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Expanding the fluorescent toolkit: molecular design, synthesis and biological application of unnatural amino acids
Get PDFFluorescence imaging has become an indispensable tool in modern biology, enabling the visualisation of dynamic molecular processes with spatial and temporal precision. Traditional strategies rely heavily on the conjugation of large, extrinsic fluorophores, such as green fluorscent protein or organic dyes, through linkers to proteins or peptides of interest. While sometimes effective, these bulky labels can interfere with native protein structure, function, and interactions, limiting their utility in studying sensitive or compact biological systems. In contrast, fluorescent unnatural amino acids that can be sitespecifically incorporated into proteins with minimal perturbation, provide high-resolution insights into molecular behaviour while preserving biological integrity. This perspective focuses on recent advances in the synthesis and application of fluorescent unnatural amino acids, particularly through the structural modification of natural aromatic-containing residues such as phenylalanine, tyrosine, and tryptophan. Additionally, the incorporation of small-molecule fluorophores as amino acid side chains to create versatile probes is also discussed. The utility of these fluorescent amino acids in biological chemistry is highlighted through their application in imaging protein dynamics, measuring enzyme activity and studying biomolecular interactions. Together, these advances establish fluorescent amino acids as a valuable and evolving toolkit for minimally invasive biological imaging
Multicompartment Darcy flow model with patient-specific parameterization: effect of heterogeneity and anisotropy in porous parameters
Get PDFBlood perfusion in cardiac tissues involves intricate interactions among vascular networks and tissue mechanics. Perfusion deficit is one of the leading causes of cardiac diseases, and modeling certain cardiac conditions that are clinically infeasible, invasive, or costly can provide valuable supplementary insights to aid clinicians. However, existing homogeneous perfusion models lack the complexity required for patient-specific simulations. In this study, we develop a computational framework for modeling perfusion using a multicompartment Darcy flow model with heterogeneous anisotropic perfusion that incorporates the nonlinear deformation and compliance of blood vessels with poroelastic parameters derived from realistic vascular data. Through numerical simulations and a comparison of pore pressure results obtained from the proposed model and the Poiseuille flow approach in a benchmark problem, we demonstrate that the heterogeneous anisotropic model outperforms homogeneous models in predicting perfusion, particularly by accurately capturing the spatial heterogeneity of the poroelastic parameters and the permeability transitions from large vessels to microvessels. Additionally, the proposed model successfully simulates patient-specific conditions, such as vessel blockages, highlighting its potential for personalized medical applications
Afrikanische Pferdepest
No full textDie Afrikanische Pferdepest ist in tropischen und subtropischen Regionen Afrikas südlich der Sahara endemisch und dort von immenser Bedeutung, wird aber allzu oft von der westlichen Welt als weit entfernt und wenig relevant abgetan. Ziel dieser Review ist es, einen Überblick über diese Erkrankung zu vermitteln und das Risiko eines Ausbruchs in Europa zu thematisieren
Equine colic outcomes and prognostic factors at a South African academic hospital (2019–2021)
No full textBackgroundColic is a common equine emergency requiring medical or surgical intervention. These interventions can be costly, making outcomes data and prognostic indicators essential for guiding referral and treatment decisions.
ObjectivesTo determine survival rates to hospital discharge and evaluate prognostic indicators in equine colic cases treated at a referral hospital (Onderstepoort Veterinary Academic Hospital [OVAH], South Africa).
MethodsThis retrospective observational cohort study analysed records from horses with colic that were presented to the OVAH from January 2019 to August 2021. Data included signalment, admission heart rate (HR) and packed cell volume (PCV), treatment type (medical vs. surgical), surgical diagnosis, postoperative complications, and survival to discharge.
ResultsOf 415 cases, 375 were treated (292 medically, 83 surgically). 91% of medically, 77% of surgically treated, and 88% overall survived. Compared to a previous study, overall survival to discharge improved by 5% (p = 0.025), mainly due to improved surgical outcomes. Survival was associated with treatment type and surgical lesion site (lower for small intestinal than large intestinal lesions). Medically treated cases with an increased HR and surgical cases with a high PCV had lower survival rates. Signalment showed no association with outcomes.
ConclusionSurvival rates to discharge were comparable to previously published international reports and showed significant improvement to previous results from the same institution, due to improved surgical outcomes. These findings can assist veterinarians in referral and treatment decisions. Further research on long-term survival and additional prognostic indicators is required to improve outcome predictions for equine colic treatment
Test of lepton flavour universality in W-boson decays into electrons and τ-leptons using pp collisions at √s = 13 TeV with the ATLAS detector
Get PDFA measurement of the ratio of the branching fractions, Rτ/e = B(W → τν)/B(W → eν), is performed using a sample of W bosons originating from top-quark decays to final states containing τ-leptons or electrons. This measurement uses pp collisions at s =13TeV, collected by the ATLAS experiment at the Large Hadron Collider during Run 2, corresponding to an integrated luminosity of 140fb−1. The W → τντ (with τ → eνeντ) and W →eνe decays are distinguished using the differences in the impact parameter distributions and transverse momentum spectra of the electrons. The measured ratio of branching fractions Rτ/e = 0.975±0.012(stat.)±0.020(syst.), is consistent with the Standard Model assumption of lepton flavour universality in W-boson decays
Reconfigurable artificial neuron and synapse enabled through a single alloyed memristor
Get PDFMemristive devices have drawn significant interest due to their use in novel paradigms such as neuromorphic computing. Neuromorphic systems are developed by implementing artificial neurons and synapses on a hardware level. Hence, memristors with multipurpose and reconfigurable neuromorphic functionalities could be highly beneficial in the design process. In this study, we experimentally verify that both neuronal and synaptic functions can be implemented on a single memristor. By controlling the device current at two different levels, the memristor operates in either a volatile or a nonvolatile retention regime. These two operation regimes are essential to mimic neuronal or synaptic behavior. Towards this end, we use an alloyed filamentary memristor (AgSn/SiO2/Pt) composed of ions with differing mobilities enabling both integrate and fire (IF) operation in the volatile regime and synaptic weights in the nonvolatile regime. By only changing the current compliance, these devices switch reliably between the aforementioned retention regimes. Additionally, our proposed training method significantly improves switching variability in the volatile regime. We show how the mean set voltage statistically reduce from 1.2 to 0.2 V; and the standard deviation of the set voltages reduced from 0.52 to 0.03 V
Large-scale epidemiology of opisthorchiasis in 21 provinces in Thailand based on diagnosis by fecal egg examination and urine antigen assay and analysis of risk factors for infection
Get PDFIntroduction:
Infection with the carcinogenic fish-borne trematode Opisthorchis viverrini, known as opisthorchiasis, is a major cause of biliary cancer (cholangiocarcinoma). Despite decades of disease prevention and control in Thailand, the parasite remains endemic. Here we apply a novel antigen assay for mass screening of opisthorchiasis and compare the prevalence against the conventional examination and analyze risk factors associated with current O. viverrini infection.
Materials and methods:
We conducted a large-scale cross-sectional survey to assess transmission of O. viverrini in the North, Northeast, and Eastern regions of Thailand. We screened randomly selected people (age 15 years and over) in 23 sub-districts, within 21 provinces, with a target sample size of 1,000 per sub-district. Each participant was screened for multiple helminth infection by fecal examination (quantitative formalin-ethyl acetate concentration technique; FECT), and the antigen assay by monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA) was applied to urine samples to detect O. viverrini. We collected risk factors for O. viverrini infection using standardized questionnaire surveys. The data were analyzed with regression models which correlated individual-level explanatory variables against i) infection status with O. viverrini and ii) the intensity of infection, as measured by the antigen assay or FECT.
Findings:
Of the 20,322 individuals enrolled, 19,465 provided urine samples for antigen detection by ELISA and 18,929 provided fecal samples for examination by FECT. The urine antigen assay revealed an overall opisthorchiasis prevalence of 50.3%, a fourfold increase over the 12.2% prevalence detected by FECT. Marked spatial heterogeneity was observed, with antigen‐based prevalence estimates ranging from 22.2% to 71.4% and several localities exceeding 60%. When assessed against a composite reference standard (combined ELISA and FECT), the urine ELISA yielded a diagnostic sensitivity of 91.6%, compared with 21.9% for FECT. We found a positive correlation between fecal egg counts and the concentration of worm antigen in urine across study sites. The ratio between the prevalence of O. viverrini observed by the antigen assay and FECT was high in provinces with a low mean number of O. viverrini eggs, and the ratio approached unity as the mean eggs per gram of stool (EPG) increased. Similar aggregate distribution patterns of fecal egg counts (EPG) and urine antigen concentrations suggest that the urine assay has potential for quantitative diagnostic evaluations. When analyzing individual-level risk factors, we further identified age, sex, occupation, a history of prior treatment with praziquantel, history of O. viverrini examination, and raw fish consumption as predictive of infection with O. viverrini, while a higher education level and certain occupations emerged as protective factors.
Conclusions and recommendations:
Application of the antigen assay to diagnose O. viverrini infection yielded a four-fold higher prevalence than the fecal egg examination, with the highest difference in low endemicity regions, which suggests that previous surveys may have underestimated the extent of opisthorchiasis in Thailand. Given the ease of urine sample collection, our study highlights the potential for application of the antigen assay as a new tool in the control of opisthorchiasis
Measurement of neutron production in atmospheric neutrino interactions at Super-Kamiokande
Get PDFWe present measurements of total neutron production from atmospheric neutrino interactions in water, analyzed as a function of electron-equivalent visible energy over a range of 30 MeV to 10 GeV. These results are based on 4,270 days of data collected by Super-Kamiokande, including 564 days with 0.011 wt% gadolinium added to enhance neutron detection. Neutron signal selection is based on a neural network trained on simulation, with its performance validated using an Am/Be neutron point source. The measurements are compared to predictions from neutrino event generators combined with various hadron-nucleus interaction models, which include an intranuclear cascade model and a nuclear deexcitation model. We observe significant variations in the predictions depending on the choice of hadron-nucleus interaction model. We discuss key factors that contribute to describing our data, such as in-medium effects in the intranuclear cascade and the accuracy of statistical evaporation modeling
Adam Smith, realism and the urban economy
No full textThis paper offers an overview of the existing literature on Smith and realism. Noting alignments drawn in the extant literature between Smith’s ‘History of Astronomy’ and The Theory of Moral Sentiments and critical realism in particular, the paper goes on to review whether further connections between Smith’s work and realism may be pointed to more broadly. In doing this, we also switch the starting point, and ask whether and in what form key foundations and principles of the realist literature may open up new perspectives on Smith’s work. The urban economy—which presents questions about how we identify causal mechanisms and the bases on which we can theorise about phenomena—is taken as a substantive domain for considering this interplay concerning Smith and realism
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