4,711 research outputs found
On the Alexandrov Topology of sub-Lorentzian Manifolds
It is commonly known that in Riemannian and sub-Riemannian Geometry, the
metric tensor on a manifold defines a distance function. In Lorentzian
Geometry, instead of a distance function it provides causal relations and the
Lorentzian time-separation function. Both lead to the definition of the
Alexandrov topology, which is linked to the property of strong causality of a
space-time. We studied three possible ways to define the Alexandrov topology on
sub-Lorentzian manifolds, which usually give different topologies, but agree in
the Lorentzian case. We investigated their relationships to each other and the
manifold's original topology and their link to causality.Comment: 20 page
Virus-Induced Cancers of the Skin and Mucosa:Are We Dealing with "Smoking Guns" or "Smoke and Mirrors" in the Operating Theatre?
Introduction: Human papillomavirus (HPV) alone is thought to cause ~610,000 cases of cancer per year, and is the dominant aetiological agent for ano-genital (esp. cervical) and head and neck cancers (esp. oropharyngeal). Merkel cell polyomavirus (MCV) is a more recently discovered virus which causes Merkel cell carcinoma, a rare but highly aggressive skin malignancy. Methods: We explored the available published evidence to see if transmission of live HPV or MCV virus in smoke generated by laser or diathermy was feasible, and would pose an infection risk. Long-term infection with such carcinogenic viruses would then pose an increased risk for the development of virus-induced cancers in medical personnel. Results: The morphological structures of both HPV and MCV are very similar, and the size, external capsids and genomic structures show striking similarity. Both viruses have a non-enveloped external protein capsid consisting of 72 capsomeres, and a double-stranded DNA core. Sizes of both viruses range from 50 to 60 nm. There are now recent data demonstrating live and infectious HPV in smoke, and that these viruses can be used to infect cells in vitro. Further, anecdotal reports of virus transmission leading to disease causation in the production of respiratory airway viral warts (benign disease), and, finally, reports of HPV-induced oropharyngeal carcinoma (malignant disease) in two gynaecological surgeons as an occupational health hazard have been published recently. Conclusion: There is now sufficient evidence to support the hypotheses that live infectious carcinogenic viruses can be transmitted via smoke generated from surgical procedures, and, in rare instances, actually cause significant disease. Protective measures such as smoke extraction and airway protection should be instituted for all healthcare personnel, particularly those with multiple repeated exposures such as gynaecological surgeons
Reduced suppressive effect of beta(2)-adrenoceptor agonist on fibrocyte function in severe asthma
Background Patients with severe asthma have increased airway remodelling and elevated numbers of circulating fibrocytes with enhanced myofibroblastic differentiation capacity, despite being treated with high doses of corticosteroids, and long acting β2-adrenergic receptor (AR) agonists (LABAs). We determined the effect of β2-AR agonists, alone or in combination with corticosteroids, on fibrocyte function. Methods Non-adherent non-T cells from peripheral blood mononuclear cells isolated from healthy subjects and patients with non-severe or severe asthma were treated with the β2-AR agonist, salmeterol, in the presence or absence of the corticosteroid dexamethasone. The number of fibrocytes (collagen I+/CD45+ cells) and differentiating fibrocytes (α-smooth muscle actin+ cells), and the expression of CC chemokine receptor 7 and of β2-AR were determined using flow cytometry. The role of cyclic adenosine monophosphate (cAMP) was elucidated using the cAMP analogue 8-bromoadenosine 3′,5′-cyclic monophosphate (8-Br-cAMP) and the phosphodiesterase type IV (PDE4) inhibitor, rolipram. Results Salmeterol reduced the proliferation, myofibroblastic differentiation and CCR7 expression of fibrocytes from healthy subjects and non-severe asthma patients. Fibrocytes from severe asthma patients had a lower baseline surface β2-AR expression and were relatively insensitive to salmeterol but not to 8-Br-cAMP or rolipram. Dexamethasone increased β2-AR expression and enhanced the inhibitory effect of salmeterol on severe asthma fibrocyte differentiation. Conclusions Fibrocytes from patients with severe asthma are relatively insensitive to the inhibitory effects of salmeterol, an effect which is reversed by combination with corticosteroids
Identification of “sarsasapogenin-aglyconed” timosaponins as novel Aβ-lowering modulators of amyloid precursor protein processing
published_or_final_versio
Dielectric and thermal relaxation in the energy landscape
We derive an energy landscape interpretation of dielectric relaxation times
in undercooled liquids, comparing it to the traditional Debye and
Gemant-DiMarzio-Bishop pictures. The interaction between different local
structural rearrangements in the energy landscape explains qualitatively the
recently observed splitting of the flow process into an initial and a final
stage. The initial mechanical relaxation stage is attributed to hopping
processes, the final thermal or structural relaxation stage to the decay of the
local double-well potentials. The energy landscape concept provides an
explanation for the equality of thermal and dielectric relaxation times. The
equality itself is once more demonstrated on the basis of literature data for
salol.Comment: 7 pages, 3 figures, 41 references, Workshop Disordered Systems,
Molveno 2006, submitted to Philosophical Magazin
Study of B -> \rho \pi decays at Belle
This paper describes a study of B meson decays to the pseudoscalar-vector
final state \rho\pi using 31.9\times 10^6 B\bar{B} events collected with the
Belle detector at KEKB. The branching fractions B(B^+ \to \rho^0\pi^+) =
(8.0^{+2.3+0.7}_{-2.0-0.7}) \times 10^{-6} and B(B^0 -> \rho^{+-} \pi^{-+}) =
(20.8^{+6.0+2.8}_{-6.3-3.1}) \times 10^{-6} are obtained. In addition, a 90%
confidence level upper limit of B(B^0 \to \rho^0\pi^0) < 5.3 \times 10^{-6}is
reported.Comment: 14 pages, 3 figures, to be submitted to Phys. Lett.
Scrotal metastases from colorectal carcinoma: a case report
A 72-year-old man presented with a two month history of rectal bleeding. Colonoscopy demonstrated synchronous lesions at 3 cm and 40 cm with histological analysis confirming synchronous adenocarcinomata. He developed bilobar hepatic metastases while undergoing neoadjuvant chemoradiotherapy. Treatment was complicated by Fournier's gangrene of the right hemiscrotum which required surgical debridement. Eight months later he re-presented with an ulcerating lesion on the right hemiscrotum. An en-bloc resection of the ulcerating scrotal lesion and underlying testis was performed. Immunohistological analysis revealed metastatic adenocarcinoma of large bowel origin. Colorectal metastasis to the urogenital tract is rare and here we report a case of rectal carcinoma metastasizing to scrotal skin
Historical inductions, Old and New
I review prominent historical arguments against scientific realism to indicate how they display a systematic overshooting in the conclusions drawn from the historical evidence. The root of the overshooting can be located in some critical, undue presuppositions regarding realism. I will highlight these presuppositions in connection with both Laudan’s ‘Old induction’ and Stanford’s New induction, and then delineate a minimal realist view that does without the problematic presuppositions
Impaired nuclear translocation of the glucocorticoid receptor in corticosteroid-insensitive airway smooth muscle in severe asthma
Rationale: Patients with severe asthma (SA) are less responsive to the beneficial effects of corticosteroid (CS) therapy, and relative CS insensitivity has been shown in airway smooth muscle cells (ASMC) from patients with SA. Objectives: We investigated whether there was a defect in the actions of the glucocorticoid receptor (GR) underlying the ability of CS to suppress the inflammatory response in ASMC of patients with SA. ASMC from healthy subjects (n = 10) and subjects with severe (n = 8) and nonsevere asthma (N-SA; n = 8) were cultured from endobronchial biopsies. Measurements and Main Results: GR expression in ASMC from SA and N-SA was reduced compared with that from healthy subjects by 49% (P < 0.01). Although baseline levels of nuclear GR were similar, GR nuclear translocation induced by dexamethasone (10−7 M) in SA was 60% of that measured in either healthy subjects or subjects with N-SA. Tumor necrosis factor (TNF)-α induced greater nuclear factor (NF)-κB (p65) mRNA expression in ASMC from subjects with SA (5.6- vs. 2.0-fold; P < 0.01), whereas baseline and TNF-α–induced nuclear translocation and dexamethasone-mediated suppression of p65 expression were similar between groups. Dexamethasone, although not modulating TNF-α–induced p65 nuclear translocation, attenuated p65 recruitment to the CCL11 promoter in the healthy and N-SA groups, but this suppressive effect was impaired in subjects with SA. Conclusions: Decreased GR expression with impaired nuclear translocation in ASMC, associated with reduced dexamethasone-mediated attenuation of p65 recruitment to NF-κB–dependent gene promoters, may underlie CS insensitivity of severe asthma
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