A Novel Control Strategy for Soft Open Point to Address Terminal Voltage Violations and Load Rate Imbalance in Low-Voltage Power Distribution Station Areas.

In low-voltage power distribution station areas (DSAs), sensor devices and communication networks are often inadequate. Therefore, the control strategies mainly used for soft open points (SOPs) based on global information in medium-voltage distribution networks are difficult to be directly applied to low-voltage DSAs. This paper proposes a novel control strategy for SOP that only requires collecting the local information of SOP and the load rate of transformers. It aims to address the issues faced of voltage violations at the end of feeders and the load rate imbalance among adjacent DSAs under the current high penetration of renewable energy sources. In this paper, first, a sensor network consisting of sensor devices located at the transformers and each port of the SOP is introduced for information collection. Then, based on the sensitivity relationship between the node voltage and the injected power, considering capacity and voltage safety constraints, the adjustable range of the active power output for each port of the SOP is derived. According to this range, the operating states of the DSAs are categorized into four scenarios. For each scenario, the adjustment amount of SOP output power is determined to achieve comprehensive regulation of terminal voltage and load rate of all DSAs interconnected by SOP. Finally, the effectiveness of the proposed strategy is verified based on a simulation model of three flexible interconnected DSAs established in MATLAB/Simulink.

Robust Free-Space Optical Communication Utilizing Polarization for the Advancement of Quantum Communication.

Free-space optical (FSO) communication can be subject to various types of distortion and loss as the signal propagates through non-uniform media. In experiment and simulation, we demonstrate that the state of polarization and degree of polarization of light passed though underwater bubbles, causing turbulence, is preserved. Our experimental setup serves as an efficient, low cost alternative approach to long distance atmospheric or underwater testing. We compare our experimental results with those of simulations, in which we model underwater bubbles, and separately, atmospheric turbulence. Our findings suggest potential improvements in polarization based FSO communication schemes.

ISO 15189 is a sufficient instrument to guarantee high-quality manufacture of laboratory developed tests for in-house-use conform requirements of the European In-Vitro-Diagnostics Regulation.

The EU In-Vitro Diagnostic Device Regulation (IVDR) aims for transparent risk-and purpose-based validation of diagnostic devices, traceability of results to uniquely identified devices, and post-market surveillance. The IVDR regulates design, manufacture and putting into use of devices, but not medical services using these devices. In the absence of suitable commercial devices, the laboratory can resort to laboratory-developed tests (LDT) for in-house use. Documentary obligations (IVDR Art 5.5), the performance and safety specifications of ANNEX I, and development and manufacture under an ISO 15189-equivalent quality system apply. LDTs serve specific clinical needs, often for low volume niche applications, or correspond to the translational phase of new tests and treatments, often extremely relevant for patient care. As some commercial tests may disappear with the IVDR roll-out, many will require urgent LDT replacement. The workload will also depend on which modifications to commercial tests turns them into an LDT, and on how national legislators and competent authorities (CA) will handle new competences and responsibilities. We discuss appropriate interpretation of ISO 15189 to cover IVDR requirements. Selected cases illustrate LDT implementation covering medical needs with commensurate management of risk emanating from intended use and/or design of devices. Unintended collateral damage of the IVDR comprises loss of non-profitable niche applications, increases of costs and wasted resources, and migration of innovative research to more cost-efficient environments. Taking into account local specifics, the legislative framework should reduce the burden on and associated opportunity costs for the health care system, by making diligent use of existing frameworks.

Hyponastic Leaves 1 protects pri-miRNAs from nuclear exosome attack.

Biogenesis of plant microRNAs (miRNAs) takes place in nuclear dicing bodies (D-bodies), where the ribonulease III-type enzyme Dicer-like 1 (DCL1) processes primary transcripts of miRNAs (pri-miRNAs) into miRNA/miRNA* (*, passenger strand) duplexes from either base-to-loop or loop-to-base directions. Hyponastic Leaves 1 (HYL1), a double-stranded RNA-binding protein, is crucial for efficient and accurate processing. However, whether HYL1 has additional function remains unknown. Here, we report that HYL1 plays a noncanonical role in protecting pri-miRNAs from nuclear exosome attack in addition to ensuring processing. Loss of functions in SOP1 or HEN2, two cofactors of the nucleoplasmic exosome, significantly suppressed the morphological phenotypes of hyl1-2 Remarkably, mature miRNAs generated from loop-to-base processing were partially but preferentially restored in the hyl1 sop1 and hyl1 hen2 double mutants. Accordingly, loop-to-base-processed pri-miRNAs accumulated to higher levels in double mutants. In addition, dysfunction of HEN2, but not of SOP1, in hyl1-2 resulted in overaccumulation of many base-to-loop-processed pri-miRNAs, with most of their respective miRNAs unaffected. In summary, our findings reveal an antagonistic action of exosome in pri-miRNA biogenesis and uncover dual roles of HYL1 in stabilizing and processing of pri-miRNAs.

Testing and Evaluation of Wi-Fi RTT Ranging Technology for Personal Mobility Applications.

The rapid growth in the technological advancements of the smartphone industry has classified contemporary smartphones as a low-cost and high quality indoor positioning tools requiring no additional infrastructure or equipment. In recent years, the fine time measurement (FTM) protocol, achieved through the Wi-Fi round trip time (RTT) observable, available in the most recent models, has gained the interest of many research teams worldwide, especially those concerned with indoor localization problems. However, as the Wi-Fi RTT technology is still new, there is a limited number of studies addressing its potential and limitations relative to the positioning problem. This paper presents an investigation and performance evaluation of Wi-Fi RTT capability with a focus on range quality assessment. A set of experimental tests was carried out, considering 1D and 2D space, operating different smartphone devices at various operational settings and observation conditions. Furthermore, in order to address device-dependent and other type of biases in the raw ranges, alternative correction models were developed and tested. The obtained results indicate that Wi-Fi RTT is a promising technology capable of achieving a meter-level accuracy for ranges both in line-of-sight (LOS) and non-line-of-sight (NLOS) conditions, subject to suitable corrections identification and adaptation. From 1D ranging tests, an average mean absolute error (MAE) of 0.85 m and 1.24 m is achieved, for LOS and NLOS conditions, respectively, for 80% of the validation sample data. In 2D-space ranging tests, an average root mean square error (RMSE) of 1.1m is accomplished across the different devices. Furthermore, the analysis has shown that the selection of the bandwidth and the initiator-responder pair are crucial for the correction model selection, whilst knowledge of the type of operating environment (LOS and/or NLOS) can further contribute to Wi-Fi RTT range performance enhancement.

Non-Invasive Disease Specific Biomarker Detection Using Infrared Spectroscopy: A Review.

Many life-threatening diseases remain obscure in their early disease stages. Symptoms appear only at the advanced stage when the survival rate is poor. A non-invasive diagnostic tool may be able to identify disease even at the asymptotic stage and save lives. Volatile metabolites-based diagnostics hold a lot of promise to fulfil this demand. Many experimental techniques are being developed to establish a reliable non-invasive diagnostic tool; however, none of them are yet able to fulfil clinicians' demands. Infrared spectroscopy-based gaseous biofluid analysis demonstrated promising results to fulfil clinicians' expectations. The recent development of the standard operating procedure (SOP), sample measurement, and data analysis techniques for infrared spectroscopy are summarized in this review article. It has also outlined the applicability of infrared spectroscopy to identify the specific biomarkers for diseases such as diabetes, acute gastritis caused by bacterial infection, cerebral palsy, and prostate cancer.

[What is the real price of SOP and OTC drugs? Pilot study on paracetamol]. / Qual è il prezzo reale dei farmaci da banco (SOP) e non soggetti a prescrizione (OTC)? Studio pilota sul paracetamolo.

OBJECTIVES: to investigate the actual selling prices of over-the-counter or self-medication (OTC) and non-prescription (SOP) packages of band C medicines, which are freely set by individual pharmacies, para-pharmacies, and corners of the large-scale retail trade. Specifically, the prices charged for paracetamol 500 mg 20 tablets (20 CPR) and 30 tablets (30 CPR) in the online sale, carried out by different retail outlets authorized by the Italian Ministry of Health, were surveyed. DESIGN: cross-sectional observational descriptive study. The availability for online purchase of one or more packages of paracetamol 500 mg 20 CPR and 30 CPR was checked for each outlet considered; for sites with at least one package available for sale, the lowest real price of each of the two packages (20 and 30 CPR) was recorded, differentiating among: 1. type of outlet (pharmacy or retail outlet); 2. originator (branded) or generic (unbranded) drug; 3. city of residence of the outlet (provincial capital city or not). SETTING AND PARTICIPANTS: the sample considered consists of 475 online retail sites (pharmacies, para-pharmacies, and large-scale retail stores) based in the 10 major Italian provincial capitals, including sites in the relevant provincial cities. MAIN OUTCOME MEASURES: the average real price, calculated as the average of all real prices recorded by packaging type; the minimum real price, i.e., or the lowest real price recorded by packaging type; the average discount, calculated as the difference between the average real price and the average value of the maximum recommended prices (set by the marketing authorization holder, AIC) for branded and unbranded packaging; the maximum discount, calculated as the difference between the minimum real price and the average value of the maximum recommended prices (set by the marketing authorization holder) for branded and unbranded packaging. RESULTS: a wide availability of paracetamol packages produced by multiple AIC holders (both branded and unbranded) was found in the country. The presence of several manufacturers of paracetamol 500 mg induces high price competition, as evident from the discounts given. However, discounts are very high on non-branded packs and lower on branded packs. However, analysis of consumption at the national level shows that price competitiveness does not reflect true market share competitiveness, as consumption is mainly concentrated on branded packs that have the highest prices. CONCLUSIONS: wide and homogeneous distribution of unbranded products from different holders is available throughout the country. These products have significantly lower prices than branded packages, and they also have heavy discounts applied (up to 70%, with minimum price per tablet going as low as 0.05 euros). However, contrary to what these premises might lead one to think, consumption is concentrated on the branded packages having the highest prices. For proper information to citizens and trade associations, it is important for the media to bring awareness of the real savings opportunities available nationwide for products of frequent and widespread use, such as the case of paracetamol 500 mg.

Advances in integrated genomic selection for rapid genetic gain in crop improvement: a review.

MAIN CONCLUSION: Genomic selection and its importance in crop breeding. Integration of GS with new breeding tools and developing SOP for GS to achieve maximum genetic gain with low cost and time. The success of conventional breeding approaches is not sufficient to meet the demand of a growing population for nutritious food and other plant-based products. Whereas, marker assisted selection (MAS) is not efficient in capturing all the favorable alleles responsible for economic traits in the process of crop improvement. Genomic selection (GS) developed in livestock breeding and then adapted to plant breeding promised to overcome the drawbacks of MAS and significantly improve complicated traits controlled by gene/QTL with small effects. Large-scale deployment of GS in important crops, as well as simulation studies in a variety of contexts, addressed G × E interaction effects and non-additive effects, as well as lowering breeding costs and time. The current study provides a complete overview of genomic selection, its process, and importance in modern plant breeding, along with insights into its application. GS has been implemented in the improvement of complex traits including tolerance to biotic and abiotic stresses. Furthermore, this review hypothesises that using GS in conjunction with other crop improvement platforms accelerates the breeding process to increase genetic gain. The objective of this review is to highlight the development of an appropriate GS model, the global open source network for GS, and trans-disciplinary approaches for effective accelerated crop improvement. The current study focused on the application of data science, including machine learning and deep learning tools, to enhance the accuracy of prediction models. Present study emphasizes on developing plant breeding strategies centered on GS combined with routine conventional breeding principles by developing GS-SOP to achieve enhanced genetic gain.

Effective methods to enhance medical students' cardioversion and transcutaneous cardiac pacing skills retention - a prospective controlled study.

BACKGROUND: Guideline-based therapy of cardiac arrhythmias is important for many physicians from the beginning of their training. Practical training of the required skills to treat cardiac arrhythmias is useful for acquiring these skills but does not seem sufficient for skill retention. The aim of this study was to compare different retention methods for skills required to treat cardiac arrhythmias with respect to the performance of these skills in an assessment. METHODS: Seventy-one final-year medical students participated in a newly designed workshop to train synchronized cardioversion (SC) and transcutaneous cardiac pacing (TCP) skills in 2020. All participants completed an objective structured clinical examination (OSCE 1) one week after the training. Afterwards, the participants were stratified and randomized into three groups. Nine weeks later, one group received a standard operating procedure (SOP) for the skills, one group participated in a second workshop (SW), and one group received no further intervention (control). Ten weeks after the first training, all groups participated in OSCE 2. RESULTS: The average score of all students in OSCE 1 was 15.6 ± 0.8 points with no significant differences between the three groups. Students in the control group reached a significantly (p < 0.001) lower score in OSCE 2 (-2.0 points, CI: [-2.9;-1.1]) than in OSCE 1. Students in the SOP-group achieved on average the same result in OSCE 2 as in OSCE 1 (0 points, CI: [-0.63;+0.63]). Students who completed a second skills training (SW-group) scored not significantly higher in OSCE 2 compared to OSCE 1 (+0.4 points, CI: [-0.29;+1.12]). The OSCE 2 scores in groups SOP and SW were neither significantly different nor statistically equivalent. CONCLUSIONS: Partial loss of SC and TCP skills acquired in a workshop can be prevented after 10 weeks by reading an SOP as well as by a second workshop one week before the second assessment. Refreshing practical skills with an SOP could provide an effective and inexpensive method for skills retention compared to repeating a training. Further studies need to show whether this effect also exists for other skills and how frequently an SOP should be re-read for appropriate long-term retention of complex skills.

Endocytosis at the Crossroad of Polarity and Signaling Regulation: Learning from Drosophila melanogaster and Beyond.

Cellular trafficking through the endosomal-lysosomal system is essential for the transport of cargo proteins, receptors and lipids from the plasma membrane inside the cells and across membranous organelles. By acting as sorting stations, vesicle compartments direct the fate of their content for degradation, recycling to the membrane or transport to the trans-Golgi network. To effectively communicate with their neighbors, cells need to regulate their compartmentation and guide their signaling machineries to cortical membranes underlying these contact sites. Endosomal trafficking is indispensable for the polarized distribution of fate determinants, adaptors and junctional proteins. Conversely, endocytic machineries cooperate with polarity and scaffolding components to internalize receptors and target them to discrete membrane domains. Depending on the cell and tissue context, receptor endocytosis can terminate signaling responses but can also activate them within endosomes that act as signaling platforms. Therefore, cell homeostasis and responses to environmental cues rely on the dynamic cooperation of endosomal-lysosomal machineries with polarity and signaling cues. This review aims to address advances and emerging concepts on the cooperative regulation of endocytosis, polarity and signaling, primarily in Drosophila melanogaster and discuss some of the open questions across the different cell and tissue types that have not yet been fully explored.

A protocol for digitizing colors: the case of measuring color variables for forested wetland soils.

A procedure is presented and discussed that highlights the use of the Nix Pro Color Sensor ("Nix") in digitizing soil colors with applications for forested wetland soils. Informed by our soil color investigations using both the Munsell Soil Color Chart (MSCC) and the Nix in forested wetlands of the northern Virginia area, we crafted a standard operating procedure (SOP), adaptable to various locations and/or soil types, that guides users-regardless of knowledge of soil ecology or familiarity with the Nix-to successfully assess and monitor soil colors at various depths. Our SOP outlines steps for digitally collecting, storing, and sharing soil color data. Through the implementation of this procedure, soil color monitoring can enter the digital age, removing barriers of entry to soil color determination and enhancing individuals' interest in monitoring and understanding of the importance of soil color as an environmental and ecological indicator. With continued refinement and adaptation to intended use, the SOP herein presented has the potential to aid wetland/watershed assessment by providing data on soil colors that can be tracked over time while also encouraging public engagement in environmental monitoring of soils.

The plasma metabolome of Atlantic salmon as studied by 1H NMR spectroscopy using standard operating procedures: effect of aquaculture location and growth stage.

INTRODUCTION: Metabolomics applications to the aquaculture research are increasing steadily. The use of standardized proton nuclear magnetic resonance (1H NMR) spectroscopy can provide the aquaculture industry with an unbiased, reproducible, and high-throughput screening tool, which can help to diagnose nutritional and disease-related metabolic disorders in farmed fish. OBJECTIVE: Standard operating procedures developed for analysing (human) plasma by 1H NMR were applied to fingerprint the metabolome in plasma samples collected from Atlantic salmon. The aim was to explore the metabolome of salmon plasma in relation to growth stage and sampling site. METHODS: A total of 72 salmon were collected from three aquaculture sites in Norway (Lat. 65, 67, and 70 °N) and over two sampling events (December 2017 and November 2018). Plasma drawn from each salmon was measured by 1H NMR and metabolites were quantified using the SigMa software. The NMR data was analysed by principal component analysis (PCA) and ANOVA-simultaneous component analysis (ASCA). RESULTS: Important metabolic differences were evidenced, with adult salmon having a much higher content of very low-density lipoproteins and cholesterol in their plasma, while smolts displayed significantly higher levels of propylene glycol. Overall, 24% of the metabolite variation was due to the growth stage, whereas 12% of the metabolite variation was related to the aquaculture site and practice (p < 0.001). CONCLUSION: This study provides a baseline investigation of the plasma metabolome of the Atlantic salmon and demonstrates how 1H NMR metabolomics can be used in future investigations for comparing aquaculture practices and their influence on the fish metabolome.

Standard operation procedure for switchSENSE DRX systems.

There is currently a large panel of technologies available to address molecular interactions in vitro. Each technology presents individual advantages and drawbacks, and it becomes challenging to choose which technology will be best suited for a molecular interaction of interest. Approaches can be broadly categorized as either microfluidic surface-bound methods (such as Surface Plasmon Resonance (SPR) or switchSENSE) or in-solution methods (such as Isothermal Titration Calorimetry (ITC) or MicroScale Thermophoresis (MST)). In-solution methods are advantageous in terms of sample preparation and ease of use as none of the binding partners are subjected to immobilization. On the other hand, surface-based techniques require only small amounts of immobilized interaction partner and provide off-rate characterization as unbound analytes can be removed from the surface to observe analyte dissociation. Here, a standard operating procedure (SOP) for the switchSENSE method is presented, which aims to guide new users through the process of a switchSENSE measurement, covering sample preparation, instrument and biochip handling as well as data acquisition and analysis. This guide will help researchers decide whether switchSENSE is the right method for their application as well as supporting novice users to get the most information out of a switchSENSE measurement. switchSENSE technology offers the unique advantage of a controlled DNA-based ligand surface within a microfluidic channel which allows the user to distribute specifically up to two different ligand molecules on the surface at a customized density and ratio. The technology offers multi-parameter characterization of binding kinetics, affinity, enzymatic activity, and changes in protein conformation.

Saturation oxygenation pressure index: a non-invasive bedside measure for severity of respiratory disease in neonates on CPAP.

The treatment of respiratory distress in neonates ranges from non-invasive continuous positive airway pressure (CPAP) to advanced invasive mechanical ventilation. Monitoring on CPAP is often done by calculating oxygenation after blood gas analysis which is an invasive procedure. Saturation oxygen pressure index (SOPI) is a simple, non-invasive, bedside tool to monitor the severity of respiratory illness in neonates on CPAP. This study was aimed at validation of SOP index against AaDO2 and determine the cut-off values of SOPI for A-aDO2 of 70, 85 and100. This was a prospective observational study on 126 neonates with respiratory distress and treated with CPAP. The correlation between SOPI and A-aDO2 was validated using Bootstrap method. There was a significant positive correlation between SOPI and A-aDO2 with the Spearman correlation coefficient (rho) being 0.815 (p = 0). The mean coefficient of correlation after Bootstrap was 0.827 (p value < 0.0001). SOPI values of 1.52, 1.57 and 1.6 predicted A-aDO2 value of 70, 85 and 100 with a sensitivity of above 80% and specificity above 90%, respectively.Conclusion: SOPI has a significant positive correlation of 82.7% against A-aDO2 and can be a valuable tool to assess respiratory distress in neonates without arterial blood gas. What is Known: • Saturation oxygen pressure index (SOPI) is a non-invasive monitoring tool for neonates on N-CPAP. • SOPI has a good correlation with AaDO2. What is New: • Correlation of SOPI with AaDO2 is now validated. • Values between 1.52 and 1.88 indicate clinically useful range of AaDO2 for escalation of respiratory support from CPAP.

Design and Implementation of Opportunity Signal Perception Unit Based on Time-Frequency Representation and Convolutional Neural Network.

The traditional signal of opportunity (SOP) positioning system is equipped with dedicated receivers for each type of signal to ensure continuous signal perception. However, it causes a low equipment resources utilization and energy waste. With increasing SOP types, problems become more serious. This paper proposes a new signal perception unit for SOP positioning systems. By extracting the perception function from the positioning system and operating independently, the system can flexibly schedule resources and reduce waste based on the perception results. Through time-frequency joint representation, time-frequency image can be obtained which provides more information for signal recognition, and is difficult for traditional single time/frequency-domain analysis. We also designed a convolutional neural network (CNN) for signal recognition and a negative learning method to correct the overfitting to noisy data. Finally, a prototype system was built using USRP and LabVIEW for a 2.4 GHz frequency band test. The results show that the system can effectively identify Wi-Fi, Bluetooth, and ZigBee signals at the same time, and verified the effectiveness of the proposed signal perception architecture. It can be further promoted to realize SOP perception in almost full frequency domain, and improve the integration and resource utilization efficiency of the SOP positioning system.

Secure Cognitive Radio-Enabled Vehicular Communications under Spectrum-Sharing Constraints.

Vehicular communication has been envisioned to support a myriad of essential fifth-generation and beyond use-cases. However, the increasing proliferation of smart and intelligent vehicles has generated a lot of design and infrastructure challenges. Of particular interest are the problems of spectrum scarcity and communication security. Consequently, we considered a cognitive radio-enabled vehicular network framework for accessing additional radio spectrum and exploit physical layer security for secure communications. In particular, we investigated the secrecy performance of a cognitive radio vehicular network, where all the nodes in the network are moving vehicles and the channels between them are modeled as double-Rayleigh fading. Furthermore, adopting an underlay approach, the communication between secondary nodes can be performed by employing two interference constraint strategies at the primary receiver; (1) Strategy I: the secondary transmitter power is constrained by the interference threshold of the primary receiver, and (2) Strategy II: the secondary transmitter power is constrained by both the interference threshold of the primary receiver and the maximum transmit power of the secondary network. Under the considered strategies, we derive the exact secrecy outage probability (SOP) and ergodic secrecy capacity (ESC) expressions over double-Rayleigh fading. Moreover, by analyzing the asymptotic SOP behavior, we show that a full secrecy diversity of 1 can be achieved, when the average channel gain of the main link goes to infinity with a fixed average wiretap channel gain. From the ESC analysis, it is revealed that the ESC follows a scaling law of ΘlnΩm2Ωe2 for large Ωm and Ωe, where Ωm and Ωe are the average channel gains of the main link and wiretap link. The numerical and simulation results verify our analytical findings.

[Integration of palliative care into acute care medicine]. / Integration der Palliativmedizin in die Akutmedizin.

Palliative care is aimed at patients with incurable oncological and non-oncological diseases and their relatives with the aim of maintaining or improving their quality of life. In order to integrate palliative care into acute care medicine, palliative care training and continuing education for medical and nursing staff is recommended. Appropriate screening tools and standard operating procedures should be implemented to identify and address palliative care needs in emergency situations. For palliative care, established specialist palliative care services can be called upon for advice and/or cotreatment. Symptom control, treatment of malignant wounds, difficult ethical decision-making, and communication difficulties with patients, their legal representatives or relatives are the tasks of palliative care experts.

SOP- habituation laboratory: An interactive tool for simulating the basic behavioral features of habituation.

This paper presents an open-source online tool for introducing psychology students to the major theoretical and empirical facts of habituation. The tool was designed in a way that combines theory and data through simulated experiments. The simulations exemplify how the priming theory of Allan R. Wagner accounts for the set of behavioral characteristics of habituation proposed by Richard F. Thompson and W. Alden Spencer in 1966. Through this interactive platform, the user can learn the basics of the theory and examine how it accounts for the empirical facts with different parameters. Instructions and commands are provided in three languages: English, Spanish, and Portuguese.

Do as I say, Not(ch) as I do: Lateral control of cell fate.

Breaking symmetry in populations of uniform cells, to induce adoption of an alternative cell fate, is an essential developmental mechanism. Similarly, domain and boundary establishment are crucial steps to forming organs during development. Notch signaling is a pathway ideally suited to mediating precise patterning cues, as both receptors and ligands are membrane-bound and can thus act as a precise switch to toggle cell fates on or off. Fine-tuning of signaling by positive or negative feedback mechanisms dictate whether signaling results in lateral induction or lateral inhibition, respectively, allowing Notch to either induce entire regions of cell specification, or dictate binary fate choices. Furthermore, pathway activity is modulated by Fringe modification of receptors or ligands, co-expression of receptors with ligands, mode of ligand presentation, and cell surface area in contact. In this review, we describe how Notch signaling is fine-tuned to mediate lateral induction or lateral inhibition cues, and discuss examples from C.elegans, D. melanogaster and M. musculus. Identifying the cellular machinery dictating the choice between lateral induction and lateral inhibition highlights the versatility of the Notch signaling pathway in development.

Sample preparation of formalin-fixed paraffin-embedded tissue sections for MALDI-mass spectrometry imaging.

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MALDI MSI) has become a powerful tool with a high potential relevance for the analysis of biomolecules in tissue samples in the context of diseases like cancer and cardiovascular or cardiorenal diseases. In recent years, significant progress has been made in the technology of MALDI MSI. However, a more systematic optimization of sample preparation would likely achieve an increase in the molecular information derived from MALDI MSI. Therefore, we have employed a systematic approach to develop, establish and validate an optimized "standard operating protocol" (SOP) for sample preparation in MALDI MSI of formalin-fixed paraffin-embedded (FFPE) tissue sample analyses within this study. The optimized parameters regarding the impact on the resulting signal-to-noise (S/N) ratio were as follows: (i) trypsin concentration, solvents, deposition method, and incubation time; (ii) tissue washing procedures and drying processes; and (iii) spray flow rate, number of layers of trypsin deposition, and grid size. The protocol was evaluated on interday variability and its applicability for analyzing the mouse kidney, aorta, and heart FFPE tissue samples. In conclusion, an optimized SOP for MALDI MSI of FFPE tissue sections was developed to generate high sensitivity, to enhance spatial resolution and reproducibility, and to increase its applicability for various tissue types. This optimized SOP will further increase the molecular information content and intensify the use of MSI in future basic research and diagnostic applications. Graphical Abstract.