Review. Literary education in the classrooms. Proposals for action

Reseña del libro "Educación literaria en las aulas. Propuestas para actuar". De María Santamarina Sancho y Pilar Núñez Delgado (eds.

Controlled Anisotropic Deformation of Ag Nanoparticles by Si Ion Irradiation

The shape and alignment of silver nanoparticles embedded in a glass matrix is controlled using silicon ion irradiation. Symmetric silver nanoparticles are transformed into anisotropic particles whose larger axis is along the ion beam. Upon irradiation, the surface plasmon resonance of symmetric particles splits into two resonances whose separation depends on the fluence of the ion irradiation. Simulations of the optical absorbance show that the anisotropy is caused by the deformation and alignment of the nanoparticles, and that both properties are controlled with the irradiation fluence.Comment: Submitted to Phys. Rev. Lett. (October 14, 2005

Invoking Chiral Vector Leptoquark to explain LFU violation in B Decays

LHCb has recently reported more than $2\sigma$ deviation from the Standard Model prediction in the observable $R_{J/\psi}$. We study this anomaly in the framework of a vector leptoquark along with other lepton flavor universality violating measurements which include $R_{K^{(*)}}$, and $R_{D^{(*)}}$. We show that a chiral vector leptoquark can explain all the aforementioned anomalies consistently while also respecting other experimental constraints

Discovery of conformationally constrained ALK2 inhibitors

Despite decades of research on new diffuse intrinsic pontine glioma (DIPG) treatments, little or no progress has been made on improving patient outcomes. In this work, we explored novel scaffold modifications of M4K2009, a 3,5-diphenylpyridine ALK2 inhibitor previously reported by our group. Here we disclose the design, synthesis, and evaluation of a first-in-class set of 5- to 7-membered ether-linked and 7-membered amine-linked constrained inhibitors of ALK2. This rigidification strategy led us to the discovery of the ether-linked inhibitors M4K2308 and M4K2281 and the amine-linked inhibitors M4K2304 and M4K2306, each with superior potency against ALK2. Notably, M4K2304 and M4K2306 exhibit exceptional selectivity for ALK2 over ALK5, surpassing the reference compound. Preliminary studies on their in vivo pharmacokinetics, including blood-brain barrier penetration, revealed that these constrained scaffolds have favorable exposure and do open a novel chemical space for further optimization and future evaluation in orthotopic models of DIPG

Development of Novel Drugs for the Treatment of Chagas Disease

Chagas disease, or American trypanosomiasis, is a zoonosis caused by the hemoflagellate parasite Trypanosoma cruzi. It is mainly transmitted by the bite of blood-sucking insects. It is endemic in Latin America and emerging in the rest of the world, affecting approximately six million people. The drugs Benznidazole and Nifurtimox currently used for its treatment are not totally effective in the chronic phase of the disease. In addition, they are toxic, and there are many resistant Trigonoscuta cruzi strains. Therefore, developing new drugs for the treatment of Chagas disease is necessary. This chapter describes the development of drugs that inhibit α-hydroxy acid dehydrogenase isoenzyme II, a key enzyme in parasite energy metabolism. These drugs have shown more significant trypanocidal activity than the currently used drugs, and they have also prevented the development of chronic Chagas disease in infected mice

Sustained proliferation in cancer: mechanisms and novel therapeutic targets

Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth. Early steps in tumor development are associated with a fibrogenic response and the development of a hypoxic environment which favors the survival and proliferation of cancer stem cells. Part of the survival strategy of cancer stem cells may manifested by alterations in cell metabolism. Once tumors appear, growth and metastasis may be supported by overproduction of appropriate hormones (in hormonally dependent cancers), by promoting angiogenesis, by undergoing epithelial to mesenchymal transition, by triggering autophagy, and by taking cues from surrounding stromal cells. A number of natural compounds (e.g., curcumin, resveratrol, indole-3-carbinol, brassinin, sulforaphane, epigallocatechin-3-gallate, genistein, ellagitannins, lycopene and quercetin) have been found to inhibit one or more pathways that contribute to proliferation (e.g., hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor receptor 1, Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling). These data, in combination with bioinformatics analyses, will be very important for identifying signaling pathways and molecular targets that may provide early diagnostic markers and/or critical targets for the development of new drugs or drug combinations that block tumor formation and progression

Rationally Designed Interfacial Peptides Are Efficient In Vitro Inhibitors of HIV-1 Capsid Assembly with Antiviral Activity

Virus capsid assembly constitutes an attractive target for the development of antiviral therapies; a few experimental inhibitors of this process for HIV-1 and other viruses have been identified by screening compounds or by selection from chemical libraries. As a different, novel approach we have undertaken the rational design of peptides that could act as competitive assembly inhibitors by mimicking capsid structural elements involved in intersubunit interfaces. Several discrete interfaces involved in formation of the mature HIV-1 capsid through polymerization of the capsid protein CA were targeted. We had previously designed a peptide, CAC1, that represents CA helix 9 (a major part of the dimerization interface) and binds the CA C-terminal domain in solution. Here we have mapped the binding site of CAC1, and shown that it substantially overlaps with the CA dimerization interface. We have also rationally modified CAC1 to increase its solubility and CA-binding affinity, and designed four additional peptides that represent CA helical segments involved in other CA interfaces. We found that peptides CAC1, its derivative CAC1M, and H8 (representing CA helix 8) were able to efficiently inhibit the in vitro assembly of the mature HIV-1 capsid. Cocktails of several peptides, including CAC1 or CAC1M plus H8 or CAI (a previously discovered inhibitor of CA polymerization), or CAC1M+H8+CAI, also abolished capsid assembly, even when every peptide was used at lower, sub-inhibitory doses. To provide a preliminary proof that these designed capsid assembly inhibitors could eventually serve as lead compounds for development of anti-HIV-1 agents, they were transported into cultured cells using a cell-penetrating peptide, and tested for antiviral activity. Peptide cocktails that drastically inhibited capsid assembly in vitro were also able to efficiently inhibit HIV-1 infection ex vivo. This study validates a novel, entirely rational approach for the design of capsid assembly interfacial inhibitors that show antiviral activity

Joint analysis of the energy spectrum of ultra-high-energy cosmic rays measured at the Pierre Auger Observatory and the Telescope Array

The measurement of the energy spectrum of ultra-high-energy cosmic rays (UHECRs) is of crucial importance to clarify their origin and acceleration mechanisms. The Pierre Auger Observatory in Argentina and the Telescope Array (TA) in the US have reported their measurements of UHECR energy spectra observed in the southern and northern hemisphere, respectively. The region of the sky accessible to both Observatories ([−15,+24] degrees in declination) can be used to cross-calibrate the two spectra. The Auger-TA energy spectrum working group was organized in 2012 and has been working to understand the uncertainties in energy scale in both experiments, their systematic differences, and differences in the shape of the spectra. In previous works, we reported that there was an overall agreement of the energy spectra measured by the two observatories below 10 EeV while at higher energies, a remaining significant difference was observed in the common declination band. We revisit this issue to understand its origin by examining the systematic uncertainties, statistical effects, and other possibilities. We will also discuss the differences in the spectra in different declination bands and a new feature in the spectrum recently reported by the Auger Collaboration

The UHECR dipole and quadrupole in the latest data from the original Auger and TA surface detectors

The sources of ultra-high-energy cosmic rays are still unknown, but assuming standard physics, they are expected to lie within a few hundred megaparsecs from us. Indeed, over cosmological distances cosmic rays lose energy to interactions with background photons, at a rate depending on their mass number and energy and properties of photonuclear interactions and photon backgrounds. The universe is not homogeneous at such scales, hence the distribution of the arrival directions of cosmic rays is expected to reflect the inhomogeneities in the distribution of galaxies; the shorter the energy loss lengths, the stronger the expected anisotropies. Galactic and intergalactic magnetic fields can blur and distort the picture, but the magnitudes of the largest-scale anisotropies, namely the dipole and quadrupole moments, are the most robust to their effects. Measuring them with no bias regardless of any higher-order multipoles is not possible except with full-sky coverage. In this work, we achieve this in three energy ranges (approximately 8--16 EeV, 16--32 EeV, and 32--∞ EeV) by combining surface-detector data collected at the Pierre Auger Observatory until 2020 and at the Telescope Array (TA) until 2019, before the completion of the upgrades of the arrays with new scintillator detectors. We find that the full-sky coverage achieved by combining Auger and TA data reduces the uncertainties on the north-south components of the dipole and quadrupole in half compared to Auger-only results