Miracle-dz/UniFAR-FTUs huggingface dataset:
Accelerated cell culture process development and characterization for cilgavimab/tixagevimab (AZD7442) for the prevention and treatment of COVID-19.

The global COVID-19 pandemic ignited an unprecedented race to develop vaccines and antibody therapeutics. AstraZeneca's pursuit to provide AZD7442 (EVUSHELD), two long-acting, SARS-CoV-2 spike receptor binding domain-specific neutralizing monoclonal antibodies, to individuals at risk on highly accelerated timelines challenged our traditional ways of process development and spurred the rapid adoption of novel approaches. Conventional upstream development processes were replaced by agile strategies that combined technological advances and highly accelerated workflows. With calculated business risks and close cross-functional collaborations, this process paved the way for hyper accelerated antibody development from discovery through manufacturing, process validation, emergency use authorization filing, and global regulatory approvals. The result was initiation of commercial manufacturing at a contract manufacturing organization less than 6 months from the selection of cilgavimab and tixagevimab - a process that historically has taken close to 10 years. This article is protected by copyright. All rights reserved.
Modelling the physiological status of yeast during wine fermentation enables the prediction of secondary metabolism

Saccharomyces non‐cerevisiae yeasts are gaining momentum in wine fermentation due to their potential to reduce ethanol content and achieve attractive aroma profiles. However, the design of the fermentation process for new species requires intensive experimentation. The use of mechanistic models could automate process design, yet to date, most fermentation models have focused on primary metabolism. Therefore, these models do not provide insight into the production of secondary metabolites essential for wine quality, such as aromas. In this work, we formulate a continuous model that accounts for the physiological status of yeast, that is, exponential growth, growth under nitrogen starvation and transition to stationary or decay phases. To do so, we assumed that nitrogen starvation is associated with carbohydrate accumulation and the induction of a set of transcriptional changes associated with the stationary phase. The model accurately described the dynamics of time series data for biomass and primary and secondary metabolites obtained for various yeast species in single culture fermentations. We also used the proposed model to explore different process designs, showing how the addition of nitrogen could affect the aromatic profile of wine. This study underlines the potential of incorporating yeast physiology into batch fermentation modelling and provides a new means of automating process design.
Co-delivery of amphotericin B and pentamidine loaded niosomal gel for the treatment of Cutaneous leishmaniasis

Abstract Topical drug delivery is preferable route over systemic delivery in case of Cutaneous leishmaniasis (CL). Among the available agents, amphotericin B (AmB) and pentamidine (PTM) showed promising result against CL. However, monotherapy is associated with incidences of reoccurrence and resistance. Combination therapy is therefore recommended. Thin film hydration method was employed for amphotericin B-pentamidine loaded niosomes (AmB-PTM-NIO) preparation followed by their incorporation into chitosan gel. The optimization of AmB-PTM-NIO was done via Box Behnken Design method and in vitro and ex vivo analysis was performed. The optimized formulation indicated 226 nm particle size (PS) with spherical morphology, 0.173 polydispersity index (PDI), −36 mV zeta potential (ZP) and with entrapment efficiency (EE) of 91% (AmB) and 79% (PTM), respectively. The amphotericin B-pentamidine loaded niosomal gel (AmB-PTM-NIO-Gel) showed desirable characteristics including physicochemical properties, pH (5.1 ± 0.15), viscosity (31870 ± 25 cP), and gel spreadability (280 ± 26.46%). In vitro release of the AmB and PTM from AmB-PTM-NIO and AmB-PTM-NIO-Gel showed more prolonged release behavior as compared to their respective drug solution. Higher skin penetration, greater percentage inhibition and lower IC50 against the promastigotes shows that AmB-PTM-NIO has better antileishmanial activity. The obtained findings suggested that the developed AmB-PTM-NIO-Gel has excellent capability of permeation via skin layers, sustained release profile and augmented anti-leishmanial outcome of the incorporated drugs.
An evolving perspective on novel modified release drug delivery systems for inhalational therapy

ABSTRACT Introduction Drugs delivered via the lungs are predominantly used to treat various respiratory disorders, including asthma, chronic obstructive pulmonary diseases, respiratory tract infections and lung cancers, and pulmonary vascular diseases such as pulmonary hypertension. To treat respiratory diseases, targeted, modified or controlled release inhalation formulations are desirable for improved patient compliance and superior therapeutic outcome. Areas covered This review summarizes the important factors that have an impact on the inhalable modified release formulation approaches with a focus toward various formulation strategies, including dissolution rate-controlled systems, drug complexes, site-specific delivery, drug-polymer conjugates, and drug-polymer matrix systems, lipid matrix particles, nanosystems, and formulations that can bypass clearance via mucociliary system and alveolar macrophages. Expert opinion Inhaled modified release formulations can potentially reduce dosing frequency by extending drug’s residence time in the lungs. However, inhalable modified or controlled release drug delivery systems remain unexplored and underdeveloped from the commercialization perspective. This review paper addresses the current state-of-the-art of inhaled controlled release formulations, elaborates on the avenues for developing newer technologies for formulating various drugs with tailored release profiles after inhalational delivery and explains the challenges associated with translational feasibility of modified release inhalable formulations.
New Blazars Discovered by Polarimetry

Optical polarimetry of a complete sample of radio sources has led to the discovery of 31 blazars and the confirmation of five others. Some of the new blazars are shown to have large redshifts and to be optically faint. It is found that there are equal numbers of objects with strong and weak emission lines, with the weak-lined objects having the largest ratios of optical to radio power. Evidence is provided for an unprecedented pair of polarized objects, only one of which is a radio source. 28 references.
Fundamental Constraints on the Electrical Characteristics of Frequency Selective Surfaces

Abstract This paper presents analytical constraints for the values which the reflection coefficient of any Frequency Selective Surface (FSS) can assume. This includes both patch and slot type FSS. The main assumption in this paper is that the FSS is a planar periodic surface constructed of infinitesimally thin conductors with a finite number of dielectric substrates and superstrates. In addition, only one periodic screen can be present, and it must be infinite in extent. Other than infinitesimal thickness, no assumptions are made on the shape of the periodic scatterer. The analysis presented in this paper includes the effects of dielectric layers, angle of incidence, and polarization. The results of the analytical constraints is the development of charts which can help one better understand fundamental FSS behavior. This includes a fundamental limit on how much power a lossy FSS can dissipate. This fundamental limit also applies to the amount of power that can be redistributed to grating lobes.
Computed Tomography Coronary Angiography on a Detector-Based Spectral Computed Tomography Platform: Evaluation of Patients With Coronary Artery Disease Reporting and Data System Score of 3 and Higher

Computed tomography (CT) coronary angiography is feasible on a detector-based spectral CT scanner, producing diagnostic quality images with spectral results that can improve confidence in diagnostic evaluation over single-energy CT angiography in patients with an original CAD-RADS score of 3 and higher. Purpose Computed tomography (CT) coronary angiography performed on a detector-based spectral scanner helps more closely approximate severity of stenosis with nuclear medicine and cardiac catheterization tests compared with single-energy CT (SECT) in patients with an original CAD-RADS score of 3 and higher. Methods This retrospective trial was conducted between January 2017 and December 2019 and included 52 patients with a CAD-RADS score of 3 and higher. Two reading sessions were performed 6 weeks apart. The first reading session was performed using only conventional images and the second reading session was performed using spectral results. Detector-based spectral CT CAD-RADS scores were compared with cardiac stress test and/or cardiac catheterization results for final characterization of stenosis in 41 segments from 32 patients. The mean CAD-RADS score was calculated for both the conventional images and spectral images. Results The CAD-RADS score for SECT and the score for spectral CT for the 41 segments were compared. Available associated stress test and/or cardiac catheterization results were also compared with CAD-RADS scores. In 51% (21/41), a diagnosis concordant with best practices results was achieved with the help of spectral CT results. A mean CAD-RADS score of 3.56 was obtained using spectral results, compared with 3.93 using conventional images. A 2-tailed paired t test determined the difference to be significant with a P value of 0.007. Conclusions Computed tomography coronary angiography is feasible on a detector-based spectral CT scanner and can improve diagnostic confidence over SECT angiography in patients with an original CAD-RADS score of 3 and higher.
Intracanal Microbiological Contamination Reduction Using Low-intensity Laser Associated with a Photosensitizer – In Vivo Study in Teeth of Dogs

This study evaluated the efficacy of photodynamic therapy using the photosensitizer azulene and low-intensity laser associated with standard root chemical-surgical preparation (performed with 0.5% sodium hypochlorite) in dogs. Twenty animals from the Veterinary Hospital of the School of Veterinary Medicine and Animal Science, University of São Paulo (HOVET-FMVZ/USP) and treated at the Compared Dentistry Laboratory (Laboratório de Odontologia Veterinária [LOC]-FMVZ/USP) were included. Each subject possessed one single rooted tooth with complete root formation, pulp necrosis, complicated crown fracture and periapical bone rarefaction at the time of the radiographic examination. The endodontic treatment was performed in all dogs, which were divided into two equal groups. For group one, the standard chemical-surgical preparation was followed by the photodynamic therapy to evaluate the role of azulene after instrumentation. For group two, the photodynamic therapy was followed by the standard chemical-surgical preparation to evaluate the antimicrobial action of azulene before instrumentation. The results show that intracanal photodynamic therapy is efficient in eliminating unspecified bacterial and Enterococcus organism loads. In addition, this therapeutic modality reduces yeast contamination. The photodynamic therapy showed similar efficacy compared to standard chemical-surgical preparation. The application order of therapeutic modalities does not influence intracanal disinfection in both cases. This study shows that photodynamic therapy with low-intensity laser and azulene as a photosensitizer is a feasible alternative for improving treatment outcomes in routine practice of veterinary dentistry.
Reliability, Validity and Minimal Detectable Change of a Power Leg Press Test in Individuals with Cerebral Palsy

Abstract Background Lower extremity muscle power influences walking ability in individuals with Cerebral Palsy (CP). Aim Determine the reliability, validity, and minimal detectable change (MDC) of a novel power leg press (PLP) test to measure muscle power in individuals with CP. Methods Individuals with spastic CP (n = 26 (10 adults, 16 children); mean (SD) age = 19.3 (7.8) years(all); 27.9 (4.89) years (adults); 13.85(2.68) years (children)) performed 2 sessions of the PLP test, 2–10 days apart. A linear position transducer and custom computer code were used to calculate mean and peak power in watts (W). Intraclass correlation coefficients (ICC), standard error of measurement, MDC, and percent change of MDC (MDC%) were calculated for 4 power measures (average and maximum of mean and peak powers) for all participants (AP) and separately for adults (A) and children (C). Validity was evaluated against isokinetic knee extensor power. Results Test-retest reliability was excellent for all measures of power (ICC = 0.94–0.99). Ranges for MDC/MDC% by the group for power measures were between 33.7–80.7W/15.5–29.4% (AP), 41.1–65.3W/10.7–22.3% (A), and 27.6–79.8W/19–34.3% (C). Correlations were good to excellent between PLP and isokinetic power at all speeds (r = 0.75–0.88, p < .001). Conclusions The PLP test demonstrates excellent validity, reliability, and precision for measuring muscle power in those with CP.
Spectroscopy and micro-luminescence mapping of Xe-implanted defects in diamond

Ion implantation in diamond creates optically active defects which have emission lines in broad spectral regions and may be used in advanced photonics and optical communication applications. A brief review of the photoluminescence properties of Xe+ ion implanted diamond is presented. The Xe-related center is of particular interest as this center is one of a few centers (Ni, Si, Cr) in diamond having sharp emission lines in the infrared spectral region, specifically at 813 and 794nm. The paper discusses an approach to determine the important and difficult to measure conversion efficiency of implanted ions into emitting optical centers. The method uses micro-luminescence confocal mapping and statistical analysis based on a compound Poisson distribution, accounting for both the implanted centers and the optically excited centers statistics. Results of numerical simulations and experimental measurements are presented.
Incidence and oncological implication of adrenal incidentalomas in esophageal cancer patients

Summary Adrenal incidentalomas are regularly encountered during imaging for esophageal cancer patients, but their oncological significance remains unknown. This study aimed to describe the incidence and etiology of adrenal incidentalomas observed throughout the diagnostic workup. This retrospective cohort study included all esophageal cancer patients referred to or diagnosed in the Amsterdam UMC between January 2012 and December 2016. Radiology and multidisciplinary team meeting reports were reviewed for adrenal incidentalomas. In case of adrenal incidentaloma, the 18FDG-PET/CT was reassessed by a radiologist blinded for the original report. In case of a metachronous incidentaloma during follow-up, visibility on previous imaging was reassessed. Primary outcome was the incidence, etiology and oncological consequence of synchronous adrenal incidentalomas. This study included 1,164 esophageal cancer patients, with a median age of 66 years. Patients were predominantly male (76.1%) and the majority had an adenocarcinoma (69.0%). Adrenal incidentalomas were documented in 138 patients (11.9%) during the diagnostic workup. At primary esophageal cancer workup, 22 incidentalomas proved malignant. However, follow-up showed that four incidentalomas were inaccurately diagnosed as benign and three malignant incidentalomas were visible on staging imaging but initially missed. Stage migration occurred in 15 of 22 (68.2%), but this would have been higher if none were missed or inaccurately diagnosed. The oncological impact of adrenal incidentalomas in patients with esophageal cancer is significant as a considerable part of incidentalomas changed treatment intent from curative to palliative. As stage migration is likely, pathological examination of a synchronous adrenal incidentaloma should be weighted in mind.
Integrated Proteomic and Metabolomic Analyses Show Differential Effects of Glucose Availability in Marine Synechococcus and Prochlorococcus

Glucose uptake by marine picocyanobacteria has been previously described and strongly suggests they are mixotrophic organisms (capable of using energy from the sun to make organic matter, but also to directly use organic matter from the environment when available). However, a detailed analysis of the effects of glucose addition on the proteome and metabolome of these microorganisms had not been carried out. ABSTRACT We compared changes induced by the addition of 100 nM and 5 mM glucose on the proteome and metabolome complements in Synechococcus sp. strains WH8102, WH7803, and BL107 and Prochlorococcus sp. strains MED4, SS120, and MIT9313, grown either under standard light conditions or in darkness. Our results suggested that glucose is metabolized by these cyanobacteria, using primarily the oxidative pentoses and Calvin pathways, while no proof was found for the involvement of the Entner-Doudoroff pathway in this process. We observed differences in the effects of glucose availability, both between genera and between Prochlorococcus MED4 and SS120 strains, which might be related to their specific adaptations to the environment. We found evidence for fermentation in Prochlorococcus sp. strain SS120 and Synechococcus sp. strain WH8102 after 5 mM glucose addition. Our results additionally suggested that marine cyanobacteria can detect nanomolar glucose concentrations in the environment and that glucose might be used to sustain metabolism under darkness. Furthermore, the KaiB and KaiC proteins were also affected in Synechococcus sp. WH8102, pointing to a direct link between glucose assimilation and circadian rhythms in marine cyanobacteria. In conclusion, our study provides a wide overview on the metabolic effects induced by glucose availability in representative strains of the diverse marine picocyanobacteria, providing further evidence for the importance of mixotrophy in marine picocyanobacteria. IMPORTANCE Glucose uptake by marine picocyanobacteria has been previously described and strongly suggests they are mixotrophic organisms (capable of using energy from the sun to make organic matter, but also to directly use organic matter from the environment when available). However, a detailed analysis of the effects of glucose addition on the proteome and metabolome of these microorganisms had not been carried out. Here, we analyzed three Prochlorococcus sp. and three Synechococcus sp. strains which were representative of several marine picocyanobacterial clades. We observed differential features in the effects of glucose availability, depending on both the genus and strain; our study illuminated the strategies utilized by these organisms to metabolize glucose and showed unexpected links to other pathways, such as circadian regulation. Furthermore, we found glucose addition had profound effects in the microbiome, favoring the growth of coexisting heterotrophic bacteria.
Ultrabroadband terahertz pulses: generation and field-resolved detection

In this paper, we discuss the latest techniques for the generation and field-resolved detection of tunable femtosecond electromagnetic field transients in a spectral regime covering the complete mid-infrared frequency range. In particular, we review the generation scheme based on phase-matched optical rectification. We also present a novel detection method, exploiting phase-matched electro-optic sampling, which extends the accessible frequency range towards the near-infrared.
Weakened untuned gain control is associated with schizophrenia while atypical orientation-tuned suppression depends on visual acuity

Perceptual distortions are core features of psychosis. Weakened contrast surround suppression has been proposed as a neural mechanism underlying atypical perceptual experiences. Although previous work has measured suppression by asking participants to report the perceived contrast of a low-contrast target surrounded by a high-contrast surround, it is possible to modulate perceived contrast solely by manipulating the orientation of a matched-contrast center and surround. Removing the bottom-up segmentation cue of contrast difference and isolating orientation-dependent suppression may clarify the neural processes responsible for atypical surround suppression in psychosis. We examined surround suppression across a spectrum of psychotic psychopathology including people with schizophrenia (PSZ; N = 31) and people with bipolar disorder (PBD; N = 29), first-degree biological relatives of these patient groups (PBDrel, PSZrel; N = 28, N = 21, respectively), and healthy controls (N = 29). PSZ exhibited reduced surround suppression across orientations; although group differences were minimal at the condition that produced the strongest suppression. PBD and PSZrel exhibited intermediate suppression, whereas PBDrel performed most similarly to controls. Intriguingly, group differences in orientation-dependent surround suppression magnitude were moderated by visual acuity. A simulation in which visual acuity and/or focal attention interact with untuned gain control reproduces the observed pattern of results, including the lack of group differences when orientation of center and surround are the same. Our findings further elucidate perceptual mechanisms of impaired center-surround processing in psychosis and provide insights into the effects of visual acuity on orientation-dependent suppression in PSZ.
Dynamics of subpicosecond dispersion-managed soliton in a fibre: a perturbative analysis

A model is studied which describes the propagation of a subpicosecond optical pulse in dispersion-managed fibre links. In the limit of weak chromatic dispersion management, the model equation is reduced to a perturbed modified NLS equation having a nonlinearity dispersion term. By means of the Riemann–Hilbert problem, a perturbation theory for the soliton of the modified NLS equation is developed. It is shown in the adiabatic approximation that there exists a unique possibility to suppress a perturbation-induced shift of the soliton centre at the cost of proper matching of the soliton width and nonlinearity dispersion parameter. In the next-order approximation, the spectral density of the radiation power emitted by a soliton is calculated.