A new paclitaxel prodrug for use in ADEPT strategy

A new paclitaxel prodrug intended for use in Antibody-Directed Prodrug Therapy (ADEPT) or Prodrug Monotherapy (PMT) has been prepared. This prodrug was originally designed to be activated into the drug by human beta-glucuronidase. In order to enhance the liberation rate of paclitaxel, an elongated spacer system including a nitro-aromatic derivative and a N,N'-methylethylenediamine was incorporated between the sugar moiety and the drug. Indeed, this new prodrug proved to be activated significantly faster than a former paclitaxel prodrug containing a conventional spacer.     

Differential diagnosis of prostate cancer and benign prostate hyperplasia using two-dimensional electrophoresis.

Prostate specific antigen (PSA) is a protease which is characteristic of the prostate. It is widely used as a serum marker for the early diagnosis of prostate cancer (PCa). Nevertheless, for concentrations between 4 and 10 ng/mL, PSA does not enable PCa to be distinguished from benign diseases, such as benign prostate hyperplasia (BPH). In sera, the use of a ratio between free PSA (PSA uncomplexed with protease inhibitor) and total PSA (free PSA and PSA bound to alpha-1 anti-chymotrypsin) enables the "gray zone" to be reduced, but an important proportion of patients are still wrongly classed. Using two-dimensional electrophoresis, we demonstrated using 52 PCa and 40 BPH well-documented clinical cases that BPH sera show a significantly greater percentage of low-molecular-weight free PSA elements (IwPSA) than PCa sera. In our study, the use of a ratio between IwPSA and standard free PSA enables the correct diagnosis of 100% of PCa and 82.5% of BPH cases as against when 73.1% and 42.5% respectively were correctly diagnozed using the total PSA and the free/total PSA ratio. This important finding may be related to differences in the mechanism secreting PSA from the prostate into the bloodstream. We have shown how a tissue marker may be turned into a powerful tumor marker by events probably unrelated to its expression.     

On the capacity of sets of divergence associated with the spherical partial integral operator

In this article, we study the pointwise convergence of the spherical partial integral operator when it is applied to functions with a certain amount of smoothness. In particular, for , , , we prove that -quasieverywhere on , where is such that almost everywhere. A weaker version of this result in the range as well as some related localisation principles are also obtained. For and , we construct a function such that diverges everywhere.

     

On the modular curves

Let denote an elliptic curve over and the modular curve classifying the elliptic curves over such that the representations of in the 7-torsion points of and of are symplectically isomorphic. In case is given by a Weierstraß equation such that the invariant is a square, we exhibit here nontrivial points of . From this we deduce an infinite family of curves for which has at least four nontrivial points.

     

Effects of temperature on the relaxation to equilibrium and stationary nonequilibrium states of some Langevin systems

We investigate the effects of temperature on the properties of the time relaxation to equilibrium and nonequilibrium steady states of correlation functions of some Langevin harmonic systems. We consider commonly used dissipative and conservative Langevin dynamics, and show that the time relaxation rate depends on the temperature in the case of thermal reservoirs at different temperatures connected to the system, but it does not happen in the case of relaxation to equilibrium, i.e., if all the heat bath are at the same temperature. Our formalism maps the initial stochastic problem on a noncanonical quantum field theory, and the calculations of the relaxation rates are based on a perturbative analysis. We argue to show the reliability of the perturbative computation.     

Reduced expression of <Emphasis Type="Italic">TAC1</Emphasis>, <Emphasis Type="Italic">PENK</Emphasis> and <Emphasis Type="Italic">SOCS2</Emphasis> in <Emphasis Type="Italic">Hcrtr-2</Emphasis> mutated narcoleptic dog brain

Background  

Narcolepsy causes dramatic behavioral alterations in both humans and dogs, with excessive sleepiness and cataplexy triggered by emotional stimuli. Deficiencies in the hypocretin system are well established as the origin of the condition; both from studies in humans who lack the hypocretin ligand (HCRT) and in dogs with a mutation in hypocretin receptor 2 (HCRTR2). However, little is known about molecular alterations downstream of the hypocretin signals.