Intermittency in a catalytic random medium

In this paper, we study intermittency for the parabolic Anderson equation $\partial u/\partial t=\kappa\Delta u+\xi u$, where $u:\mathbb{Z}^d\times [0,\infty)\to\mathbb{R}$, $\kappa$ is the diffusion constant, $\Delta$ is the discrete Laplacian and $\xi:\mathbb{Z}^d\times[0,\infty)\to\mathbb {R}$ is a space-time random medium. We focus on the case where $\xi$ is $\gamma$ times the random medium that is obtained by running independent simple random walks with diffusion constant $\rho$ starting from a Poisson random field with intensity $\nu$. Throughout the paper, we assume that $\kappa,\gamma,\rho,\nu\in (0,\infty)$. The solution of the equation describes the evolution of a ``reactant'' $u$ under the influence of a ``catalyst'' $\xi$. We consider the annealed Lyapunov exponents, that is, the exponential growth rates of the successive moments of $u$, and show that they display an interesting dependence on the dimension $d$ and on the parameters $\kappa,\gamma,\rho,\nu$, with qualitatively different intermittency behavior in $d=1,2$, in $d=3$ and in $d\geq4$. Special attention is given to the asymptotics of these Lyapunov exponents for $\kappa\downarrow0$ and $\kappa \to\infty$.Comment: Published at http://dx.doi.org/10.1214/009117906000000467 in the Annals of Probability (http://www.imstat.org/aop/) by the Institute of Mathematical Statistics (http://www.imstat.org

Intermittency on catalysts: Voter model

In this paper we study intermittency for the parabolic Anderson equation $\partial u/\partial t=\kappa\Delta u+\gamma\xi u$ with $u:\mathbb{Z}^d\times[0,\infty)\to\mathbb{R}$, where $\kappa\in[0,\infty)$ is the diffusion constant, $\Delta$ is the discrete Laplacian, $\gamma\in(0,\infty)$ is the coupling constant, and $\xi:\mathbb{Z}^d\times[0,\infty)\to\mathbb{R}$ is a space--time random medium. The solution of this equation describes the evolution of a ``reactant'' $u$ under the influence of a ``catalyst'' $\xi$. We focus on the case where $\xi$ is the voter model with opinions 0 and 1 that are updated according to a random walk transition kernel, starting from either the Bernoulli measure $\nu_{\rho}$ or the equilibrium measure $\mu_{\rho}$, where $\rho\in(0,1)$ is the density of 1's. We consider the annealed Lyapunov exponents, that is, the exponential growth rates of the successive moments of $u$. We show that if the random walk transition kernel has zero mean and finite variance, then these exponents are trivial for $1\leq d\leq4$, but display an interesting dependence on the diffusion constant $\kappa$ for $d\geq 5$, with qualitatively different behavior in different dimensions. In earlier work we considered the case where $\xi$ is a field of independent simple random walks in a Poisson equilibrium, respectively, a symmetric exclusion process in a Bernoulli equilibrium, which are both reversible dynamics. In the present work a main obstacle is the nonreversibility of the voter model dynamics, since this precludes the application of spectral techniques. The duality with coalescing random walks is key to our analysis, and leads to a representation formula for the Lyapunov exponents that allows for the application of large deviation estimates.Comment: Published in at http://dx.doi.org/10.1214/10-AOP535 the Annals of Probability (http://www.imstat.org/aop/) by the Institute of Mathematical Statistics (http://www.imstat.org

Drug combination and repurposing for cancer therapy: the example of breast cancer

Cancer is a set of extremely complex diseases, which are increasingly prominent today, as it affects and kills millions of people worldwide, being the subject of intense study both in its pathophysiology and therapy. Especially in women, breast cancer is still a cancer with a high incidence and mortality. Even though mortality rates for this type of cancer have declined in recent years, it remains challenging at the treatment level, especially the metastatic type. Due to all the impact on health, cancer therapy is the subject of costly and intense research. To enrich this therapy, as well as decrease its underlying high associated costs, drug repurposing and drug combinations are strategies that have been increasingly studied and addressed. As the name implies, drug repurposing presupposes giving new purposes to agents which, in this case, are approved for the therapy of other diseases (for example, cardiovascular or metabolic diseases), but are not approved for cancer therapy. Therefore, a better knowledge of these therapeutic modalities for breast cancer therapy is crucial for improved therapy. In this particular review, we will discuss some relevant aspects of cancer and, particularly, breast cancer and its therapy. Also, drug combination and repurposing will be highlighted, together with relevant examples. Despite some limitations that need to be overcome, these methodologies are extremely important and advantageous in combating several current problems of cancer therapy, namely in terms of costs and resistance to current therapeutic modalities. These approaches will be explored with a special focus on breast cancer.This work was supported by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia , in the framework of the projects supported by National Funds through FCT, within CINTESIS, R&D Unit (reference UIDB/4255/2020). N. Vale was supported by FCT and FEDER (European Union), award number IF/00092/2014/CP1255/CT0004

Amphritea atlantica gen. nov., sp. nov., a gammaproteobacterium from the Logatchev hydrothermal vent field

A novel Gram-negative, motile, aerobic rod-shaped bacterium was isolated from a Bathymodiolus sp. specimen collected from the Logatchev hydrothermal vent field at the Mid-Atlantic Ridge. The novel strain, M41(T), was catalase- and oxidase-positive and metabolised various carbohydrates and amino acids. It grew well in marine broth with an optimal growth temperature of 31 degrees C to 34 degrees C (range 4-40 degrees C and salinity requirement of 3% (range 0.3-9%). The pH range for growth was pH 4.6 to 9.5, with an optimum at pH 8.0. The predominant fatty acids were C-16: (1)omega 7c, C-16: 0 and C-18: 1 omega 7c. The DNA G + C content of strain M41(T) was 52.2 mol%. The 16S rRNA gene sequence was 94 % similar to that of the type strain of Oceanospirillum beijerinckii, the closest cultivated relative. Other related type strains were Oceanospirillum multiglobuliferum (93% gene sequence similarity), Neptunomonas naphthovorans (92%) and Marinobacterium jannaschii (92 %). According to phylogenetic analysis and physiological characteristics, it is suggested that strain M41(T) represents a new genus and novel species for which the name Amphritea atlantica gen. nov., sp. nov. is proposed. The type strain is M41(T) (= DSM 18887(T) = LMG 24143(T))

Nipple Hibernoma in a Dog: A Case Report With Literature Review

This report provides a clinical, histological, and immunohistochemical description of an unusual hibernoma (pale cell variant) in the subepidermal area of the nipple of a six-year-old bitch. Furthermore, an extensive literature review of hibernomas in animals was made. Physical examination revealed a nodular lesion in the subepidermal area of the third nipple of the left mammary chain. The histopathological findings included lobules of round to oval cells with abundant pale to eosinophilic cytoplasm, containing one or multiple optically empty vacuoles, consistent with nipple hibernoma. Immunohistochemically, the neoplastic cells were negative for cytokeratin AE1/AE3 and p53 but showed strong immunoreaction for vimentin and uncoupling protein-1, thus confirming the brown adipose tissue origin. Local recurrence was not detected after 18 months of follow-up. Hibernomas are rare and benign neoplastic lesions, originating from brown adipose tissue. Due to their histological and molecular resemblance with liposarcoma, a correct diagnosis of these neoplasms is required. In addition, the literature review suggests that hibernomas may present different features, according to species.IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT, the Portuguese Foundation for Science and Technology

Relationship between PD-L1 expression and tumor-infiltrating lymphocytes in canine mammary tumor

Background: Studies pointed out that the tumor-infiltrating lymphocytes (TILs) have considerable importance in canine mammary tumor (CMT). On the other hand, cancer cells sometimes find ways to use immune checkpoint proteins as a shield to avoid being identified and attacked by the immune system as programmed death 1 ligand 1 (PD-L1). In this study, it was investigated the relationship between PD-L1 expression, stromal tumor-infiltrating lymphocytes (TILs) in canine mammary tumor (CMT), and the association with clinical and pathological characteristics of the tumors. Materials, Methods & Results: PD-L1 expression and TILs were assessed in 23 female dogs with CMT. The tumors were grouped into simple carcinoma (CA, n = 8) and complex carcinoma (CC, n = 15). Stromal TILs were assessed using two thresholds as TILs-Low representing < 50% of infiltrate within stromal area and TILs-High representing = 50% of stromal area. Clinicopathological data of CMT was characterized according to key parameters, as well as survival rates. TILs evaluation within tumor stroma revealed that 65.2% (n = 15) of tumors had TILs-Low. PD-L1 expression and stromal TILs were significantly associated (P = 0.009). PD-L1 expression was observed in 39% (n = 9) of all tumors of which 17.4% (n = 4) were from CA group and 21.7% (n = 5) were from CC group. PD-L1 expression within TILs was observed in 39% (n = 9) of the tumors. PD-L1 in malignant epithelium was present in all lymph node metastasis (n = 5). PD-L1 was associated with involvement of regional lymph nodes (P = 0.034). Survival curves demonstrated TILs-Low had higher (P = 0.010) overall survival (OS) compared with TILs-High, and PD-L1+ and PD-L1– (P = 0.06) did not differed. The clinicopathological variables significantly correlated with OS by univariate analysis were the histological grade (P = 0.009), lymph node involvement (P = 0.004), stromal TILs (P = 0.016), and PD-L1+/TILs-High vs. PD-L1–/TILs-Low (P = 0.010). Multivariate analysis revealed that group of tumors with grade II-III was independent and negative prognostic factors for OS. Discussion: In this study, PD-L1 was differently expressed according to the histologic subtypes of TMC. Currently, has been showed the presence of PD-L1 in several canine cancer. Nevertheless, only a few studies have described PD-L1 protein expression in dog tumors and showed PD-L1 was constitutively expressed on canine tumor cell lines, although the levels of basal expression were very variable. This expression can be modulated by IFN-¿ exposure. In the present study, it was found a strong PD-L1 expression on TILs. The increase in PD-L1 cell surface expression by tumor cells can lead to decreased T-cell proliferation and increased apoptosis. In human breast cancer (BC) the PD-L1 expression was expressed in TILs and tumor epithelium. It has been reported the association of stromal TILs and PD-L1 expression with aggressive types and stages of BC. In this study, it was detected PD-L1 expression in malignant epithelium in all lymph node metastasis. PD-L1 overexpression was significantly associated with a series of clinicopathological parameters. It was demonstrated that PD-L1+/TILs-High had higher risk of overall survival (OS) than another group of interaction. High PDL1 expression may be a prognostic indicator for reduced OS, while tumor PD-L1+ was associated with poorer disease-free survival. The presence of TILs has shown to be potentially predictive and a prognostic factor in BC subtypes. In CMT, it has been reported that a high proportion of TILs was correlated to several malignancy characteristics. In relation to PDL1, further research is necessary to clarify this immune checkpoint as a potential therapeutic target and its application in clinical practice in CMT

Ten steps toward a better personality science - How quality may be rewarded more in research evaluation

This target article is part of a theme bundle including open peer commentaries (https://doi.org/10.5964/ps.9227) and a rejoinder by the authors (https://doi.org/10.5964/ps.7961). We point out ten steps that we think will go a long way in improving personality science. The first five steps focus on fostering consensus regarding (1) research goals, (2) terminology, (3) measurement practices, (4) data handling, and (5) the current state of theory and evidence. The other five steps focus on improving the credibility of empirical research, through (6) formal modelling, (7) mandatory pre-registration for confirmatory claims, (8) replication as a routine practice, (9) planning for informative studies (e.g., in terms of statistical power), and (10) making data, analysis scripts, and materials openly available. The current, quantity-based incentive structure in academia clearly stands in the way of implementing many of these practices, resulting in a research literature with sometimes questionable utility and/or integrity. As a solution, we propose a more quality-based reward scheme that explicitly weights published research by its Good Science merits. Scientists need to be increasingly rewarded for doing good work, not just lots of work

Analysis of risk factors for canine mast cell tumors based on the Kiupel and Patnaik grading system among dogs with skin tumors

Background: Skin tumors are the most frequently diagnosed lesions, of which 7%-21% are mast cell tumors (MCTs). There is a great effort to identify factors that can influence the prospective course of MCTs. Although, the histological grade is considering an important predictor helping to determine the malignancy and metastatic potential of MCTs. Aim: In this study, an epidemiological analysis of risk factors (breed, age, sex, and anatomical site) for dogs having MCTs was evaluated considering the respective MCTs histological grade in comparison to other skin tumors. Methods: The study included 244 dogs affected by cutaneous MCTs from a universe of 1,185 dogs diagnosed with skin tumors. A univariable analysis with Fisher exact test was performed to determine the odds ratios (ORs) with 95% confidence intervals (CIs). Results: Boxers had a higher predisposition to Patnaik's grade I (OR = 5.9, 95% CI 2.648-13.152) and to Kiupel's low-grade MCTs (OR = 2.6, 95% CI 1.539-4.447). Labrador retrievers (OR = 2.1, 95% CI 1.423-3.184), and pugs (OR = 12.9, 95% CI 2.336-70.931) had a predisposition for Patnaik's grade II MCTs and Kiupel's low-grade lesions (OR = 2.3, 95% CI 1.478-3.597; OR = 17.1, 95% CI 3.093-94.377, respectively). French bulldogs had a higher risk to grade III MCTs (OR = 7.9, 95% CI 2.381-26.072). Pit bulls had a predisposition to grade III MCTs and Kiupel's high-grade tumors (OR = 4.4, 95% CI 1.221-16.1 and OR = 4.962, 95% CI 1.362-18.077, respectively). Bull terriers (OR = 12.7, 95% CI 2.098-76.818) presented higher risk for having low-grade MCTs. The perigenital area and trunk exhibit a greater risk for high grading lesion (OR = 6.6, 95% CI 2.679-16.334; OR = 1.9, 95% CI 1.028-3.395, respectively) and the limbs had a predisposition to grade II tumor (OR = 1.6, 95% CI 1.134-2.395). A decreased risk of having MCT was seen in older dogs (from 7-10 years to 11-18 years) compared to that in the reference group (4-6 years). Conclusion: When comparing to canine skin tumors, this study showed a relationship between MCT histological grading and the risk factors, age, breed, and topography of canine MCTs. The variations noted in the clinical presentation of MCTs amongst predisposed dog breeds reinforces the relevance of the genetic background in MCTs carcinogenesis

New insight into breast cancer cells involving drug combinations for dopamine and serotonin receptors

The breast cancer therapies available are insufficient, especially since first-line treatments, such as paclitaxel, result in drug resistance and their toxicity often limits their concentration. Strategies like drug repurposing are beneficial, and novel treatments can emerge by repurposing drugs that interfere with the dopamine and serotonin receptors, and thus influence tumor growth. In this study, the MTT assay was used to test the efficacy of such repurposed drugs commonly used for neurodegenerative disorders that act on the dopamine and serotonin receptors to reduce the MCF7 cell’s viability, either by their single use or in combination with the reference drug paclitaxel. Furthermore, the expression of vimentin and E-cadherin was assayed by immunofluorescence. The dopamine receptor-altering drugs benztropine and thioridazine resulted in the strongest reduction of cell viability when combined with paclitaxel, which may be connected to the alteration of E-cadherin rather than vimentin expression. More studies are needed to understand the mechanism of action of the combinations tested and the efficacious role of dopamine and serotonin.This work was supported by Fundação para a Ciência e Tecnologia (FCT, Portugal) and FEDER (Fundo Europeu de Desenvolvimento Regional) funds through the COMPETE 2020 Operational Programme for Competitiveness and Internationalisation (POCI), Portugal, in the framework of the project IF/00092/2014/CP1255/CT0004. N.V. thanks Fundação para a Ciência e a Tecnologia (FCT, Portugal) for supporting these studies through nationally-funded projects within the CINTESIS R&D unit (reference UIDB/4255/2020). The contents of this report are solely the responsibility of the authors and do not necessarily represent the official view of the FCT