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Violet and purple bacterial pigmentations are uncommon when considering strict aerobes. Here we report discovery of two novel isolates, P102 and P117 from the freshwater Lake Winnipeg, each with violet to deep purple colony colouration. The relationship between pigment production and growth was investigated under different conditions, including a variety of carbon sources, pH, and temperatures. The violet compounds were purified using polar organic solvents, and then structurally characterized via mass spectrometry and nuclear magnetic resonance to be violacein and deoxyviolacein. Strain P117 produced higher concentrations of the darker pigment deoxyviolacein, which resulted in a deeper hue of violet than in cultures of P102. Strain P102, synthesized violacein maximally in liquid rich organic medium at pH 8 and 20 °C, and had 99.3% sequence similarity to the 16S rDNA from Janthinobacterium lividum. Strain P117, related to Massilia violaceinigra sharing 99.2% 16S rDNA sequence similarity, also produced violacein at similar optimal conditions, but developed higher concentrations of pigment at 15 °C. Culture-based methods found that violacein producers composed 0.001% or 0.023% CFU of environmental heterotrophic populations using BG-11 and potato-based media, respectively. Culture-independent high-throughput ribosomal 16S V4 sequencing of environmental DNA was used to detect Gram-negative species known for their production of violacein. Of all bacterial and archaeal sequences present during the fall in littoral waters and sediment of Lake Winnipeg, 5.5% and 6.3%, respectively, belonged to species that have similar pigment, demonstrating the scarcity of violacein producers in this aquatic freshwater system.

Sinonasal papillomas are benign epithelial tumors of the sinonasal tract that are associated with a synchronous or metachronous sinonasal carcinoma in a subset of cases. Our group recently identified mutually exclusive EGFR mutations and human papillomavirus (HPV) infection in inverted sinonasal papillomas and frequent KRAS mutations in oncocytic sinonasal papillomas. We also demonstrated concordant mutational and HPV infection status in sinonasal papilloma-associated sinonasal carcinomas, confirming a clonal relationship between these tumors. Despite our emerging understanding of the oncogenic mechanisms driving formation of sinonasal papillomas, little is currently known about the molecular mechanisms of malignant progression to sinonasal carcinoma. In the present study, we utilized targeted next-generation DNA sequencing to characterize the molecular landscape of a large cohort of sinonasal papilloma-associated sinonasal carcinomas. As expected, EGFR or KRAS mutations were present in the vast majority of tumors. In addition, highly recurrent TP53 mutations, CDKN2A mutations, and/or CDKN2A copy-number losses were detected; overall, nearly all tumors (n = 28/29; 96.6%) harbored at least one TP53 or CDKN2A alteration. TERT copy-number gains also occurred frequently (27.6%); however, no TERT promoter mutations were identified. Other recurrent molecular alterations included NFE2L2 and PIK3CA mutations and SOX2, CCND1, MYC, FGFR1, and EGFR copy-number gains. Importantly, TP53 mutations and CDKN2A alterations were not detected in matched sinonasal papillomas, suggesting that these molecular events are associated with malignant transformation. Compared to aerodigestive tract squamous cell carcinomas from The Cancer Genome Atlas (TCGA) project, sinonasal papilloma-associated sinonasal carcinomas have a distinct molecular phenotype, including more frequent EGFR, KRAS, and CDKN2A mutations, TERT copy-number gains, and low-risk human papillomavirus (HPV) infection. These findings shed light on the molecular mechanisms of malignant progression of sinonasal papillomas and may have important diagnostic and therapeutic implications for patients with advanced sinonasal cancer.

Making correct decisions regarding the merit of sales opportunities, as well as deciding which opportunities to pursue and which to abandon, is one of the most critical tasks sales managers and salespeople grapple with. These frontline assessments typically become sales forecasts that are used to allocate resources within the firm. Assessments of future sales, however, are often inaccurate and little is known about how salespeople and sales managers make decisions about sales opportunities, or if they differ in their ability to (correctly) assess the merits of such opportunities. To address this research gap, we explore several decision-making biases – namely optimism, confidence, and overconfidence – through the lenses of both Psychological Momentum (PM) and Strategic Reference Point (SRP) theory. Analysis of rich CRM data from a Fortune 500 medical products company, across three studies, demonstrates notable differences between salespeople and sales managers concerning decision-making biases that influence their evaluations of sales opportunities.

Microcystic adnexal carcinoma is a locally aggressive sweat gland carcinoma characterized by its infiltrative growth and histopathologic overlap with benign adnexal tumors, often posing challenges to both diagnosis and management. Understanding the molecular underpinnings of microcystic adnexal carcinoma may allow for more accurate diagnosis and identify potential targetable oncogenic drivers. We characterized 18 microcystic adnexal carcinomas by targeted, multiplexed PCR-based DNA next-generation sequencing of the coding sequence of over 400 cancer-relevant genes. The majority of cases had relatively few (

Little is known about antecedents of salesperson influence tactic usage or how and which influence tactics impact buying agent purchase decisions. To aid such understanding, we draw from the relationship selling literature, and both regulatory fit and focus theories, to propose a novel theoretical framework and test hypotheses. The study's findings, derived by applying the critical incidence methodology to a heterogeneous dataset of buying agents (n > 200) representing small and medium enterprises and acting as key informants on salespeople, show that: (i) salesperson influence tactics heterogeneously explain the buying agent's trust of the salesperson, (ii) trust of the salesperson serves as a mechanism through which influence tactics impact the buying agent's purchase decision, (iii) buying agent's regulatory orientation moderates the relationship between salesperson influence tactics and buying agent's trust of the salesperson, and (iv) salesperson regulatory orientation predicts a salesperson's use of particular influence tactics. The article concludes with a discussion of the practical and theoretical implications of the research.

A method to calculate the local damping coefficient and the bond Young's modulus of a flexible fibre for use in the discrete element method (DEM) was proposed and validated. Segments of harvested wheat straw were clamped on one end while the other end was deflected a set distance, released, and allowed to vibrate freely. This cantilever beam motion was captured by a high-speed camera (960 fps). The red-band of the images were isolated and used to calculate the x-section height (mm) along the stem in time. This data was then fit to a non-linear function, which conforms to beam theory. The global bond damping coefficient, as a function of x-section height, was then calculated and found to be in the range of −0.5 to −0.2. The cantilever beam experiment was then repeated in the DEM software LIGGGHTS, where the wheat straw was modelled as a single line of spheres connected by stiff-flexible bonds. A design of experiment (DOE) was ran varying bond Young's modulus and local bond damping, to determine the linear relationships with the global bond damping coefficient and the frequency of oscillation of the DEM particle respectively. With the proposed method the DEM local bond damping coefficient and the DEM bond Young's modulus were calibrated with relative errors of 0.9% and 1.8% respectively to laboratory estimated values. Utilising the linear relationships found from the DEM simulations, the bond Young's modulus was found to be in the range of 0.42–4.84 GPa.

The Bonaparte Lake area in southern part of the Quesnellia terrane of the Canadian Cordillera is proximal ( Au and Cu Mo deposits. This area has potential for finding more porphyry type Cu deposits, but is overlain by a thick and nearly continuous cover of glacial sediments, which adds difficulty in finding mineral deposits in underlying bedrocks. This study uses geochemical data following an aqua regia leach on the clay fraction (

We leverage a ‘catch-all’ measure of financial innovation—research and development spending in the financial sector—to assess the net relationship between financial innovation and economic growth and evaluate the influence of macroprudential policy on this relationship. Using a panel of 23 countries over the period of 1996–2014, our results demonstrate a net-positive relationship between financial innovation and gross capital formation. We find no evidence of a net-negative impact of financial innovation on economic growth, challenging the popular and political stigma surrounding financial innovation. We also find little robust evidence of macroprudential policy influencing the relationship between financial innovation and economic growth. Our results support a functional approach to the regulation of financial innovation, which improves the intermediation process, leading to increased capital formation.

Background: Dendritic cells (DCs) are usually very efficient at activating CD8 T cells. However, their capacity to cross-present soluble antigens can be limited by non-specific degradation of captured antigens during endosome maturation, which would lead to the destruction of immunogenic epitopes. To bypass this limitation, we tested a new antigen formulation using AccumTM, a technology originally designed to enhance accumulation of antibody-drug conjugate in target cells by promoting endosome-to-cytosol escape. Methods: Following chemical linking and characterization of the Accum-antigen complex, a series of in vitro antigen presentation assays were conducted to assess the T-cell activation potency of the antigen formulation. The generated cellular product was then tested in vivo for its capacity to elicit anti-tumoral responses in both prophylactic and therapeutic vaccination settings. Finally, allogeneic DCs pulsed with tumor lysate linked to AccumTM were characterized for their therapeutic potency. Results: Linking the Accum moiety to the experimental xenoantigen ovalbumin caused endosomal damages resulting in enhanced intracellular protein processing by primary DCs. As a result, production of pro-inflammatory cytokines and chemokines was enhanced by responding T cells. When evaluated for their anti-tumoral properties, Accum-ovalbumin-pulsed DCs elicited potent effector and central memory CD8 T cells, which explains the complete and long-lasting protection observed in vaccinated mice despite multiple EG.7 T-cell lymphoma challenges. When combined with the anti-PD-1 immune checkpoint inhibitor, therapeutic vaccination using both syngeneic and allogeneic DCs pulsed with Accum-linked ovalbumin triggered potent anti-tumoral responses; an observation further enhanced using Accum-linked lymphoma tumor lysate proteins. Conclusion: These highly favorable therapeutic effects highlight the promising potential of AccumTM as a distinct and potent technology platform suitable for the design of next generation cell cancer vaccines.

The cross-presenting capacity of dendritic cells (DCs) can be limited by non-specific degradation during endosome maturation. To bypass this limitation, we present in this study a new Accum-based formulation designed to promote endosome-to-cytosol escape. Treatment of primary DCs with Accum linked to the xenoantigen ovalbumin (OVA) triggers endosomal damages and enhances protein processing. Despite multiple challenges using ascending doses of tumor cells, DC prophylactic vaccination results in complete protection due to increased levels of effector CD4 and CD8 T cells as well as high production of pro-inflammatory mediators. When combined with anti-PD-1, therapeutic vaccination using both syngeneic and allogeneic Accum-OVA-pulsed DCs triggers potent anti-tumoral responses. The net outcome culminates in increased CD11c, CD8, and NK infiltration along with a high CD8/Treg ratio. These highly favorable therapeutic effects highlight the promising potential of Accum as a distinct and potent technology platform suitable for the design of next generation cell cancer vaccines.

The effect of geometrical arrangements of a residence time channel (RTC) positioned in between LL-Rhombus static mixing elements on interphase mass transfer rates is investigated. Four variations of a micro-reactor plate are tested with four immiscible aqueous-organic systems: water coupled with n-butanol, n-hexanol, methyl tert-butyl ether and toluene. The alkaline hydrolysis of 4-nitrophenyl acetate is used to determine the overall volumetric mass transfer coefficient (Kda). For all solvent pairs, the micro-reactor without a RTC has the greatest Kda at a given flow rate due to a greater energy dissipation rate (ɛ) and the fact that drops can re-coalesce leading to reduced advective transfer in the RTC pending the flow regime. An increase in flow rate results in a rise in conversion up to a maximum, after which viscous dissipation impedes further turbulent breakdown of the droplets as they near the Kolmogorov length scale. When the resulting flow is finely dispersed, interphase mass transfer rates no longer depend on reactor geometry but was correlated to the solvent system and rate of energy dissipated. The negative impact of operating at greater ɛ values than at maximum conversion is shown via the required pressure loss to achieve a certain conversion or residence time. Lastly, relevant to production rates in the fine chemical and pharmaceutical industry, an algorithm for scaling a generic mass transfer-limited liquid-liquid reaction at identified optimal operating conditions is presented.

The Hippo pathway plays an important role in regulating tissue homeostasis, and its effectors, the transcriptional co-activators Yes-associated protein (YAP) and WW domain-containing transcription regulator 1 (WWTR1 or TAZ), are responsible for mediating the vast majority of its physiological functions. Although YAP and TAZ are thought to be largely redundant and similarly regulated by Hippo signaling, they have developmental, structural, and physiological differences that suggest they may differ in their regulation and downstream functions. To better understand the functions of YAP and TAZ in the Hippo pathway, using CRISPR/Cas9, we generated YAP KO, TAZ KO, and YAP/TAZ KO cell lines in HEK293A cells. We evaluated them in response to many environmental conditions and stimuli and used RNA-Seq to compare their transcriptional profiles. We found that YAP inactivation has a greater effect on cellular physiology (namely, cell spreading, volume, granularity, glucose uptake, proliferation, and migration) than TAZ inactivation. However, functional redundancy between YAP and TAZ was also observed. In summary, our findings confirm that the Hippo pathway effectors YAP and TAZ are master regulators for multiple cellular processes but also reveal that YAP has a stronger influence than TAZ.

The current research evaluated the impact of personality questionnaire item content saturation, item social desirability, and mean item responses on the overall convergent validity of three well-known personality measures. Archival data representing groups of same-sex undergraduate roommate dyads were used for this research. Results demonstrated that content saturation, measured using item-total correlations, was the most consistent predictor of item convergent validity, measured using self-peer item response correlations. In order to predict outcome variables in education, clinical, and vocational contexts using scores on personality questionnaires, it is important for researchers to employ item selection procedures that take into account the item properties that affect the test's convergent validity.

This study examined the relationship of the Dark Tetrad with core values, and the role of honesty-humility as a moderator of the “dark” personality-core values link. A sample of 183 participants (57 male, 126 female; Mage = 18.39 years, SD = 1.12) completed an online survey assessing the Dark Tetrad, the 10 values from the Schwartz Value Typology, and honesty-humility from the HEXACO. Several Dark Triad-core value correlations were replicated. Furthermore, some of the predicted links between sadism and values were also corroborated using both novel and established sadism measures. The moderating role of honesty-humility on the link between each Dark Tetrad member and aggregated core values was explored. Honesty-humility moderated only the following relationships: psychopathy and Self-Enhancement Plus Openness to Change values, and narcissism and Self-Enhancement Plus Openness to Change values. These findings contribute to understanding how personality traits and values describe people's behaviour in interpersonal contexts.

The current study extends findings from previous literature examining the moderating effect of religious beliefs on the relationship between negative life circumstances and life satisfaction. Specifically, the current study investigates the moderating effect of religious belief on the relationship between income and life satisfaction at the individual and country level using multilevel modeling procedures. It was hypothesized that there would be a positive effect of income on life satisfaction at both the individual and country level, but as levels of religious belief increased (at the individual and country level), these relationships would be attenuated. A group of 85,072 individuals nested within 59 countries (43,541 females, 41,443 males, 88 unknown) between the ages of 16 and 99 (Mage = 41.63, SD = 16.56) completed the World Values Survey including questions reflecting income, religious belief, and life satisfaction. Results showed positive main effects of individual-level income and religious belief on life satisfaction. Contrary to prediction, there was a negative main effect of country-level religious belief on life satisfaction, and no main effect of country-level income on life satisfaction. Religious belief did not moderate the relationship between income and life satisfaction at the individual or country level. Theoretical explanations and implications are discussed.

Recent research suggests that subclinical sadism should be included in the Dark Triad. However, research on the assessment of sadism as a trait is lacking. To address this, we developed a new self-report measure, the Assessment of Sadistic Personality (ASP). In Study 1, 199 university students completed a preliminary 20-item version of the ASP, measures of the Dark Triad, agreeableness, honesty-humility, emotional intelligence, and sadistic tendencies. Internal consistency was acceptable and convergent validity was supported. After reducing the ASP to nine items, 202 university students completed a replication of Study 1. Internal consistency and convergent validity were again supported. When ASP items were combined with Dark Triad items, exploratory factor analysis supported the anticipated four-factor structure. These results provide preliminary evidence for the reliability and validity of the ASP as a new measure of subclinical sadism appropriate for use in conjunction with existing measures of the Dark Triad.

l-lysine (Lys) is an essential amino acid that is added to foods and dietary supplements. Lys may interact with mineral nutrients and affect their metabolism. This study examined the effect of dietary Lys supplementation on the bioavailability of copper (Cu) and iron (Fe). Weanling male Sprague-Dawley rats were fed one of five diets (20% casein) for 4 weeks containing normal Cu and Fe (control) or low Cu or Fe without (LCu, LFe) or with (LCu+Lys, LFe+Lys) addition of 1.5% Lys. Final body weights, body weight gains and food consumption of the rats did not differ (P≥0.05) among diet groups. Rats fed the low Cu or Fe diets showed changes in nutritional biomarkers compared to control rats, demonstrating reduced Cu and Fe status, respectively. Hematological parameters, serum ceruloplasmin activity and Cu and Fe concentrations in serum, liver, kidney and intestinal mucosa were unaffected (P≥0.05) by Lys supplementation. These results indicate that in the context of an adequate protein diet, Lys supplementation at a relatively high level does not affect Cu or Fe bioavailability in rats.