PR-39, a syndecan-inducing antimicrobial peptide, binds and affects p130(Cas)

PR-39 is a proline-arginine-rich antimicrobial peptide and an important component of innate immunity. In addition to its antimicrobial effects, PR-39 can alter mammalian cell gene expression and behavior. To determine the mechanism through which PR-39 affects mesenchymal cells, we identify a number of binding targets for PR-39 using a biologically active fragment of PR-39 (PR-39(15)). We found that PR-39 binds NIH 3T3 in a saturable manner consistent with the existence of a binding target. Similar to full-length PR-39, PR-39(15) interacts with lipid bilayers. After interacting with the membrane, PR-39(15) rapidly enters human microvascular endothelial cells and binds a number of cytoplasmic proteins. PR-39 selectively binds recombinant SH3-containing proteins and was also found to bind a native SH3-containing protein, p130(Cas). PR-39(15) treatment of endothelial cells results in altered p130 localization. These results show that PR-39(15) binds an SH3-containing signal transduction molecule that has the potential to explain a myriad of effects PR-39 has on mammalian cell behaviors.     

ADSL向低成本多功能双向发展

尽管ADSL的高速和畅通无阻的特性引起了用户的关注,但是,要想真正成为拨号调制解调器的替代产品,硬件成本必须降低。设计人员必须把研发重点放在调制解调器内的芯片组上,才能降低硬件成本,因为芯片组是决定产品特性和综合成本的关键元素。     

Phase I trial of the thymidylate synthase inhibitor AG331 as a 5-day continuous infusion

AG331 (N6-[4-(morpholinosulfonyl)benzyl]-N6-methyl-2, 6-diaminobenz-[c,d]-indole glucuronate) is a lipophilic thymidylate synthase inhibitor with activity in solid tumor models. On the basis of preclinical data supporting regimens of frequent drug administration, we performed a Phase I trial of AG331 as a 5-day continuous infusion repeated every 3 weeks. Twenty-nine patients were entered at doses ranging from 25 to 1000 mg/m2/day. The major side effects were mild to moderate fatigue, nausea, vomiting, diarrhea, and fever. At doses >/=400 mg/m2, acute reversible elevation of bilirubin, aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltranspeptidase was observed. All patients who received >/=600 mg/m2/day experienced elevated alanine aminotransferase. Elevated liver function tests were evident by day 3 of the infusion and had resolved by day 8 in the majority. This toxicity was dose limiting at 1000 mg/m2/day, at which dose two of two patients developed grade 4 reversible hyperbilirubinemia in addition to the enzyme elevations. Serum and urine samples were analyzed by a novel high-pressure liquid chromatography method for the determination of the pharmacokinetics of AG331. Over the 50-1000 mg/m2/day dose range, mean total clearance ranged from 11.6 to 30.0 liters/h/m2, and volume of distribution at steady state ranged from 279.5 to 758.7 liters/m2. These parameters were dose independent over the dose range tested. The harmonic mean terminal half-life of AG331 was 20.2 h. Less than 5% of an AG331 dose is eliminated unchanged in the urine. Both the administered dose and exposure to the drug were related to the changes in bilirubin and aminotransferase blood levels. Evidence for inhibition of thymidylate synthase was obtained at doses ranging from 100 to 1000 mg/m2 in seven patients; plasma deoxyuridine concentrations at end-infusion were 1.8-3.8-fold higher than pretreatment values. Because of the nature of toxicity on this schedule, more extensive Phase II evaluation is not recommended, although an AG331 dose of 800 mg/m2/day for 5 days is tolerable. Exploration of less frequent dose administration is under way.     

Fibrillary glomerulonephritis related to serum fibrillar immunoglobulin-fibronectin complexes

Fibrillary glomerulonephritis is a disease of uncertain origin and pathogenesis characterized by nonamyloidotic fibrils in glomeruli. We report immunohistological, immunochemical, and biochemical studies of a serum fibrillar cryoprecipitate obtained from a patient with fibrillary glomerulonephritis, that formed on prolonged storage at 4 degrees C. By Western blot and amino acid sequence analysis, the cryoprecipitated fibril components consisted of immunoglobulins, heavy chains gamma and mu, light chains kappa and lambda, and fibronectin, similar to the proteins identified by immunofluorescence and immunoelectron microscopy in the glomerular fibrils. These findings support the hypothesis that serum precursors may be the source of the fibrillar deposits and suggest a role for immunoglobulin-fibronectin complexes in the pathogenesis of fibrillary glomerulonephritis.     

Network function virtualization: through the looking-glass

The fields of networking and telecommunications are presently witnessing the transition of a number of Network Function Virtualization (NFV) principles and techniques from research into practice. This survey attempts to capture the NFV phenomenon in its multi-faceted historical development over the last two decades, by answering the question “What are the main goals of NFV systems?” and by highlighting the advantages and technical limits of NFV in supporting those goals. By focusing on the whys and hows of NFV, we propose a reasoned overview of the most significant design elements of NFV as a complementary synthesis to the analytical taxonomies of papers and standards that are usually found in survey documents.     

Synthesis and anticancer activity of (R,S)-9-(2,3-dihydro-1,4-benzoxathiin-3-ylmethyl)-9H-purines

A series of eleven 2- and 6-substituted (R,S)-9-(2,3-dihydro-1,4-benzoxathiin-3-ylmethyl)-9H-purine derivatives was obtained by applying a standard Mitsunobu protocol that led to a six-membered ring contraction from (R,S)-3,4-dihydro-2H-1,5-benzoxathiepin-3-ol via an episulfonium intermediate. The signal approximately delta=151 ppm, which corresponds to the C4' carbon atom, is unequivocal proof of the N9' regioisomer. The potential of the target molecules as anticancer agents is reflected in their activity against the MCF-7 cancer cell line. The most active compounds have IC(50) values of (6.18+/-1.70) and (8.97+/-0.83) microM. The results indicate that the anticancer activity for the most active compounds is correlated with their capacity to induce apoptosis.     

Beneficial effects of Trichoderma genus microbes on qualitative parameters of Brassica rapa L. subsp. sylvestris L. Janch. var. esculenta Hort.

The consumption of vegetables and fruits has always been seen as health promoting. One group of vegetables that were already used for medicinal purposes in ancient times and are now seen as possibly cancer protective are vegetables of the Brassica genus. The protective effect of brassicas against cancer may be due to their relatively high content of glucosinolates. Certain hydrolysis products of glucosinolates have shown anticarcinogenic properties. However, not properly cooking procedures and storage could drastically reduce the content of glucosinolates in Brassicaceae plants. This study aims to assess whether the use of agronomic techniques can increase the content of glucosinolates in Brassica plants, in order to offset these losses. For this purpose were used strains of beneficial microorganisms of Trichoderma harzianum TM10, T. atroviride P1, already known biocontrol agents, and their metabolites harzianum acid and 6-pentyl-α-pyrone on plants of Brassica rapa subsp. sylvestris var. esculenta ecotype “Sessantino” (called with the trivial name “friarielli” in the south of Italy where this variety is very popular and consumed). Moreover, the antioxidant activity and ascorbic acid content were determined on plant extracts, followed by liquid chromatography–mass spectrometry analysis of glucosinolates. In order to obtain the extraction of constituents from plant material, microwave-assisted extraction was used. Results obtained showed that the use of Trichoderma and its metabolites determined an increase in glucosinolates in plants of B. rapa. Accordingly, the proposed method could be used on other plants of food interest to increase their nutritional properties.     

Numerical Modeling and Design of Thermoelectric Cooling Systems and Its Application to Manufacturing Machines

In this work the properties of thermoelectric modules (TEMs) and their behavior have been numerically modeled. Moreover, their applications very often require modeling not only of the TEM but also of the working environment and the product in which they will be working. A clear example is the fact that TEMs are very often installed with heat-dissipating elements such as fans, heat sinks, and heat exchangers; thus, the module will only work according to the heat dissipation conditions that these external sources can provide in a certain environment. In this context, analytic approaches, even though they have been proved to be useful, do not provide enough, accurate information in this regard. Therefore, numerical modeling has been identified as a powerful tool to improve detailed designs of thermoelectric solutions. This paper presents numerical simulations of a TEM in different working conditions, as well as with different commercial dissipation devices. The objective is to obtain the characteristic curve of a TEM using a valid numerical model that can be introduced into larger models of different applications. Also, the numerical model of the module and different cooling devices is provided. Both of them are compared against real tested modules, so that the deviation between them can be measured and discussed. Finally, the TEM is introduced into a manufacturing application and results are discussed to validate the model for further use.     

A guide for establishing a practice in police preemployment postoffer psychological evaluations.

This article provides a guide that focuses on ethics and competence issues for psychologists considering a specialization in conducting police preemployment postoffer psychological evaluations (PEPOPEs). The discussion first addresses the importance of relevant training and practical experiences, involvement in pertinent professional associations, and adherence to rigorous standards and guidelines for conducting this specialized form of assessment. The specific components of a comprehensive assessment are then enumerated and discussed. The article concludes with a consideration of ethical dilemmas and challenges involved in this realm of psychological practice, and a vignette highlights some possible pitfalls for psychologists who are insufficiently prepared for conducting PEPOPEs. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Technical note: quantification of zeins from corn, high-moisture corn, and corn silage using a turbidimetric method: comparative efficiencies of isopropyl and tert-butyl alcohols

Zeins are corn endosperm storage proteins that encapsulate starch granules into a protein matrix, which can act as a barrier to starch accessibility and digestion. Laboratory methods to quantify zein are seldom used because they are considered arduous and time-consuming. A recently published rapid turbidimetric method (mTM) was reinvestigated by changing the solution originally used for the zein solubilization step. In particular, the aim was to explore whether, and to what extent, the use of tert-butyl alcohol (t-BuOH-mTM) in lieu of isopropyl alcohol (i-PrOH-mTM) was able to improve the quantification of zeins from dry corn, high-moisture corn, and corn silage samples. The nature of the alcohol influenced the zein extraction values, and t-BuOH-mTM gave higher zein values in corn (3.6 vs. 3.3 g/100 g of dry matter) and corn silage samples (1.2 vs. 0.9 g/100 g of dry matter) compared with i-PrOH-mTM. In contrast, similar zein extraction values were obtained for high-moisture corn (2.1 vs. 1.9 g/100 g of dry matter, respectively). Sodium dodecyl sulfate-PAGE analysis revealed no contamination by nonzein proteins with the use of tert-butyl alcohol. Overall, these findings indicated that tert-butyl alcohol has a greater ability to solubilize zein compared with isopropyl alcohol and thus the t-BuOH-mTM allowed greater extraction of zeins. Considering the growing interest of animal nutritionists in zein proteins, such results should provide useful information for routine laboratory analysis.