404 research outputs found

    Reconsiderando el significado de Hogar en la Rehabilitación: hacia una ciudad histórica sostenible

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    Despite the significant literature about the meaning of home and the scholars’ research concerning the home environment, the concept of home didn’t filter into the rehabilitation process. The conservation theory and the rehabilitation methodology are still concentrating on the material aspects of the built environment and ignoring the immaterial aspects and meanings. In view of that the dwellings are not only artifacts but they are a livable example of the social structure and behavioral patterns. Understanding the dwellers relationship with their dwellings will be helpful in establishing a connection between the rehabilitation of the historical domestic architecture and the concept of home. This requires reconsidering the theoretical frame work of the rehabilitation process so as to be able to recognize the change in the historical house’s spatial structure and order and to link them to the social structure and pattern of use.A pesar de la gran cantidad de literatura sobre el significado del hogar y las investigaciones hechas por académicos sobre el ambiente del hogar, el concepto de hogar no se filtró en el proceso de rehabilitación. La teoría de la conservación y la metodología de rehabilitación siguen concentrándose en los aspectos materiales del ambiente construido e ignoran los aspectos inmateriales. Tomando en cuenta que las viviendas no son sólo objetos, sino ejemplos de estructuras sociales, y patrones de conducta, el entendimiento de la relación entre habitantes y sus viviendas será de utilidad para establecer una conexión entre la rehabilitación de la arquitectura doméstica histórica y el concepto del hogar. Para ello es necesario reconsiderar el marco de trabajo teórico del proceso de rehabilitación con el fin de ser capaz de reconocer el cambio en la estructura espacial del hogar histórico y el orden, y vincularlos a la estructura social

    Copper trafficking in eukaryotic systems: current knowledge from experimental and computational efforts

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    Copper plays a vital role in fundamental cellular functions, and its concentration in the cell must be tightly regulated, as dysfunction of copper homeostasis is linked to severe neurological diseases and cancer. This review provides a compendium of current knowledge regarding the mechanism of copper transfer from the blood system to the Golgi apparatus; this mechanism involves the copper transporter hCtr1, the metallochaperone Atox1, and the ATPases ATP7A/B. We discuss key insights regarding the structural and functional properties of the hCtr1-Atox1-ATP7B cycle, obtained from diverse studies relying on distinct yet complementary biophysical, biochemical, and computational methods. We further address the mechanistic aspects of the cycle that continue to remain elusive. These knowledge gaps must be filled in order to be able to harness our understanding of copper transfer to develop therapeutic approaches with the capacity to modulate copper metabolism

    Manufacturing Consent Over Statehood Recognition: The New York Times Coverage Of Palestine And Kosovo Statehood Recognition

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    The mainstream media in democratic societies play a key role in shaping the audience perceptions, especially in relation to international affairs. They have the ability to “manufacture” the public consent over the state’s foreign policies. Recognizing or opposing an emerging state is deemed one significant policy at the agenda of governments’ diplomatic foreign affairs. Still, the international recognition by superpower states (i.e. the United States) is influential. The U.S. foreign policy of Palestine and Kosovo statehood recognition constitutes a clear example of the administration’s double standards. Although both states fulfil the minimum criteria of statehood, the U.S. opposes the recognition of the State of Palestine and supports Kosovo’s one. This research examines how the New York Times (NYT)—as a dominant U.S. media—manufactures consent pertaining to the U.S. foreign policy of statehood recognition. The current research employs the Propaganda Model of Herman and Chomsky (1988) as a theoretical thrust. It examines the occurrence of both reporting and ideological biases. Subsequently, three variables are investigated: the degree of reliance on U.S. official news sources; the degree of attention paid to issues under scrutiny; and the representation of the social actors and practices within the related discourse. Both quantitative content analysis and Critical Discourse Analysis (CDA) are adopted. The findings demonstrate that the NYT has offered a fake balance of voices within its related coverage

    Selection Of A Novel Aptamer Against Vitronectin Using Capillary Electrophoresis And Next Generation Sequencing

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    Breast cancer (BC) results in ≃40,000 deaths each year in the United States and even among survivors treatment of the disease may have devastating consequences, including increased risk for heart disease and cognitive impairment resulting from the toxic effects of chemotherapy. Aptamer-mediated drug delivery can contribute to improved treatment outcomes through the selective delivery of chemotherapy to BC cells, provided suitable cancer-specific antigens can be identified. We report here the use of capillary electrophoresis in conjunction with next generation sequencing to develop the first vitronectin (VN) binding aptamer (VBA-01; Kd 405 nmol/l, the first aptamer to vitronectin (VN; Kd = 405 nmol/l), a protein that plays an important role in wound healing and that is present at elevated levels in BC tissue and in the blood of BC patients relative to the corresponding nonmalignant tissues. We used VBA-01 to develop DVBA-01, a dimeric aptamer complex, and conjugated doxorubicin (Dox) to DVBA-01 (7:1 ratio) using pH-sensitive, covalent linkages. Dox conjugation enhanced the thermal stability of the complex (60.2 versus 46.5°C) and did not decrease affinity for the VN target. The resulting DVBA-01-Dox complex displayed increased cytotoxicity to MDA-MB-231 BC cells that were cultured on plasticware coated with VN (1.8 × 10⁻⁶mol/l) relative to uncoated plates (2.4 × 10⁻⁶ mol/l), or plates coated with the related protein fibronectin (2.1 × 10⁻⁶ mol/l). The VBA-01 aptamer was evaluated for binding to human BC tissue using immunohistochemistry and displayed tissue specific binding and apparent association with BC cells. In contrast, a monoclonal antibody that preferentially binds to multimeric VN primarily stained extracellular matrix and vessel walls of BC tissue. Our results indicate a strong potential for using VN-targeting aptamers to improve drug delivery to treat BC

    Phenomenological covariant approach to gravity

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    We covariantly modify the Einstein-Hilbert action such that the modified action perturbatively resolves the flat rotational velocity curve of the spiral galaxies and gives rise to the Tully-Fisher relation, and dynamically generates the cosmological constant. This modification requires introducing just a single new universal parameter.Comment: v6: a mistake in deriving the equation of the cosmological constant corrected, refs adde

    Unraveling the impact of cysteine-to-serine mutations on the structural and functional properties of Cu(I)-binding proteins

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    Appropriate maintenance of Cu(I) homeostasis is an essential requirement for proper cell function because its misregulation induces the onset of major human diseases and mortality. For this reason, several research efforts have been devoted to dissecting the inner working mechanism of Cu(I)-binding proteins and transporters. A commonly adopted strategy relies on mutations of cysteine residues, for which Cu(I) has an exquisite complementarity, to serines. Nevertheless, in spite of the similarity between these two amino acids, the structural and functional impact of serine mutations on Cu(I)-binding biomolecules remains unclear. Here, we applied various biochemical and biophysical methods, together with all-atom simulations, to investigate the effect of these mutations on the stability, structure, and aggregation propensity of Cu(I)-binding proteins, as well as their interaction with specific partner proteins. Among Cu(I)-binding biomolecules, we focused on the eukaryotic Atox1-ATP7B system, and the prokaryotic CueR metalloregulator. Our results reveal that proteins containing cysteine-to-serine mutations can still bind Cu(I) ions; however, this alters their stability and aggregation propensity. These results contribute to deciphering the critical biological principles underlying the regulatory mechanism of the in-cell Cu(I) concentration, and provide a basis for interpreting future studies that will take advantage of cysteine-to-serine mutations in Cu(I)-binding systems

    Solving Cell Placement Problem Using Harmony Search Algorithms

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    Cell placement is a phase in the chip design process, in which cells are assigned to physical locations. A placement algorithm is a way that satisfies the objectives and minimizes the total area while keeping enough space for routing. Cell placement is an NP-complete problem of very large size. In order to solve this problem, diversified heuristic algorithms are used. In this work, a new algorithm is proposed based on the harmony search algorithm. The harmony search algorithm mimics music improvisation process to find the optimal solution. Cell placement problem has many constraints, so in this work, the harmony search algorithm is modified to adapt to these constraints. Experiment results show that this algorithm is efficient for solving cell placement and is characterized by good performance, solution quality and likelihood of optimality

    Constraints on f(RijklRijkl)f(R_{ijkl}R^{ijkl}) gravity: An evidence against the covariant resolution of the Pioneer anomaly

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    We consider corrections in the form of ΔL(RijklRijkl)\Delta L(R_{ijkl}R^{ijkl}) to the Einstein-Hilbert Lagrangian. Then we compute the corrections to the Schwarszchild geometry due to the inclusion of this general term to the Lagrangian. We show that ΔL3=α1/3(RijklRijkl)1/3\Delta L_3=\alpha_{{1/3}}(R_{ijkl}R^{ijkl})^{{1/3}} gives rise to a constant anomalous acceleration for objects orbiting the Sun onward the Sun. This leads to the conclusion that α1/3=(13.91±2.11)×1026(1meters)2/3\alpha_{{1/3}}=(13.91\pm 2.11) \times 10^{-26}(\frac{1}{\text{meters}})^{{2/3}} would have covariantly resolved the Pioneer anomaly if this value of α1/3\alpha_{{1/3}} had not contradicted other observations. We notice that the experimental bounds on ΔL3\Delta L_3 grows stronger in case we examine the deformation of the space-time geometry around objects lighter than the Sun. We therefore use the high precision measurements around the Earth (LAGEOS and LLR) and obtain a very strong constraint on the corrections in the form of ΔL(RijklRijkl)\Delta L(R_{ijkl}R^{ijkl}) and in particular ΔL=αn(RijklRijkl)n\Delta L=\alpha_n(R_{ijkl}R^{ijkl})^n. This bound requires α1/36.12×1029(1meters)2/3\alpha_{{1/3}}\leq6.12\times 10^{-29}(\frac{1}{\text{meters}})^{{2/3}}. Therefore it refutes the covariant resolution of the Pioneer anomaly.Comment: ...v5: references added, new discussions adde

    Triangular Ring Resonator: Direct measurement of the parity-odd parameters of the photon sector of SME

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    We introduce the the Triangular Ring (TR) resonator. We show that the difference between the clockwise and anti-clockwise resonant frequencies of a vacuum TR resonator is sensitive to the birefringence parity-odd parameters of the photon's sector of the minimal Standard Model Extension (mSME): the Standard Model plus all the perturbative parameters encoding the break the Lorentz symmetry. We report that utilizing the current technology allows for direct measurement of these parameters with a sensitivity of the parity even ones and improves the best current resonator bounds by couple of orders of magnitudes. We note that designing an optical table that rotates perpendicular to the gravitational equipotential surface (geoid) allows for direct measurement of the constancy of the light speed at the vicinity of the earth in all directions in particular perpendicular to the geoid. If this table could achieve the precision of the ordinary tables, then it would improve the GPS bounds on the constancy of the light speed perpendicular to geoid by about eight orders of magnitude.Comment: ref. added, minor corrections, matches the published versio
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