Renormalization Group and Grand Unification with 331 Models

By making a renormalization group analysis we explore the possibility of having a 331 model as the only intermediate gauge group between the standard model and the scale of unification of the three coupling constants. We shall assume that there is no necessarily a group of grand unification at the scale of convergence of the couplings. With this scenario, different 331 models and their corresponding supersymmetric versions are considered, and we find the versions that allow the symmetry breaking described above. Besides, the allowed interval for the 331 symmetry breaking scale, and the behavior of the running coupling constants are obtained. It worths saying that some of the supersymmetric scenarios could be natural frameworks for split supersymmetry. Finally, we look for possible 331 models with a simple group at the grand unification scale, that could fit the symmetry breaking scheme described above.Comment: 18 pages. 3 figures. Some results reinterpreted, a new section and references added. Version to appear in International Journal of Modern Physics

Lipid nanoparticles decorated with TNF-related aptosis-inducing ligand (TRAIL) are more cytotoxic than soluble recombinant TRAIL in sarcoma

Sarcomas are rare and heterogeneous cancers classically associated with a poor outcome. Sarcomas are 1% of the cancer but recent estimations indicate that sarcomas account for 2% of the estimated cancer-related deaths. Traditional treatment with surgery, radiotherapy, and chemotherapy has improved the outcome for some types of sarcomas. However, novel therapeutic strategies to treat sarcomas are necessary. TNF-related apoptosis-inducing ligand (TRAIL) is a death ligand initially described as capable of inducing apoptosis on tumor cell while sparing normal cells. Only few clinical trials have used TRAIL-based treatments in sarcoma, but they show only low or moderate efficacy of TRAIL. Consequently, novel TRAIL formulations with an improved TRAIL bioactivity are necessary. Our group has developed a novel TRAIL formulation based on tethering this death ligand on a lipid nanoparticle surface (LUV-TRAIL) resembling the physiological secretion of TRAIL as a trasmembrane protein inserted into the membrane of exosomes. We have already demonstrated that LUV-TRAIL shows an improved cytotoxic activity when compared to soluble recombinant TRAIL both in hematological malignancies and epithelial-derived cancers. In the present study, we have tested LUV-TRAIL in several human sarcoma tumor cell lines with different sensitivity to soluble recombinant TRAIL, finding that LUV-TRAIL was more efficient than soluble recombinant TRAIL. Moreover, combined treatment of LUV-TRAIL with distinct drugs proved to be especially effective, sensitizing even more resistant cell lines to TRAIL

Compressive Review about Taxol: History and Future Challenges

© 2020. The authors. This document is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by /4.0/ This document is the Published version of a Published Work that appeared in final form in Molecules. To access the final edited and published work see DOI: 10.3390/molecules25245986Taxol®, which is also known as paclitaxel, is a chemotherapeutic agent widely used to treat different cancers. Since the discovery of its antitumoral activity, Taxol® has been used to treat over one million patients, making it one of the most widely employed antitumoral drugs. Taxol® was the first microtubule targeting agent described in the literature, with its main mechanism of action consisting of the disruption of microtubule dynamics, thus inducing mitotic arrest and cell death. However, secondary mechanisms for achieving apoptosis have also been demonstrated. Despite its wide use, Taxol® has certain disadvantages. The main challenges facing Taxol® are the need to find an environmentally sustainable production method based on the use of microorganisms, increase its bioavailability without exerting adverse effects on the health of patients and minimize the resistance presented by a high percentage of cells treated with paclitaxel. This review details, in a succinct manner, the main aspects of this important drug, from its discovery to the present day. We highlight the main challenges that must be faced in the coming years, in order to increase the effectiveness of Taxol® as an anticancer agent

Testing the gravitational theory with short-period stars around our Galactic Center

Motion of short-period stars orbiting the supermassive black hole in our Galactic Center has been monitored for more than 20 years. These observations are currently offering a new way to test the gravitational theory in an unexplored regime: in a strong gravitational field, around a supermassive black hole. In this proceeding, we present three results: (i) a constraint on a hypothetical fifth force obtained by using 19 years of observations of the two best measured short-period stars S0-2 and S0-38 ; (ii) an upper limit on the secular advance of the argument of the periastron for the star S0-2 ; (iii) a sensitivity analysis showing that the relativistic redshift of S0-2 will be measured after its closest approach to the black hole in 2018.Comment: 4 pages, 2 figures, proceedings of the 52nd Rencontres de Moriond, Gravitation Sessio

Sex and gender disparities in patients with advanced gastroesophageal adenocarcinoma: data from the AGAMENON-SEOM registry

Gastroesophageal cancer; Gender; SexCáncer gastroesofágico; Género; SexoCàncer gastroesofàgic; Gènere; SexeBackground Recommendations for research articles include the use of the term sex when reporting biological factors and gender for identities or psychosocial or cultural factors. There is an increasing awareness of incorporating the effect of sex and gender on cancer outcomes. Thus, these types of analyses for advanced gastroesophageal adenocarcinoma are relevant. Patients and methods Patients with advanced gastroesophageal adenocarcinoma from the Spanish AGAMENON-SEOM registry treated with first-line combination chemotherapy were selected. Epidemiology, characteristics of the disease, treatment selection, and results were examined according to sex. Results This analysis included 3274 advanced gastroesophageal adenocarcinoma patients treated with combination chemotherapy between 2008 and 2021: 2313 (70.7%) men and 961 (29.3%) women. Tumors in females were more frequently HER2-negative (67.8% versus 60.8%; P < 0.0001), grade 3 (45.4% versus 36.8%; P < 0.001), diffuse (43.3% versus 26.5%; P < 0.0001), and signet ring cell histology (40.5 versus 23.9%; P < 0.0001). Peritoneal spread was more common in women (58.6% versus 38.9%; P < 0.0001), while liver burden was lower (58.9% versus 71.1%; P < 0.0001). There were no significant differences in treatment recommendation. Treatment doses, density, and duration were comparable between sexes. Women experienced more diarrhea (46% versus 37%; P < 0.0001), neutropenia (51% versus 43%; P < 0.0001), and anemia (62% versus 57%; P < 0.0001). After a median 59.6-month follow-up [95% confidence interval (CI) 54.5-70.8], there were no statistically significant differences between the sexes in progression-free survival [6.21 months (95% CI 5.8-6.5 months) versus 6.08 months (95% CI 5.8-6.3 months); log-rank test, χ2 = 0.1, 1 df, P = 0.8] or in overall survival [10.6 months (95% CI 9.8-11.1 months) versus 10.9 months (95% CI 10.4-11.4 months); log-rank test: χ2 = 0.6, 1 df, P = 0.5]. Conclusion This sex analysis of patients with advanced gastroesophageal adenocarcinoma from the AGAMENON-SEOM registry receiving first-line polychemotherapy found no differences in survival. Although women had worse prognostic histopathology, metastatic disease pattern, and greater toxicity, treatment allocation and compliance were equivalent

Estradiol regulates brown adipose tissue thermogenesis via hypothalamic AMPK

Copyright © 2014 Elsevier Inc. All rights reserved.Peer reviewedPublisher PD

Natural language processing for aviation safety: Extracting knowledge from publicly-available loss of separation reports

Background: The air traffic management (ATM) system has historically coped with a global increase in traffic demand ultimately leading to increased operational complexity. When dealing with the impact of this increasing complexity on system safety it is crucial to automatically analyse the losses of separation (LoSs) using tools able to extract meaningful and actionable information from safety reports. Current research in this field mainly exploits natural language processing (NLP) to categorise the reports,with the limitations that the considered categories need to be manually annotated by experts and that general taxonomies are seldom exploited. Methods: To address the current gaps,authors propose to perform exploratory data analysis on safety reports combining state-of-the-art techniques like topic modelling and clustering and then to develop an algorithm able to extract the Toolkit for ATM Occurrence Investigation (TOKAI) taxonomy factors from the free-text safety reports based on syntactic analysis. TOKAI is a tool for investigation developed by EUROCONTROL and its taxonomy is intended to become a standard and harmonised approach to future investigations. Results: Leveraging on the LoS events reported in the public databases of the Comisión de Estudio y Análisis de Notificaciones de Incidentes de Tránsito Aéreo and the United Kingdom Airprox Board,authors show how their proposal is able to automatically extract meaningful and actionable information from safety reports,other than to classify their content according to the TOKAI taxonomy. The quality of the approach is also indirectly validated by checking the connection between the identified factors and the main contributor of the incidents. Conclusions: Authors' results are a promising first step toward the full automation of a general analysis of LoS reports supported by results on real-world data coming from two different sources. In the future,authors' proposal could be extended to other taxonomies or tailored to identify factors to be included in the safety taxonomies

Early distant relapse after optimal local control in locally advanced rectal cancer

We present a case of locally advanced rectal cancer with initial optimal local control after neoadjuvant concurrent chemoradiotherapy followed by surgery; early liver recurrence then occurred and was treated again with curative intent with neoadjuvant combination chemotherapy followed by liver surgery. We reflect on this difficult problem and discuss relevant topics to this case report

A Multi-wavelength analysis of M81: insight on the nature of Arp's loop

Context: The optical ring like structure detected by Arp (1965) around M81 (commonly referenced as "Arp's loop") represents one of the most spectacular feature observed in nearby galaxies. Arp's loop is commonly interpreted as a tail resulting from the tidal interaction between M81 and M82. However, since its discovery the nature of this feature has remained controversial. Aims: Our primary purpose was to identify the sources of optical and infrared emission observed in Arp's loop. Methods: The morphology of the Arp's loop has been investigated with deep wide-field optical images. We also measured its colors using IRAS and Spitzer-MIPS infrared images and compared them with those of the disk of M81 and Galactic dust cirrus that fills the area where M81 is located. Results: Optical images reveal that this peculiar object has a filamentary structure characterized by many dust features overlapping M81's field. The ratios of far-infrared fluxes and the estimated dust-to-gas ratios indicate the infrared emission of Arp's loop is dominated by the contribution of cold dust that is most likely from Galactic cirrus. Conclusions: The above results suggest that the light observed at optical wavelengths is a combination of emission from i) a few recent star forming regions located close to M81, where both bright UV complexes and peaks in the HI distribution are found, ii) the extended disk of M81 and iii) scattered light from the same Galactic cirrus that is responsible for the bulk of the far infrared emission.Comment: 7 pages, 7 figures, accepted for publication by A&

High-order TRAIL oligomer formation in TRAIL-coated lipid nanoparticles enhances DR5 cross-linking and increases antitumour effect against colon cancer

During the last years, a great effort has been invested into developing new TRAIL formulations with increased bioactivity, trying to overcome the resistance to conventional soluble TRAIL (sTRAIL) exhibited by many primary tumours. In our group, we have generated artificial lipid nanoparticles decorated with sTRAIL (LUV-TRAIL), emulating the physiological TRAIL-containing exosomes by which T-cells release TRAIL upon activation. We already demonstrated that LUV-TRAIL has greater cytotoxicity against both chemoresistant haematologic tumour cells and epithelial carcinoma cells compared to a form of sTRAIL similar to that used in clinical trials. In this study we have tested LUV-TRAIL in several human colon cancer cell lines with different sensitivity to sTRAIL. LUV-TRAIL significantly improved sTRAIL cytotoxicity in all colon cancer cell lines tested. Trying to ascertain the molecular mechanism by which LUV-TRAIL exhibited improved cytotoxicity, we demonstrated that TRAIL-coated lipid nanoparticles were able to activate DR5 more efficiently than sTRAIL, and this relied on LUV-TRAIL ability to promote DR5 clustering on the cell surface. Moreover, we show that TRAIL molecules are arranged in higher order oligomers only in LUV-TRAIL, which may explain their enhanced DR5 clustering ability. Finally, LUV-TRAIL showed significantly better antitumour activity than sTRAIL in an in vivo model using HCT-116 xenograft tumours in nude mice, validating its potential clinical application