bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Analytic Surface and the Theory of Technique
Authors: Levy Steven T. , Inderbitzin Lawrence B. 
Published: June 2009

This paper examines the concept of the analytic surface as a starting point for the interpretive process in relation to the theory of psychoanalytic technique. The history of the concept of the analytic surface within psychoanalysis is reviewed. Four different conceptualizations of analytic surfaces are described (M. M. Gill, P. Gray, A. Kris, E. A. Schwaber). The advantages of a “surface” approach are explored in relation to clinical work, the teaching of psychoanalytic technique, and opportunities for research. Some criticisms of the concept are explored. “Nothing is rich but the inexhaustible wealth of nature. She shows us only surfaces, but she is a million fathoms deep.” Ralph Waldo Emerson
Castration
Authors: Rangell Leo 
Published: June 2009

Castration is not a metaphor within the array of psychoanalytic theories, but a pathological belief operative in the unconscious, which originated during the period of childhood sexuality. Of the two major anxieties, separation and castration, castration anxiety is the most overlooked in clinical discourse and theoretical awareness. Castration conflicts have a developmental history and are composed of phases as much as separation-individuation is. These extend from the preoedipal to the oedipal years and beyond and, as separation conflicts, persist throughout life. Clinical material is demonstrated from across the diagnostic spectrum and all developmental levels. Phylogenetic studies are corroborative. As loss of love is a wider derivative of separation anxiety, castration anxiety radiates out to wider fears of invasion and injury to the body. The transference neurosis is more attuned to encompass separation than castration conflicts. This stratum of psychopathology makes reconstruction and the recovery of historical data indispensable.
The Deficit Syndrome in Schizophrenia: Psychoanalytic and Neurobiological Perspectives
Authors: Willick Martin S. 
Published: June 2009

The author summarizes recent advances in neurobiological research which appear to offer compelling evidence that the most pathognomonic feature of schizophrenia, the deficit or negative syndrome, is associated with functional abnormalities in the frontal lobe of the brain. These brain abnormalities are correlated with those conceptualized by psychoanalytic theories of withdrawal of libido and loss of mental representation. In the light of this data, the author expresses serious reservations about three psychoanalytic formulations concerning the causes of the deficit syndrome: (1) the syndrome represents, in a primary rather than a secondary way, a psychological defense; (2) it is caused by severe conflicts or neglect during early childhood which lead to impairments in the building up of psychic structure and mental representation; (3) difficulties with the aggressive drive play a primary etiological role.
Idols of Our Tribes?
Authors: Shanafelt Robert 
Published: June 2009

This article discusses relativism and the evaluation of belief in contemporary ethnography. Various examples of conflicting beliefs are described, as well as the author's experience of a disagreement with members of a Christian community, the New Order Amish, over the nature of evolution and spirituality. Because conflicts over `truth' are an increasingly prominent feature of our globalizing world, now more than ever they must be dealt with directly. With this in mind, pragmatic suggestions are given about how to evaluate beliefs in terms of differing domains of truth. If we believe in any revealed religion and, for instance, we have to admit that Christ is the son of God, then he is not the Messiah still awaiting in Jerusalem. And if Mohammed is the prophet of Allah, then it is mistaken to offer sacrifices to the Plumed Serpent. If we follow the most enlightened and indulgent of deisms, prepared to believe at once in the Communion of Saints and the Great Wheel of the Tao, then we will reject, as fruit of error, the massacre of infidels and heretics. If we are worshipers of Satan, we will consider puerile the Sermon on the Mount. If we are radical atheists, every faith will be nothing but misunderstanding. Therefore, given that in the course of history many have acted on beliefs in which many others did not believe, we must perforce admit that for each, to a different degree, history has been largely the Theater of an Illusion. (Eco, 1988: 2—3)
Spatiotemporal regulation of intracellular trafficking of Toll-like receptor 9 by an inhibitory receptor, Ly49Q
Authors: Yoshizaki Mariko , Tazawa Aya , Kasumi Eiji , Sasawatari Shigemi , Itoh Kenji , Dohi Taeko , Sasazuki Takehiko , Inaba Kayo , Makrigiannis Andrew P. , Toyama-Sorimachi Noriko 
Published: June 2009

AbstractToll-like receptor (TLR) 9 recognizes unmethylated microorganismal cytosine guanine dinucleotide (CpG) DNA and elicits innate immune responses. However, the regulatory mechanisms of the TLR signaling remain elusive. We recently reported that Ly49Q, an immunoreceptor tyrosine-based inhibitory motif–bearing inhibitory receptor belonging to the natural killer receptor family, is crucial for TLR9-mediated type I interferon production by plasmacytoid dendritic cells. Ly49Q is expressed in plasmacytoid dendritic cells, macrophages, and neutrophils, but not natural killer cells. In this study, we showed that Ly49Q regulates TLR9 signaling by affecting endosome/lysosome behavior. Ly49Q colocalized with CpG in endosome/lysosome compartments. Cells lacking Ly49Q showed a disturbed redistribution of TLR9 and CpG. In particular, CpG-induced tubular endolysosomal extension was impaired in the absence of Ly49Q. Consistent with these findings, cells lacking Ly49Q showed impaired cytokine production in response to CpG-oligodeoxynucleotide. Our data highlight a novel mechanism by which TLR9 signaling is controlled through the spatiotemporal regulation of membrane trafficking by the immunoreceptor tyrosine-based inhibitory motif–bearing receptor Ly49Q.
Factor H–related protein 1 (CFHR-1) inhibits complement C5 convertase activity and terminal complex formation
Authors: Heinen Stefan , Hartmann Andrea , Lauer Nadine , Wiehl Ulrike , Dahse Hans-Martin , Schirmer Sylvia , Gropp Katharina , Enghardt Tina , Wallich Reinhard , Hälbich Steffi , Mihlan Michael , Schlötzer-Schrehardt Ursula , Zipfel Peter F. , Skerka Christine 
Published: June 2009

AbstractHomozygous deletion of a 84-kb genomic fragment in human chromosome 1 that encompasses the CFHR1 and CFHR3 genes represents a risk factor for hemolytic uremic syndrome (HUS) but has a protective effect in age-related macular degeneration (AMD). Here we identify CFHR1 as a novel inhibitor of the complement pathway that blocks C5 convertase activity and interferes with C5b surface deposition and MAC formation. This activity is distinct from complement factor H, and apparently factor H and CFHR1 control complement activation in a sequential manner. As both proteins bind to the same or similar sites at the cellular surfaces, the gain of CFHR1 activity presumably is at the expense of CFH-mediated function (inhibition of the C3 convertase). In HUS, the absence of CFHR1 may result in reduced inhibition of terminal complex formation and in reduced protection of endothelial cells upon complement attack. These findings provide new insights into complement regulation on the cell surface and biosurfaces and likely define the role of CFHR1 in human diseases.
Correcting for bias in estimation of quantitative trait loci effects
Authors: Weller Joel Ira , Shlezinger Meital , Ron Micha 
Published: June 2009

Abstract
Estimates of quantitative trait loci (QTL) effects derived from complete genome scans are biased, if no assumptions are made about the distribution of QTL effects. Bias should be reduced if estimates are derived by maximum likelihood, with the QTL effects sampled from a known distribution. The parameters of the distributions of QTL effects for nine economic traits in dairy cattle were estimated from a daughter design analysis of the Israeli Holstein population including 490 marker-by-sire contrasts. A separate gamma distribution was derived for each trait. Estimates for both the α and β parameters and their SE decreased as a function of heritability. The maximum likelihood estimates derived for the individual QTL effects using the gamma distributions for each trait were regressed relative to the least squares estimates, but the regression factor decreased as a function of the least squares estimate. On simulated data, the mean of least squares estimates for effects with nominal 1% significance was more than twice the simulated values, while the mean of the maximum likelihood estimates was slightly lower than the mean of the simulated values. The coefficient of determination for the maximum likelihood estimates was five-fold the corresponding value for the least squares estimates.
Oxidative stress augments toll-like receptor 8 mediated neutrophilic responses in healthy subjects
Authors: Yanagisawa Satoru , Koarai Akira , Sugiura Hisatoshi , Ichikawa Tomohiro , Kanda Masae , Tanaka Rie , Akamatsu Keiichiro , Hirano Tsunahiko , Matsunaga Kazuto , Minakata Yoshiaki , Ichinose Masakazu 
Published: June 2009

Abstract

Background
Excessive oxidative stress has been reported to be generated in inflamed tissues and contribute to the pathogenesis of inflammatory lung diseases, exacerbations of which induced by viral infections are associated with toll-like receptor (TLR) activation. Among these receptors, TLR8 has been reported as a key receptor that recognizes single-strand RNA virus. However, it remains unknown whether TLR8 signaling is potentiated by oxidative stress. The aim of this study is to examine whether oxidative stress modulates TLR8 signaling in vitro.

Methods
Human peripheral blood neutrophils were obtained from healthy non-smokers and stimulated with TLR 7/8 agonist imidazoquinoline resiquimod (R848) in the presence or absence of hydrogen peroxide (H2O2). Neutrophilic responses including cytokine release, superoxide production and chemotaxis were examined, and the signal transduction was also analyzed.

Results
Activation of TLR8, but not TLR7, augmented IL-8 release. The R848-augmented IL-8 release was significantly potentiated by pretreatment with H2O2 (p < 0.01), and N-acetyl-L-cysteine reversed this potentiation. The combination of H2O2 and R848 significantly potentiated NF-kB phosphorylation and IkBα degradation. The H2O2-potentiated IL-8 release was suppressed by MG-132, a proteosome inhibitor, and by dexamethasone. The expressions of TLR8, myeloid differentiation primary response gene 88 (MyD88), and tumor necrosis factor receptor-associated factor 6 (TRAF6) were not affected by H2O2.

Conclusion
TLR8-mediated neutrophilic responses were markedly potentiated by oxidative stress, and the potentiation was mediated by enhanced NF-kB activation. These results suggest that oxidative stress might potentiate the neutrophilic inflammation during viral infection.
FuGEFlow: data model and markup language for flow cytometry
Authors: Qian Yu , Tchuvatkina Olga , Spidlen Josef , Wilkinson Peter , Gasparetto Maura , Jones Andrew R , Manion Frank J , Scheuermann Richard H , Sekaly Rafick-Pierre , Brinkman Ryan R 
Published: June 2009

Abstract

Background
Flow cytometry technology is widely used in both health care and research. The rapid expansion of flow cytometry applications has outpaced the development of data storage and analysis tools. Collaborative efforts being taken to eliminate this gap include building common vocabularies and ontologies, designing generic data models, and defining data exchange formats. The Minimum Information about a Flow Cytometry Experiment (MIFlowCyt) standard was recently adopted by the International Society for Advancement of Cytometry. This standard guides researchers on the information that should be included in peer reviewed publications, but it is insufficient for data exchange and integration between computational systems. The Functional Genomics Experiment (FuGE) formalizes common aspects of comprehensive and high throughput experiments across different biological technologies. We have extended FuGE object model to accommodate flow cytometry data and metadata.

Methods
We used the MagicDraw modelling tool to design a UML model (Flow-OM) according to the FuGE extension guidelines and the AndroMDA toolkit to transform the model to a markup language (Flow-ML). We mapped each MIFlowCyt term to either an existing FuGE class or to a new FuGEFlow class. The development environment was validated by comparing the official FuGE XSD to the schema we generated from the FuGE object model using our configuration. After the Flow-OM model was completed, the final version of the Flow-ML was generated and validated against an example MIFlowCyt compliant experiment description.

Results
The extension of FuGE for flow cytometry has resulted in a generic FuGE-compliant data model (FuGEFlow), which accommodates and links together all information required by MIFlowCyt. The FuGEFlow model can be used to build software and databases using FuGE software toolkits to facilitate automated exchange and manipulation of potentially large flow cytometry experimental data sets. Additional project documentation, including reusable design patterns and a guide for setting up a development environment, was contributed back to the FuGE project.

Conclusion
We have shown that an extension of FuGE can be used to transform minimum information requirements in natural language to markup language in XML. Extending FuGE required significant effort, but in our experiences the benefits outweighed the costs. The FuGEFlow is expected to play a central role in describing flow cytometry experiments and ultimately facilitating data exchange including public flow cytometry repositories currently under development.
Automated genome mining for natural products
Authors: Li Michael HT , Ung Peter MU , Zajkowski James , Garneau-Tsodikova Sylvie , Sherman David H 
Published: June 2009

Abstract

Background
Discovery of new medicinal agents from natural sources has largely been an adventitious process based on screening of plant and microbial extracts combined with bioassay-guided identification and natural product structure elucidation. Increasingly rapid and more cost-effective genome sequencing technologies coupled with advanced computational power have converged to transform this trend toward a more rational and predictive pursuit.

Results
We have developed a rapid method of scanning genome sequences for multiple polyketide, nonribosomal peptide, and mixed combination natural products with output in a text format that can be readily converted to two and three dimensional structures using conventional software. Our open-source and web-based program can assemble various small molecules composed of twenty standard amino acids and twenty two other chain-elongation intermediates used in nonribosomal peptide systems, and four acyl-CoA extender units incorporated into polyketides by reading a hidden Markov model of DNA. This process evaluates and selects the substrate specificities along the assembly line of nonribosomal synthetases and modular polyketide synthases.

Conclusion
Using this approach we have predicted the structures of natural products from a diverse range of bacteria based on a limited number of signature sequences. In accelerating direct DNA to metabolomic analysis, this method bridges the interface between chemists and biologists and enables rapid scanning for compounds with potential therapeutic value.
Statistical assessment of discriminative features for protein-coding and non coding cross-species conserved sequence elements
Authors: Creanza Teresa M , Horner David S , D'Addabbo Annarita , Maglietta Rosalia , Mignone Flavio , Ancona Nicola , Pesole Graziano 
Published: June 2009

AbstractBackgroundThe identification of protein coding elements in sets of mammalian conserved elements is one of the major challenges in the current molecular biology research. Many features have been proposed for automatically distinguishing coding and non coding conserved sequences, making so necessary a systematic statistical assessment of their differences. A comprehensive study should be composed of an association study, i.e. a comparison of the distributions of the features in the two classes, and a prediction study in which the prediction accuracies of classifiers trained on single and groups of features are analyzed, conditionally to the compared species and to the sequence lengths.ResultsIn this paper we compared distributions of a set of comparative and non comparative features and evaluated the prediction accuracy of classifiers trained for discriminating sequence elements conserved among human, mouse and rat species. The association study showed that the analyzed features are statistically different in the two classes. In order to study the influence of the sequence lengths on the feature performances, a predictive study was performed on different data sets composed of coding and non coding alignments in equal number and equally long with an ascending average length. We found that the most discriminant feature was a comparative measure indicating the proportion of synonymous nucleotide substitutions per synonymous sites. Moreover, linear discriminant classifiers trained by using comparative features in general outperformed classifiers based on intrinsic ones. Finally, the prediction accuracy of classifiers trained on comparative features increased significantly by adding intrinsic features to the set of input variables, independently on sequence length (Kolmogorov-Smirnov P-value ≤ 0.05).ConclusionWe observed distinct and consistent patterns for individual and combined use of comparative and intrinsic classifiers, both with respect to different lengths of sequences/alignments and with respect to error rates in the classification of coding and non-coding elements. In particular, we noted that comparative features tend to be more accurate in the classification of coding sequences – this is likely related to the fact that such features capture deviations from strictly neutral evolution expected as a consequence of the characteristics of the genetic code.
Human microRNA target analysis and gene ontology clustering by GOmir, a novel stand-alone application
Authors: Roubelakis Maria G , Zotos Pantelis , Papachristoudis Georgios , Michalopoulos Ioannis , Pappa Kalliopi I , Anagnou Nicholas P , Kossida Sophia 
Published: June 2009

Abstract

Background
microRNAs (miRNAs) are single-stranded RNA molecules of about 20–23 nucleotides length found in a wide variety of organisms. miRNAs regulate gene expression, by interacting with target mRNAs at specific sites in order to induce cleavage of the message or inhibit translation. Predicting or verifying mRNA targets of specific miRNAs is a difficult process of great importance.

Results
GOmir is a novel stand-alone application consisting of two separate tools: JTarget and TAGGO. JTarget integrates miRNA target prediction and functional analysis by combining the predicted target genes from TargetScan, miRanda, RNAhybrid and PicTar computational tools as well as the experimentally supported targets from TarBase and also providing a full gene description and functional analysis for each target gene. On the other hand, TAGGO application is designed to automatically group gene ontology annotations, taking advantage of the Gene Ontology (GO), in order to extract the main attributes of sets of proteins. GOmir represents a new tool incorporating two separate Java applications integrated into one stand-alone Java application.

Conclusion
GOmir (by using up to five different databases) introduces miRNA predicted targets accompanied by (a) full gene description, (b) functional analysis and (c) detailed gene ontology clustering. Additionally, a reverse search initiated by a potential target can also be conducted. GOmir can freely be downloaded BRFAA.
Massive non-natural proteins structure prediction using grid technologies
Authors: Minervini Giovanni , Evangelista Giuseppe , Villanova Laura , Slanzi Debora , De Lucrezia Davide , Poli Irene , Luisi Pier Luigi , Polticelli Fabio 
Published: June 2009

Abstract

Background
The number of natural proteins represents a small fraction of all the possible protein sequences and there is an enormous number of proteins never sampled by nature, the so called "never born proteins" (NBPs). A fundamental question in this regard is if the ensemble of natural proteins possesses peculiar chemical and physical properties or if it is just the product of contingency coupled to functional selection. A key feature of natural proteins is their ability to form a well defined three-dimensional structure. Thus, the structural study of NBPs can help to understand if natural protein sequences were selected for their peculiar properties or if they are just one of the possible stable and functional ensembles.

Methods
The structural characterization of a huge number of random proteins cannot be approached experimentally, thus the problem has been tackled using a computational approach. A large random protein sequences library (2 × 104 sequences) was generated, discarding amino acid sequences with significant similarity to natural proteins, and the corresponding structures were predicted using Rosetta. Given the highly computational demanding problem, Rosetta was ported in grid and a user friendly job submission environment was developed within the GENIUS Grid Portal. Protein structures generated were analysed in terms of net charge, secondary structure content, surface/volume ratio, hydrophobic core composition, etc.

Results
The vast majority of NBPs, according to the Rosetta model, are characterized by a compact three-dimensional structure with a high secondary structure content. Structure compactness and surface polarity are comparable to those of natural proteins, suggesting similar stability and solubility. Deviations are observed in α helix-β strands relative content and in hydrophobic core composition, as NBPs appear to be richer in helical structure and aromatic amino acids with respect to natural proteins.

Conclusion
The results obtained suggest that the ability to form a compact, ordered and water-soluble structure is an intrinsic property of polypeptides. The tendency of random sequences to adopt α helical folds indicate that all-α proteins may have emerged early in pre-biotic evolution. Further, the lower percentage of aromatic residues observed in natural proteins has important evolutionary implications as far as tolerance to mutations is concerned.