bluuebunny/crossref_metadata_2025_split huggingface dataset:
An EGFR-ERK-SOX9 Signaling Cascade Links Urothelial Development and Regeneration to Cancer
Authors: Ling Shizhang , Chang Xiaofei , Schultz Luciana , Lee Thomas K. , Chaux Alcides , Marchionni Luigi , Netto George J. , Sidransky David , Berman David M. 
Published: April 2011

Abstract
Like many carcinomas, urothelial carcinoma (UroCa) is associated with chronic injury. A better understanding of this association could inform improved strategies for preventing and treating this disease. We investigated the expression, regulation, and function of the transcriptional regulator SRY-related high-mobility group box 9 (Sox9) in urothelial development, injury repair, and cancer. In mouse bladders, Sox9 levels were high during periods of prenatal urothelial development and diminished with maturation after birth. In adult urothelial cells, Sox9 was quiescent but was rapidly induced by a variety of injuries, including exposure to the carcinogen cyclophosphamide, culture with hydrogen peroxide, and osmotic stress. Activation of extracellular signal–regulated kinases 1/2 (ERK1/2) was required for Sox9 induction in urothelial injury and resulted from activation of the epidermal growth factor receptor (Egfr) by several Egfr ligands that were dramatically induced by injury. In UroCa cell lines, SOX9 expression was constitutively upregulated and could be suppressed by EGFR or ERK1/2 blockade. Gene knockdown showed a role for SOX9 in cell migration and invasion. Accordingly, SOX9 protein levels were preferentially induced in invasive human UroCa tissue samples (n = 84) compared with noninvasive cancers (n = 56) or benign adjacent urothelium (n = 49). These results identify a novel, potentially oncogenic signaling axis linking urothelial injury to UroCa. Inhibiting this axis is feasible through a variety of pharmacologic approaches and may have clinical utility. Cancer Res; 71(11); 3812–21. ©2011 AACR.
Chronic Inflammatory IFN-γ Signaling Suppresses Hepatocarcinogenesis in Mice by Sensitizing Hepatocytes for Apoptosis
Authors: Lüth Stefan , Schrader Jörg , Zander Stefan , Carambia Antonella , Buchkremer Juliane , Huber Samuel , Reifenberg Kurt , Yamamura Ken-Ichi , Schirmacher Peter , Lohse Ansgar W. , Herkel Johannes 
Published: April 2011

Abstract
Chronic liver inflammation is a critical component of hepatocarcinogenesis. Indeed, inflammatory mediators are believed to promote liver cancer by upholding compensatory proliferation of hepatocytes in response to tissue damage. However, inflammation can also mediate the depletion of malignant cells, but the difference between tumor-suppressive and tumor-promoting inflammation is not defined at the molecular level. Here, we analyzed the role of the major inflammatory mediator IFN-γ in chemical hepatocarcinogenesis of transgenic mice that overexpress IFN-γ in the liver; these mice manifest severe chronic inflammatory liver damage and lasting compensatory regeneration. We found that chronic exposure to IFN-γ suppressed chemical hepatocarcinogenesis, despite overt liver injury. Indeed, IFN-γ–transgenic mice had significantly fewer and significantly less advanced malignant lesions than nontransgenic mice. This tumor-suppressive effect of IFN-γ seemed to be mediated in part by its known immune activating function, indicated by infiltration of IFN-γ–transgenic livers with CD8 T cells, natural killer T cells, and natural killer cells. However, IFN-γ seemed to prevent carcinogenesis also by activating the cell-intrinsic p53 tumor suppressor pathway. Indeed, exposure to IFN-γ in vivo or in vitro was associated with accumulation of p53 in hepatocytes and the sensitization of hepatocytes to apoptosis induced by genotoxic stress. The IFN-γ–induced increase in apoptosis of hepatocytes seemed to be p53 dependent. Thus, chronic inflammation dominated by IFN-γ may prevent hepatocarcinogenesis, despite continued inflammatory liver injury and regeneration. Therefore, the carcinogenic potential of inflammation seems to be determined by type and composition of its mediators and manipulating the type of chronic inflammation may serve the prevention of cancer. Cancer Res; 71(11); 3763–71. ©2011 AACR.
Bone Marrow Stroma–Secreted Cytokines Protect JAK2V617F-Mutated Cells from the Effects of a JAK2 Inhibitor
Authors: Manshouri Taghi , Estrov Zeev , Quintás-Cardama Alfonso , Burger Jan , Zhang Ying , Livun Ana , Knez Liza , Harris David , Creighton Chad J. , Kantarjian Hagop M. , Verstovsek Srdan 
Published: April 2011

Abstract
Signals emanating from the bone marrow microenvironment, such as stromal cells, are thought to support the survival and proliferation of the malignant cells in patients with myeloproliferative neoplasms (MPN). To examine this hypothesis, we established a coculture platform [cells cocultured directly (cell-on-cell) or indirectly (separated by micropore membrane)] designed to interrogate the interplay between Janus activated kinase 2-V617F (JAK2V617F)–positive cells and the stromal cells. Treatment with atiprimod, a potent JAK2 inhibitor, caused marked growth inhibition and apoptosis of human (SET-2) and mouse (FDCP-EpoR) JAK2V617F-positive cells as well as primary blood or bone marrow mononuclear cells from patients with polycythemia vera; however, these effects were attenuated when any of these cell types were cocultured (cell-on-cell) with human marrow stromal cell lines (e.g., HS5, NK.tert, TM-R1). Coculture with stromal cells hampered the ability of atiprimod to inhibit phosphorylation of JAK2 and the downstream STAT3 and STAT5 pathways. This protective effect was maintained in noncontact coculture assays (JAK2V617F-positive cells separated by 0.4-μm-thick micropore membranes from stromal cells), indicating a paracrine effect. Cytokine profiling of supernatants from noncontact coculture assays detected distinctly high levels of interleukin 6 (IL-6), fibroblast growth factor (FGF), and chemokine C-X-C-motif ligand 10 (CXCL-10)/IFN-γ–inducible 10-kD protein (IP-10). Anti-IL-6, -FGF, or -CXCL-10/IP-10 neutralizing antibodies ablated the protective effect of stromal cells and restored atiprimod-induced apoptosis of JAK2V617F-positive cells. Therefore, our results indicate that humoral factors secreted by stromal cells protect MPN clones from JAK2 inhibitor therapy, thus underscoring the importance of targeting the marrow niche in MPN for therapeutic purposes. Cancer Res; 71(11); 3831–40. ©2011 AACR.
c-Myc Regulates RNA Splicing of the A-Raf Kinase and Its Activation of the ERK Pathway
Authors: Rauch Jens , Moran-Jones Kim , Albrecht Valerie , Schwarzl Thomas , Hunter Keith , Gires Olivier , Kolch Walter 
Published: April 2011

Abstract
A-Raf kinase can inhibit apoptosis by binding to the proapoptotic mammalian sterile 20-like kinase (MST2). This function relies on expression of hnRNP H, which ensures the correct splicing of a-raf mRNA needed to produce full-length A-Raf protein. Here, we showed that expression of hnRNP H and production of full-length A-Raf is positively controlled by c-Myc. Low c-Myc reduces hnRNP H expression and switches a-raf splicing to produce A-Rafshort, a truncated protein. Importantly, A-Rafshort fails to regulate MST2 but retains the Ras-binding domain such that it functions as a dominant negative mutant suppressing Ras activation and transformation. Human colon and head and neck cancers exhibit high hnRNP H and high c-Myc levels resulting in enhanced A-Raf expression and reduced expression of A-Rafshort. Conversely, in normal cells and tissues in which c-Myc and hnRNP H are low, A-Rafshort suppresses extracellular signal regulated kinase activation such that it may act as a safeguard against oncogenic transformation. Our findings offered a new paradigm to understand how c-Myc coordinates diverse cell functions by directly affecting alternate splicing of key signaling components. Cancer Res; 71(13); 4664–74. ©2011 AACR.
LIN28B Promotes Colon Cancer Progression and Metastasis
Authors: King Catrina E. , Cuatrecasas Miriam , Castells Antoni , Sepulveda Antonia R. , Lee Ju-Seog , Rustgi Anil K. 
Published: April 2011

Abstract
LIN28B is a homologue of LIN28 that induces pluripotency when expressed in conjunction with OCT4, SOX2, and KLF4 in somatic fibroblasts. LIN28B represses biogenesis of let-7 microRNAs and is implicated in both development and tumorigenesis. Recently, we have determined that LIN28B overexpression occurs in colon tumors. We conducted a comprehensive analysis of LIN28B protein expression in human colon adenocarcinomas. We found that LIN28B overexpression correlates with reduced patient survival and increased probability of tumor recurrence. To elucidate tumorigenic functions of LIN28B, we constitutively expressed LIN28B in colon cancer cells and evaluated tumor formation in vivo. Tumors with constitutive LIN28B expression exhibit increased expression of colonic stem cell markers LGR5 and PROM1, mucinous differentiation, and metastasis. Together, our findings point to a function for LIN28B in promoting colon tumor pathogenesis, especially metastasis. Cancer Res; 71(12); 4260–8. ©2011 AACR.
Detection of Extra Components of T Wave by Independent Component Analysis in Congenital Long-QT Syndrome
Authors: Horigome Hitoshi , Ishikawa Yasuhiro , Shiono Junko , Iwamoto Mari , Sumitomo Naokata , Yoshinaga Masao 
Published: April 2011

Background—
The main ECG criteria for the diagnosis of long-QT syndrome (LQTS) include abnormal T-wave morphology as well as prolonged QT interval. The T wave in LQTS probably includes additional components of the myocardial repolarization process, which are derived from aberrant ion currents. We investigated whether independent component analysis (ICA) can extract such abnormal repolarization components.

Methods and Results—
Digital ECG data were obtained as a time series from 10 channels using 20 surface electrodes in 22 patients with genetically confirmed LQTS type 1 (LQT1) and 30 normal subjects. In each case, T-wave area was analyzed by radical ICA after noise reduction by the wavelet thresholding method. Furthermore, inverse ICA was applied to determine the origin of each independent component (IC). Radical ICA revealed that a T-wave consisted of 4 basic ICs in all control subjects, whereas ≥5 (mostly 6) ICs were identified in all 22 patients with LQT1. The extra ICs, which were not evident in normal subjects, were assumed to contribute to the formation of abnormal T-wave morphology. The extra ICs were identified even in patients with normal QTc values and in those taking β-blockers. Inverse ICA indicated that the additional ICs originate predominantly from the late phase of the T wave of the left ventricle.

Conclusions—
Extra ICs appear during repolarization in all patients with LQT1 but not in normal subjects. ICA is a potentially useful multivariate statistical method to differentiate patients with LQT1 from normal subjects.
Cocteau’s Chimney, Carter’s Cadenza: ‘Dream Time’ Symbols in Sight and Sound
Authors: Wierzbicki James 
Published: April 2011

AbstractThe idea of ‘dream time’, or oneiric time, has doubtless been with us since the dawn of human consciousness. But ‘dream time’ is a special kind of time that does not really take time or occupy time, and thus to depict it in a temporal, linear medium is patently impossible. The French filmmaker Jean Cocteau and the American composer Elliott Carter were fully aware of this when they sought to create symbols of the familiar yet ineffable ‘dream time’ phenomenon. This essay examines the interrupted ‘falling chimney’ sequence that frames Cocteau’s 1930 surrealist film Le Sang d’une poète and the cello/violin cadenza, inspired by Cocteau’s gesture, that similarly frames Carter’s 1951 String Quartet No. 1. It argues that Cocteau’s and Carter’s efforts are successful, but largely to the extent that they remind audience members of their own dream-time experiences.
Recursion, Supplementarity, and the Limits of Subjectivity in John Barth’s “Menelaiad”
Authors: Singer Marc 
Published: April 2011

Abstract“Menelaiad,” an experimental short story from John Barth’s Lost in the Funhouse, consists of a series of multiply nested narratives in which each layer recursively generates the next, chronologically earlier one. The story presents narrative and memory as supplemental processes that look back in time to recover or replace a lost moment of presence and completion. Barth suggests these supplements are imperfect and self-defeating means of recapturing the past, however, as they further separate the narrator from his tale’s irretrievable origins. The story structures human subjectivity along similarly self-deferring lines, portraying the self not as an essential whole but as a sequence of narrative supplements organized around an absence that no supplement can redress. Paralleling contemporary developments in poststructuralist theory yet not inspired by, beholden to, or even necessarily aware of them, “Menelaiad” delivers an original illustration of the recursive and supplemental processes that, Barth believes, define and demarcate the human subject.
Memory as a String of Pearls
Authors: Hancock Peter A. , Shahnami Nushien 
Published: April 2011

AbstractWhich representational metaphor one chooses serves to exert a powerful influence upon how we conceive of and subsequently think about time. In the human perception of time, one of the most critical faculties is that of memory, since it appears that we remember the past and anticipate the future while simultaneously experiencing the present. We here present a ‘string of pearls’ metaphor which captures the features of episodic memories (both retrospective and prospective) as the pearls on the string. The underlying continuity of lived experience of existence is equated with the thread of the string itself upon which these respective episodic pearls are mounted. The advantages, nuances, and drawbacks of the use of this metaphor to the understanding of time perception are discussed.
Reading between the Lines: The Compilation of Hadīt and the Authorial Voice
Authors: Burge S. R. 
Published: April 2011

AbstractIn the nineteenth and twentieth centuries there were numerous studies of the isnād in Hadīt Studies, but more recently the discipline has focused on the role that Hadīt played in the development of the four schools of Sunnī law. These studies have still had a tendency to focus on the isnād. However, there is a second stage in the compilation of Hadīt that has received little attention, namely a study of the way in which Hadīt have been compiled and presented. The form and structure of a work should be able to give insights into a compiler’s viewpoints and beliefs. This article draws on two methodologies from Biblical Studies (Canonical and Redaction Criticism), as a means to approach and understand the (theological) statements lying behind the compilation of Hadīt collections, using two case studies from al-Buhārī’s Sahīh to explore the potential benefit of analysing the way Hadīts are compiled: (i) the opening book of the work: Kitāb Bad al-wahy and (ii) the Kitāb al-Atima. By exploring the way in which a Kitāb has been compiled, it may be possible to reveal the authorial voice and opinions.
Le poème en lām d’Abū Kabīr al-Hudalī : introduction, traduction et notes
Authors: Larcher Pierre 
Published: April 2011

AbstractThe lāmiyya is the most famous poem by Abū Kabīr al-Hudalī, who is one of the most famous poets of the Hudayl tribe. According to Blachère, it is an “exercice d’école”. If so, it is a successful one, both thematically and stylistically. Thematically, nostalgia for youth serves as a frame for the evocation of mankind’s great deeds, such as love and war. Stylistically, the poem is made up of parallelisms. The annotation consists mainly of a linguistic and literary commentary. We have opted for a poetic translation.
Legal Remedies for Human Rights Violations in the Armed Conflict in Chechnya: The Approach of the European Court of Human Rights in Context
Authors: Koroteev Kirill 
Published: April 2011

AbstractThe article discusses the efficacy of the remedies offered to successful applicants by the European Court of Human Rights in the cases coming from the armed conflict in the Chechen Republic of the Russian Federation. It submits, firstly, that proper establishment of facts constitutes a remedy in itself for victims of human rights violations in an armed conflict. It then analyses the establishment of facts by the Court in the Chechen cases and argues that the assessment of evidence under the Court's burden of proof 'beyond reasonable doubt' was applied unevenly in different cases. The paper suggests that the Court obtains evidence proprio motu, which it has never done in the Chechen cases. Secondly, this paper evaluates the European Court's practice to limit the just satisfaction by monetary awards and to consistently deny the applicants' requests for non-monetary awards. It then discusses the developments in the international law on reparations for human rights violations under the ECHR and in the Inter-American and UN systems, and argues for a need to enhance the European Court's awards of just satisfaction. Finally, the paper assesses the supervision of the execution of judgments in the Chechen cases, finds it ineffective, and suggests that more actions are required from the Court in order to deal effectively with alleged human rights violations arising from armed conflicts.
The Interplay Between International Humanitarian Law and Refugee Law
Authors: Fernández-Sánchez Pablo Antonio 
Published: April 2011

AbstractInternational humanitarian law (IHL) is not the sole body of international law that applies in armed conflicts. Among the different legal bodies that may be subject to the simultaneous application during armed conflicts is refugee law. The questions considered in this article are the protection of refugees under IHL, including the right of non-refoulement during armed conflicts. The cumulative application of IHL and refugee law is another focus of analysis. This article deals with inter alia the reinforced extension of alien rights to refugees during armed conflict, the possibility to grant refugee status to new actors which appear during armed conflict, the obligation to disarm and separate armed elements, the forced transfer of refugees for military or humanitarian reasons, and the right of ex-combatants to be treated as civilian refugees once they have disarmed and their legal status can be determined.
Who Are the Winners and the Losers? Transitions in the U.S. Household Income Distribution
Authors: Hisnanick John J. 
Published: April 2011

In the five decades since Kuznets (1955) published his hypothesis on income inequality, a large and significant portion of the work on income distribution and inequality has involved using cross-sectional data for developmental comparisons at the intra- and international levels. Using cross-sectional data, these studies have tracked inequality trends that were deemed the consequence of growth and technical progress due to fiscal manipulations, such as levying taxes and granting subsidies to satisfy some welfare target. While this prior work provided valuable insight at the macroeconomic level on the interrelationship of development, economic growth, and income inequality, only over the last few decades has the research emphasis shifted from an understanding of the implications of income inequality at the aggregate level to that at the individual level. Using cross-sectional data it is possible to track income groups over time, but not the composition nor the characteristics of these groups, which are likely to change over time and affect their position in the income distribution. On the other hand, with the availability of longitudinal, micro-level data it has become possible to investigate in more detail underlying facets of income distribution, such as income mobility, and the lack of it, among households. Using three panels of the Survey of Income and Program Participation (SIPP) (1993, 1996, and 2001) and building upon the methodological suggestions of Jarvis and Jenkins (1998) and Jenkins (2000), this paper looks at a household’s economic and demographic characteristics relative to their position in the income distribution. For example, results indicate that between 1996-1999, 13 million households experienced changes in their annual income that resulted in their moving up or down two or more quintiles in the income distribution. On the other hand, 39 percent of households (38.5 million) remained in the same quintile between 1996-1999 with the majority of these households experiencing intra-quintile movements. Of notable interest is that of those households remaining in the fourth and top quintiles between 1996-1999; 70 percent and 65 percent, respectively, experienced positive intra-quintile gains in income ranging, on average, from $3,550 to $10,812 annually. JEL classification: C81, D31, O15
Capranicaite, (K,☐)(Ca,Na)Al4B4Si2O18: a new inosilicate from Capranica, Italy, with a peculiar topology of the periodic single chain [Si2O6]
Authors: Callegari A. M. , Boiocchi M. , Bellatreccia F. , Caprilli E. , Medenbach O. , Cavallo A. 
Published: April 2011

AbstractCapranicaite, ideally (K,☐)(Ca,Na)Al4B4Si2O18, is a new inosilicate mineral from the Vico volcanic complex collected at Capranica, Viterbo Province, Latium, Italy. It occurs in miarolitic cavities of a feldspathoid-bearing syenite ejectum and formed by late-stage metasomatic processes related to the activity of theVico volcano.Capranicaite occurs as thin, tabular crystals no larger than 0.1 mm. Crystals are colourless, with a white streak and a vitreous lustre; they are brittle and their Mohs hardness is certainly <6. Capranicaite is non-fluorescent with good {001} cleavage and no observable parting. The calculated density is 2.41 g/cm3. Crystals are biaxial negative, non pleochroic, with α = 1.495(1), β = 1.543(1), γ = 1.544(1), 2Vobs = 7.3(2)°, 2Vcalc = 16.0°.Capranicaiteis monoclinic P21/n, with a = 4.8507(2), b = 16.6156(6), c = 20.5445(7) Å, β = 90.245(1)°, V = 1655.82(17) Å3, Z = 4. The strongest six X-ray diffraction lines in the simulated powder pattern are [d in Å (I) (hkl)]: 3.234 (10) (124; 044), 4.104 (9) (1̄21; 121), 3.424 (8) (006), 2.184 (4) (048; 1̄64), 2.405 (4) (160), 2.425 (3) (200). EMP-WDS analysis gives: SiO2 20.70, Al2O3 32.91, B2O3 22.90, K2O 5.36, CaO 11.04, Na2O 4.08, Cs2O 2.20, sum 99.19%; the formula, based on 18 oxygens, is: (K0.69Cs0.10)Σ0.79(Ca1.19Na0.80)Σ1.99Al3.91B3.99Si2.09O18, corresponding to the ideal formula: (K,☐)(Ca,Na)Al4B4Si2O18. The crystal structure shows three overlapping layers of polyhedra parallel to (001): (1) the A layer contains periodic single chains formed by Si2O6 units with a topology not previously observed; (2) the B layer contains isolated AlO4 tetrahedra and BO3 triangles forming a sheet of six-fold rings (3Al + 3B); (3) the C layer contains two octahedral sites: M(1) and M(2), with a mixed (Ca, Na) population. Two B layers and an intermediate A layer are vertex-connected to form a bi-dimensional B-A-B network characterized by large channels not completely populated and accommodating K and minor Cs. Along c from the origin the following layer sequence results: C-[B-A-B]-C-[B-A-B]-C.