Dry selection and wet evaluation for the rational discovery of new anthelmintics

Helminths infections remain a major problem in medical and public health. In this report, atom-based 2D bilinear indices, a TOMOCOMD-CARDD (QuBiLs-MAS module) molecular descriptor family and linear discriminant analysis (LDA) were used to find models that differentiate among anthelmintic and non-anthelmintic compounds. Two classification models obtained by using non-stochastic and stochastic 2D bilinear indices, classified correctly 86.64% and 84.66%, respectively, in the training set. Equation 1(2) correctly classified 141(135) out of 165 [85.45%(81.82%)] compounds in external validation set. Another LDA models were performed in order to get the most likely mechanism of action of anthelmintics. The model shows an accuracy of 86.84% in the training set and 94.44% in the external prediction set. Finally, we carry out an experiment to predict the biological profile of our ‘in-house’ collections of indole, indazole, quinoxaline and cinnoline derivatives (∼200 compounds). Subsequently, we selected a group of nine of the theoretically most active structures. Then, these chemicals were tested in an invitro assay and one good candidate (VA5-5c) as fasciolicide compound (100% of reduction at concentrations of 50 and 10 mg/L) was discovered.Yovani Marrero-Ponce acknowledges the support from USFQ with partial finance of project ID5455Peer Reviewe

Diseño estructural de carcasa para impresoras 3D RepRab

Uno de los problemas fundamentales de algunas impresoras 3D hace referencia al control de la temperatura en el momento de la impresión. Este efecto denominado "warping" sucede al depositar plástico caliente que es enfriado rápidamente induciendo una contracción que provoca que las capas superiores "arrastren" de las inferiores y que la base se levante y despegue. Este trabajo presenta el diseño y construcción de una carcasa, para los modelos RepRap (Replicating Rapid Prototyper), que mejore y garantice el entorno de las operaciones de impresión 3D y el resultado final. El producto es modulable y adaptable a los modelos de impresoras RepRap del mercado, capaz de controlar el ambiente en el interior del habitáculo, permitiendo un máximo ahorro de material en su fabricación, reduciendo los costes por reprocesado en la fabricación de piezas, permitiendo una máxima visibilidad del interior, una utilización de materiales respetuosos con el medio ambiente y una facilidad de montaje, Design for assembly. El diseño de las piezas se realizó de forma que permitiese el cumplimiento de las limitaciones de impresión en cuanto a tamaño, complejidad geométrica, regla de los 45o, precisión de capa, margen de tolerancias, orientación en la base de impresión para mejorar la funcionalidad y la resistencia mecánica.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Cytogenetic and genomic analysis of a patient with turner syndrome and t(2;12): a case report

Background: Turner syndrome is a genetic disorder that afects women. It is caused by an absent or incomplete X chromosome, which can be presented in mosaicism or not. There are 12 cases of Turner syndrome patients who present structural alterations in autosomal chromosomes. Case presentation: The present case report describes a patient with a reciprocal, maternally inherited translocation between chromosomes 2 and 12 with a mosaicism of X monosomy 45,X,t(2;12)(p13;q24)[95]/46,XX,t(2;12)(p13;q24) [5]. Through genetic mapping arrays, altered genes in the patient were determined within the 23 chromosome pairs. These genes were associated with the patient’s clinical features using a bioinformatics tool Conclusion: To our knowledge, this is the frst case in which a translocation (2;12) is reported in a patient with Turner syndrome and confrmed by conventional cytogenetics, FISH and molecular genetics. Clinical features of our patient are closely related with the loss of one X chromosome, however mild intellectual disability can be likely explained by autosomal genes. The presence of familial translocations was a common fnding, thus emphasizing the need for familiar testing for further genetic counselling

The effects of thymoquinone on pancreatic cancer: Evidence from preclinical studies

Thymoquinone (TQ) is a secondary metabolite found in abundance in very few plant species including Nigella sativa L., Monarda fistulosa L., Thymus vulgaris L. and Satureja montana L. Preclinical pharmacological studies have shown that TQ has many biological activities, such as anti-inflammatory, antioxidant and anticancer. Both in vivo and in vitro experiments have shown that TQ acts as an antitumor agent by altering cell cycle progression, inhibiting cell proliferation, stimulating apoptosis, inhibiting angiogenesis, reducing metastasis and affecting autophagy. In this comprehensive study, the evidence on the pharmacological potential of TQ on pancreatic cancer is reviewed. The positive results of preclinical studies support the view that TQ can be considered as an additional therapeutic agent against pancreatic cancer. The possibilities of success for this compound in human medicine should be further explored through clinical trials. © 2022 The Author

Calibration of the Logarithmic-Periodic Dipole Antenna (LPDA) Radio Stations at the Pierre Auger Observatory using an Octocopter

An in-situ calibration of a logarithmic periodic dipole antenna with a frequency coverage of 30 MHz to 80 MHz is performed. Such antennas are part of a radio station system used for detection of cosmic ray induced air showers at the Engineering Radio Array of the Pierre Auger Observatory, the so-called Auger Engineering Radio Array (AERA). The directional and frequency characteristics of the broadband antenna are investigated using a remotely piloted aircraft (RPA) carrying a small transmitting antenna. The antenna sensitivity is described by the vector effective length relating the measured voltage with the electric-field components perpendicular to the incoming signal direction. The horizontal and meridional components are determined with an overall uncertainty of 7.4^{+0.9}_{-0.3} % and 10.3^{+2.8}_{-1.7} % respectively. The measurement is used to correct a simulated response of the frequency and directional response of the antenna. In addition, the influence of the ground conductivity and permittivity on the antenna response is simulated. Both have a negligible influence given the ground conditions measured at the detector site. The overall uncertainties of the vector effective length components result in an uncertainty of 8.8^{+2.1}_{-1.3} % in the square root of the energy fluence for incoming signal directions with zenith angles smaller than 60{\deg}.Comment: Published version. Updated online abstract only. Manuscript is unchanged with respect to v2. 39 pages, 15 figures, 2 table

Multi-resolution anisotropy studies of ultrahigh-energy cosmic rays detected at the Pierre Auger Observatory

We report a multi-resolution search for anisotropies in the arrival directions of cosmic rays detected at the Pierre Auger Observatory with local zenith angles up to $80^\circ$ and energies in excess of 4 EeV ($4 \times 10^{18}$ eV). This search is conducted by measuring the angular power spectrum and performing a needlet wavelet analysis in two independent energy ranges. Both analyses are complementary since the angular power spectrum achieves a better performance in identifying large-scale patterns while the needlet wavelet analysis, considering the parameters used in this work, presents a higher efficiency in detecting smaller-scale anisotropies, potentially providing directional information on any observed anisotropies. No deviation from isotropy is observed on any angular scale in the energy range between 4 and 8 EeV. Above 8 EeV, an indication for a dipole moment is captured; while no other deviation from isotropy is observed for moments beyond the dipole one. The corresponding $p$-values obtained after accounting for searches blindly performed at several angular scales, are $1.3 \times 10^{-5}$ in the case of the angular power spectrum, and $2.5 \times 10^{-3}$ in the case of the needlet analysis. While these results are consistent with previous reports making use of the same data set, they provide extensions of the previous works through the thorough scans of the angular scales.Comment: Published version. Added journal reference and DOI. Added Report Numbe

Ultrahigh-energy neutrino follow-up of Gravitational Wave events GW150914 and GW151226 with the Pierre Auger Observatory

On September 14, 2015 the Advanced LIGO detectors observed their first gravitational-wave (GW) transient GW150914. This was followed by a second GW event observed on December 26, 2015. Both events were inferred to have arisen from the merger of black holes in binary systems. Such a system may emit neutrinos if there are magnetic fields and disk debris remaining from the formation of the two black holes. With the surface detector array of the Pierre Auger Observatory we can search for neutrinos with energy above 100 PeV from point-like sources across the sky with equatorial declination from about -65 deg. to +60 deg., and in particular from a fraction of the 90% confidence-level (CL) inferred positions in the sky of GW150914 and GW151226. A targeted search for highly-inclined extensive air showers, produced either by interactions of downward-going neutrinos of all flavors in the atmosphere or by the decays of tau leptons originating from tau-neutrino interactions in the Earth's crust (Earth-skimming neutrinos), yielded no candidates in the Auger data collected within $\pm 500$ s around or 1 day after the coordinated universal time (UTC) of GW150914 and GW151226, as well as in the same search periods relative to the UTC time of the GW candidate event LVT151012. From the non-observation we constrain the amount of energy radiated in ultrahigh-energy neutrinos from such remarkable events.Comment: Published version. Added journal reference and DOI. Added Report Numbe

Charge separation relative to the reaction plane in Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}}= 2.76 TeV

Measurements of charge dependent azimuthal correlations with the ALICE detector at the LHC are reported for Pb-Pb collisions at $\sqrt{s_{\rm NN}} = 2.76$ TeV. Two- and three-particle charge-dependent azimuthal correlations in the pseudo-rapidity range $|\eta| < 0.8$ are presented as a function of the collision centrality, particle separation in pseudo-rapidity, and transverse momentum. A clear signal compatible with a charge-dependent separation relative to the reaction plane is observed, which shows little or no collision energy dependence when compared to measurements at RHIC energies. This provides a new insight for understanding the nature of the charge dependent azimuthal correlations observed at RHIC and LHC energies.Comment: 12 pages, 3 captioned figures, authors from page 2 to 6, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/286