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The use of CRISPR-Cas bacterial adaptive immunity system components for targeted DNA changes has opened broad prospects for programmable genome editing of higher organisms. The most widely used gene editors are based on the Cas9 effectors of the type II CRISPR-Cas systems. In complex with guide RNAs, Cas9 proteins are able to directionally introduce double-stranded breaks into DNA regions that are
Starting with the lead compound roquinimex, a selection of 3-quinolinecarboxamide derivatives were synthesized and evaluated for the treatment of the autoimmune disease multiple sclerosis. Structure-activity relationships were established in animal studies and from these, laquinimod was chosen as the drug candidate due to its superior potency and toxicological profile as compared to roquinimex. Ho
The current novel study aims was to development and characterization of gum based (guar gum: almond gum) composite formulations with or without addition of oregano essential oils to extend the shelf life of okra at ambient condition. In this study, the optimized composite of guar gum: almond gum (75:25 V/V) prepared with addition of different concentrations (0.05, 0.1 and 0.15 % (V/V) of oregano e
This chapter explores key developments in international tax law amid the digitalization of the global economy. It examines challenges in taxing multinational enterprises (MNEs) and the OECD’s reform efforts under “Pillars One and Two”. The current tax system, designed for a pre-digital era, struggles to capture revenue from digital businesses, enabling profit shifting to low-tax jurisdictions and
Single-cell technologies have transformed our understanding of cellular heterogeneity through multimodal data acquisition. However, robust cell alignment remains a major challenge for data integration and harmonization, including batch correction, label transfer, and multi-omics integration. Many existing methods constrain alignment based on rigid feature-wise distance metrics, limiting their abil
DNA replication relies on precise coordination between proteins, including the sliding clamp proliferating cell nuclear antigen (PCNA), which encircles DNA to interact with key players in replication and repair. While biochemical studies have demonstrated interactions between PCNA and DNA polymerases δ and ε during DNA synthesis, the functional role of the Pol ε–PCNA interaction in vivo, particula
The testing and safety cases of assisted and automated driving (AAD) functions require considerations for nonideal environmental conditions, such as adverse and extreme weather. In these extreme conditions, perception sensors (e.g., camera, LiDAR, and RADAR), which build the situational awareness of the vehicle, might produce noisy and degraded data. Therefore, it is key to consider: 1) how to rel
Reliable and cost-effective operation of structural systems over their service life depends on the implementation of Structural Health Monitoring (SHM) and maintenance activities, which influence operational costs, the expected costs of failure and downtime. Decision Value Analysis (DVA) provides a framework to quantify the value of such activities by evaluating their effect on total expected life
Context. The Milky Way nuclear star cluster (MWNSC) is located in the Galactic centre, together with the Milky Way nuclear stellar disc (MWNSD), and they dominate the gravitational potential within the inner 300 pc. However, the formation and evolution of the two systems and their possible connections are still under debate. Aims. We reanalysed the low-resolution KMOS spectra in the MWNSC with the
IntroductionSport-related concussion (SRC) is a pressing issue in Para sport, yet biomechanical mechanisms remain poorly understood. Athletes with visual impairment face elevated risks due to sport-specific demands, such as frequent collisions in blind football. This pilot study examined head acceleration responses in blind football players compared with non-disabled football players, and between
IntroductionSport-related concussion (SRC) is a major health concern in contact sports. Linear head acceleration (LHA) and rotational head acceleration (RHA) are central biomechanical markers, and anticipatory neck muscle activation may mitigate these forces. Evidence on how anticipation influences head kinematics, and whether sex differences exist, remains limited. This study compared head accele
Take Home Message Using Germany as a case example, a comparison between organized mammography screening and contemporary, risk-adapted screening for prostate cancer suggests that prostate-specific antigen–based early detection with incorporation of magnetic resonance imaging and active surveillance can achieve benefits comparable to those of mammography while addressing previous concerns about ove
Background:Trauma patients present with heterogeneous injury patterns that are challenging to represent in statistical models. Traditional approaches either use high-dimensional one-hot encoding, resulting in sparse features, or aggregate injuries into summary scores that lose patient-specific detail.Objective:This study developed data-driven ICD-10 embeddings for trauma injuries and evaluated the
Aim: This paper aims to describe what constitutes good-quality, accessible, affordable and acceptable primary care for migrants. This includes identifying system adaptations and offering evidence- and practice-based recommendations and guidance for primary care organizations and professionals on how to deliver such care.Background: Migration has significantly diversified European populations. Migr
The increasing prevalence of antimicrobial-resistant bacterial infections has ushered in a major global public health crisis. Judicious or restricted antimicrobial use in animal agriculture, aiming to confine the use for the treatment of infections, is the most commonly proposed solution to reduce selection pressure for resistant bacterial strains and resistance genes. However, a multifaceted solu
The chaperone DNAJB6b (JB6) plays important roles in increasing amyloid protein solubility and inhibiting amyloid fibril formation, a causative factor for neurodegenerative diseases like Alzheimer's and Parkinson's disease. Insights into the biophysical properties of JB6, including its structure, self-assembly and stability towards denaturation, may enhance the understanding of the physicochemical
Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the benefits and harms of individualized developmental care interventions for promoting development and preventing morbidity in preterm infants.
In this paper, we present a method for in situ coating of individual protein particles in a respirable size. The aim of the coating was to influence the particle/powder properties, and to reduce or prevent surface-induced conformational changes of the protein, during spray-drying, which was the method used for simultaneously preparing and coating particles. The investigated formulations included b
