Synthesis, Conformation and Antiproliferative Activity of Isothiazoloisoxazole 1,1-dioxides

Sixteen new isothiazoloisoxazole 1,1-dioxides, one new isothiazolotriazole and one new isothiazolopyrazole have been synthesised by using 1,3-dipolar cycloadditions to isothiazole 1,1-dioxides. One sub-set of these isothiazoloisoxazoles showed low μM activity against a human breast carcinoma cell line, whilst a second sub-set plus the isothiazolotriazole demonstrated an interesting restricted rotation of sterically hindered bridgehead substituents. A thiazete 1,1-dioxide produced from one of the isothiazole 1,1-dioxides underwent conversion into an unknown 1,2,3-oxathiazolin-2-oxide upon treatment with Lewis acids, but was inert towards 1,3-dipoles and cyclopropenones. Six supporting crystal structures are included

Reply to Comment on: Hawking radiation from ultrashort laser pulse filaments

A comment by R. Schutzhold et al. raises possible concerns and questions regarding recent measurements of analogue Hawking radiation. We briefly reply to the opinions expressed in the comment and sustain that the origin of the radiation may be understood in terms of Hawking emission

Zeolites for Fine Chemical Production State of Art and Perspectives

The paper analyses the role of catalysis and that of renewable resources in the frame of a sustainable development. The possible uses of natural feedstocks for chemical production and the application of catalytic methods to their transformations are reviewed, with emphasis on carbohydrates and vegetable oils and on zeolite catalysts, respectively. The problems arising from the embedment of active sites on the catalyst surface are discussed, with the aid of specific examples taken from oxidation and acid catalysed reactions

The breakdown of the cytokine network subsequent to human immunodeficiency virus infection

The acquired immunodeflciency syndrome (AIDS) is a clinically multifaceted disease induced by infection with the human immunodeficiency virus (HIV). HIV infection results in a complex pattern of immunologic alterations that leads to the development of AIDS in the majority of HIV seropositive (HIV+) individuals. The reduction in CD4 T lymphocyte counts is the hallmark of HIV infection; nevertheless, long before the reduction in CD4 counts reaches critical levels, a series of profound and complex defects that impair the function of CD4 T lymphocytes can be detected. Thus, HIV infection is characterized by quantitative and qualitative defects affecting CD4 T lymphocytes. It was suggested recently that programmed cell death (PCD) is an important mechanism leading to CD4 depletion in HIV infection, and that susceptibility of peripheral lymphocytes to PCD is differentially regulated by diverse cytokines. Thus, type 1 cytokines would protect CD4 lymphocytes against PCD, whereas type 2 cytokines would not protect against, and could augment, PCD. We suggest that the qualitative alterations of the immune response provoke the CD4 depletion characteristic of HIV disease via type 2 cytokinemediated augmentation of PCD, and are therefore ultimately responsible for the progression of HIV infection. Finally, we summarize recent data showing that three correlates of disease progression: emergence of HIV strains with syncitium-inducing ability (SI), type 1-to-type 2 cytokine shift, and CD4 depletion, are significantly associated, suggesting a complex interconnected virologic-immunologic pathogenesis of HIV infection

Predictive Values of Transcutaneous Oxygen Tension for Above-the-ankle Amputation in Diabetic Patients with Critical Limb Ischemia

ObjectiveTo assess the values of transcutaneous oxygen tension (TcPO2) capable of predicting above-the-ankle amputation in diabetic patients diagnosed for critical limb ischemia (CLI) according to the criteria of the TransAtlantic Inter-Society Consensus.DesignRetrospective study.MethodsFrom January 1999 to December 2003, 564 diabetic patients were consecutively hospitalized for CLI in one limb. Revascularization with angioplasty or bypass graft was performed when possible and, if not possible, prostanoid therapy was used. In patients in whom therapies did not relieve the rest pain or the gangrene was extended above the Chopart joint, an above-the-ankle-amputation was performed. After treatment TcPO2 values were evaluated in all patients at the dorsum of the foot.ResultsFifty-five (9.8%) patients underwent an above-the-ankle amputation: 22 of 420 patients who underwent angioplasty, 17 of 117 patients who underwent bypass (14.5%) and 16 of 27 patients in whom revascularization was not possible. Post-treatment TcPO2, measured by a receiver operating characteristic (ROC) curve, showed a value 34mmHg as the best threshold for determining the need for revascularization, with an area under the curve of 0.89 (95%CI 0.85–0.94).Using logistic regression analysis the probability of above-the-ankle amputation for this threshold is 9.7% and reduces to 3% for TcPO2>40mmHg.ConclusionTcPO2 levels<34mmHg indicate the need for revascularization, while for values ≥ 34<40mmHg this need appears less pressing, although there remains a considerable probability of amputation. TcPO2 levels greater than 40mmHg suggest that revascularization is dependent on the severity of tissue loss and possible morbidity caused by the procedure

Wideband THz time domain spectroscopy based on optical rectification and electro-optic sampling

We present an analytical model describing the full electromagnetic propagation in a THz time-domain spectroscopy (THz-TDS) system, from the THz pulses via Optical Rectification to the detection via Electro Optic-Sampling. While several investigations deal singularly with the many elements that constitute a THz-TDS, in our work we pay particular attention to the modelling of the time-frequency behaviour of all the stages which compose the experimental set-up. Therefore, our model considers the following main aspects: (i) pump beam focusing into the generation crystal; (ii) phase-matching inside both the generation and detection crystals; (iii) chromatic dispersion and absorption inside the crystals; (iv) Fabry-Perot effect; (v) diffraction outside, i.e. along the propagation, (vi) focalization and overlapping between THz and probe beams, (vii) electro-optic sampling. In order to validate our model, we report on the comparison between the simulations and the experimental data obtained from the same set-up, showing their good agreement

The geometrical nature of optical resonances : from a sphere to fused dimer nanoparticles

We study the electromagnetic response of smooth gold nanoparticles with shapes varying from a single sphere to two ellipsoids joined smoothly at their vertices. We show that the plasmonic resonance visible in the extinction and absorption cross sections shifts to longer wavelengths and eventually disappears as the mid-plane waist of the composite particle becomes narrower. This process corresponds to an increase of the numbers of internal and scattering modes that are mainly confined to the surface and coupled to the incident field. These modes strongly affect the near field, and therefore are of great importance in surface spectroscopy, but are almost undetectable in the far field