Single IP Research Articles

The Effect of IL‐6 in the Anemia of Inflammation

Anemia of inflammation (AI anemia of chronic disease), results from a large variety of inflammatory conditions. Hepcidin, the principal systemic iron regulatory hormone, is increased during inflammation and limits the availability of iron for erythropoiesis. IL‐6, an inflammatory cytokine, has been shown to be necessary for the elevation of hepcidin during acute inflammation (Nemeth et al, Blood, 2004). However, it has been shown that IL‐1 can also induce hepcidin in vitro (Lee et al, PNAS, 2005). To explore whether IL‐6 is necessary for the development of AI we used a mouse model of AI induced by a single IP injection of complete Freund's adjuvant in IL‐6 KO and WT mice. Hemoglobin concentration decreased to the same extent in WT and KO mice. Hepcidin increased in WT mice but did not change in KO mice. Mean corpuscular volume (MCV) decreased in WT mice but increased in KO mice. Hepatic serum amyloid A mRNA, a marker of hepatic IL‐6 responsiveness, increased in WT but not IL‐6 KO mice indicating that the anemia was not a result of IL‐6‐like cytokines. IL‐6 is not necessary to develop AI. However, IL‐6 does effect the handling of iron as evidenced by the difference in cell size and hepcidin production.

Testbed System of Inter-Radio System Switching for Cognitive Radio

The cognitive radio system consists of multiple wireless access systems that cover overlapping areas and cognitive terminals that use one or more of the wireless accesses simultaneously. In this paper, we describe the architecture of the cognitive radio system and the inter-system handover protocols. In the architecture, each cognitive terminal, which can access multiple radio systems, operates with a single local IP address. The control sequence and packet format are designed to achieve fast handover among the radio systems. Based on the architecture, we have developed a testbed system. On this system, we demonstrate that data can be delivered continuously and radio systems can be switched correctly without any packet loss. In addition, we present the result of the evaluation of the end-to-end latency on the testbed system. These testbed results demonstrate the system architecture described in the paper can achieve a cognitive radio system.

A Kinetic Model of Single and Clustered IP 3 Receptors in the Absence of Ca 2+ Feedback

Ca 2+ liberation through inositol 1,4,5-trisphosphate receptor (IP 3R) channels generates complex patterns of spatiotemporal cellular Ca 2+ signals owing to the biphasic modulation of channel gating by Ca 2+ itself. These processes have been extensively studied in Xenopus oocytes, where imaging studies have revealed local Ca 2+ signals (“puffs”) arising from clusters of IP 3R, and patch-clamp studies on isolated oocyte nuclei have yielded extensive data on IP 3R gating kinetics. To bridge these two levels of experimental data, we developed an IP 3R model and applied stochastic simulation and transition matrix theory to predict the behavior of individual and clustered IP 3R channels. The channel model consists of four identical, independent subunits, each of which has an IP 3-binding site together with one activating and one inactivating Ca 2+-binding site. The channel opens when at least three subunits undergo a conformational change to an “active” state after binding IP 3 and Ca 2+. The model successfully reproduces patch-clamp data; including the dependence of open probability, mean open duration, and mean closed duration on [IP 3] and [Ca 2+]. Notably, the biexponential distribution of open-time duration and the dependence of mean open time on [Ca 2+] are explained by populations of openings involving either three or four active subunits. As a first step toward applying the single IP 3R model to describe cellular responses, we then simulated measurements of puff latency after step increases of [IP 3]. Assuming that stochastic opening of a single IP 3R at basal cytosolic [Ca 2+] and any given [IP 3] has a high probability of rapidly triggering neighboring channels by calcium-induced calcium release to evoke a puff, optimal correspondence with experimental data of puff latencies after photorelease of IP 3 was obtained when the cluster contained a total of 40–70 IP 3Rs.

Multicast Flow Aggregation in IP over Optical Networks

It is widely believed that IP over optical networks will be a major component of the next generation Internet However, it is not efficient to map a single multicast IP flow into one light-tree, since the bandwidth of an IP flow required is usually much less than that of a light-tree. In this paper, we study the problem of multicast flow aggregation (MFA) in the IP over optical two-layered networks under the overlay model, which can be defined as follows: given a set of head ends (i.e. optical multicasting sources), each of which can provide a set of contents (i.e. multicast IP flows) with different required transmission bandwidth, and a set of requested content at the access routers (i.e. optical multicasting destinations), find a set of light-trees as well as the optimal aggregation of multicast IP flows in each light-tree. We model MFA by a tri-partite graph with multiple criteria and show that the problem is NP-complete. Optimal solutions are designed by exploiting MFA to formulate an integer linear programming (ILP), with two parameters: the multicast receiving index alpha and the redundant transmitting index beta. We also propose a heuristic algorithm. Finally, we compare the performance of MFA for different combination of alpha and beta via experiments and show our heuristic algorithm is effective for large-scale network in numerical results

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A study of the application of mobile IP to IP‐VPN and the development of mobile foreign agent

AbstractMobile IP is a protocol which provides a function by which a mobile node (MN) continuously retains a single IP address and continues to use the same IP address, even if the MN moves from the network to which it originally connected (Home Network) to another network. This paper is a study of the advantages of IPsec for MIP applied to IP‐VPN, with a small number of terminals per node and where the subject devices are integrated devices such as non‐personal computer terminals. In order to apply MIP to such an IP‐VPN, a new MFA mode is proposed, in addition to the FA mode and CoA mode which have previously been provided to Mobile IP. In the MFA mode, both the MN and MFA move together. Furthermore, it is proposed to include an autoconfiguration function as well. This can be expected to result in reduced terminal shipping costs. © 2007 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 90(7): 9–17, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.20385

Biological activity of AC3174, a peptide analog of exendin-4

Exenatide, the active ingredient of BYETTA® (exenatide injection), is an incretin mimetic that has been developed for the treatment of patients with type 2 diabetes. Exenatide binds to and activates the known GLP-1 receptor with a potency comparable to that of the mammalian incretin GLP-1(7-36), thereby acting as a glucoregulatory agent. AC3174 is an analog of exenatide with leucine substituted for methionine at position 14, [Leu 14]exendin-4. The purpose of these studies was to evaluate the glucoregulatory activity and pharmacokinetics of AC3174. In RINm5f cell membranes, the potency of AC3174 for the displacement of [ 125I]GLP-1 and activation of adenylate cyclase was similar to that of exenatide and GLP-1. In vivo, AC3174, administered as a single IP injection, significantly decreased plasma glucose concentration and glucose excursion following the administration of an oral glucose challenge in both non-diabetic (C57BL/6) and diabetic db/db mice ( P < 0.05 vs. vehicle-treated). The magnitude of glucose lowering of AC3174 was comparable to exenatide. The ED 50 values of AC3174 for glucose lowering (60 minute post-dose) were 1.2 μg/kg in db/db mice and 1.3 μg/kg in C57BL/6 mice. AC3174 has insulinotropic activity in vivo. Administration of AC3174 resulted in a 4-fold increase in insulin concentrations in normal mice following an IP glucose challenge. AC3174 was also shown to inhibit food intake and decrease gastric emptying in rodent models. AC3174 was stable in human plasma (> 90% of parent peptide was present after 5 h of incubation). In rats, the in vivo half-life of AC3174 was 42–43 min following SC administration. In summary, AC3174 is an analog of exenatide that binds to the GLP-1 receptor in vitro and shares many of the biological and glucoregulatory activities of exenatide and GLP-1 in vivo.

A Stereological Analysis of the Response of Spermatogenesis to an Acute Inflammatory Episode in Adult Rats

Male fertility is inhibited by inflammatory disease, but the mechanisms responsible are poorly defined. The effects of acute systemic inflammation induced by a single IP injection of lipopolysaccharide (LPS) on spermatogenic function in adult male rats were investigated using detailed stereological analysis. The earliest effect observed was a significant maturational delay of meiosis during the leptotene/zygotene phase (at stages IX-XIII) within 24 hours. This was followed within 6 days by an increase in premature release of these cells and the adjacent, more luminally located generation of round spermatids from the seminiferous epithelium. An increase in germ cell apoptosis within stages IX-XIII also occurred at this time. These data indicate that the initial effects of acute inflammation on the seminiferous epithelium are most pronounced on stages IX-XIII. The effects were not consistent with a loss of hormonal regulation, suggesting that a direct effect of inflammation on the function of the Sertoli cell during this critical stage of meiosis is involved. In the longer term, however, the consequences of this acute inflammatory episode were relatively minor: within 28 days there had been a compensatory increase in the efficiency of the seminiferous epithelium, restoring the spermatogenic capacity of the testis towards preinflammation levels.

Single packet IP traceback in AS-level partial deployment scenario

Denial-of-Service (DoS) attacks commonly use IP spoofing to hide the identity and the location of the attack origin. To defend against various DoS attacks and make the attacker accountable, it is necessary to trace IP packets regardless of their source addresses. In this direction, log-based IP traceback is a promising and powerful approach due to its ability to traceback even a single packet. However, the global deployment of log-based IP traceback at all the routers in the internet requires a significant amount of modifications in the routers and introduces a serious operation and management overhead. To facilitate global deployment, we consider the Autonomous Systems (AS) level deployment of log-based IP traceback and accordingly propose a new mechanism called AS-level Single Packet Traceback (AS-SPT). We then evaluate the performance and overhead of the proposed AS-SPT under various partial deployment scenarios.

Effect of 1,25-dihydroxy-vitamin D3 in experimental sepsis

In addition to the regulation of calcium homeostasis, vitamin D affects the cellular immune system, targets the TNF-alpha pathway and increases vasoconstrictor response to angiotensin II. We therefore examined the effect of 1,25-dihydroxy-vitamin D(3) on coagulation and organ failure in experimental sepsis in the rat. Three series of placebo-controlled studies were conducted. All rats were pre-treated with daily SC injections of 1,25-dihydroxy-vitamin D(3) 100 ng/kg or placebo vehicle for 3 days. In study 1, sepsis was accomplished by abdominal surgery comprising a coecal ligation and puncture with a 1,2 mm needle, or sham surgery. In study 2, the rats had a single IP injection of lipopolysaccharide from E. Coli 0111:B4 (LPS) 8 mg/kg, or placebo. In study 3, an hour-long IV infusion of LPS 7 mg/kg, or placebo was given. All three models of sepsis showed significant effects on coagulation and liver function with reduced thrombocyte count and prothrombin time together with elevated ALT and bilirubin (p<0.05) as compared to controls. In study 1, the vitamin D treated rats maintained normal platelet count, whereas the vehicle treated rats showed a significant reduction (p<0.05). This effect of vitamin D on platelets was not found in the LPS-treated groups. We found no significant differences between vitamin D and placebo-treated rats with regards to liver function. The present data suggest a positive modulating effect of 1,25-dihydroxy-vitamin D(3) supplementation on sepsis-induced coagulation disturbances in the coecal ligation and puncture model. No such effect was found in LPS-induced sepsis.

An IP-Decoupling Approach to Host Mobility *

This paper presents the design, implementation, and performance evaluation of an approach to supporting host mobility in the wireless Internet. We observe that a single IP address conventionally serves dual purposes: a network-level routing directive and an endpoint identity of a certain session in transport or upper layers. Therefore, when a host affiliates with a new IP address due to movements, any pre-established active session thereupon suffers outage. Unlike prior schemes exploiting mobility agents, we propose to let a host use two IP addresses for network- and transport-layer identifications, respec- tively, and introduce a translation table that associates the two identities. Such an asso- ciation results from querying or dynamic updates to the Domain Name System, or from direct message exchanges between two communication peers so as to optimize delivery paths. Simulation results show that our scheme outperforms counterpart Mobile IP and Mobile IPv6, in terms of communication delay, packet error rate, message space over- head, and potential packet loss during handoffs. Additionally, qualitative discussions conclude that our proposal lends itself to IPv4 and IPv6 interconnected networks, or multi-tier environment such as wireless Local Area Networks and mobile telecommuni- cation overlay systems.

Suppression of peroxisomal enzyme activities and cytochrome P450 4A isozyme expression by congeneric polybrominated and polychlorinated biphenyls.

The purpose of this study was to determine the effects of PCBs and PBBs on peroxisome proliferator-activated receptor--(PPAR-) associated enzyme activities or protein levels. Male Sprague-Dawley rats were administered a single IP injection (150 μ mol/kg) of either 3,3′,4,4′-tetrabromobiphenyl, 3,3′,4,4′-tetrachlorobiphenyl, 3,3′,5,5′-tetrabromobiphenyl, 2′,3,3′,4,5-pentachlorobiphenyl, 3,3′,4,4′,5-pentachlorobiphenyl, 2,2′,3,3′,5,5′-hexachlorobiphenyl, or 3,3′,4,4′,5,5′-hexabromobiphenyl in corn oil (10 ml/kg). One week later, the activities of catalase, peroxisomal fatty acyl-CoA oxidase, and peroxisomal beta-oxidation as well as cytochrome P450 4A (CYP4A) protein content were determined in subcellular liver fractions. None of the peroxisomal enzyme activities were significantly increased by any of the halogenated biphenyl congeners tested. Except for minor (approx. 25%) increases in the total CYP4A content following treatment with 2,2′,3,3′,5,5′-hexachlorobiphenyl and 3,3′,5,5′-tetrabromobiphenyl, CYP4A protein contents were not increased by any treatment. The two Ah receptor agonists, 3,3′,4,4′-tetrabromobiphenyl and 3,3′,4,4′,5-pentachlorobiphenyl, significantly diminished the liver content of CYP4A proteins and activities of the peroxisomal enzymes studied. Since a range of congeners with different biologic and toxicologic activities were selected for this study, it may be concluded that the polyhalogenated biphenyls do not induce peroxisome proliferation in the male rat, but rather certain members of this class of compounds down regulate peroxisome-associated enzymes. Since PCBs and PBBs do not increase enzyme activities and expression of proteins associated with PPAR, these agents are therefore exerting their carcinogenic and promoting activities by some other mechanism.

‘Trigger’ Events Precede Calcium Puffs in Xenopus Oocytes

The liberation of calcium ions sequestered in the endoplasmic reticulum through inositol 1,4,5-trisphosphate receptors/channels (IP 3Rs) results in a spatiotemporal hierarchy of calcium signaling events that range from single-channel openings to local Ca 2+ puffs believed to arise from several to tens of clustered IP 3Rs to global calcium waves. Using high-resolution confocal linescan imaging and a sensitive Ca 2+ indicator dye (fluo-4-dextran), we show that puffs are often preceded by small, transient Ca 2+ elevations that we christen “trigger events”. The magnitude of triggers is consistent with their arising from the opening of a single IP 3 receptor/channel, and we propose that they initiate puffs by recruiting neighboring IP 3Rs within the cluster by a regenerative process of Ca 2+-induced Ca 2+ release. Puff amplitudes (fluorescence ratio change) are on average ∼6 times greater than that of the triggers, suggesting that at least six IP 3Rs may simultaneously be open during a puff. Trigger events have average durations of ∼12 ms, as compared to 19 ms for the mean rise time of puffs, and their spatial extent is ∼3 times smaller than puffs (respective widths at half peak amplitude 0.6 and 1.6 μm). All these parameters were relatively independent of IP 3 concentration, although the proportion of puffs showing resolved triggers was greatest (∼80%) at low [IP 3]. Because Ca 2+ puffs constitute the building blocks from which cellular IP 3-mediated Ca 2+ signals are constructed, the events that initiate them are likely to be of fundamental importance for cell signaling. Moreover, the trigger events provide a useful yardstick by which to derive information regarding the number and spatial arrangement of IP 3Rs within clusters.

The Number and Spatial Distribution of IP 3 Receptors Underlying Calcium Puffs in Xenopus Oocytes

Calcium puffs are local Ca 2+ release events that arise from a cluster of inositol 1,4,5-trisphosphate receptor channels (IP 3Rs) and serve as a basic “building block” from which global Ca 2+ waves are generated. Important questions remain as to the number of IP 3Rs that open during a puff, their spatial distribution within a cluster, and how much Ca 2+ current flows through each channel. The recent discovery of “trigger” events—small Ca 2+ signals that immediately precede puffs and are interpreted to arise through opening of single IP 3R channels—now provides a useful yardstick by which to calibrate the Ca 2+ flux underlying puffs. Here, we describe a deterministic numerical model to simulate puffs and trigger events. Based on confocal linescan imaging in Xenopus oocytes, we simulated Ca 2+ release in two sequential stages; representing the trigger by the opening of a single IP 3R in the center of a cluster for 12 ms, followed by the concerted opening of some number of IP 3Rs for 19 ms, representing the rising phase of the puff. The diffusion of Ca 2+ and Ca 2+-bound indicator dye were modeled in a three-dimensional cytosolic volume in the presence of immobile and mobile Ca 2+ buffers, and were used to predict the observed fluorescence signal after blurring by the microscope point-spread function. Optimal correspondence with experimental measurements of puff spatial width and puff/trigger amplitude ratio was obtained assuming that puffs arise from the synchronous opening of 25–35 IP 3Rs, each carrying a Ca 2+ current of ∼0.4 pA, with the channels distributed through a cluster 300–800 nm in diameter.

Increased oxidative stress in submitochondrial particles after chronic amphetamine exposure

Previous studies have suggested that reactive oxygen species (ROS) production may play a role in the pathophysiology of many neuropsychiatric disorders, such as bipolar disorder (BD) and schizophrenia (SCZ). In addition, there is an emerging body of data indicating that BD and SCZ may be associated with mitochondrial dysfunction. We studied the effects of acute and chronic d-amphetamine on ROS production in submitochondrial particles of rat brain. Male Wistar rats were divided in two experimental groups: acute and chronic treatment. In the acute treatment, rats received one single IP injection of d-amphetamine (1, 2 or 4 mg/kg) or saline (control group). In the chronic treatment, rats received one daily IP injection of d-amphetamine (1, 2 or 4 mg/kg) or saline for 7 days. Locomotor activity was assessed with the open field task, and thiobarbituric acid reactive substances (TBARS) and superoxide production were measured in submitochondrial particles of the prefrontal cortex and hippocampus. Both acute and chronic amphetamine treatment increased locomotor behavior. Chronic amphetamine exposure induced a 3- to 6-fold increase of TBARS and a 1.5- to 2-fold increase of superoxide production in submitochondrial particles of prefrontal cortex and hippocampus ( P < 0.05). No effects on superoxide or TBARS were observed with acute treatment. These findings suggest that amphetamine-induced mitochondrial ROS generation may be a useful model to investigate the hypothesis of altered brain energy metabolism associated with BD and SCZ. Further studies assessing the effects of mood stabilizers and antipsychotics in preventing mitochondrial oxidative stress are necessary.

Changes in Antioxidant Defense Enzymes after d-amphetamine Exposure: Implications as an Animal Model of Mania

Studies have demonstrated that oxidative stress is associated with amphetamine-induced neurotoxicity, but little is known about the adaptations of antioxidant enzymes in the brain after amphetamine exposure. We studied the effects of acute and chronic amphetamine administration on superoxide dismutase (SOD) and catalase (CAT) activity, in a rodent model of mania. Male Wistar rats received either a single IP injection of D-: amphetamine (1 mg/kg, 2 mg/kg, or 4 mg/kg) or vehicle (acute treatment). In the chronic treatment rats received a daily IP injection of either D-: amphetamine (1 mg/kg, 2 mg/kg, or 4 mg/kg) or vehicle for 7 days. Locomotor behavior was assessed using the open field test. SOD and CAT activities were measured in the prefrontal cortex, hippocampus, and striatum. Acute and to a greater extent chronic amphetamine treatment increased locomotor behavior and affected SOD and CAT activities in the prefrontal cortex, hippocampus and striatum. Our findings suggest that amphetamine exposure is associated with an imbalance between SOD and CAT activity in the prefrontal cortex, hippocampus and striatum.

Phase III Trial of Intraperitoneal Therapy With Yttrium-90–Labeled HMFG1 Murine Monoclonal Antibody in Patients With Epithelial Ovarian Cancer After a Surgically Defined Complete Remission

This was a multinational, open-label, randomized phase III trial comparing yttrium-90-labeled murine HMFG1 (90Y-muHMFG1) plus standard treatment versus standard treatment alone in patients with epithelial ovarian cancer (EOC) who had attained a complete clinical remission after cytoreductive surgery and platinum-based chemotherapy. In total, 844 International Federation of Gynecology and Obstetrics stage Ic to IV patients were initially screened, of whom 447 patients with a negative second-look laparoscopy (SLL) were randomly assigned to receive either a single dose of 90Y-muHMFG1 plus standard treatment (224 patients) or standard treatment alone (223 patients). Patients in the active treatment arm received a single intraperitoneal dose of 25 mg of 90Y-muHMFG1 (target dose 666 MBq/m2). The primary end point was length of survival; secondary end points included time to relapse and safety. The study had an 80% power to detect a 15% change in survival. After a median follow-up of 3.5 years (range, 1 to 6 years), 70 patients had died in the active treatment arm compared with 61 patients in the control arm. Cox proportional hazards analysis of survival demonstrated no difference between treatment arms. In the study drug arm, 104 patients experienced relapse compared with 98 patients in the standard treatment arm. No difference in time to relapse was observed between the two study arms. Active therapy was associated with occasional grade 3 or 4 thrombocytopenia and neutropenia and grade 1 or 2 GI symptoms, abdominal discomfort, arthralgia, and myalgia. CONCLUSION A single IP administration of 90Y-muHMFG1 to patients with EOC who had a negative SLL after primary therapy did not extend survival or time to relapse.

330. Effect of Different Inducible Minimal Promoters in the RheoSwitch® Therapeutic System That Give Robust and Long-Term In Vivo Gene Expression

The RheoSwitch|[reg]| Therapeutic System (RTS) is used to regulate gene expression in a ligand-dependent manner, and may have utility in human gene therapies that require the specific regulation of the level of gene expression, or where it is desirable to terminate therapy either when it is no longer required, or where continuation of the therapy would be unsafe. One version of the RTS is comprised of an ecdysone receptor (EcR) fused to a GAL4 DNA binding domain, a chimeric retinoid X receptor fused to a VP16 activation domain (pVP16-Hs-LmRXR), a reporter gene, such as human secreted alkaline phosphatase (hSEAP) placed under the control of a 6xGAL4 response element, and an inducible minimal promoter (p6xGAL4RE- Inducible Promoter- hSEAP). Studies are described that have evaluated the effects of 10 different inducible promoters on ligand- dependent hSEAP transgene expression in vitro in NIH 3T3 cells and in vivo following quadriceps electroporation in C57BL/6 mice. These data can be interpreted to classify the inducible promoters into three performance groups: 1) low expression and undetectable basal expression, 2) intermediate expression with some basal activity in cells, and 3) robust expression in cells and in vivo. One inducible promoter constructed with a consensus TATA box (TATA3) induced only low levels of expression until three Sp1 binding sites (SP1- TATA) were inserted into the promoter, yielding much higher expression. Additionally, a minimal transthyretin (TTR) promoter showed high levels of expression in response to ligand both in cell culture and in vivo. Of these two minimal promoters, Sp1-TATA3 gave higher expression, but higher basal expression was also observed. Additional evaluation of the Sp1-TATA3 and the TTR minimal promoters showed that insulating these promoters with chicken beta globin insulator further increased the expression levels. The expression cassette containing the TTR minimal promoter was chosen to evaluate the long-term expression of the RTS in vivo due to its high ligand-dependent transgene induction relative to basal expression. To assess long-term induction of in vivo expression, hSEAP protein levels and mRNA levels of hSEAP were analyzed in two groups of C57BL/6 mice electroporated (quadriceps muscle) with the RTS. Group one received a single IP dose of ligand 3 days after electroporation. The second group received a single IP dose of ligand on days 3, 185, and 353 after electroporation. Levels of hSEAP protein in serum were assayed over a series of time points and hSEAP was induced at all times. In addition, animals were sacrificed on day 17 and 365, respectively, and muscle tissue was collected for mRNA analysis by RT-QPCR. Levels of mRNA hSEAP were comparable at both 17 and 365 days after RTS electroporation. These studies establish that RTS containing the TTR minimal promoter both induces high levels of gene expression in vivo as well as sustained performance one year after electroporation.

Effects of long-acting recombinant human follicle-stimulating hormone analogs containing N-linked glycosylation on murine folliculogenesis

To evaluate the efficacy of two novel long-acting rhFSH analogs, rhFSH-N2 and rhFSH-N4, in stimulating murine folliculogenesis. Experimental study. Academic research environment. Immature female mice. Recombinant hFSH-N2 and -N4 were administered via single IP injection to 3-week-old female mice (n = 10) who were killed 48 hours later for dissection and histologic examination of reproductive organs and serum inhibin A. Results were compared with other groups of mice who received either single or q 12 hour injections for 48 hours of commercial rhFSH, or a single injection of pregnant mare serum gonadotropin (PMSG). A subgroup of the mice receiving rhFSH-N4 was supplemented with daily injections of small doses of hCG to simulate LH add-back. Serum inhibin A levels, ovarian and uterine weights, and ovarian antral follicle counts. Recombinant human FSH-N2 and -N4 administration induced a statistically significant increase in ovarian weights, uterine weights, and inhibin A levels compared with single and twice-daily injection of rhFSH. PMSG induced the greatest increases in all three measured parameters. There was no statistical difference between rhFSH-N2 and rhFSH-N4 for any parameter analyzed. A single injection of rhFSH-N2 or -N4 induced a greater number of antral follicles than did either single or q 12 hour injections of rhFSH. The addition of small doses of hCG to rhFSH-N4 increased inhibin A levels and antral follicle number to reach statistical equivalence to PMSG treatment. Addition of a synthetic polypeptide containing two or four N-linked glycosylation sites to rhFSH increases in vivo bioactivity of the hormone compared to commercial rhFSH. After a single injection, both rhFSH-N2 and rhFSH-N4 effectively induced a greater follicular response in the mouse than did rhFSH.

Building converged networks with IMS technology

For several years, telecommunications providers have touted the potential of converged networks that offer a wide range of voice, data, and multimedia services, all over a single IP infrastructure. These networks - which differ from today's disparate voice, data, signaling, and control networks - would be based on open standards rather than proprietary approaches and let users work with applications or one another across wireless or wireline platforms. However, these networks have been just a vision until recently. Now, though, a growing number of telecommunications carriers and equipment vendors-including Alcatel, British Telecommunication, Ericsson, Lucent Technologies, Motorola, and Nokia - are beginning to release devices and services based on a convergence approach called IP Multimedia Subsystem.