Lower bounds for Mahler measure that depend on the number of monomials

We prove a new lower bound for the Mahler measure of a polynomial in one and in several variables that depends on the complex coefficients, and the number of monomials. In one variable our result generalizes a classical inequality of Mahler. In $M$ variables our result depends on $\mathbb{Z}^M$ as an ordered group, and in general our lower bound depends on the choice of ordering

Independent relative units of low height

We prove inequalities that compare the relative regulator of an extension of number fields with a product of heights of multiplicatively independent relative units

Down-regulation of miR-135b in colon adenocarcinoma induced by a TGF-β receptor i kinase inhibitor (SD-208)

Objective(s): Transforming growth factor-β (TGF-β) is involved in colorectal cancer (CRC). The SD-208 acts as an anti-cancer agent in different malignancies via TGF-β signaling. This work aims to show the effect of manipulation of TGF-β signaling on some miRNAs implicated in CRC. Materials and Methods: We investigated the effects of SD-208 on SW-48, a colon adenocarcinoma cell line. The cell line was treated with 0.5, 1 and 2 μM concentrations of SD-208. Then, the xenograft model of colon cancer was established by subcutaneous inoculation of SW-48 cell line into the nude mice. The animals were treated with SD-208 for three weeks. A quantitative real-time PCR was carried out for expression level analysis of selected oncogenic (miR-21, 31, 20a and 135b) and suppressormiRNAs (let7-g, miR-133b, 145 and 200c). Data were analyzed using the 2-��CT method through student�s t-test via the GraphPad Prism software. Results: Our results revealed that SD-208 could significantly down-regulate the expression of one key onco-miRNA, miR-135b, in either SW-48 colon cells (P=0.006) or tumors orthotopically implanted in nude mice (P=0.018). Our in silico study also predicted that SD-208 could modulate the expression of potential downstream tumor suppressor targets of the miR135b. Conclusion: Our data provide novel evidence that anticancer effects of SD-208 (and likely other TGF-β inhibitors) may be owing to their ability to regulate miRNAs expression. © 2015, Mashhad University of Medical Sciences. All rights reserved

Genetic and morphological diversity of the genus penicillium from mazandaran and tehran provinces, Iran

Background: The genus Penicillium contains a large number of ubiquitous environmental taxa, of which some species are clinically important. Identification of Penicillium down to the species level is currently based on polyphasic criteria, including phenotypic features and genetic markers. Biodiversity of the genus Penicillium from Mazandaran and Tehran provinces has not been described. Objectives: The current paper focused on the environmental biodiversity of Penicillium isolates within some areas of Mazandaran and Tehran provinces, based on morphological traits and the molecular data from partial sequence of the β-tubulin (BT2) gene. Materials and Methods: A total of 400 strains were isolated from the environment and investigated using morphological tests and sequencing of BT2, in order to characterize the spectrum of the Penicillium species. Results: Sequence analysis of BT2 and morphological criteria of 20 strains representative of 10 species showed that Penicillium chrysogenum was the most prevalent species (n = 6), followed by P. polonicum (n = 3), P. glabrum (n = 2), P. palitans (n = 2), P. melanoconidium (n = 2), and other species, including P. expansum, P. canescense, P. griseofulvum, P. italicum, and P. raistrickii with one case each. Conclusions: It was shown that partial β-tubulin sequence, as a reliable genetic target, supported specific morphological criteria for identification of the Penicillium species. Like other assessments throughout the world, P. chrysogenum remains the most frequent environmental Penicillium species in Mazandaran and Tehran Provinces. © 2016 Ahvaz Jundishapur University of Medical Sciences

Staphylococcus aureus enterotoxin b down-regulates the expression of transforming growth factor-beta (TGF-β) signaling transducers in human glioblastoma

Background: It has been revealed that Staphylococcus aureus enterotoxin B (SEB) may feature anti-cancer and anti-metastatic advantages due to its ability to modify cell immunity processes and signaling pathways. Glioblastoma is one of the most aggressive human cancers; it has a high mortality nature, which makes it an attractive area for the development of novel therapies. Objectives: We examined whether the SEB could exert its growth inhibitory effects on glioblastoma cells partially through the manipulation of a key tumor growth factor termed transforming growth factor-beta (TGF-β). Materials and Methods: A human primary glioblastoma cell line, U87, was treated with different concentrations of SEB. The cell quantity was measured by the MTT assay at different exposure times. For molecular assessments, total ribonucleic acid (RNA) was extracted from either non-treated or SEB-treated cells. Subsequently, the gene expression of TGF-β transducers, smad2/3, at the messenger RNA (mRNA) level, was analyzed via a quantitative real-time polymerase chain reaction (qPCR) using the SYBR Green method. Significant differences between cell viability and gene expression levels were determined (Prism 5.0 software) using a one-way analysis of variance (ANOVA) test. Results: We reported that SEB could effectively down-regulate smad2/3 expression in glioblastoma cells at concentrations as quantity as 1 µg/mL and 2 µg/mL (P < 0.05 and P < 0.01, respectively). The SEB concentrations effective at regulating smad2/3 expression were correlated with those used to inhibit the proliferation of glioblastoma cells. Our results also showed that SEB was able to decrease smad2/3 expression at the mRNA level in a concentration- and time-dependent manner. Conclusions: We suggested that SEB could represent an agent that can significantly decrease smad2/3 expression in glioblastoma cells, leading to moderate TGF-β growth signaling and the reduction of tumor cell proliferation. © 2016, Ahvaz Jundishapur University of Medical Sciences

Variable Anisotropic Brain Electrical Conductivities in Epileptogenic Foci

Source localization models assume brain electrical conductivities are isotropic at about 0.33 S/m. These assumptions have not been confirmed ex vivo in humans. This study determined bidirectional electrical conductivities from pediatric epilepsy surgery patients. Electrical conductivities perpendicular and parallel to the pial surface of neocortex and subcortical white matter (n = 15) were measured using the 4-electrode technique and compared with clinical variables. Mean (±SD) electrical conductivities were 0.10 ± 0.01 S/m, and varied by 243% from patient to patient. Perpendicular and parallel conductivities differed by 45%, and the larger values were perpendicular to the pial surface in 47% and parallel in 40% of patients. A perpendicular principal axis was associated with normal, while isotropy and parallel principal axes were linked with epileptogenic lesions by MRI. Electrical conductivities were decreased in patients with cortical dysplasia compared with non-dysplasia etiologies. The electrical conductivity values of freshly excised human brain tissues were approximately 30% of assumed values, varied by over 200% from patient to patient, and had erratic anisotropic and isotropic shapes if the MRI showed a lesion. Understanding brain electrical conductivity and ways to non-invasively measure them are probably necessary to enhance the ability to localize EEG sources from epilepsy surgery patients

Weather effects on the patterns of people's everyday activities: a study using GPS traces of mobile phone users

This study explores the effects that the weather has on people's everyday activity patterns. Temperature, rainfall, and wind speed were used as weather parameters. People's daily activity patterns were inferred, such as place visited, the time this took place, the duration of the visit, based on the GPS location traces of their mobile phones overlaid upon Yellow Pages information. Our analysis of 31,855 mobile phone users allowed us to infer that people were more likely to stay longer at eateries or food outlets, and (to a lesser degree) at retail or shopping areas when the weather is very cold or when conditions are calm (non-windy). When compared to people's regular activity patterns, certain weather conditions affected people's movements and activities noticeably at different times of the day. On cold days, people's activities were found to be more diverse especially after 10AM, showing greatest variations between 2PM and 6PM. A similar trend is observed between 10AM and midnight on rainy days, with people's activities found to be most diverse on days with heaviest rainfalls or on days when the wind speed was stronger than 4 km/h, especially between 10AM–1AM. Finally, we observed that different geographical areas of a large metropolis were impacted differently by the weather. Using data of urban infrastructure to characterize areas, we found strong correlations between weather conditions upon people's accessibility to trains. This study sheds new light on the influence of weather conditions on human behavior, in particular the choice of daily activities and how mobile phone data can be used to investigate the influence of environmental factors on urban dynamics

Race and smoking status associated with paclitaxel drug response in patient-derived lymphoblastoid cell lines

The use of ex-vivo model systems to provide a level of forecasting for in-vivo characteristics remains an important need for cancer therapeutics. The use of lymphoblastoid cell lines (LCLs) is an attractive approach for pharmacogenomics and toxicogenomics, due to their scalability, efficiency, and cost-effectiveness. There is little data on the impact of demographic or clinical covariates on LCL response to chemotherapy. Paclitaxel sensitivity was determined in LCLs from 93 breast cancer patients from the University of North Carolina Lineberger Comprehensive Cancer Center Breast Cancer Database to test for potential associations and/or confounders in paclitaxel dose-response assays. Measures of paclitaxel cell viability were associated with patient data included treatment regimens, cancer status, demographic and environmental variables, and clinical outcomes. We used multivariate analysis of variance to identify the in-vivo variables associated with ex-vivo dose-response. In this unique dataset that includes both in-vivo and ex-vivo data from breast cancer patients, race (P = 0.0049) and smoking status (P = 0.0050) were found to be significantly associated with ex-vivo dose-response in LCLs. Racial differences in clinical dose-response have been previously described, but the smoking association has not been reported. Our results indicate that in-vivo smoking status can influence ex-vivo dose-response in LCLs, and more precise measures of covariates may allow for more precise forecasting of clinical effect. In addition, understanding the mechanism by which exposure to smoking in-vivo effects ex-vivo dose-response in LCLs may open up new avenues in the quest for better therapeutic prediction

Questionnaire-Based Polyexposure Assessment Outperforms Polygenic Scores for Classification of Type 2 Diabetes in a Multiancestry Cohort

OBJECTIVE Environmental exposures may have greater predictive power for type 2 diabetes than polygenic scores (PGS). Studies examining environmental risk factors, however, have included only individuals with European ancestry, limiting the applicability of results. We conducted an exposome-wide association study in the multiancestry Personalized Environment and Genes Study to assess the effects of environmental factors on type 2 diabetes. RESEARCH DESIGN AND METHODS Using logistic regression for single-exposure analysis, we identified exposures associated with type 2 diabetes, adjusting for age, BMI, household income, and self-reported sex and race. To compare cumulative genetic and environmental effects, we computed an overall clinical score (OCS) as a weighted sum of BMI and prediabetes, hyperten-sion, and high cholesterol status and a polyexposure score (PXS) as a weighted sum of 13 environmental variables. Using UK Biobank data, we developed a multiancestry PGS and calculated it for participants. RESULTS We found 76 significant associations with type 2 diabetes, including novel associations of asbestos and coal dust exposure. OCS, PXS, and PGS were significantly associated with type 2 diabetes. PXS had moderate power to determine associations, with larger effect size and greater power and reclassification improvement than PGS. For all scores, the results differed by race. CONCLUSIONS Our findings in a multiancestry cohort elucidate how type 2 diabetes odds can be at-tributed to clinical, genetic, and environmental factors and emphasize the need for exposome data in disease-risk association studies. Race-based differences in predictive scores highlight the need for genetic and exposome-wide studies in diverse populations. EmR2TaFJ

Evaluation of TAK-242 (Resatorvid) effects on inflammatory status of fibroblast-like synoviocytes in rheumatoid arthritis and trauma patients

Fibroblast-like synoviocytes (FLSs) produce lots of inflammatory molecules that trigger immune responses and intensification the inflammation and thereby play important roles in Rheumatoid Arthritis)RA(pathogenesis. Due to the important roles of toll-like receptor 4 (TLR4) in cytokine production and inflammation, we aimed to evaluate the effects of TAK-242 (Resatorvid) on interleukin (IL)1-β, IL-6, TNF-α, and TLR4 expression and two important proteins of nuclear factor-κB (NF-κB) signaling pathway (Ikβα and pIkβα) in RA and trauma FLSs. FLSs were isolated from synovial tissues of trauma (n=10) and RA (n=10) patients and cultured in Dulbecco's Modified Eagle Medium (DMEM). 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) was performed to evaluate the cytotoxicity effects of TAK-242 on the RA FLSs. Real-time PCR was performed to measure the expression level of IL1-β, IL-6, TNF-α, and TLR4 genes in Lipopolysaccharide (LPS) and TAK-242 treated FLSs. Furthermore, the treated FLSs were evaluated for protein levels of Ikβα and pIkβα by western blot. The baseline expression of IL1-β, IL-6, TNF-α, and TLR4 showed no significant differences between healthy and RA FLSs. LPS stimulated FLSs significantly increased mRNA levels of IL-1β, IL-6, TNF-α, and TLR4 genes in both the healthy and RA FLSs compared with that of their control groups, and pretreatment with TAK-242 reversed the effect. Furthermore, LPS-stimulated FLSs significantly increased the level of pIkβα in both the healthy and RA FLSs compared with that of their control groups, and pretreatment with TAK-242 reversed the effect. We provide the data that TAK-242 through inhibiting the NF-κB signaling pathway may modulate TLR4-mediated inflammatory responses and could be considered as a potential therapeutic agent for RA patients. Copyright © 2021 Karami et al