On integrating a proprietary and a commercial architecture for optimal BIST performances in SoCs

This paper presents the integration of a proprietary hierarchical and distributed test access mechanism called HD2BIST and a BIST insertion commercial tool. The paper briefly describes the architecture and the features of both the environments and it presents some experimental results obtained on an industrial So

Hotel Boulevard Atlántico: un trabajo de cooperación cultural para su recuperación

El Patrimonio ocupa un lugar importante en el Turismo, una de sus etapas fundamentales son aquellas acciones vinculadas a cómo comunicar y difundir su importancia, sus alcances, sus connotaciones y la necesidad y el porqué de su preservación. En este sentido, el Grupo de Extensión en Gestión Cultural de la Facultad de Arquitectura, Urbanismo y Diseño de la Universidad Nacional Mar del Plata, la Dirección de Cultura del Partido de General Alvarado y el Programa de Rehabilitación de Áreas Históricas de Cochabamba de la Universidad Mayor de San Simón-Bolivia trabajaron en la investigación histórica del entorno de Mar del Sud y del Hotel Boulevard Atlántico. Asimismo, se realizó un relevamiento planimétrico y fotográfico del bien como también el análisis tipológico, estilístico y artístico. Este relevamiento permitió realizar un registro del estado actual de los componentes del hotel con la finalidad de establecer el estado de conservación y contribuir en recuperar la legitimidad del documento. A partir de este trabajo se busca potenciar la identidad local; esto nos llevó a determinar que el desarrollo económico local depende de la capacidad de integrar el aprovechamiento sostenible de los recursos naturales y paisajísticos que conforma el entorno del majestuoso Hotel, único en su estilo en la provincia de Buenos Aires

Human replication protein A can suppress the intrinsic in vitro mutator phenotype of human DNA polymerase λ

DNA polymerase λ (pol λ) is a member of the X family DNA polymerases and is endowed with multiple enzymatic activities. In this work we investigated the in vitro miscoding properties of full-length, human pol λ either in the absence or in the presence of the human auxiliary proteins proliferating cell nuclear antigen (PCNA) and replication protein A (RP-A). Our data suggested that (i) pol λ had an intrinsic ability to create mismatches and to incorporate ribonucleotides at nearly physiological Mn++ and Mg++ concentrations; (ii) the sequence of the template-primer could influence the misincorporation frequency of pol λ; (iii) pol λ preferentially generated G:T and G:G mismatches; (iv) RP-A, but not PCNA, selectively prevented misincorporation of an incorrect nucleotide by pol λ, without affecting correct incorporation and (v) this inhibitory effect required a precise ratio between the concentrations of pol λ and RP-A. Possible physiological implications of these findings for the in vivo fidelity of pol λ are discusse

ScFv from antibody that mimics gp43 modulates the cellular and humoral immune responses during Experimental Paracoccidioidomycosis

Paracoccidioidomycosis (PCM), caused by Paracoccidioides species is a prevalent systemic and progressive mycosis that occurs in Latin America. It is caused by Paracoccidioides species. Immunization with dendritic cells transfected with a plasmid encoding the scFv (pMAC/PS-scFv) that mimics the main antigen of P. brasiliensis (gp43) confers protection in experimental PCM. DCs link innate and adaptive immunity by recognizing invading pathogens and selecting the type of effector T cell to mediate the immune response. Here, we showed that DC-pMAC/PS-scFv induces the activation of CD4+ and CD8+ T cells. Moreover, our results demonstrated that BALB/c mice infected with P. brasiliensis and treated with DC-pMAC/PS-scFv showed the induction of specific IgG production against gp43 and IFN-γ, IL-12 and IL-4 cytokines. Analysis of regional lymph nodes revealed increases in the expression of clec7a, myd88, tlr2, gata3 and tbx21, which are involved in the immune response. Taken together, our results indicate that the scFv modulates the humoral and cellular immune responses and presents epitopes to CD4+ and CD8+ T cells

Incorporation of non-nucleoside triphosphate analogues opposite to an abasic site by human DNA polymerases β and λ

A novel class of non-nucleoside triphosphate analogues, bearing hydrophobic groups sterically similar to nucleosides linked to the α-phosphate but lacking the chemical functional groups of nucleic acids, were tested against six different DNA polymerases (polymerases). Human polymerases α, β and λ, and Saccharomyces cerevisiae polymerase IV, were inhibited with different potencies by these analogues. On the contrary, Escherichia coli polymerase I and HIV-1 reverse transcriptase were not. Polymerase β incorporated these derivatives in a strictly Mn++-dependent manner. On the other hand, polymerase λ could incorporate some alkyltriphosphate derivatives with both Mg++ and Mn++, but only opposite to an abasic site on the template strand. The active site mutant polymerase λ Y505A showed an increased ability to incorporate the analogues. These results show for the first time that neither the base nor the sugar moieties of nucleotides are required for incorporation by family X DNA polymerase

Expanding the repertoire of DNA polymerase substrates: template-instructed incorporation of non-nucleoside triphosphate analogues by DNA polymerases β and λ

We have recently shown that neither the base nor the sugar moieties of a nucleotide is an essential feature for its incorporation by DNA polymerases (pols) λ and β. Here we present the identification of novel non-nucleoside triphosphate (NNTP) derivatives belonging to three classes: (i) non-substrate-specific inhibitors of DNA pol λ; (ii) substrate inhibitors which could preferentially be incorporated by either DNA pol λ wild type or its Y505A mutant and (iii) the substrate inhibitor N-(Biphenylcarbonyl)-4-oxobutyl triphosphate which could be incorporated exclusively by DNA pol β in a Mg2+-dependent manner, and preferentially pairs with A on the template. This compound represents the first example of a substrate lacking both nucleobase and ribose residue, showing distinct base-pairing properties with normal bases. Therefore, this NNTP analog can be considered as the prototype of an entirely novel class of DNA pol substrate

Molecular basis for the enantioselectivity of HIV-1 reverse transcriptase: Role of the 3′-hydroxyl group of the L-(β)-ribose in chiral discrimination between D- and L-enantiomers of deoxy- and dideoxy-nucleoside triphosphate analogs

In order to identify the basis for the relaxed enantioselectivity of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and to evaluate possible cross-resistance patterns between L-nucleoside-, D-nucleoside- and non-nucleoside RT inhibitors, to be utilised in anti-HIV-1 combination therapy, we applied an in vitro approach based on the utilisation of six recombinant HIV-1 RT mutants containing single amino acid substitutions known to confer Nevirapine resistance in treated patients. The mutants were compared on different RNA/DNA and DNA/DNA substrates to the wild type (wt) enzyme for their sensitivity towards inhibition by the D- and L-enantiomers of 2′-deoxy- and 2′,3′-dideoxynucleoside triphosphate analogs. The results showed that the 3′-hydroxyl group of the L-(β)-2′-deoxyribose moiety caused an unfavourable steric hindrance with critic residues in the HIV-1 RT active site and this steric barrier was increased by the Y181I mutation. Elimination of the 3′-hydroxyl group removed this hindrance and significantly improved binding to the HIV-1 RT wt and to the mutants. These results demonstrate the critical role of both the tyrosine 181 of RT and the 3′-position of the sugar ring, in chiral discrimination between D- and L-nucleoside triphosphates. Moreover, they provide an important rationale for the combination of D- and L-(β)-dideoxynucleoside analogs with non-nucleoside RT inhibitors in anti-HIV chemotherapy, since non-nucleoside inhibitors resistance mutations did not confer crossresistance to dideoxynucleoside analog

Innovative Approaches to System Architecture in Modern Engineering Applications

This paper investigates innovative approaches to system architecture in modern engineering applications, focusing on the evaluation and implementation of various architectural frameworks. Through qualitative analysis, including case studies and comparative analysis, the research highlights the effectiveness of hybrid architectures, which combine elements of traditional models such as microservices and layered frameworks. The study also examines the role of emerging technologies, including artificial intelligence (AI) and the Internet of Things (IoT), in enhancing system performance, scalability, and flexibility. Key findings reveal that hybrid architectures and AI integrations significantly improve system scalability by up to 30%, while IoT and edge computing enhance real-time data processing. The implications of these findings suggest a paradigm shift in architectural strategies for future engineering applications, emphasizing adaptability and the integration of emerging technologies