bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal changes in species composition of mixedwood stands in northwest New Brunswick: 1946–2008
Authors: Amos-Binks Luke J. , MacLean David A. , Wilson Jeremy S. , Wagner Robert G. 
Published: January 2010

Patterns of softwood (SW) – hardwood (HW) change from 1946 to 2006 in 32 unharvested mixedwood (MW) stands in northern New Brunswick were analyzed using aerial photographs (1946, 1966, 1982, and 2006), sampled, and related to disturbance and stand conditions. Five stand development patterns were identified based on 1946 SW content (70%–80%, termed SW versus 30%–60%, termed MW) and change in SW content from 1946 to 2006 (SW-stable, SW-declining, MW-fluctuating, MW-stable, or MW-declining). Species composition was surprisingly changeable over this 60-year period, with change in SW content varying from +18% to –62%. High canopy cover reduction from 1946 to 1966 resulted from balsam fir ( Abies balsamea (L.) Mill.) mortality due to old age and a 1950s spruce budworm ( Choristoneura fumiferana Clem.) outbreak plus birch ( Betula sp.) dieback. SW-stable stands that maintained SW composition from 1946 to 2006 (+7%) had more red spruce ( Picea rubens Sarg.) than all other classes in which SW declined by 15%–47%. SW-declining stands were located on southerly aspects (189°) and had higher mean elevations (423 m) than other classes. Results suggest that balsam fir – tolerant HW MW stands may be naturally transitional due to disturbance, species, and stand conditions, which has significant implications for forest management designed to maintain static proportions of MW and SW stands.
A Flow Cytometry Method to Quantitate Internalized Immunotoxins Shows that Taxol Synergistically Increases Cellular Immunotoxins Uptake
Authors: Zhang Yujian , Hansen Johanna K. , Xiang Laiman , Kawa Seiji , Onda Masanori , Ho Mitchell , Hassan Raffit , Pastan Ira 
Published: January 2010

Abstract
Tumor microenvironments present significant barriers to penetration by antibodies, immunoconjugates, and other immunotoxins. In this report, we illustrate a novel strategy to increase tumor cell uptake of immunotoxin by combination with Taxol. SS1P is an immunotoxin composed of the Fv portion of a mesothelin-specific antibody fused to a bacterial toxin that is presently undergoing phase II testing in mesothelioma. Using novel flow cytometry and gel filtration methods, we quantified SS1P uptake in individual tumor cells along with levels of shed mesothelin (sMSLN), a barrier of SS1P therapy. The validity of our flow cytometric method was confirmed by the ability to similarly quantitate tumor cell uptake of Herceptin and an immunotoxin targeting HER2/neu. SS1P uptake peaked several hours after SS1P was cleared from the blood, reflecting an intratumor distribution process of SS1P that is independent of blood supply. Using the methods developed, we demonstrated that Taxol could improve SS1P penetration into tumors in parallel with an associated reduction of sMSLN in tumor extracellular fluid. Our findings offer a mechanistic rationale to combine SS1P with Taxol or another cytotoxic drug as a strategy to increase immunotoxin uptake by tumor cells. Further, we suggest one basis to understand why chemotherapy and antibody-based therapies cooperate when combined in cancer treatment. Cancer Res; 70(3); 1082–9
Definition of a Functional Single Nucleotide Polymorphism in the Cell Migration Inhibitory Gene MIIP That Affects the Risk of Breast Cancer
Authors: Song Fangfang , Ji Ping , Zheng Hong , Song Fengju , Wang Yingmei , Hao Xishan , Wei Qingyi , Zhang Wei , Chen Kexin 
Published: January 2010

Abstract
The migration and invasion inhibitory protein MIIP is an inhibitor of cancer cell migration and invasion that inhibits breast tumorigenesis. In this case-control study, we evaluated the MIIP single nucleotide polymorphism (SNP) rs2295283 (codon 167, A&gt;G, K&gt;E) from 1,524 breast cancer patients and 1,592 age-matched controls for its association with breast cancer risk. SNP analysis included a validation set of 736 cases and 760 controls. Colony formation and cell migration assays were then conducted to functionally interrogate the genotype difference. When compared with the AA genotype, the combined AG + GG genotypes (167E) were associated with a significantly lower risk of breast cancer. In the test set, the protective effects of the AG + GG genotypes were more evident among participants with a family history of cancer. Further case series analysis revealed that the GG genotype was associated with reduced breast cancer susceptibility in cases of tumor size &gt;2 cm and late clinical stage (II + III + IV). Colony formation assays showed that MIIP 167E (the G variant) was a more potent inhibitor of colony formation but not cell migration. These results suggest MIIP K167E as a functional genetic marker of breast cancer development and prognosis. Cancer Res; 70(3); 1024–32
Heterogeneity for Stem Cell–Related Markers According to Tumor Subtype and Histologic Stage in Breast Cancer
Authors: Park So Yeon , Lee Hee Eun , Li Hailun , Shipitsin Michail , Gelman Rebecca , Polyak Kornelia 
Published: January 2010

AbstractPurpose: To evaluate the expression of stem cell–related markers at the cellular level in human breast tumors of different subtypes and histologic stage.Experimental Design: We performed immunohistochemical analyses of 12 proteins [CD44, CD24, ALDH1, vimentin, osteonectin, EPCR, caveolin 1, connexin 43, cytokeratin 18 (CK18), MUC1, claudin 7, and GATA3] selected based on their differential expression in breast cancer cells with more differentiated and stem cell–like characteristics in 47 cases of invasive ductal carcinoma (IDC) only, 135 cases of IDC with ductal carcinoma in situ (DCIS), 35 cases of DCIS with microinvasion, and 58 cases of pure DCIS. We also analyzed 73 IDCs with adjacent DCIS to determine the differences in the expression of markers by histology within individual tumors. CD44+/CD24− and CD24−/CD24+ cells were detected using double immunohistochemistry.Results: CD44 and EPCR expression was different among the four histologic groups and was lower in invasive compared with in situ tumors, especially in luminal A subtype. The expression of vimentin, osteonectin, connexin 43, ALDH1, CK18, GATA3, and MUC1 differed by tumor subtype in some histologic groups. ALDH1-positive cells were more frequent in basal-like and HER2+ than in luminal tumors. CD44+/CD24− cells were detected in 69% of all tumors with 100% of the basal-like and 52% of HER2+ tumors having some of these cells.Conclusions: Our findings suggest that in breast cancer, the frequency of tumor cells positive for stem cell–like and more differentiated cell markers varies according to tumor subtype and histologic stage. Clin Cancer Res; 16(3); 876–87
18F-Fluorodeoxyglucose Positron Emission Tomography Predicts Survival of Patients with Neuroendocrine Tumors
Authors: Binderup Tina , Knigge Ulrich , Loft Annika , Federspiel Birgitte , Kjaer Andreas 
Published: January 2010

Abstract
Purpose: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is currently not used on a routine basis for imaging of neuroendocrine (NE) tumors. The aim of this study was to investigate the prognostic value of FDG-PET in patients with NE tumors.
Experimental Design: Ninety-eight prospectively enrolled patients with NE tumors underwent FDG-PET imaging. FDG uptake was quantified by maximal standardized uptake value (SUVmax). The prognostic value of FDG uptake, proliferation index, chromogranin A, and liver metastases were assessed.
Results: During the 1-year follow-up, 14 patients died. The diagnostic sensitivity of FDG-PET was 58% (n = 57) and a positive FDG-PET result was associated with a significantly higher risk of death with a hazard ratio (HR) of 10.3 [95% confidence interval (CI), 1.3-78.9]. Thirteen of the 57 (23%) FDG-PET–positive patients died compared with 1 of 41 (2%) FDG-PET–negative patients. By univariate analysis, a SUVmax of &gt;9 and a high Ki67 index were significant predictors of overall survival with a HR of 8.8 (95% CI, 2.7-28.7) and a HR of 2.6 (95% CI, 1.3-5.1), respectively. In a multivariate analysis including a SUVmax of &gt;3, Ki67, and chromogranin A, SUVmax of &gt;3 was the only predictor of progression-free survival (HR, 8.4; P &lt; 0.001).
Conclusions: This study shows a strong prognostic value of FDG-PET for NE tumors, which exceeds the prognostic value of traditional markers such as Ki67, chromogranin A, and liver metastases. FDG-PET may obtain an important role for NE tumors. Clin Cancer Res; 16(3); 978–85
Efficacy of Combining GMX1777 with Radiation Therapy for Human Head and Neck Carcinoma
Authors: Kato Hisayuki , Ito Emma , Shi Wei , Alajez Nehad M. , Yue Shijun , Lee Carolina , Chan Norman , Bhogal Nirmal , Coackley Carla L. , Vines Doug , Green David , Waldron John , Gullane Patrick , Bristow Rob , Liu Fei-Fei 
Published: January 2010

Abstract
Purpose: Rapidly metabolizing tumor cells have elevated levels of nicotinamide phosphoribosyltransferase, an enzyme involved in NAD+ biosynthesis, which serves as an important substrate for proteins involved in DNA repair. GMX1777, which inhibits nicotinamide phosphoribosyltransferase, was evaluated in two human head and neck cancer models in combination with radiotherapy.
Experimental Design: Effects of GMX1777-mediated radiosensitization were examined via metabolic and cytotoxicity assays in vitro; mechanism of action, in vivo antitumor efficacy, and radiosensitization were also investigated.
Results: IC50 values of GMX1777 for FaDu and C666-1 cells were 10 and 5 nmol/L, respectively, which interacted synergistically with radiotherapy. GMX1777 induced a rapid decline in intracellular NAD+ followed by ATP reduction associated with significant cytotoxicity. These metabolic changes were slightly increased with the addition of radiotherapy, although poly(ADP-ribose) polymerase activity was significantly reduced when GMX1777 was combined with radiotherapy, thereby accounting for the synergistic cytotoxicity of these two modalities. Systemic GMX1777 administration with local tumor radiotherapy caused complete disappearance of FaDu and C666-1 tumors for 50 and 20 days, respectively. There was also significant reduction in tumor vascularity, particularly for the more sensitive FaDu model. [18F]FDG-positron emission tomography/computed tomography images showed reduction in [18F]FDG uptake after GMX1777 administration, showing decreased glucose metabolism in vivo.
Conclusions: Our data represent the first report showing that GMX1777 plus radiotherapy is an effective therapeutic strategy for head and neck cancer, mediated via pleiotropic effects of inhibition of DNA repair and tumor angiogenesis, while sparing normal tissues. Therefore, GMX1777 combined with radiotherapy definitely warrants clinical evaluation in human head and neck cancer patients. Clin Cancer Res; 16(3); 898–911
Associations between Radiocurability and Interstitial Fluid Pressure in Human Tumor Xenografts without Hypoxic Tissue
Authors: Rofstad Einar K. , Ruud Else-Beate M. , Mathiesen Berit , Galappathi Kanthi 
Published: January 2010

Abstract
Purpose: The interstitial fluid pressure (IFP) of the primary tumor is an independent prognostic parameter for cervical cancer patients treated with radiation therapy. The aim of this preclinical study was to investigate whether tumor radiocurability may be associated with IFP through hypoxia-independent mechanisms.
Experimental Design: Small A-07 and R-18 melanoma xenografts without hypoxic tissue were used as preclinical tumor models. IFP was measured by using the wick-in-needle method. Radiation dose resulting in 50% local tumor control (TCD50), cell density, cell tumorigenicity, plating efficiency in vitro, mitotic index, fraction of Ki67-positive cells, vascular endothelial growth factor-A (VEGF-A) concentration, and radiation-induced endothelial cell apoptosis were assessed in tumors with low and high IFP.
Results: TCD50 was found to be higher for tumors with high IFP than for tumors with low IFP by factors of 1.13 ± 0.03 (A-07; P &lt; 0.0001) and 1.10 ± 0.03 (R-18; P &lt; 0.0001). In the A-07 line, tumors with high IFP showed a larger number of clonogenic cells and a higher rate of cell proliferation than tumors with low IFP. In the R-18 line, tumors with high IFP showed a higher concentration of VEGF-A and a lower endothelial cell apoptotic index after irradiation than tumors with low IFP.
Conclusions: The radiation resistance of normoxic tumor tissue with highly elevated IFP may be an indirect consequence of increased tumor cell clonogenicity as well as increased VEGF-A expression, possibly caused by hypertension-induced modifications of signaling pathways regulating cell proliferation, cell survival, and/or angiogenesis. Clin Cancer Res; 16(3); 936–45
Monitoring Drug-Induced γH2AX as a Pharmacodynamic Biomarker in Individual Circulating Tumor Cells
Authors: Wang Lihua H. , Pfister Thomas D. , Parchment Ralph E. , Kummar Shivaani , Rubinstein Larry , Evrard Yvonne A. , Gutierrez Martin E. , Murgo Anthony J. , Tomaszewski Joseph E. , Doroshow James H. , Kinders Robert J. 
Published: January 2010

AbstractPurpose: Circulating tumor cells (CTC) in peripheral blood of patients potentially represent a fraction of solid tumor cells available for more frequent pharmacodynamic assessment of drug action than is possible using tumor biopsy. However, currently available CTC assays are limited to cell membrane antigens. Here, we describe an assay that directly examines changes in levels of the nuclear DNA damage marker γH2AX in individual CTCs of patients treated with chemotherapeutic agents.Experimental Design: An Alexa Fluor 488–conjugated monoclonal γH2AX antibody and epithelial cancer cell lines treated with topotecan and spiked into whole blood were used to measure DNA damage–dependent nuclear γH2AX signals in individual CTCs. Time-course changes in both CTC number and γH2AX levels in CTCs were also evaluated in blood samples from patients undergoing treatment.Results: The percentage of γH2AX-positive CTCs increased in a concentration-dependent manner in cells treated with therapeutically relevant concentrations of topotecan ex vivo. In samples from five patients, percent γH2AX-positive cells increased post-treatment from a mean of 2% at baseline (range, 0-6%) to a mean of 38% (range, 22-64%) after a single day of drug administration; this increase was irrespective of increases or decreases in the total CTC count.Conclusions: These data show promise for monitoring dynamic changes in nuclear biomarkers in CTCs (in addition to CTC count) for rapidly assessing drug activity in clinical trials of molecularly targeted anticancer therapeutics as well as for translational research. Clin Cancer Res; 16(3); 1073–84
Short Note The Jubilee: Its Reckoning and Inception Day
Authors: Kim Young Hye 
Published: January 2010

AbstractNew solutions are proposed to the puzzles of how the Jubilee Year is reckoned and why the Jubilee begins on the Day of Atonement. The Jubilee cycle begins not in the first year of the Sabbath-year cycle, but the seventh, fallow year. The Jubilee begins on the Day of Atonement because of its Sabbath associations.
“A Young Goat in Its Mother’s Milk”? Understanding an Ancient Prohibition
Authors: Schorch Stefan 
Published: January 2010

AbstractThe passage should be understood as “you shall not cook (for eating purposes) a sucking kid”. This is not only the meaning of the passage in the Covenant Code (Exod 23:19) and in the so-called “Privilegrecht” (Exod 34:26), but it was the way as well in which this passage was understood by the authors of Deuteronomy (Deut 14:21). Amos 6:4 seems to contain an early reference to the prohibition of the sucking kid.
'Fortress Europe' and FRONTEX: Within or Without International Law?
Authors: Papastavridis Efthymios 
Published: January 2010

AbstractIt is true that the problem of interception of human beings on the high seas is more acute than ever, not only in terms of the number of vessels intercepted but also in terms of the variety of legal issues that it raises. The most worrisome observation, however, is that while interception of human beings has been practiced for centuries, currently the pendulum has swung from interception to free and save lives, for example, in the context of chattel slavery, to interception to prevent people from entering developed States and claiming a better future. This is particularly reflected in the practice of EU Member States, which have taken many initiatives in the maritime domain to strengthen the external borders of 'fortress' Europe. Lately, this practice is coordinated by a European Agency, commonly referred to as FRONTEX, which was established in 2004 in order to "coordinate the operational cooperation between Member States in the field of external borders management". To this end, FRONTEX has launched a number of maritime interdiction operations carried out on the high seas and even further, i.e. in the territorial seas of States of departure or transit, such as Mauritania, Senegal, Cape Verde. The purpose of this article is to address the most important questions that these maritime operations of FRONTEX raise, analysing them through the lens of the law of the sea and other rules of corpus juris gentium. Accordingly, in the first part there will be a thorough discussion of the pertinent legal bases of the interception operations on the high seas and in the territorial waters, while in the second the analysis will focus more on the relevance of other international rules like the use of force or the principle of non-refoulement to the present context. The application of the latter principle appears to be especially problematic in the majority of these operations since it is very likely that the persons onboard the intercepted vessels would be forced to return to their countries of origin, where they may be subjected to torture or inhuman or degrading treatment.
The Competency of Children to Testify: Psychological Research Informing Canadian Law Reform
Authors: Lee Kang ,   Lindsay, Talwar Victoria , Bala Nicholas 
Published: January 2010

AbstractThe competency inquiry has traditionally been a critical initial challenge for child witnesses, most of who are called to testify about their own victimization or as witnesses of family violence. In most common law countries children can only testify if they can correctly answer questions about such abstract concepts as the “oath,” the “promise” and “truth.” These inquiries can be confusing to children, and may prevent children who are capable of giving important evidence from testifying. Recent psychological research establishes that the ability of children to answer questions about the meaning of such concepts as “truth” and “promise” is not related to whether they will actually tell the truth, but the act of “promising to tell the truth” increases the likelihood that children will tell the truth. Informed by this research, in 2006 Canada significantly reformed its laws governing the process for determining the competence of child witnesses. The last section of the paper briefly surveys laws that govern the competency of child witnesses in a number of other jurisdictions and offers proposals for reform.
Gastrointestinal Neoplasms in Nonhuman Primates: A Review and Report of Eleven New Cases
Authors: DePaoli A. , McClure H. M. 
Published: January 2010

Reported gastrointestinal neoplasms in nonhuman primates are reviewed, and the clinical and pathologic features of 11 new cases are described. The 11 monkeys had a total of 12 malignant gastrointestinal neoplasms; one had two primary carcinomas, one in the colon and one in the duodenum. Ten of the 12 tumors were adenocarcinomas: two in the duodenum, one in the jejunum, four in the distal ileum or region of the ileocecal valve and three in the large intestine. The remaining two lesions were a histiocytic lymphosarcoma of the stomach and a poorly differentiated sarcoma of the cecum. The 11 animals included nine Macaca mulatta, one Saguinus oedipus oedipus and one Galago crassicaudatus. All were adults and most were aged. There were six females and five males. Clinical signs included progressive weight loss, a palpable abdominal mass and intermittent diarrhea. Grossly, five of the adenocarcinomas were annular, and constricted the intestinal lumen. Microscopically, the carcinomas generally were well differentiated, and two produced mucin in quantities warranting the modifier “mucinous” adenocarcinoma. All tumors were locally invasive and six of nine monkeys with carcinomas had metastases, with the regional lymph nodes the principal site of involvement.
Oral History of McCreesh Place, Apartment Building for (Formerly) Homeless Men: Advancing the Warp and Balancing the Weave
Authors: Davis Christine S. , Delynko Kristi AnaMaria , Cook Jermayne 
Published: January 2010

Colors of gold, blue, green, and brown— Bold colors, timid colors, quiet colors, exotic colors— colors of the brave, and the weak. Like society’s discarded yarn, warp threads, tangled threads, they spin and choke, beaten and wound, balanced and counterbalanced and framed by handouts and handsup, until each voice clearly distinct and yet clearly different E- merges to create a new voice. A new voice. A new story. Our story. The story of McCreesh Place. Apartment building for (formerly) homeless men.
Low physiologic oxygen tensions reduce proliferation and differentiation of human multipotent mesenchymal stromal cells
Authors: Holzwarth Christina , Vaegler Martin , Gieseke Friederike , Pfister Stefan M , Handgretinger Rupert , Kerst Gunter , Müller Ingo 
Published: January 2010

Abstract

Background
Human multipotent mesenchymal stromal cells (MSC) can be isolated from various tissues including bone marrow. Here, MSC participate as bone lining cells in the formation of the hematopoietic stem cell niche. In this compartment, the oxygen tension is low and oxygen partial pressure is estimated to range from 1% to 7%. We analyzed the effect of low oxygen tensions on human MSC cultured with platelet-lysate supplemented media and assessed proliferation, morphology, chromosomal stability, immunophenotype and plasticity.

Results
After transferring MSC from atmospheric oxygen levels of 21% to 1%, HIF-1α expression was induced, indicating efficient oxygen reduction. Simultaneously, MSC exhibited a significantly different morphology with shorter extensions and broader cell bodies. MSC did not proliferate as rapidly as under 21% oxygen and accumulated in G1 phase. The immunophenotype, however, was unaffected. Hypoxic stress as well as free oxygen radicals may affect chromosomal stability. However, no chromosomal abnormalities in human MSC under either culture condition were detected using high-resolution matrix-based comparative genomic hybridization. Reduced oxygen tension severely impaired adipogenic and osteogenic differentiation of human MSC. Elevation of oxygen from 1% to 3% restored osteogenic differentiation.

Conclusion
Physiologic oxygen tension during in vitro culture of human MSC slows down cell cycle progression and differentiation. Under physiological conditions this may keep a proportion of MSC in a resting state. Further studies are needed to analyze these aspects of MSC in tissue regeneration.