Issue 9: From the Guest Editors

Welcome to Issue 9 of the Online Journal of Space Communication as we discuss the Global Navigation Satellite System, its past, present and the direction its taking us

Conclusions from CDF Results on CP Violation in D^0 \to \pi^+\pi^-, K^+K^- and Future Tasks

Within the Standard Model (SM) one predicts both direct and indirect CP violation in D^0 \to \pi^+\pi^-, K^+K^- transitions, although the effects are tiny: Indirect CP asymmetry cannot exceed O(10^{-4}), probably even O(10^{-5}); direct effects are estimated at not larger than 10^{-4}. At B factories direct and indirect asymmetries have been studied with /\tau_{D^0} ~ 1; no CP asymmetry was found with an upper bound of about 1%. CDF has shown intriguing data on CP violation in D^0 \to \pi^+\pi^- [K^+K^-] with /\tau_{D^0} ~ 2.4 [2.65]. Also, CDF has not seen any CP violation. For direct CP asymmetry, CDF has a sensitivity similar to the combination of the B factories, yet for indirect CP violation it yields a significantly smaller sensitivity of a_{cp}^{ind}=(-0.01 +- 0.06_{stat} +- 0.05_{syst})% due to it being based on longer decay times. New Physics models (NP) like Little Higgs Models with T-Parity (LHT) can produce an indirect CP asymmetry up to 1%; CDF's findings thus cover the upper range of realistic NP predictions ~ 0.1 - 1%. One hopes that LHCb and a Super-Flavour Factory will probe the lower range down to ~0.01%. Such non-ad-hoc NP like LHT cannot enhance direct CP violation significantly over the SM level in D^0 \to \pi^+\pi^-, K^+K^- and D^{\pm} \to \pi^{\pm}K^+K^- transitions, but others might well do so.Comment: 11 pages, 1 figure. V2 has minor corrections and corresponds to the published versio

On CP Asymmetries in Two-, Three- and Four-Body D Decays

Indirect and direct CP violations have been established in K_L and B_d decays. They have been found in two-body decay channels -- with the exception of K_L to pi^+ pi^- e^+ e^- transitions. Evidence for direct CP asymmetry has just appeared in LHCb data on A_{CP}(D^0 to K^+ K^-) - A_{CP}(D^0 to pi^+ pi^-) with 3.5 sigma significance. Manifestations of New Dynamics (ND) can appear in CP asymmetries just below experimental bounds. We discuss D^{\pm}_{(s)}, D^0/\bar D^0 and D_L/D_S transitions to 2-, 3- and 4-body final states with a comment on predictions for inclusive vs. exclusive CP asymmetries. In particular we discuss T asymmetries in D to h_1 h_2 l^+ l^- in analogy with K_L to pi^+ pi^- e^+ e^- transitions due to interference between M1, internal bremsstrahlung and possible E1 amplitudes. Such an effect depends on the strength of CP violation originating from the ND -- as discussed here for Little Higgs Models with T parity and non-minimal Higgs sectors -- but also in the interferences between these amplitudes even in the Standard Model (SM). More general lessons can be learnt for T asymmetries in non-leptonic D decays like D to h_1h_2 h_3 h_4. Such manifestations of ND can be tested at LHCb and other Super-Flavour Factories like the projects at KEK near Tokyo and at Tor Vergata/Frascati near Rome.Comment: 27 pages, 6 figures. Revised with current results from LHCb and HFAG and further interpretation

Dietary antioxidants protect gut epithelial cells from oxidant-induced apoptosis

BACKGROUND: The potential of ascorbic acid and two botanical decoctions, green tea and cat's claw, to limit cell death in response to oxidants were evaluated in vitro. METHODS: Cultured human gastric epithelial cells (AGS) or murine small intestinal epithelial cells (IEC-18) were exposed to oxidants – DPPH (3 μM), H(2)O(2) (50 μM), peroxynitrite (300 μM) – followed by incubation for 24 hours, with antioxidants (10 μg/ml) administered as a 1 hour pretreatment. Cell number (MTT assay) and death via apoptosis or necrosis (ELISA, LDH release) was determined. The direct interactions between antioxidants and DPPH (100 μM) or H(2)O(2) (50 μM) were evaluated by spectroscopy. RESULTS: The decoctions did not interact with H(2)O(2), but quenched DPPH although less effectively than vitamin C. In contrast, vitamin C was significantly less effective in protecting human gastric epithelial cells (AGS) from apoptosis induced by DPPH, peroxynitrite and H(2)O(2) (P < 0.001). Green tea and cat's claw were equally protective against peroxynitrite and H(2)O(2), but green tea was more effective than cat's claw in reducing DPPH-induced apoptosis (P < 0.01). Necrotic cell death was marginally evident at these low concentrations of peroxynitrite and H(2)O(2), and was attenuated both by cat's claw and green tea (P < 0.01). In IEC-18 cells, all antioxidants were equally effective as anti-apoptotic agents. CONCLUSIONS: These results indicate that dietary antioxidants can limit epithelial cell death in response to oxidant stress. In the case of green tea and cat's claw, the cytoprotective response exceed their inherent ability to interact with the injurious oxidant, suggestive of actions on intracellular pathways regulating cell death

The chrondoprotective actions of a natural product are associated with the activation of IGF-1 production by human chondrocytes despite the presence of IL-1β

BACKGROUND: Cartilage loss is a hallmark of arthritis and follows activation of catabolic processes concomitant with a disruption of anabolic pathways like insulin-like growth factor 1 (IGF-1). We hypothesized that two natural products of South American origin, would limit cartilage degradation by respectively suppressing catabolism and activating local IGF-1 anabolic pathways. One extract, derived from cat's claw (Uncaria guianensis, vincaria(®)), is a well-described inhibitor of NF-κB. The other extract, derived from the vegetable Lepidium meyenii (RNI 249), possessed an uncertain mechanism of action but with defined ethnomedical applications for fertility and vitality. METHODS: Human cartilage samples were procured from surgical specimens with consent, and were evaluated either as explants or as primary chondrocytes prepared after enzymatic digestion of cartilage matrix. Assessments included IGF-1 gene expression, IGF-1 production (ELISA), cartilage matrix degradation and nitric oxide (NO) production, under basal conditions and in the presence of IL-1β. RESULTS: RNI 249 enhanced basal IGF-1 mRNA levels in human chondrocytes by 2.7 fold, an effect that was further enhanced to 3.8 fold by co-administration with vincaria. Enhanced basal IGF-1 production by RNI 249 alone and together with vincaria, was confirmed in both explants and in primary chondrocytes (P <0.05). As expected, IL-1β exposure completely silenced IGF-1 production by chondrocytes. However, in the presence of IL-1β both RNI 249 and vincaria protected IGF-1 production in an additive manner (P <0.01) with the combination restoring chondrocyte IGF-1 production to normal levels. Cartilage NO production was dramatically enhanced by IL-1β. Both vincaria and RNI 249 partially attenuated NO production in an additive manner (p < 0.05). IL-1β – induced degradation of cartilage matrix was quantified as glycosaminoglycan release. Individually RNI 249 or vincaria, prevented this catabolic action of IL-1β. CONCLUSION: The identification of agents that activate the autocrine production of IGF-1 in cartilage, even in the face of suppressive pro-inflammatory, catabolic cytokines like IL-1β, represents a novel therapeutic approach to cartilage biology. Chondroprotection associated with prevention of the catabolic events and the potential for sustained anabolic activity with this natural product suggests that it holds significant promise in the treatment of debilitating joint diseases

Das Arbeitsrecht

xvi,377 hal,;22c

The chrondoprotective actions of a natural product are associated with the activation of IGF-1 production by human chondrocytes despite the presence of IL-1β

Abstract Background Cartilage loss is a hallmark of arthritis and follows activation of catabolic processes concomitant with a disruption of anabolic pathways like insulin-like growth factor 1 (IGF-1). We hypothesized that two natural products of South American origin, would limit cartilage degradation by respectively suppressing catabolism and activating local IGF-1 anabolic pathways. One extract, derived from cat's claw (Uncaria guianensis, vincaria®), is a well-described inhibitor of NF-κB. The other extract, derived from the vegetable Lepidium meyenii (RNI 249), possessed an uncertain mechanism of action but with defined ethnomedical applications for fertility and vitality. Methods Human cartilage samples were procured from surgical specimens with consent, and were evaluated either as explants or as primary chondrocytes prepared after enzymatic digestion of cartilage matrix. Assessments included IGF-1 gene expression, IGF-1 production (ELISA), cartilage matrix degradation and nitric oxide (NO) production, under basal conditions and in the presence of IL-1β. Results RNI 249 enhanced basal IGF-1 mRNA levels in human chondrocytes by 2.7 fold, an effect that was further enhanced to 3.8 fold by co-administration with vincaria. Enhanced basal IGF-1 production by RNI 249 alone and together with vincaria, was confirmed in both explants and in primary chondrocytes (P Conclusion The identification of agents that activate the autocrine production of IGF-1 in cartilage, even in the face of suppressive pro-inflammatory, catabolic cytokines like IL-1β, represents a novel therapeutic approach to cartilage biology. Chondroprotection associated with prevention of the catabolic events and the potential for sustained anabolic activity with this natural product suggests that it holds significant promise in the treatment of debilitating joint diseases.</p