Electrochemical Detection o f Chemical Warfare Agent Mimics

Rising concern over the use of chemical warfare agents (CWAs) in criminal terrorist attacks has attracted a great deal of interest in having rapid, reliable and affordable methods for the detection of CWAs and their related degradation products. Four ferrocene-amino acid / peptide conjugates, Fc-CO-Lys(Boc), Fc-CO- Leu-Lys(Boc), Fc-CO-Lys(Boc)-Leu, and (Boc)Arg(N02)-NH(CH2)4NH-CO-Fc were synthesized and used to modify acid-treated multi-walled carbon nanotubes (MWCNTs) chemically. Fc-conjugate-modified-MWCNTs were deposited on ITO surfaces as the key component for electrochemical detection sensors for chemical warfare agent (CWA) mimics and their decomposed products in water. The electrical properties of the MWCNTs and Fc group were affected significantly upon the adding of CWA mimics to the system. In some cases, new peaks were observed at the presence of CWA mimics. Presumably, electrochemical changes are caused by the intermolecular interaction of the CWA with the peptide component of the sensors. This kind of electrochemical sensors were found stable and allowed trace-level detection of CWA mimics in aqueous solutions

Tetra-n-butyl­ammonium tricyanido[N-(2-pyridyl­carbon­yl)pyridine-2-carbox­imidato]ferrate(III) dihydrate

In the title compound, (C16H36N)[Fe(C12H8N3O2)(CN)3]·2H2O, the tetra-n-butyl­ammonium ion has a tetra­hedral configuration around the N atom, while the FeIII atom of the tricyanido[N-(2-pyridyl­carbon­yl)pyridine-2-carboximidato]iron(III) anion adopts a distorted octa­hedral geometry. O—H⋯O and O—H⋯N hydrogen bonds link the components in the crystal structure

A pH-Sensitive Delivery System for the Prevention of Dental Caries Using Salivary Protein

Dental caries remains one of the most common chronic diseases worldwide. In previous studies, salivary proteins (e.g. histatin 3, statherin) have demonstrated biological functions including the inhibition of crystal growth, antibacterial activities, which are directly related to tooth homeostasis and prevention of dental caries. However, proteins are susceptible to the high proteolytic activities in the oral environment. Therefore, pH-sensitive chitosan nanoparticles (CNs) have been proposed as potential carriers to protect proteins against enzymatic degradation at physiological salivary pH, in addition to swell selectively at lower pH conditions to facilitate the release of the encapsulated proteins, as major oral complications occur under acidic conditions (e.g. dental caries and dental erosion). Four different types of chitosan polymers were investigated and the optimal CNs formulation was selected, the chosen formulation had a good batch to batch reproducibility with an average hydrodynamic diameter of 144 ± 6 nm, a polydispersity index of 0.15 ± 0.04, and a zeta potential of 18 ± 4 mV at the final pH of 6.2. Histatin 3 encapsulation and release profiles were characterized by cationic polyacrylamide gel electrophoresis. The CNs successfully encapsulated histatin 3 at 2%, 5% and 10% w/w loading ratios, they also selectively released histatin 3 under acidic conditions. Through protein degradation study in whole saliva supernatant, histatin 3 encapsulated inside the delivery system demonstrated a prolonged survival time compared to the free histatin 3. The results of this study have demonstrated the pH-responsive property and the protection offered by CNs

Length is a Curse and a Blessing for Document-level Semantics

In recent years, contrastive learning (CL) has been extensively utilized to recover sentence and document-level encoding capability from pre-trained language models. In this work, we question the length generalizability of CL-based models, i.e., their vulnerability towards length-induced semantic shift. We verify not only that length vulnerability is a significant yet overlooked research gap, but we can devise unsupervised CL methods solely depending on the semantic signal provided by document length. We first derive the theoretical foundations underlying length attacks, showing that elongating a document would intensify the high intra-document similarity that is already brought by CL. Moreover, we found that isotropy promised by CL is highly dependent on the length range of text exposed in training. Inspired by these findings, we introduce a simple yet universal document representation learning framework, LA(SER)$^{3}$: length-agnostic self-reference for semantically robust sentence representation learning, achieving state-of-the-art unsupervised performance on the standard information retrieval benchmark.Comment: Accepted at EMNLP 2023. Our code is publicly available at https://github.com/gowitheflow-1998/LA-SER-cube

Ph-sensitive chitosan nanoparticles for salivary protein delivery

Salivary proteins such as histatins (HTNs) have demonstrated critical biological functions directly related to tooth homeostasis and prevention of dental caries. However, HTNs are susceptible to the high proteolytic activities in the oral environment. Therefore, pH-sensitive chitosan nanoparti-cles (CNs) have been proposed as potential carriers to protect proteins from enzymatic degradation at physiological salivary pH. Four different types of chitosan polymers were investigated and the optimal formulation had good batch to batch reproducibility, with an average hydrodynamic diame-ter of 144 ± 6 nm, a polydispersity index of 0.15 ± 0.04, and a zeta potential of 18 ± 4 mV at a final pH of 6.3. HTN3 encapsulation and release profiles were characterized by cationic polyacrylamide gel electrophoresis. The CNs successfully encapsulated HTN3 and selectively swelled at acidic pH to facilitate HTN3 release. Protection of HTN3 against enzymatic degradation was investigated in diluted whole saliva. HTN3 encapsulated in the CNs had a prolonged survival time compared to the free HTN3. CNs with and without HTN3 also successfully reduced biofilm weight and bacterial viability. The results of this study have demonstrated the suitability of CNs as potential protein carriers for oral applications, especially for complications occurring at acidic conditions

Audio Contrastive based Fine-tuning

Audio classification plays a crucial role in speech and sound processing tasks with a wide range of applications. There still remains a challenge of striking the right balance between fitting the model to the training data (avoiding overfitting) and enabling it to generalise well to a new domain. Leveraging the transferability of contrastive learning, we introduce Audio Contrastive-based Fine-tuning (AudioConFit), an efficient approach characterised by robust generalisability. Empirical experiments on a variety of audio classification tasks demonstrate the effectiveness and robustness of our approach, which achieves state-of-the-art results in various settings.Comment: Under revie

Proteomic signature of the murine intervertebral disc

© 2015 McCann et al. Low back pain is the most common musculoskeletal problem and the single most common cause of disability, often attributed to degeneration of the intervertebral disc. Lack of effective treatment is directly related to our limited understanding of the pathways responsible for maintaining disc health. While transcriptional analysis has permitted initial insights into the biology of the intervertebral disc, complete proteomic characterization is required. We therefore employed liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) protein/peptide separation and mass spectrometric analyses to characterize the protein content of intervertebral discs from skeletally mature wild-type mice. A total of 1360 proteins were identified and categorized using PANTHER. Identified proteins were primarily intracellular/plasma membrane (35%), organelle (30%), macromolecular complex (10%), extracellular region (9%). Molecular function categorization resulted in three distinct categories: catalytic activity (33%), binding (molecule interactions) (29%), and structural activity (13%). To validate our list, we confirmed the presence of 14 of 20 previously identified IVD-associated markers, including matrix proteins, transcriptional regulators, and secreted proteins. Immunohistochemical analysis confirmed distinct localization patterns of select protein with the intervertebral disc. Characterization of the protein composition of healthy intervertebral disc tissue is an important first step in identifying cellular processes and pathways disrupted during aging or disease progression

The Bromodomain and Extra-Terminal Protein Inhibitor OTX015 Suppresses T Helper Cell Proliferation and Differentiation

BACKGROUND: Dynamic epigenetic alterations accompanying CD4+ T helper cell differentiation have been implicated in multiple autoimmune diseases. The bromodomain and extra-terminal (BET) proteins are epigenetic regulators that recognize and bind to acetylated histones in chromatin and are targets for pharmacological inhibition. In this study we tested a new BET inhibitor under clinical development, OTX015, to interrogate its effects on key CD4+ T cell subsets associated with autoimmunity. METHODS: Naïve and memory murine and human CD4+ T cells were isolated and differentiated into populations characterized by the expression of interferon (IFN)-γ and interleukin (IL)-17. Cultured cells were then exposed to varying concentrations of OTX015 in vitro, and its impact on cytokine expression was quantified by flow cytometry. In parallel, the expression of the transcription factors TBX21 and RORC was quantified by PCR. A previously studied BET inhibitor JQ1 was used as a pharmacological control. RESULTS: OTX015 suppressed both murine and human CD4+ T cell proliferation. Its impact on cytokine expression varied in murine and human naïve and memory subsets. OTX015 was similarly effective as JQ1 in the suppression of cytokines and T helper cell proliferation. Higher concentrations of OTX015 also had a greater impact on the viability of murine versus human cells. IL-17 and IFN-γ expression was not altered in murine memory CD4+ T cells, whereas in human memory CD4+ T cells, OTX015 inhibited IL-17, but not IFN-γ. Across all human T cell subsets OTX015 suppressed IL-17 more effectively than IFN-γ. CONCLUSION: Our studies demonstrate that OTX015 has anti-inflammatory effects by suppressing murine and human CD4+ T cell proliferation and subset-dependent proinflammatory cytokine expression, including the selective suppression of IL-17 in human memory CD4+ T cells

Quantitative Proteomic Analysis of the Effect of Fluoride on the Acquired Enamel Pellicle

The acquired enamel pellicle (AEP) is a thin film formed by the selective adsorption of salivary proteins onto the enamel surface of teeth. The AEP forms a critical interface between the mineral phase of teeth (hydroxyapatite) and the oral microbial biofilm. This biofilm is the key feature responsible for the development of dental caries. Fluoride on enamel surface is well known to reduce caries by reducing the solubility of enamel to acid. Information on the effects of fluoride on AEP formation is limited. This study aimed to investigate the effects of fluoride treatment on hydroxyapatite on the subsequent formation of AEP. In addition, this study pioneered the use of label-free quantitative proteomics to better understand the composition of AEP proteins. Hydroxyapatite discs were randomly divided in 4 groups (n = 10 per group). Each disc was exposed to distilled water (control) or sodium fluoride solution (1, 2 or 5%) for 2 hours. Discs were then washed and immersed in human saliva for an additional 2 hours. AEP from each disc was collected and subjected to liquid chromatography electrospray ionization mass spectrometry for protein identification, characterization and quantification. A total of 45 proteins were present in all four groups, 12 proteins were exclusively present in the control group and another 19 proteins were only present in the discs treated with 5% sodium fluoride. Relative proteomic quantification was carried out for the 45 proteins observed in all four groups. Notably, the concentration of important salivary proteins, such as statherin and histatin 1, decrease with increasing levels of fluoride. It suggests that these proteins are repulsed when hydroxyapatite surface is coated with fluoride. Our data demonstrated that treatment of hydroxyapatite with fluoride (at high concentration) qualitatively and quantitatively modulates AEP formation, effects which in turn will likely impact the formation of oral biofilms.Natural Sciences and Engineering Research Council of Canada (NSERC) [371813]Natural Sciences and Engineering Research Council of Canada (NSERC)Canadian Institutes of Health Research (CIHR)Canadian Institutes of Health Research (CIHR) [106657, 97577]Canada Foundation for Innovation - Leaders Opportunity Fund (CFI-LOF) [25116]Canada Foundation for Innovation Leaders Opportunity Fund (CFILOF)CIHR New Investigator AwardCIHR New Investigator Award [113166