Queuing analysis of shared-buffer switches with control scheme under bursty traffic

Shared-buffer switches have many advantages such as relatively low cell loss rate and good buffer utilization, and they are increasingly favoured in recent VLSI switch designs for ATM. However, their performance degrades dramatically under nonuniform traffic due to the monopolization of the buffer by some favoured cells. To overcome this, restricted types of sharing and hot-spot pushout (HSPO) have been proposed, and the latter has been shown by simulation to perform better in all situations. In this paper we develop an analytical model for performance evaluation of a shared-buffer asynchronous transfer mode (ATM) switch with HSPO under bursty traffic. This analytical model is an improved version of the first model ever developed for this purpose. We balance the relative queues to approximate the effects of pushout, while keeping only four state-variables, and our model gives a good agreement with simulation, for calculating throughput and cell loss.     

High PCO does not alter pHi, but raises [Ca2+]i in cultured rat carotid body glomus cells in the absence and presence of CdC12

We measured the effect of high PCO (500-550 Torr) on the pHi and [Ca2+]i in cultured glomus cells of adult rat carotid body (CB) as a test of the two models currently proposed for the mechanism of CB chemoreception. The metabolic model postulates that the rise in glomus cell [Ca2+]i, the initiating reaction in the signalling pathway leading to chemosensory neural discharge, is due to [Ca2+] release from intracellular Ca2+ stores. The membrane potential model postulates that the rise in [Ca2+]i comes from influx of extracellular Ca2+ through voltage-dependent Ca2+ channels (VDCC) of the L-type. High PCO did not change pHi at PO2 of 120-135 Torr, showing that CO-induced changes in [Ca2+]i are not due to changes in pHi. High PCO caused a highly significant rise in [Ca2+]i from 90+/-12 nM to 675+/-65 nM, both in the absence and in the presence of 200 microM CdCl2, a potent blocker of L-type VDCCs. This result is fully consistent with release of Ca2+ from glomus cell intracellular stores according to metabolic model, but inconsistent with influx of extracellular Ca2+ through VDCCs according to the membrane potential model.     

Leukemic predisposition of mice transplanted with gene-modified hematopoietic precursors expressing flt3 ligand

flt3/flk-2 ligand (FL) is a cytokine that exhibits synergistic activities in combination with other early acting factors on subpopulations of hematopoietic stem/progenitor cells. In addition to normal hematopoietic precursors, expression of the FL receptor, flt3R, has been frequently demonstrated on the blast cells from patients with acute B-lineage lymphoblastic, myeloid, and biphenotypic (also known as hybrid or mixed) leukemias. Because many of these leukemic cell types express FL, the possibility has been raised that altered regulation of FL-mediated signaling might contribute to malignant transformation or expansion of the leukemic clone. In humans, FL is predominantly synthesized as a transmembrane protein that must undergo proteolytic cleavage to generate a soluble form. To investigate the consequences of constitutively expressing the analogous murine FL isoform in murine hematopoietic stem/progenitor cells, lethally irradiated syngeneic mice (18 total) were engrafted with post-5-fluorouracil-treated bone marrow cells transduced ex vivo with a recombinant retroviral vector (MSCV-FL) encoding murine transmembrane FL. Compared with control mice (8 total), MSCV-FL mice presented with a mild macrocytic anemia but were otherwise healthy for more than 5 months posttransplant (until 22 weeks). Subsequently, all primary MSCV-FL recipients observed for up to 1 year plus 83% (20 of 24) of secondary MSCV-FL animals that had received bone marrow from asymptomatic primary hosts reconstituted for 4 to 5 months developed transplantable hematologic malignancies (with mean latency periods of 30 and 23 weeks, respectively). Phenotypic and molecular analyses indicated that the tumor cells expressed flt3R and displayed B-cell and/or myeloid markers. These data, establishing that dysregulated expression of FL in primitive hematopoietic cells predisposes flt3R+ precursors to leukemic transformation, underscore a potential role of this cytokine/receptor combination in certain human leukemias.     

The metabolism of phytanic acid and pristanic acid in man: a review

The branched-chain fatty acid phytanic acid is a constituent of the diet, present in diary products, meat and fish. Degradation of this fatty acid in the human body is preceded by activation to phytanoyl-CoA and starts with one cycle of alpha-oxidation. Intermediates in this pathway are 2-hydroxy-phytanoyl-CoA and pristanal; the product is pristanic acid. After activation, pristanic acid is degraded by peroxisomal beta-oxidation. Several disorders have been described in which phytanic acid accumulates, in some cases in combination with pristanic acid. In classical Refsum disease, the enzyme that converts phytanoyl-CoA into 2-hydroxyphytanoyl-CoA--phytanoyl-CoA hydroxylase--is deficient, resulting in highly elevated levels of phytanic acid in blood and tissues. Also in rhizomelic chondrodysplasia punctata, phytanic acid accumulates, owing to a deficiency in the peroxisomal import of proteins with a peroxisomal targeting sequence type 2. In patients affected with generalized peroxisomal disorders, degradation of both phytanic acid and pristanic acid is impaired owing to absence of functional peroxisomes. In bifunctional protein deficiency, the disturbed oxidation of pristanic acid results in elevated levels of this fatty acid and a secondary elevation of phytanic acid. In addition, several variant peroxisomal disorders with unknown aetiology have been described in which phytanic acid and/or pristanic acid accumulate. This review describes the discovery of phytanic acid and pristanic acid and the initial attempts to elucidate the origins and fates of these fatty acids. The current knowledge on the alpha-oxidation and beta-oxidation of these branched-chain fatty acids is summarized. The disorders in which phytanic acid and/or pristanic acid accumulate are described and some remarks are made on the pathogenic mechanisms of elevated levels of phytanic acid and pristanic acid.     

A novel role for ursodeoxycholic acid in inhibiting apoptosis by modulating mitochondrial membrane perturbation

The hydrophilic bile salt ursodeoxycholic acid (UDCA) protects against the membrane-damaging effects associated with hydrophobic bile acids. This study was undertaken to (a) determine if UDCA inhibits apoptosis from deoxycholic acid (DCA), as well as from ethanol, TGF-beta1, Fas ligand, and okadaic acid; and to (b) determine whether mitochondrial membrane perturbation is modulated by UDCA. DCA induced significant hepatocyte apoptosis in vivo and in isolated hepatocytes determined by terminal transferase-mediated dUTP-digoxigenin nick end-labeling assay and nuclear staining, respectively (P < 0.001). Apoptosis in isolated rat hepatocytes increased 12-fold after incubation with 0.5% ethanol (P < 0.001). HuH-7 cells exhibited increased apoptosis with 1 nM TGF-beta1 (P < 0. 001) or DCA at >/= 100 microM (P < 0.001), as did Hep G2 cells after incubation with anti-Fas antibody (P < 0.001). Finally, incubation with okadaic acid induced significant apoptosis in HuH-7, Saos-2, Cos-7, and HeLa cells. Coadministration of UDCA with each of the apoptosis-inducing agents was associated with a 50-100% inhibition of apoptotic changes (P < 0.001) in all the cell types. Also, UDCA reduced the mitochondrial membrane permeability transition (MPT) in isolated mitochondria associated with both DCA and phenylarsine oxide by > 40 and 50%, respectively (P < 0.001). FACS(R) analysis revealed that the apoptosis-inducing agents decreased the mitochondrial transmembrane potential and increased reactive oxygen species production (P < 0.05). Coadministration of UDCA was associated with significant prevention of mitochondrial membrane alterations in all cell types. The results suggest that UDCA plays a central role in modulating the apoptotic threshold in both hepatocytes and nonliver cells, and inhibition of MPT is at least one pathway by which UDCA protects against apoptosis.     

Evaluating non-speech sound visualizations for the deaf

Sounds such as co-workers chatting nearby or a dripping faucet help us maintain awareness of and respond to our surroundings. Without a tool that communicates ambient sounds in a non-auditory manner, maintaining this awareness is difficult for people who are deaf. We present an iterative investigation of peripheral, visual displays of ambient sounds. Our major contributions are: (1) a rich understanding of what ambient sounds are useful to people who are deaf, (2) a set of visual and functional requirements for a peripheral sound display, based on feedback from people who are deaf, (3) lab-based evaluations investigating the characteristics of four prototypes, and (4) a set of design guidelines for successful ambient audio displays, based on a comparison of four implemented prototypes and user feedback. Our work provides valuable information about the sound awareness needs of the deaf and can help to inform further design of such applications.