Eluding SUSY at every genus on stable closed string vacua

In closed string vacua, ergodicity of unipotent flows provide a key for relating vacuum stability to the UV behavior of spectra and interactions. Infrared finiteness at all genera in perturbation theory can be rephrased in terms of cancelations involving only tree-level closed strings scattering amplitudes. This provides quantitative results on the allowed deviations from supersymmetry on perturbative stable vacua. From a mathematical perspective, diagrammatic relations involving closed string amplitudes suggest a relevance of unipotent flows dynamics for the Schottky problem and for the construction of the superstring measure.Comment: v2, 17 pages, 8 figures, typos corrected, new figure added with 3 modular images of long horocycles,(obtained with Mathematica

Aspirin-induced nuclear translocation of NFκB and apoptosis in colorectal cancer is independent of p53 status and DNA mismatch repair proficiency

Substantial evidence indicates nonsteroidal anti-inflammatory drugs (NSAIDs) protect against colorectal cancer (CRC). However, the molecular basis for this anti-tumour activity has not been fully elucidated. We previously reported that aspirin induces signal-specific IκBα degradation followed by NFκB nuclear translocation in CRC cells, and that this mechanism contributes substantially to aspirin-induced apoptosis. We have also reported the relative specificity of this aspirin-induced NFκB-dependent apoptotic effect for CRC cells, in comparison to other cancer cell types. It is now important to establish whether there is heterogeneity within CRC, with respect to the effects of aspirin on the NFκB pathway and apoptosis. p53 signalling and DNA mismatch repair (MMR) are known to be deranged in CRC and have been reported as potential molecular targets for the anti-tumour activity of NSAIDs. Furthermore, both p53 and MMR dysfunction have been shown to confer resistance to chemotherapeutic agents. Here, we set out to determine the p53 and hMLH1 dependency of the effects of aspirin on NFκB signalling and apoptosis in CRC. We specifically compared the effects of aspirin treatment on cell viability, apoptosis and NFκB signalling in an HCT-116 CRC cell line with the p53 gene homozygously disrupted (HCT-116p53−/−) and an HCT-116 cell line rendered MMR proficient by chromosomal transfer (HCT-116+ch3), to the parental HCT-116 CRC cell line. We found that aspirin treatment induced apoptosis following IκBα degradation, NFκB nuclear translocation and repression of NFκB-driven transcription, irrespective of p53 and DNA MMR status. These findings are relevant for design of both novel chemopreventative agents and chemoprevention trials in CRC

Aspirin induces cell death and caspase-dependent phosphatidylserine externalization in HT-29 human colon adenocarcinoma cells

The induction of cell death by aspirin was analysed in HT-29 colon carcinoma cells. Aspirin induced two hallmarks of apoptosis: nuclear chromatin condensation and increase in phosphatidylserine externalization. However, aspirin did not induce either oligonucleosomal fragmentation of DNA, decrease in DNA content or nuclear fragmentation. The effect of aspirin on Annexin V binding was inhibited by the caspase inhibitor Z-VAD.fmk, indicating the involvement of caspases in the apoptotic action of aspirin. However, aspirin did not induce proteolysis of PARP, suggesting that aspirin does not increase nuclear caspase 3-like activity in HT-29 cells. This finding may be related with the ‘atypical’ features of aspirin-induced apoptosis in HT-29 cells. © 1999 Cancer Research Campaig

Chagas Cardiomiopathy: The Potential of Diastolic Dysfunction and Brain Natriuretic Peptide in the Early Identification of Cardiac Damage

Chagas disease remains a major cause of morbidity and mortality in several countries of Latin America and has become a potential public health problem in countries where the disease is not endemic as a result of migration flows. Cardiac involvement represents the main cause of mortality, but its diagnosis is still based on nonspecific criteria with poor sensitivity. Early identification of patients with cardiac damage is desirable, since early treatment may improve prognosis. Diastolic dysfunction and elevated brain natriuretic peptide levels are present in different cardiomyopathies and in advanced phases of Chagas disease. However, there are scarce data about the role of these parameters in earlier forms of the disease. We conducted a study to assess the diastolic function, regional systolic abnormalities and brain natriuretic peptide levels in the different forms of Chagas disease. The main finding of our investigation is that diastolic dysfunction occurs before any cardiac dilatation or motion abnormality. In addition, BNP levels identify patients with diastolic dysfunction and Chagas disease with high specificity. The results reported in this study could help to early diagnose myocardial involvement and better stratify patients with Chagas disease

Therapeutic utility of aspirin in the Apc(Min/+) murine model of colon carcinogenesis

BACKGROUND: In recent years it has become evident that nonsteroidal anti-inflammatory drugs, in particular aspirin represent a potential class of cancer chemotherapeutic agents. Despite the wealth of knowledge gained from epidemiological, clinical and animal studies, the effectiveness of aspirin to treat established gastrointestinal cancer has not been determined. The present study examines the ability of aspirin to treat established polyposis in Min/+ mice. METHODS: Min/+ mice with established polyposis were treated orally once daily from 12–16 weeks of age with either drug vehicle or aspirin (25 mg/kg). Upon completion of treatment, the number, location and size of intestinal tumours was determined. Additional variables examined were the number of apoptotic cells within tumours and COX activity. RESULTS: Administration of aspirin for 4 weeks to Min/+ mice produce no effect on tumour number compared to vehicle-treated Min/+ mice (65 ± 8 vs. 63 ± 9, respectively). In addition, aspirin had no effect on tumour size or location. However, aspirin treatment produced a greater than 2-fold (p < 0.05) increase in the number of apoptotic positive cells within tumours and significantly decreased hepatic PGE(2) content. CONCLUSIONS: Aspirin was found to have no effect on tumour number and size when administered to Min/+ mice with established polyposis. The findings in the present study call in to question the utility of aspirin as a stand-alone treatment for established GI cancer. However, aspirin's ability to significantly promote apoptosis may render it suitable for use in combinatorial chemotherapy

Determination of an optimal dosing regimen for aspirin chemoprevention of 1,2-dimethylhydrazine-induced colon tumours in rats

In order to establish an optimal timing and duration of aspirin treatment in the chemoprevention of 1,2-dimethylhydrazine (DMH)-induced colon cancer in rats, colon tumours were induced using an established protocol and aspirin was given in the diet at 500 p.p.m. during various stages of colon carcinogenesis. Results indicate that only aspirin treatment throughout the entire carcinogenic period significantly reduced tumour incidence and volume whereas intermittent aspirin dosing increased tumour number and/or volume, suggesting that aspirin must be used for an extended period in order to gain any chemopreventive benefit. © 1999 Cancer Research Campaig

Vesicular Egress of Non-Enveloped Lytic Parvoviruses Depends on Gelsolin Functioning

The autonomous parvovirus Minute Virus of Mice (MVM) induces specific changes in the cytoskeleton filaments of infected permissive cells, causing in particular the degradation of actin fibers and the generation of “actin patches.” This is attributed to a virus-induced imbalance between the polymerization factor N-WASP (Wiscott-Aldrich syndrome protein) and gelsolin, a multifunctional protein cleaving actin filaments. Here, the focus is on the involvement of gelsolin in parvovirus propagation and virus-induced actin processing. Gelsolin activity was knocked-down, and consequences thereof were determined for virus replication and egress and for actin network integrity. Though not required for virus replication or progeny particle assembly, gelsolin was found to control MVM (and related H1-PV) transport from the nucleus to the cell periphery and release into the culture medium. Gelsolin-dependent actin degradation and progeny virus release were both controlled by (NS1)/CKIIα, a recently identified complex between a cellular protein kinase and a MVM non-structural protein. Furthermore, the export of newly synthesized virions through the cytoplasm appeared to be mediated by (virus-modified) lysomal/late endosomal vesicles. By showing that MVM release, like entry, is guided by the cytoskeleton and mediated by vesicles, these results challenge the current view that egress of non-enveloped lytic viruses is a passive process