Development and Evaluation of Feline Tailored Amlodipine Besylate Mini-Tablets Using l-lysine as a Candidate Flavouring Agent

Felines may find orally administered medicines unpalatable, thus presenting a problem in the treatment of chronic conditions such as hypertension, a commonly diagnosed condition in felines requiring daily administration of medication. A pertinent example is amlodipine besylate, formulations of which are known to be poorly tolerated by cats. There is therefore a need to develop feline-specific delivery approaches that are both simple to administer and mask the taste of the drug, thereby enhancing the owner's commitment to treatment and the associated therapeutic outcome for the companion animal. In addition, it is helpful to develop accessible and reproducible means of assessing taste for pre-clinical selection, hence the use of recently developed taste biosensor systems for veterinary applications is an area of interest. This study focuses on developing feline-specific amlodipine besylate formulations by improving the taste using a suitable flavouring agent while reducing dosage form size to a 2 mm diameter mini-tablet. The choice of L-lysine as a flavouring agent was based on the dietary and taste preference of cats. The impact of L-lysine on the taste perception of the formulation was evaluated using a biosensor system (E-tongue) fitted with sensors sensitive to bitter tastes. The results showed L-lysine successfully masked bitterness, while the drug release studies suggest that it has no impact on drug dissolution. In addition, tableting parameters such as tablet mass uniformity, content uniformity, tablet diameter, thickness and hardness were all satisfactory. The present study suggests that amlodipine besylate mini-tablets containing L-lysine could improve the palatability and in turn support product acceptability and ease of administration. These data could have an impact on orally administered medicines for cats and other veterinary species through product differentiation and competitive advantage in the companion animal market sector. The study also outlines the use of the electronic tongue as a tool for formulation selection in the veterinary field

A RAMP marker linked to the tobacco black shank resistant gene

Bulk segregant analysis (BSA) and randomly amplified microsatellite polymorphism (RAMP) were employed to analyze F2 individuals of the Yunyan 317×Hubei 517 to screen and characterize molecularmarkers linked to black shank resistant gene. A total of 800 arbitrary decamer oligonucleotide primerpairs were used for RAMP analysis. Primer pair GT (CA) 4/S89, producing one RAMP marker GT (CA)4/S89550, was tightly linked to the black shank resistant gene. Results of Southern blot suggest that the fragment GT (CA) 4/S89550 was existed in Yunyan 317 and resistant plants, and absent in Hubei 517.Linkage analysis was carried out using marker GT (CA) 4/S89550 on 752 black shank high-resistant individuals of F2 progenies from crossing between Yunyan 317 and Hubei 517. Our results indicated thatthe genetic distances between GT (CA) 4/S89550 and black shank resistant gene was 1.4cM

Potentiation of sensory responses in ventrobasal thalamus in vivo via selective modulation of mGlu1 receptors with a positive allosteric modulator.

Metabotropic glutamate subtype 1 (mGlu1) receptor is thought to play a role in synaptic responses in thalamic relay nuclei. The aim of this study was to evaluate the positive allosteric modulator (PAM) Ro67-4853 as a tool to modulate thalamic mGlu1 receptors on single thalamic neurones in vivo. Ro67-4853, applied by iontophoresis onto ventrobasal thalamus neurones of urethane-anaesthetised rats, selectively enhanced responses to the agonist (S)-3,5-dihydroxy-phenylglycine (DHPG), an effect consistent with mGlu1 potentiation. The PAM was also able to enhance maintained responses to 10 Hz trains of sensory stimulation of the vibrissae, but had little effect on responses to single sensory stimuli. Thus Ro67-4853 appears to be a highly selective tool that can be useful in investigating how mGlu1 receptor potentiation can alter neural processing in vivo. Our results show the importance of mGlu1 in sensory processing and attention mechanisms at the thalamic level and suggest that positive modulation of mGlu1 receptors might be a useful mechanism for enhancing cognitive and attentional processes

Finding the Missing-half: Graph Complementary Learning for Homophily-prone and Heterophily-prone Graphs

Real-world graphs generally have only one kind of tendency in their connections. These connections are either homophily-prone or heterophily-prone. While graphs with homophily-prone edges tend to connect nodes with the same class (i.e., intra-class nodes), heterophily-prone edges tend to build relationships between nodes with different classes (i.e., inter-class nodes). Existing GNNs only take the original graph during training. The problem with this approach is that it forgets to take into consideration the ``missing-half" structural information, that is, heterophily-prone topology for homophily-prone graphs and homophily-prone topology for heterophily-prone graphs. In our paper, we introduce Graph cOmplementAry Learning, namely GOAL, which consists of two components: graph complementation and complemented graph convolution. The first component finds the missing-half structural information for a given graph to complement it. The complemented graph has two sets of graphs including both homophily- and heterophily-prone topology. In the latter component, to handle complemented graphs, we design a new graph convolution from the perspective of optimisation. The experiment results show that GOAL consistently outperforms all baselines in eight real-world datasets.Comment: Accepted by ICML 202

Classification on imbalanced data sets, taking advantage of errors to improve performance

Classification methods usually exhibit a poor performance when they are applied on imbalanced data sets. In order to overcome this problem, some algorithms have been proposed in the last decade. Most of them generate synthetic instances in order to balance data sets, regardless the classification algorithm. These methods work reasonably well in most cases; however, they tend to cause over-fitting. In this paper, we propose a method to face the imbalance problem. Our approach, which is very simple to implement, works in two phases; the first one detects instances that are difficult to predict correctly for classification methods. These instances are then categorized into “noisy” and “secure”, where the former refers to those instances whose most of their nearest neighbors belong to the opposite class. The second phase of our method, consists in generating a number of synthetic instances for each one of those that are difficult to predict correctly. After applying our method to data sets, the AUC area of classifiers is improved dramatically. We compare our method with others of the state-of-the-art, using more than 10 data sets

Flavor SU(3) symmetry and QCD factorization in B→PPB \to PP and PVPV decays

Using flavor SU(3) symmetry, we perform a model-independent analysis of charmless $\bar B_{u,d} (\bar B_s) \to PP, ~PV$ decays. All the relevant topological diagrams, including the presumably subleading diagrams, such as the QCD- and EW-penguin exchange diagrams and flavor-singlet weak annihilation ones, are introduced. Indeed, the QCD-penguin exchange diagram turns out to be important in understanding the data for penguin-dominated decay modes. In this work we make efforts to bridge the (model-independent but less quantitative) topological diagram or flavor SU(3) approach and the (quantitative but somewhat model-dependent) QCD factorization (QCDF) approach in these decays, by explicitly showing how to translate each flavor SU(3) amplitude into the corresponding terms in the QCDF framework. After estimating each flavor SU(3) amplitude numerically using QCDF, we discuss various physical consequences, including SU(3) breaking effects and some useful SU(3) relations among decay amplitudes of $\bar B_s \to PV$ and $\bar B_d \to PV$.Comment: 47 pages, 3 figures, 28 table

A pilot study of the King LT supralaryngeal airway use in a rural Iowa EMS system

Introduction In 2003, the King Laryngeal Tube (LT) received FDA approval for US sales. Prehospital systems in urban setting have begun evaluating and adopting the LT for clinical airway management. However, it is not routinely approved by State EMS Boards for use by all prehospita

The mechanism of supplementary cementitious materials enhancing the water resistance of magnesium oxychloride cement (MOC): A comparison between pulverized fuel ash and incinerated sewage sludge ash

Magnesium oxychloride cement (MOC) pastes incorporating supplementary cementitious materials (SCMs) including pulverized fuel ash (PFA) and incinerated sewage sludge ash (ISSA) were examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) with energy dispersive X-ray spectrometry (EDX). The result showed that the mechanism of PFA and ISSA in improving the water resistance of MOC paste is similar, even though the molar ratios of the hydration product in the ISSA-incorporated paste and the PFA-incorporated paste were different. The active phases in PFA or ISSA could react with MgO and produce an amorphous phase (amorphous magnesium aluminosilicate gel), which was interspersed with Phase 5 and changed the morphology of Phase 5 to fibroid or lath-like phases. These fibroid or lath-like phases interlocked with each other and also connected with the amorphous phase in the matrix to form a stable compact structure. Therefore, the water resistance of MOC was improved. The ISSA-blended MOC paste had higher water resistance compared to the PFA-blended MOC, which may be due to the different chemical composition of amorphous phase and the dissolved phosphorus from ISSA

How nostalgic brand positioning shapes brand equity: differences between emerging and developed markets

Extant research has established the effects of nostalgic brand positioning on brand equity, but studies have only examined individual nostalgic brand relationship dimensions separately. Combining these strands, we offer a holistic perspective of the mediating processes and identify contextual and firm-related moderators that affect the individual linkages. We draw on construal level theory and develop a multilevel model in which emotional attachment, brand local iconness, and brand authenticity explain how nostalgic brand positioning creates brand equity. We posit that country differences between emerging and developed markets and brand innovativeness moderate these mediating effects. The results from large consumer samples suggest that emotional attachment and brand local iconness play a weaker role in mediating the connection of nostalgic brand positioning and brand equity in emerging markets. However, this disadvantage in creating brand equity through nostalgic brand positioning in emerging markets can be attenuated with increasing levels of brand innovativeness