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Selected AbstractsI,Varieties of Support and Confirmation of Climate ModelsARISTOTELIAN SOCIETY SUPPLEMENTARY VOLUME, Issue 1 2009Elisabeth A. Lloyd Today's climate models are supported in a couple of ways that receive little attention from philosophers or climate scientists. In addition to standard ,model fit', wherein a model's simulation is compared to observational data, there is an additional type of confirmation available through the variety of instances of model fit. When a model performs well at fitting first one variable and then another, the probability of the model under some standard confirmation function, say, likelihood, goes up more than under each individual case of fit alone. Thus, two instances of fit of distinct variables of a global climate model using distinct data sets considered collectively will provide stronger evidence for a model than either one of the instances considered individually. This has consequences for model robustness. Sets of models that produce robust results will, if their assumptions vary enough and they each are observationally sound, provide reasons to endorse common structures found in those models. Finally, independent empirical support for aspects and assumptions of the model provides an additional confirmational virtue for climate models, contrary to what is implied by some current philosophical writing on this topic. [source] Targeting Conservation Action through Assessment of Protection and Exurban ThreatsCONSERVATION BIOLOGY, Issue 6 2003DAVID M. THEOBALD I developed a methodology to assess the level of threat to conservation of biodiversity to help guide conservation action. This method incorporates socioeconomic indicators of risk, including developed and roaded areas, and measures the proportion of conservation lands affected by developed areas. In addition, I developed a metric called conservation potential to measure the degree of fragmentation of patches caused by development. As an illustration I applied this methodology to Colorado (U.S.A.). Protection levels were determined by examining land ownership, resulting in protected lands (status levels 1 and 2) and unprotected lands (status levels 3 and 4). Areas were considered threatened (at risk) if a land-cover patch had >20% roaded area, >15% developed area, or was highly fragmented. Although 24 of 43 natural land-cover types were unprotected (49% of the state), 9 additional types were threatened. Combining conservation-status protection levels with patterns of threat targets the geographic area where conservation action is needed, provides a way to determine where so-called protected areas are at risk, and allows conservation strategies to be better refined. Resumen: Las evaluaciones de biodiversidad a nivel de paisaje se esfuerzan por proporcionar información para la planificación del uso del suelo y actividades de conservación mediante datos sobre áreas de alto valor de biodiversidad y bajo estatus de protección. Desarrollé una metodología para evaluar el nivel de amenaza para la conservación de la biodiversidad para ayudar a guiar acciones de conservación. Este método incorpora indicadores socioeconómicos de riesgo, incluyendo áreas desarrolladas y con caminos, y mide la proporción de tierras de conservación afectadas por áreas desarrolladas. Adicionalmente, desarrollé una medida llamada potencial de conservación para cuantificar el grado de fragmentación debido al desarrollo. Como un ejemplo, apliqué esta metodología a Colorado (E. U. A). Los niveles de protección se determinaron examinando la propiedad, resultando en tierras protegidas (niveles 1 y 2) y no protegidas (niveles 3 y 4). Las áreas se consideraron amenazadas (en riesgo) si tenían >20% de su superficie con caminos, >15% del área desarrollada o si estaban muy fragmentadas. Aunque 24 de los 43 tipos de cobertura natural no estaban protegidos (49% del estado), 9 más estaban amenazados. La combinación de estatus de conservación y niveles de protección con patrones de amenazas identifica al área geográfica donde se requieren acciones de conservación, proporciona una forma de examinar donde están en riesgo las llamadas áreas protegidas y permite que las estrategias de conservación sean mejor ajustadas. [source] Broad tumor spectrum in a mouse model of multiple endocrine neoplasia type 1INTERNATIONAL JOURNAL OF CANCER, Issue 2 2007Kelly A. Loffler Abstract Multiple endocrine neoplasia type 1 (MEN1) is an inherited cancer predisposition syndrome typified by development of tumors in parathyroid, pituitary and endocrine pancreas, as well as less common sites including both endocrine and nonendocrine organs. Deletion or mutation of the tumor suppressor gene MEN1 on chromosome 11 has been identified in many cases of MEN1 as well as in sporadic tumors. The molecular biology of menin, the protein encoded by MEN1, remains poorly understood. Here we describe a mouse model of MEN1 in which tumors were seen in pancreatic islets, pituitary, thyroid and parathyroid, adrenal glands, testes and ovaries. The observed tumor spectrum therefore includes types commonly seen in MEN1 patients and additional types. Pancreatic pathology was most common, evident in over 80% of animals, while other tumor types developed with lower frequency and generally later onset. Tumors of multiple endocrine organs were observed frequently, but progression to carcinoma and metastasis were not evident. Tumors in all sites showed loss of heterozygosity at the Men1 locus, though the frequency in testicular tumors was only 36%, indicating that a different molecular mechanism of tumorigenesis occurs in those Leydig tumors that do not show loss of the normal Men1 allele. Menin expression was below the level of detection in ovary, thyroid and testis, but loss of nuclear menin immunoreactivity was observed uniformly in all pancreatic islet adenomas and in some hyperplastic islet cells, suggesting that complete loss of Men1 is a critical point in islet tumor progression in this model. © 2006 Wiley-Liss, Inc. [source] The role of the cyclic imide in alternate degradation pathways for asparagine-containing peptides and proteinsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2007Michael P. DeHart Abstract Peptides and proteins exhibit enhanced reactivity at asparagine residues due to the formation of a reactive succinimide intermediate that produces normal and isoaspartyl deamidation products along with significant racemization. This study examines the potential for attack of amine nucleophiles at the succinimide carbonyls to generate alternate decomposition products, depending on the nucleophile involved in the reaction. The reactions of the model peptides Phe-Asn-Gly (FNG) and Phe-isoAsn-Gly (FisoNG) were explored as a function of pH (8.5,10.5) in the presence and absence of ammonia buffer (0.2,2 M) using an isocratic HPLC method to monitor reactant disappearance and product formation. In addition to deamidation to form isoAsp and Asp peptides, two additional types of reactions were found to occur via the succinimide intermediate under these conditions. Back-reaction of the succinimide with ammonia led to peptide backbone isomerization while intramolecular attack by the amino terminus produced diketopiperazines. A kinetic model assuming a central role for the succinimide intermediate was derived to fit the concentration versus time data. These studies implicate the cyclic imide as a key intermediate in the formation of alternate peptide and protein degradants, including possible covalent amide-linked aggregates that may form from intermolecular attack of the cyclic imide by neighboring amino groups. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2667,2685, 2007 [source] Self-burning versus self-cutting: Patterns and implications of self-mutilation; a preliminary study of differences between self-cutting and self-burning in a Japanese juvenile detention centerPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 1 2005TOSHIHIKO MATSUMOTO md Abstract, The purpose of the present paper was to examine the differences in clinical features between self-cutters and, self-burners,, to, clarify, clinical, implications, of, self-mutilating, behaviors, other than self-cutting. Subjects were 201 delinquent adolescents consecutively entering a Japanese juvenile detention center from February 2003 to March 2003. The subjects were assessed using a self-reporting questionnaire to evaluate self-mutilation, traumatic events, and problematic behaviors. Beck Depression Inventory-2 (BDI-2) and Adolescent Dissociative Experience Scale (A-DES) were also tested. Subjects were classified into four groups according to self-mutilating behaviors: non-self-cutting or -burning (NSCB), self-cutting (SC), self-burning (SB), and self-cutting and self-burning (SCB). The questionnaire answers and scores of the BDI-2 and A-DES were compared between the four groups. Of 201 subjects, 33 (16.4%) had cut their wrists or forearms at least once, and 72 of 201 (35.8%) had burned themselves at least once. The SC and SCB group had traumatic events, problematic behavior, and various types of self-mutilating behavior more frequently than the other two groups. The SCB group reported additional types of self-mutilating behavior more than the SC group. The SCB group also experienced multiple body customizations compared to the SC group, and exhibited higher scores on the BDI-2 and A-DES than the other three groups. The self-burning without self-cutting may have limited clinical implications. However, the self-burning with self-cutting may suggest depression and dissociation, as well as possible indication of self-mutilating behavior. [source] Morphology and mosaics of melanopsin-expressing retinal ganglion cell types in miceTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 13 2010David M. Berson Abstract Melanopsin is the photopigment of intrinsically photosensitive retinal ganglion cells (ipRGCs). Melanopsin immunoreactivity reveals two dendritic plexuses within the inner plexiform layer (IPL) and morphologically heterogeneous retinal ganglion cells. Using enhanced immunohistochemistry, we provide a fuller description of murine cell types expressing melanopsin, their contribution to the plexuses of melanopsin dendrites, and mosaics formed by each type. M1 cells, corresponding to the originally described ganglion-cell photoreceptors, occupy the ganglion cell or inner nuclear layers. Their large, sparsely branched arbors (mean diameter 275 ,m) monostratify at the outer limit of the OFF sublayer. M2 cells also have large, monostratified dendritic arbors (mean diameter 310 ,m), but ramify in the inner third of the IPL, within the ON sublayer. There are ,900 M1 cells and 800 M2 cells per retina; each type comprises roughly 1,2% of all ganglion cells. The cell bodies of M1 cells are slightly smaller than those of M2 cells (mean diameters: 13 ,m for M1, 15 ,m for M2). Dendritic field overlap is extensive within each type (coverage factors ,3.8 for M1 and 2.5 for M2 cells). Rare bistratified cells deploy terminal dendrites within both melanopsin-immunoreactive plexuses. Because these are too sparsely distributed to permit complete retinal tiling, they lack a key feature of true ganglion cell types and may be anomalous hybrids of the M1 and M2 types. Finally, we observed weak melanopsin immunoreactivity in other ganglion cells, mostly with large somata, that may constitute one or more additional types of melanopsin-expressing cells. J. Comp. Neurol. 518:2405,2422, 2010. © 2010 Wiley-Liss, Inc. [source] Morphology and mosaics of melanopsin-expressing retinal ganglion cell types in mice,THE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 13 2010David M. Berson Abstract Melanopsin is the photopigment of intrinsically photosensitive retinal ganglion cells (ipRGCs). Melanopsin immunoreactivity reveals two dendritic plexuses within the inner plexiform layer (IPL) and morphologically heterogeneous retinal ganglion cells. Using enhanced immunohistochemistry, we provide a fuller description of murine cell types expressing melanopsin, their contribution to the plexuses of melanopsin dendrites, and mosaics formed by each type. M1 cells, corresponding to the originally described ganglion-cell photoreceptors, occupy the ganglion cell or inner nuclear layers. Their large, sparsely branched arbors (mean diameter 275 ,m) monostratify at the outer limit of the OFF sublayer. M2 cells also have large, monostratified dendritic arbors (mean diameter 310 ,m), but ramify in the inner third of the IPL, within the ON sublayer. There are ,900 M1 cells and 800 M2 cells per retina; each type comprises roughly 1,2% of all ganglion cells. The cell bodies of M1 cells are slightly smaller than those of M2 cells (mean diameters: 13 ,m for M1, 15 ,m for M2). Dendritic field overlap is extensive within each type (coverage factors ,3.8 for M1 and 4.6 for M2 cells). Rare bistratified cells deploy terminal dendrites within both melanopsin-immunoreactive plexuses. Because these are too sparsely distributed to permit complete retinal tiling, they lack a key feature of true ganglion cell types and may be anomalous hybrids of the M1 and M2 types. Finally, we observed weak melanopsin immunoreactivity in other ganglion cells, mostly with large somata, that may constitute one or more additional types of melanopsin-expressing cells. J. Comp. Neurol. 518:2405,2422, 2010. © 2010 Wiley-Liss, Inc. [source] Proteomics: Recent Applications and New TechnologiesBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2006Mollisa M. Elrick Proteomic analyses have recently been conducted on tissues, biofluids, subcellular components and enzymatic pathways as well as various disease and toxicological states, in both animal models and man. In addition, several recent studies have attempted to integrate proteomics data with genomics and/or metabonomics data in a systems biology approach. The translation of proteomic technology and bioinformatics tools to clinical samples, such as in the areas of disease and toxicity biomarkers, represents one of the major opportunities and challenges facing this field. An ongoing challenge in proteomics continues to be the analysis of the serum proteome due to the vast number and complexity of proteins estimated to be present in this biofluid. Aside from the removal of the most abundant proteins, a number of interesting approaches have recently been suggested that may help reduce the overall complexity of serum analysis. In keeping with the increasing interest in applications of proteomics, the tools available for proteomic analyses continue to improve and expand. For example, enhanced tools (such as software and labeling procedures) continue to be developed for the analysis of 2D gels and protein quantification. In addition, activity-based probes are now being used to tag, enrich and isolate distinct sets of proteins based on enzymatic activity. One of the most active areas of development involves microarrays. Antibody-based microarrays have recently been released as commercial products while numerous additional capture agents (e.g. aptamers) and many additional types of microarrays are being explored. [source] Toward Safe Genetically Modified Organisms through the Chemical Diversification of Nucleic AcidsCHEMISTRY & BIODIVERSITY, Issue 6 2009Piet Herdewijn Abstract It is argued that genetic proliferation should be rationally extended so as to enable the propagation in vivo of additional types of nucleic acids (XNA for ,xeno-nucleic acids'), whose chemical backbone motifs would differ from deoxyribose and ribose, and whose polymerization would not interfere with DNA and RNA biosynthesis. Because XNA building blocks do not occur in nature, they would have to be synthesized and supplied to cells which would be equipped with an appropriate enzymatic machinery for polymerizing them. The invasion of plants and animals with XNA replicons can be envisioned in the long run, but it is in microorganisms, and more specifically in bacteria, that the feasibility of such chemical systems and the establishment of genetic enclaves separated from DNA and RNA is more likely to take place. The introduction of expanded coding through additional or alternative pairing will be facilitated by the propagation of replicons based on alternative backbone motifs and leaving groups, as enabled by XNA polymerases purposefully evolved to this end. [source] | ||||||||||||||||