A reduced-load equivalence for generalised processor sharing networks with heavy-tailed input flows

We consider networks where traffic is served according to the Generalised Processor Sharing (GPS) principle. GPS-based scheduling algorithms are considered important for providing differentiated quality of service in integrated-services networks. We are interested in the workload of a particular flow~$i$ at the bottleneck node on its path. Flow $i$ is assumed to have long-tailed traffic characteristics. We distinguish between two traffic scenarios, (i) flow~$i$ generates instantaneous traffic bursts and (ii) flow $i$ generates traffic according to an on/off process. In addition, we consider two configurations of feed-forward networks. First we focus on the situation where other flows join the path of flow~$i$. Then we extend the model by adding flows which can branch off at any node, with cross traffic as a special case. We prove that under certain conditions the tail behaviour of the workload distribution of flow~$i$ is equivalent to that in a {em two-node tandem network where flow~$i$ is served in isolation at {em constant rates. These rates only depend on the traffic characteristics of the other flows through their average rates. This means that the results do not rely on any specific assumptions regarding the traffic processes of the other flows. In particular, flow~$i$ is not affected by excessive activity of flows with `heavier-tailed' traffic characteristics. This confirms that GPS has the potential to protect individual flows against extreme behaviour of other flows, while obtaining substantial multiplexing gains

A reduced-load equivalence for generalised processor sharing networks with heavy-tailed input flows

We consider networks where traffic is served according to the Generalised Processor Sharing (GPS) principle. GPS-based scheduling algorithms are considered important for providing differentiated quality of service in integrated-services networks. We are interested in the workload of a particular flow~$i$ at the bottleneck node on its path. Flow $i$ is assumed to have long-tailed traffic characteristics. We distinguish between two traffic scenarios, (i) flow~$i$ generates instantaneous traffic bursts and (ii) flow $i$ generates traffic according to an on/off process. In addition, we consider two configurations of feed-forward networks. First we focus on the situation where other flows join the path of flow~$i$. Then we extend the model by adding flows which can branch off at any node, with cross traffic as a special case. We prove that under certain conditions the tail behaviour of the workload distribution of flow~$i$ is equivalent to that in a {em two-node tandem network where flow~$i$ is served in isolation at {em constant rates. These rates only depend on the traffic characteristics of the other flows through their average rates. This means that the results do not rely on any specific assumptions regarding the traffic processes of the other flows. In particular, flow~$i$ is not affected by excessive activity of flows with `heavier-tailed' traffic characteristics. This confirms that GPS has the potential to protect individual flows against extreme behaviour of other flows, while obtaining substantial multiplexing gains

Generalized processor sharing queues with heterogenous traffic classes

We consider a queue fed by a mixture of light-tailed and heavy-tailed traffic. The two traffic flows are served in accordance with the Generalized Processor Sharing (GPS) discipline. GPS-based scheduling algorithms, such as Weighted Fair Queueing (WFQ), have emerged as an important mechanism for achieving service differentiation in integrated networks. We derive the asymptotic workload behavior of the light-tailed traffic flow under the assumption that its GPS weight is larger than its traffic intensity. The GPS mechanism ensures that the workload is bounded above by that in an isolated system with the light-tailed flow served in isolation at a constant rate equal to its GPS weight. We show that the workload distribution is in fact asymptotically equivalent to that in the isolated system, multiplied with a certain pre-factor, which accounts for the interaction with the heavy-tailed flow. Specifically, the pre-factor represents the probability that the heavy-tailed flow is backlogged long enough for the light-tailed flow to reach overflow. The results provide crucial qualitative insight in the typical overflow scenario

User-level performance of elastic traffic in a differentiated-services environment

We consider a system with two service classes, one of which supports elastic traffic. The traffic characteristics of the other class can be completely general, allowing streaming applications as an important special case. The link capacity is shared between the two traffic classes in accordance with the Generalized Processor Sharing (GPS) discipline. GPS-based scheduling algorithms, such as Weighted Fair Queueing, provide a flexible mechanism for service differentiation and prioritization. We examine the user-level performance of the elastic traffic. The elastic traffic users randomly initiate file transfers with a heavy-tailed distribution. Within the elastic traffic class, the active flows share the available bandwidth in an ordinary Processor-Sharing (PS) fashion. The PS discipline has emerged as a natural paradigm for evaluating the user-perceived performance of bandwidth sharing algorithms like TCP. For a certain parameter range, we establish that the transfer delay incurred by the elastic traffic flows is asymptotically equivalent to that in an isolated PS system with constant service rate. This service rate is only affected by the streaming traffic through its average rate. Specifically, the elastic traffic is largely immune from possible adverse traffic characteristics or performance degradation due to prioritization of the streaming traffic. This confirms that GPS-based multiplexing mechanisms achieve significantly better performance for bot

Cellular IP₆ Levels Limit HIV Production while Viruses that Cannot Efficiently Package IP₆ Are Attenuated for Infection and Replication

Summary: HIV-1 hijacks host proteins to promote infection. Here we show that HIV is also dependent upon the host metabolite inositol hexakisphosphate (IP6) for viral production and primary cell replication. HIV-1 recruits IP6 into virions using two lysine rings in its immature hexamers. Mutation of either ring inhibits IP6 packaging and reduces viral production. Loss of IP6 also results in virions with highly unstable capsids, leading to a profound loss of reverse transcription and cell infection. Replacement of one ring with a hydrophobic isoleucine core restores viral production, but IP6 incorporation and infection remain impaired, consistent with an independent role for IP6 in stable capsid assembly. Genetic knockout of biosynthetic kinases IPMK and IPPK reveals that cellular IP6 availability limits the production of diverse lentiviruses, but in the absence of IP6, HIV-1 packages IP5 without loss of infectivity. Together, these data suggest that IP6 is a critical cofactor for HIV-1 replication

Enhancing Production of Recombinant Proteins from Mammalian Cells

The bio-manufacturing of recombinant proteins from mammalian cell cultures requires robust processes that can maximize protein yield while ensuring the efficacy of these proteins as human therapeutics. Recognizing that the challenge of improving protein yield and quality can be met through various approaches, this paper presents three strategies currently being developed in our group. A method for rapidly selecting subpopulations of cells with high production characteristics is proposed. This method combines the efficiency of green fluorescent protein/fluorescence-activated cell sorting (GFP/FACS)–based screening with homologous recombination to generate and select high-producing subclones. Next, the development of chemically defined, protein-free media for enhancing monoclonal antibody production is described. Analysis of culture media effects on the genome-wide transcriptional program of the cell is presented as a means to optimize the culture media and identify potential targets for genetic manipulation. Finally, we propose a method for increasing the extent of intracellular sialylation by improving the transport of CMP-sialic acid into the trans-Golgi. This is hypothesized to increase the sialic acid availability, and may enhance the degree of sialylation in the glycoprotein product.Singapore-MIT Alliance (SMA

Two coupled queues with heterogeneous traffic

We consider a system with two heterogeneous traffic classes, one having light-tailed characteristics, the other one exhibiting heavy-tailed properties. When both classes are backlogged, the two corresponding queues are each served at a certain nominal rate. However, when one queue empties, the service rate for the other class increases. This dynamic sharing of surplus service capacity is reminiscent of the Generalized Processor Sharing (GPS) discipline. GPS-based scheduling algorithms, such as Weighted Fair Queueing, provide a candidate implementation mechanism for achieving differentiated Quality-of-Service in a DiffServ architecture. We characterize the asymptotic workload behavior of both traffic classes. The tail of the workload distribution of the {em heavy-tailed/ class is asymptotically equivalent to that of the heavy-tailed class in isolation -- but with its nominal service rate inflated by the slack capacity of the light-tailed class. For the {em light-tailed/ class, we show a sharp dichotomy in the qualitative behavior, depending on whether its load exceeds its nominal service rate or not. In underload scenarios, the tail of its workload distribution is equivalent to that of the light-tailed class in isolation, multiplied with a certain pre-factor. The pre-factor represents the probability that the heavy-tailed class is backlogged long enough for the light-tailed class to build up a large workload. This provides a measure for the extent to which the light-tailed class benefits from sharing surplus capacity with the heavy-tailed class. In contrast, in overload situations, the light-tailed class is adversely affected by the heavy-tailed class, and inherits its traffic characteristics

Engineering Mammalian Cells for Improved Recombinant Protein Production

The production of recombinant glycoproteins from mammalian cell cultures requires robust processes that can achieve high protein yield while ensuring the efficacy of these proteins as human therapeutics. We describe two approaches currently being developed in our group to genetically engineer cell lines with desirable characteristics for recombinant protein production. To enhance the degree of sialylation in the glycoprotein product, we propose to increase intracellular sialic acid availability by overexpressing the CMP-sialic acid transporters. We are also interested in engineering mammalian cells that can proliferate at reduced cultivation temperatures. Low temperature cultivation of mammalian cells has been shown to enhance glycoprotein production but reduces cell growth. It is hypothesized that a mutant cell line that can proliferate at low temperatures may be coupled with low temperature cultivation to improve recombinant protein production.Singapore-MIT Alliance (SMA