bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cold pre‐conditioning neuroprotection depends on TNF‐α and is enhanced by blockade of interleukin‐11
Authors: Mitchell Heidi M. , White David M. , Domowicz Miriam S. , Kraig Richard P. 
Published: November 2010

J. Neurochem. (2011) 117, 187–196.AbstractCold pre‐conditioning reduces subsequent brain injury in small animals but the underlying mechanisms remain undefined. As hypothermia triggers systemic macrophage tumor necrosis factor alpha (TNF‐α) production and other neural pre‐conditioning stimuli depend on this cytokine, we reasoned that microglia and TNF‐α would be similarly involved with cold pre‐conditioning neuroprotection. Also, as slice cultures closely approximate their in vivo counterpart and include quiescent microglia, we used rat hippocampal slice cultures to confirm this hypothesis. Furthermore, inflammatory cytokine gene screening with subsequent PCR and immunostaining confirmation of targeted mRNA and related protein changes showed that cold pre‐conditioning triggered a significant rise in TNF‐α that localized to microglia and a significant rise in interleukin (IL)‐11 that localized mainly to hippocampal pyramidal neurons and, more rarely, astrocytes. Importantly, co‐stimulation with cold and IL‐11, an anti‐inflammatory cytokine that inhibits TNF‐α expression, abrogated the otherwise evident protection. Instead, cold pre‐conditioning coupled with blockade of IL‐11 signaling further enhanced neuroprotection from that seen with cold pre‐conditioning alone. Thus, physiological activation of brain pro‐inflammatory cytokine signaling, and its amplification by inhibition of coincident anti‐inflammatory cytokine signaling, may be opportune targets for the development of novel therapeutics that can mimic the protection seen in cold pre‐conditioning.
Using OR to adapt supply chain management best practices to humanitarian logistics
Authors: Van Wassenhove Luk N. , Pedraza Martinez Alfonso J. 
Published: November 2010

AbstractThe demand for humanitarian aid is extraordinarily large and it is increasing. In contrast, the funding for humanitarian operations does not seem to be increasing at the same rate. Humanitarian logistics has the challenge of allocating scarce resources to complex operations in an efficient way. After acquiring sufficient contextual knowledge, academics can use operations research (OR) to adapt successful supply chain management best practices to humanitarian logistics. We present two cases of OR applications to field vehicle fleet management in humanitarian operations. Our research shows that by using OR to adapt supply chain best practices to humanitarian logistics, significant improvements can be achieved.
Will seizure control improve by switching from the modified Atkins diet to the traditional ketogenic diet?
Authors: Kossoff Eric H. , Bosarge Jennifer L. , Miranda Maria J. , Wiemer‐Kruel Adelheid , Kang Hoon Chul , Kim Heung Dong 
Published: November 2010

SummaryIt has been reported that children can maintain seizure control when the ketogenic diet (KD) is transitioned to the less‐restrictive modified Atkins diet (MAD). What is unknown, however, is the likelihood of additional seizure control from a switch from the MAD to the KD. Retrospective information was obtained from 27 patients who made this dietary change from four different institutions. Ten (37%) patients had ≥10% additional seizure reduction with the KD over the MAD, of which five became seizure‐free. The five children who did not improve on the MAD failed to improve when transitioned to the KD. A higher incidence of improvement with the KD occurred for those with myoclonic–astatic epilepsy (70% vs. 12% for all other etiologies, p = 0.004), including all who became seizure‐free. These results suggest that the KD probably represents a “higher dose” of dietary therapy than the MAD, which may particularly benefit those with myoclonic–astatic epilepsy.
Mammalian Endothermy Optimally Restricts Fungi and Metabolic Costs
Authors: Bergman Aviv , Casadevall Arturo 
Published: November 2010

ABSTRACT
Endothermy and homeothermy are mammalian characteristics whose evolutionary origins are poorly understood. Given that fungal species rapidly lose their capacity for growth above ambient temperatures, we have proposed that mammalian endothermy enhances fitness by creating exclusionary thermal zones that protect against fungal disease. According to this view, the relative paucity of invasive fungal diseases in immunologically intact mammals relative to other infectious diseases would reflect an inability of most fungal species to establish themselves in a mammalian host. In this study, that hypothesis was tested by modeling the fitness increase with temperature versus its metabolic costs. We analyzed the tradeoff involved between the costs of the excess metabolic rates required to maintain a body temperature and the benefit gained by creating a thermal exclusion zone that protects against environmental microbes such as fungi. The result yields an optimum at 36.7°C, which closely approximates mammalian body temperatures. This calculation is consistent with and supportive of the notion that an intrinsic thermally based resistance against fungal diseases could have contributed to the success of mammals in the Tertiary relative to that of other vertebrates.

IMPORTANCE
Mammals are characterized by both maintaining and closely regulating high body temperatures, processes that are known as endothermy and homeothermy, respectively. The mammalian lifestyle is energy intensive and costly. The evolutionary mechanisms responsible for the emergence and success of these mammalian characteristics are not understood. This work suggests that high mammalian temperatures represent optima in the tradeoff between metabolic costs and the increased fitness that comes with resistance to fungal diseases.
The characteristics of rare earth elements in bulk precipitation, throughfall, foliage and lichens in the Lesní potok catchment and its vicinity, Czech Republic
Authors: Špičková Jitka , Navrátil Tomáš , Rohovec Jan , Mihaljevič Martin , Kubínová Petra , Minařík Luděk , Skřivan Petr 
Published: November 2010

ABSTRACT

A comparison of rare earth elements' (REE) atmospheric signatures in various ecosystem compartments was carried out in the vicinity of the Lesní potok catchment (LP), Czech Republic. REE signatures were investigated from 2004 to 2006 in rainwater, throughfall, tree foliage (
Picea abies
,
Fagus sylvatica
) and lichens (
Hypogymnia physodes
) for selected elements (Al, Ca, Fe, K, Mg, Mn, Na, P, S, Si). REE concentrations increased in the following sequences: bulk precipitation < beech throughfall < spruce throughfall and spruce needles < beech leaves ≪ lichens.

The crustal origin of REEs in bulk precipitation was confirmed by its high correlation with lithogenic elements, by the seasonal variation in REE concentrations and by comparison of REE distribution patterns of the upper continental crust, local granites and soil. Enrichment factors calculated in relation to bulk precipitation and normalized to Na enabled elimination of the influence of dry deposition and wash-out. Higher REE concentrations in throughfall were then identified to be the result of the wash-out of dry deposition, while REEs were found to bioaccumulate in vegetation, although at a much smaller rate than the essential elements K, Mn, P, Mg and Ca.

Supplementary material:
various REE and major ions concentrations are available at http://www.geolsoc.org.uk/SUP18437.
Hepatocyte Nuclear Factor-4α Promotes Gut Neoplasia in Mice and Protects against the Production of Reactive Oxygen Species
Authors: Darsigny Mathieu , Babeu Jean-Philippe , Seidman Ernest G. , Gendron Fernand-Pierre , Levy Emile , Carrier Julie , Perreault Nathalie , Boudreau François 
Published: November 2010

Abstract
Hepatocyte nuclear factor-4α (Hnf4α) is a transcription factor that controls epithelial cell polarity and morphogenesis. Hnf4α conditional deletion during postnatal development has minor effects on intestinal epithelium integrity but promotes activation of the Wnt/β-catenin pathway without causing tumorigenesis. Here, we show that Hnf4α does not act as a tumor-suppressor gene but is crucial in promoting gut tumorigenesis in mice. Polyp multiplicity in ApcMin mice lacking Hnf4α is suppressed compared with littermate ApcMin controls. Analysis of microarray gene expression profiles from mice lacking Hnf4α in the intestinal epithelium identifies novel functions of this transcription factor in targeting oxidoreductase-related genes involved in the regulation of reactive oxygen species (ROS) levels. This role is supported with the demonstration that HNF4α is functionally involved in the protection against spontaneous and 5-fluorouracil chemotherapy-induced production of ROS in colorectal cancer cell lines. Analysis of a colorectal cancer patient cohort establishes that HNF4α is significantly upregulated compared with adjacent normal epithelial resections. Several genes involved in ROS neutralization are also induced in correlation with HNF4A expression. Altogether, the findings point to the nuclear receptor HNF4α as a potential therapeutic target to eradicate aberrant epithelial cell resistance to ROS production during intestinal tumorigenesis. Cancer Res; 70(22); 9423–33. ©2010 AACR.
Mammalian Target of Rapamycin–Dependent Acinar Cell Neoplasia after Inactivation of Apc and Pten in the Mouse Salivary Gland: Implications for Human Acinic Cell Carcinoma
Authors: Diegel Cassandra R. , Cho Kathleen R. , El-Naggar Adel K. , Williams Bart O. , Lindvall Charlotta 
Published: November 2010

Abstract
Cross-talk between the canonical Wnt and mammalian target of rapamycin (mTOR) signaling pathways occurs at multiple levels in the cell and likely contributes to the oncogenic effects of these pathways in human cancer. To gain more insight into the interplay between Wnt and mTOR signaling in salivary gland tumorigenesis, we developed a mouse model in which both pathways are constitutively activated by the conditional inactivation of the Apc and Pten tumor suppressor genes. Loss of either Apc or Pten alone did not cause tumor development. However, deletion of both genes resulted in the formation of salivary gland tumors with 100% penetrance and short latency that showed a remarkable morphologic similarity to human acinic cell carcinoma. Treatment of tumor-bearing mice using the mTOR inhibitor rapamycin led to complete regression of tumors, indicating that tumor growth was dependent on continued mTOR signaling. Importantly, we found that human salivary gland acinic cell carcinomas also express markers of activated mTOR signaling. Together, these results suggest that aberrant activation of mTOR signaling plays a pivotal role in acinar cell neoplasia of the salivary gland. Because rapamycin analogues are approved for treating other types of human malignancies, our findings suggest that rapamycin therapy should be evaluated for treating patients with salivary gland acinic cell carcinoma. Cancer Res; 70(22); 9143–52. ©2010 AACR.
High-Throughput Characterization of 10 New Minor Histocompatibility Antigens by Whole Genome Association Scanning
Authors: Van Bergen Cornelis A.M. , Rutten Caroline E. , Van Der Meijden Edith D. , Van Luxemburg-Heijs Simone A.P. , Lurvink Ellie G.A. , Houwing-Duistermaat Jeanine J. , Kester Michel G.D. , Mulder Arend , Willemze Roel , Falkenburg J.H. Frederik , Griffioen Marieke 
Published: November 2010

Abstract
Patients with malignant diseases can be effectively treated with allogeneic hematopoietic stem cell transplantation (allo-SCT). Polymorphic peptides presented in HLA molecules, the so-called minor histocompatibility antigens (MiHA), play a crucial role in antitumor immunity as targets for alloreactive donor T cells. Identification of multiple MiHAs is essential to understand and manipulate the development of clinical responses after allo-SCT. In this study, CD8+ T-cell clones were isolated from leukemia patients who entered complete remission after allo-SCT, and MiHA-specific T-cell clones were efficiently selected for analysis of recognition of a panel of EBV-transformed B cells positive for the HLA restriction elements of the selected T-cell clones. One million single nucleotide polymorphisms (SNP) were determined in the panel cell lines and investigated for matching with the T-cell recognition data by whole genome association scanning (WGAs). Significant association with 12 genomic regions was found, and detailed analysis of genes located within these genomic regions revealed SNP disparities encoding polymorphic peptides in 10 cases. Differential recognition of patient-type, but not donor-type, peptides validated the identification of these MiHAs. Using tetramers, distinct populations of MiHA-specific CD8+ T cells were detected, demonstrating that our WGAs strategy allows high-throughput discovery of relevant targets in antitumor immunity after allo-SCT. Cancer Res; 70(22); 9073–83. ©2010 AACR.
A Sense of Urgency: Evaluating the Link between Clinical Trial Development Time and the Accrual Performance of Cancer Therapy Evaluation Program (NCI-CTEP) Sponsored Studies
Authors: Cheng Steven K. , Dietrich Mary S. , Dilts David M. 
Published: November 2010

Abstract
Purpose: Postactivation barriers to oncology clinical trial accruals are well documented; however, potential barriers prior to trial opening are not. We investigate one such barrier: trial development time.
Experimental Design: National Cancer Institute Cancer Therapy Evaluation Program (CTEP)–sponsored trials for all therapeutic, nonpediatric phase I, I/II, II, and III studies activated between 2000 and 2004 were investigated for an 8-year period (n = 419). Successful trials were those achieving 100% of minimum accrual goal. Time to open a study was the calendar time from initial CTEP submission to trial activation. Multivariate logistic regression analysis was used to calculate unadjusted and adjusted odds ratios (OR), controlling for study phase and size of expected accruals.
Results: Among the CTEP-approved oncology trials, 37.9% (n = 221) failed to attain the minimum accrual goals, with 70.8% (n = 14) of phase III trials resulting in poor accrual. A total of 16,474 patients (42.5% of accruals) accrued to those studies were unable to achieve the projected minimum accrual goal. Trials requiring less than 12 months of development were significantly more likely to achieve accrual goals (OR, 2.15; 95% confidence interval, 1.29-3.57, P = 0.003) than trials with the median development times of 12 to 18 months. Trials requiring a development time of greater than 24 months were significantly less likely to achieve accrual goals (OR, 0.40; 95% confidence interval, 0.20-0.78; P = 0.011) than trials with the median development time.
Conclusions: A large percentage of oncology clinical trials do not achieve minimum projected accruals. Trial development time appears to be one important predictor of the likelihood of successfully achieving the minimum accrual goals. Clin Cancer Res; 16(22); 5557–63. ©2010 AACR.
Atu027 Prevents Pulmonary Metastasis in Experimental and Spontaneous Mouse Metastasis Models
Authors: Santel Ansgar , Aleku Manuela , Röder Nadine , Möpert Kristin , Durieux Birgit , Janke Oliver , Keil Oliver , Endruschat Jens , Dames Sibylle , Lange Christian , Eisermann Mona , Löffler Kathrin , Fechtner Melanie , Fisch Gerald , Vank Christiane , Schaeper Ute , Giese Klaus , Kaufmann Jörg 
Published: November 2010

Abstract
Purpose: Atu027, a novel RNA interference therapeutic, has been shown to inhibit lymph node metastasis in orthotopic prostate cancer mouse models. The aim of this study is to elucidate the pharmacologic activity of Atu027 in inhibiting hematogenous metastasis to the target organ lung in four different preclinical mouse models.
Experimental Design: Atu027 compared with vehicle or control small interfering RNA lipoplexes was tested in two experimental lung metastasis models (Lewis lung carcinoma, B16V) and spontaneous metastasis mouse models (MDA-MB-435, MDA-MB-231, mammary fat pad). Different dosing schedules (repeated low volume tail vein injections) were applied to obtain insight into effective Atu027 treatment. Primary tumor growth and lung metastasis were measured, and tissues were analyzed by immunohistochemistry and histology. In vitro studies in human umbilical vein endothelial cells were carried out to provide an insight into molecular changes on depletion of PKN3, in support of efficacy results.
Results: Intravenous administration of Atu027 prevents pulmonary metastasis. In particular, formation of spontaneous lung metastasis was significantly inhibited in animals with large tumor grafts as well as in mice with resected primary mammary fat pad tumors. In addition, we provide evidence that an increase in VE-cadherin protein levels as a downstream result of PKN3 target gene inhibition may change endothelial function, resulting in reduced colonization and micrometastasis formation.
Conclusion: Atu027 can be considered as a potent drug for preventing lung metastasis formation, which might be suitable for preventing hematogenous metastasis in addition to standard cancer therapy. Clin Cancer Res; 16(22); 5469–80. ©2010 AACR.
Adamantyl-Substituted Retinoid-Related Molecules Induce Apoptosis in Human Acute Myelogenous Leukemia Cells
Authors: Farhana Lulu , Dawson Marcia I. , Xia Zebin , Aboukameel Amro , Xu Liping , Liu Gang , Das Jayanta K. , Hatfield James , Levi Edi , Mohammad Ramzi , Fontana Joseph A. 
Published: November 2010

Abstract
The adamantyl-substituted retinoid-related (ARR) compounds 3-Cl-AHPC and AHP3 induce apoptosis in vitro and in vivo in a newly established human acute myelogenous leukemia (AML) cell line, FFMA-AML, and in the established TF(v-SRC) AML cell line. FFMA-AML and TF(v-SRC) cells displayed resistance to apoptosis mediated by the standard retinoids (including trans-retinoic acid, 9-cis-retinoic acid, and the synthetic retinoid TTNPB) but showed sensitivity to apoptosis mediated by 3-Cl-AHPC– and AHP3 in vitro and in vivo as documented by poly(ADP-ribose) polymerase (PARP) cleavage and apoptosis terminal deoxyribonucleotidyl transferase–mediated dUTP nick end labeling assay. 3-Cl-AHPC or AHP3 exposure in vitro resulted in decreased expression of the antiapoptotic proteins (cellular inhibitor of apoptosis 1, X-linked inhibitor of apoptosis protein) and phospho-Bad and activated the NF-κB canonical pathway. A significant prolongation of survival was observed both in nonobese diabetic severe combined immunodeficient mice carrying FFMA-AML cells and treated with either 3-Cl-AHPC or AHP3 and in severe combined immunodeficient mice carrying TF(v-SRC) cells and treated with AHP3. We have previously shown that ARRs bind to the orphan nuclear receptor small heterodimer partner (SHP) and that the expression of SHP is required for ARR-mediated apoptosis. Induced loss of SHP in these AML cells blocked 3-Cl-AHPC– and AHP3-mediated induction of apoptosis. These results support the further development of 3-Cl-AHPC and AHP3 as potential therapeutic agents in the treatment of AML patients. Mol Cancer Ther; 9(11); 2903–13. ©2010 AACR.
The Marginal as Central: Al-Jadid and the Development of a Palestinian Public Sphere, 1953–1970
Authors: Nassar Maha 
Published: November 2010

AbstractThis article argues that throughout the 1950s and 1960s the communist-sponsored Arabic literary journal al-Jadid played a central role in creating a Palestinian-Arab counterpublic within Israel by challenging Zionist discourses and championing Arab and Palestinian causes. As a result, when Palestinian writers, activists and intellectuals in Israel were reconnected with Palestinians outside Israel after the 1967 War, they played a vital role in the development of a broader Palestinian public sphere that emphasized perseverance, ties to the land, and resistance to Zionist hegemony. rough content analysis of over 140 issues of al-Jadid published between 1953 and 1967, this article demonstrates al-Jadid's signifi cant role in communicating politically subversive discourses to an increasingly literate public living under military rule, as well as its part in the social circulation of these discourses in the region following the 1967 War. In doing so, it sheds new light on the nexus of media, literature and nationalism in the Palestinian context.
Kafah and the Non-Profit Globalization of Palestinian Media
Authors: Sienkiewicz Matt 
Published: November 2010

AbstractThis article provides a close analysis of the Ma'an Network's made-for-television film, Kafah, placing it within the context of major debates in the field of Palestinian media scholarship. It argues that Kafah challenges many historical limitations that scholars have attributed to media in the Palestinian territories and introduces new and potentially problematic power dynamics. As an international co-production between Western NGOs and Palestinian producers intended to impact Palestinian culture and media, Kafah exists both as a tool of local expression and as a means of foreign influence. The article attempts to identify the true balance of power driving the film's content through close textual analyses, reviews of internal documents and interviews with the film's creators and funding partners. Ultimately, it claims that while both internal and external pressures exert strong influence over the possibilities for the project, the producers are nonetheless able to express their own ideas and make a noteworthy contribution to the Palestinian mediated public sphere.
The Production and Interpretation of Anaphora and Ellipsis
Authors: Zeevat Henk 
Published: November 2010

AbstractThe paper tries to apply a psychological theory of language production and interpretation to the linguistic description of pronouns. The claim is that this is possible and helpful and that a full theory of the use and interpretation of pronouns is possible from this perspective, i.e.one that can both predict when pronouns are used and what is their antecedent. In particular, the theory should be able to explain the properties of pronoun resolution, pronoun selection in natural language generation and the grammaticalisation processes that lead to pronouns. The psychological theory proposed is motivated as an account of parity: the probable identity between the speaker intention and the hearer interpretation. It has four components: a minimal account of legal forms for a given input, speaker self-monitoring for a prioritised set of features, cue-based understanding and filtering by production. A good form for an intention is legal and marks the most prioritised features best, a good interpretation meets the production filter and is most strongly cued by the signal. Descriptively, the main component of self-monitoring for pronouns is an extension of the referential hierarchy (Gundel et al., 1993). Recency, frequency and relevance are effects of cue-based interpretation and central to pronoun resolution. The role of syntax is limited to the agreement features and subclassification of pronouns. The aim of the paper is not to contribute to pronoun resolution or generation but to explore the descriptive potential of a psychologically inspired account of parity in linguistic communication, with of course the hope that the understanding of pronouns benefits from this exercise.