bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modification of pharmacokinetic and abuse‐related effects of cocaine by human‐derived cocaine hydrolase in monkeys
Authors: Schindler Charles W. , Justinova Zuzana , Lafleur David , Woods Doug , Roschke Viktor , Hallak Hussein , Sklair‐Tavron Liora , Redhi Godfrey H. , Yasar Sevil , Bergman Jack , Goldberg Steven R. 
Published: January 2012

ABSTRACTAlthough substantial research effort has focused on developing pharmacological treatments for cocaine abuse, no effective medications have been developed. Recent studies show that enzymes that metabolize cocaine in the periphery, forestalling its entry into the brain, can prevent cocaine toxicity and its behavioral effects in rodents. Here we report on effects of one such enzyme (Albu‐CocH) on the pharmacokinetic and behavioral effects of cocaine in squirrel monkeys. Albu‐CocH was developed from successive mutations of human butyrylcholinesterase (BChE) and has 1000‐fold greater catalytic activity against cocaine than naturally occurring BChE. Pharmacokinetic studies showed that Albu‐CocH (5 mg/kg) had a half‐life of 56.6 hours in squirrel monkeys. In these studies, plasma levels of cocaine following i.v. 1 mg/kg cocaine were reduced 2 hours after administration of Albu‐CocH, whereas plasma levels of the cocaine metabolite ecgonine methyl ester were increased. These effects were still evident 72 hours following Albu‐CocH administration. In behavioral experiments in monkeys, pre‐treatment with 5 mg/kg Albu‐CocH dramatically decreased self‐administration of a reinforcing dose of i.v. cocaine (30 µg/kg/injection) for over 24 hours. Pre‐treatment with 5 mg/kg Albu‐CocH also attenuated the reinstatement of extinguished cocaine self‐administration by an i.v. priming injection of cocaine (0.1 or 0.3 mg/kg) and, in separate studies, attenuated the discriminative‐stimulus effects of cocaine. The ability of Albu‐CocH to attenuate the abuse‐related effects of cocaine in squirrel monkeys indicates that further investigation of BChE mutants as potential treatment for cocaine abuse and toxicity is warranted.
“Am I Getting It or Not?” The Practices Involved in “Trying to Consume” a New Technology
Authors: Ziamou Paschalina (Lilia) , Gould Stephen , Venkatesh Alladi 
Published: January 2012

In recent years, high rates of failure of technology‐based products have spurred interest in understanding the psychological and sociological barriers to consumer learning of technological innovations. The main focus of this research was to examine the learning process and consumers’ coping mechanisms when they encounter technological innovations. A study was designed to understand the learning process in real time as consumers engaged in a set of activities associated with the novel interface. The goal was to investigate how consumers cope with high levels of complexity during their initial interactions with a technology‐based product and how their coping strategies may hinder the learning process.Verbal protocol measures were used in order to understand the consumer's learning process as he or she interacts with a technology‐based product in real time. They were told that they would have to think aloud while performing certain tasks and that their thoughts would be recorded for further analysis. The personal digital assistant (PDA) with handwriting recognition as its interface was chosen for this study. The main task for the participants was to learn how to use Graffiti writing—i.e., the product's handwriting recognition software. We proceeded to a thematic analysis in which interpretations were generated by the researchers going back and forth between the transcribed texts, the developing interpretation, the new interface itself, and also the relevant literature.The results suggest that the new product's interface serves to structure the consumer's learning process even as he or she responds in relatively unstructured ways. The findings identify three basic factors that interfere with the learning process during consumers’ initial interactions with a technological innovation: interface and functionality practices, social influence, and causal attributions. Specifically, the results suggest that in designing technology‐based products there is a gap between the levels of know‐how between the manufacturer and the user. The challenge for manufacturers is to understand the consumer's learning experience and coping strategies and provide mechanisms that would make the transition easy and intuitive. This could be achieved by incorporating into the new interface some degree of flexibility that will allow consumers to modify tasks based on their preferences, or by including indicators that will provide feedback to the user. Furthermore, in the context of communication strategies, in order to minimize the negative impact that prior knowledge and social influence may have on learning, marketers could communicate specific steps describing how to use the new interface.
A THREAD IN THE LABYRINTH: RETURNING TO MELANIE KLEIN'S CONCEPT OF PROJECTIVE IDENTIFICATION
Authors: Buckingham Linda 
Published: January 2012

abstractThis is an attempt to clarify the confusions which, I argue, have accumulated in the uses and meanings of the term ‘projective identification’. As a remedy, I propose a return to Melanie Klein's original concept which focuses on the mental activity of the person in whose mind the projective identification takes place. I cover the early territory of Klein's definition and Bion's alteration of this, with its sole focus on PI as a communication which is dealt with in various ways by its object. Thomas Ogden followed his example. This narrowed the field opened by Klein. The confusions caused at this time persist today and render the concept less useful than it could be. I distinguish between projections and projective identifications. Further, I discuss five main types of projective identification and try to show that only one of these is evocatory; that is, only one involves a responding object.I hope to show that the concept, as devised by Klein, has a family of uses, all of which can be grasped fairly easily if we concentrate on the state of mind of the subject ‘owning’ the projective identification. While evocatory PIs, which affect their objects and prompt certain responses, are part of the therapeutic process, other types of PI are equally important although harder to grasp.
Development of conserved microsatellite markers of high cross‐species utility in bat species (Vespertilionidae, Chiroptera, Mammalia)
Authors: JAN CAMILLE , DAWSON DEBORAH A. , ALTRINGHAM JOHN D. , BURKE TERRY , BUTLIN ROGER K. 
Published: January 2012

AbstractComparative ecological and behavioural studies of the widespread and diverse Vespertilionidae, which comprise almost 400 of the 1100 bat species, have been limited by the availability of markers. The potential of new methods for developing conserved microsatellite markers that possess enhanced cross‐species utility has recently been illustrated in studies of birds. We have applied these methods to develop enhanced microsatellite markers for vespertilionid bats, in particular for the genus Myotis (103 species). We compared published bat microsatellites with their homologues in the genome sequence of the little brown bat, Myotis lucifugus, to create consensus sequences that were used to design candidate primer sets. Primer sets were then tested for amplification and polymorphism in 22 species of bat from nine of the largest families (including 11 Vespertilionidae). Of 46 loci tested, 33 were polymorphic, on average, in each of seven Myotis species tested, 20 in each of four species in other vespertilionid genera, and two in 11 nonvespertilionid species.
Mammographic Breast Density and Breast Cancer: Evidence of a Shared Genetic Basis
Authors: Varghese Jajini S. , Thompson Deborah J. , Michailidou Kyriaki , Lindström Sara , Turnbull Clare , Brown Judith , Leyland Jean , Warren Ruth M.L. , Luben Robert N. , Loos Ruth J. , Wareham Nicholas J. , Rommens Johanna , Paterson Andrew D. , Martin Lisa J. , Vachon Celine M. , Scott Christopher G. , Atkinson Elizabeth J. , Couch Fergus J. , Apicella Carmel , Southey Melissa C. , Stone Jennifer , Li Jingmei , Eriksson Louise , Czene Kamila , Boyd Norman F. , Hall Per , Hopper John L. , Tamimi Rulla M. , Rahman Nazneen , Easton Douglas F. 
Published: January 2012

Abstract
Percent mammographic breast density (PMD) is a strong heritable risk factor for breast cancer. However, the pathways through which this risk is mediated are still unclear. To explore whether PMD and breast cancer have a shared genetic basis, we identified genetic variants most strongly associated with PMD in a published meta-analysis of five genome-wide association studies (GWAS) and used these to construct risk scores for 3,628 breast cancer cases and 5,190 controls from the UK2 GWAS of breast cancer. The signed per-allele effect estimates of single-nucleotide polymorphisms (SNP) were multiplied with the respective allele counts in the individual and summed over all SNPs to derive the risk score for an individual. These scores were included as the exposure variable in a logistic regression model with breast cancer case–control status as the outcome. This analysis was repeated using 10 different cutoff points for the most significant density SNPs (1%–10% representing 5,222–50,899 SNPs). Permutation analysis was also conducted across all 10 cutoff points. The association between risk score and breast cancer was significant for all cutoff points from 3% to 10% of top density SNPs, being most significant for the 6% (2-sided P = 0.002) to 10% (P = 0.001) cutoff points (overall permutation P = 0.003). Women in the top 10% of the risk score distribution had a 31% increased risk of breast cancer [OR = 1.31; 95% confidence interval (CI), 1.08–1.59] compared with women in the bottom 10%. Together, our results show that PMD and breast cancer have a shared genetic basis that is mediated through a large number of common variants. Cancer Res; 72(6); 1478–84. ©2012 AACR.
DNA Methylation Profiling Defines Clinically Relevant Biological Subsets of Non–Small Cell Lung Cancer
Authors: Walter Kim , Holcomb Thomas , Januario Tom , Du Pan , Evangelista Marie , Kartha Nithya , Iniguez Leonardo , Soriano Robert , Huw Ling , Stern Howard , Modrusan Zora , Seshagiri Somasekar , Hampton Garret M. , Amler Lukas C. , Bourgon Richard , Yauch Robert L. , Shames David S. 
Published: January 2012

AbstractPurpose: Non–small cell lung cancers (NSCLC) comprise multiple distinct biologic groups with different prognoses. For example, patients with epithelial-like tumors have a better prognosis and exhibit greater sensitivity to inhibitors of the epidermal growth factor receptor (EGFR) pathway than patients with mesenchymal-like tumors. Here, we test the hypothesis that epithelial-like NSCLCs can be distinguished from mesenchymal-like NSCLCs on the basis of global DNA methylation patterns.Experimental Design: To determine whether phenotypic subsets of NSCLCs can be defined on the basis of their DNA methylation patterns, we combined microfluidics-based gene expression analysis and genome-wide methylation profiling. We derived robust classifiers for both gene expression and methylation in cell lines and tested these classifiers in surgically resected NSCLC tumors. We validate our approach using quantitative reverse transcriptase PCR and methylation-specific PCR in formalin-fixed biopsies from patients with NSCLC who went on to fail front-line chemotherapy.Results: We show that patterns of methylation divide NSCLCs into epithelial-like and mesenchymal-like subsets as defined by gene expression and that these signatures are similarly correlated in NSCLC cell lines and tumors. We identify multiple differentially methylated regions, including one in ERBB2 and one in ZEB2, whose methylation status is strongly associated with an epithelial phenotype in NSCLC cell lines, surgically resected tumors, and formalin-fixed biopsies from patients with NSCLC who went on to fail front-line chemotherapy.Conclusions: Our data show that patterns of DNA methylation can divide NSCLCs into two phenotypically distinct subtypes of tumors and provide proof of principle that differences in DNA methylation can be used as a platform for predictive biomarker discovery and development. Clin Cancer Res; 18(8); 2360–73. ©2012 AACR.
Spectral Energy Dissipation due to Surface Wave Breaking
Authors: Romero Leonel , Melville W. Kendall , Kleiss Jessica M. 
Published: January 2012

Abstract
A semiempirical determination of the spectral dependence of the energy dissipation due to surface wave breaking is presented and then used to propose a model for the spectral dependence of the breaking strength parameter b, defined in the O. M. Phillips’s statistical formulation of wave breaking dynamics. The determination of the spectral dissipation is based on closing the radiative transport equation for fetch-limited waves, measured in the Gulf of Tehuantepec Experiment, by using the measured evolution of the directional spectra with fetch, computations of the four-wave resonant interactions, and three models of the wind input source function. The spectral dependence of the breaking strength is determined from the Kleiss and Melville measurements of the breaking statistics and the semiempirical spectral energy dissipation, resulting in b = b(k, cp/u*), where k is the wavenumber and the parametric dependence is on the wave age, cp/u*. Guided by these semiempirical results, a model for b(k, cp/u*) is proposed that uses laboratory data from a variety of sources, which can be represented by b = a(S − S0)n, where S is a measure of the wave slope at breaking, a is a constant, S0 is a threshold slope for breaking, and 2.5 &lt; n &lt; 3 is a power law consistent with inertial wave dissipation scaling and laboratory measurements. The relationship between b(S) in the laboratory and b(k) in the field is based on the relationship between the saturation and mean square slope of the wave field. The results are discussed in the context of wind wave modeling and improved measurements of breaking in the field.
Evaluating Satellite-Based Cloud Persistence and Displacement Nowcasting Techniques over Complex Terrain
Authors: Guillot Eric M. , Vonder Haar Thomas H. , Forsythe John M. , Fletcher Steven J. 
Published: January 2012

Abstract
The Moderate Resolution Imaging Spectroradiometer (MODIS) sensor aboard the Terra and Aqua satellites allows roughly for the same region of Earth to be sampled twice in a nowcasting time frame. Using the MODIS cloud mask at 5-km resolution and radiosonde data, cloud nowcasting methods were evaluated from December 2008 through November 2009 over Utah and southwestern Wyoming (207 cases), a region with a variety of terrain. The hypothesis that a combination of persistence and displacement techniques (i.e., a hybrid technique) in regions of complex terrain should yield a better forecast than either method alone is tested; clouds forced by complex terrain often appear to persist along topographic barriers. A new forecast skill evaluation method is introduced, designed to equate correct cloudy and correct clear areas. The persistence nowcasting method demonstrated the highest skill [as much as 10% critical success index improvement (CSI) over other methods]. However, all nowcasting techniques performed similarly during the summer months (~65% CSI). It is concluded that cloud nowcasts at 5-km resolution over complex terrain in the forecast area, using no model wind or moisture data, do not improve upon a persistence nowcast. However, because these basic nowcasting methods are computationally fast, educated decisions on minute to hour time scales can be made nearly instantaneously.
CIN85 is required for Cbl-mediated regulation of antigen receptor signaling in human B cells
Authors: Niiro Hiroaki , Jabbarzadeh-Tabrizi Siamak , Kikushige Yoshikane , Shima Takahiro , Noda Kumiko , Ota Shun-ichiro , Tsuzuki Hirofumi , Inoue Yasushi , Arinobu Yojiro , Iwasaki Hiromi , Shimoda Shinji , Baba Eishi , Tsukamoto Hiroshi , Horiuchi Takahiko , Taniyama Tadayoshi , Akashi Koichi 
Published: January 2012

AbstractThe aberrant regulation of B-cell receptor (BCR) signaling allows unwanted B cells to persist, thereby potentially leading to autoimmunity and B-cell malignancies. Casitas B-lineage lymphoma (Cbl) proteins suppress BCR signaling; however, the molecular mechanisms that control Cbl function in human B cells remain unclear. Here, we demonstrate that CIN85 (c-Cbl interacting protein of 85 kDa) is constitutively associated with c-Cbl, Cbl-b, and B-cell linker in B cells. Experiments using CIN85-overexpressing and CIN85-knockdown B-cell lines revealed that CIN85 increased c-Cbl phosphorylation and inhibited BCR-induced calcium flux and phosphorylation of Syk and PLCγ2, whereas it did not affect BCR internalization. The Syk phosphorylation in CIN85-overexpressing and CIN85-knockdown cells was inversely correlated with the ubiquitination and degradation of Syk. Moreover, CIN85 knockdown in primary B cells enhanced BCR-induced survival and growth, and increased the expression of BcLxL, A1, cyclin D2, and myc. Following the stimulation of BCR and Toll-like receptor 9, B-cell differentiation- associated molecules were up-regulated in CIN85-knockdown cells. Together, these results suggest that CIN85 is required for Cbl-mediated regulation of BCR signaling and for downstream events such as survival, growth, and differentiation of human B cells.
Fascin overexpression promotes neoplastic progression in oral squamous cell carcinoma
Authors: Alam Hunain , Bhate Amruta V , Gangadaran Prakash , Sawant Sharda S , Salot Shimul , Sehgal Lalit , Dange Prerana P , Chaukar Devendra A , D'cruz Anil K , Kannanl Sadhna , Gude Rajiv , Kane Shubhada , Dalal Sorab N , Vaidya Milind M 
Published: January 2012

Abstract

Background
Fascin is a globular actin cross-linking protein, which plays a major role in forming parallel actin bundles in cell protrusions and is found to be associated with tumor cell invasion and metastasis in various type of cancers including oral squamous cell carcinoma (OSCC). Previously, we have demonstrated that fascin regulates actin polymerization and thereby promotes cell motility in K8-depleted OSCC cells. In the present study we have investigated the role of fascin in tumor progression of OSCC.

Methods
To understand the role of fascin in OSCC development and/or progression, fascin was overexpressed along with vector control in OSCC derived cells AW13516. The phenotype was studied using wound healing, Boyden chamber, cell adhesion, Hanging drop, soft agar and tumorigenicity assays. Further, fascin expression was examined in human OSCC samples (N = 131) using immunohistochemistry and level of its expression was correlated with clinico-pathological parameters of the patients.

Results
Fascin overexpression in OSCC derived cells led to significant increase in cell migration, cell invasion and MMP-2 activity. In addition these cells demonstrated increased levels of phosphorylated AKT, ERK1/2 and JNK1/2. Our in vitro results were consistent with correlative studies of fascin expression with the clinico-pathological parameters of the OSCC patients. Fascin expression in OSCC showed statistically significant correlation with increased tumor stage (P = 0.041), increased lymph node metastasis (P = 0.001), less differentiation (P = 0.005), increased recurrence (P = 0.038) and shorter survival (P = 0.004) of the patients.

Conclusion
In conclusion, our results indicate that fascin promotes tumor progression and activates AKT and MAPK pathways in OSCC-derived cells. Further, our correlative studies of fascin expression in OSCC with clinico-pathological parameters of the patients indicate that fascin may prove to be useful in prognostication and treatment of OSCC.
The DARE study of relapse prevention in depression: design for a phase 1/2 translational randomised controlled trial involving mindfulness-based cognitive therapy and supported self monitoring
Authors: Shawyer Frances , Meadows Graham N , Judd Fiona , Martin Paul R , Segal Zindel , Piterman Leon 
Published: January 2012

AbstractBackgroundDepression is a common condition that typically has a relapsing course. Effective interventions targeting relapse have the potential to dramatically reduce the point prevalence of the condition. Mindfulness-based cognitive therapy (MBCT) is a group-based intervention that has shown efficacy in reducing depressive relapse. While trials of MBCT to date have met the core requirements of phase 1 translational research, there is a need now to move to phase 2 translational research - the application of MBCT within real-world settings with a view to informing policy and clinical practice. The aim of this trial is to examine the clinical impact and health economics of MBCT under real-world conditions and where efforts have been made to assess for and prevent resentful demoralization among the control group. Secondary aims of the project involve extending the phase 1 agenda to an examination of the effects of co-morbidity and mechanisms of action.Methods/DesignThis study is designed as a prospective, multi-site, single-blind, randomised controlled trial using a group comparison design between involving the intervention, MBCT, and a self-monitoring comparison condition, Depression Relapse Active Monitoring (DRAM). Follow-up is over 2 years. The design of the study indicates recruitment from primary and secondary care of 204 participants who have a history of 3 or more episodes of Major Depression but who are currently well. Measures assessing depressive relapse/recurrence, time to first clinical intervention, treatment expectancy and a range of secondary outcomes and process variables are included. A health economics evaluation will be undertaken to assess the incremental cost of MBCT.DiscussionThe results of this trial, including an examination of clinical, functional and health economic outcomes, will be used to assess the role that this treatment approach may have in recommendations for treatment of depression in Australia and elsewhere. If the findings are positive, we expect that this research will consolidate the evidence base to guide the decision to fund MBCT and to seek to promote its availability to those who have experienced at least 3 episodes of depression.Trial RegistrationAustralian New Zealand Clinical Trials Registry:ACTRN12607000166471