bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immuno-Oncology biomarkers 2010 and beyond: Perspectives from the iSBTc/SITC biomarker task force
Authors: Butterfield Lisa H , Disis Mary L , Khleif Samir N , Balwit James M , Marincola Francesco M 
Published: December 2010

Abstract
The International Society for Biological Therapy of Cancer (iSBTc, recently renamed the Society for Immunotherapy of Cancer, SITC) hosted a one-day symposium at the National Institutes of Health on September 30, 2010 to address development and application of biomarkers in cancer immunotherapy. The symposium, titled Immuno-Oncology Biomarkers 2010 and Beyond: Perspectives from the iSBTc/SITC Biomarker Task Force, gathered approximately 230 investigators equally from academia, industry and governmental/regulatory agencies from around the globe for panel discussions and presentations on the following topics: 1) immunologic monitoring: standardization and validation of assays; 2) correlation of immunity to biologic activity, clinical response and potency assays; 3) novel methodologies for assessing the immune landscape: clinical utility of novel technologies; and 4) recommendations on incorporation of biomarkers into the clinical arena. The presentations are summarized in this report; additional program information and slides are available online at the iSBTc/SITC website.
Protection against H1N1 influenza challenge by a DNA vaccine expressing H3/H1 subtype hemagglutinin combined with MHC class II-restricted epitopes
Authors: Tan Lei , Lu Huijun , Zhang Dan , Tian Mingyao , Hu Bo , Wang Zhuoyue , Jin Ningyi 
Published: December 2010

Abstract

Background
Multiple subtypes of avian influenza viruses have crossed the species barrier to infect humans and have the potential to cause a pandemic. Therefore, new influenza vaccines to prevent the co-existence of multiple subtypes within a host and cross-species transmission of influenza are urgently needed.

Methods
Here we report a multi-epitope DNA vaccine targeted towards multiple subtypes of the influenza virus. The protective hemagglutinin (HA) antigens from H5/H7/H9 subtypes were screened for MHC II class-restricted epitopes overlapping with predicted B cell epitopes. We then constructed a DNA plasmid vaccine, pV-H3-EHA-H1, based on HA antigens from human influenza H3/H1 subtypes combined with the H5/H7/H9 subtype Th/B epitope box.

Results
Epitope-specific IFN-γ ELISpot responses were significantly higher in the multi-epitope DNA group than in other vaccine and control groups (P < 0.05). The multi-epitope group significantly enhanced Th2 cell responses as determined by cytokine assays. The survival rate of mice given the multi-epitope vaccine was the highest among the vaccine groups, but it was not significantly different compared to those given single antigen expressing pV-H1HA1 vaccine and dual antigen expressing pV-H3-H1 vaccine (P > 0.05). No measurable virus titers were detected in the lungs of the multi-epitope immunized group. The unique multi-epitope DNA vaccine enhanced virus-specific antibody and cellular immunity as well as conferred complete protection against lethal challenge with A/New Caledonia/20/99 (H1N1) influenza strain in mice.

Conclusions
This approach may be a promising strategy for developing a universal influenza vaccine to prevent multiple subtypes of influenza virus and to induce long-term protective immune against cross-species transmission.
Therapeutic activity of two xanthones in a xenograft murine model of human chronic lymphocytic leukemia
Authors: Loisel Séverine , Le Ster Karine , Meyer Michèle , Berthou Christian , Youinou Pierre , Kolb Jean-Pierre , Billard Christian 
Published: December 2010

Abstract

Background
We previously reported that allanxanthone C and macluraxanthone, two xanthones purified from Guttiferae trees, display in vitro antiproliferative and proapoptotic activities in leukemic cells from chronic lymphocytic leukemia (CLL) and leukemia B cell lines.

Results
Here, we investigated the in vivo therapeutic effects of the two xanthones in a xenograft murine model of human CLL, developed by engrafting CD5-transfected chronic leukemia B cells into SCID mice. Treatment of the animals with five daily injections of either allanxanthone C or macluraxanthone resulted in a significant prolongation of their survival as compared to control animals injected with the solvent alone (p = 0.0006 and p = 0.0141, respectively). The same treatment of mice which were not xenografted induced no mortality.

Conclusion
These data show for the first time the in vivo antileukemic activities of two plant-derived xanthones, and confirm their potential interest for CLL therapy.
Phase III Comparison of Prophylactic Cranial Irradiation Versus Observation in Patients With Locally Advanced Non–Small-Cell Lung Cancer: Primary Analysis of Radiation Therapy Oncology Group Study RTOG 0214
Authors: Gore Elizabeth M. , Bae Kyounghwa , Wong Stuart J. , Sun Alexander , Bonner James A. , Schild Steven E. , Gaspar Laurie E. , Bogart Jeffery A. , Werner-Wasik Maria , Choy Hak 
Published: December 2010

PurposeThis study was conducted to determine if prophylactic cranial irradiation (PCI) improves survival in locally advanced non–small-cell lung cancer (LA-NSCLC).Patients and MethodsPatients with stage III NSCLC without disease progression after treatment with surgery and/or radiation therapy (RT) with or without chemotherapy were eligible. Participants were stratified by stage (IIIA v IIIB), histology (nonsquamous v squamous), and therapy (surgery v none) and were randomly assigned to PCI or observation. PCI was delivered to 30 Gy in 15 fractions. The primary end point of the study was overall survival (OS). Secondary end points were disease-free survival (DFS), neurocognitive function (NCF), and quality of life. Kaplan-Meier and log-rank analyses were used for OS and DFS. The incidence of brain metastasis (BM) was evaluated with the logistic regression model.ResultsOverall, 356 patients were accrued of the targeted 1,058. The study was closed early because of slow accrual; 340 of the 356 patients were eligible. The 1-year OS (P = .86; 75.6% v 76.9% for PCI v observation) and 1-year DFS (P = .11; 56.4% v 51.2% for PCI v observation) were not significantly different. The hazard ratio for observation versus PCI was 1.03 (95% CI, 0.77 to 1.36). The 1-year rates of BM were significantly different (P = .004; 7.7% v 18.0% for PCI v observation). Patients in the observation arm were 2.52 times more likely to develop BM than those in the PCI arm (unadjusted odds ratio, 2.52; 95% CI, 1.32 to 4.80).ConclusionIn patients with stage III disease without progression of disease after therapy, PCI decreased the rate of BM but did not improve OS or DFS.
A mouse model for monitoring islet cell genesis and developing therapies for diabetes
Authors: Shimajiri Yoshinori , Kosaka Yasuhiro , Scheel David W. , Lynn Francis C. , Kishimoto Nina , Wang Juehu , Zhao Shuhong , German Michael S. 
Published: December 2010

SUMMARYTransient expression of the transcription factor neurogenin-3 marks progenitor cells in the pancreas as they differentiate into islet cells. We developed a transgenic mouse line in which the surrogate markers secreted alkaline phosphatase (SeAP) and enhanced green florescent protein (EGFP) can be used to monitor neurogenin-3 expression, and thus islet cell genesis. In transgenic embryos, cells expressing EGFP lined the pancreatic ducts. SeAP was readily detectable in embryos, in the media of cultured embryonic pancreases and in the serum of adult animals. Treatment with the γ-secretase inhibitor DAPT, which blocks Notch signaling, enhanced SeAP secretion rates and increased the number of EGFP-expressing cells as assayed by fluorescence-activated cell sorting (FACS) and immunohistochemistry in cultured pancreases from embryos at embryonic day 11.5, but not in pancreases harvested 1 day later. By contrast, treatment with growth differentiation factor 11 (GDF11) reduced SeAP secretion rates. In adult mice, partial pancreatectomy decreased, whereas duct ligation increased, circulating SeAP levels. This model will be useful for studying signals involved in islet cell genesis in vivo and developing therapies that induce this process.
Impaired remodeling phase of fracture repair in the absence of matrix metalloproteinase-2
Authors: Lieu Shirley , Hansen Erik , Dedini Russell , Behonick Danielle , Werb Zena , Miclau Theodore , Marcucio Ralph , Colnot Céline 
Published: December 2010

SUMMARY
The matrix metalloproteinase (MMP) family of extracellular proteases performs crucial roles in development and repair of the skeleton owing to their ability to remodel the extracellular matrix (ECM) and release bioactive molecules. Most MMP-null skeletal phenotypes that have been previously described are mild, thus permitting the assessment of their functions during bone repair in the adult. In humans and mice, MMP2 deficiency causes a musculoskeletal phenotype. In this study, we assessed the role of MMP2 during mouse fracture repair and compared it with the roles of MMP9 and MMP13. Mmp2 was expressed at low levels in the normal skeleton and was broadly expressed in the fracture callus. Treatment of wild-type mice with a general MMP inhibitor, GM6001, caused delayed cartilage remodeling and bone formation during fracture repair, which resembles the defect observed in Mmp9–/– mice. Unlike Mmp9- and Mmp13-null mutations, which affect both cartilage and bone in the callus, the Mmp2-null mutation delayed bone remodeling but not cartilage remodeling. This remodeling defect occurred without changes in either osteoclast recruitment or vascular invasion of the fracture callus compared with wild type. However, we did not detect changes in expression of Mmp9, Mmp13 or Mt1-Mmp (Mmp14) in the calluses of Mmp2-null mice compared with wild type by in situ hybridization, but we observed decreased expression of Timp2 in the calluses of Mmp2-, Mmp9- and Mmp13-null mice. In keeping with the skeletal phenotype of Mmp2-null mice, MMP2 plays a role in the remodeling of new bone within the fracture callus and impacts later stages of bone repair compared with MMP9 and MMP13. Taken together, our results indicate that MMPs play unique and distinct roles in regulating skeletal tissue deposition and remodeling during fracture repair.
RIP2-mediated LKB1 deletion causes axon degeneration in the spinal cord and hind-limb paralysis
Authors: Sun Gao , Reynolds Richard , Leclerc Isabelle , Rutter Guy A. 
Published: December 2010

SUMMARY
Axon degeneration is observed in neurodegenerative diseases and neuroinflammatory disorders, such as Alzheimer’s disease, Parkinson’s disease and multiple sclerosis. The molecular basis of this process remains largely unknown. Here, we show that mice deleted for the tumour suppressor LKB1 (also called STK11) in the spinal cord, some parts of the brain and in the endocrine pancreas (βLKB1KO mice) develop hind-limb dysfunction and axon degeneration at about 7 weeks. Demyelination and macrophage infiltration are observed in the white matter of these mice, predominantly in the bilateral and anterior funiculi of the thoracic segment of the spinal cord, suggesting damage to the ascending sensory signalling pathway owing to LKB1 deletion in the brain. Microtubule structures were also affected in the degenerated foci, with diminished neurofilament and tubulin expression. Deletion of both PRKAA1 genes, whose products AMPKα1 and AMPKα2 are also downstream targets of LKB1, with the same strategy was without effect. We thus define LKB1 as an intrinsic suppressor of axon degeneration and a possible target for strategies that can reverse this process.
Contemporary Stories: American Indian and Thai
Authors: Frey Rodney 
Published: December 2010

Mary Dougherty Bartlett. ed. The New Native American Novel: Works in Progress. Albuquerque: The University of New Mexico Press, 1986. viii. 132 pp. $22.50 (cloth), $10.95 (paper).Herbert P. Phillips in association with Vinita Almiyanandana Lawler, Amnuaycaj Patipat, Likhit Dhiravegin. Modern Thai Literature: With an Ethnographic Interpretation. Honolulu:University of Hawaii Press, 1987. xiii. 391 pp. $26.00 (cloth).
Single Question, Two Replies
Authors: Teski Marea 
Published: December 2010

Gregory Bateson and Mary Catherine Bateson. Angels Fear: Towards an Epistemology of the Sacred. New York: McMillan, 1987. 224 pp. $18.95 (cloth).Allen Johnson and Timothy Earle. The Evolution of Human Societies: From Foraging Group to Agrarian State. Stanford, California: Stanford University Press, 1987. 360 pp. $39.50 (cloth).
Plasticity in the Purine–Thiamine Metabolic Network of Salmonella
Authors: Bazurto Jannell V , Downs Diana M 
Published: December 2010

Abstract
In Salmonella enterica, 5-aminoimidazole ribonucleotide (AIR) is the precursor of the 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP) pyrophosphate moiety of thiamine and the last intermediate in the common HMP/purine biosynthetic pathway. AIR is synthesized de novo via five reactions catalyzed by the purF, -D, -T, -G, and -I gene products. In vivo genetic analysis demonstrated that in the absence of these gene products AIR can be generated if (i) methionine and lysine are in the growth medium, (ii) PurC is functional, and (iii) 5-amino-4-imidazolecarboxamide ribotide (AICAR) has accumulated. This study provides evidence that the five steps of the common HMP/purine biosynthetic pathway can be bypassed in the synthesis of AIR and thus demonstrates that thiamine synthesis can be uncoupled from the early purine biosynthetic pathway in bacteria.
The Cik1/Kar3 Motor Complex Is Required for the Proper Kinetochore–Microtubule Interaction After Stressful DNA Replication
Authors: Liu Hong , Jin Fengzhi , Liang Fengshan , Tian Xuemei , Wang Yanchang 
Published: December 2010

Abstract
In budding yeast Saccharomyces cerevisiae, kinetochores are attached by microtubules during most of the cell cycle, but the duplication of centromeric DNA disassembles kinetochores, which results in a brief dissociation of chromosomes from microtubules. Kinetochore assembly is delayed in the presence of hydroxyurea, a DNA synthesis inhibitor, presumably due to the longer time required for centromeric DNA duplication. Some kinetochore mutants are sensitive to stressful DNA replication as these kinetochore proteins become essential for the establishment of the kinetochore–microtubule interaction after treatment with hydroxyurea. To identify more genes required for the efficient kinetochore–microtubule interaction under stressful DNA replication conditions, we carried out a genome-wide screen for yeast mutants sensitive to hydroxyurea. From this screen, cik1 and kar3 mutants were isolated. Kar3 is the minus-end-directed motor protein; Cik1 binds to Kar3 and is required for its motor function. After exposure to hydroxyurea, cik1 and kar3 mutant cells exhibit normal DNA synthesis kinetics, but they display a significant anaphase entry delay. Our results indicate that cik1 cells exhibit a defect in the establishment of chromosome bipolar attachment in the presence of hydroxyurea. Since Kar3 has been shown to drive the poleward chromosome movement along microtubules, our data support the possibility that this chromosome movement promotes chromosome bipolar attachment after stressful DNA replication.
New Developments in Hormone Receptor–Positive Disease
Authors: Piccart-Gebhart Martine J. 
Published: December 2010

AbstractOf more than one million women diagnosed with breast cancer each year, approximately 700,000 have hormone receptor (HR)+ disease. Although endocrine therapy has revolutionized breast cancer management and substantially improved outcomes in these patients, the optimal management of these patients remains a significant challenge. For instance, the threshold for adding adjuvant chemotherapy is a topic of continuing debate, and the most effective regimens that include endocrine therapy and chemotherapy are still under debate as well. Tumor markers, such as Ki-67, and host markers, such as cytochrome P450 2D6, are being studied as potential tools to offer more tailored adjuvant endocrine therapy. Current research suggests that luminal A and luminal B cancers are two completely different diseases, and work is being performed to better distinguish between these two disease types and deliver more effective therapy to individual patients. This article addresses these important outstanding issues with respect to HR+ disease.
A New Look at Node-Negative Breast Cancer
Authors: Harbeck Nadia , Thomssen Christoph 
Published: December 2010

Abstract
Node-negative breast cancer is a prevalent form of the disease worldwide, particularly in regions with rigorous screening and disease awareness efforts. Although there is a common biology between node-negative and node-positive breast tumors, it is still important to specifically address risk assessment and predictive factors in node-negative breast cancer. The relative risks and benefits are more pronounced in these patients, but there is no single prognostic factor available for deciding whether to administer chemotherapy and selecting the best adjuvant chemotherapy regimen. In the absence of universal predictive factors, the trend is to give chemotherapy to all patients to ensure the highest possibility for cure. Tumor grade is important in that it is predictive of risk over time, but lacks standardization. Adjuvant! Online, a web-based algorithm, is also used to guide treatment decisions. Recently, the urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) biomarkers have been used to determine disease risk and, consequently, determine whether or not chemotherapy is needed. However, the assay requires a fresh-frozen tissue sample, which is not always feasible. The oncotype DX® genomic assay has also been used to help prognosis estimation and treatment decisions. It is currently under evaluation in conjunction with the uPA/PAI-1 assay in the Plan B trial. The question that remains in adjuvant chemotherapy today for patients with node-negative disease is proper patient selection. Node-negative breast cancer does not automatically suggest a good prognosis, or the preclusion of chemotherapy benefits, and additional biomarkers are needed to help identify patients who do benefit from chemotherapy.
Histologic Evaluation of the Buccal and Lingual Bone Plates in Anterior Dog Teeth: Possible Influence on Implant Dentistry
Authors: Novaes Arthur B. , Macedo Guilherme O. , Suaid Flávia A. , Barros Raquel R.M. , Souza Sérgio L.S. , Silveira e Souza Adriana M.M. 
Published: December 2010

Background: Recent studies in animals have shown pronounced resorption of buccal bone plate after immediate implantation. The sectioning of experimental material for histologic evaluation of the bone plates could provide valuable information about the possible effect of bone exposure in periodontal and implant surgeries.Methods: Twenty‐four incisors were collected from dogs. After decalcification, the blocks were immersed in paraffin and bucco‐lingual histologic sections were examined under light microscope. Some sections were reserved for immunohistochemical analysis.Results: The bone density, the width of the bone plates, and the percentage of vessels presented in the periodontal ligament and periosteum were analyzed in the buccal and lingual bone plates, which were divided corono‐apically into thirds. The buccal bone plates showed statistically higher bone density compared to the lingual bone plates in the coronal thirds. The width of both bone plates increased from the coronal to the apical third, but all the buccal thirds were significantly thinner compared to the lingual thirds. No statistically significant differences were found between the bone plates for the percentage of area occupied by the blood vessels in the periodontal ligament or periosteum.Conclusion: It is reasonable to conclude that the higher bone density, represented by the lower number of marrow spaces, in association with the thinner aspect of the buccal bone plates made them more fragile to absorb compared to the lingual bone plates, especially during mucoperiosteal procedures.
Treatment of Intrabony Periodontal Defects With Platelet‐Rich Plasma Versus Platelet‐Poor Plasma Combined With a Bovine‐Derived Xenograft: A Controlled Clinical Trial
Authors: Yilmaz Selcuk , Kabadayi Canan , Ipci Sebnem Dirikan , Cakar Gokser , Kuru Bahar 
Published: December 2010

Background: The purpose of this study is to assess the healing outcomes of intrabony defects after treatment with platelet‐rich plasma (PRP) versus platelet‐poor plasma (PPP) combined with bovine‐derived xenograft (BDX).Methods: Using a split‐mouth design, a total of 79 intrabony defects with an intrabony component of ≥3 mm in 20 patients were treated either with PRP/BDX (group 1) or PPP/BDX (group 2). At baseline and 12 months after surgery, plaque and sulcus bleeding indices, probing depth (PD), relative attachment level, recession, and probing and radiographic bone levels were recorded.Results: After 12 months, groups 1 and 2 presented a mean PD reduction of 3.87 ± 0.86 and 3.76 ± 0.80 mm, recession of 1.35 ± 0.68 and 1.58 ± 0.54 mm, attachment gain of 2.51 ± 0.97 and 2.18 ± 0.87 mm, clinical bone gain of 2.18 ± 0.86 and 2.09 ± 0.89 mm, and radiographic bone gain of 2.11 ± 0.87 and 2.19 ± 0.96 mm, respectively. Intergroup differences were found to be insignificant.Conclusions: Within its limits, these results suggest that the outcomes of the treatment after PRP/BDX and PPP/BDX applications in intrabony defects are similar. When the platelet counts are taken into consideration, PPP seems to demonstrate similar clinical efficacy as the PRP.
Experimental and Numerical Simulation of CO2 Injection Into Upper-Triassic Sandstones in Svalbard, Norway
Authors: Farokhpoor R.. , Torsæter O.. , Baghbanbashi T.. , Mork A.. , Lindeberg E.G.B.. G.B. 
Published: December 2010

AbstractSequestration of carbon dioxide in a saline aquifer is currently being evaluated as a possible way to handle carbon dioxide emitted from a coal-fuelled power plant in Svalbard. The chosen reservoir is a 300 m thick, laterally extensive, shallow marine formation of late Triassic-mid Jurassic age, located below Longyearbyen in Svalbard. The reservoir consists of 300 m of alternating sandstone and shale and is capped by 400 meter shale.Experimental and numerical studies have been performed to evaluate CO2 storage capacity and long term behaviour of the injected CO2 in rock pore space. Laboratory core flooding experiments were conducted during which air was injected into brine saturated cores at standard conditions. Analysis of the results shows that the permeability is generally less than 2 millidarcies and the capillary entry pressure is high. For most samples, no gas flow was detected in the presence of brine, when employing a reasonable pressure gradient. This poses a serious challenge with respect to achieving viable levels of injectivity and injection pressure.A conceptual numerical simulation of CO2 injection into a segment of the planned reservoir was performed using commercial reservoir simulation software and available petrophysical data. The results show that injection using vertical wells yields the same injectivity but more increases in field pressure compare to injection through horizontal wells. In order to keep induced pressure below top-seal fracturation pressure and preventing the fast propagation and migration of CO2 plume, slow injection through several horizontal wells into the lower part of the "high" permeability beds appears to offer the best solution.The high capillary pressure causes slow migration of the CO2 plume, and regional groundwater flow provides fresh brine for CO2 dissolution. In our simulations, half of the CO2 was dissolved in brine and the other half dispersed within a radius of 1000 meter from the wells after 4000 years. Dissolution of CO2 in brine and lateral convective mixing from CO2 saturated brine to surrounding fresh brine are the dominant mechanisms for CO2 storage in this specific site and this guarantees that the CO2 plume will be stationary for thousands of years.