bluuebunny/crossref_metadata_2025_split huggingface dataset:
On Series-Like Iterative Equation with a General Boundary Restriction
Authors: Song Wei , Yang Guo-qiu , Lei Feng-chun 
Published: April 2009

AbstractBy means of Schauder fixed point theorem and Banach contraction principle, we investigate the existence and uniqueness of Lipschitz solutions of the equation"Equation missing". Moreover, we get that the solution"Equation missing" depends continuously on"Equation missing". As a corollary, we investigate the existence and uniqueness of Lipschitz solutions of the series-like iterative equation"Equation missing" with a general boundary restriction, where"Equation missing" is a given Lipschitz function, and"Equation missing" are compact convex subsets of"Equation missing" with nonempty interior.
Cellular Source and Amount of Vascular Endothelial Growth Factor and Platelet-Derived Growth Factor in Tumors Determine Response to Angiogenesis Inhibitors
Authors: Sennino Barbara , Kuhnert Frank , Tabruyn Sebastien P. , Mancuso Michael R. , Hu-Lowe Dana D. , Kuo Calvin J. , McDonald Donald M. 
Published: April 2009

Abstract
Vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and their receptors are important targets in cancer therapy based on angiogenesis inhibition. However, it is unclear whether inhibition of VEGF and PDGF together is more effective than inhibition of either one alone. Here, we used two contrasting tumor models to compare the effects of inhibiting VEGF or PDGF alone, by adenovirally generated soluble receptors, to the effects of inhibiting both together. In RIP-Tag2 tumors, VEGF and PDGF inhibition together reduced tumor vascularity and abundance of pericytes. However, VEGF inhibition reduced tumor vascularity without decreasing pericyte density, and PDGF inhibition reduced pericytes without reducing tumor vascularity. By contrast, in Lewis lung carcinomas (LLC), inhibition of VEGF or PDGF reduced blood vessels and pericytes to the same extent as did inhibition of both together. Similar results were obtained using tyrosine kinase inhibitors AG-013736 and imatinib. In LLC, VEGF expression was largely restricted to pericytes and PDGF was largely restricted to endothelial cells, but, in RIP-Tag2 tumors, expression of both growth factors was more widespread and significantly greater than in LLC. These findings suggest that inhibition of PDGF in LLC reduced pericytes, and then tumor vessels regressed because pericytes were the main source of VEGF. The vasculature of RIP-Tag2 tumors, in which most VEGF is from tumor cells, was more resistant to PDGF inhibition. The findings emphasize the interdependence of pericytes and endothelial cells in tumors and the importance of tumor phenotype in determining the cellular effects of VEGF and PDGF inhibitors on tumor vessels. [Cancer Res 2009;69(10):4527–36]
Identification of PDE4D as a Proliferation Promoting Factor in Prostate Cancer Using a Sleeping Beauty Transposon-Based Somatic Mutagenesis Screen
Authors: Rahrmann Eric P. , Collier Lara S. , Knutson Todd P. , Doyal Meghan E. , Kuslak Sheri L. , Green Laura E. , Malinowski Rita L. , Roethe Laura , Akagi Keiko , Waknitz Michelle , Huang Wei , Largaespada David A. , Marker Paul C. 
Published: April 2009

Abstract
Retroviral and transposon-based mutagenesis screens in mice have been useful for identifying candidate cancer genes for some tumor types. However, many of the organs that exhibit the highest cancer rates in humans, including the prostate, have not previously been amenable to these approaches. This study shows for the first time that the Sleeping Beauty transposon system can be used to identify candidate prostate cancer genes in mice. Somatic mobilization of a mutagenic transposon resulted in focal epithelial proliferation and hyperplasia in the prostate. Efficient methods were established to identify transposon insertion sites in these lesions, and analysis of transposon insertions identified candidate prostate cancer genes at common insertion sites, including Pde4d. PDE4D was also overexpressed in human prostate cancer patient samples and cell lines, and changes in PDE4D mRNA isoform expression were observed in human prostate cancers. Furthermore, knockdown of PDE4D reduced the growth and migration of prostate cancer cells in vitro, and knockdown of PDE4D reduced the growth and proliferation rate of prostate cancer xenografts in vivo. These data indicate that PDE4D functions as a proliferation promoting factor in prostate cancer, and the Sleeping Beauty transposon system is a useful tool for identifying candidate prostate cancer genes. [Cancer Res 2009;69(10):4388–97]
Treatment of Chronic Lymphocytic Leukemia with a Hypomethylating Agent Induces Expression of NXF2, an Immunogenic Cancer Testis Antigen
Authors: Dubovsky Jason A. , McNeel Douglas G. , Powers John J. , Gordon John , Sotomayor Eduardo M. , Pinilla-Ibarz Javier A. 
Published: April 2009

Abstract
Purpose: Critical to the success of active immunotherapy against cancer is the identification of immunologically recognized cancer-specific proteins with low tolerogenic potential. Cancer testis antigens (CTA), in particular, fulfill this requirement as a result of their aberrant expression restricted to cancer cells and lack of expression in normal tissues bypassing tolerogenic mechanisms against self. Although CTAs have been extensively studied in solid malignancies, little is known regarding their expression in chronic lymphocytic leukemia (CLL).
Experimental Design: Using a two-pronged approach we evaluated the immunogenicity of 29 CTAs in 22 patients with CLL and correlated these results to reverse transcriptase PCR data from CLL cell lines and patient cells.
Results: We identified IgG-specific antibodies for one antigen, NXF2, and confirmed this response by ELISA and Western blot. We found that treatment of CLL with 5-aza-2′-deoxycytidine can induce expression of NXF2 that lasted for several weeks after treatment. Treatment also increased levels of MHC and costimulatory molecules (CD80, CD86, and CD40) necessary for antigen presentation. In addition, we identified other promising antigens that may have potential immunotherapeutic application.
Conclusions: Our findings suggest that NXF2 could be further pursued as an immunotherapeutic target in CLL, and that treatment with demethylating agents could be exploited to specifically modulate CTA expression and effective antigen presentation in malignant B cells.
Ratio of 17HSD1 to 17HSD2 Protein Expression Predicts the Outcome of Tamoxifen Treatment in Postmenopausal Breast Cancer Patients
Authors: Jansson Agneta , Delander Lovisa , Gunnarsson Cecilia , Fornander Tommy , Skoog Lambert , Nordenskjöld Bo , Stål Olle 
Published: April 2009

Abstract
Purpose: Estrogens have great significance in the development of breast cancer. After menopause, most estrogen biosynthesis is done in peripheral tissue, and the main enzymes involved in balancing the amount of estrone against estradiol are 17β-hydroxysteroid dehydrogenases (17HSD). The aim of this study was to investigate the prognostic and tamoxifen predictive values of 17HSD1 and 17HSD2 expression.
Experimental Design: Tumors from low-risk breast cancer patients randomized to adjuvant tamoxifen therapy or no adjuvant treatment were analyzed with immunohistochemistry to investigate protein expression of 17HSD1 and 17HSD2 in 912 cases. All patients had lymph node-negative breast cancer and were postmenopausal at the time of diagnosis.
Results: Low 17HSD1 expression was associated with significant benefit from tamoxifen treatment among patients with estrogen receptor (ER)-positive tumors (P &lt; 0.001). For patients with a 17HSD1 score not exceeding that of 17HSD2, tamoxifen increased the rate of distant recurrence-free survival (hazard ratio, 0.37; 95% confidence interval, 0.23-0.60) and breast cancer-specific survival (hazard ratio, 0.30; 95% confidence interval, 0.16-0.54), whereas no apparent effect was observed when the 17HSD1 score was higher than that of 17HSD2. The interaction was significant for both distant recurrence-free survival (P = 0.036) and breast cancer-specific survival (P = 0.014). In the cohort of systemically untreated patients, no prognostic importance was observed.
Conclusions: This is the first report that clearly distinguishes between the prognostic and predictive importance of 17HSD1 and 17HSD2 in ER-positive breast cancer treated with or without tamoxifen. Our data suggest that the 17HSD1/17HSD2 ratio might be useful as a predictive factor for tamoxifen treatment in ER-positive breast cancer patients.
γH2AX Expression in Tumors Exposed to Cisplatin and Fractionated Irradiation
Authors: Bañuelos C. Adriana , Banáth Judit P. , Kim Joo-Young , Aquino-Parsons Christina , Olive Peggy L. 
Published: April 2009

Abstract
Purpose: Is retention of γH2AX foci useful as a biomarker for predicting the response of xenograft tumors to cisplatin with X-ray? Is a similar approach feasible using biopsies from patients with cervical cancer?
Experimental Design: Mice bearing SiHa, WiDr, or HCT116 xenograft tumors were exposed to cisplatin and/or three daily doses of 2 Gy. Tumors were excised 24 h after treatment and single cells were analyzed for clonogenic fraction and retention of γH2AX foci. Tumor biopsies were examined using 47 paraffin-embedded sections from untreated tumors and 24 sections from 8 patients undergoing radiochemotherapy for advanced cancer of the cervix.
Results: Residual γH2AX measured 24 h after cisplatin injection accurately predicted surviving fraction in SiHa and WiDr xenografts. When a clinically equivalent protocol using cisplatin and fractionated irradiation was employed, the fraction of xenograft cells lacking γH2AX ranked survival accurately but underestimated tumor cell kill. Residual γH2AX foci were detected in clinical samples; on average, only 25% of tumor nuclei exhibited one or more γH2AX foci before treatment and 74% after the start of treatment.
Conclusion: γH2AX can provide useful information on the response of human tumors to the combination of cisplatin and radiation, but prediction becomes less accurate as more time elapses between treatment and tumor biopsy. Use of residual γH2AX as a biomarker for response is feasible when cell survival exceeds ∼20%, but heterogeneity in endogenous and treatment-induced γH2AX must be considered.
A Combination of Micronutrients Is Beneficial in Reducing the Incidence of Prostate Cancer and Increasing Survival in theLadyTransgenic Model
Authors: Venkateswaran Vasundara , Klotz Laurence H. , Ramani Meera , Sugar Linda M. , Jacob Latha E. , Nam Robert K. , Fleshner Neil E. 
Published: April 2009

AbstractWe have previously shown that administration of a combination of micronutrients (selenium, vitamin E, and lycopene) inhibits prostate cancer (PCa) development in the Lady transgenic model. In the present study, we examine timing of initiation of micronutrients, and the effect of micronutrient combinations, on PCa development in Lady transgenic model.Transgenic males were randomized to either a control diet; control diet supplemented with human equivalent doses of vitamin E, selenium, and lycopene (E+S+L); or control diet supplemented with vitamin E and selenium (E+S). In separate experiments, the combination of E+S+L was initiated at varying time points (4, 8, 20, and 36 weeks of age).A combination of E+S+L resulted in a significant reduction in PCa and liver metastasis when intervention was commenced within 8 weeks of age (P &lt; 0.0001). Immunohistochemical analysis revealed a strong correlation between disease-free state with up-regulation of the prognostic marker p27Kip1 (P &lt; 0.0001) and decreased expression of proliferating cell nuclear antigen and significantly increased apoptotic index (P &lt; 0.0001). On the contrary, a combination of E+S was not effectual in preventing PCa, with a high proportion (84.6%) of animals developing PCa and a small proportion (11.5%) developing high-grade PIN.Early commencement of micronutrients (E+S+L) is beneficial in reducing PCa. Lycopene is an essential component of the combination and effective (when used with E+S) for PCa prevention. These observations provide support for their chemopreventive effect and some clues about their mechanism of action. These key findings will be complementary to the outcome from the Selenium and Vitamin E Chemoprevention Trial.
Nonsteroidal Anti-Inflammatory Drug Use and Endometrial Cancer Risk in the NIH-AARP Diet and Health Study
Authors: Danforth Kim N. , Gierach Gretchen L. , Brinton Louise A. , Hollenbeck Albert R. , Katki Hormuzd A. , Leitzmann Michael F. , Schatzkin Arthur , Lacey James V. 
Published: April 2009

Abstract
Chronic inflammation may play an etiologic role in endometrial cancer. Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce inflammatory activity by inhibiting the proinflammatory cyclooxygenase enzymes and, therefore, may decrease cancer risk. However, few studies have examined the association between NSAID use and endometrial cancer. We conducted a prospective study among 72,524 women in the NIH-AARP Diet and Health Study. Women completed a questionnaire in 1996–1997 on lifestyle and health-related factors, including type and frequency of NSAID use within the past year, and were followed through 2003 by linkages to cancer registries and vital status databases. During 488,261 person-years of follow-up, there were 732 incident endometrial cancers. NSAID use, compared with nonuse of NSAIDs, was not significantly associated with endometrial cancer risk [relative risk (RR), 0.90; 95% confidence interval (95% CI), 0.74–1.09]. Null associations were also observed by type of NSAID use [aspirin only: RR, 0.88; 95% CI, 0.70–1.11; nonaspirin NSAID (NA-NSAID) only: RR, 1.01; 95% CI, 0.79–1.29; both aspirin and NA-NSAIDs: RR, 0.85; 95% CI, 0.68–1.06]. Generally, results were not statistically significant by frequency of use for aspirin or NA-NSAIDs. Results did not change when women with a history of heart disease, hypertension, or diabetes were excluded to minimize the potential for confounding by indication. Overall, our data do not support an association between aspirin or NA-NSAID use and endometrial cancer risk.
Remember the Source: Dissociating Frontal and Parietal Contributions to Episodic Memory
Authors: Donaldson David I. , Wheeler Mark E. , Petersen Steve E. 
Published: April 2009

Abstract
Event-related fMRI studies reveal that episodic memory retrieval modulates lateral and medial parietal cortices, dorsal middle frontal gyrus (MFG), and anterior PFC. These regions respond more for recognized old than correctly rejected new words, suggesting a neural correlate of retrieval success. Despite significant efforts examining retrieval success regions, their role in retrieval remains largely unknown. Here we asked the question, to what degree are the regions performing memory-specific operations? And if so, are they all equally sensitive to successful retrieval, or are other factors such as error detection also implicated? We investigated this question by testing whether activity in retrieval success regions was associated with task-specific contingencies (i.e., perceived targetness) or mnemonic relevance (e.g., retrieval of source context). To do this, we used a source memory task that required discrimination between remembered targets and remembered nontargets. For a given region, the modulation of neural activity by a situational factor such as target status would suggest a more domain-general role; similarly, modulations of activity linked to error detection would suggest a role in monitoring and control rather than the accumulation of evidence from memory per se. We found that parietal retrieval success regions exhibited greater activity for items receiving correct than incorrect source responses, whereas frontal retrieval success regions were most active on error trials, suggesting that posterior regions signal successful retrieval whereas frontal regions monitor retrieval outcome. In addition, perceived targetness failed to modulate fMRI activity in any retrieval success region, suggesting that these regions are retrieval specific. We discuss the different functions that these regions may support and propose an accumulator model that captures the different pattern of responses seen in frontal and parietal retrieval success regions.
Bending the Rules: Strategic Behavioral Differences Are Reflected in the Brain
Authors: Wolfensteller Uta , von Cramon D. Yves 
Published: April 2009

Abstract
The implementation of higher-order conditional motor behavior was investigated in the present fMRI study with the objective of answering three questions: (a) what happens in situations where one stimulus dimension alone does not sufficiently determine the correct response?; (b) does the implementation of second-order stimulus–response (S–R) rules on the basis of matching (congruent) or nonmatching (incongruent) S–R associations differ from the implementation of congruent and incongruent first-order S–R rules?; and (c) is the cerebral implementation of second-order rules influenced by interindividual behavioral differences arising from the use of different strategies? The findings indicate that several cortical areas were more strongly engaged for second-order rules. More specifically, rule integration based on a rule match led to enhanced activation in posterior parietal cortex, whereas rule integration based on a rule mismatch was associated with enhanced activation in dorsal premotor cortex and left rostrolateral prefrontal cortex. Interindividual strategy differences were revealed by strikingly different behavioral data patterns: One subgroup of participants displayed strong congruency effects for second-order rules, whereas another subgroup displayed nonsignificant or even reversed congruency effects. Importantly, these strategy differences strongly modulated the cerebral implementation of second-order rules based on a rule mismatch. Together, the present findings reveal differential brain activation patterns for higher-order S–R rules depending on rule congruency and interindividual strategy differences. Moreover, they emphasize the necessity of taking interindividual behavioral differences into account when investigating the cerebral implementation of cognitive processes even in rather simple and well-controlled experimental paradigms.
Prefrontal Control of Familiarity and Recollection in Working Memory
Authors: Feredoes Eva , Postle Bradley R. 
Published: April 2009

Abstract
Left inferior frontal gyrus (IFG) is a critical neural substrate for the resolution of proactive interference (PI) in working memory. We hypothesized that left IFG achieves this by controlling the influence of familiarity- versus recollection-based information about memory probes. Consistent with this idea, we observed evidence for an early (200 msec)-peaking signal corresponding to memory probe familiarity and a late (500 msec)-resolving signal corresponding to full accrual of trial-related contextual (“recollection-based”) information. Next, we applied brief trains of repetitive transcranial magnetic stimulation (rTMS) time locked to these mnemonic signals, to left IFG and to a control region. Only early rTMS of left IFG produced a modulation of the false alarm rate for high-PI probes. Additionally, the magnitude of this effect was predicted by individual differences in susceptibility to PI. These results suggest that left IFG-based control may bias the influence of familiarity- and recollection-based signals on recognition decisions.
Generation Mechanism of Spiciness Anomalies: An OGCM Analysis in the North Atlantic Subtropical Gyre
Authors: Laurian Audine , Lazar Alban , Reverdin Gilles 
Published: April 2009

Abstract
Oceanic teleconnections between the low and midlatitudes are a key mechanism to understanding the climate variability. Spiciness anomalies (density-compensated anomalies) have been shown to transport temperature and salinity signals when propagating along current streamlines in the subtropical gyres of the Atlantic and Pacific Oceans. The generation mechanism of spiciness anomalies in the North Atlantic subtropical gyre is investigated using an analytical model based on the late-winter subduction of salinity and temperature anomalies along isopycnal surfaces. The keystone of this approach is the change of the coordinates frame from isobaric to isopycnic surfaces, suited for subduction problems. The isopycnal nature of spiciness anomalies and the use of a linear density equation allows for the analytical model to depend only upon surface temperature and salinity anomalies, the mean thermocline currents, and the surface density ratio. This model clarifies and above all quantifies the mechanism by which surface temperature and salinity anomalies are modulated by density ratios to produce fully different isopycnal temperature and salinity anomalies.
A global run from the ocean GCM (OGCM) Océan Parallélisé (OPA) over the period 1948–2002 provides the reference data in which the North Atlantic subtropical thermocline spiciness variability is analyzed. Two EOF modes are sufficient to explain half of the low-frequency variability in the OGCM: one is maximum over the northeastern subtropics, and the other is in the central basin. The analytical model reproduces well the spatial pattern, amplitude, and sign of these two main modes. It confirms that the two centers of action of the anomalies are conditioned by the surface density ratio, the first corresponding to null salinity gradients and the second to near-density-compensated temperature gradients. Considering that the analytical model has good skills at reproducing the decadal variability of the OGCM spiciness anomalies in the permanent thermocline, it is believed that this is an interesting tool to understand and forecast the ventilation of the North Atlantic subtropical gyre at this time scale.
Global Extratropical Response to Diabatic Heating Variability of the Asian Summer Monsoon
Authors: Lin Hai 
Published: April 2009

Abstract
Global teleconnections associated with the Asian summer monsoon convective activities are investigated based on monthly data of 29 Northern Hemisphere summers defined as June–September (JJAS). Two distinct teleconnection patterns are identified that are associated respectively with variabilities of the Indian summer monsoon and the western North Pacific summer monsoon. The Indian summer monsoon convective activity is associated with a global pattern that has a far-reaching connection in both hemispheres, whereas the western North Pacific summer monsoon convective activity is connected to a Southern Hemisphere wave train that influences the high-latitude South Pacific and South America. A global primitive equation model is utilized to assess the cause of the global circulation anomalies. The model responses to anomalous heatings of both monsoon systems match the general features of the observed circulation anomalies well, and they are mainly controlled by linear processes. The response patterns are largely determined by the summertime large-scale background mean flow and the location of the heating anomaly relative to the upper easterly jet in the monsoon region.