Physical Constraints and Functional Characteristics of Transcription Factor-DNA Interaction

We study theoretical ``design principles'' for transcription factor-DNA interaction in bacteria, focusing particularly on the statistical interaction of the transcription factors (TF's) with the genomic background (i.e., the genome without the target sites). We introduce and motivate the concept of `programmability', i.e. the ability to set the threshold concentration for TF binding over a wide range merely by mutating the binding sequence of a target site. This functional demand, together with physical constraints arising from the thermodynamics and kinetics of TF-DNA interaction, leads us to a narrow range of ``optimal'' interaction parameters. We find that this parameter set agrees well with experimental data for the interaction parameters of a few exemplary prokaryotic TF's. This indicates that TF-DNA interaction is indeed programmable. We suggest further experiments to test whether this is a general feature for a large class of TF's.Comment: 9 pages, 4 figures; revised version as published in PNA

García Avilés, Alejandro. Imágenes encantadas. Los poderes de la imagen en la Edad Media

Es reseña de: Imágenes encantadas: los poderes de la imagen en la Edad Media Alejandro García Avilés Árbol académico Sans Soleil Ediciones, 2021. ISBN 978-84-120097-5-0Universidad Pablo de Olavid

Additamenta quaedam ad virtutes chemicas et physiologicas resinarum quarundam comparatas : dissertatio inauguralis medica

http://tartu.ester.ee/record=b2522690~S1*es

Engrailed (Gln50→Lys) homeodomain–DNA complex at 1.9 Å resolution: structural basis for enhanced affinity and altered specificity

AbstractBackground: The homeodomain is one of the key DNA-binding motifs used in eukaryotic gene regulation, and homeodomain proteins play critical roles in development. The residue at position 50 of many homeodomains appears to determine the differential DNA-binding specificity, helping to distinguish among binding sites of the form TAATNN. However, the precise role(s) of residue 50 in the differential recognition of alternative sites has not been clear. None of the previously determined structures of homeodomain–DNA complexes has shown evidence for a stable hydrogen bond between residue 50 and a base, and there has been much discussion, based in part on NMR studies, about the potential importance of water-mediated contacts. This study was initiated to help clarify some of these issues.Results: The crystal structure of a complex containing the engrailed Gln50→Lys variant (QK50) with its optimal binding site TAATCC (versus TAATTA for the wild-type protein) has been determined at 1.9 Å resolution. The overall structure of the QK50 variant is very similar to that of the wild-type complex, but the sidechain of Lys50 projects directly into the major groove and makes several hydrogen bonds to the O6 and N7 atoms of the guanines at base pairs 5 and 6. Lys50 also makes an additional water-mediated contact with the guanine at base pair 5 and has an alternative conformation that allows a hydrogen bond with the O4 of the thymine at base pair 4.Conclusions: The structural context provided by the folding and docking of the engrailed homeodomain allows Lys50 to make remarkably favorable contacts with the guanines at base pairs 5 and 6 of the binding site. Although many different residues occur at position 50 in different homeodomains, and although numerous position 50 variants have been constructed, the most striking examples of altered specificity usually involve introducing or removing a lysine sidechain from position 50. This high-resolution structure also confirms the critical role of Asn51 in homeodomain–DNA recognition and further clarifies the roles of water molecules near residues 50 and 51

Assessment of the optimization of affinity and specificity at protein–DNA interfaces

The biological functions of DNA-binding proteins often require that they interact with their targets with high affinity and/or high specificity. Here, we describe a computational method that estimates the extent of optimization for affinity and specificity of amino acids at a protein–DNA interface based on the crystal structure of the complex, by modeling the changes in binding-free energy associated with all individual amino acid and base substitutions at the interface. The extent to which residues are predicted to be optimal for specificity versus affinity varies within a given protein–DNA interface and between different complexes, and in many cases recapitulates previous experimental observations. The approach provides a complement to traditional methods of mutational analysis, and should be useful for rapidly formulating hypotheses about the roles of amino acid residues in protein–DNA interfaces

An analysis and characterisation of publicly available conceptual models

Multiple conceptual data modelling languages exist, with newer version typically having more features to model the universe of discourse more precisely. The question arises, however, to what extent those features are actually used in extant models, and whether characteristic profiles can be discerned. We quantitatively evaluated this with a set of 105 UML Class Diagrams, ER and EER models, and ORM and ORM2 diagrams. When more features are available, they are used, but few times. Only 64\% of the entities are the kind of entities that appear in all three language families. Different profiles are identified that characterise how a typical UML, (E)ER and ORM diagram looks like

An ontology-driven unifying metamodel of UML Class Diagrams, EER, and ORM2

Software interoperability and application integration can be realized \linebreak through using their respective conceptual data models, which may be represented in different conceptual data modeling languages. Such modeling languages seem similar, yet are known to be distinct. Several translations between subsets of the languages' features exist, but there is no unifying framework that respects most language features of the static structural components and constraints. We aim to fill this gap. To this end, we designed a common and unified ontology-driven metamodel of the static, structural components and constraints in such a way that it unifies ER, EER, UML Class Diagrams v2.4.1, and ORM and ORM2 such that each one is a proper fragment of the consistent metamodel. The paper also presents some notable insights into the relatively few common entities and constraints, an analysis on roles, relationships, and attributes, and other modeling motivations are discussed. We describe two practical use cases of the metamodel, being a quantitative assessment of the entities of 30 models in ER/EER, UML, and ORM/ORM2, and a qualitative evaluation of inter-model assertions

Evaluating the SEE sensitivity of a 45nm SOI Multi-core Processor due to 14 MeV Neutrons

The aim of this work is to evaluate the SEE sensitivity of a multi-core processor having implemented ECC and parity in their cache memories. Two different application scenarios are studied. The first one configures the multi-core in Asymmetric Multi-Processing mode running a memory-bound application, whereas the second one uses the Symmetric Multi-Processsing mode running a CPU-bound application. The experiments were validated through radiation ground testing performed with 14 MeV neutrons on the Freescale P2041 multi-core manufactured in 45nm SOI technology. A deep analysis of the observed errors in cache memories was carried-out in order to reveal vulnerabilities in the cache protection mechanisms. Critical zones like tag addresses were affected during the experiments. In addition, the results show that the sensitivity strongly depends on the application and the multi-processsing mode used

Precise targeted integration by a chimaeric transposase zinc-finger fusion protein

Transposons of the Tc1/mariner family have been used to integrate foreign DNA stably into the genome of a large variety of different cell types and organisms. Integration is at TA dinucleotides located essentially at random throughout the genome, potentially leading to insertional mutagenesis, inappropriate activation of nearby genes, or poor expression of the transgene. Here, we show that fusion of the zinc-finger DNA-binding domain of Zif268 to the C-terminus of ISY100 transposase leads to highly specific integration into TA dinucleotides positioned 6-17 bp to one side of a Zif268 binding site. We show that the specificity of targeting can be changed using Zif268 variants that bind to sequences from the HIV-1 promoter, and demonstrate a bacterial genetic screen that can be used to select for increased levels of targeted transposition. A TA dinucleotide flanked by two Zif268 binding sites was efficiently targeted by our transposase-Zif268 fusion, suggesting the possibility of designer ‘Z-transposases’ that could deliver transgenic cargoes to chosen genomic locations

Dye-sensitized Solar Cell (DSSC) Menggunakan Ekstrak Limbah Teh Padat Hasil Pabrik

As the seventh largest tea producer in tea world, Indonesia generates an estimated total of 137.803 tons in 2019 with large quantities of wastes from tea industries. In this project, zero waste concept was implemented from farm to tea factory to minimize waste generation. Tea objective of this study is to fabricate light trap based on DSSC derived from tea factory waste. Both modified carbon and dyes from tea waste were investigated to develop DSSC prototype using sandwich method by coating TiO2 on ITO (Indium Tin Oxide) glass. The counter electrode and dyes were prepared by calcinating tea plant waste (stem, leaves, etc.). Extracting processed tea waste, respectively leaves used (black tea, green tea, and white tea) and cathode type carbon and strained-iron were compared. Variations in tea thickness of counter modified carbon electrode and area were performed. Tea efficiency and amount of energy generated in tea application of DSSC in light traps was estimated. The best DSSC voltage is found in size of 100 cm2 with a black tea dye of 612.4 mV with an efficiency of 1.2002% using strained-iron electrode