Automated design of gene circuits with optimal mushroom-bifurcation behavior

Recent advances in synthetic biology are enabling exciting technologies, including the next generation of biosensors, the rational design of cell memory, modulated synthetic cell differentiation, and generic multifunctional biocircuits. These novel applications require the design of gene circuits leading to sophisticated behaviors and functionalities. At the same time, designs need to be kept minimal to avoid compromising cell viability. Bifurcation theory addresses such challenges by associating circuit dynamical properties with molecular details of its design. Nevertheless, incorporating bifurcation analysis into automated design processes has not been accomplished yet. This work presents an optimization-based method for the automated design of synthetic gene circuits with specified bifurcation diagrams that employ minimal network topologies. Using this approach, we designed circuits exhibiting the mushroom bifurcation, distilled the most robust topologies, and explored its multifunctional behavior. We then outline potential applications in biosensors, memory devices, and synthetic cell differentiation

Functional Effects of Nanoparticle Exposure on Calu-3 Airway Epithelial Cells

High concentrations of manufactured carbon nanoparticles (CNP) are known to cause oxidative stress, inflammatory responses and granuloma formation in respiratory epithelia. To examine the effects of lower, more physiologically relevant concentrations, the human airway epithelial cell line, Calu-3, was used to evaluate potential alterations in transepithelial permeability and cellular function of airway epithelia after exposure to environmentally realistic concentrations of carbon nanoparticles. Three common carbon nanoparticles, fullerenes, single- and multi-wall carbon nanotubes (SWCNT, MWCNT) were used in these experiments. Electrophysiological measurements were performed to assay transepithelial electrical resistance (TEER) and epinephrine-stimulated chloride (Cl(-)) ion secretion of epithelial cell monolayers that had been exposed to nanoparticles for three different times (1 h, 24 h and 48 h) and over a 7 log unit range of concentrations. Fullerenes did not have any effect on the TEER or stimulated ion transport. However, the carbon nanotubes (CNT) significantly decreased TEER and inhibited epinephrine-stimulated Cl(-) secretion. The changes were time dependent and at more chronic exposures caused functional effects which were evident at concentrations substantially lower than have been previously examined. The functional changes manifested in response to physiologically relevant exposures would inhibit mucociliary clearance mechanisms and compromise the barrier function of airway epithelia

A candidate gene-based association study of introgressed pod shatter resistance in Brassica napus

267-276Yield losses at maturity due to unsynchronized pod shattering remain a major rapeseed breeding challenge. Variation for shatter resistance in the germplasm collections is inadequate for breeding manipulations. We have recently transferred resistance to pod shattering from Brassica carinata to Brassica napus. Introgression lines (ILs) were phenotyped for shatter resistance using the pendulum machine. Introgressive breeding was successful in enhancing rupture energy in the ILs, which varied from 1.8 to 7.2 milli Joules (mJ) for Environment 1 (E1) and 2.7 to 6.5 mJ for E2 while the corresponding values for natural B. napus ranged from 2.2-3.5 mJ (E1) and 2.2-4.3 mJ (E2), respectively. B. carinata had average rupture energy of 6.3 mJ (pooled over environments). On the basis of data averaged over two environments, I2 (6.3 mJ), I3 (5.2 mJ), I8 (5.6 mJ), I22 (5.1 mJ), I32 (5.2 mJ) and I41 (5.2 mJ) appeared very promising as germplasm resources for future breeding. Significant marker trait association between candidate gene NAC NAM (no apical meristem, Petunia), ATAF1/2 (Arabidopsis thaliana activating factor) and CUC2 (cup-shaped cotyledon, Arabidopsis) and rupture energy explained 19% of variation for the trait. IND3 (indehescent 3) also appeared to be associated with rupture energy under E1. These polymorphisms serve as encouraging candidates for developing molecular markers useful in marker-assisted deployment of introgressed shatter resistance

Evaluation de l’utilisation du pepsinogène sanguin comme biomarqueur de l’intégrité de la muqueuse gastrique chez le porc. 2. Méthodes de dosage et intérêt en pathologie porcine

Pepsinogen is one component of the gastric juice which participes in the digestion. This macromolecule enters the blood circulation in a small measurable quantities in healthy subjects. Therefore, blood pepsinogen is claimed to be an indicator of the integrity of the gastric mucosa. This paper was written to review the use of porcine in the diagnostic of stomach ulcers and Hyostrongylus rubidus infection. The methods of measurement of blood pepsinogen and the diagnostic values are discussed.Le pepsinogène est une composante du suc gastrique qui participe à la digestion des protéines alimentaires. Il est aussi parmi les macromolécules qui entrent dans la circulation sanguine en faibles quantités mesurables chez des sujets normaux. Son dosage est utilisé dans la mise en évidence de certaines pathologies gastriques chez le porc. Cette synthèse décrit les méthodes de dosage et des valeurs sériques ou plasmatiques du pepsinogène en relation avec des ulcères ou les infestations parasitaires à Hyostrongylus rubidus chez le por

Dentinal microcracks after root canal instrumentation using instruments manufactured with different NiTi alloys and the SAF system: A systematic review

Aim: The aim of this systematic analysis was to assess the prevalence of dentinal microcracks at various levels (3, 6, and 9mm from the apex) after using instruments made with conventional, R-Phase, and M-Wire NiTi alloys and the SAF system. Materials and Methods: Electronic searches were conducted in the databases Embase, Cochrane Library, Scopus, PubMed, andWeb of Science. To arrange search methods, “MeSH” terms and/or keywords typically associated with the subject were paired with the Boolean operators “AND” and “OR.” Additional searches were conducted on the websites of four separate endodontic journals. After reading the titles and excluding duplicates, 1000 of the 1343 documents originally found were eliminated. Upon reviewing the abstracts, 310 of the remaining 343 experiments were also eliminated. Based on qualifying requirements, only 13 of the remaining 33 articles were included in the qualitative review. Results: All systems triggered dentinal microcracks; however, when chemo-mechanical preparation was performed using Self-Adjusting File (SAF) and systems manufactured with R-phase technology—K3XF and Twisted File Adaptive (TFA)—less of these defects were found when compared to those manufactured with traditional NiTi—ProTaper Universal and Mtwo—and with M-Wire—ProTaper Next, Reciproc, and WaveOne. Conclusions: A lower prevalence of dentinal microcracks was observed after using SAF and endodontic systems manufactured with R-phase

Optimization of the cycle time of robotics resistance spot welding for automotive applications

In the automobile manufacturing industry, resistance spot welding (RSW) is widely used, especially to build the car's body. The RSW is a standard and wide‐ranging joining technique in several assembling ventures, showing a wide range of possibilities for a competent procedure. Robots are commonly used for spot welding in various industrial applications. After completing assembling design, interest increases to improve the designed processes, cost‐reduction, environmental impact, and increase time productivity when all is said to be done. In this paper, the robot movement between two welding points, a path followed while spotting, gripping and payload‐carrying activities, numbers of holds, moves, and a possibility to enhance interaction between four Robots were analyzed using an offline Robot simulation software 'DELMIA‐V5'. The body shop assembly line of the SML ISUZU plant has four robots that perform about 209 welding spots in 532 sec. The optimal model reduced the whole welding cycle time by 68 sec, and after modification and proper sequencing, a12.7% reduction in cycle time was achieved. The offline Robot simulation software 'DELMIA‐V5' has good potential to produce optimal algorithms while saving precious time. It enables an organization to promote higher quality and to encourage meaningful creativity by reducing design flaws

A prospective study of risk factor profile & incidence of deep venous thrombosis among medically-ill hospitalized patients at a tertiary care hospital in Northern India

Background & Objective: Hospitalization for medical-illness is associated with an increased risk of deep venous thrombosis (DVT). However, there are no published data from India addressing at this issue. We sought to study the risk factor profile and the incidence of DVT among hospitalized medically-ill patients, a tertiary care hospital in northern India. Methods: All adults admitted to the medical wards and intensive care unit with level 1 or 2 mobility over a period of two years (July 2006 to July 2008) at the All India Institute of Medical Sciences hospital, New Delhi, were prospectively studied. Patients having DVT at admission or an anticipated hospital stay less than 48 h were excluded. The presence of clinical risk factors for DVT was recorded and laboratory evaluation was done for hypercoagulable state. A routine surveillance venous compression Doppler ultrasonography was performed 12 ± 8 days after hospital admission. Results: Of the 163 patients, 77 (47%) had more than one risk factor for DVT. Five (3%) patients developed DVT; none of them had symptomatic DVT. None of these patients received anticoagulation prior to the development of DVT. The mean age of those who developed DVT was 40 ± 13 (25-50) yr; two of five were male. The incidence rate of DVT was 2.7 per 1000 person-days of hospital stay [95% confidence interval (CI): 0.87 to 6.27]. None of the factors was found to be significantly associated with the risk of DVT. Interpretation & Conclusion: In our setting, although many hospitalized medically-ill patients had risk factors for DVT, the absolute risk of DVT was low compared to the western population but clearly elevated compared to non hospitalized patients. Large studies from India are required to confirm our findings

Robot-assisted kidney transplantation (RAKT) from living donors using right- versus left-sided grafts: Results from the EAU Robotic Urology Section (ERUS)-RAKT working group

Introduction & Objectives: RAKT from living donors (LD) is increasingly performed in selected centers with experience in robotic surgery and kidney transplantation (KT). Of note, KT from LD using right-sided graft (RSG) is challenging due to the brevity of the right renal vein and has been associated with a higher risk of perioperative complications in selected series. In this scenario, RAKT may facilitate the performance of vascular anastomoses in case of short renal vessels thanks to the advantages of the robotic platform. However, the evidence on the safety and feasibility of RAKT using RSGs is lacking. The aim of this study is to compare the surgical and early perioperative outcomes after RAKT from LD using right- vs. left-sided grafts in a large prospective multicenter cohort (ERUS-RAKT working group)

Detection of autoantibodies against reactive oxygen species modified glutamic acid decarboxylase-65 in type 1 diabetes associated complications

<p>Abstract</p> <p>Background</p> <p>Autoantibodies against glutamate decarboxylase-65 (GAD₆₅Abs) are thought to be a major immunological tool involved in pathogenic autoimmunity development in various diseases. GAD₆₅Abs are a sensitive and specific marker for type 1 diabetes (T1D). These autoantibodies can also be found in 6-10% of patients classified with type 2 diabetes (T2D), as well as in 1-2% of the healthy population. The latter individuals are at low risk of developing T1D because the prevalence rate of GAD₆₅Abs is only about 0.3%. It has, therefore, been suggested that the antibody binding to GAD₆₅in these three different GAD₆₅Ab-positive phenotypes differ with respect to epitope specificity. The specificity of reactive oxygen species modified GAD₆₅(ROS-GAD₆₅) is already well established in the T1D. However, its association in secondary complications of T1D has not yet been ascertained. Hence this study focuses on identification of autoantibodies against ROS-GAD₆₅(ROS-GAD₆₅Abs) and quantitative assays in T1D associated complications.</p> <p>Results</p> <p>From the cohort of samples, serum autoantibodies from T1D retinopathic and nephropathic patients showed high recognition of ROS-GAD₆₅as compared to native GAD₆₅(N-GAD₆₅). Uncomplicated T1D subjects also exhibited reactivity towards ROS-GAD₆₅. However, this was found to be less as compared to the binding recorded from complicated subjects. These results were further proven by competitive ELISA estimations. The apparent association constants (AAC) indicate greater affinity of IgG from retinopathic T1D patients (1.90 × 10^-6M) followed by nephropathic (1.81 × 10^-6M) and uncomplicated (3.11 × 10^-7M) T1D patients for ROS-GAD₆₅compared to N-GAD₆₅.</p> <p>Conclusion</p> <p>Increased oxidative stress and blood glucose levels with extended duration of disease in complicated T1D could be responsible for the gradual formation and/or exposing cryptic epitopes on GAD₆₅that induce increased production of ROS-GAD₆₅Abs. Hence regulation of ROS-GAD₆₅Abs could offer novel tools for analysing and possibly treating T1D complications.</p