156 research outputs found
On convexity of solutions of ordinary differential equations
We prove a result on the convex dependence of solutions of ordinary
differential equations on an ordered finite-dimensional real vector space with
respect to the initial data.Comment: 10 page
Exponential moments of affine processes
We investigate the maximal domain of the moment generating function of affine
processes in the sense of Duffie, Filipovi\'{c} and Schachermayer [Ann. Appl.
Probab. 13 (2003) 984-1053], and we show the validity of the affine transform
formula that connects exponential moments with the solution of a generalized
Riccati differential equation. Our result extends and unifies those preceding
it (e.g., Glasserman and Kim [Math. Finance 20 (2010) 1-33], Filipovi\'{c} and
Mayerhofer [Radon Ser. Comput. Appl. Math. 8 (2009) 1-40] and Kallsen and
Muhle-Karbe [Stochastic Process Appl. 120 (2010) 163-181]) in that it allows
processes with very general jump behavior, applies to any convex state space
and provides both sufficient and necessary conditions for finiteness of
exponential moments.Comment: Published in at http://dx.doi.org/10.1214/14-AAP1009 the Annals of
Applied Probability (http://www.imstat.org/aap/) by the Institute of
Mathematical Statistics (http://www.imstat.org
Affine processes on symmetric cones
We consider affine Markov processes taking values in convex cones. In
particular, we characterize all affine processes taking values in an
irreducible symmetric cone in terms of certain L\'evy-Khintchine triplets. This
is the complete classification of affine processes on these conic state spaces,
thus extending the theory of Wishart processes on positive semidefinite
matrices, as put forward by Bru (1991)
A local and global tour on MOMoT
Many model transformation scenarios require flexible execution strategies as they should produce models with the highest
possible quality. At the same time, transformation problems often span a very large search space with respect to possible
transformation results. Recently, different proposals for finding good transformation results without enumerating the
complete search space have been proposed by using meta-heuristic search algorithms. However, determining the impact of
the different kinds of search algorithms, such as local search or global search, on the transformation results is still an open
research topic. In this paper, we present an extension to MOMoT, which is a search-based model transformation tool, for
supporting not only global searchers for model transformation orchestrations, but also local ones. This leads to a model
transformation framework that allows as the first of its kind multi-objective local and global search. By this, the advantages
and disadvantages of global and local search for model transformation orchestration can be evaluated. This is done in a
case-study-based evaluation, which compares different performance aspects of the local- and global-search algorithms
available in MOMoT. Several interesting conclusions have been drawn from the evaluation: (1) local-search algorithms
perform reasonable well with respect to both the search exploration and the execution time for small input models, (2) for
bigger input models, their execution time can be similar to those of global-search algorithms, but global-search algorithms
tend to outperform local-search algorithms in terms of search exploration, (3) evolutionary algorithms show limitations in
situations where single changes of the solution can have a significant impact on the solutionās fitness.Ministerio de Economia y Competitividad TIN2015-70560-RJunta de AndalucĆa P12-TIC-186
Cyclooxygenase-2 and prostaglandin F2Ī± in syrian hamster leydig cells : Inhibitory role on luteinizing hormone/human chorionic gonadotropin-stimulated testosterone production
We have previously found that cyclooxygenase-2 (COX-2), a key enzyme in the biosynthesis of prostaglandins (PGs), is present in the testicular interstitial cells of infertile men, whereas it is absent in human testes with no evident morphological changes or abnormalities. To find an animal model for further investigating COX-2 and its role in testicular steroidogenesis, we screened testes from adult species ranging from mice to monkeys. By using immunohistochemical assays, we found COX-2 expression only in Leydig cells of the reproductively active (peripubertal, pubertal, and adult) seasonal breeder Syrian hamster. COX-2 expression in hamster Leydig cells was confirmed by RT-PCR. In contrast, COX-1 expression was not detected in hamster testes. Because COX-2 expression implies PG synthesis, we investigated the effect of various PGs on testosterone production and found that PGF2Ī± stood out because it significantly reduced human chorionic gonadotropin-stimulated testosterone release from isolated hamster Leydig cells in a dose-dependent manner. This mechanism involves a decreased expression of testicular steroidogenic acute regulatory protein and 17Ī²-hydroxysteroid dehydrogenase. Testicular concentration and content of PGF2Ī± in reproductively active hamsters as well as production of PGF2Ī± from isolated hamster Leydig cells were also determined. Moreover, PGF2Ī± receptors were localized in Leydig cells of hamsters and testicular biopsies from patients with Sertoli cell only and germ arrest syndromes. Thus, in this study, we described a COX-2-initiated pathway that via PGF2Ī± production, PGF2Ī± receptors, steroidogenic acute regulatory protein, and 17Ī²-hydroxysteroid dehydrogenase represents a physiological local inhibitory system of human chorionic gonadotropin-stimulated testosterone production in the Syrian hamster testes.Instituto Multidisciplinario de BiologĆa Celula
Cyclooxygenase-2 and prostaglandin F2Ī± in syrian hamster leydig cells : Inhibitory role on luteinizing hormone/human chorionic gonadotropin-stimulated testosterone production
We have previously found that cyclooxygenase-2 (COX-2), a key enzyme in the biosynthesis of prostaglandins (PGs), is present in the testicular interstitial cells of infertile men, whereas it is absent in human testes with no evident morphological changes or abnormalities. To find an animal model for further investigating COX-2 and its role in testicular steroidogenesis, we screened testes from adult species ranging from mice to monkeys. By using immunohistochemical assays, we found COX-2 expression only in Leydig cells of the reproductively active (peripubertal, pubertal, and adult) seasonal breeder Syrian hamster. COX-2 expression in hamster Leydig cells was confirmed by RT-PCR. In contrast, COX-1 expression was not detected in hamster testes. Because COX-2 expression implies PG synthesis, we investigated the effect of various PGs on testosterone production and found that PGF2Ī± stood out because it significantly reduced human chorionic gonadotropin-stimulated testosterone release from isolated hamster Leydig cells in a dose-dependent manner. This mechanism involves a decreased expression of testicular steroidogenic acute regulatory protein and 17Ī²-hydroxysteroid dehydrogenase. Testicular concentration and content of PGF2Ī± in reproductively active hamsters as well as production of PGF2Ī± from isolated hamster Leydig cells were also determined. Moreover, PGF2Ī± receptors were localized in Leydig cells of hamsters and testicular biopsies from patients with Sertoli cell only and germ arrest syndromes. Thus, in this study, we described a COX-2-initiated pathway that via PGF2Ī± production, PGF2Ī± receptors, steroidogenic acute regulatory protein, and 17Ī²-hydroxysteroid dehydrogenase represents a physiological local inhibitory system of human chorionic gonadotropin-stimulated testosterone production in the Syrian hamster testes.Instituto Multidisciplinario de BiologĆa Celula
Transcriptome analysis of human cancer reveals a functional role of Heme Oxygenase-1 in tumor cell adhesion
<p>Abstract</p> <p>Background</p> <p>Heme Oxygenase-1 (HO-1) is expressed in many cancers and promotes growth and survival of neoplastic cells. Recently, HO-1 has been implicated in tumor cell invasion and metastasis. However, the molecular mechanisms underlying these biologic effects of HO-1 remain largely unknown. To identify a common mechanism of action of HO-1 in cancer, we determined the global effect of HO-1 on the transcriptome of multiple tumor entities and identified a universal HO-1-associated gene expression signature.</p> <p>Results</p> <p>Genome-wide expression profiling of Heme Oxygenase-1 expressing versus HO-1 silenced BeWo choriocarcinoma cells as well as a comparative meta-profiling of the preexisting expression database of 190 human tumors of 14 independent cancer types led to the identification of 14 genes, the expression of which correlated strongly and universally with that of HO-1 (P = 0.00002). These genes included regulators of cell plasticity and extracellular matrix (ECM) remodeling (MMP2, ADAM8, TGFB1, BGN, COL21A1, PXDN), signaling (CRIP2, MICB), amino acid transport and glycosylation (SLC7A1 and ST3GAL2), estrogen and phospholipid biosynthesis (AGPAT2 and HSD17B1), protein stabilization (IFI30), and phosphorylation (ALPPL2). We selected PXDN, an adhesion molecule involved in ECM formation, for further analysis and functional characterization. Immunofluorescence and Western blotting confirmed the positive correlation of expression of PXDN and HO-1 in BeWo cancer cells as well as co-localization of these two proteins in invasive extravillous trophoblast cells. Modulation of HO-1 expression in both loss-of and gain-of function cell models (BeWo and 607B melanoma cells, respectively) demonstrated a direct relationship of HO-1 expression with cell adhesion to Fibronectin and Laminin coated wells. The adhesion-promoting effects of HO-1 were dependent on PXDN expression, as loss of PXDN in HO-1 expressing BeWo and 607B cells led to reduced cell attachment to Laminin and Fibronectin coated wells.</p> <p>Conclusions</p> <p>Collectively, our results show that HO-1 expression determines a distinct 'molecular signature' in cancer cells, which is enriched in genes associated with tumorigenesis. The protein network downstream of HO-1 modulates adhesion, signaling, transport, and other critical cellular functions of neoplastic cells and thus promotes tumor cell growth and dissemination.</p
Dipeptidylpeptidase IV (CD26) defines leukemic stem cells (LSC) in chronic myeloid leukemia
Chronic myeloid leukemia (CML) is a stem cell (SC) neoplasm characterized by the BCR/ABL1 oncogene. Although mechanisms of BCR/ABL1-induced transformation are well-defined, little is known about effector-molecules contributing to malignant expansion and the extramedullary spread of leukemic SC (LSC) in CML. We have identified the cytokine-targeting surface enzyme dipeptidylpeptidase-IV (DPPIV/CD26) as a novel, specific and pathogenetically relevant biomarker of CD34+/CD38ā CML LSC. In functional assays, CD26 was identified as target enzyme disrupting the SDF-1-CXCR4-axis by cleaving SDF-1, a chemotaxin recruiting CXCR4+ SC. CD26 was not detected on normal SC or LSC in other hematopoietic malignancies. Correspondingly, CD26+ LSC decreased to low or undetectable levels during successful treatment with imatinib. CD26+ CML LSC engrafted NOD-SCID-IL-2RĪ³ā/ā (NSG) mice with BCR/ABL1+ cells, whereas CD26ā SC from the same patients produced multilineage BCR/ABL1ā engraftment. Finally, targeting of CD26 by gliptins suppressed the expansion of BCR/ABL1+ cells. Together, CD26 is a new biomarker and target of CML LSC. CD26 expression may explain the abnormal extramedullary spread of CML LSC, and inhibition of CD26 may revert abnormal LSC function and support curative treatment approaches in this malignancy
Recently photoassimilated carbon and fungus-delivered nitrogen are spatially correlated in the ectomycorrhizal tissue of Fagus sylvatica
Ectomycorrhizal plants trade plantāassimilated carbon for soil nutrients with their fungal partners. The underlying mechanisms, however, are not fully understood. Here we investigate the exchange of carbon for nitrogen in the ectomycorrhizal symbiosis of Fagus sylvatica across different spatial scales from the root system to the cellular level. We provided (15)Nālabelled nitrogen to mycorrhizal hyphae associated with one half of the root system of young beech trees, while exposing plants to a (13)CO(2) atmosphere. We analysed the shortāterm distribution of (13)C and (15)N in the root system with isotopeāratio mass spectrometry, and at the cellular scale within a mycorrhizal root tip with nanoscale secondary ion mass spectrometry (NanoSIMS). At the root system scale, plants did not allocate more (13)C to root parts that received more (15)N. Nanoscale secondary ion mass spectrometry imaging, however, revealed a highly heterogenous, and spatially significantly correlated distribution of (13)C and (15)N at the cellular scale. Our results indicate that, on a coarse scale, plants do not allocate a larger proportion of photoassimilated C to root parts associated with Nādelivering ectomycorrhizal fungi. Within the ectomycorrhizal tissue, however, recently plantāassimilated C and fungusādelivered N were spatially strongly coupled. Here, NanoSIMS visualisation provides an initial insight into the regulation of ectomycorrhizal C and N exchange at the microscale
Cyclooxygenase-2 and prostaglandin F2Ī± in syrian hamster leydig cells : Inhibitory role on luteinizing hormone/human chorionic gonadotropin-stimulated testosterone production
We have previously found that cyclooxygenase-2 (COX-2), a key enzyme in the biosynthesis of prostaglandins (PGs), is present in the testicular interstitial cells of infertile men, whereas it is absent in human testes with no evident morphological changes or abnormalities. To find an animal model for further investigating COX-2 and its role in testicular steroidogenesis, we screened testes from adult species ranging from mice to monkeys. By using immunohistochemical assays, we found COX-2 expression only in Leydig cells of the reproductively active (peripubertal, pubertal, and adult) seasonal breeder Syrian hamster. COX-2 expression in hamster Leydig cells was confirmed by RT-PCR. In contrast, COX-1 expression was not detected in hamster testes. Because COX-2 expression implies PG synthesis, we investigated the effect of various PGs on testosterone production and found that PGF2Ī± stood out because it significantly reduced human chorionic gonadotropin-stimulated testosterone release from isolated hamster Leydig cells in a dose-dependent manner. This mechanism involves a decreased expression of testicular steroidogenic acute regulatory protein and 17Ī²-hydroxysteroid dehydrogenase. Testicular concentration and content of PGF2Ī± in reproductively active hamsters as well as production of PGF2Ī± from isolated hamster Leydig cells were also determined. Moreover, PGF2Ī± receptors were localized in Leydig cells of hamsters and testicular biopsies from patients with Sertoli cell only and germ arrest syndromes. Thus, in this study, we described a COX-2-initiated pathway that via PGF2Ī± production, PGF2Ī± receptors, steroidogenic acute regulatory protein, and 17Ī²-hydroxysteroid dehydrogenase represents a physiological local inhibitory system of human chorionic gonadotropin-stimulated testosterone production in the Syrian hamster testes.Instituto Multidisciplinario de BiologĆa Celula
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