Aggregation and Calibration of Agricultural Sector Models Through Crop Mix Restrictions and Marginal Profit Adjustments

All agricultural sector models must deal with aggregation and calibration somehow. The aggregation problem involves treating a group of producers as if they all responded in the same way as a single representative unit. The calibration problem concerns making a model reproduce as closely as possible an empirically observed set of decision maker actions. This paper shows how both calibration and aggregation are addressed through crop mix restrictions combined with marginal profit adjust-ments.mathematical programming, aggregation, calibration, crop mix, marginal cost, agricultural sector model, Agribusiness, C6, C61, Q1, Q11, Q17, Q18, R12, R13, R14,

Blood-Brain Barrier Transport of Transferrin Receptor-Targeted Nanoparticles

The blood–brain barrier (BBB), built by brain endothelial cells (BECs), is impermeable to biologics. Liposomes and other nanoparticles are good candidates for the delivery of biologics across the BECs, as they can encapsulate numerous molecules of interest in an omnipotent manner. The liposomes need attachment of a targeting molecule, as BECs unfortunately are virtually incapable of uptake of non-targeted liposomes from the circulation. Experiments of independent research groups have qualified antibodies targeting the transferrin receptor as superior for targeted delivery of nanoparticles to BECs. Functionalization of nanoparticles via conjugation with anti-transferrin receptor antibodies leads to nanoparticle uptake by endothelial cells of both brain capillaries and post-capillary venules. Reducing the density of transferrin receptor-targeted antibodies conjugated to liposomes limits uptake in BECs. Opposing the transport of nanoparticles conjugated to high-affine anti-transferrin receptor antibodies, lowering the affinity of the targeting antibodies or implementing monovalent antibodies increase uptake by BECs and allows for further transport across the BBB. The novel demonstration of transport of targeted liposomes in post-capillary venules from blood to the brain is interesting and clearly warrants further mechanistic pursuit. The recent evidence for passing targeted nanoparticles through the BBB shows great promise for future drug delivery of biologics to the brain

The blood-brain barrier studied in vitro across species

The blood-brain barrier (BBB) is formed by brain capillary endothelial cells (BECs) supported by pericytes and astrocytes. The BBB maintains homeostasis and protects the brain against toxic substances circulating in the blood, meaning that only a few drugs can pass the BBB. Thus, for drug screening, understanding cell interactions, and pathology, in vitro BBB models have been developed using BECs from various animal sources. When comparing models of different species, differences exist especially in regards to the transendothelial electrical resistance (TEER). Thus, we compared primary mice, rat, and porcine BECs (mBECs, rBECs, and pBECs) cultured in mono- and co-culture with astrocytes, to identify species-dependent differences that could explain the variations in TEER and aid to the selection of models for future BBB studies. The BBB models based on primary mBECs, rBECs, and pBECs were evaluated and compared in regards to major BBB characteristics. The barrier integrity was evaluated by the expression of tight junction proteins and measurements of TEER and apparent permeability (Papp). Additionally, the cell size, the functionality of the P-glycoprotein (P-gp) efflux transporter, and the expression of the transferrin receptor were evaluated and compared. Expression and organization of tight junction proteins were in all three species influenced by co-culturing, supporting the findings, that TEER increases after co-culturing with astrocytes. All models had functional polarised P-gp efflux transporters and expressed the transferrin receptor. The most interesting discovery was that even though the pBECs had higher TEER than rBECs and mBECs, the Papp did not show the same variation between species, which could be explained by a significantly larger cell size of pBECs. In conclusion, our results imply that the choice of species for a given BBB study should be defined from its purpose, instead of aiming to reach the highest TEER, as the models studied here revealed similar BBB properties

Assessing Lumbar Plexus and Sciatic Nerve Damage in Relapsing-Remitting Multiple Sclerosis Using Magnetisation Transfer Ratio

Neurografia de ressonància magnètica (MRN); Relació de transferència de magnetització (MTR); Esclerosi múltiple del sistema nerviós perifèric (SNP)Neurografía de resonancia magnética (MRN); Relación de transferencia de magnetización (MTR); Esclerosis múltiple del sistema nervioso periférico (SNP)Magnetic resonance neurography (MRN); Magnetisation transfer ratio (MTR); Multiple sclerosis peripheral nervous system (PNS)Background: Multiple sclerosis (MS) has traditionally been regarded as a disease confined to the central nervous system (CNS). However, neuropathological, electrophysiological, and imaging studies have demonstrated that the peripheral nervous system (PNS) is also involved, with demyelination and, to a lesser extent, axonal degeneration representing the main pathophysiological mechanisms. Aim: The purpose of this study was to assess PNS damage at the lumbar plexus and sciatic nerve anatomical locations in people with relapsing-remitting MS (RRMS) and healthy controls (HCs) in vivo using magnetisation transfer ratio (MTR), which is a known imaging biomarker sensitive to alterations in myelin content in neural tissue, and not previously explored in the context of PNS damage in MS. Method: Eleven HCs (7 female, mean age 33.6 years, range 24-50) and 15 people with RRMS (12 female, mean age 38.5 years, range 30-56) were recruited for this study and underwent magnetic resonance imaging (MRI) investigations together with clinical assessments using the expanded disability status scale (EDSS). Magnetic resonance neurography (MRN) was first used for visualisation and identification of the lumbar plexus and the sciatic nerve and MTR imaging was subsequently performed using identical scan geometry to MRN, enabling straightforward co-registration of all data to obtain global and regional mean MTR measurements. Linear regression models were used to identify differences in MTR values between HCs and people with RRMS and to identify an association between MTR measures and EDSS. Results: MTR values in the sciatic nerve of people with RRMS were found to be significantly lower compared to HCs, but no significant MTR changes were identified in the lumbar plexus of people with RRMS. The median EDSS in people with RRMS was 2.0 (range, 0-3). No relationship between the MTR measures in the PNS and EDSS were identified at any of the anatomical locations studied in this cohort of people with RRMS. Conclusion: The results from this study demonstrate the presence of PNS damage in people with RRMS and support the notion that these changes, suggestive of demyelination, maybe occurring independently at different anatomical locations within the PNS. Further investigations to confirm these findings and to clarify the pathophysiological basis of these alterations are warranted.The UK MS Society and the UCL-UCLH Biomedical Research Centre for ongoing support. CGW-K receives funding from the MS Society (#77), Wings for Life (#169111), BRC (#BRC704/CAP/CGW), UCL Global Challenges Research Fund (GCRF), MRC (#MR/S026088/1), Ataxia UK. FP had a non-clinical Postdoctoral Guarantors of Brain fellowship (2017-2020). FP was supported by the National Institute for Health Research, UCL Hospitals Biomedical Research Centre. CT is being funded by a Junior Leader La Caixa Fellowship (fellowship code is LCF/BQ/PI20/11760008), awarded by la Caixa Foundation (ID 100010434). She has also received the 2021 Merck's Award for the Investigation in MS, awarded by Fundación Merck Salud (Spain). In 2015, she received an ECTRIMS Post-doctoral Research Fellowship and has received funding from the UK MS Society. She has also received honoraria from Roche and Novartis, and is a steering committee member of the O'HAND trial and of the Consensus group on Follow-on DMTs. This project has received funding under the European Union's Horizon 2020 research and innovation programme under grant agreement No. 634541 and from the Engineering and Physical Sciences Research Council (EPSRC EP/R006032/1), funding FG. FG was currently supported by PREdICT, a study at the Vall d'Hebron Institute of Oncology in Barcelona funded by AstraZeneca

Transfection of brain capillary endothelial cells in primary culture with defined blood-brain barrier properties

BACKGROUND: Primary brain capillary endothelial cells (BCECs) are a promising tool to study the blood–brain barrier (BBB) in vitro, as they maintain many important characteristics of the BBB in vivo, especially when co-cultured with pericytes and/or astrocytes. A novel strategy for drug delivery to the brain is to transform BCECs into protein factories by genetic modifications leading to secretion of otherwise BBB impermeable proteins into the central nervous system. However, a huge challenge underlying this strategy is to enable transfection of non-mitotic BCECs, taking a non-viral approach. We therefore aimed to study transfection in primary, non-mitotic BCECs cultured with defined BBB properties without disrupting the cells’ integrity. METHODS: Primary cultures of BCECs, pericytes and astrocytes were generated from rat brains and used in three different in vitro BBB experimental arrangements, which were characterised based on a their expression of tight junction proteins and other BBB specific proteins, high trans-endothelial electrical resistance (TEER), and low passive permeability to radiolabeled mannitol. Recombinant gene expression and protein synthesis were examined in primary BCECs. The BCECs were transfected using a commercially available transfection agent Turbofect™ to express the red fluorescent protein HcRed1-C1. The BCECs were transfected at different time points to monitor transfection in relation to mitotic or non-mitotic cells, as indicated by fluorescence-activated cell sorting analysis after 5-and 6-carboxylfluorescein diacetate succinidyl ester incorporation. RESULTS: The cell cultures exhibited important BBB characteristics judged from their expression of BBB specific proteins, high TEER values, and low passive permeability. Among the three in vitro BBB models, co-culturing with BCECs and astrocytes was well suited for the transfection studies. Transfection was independent of cell division and with equal efficacy between the mitotic and non-mitotic BCECs. Importantly, transfection of BCECs exhibiting BBB characteristics did not alter the integrity of the BCECs cell layer. CONCLUSIONS: The data clearly indicate that non-viral gene therapy of BCECs is possible in primary culture conditions with an intact BBB

SENSE EPI reconstruction with 2D phase error correction and channel-wise noise removal

Nyquist ghost; Denoising; DiffusionFantasma de Nyquist; Eliminación de ruido; DifusiónFantasma de Nyquist; Eliminació de soroll; DifusióPurpose To develop a robust reconstruction pipeline for EPI data that enables 2D Nyquist phase error correction using sensitivity encoding without incurring major noise artifacts in low SNR data. Methods SENSE with 2D phase error correction (PEC-SENSE) was combined with channel-wise noise removal using Marcenko–Pastur principal component analysis (MPPCA) to simultaneously eliminate Nyquist ghost artifacts in EPI data and mitigate the noise amplification associated with phase correction using parallel imaging. The proposed pipeline (coined SPECTRE) was validated in phantom DW-EPI data using the accuracy and precision of diffusion metrics; ground truth values were obtained from data acquired with a spin echo readout. Results from the SPECTRE pipeline were compared against PEC-SENSE reconstructions with three alternate denoising strategies: (i) no denoising; (ii) denoising of magnitude data after image formation; (iii) denoising of complex data after image formation. SPECTRE was then tested using high -value (i.e., low SNR) diffusion data (up to  s/mm ) in four healthy subjects. Results Noise amplification associated with phase error correction incurred a 23% bias in phantom mean diffusivity (MD) measurements. Phantom MD estimates using the SPECTRE pipeline were within 8% of the ground truth value. In healthy volunteers, the SPECTRE pipeline visibly corrected Nyquist ghost artifacts and reduced associated noise amplification in high -value data. Conclusion The proposed reconstruction pipeline is effective in correcting low SNR data, and improves the accuracy and precision of derived diffusion metrics.EPSRC-funded UCL Centre for Doctoral Training in Medical Imaging, Grant/Award Number: EP/L016478/

Oscillatory variations in the Q factors of high quality micropillar cavities

We report on the observation of oscillatory variations in the quality (Q) factor of quantum dot-micropillar cavities based on planar Bragg reflectors. The oscillatory behavior in the Q versus diameter dependence appears in the diameter range between 1.0 and 4.0 mu m, has a characteristic period of a few hundred nanometers and increases in amplitude with increasing reflectivity of the planar microcavity structures. The experimental results are well reproduced by numerical calculations which support the interpretation that the Q oscillations are caused by coupling of propagating Bloch modes of different orders at the mirror interfaces.</p