bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical Studies of Celastrol and Acetyl Isogambogic Acid in Melanoma
Authors: Abbas Sabiha , Bhoumik Anindita , Dahl Russell , Vasile Stefan , Krajewski Stan , Cosford Nicholas D.P. , Ronai Ze'ev A. 
Published: November 2007

Abstract
Purpose: Sensitize melanomas to apoptosis and inhibit their growth and metastatic potential by compounds that mimic the activities of activating transcription factor 2 (ATF2)-driven peptides.
Experimental Design: Small-molecule chemical library consisting of 3,280 compounds was screened to identify compounds that elicit properties identified for ATF2 peptide, including (a) sensitization of melanoma cells to apoptosis, (b) inhibition of ATF2 transcriptional activity, (c) activation of c-Jun NH2-terminal kinase (JNK) and c-Jun transcriptional activity, and (d) inhibition of melanoma growth and metastasis in mouse models.
Results: Two compounds, celastrol (CSL) and acetyl isogambogic acid, could, within a low micromolar range, efficiently elicit cell death in melanoma cells. Both compounds efficiently inhibit ATF2 transcriptional activities, activate JNK, and increase c-Jun transcriptional activities. Similar to the ATF2 peptide, both compounds require JNK activity for their ability to inhibit melanoma cell viability. Derivatives of CSL were identified as potent inducers of cell death in mouse and human melanomas. CSL and a derivative (CA19) could also efficiently inhibit growth of human and mouse melanoma tumors and reduce the number of lung metastases in syngeneic and xenograft mouse models.
Conclusions: These studies show for the first time the effect of CSL and acetyl isogambogic acid on melanoma. These compounds elicit activities that resemble the well-characterized ATF2 peptide and may therefore offer new approaches for the treatment of this tumor type.
Immunity against Tumor Angiogenesis Induced by a Fusion Vaccine with Murine β-Defensin 2 and mFlk-1
Authors: Wang Yong-sheng , Wang Guo-qing , Wen Yan-jun , Wang Lian , Chen Xian-cheng , Chen Ping , Kan Bin , Li Jiong , Huang Canhua , Lu You , Zhou Qin , Xu Ning , Li Dan , Fan Ling-yu , Yi Tao , Wu Hong-bo , Wei Yu-quan 
Published: November 2007

Abstract
Purpose: Previous studies indicated that humoral or cellular immunity against murine vascular endothelial growth factor 2 (mFlk-1) was elicited to inhibit tumor growth. Here we describe a genetic fusion vaccine, pMBD2-mFlk-1, based on the targeting of a modified mFlk-1 to antigen-presenting cells by a murine β-defensin 2 (MBD2) protein to induce both humoral and cellular immunity against mFlk-1, with the targeting especially focused on immature dendritic cells.
Experimental Design: The protective and therapeutic antitumor immunity of the fusion vaccine was investigated in mouse models. Antiangiogenesis effect was detected by immunohistochemical staining and alginate-encapsulate tumor cell assay. The mechanisms of the fusion vaccine were primarily explored by detection of autoantibodies and CTL activity and confirmed by the deletion of immune cell subsets.
Results: The fusion vaccine elicited a strong protective and therapeutic antitumor immunity through antiangiogenesis in mouse models, and this worked through stimulation of an antigen-specific CD8+ T-cell response as well as a specific B-cell response against mFlk-1. The findings were confirmed by depletion of immune cell subsets and in knockout mice.
Conclusion: Our study showed that a fusion vaccine based on self immune peptide (MBD2) and self antigen (mFlk-1) induced autoimmunity against endothelial cells, resulting in inhibition of tumor growth, and could be further exploited in clinical applications of cancer immunotherapy.
Deficient TP53 Expression, Function, and Cisplatin Sensitivity Are Restored by Quinacrine in Head and Neck Cancer
Authors: Friedman Jay , Nottingham Liesl , Duggal Praveen , Pernas Francisco G. , Yan Bin , Yang Xin Ping , Chen Zhong , Van Waes Carter 
Published: November 2007

Abstract
Purpose: To determine the nature and potential pharmacologic reversibility of deficient TP53 expression and function in head and neck squamous cell carcinomas (HNSCC) with wild-type TP53, previously associated with decreased sensitivity to cisplatin therapy.
Experimental Design: TP53 genotype, mRNA and protein expression, TP53-induced p21 expression, and TP53 DNA–binding and reporter gene function were determined in a panel of nine previously characterized HNSCC cell lines from the University of Michigan squamous cell carcinoma (UM-SCC) series. The genotoxic drug doxorubicin and the anti-inflammatory and antimalarial drug quinacrine, previously identified as inducers of TP53, were used to examine the nature and potential reversibility of deficient TP53 expression and function. The specific role of inducible TP53 on function and cellular proliferation was confirmed using selective TP53 inhibitor pifithrin-α or short hairpin RNA knockdown. The capability of quinacrine to sensitize HNSCC to the cytotoxic effects of cisplatin was assessed.
Results: UM-SCC cell lines with wild-type TP53 genotype underexpressed TP53 mRNA and protein when compared with normal human keratinocytes or UM-SCC with mutant TP53. Although doxorubicin failed to induce TP53 expression or functional activity, quinacrine induced TP53 mRNA and protein expression, increased TP53 reporter activity and p21 protein expression, and induced growth inhibition in these wild-type TP53 cell lines. Quinacrine-induced TP53 reporter activity and growth suppression were attenuated by pifithrin-α and TP53 short hairpin RNA knockdown. Furthermore, quinacrine sensitized UM-SCC to cisplatin in vitro.
Conclusions: Deficient TP53 mRNA and protein expression underlies decreased function in a subset of HNSCC with wild-type TP53 and can be restored together with cisplatin sensitization by quinacrine.
New Approaches to Assessing and Treating Early-Stage Colon and Rectal Cancer: Summary Statement from 2007 Santa Monica Conference
Authors: Rosen Lee S. , Bilchik Anton J. , Beart Robert W. , Benson Al B. , Chang Kenneth J. , Compton Carolyn C. , Grothey Axel , Haller Daniel G. , Ko Clifford Y. , Lynch Patrick M. , Nelson Heidi , Stamos Michael J. , Turner Roderick R. , Willett Christopher G. 
Published: November 2007

Abstract
The 2007 Santa Monica Conference on Assessing and Treating Early-Stage Colon and Rectal Cancer, a multidisciplinary meeting of leaders in surgery, medical and radiation oncology, and pathology, was convened on January 12 to 13, 2007. The purpose of the meeting was to assess current data and issues in the field and to develop recommendations for advancing patient care and clinical research. Topics included pathologic assessment and staging, transanal versus laparoscopic versus open resection, adjuvant therapy, genetic testing and counseling, cooperative group strategies, and the use of biological therapies and novel agents. A review of the key issues discussed, as well as conclusions and recommendations considered significant to the field, is summarized below and presented at greater length in the individual manuscripts and accompanying discussion that comprise the full conference proceedings. Although the management of early-stage colon and rectal cancers remains a challenge for all of us, the development and use of new technologies and methods of assessment and treatment over the past several decades is yielding encouraging results. A variety of opportunities to further improve outcomes were addressed in this forum, including recommendations that specific protocols be adopted regarding surgical and pathologic dissection and reporting, particularly for stage II disease; the corollary need to increase active multidisciplinary collaboration; and the development of comprehensive consensus guidelines and recommendations to standardize care in early-stage colorectal cancer.
Neural Correlates of Morphological Processes in Hebrew
Authors: Bick Atira , Goelman Gadi , Frost Ram 
Published: November 2007

Abstract
Is morphology a discrete and independent element of lexical structure or does it simply reflect a fine tuning of the system to the statistical correlation that exists among the orthographic and semantic properties of words? Imaging studies in English failed to show unequivocal morphological activation that is distinct from semantic or orthographic activation. Cognitive research in Hebrew has revealed that morphological decomposition is an important component of print processing. In Hebrew, morphological relatedness does not necessarily induce a clear semantic relatedness, thus, Hebrew provides a unique opportunity to investigate the neural substrates of morphological processing. In this functional magnetic resonance imaging study, participants were required to perform judgment tasks of morphological relatedness, semantic relatedness, rhyming, and orthographic similarity. Half of the morphologically related words were semantically related and half were semantically unrelated. This design was chosen to induce explicit morphological processing. We identified two locations involved in morphological processing: the left middle frontal gyrus and the left inferior parietal sulcus. Comparing locations of morphological related activation to the locations of semantic and orthographic related activation, we found that the areas neighbored but only partially overlapped. The similarity in activation between the two morphological conditions eliminates the possibility that morphological activation simply results from the semantic properties of the words. These results demonstrate the important role of morphological processing in reading and suggest that morphological analysis is a distinct process of visual word recognition.
Parallel Response Selection after Callosotomy
Authors: Hazeltine Eliot , Weinstein Andrea , Ivry Richard B. 
Published: November 2007

Abstract
Two studies [Ivry, R. B., Franz, E. A., Kingstone, A., & Johnston, J. C. The psychological refractory period effect following callosotomy: Uncoupling of lateralized response codes. Journal of Experimental Psychology: Human Perception and Performance, 24, 463–480, 1998; Pashler, H., Luck, S., Hillyard, S. A., Mangun, G. R., O'Brien, S., & Gazzaniga, M. S. Sequential operation of disconnected hemispheres in split-brain patients. NeuroReport, 5, 2381–2384, 1994] reported robust dual-task costs in split-brain patients even when the two tasks were associated with separate cerebral hemispheres. Although the patients failed to demonstrate specific forms of interference observed in control participants, the timing of the two responses suggested that performance was constrained such that the responses could not be initiated independently. Alternatively, the split-brain participants may have adopted a strategy in which the second response was withheld until the first was initiated. The present study revisits this phenomenon using a procedure in which the stimuli for both tasks are presented simultaneously and neither is given priority over the other. Under these conditions, neurologically intact participants show robust dual-task costs that are mediated by compatibility effects between the responses of the two hands. In contrast, the split-brain participants show greatly reduced dual-task costs and compatibility effects. The minimal dual-task costs observed in the current study indicate that previous dual-task costs in split-brain patients may be strategic, reflecting experimental instructions to prioritize one task, rather than reflect fundamental constraints of the cognitive architecture.
The Hippocampus is Preferentially Associated with Memory for Spatial Context
Authors: Ross Robert S. , Slotnick Scott D. 
Published: November 2007

Abstract
The existence of a functional-anatomic dissociation for retrieving item versus contextual information within subregions of the medial temporal lobe (MTL) is currently under debate. We used a spatial source memory paradigm during event-related functional magnetic resonance imaging to investigate this issue. At study, abstract shapes were presented to the left or right of fixation. During test, old and new shapes were presented at fixation. Participants responded whether each shape had been previously presented on the “left,” the “right,” or was “new.” Activity associated with contextual memory (i.e., source memory) was isolated by contrasting accurate versus inaccurate memory for spatial location. Item-memory-related activity was isolated by contrasting accurate item recognition without contextual memory with forgotten items. Source memory was associated with activity in the hippocampus and parahippocampal cortex. Although item memory was not associated with unique MTL activity at our original threshold, a region-of-interest (ROI) analysis revealed item-memory-related activity in the perirhinal cortex. Furthermore, a functional-anatomic dissociation within the parietal cortex for retrieving item and contextual information was not found in any of three ROIs. These results support the hypothesis that specific subregions in the MTL are associated with item memory and memory for context.
Going AWOL in the Brain: Mind Wandering Reduces Cortical Analysis of External Events
Authors: Smallwood Jonathan , Beach Emily , Schooler Jonathan W. , Handy Todd C. 
Published: November 2007

Abstract
Converging evidence from neuroscience suggests that our attention to the outside world waxes and wanes over time. We examined whether these periods of “mind wandering” are associated with reduced cortical analysis of the external environment. Participants performed a sustained attention to response task in which they responded to frequent “nontargets” (digits 0–9) and withheld responses for infrequent “targets” (the letter X). Mind wandering was defined both behaviorally, indicated by a failure to withhold a response to a target, and subjectively, via self-report at a thought probe. The P300 event-related potential component for nontargets was reduced prior to both the behavioral and subjective reports of mind wandering, relative to periods of being “on-task.” Regression analysis of P300 amplitude revealed significant common variance between behavioral and subjective markers of mind wandering, suggesting that both markers reflect a common underlying mental state. Finally, control analysis revealed that the effect of mind wandering on the P300 could not be ascribed to changes in motor activity nor was it associated with general arousal. Our data suggest that when trying to engage attention in a sustained manner, the mind will naturally ebb and flow in the depth of cognitive analysis it applies to events in the external environment.
Yes/No Recognition, Forced-choice Recognition, and the Human Hippocampus
Authors: Bayley P. J. , Wixted J. T. , Hopkins R. O. , Squire L. R. 
Published: November 2007

Abstract
Two recent studies reported that yes/no recognition can be more impaired by hippocampal lesions than forced-choice recognition when the targets and foils are highly similar. This finding has been taken in support of two fundamental proposals: (1) yes/no recognition tests depend more on recollection than do forced-choice tests; and (2) the hippocampus selectively supports the recollection process. Using the same stimulus materials as in the earlier studies, we tested five memory-impaired patients with circumscribed hippocampal lesions and 15 controls. As in the earlier studies, participants studied 12 pictures of objects and then took either a 12-item forced-choice test with four alternatives or a 60-item yes/no test. Patients were impaired on both tests but did more poorly on the yes/no test. However, a yes/no test based on 12 study items would conventionally involve only 24 test items (i.e., 12 study items and 12 foil items). When we scored only the first 24 test items, the patients performed identically on the yes/no and forced-choice tests. Examination of the data in blocks of 12 trials indicated that the scores of the patients declined as testing continued. We suggest that a yes/no test of 60 items is difficult relative to a 12-item forced-choice test due to the increased study-test delay and due to increased interference, not because of any fundamental difference between the yes/no and forced-choice formats. We conclude that hippocampal lesions impair yes/no and forced-choice recognition to the same extent.
Remember/Know Judgments Probe Degrees of Recollection
Authors: Wais Peter E. , Mickes Laura , Wixted John T. 
Published: November 2007

Abstract
Remembering and knowing are states of awareness that accompany the retrieval of facts, faces, and experiences from our past. Although originally intended to separate episodic from semantic memory, the dominant view today is that recollection-based decisions underlie remember responses, whereas familiarity-based decisions underlie know responses. Many functional magnetic resonance imaging (fMRI) studies as well as lesion studies have relied on the remember/know procedure to identify the neural correlates of recollection and familiarity. An implicit assumption of this approach is that know responses, which are thought to tap familiarity-based decisions, are devoid of recollection. We investigated this issue by using a source memory procedure and found that the accuracy of source recollection was significantly above chance for studied words that were declared to be old and known. Critically, this held true even when the source decision was made before the old/new decision (i.e., even after successful recollection had just occurred). Our results show that although recollection and familiarity may be different processes, the remember/know paradigm does not probe them directly. As such, dissociations involving remember/know judgments in fMRI studies and in studies involving amnesic patients should not be construed as dissociations between recollection and familiarity.
Local Ensemble Transform Kalman Filtering with an AGCM at a T159/L48 Resolution
Authors: Miyoshi Takemasa , Yamane Shozo 
Published: November 2007

Abstract
A local ensemble transform Kalman filter (LETKF) is developed and assessed with the AGCM for the Earth Simulator at a T159 horizontal and 48-level vertical resolution (T159/L48), corresponding to a grid of 480 × 240 × 48. Following the description of the LETKF implementation, perfect model Observing Systems Simulation Experiments (OSSEs) with two kinds of observing networks and an experiment with real observations are performed. First, a regular observing network with approximately 1% observational coverage of the system dimension is applied to investigate computational efficiency and sensitivities with the ensemble size (up to 1000) and localization scale. A 10-member ensemble is large enough to prevent filter divergence. Using 20 or more members significantly stabilizes the filter, with the analysis errors less than half as large as the observation errors. There is nonnegligible dependence on the localization scale; tuning is suggested for a chosen ensemble size. The sensitivities of analysis accuracies and timing on the localization parameters are investigated systematically. A computational parallelizing ratio as large as 99.99% is achieved. Timing per analysis is less than 4 min on the Earth Simulator, peak performance of 64 GFlops per computational node, provided that the same number of nodes as the ensemble size is used, and the ensemble size is less than 80. In the other set of OSSEs, the ensemble size is fixed to 40, and the real observational errors and locations are adapted from the Japan Meteorological Agency’s (JMA’s) operational numerical weather prediction system. The analysis errors are as small as 0.5 hPa, 2.0 m s−1, and 1.0 K in major areas for sea level pressure, zonal and meridional winds, and temperature, respectively. Larger errors are observed in data-poor regions. The ensemble spreads capture the actual error structures, generally representing the observing network. However, the spreads are larger than the actual errors in the Southern Hemisphere; the opposite is true in the Tropics, which suggests the spatial dependence of the optimal covariance inflation. Finally, real observations are assimilated. The analysis fields look almost identical to the JMA operational analysis; 48-h forecast experiments initiated from the LETKF analysis, JMA operational analysis, and NCEP–NCAR reanalysis are performed, and the forecasts are compared with their own analyses. The 48-h forecast verifications suggest a similar level of accuracy when comparing LETKF to the operational systems. Overall, LETKF shows encouraging results in this study.
Radar and Lightning Observations of Normal and Inverted Polarity Multicellular Storms from STEPS
Authors: Tessendorf Sarah A. , Rutledge Steven A. , Wiens Kyle C. 
Published: November 2007

Abstract
This study discusses radar and lightning observations of two multicellular storms observed during the Severe Thunderstorm Electrification and Precipitation Study. The Lightning Mapping Array data indicated that the charge structure of the 19 June 2000 storm was consistent with a normal polarity tripole, while the 22 June 2000 storm exhibited an overall inverted tripolar charge structure. The 19 June storm consisted of weaker convection and produced little to no hail and moderate total flash rates peaking between 80 and 120 min−1. The cells in the 22 June 2000 storm were much more vigorous, exhibited strong, broad updrafts, and produced large quantities of hail, as well as extraordinary total flash rates as high as 500 min−1. The National Lightning Detection Network (NLDN) indicated that the 19 June storm produced mostly negative cloud-to-ground (CG) lightning, while the 22 June storm produced predominantly positive CG lightning, peaking at 10 min−1 just after two cells merged. However, the Los Alamos Sferic Array indicated that many of the positive CG strokes reported by the NLDN in the 22 June storm were intracloud discharges known as narrow bipolar events. Negative CG lightning was also observed in the 22 June storm, but typically came to ground beneath an inverted dipole in the storm anvil.
Novel definition files for human GeneChips based on GeneAnnot
Authors: Ferrari Francesco , Bortoluzzi Stefania , Coppe Alessandro , Sirota Alexandra , Safran Marilyn , Shmoish Michael , Ferrari Sergio , Lancet Doron , Danieli Gian Antonio , Bicciato Silvio 
Published: November 2007

Abstract

Background
Improvements in genome sequence annotation revealed discrepancies in the original probeset/gene assignment in Affymetrix microarray and the existence of differences between annotations and effective alignments of probes and transcription products. In the current generation of Affymetrix human GeneChips, most probesets include probes matching transcripts from more than one gene and probes which do not match any transcribed sequence.

Results
We developed a novel set of custom Chip Definition Files (CDF) and the corresponding Bioconductor libraries for Affymetrix human GeneChips, based on the information contained in the GeneAnnot database. GeneAnnot-based CDFs are composed of unique custom-probesets, including only probes matching a single gene.

Conclusion
GeneAnnot-based custom CDFs solve the problem of a reliable reconstruction of expression levels and eliminate the existence of more than one probeset per gene, which often leads to discordant expression signals for the same transcript when gene differential expression is the focus of the analysis. GeneAnnot CDFs are freely distributed and fully compliant with Affymetrix standards and all available software for gene expression analysis. The CDF libraries are available from http://www.xlab.unimo.it/GA_CDF, along with supplementary information (CDF libraries, installation guidelines and R code, CDF statistics, and analysis results).