Robust Design of Biological Circuits: Evolutionary Systems Biology Approach

Artificial gene circuits have been proposed to be embedded into microbial cells that function as switches, timers, oscillators, and the Boolean logic gates. Building more complex systems from these basic gene circuit components is one key advance for biologic circuit design and synthetic biology. However, the behavior of bioengineered gene circuits remains unstable and uncertain. In this study, a nonlinear stochastic system is proposed to model the biological systems with intrinsic parameter fluctuations and environmental molecular noise from the cellular context in the host cell. Based on evolutionary systems biology algorithm, the design parameters of target gene circuits can evolve to specific values in order to robustly track a desired biologic function in spite of intrinsic and environmental noise. The fitness function is selected to be inversely proportional to the tracking error so that the evolutionary biological circuit can achieve the optimal tracking mimicking the evolutionary process of a gene circuit. Finally, several design examples are given in silico with the Monte Carlo simulation to illustrate the design procedure and to confirm the robust performance of the proposed design method. The result shows that the designed gene circuits can robustly track desired behaviors with minimal errors even with nontrivial intrinsic and external noise

Hydrate-based CO2 (carbon dioxide) capture from IGCC (integrated gasification combined cycle) synthesis gas using bubble method with a set of visual equipment

The hydrate-based carbon dioxide (CO2) capture from the integrated gasification combined cycle (IGCC) synthesis gas using the bubble method is investigated with a set of visual equipment in this work. The gas bubble is created with a bubble plate on the bottom of the equipment. By the visual equipment, the hydrate formation and the hydrate shape are visually captured. With the move of the gas bubble from the bottom to the top of the reactor, gas hydrate forms firstly from the gas-liquid boundary around the bubble, then the hydrate gradually grows up and piles up in the bottom side of the bubble to form a hydrate particle. The gas hydrate shape is affected by the gas flow rate. The hydrate is acicular crystal at the low gas flow rate while the hydrate is fine sand-like crystal at the high gas flow rate. The bubble size and the gas flow rate have an obvious impact on the hydrate-based CO2 separation process. The experimental results show the gas bubble of 50 mu m and the gas flow rate of 6.75 mL/min/L are ideal for CO2 capture from IGCC synthesis gas under the condition of 3.0 MPa and 274.15 K. (C) 2012 Elsevier Ltd. All rights reserved.</p

Clinicopathological features and CCT2 and PDIA2 expression in gallbladder squamous/adenosquamous carcinoma and gallbladder adenocarcinoma

BACKGROUND: Gallbladder cancer (GBC) is a relatively uncommon carcinoma among gastrointestinal cancers and usually has a rather poor prognosis. The most common subtype of GBC is adenocarcinoma (AC), which accounts for about 90% of GBC. Squamous carcinoma/adenosquamous carcinoma (SC/ASC) are comparatively rare histopathological subtypes of GBC. The clinicopathological features and biological behaviors of SC/ASC have not been well-characterized. No molecular biomarkers are currently available for predicting the progression, metastasis, and prognosis of the SC/ASC subtype of GBC. METHODS: We examined the expression levels of CCT2 and PDIA3 by immunohistochemistry (IHC) staining in human GBC tissue samples collected from 46 patients with SC/ASC and evaluated the clinicopathological significance of both CCT2 and PDIA3 expression in the SC/ASC subtypes of GBC by Kaplan-Meier analysis and multivariate Cox regression analysis. For comparison, we included specimens from 80 AC patients in our study to investigate the specificity of CCT2 and PDIA3 expression in GBC subtypes. RESULTS: We found that the positive expression of CCT2 and PDIA3 was significantly associated with clinicopathological features of both SC/ASC and AC specimens, including high TNM stage and lymph node metastasis. Univariate analysis revealed that the two-year survival rate was significantly lower for patients with positive expression of CCT2 and PDIA3 than for those with negative expression. Multivariate analysis also indicated that the positive expression of CCT2 and PDIA3 was negatively correlated with poor postoperative patient survival and positively correlated with high mortality. CONCLUSIONS: Our study suggests that positive expression of CCT2 or PDIA3 is associated with tumor progression and the clinical behavior of gallbladder carcinoma. Therefore, CCT2 and PDIA3 could be potentially important diagnostic and prognostic biomarkers for both SC/ASC and AC subtypes of GBC

Rv1985c, a promising novel antigen for diagnosis of tuberculosis infection from BCG-vaccinated controls

<p>Abstract</p> <p>Background</p> <p>Antigens encoded in the region of difference (RD) of <it>Mycobacterium tuberculosis </it>constitute a potential source of specific antigens for immunodiagnosis. In the present study, recombinant protein Rv1985c from RD2 was cloned, expressed, purified, immunologically characterized and investigated for its potentially diagnostic value for tuberculosis (TB) infection among BCG-vaccinated individuals.</p> <p>Methods</p> <p>T-cell response to Rv1985c was evaluated by IFN-γ ELISPOT in 56 TB patients, 20 latent TB infection (LTBI) and 30 BCG-vaccinated controls in comparison with the commercial T-SPOT. <it>TB </it>kit. Humoral response was evaluated by ELISA in 117 TB patients, 45 LTBI and 67 BCG-vaccinated controls, including all those who had T-cell assay, in comparison with a commercial IgG kit.</p> <p>Results</p> <p>Rv1985c was specifically recognized by cellular and humoral responses from both TB and LTBI groups compared with healthy controls. Rv1985c IgG-ELISA achieved 52% and 62% sensitivity respectively, which outperformed the sensitivity of PATHOZYME-MYCO kit (34%) in detecting active TB (P = 0.011), whereas IFN-γ Rv1985c-ELISPOT achieved 71% and 55% sensitivity in detecting active and LTBI, respectively. Addition of Rv1985c increased sensitivities of ESAT-6, CFP-10 and ESAT-6/CFP-10 combination in detecting TB from 82.1% to 89.2% (P = 0.125), 67.9% to 87.5% (P < 0.001) and 85.7% to 92.9% (P = 0.125), respectively.</p> <p>Conclusions</p> <p>In conclusion, Rv1985c is a novel antigen which can be used to immunologically diagnose TB infection along with other immunodominant antigens among BCG-vaccinated population.</p