Desarrollo sostenible a la luz de la filosofía de la ciencia y la ética

El presente artículo fundamenta la necesidad de utilizar el potencial de la filosofía de la ciencia en el diseño de un proyecto de desarrollo sostenible. Junto con las matemáticas y la informática, la filosofía de la ciencia se considera una ciencia auxiliar diseñada para ayudar a aclarar la naturaleza conceptual y metodológica de las teorías científicas. Se presentan nuevas disposiciones de la filosofía de la ciencia. Se prueba la proposición de que todas las teorías axiológicas culminan en la ética. También se fundamenta que las ciencias naturales demuestran la relatividad ética. El proyecto, es decir, tanto el concepto como la concepción (teoría) del desarrollo sostenible, se diseñó sin tener en cuenta los logros de la filosofía de la ciencia, incluida la ética científica. A medida que el proyecto se desarrolló, su contenido no se hizo más claro sino, por el contrario, más oscuro. El proyecto de desarrollo sustentable se reevalúa a la luz de la filosofía de la ciencia. Resulta ser nada más que una paráfrasis de la necesidad del adecuado desarrollo de la relatividad ética de la ecología y su lugar en el sistema de ética científica equilibrada. El proyecto de desarrollo sostenible presenta una paráfrasis de cierto contenido científico que debe ser abordado adecuadamente. Sin esto, no tiene significado científico y debe atribuirse al campo del lenguaje cotidiano. Por tanto, ha llegado el momento de poner el proyecto de desarrollo sostenible en una vía científic

Near-optimal Linear Decision Trees for k-SUM and Related Problems

We construct near-optimal linear decision trees for a variety of decision problems in combinatorics and discrete geometry. For example, for any constant k , we construct linear decision trees that solve the k -SUM problem on n elements using O ( n log 2 n ) linear queries. Moreover, the queries we use are comparison queries, which compare the sums of two k -subsets; when viewed as linear queries, comparison queries are 2 k -sparse and have only { −1,0,1} coefficients. We give similar constructions for sorting sumsets A+B and for solving the SUBSET-SUM problem, both with optimal number of queries, up to poly-logarithmic terms. Our constructions are based on the notion of “inference dimension,” recently introduced by the authors in the context of active classification with comparison queries. This can be viewed as another contribution to the fruitful link between machine learning and discrete geometry, which goes back to the discovery of the VC dimension

MuSR method and tomographic probability representation of spin states

Muon spin rotation/relaxation/resonance (MuSR) technique for studying matter structures is considered by means of a recently introduced probability representation of quantum spin states. A relation between experimental MuSR histograms and muon spin tomograms is established. Time evolution of muonium, anomalous muonium, and a muonium-like system is studied in the tomographic representation. Entanglement phenomenon of a bipartite muon-electron system is investigated via tomographic analogues of Bell number and positive partial transpose (PPT) criterion. Reconstruction of the muon-electron spin state as well as the total spin tomography of composed system is discussed.Comment: 20 pages, 4 figures, LaTeX, submitted to Journal of Russian Laser Researc

Design, synthesis and biological evaluation of edaravone derivatives bearing the N-benzyl pyridinium moiety as multifunctional anti-Alzheimer’s agents

A series of multi-target directed edaravone derivatives bearing N-benzyl pyridinium moieties were designed and synthesised. Edaravone is a potent antioxidant with significant neuroprotective effects and N-benzyl pyridinium has previously exhibited positive results as part of a dual-site binding, peripheral anionic site (PAS) and catalytic anionic site (CAS), acetylcholinesterase (AChE) inhibitor. The designed edaravone-N-benzyl pyridinium hybrid compounds were docked within the AChE active site. The results indicated interactions with conserved amino acids (Trp279 in PAS and Trp84 in CAS), suggesting good dual-site inhibitory activity. Significant in vitro AChE inhibitory activities were observed for selected compounds (IC50: 1.2–4.6 µM) with limited butyrylcholinesterase inhibitory activity (IC50’s >160 µM), indicating excellent selectivity towards AChE (SI: 46–>278). The compounds also showed considerable antioxidant ability, similar to edaravone

Inverse spin-s portrait and representation of qudit states by single probability vectors

Using the tomographic probability representation of qudit states and the inverse spin-portrait method, we suggest a bijective map of the qudit density operator onto a single probability distribution. Within the framework of the approach proposed, any quantum spin-j state is associated with the (2j+1)(4j+1)-dimensional probability vector whose components are labeled by spin projections and points on the sphere. Such a vector has a clear physical meaning and can be relatively easily measured. Quantum states form a convex subset of the 2j(4j+3) simplex, with the boundary being illustrated for qubits (j=1/2) and qutrits (j=1). A relation to the (2j+1)^2- and (2j+1)(2j+2)-dimensional probability vectors is established in terms of spin-s portraits. We also address an auxiliary problem of the optimum reconstruction of qudit states, where the optimality implies a minimum relative error of the density matrix due to the errors in measured probabilities.Comment: 23 pages, 4 figures, PDF LaTeX, submitted to the Journal of Russian Laser Researc

Free Cysteine Modulates the Conformation of Human C/EBP Homologous Protein

The C/EBP Homologous Protein (CHOP) is a nuclear protein that is integral to the unfolded protein response culminating from endoplasmic reticulum stress. Previously, CHOP was shown to comprise extensive disordered regions and to self-associate in solution. In the current study, the intrinsically disordered nature of this protein was characterized further by comprehensive in silico analyses. Using circular dichroism, differential scanning calorimetry and nuclear magnetic resonance, we investigated the global conformation and secondary structure of CHOP and demonstrated, for the first time, that conformational changes in this protein can be induced by the free amino acid l-cysteine. Addition of l-cysteine caused a significant dose-dependent decrease in the protein helicity – dropping from 69.1% to 23.8% in the presence of 1 mM of l-cysteine – and a sequential transition to a more disordered state, unlike that caused by thermal denaturation. Furthermore, the presence of small amounts of free amino acid (80 µM, an 8∶1 cysteine∶CHOP ratio) during CHOP thermal denaturation altered the molecular mechanism of its melting process, leading to a complex, multi-step transition. On the other hand, high levels (4 mM) of free l-cysteine seemed to cause a complete loss of rigid cooperatively melting structure. These results suggested a potential regulatory function of l-cysteine which may lead to changes in global conformation of CHOP in response to the cellular redox state and/or endoplasmic reticulum stress

Qubit portrait of the photon-number tomogram and separability of two-mode light states

In view of the photon-number tomograms of two-mode light states, using the qubit-portrait method for studying the probability distributions with infinite outputs, the separability and entanglement detection of the states are studied. Examples of entangled Gaussian state and Schr\"{o}dinger cat state are discussed.Comment: 20 pages, 6 figures, TeX file, to appear in Journal of Russian Laser Researc

Disorder Predictors Also Predict Backbone Dynamics for a Family of Disordered Proteins

Several algorithms have been developed that use amino acid sequences to predict whether or not a protein or a region of a protein is disordered. These algorithms make accurate predictions for disordered regions that are 30 amino acids or longer, but it is unclear whether the predictions can be directly related to the backbone dynamics of individual amino acid residues. The nuclear Overhauser effect between the amide nitrogen and hydrogen (NHNOE) provides an unambiguous measure of backbone dynamics at single residue resolution and is an excellent tool for characterizing the dynamic behavior of disordered proteins. In this report, we show that the NHNOE values for several members of a family of disordered proteins are highly correlated with the output from three popular algorithms used to predict disordered regions from amino acid sequence. This is the first test between an experimental measure of residue specific backbone dynamics and disorder predictions. The results suggest that some disorder predictors can accurately estimate the backbone dynamics of individual amino acids in a long disordered region

Mechanism of the Interaction between the Intrinsically Disordered C-Terminus of the Pro-Apoptotic ARTS Protein and the Bir3 Domain of XIAP

ARTS (Sept4_i2) is a mitochondrial pro-apoptotic protein that functions as a tumor suppressor. Its expression is significantly reduced in leukemia and lymphoma patients. ARTS binds and inhibits XIAP (X-linked Inhibitor of Apoptosis protein) by interacting with its Bir3 domain. ARTS promotes degradation of XIAP through the proteasome pathway. By doing so, ARTS removes XIAP inhibition of caspases and enables apoptosis to proceed. ARTS contains 27 unique residues in its C-terminal domain (CTD, residues 248–274) which are important for XIAP binding. Here we characterized the molecular details of this interaction. Biophysical and computational methods were used to show that the ARTS CTD is intrinsically disordered under physiological conditions. Direct binding of ARTS CTD to Bir3 was demonstrated using NMR and fluorescence spectroscopy. The Bir3 interacting region in ARTS CTD was mapped to ARTS residues 266–274, which are the nine C-terminal residues in the protein. Alanine scan of ARTS 266–274 showed the importance of several residues for Bir3 binding, with His268 and Cys273 contributing the most. Adding a reducing agent prevented binding to Bir3. A dimer of ARTS 266–274 formed by oxidation of the Cys residues into a disulfide bond bound with similar affinity and was probably required for the interaction with Bir3. The detailed analysis of the ARTS – Bir3 interaction provides the basis for setting it as a target for anti cancer drug design: It will enable the development of compounds that mimic ARTS CTD, remove IAPs inhibition of caspases, and thereby induce apoptosis

Influence of Sequence Changes and Environment on Intrinsically Disordered Proteins

Many large-scale studies on intrinsically disordered proteins are implicitly based on the structural models deposited in the Protein Data Bank. Yet, the static nature of deposited models supplies little insight into variation of protein structure and function under diverse cellular and environmental conditions. While the computational predictability of disordered regions provides practical evidence that disorder is an intrinsic property of proteins, the robustness of disordered regions to changes in sequence or environmental conditions has not been systematically studied. We analyzed intrinsically disordered regions in the same or similar proteins crystallized independently and studied their sensitivity to changes in protein sequence and parameters of crystallographic experiments. The observed changes in the existence, position, and length of disordered regions indicate that their appearance in X-ray structures dramatically depends on changes in amino acid sequence and peculiarities of the crystallographic experiment. Our study also raises general questions regarding protein evolution and the regulation of protein structure, dynamics, and function via variations in cellular and environmental conditions