Reclaiming behaviour settings: reviewing empirical applications of Barker's behaviour settings theory.

Behaviour settings theory is the product of Roger Barker and Herbert F. Wright's decades-long Midwest Field Station research programme. The theory followed from the demonstration that the best predictor of a person's behaviour was the setting (i.e. location, timing and activity) in which their behaviour took place, rather than any individual trait (e.g. personality). Now little known in psychology, behaviour settings theory is often further obscured by being presented as a theory only, neglecting the clear methodology Barker provided for investigating the question: 'What do people do in everyday life?' This literature review takes a comprehensive look at Barker's contributions both within and outside of psychology. The corpus comprises both theoretical and empirical articles; however, our primary interest is in the empirical articles. We describe the who, when and where of behaviour settings research over the past half-century, and we identify branches and neighbours of behaviour settings research (e.g. manning theory, behaviour mapping and activity settings theory). Primarily, however, we attempt to answer the following questions: (i) Are any of Barker's tools for studying people in everyday settings being used currently? (ii) How accurately has Barker's theory been explained, or his methods applied? (iii) Does such work contribute to behaviour settings theory in a meaningful way? This article is part of the theme issue 'People, places, things and communities: expanding behaviour settings theory in the twenty-first century'.

A practitioner's field guide to the behaviour settings method.

Since the 1950s, Roger Barker's theory of behaviour settings has been useful for a wide number of disciplines. Few realize, however, that behaviour settings theory is also a methodology. Barker fully describes how to identify, describe and measure behaviour settings in his seminal book Ecological psychology: concepts and methods for studying the environment of human behavior (1968), and this method is further delineated in Phil Schoggen's Behavior settings: a revision and extension of Roger G. Barker's ecological psychology (1989). Nevertheless, beyond these two (rather expensive) books there are few other resources available to twenty-first century researchers who wish to systematically describe and measure behaviour in its ecological context using the principles of behaviour settings theory. In this article, I offer a practitioner's field guide to implementing the behaviour settings method, which includes a contemporary illustration of defining a behaviour setting using a recent observational study of an art gallery in Lethbridge, Canada. I discuss how researchers can use Barker's original methodology to determine what is a behaviour setting and how to define its boundaries, and I suggest best practices, offering practitioners the tools to replicate Barker's procedures. This article is part of the theme issue 'People, places, things, and communities: expanding behaviour settings theory in the twenty-first century'.

Newly discovered clouting interplay between matrix metalloproteinases structures and novel quaternary Ammonium K21: computational and in-vivo testing.

AIMS AND OBJECTIVES: To analyze anti-MMP mode of action of Quaternary Ammonium Silane (QAS, codenamed as k21) by binding onto specific MMP site using computational molecular simulation and Anti-Sortase A (SrtA) mode of action by binding onto specific site using computational molecular simulation. MATERIALS AND METHODS: In silico Molecular Dynamics (MD) was used to determine the interactions of K21 inside the pocket of the targeted protein (crystal structure of fibroblast collagenase-1 complexed to a diphenyl-ether sulphone based hydroxamic acid; PDB ID: 966C; Crystal structure of MMP-2 active site mutant in complex with APP-derived decapeptide inhibitor. MD simulations were accomplished with the Desmond package in Schrödinger Drug Discovery Suite. Blood samples (~ 0.5 mL) collected into K2EDTA were immediately transferred for further processing using the Litron MicroFlow® PLUS micronucleus analysis kit for mouse blood according to the manufacturer's instructions. Bacterial Reverse Mutation Test of K21 Molecule was performed to evaluate K21 and any possible metabolites for their potential to induce point mutations in amino acid-requiring strains of Escherichia coli (E. coli) (WP2 uvrA (tryptophan-deficient)). RESULTS: Molecular Simulation depicted that K21 has a specific pocket binding on various MMPs and SrtA surfaces producing a classical clouting effect. K21 did not induce micronuclei, which are the result of chromosomal damage or damage to the mitotic apparatus, in the peripheral blood reticulocytes of male and female CD-1 mice when administered by oral gavage up to the maximum recommended dose of 2000 mg/kg. The test item, K21, was not mutagenic to Salmonella typhimurium (S. typhimurium) strains TA98, TA100, TA1535 and TA1537 and E. coli strain WP2 uvrA in the absence and presence of metabolic activation when tested up to the limit of cytotoxicity or solubility under the conditions of the test. CONCLUSION: K21 could serve as a potent protease inhibitor maintaining the physical and biochemical properties of dental structures.

Antimicrobial FiteBac® K21 promotes antimicrobial Potency and wound healing.

Objectives: Successful root canal therapy is dependent on the efficacy of complete instrumentation and adequate use of chemical irrigant to eliminate the biofilm from dentin surface. The aim of the study was to examine antibiofilm and antimicrobial effectiveness of newly formulated Quaternary ammonium silane (QAS/also codenamed K21; against Fusobacterium nucleatum (F. nucleatum) and Enterococcus faecalis (E. faecalis) biofilm on radicular dentin with evaluation of the anti-inflammatory consequence in vivo. Methods: Fourier Transform Infrared Spectroscopy (FTIR) was performed after complete hydrolysis of K21 solution. Human teeth were inoculated with biofilms for 7-days followed by treatment with various irrigants. The irrigant groups were Sodium hypochlorite [NaOCl (6%)], Chlorhexidine [CHX (2%)], K21 (0.5%), K21 (1%) and Saline. Scanning electron microscopy (SEM) was performed for biofilm and resin-dentin penetration. Transmission Electron Microscopy (TEM) of biofilms was done to evaluate application of K21. For in vivo evaluation, Albino wistar rats were injected subcutaneously and sections were stained with haematoxylin/eosin. Macrophage, M1/M2 expression were evaluated along with molecular simulation. Raman measurements were done on dried biofilms. Results: FTIR K21 specimens demonstrated presence of ethanol/silanol groups. Raman band at 1359 cm-1 resemble to -CH2- wagging displaying 29Si atoms in Nuclear Magnetic Resonance (NMR). 0.5%K21 showed cells exhibiting folded membranes. SEM showed staggering amount of resin tags with 0.5% K21 group. TEM showed membrane disruption in K21-groups. K21 groups were initially irritant, which subsided completely afterwards showing increased CD68. K21 and MMP/collagen complex was thermodynamically favourable. Conclusion: K21 root canal irrigant was able to penetrate bacterial wall and can serve as a potential irrigant for therapeutic benefits. Expression of M2 polarized subsets showed K21 can serve in resolving inflammation and potentiate tissue repair.

Cathepsin-K inhibition enhances anti-cancerous activity within oral squamous cell carcinoma cells: Uncloaking the potency of new K21 formulation.

BACKGROUND: The ability of cancer cells to be invasive and metastasize depend on several factors, of which the action of protease activity takes center stage in disease progression. PURPOSE/OBJECTIVE: To analyze function of new K21 molecule in the invasive process of oral squamous cell carcinoma (OSCC) cell line. MATERIALS & METHODS: The Fusobacterium (ATCC 23726) streaks were made, and pellets were resuspended in Cal27 (ATCC CRL-2095) OSCC cell line spheroid cell microplate. Cells were seeded and Lysotracker staining performed for CathepsinK red channel. Cell and morphology were evaluated using Transmission Electron microscopy. Thiobarbituric acid assay was performed. OSCC was analyzed for Mic60. Raman spectra were collected from the cancer cell line. L929 dermal fibroblast cells were used for Scratch Assay. ELISA muti arrays were used for cytokines and matrix molecules. Internalization ability of fibroblast cells were also analyzed. Structure of K21 as a surfactant molecule with best docked poses were presented. RESULTS: Decrease in lysosomal staining was observed after 15 and 30 min of 0.1% treatment. Tumor clusters were associated with cell membrane destruction in K21 primed cells. There was functional silencing of Mic60 via K21, especially with 1% concentration with reduced cell migration and invasiveness. Raman intensity differences were seen at 700 cm-1, 1200 cm-1 and 1600 cm-1 regions. EVs were detected within presence of fibroblast cells amongst K21 groups. Wound area and wound closure showed the progress of wound healing. CONCLUSION: Over expression of CatK can be reduced by a newly developed targeted K21 based drug delivery system leading to reduced migration and adhesion of oral squamous cell carcinoma cells. The K21 drug formulation can have great potential for cancer therapies due to targeting and cytotoxicity effects.

LncRNA RP5-857K21.7 inhibits PDGF-BB-induced proliferation and migration of airway smooth muscle cells through the miR-508-3p/PI3K/AKT/mTOR axis.

The continuous increase in the prevalence of asthma poses a threat to human health. Despites numerous researches, the understanding of asthma development still remain elusive, hindering the development of effective treatment. Here, we explored the role of lncRNA RP5-857K21.7 (RP5-857K21.7) in the development of asthma and its potential molecular mechanism of regulation. Airway smooth muscle cells (ASMCs) were isolated and cultured after which some of the cells were induced with PDGF-BB to build an asthma cell model, and then, qRT-PCR analysis was used to measure the expression level of RP5-857K21.7 in the cell model. Result shows that the RP5-857K21.7 is significantly downregulated in PDGF-BB-induced ASMCs cells. Through CCK-8, transwell, and flow cytometry assay, we examined the functional impact of RP5-857K21.7 on the proliferation, migration, and apoptosis of the ASMCs, respectively, and found that the overexpression of RP5-857K21.7 markedly inhibit PDGF-BB-induced ASMCs cell proliferation, migration and induce apoptosis. Bioinformatics analysis predicted that the RP5-857K21.7 could sponge miR-508-3p and result was validated through a dual-luciferase reporter assay, biotinylated RNA pull-down assay, and RIP-qRT-PCR analysis. Mechanistically, RP5-857K21.7 regulates the PI3K/AKT/mTOR pathway by endogenously sponging miR-508-3p to inhibit PDGF-BB-induced ASMCs cell proliferation, migration and induce apoptosis. The current research suggests that the RP5-857K21.7 and its associated molecular pathway (miR-508-3p/PI3K/AKT/mTOR axis) might be a useful therapeutic target for the treatment of asthma disease.

Optimal transport of vector measures.

We develop and study a theory of optimal transport for vector measures. We resolve in the negative a conjecture of Klartag, that given a vector measure on Euclidean space with total mass zero, the mass of any transport set is again zero. We provide a counterexample to the conjecture. We generalise the Kantorovich-Rubinstein duality to the vector measures setting. Employing the generalisation, we answer the conjecture in the affirmative provided there exists an optimal transport with absolutely continuous marginals of its total variation.

Antibacterial and antibiofilm efficacy of k21-E in root canal disinfection.

OBJECTIVES: The aim of the current project was to study the antimicrobial efficacy of a newly developed irrigant, k21/E against E. faecalis biofilm. METHODS: Root canals were instrumented and randomly divided into the following groups: irrigation with saline, 6% NaOCl (sodium hypochlorite), 6% NaOCl+2% CHX (Chlorhexidine), 2% CHX, 0.5% k21/E (k21 - quaternary ammonium silane) and 1% k21/E. E. faecalis were grown (3-days) (1×107CFU mL-1), treated, and further cultured for 11-days. Specimens were subjected to SEM, confocal and Raman analysis and macrophage vesicles characterized along with effect of lipopolysaccharide treatment. 3T3 mouse-fibroblasts were cultured for alizarin-red with Sortase-A active sites and Schrödinger docking was performed. TEM analysis of root dentin substrate with matrix metalloproteinases profilometry was also included. A cytotoxic test analysis for cell viability was measured by absorbance of human dental pulp cells after exposure to different irrigant solutions for 24h. The test percentages have been highlighted in Table 1. RESULTS: Among experimental groups, irrigation with 0.5% k21/E showed phase separation revealing significant bacterial reduction and lower phenylalanine 1003cm-1 and Amide III 1245cm-1 intensities. Damage was observed on bacterial cell membrane after use of k21/E. No difference in exosomes distribution between control and 0.5%k21/E was observed with less TNFα (*p<0.05) and preferential binding of SrtA. TEM images demonstrated integrated collagen fibers in control and 0.5%k21/E specimens and inner bacterial membrane damage after k21/E treatment. The k21 groups appeared to be biocompatible to the dental pulpal cells grown for 24h. SIGNIFICANCE: Current investigations highlight potential advantages of 0.5% k21/E as irrigation solution for root canal disinfection.

Molecular Dynamic Simulation Search for Possible Amphiphilic Drug Discovery for Covid-19.

To determine whether quaternary ammonium (k21) binds to Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) spike protein via computational molecular docking simulations, the crystal structure of the SARS-CoV-2 spike receptor-binding domain complexed with ACE-2 (PDB ID: 6LZG) was downloaded from RCSB PD and prepared using Schrodinger 2019-4. The entry of SARS-CoV-2 inside humans is through lung tissues with a pH of 7.38-7.42. A two-dimensional structure of k-21 was drawn using the 2D-sketcher of Maestro 12.2 and trimmed of C18 alkyl chains from all four arms with the assumption that the core moiety k-21 was without C18. The immunogenic potential of k21/QA was conducted using the C-ImmSim server for a position-specific scoring matrix analyzing the human host immune system response. Therapeutic probability was shown using prediction models with negative and positive control drugs. Negative scores show that the binding of a quaternary ammonium compound with the spike protein's binding site is favorable. The drug molecule has a large Root Mean Square Deviation fluctuation due to the less complex geometry of the drug molecule, which is suggestive of a profound impact on the regular geometry of a viral protein. There is high concentration of Immunoglobulin M/Immunoglobulin G, which is concomitant of virus reduction. The proposed drug formulation based on quaternary ammonium to characterize affinity to the SARS-CoV-2 spike protein using simulation and computational immunological methods has shown promising findings.

The novel male meiosis recombination regulator coordinates the progression of meiosis prophase I.

Meiosis is a specialized cell division for producing haploid gametes in sexually reproducing organisms. In this study, we have independently identified a novel meiosis protein male meiosis recombination regulator (MAMERR)/4930432K21Rik and showed that it is indispensable for meiosis prophase I progression in male mice. Using super-resolution structured illumination microscopy, we found that MAMERR functions at the same double-strand breaks as the replication protein A and meiosis-specific with OB domains/spermatogenesis associated 22 complex. We generated a Mamerr-deficient mouse model by deleting exons 3-6 and found that most of Mamerr-/- spermatocytes were arrested at pachynema and failed to progress to diplonema, although they exhibited almost intact synapsis and progression to the pachytene stage along with XY body formation. Further mechanistic studies revealed that the recruitment of DMC1/RAD51 and heat shock factor 2-binding protein in Mamerr-/- spermatocytes was only mildly impaired with a partial reduction in double-strand break repair, whereas a substantial reduction in ubiquitination on the autosomal axes and on the XY body appeared as a major phenotype in Mamerr-/- spermatocytes. We propose that MAMERR may participate in meiotic prophase I progression by regulating the ubiquitination of key meiotic proteins on autosomes and XY chromosomes, and in the absence of MAMERR, the repressed ubiquitination of key meiotic proteins leads to pachytene arrest and cell death.

Properties of a modified quaternary ammonium silane formulation as a potential root canal irrigant in endodontics.

OBJECTIVES: Evaluate a new modified quaternary ammonium silane irrigant solution for its antimicrobial, cytotoxic and mechanical properties of dentine substrate. METHODS: Root canal preparation was performed using stainless steel K-files™ and F4 size protaper with irrigation protocols of 6% NaOCl + 2% CHX; 3.5% QIS; 2% QIS and sterile saline. Biofilms were prepared using E. faecalis adjusted and allowed to grow for 3 days, treated with irrigants, and allowed to grow for 7 days. AFM was performed and surface free energy calculated. MC3T3 cells were infected with endo irrigant treated E. faecalis biofilms. Raman spectroscopy of biofilms were performed after bacterial re-growth on root dentine and exposed to different irrigation protocols and collagen fibers analysed collagen fibers using TEM. Antimicrobial potency against E. faecalis biofilms and cytoxicity against 3T3 NIH cells were also. Resin penetration and MitoTracker green were also evaluated for sealer penetration and mitochondrial viability. Data were analysed using One-way ANOVA, principal component analysis and post-hoc Fisher's least-significant difference. RESULTS: Elastic moduli were maintained amongst control (5.5 ± 0.9) and 3.5% QIS (4.4 ± 1.1) specimens with surface free energy higher in QIS specimens. MC3T3 cells showed reduced viability in 6%NaOCl+2%CHX specimens compared to QIS specimens. DNA/purine were expressed in increased intensities in control and 6% NaOCl + 2% CHX specimens with bands around 480-490 cm-1 reduced in QIS specimens. 3.5% QIS specimens showed intact collagen fibrillar network and predominantly dead bacterial cells in confocal microscopy. 3.5% QIS irrigant formed a thin crust-type surface layer with cytoplasmic extensions of 3T3NIH spread over root dentine. Experiments confirmed MitoTracker accumulation in 3.5% treated cells. SIGNIFICANCE: Novel QIS root canal irrigant achieved optimum antimicrobial protection inside the root canals facilitating a toxic effect against the Enterococcus faecalis biofilm. Root dentine substrates exhibited optimum mechanical properties and there was viability of fibroblastic mitochondria.

Patent implications in the pharmaceutical industry: Are static high prices leading to dynamic innovations?

Agreement on Trade Related aspects of Intellectual Property Rights (TRIPS) was laid on the premises of rewarding monopolistic patent rights to the innovator. Stronger patent protection was advocated to promote technology transfer from developed nations to the rest of the world. To boost domestic innovative potential and to maintain trade ties, most developing countries signed the TRIPS agreement. Impact of patent laws in the pharmaceutical industry was crucial as it posed threat to access health. This paper aims to analyze the impact of pharmaceutical product patent laws incorporated under the TRIPS agreement using 65 countries panel dataset from 1995 to 2016. The data is empirically analyzed using negative binomial regression and Poisson regression. Results clearly indicate that the number of pharmaceutical patents filed in US Patent and Trademark Office (USPTO) has decreased after TRIPS compliance in both low and middle income countries. However, the decline is larger in upper middle and lower middle income countries than in low income countries. The phenomenon of low patent activity has an increasingly declining trend across low and middle income countries. Hence the claimed hypothesis that stronger patent rights would increase innovative potential does not seem to stand true, which raises serious affordability concerns of bringing patents in the pharmaceutical sector.

Major tdh(+)Vibrio parahaemolyticus serotype changes temporally in the Bay of Bengal estuary of Bangladesh.

Vibrio parahaemolyticus is responsible for seafood-related gastroenteritis worldwide. In Bangladesh, diarrhea is endemic and diarrheagenic V. parahaemolyticus serotypes occur naturally in the coastal and estuarine aquatic environment. V. parahaemolyticus strains, isolated from estuarine surface water of the Bay of Bengal villages of Bangladesh during 2006-2008, were tested for the presence of virulence and pandemic-marker genes, serodiversity, and phylogenetic relatedness. PCR analysis of V. parahaemolyticus (n=175) showed 53 (30.3%) strains to possess tdh, the major virulence gene encoding thermostable direct hemolysin. Serotyping results revealed the tdh(+)V. parahaemolyticus strains to belong to 10 different serotypes, of which the O8:K21 (30.2%) and O3:K6 (24.5%) were predominantly non-pandemic and pandemic serotypes, respectively; while O5:K30 and O9:KUT were new. The pandemic markers, orf8 and toxRS(variant), were present only in the pandemic serotype O3:K6 (n=13) and its serovariant O4:K68 (n=2). Temporal distribution of the tdh(+) serotypes revealed the O8:K21 to be predominant in 2006 and 2007, while O3:K6 was the predominant tdh(+) serotype in 2008. Pulsed-field gel electrophoresis (PFGE) of SfiI-digested genomic DNA revealed high genetic diversity among the V. parahaemolyticus strains, while dendrogram constructed with the PFGE patterns formed two major clusters separating the tdh(+) O3:K6 and its pandemic serovariants from the tdh(+) non-pandemic (O8:K21) strains, suggesting different lineages for them. The potential health risk related to the prevalent tdh(+) strains, including the observed temporal change of the predominant tdh(+) serotype, from O8:K21 to the pandemic serotype O3:K6 in estuarine surface waters serving as the major source of drinking water suggests the need for routine environmental monitoring to prevent V. parahaemolyticus infection in Bangladesh.

Bioethanol production from taro waste using thermo-tolerant yeast Kluyveromyces marxianus K21.

In the present study, evaluation and optimization of taro waste (TW), which was mainly composed of taro peels that contain many starch residues, as the main carbon source in medium were studied. The flask studies showed the optimal medium was using 170g/L of TW which is about 100g/L of glucose and 9g/L of CGM as alternative nitrogen source. Simultaneous saccharification and fermentation (SSF) exhibited higher bioethanol productivity toward separation hydrolysis and fermentation (SHF). The optimal condition of SSF was 5% of Kluyveromyces marxianus K21 inoculum at 40°C resulting in the maximum ethanol concentration (48.98g/L) and productivity (2.23g/L/h) after 22h of cultivation. The scaling up experiment in a 5L bioreactor demonstrated that K21 can still maintain its capability. After 20h of cultivation, 43.78g/L of ethanol (2.19g/L/h of productivity) was achieved corresponding to a 94.2% theoretical ethanol yield.

Systemic in vitro and in vivo evaluation for determining the feasibility of making an amorphous solid dispersion of a B-Raf (rapidly accelerated fibrosarcoma) inhibitor.

It is well acknowledged that oral bioavailability of a drug candidate is often influenced by factors such as the permeability, physico-chemical properties, and metabolism of the drug. Among the physico-chemical properties, solubility and dissolution rate are considered the most critical factors affecting the oral bioavailability of a compound G-F is a potent and selective B-Raf inhibitor with poor solubility and adsorption is limited by solubility at high doses. In order to overcome this issue using a spray-dried amorphous dispersion (SDD) formulation was evaluated. A combination of theoretical solubility prediction and in vitro dissolution, were used to predict the in vivo exposure of G-F. The predicted value was found to have good agreement with the in vivo exposure from dosing the crystalline and amorphous form of G-F. In general, this combined approach demonstrated that the amorphous form of G-F offers an advantage over the crystalline form of G-F in terms of solubility; in vitro dissolution and in vivo absorption were predictable and consistent with the literature. This systemic approach provides a great value for compound development.