Lily Li | Universitas Syiah Kuala Banda Aceh (original) (raw)

Papers by Lily Li

Mechanisms that initiate lupus nephritis and cause progression to end-stage renal disease remain ... more Mechanisms that initiate lupus nephritis and cause progression to end-stage renal disease remain poorly understood. In this study, we show that lupus-prone New Zealand Mixed 2410 mice that develop a severe glomerulosclerosis and rapidly progressive renal disease overexpress IL-4 in vivo. In these mice, STAT6 deficiency or anti-IL-4 Ab treatment decreases type 2 cytokine responses and ameliorates kidney disease, particularly glomerulosclerosis, despite the presence of high levels of IgG anti-dsDNA Abs. STAT4 deficiency, however, decreases type 1 and increases type 2 cytokine responses, and accelerates nephritis, in the absence of high levels of IgG anti-dsDNA Abs. Thus, STAT6 and IL-4 may selectively contribute to the development of glomerulosclerosis, whereas STAT4 may play a role in autoantibody production.

International Immunology, 2001

Taken together, these observations demonstrate that the effects of SAg on in vivo humoral immune ... more Taken together, these observations demonstrate that the effects of SAg on in vivo humoral immune responses are highly CD4 ⍣ cell dependent, are substantially CD8 ⍣ cell independent and can be successfully investigated using human MHC class II-transgenic mice. This model system may be useful in investigating the polyclonally activating effects of microbial products (prototypic environmental insults) on the development of systemic autoimmunity.

The relative contribution of Th2 and Th1 cytokines to the pathogenesis of lesions of chronic asth... more The relative contribution of Th2 and Th1 cytokines to the pathogenesis of lesions of chronic asthma remains poorly understood. To date, therapeutic inhibition of Th2 cytokines has proved disappointing. We used a clinically relevant model of chronic allergic asthma in mice to compare the effects of administering neutralizing antibodies to interleukin (IL)-13, IL-5, and interferon-gamma (IFN-gamma) to animals with established disease. As has been observed in clinical studies, anti-IL-5 inhibited both inflammation and remodeling but had no effect on airway responsiveness to methacholine. Anti-IL-13 effectively suppressed eosinophil recruitment and accumulation of chronic inflammatory cells in the airways. This treatment also partially suppressed changes of airway wall remodeling, including goblet cell hyperplasia/metaplasia and subepithelial fibrosis, but had limited ability to inhibit airway hyperreactivity (AHR). In contrast, treatment with anti-IFN-gamma markedly suppressed AHR. This antibody inhibited accumulation of chronic inflammatory cells but did not affect eosinophil recruitment or changes of remodeling. We conclude that inhibition of IL-5 is beneficial and that inhibition of IL-13 has considerable potential as a therapeutic strategy in chronic asthma, that IFN-gamma may play an important role in the pathogenesis of AHR, and that co-operative interaction between Th2 and Th1 cytokines contributes to the pathogenesis of the lesions of chronic asthma.

IEEE Transactions on Mobile Computing, 2007

Delay-tolerant networks (DTNs) have the potential to connect devices and areas of the world that ... more Delay-tolerant networks (DTNs) have the potential to connect devices and areas of the world that are under-served by current networks. A critical challenge for DTNs is determining routes through the network without ever having an end-to-end connection, or even knowing which "routers" will be connected at any given time. Prior approaches have focused either on epidemic message replication or on knowledge of the connectivity schedule. The epidemic approach of replicating messages to all nodes is expensive and does not appear to scale well with increasing load. It can, however, operate without any prior network configuration. The alternatives, by requiring a priori connectivity knowledge, appear infeasible for a self-configuring network.

There has been much debate over the past few years about the practice of moving traditional user-... more There has been much debate over the past few years about the practice of moving traditional user-space applications, such as web servers, into the kernel for better performance. Recently, the user-space ¤ server web server has shown promising performance for delivering static content. In this paper we first describe how we augmented the ¤ server to enable it to serve dynamic content. We then evaluate the performance of the ¤ server and the kernelspace TUX web server, using the SPECweb99 workload generator under a variety of static and dynamic workloads. We demonstrate that the gap in the performance of the two servers becomes less significant as the proportion of dynamic-content requests increases. In fact, for workloads with a majority of dynamic requests, the ¤ server outperforms TUX. We conclude that a well-designed user-space web server can compete with an in-kernel server on performance, while retaining the reliability and security benefits that come from operating in user space. The results presented in this paper will help system developers and administrators in choosing between the in-kernel and the user-space approach for web servers.

Delay-tolerant networks (DTNs) have the potential to connect devices and areas of the world that ... more Delay-tolerant networks (DTNs) have the potential to connect devices and areas of the world that are under-served by current networks. A critical challenge for DTNs is determining routes through the network without ever having an end-to-end connection, or even knowing which "routers" will be connected at any given time. Prior approaches have focused either on epidemic message replication or on knowledge of the connectivity schedule. The epidemic approach of replicating messages to all nodes is expensive and does not appear to scale well with increasing load. It can, however, operate without any prior network configuration. The alternatives, by requiring a priori connectivity knowledge, appear infeasible for a self-configuring network.

Nature, 2001

Programmed cell death (apoptosis) is a tightly regulated process of cell disassembly in which dyi... more Programmed cell death (apoptosis) is a tightly regulated process of cell disassembly in which dying cells and their nuclei shrink and fragment and the chromosomal DNA is degraded into internucleosomal repeats. Here we report the characterization of the cps-6 gene, which appears to function downstream of, or in parallel to, the cell-death protease CED-3 of Caenorhabditis elegans in the DNA degradation process during apoptosis. cps-6 encodes a homologue of human mitochondrial endonuclease G, and its protein product similarly localizes to mitochondria in C. elegans. Reduction of cps-6 activity caused by a genetic mutation or RNA-mediated interference (RNAi) affects normal DNA degradation, as revealed by increased staining in a TUNEL assay, and results in delayed appearance of cell corpses during development in C. elegans. This observation provides in vivo evidence that the DNA degradation process is important for proper progression of apoptosis. CPS-6 is the first mitochondrial protein identified to be involved in programmed cell death in C. elegans, underscoring the conserved and important role of mitochondria in the execution of apoptosis.

Cell, 2000

cytochrome c complex then recruits the initiator caspase of this pathway, procaspase-9 and induce... more cytochrome c complex then recruits the initiator caspase of this pathway, procaspase-9 and induces its autoactivation (Li et al., 1997b; Zou et al., 1999). Caspase-9 in turn activates downstream caspases including caspase-3, -6, and -7 (Li et al., 1997b; Srinivasula et al., ). University of Texas Southwestern Proteins of the Bcl-2 family are major regulators of Medical Center at Dallas the mitochondria-initiated caspase activation pathway Dallas, Texas 75235 (reviewed by Adams and Cory, 1998). The anti-apoptotic members of this family, including Bcl-2 and Bcl-X L , preserve mitochondrial integrity and prevent the release of Summary cytochrome c in the presence of apoptotic stimuli (Kluck et al., 1997; Yang et al., 1997). Conversely, the proapo-We report here the identification of a novel protein, ptotic members of this family such as Bad, Bax, Bid, Smac, which promotes caspase activation in the cytoand Bim move from other cellular compartments to mitochrome c/Apaf-1/caspase-9 pathway. Smac promotes chondria in response to apoptotic stimuli and promote caspase-9 activation by binding to inhibitor of apocytochrome c release (reviewed by Gross et al., 1999). Inhibitors of apoptosis proteins, IAPs, are another ptosis proteins, IAPs, and removing their inhibitory family of proteins that regulate the cytochrome c/Apaf-1 activity. Smac is normally a mitochondrial protein but caspase activating pathway (reviewed by Deveraux is released into the cytosol when cells undergo apoand Reed, 1999). Initially identified in the genome of a ptosis. Mitochondrial import and cleavage of its signal baculovirus as suppressors of apoptosis in host cells, peptide are required for Smac to gain its apoptotic endogenous IAPs have been found in a variety of organactivity. Overexpression of Smac increases cells' senisms including seven in mammals so far (Crook et al., sitivity to apoptotic stimuli. Smac is the second mito-1993; Deveraux and Reed, 1999). The antiapoptotic acchondrial protein, along with cytochrome c, that protivity of IAPs has been attributed to the conserved bacumotes apoptosis by activating caspases. lovirus IAP repeat (BIR) domain (Takahashi et al., 1998). Three human IAPs, XIAP, c-IAP-1, and c-IAP-2 have Introduction been shown to bind procaspase-9 and prevent its activation (Deveraux et al., 1998). These IAPs can also di-One of the key regulatory steps for apoptosis is the rectly bind and inhibit active caspases (Deveraux et al., activation of caspases, the intracellular cysteine prote-1998). In Drosophila, the anti-apoptotic activity of IAPs ases that cleave substrates after aspartic acid residues is countered by Reaper, Hid, and Grim (Vucic et al., (reviewed by Thornberry and Lezebnik, 1998). Existing 1998; McCarthy and Dixit, 1998; Goyal et al., 2000). as inactive zymogens in living cells, apoptotic caspases Mammalian homologs of Reaper, Hid, and Grim have become activated during apoptosis either through autonot been identified. catalysis or cleavage by other caspases. Active caspases Despite significant progress in dissecting the cytothen cleave many important intracellular substrates, chrome c-mediated apoptotic pathway, several puzleading to the characteristic morphological changes aszling experimental observations remain to be explained. sociated with apoptotic cells. These changes include First of all, certain types of cells are responsive to michromatin condensation, DNA fragmentation into nucleocroinjected cytochrome c while others are not (Li et somal fragments, nuclear membrane break down, exteral., 1997a). Second, healthy neurons do not respond nalization of phosphatidylserine, and formation of apoto microinjected cytochrome c unless they have been ptotic bodies that are readily taken up by phagocytosis subjected to NGF withdrawal for a certain period of time, gaining the status of "competent to die" (Deshmukh and (reviewed by Thornberry and Lezebnik, 1998).

Mechanisms that initiate lupus nephritis and cause progression to end-stage renal disease remain ... more Mechanisms that initiate lupus nephritis and cause progression to end-stage renal disease remain poorly understood. In this study, we show that lupus-prone New Zealand Mixed 2410 mice that develop a severe glomerulosclerosis and rapidly progressive renal disease overexpress IL-4 in vivo. In these mice, STAT6 deficiency or anti-IL-4 Ab treatment decreases type 2 cytokine responses and ameliorates kidney disease, particularly glomerulosclerosis, despite the presence of high levels of IgG anti-dsDNA Abs. STAT4 deficiency, however, decreases type 1 and increases type 2 cytokine responses, and accelerates nephritis, in the absence of high levels of IgG anti-dsDNA Abs. Thus, STAT6 and IL-4 may selectively contribute to the development of glomerulosclerosis, whereas STAT4 may play a role in autoantibody production.

International Immunology, 2001

Taken together, these observations demonstrate that the effects of SAg on in vivo humoral immune ... more Taken together, these observations demonstrate that the effects of SAg on in vivo humoral immune responses are highly CD4 ⍣ cell dependent, are substantially CD8 ⍣ cell independent and can be successfully investigated using human MHC class II-transgenic mice. This model system may be useful in investigating the polyclonally activating effects of microbial products (prototypic environmental insults) on the development of systemic autoimmunity.

The relative contribution of Th2 and Th1 cytokines to the pathogenesis of lesions of chronic asth... more The relative contribution of Th2 and Th1 cytokines to the pathogenesis of lesions of chronic asthma remains poorly understood. To date, therapeutic inhibition of Th2 cytokines has proved disappointing. We used a clinically relevant model of chronic allergic asthma in mice to compare the effects of administering neutralizing antibodies to interleukin (IL)-13, IL-5, and interferon-gamma (IFN-gamma) to animals with established disease. As has been observed in clinical studies, anti-IL-5 inhibited both inflammation and remodeling but had no effect on airway responsiveness to methacholine. Anti-IL-13 effectively suppressed eosinophil recruitment and accumulation of chronic inflammatory cells in the airways. This treatment also partially suppressed changes of airway wall remodeling, including goblet cell hyperplasia/metaplasia and subepithelial fibrosis, but had limited ability to inhibit airway hyperreactivity (AHR). In contrast, treatment with anti-IFN-gamma markedly suppressed AHR. This antibody inhibited accumulation of chronic inflammatory cells but did not affect eosinophil recruitment or changes of remodeling. We conclude that inhibition of IL-5 is beneficial and that inhibition of IL-13 has considerable potential as a therapeutic strategy in chronic asthma, that IFN-gamma may play an important role in the pathogenesis of AHR, and that co-operative interaction between Th2 and Th1 cytokines contributes to the pathogenesis of the lesions of chronic asthma.

IEEE Transactions on Mobile Computing, 2007

Delay-tolerant networks (DTNs) have the potential to connect devices and areas of the world that ... more Delay-tolerant networks (DTNs) have the potential to connect devices and areas of the world that are under-served by current networks. A critical challenge for DTNs is determining routes through the network without ever having an end-to-end connection, or even knowing which "routers" will be connected at any given time. Prior approaches have focused either on epidemic message replication or on knowledge of the connectivity schedule. The epidemic approach of replicating messages to all nodes is expensive and does not appear to scale well with increasing load. It can, however, operate without any prior network configuration. The alternatives, by requiring a priori connectivity knowledge, appear infeasible for a self-configuring network.

There has been much debate over the past few years about the practice of moving traditional user-... more There has been much debate over the past few years about the practice of moving traditional user-space applications, such as web servers, into the kernel for better performance. Recently, the user-space ¤ server web server has shown promising performance for delivering static content. In this paper we first describe how we augmented the ¤ server to enable it to serve dynamic content. We then evaluate the performance of the ¤ server and the kernelspace TUX web server, using the SPECweb99 workload generator under a variety of static and dynamic workloads. We demonstrate that the gap in the performance of the two servers becomes less significant as the proportion of dynamic-content requests increases. In fact, for workloads with a majority of dynamic requests, the ¤ server outperforms TUX. We conclude that a well-designed user-space web server can compete with an in-kernel server on performance, while retaining the reliability and security benefits that come from operating in user space. The results presented in this paper will help system developers and administrators in choosing between the in-kernel and the user-space approach for web servers.

Delay-tolerant networks (DTNs) have the potential to connect devices and areas of the world that ... more Delay-tolerant networks (DTNs) have the potential to connect devices and areas of the world that are under-served by current networks. A critical challenge for DTNs is determining routes through the network without ever having an end-to-end connection, or even knowing which "routers" will be connected at any given time. Prior approaches have focused either on epidemic message replication or on knowledge of the connectivity schedule. The epidemic approach of replicating messages to all nodes is expensive and does not appear to scale well with increasing load. It can, however, operate without any prior network configuration. The alternatives, by requiring a priori connectivity knowledge, appear infeasible for a self-configuring network.

Nature, 2001

Programmed cell death (apoptosis) is a tightly regulated process of cell disassembly in which dyi... more Programmed cell death (apoptosis) is a tightly regulated process of cell disassembly in which dying cells and their nuclei shrink and fragment and the chromosomal DNA is degraded into internucleosomal repeats. Here we report the characterization of the cps-6 gene, which appears to function downstream of, or in parallel to, the cell-death protease CED-3 of Caenorhabditis elegans in the DNA degradation process during apoptosis. cps-6 encodes a homologue of human mitochondrial endonuclease G, and its protein product similarly localizes to mitochondria in C. elegans. Reduction of cps-6 activity caused by a genetic mutation or RNA-mediated interference (RNAi) affects normal DNA degradation, as revealed by increased staining in a TUNEL assay, and results in delayed appearance of cell corpses during development in C. elegans. This observation provides in vivo evidence that the DNA degradation process is important for proper progression of apoptosis. CPS-6 is the first mitochondrial protein identified to be involved in programmed cell death in C. elegans, underscoring the conserved and important role of mitochondria in the execution of apoptosis.

Cell, 2000

cytochrome c complex then recruits the initiator caspase of this pathway, procaspase-9 and induce... more cytochrome c complex then recruits the initiator caspase of this pathway, procaspase-9 and induces its autoactivation (Li et al., 1997b; Zou et al., 1999). Caspase-9 in turn activates downstream caspases including caspase-3, -6, and -7 (Li et al., 1997b; Srinivasula et al., ). University of Texas Southwestern Proteins of the Bcl-2 family are major regulators of Medical Center at Dallas the mitochondria-initiated caspase activation pathway Dallas, Texas 75235 (reviewed by Adams and Cory, 1998). The anti-apoptotic members of this family, including Bcl-2 and Bcl-X L , preserve mitochondrial integrity and prevent the release of Summary cytochrome c in the presence of apoptotic stimuli (Kluck et al., 1997; Yang et al., 1997). Conversely, the proapo-We report here the identification of a novel protein, ptotic members of this family such as Bad, Bax, Bid, Smac, which promotes caspase activation in the cytoand Bim move from other cellular compartments to mitochrome c/Apaf-1/caspase-9 pathway. Smac promotes chondria in response to apoptotic stimuli and promote caspase-9 activation by binding to inhibitor of apocytochrome c release (reviewed by Gross et al., 1999). Inhibitors of apoptosis proteins, IAPs, are another ptosis proteins, IAPs, and removing their inhibitory family of proteins that regulate the cytochrome c/Apaf-1 activity. Smac is normally a mitochondrial protein but caspase activating pathway (reviewed by Deveraux is released into the cytosol when cells undergo apoand Reed, 1999). Initially identified in the genome of a ptosis. Mitochondrial import and cleavage of its signal baculovirus as suppressors of apoptosis in host cells, peptide are required for Smac to gain its apoptotic endogenous IAPs have been found in a variety of organactivity. Overexpression of Smac increases cells' senisms including seven in mammals so far (Crook et al., sitivity to apoptotic stimuli. Smac is the second mito-1993; Deveraux and Reed, 1999). The antiapoptotic acchondrial protein, along with cytochrome c, that protivity of IAPs has been attributed to the conserved bacumotes apoptosis by activating caspases. lovirus IAP repeat (BIR) domain (Takahashi et al., 1998). Three human IAPs, XIAP, c-IAP-1, and c-IAP-2 have Introduction been shown to bind procaspase-9 and prevent its activation (Deveraux et al., 1998). These IAPs can also di-One of the key regulatory steps for apoptosis is the rectly bind and inhibit active caspases (Deveraux et al., activation of caspases, the intracellular cysteine prote-1998). In Drosophila, the anti-apoptotic activity of IAPs ases that cleave substrates after aspartic acid residues is countered by Reaper, Hid, and Grim (Vucic et al., (reviewed by Thornberry and Lezebnik, 1998). Existing 1998; McCarthy and Dixit, 1998; Goyal et al., 2000). as inactive zymogens in living cells, apoptotic caspases Mammalian homologs of Reaper, Hid, and Grim have become activated during apoptosis either through autonot been identified. catalysis or cleavage by other caspases. Active caspases Despite significant progress in dissecting the cytothen cleave many important intracellular substrates, chrome c-mediated apoptotic pathway, several puzleading to the characteristic morphological changes aszling experimental observations remain to be explained. sociated with apoptotic cells. These changes include First of all, certain types of cells are responsive to michromatin condensation, DNA fragmentation into nucleocroinjected cytochrome c while others are not (Li et somal fragments, nuclear membrane break down, exteral., 1997a). Second, healthy neurons do not respond nalization of phosphatidylserine, and formation of apoto microinjected cytochrome c unless they have been ptotic bodies that are readily taken up by phagocytosis subjected to NGF withdrawal for a certain period of time, gaining the status of "competent to die" (Deshmukh and (reviewed by Thornberry and Lezebnik, 1998).