Zuo Wenxiang gong pi zha, [6 juan]

Running title: Pi zha

Sbornik stateĭ v chestʹ Dmitrīi︠a︡ Aleksandrovicha Korsakova : po povodu sorokali︠e︡tīi︠a︡ ego uchenoĭ i pi︠a︡tidesi︠a︡tili︠e︡tīi︠a︡ ucheno-literaturnoĭ di︠e︡i︠a︡telʹnosti : istorīi︠a︡, istorīi︠a︡ literatury, arkheologīi︠a︡, i︠a︡zykovi︠e︡di︠e︡nīe filosofīi︠a︡, pedagogike = Mélanges Korsakoff : recueil de travaux, offert à M-r Dmitry Korsakoff, d-r et prof. émer. de l'Université de Kazan, à l'occasion du XL anniversaire de son professorat et de L ans d'activité comme savant et écrivain.

By D.V. Aĭnalov et al.

Opere volgari di Leon Batt : Alberti, per la più parte inedite et tratte dagli autografi annotate e illustrate dal Dott /

t. 4. Della pittura. Della prospettiva. Della statua. Arte edificatoria. Sulla cupola della chiesa di San Francesco di Rimini, lettera. De' ludi matematici -- t. 5. Trattato del governo della famiglia. Epistola consolatoria. Amiria. Efebie ovvero disputazion amatorie. Lettere amatorie. Poesie.

Literatura polska od poczatków do powstania styczniowego Ksi̧ażka podrȩczna informacyjna dla studjuj̧acych naukowo dzieje rozwoju piśmiennictwa polskiego.

At head of title: Gabrjel Korbut.

Guangdong xiang zhou shang bu bing feng pi zhun zhou zi cun an zhang cheng fu ben bu yu tu.

Mode of access: Internet.

Rossiada : poėma v XII-ti [i.e. dvi͡enadt͡sati] pi͡esni͡akh : polnyĭ tekst poėmy : obʺi͡asnitelʹnyi͡a statʹi /

Mode of access: Internet.

Raccolta dei monumenti più interessanti del real museo borbonico e di varie collezione private.

Mode of access: Internet.

Synthesis, biological activity, and preliminary pharmacokinetic evaluation of analogues of a phosphosulfomannan angiogenesis inhibitor (PI-88)

The phosphosulfomannan 1 (PI-88) is a mixture of highly sulfated oligosaccharides that is currently undergoing clinical evaluation in cancer patients. As well as it's anticancer properties, 1 displays a number of other interesting biological activities. A series of analogues of 1 were synthesized with a single carbon (pentasaccharide) backbone to facilitate structural characterization and interpretation of biological results. In a fashion similar to 1, all compounds were able to inhibit heparanase and to bind tightly to the proangiogenic growth factors FGF-1, FGF-2, and VEGF. The compounds also inhibited the infection of cells and cell-to-cell spread of herpes simplex virus (HSV-1). Preliminary pharmacokinetic data indicated that the compounds displayed different pharmacokinetic behavior compared with 1. Of particular note was the n-octyl derivative, which was cleared 3 times less rapidly than 1 and may provide increased systemic exposure.

A phase I biological and pharmacologic study of the heparanase inhibitor PI-88 in patients with advanced solid tumors

Purpose: PI-88 is a mixture of highly sulfated oligosaccharides that inhibits heparanase, an extracellular matrix endoglycosidase, and the binding of angiogenic growth factors to heparan sulfate. This agent showed potent inhibition of placental blood vessel angiogenesis as well as growth inhibition in multiple xenograft models, thus forming the basis for this study. Experimental Design: This study evaluated the toxicity and pharmacokinetics of PI-88 (80-315 mg) when administered s.c. daily for 4 consecutive days bimonthly (part 1) or weekly (part 2). Results: Forty-two patients [median age, 53 years (range, 19-78 years); median performance status, 1] with a range of advanced solid tumors received a total of 232 courses. The maximum tolerated dose was 250 mg/d. Dose-limiting toxicity consisted of thrombocytopenia and pulmonary embolism. Other toxicity was generally mild and included prolongation of the activated partial thromboplastin time and injection site echymosis. The pharmacokinetics were linear with dose. Intrapatient variability was low and interpatient variability was moderate. Both AUC and C-max correlated with the percent increase in activated partial thromboplastin time, showing that this pharmacodynamic end point can be used as a surrogate for drug exposure, No association between PI-88 administration and vascular endothelial growth factor or basic fibroblast growth factor levels was observed. One patient with melanoma had a partial response, which was maintained for >50 months, and 9 patients had stable disease for >= 6 months. Conclusion: The recommended dose of PI-88 administered for 4 consecutive days bimonthly or weekly is 250 mg/d. PI-88 was generally well tolerated. Evidence of efficacy in melanoma supports further evaluation of PI-88 in phase II trials.

APP controls the formation of PI(3,5)P2 vesicles through its binding of the PIKfyve complex

Phosphoinositides are signalling lipids that are crucial for major signalling events as well as established regulators of membrane trafficking. Control of endosomal sorting and endosomal homeostasis requires phosphatidylinositol-3-phosphate (PI(3)P) and phosphatidylinositol-3,5-bisphosphate (PI(3,5)P2), the latter a lipid of low abundance but significant physiological relevance. PI(3,5)P2 is formed by phosphorylation of PI(3)P by the PIKfyve complex which is crucial for maintaining endosomal homeostasis. Interestingly, loss of PIKfyve function results in dramatic neurodegeneration. Despite the significance of PIKfyve, its regulation is still poorly understood. Here we show that the Amyloid Precursor Protein (APP), a central molecule in Alzheimer’s disease, associates with the PIKfyve complex (consisting of Vac14, PIKfyve and Fig4) and that the APP intracellular domain directly binds purified Vac14. We also show that the closely related APP paralogues, APLP1 and 2 associate with the PIKfyve complex. Whether APP family proteins can additionally form direct protein–protein interaction with PIKfyve or Fig4 remains to be explored. We show that APP binding to the PIKfyve complex drives formation of PI(3,5)P2 positive vesicles and that APP gene family members are required for supporting PIKfyve function. Interestingly, the PIKfyve complex is required for APP trafficking, suggesting a feedback loop in which APP, by binding to and stimulating PI(3,5)P2 vesicle formation may control its own trafficking. These data suggest that altered APP processing, as observed in Alzheimer’s disease, may disrupt PI(3,5)P2 metabolism, endosomal sorting and homeostasis with important implications for our understanding of the mechanism of neurodegeneration in Alzheimer’s disease.

Dr. Rene Price (FCE LTER co-PI) installing a meteorological tower, Taylor Slough

This material is based upon work supported by the National Science Foundation through the Florida Coastal Everglades Long-Term Ecological Research program under Cooperative Agreements #DBI-0620409 and #DEB-9910514. This image is made available for non-commercial or educational use only.