Load capacity improvements in transcriptional systems using discrete-time L1-adaptive control

DNA-based circuits relying on predictable thermodynamics and kinetics of DNA strand interactions impart flexibility in synthesizing synthetic biological constructs and in coupling these circuits to in vivo processes [1, 2, 6, 7]. Here, we focus on the synthetic Kim-Winfree oscillator network, illustrated in Fig. 1(i), which is a simple but effective coupled oscillator system in which two DNA switches SW1 and SW2 are coupled through activator and inhibitor blocks realized by RNA signals and auxiliary DNA species (see [3]). A typical experimental realization is closed in the sense that once the operation starts, we do not either add any chemicals, especially NTP fuel, externally into the wet-lab apparatus or remove any chemicals, especially waste products, from the apparatus. Within the closed system, the oscillations are bound to die out sooner or later diminishing NTP fuel eventually stops supporting the production of RNA signals and accumulating waste products clog down the toeholds and, as a result, adversely affect the signal propagation. Furthermore, the oxidation effects and the pH variations tend to deactivate the enzymes. Loading poses an additional challenge since it increases the order and the uncertainty of the system indeed, these oscillators have recently been used in [8] to drive conformational changes of a DNA nanomechanical device called DNA tweezers. We show how L1-adaptive control can be used to mitigate these effects

Aerospace medicine and biology: A continuing bibliography with indexes, supplement 197, September 1979

This bibliography lists 193 reports, articles, and other documents introduced into the NASA scientific and technical information system in August 1979

DNA Logic-A novel approach to semiconductor based genetics

In the coming years, genetic test results will be increasingly used as indicators that influence medical decision-making. With chronic disease on the rise and the continuing global spread of infectious disease, novel instruments able to detect relevant mutations in a point-of-care setting are being developed to facilitate this increased demand in personalized health care. However, diagnosis for such demand often requires laboratory facilities and skilled personnel, meaning that diagnostic tests are restricted by time and access. This thesis presents a novel configuration for Ion sensitive Field Effect Transistors (ISFETs) to be used as a threshold detector during nucleic acid base pairs match. ISFET-based inverters are used as reaction threshold detectors to convey the chemical reaction level to a logic output once a threshold has been reached. Using this method, novel DNA logic functions are derived for nucleotides allowing local digital computations. The thesis also presents business models that enable such technology to be utilised in point of care applications, and experiment as results and business models given for an HIV point of care example are proposed

Aerospace Medicine and Biology: A continuing bibliography with indexes, supplement 192

This bibliography lists 247 reports, articles, and other documents introduced into the NASA scientific and technical information system in March 1979

Whole synthetic pathway engineering of recombinant protein production

The output from protein biomanufacturing systems is a function of total host cell biomass synthetic capacity and recombinant protein production per unit cell biomass. In this study, we describe how these two properties can be simultaneously optimized via design of a product-specific combination of synthetic DNA parts to maximize flux through the protein synthetic pathway and the use of a host cell chassis with an increased capability to synthesize both cell and product biomass. Using secreted alkaline phosphatase (SEAP) production in Chinese hamster ovary cells as our example, we demonstrate how an optimal composition of input components can be assembled from a minimal toolbox containing rationally designed promoters, untranslated regions, signal peptides, product coding sequences, cell chassis, and genetic effectors. Product titer was increased 10-fold, compared with a standard reference system by (a) identifying genetic components that acted in concert to maximize the rates of SEAP transcription, translation, and translocation, (b) selection of a cell chassis with increased biomass synthetic capacity, and (c) engineering the host cell factory's capacity for protein folding and secretion. This whole synthetic pathway engineering process to design optimal expression cassette-chassis combinations should be applicable to diverse recombinant protein and host cell-type contexts

Aerospace medicine and biology: A continuing bibliography with indexes

This bibliography lists 223 reports, articles, and other documents introduced into the NASA scientific and technical information system in December, 1988

Domestication and divergence of Saccharomyces cerevisiae beer yeasts

Whereas domestication of livestock, pets, and crops is well documented, it is still unclear to what extent microbes associated with the production of food have also undergone human selection and where the plethora of industrial strains originates from. Here, we present the genomes and phenomes of 157 industrial Saccharomyces cerevisiae yeasts. Our analyses reveal that today's industrial yeasts can be divided into five sublineages that are genetically and phenotypically separated from wild strains and originate from only a few ancestors through complex patterns of domestication and local divergence. Large-scale phenotyping and genome analysis further show strong industry-specific selection for stress tolerance, sugar utilization, and flavor production, while the sexual cycle and other phenotypes related to survival in nature show decay, particularly in beer yeasts. Together, these results shed light on the origins, evolutionary history, and phenotypic diversity of industrial yeasts and provide a resource for further selection of superior strains

Control Theory for Synthetic Biology: Recent Advances in System Characterization, Control Design, and Controller Implementation for Synthetic Biology

Living organisms are differentiated by their genetic material-millions to billions of DNA bases encoding thousands of genes. These genes are translated into a vast array of proteins, many of which have functions that are still unknown. Previously, it was believed that simply knowing the genetic sequence of an organism would be the key to unlocking all understanding. However, as DNA sequencing technology has become affordable, it has become clear that living cells are governed by complex, multilayered networks of gene regulation that cannot be deduced from sequence alone. Synthetic biology as a field might best be characterized as a learn-by-building approach, in which scientists attempt to engineer molecular pathways that do not exist in nature. In doing so, they test the limits of both natural and engineered organisms

Physiologic, psychologic, and oxidative stress responses to multimodal exercise in an endometrial cancer survivor undergoing high-dose chemotherapy: a case study

Exercise training, as a rehabilitative strategy, may be a vital factor in combatting the noxious toxicities related to cancer treatment. Research employing mixed modality exercise consistently demonstrates health benefits ranging from enhanced aerobic capacity and muscular strength to attenuated psychological distress. The primary aim of this case study was to examine the effects of exercise training on physiological and psychological parameters in an endometrial cancer survivor undergoing high-dose chemotherapy. Secondly, believed to play a role in toxicity development and progression, oxidative stress has yet to be studied in cancer survivors. The second aim of this case study was to determine the effects of exercise on a selection of blood parameters including reactive carbonyl derivatives, a marker of protein degradation. The case study subject was a 60-yr-old female, diagnosed with stage IIIC1 endometrial cancer, undergoing chemotherapy (paclitaxel and carboplatin, [PC]). Assessments (e.g., body composition, VO2peak, 1-RM, pulmonary spirometry, fatigue and quality of life [QoL] indexes) were performed 1 day prior to the first PC cycle and again at 3- and 6-months. Exercise was performed 3 days/week (Tues, Thurs, and Sat) of each week for 21 weeks. Each 1 hour session consisted of treadmill walking and total body strength exercises. Blood pressure (BP), heart rate (HR), and ratings of perceived exertion (RPE) were recorded during training sessions. Over 141 calendar days, the case study completed 63 exercise sessions (~45%). Physical characteristics remained relatively stable. VO2peak improved approx. 16% over the 6-month period (23.0 to 27.3 mL·kg-1·min-1). Decrements in lung function were evidenced by spirometry parameters, FVC (-10%) and FEV1 (-9%). Changes in global fatigue were not significant (p=.17) but affective and sensory subscales increased significantly between baseline and 3-months (p=.05). Subject-reported RPE scores during Phase I Nadir training were significantly lower than the prescribed range (p=.008). Also, Phase II Nadir scores were significantly lower than those reported in phase I (p=.003), suggesting the capacity to maintain exercise participation. Comparison of mean arterial pressure (MAP) between Phases I and II were not significantly different for Nadir (p=.74) or standard (p=.12) training. MAP was significantly reduced for Nadir compared to standard training (p=.005). ELISA results of oxidative stress markers illustrated a significant reduction of protein carbonyl concentration with programmed exercise (p=.03). Reduced protein oxidation may explicate the observed gains in muscular strength. Furthermore, results of complete hematology panels (e.g., WBC, RBC, HGB, and PLT) depicted a collective attenuation of treatment-related damage as per the recurring escalation toward initial (e.g., baseline) cellular concentrations. Multimodal exercise, as a remedial approach, appears to be well tolerated and appropriate for the preservation of physical and psychological capacities in an endometrial cancer survivor undergoing treatment