Stable, scalable, fair congestion control and AQM schemes that achieve high utilization in the Internet

Virtual queue-based active queue management schemes have been proposed to provide low-loss, low-delay service in the Internet. In an earlier work, we had proposed a particular scheme called the adaptive virtual queue (AVQ) algorithm where the capacity of the virtual queue is adapted to the traffic conditions to achieve a desired level of utilization in the network. Here, we study the choice of the parameters of the congestion-controllers at the sources and the AVQ scheme at the links that is required to ensure stability. In particular, we consider a system in which users with diverse round-trip delays and fairness requirements access a general topology network. For this system, we show that, by choosing the speed of adaptation at the sources and the links appropriately, one can guarantee the stability of the network.     

Synthesis and structural characterization of (Bi2O3)1?x (Y2O3)x and (Bi2O3)1?x (Gd2O3)x solid solutions

Solid solution series, (Bi₂O₃)_1−x (Y₂O₃)_x and (Bi₂O₃)_1−x (Gd₂O₃)_x, forx = 0.10, 0.20, 0.30 and 0.40 were synthesized by standard ceramic technique. The structural phase characterization was carried out using X-ray powder diffraction technique. It was found that the solid solution containing 20–40 mole% of Y₂O₃ had face-centred cubic structure. All samples of the solid solution series, (Bi₂O₃)_1−x (Gd₂O₃)_x, had rhombohedral single phase in the concentration range 0.10 ≤x ≤ 0.40. Lattice parameters offcc phase of Y₂O₃ doped samples were calculated from the X-ray diffraction data. The lattice constant ‘a’ gradually decreases with increasing content of dopant concentration (x) for the Y₂O₃ doped system and obeys Vegard’s rule. The unit cell parameters for the (Bi₂O₃)_1−x (Gd₂O₃)_x doped samples showing rhombohedral phase were obtained on hexagonal setting.     

In vitro displacement by rat serum of adsorbed radiolabeled poloxamer and poloxamine copolymers from model and biodegradable nanospheres

Poloxamer 407 and poloxamine 908 have been used by many research groups to modify the surface of both model latex and biodegradable nanospheres, thereby producing nanospheres that have shown reduced protein adsorption in vitro and extended circulation times in vivo. A potential limitation of such systems is the desorption of the copolymer coating layer. We describe a two-stage process to radiolabel poloxamer 407 and poloxamine 908 that has facilitated an investigation into this potential desorption, in vitro. The first stage of the labeling procedure involved the substitution of the terminal hydroxyl groups in each poly(ethylene oxide) (PEO) chain of poloxamer 407 and poloxamine 908 with an amino group. The aminated copolymers were then radiolabeled with 125Iodine Bolton-Hunter reagent. The efficiency of labeling was calculated to be approximately 20% for the tetramine poloxamine 908 and approximately 33% for the diamine poloxamer 407. Remaining free amino groups were then either acetylated, using acetic anhydride, or left in the free amino form. Covalent linkage of the radiolabel to the copolymer was confirmed by nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy. The stability of the link between radiolabel and copolymer to hydrolysis was also confirmed; <4% loss of radiolabel occurred from poloxamine 908 after incubation in phosphate-buffered saline (PBS) at 37 degrees C for 8 days. The radiolabeled copolymers (with the free amino groups acetylated) were then used in experiments that have given the first direct evidence that adsorbed copolymers can be displaced by serum proteins in significant amounts from the surface of model and biodegradable nanospheres. The displacement was highly dependent on copolymer-nanosphere compatibility, with up to 78% of 125I tetramine poloxamine 908 being displaced from poly(lactide-co-glycolide) (PLGA) nanospheres in 24 h, compared with 20% displacement of 125I tetramine poloxamine 908 in 24 h from polystyrene nanospheres. These results have direct implication for the future design of drug delivery systems based on coated nanospheres.     

Identification and characterization of a novel human aldose reductase-like gene

We have identified a novel human protein that is highly homologous to aldose reductase (AR). This protein, which we called ARL-1, consists of 316 amino acids, the same size as AR, and its amino acid sequence is 71% identical to that of AR. It is more closely related to the AR-like proteins such as mouse vas deferens protein, fibroblast growth factor-regulated protein, and Chinese hamster ovary reductase, with 81, 82, and 83%, respectively, of its amino acid sequence identical to the amino acid sequence of these proteins. The cDNA of ARL-1 was expressed in Escherichia coli to obtain recombinant protein for characterization of its enzymatic activities. For comparison, the cDNA of human AR was also expressed in E. coli and analyzed in parallel. These two enzymes differ in their pH optima and salt requirement, but they act on a similar spectrum of substrates. Similar to AR, ARL-1 can efficiently reduce aliphatic and aromatic aldehydes, and it is less active on hexoses. While AR mRNA is found in most tissues studied, ARL-1 is primarily expressed in the small intestines and in the colon, with a low level of its mRNA in the liver. The ability of ARL-1 to reduce various aldehydes and the locations of expression of this gene suggest that it may be responsible for detoxification of reactive aldehydes in the digested food before the nutrients are passed on to other organs. Interestingly, ARL-1 and AR are overexpressed in some liver cancers, but it is not clear if they contribute to the pathogenesis of this disease.     

Detection and characterization of the electron paramagnetic resonance-silent glutathionyl-5,5-dimethyl-1-pyrroline N-oxide adduct derived from redox cycling of phenoxyl radicals in model systems and HL-60 cells

Rapidly growing knowledge about the nature and behaviour of breast cancer has led to many treatment modalities. Consequently, the possibilities of individualizing the treatment of breast cancer increase. The major tool for the determination of an optimal treatment plan is the estimation of the extent of the disease: in other words, staging. As a consequence, together with the expected result of the treatment, the stage of the disease gives information on the prognosis of the patient. Current staging systems insufficiently describe the clinically important features of breast cancer with respect to management and outcome: local and regional extent, invasiveness, aggressiveness, the state of dissemination, and the effectiveness of different treatment modalities. For staging of the local and regional extent, histology plays a prominent role and should be incorporated in future staging systems. Histological workup therefore needs standardisation. Histological parameters as tumour size, grade, nodal status, and vascular invasion are also the most important prognostic factors. Many so-called biological prognostic factors are related to the invasiveness and aggressiveness (metastatic potential) of the tumour, and therefore to the prognosis of the patient. However, these factors do not necessarily predict the effectiveness of certain systemic treatments. Only if the biological foundation of a prognostic factor is completely clarified can treatment be based on this knowledge, and the factor will become a predictor for the treatment effect. Many "biological" prognostic factors do not fulfil this main criterion and are therefore not useful for clinical decision making. A clinically useful staging system covers three primary aims: (1) to guide locoregional treatment, (2) to prognosticate the chance of survival, and (3) to indicate who needs what kind of adjuvant treatment. For the conception of a new staging system the following steps should be taken: standardization of all aspects of histology, identification of regional nodal involvement, and validation of prognostic factors with respect to their predictive value to treatment outcome.     

Ultrastructural features of cystic and merogonic stages of Hepatozoon sipedon (Apicomplexa: Adeleorina) in northern leopard frogs (Rana pipiens) and northern water snakes (Nerodia sipedon) from Ontario, Canada

This article describes the long-term consequences of successful cardiovascular disease (CVD) prevention and its influence on premature mortality in Finland, with special reference to North Karelia. Active community-based CVD prevention began in 1972 in the province of North Karelia (population, 180,000). Since 1977, active preventive work has been carried out nationwide, taking advantage of the experience from North Karelia, which continued as a demonstration area for integrated prevention of noncommunicable diseases. Comprehensive community-based interventions as part of WHO interhealth and CINDI programmes in North Karelia and nationwide aimed at changing the target risk factors and health behaviours (serum cholesterol, blood pressure, smoking, diet) at the population level. Age-adjusted mortality rates for CVD, coronary heart disease (CHD), cerebrovascular disease, all cancers, lung cancer, accidents and violence, and all causes in the population aged 35-64 years from the pre-programme period (1969-71) to 1995 were the main measures of the outcome. Among men there was a great reduction in deaths from CHD, CVD, cancer, and all causes in the whole country. From 1969-71 to 1995 the age-standardized CHD mortality (per 100,000) decreased in North Karelia by 73% (from 672 to 185) and nationwide by 65% (from 465 to 165). The reduction in CVD mortality was of the same magnitude. Among men, CHD mortality decreased in the 1970s, as did lung cancer mortality in the 1980s and 1990s, significantly more in North Karelia than in all of Finland. Among women there was a great reduction in CVD (including CHD and stroke) mortality and all-causes mortality, but only a small reduction in cancer mortality. These results show that a major reduction in CVD mortality among the working-age population can take place in association with active reduction of major risk factors, with a favourable impact on cancer and all-causes mortality.     

The control of protein release from poly(DL-lactide co-glycolide) microparticles by variation of the external aqueous phase surfactant in the water-in oil-in water method

A unique feature of p21 that distinguishes it from the other cyclin-dependent kinase (CDK) inhibitors is its ability to associate with the proliferating cell nuclear antigen (PCNA), an auxiliary factor for DNA polymerases delta and epsilon. While it is now well established that inhibition of cyclin/CDK complexes by p21 can result in G1 cell cycle arrest, the consequences of p21/PCNA interaction on cell cycle progression have not yet been determined. Here, we show, using a tetracycline-regulated system, that expression of wild-type p21 in p53-deficient DLD1 human colon cancer cells inhibits DNA synthesis and causes G1 and G2 cell cycle arrest. Similar effects are observed in cells expressing p21CDK-, a mutant impaired in the interaction with CDKs, but not in cells expressing p21PCNA-, a mutant deficient for the interaction with PCNA. Analysis of cells treated with a p21-derived PCNA-binding peptide provides additional evidence that the growth inhibitory effects of p21 and p21CDK result from their ability to bind to PCNA. Our results suggest that p21 might inhibit cell cycle progression by two independent mechanisms, inhibition of cyclin/CDK complexes, and inhibition of PCNA function resulting in both G1 and G2 arrest.