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Spatio-temporal pattern recognition is a fundamental ability of the brain which is required for numerous real-world applications. Recent deep learning approaches have reached outstanding accuracy in such tasks, but their implementation on conventional embedded solutions is still very computationally and energy expensive. Tactile sensing in robotic applications is a representative example where real-time processing and energy-efficiency are required. Following a brain-inspired computing approach, we propose a new benchmark for spatio-temporal tactile pattern recognition at the edge through braille letters reading. We recorded a new braille letters dataset based on the capacitive tactile sensors/fingertip of the iCub robot, then we investigated the importance of temporal information and the impact of event-based encoding for spike-based/event-based computation. Afterwards, we trained and compared feed-forward and recurrent spiking neural networks (SNNs) offline using back-propagation through time with surrogate gradients, then we deployed them on the Intel Loihi neuromorphic chip for fast and efficient inference. We confronted our approach to standard classifiers, in particular to a Long Short-Term Memory (LSTM) deployed on the embedded Nvidia Jetson GPU in terms of classification accuracy, power/energy consumption and computational delay. Our results show that the LSTM outperforms the recurrent SNN in terms of accuracy by 14%. However, the recurrent SNN on Loihi is 237 times more energy-efficient than the LSTM on Jetson, requiring an average power of only 31mW. This work proposes a new benchmark for tactile sensing and highlights the challenges and opportunities of event-based encoding, neuromorphic hardware and spike-based computing for spatio-temporal pattern recognition at the edge.

The hepatic Na+/taurocholate co-transporting polypeptide (NTCP in man, Ntcp in animals) is the high-affinity receptor for the hepatitis B (HBV) and hepatitis D (HDV) viruses. Species barriers for human HBV/HDV within the order Primates were previously attributed to Ntcp sequence variations that disable virus-receptor interaction. However, only a limited number of primate Ntcps have been analysed so far. In the present study, a total of 11 Ntcps from apes, Old and New World monkeys were cloned and expressed in vitro to characterise their interaction with HBV and HDV. All Ntcps showed intact bile salt transport. Human NTCP as well as the Ntcps from the great apes chimpanzee and orangutan showed transport-competing binding of HBV derived myr-preS1-peptides. In contrast, all six Ntcps from the group of Old World monkeys were insensitive to HBV myr-preS1-peptide binding and HBV/HDV infection. This is basically predetermined by the amino acid arginine at position 158 of all studied Old World monkey Ntcps. An exchange from arginine to glycine (as present in humans and great apes) at this position (R158G) alone was sufficient to achieve full transport-competing HBV myr-preS1-peptide binding and susceptibility for HBV/HDV infection. New World monkey Ntcps showed higher sequence heterogeneity, but in two cases with 158G showed transport-competing HBV myr-preS1-peptide binding, and in one case (Saimiri sciureus) even susceptibility for HBV/HDV infection. In conclusion, amino acid position 158 of NTCP/Ntcp is sufficient to discriminate between the HBV/HDV susceptible group of humans and great apes (158G) and the non-susceptible group of Old World monkeys (158R). In the case of the phylogenetically more distant New World monkey Ntcps amino acid 158 plays a significant, but not exclusive role.

Fibroblast growth factor-23 (FGF-23) is a phosphaturic hormone used to monitor chronic kidney disease (CKD) in humans. The aim of this pilot study was to compare three diagnostic assays and to assess how the results correlate with parameters of renal dysfunction in cats. Four groups of 10 cats each were formed retrospectively according to creatinine, based on IRIS staging. FGF-23 was measured using two different ELISAs (MyBioSource and Kainos ELISA FGF-23 Kit) and an automated assay on the DiaSorin Liaison platform. Measurements were performed in 40 cats. Spearman’s rank correlation coefficient showed a strong correlation between the Kainos and DiaSorin assays (ρ = 0.742/p < 0.001) and a low correlation (ρ = 0.443/p = 0.005) between the Kainos and MyBioSource assays. The measurements with the Kainos assay strongly correlated with urea (ρ = 0.835/p < 0.001) and creatinine (ρ = 0.764/p < 0.001), and moderately correlated with SDMA (ρ = 0.580/p < 0.001) and phosphorus (ρ = 0.532/p < 0.001). The results of the MyBioSource and DiaSorin assays only showed a moderate correlation with urea (ρ = 0.624/0.572) and creatinine (ρ = 0.622/0.510) concentrations (p = 0.001 each). The Kainos assay showed the strongest correlation (ρ = 0.806) with the various creatinine concentrations according to the IRIS, followed by the MyBioSource (ρ = 0.663/p < 0.001) and DiaSorin assays (ρ = 0.580/p < 0.001). Overall, the Kainos assay demonstrated the best correlations with both biomarkers and various creatinine concentrations according to the IRIS. Individual assay-based reference values should be established to make a reliable interpretation of FGF-23 levels possible to diagnose or monitor feline CKD.

The multidrug resistance gene MDR1 encodes for an efflux transporter called P-glycoprotein (P-gp). In the canine Mdr1 gene, a nonsense mutation was identified in certain dog breeds causing increased drug sensitivity to various P-gp substrates such as antiparasitic macrocyclic lactones. Symptoms of neurologic toxicity include ataxia, depression, salivation, tremor, apparent blindness, and mydriasis. In the current report, a Thuringian goat developed similar neurological signs after treatment with doramectin, a compound from the macrocyclic lactone class. Therefore, Mdr1 might be defective in this individual goat. For diagnostic purposes, sequencing of the complete mRNA transcript coding for caprine Mdr1 was performed to investigate a potential missense mutation. The Mdr1 transcripts of two related goats without drug sensitivity were also sequenced to allow differential diagnosis and were compared to the suspected drug-sensitive goat. The only position where the Mdr1 sequence from the suspected drug-sensitive goat differed was in the 3′-untranslated region, being a heterozygous single nucleotide polymorphism c.3875C>A. It can be suspected that this variant affects the expression level, stability, or translation efficiency of the Mdr1 mRNA transcript and therefore might be associated with the suspected drug sensitivity. To clarify this, further studies are needed, particularly investigating the Mdr1 mRNA and protein expression levels from brain material of affected goats. In conclusion, Mdr1 variants may exist not only in dogs, but also in individual goats. The current report provides the first Mdr1 mRNA transcript sequence of a goat and therefore represents the basis for more detailed Mdr1 sequence and expression analyses.

Background Canine obesity is a significant health concern in spite of current feeding trends claiming healthier diets. Among these trends, raw meat-based diets (RMBD) have gained in popularity. Scientific evidence supporting these claims is limited, and nutritional imbalances are of concern in RMBD-fed dogs. This study aimed to assess the impact of RMBD-feeding on body condition in dogs in comparison to feeding a commercial complete diet (CD). A total of 104 healthy dogs were included, of which 51 dogs (age median: 4.1 years, interquartile range [IQR]: 3.2–5.9 years; body weight (BW) median: 24.8 kg, IQR: 16.3–31.9 kg) were fed an RMBD and 53 dogs (age median: 4.8 years, IQR: 3.3–5.8 years; BW median: 25.4 kg, IQR: 18.9–27.7 kg) received a CD, both for at least 12 months prior to enrollment. Enrolled dogs underwent two clinical evaluations 3–5 months apart. During these evaluations, blood, urine, and fecal samples were collected, and the patient and diet history was obtained. Results RMBD-fed dogs had lower body condition scores (BCS; median: 5, IQR: 4–5) compared to CD-fed dogs (median: 6, IQR: 5–7, P  < 0.001). Energy intake was lower with RMBD rations (median coverage of the daily recommended metabolizable energy [ME]: 89%) compared to CD rations (median coverage of the daily recommended ME: 102%, P  = 0.015). Coverage of the daily energy intake was inversely correlated with BCS. In RMBD rations, the calcium (Ca): phosphorus (P) ratio (median: 1.0), failed to meet the recommended ratio of 1.4 and was lower than with CD rations (median: 1.4, P < 0.001); estimated intakes of Ca ( P  < 0.001), P ( P  < 0.001), sodium ( P  < 0.001) and magnesium ( P  = 0.004) were lower than in CD rations but close to the recommendations. Estimated intakes of Ca, P, and sodium in CD rations were at least twice the recommended amounts. Blood serum analysis revealed lower serum iodine ( P  = 0.001), copper ( P  = 0.005), zinc ( P  < 0.001), and manganese ( P  = 0.035) concentrations in RMBD-fed dogs than in CD-fed dogs. Conclusion While RMBD-feeding might offer the advantage of a leaner body condition, concerns about nutritional imbalances warrant further investigation, even though RMBD-fed dogs do not show clinical signs of nutrient deficiencies.

Background: The muscarinic receptor antagonist trospium chloride (TCl) is used for pharmacotherapy of the overactive bladder syndrome. TCl is a hydrophilic positively charged drug. Therefore, it has low permeability through biomembranes and requires drug transporters for distribution and excretion. In humans, the organic cation transporters OCT1 and OCT2 and the multidrug and toxin extrusion MATE1 and MATE2-K carriers showed TCl transport. However, their individual role for distribution and excretion of TCl is unclear. Knockout mouse models lacking mOct1/mOct2 or mMate1 might help to clarify their role for the overall pharmacokinetics of TCl. Method: In preparation of such experiments, TCl transport was analyzed in HEK293 cells stably transfected with the mouse carriers mOct1, mOct2, mMate1, and mMate2, respectively. Results: Mouse mOct1, mOct2, and mMate1 showed significant TCl transport with Km values of 58.7, 78.5, and 29.3 µM, respectively. In contrast, mMate2 did not transport TCl but showed MPP+ transport with Km of 60.0 µM that was inhibited by the drugs topotecan, acyclovir, and levofloxacin. Conclusion: TCl transport behavior as well as expression pattern were quite similar for the mouse carriers mOct1, mOct2, and mMate1 compared to their human counterparts.

This paper presents a neuromorphic, event-driven tactile sensing system for soft, large-area skin, based on the Dynamic Vision Sensors (DVS) integrated with a flexible silicone optical waveguide skin. Instead of repetitively scanning embedded photoreceivers, this design uses a stereo vision setup comprising two DVS cameras looking sideways through the skin. Such a design produces events as changes in brightness are detected, and estimates press positions on the 2D skin surface through triangulation, utilizing Density-Based Spatial Clustering of Applications with Noise (DBSCAN) to find the center of mass of contact events resulting from pressing actions. The system is evaluated over a 4,620 mm probed area of the skin using a meander raster scan. Across 95 % of the presses visible to both cameras, the press localization achieved a Root-Mean-Squared Error (RMSE) of 4.66 mm. The results highlight the potential of this approach for wide-area flexible and responsive tactile sensors in soft robotics and interactive environments. Moreover, we examined how the system performs when the amount of event data is strongly reduced. Using stochastic down-sampling, the event stream was reduced to 1/1,024 of its original size. Under this extreme reduction, the average localization error increased only slightly (from 4.66 mm to 9.33 mm), and the system still produced valid press localizations for 85 % of the trials. This reduction in pass rate is expected, as some presses no longer produce enough events to form a reliable cluster for triangulation. These results show that the sensing approach remains functional even with very sparse event data, which is promising for reducing power consumption and computational load in future implementations. The system exhibits a detection latency distribution with a characteristic width of 31 ms.

The hepatic Na.sup.+ /taurocholate co-transporting polypeptide (NTCP in man, Ntcp in animals) is the high-affinity receptor for the hepatitis B (HBV) and hepatitis D (HDV) viruses. Species barriers for human HBV/HDV within the order Primates were previously attributed to Ntcp sequence variations that disable virus-receptor interaction. However, only a limited number of primate Ntcps have been analysed so far. In the present study, a total of 11 Ntcps from apes, Old and New World monkeys were cloned and expressed in vitro to characterise their interaction with HBV and HDV. All Ntcps showed intact bile salt transport. Human NTCP as well as the Ntcps from the great apes chimpanzee and orangutan showed transport-competing binding of HBV derived myr-preS1-peptides. In contrast, all six Ntcps from the group of Old World monkeys were insensitive to HBV myr-preS1-peptide binding and HBV/HDV infection. This is basically predetermined by the amino acid arginine at position 158 of all studied Old World monkey Ntcps. An exchange from arginine to glycine (as present in humans and great apes) at this position (R158G) alone was sufficient to achieve full transport-competing HBV myr-preS1-peptide binding and susceptibility for HBV/HDV infection. New World monkey Ntcps showed higher sequence heterogeneity, but in two cases with 158G showed transport-competing HBV myr-preS1-peptide binding, and in one case (Saimiri sciureus) even susceptibility for HBV/HDV infection. In conclusion, amino acid position 158 of NTCP/Ntcp is sufficient to discriminate between the HBV/HDV susceptible group of humans and great apes (158G) and the non-susceptible group of Old World monkeys (158R). In the case of the phylogenetically more distant New World monkey Ntcps amino acid 158 plays a significant, but not exclusive role.

Overexpression of single genes in mammalian cells is widely used to investigate protein function in basic and applied biosciences and in drug research. A better understanding of interactions of two proteins is an important next step in the advancement of our understanding of complex biological systems. However, simultaneous and robust overexpression of two or more genes is challenging. The Flp-In system integrates a vector into cell lines at a specific genomic locus, but has not been used for integration of more than one gene. Here we present a modification of the Flp-In system that enables the simultaneous targeted integration of two genes. We describe the modification and generation of the vectors required and give the complete protocol for transfection and validation of correct genomic integration and expression. We also provide results on the stability and reproducibility, and we functionally validated this approach with a pharmacologically relevant combination of a membrane transporter facilitating drug uptake and an enzyme mediating drug metabolism.

The multidrug resistance gene MDR1 (syn. ABCB1) encodes for the multidrug efflux transporter P-glycoprotein (P-gp), which is highly expressed at the blood-brain barrier and protects the brain from potentially neurotoxic compounds, such as ivermectin. MDR1 mutation in dogs is known to be linked to dramatically increased brain accumulation of ivermectin and life-threatening neurological toxicity. The present report describes two suspected ivermectin-sensitive Maine Coon cats, which exhibited neurological toxicity following subcutaneous application of therapeutic doses of ivermectin. Both cats showed a homozygous 2-bp deletion in the MDR1/ABCB1 coding sequence ( ABCB1 1930_1931del TC, syn. MDR1 nt1930(del2)) that had previously been associated with a drug-sensitive phenotype in cats. For cat MDR1 genotyping, a novel TaqMan allelic discrimination assay was established and validated. This assay was used for ABCB1 1930_1931del TC genotyping of the drug-sensitive cats as well as of more than 50 relatives. About half of them had the heterozygous MDR1(+/-) genotype, while none of these related cats with former ivermectin treatment had a history of drug-sensitivity. In conclusion: The present study supports previous findings on drug-sensitivity in cats with homozygous ABCB1 1930_1931del TC mutation. The newly established TaqMan allelic discrimination assay provides a useful and reliable method for routine MDR1 genotyping in cats in order to identify drug-sensitive cats prior to treatment with established P-gp substrates such as ivermectin and other macrocyclic lactones and thus to improve therapeutic safety.