336 research outputs found

    Torus invariant divisors

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    Using the language of polyhedral divisors and divisorial fans we describe invariant divisors on normal varieties X which admit an effective codimension one torus action. In this picture X is given by a divisorial fan on a smooth projective curve Y. Cartier divisors on X can be described by piecewise affine functions h on the divisorial fan S whereas Weil divisors correspond to certain zero and one dimensional faces of it. Furthermore we provide descriptions of the divisor class group and the canonical divisor. Global sections of line bundles O(D_h) will be determined by a subset of a weight polytope associated to h, and global sections of specific line bundles on the underlying curve Y.Comment: 16 pages; 5 pictures; small changes in the layout, further typos remove

    The pancreas responds to remote damage and systemic stress by secretion of the pancreatic secretory proteins PSP/regI and PAP/regIII.

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    In patients with infection and sepsis serum levels of Pancreatic Stone protein/regenerating protein I (PSP) are highly elevated. The origin of PSP during these conditions is presumably the pancreas, however, an intestinal origin cannot be excluded. Similarly, pancreatitis-associated protein (PAP) was identified in the pancreas. These proteins were also localized in intestinal organs. Here we aim to elucidate the bio-distribution of PSP and PAP in animal models of sepsis and in healthy humans. PSP and PAP responded to remote lesions in rats although the pancreatic response was much more pronounced than the intestinal. Tissue distribution of PSP demonstrated a 100-fold higher content in the pancreas compared to any other organ while PAP was most abundant in the small intestine. Both proteins responded to CLP or sham operation in the pancreas. PSP also increased in the intestine during CLP. The distribution of PSP and PAP in human tissue mirrored the distribution in the murine models. Distribution of PSP and PAP was visualized by immunohistochemistry. Rats and mice underwent midline laparotomies followed by mobilization of tissue and incision of the pancreatic duct or duodenum. Standard cecum-ligation-puncture (CLP) procedures or sham laparotomies were performed. Human tissue extracts were analyzed for PSP and PAP. The pancreas reacts to remote lesions and septic insults in mice and rats with increased PSP synthesis, while PAP is selectively responsive to septic events. Furthermore, our results suggest that serum PSP in septic patients is predominantly derived through an acute phase response of the pancreas

    Cavity-enhanced high harmonic generation for XUV time-resolved ARPES

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    With its direct correspondence to electronic structure, angle-resolved photoemission spectroscopy (ARPES) is a ubiquitous tool for the study of solids. When extended to the temporal domain, time-resolved (TR)-ARPES offers the potential to move beyond equilibrium properties, exploring both the unoccupied electronic structure as well as its dynamical response under ultrafast perturbation. Historically, ultrafast extreme ultraviolet (XUV) sources employing high-order harmonic generation (HHG) have required compromises that make it challenging to achieve a high energy resolution - which is highly desirable for many TR-ARPES studies - while producing high photon energies and a high photon flux. We address this challenge by performing HHG inside a femtosecond enhancement cavity (fsEC), realizing a practical source for TR-ARPES that achieves a flux of over 1011^{11} photons/s delivered to the sample, operates over a range of 8-40 eV with a repetition rate of 60 MHz. This source enables TR-ARPES studies with a temporal and energy resolution of 190 fs and 22 meV, respectively. To characterize the system, we perform ARPES measurements of polycrystalline Au and MoTe2_2, as well as TR-ARPES studies on graphite.Comment: 11 pages, 5 figure

    Identification and characterization of dairy cows with different backfat thickness antepartum in relation to postpartum loss of backfat thickness: a cluster analytic approach

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    The objectives of this study were (1) to characterize the interindividual variation in the relationship between antepartum (ap) backfat thickness (BFT) and subsequent BFT loss during early lactation in a large dairy herd using cluster analysis; (2) to compare the serum concentrations of metabolites (nonesterified fatty acids, β-hydroxybutyrate), metabolic hormones (leptin and adiponectin), and an inflammatory marker (haptoglobin) among the respective clusters; and (3) to compare lactation performance and uterine health status in the different clusters. An additional objective was (4) to investigate differences in these serum variables and in milk yield of overconditioned (OC) cows that differed in the extent of BFT loss. Using data from a large study of 1,709 multiparous Holstein cows, we first selected those animals from which serum samples and BFT results (mm) were available at d 25 (±10) ap and d 31 (±3 d) postpartum (pp). The remaining 713 cows (parity of 2 to 7) were then subjected to cluster analysis: different approaches based on the BFT of the cows were performed. K-means (unsupervised machine learning algorithm) clustering based on BFT-ap alone identified 5 clusters: lean (5–8 mm BFT, n = 50), normal (9–12 mm, n = 206), slightly fat (SF; 13–16 mm, n = 203), just fat (JF; 16–22 mm, n = 193), and very fat (VF; 23–43 mm, n = 61). Clustering by difference between BFT-ap and BFT-pp (ΔBFT) also revealed 5 clusters: extreme loss (17–23 mm ΔBFT, n = 16), moderate loss (9–15 mm, n = 119), little loss (4–8 mm, n = 326), no loss (0–3 mm, n = 203), and gain (−8 to −1 mm, n = 51). Based on the blood variables measured, our results confirm that cows with greater BFT losses had higher lipid mobilization and ketogenesis than cows with less BFT loss. The serum variables of cows that gained BFT did not differ from normal cows. Milk yield was affected by the BFT-ap cluster, but not by the ΔBFT cluster. Cows categorized as VF had lesser milk yield than other clusters. We further compared the OC cows that had little or no BFT loss (i.e., 2% of VF, 12% of JF, and 31% of SF, OC-no loss, n = 85) with the OC cows that lost BFT (OC-loss, n = 135). Both NEFA and BHB pp concentrations and milk yield were greater in OC-loss cows compared with the OC-no loss cows. The serum concentration of leptin ap was greater in OC-loss than in the OC-no loss cows. Overall, OC cows lost more BFT than normal or lean cows. However, those OC cows with a smaller loss of BFT produced less milk than OC cows with greater losses

    Somatostatin subtype-2 receptor-targeted metal-based anticancer complexes

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    Conjugates of a dicarba analogue of octreotide, a potent somatostatin agonist whose receptors are overexpressed on tumor cells, with [PtCl 2(dap)] (dap = 1-(carboxylic acid)-1,2-diaminoethane) (3), [(η 6-bip)Os(4-CO 2-pico)Cl] (bip = biphenyl, pico = picolinate) (4), [(η 6-p-cym)RuCl(dap)] + (p-cym = p-cymene) (5), and [(η 6-p-cym)RuCl(imidazole-CO 2H)(PPh 3)] + (6), were synthesized by using a solid-phase approach. Conjugates 3-5 readily underwent hydrolysis and DNA binding, whereas conjugate 6 was inert to ligand substitution. NMR spectroscopy and molecular dynamics calculations showed that conjugate formation does not perturb the overall peptide structure. Only 6 exhibited antiproliferative activity in human tumor cells (IC 50 = 63 ± 2 μ in MCF-7 cells and IC 50 = 26 ± 3 μ in DU-145 cells) with active participation of somatostatin receptors in cellular uptake. Similar cytotoxic activity was found in a normal cell line (IC 50 = 45 ± 2.6 μ in CHO cells), which can be attributed to a similar level of expression of somatostatin subtype-2 receptor. These studies provide new insights into the effect of receptor-binding peptide conjugation on the activity of metal-based anticancer drugs, and demonstrate the potential of such hybrid compounds to target tumor cells specifically. © 2012 American Chemical Society

    Differentiation of Mesenchymal Stem Cells Derived from Pancreatic Islets and Bone Marrow into Islet-Like Cell Phenotype

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    BACKGROUND:Regarding regenerative medicine for diabetes, accessible sources of Mesenchymal Stem Cells (MSCs) for induction of insular beta cell differentiation may be as important as mastering the differentiation process itself. METHODOLOGY/PRINCIPAL FINDINGS:In the present work, stem cells from pancreatic islets (human islet-mesenchymal stem cells, HI-MSCs) and from human bone marrow (bone marrow mesenchymal stem cells, BM-MSCs) were cultured in custom-made serum-free medium, using suitable conditions in order to induce differentiation into Islet-like Cells (ILCs). HI-MSCs and BM-MSCs were positive for the MSC markers CD105, CD73, CD90, CD29. Following this induction, HI-MSC and BM-MSC formed evident islet-like structures in the culture flasks. To investigate functional modifications after induction to ILCs, ultrastructural analysis and immunofluorescence were performed. PDX1 (pancreatic duodenal homeobox gene-1), insulin, C peptide and Glut-2 were detected in HI-ILCs whereas BM-ILCs only expressed Glut-2 and insulin. Insulin was also detected in the culture medium following glucose stimulation, confirming an initial differentiation that resulted in glucose-sensitive endocrine secretion. In order to identify proteins that were modified following differentiation from basal MSC (HI-MSCs and BM-MSCs) to their HI-ILCs and BM-ILCs counterparts, proteomic analysis was performed. Three new proteins (APOA1, ATL2 and SODM) were present in both ILC types, while other detected proteins were verified to be unique to the single individual differentiated cells lines. Hierarchical analysis underscored the limited similarities between HI-MSCs and BM-MSCs after induction of differentiation, and the persistence of relevant differences related to cells of different origin. CONCLUSIONS/SIGNIFICANCE:Proteomic analysis highlighted differences in the MSCs according to site of origin, reflecting spontaneous differentiation and commitment. A more detailed understanding of protein assets may provide insights required to master the differentiation process of HI-MSCs to functional beta cells based only upon culture conditioning. These findings may open new strategies for the clinical use of BM-MSCs in diabetes

    Persistence of Pathogens with Short Infectious Periods in Seasonal Tick Populations: The Relative Importance of Three Transmission Routes

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    BACKGROUND: The flaviviruses causing tick-borne encephalitis (TBE) persist at low but consistent levels in tick populations, despite short infectious periods in their mammalian hosts and transmission periods constrained by distinctly seasonal tick life cycles. In addition to systemic and vertical transmission, cofeeding transmission has been proposed as an important route for the persistence of TBE-causing viruses. Because cofeeding transmission requires ticks to feed simultaneously, the timing of tick activity may be critical to pathogen persistence. Existing models of tick-borne diseases do not incorporate all transmission routes and tick seasonality. Our aim is to evaluate the influence of seasonality on the relative importance of different transmission routes by using a comprehensive mathematical model. METHODOLOGY/PRINCIPAL FINDINGS: We developed a stage-structured population model that includes tick seasonality and evaluated the relative importance of the transmission routes for pathogens with short infectious periods, in particular Powassan virus (POWV) and the related "deer tick virus," emergent encephalitis-causing flaviviruses in North America. We used the next generation matrix method to calculate the basic reproductive ratio and performed elasticity analyses. We confirmed that cofeeding transmission is critically important for such pathogens to persist in seasonal tick populations over the reasonable range of parameter values. At higher but still plausible rates of vertical transmission, our model suggests that vertical transmission can strongly enhance pathogen prevalence when it operates in combination with cofeeding transmission. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that the consistent prevalence of POWV observed in tick populations could be maintained by a combination of low vertical, intermediate cofeeding and high systemic transmission rates. When vertical transmission is weak, nymphal ticks support integral parts of the transmission cycle that are critical for maintaining the pathogen. We also extended the model to pathogens that cause chronic infections in hosts and found that cofeeding transmission could contribute to elevating prevalence even in these systems. Therefore, the common assumption that cofeeding transmission is not relevant in models of chronic host infection, such as Lyme disease, could lead to underestimating pathogen prevalence
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