Different populations of RNA polymerase II in living mammalian cells

RNA polymerase II is responsible for transcription of most eukaryotic genes, but, despite exhaustive analysis, little is known about how it transcribes natural templates in vivo. We studied polymerase dynamics in living Chinese hamster ovary cells using an established line that expresses the largest (catalytic) subunit of the polymerase (RPB1) tagged with the green fluorescent protein (GFP). Genetic complementation has shown this tagged polymerase to be fully functional. Fluorescence loss in photobleaching (FLIP) reveals the existence of at least three kinetic populations of tagged polymerase: a large rapidly-exchanging population, a small fraction resistant to 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole (DRB) but sensitive to a different inhibitor of transcription (i.e. heat shock), and a third fraction sensitive to both inhibitors. Quantitative immunoblotting shows the largest fraction to be the inactive hypophosphorylated form of the polymerase (i.e. IIA). Results are consistent with the second (DRB-insensitive but heat-shock-sensitive) fraction being bound but not engaged, while the third (sensitive to both DRB and heat shock) is the elongating hyperphosphorylated form (i.e. IIO)

Critical Evaluation of Euler-Euler and Euler-Lagrangian Modelling Strategies in a 2-D Gas Fluidized Bed

Two-phase granular systems are commonly encountered in industry, and fluidized beds are particularly important due to their excellent heat and mass transfer characteristics. Here, we critically evaluate the differences between two modelling strategies, Euler-Euler and Euler-Lagrangian models. Euler-Euler simulations were performed using MFIX and an in-house code was used for Euler-Lagrangian simulations. A 2D bed of width, height and transverse thickness of respectively, 0.2 m, 0.5 m and 0.01 m, served as a test case. The settled bed height was H0 = 0.2 m. Particles of density ρ = 1000 kg/m³ and diameter dp = 1.2 mm were fluidized with air. The drag-law proposed by Benyahia et al. (10) was used in both models. Comparison between the simulation results was based on both instantaneous and time-averaged properties. A particular focus of this study was the influence of the coefficients of restitution and friction on the simulation results

Connecting Variability in Global Transcription Rate to Mitochondrial Variability

The authors demonstrate a connection between variability in the rate of transcription and differences in cellular mitochondrial content

Estudio de calidad de vida de pacientes con coxartrosis

La artroplastia de cadera secundaria a artrosis es una de las intervenciones más frecuentes dentro de la cirugía ortopédica. La coxartrosis produce una limitación funcional severa, que invalida a los pacientes y los hace dependientes para sus actividades cotidianas. Se calcula la calidad de vida aportada en las intervenciones de reemplazo articular de cadera de 85 pacientes con coxartrosis utilizando el “EQ-5D”. La puntuación media preoperatoria fue 0,222 ± 0,320 y la postoperatoria 0,794 ± 0,251. El incremento de calidad de vida en función de la edad de los pacientes siguió una tendencia descendente (β= −0,010), sin diferencias significativas (p=0,214). El incremento de calidad de vida no se vió condicionado por la presencia de infección (p>0,5), duración de la intervención (p>0,5) ni tiempo de estancia hospitalaria (p>0,5). La sustitución de esta articulación ha transformado la vida de muchos de los pacientes incrementando su calidad de vida, principalmente en pacientes que ingresan por coxartrosis en comparación con otros diagnósticos.Hip replacement secondary to osteoarthritis is one of the most performed surgeries in orthopaedic surgery. Osteoarthritis produces a severe functional limitation that invalidates patients and makes them dependent for their daily activities. It is calculated the quality of life provided by hip replacement procedure in 85 osteoarthritis patients using the “EQ-5D”. The mean preoperative score was 0.222 ± 0.320 and the postoperative score 0.794 ± 0.251. The increase in quality of life according to patients age followed a descendent tendency (β= −0.010), without a statitically relationship (p=0.214). The increase in quality of life was not conditioned by infection (p>0.5), length of stay (p>0.5) or length of the procedure (p>0.5). Joint replacement has changed the lives of many patients, increasing their quality of life, mainly in osteoarthritis patients compared to patients with other diagnosis

Catalytic activity and accessibility of acidic ion-exchange resins in liquid phase etherification reactions

Abstract Although macroreticular acidic ion-exchange resins have been widely used as catalysts in the industrial world for decades, their catalytic behavior is still far from being completely understood at a molecular level. Several characterization techniques coexist, which provide information about their properties. Only few of these techniques give an actual picture of their working-state features when swollen in anhydrous polar reactive media such as in etherification processes, where they are extensively used. The inverse steric exclusion chromatography technique, based on modeling the micropores structure, or gel-phase, as a set of discrete volume fractions with a characteristic polymer chain density, constitutes an appropriate procedure to assess the morphology of ion-exchangers in the swollen state. Present work proposes an empirical model to correlate the properties of the volume fractions with their catalytic activity in the etherification reaction rates of isobutene by addition of C1 to C4 linear primary alcohols. Sixteen different macroreticular acidic ion-exchange catalysts, both commercial and lab-made, have been used, which differ in acid capacity, sulfonation type, cross-linking degree and swollen-phase volume fractions distribution. Experimental reaction rates have been expressed as a sum of contributions of each individual volume fraction. The contribution of each polymer volume fraction corresponds to the product of the catalyst acidity, the characteristic volume fraction within the gel-phase of the catalyst, and a specific turnover frequency (TOF) of that fraction. Accessibility of the reacting alcohol, expressed in terms of the Ogston coefficient, has been also included in the empirical dependency equation presented in this work

MIGRATE: mobile device virtualisation through state transfer

Delegation of processing tasks to the network has moved from cloud-based schemes to edge computing solutions where nearby servers process requests in a timely manner. Virtualisation technologies have recently given data cloud and network providers the required flexibility to offer such on-demand resources. However, the maintenance of close computing resources presents a challenge when the served devices are on the move. In this case, if processing continuity is desired, a transference of processing resources and task state should be committed to maintain the service to end devices. The solution here presented, MIGRATE, proposes the concept of virtual mobile devices (vMDs) implemented as Virtual Functions (VxF) and acting as virtual representatives of physical processing devices. vMDs are instantiated at the edge of the access network, following a Multi-Access Edge Computing (MEC) approach, and move across different virtualisation domains. MIGRATE provides seamless and efficient transference of these software entities to follow the real location of mobile devices and continue supporting their physical counterparts. Software Defined Networks and Management and Operation functions are exploited to “migrate” vMDs to new virtualisation domains by forwarding data flows to the former domain until the new one is prepared, while a distributed data base avoids the transference of data. The solution has been deployed in a reference vehicular scenario at the Institute of Telecommunications Aveiro premises within the 5GINFIRE European project. In particular, the system has been evaluated under different virtualisation domains to study the operation of the migration approach in a vehicular monitoring scenario. The results validate the system from the application viewpoint with a Web monitoring tool, and the migration of the digital twin provided as VxF is analysed attending to the modification of data flows, indicating a seamless transition between virtualisation domains in a timely manner.publishe

Optimizing the clinical utility of PCA3 to diagnose prostate cancer in initial prostate biopsy

Background: PCA3 has been included in a nomogram outperforming previous clinical models for the prediction of any prostate cancer (PCa) and high grade PCa (HGPCa) at the initial prostate biopsy (IBx). Our objective is to validate such IBx-specific PCA3-based nomogram. We also aim to optimize the use of this nomogram in clinical practice through the definition of risk groups. Methods: Independent external validation. Clinical and biopsy data from a contemporary cohort of 401 men with the same inclusion criteria to those used to build up the reference’s nomogram in IBx. The predictive value of the nomogram was assessed by means of calibration curves and discrimination ability through the area under the curve (AUC). Clinical utility of the nomogram was analyzed by choosing thresholds points that minimize the overlapping between probability density functions (PDF) in PCa and no PCa and HGPCa and no HGPCa groups, and net benefit was assessed by decision curves. Results: We detect 28 % of PCa and 11 % of HGPCa in IBx, contrasting to the 46 and 20 % at the reference series. Due to this, there is an overestimation of the nomogram probabilities shown in the calibration curve for PCa. The AUC values are 0.736 for PCa (C.I.95 %:0.68–0.79) and 0.786 for HGPCa (C.I.95 %:0.71–0.87) showing an adequate discrimination ability. PDF show differences in the distributions of nomogram probabilities in PCa and not PCa patient groups. A minimization of the overlapping between these curves confirms the threshold probability of harboring PCa >30 % proposed by Hansen is useful to indicate a IBx, but a cut-off > 40 % could be better in series of opportunistic screening like ours. Similar results appear in HGPCa analysis. The decision curve also shows a net benefit of 6.31 % for the threshold probability of 40 %. Conclusions: PCA3 is an useful tool to select patients for IBx. Patients with a calculated probability of having PCa over 40 % should be counseled to undergo an IBx if opportunistic screening is required