Exact Solution of Photon Equation in Stationary G\"{o}del-type and G\"{o}del Space-Times

In this work the photon equation (massless Duffin-Kemmer-Petiau equation) is written expilicitly for general type of stationary G\"{o}del space-times and is solved exactly for G\"{o}del-type and G\"{o}del space-times. Harmonic oscillator behaviour of the solutions is discussed and energy spectrum of photon is obtained.Comment: 9 pages,RevTeX, no figure, revised for publicatio

Cancer Associated Fibroblasts and Senescent Thyroid Cells in the Invasive Front of Thyroid Carcinoma

Thyroid carcinoma (TC) comprises several histotypes with different aggressiveness, from well (papillary carcinoma, PTC) to less differentiated forms (poorly differentiated and anaplastic thyroid carcinoma, PDTC and ATC, respectively). Previous reports have suggested a functional role for cancer-associated fibroblasts (CAFs) or senescent TC cells in the progression of PTC. In this study, we investigated the presence of CAFs and senescent cells in proprietary human TCs including PTC, PDTC, and ATC. Screening for the driving lesions BRAFV600E and N/H/KRAS mutations, and gene fusions was also performed to correlate results with tumor genotype. In samples with unidentified drivers, transcriptomic profiles were used to establish a BRAF- or RAS-like molecular subtype based on a gene signature derived from The Cancer Genome Atlas. By using immunohistochemistry, we found co-occurrence of stromal CAFs and senescent TC cells at the tumor invasive front, where deposition of collagen (COL1A1) and expression of lysyl oxidase (LOX) enzyme were also detected, in association with features of local invasion. Concurrent high expression of CAFs and of the senescent TC cells markers, COL1A1 and LOX was confirmed in different TC histotypes in proprietary and public gene sets derived from Gene Expression Omnibus (GEO) repository, and especially in BRAF mutated or BRAF-like tumors. In this study, we show that CAFs and senescent TC cells co-occur in various histotypes of BRAF-driven thyroid tumors and localize at the tumor invasive front

Landscape of immune-related signatures induced by targeting of different epigenetic regulators in melanoma: implications for immunotherapy

Background Improvement of efficacy of immune checkpoint blockade (ICB) remains a major clinical goal. Association of ICB with immunomodulatory epigenetic drugs is an option. However, epigenetic inhibitors show a heterogeneous landscape of activities. Analysis of transcriptional programs induced in neoplastic cells by distinct classes of epigenetic drugs may foster identification of the most promising agents. Methods Melanoma cell lines, characterized for mutational and differentiation profile, were treated with inhibitors of DNA methyltransferases (guadecitabine), histone deacetylases (givinostat), BET proteins (JQ1 and OTX-015), and enhancer of zeste homolog 2 (GSK126). Modulatory effects of epigenetic drugs were evaluated at the gene and protein levels. Master molecules explaining changes in gene expression were identified by Upstream Regulator (UR) analysis. Gene set enrichment and IPA were used respectively to test modulation of guadecitabine-specific gene and UR signatures in baseline and on-treatment tumor biopsies from melanoma patients in the Phase Ib NIBIT-M4 Guadecitabine + Ipilimumab Trial. Prognostic significance of drug-specific immune-related genes was tested with Timer 2.0 in TCGA tumor datasets. Results Epigenetic drugs induced different profiles of gene expression in melanoma cell lines. Immune-related genes were frequently upregulated by guadecitabine, irrespective of the mutational and differentiation profiles of the melanoma cell lines, to a lesser extent by givinostat, but mostly downregulated by JQ1 and OTX-015. GSK126 was the least active drug. Quantitative western blot analysis confirmed drug-specific modulatory profiles. Most of the guadecitabine-specific signature genes were upregulated in on-treatment NIBIT-M4 tumor biopsies, but not in on-treatment lesions of patients treated only with ipilimumab. A guadecitabine-specific UR signature, containing activated molecules of the TLR, NF-kB, and IFN innate immunity pathways, was induced in drug-treated melanoma, mesothelioma and hepatocarcinoma cell lines and in a human melanoma xenograft model. Activation of guadecitabine-specific UR signature molecules in on-treatment tumor biopsies discriminated responding from non-responding NIBIT-M4 patients. Sixty-five % of the immune-related genes upregulated by guadecitabine were prognostically significant and conferred a reduced risk in the TCGA cutaneous melanoma dataset. Conclusions The DNMT inhibitor guadecitabine emerged as the most promising immunomodulatory agent among those tested, supporting the rationale for usage of this class of epigenetic drugs in combinatorial immunotherapy approaches. © 2022, The Author(s)

The antiinflammatory potential of phenolic compounds from Emblica officinalis L. in rat

Antiinflammatory effects of phenolic compounds from Emblica officinalis were evaluated in carrageenan and cotton pellet induced acute and chronic inflammatory animal model. Fractions of E. officinalis containing free (FPEO) and bounded (BPEO) phenolic compounds were assessed by HPLC technique. The free and bound phenolic compounds were studied for their acute and chronic antiinflammatory activity at dose level of 20 and 40 mg/kg. The carrageenan induced acute inflammation was assessed by measuring rat paw volume at different time of intervals. Further, cotton pellet induced chronic inflammation was assessed by granulomatous tissue mass estimation along with the estimation of tissue biomarker changes (i.e. lipid peroxidation, reduced glutathione, myeloperoxidase and plasma extravasation). The results indicated that in both acute and chronic inflammation, FPEO and BPEO show reduction in the inflammation, but significant effects was observed only at high doses of both fractions which was comparable to diclofenac treated group. In conclusion, phenolic compounds of E. officinalis may serve as potential herbal candidate for amelioration of acute and chronic inflammation due to their modulatory action of free radicals

Identification of Stk25 as a genetic modifier of Tau phosphorylation in Dab1-mutant mice.

Hyperphosphorylation of the microtubule binding protein Tau is a feature of a number of neurodegenerative diseases, including Alzheimer's disease. Tau is hyperphosphorylated in the hippocampus of dab1-null mice in a strain-dependent manner; however, it has not been clear if the Tau phosphorylation phenotype is a secondary effect of the morbidity of these mutants. The dab1 gene encodes a docking protein that is required for normal brain lamination and dendritogenesis as part of the Reelin signaling pathway. We show that dab1 gene inactivation after brain development leads to Tau hyperphosphorylation in anatomically normal mice. Genomic regions that regulate the phospho Tau phenotype in dab1 mutants have previously been identified. Using a microarray gene expression comparison between dab1-mutants from the high-phospho Tau expressing and low-phospho Tau expressing strains, we identified Stk25 as a differentially expressed modifier of dab1-mutant phenotypes. Stk25 knockdown reduces Tau phosphorylation in embryonic neurons. Furthermore, Stk25 regulates neuronal polarization and Golgi morphology in an antagonistic manner to Dab1. This work provides insights into the complex regulation of neuronal behavior during brain development and provides insights into the molecular cascades that regulate Tau phosphorylation

FLUORESCENT SIGN COLORS FOR INCIDENT MANAGEMENT TRAILBLAZING: EVALUATION OF ASSIGNMENTS IN MANUAL ON UNIFORM TRAFFIC CONTROL DEVICES

Previous research evaluated the use of unassigned sign colors from the Manual on Uniform Traffic Control Devices for incident management trailblazing; however, fluorescent sign colors were not evaluated. Since evidence suggests that fluorescence on signs improves conspicuity, the following colors were evaluated along a contrived test route with an instrumented vehicle: black on fluorescent coral, fluorescent yellow on fluorescent purple, black on fluorescent yellow-green, and yellow on purple in nonfluorescent colors. No significant differences in driving performance were exhibited among the four experimental sign-color combinations. Based on questionnaire results, the black on fluorescent yellow-green sign was preferred by younger and older drivers during both day and night visibility conditions. However, fluorescent yellow-green was subsequently assigned by the Federal Highway Administration for pedestrian, school, and bicycle crossings. For the remaining colors, black on fluorescent coral was ranked highest for visibility and overall preference, followed by fluorescent yellow on fluorescent purple, with nonfluorescent yellow on purple least preferred. Black on fluorescent coral was preferred over fluorescent yellow on fluorescent purple during daytime viewing conditions, while the reverse was true for nighttime. Drivers also commented that the arrow on the sign was too small to determine directional information from a comfortable distance

Uso profiláctico de antibióticos previos a la cesárea Profilactic use of antibiotics prior to a cesarean section

La cesárea es el procedimiento quirúrgico que se realiza con mayor frecuencia en la práctica obstétrica, siendo su principal complicación la endometritis puerperal. El presente estudio pretende determinar la efectividad de la profilaxis antibiótica previa a una cesárea para prevenir las infecciones puerperales. Se revisó la literatura publicada entre el año 1994 y el año 2009 relacionada con el tema de profilaxis antibiótica previa a la cesárea utilizando las bases de datos (MD Consult y EBSCO), clasificando las publicaciones entre aquellas que apoyan la profilaxis y las que no lo recomienda. También se determinó el antibiótico de mayor eficacia. En el 99% de las investigaciones consultadas, la utilización de antibióticos profilácticos fue efectiva. Además, el 71.4% de los estudios concluye que la profilaxis antibiótica es más efectiva si se aplica previa a la incisión quirúrgica de la cesárea, mientras que en el 28.6% se concluyó que no existe correlación con el momento de la aplicación. Basándose en estos datos, se concluye que la profilaxis antibiótica previa a la cesárea es efectiva. El momento ideal de la aplicación de la profilaxis es previo a la incisión quirúrgica de la cesárea y no tiene efectos adversos en el resultado neonatal.Caesarean section is the most often performed surgical procedure in obstetric practice, and puerperal endometritis is the most common complication. This study evaluated the effectiveness of antibiotic prophylaxis prior to a cesarean section to prevent puerperal infection. We reviewed published literature between 1994 and 2009 related to antibiotic prophylaxis prior to caesarean section using the MD Consult and EBSCO databases. Published works were classified in two groups: those supporting the prophylaxis and those against such practice. We also recorded antibiotic effectiveness. The majority of published works 99% concluded that the use of prophylactic antibiotics was an effective measure against infection. Additionally, 71.4% of the studies concluded that antibiotic prophylaxis is most effective if applied prior to surgical incision, while 28.6% found no correlation with the time of application. According to the data, antibiotic prophylaxis prior to caesarean section is an effective measure against puerperal infection. The ideal time for the implementation of prophylaxis is prior to surgical incision in caesarean section and has no adverse effects on newborn infants