The purpose of this paper is to select a model for HIV that uses few parameters while fitting the world prevalence and death data well. Here we consider a set of models based on Erlang's method of stages, including some with and some without social distancing. The use of stages is supported by biological studies which suggest that HIV passes through stages in each individual, although the exact number is not known. This set of models can represent such stages using a successive number of classes. To perform model selection, we compute R 0 and use it to estimate initial values of the parameters in this model. We run thousands of iterations of a Nelder-Mead simplex search algorithm to determine the optimal values of parameters for each model and the error associated with each model. These errors are used to compute AIC c values and then the AIC c values are compared to select the most likely model. The selected model from this experiment contains the social distancing term as well as four infected classes/stages. We then perform identifiability analysis and determine that the "true values" of the parameters for this model are uniquely determinable based on the data points.
Porcine placenta extract (PPE) is known to possess anti-inflammatory properties owing to its high concentration of bioactive substances. However, the need to eliminate blood-borne infectious agents while maintaining biological efficacy raises concerns about the optimal method for sterilizing PPE. Therefore, the objective of this study was to compare the effects of the standard pressurized heat (autoclaving) method of sterilization with γ-irradiation on the anti-inflammatory effects of PPE. The anti-inflammatory actions of these two preparations of PPE were evaluated by measuring their inhibitory effects on the production of NO, the expression of iNOS protein, and the expression of iNOS, COX2, TNF-α, IL-1β, and IL-6 mRNA in lipopolysaccharide-stimulated RAW 264.7 cells. Compared with autoclaved PPE, γ-irradiated PPE showed significantly greater inhibition of NO production and iNOS protein expression, and produced a greater reduction in the expression of iNOS, COX2, TNF-α, IL-1β, and IL-6 mRNA. These results provide evidence that the sterilization process is crucial in determining the biological activity of PPE, especially its anti-inflammatory activity. Collectively, our data suggest that γ-irradiated PPE acts at the transcriptional level to effectively and potently suppresses the production of NO and the expression of pro-inflammatory cytokines.
IntroductionThe first identification of swine-originated influenza A/CA/04/2009 (pH1N1) as the cause of an outbreak of human influenza accelerated efforts to develop vaccines to prevent and control influenza viruses. The current norm in many countries is to prepare influenza vaccines using cell-based or egg-based killed vaccines, but it is difficult to elicit a sufficient immune response using this approach. To improve immune responses, researchers have examined the use of cytokines as vaccine adjuvants, and extensively investigated their functions as chemoattractants of immune cells and boosters of vaccine-mediated protection. Here, we evaluated the effect of Granulocyte-macrophage Colony-Stimulating Factor (GmCSF) as an influenza vaccine adjuvant in BALB/c mice.Method and ResultsFemale BALB/c mice were immunized with killed vaccine together with a murine GmCSF gene delivered by human endogenous retrovirus (HERV) envelope coated baculovirus (1×107 FFU AcHERV-GmCSF, i.m.) and were compared with mice immunized with the killed vaccine alone. On day 14, immunized mice were challenged with 10 median lethal dose of mouse adapted pH1N1 virus. The vaccination together with GmCSF treatment exerted a strong adjuvant effect on humoral and cellular immune responses. In addition, the vaccinated mice together with GmCSF were fully protected against infection by the lethal influenza pH1N1 virus.ConclusionThus, these results indicate that AcHERV-GmCSF is an effective molecular adjuvant that augments immune responses against influenza virus.
A PnFL-2 gene is a single copy gene that was isolated from the flower-induced cotyledons of Pharbitis nil. The deduced amino acid sequence of the PnFL-2 includes two functional domains, a single TIFY (ZIM) motif and nuclear localization signal CCT motif. The TIFY family is a novel plant specific gene involved in the regulation of diverse plant specific biological process, such as development and responses to phytochrome, implying that PnFL-2 may play a role in the mechanism of flowering induction. Subcelluar localization analysis confirmed that PnFL-2 is localized in the nucleus. Expression of PnFL-2 was induced during 16h-long inductive night, whereas accumulation of its transcripts significantly abolished by night-break, completely eliminated flowering induction of Pharbitis nil. Accumulation of its induced PnFL-2 transcripts depends on tissue, such as the cotyledons and the leaves. To study its biological functions directly, we have characterized gain of function transgenic over-expression plants for PnFL-2 in Arabidopsis. Transgenic plants that constitutively over-express PnFL-2 displayed slightly early flowering time under the long day condition as compare to those in wild type. These results indicate that PnFL-2 is potentially involved in the regulation of flowering induction in Pharbitis nil.
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