1,554 research outputs found
Parrondo's games with chaotic switching
This paper investigates the different effects of chaotic switching on
Parrondo's games, as compared to random and periodic switching. The rate of
winning of Parrondo's games with chaotic switching depends on coefficient(s)
defining the chaotic generator, initial conditions of the chaotic sequence and
the proportion of Game A played. Maximum rate of winning can be obtained with
all the above mentioned factors properly set, and this occurs when chaotic
switching approaches periodic behavior.Comment: 11 pages, 9 figure
Transcriptional networks governing plant metabolism
AbstractEfficiently obtaining and utilizing energy and elements is critical for an organism to maximize its fitness. Optimizing these processes requires precise regulation and coordination of an organismâs metabolic networks in response to diverse environmental conditions and developmental stages. Metabolic regulation is often considered to largely occur by allosteric feedback where the metabolites directly influence the enzymes function. Recent work is showing that there is also an extensive role for transcriptional control of the enzyme encoding genes to construct the metabolic network in response to developmental and environmental stimuli. Within this review, we go through the extensive evidence of how transcription can coordinate the necessary metabolic shifts required to coordinate a plants metabolism with its development and environment. Additionally, we discuss evidence that the metabolites not only feed-back regulate the enzymes but also the upstream transcriptional processes, possibly to stabilize the system
Endoglin Is Essential for the Maintenance of Self-Renewal and Chemoresistance in Renal Cancer Stem Cells.
Renal cell carcinoma (RCC) is a deadly malignancy due to its tendency to metastasize and resistance to chemotherapy. Stem-like tumor cells often confer these aggressive behaviors. We discovered an endoglin (CD105)-expressing subpopulation in human RCC xenografts and patient samples with a greater capability to form spheres in vitro and tumors in mice at low dilutions than parental cells. Knockdown of CD105 by short hairpin RNA and CRISPR/cas9 reduced stemness markers and sphere-formation ability while accelerating senescence in vitro. Importantly, downregulation of CD105 significantly decreased the tumorigenicity and gemcitabine resistance. This loss of stem-like properties can be rescued by CDA, MYC, or NANOG, and CDA might act as a demethylase maintaining MYC and NANOG. In this study, we showed that Endoglin (CD105) expression not only demarcates a cancer stem cell subpopulation but also confers self-renewal ability and contributes to chemoresistance in RCC
Qualitative Study on Chinese Studentsâ Perception of U.S. University Life
This qualitative research was conducted on Chinese international students preparing to study in the United States about their expectation and perception of American universities. It explored motivation for pursuing degrees in the United States, expectations of life in the United States, and plans post-graduation. Findings suggest that these students foresee U.S. classes to be rigorous due to two notable barriers: English proficiency issue and difference in learning environment. Furthermore, the students promoted desires to build relationships with domestic students but already internalized beliefs that this action was unlikely. They presumed that most networking would occur with co-nationals due to comfort and ease. Finally, parental expectations emerged as a significant factor that influence Chinese international studentsâ desire to study in the United States and post-graduation plans
The Feasibility and Validity of a Remote Pulse Oximetry System for Pulmonary Rehabilitation: A Pilot Study
Pulmonary rehabilitation is an effective treatment for people with chronic obstructive pulmonary disease. However, access to these services is limited especially in rural and remote areas. Telerehabilitation has the potential to deliver pulmonary rehabilitation programs to these communities. The aim of this study was threefold: to establish the technical feasibility of transmitting realtime pulse oximetry data, determine the validity of remote measurements compared to conventional face-to-face measures, and evaluate the participants' perception of the usability of the technology. Thirty-seven healthy individuals participated in a single remote pulmonary rehabilitation exercise session, conducted using the eHAB telerehabilitation system. Validity was assessed by comparing the participant's oxygen saturation and heart rate with the data set received at the therapist's remote location. There was an 80% exact agreement between participant and therapist data sets. The mean absolute difference and Bland and Altman's limits of agreement fell within the minimum clinically important difference for both oxygen saturation and heart rate values. Participants found the system easy to use and felt confident that they would be able to use it at home. Remote measurement of pulse oximetry data for a pulmonary rehabilitation exercise session was feasible and valid when compared to conventional face-toface methods
From UV to NIR: A Full-Spectrum Metal-Free Photocatalyst for Efficient Polymer Synthesis in Aqueous Conditions
Photoâmediation offers unparalleled spatiotemporal control over controlled radical polymerizations (CRP). Photoâinduced electron/energy transfer reversible additionâfragmentation chain transfer (PETâRAFT) polymerization is particularly versatile owing to its oxygen tolerance and wide range of compatible photocatalysts. In recent years, broadbandâ and nearâinfrared (NIR)âmediated polymerizations have been of particular interest owing to their potential for solarâdriven chemistry and biomedical applications. In this work, we present the first example of a novel photocatalyst for both full broadbandâ and NIRâmediated CRP in aqueous conditions. Wellâdefined polymers were synthesized in water under blue, green, red, and NIR light irradiation. Exploiting the oxygen tolerant and aqueous nature of our system, we also report PETâRAFT polymerization at the microliter scale in a mammalian cell culture medium
Two-Plasmid Packaging System for Recombinant Adeno-Associated Virus
A number of packaging systems are available for production of recombinant adeno-associated virus vectors (rAAVs). Among these, the use of a two-plasmid cotransfection system, in which Rep and Cap genes and Ad helper genes are on the same plasmid, has not been frequently employed for good manufacturing practices (GMP) production, even though it presents some practical advantages over the common three-plasmid (triple) transfection method. To confirm and expand the utility of the two-plasmid system, we generated GMP-compatible versions of this system and used those package reporter genes in multiple capsid variants in direct comparison with triple transfection. Vector yields, purity, and empty-to-full ratios were comparable between double and triple transfection methods for all capsid variants tested. We performed an in vivo side-by-side comparison of double and triple transfection vectors following both intravenous injection and intramuscular injection in mice. Expression and transduction were evaluated in muscle and liver 4 weeks after injection. Additional studies of bioactivity were conducted in vivo using packaged vectors carrying a variety of cargos, including the therapeutic transgene, microRNA, and single- or double-stranded vector. Results showed that cargos packaged using double transfection were equivalently bioactive to those packaged using a triple transfection system. In conclusion, these data suggest the utility of midrange (1E12-1E16) GMP-compatible packaging of adeno-associated virus (AAV) vectors for several AAV capsids
The Spin-Resolved Atomic Velocity Distribution and 21-cm Line Profile of Dark-Age Gas
The 21-cm hyperfine line of atomic hydrogen (HI) is a promising probe of the
cosmic dark ages. In past treatments of 21-cm radiation it was assumed the
hyperfine level populations of HI could be characterized by a
velocity-independent ``spin temperature'' T_s determined by a competition
between 21-cm radiative transitions, spin-changing collisions, and (at lower
redshifts) Lyman-alpha scattering. However we show here that, if the
collisional time is comparable to the radiative time, the spin temperature will
depend on atomic velocity, T_s=T_s(v), and one must replace the usual hyperfine
level rate equations with a Boltzmann equation describing the spin and velocity
dependence of the HI distribution function. We construct here the Boltzmann
equation relevant to the cosmic dark ages and solve it using a basis-function
method. Accounting for the actual spin-resolved atomic velocity distribution
results in up to a 2 per cent suppression of the 21-cm emissivity, and a
redshift and angular-projection dependent suppression or enhancement of the
linear power spectrum of 21-cm fluctuations of up to 5 per cent. The effect on
the 21-cm line profile is more dramatic -- its full-width at half maximum
(FWHM) can be enhanced by up to 60 per cent relative to the
velocity-independent calculation. We discuss the implications for 21-cm
tomography of the dark ages.Comment: 25 pages, 6 figures, submitted to Mon. Not. Roy. Astron. So
Origin and Control of Chemoselectivity in Cytochrome c Catalyzed Carbene Transfer into SiâH and NâH bonds
A cytochrome c heme protein was recently engineered to catalyze the formation of carbonâsilicon bonds via carbene insertion into SiâH bonds, a reaction that was not previously known to be catalyzed by a protein. High chemoselectivity toward CâSi bond formation over competing CâN bond formation was achieved, although this trait was not screened for during directed evolution. Using computational and experimental tools, we now establish that activity and chemoselectivity are modulated by conformational dynamics of a protein loop that covers the substrate access to the ironâcarbene active species. Mutagenesis of residues computationally predicted to control the loop conformation altered the proteinâs chemoselectivity from preferred silylation to preferred amination of a substrate containing both NâH and SiâH functionalities. We demonstrate that information on protein structure and conformational dynamics, combined with knowledge of mechanism, leads to understanding of how non-natural and selective chemical transformations can be introduced into the biological world
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Phase I study of nab-paclitaxel, gemcitabine, and bevacizumab in patients with advanced cancers.
BackgroundWe performed a phase I modified 3â+â3 dose escalation study to evaluate the safety and activity of bevacizumab plus gemcitabine and nab-paclitaxel in patients with advanced solid tumours.MethodsPatients were given fixed dose gemcitabine plus increasing doses of nab-paclitaxel and bevacizumab. Toxicity, response, and association with VEGF polymorphism was analysed.ResultsThe study enrolled 110 patients who had undergone a median of 3 prior lines of therapy. The median age was 60 years (range, 17-85 years), and 55 patients (50%) had gemcitabine-refractory disease. We observed 3 dose-limiting toxicities during dose escalation and 3 DLTs in expansion cohorts. Dose escalation to 150âmg/m2 nab-paclitaxel and 15âmg/kg bevacizumab with 1000âmg/m2 of gemcitabine was well tolerated with no MTD. One patient with gemcitabine-refractory peritoneal papillary carcinoma had a complete response, 13 patients (13%) had partial responses, and 54 patients (52%) had stable disease â„12 weeks. Exploratory VEGF single nucleotide polymorphism (SNP) analysis was performed on 13 patients.ConclusionsThe combination of gemcitabine, nab-paclitaxel, and bevacizumab is safe, well-tolerated, and has activity in advanced malignancies, including gemcitabine-refractory tumours. Based on this study, the recommended phase 2 dose is gemcitabine 1000âmg/m2, nab-paclitaxel 125âmg/m2, and bevacizumab 15âmg/kg. VEGF polymorphism data should be evaluated in future bevacizumab-based trials
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