bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recovery of acid damaged zooplankton communities: measurement, extent, and limiting factors
Authors: Gray Derek K. , Arnott Shelley E. 
Published: January 2010

Anthropogenic acidification has affected biota in thousands of lakes in eastern North America and Europe. To measure the degree and extent of biological recovery following pH recovery in acidified lakes, many studies have assessed changes occurring in acid-damaged zooplankton communities. In this review we synthesize studies of zooplankton recovery from regions severely affected by acidification. In doing so, we provide a critical overview of: (1) the design of studies used to detect recovery; (2) the status of communities in acidified regions; and (3) our current understanding of the factors that limit recovery. The design of most studies assessing zooplankton recovery fall into three categories based on their selection of data to be used for recovery benchmarks: (1) historical; (2) reference-lakes; and (3) temporal. Within these study designs, the most commonly used metrics include species richness, indicator species, and relative species abundances. Many studies have used species richness as the sole indicator of recovery; however, we argue that additional metrics should be considered in analyses to make conclusions more robust. Studies conducted in eastern North America and Northern Europe have demonstrated significant, though often incomplete, recovery of zooplankton communities in lakes that reach a pH > 6.0. Data collected in central Europe indicate little recovery in the heavily affected Bohemian Forest lakes, but complete recovery of species richness in the moderately acidified Tatra Mountain lakes. Factors limiting biological recovery, including slow chemical recovery, dispersal limitation, and community resistance, vary in importance among and within regions, suggesting that region- and lake-specific management approaches may be required.
Towards an integrated approach to modelling the risks and impacts of invasive forest species
Authors: Yemshanov Denys , McKenney Daniel W. , Pedlar John H. , Koch Frank H. , Cook David 
Published: January 2010

In this paper we provide an overview of an integrated approach to modelling the risks and impacts associated with non-indigenous forest pest species. This is a broad and important topic given the scale of ecological and economic consequences associated with non-indigenous species in North America and elsewhere. Assessments of risks and impacts remain difficult due to complexities and interactions between the many factors driving invasions and outcomes. These processes occur across various spatial and temporal scales, and are often influenced and complicated by human activities. For each component of an ecological invasion (i.e., arrival, establishment, and spread), we review general approaches for modelling the phenomenon and identify data and knowledge gaps. With the greater availability of various spatial data and computational power we suggest the possibility of linking the models for each invasion component into a more integrated framework, thus allowing interactions and feedbacks between components to be better incorporated into risk modelling efforts. The approach is illustrated using examples from current work with Sirex noctilio Fabricius — a relatively new invasive wood wasp in eastern North America.
Damage and cost simulation in pumped storm sewers
Authors: Imam E. H. , McCorquodale J A , Bewtra J K 
Published: January 2010

A flow-damage model has been developed to predict the annual probable damage due to basement and street floodings in relatively flat urban areas where pumping is required. The damage cost is obtained by integrating damages due to high as well as low probability storms. Annual capital recovery costs are also computed. The flow simulation is based on the Road Research Laboratory model, the Muskingum method, and a relaxation procedure for computation of surcharge conditions. The model can be used for design purposes or to evaluate existing systems. A suggested design procedure incorporating the flow-damage and installation cost models along with linear programming has been used to obtain an optimum design for a given pumped storm-sewer system. The optimal design is achieved when the combined cost of annual operating capital recovery, and annual probable damage is minimum. The design variables include the depths, slopes and diameters of the sewers. as well as sump area, rated pumping head, and discharge.
Trace-Inequalities and Matrix-Convex Functions
Authors: Ando Tsuyoshi 
Published: January 2010

AbstractA real-valued continuous function "Equation missing" on an interval "Equation missing" gives rise to a map "Equation missing" via functional calculus from the convex set of "Equation missing" Hermitian matrices all of whose eigenvalues belong to the interval. Since the subpace of Hermitian matrices is provided with the order structure induced by the cone of positive semidefinite matrices, one can consider convexity of this map. We will characterize its convexity by the following trace-inequalities: "Equation missing" for "Equation missing". A related topic will be also discussed.
Regularization and Iterative Methods for Monotone Variational Inequalities
Authors: Xu Xiubin , Xu Hong-Kun 
Published: January 2010

AbstractWe provide a general regularization method for monotone variational inequalities, where the regularizer is a Lipschitz continuous and strongly monotone operator. We also introduce an iterative method as discretization of the regularization method. We prove that both regularization and iterative methods converge in norm.
Sodium Orthovanadate Inhibits p53-Mediated Apoptosis
Authors: Morita Akinori , Yamamoto Shinichi , Wang Bing , Tanaka Kaoru , Suzuki Norio , Aoki Shin , Ito Azusa , Nanao Tomohisa , Ohya Soichiro , Yoshino Minako , Zhu Jin , Enomoto Atsushi , Matsumoto Yoshihisa , Funatsu Osamu , Hosoi Yoshio , Ikekita Masahiko 
Published: January 2010

Abstract
Sodium orthovanadate (vanadate) inhibits the DNA-binding activity of p53, but its precise effects on p53 function have not been examined. Here, we show that vanadate exerts a potent antiapoptotic activity through both transcription-dependent and transcription-independent mechanisms relative to other p53 inhibitors, including pifithrin (PFT) α. We compared the effects of vanadate to PFTα and PFTμ, an inhibitor of transcription-independent apoptosis by p53. Vanadate suppressed p53-associated apoptotic events at the mitochondria, including the loss of mitochondrial membrane potential, the conformational change of Bax and Bak, the mitochondrial translocation of p53, and the interaction of p53 with Bcl-2. Similarly, vanadate suppressed the apoptosis-inducing activity of a mitochondrially targeted temperature-sensitive p53 in stable transfectants of SaOS-2 cells. In radioprotection assays, which rely on p53, vanadate completely protected mice from a sublethal dose of 8 Gy and partially from a lethal dose of 12 Gy. Together, our findings indicated that vanadate effectively suppresses p53-mediated apoptosis by both transcription-dependent and transcription-independent pathways, and suggested that both pathways must be inhibited to completely block p53-mediated apoptosis. Cancer Res; 70(1); 257–65
Nucleolar Targeting of RelA(p65) Is Regulated by COMMD1-Dependent Ubiquitination
Authors: Thoms Hazel C. , Loveridge Carolyn J. , Simpson James , Clipson Alexandra , Reinhardt Karina , Dunlop Malcolm G. , Stark Lesley A. 
Published: January 2010

Abstract
Stimulation of the NF-κB pathway can have proapoptotic or antiapoptotic consequences, and one mechanism that determines the outcome is the nuclear distribution of RelA. Certain stress stimuli induce nucleolar accumulation of RelA thereby mediating apoptosis, whereas others induce nucleoplasmic accumulation and inhibition of apoptosis. Here we investigated the mechanisms that regulate the nuclear distribution of RelA, specifically, the role of the ubiquitin/proteasome system. We found that stress-induced nucleolar translocation of RelA is preceded by ubiquitination of the protein. We also found that chemical proteasome inhibitors induce the ubiquitination and nucleolar translocation of RelA and that this is required for the apoptotic response to these agents. We show that the RelA nucleolar localization signal (amino acids 27–30) is a critical domain for ubiquitination of the protein but that the lysine residue within this motif is not a direct target. We show that RelA binds COMMD1, the rate-limiting component of the RelA ubiquitin ligase complex, in response to stress. Furthermore, we show that overexpression of COMMD1 promotes stress-mediated nucleolar targeting of RelA, whereas knockdown of COMMD1 blocks this effect, causing RelA to remain in the nucleoplasm. These data identify a new role for COMMD1 in regulating the nuclear/nucleolar distribution of RelA and suggest that ubiquitination acts as a signal for transport of RelA to the nucleolus. These findings have relevance to the design of chemopreventative/anticancer agents that act by targeting RelA to the nucleolar compartment. Cancer Res; 70(1); 139–49
Recurrent Focal Copy-Number Changes and Loss of Heterozygosity Implicate Two Noncoding RNAs and One Tumor Suppressor Gene at Chromosome 3q13.31 in Osteosarcoma
Authors: Pasic Ivan , Shlien Adam , Durbin Adam D. , Stavropoulos Dimitrios J. , Baskin Berivan , Ray Peter N. , Novokmet Ana , Malkin David 
Published: January 2010

Abstract
Osteosarcomas are copy number alteration (CNA)–rich malignant bone tumors. Using microarrays, fluorescence in situ hybridization, and quantitative PCR, we characterize a focal region of chr3q13.31 (osteo3q13.31) harboring CNAs in 80% of osteosarcomas. As such, osteo3q13.31 is the most altered region in osteosarcoma and contests the view that CNAs in osteosarcoma are nonrecurrent. Most (67%) osteo3q13.31 CNAs are deletions, with 75% of these monoallelic and frequently accompanied by loss of heterozygosity (LOH) in flanking DNA. Notably, these CNAs often involve the noncoding RNAs LOC285194 and BC040587 and, in some cases, a tumor suppressor gene that encodes the limbic system-associated membrane protein (LSAMP). Ubiquitous changes occur in these genes in osteosarcoma, usually involving loss of expression. Underscoring their functional significance, expression of these genes is correlated with the presence of osteo3q13.31 CNAs. Focal osteo3q13.31 CNAs and LOH are also common in cell lines from other cancers, identifying osteo3q13.31 as a generalized candidate region for tumor suppressor genes. Osteo3q13.31 genes may function as a unit, given significant correlation in their expression despite the great genetic distances between them. In support of this notion, depleting either LSAMP or LOC285194 promoted proliferation of normal osteoblasts by regulation of apoptotic and cell-cycle transcripts and also VEGF receptor 1. Moreover, genetic deletions of LOC285194 or BC040587 were also associated with poor survival of osteosarcoma patients. Our findings identify osteo3q13.31 as a novel region of cooperatively acting tumor suppressor genes. Cancer Res; 70(1); 160–71
Combining Human and Rat Sequences in Her-2 DNA Vaccines Blunts Immune Tolerance and Drives Antitumor Immunity
Authors: Jacob Jennifer B. , Quaglino Elena , Radkevich-Brown Olga , Jones Richard F. , Piechocki Marie P. , Reyes Joyce D. , Weise Amy , Amici Augusto , Wei Wei-Zen 
Published: January 2010

AbstractImmune tolerance to tumor-associated self-antigens poses a major challenge in the ability to mount an effective cancer vaccine response. To overcome immune tolerance to HER-2, we formulated DNA vaccines that express both human HER-2 and heterologous rat Neu sequences in separate plasmids or as single hybrid constructs that encode HER-2/Neu fusion proteins. Candidate vaccines were tested in Her-2 transgenic (Tg) mice of BALB/c (BALB), BALB/c × C57BL/6 F1 (F1), or C57BL/6 (B6) background, which exhibit decreasing immune responsiveness to HER-2. Analysis of various cocktails or hybrid vaccines defined a requirement for particular combination of HER/2/Neu sequences to effectively prime immune effector cells in HER-2 Tg mice. In B6 HER-2 Tg mice, rejection of HER-2–positive tumors protected mice from HER-2–negative tumors, providing evidence of epitope spreading. Our findings show that a strategy of combining heterologous antigen with self-antigens could produce a potent DNA vaccine that may be applicable to other tumor-associated antigens. Cancer Res; 70(1); 119–28
A Novel Mouse Model for De novo Melanoma
Authors: Kumasaka Mayuko Y. , Yajima Ichiro , Hossain Khaled , Iida Machiko , Tsuzuki Toyonori , Ohno Tamio , Takahashi Masahide , Yanagisawa Masashi , Kato Masashi 
Published: January 2010

Abstract
Nevus-associated melanomas arise from pre-existing benign lesions, but de novo melanomas can also develop in the absence of such lesions. Few studies have addressed the latter phenomenon because no animal models have been described in which melanomas clearly develop in a de novo manner. In this study, we have address this need in defining RFP-RET-transgenic mice (RET mice) as a mouse model for multi-step melanomagenesis that proceeds via tumor-free, benign, premalignant, and malignant stages. Melanomas from RET mice exhibited decreased expression levels of endothelin receptor B (Ednrb) compared with benign tumors. In RET mice that were heterozygous for Ednrb (Ednrb+/−;RET mice), &gt;80% of the arising primary tumors were malignant. Life span after tumor development in the mice was significantly shorter than in RET mice. Lung metastasis after tumor development was significantly higher than in RET mice. The observed process of melanomagenesis in Ednrb+/−;RET mice, which proceeded without a pre-existing benign lesion, along with the emergent characteristics in the model after tumor development corresponded well with the formation of de novo melanoma in humans. Our findings define a novel transgenic mouse model for de novo melanoma and suggest that reduced expression of Ednrb might facilitate the development of de novo melanoma in humans. Cancer Res; 70(1); 24–9
Cancer Stem Cell Tumor Model Reveals Invasive Morphology and Increased Phenotypical Heterogeneity
Authors: Sottoriva Andrea , Verhoeff Joost J.C. , Borovski Tijana , McWeeney Shannon K. , Naumov Lev , Medema Jan Paul , Sloot Peter M.A. , Vermeulen Louis 
Published: January 2010

Abstract
The recently developed concept of cancer stem cells (CSC) sheds new light on various aspects of tumor growth and progression. Here, we present a mathematical model of malignancies to investigate how a hierarchical organized cancer cell population affects the fundamental properties of solid malignancies. We establish that tumors modeled in a CSC context more faithfully resemble human malignancies and show invasive behavior, whereas tumors without a CSC hierarchy do not. These findings are corroborated by in vitro studies. In addition, we provide evidence that the CSC model is accompanied by highly altered evolutionary dynamics compared with the ones predicted to exist in a stochastic, nonhierarchical tumor model. Our main findings indicate that the CSC model allows for significantly higher tumor heterogeneity, which may affect therapy resistance. Moreover, we show that therapy which fails to target the CSC population is not only unsuccessful in curing the patient, but also promotes malignant features in the recurring tumor. These include rapid expansion, increased invasion, and enhanced heterogeneity. Cancer Res; 70(1); 46–56
K562/GM-CSF Immunotherapy Reduces Tumor Burden in Chronic Myeloid Leukemia Patients with Residual Disease on Imatinib Mesylate
Authors: Smith B. Douglas , Kasamon Yvette L. , Kowalski Jeanne , Gocke Christopher , Murphy Kathleen , Miller Carole B. , Garrett-Mayer Elizabeth , Tsai Hua-Ling , Qin Lu , Chia Christina , Biedrzycki Barbara , Harding Thomas C. , Tu Guang Haun , Jones Richard , Hege Kristen , Levitsky Hyam I. 
Published: January 2010

Abstract
Purpose: Chronic myeloid leukemia (CML) can be responsive to T-cell–mediated immunity. K562/granulocyte macrophage-colony stimulating factor (GM-CSF) is a GM-CSF producing vaccine derived from a CML cell line that expresses several CML-associated antigens. A pilot study was developed to determine if K562/GM-CSF immunotherapy could improve clinical responses to imatinib mesylate (IM) in patients with chronic myeloid leukemia.
Experimental Design: Patients with chronic phase CML who achieved at least a major cytogeneic response but remained with persistent, measurable disease despite one or more years on imatinib mesylate were eligible. Each was given a series of four vaccines administered in three-week intervals, with or without topical imiquimod, while remaining on a stable dose of imatinib mesylate. CML disease burden was measured serially before and after vaccination.
Results: Nineteen patients were vaccinated, with a median duration of previous imatinib mesylate therapy of 37 (13–53) months. Mean PCR measurements of BCR-ABL for the group declined significantly following the vaccines (P = 0.03). Thirteen patients had a progressive decline in disease burden, 8 of whom had increasing disease burden before vaccination. Twelve patients achieved their lowest tumor burden measurements to date following vaccine, including seven subjects who became PCR-undetectable.
Conclusions: K562/GM-CSF vaccine appears to improve molecular responses in patients on imatinib mesylate, including achieving complete molecular remissions, despite long durations of previous imatinib mesylate therapy. Clin Cancer Res; 16(1); 338–47
The Telomerase Antagonist, Imetelstat, Efficiently Targets Glioblastoma Tumor-Initiating Cells Leading to Decreased Proliferation and Tumor Growth
Authors: Marian Calin O. , Cho Steve K. , Mcellin Brian M. , Maher Elizabeth A. , Hatanpaa Kimmo J. , Madden Christopher J. , Mickey Bruce E. , Wright Woodring E. , Shay Jerry W. , Bachoo Robert M. 
Published: January 2010

Abstract
Purpose: Telomerase activity is one of the hallmarks of cancer and is a highly relevant therapeutic target. The effects of a novel human telomerase antagonist, imetelstat, on primary human glioblastoma (GBM) tumor-initiating cells were investigated in vitro and in vivo.
Experimental Design: Tumor-initiating cells were isolated from primary GBM tumors and expanded as neurospheres in vitro. The GBM tumor-initiating cells were treated with imetelstat and examined for the effects on telomerase activity levels, telomere length, proliferation, clonogenicity, and differentiation. Subsequently, mouse orthotopic and subcutaneous xenografts were used to assess the in vivo efficacy of imetelstat.
Results: Imetelstat treatment produced a dose-dependent inhibition of telomerase (IC50 0.45 μmol/L). Long-term imetelstat treatment led to progressive telomere shortening, reduced rates of proliferation, and eventually cell death in GBM tumor-initiating cells. Imetelstat in combination with radiation and temozolomide had a dramatic effect on cell survival and activated the DNA damage response pathway. Imetelstat is able to cross the blood-brain barrier in orthotopic GBM xenograft tumors. Fluorescently labeled GBM tumor cells isolated from orthotopic tumors, following systemic administration of imetelstat (30 mg/kg every day for three days), showed ∼70% inhibition of telomerase activity. Chronic systemic treatment produced a marked decrease in the rate of xenograft subcutaneous tumor growth.
Conclusion: This preclinical study supports the feasibility of testing imetelstat in the treatment of GBM patients, alone or in combination with standard therapies. Clin Cancer Res; 16(1); 154–63
ERP Correlates of Word Production before and after Stroke in an Aphasic Patient
Authors: Laganaro Marina , Morand Stéphanie , Michel Christoph M. , Spinelli Laurent , Schnider Armin 
Published: January 2010

Abstract
Changes in brain activity characterizing impaired speech production after brain damage have usually been investigated by comparing aphasic speakers with healthy subjects because prestroke data are normally not available. However, when interpreting the results of studies of stroke patients versus healthy controls, there is an inherent difficulty in disentangling the contribution of neuropathology from other sources of between-subject variability. In the present work, we had an unusual opportunity to study an aphasic patient with severe anomia who had incidentally performed a picture naming task in an ERP study as a control subject one year before suffering a left hemisphere stroke. The fortuitous recording of this patient's brain activity before his stroke allows direct comparison of his pre- and poststroke brain activity in the same language production task. The subject did not differ from other healthy subjects before his stroke, but presented major electrophysiological differences after stroke, both in comparison to himself before stroke and to the control group. ERP changes consistently appeared after stroke in a specific time window starting about 250 msec after picture onset, characterized by a single divergent but stable topographic configuration of the scalp electric field associated with a cortical generator abnormally limited to left temporal posterior perilesional areas. The patient's pattern of anomia revealed a severe lexical–phonological impairment and his ERP responses diverged from those of healthy controls in the time window that has previously been associated with lexical–phonological processes during picture naming. Given that his prestroke ERPs were indistinguishable from those of healthy controls, it seems highly likely that the change in his poststroke ERPs is due to changes in language production processes as a consequence of stroke. The patient's neurolinguistic deficits, combined with the ERPs results, provide unique evidence for the role of left temporal cortex in lexical–phonological processing from about 250 to 450 msec during word production.
Musicians and the Metric Structure of Words
Authors: Marie Céline , Magne Cyrille , Besson Mireille 
Published: January 2010

Abstract
The present study aimed to examine the influence of musical expertise on the metric and semantic aspects of speech processing. In two attentional conditions (metric and semantic tasks), musicians listened to short sentences ending in trisyllabic words that were semantically and/or metrically congruous or incongruous. Both ERPs and behavioral data were analyzed and the results were compared to previous nonmusicians' data. Regarding the processing of meter, results showed that musical expertise influenced the automatic detection of the syllable temporal structure (P200 effect), the integration of metric structure and its influence on word comprehension (N400 effect), as well as the reanalysis of metric violations (P600 and late positivities effects). By contrast, results showed that musical expertise did not influence the semantic level of processing. These results are discussed in terms of transfer of training effects from music to speech processing.