Vascular manifestations in systemic sclerosis (scleroderma)

Progressive systemic sclerosis (PSS), a disease still of unknown origin, is a generalized autoimmune disorder characterized by immunological abnormalities, microvascular dysfunction, and tissue fibrosis. The mechanism leading to selective microvascular injury in PSS is not completely known, however it is now clear that neuropeptides, vascular endothelium, and disturbances in the regulation of fibroblast function are the three major contributors to the increased fibrosis of skin and internal organs. Thus, endothelial cell and fibroblast dysfunction may be linked through the paracrine activity of soluble endothelial cell products: the cytokine cascade (IL-1, TGF-beta-1, PDGF, TNF, etc.). In systemic sclerosis, the exaggerated generalized vasospastic tendency is clinically represented by Raynaud's phenomenon as shown by an early digital arterial closure after cold stimulation, and by an inadequate vasodilatory response to heat. In this review we summarize recently established data that center around the role of adhesion molecules, immune reactions, and aberrant fibroblast biology and metabolism in effecting vascular and connective tissue alterations in this disease. Only a better knowledge of the pathophysiological process involved in scleroderma might lead to the development of new therapeutic approaches.     

Anatomy of a software start-up

Discusses starting and building a business, what an entrepreneur is, and what sets entrepreneurs apart from normal people. The first thing is to plant your stake in the ground. Figure out where you're going and tell everybody about it. The second is never give up. If there's anything that sets entrepreneurs apart from everybody else, it's the ability to get up after you get knocked down. Third, take care of yourself. The government's not there to help you, the bank's not there to help you, nobody's there to help you. You're there to help you, so take care of yourself. Fourth, life's too short to deal with jerks. Don't compromise your plan, your principles, your people, or your purpose. Fifth, balance the needs of your customers, your employees, your investors, and the community. And the bottom line: try to have fun while you're doing it     

Electrochemical,FTIR and morphological study of polypyrrole—Polystyrenesulphonate conducting films

The electrochemical behaviour, FTIR spectrum and the morphology of polypyrrole-polystyrenesulphonate (PPy-PSS) films obtained potentiostatically at 0.6 V in a 0.05m Py + 1.7 × 10^?2m NaPSS medium have been analysed. Different electrochemical parameters have been modified in order to establish the first polaron formation, the reversibility of the redox process and the doping mechanism. The FTIR spectrum confirms the existence of C?O groups in the film structure and two possible explanations are suggested. SEM reveals a higher homogeneity in these films than in PPy films doped with smaller counterions.     

Statistical analysis of decision threshold for parallel acquisitionwith reference filtering in Rician fading channel

Statistical analysis of the decision threshold for parallel PN code acquisition in a Rician fading channel is presented. It is shown that in the performance analysis of the acquisition system with reference filtering, the statistical evaluation of the decision threshold seems more appropriate than the approximation of the decision threshold     

KNOWLEDGE-BASED FEATURE DISCOVERY FOR EVALUATION FUNCTIONS

Since Samuel's work on checkers over thirty years ago, much effort has been devoted to learning evaluation functions. However, all such methods are sensitive to the feature set chosen to represent the examples. If the features do not capture aspects of the examples significant for problem solving, the learned evaluation function may be inaccurate or inconsistent. Typically, good feature sets are carefully handcrafted and a great deal of time and effort goes into refining and tuning them. This paper presents an automatic knowledge-based method for generating features for evaluation functions. The feature set is developed iteratively: features are generated, then evaluated, and this information is used to develop new features in turn. Both the contribution of a feature and its computational expense are considered in determining whether and how to develop it further.
This method has been applied to two problem-solving domains: the Othello board game and the domain of telecommunications network management. Empirical results show that the method is able to generate many known features and several novel features and to improve concept accuracy in both domains.     

Demonstration of the expression of CD95 ligand transcript and protein in human placenta

Thrombopoietin (TPO) or Mpl ligand is the primary physiological regulator of platelet production. This cytokine is the most potent stimulator of the proliferation and differentiation of MK progenitor and precursor cells in vitro. It also acts additively or synergistically with several cytokines on progenitor cells from various hematopoietic lineages, including the primitive stem cells. The factor is an extremely potent thrombocytopoietic agent when administrated to normal animals, and it accelerates platelet and erythropoietic recovery in several models of myelosuppression. Phase I/II clinical trials are ongoing with no detectable adverse effects. Mpl ligand does not induce platelet aggregation, but it lowers the platelet sensitivity to physiological dose of agonists. In experimental mouse models, high and chronic dose of Mpl ligand results in myelofibrosis. TPO is constantly produced by the liver and the kidney; its plasmatic clearance occurs by binding to its receptor expressed on megakaryocytes and platelets. However, the full spectrum of the biological effects of this new cytokine is not fully understood, in particular its the role in the terminal stage of platelet production. In the near future, it is likely that new insights will be obtained in the physiopathological mechanisms underlying abnormal platelet production in human.     

Significant amounts of glycogen are synthesized from 3-carbon compounds in astroglial primary cultures from mice with participation of the mitochondrial phosphoenolpyruvate carboxykinase isoenzyme

The incorporation was studied of the gluconeogenic substrates lactate, alanine, aspartate and glutamate into glycogen of astroglial primary cultures derived from mouse brain. The incorporation was inhibited by 3-mercaptopicolinate, an inhibitor of one of the characteristic gluconeogenic enzymes, phosphoenolpyruvate carboxykinase. Only the mitochondrial isoenzyme of phosphoenolpyruvate carboxykinase was detectable in the astroglial primary cultures. After the incubation of glucose-starved cells with medium containing a mixture of [6-3H]glucose and [U-14C]glucose, the newly synthesized glycogen showed a 3H/14C ratio which was approximately 15% less than the isotope ratio for the medium. The decrease of the isotope ratio was not significantly inhibited by 3-mercaptopicolinate, indicating a cycling of approximately 15% of the glucose to the level of the triose phosphates before its incorporation into astroglial glycogen. During the initial phase of glycogen resynthesis, the contribution of the gluconeogenic substrates appeared to be higher. This was in agreement with the accumulation of fructose 2,6-bisphosphate during refeeding. A participation of gluconeogenic substrates in glycogen metabolism was also detectable when the glycogen content was not changing significantly.