The Berry phase and the pump flux in stochastic chemical kinetics

We study a classical two-state stochastic system in a sea of substrates and products (absorbing states), which can be interpreted as a single Michaelis-Menten catalyzing enzyme or as a channel on a cell surface. We introduce a novel general method and use it to derive the expression for the full counting statistics of transitions among the absorbing states. For the evolution of the system under a periodic perturbation of the kinetic rates, the latter contains a term with a purely geometrical (the Berry phase) interpretation. This term gives rise to a pump current between the absorbing states, which is due entirely to the stochastic nature of the system. We calculate the first two cumulants of this current, and we argue that it is observable experimentally

Agarose gel as a medium for growing and tailoring protein crystals

The nucleation inducing ability of agarose gels has been exploited to study the crystallization of proteins in diffusion-dominated environments. The crystal size was successfully tuned in a wide range of gel, protein, and precipitant concentrations. The impact of the gel content on crystal size was independent of the specific protein, allowing the mathematical prediction of crystal size and pointing out the exclusivity of physical interactions between the gel and the protein. The versatility of the technique and the fine-tuning of the nucleation flux was demonstrated by crystallizing five different proteins and implementing batch and counter-diffusion crystallization. In addition, the potential of agarose gel to be used not only as a growth but also as a delivery medium for serial crystallography applications has been proven by preparing unidimensional microcrystal slurries with 0.1% (w/v) gel

Time-Frequency Coupled Proportional Fair Scheduler with Multicarrier Awareness for LTE Downlink

Abstract-Proportional fair schedulers have been thoroughly used in Long Term Evolution (LTE) due to their ability to provide a good trade-off between cell spectral efficiency and user fairness. Current algorithms provide suboptimum solutions at a low computational cost, but present several drawbacks. This paper proposes a Coupled and Multicarrier Aware PFS (CMA-PFS) for LTE downlink that increases efficiency as compared with current algorithms with independent time and frequency domain scheduling, referred to as Decoupled PFS (D-PFS). The proposed algorithm includes new features such as tight coupling between time and frequency domain scheduling and multicarrier transmission awareness. Simulations have been conducted using an International Mobile Telecommunications Advanced (IMT-Advanced) compliant semi-static simulator. Results show that the CMA-PFS improves proportional fairness as compared with D-PFS that is reflected both in an increase of cell spectral efficiency (around +2%) and a higher cell-edge user spectral efficiency (around +10%) in a Single User MIMO (SU-MIMO) system

Novel utility-scale photovoltaic plant electroluminescence maintenance technique by means of bidirectional power inverter controller

Nowadays, photovoltaic (PV) silicon plants dominate the growth in renewable energies generation. Utility-scale photovoltaic plants (USPVPs) have increased exponentially in size and power in the last decade and, therefore, it is crucial to develop optimum maintenance techniques. One of the most promising maintenance techniques is the study of electroluminescence (EL) images as a complement of infrared thermography (IRT) analysis. However, its high cost has prevented its use regularly up to date. This paper proposes a maintenance methodology to perform on-site EL inspections as efficiently as possible. First, current USPVP characteristics and the requirements to apply EL on them are studied. Next, an increase over the automation level by means of adding automatic elements in the current PV plant design is studied. The new elements and their configuration are explained, and a control strategy for applying this technique on large photovoltaic plants is developed. With the aim of getting on-site EL images on a real plant, a PV inverter has been developed to validate the proposed methodology on a small-scale solar plant. Both the electrical parameters measured during the tests and the images taken have been analysed. Finally, the implementation cost of the solution has been calculated and optimised. The results conclude the technical viability to perform on-site EL inspections on PV plants without the need to measure and analyse the panel defects out of the PV installation

Investigation of PTC124-mediated translational readthrough in a retinal organoid model of AIPL1-associated Leber congenital amaurosis

Leber congenital amaurosis type 4 (LCA4), caused by AIPL1 mutations, is characterized by severe sight impairment in infancy and rapidly progressing degeneration of photoreceptor cells. We generated retinal organoids using induced pluripotent stem cells (iPSCs) from renal epithelial cells obtained from four children with AIPL1 nonsense mutations. iPSC-derived photoreceptors exhibited the molecular hallmarks of LCA4, including undetectable AIPL1 and rod cyclic guanosine monophosphate (cGMP) phosphodiesterase (PDE6) compared with control or CRISPR-corrected organoids. Increased levels of cGMP were detected. The translational readthrough-inducing drug (TRID) PTC124 was investigated as a potential therapeutic agent. LCA4 retinal organoids exhibited low levels of rescue of full-length AIPL1. However, this was insufficient to fully restore PDE6 in photoreceptors and reduce cGMP. LCA4 retinal organoids are a valuable platform for in vitro investigation of novel therapeutic agents

Diagnosis, management, and outcomes of patients with syncope and bundle branch block

Although patients with syncope and bundle branch block (BBB) are at high risk of developing atrio-ventricular block, syncope may be due to other aetiologies. We performed a prospective, observational study of the clinical outcomes of patients with syncope and BBB following a systematic diagnostic approach. Patients with ≥1 syncope in the last 6 months, with QRS duration ≥120 ms, were prospectively studied following a three-phase diagnostic strategy: Phase I, initial evaluation; Phase II, electrophysiological study (EPS); and Phase III, insertion of an implantable loop recorder (ILR). Overall, 323 patients (left ventricular ejection fraction 56 ± 12%) were studied. The aetiological diagnosis was established in 267 (82.7%) patients (102 at initial evaluation, 113 upon EPS, and 52 upon ILR) with the following aetiologies: bradyarrhythmia (202), carotid sinus syndrome (20), ventricular tachycardia (18), neurally mediated (9), orthostatic hypotension (4), drug-induced (3), secondary to cardiopulmonary disease (2), supraventricular tachycardia (1), bradycardia-tachycardia (1), and non-arrhythmic (7). A pacemaker was implanted in 220 (68.1%), an implantable cardioverter defibrillator in 19 (5.8%), and radiofrequency catheter ablation was performed in 3 patients. Twenty patients (6%) had died at an average follow-up of 19.2 ± 8.2 months. In patients with syncope, BBB, and mean left ventricular ejection fraction of 56 ± 12%, a systematic diagnostic approach achieves a high rate of aetiological diagnosis and allows to select specific treatment

Ti6Al4V metal cutting chip formation experiments and modelling over a wide range of cutting speeds

Measured forces, chip geometry and tool temperatures from machining a mill annealed Ti6Al4V at cutting speeds mainly from 1 to 100 m/min, but in some cases down to 0.1 m/min, are reported, as well as mechanical testing of the material. Finite element simulations with inputs the measured flow stress, and subsequently a small high temperature strain hardening recovery correction, and a failure model calibrated from the cutting tests at speeds from 1 to 10 m/min, give satisfactory agreement with the higher speed tests once surface strain hardening and damage from the previous pass of the tool are taken into account. This paper’s originality is firstly to show that more complicated flow stress models involving large strain softening are not needed provided shear failure is included; and secondly its failure model: this proposes a non-zero failed shear stress depending on local pressure and temperature. The simulations provide relations between tool mechanical and thermal loading and cutting conditions to aid process improvement

An aphasia research agenda - a consensus statement from the collaboration of aphasia trialists.

Coordination of international aphasia research would minimise duplication of effort, support synergistic international activities across languages and multidisciplinary perspectives, and promote high-quality conduct and reporting of aphasia research, thereby increasing the relevance, transparency, and implementation of findings. The Collaboration of Aphasia Trialists (CATs) sought to develop an aphasia research agenda to direct future research activities, based on priorities shared by people with aphasia, family members, and healthcare professionals. Our established international research network spanning 33 countries contributed to this activity. Research literature reporting the priorities of stakeholders was reviewed and synthesised (phase 1). Representatives from Working Groups on Aphasia Assessment & Outcomes, Prognosis & Predictors of Recovery, Effectiveness of Interventions, and Societal Impact & Reintegration participated in a two-day research agenda setting meeting. The CATs expert panel refined research objectives and identified constituent components of research and methodological developments required to address these research components. The objectives and research components were grouped into overarching themes (phase 2). The resultant list was then circulated to more than 180 CATs members for review, revision, and approval. Consensus on the final aphasia research agenda and road-map was reached by CATs executive committee (phase 3). The expert panel identified five overarching research themes: (i) evidence-based interventions for people with aphasia, (ii) effective interventions to support those communicating with people with aphasia, (iii) cross-linguistic assessment and core outcomes for aphasia research, (iv) predictors of language recovery, and (v) clinical implementation of research findings. Within these broad themes, 30 research objectives and 91 individual aphasia research components were identified and sequentially ordered. This agenda builds on research priorities identified by people with aphasia and their families, and includes priorities of healthcare professionals and researchers, and will support the rehabilitation and recovery of people with aphasia. Our internationally relevant research agenda promotes rigour in methodology, considers international applicability, synergistic activities, and sharing of resources and expertise