bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms Involved in the Amplification of the 11-yr Solar Cycle Signal in the Tropical Pacific Ocean
Authors: Misios Stergios , Schmidt Hauke 
Published: March 2012

Abstract
It is debated whether the response of the tropical Pacific Ocean to the 11-yr solar cycle forcing resembles a La Niña– or El Niño–like signal. To address this issue, ensemble simulations employing an atmospheric general circulation model with and without ocean coupling are conducted. The coupled simulations show no evidence for a La Niña–like cooling in solar maxima. Instead, the tropical sea surface temperature rises almost in phase with the 11-yr solar cycle. A basinwide warming of about 0.1 K is simulated in the tropical Pacific, whereas the warming in the tropical Indian and Atlantic Oceans is weaker. In the western Pacific, the region of deep convection shifts to the east, thus reducing the surface easterlies. This shift is independent of the ocean coupling because deep convection moves to the east in the uncoupled simulations too. The reduced surface easterlies cool the subsurface but warm the surface due to the reduction of heat transport divergence. The latter mechanism operates together with water vapor feedback, resulting in a stronger tropical Pacific warming relative to the warming over the tropical Indian and Atlantic Oceans. These results suggest that the atmospheric response to the 11-yr solar cycle drives the tropical Pacific response, which is amplified by atmosphere–ocean feedbacks operating on decadal time scales. Based on the coupled simulations, it is concluded that the tropical Pacific Ocean should warm when the sun is more active.
Large-Scale Atmospheric Circulation Favoring Deep- and Intermediate-Water Formation in the Mediterranean Sea
Authors: Papadopoulos Vassilis P. , Josey Simon A. , Bartzokas Aristides , Somot Samuel , Ruiz Simon , Drakopoulou Paraskevi 
Published: March 2012

Abstract
Atmospheric circulation patterns that are conducive to extreme ocean heat loss are investigated at four sites of special interest in the Mediterranean Sea. The Gulf of Lions, the South Adriatic Sea, the Cretan Sea, and the Levantine Sea are areas where anomalously high winter heat loss may lead to deep- or intermediate-water formation. At each of the above sites, the atmospheric circulation during such events is derived by averaging the sea level pressure (SLP) fields during the lower decile of the wintertime series of the net heat exchange. A relatively simple SLP pattern dominated by an anticyclone over northwestern Europe with a weaker cyclone to the southeast is found to be associated with strong heat loss in the selected sites with minor variations in pattern structure depending on the site. The SLP composite pattern reflects the combined effect of different atmospheric modes of variability and the authors consider the impacts on heat loss of a number of these modes (North Atlantic Oscillation, east Atlantic pattern, east Atlantic–west Russia pattern, and Scandinavian pattern), together with the North Sea–Caspian pattern and the Mediterranean index. The extremes in heat loss are strongly connected with the intensity and the positions of the poles of these patterns that modulate, through the necessary SLP gradient and associated northerlies, the transfer of cold and dry air over the areas of dense-water formation. Analysis of air–sea temperature difference, specific humidity, and evaporation anomalies indicates that the extremes of the net heat fluxes are primarily due to the latent and sensible heat flux components.
Observations of Ice Crystal Habits with a Scanning Polarimetric W-Band Radar at Slant Linear Depolarization Ratio Mode
Authors: Matrosov Sergey Y. , Mace Gerald G. , Marchand Roger , Shupe Matthew D. , Hallar Anna G. , McCubbin Ian B. 
Published: March 2012

Abstract
Scanning polarimetric W-band radar data were evaluated for the purpose of identifying predominant ice hydrometeor habits. Radar and accompanying cloud microphysical measurements were conducted during the Storm Peak Laboratory Cloud Property Validation Experiment held in Steamboat Springs, Colorado, during the winter season of 2010/11. The observed ice hydrometeor habits ranged from pristine and rimed dendrites/stellars to aggregates, irregulars, graupel, columns, plates, and particle mixtures. The slant 45° linear depolarization ratio (SLDR) trends as a function of the radar elevation angle are indicative of the predominant hydrometeor habit/shape. For planar particles, SLDR values increase from values close to the radar polarization cross coupling of about −21.8 dB at zenith viewing to maximum values at slant viewing. These maximum values depend on predominant aspect ratio and bulk density of hydrometeors and also show some sensitivity to particle characteristic size. The highest observed SLDRs were around −8 dB for pristine dendrites. Unlike planar-type hydrometeors, columnar-type particles did not exhibit pronounced depolarization trends as a function of viewing direction. A difference in measured SLDR values between zenith and slant viewing can be used to infer predominant aspect ratios of planar hydrometeors if an assumption about their bulk density is made. For columnar hydrometeors, SLDR offsets from the cross-coupling value are indicative of aspect ratios. Experimental data were analyzed for a number of events with prevalence of planar-type hydrometeors and also for observations when columnar particles were the dominant species. A relatively simple spheroidal model and accompanying T-matrix calculations were able to approximate most radar depolarization changes with viewing angle observed for different hydrometeor types.
Development of an algorithm for quality inspection of welded structures
Authors: Stenberg Thomas , Lindgren Eric , Barsoum Zuheir 
Published: March 2012

A selection of reliable measurement systems that are able to measure the toe radius along the weld bead in a T-joint has been studied. The results show that the currently used methods and gauges do not provide the required accuracy when measuring the toe radius. The gauges are handled differently by different operators – even when using a vision system – which makes the current evaluation methods subjective and unreliable.  Therefore, an algorithm has been developed that assesses weld bead surface data and automatically identifies and calculates the toe radius and the toe angle along the weld. The results obtained by the algorithm are consistent with reference measurements and it is possible for the algorithm to be used in improving the process and quality control during welding.
DOCK8 is a Cdc42 activator critical for interstitial dendritic cell migration during immune responses
Authors: Harada Yosuke , Tanaka Yoshihiko , Terasawa Masao , Pieczyk Markus , Habiro Katsuyoshi , Katakai Tomoya , Hanawa-Suetsugu Kyoko , Kukimoto-Niino Mutsuko , Nishizaki Tomoko , Shirouzu Mikako , Duan Xuefeng , Uruno Takehito , Nishikimi Akihiko , Sanematsu Fumiyuki , Yokoyama Shigeyuki , Stein Jens V. , Kinashi Tatsuo , Fukui Yoshinori 
Published: March 2012

Abstract
To migrate efficiently through the interstitium, dendritic cells (DCs) constantly adapt their shape to the given structure of the extracellular matrix and follow the path of least resistance. It is known that this amoeboid migration of DCs requires Cdc42, yet the upstream regulators critical for localization and activation of Cdc42 remain to be determined. Mutations of DOCK8, a member of the atypical guanine nucleotide exchange factor family, causes combined immunodeficiency in humans. In the present study, we show that DOCK8 is a Cdc42-specific guanine nucleotide exchange factor that is critical for interstitial DC migration. By generating the knockout mice, we found that in the absence of DOCK8, DCs failed to accumulate in the lymph node parenchyma for T-cell priming. Although DOCK8-deficient DCs migrated normally on 2-dimensional surfaces, DOCK8 was required for DCs to crawl within 3-dimensional fibrillar networks and to transmigrate through the subcapsular sinus floor. This function of DOCK8 depended on the DHR-2 domain mediating Cdc42 activation. DOCK8 deficiency did not affect global Cdc42 activity. However, Cdc42 activation at the leading edge membrane was impaired in DOCK8-deficient DCs, resulting in a severe defect in amoeboid polarization and migration. Therefore, DOCK8 regulates interstitial DC migration by controlling Cdc42 activity spatially.
Pan-genomic analysis of bovine monocyte-derived macrophage gene expression in response to in vitro infection with Mycobacterium avium subspecies paratuberculosis
Authors: MacHugh David E , Taraktsoglou Maria , Killick Kate E , Nalpas Nicolas C , Browne John A , DE Park Stephen , Hokamp Karsten , Gormley Eamonn , Magee David A 
Published: March 2012

AbstractMycobacterium aviumsubspeciesparatuberculosisis the causative agent of Johne’s disease, an intestinal disease of ruminants with major economic consequences. Infectious bacilli are phagocytosed by host macrophages upon exposure where they persist, resulting in lengthy subclinical phases of infection that can lead to immunopathology and disease dissemination. Consequently, analysis of the macrophage transcriptome in response toM. aviumsubsp.paratuberculosisinfection can provide valuable insights into the molecular mechanisms that underlie Johne’s disease. Here, we investigate pan-genomic gene expression in bovine monocyte-derived macrophages (MDM) purified from seven age-matched females, in response to in vitro infection withM. aviumsubsp.paratuberculosis(multiplicity of infection 2:1) at intervals of 2 hours, 6 hours and 24 hours post-infection (hpi). Differentially expressed genes were identified by comparing the transcriptomes of the infected MDM to the non-infected control MDM at each time point (adjustedP-value threshold ≤ 0.10). 1050 differentially expressed unique genes were identified 2 hpi, with 974 and 78 differentially expressed unique genes detected 6 and 24 hpi, respectively. Furthermore, in the infected MDM the number of upregulated genes exceeded the number of downregulated genes at each time point, with the fold-change in expression for the upregulated genes markedly higher than that for the downregulated genes. Inspection and systems biology analysis of the differentially expressed genes revealed an enrichment of genes involved in the inflammatory response, cell signalling pathways and apoptosis. The transcriptional changes associated with cellular signalling and the inflammatory response may reflect different immuno-modulatory mechanisms that underlie host-pathogen interactions during infection.
Characterization of an inducible promoter in different DNA copy number conditions
Authors: Zucca Susanna , Pasotti Lorenzo , Mazzini Giuliano , Cusella De Angelis Maria Gabriella , Magni Paolo 
Published: March 2012

Abstract

Background
The bottom-up programming of living organisms to implement novel user-defined biological capabilities is one of the main goals of synthetic biology. Currently, a predominant problem connected with the construction of even simple synthetic biological systems is the unpredictability of the genetic circuitry when assembled and incorporated in living cells. Copy number, transcriptional/translational demand and toxicity of the DNA-encoded functions are some of the major factors which may lead to cell overburdening and thus to nonlinear effects on system output. It is important to disclose the linearity working boundaries of engineered biological systems when dealing with such phenomena.

Results
The output of an N-3-oxohexanoyl-L-homoserine lactone (HSL)-inducible RFP-expressing device was studied in Escherichia coli in different copy number contexts, ranging from 1 copy per cell (integrated in the genome) to hundreds (via multicopy plasmids). The system is composed by a luxR constitutive expression cassette and a RFP gene regulated by the luxI promoter, which is activated by the HSL-LuxR complex. System output, in terms of promoter activity as a function of HSL concentration, was assessed relative to the one of a reference promoter in identical conditions by using the Relative Promoter Units (RPU) approach. Nonlinear effects were observed in the maximum activity, which is identical in single and low copy conditions, while it decreases for higher copy number conditions. In order to properly compare the luxI promoter strength among all the conditions, a mathematical modeling approach was used to relate the promoter activity to the estimated HSL-LuxR complex concentration, which is the actual activator of transcription. During model fitting, a correlation between the copy number and the dissociation constant of HSL-LuxR complex and luxI promoter was observed.

Conclusions
Even in a simple inducible system, nonlinear effects are observed and non-trivial data processing is necessary to fully characterize its operation. The in-depth analysis of model systems like this can contribute to the advances in the synthetic biology field, since increasing the knowledge about linearity and working boundaries of biological phenomena could lead to a more rational design of artificial systems, also through mathematical models, which, for example, have been used here to study hard-to-predict interactions.
Towards linked open gene mutations data
Authors: Zappa Achille , Splendiani Andrea , Romano Paolo 
Published: March 2012

AbstractBackgroundWith the advent of high-throughput technologies, a great wealth of variation data is being produced. Such information may constitute the basis for correlation analyses between genotypes and phenotypes and, in the future, for personalized medicine. Several databases on gene variation exist, but this kind of information is still scarce in the Semantic Web framework.In this paper, we discuss issues related to the integration of mutation data in the Linked Open Data infrastructure, part of the Semantic Web framework. We present the development of a mapping from the IARC TP53 Mutation database to RDF and the implementation of servers publishing this data.MethodsA version of the IARC TP53 Mutation database implemented in a relational database was used as first test set. Automatic mappings to RDF were first created by using D2RQ and later manually refined by introducing concepts and properties from domain vocabularies and ontologies, as well as links to Linked Open Data implementations of various systems of biomedical interest.Since D2RQ query performances are lower than those that can be achieved by using an RDF archive, generated data was also loaded into a dedicated system based on tools from the Jena software suite.ResultsWe have implemented a D2RQ Server for TP53 mutation data, providing data on a subset of the IARC database, including gene variations, somatic mutations, and bibliographic references. The server allows to browse the RDF graph by using links both between classes and to external systems. An alternative interface offers improved performances for SPARQL queries. The resulting data can be explored by using any Semantic Web browser or application.ConclusionsThis has been the first case of a mutation database exposed as Linked Data. A revised version of our prototype, including further concepts and IARC TP53 Mutation database data sets, is under development.The publication of variation information as Linked Data opens new perspectives: the exploitation of SPARQL searches on mutation data and other biological databases may support data retrieval which is presently not possible. Moreover, reasoning on integrated variation data may support discoveries towards personalized medicine.
Fine-tuning anti-tumor immunotherapies via stochastic simulations
Authors: Caravagna Giulio , Barbuti Roberto , d'Onofrio Alberto 
Published: March 2012

AbstractBackgroundAnti-tumor therapies aim at reducing to zero the number of tumor cells in a host within their end or, at least, aim at leaving the patient with a sufficiently small number of tumor cells so that the residual tumor can be eradicated by the immune system. Besides severe side-effects, a key problem of such therapies is finding a suitable scheduling of their administration to the patients. In this paper we study the effect of varying therapy-related parameters on the final outcome of the interplay between a tumor and the immune system.ResultsThis work generalizes our previous study on hybrid models of such an interplay where interleukins are modeled as a continuous variable, and the tumor and the immune system as a discrete-state continuous-time stochastic process. The hybrid model we use is obtained by modifying the corresponding deterministic model, originally proposed by Kirschner and Panetta. We consider Adoptive Cellular Immunotherapies and Interleukin-based therapies, as well as their combination. By asymptotic and transitory analyses of the corresponding deterministic model we find conditions guaranteeing tumor eradication, and we tune the parameters of the hybrid model accordingly. We then perform stochastic simulations of the hybrid model under various therapeutic settings: constant, piece-wise constant or impulsive infusion and daily or weekly delivery schedules.ConclusionsResults suggest that, in some cases, the delivery schedule may deeply impact on the therapy-induced tumor eradication time. Indeed, our model suggests that Interleukin-based therapies may not be effective for every patient, and that the piece-wise constant is the most effective delivery to stimulate the immune-response. For Adoptive Cellular Immunotherapies a metronomic delivery seems more effective, as it happens for other anti-angiogenesis therapies and chemotherapies, and the impulsive delivery seems more effective than the piece-wise constant. The expected synergistic effects have been observed when the therapies are combined.
Identification of bovine leukemia virus tax function associated with host cell transcription, signaling, stress response and immune response pathway by microarray-based gene expression analysis
Authors: Arainga Mariluz , Takeda Eri , Aida Yoko 
Published: March 2012

Abstract

Background
Bovine leukemia virus (BLV) is associated with enzootic bovine leukosis and is closely related to human T-cell leukemia virus type I. The Tax protein of BLV is a transcriptional activator of viral replication and a key contributor to oncogenic potential. We previously identified interesting mutant forms of Tax with elevated (TaxD247G) or reduced (TaxS240P) transactivation effects on BLV replication and propagation. However, the effects of these mutations on functions other than transcriptional activation are unknown. In this study, to identify genes that play a role in the cascade of signal events regulated by wild-type and mutant Tax proteins, we used a large-scale host cell gene-profiling approach.

Results
Using a microarray containing approximately 18,400 human mRNA transcripts, we found several alterations after the expression of Tax proteins in genes involved in many cellular functions such as transcription, signal transduction, cell growth, apoptosis, stress response, and immune response, indicating that Tax protein has multiple biological effects on various cellular environments. We also found that TaxD247G strongly regulated more genes involved in transcription, signal transduction, and cell growth functions, contrary to TaxS240P, which regulated fewer genes. In addition, the expression of genes related to stress response significantly increased in the presence of TaxS240P as compared to wild-type Tax and TaxD247G. By contrast, the largest group of downregulated genes was related to immune response, and the majority of these genes belonged to the interferon family. However, no significant difference in the expression level of downregulated genes was observed among the Tax proteins. Finally, the expression of important cellular factors obtained from the human microarray results were validated at the RNA and protein levels by real-time quantitative reverse transcription-polymerase chain reaction and western blotting, respectively, after transfecting Tax proteins into bovine cells and human HeLa cells.

Conclusion
A comparative analysis of wild-type and mutant Tax proteins indicates that Tax protein exerts a significant impact on cellular functions as diverse as transcription, signal transduction, cell growth, stress response and immune response. Importantly, our study is the first report that shows the extent to which BLV Tax regulates the innate immune response.
Characterization of a pneumococcal meningitis mouse model
Authors: Mook-Kanamori Barry , Geldhoff Madelijn , Troost Dirk , van der Poll Tom , van de Beek Diederik 
Published: March 2012

AbstractBackgroundS. pneumoniaeis the most common causative agent of meningitis, and is associated with high morbidity and mortality. We aimed to develop an integrated and representative pneumococcal meningitis mouse model resembling the human situation.MethodsAdult mice (C57BL/6) were inoculated in the cisterna magna with increasing doses ofS. pneumoniaeserotype 3 colony forming units (CFU; n = 24, 104, 105, 106and 107CFU) and survival studies were performed. Cerebrospinal fluid (CSF), brain, blood, spleen, and lungs were collected. Subsequently, mice were inoculated with 104CFUS. pneumoniaeserotype 3 and sacrificed at 6 (n = 6) and 30 hours (n = 6). Outcome parameters were bacterial outgrowth, clinical score, and cytokine and chemokine levels (using Luminex®) in CSF, blood and brain. Meningeal inflammation, neutrophil infiltration, parenchymal and subarachnoidal hemorrhages, microglial activation and hippocampal apoptosis were assessed in histopathological studies.ResultsLower doses of bacteria delayed onset of illness and time of death (median survival CFU 104, 56 hrs; 105, 38 hrs, 106, 28 hrs. 107, 24 hrs). Bacterial titers in brain and CSF were similar in all mice at the end-stage of disease independent of inoculation dose, though bacterial outgrowth in the systemic compartment was less at lower inoculation doses. At 30 hours after inoculation with 104CFU ofS. pneumoniae, blood levels of KC, IL6, MIP-2 and IFN- γ were elevated, as were brain homogenate levels of KC, MIP-2, IL-6, IL-1β and RANTES. Brain histology uniformly showed meningeal inflammation at 6 hours, and, neutrophil infiltration, microglial activation, and hippocampal apoptosis at 30 hours. Parenchymal and subarachnoidal and cortical hemorrhages were seen in 5 of 6 and 3 of 6 mice at 6 and 30 hours, respectively.ConclusionWe have developed and validated a murine model of pneumococcal meningitis.