL-sensitive parental cell line. Although diverse classes of anticancer drugs were all able to synergize with TRAIL in sensitive cells, most agents were unable to overcome resistance and there was no relationship between the amount of synergy seen with a particular agent and its ability to overcome acquired resistance. An important exception was proteasome inhibitors, which were, however, able to overcome diverse resistance mechanisms. Our findings suggest that one should select drugs for TRAIL receptor agonist combination therapy based not just on their ability to synergize, but rather on their ability to overcome resistance as well as synergize. Cancer Res; 71(5); 1883–92. ©2011 AACR.
Reduced VEGF Production, Angiogenesis, and Vascular Regrowth Contribute to the Antitumor Properties of Dual mTORC1/mTORC2 Inhibitors
Authors: Falcon Beverly L. , Barr Sharon , Gokhale Prafulla C. , Chou Jeyling , Fogarty Jennifer , Depeille Philippe , Miglarese Mark , Epstein David M. , McDonald Donald M. 
Published: March 2011

Abstract
The mammalian target of rapamycin (mTOR) pathway is implicated widely in cancer pathophysiology. Dual inhibition of the mTOR kinase complexes mTORC1 and mTORC2 decreases tumor xenograft growth in vivo and VEGF secretion in vitro, but the relationship between these two effects are unclear. In this study, we examined the effects of mTORC1/2 dual inhibition on VEGF production, tumor angiogenesis, vascular regression, and vascular regrowth, and we compared the effects of dual inhibition to mTORC1 inhibition alone. ATP-competitive inhibitors OSI-027 and OXA-01 targeted both mTORC1 and mTORC2 signaling in vitro and in vivo, unlike rapamycin that only inhibited mTORC1 signaling. OXA-01 reduced VEGF production in tumors in a manner associated with decreased vessel sprouting but little vascular regression. In contrast, rapamycin exerted less effect on tumoral production of VEGF. Treatment with the selective VEGFR inhibitor OSI-930 reduced vessel sprouting and caused substantial vascular regression in tumors. However, following discontinuation of OSI-930 administration tumor regrowth could be slowed by OXA-01 treatment. Combining dual inhibitors of mTORC1 and mTORC2 with a VEGFR2 inhibitor decreased tumor growth more than either inhibitor alone. Together, these results indicate that dual inhibition of mTORC1/2 exerts antiangiogenic and antitumoral effects that are even more efficacious when combined with a VEGFR antagonist. Cancer Res; 71(5); 1573–83. ©2011 AACR.
Ironing Out Cancer
Authors: Torti Suzy V. , Torti Frank M. 
Published: March 2011

Abstract
New insights into the roles of proteins that regulate cellular iron in cancer growth, angiogenesis, and metastasis have recently emerged. Discoveries of the roles of ferroportin, hepcidin, lipocalin 2, and members of the six transmembrane epithelial antigen of the prostate (STEAP) and iron regulatory protein (IRP) families in cancer have provided specificity and molecular definition to the role of iron homeostasis in cancer growth and metastasis. A number of studies directly support a role of these proteins in modifying bioavailable iron, whereas other studies suggest that at least some of their effects are independent of their role in iron biology. Cancer Res; 71(5); 1511–4. ©2011 AACR.
Immunotherapy With Tolerogenic Apolipoprotein B-100–Loaded Dendritic Cells Attenuates Atherosclerosis in Hypercholesterolemic Mice
Authors: Hermansson Andreas , Johansson Daniel K. , Ketelhuth Daniel F.J. , Andersson John , Zhou Xinghua , Hansson Göran K. 
Published: March 2011

Background—
Atherosclerosis is a chronic inflammatory disease characterized by a massive intimal accumulation of low-density lipoprotein that triggers chronic vascular inflammation with an autoimmune response to low-density lipoprotein components.

Methods and Results—

To dampen the inflammatory component of atherosclerosis, we injected hypercholesterolemic huB100
tg
×
Ldlr
−/−
mice (mice transgenic for human apolipoprotein B100 [ApoB100] and deficient for the low-density lipoprotein receptor) intravenously with dendritic cells (DCs) that had been pulsed with the low-density lipoprotein protein ApoB100 in combination with the immunosuppressive cytokine interleukin-10. DCs treated with ApoB100 and interleukin-10 reduced proliferation of effector T cells, inhibited production of interferon-γ, and increased de novo generation of regulatory T cells in vitro. Spleen cells from mice treated with DCs plus ApoB100 plus interleukin-10 showed diminished proliferative responses to ApoB100 and significantly dampened T-helper 1 and 2 immunity to ApoB100. Spleen CD4
+
T cells from these mice suppressed activation of ApoB100-reactive T cells in a manner characteristic of regulatory T cells, and mRNA analysis of lymphoid organs showed induction of transcripts characteristic of these cells. Treatment of huB100
tg
×
Ldlr
−/−
mice with ApoB100-pulsed tolerogenic DCs led to a significant (70%) reduction of atherosclerotic lesions in the aorta, with decreased CD4
+
T-cell infiltration and signs of reduced systemic inflammation.

Conclusions—
Tolerogenic DCs pulsed with ApoB100 reduced the autoimmune response against low-density lipoprotein and may represent a novel possibility for treatment or prevention of atherosclerosis.
Some Issues in the Study of Language Contact
Authors: Winford Donald 
Published: March 2011

AbstractThis paper provides an overview of various approaches to contact-induced change, and assesses their contribution to a unified theory of the processes involved in such change, and the outcomes they produce. I argue that clarification of the terminology and classifications we apply to contact languages can lead to better understanding of the types of contact languages, and the kinds of process that produce them. I further suggest that van Coetsem's framework offers a more uniform terminology and classification, and that it clarifies the distinction between the two major transfer types involved in contact induced change – borrowing via recipient language agentivity, and imposition via source language agentivity. Failure to distinguish these two mechanisms accurately has negative implications for our understanding of the processes by which various contact languages are created. I apply this model to two broad categories of contact languages, bilingual mixed languages, and creoles, and I argue that the differences in transfer type identified by Van Coetsem correspond to differences in the language production processes underlying the two broad types of contact-induced change. Finally, I suggest that psycholinguistic models of language or speech production can contribute significantly to our understanding of the different processes involved in the creation of different types of contact languages.
Apprendre une langue et devenir bilingue : un eclairage acquisitionniste sur les contacts de langues
Authors: Py Bernard 
Published: March 2011

AbstractIl est ici proposé une synthèse de la problématique acquisitionniste confrontée à la réalité du bilinguisme et du contact des langues dans le cadre d'apprentissages formels et informels appréhendés en situation. Une question fondamentale : « Comment devient-on bilingue lorsqu'on est immergé dans une communauté alloglotte ou diglossique particulière, que l'on y pratique la communication bilingue ou exolingue et qu'on y occupe une position socioculturelle déterminée ? ». A partir de là, il s'agit de dépasser les notions abstraites d'exposition à la langue cible et de système qui ne prennent pas en compte les circonstances et la contextualisation de l'acquisition ; de mettre l'accent sur la pertinence de l'asymétrie de la communication exolingue. On développe alors une réflexion sur la dynamique de l'apprenant qui décontextualise les données linguistiques auxquelles il est confronté afin de constituer un ensemble de ressources stabilisées, fonctionnalisables à toutes fins utiles dans les contextes d'usage. Cela conduit à mettre en question l'intérêt de la notion de compétence, et le bilinguisme se définit alors autrement : par un accès à des ressources (issues de deux langues) actualisables dans des contextes sociaux particuliers.
Language Contact and Deliberate Change
Authors: Thomason Sarah 
Published: March 2011

AbstractThis paper explores the process of "negotiation", whereby speakers of two or more languages converge on a partially or entirely shared linguistic system. This process is surely unconscious in many or most instances, but sometimes speakers are aware of what they are doing as they "negotiate" the linguistic outcome of language contact. I provide evidence for the latter assertion, and discuss the difficulties inherent in any attempt to generalize about conscious vs. unconscious negotiation. I also contrast the process of negotiation with some other views of linguistic convergence. Finally, summarizing previous results, I argue that the existence of deliberate contact-induced (and other) linguistic change vitiates all efforts to achieve a deterministic predictive theory of contact-induced language change.
Layered, zippered and buttoned: the importation of Hebrew into "Dos Yidishe Vort"
Authors: Newman Zelda Kahan 
Published: March 2011

AbstractThis paper examines the ways in which Biblical, rabbinic and the Hebrew of modern Israel are imported into the Yiddish publication Dos Yidishe Vort. Three strategies are examined. The first strategy, "layering", occurs when the imported Hebrew elements appear without their connective tissue. We examine the cases when this can be done easily. The second strategy, "zippering", occurs when there is a 1:1 alignment between the morphemes of the two languages. In such cases, a text can, and does, slip easily from one language to the other. The third strategy, "buttoning", occurs when the host language incorporates the foreign elements by creating a structure that "nativizes" the foreign element and thereby draws it into the host language. This productive process sometimes stretches and sometimes shrinks the original material.
Langues en contact : l'expression contact comme révélatrice de la dynamique des langues. Persistance et intérêt de la métaphore
Authors: Tabouret-Keller Andrée 
Published: March 2011

AbstractL'usage du terme contact se maintient depuis quatre siècles : ses emplois se diversifient de même que la référence généralement implicite à ce qui fait contact, par quoi ça passe et qu'est-ce que ça produit ? est-ce que ces questions sont valables pour ces objets particuliers que sont le langage et les langues ? La première partie de ce texte a pour objet une esquisse historique de la notion de contact, la seconde examine un certain nombre de problèmes résultant des emplois du trio de métaphores contact, évolution du langage et dynamique des langues Cet examen conduit à dégager des questions concernant le rapport entre déterminismes biologiques et facteurs sociaux, l'hétérogénéité des contraintes fonctionnelles du langage et celle des temporalités. L'idéal d'un modèle unique est vain, la complexité et l'hétérogénéité des langues et de leurs réalités langagières entraînent l'élaboration de modèles de portée relative en rapport avec des niveaux d'abstraction variables.
Relabelling: A Major Process in Language Contact
Authors: Lefebvre Claire 
Published: March 2011

AbstractThe problem of language contact may be taken up from two opposite angles: the processes at work in language contact situations or the language contact varieties. In this paper, I look at contact phenomena from the former angle. I focus on one process: relabelling, a mental operation that consists in assigning a lexical entry of a given language, L1, a new label taken from another language, L2. The aim of this paper is threefold: first, to assess the extent of relabelling across language contact situations; second, to assess the extent of relabelling across lexicons; and third, to assess the possibility of relabelling in cases of agglutinative languages. The approach taken in this paper highlights the importance of the process of relabelling in a variety of language contact situations. Furthermore, it makes it possible to analyse in a unified way the contribution of a single process to the makeup of various language varieties arising in different contact situations, and thus to link a number of contact phenomena and situations that would otherwise remain separate.
Mixed Languages as Outcomes of Code-Switching: Recent Examples from Australia and Their Implications
Authors: McConvell Patrick 
Published: March 2011

AbstractThere has been much debate about whether mixed languages arise from code-switching. This paper presents one clear example of this kind of genesis, Gurindji Kriol, and other probable examples, from recent language contact in Australia between traditional Australian languages and English-based pidgins/creoles. In particular the paper focuses on what has been called the Verbal-Nominal split in the genesis of these languages, which is parallel to other cases elswhete in the world, such as Michif. Here the Verbal-Nominal split is reanalysed as a split between INFL (Tense-Aspect-Mood) dominated elements and the rest of the clause. There are two classes of such INFL mixed languages with contrasting characteristics: those in which the new language takes over the INFL elements and the nominal morphology is still drawn from the old language, like Gurindji Kriol; and those in which the verb and its morphology is retained from the old language but other elements are drawn from the new language. This is explained in terms of the 'arrested turnover' hypothesis of Myers-Scotton. The original 'centre of gravity' hypothesis of McConvell related the two kinds of mixed language outcomes to the grammatical type of the old language: whether it was 'dependent-marking' or 'headmarking'. In this paper this hypothesis is modified by seeing the important causal factor in the second type as incorporation of INFL and pronouns in the verb in head-marking and polysynthetic languages. Finally some other examples of mixed languages of the INFL-split type are mentioned, and a research program outlined aiming to detect where this kind of language-mixing forms part of the history of other languages by looking at the current pattern of composition of elements from different language sources.
How languages Change and How They Adapt: Some Challenges for the Future Dynamique du langage et élaboration des langues : quelques défis à relever
Authors: Nicolaï Robert 
Published: March 2011

AbstractAujourd'hui l'étude du multiple, de la variabilité et l'hétérogène va de soi dans les recherches sur l'évolution des langues et le changement linguistique. Corrélativement, des modèles évolutionnistes ont été proposés (cf. Lass 1997, Croft 2000, Mufwene 2001, etc.) ce qui suppose d'engager une réflexion sur leur pouvoir de description et leur degré d'adéquation aux phénomènes. Je m'intéresse ainsi aux 'modélisations métaphoriques' parce qu'elles témoignent de changements importants dans notre perception de la dynamique des langues, et parce que chaque fois qu'on envisage d'exporter un modèle se pose la question cruciale de savoir ce qu'on modélise dans le transfert. Un modèle néo-darwinien va introduire de nouveaux questionnements et conduira à précontraindre et à transformer les problématiques linguistiques. Il importe donc de s'intéresser au risque de surmodélisation qu'il est susceptible d'introduire : cela demande de s'interroger sur certains aspects fondamentaux et nécessaires à l'élaboration du linguistique (variabilité dans les langues, sémiotisation des formes) mais aussi sur la place des 'acteurs' dans les procès de communication.En considérant ces aspects on atteint l'interface où, activement, les acteurs construisent de l'unitaire à partir du variable, de l'hétérogène et du multiple, dans l'espace anthropo-linguistique dont ils sont partie prenante ; ce qui ne veut pas dire que cela résulte d'un procès délibéré. Cette construction se matérialise à travers diverses modalités de saisie des phénomènes. J'en présenterai trois (linéarisation, massification et Gestalt) qui illustrent 'l'activisme' des acteurs dans les dynamiques de l'élaboration de leurs langues.
Constraints on Contact-Induced Linguistic Change
Authors: Heine Bernd , Kuteva Tania 
Published: March 2011

AbstractIn a recent paper on "Social and Linguistic Factors as Predictors of Contact-Induced Change" Thomason (2007) reiterates the claim made earlier by Thomason & Kaufman (1988) and others (e.g., Harris & Campbell 1995; Curnow 2001) that there are no linguistic constraints on interference in language contact, in that any linguistic feature can be transferred to any language, and any change can occur as a direct or indirect result of language contact, and she is satisfied to observe that all the specific constraints on contact-induced change that have been proposed have been counterexemplified.The present paper takes issue with this stance, arguing that it might be in need of reconsideration, in that there are in fact some constraints on contact-induced linguistic change. These constraints relate to grammatical replication, as it has been described in Heine & Kuteva (2003; 2005; 2006), thus lending further support to the generalizations on language contact proposed there.
Informal Economy of Translocations. The Case of the Twin City of Blagoveshensk-Heihe
Authors: Ryzhova Natalia 
Published: March 2011

AbstractThe article evaluates economic interactions between people in the adjacent border cities of Blagoveshensk (Russia) and Heihe (China). The article reveals the conflict between the development of translocality around the border of the two countries and recent Russian policy to strengthen the position of the nation-state.
Language and Ethnicity: Cadre-Speak in Contemporary Tibet
Authors: Barnett Robert 
Published: March 2011

AbstractThe paper looks at changes over time in the ways that leading nationality cadres use formalistic language conventions within a communist society to convey apparently heterodox opinions. It notes in particular how those changes are related to economic and developmental conditions. These produce shifts in meanings as a side-effect of changes in the relationships that nationality or religious leaders have with the state, so that what might look to outsiders like expressions of dissent may be, more precisely, reminders by those who once had significant stakes in the 'old society' of their original promissory or contractual relations with the Communist Party. In contrast to views of formalistic texts as moribund, official texts in the Tibetan case can be seen in terms of their 'liveliness', a result of reading practices which are highly attuned to the local effects of power and to ethnicity, with frequent interpretational tensions over questions of compliance and disloyalty. Detailed examples are given of writing conventions found in major texts produced by leading Chinese and Tibetan cadres in Tibet in the 1960s and after 1980. Particular attention is given to block writing and the use of standard formulations. A brief historical overview is given of the rise of such cases among leading Tibetan cadres in the late 1980s, and their subsequent decline as the economy surged and the first generation of nationality leaders anointed by the CCP aged and became less active, giving way to the current group of largely marginalised public intellectuals.
The 'Creative Bureaucrat': Conflicts in the Production of Soviet Communist Party Discourse
Authors: Humphrey Caroline 
Published: March 2011

AbstractThe paper explores the politics of language of the Soviet Communist Party bureaucracy. It argues against the recent conceptualisation of late socialist discourse as basically 'performative', i.e. as a vehicle for action that was virtually independent of its propositional dimension. Contrary to this, it is suggested that if the analysis is broadened to include the process of producing texts (drafts, censored passages, oral discussions, etc.) we see marked concern, and, indeed, conflict over the ideological meaning of the content. The argument is made through detailed analysis of the memoirs of one Party official, Georgii Lukich Smirnov. This case also shows that Party cadres were far from 'faceless' or without feelings. The ideological battles throughout the late Soviet period, which scarred Smirnov, were what led to perestroika (reconstruction) and glasnost' (transparency) under Gorbachev.
Intensive Contact and the Copying of Paradigms: An Éven Dialect in Contact with Sakha (Yakut)
Authors: Pakendorf Brigitte 
Published: March 2011

AbstractThe development of the unique structure of Copper Island Aleut, which displays a combination of Russian finite verb morphology and Aleut nominal and non-finite verbal morphology as well as lexicon has been the subject of heated debate. In the absence of other examples of similar inflectional paradigm copying, the processes leading to this development are hard to elucidate. This paper discusses examples of paradigms copied from the Siberian Turkic language Sakha (Yakut) into a dialect of the Northern Tungusic language Éven spoken in the village of Sebjan-Küöl in northeastern Siberia. These data demonstrate that paradigm copying can take place in a situation of widespread bilingualism, with code-switching playing a vital role. Furthermore, they provide evidence that such mixed forms have the potential of serving as conduits for further copying of grammatical forms, and that they play an important role in the linguistic identity of the speakers, as has been suggested previously for mixed languages such as Copper Island Aleut.