Una licitación combinatorial aplicada a la provisión de Internet a las escuelas de Buenos Aires

Una de las clases de licitación más estudiadas en la literatura es la multi-unidades, aquella en la que se licitan varios ítems idénticos. En este trabajo, definimos una nueva subclase de las licitaciones multi-unidades, que llamamos multi-unidades logística. La característica central de una licitación multi-unidades logística es que existen fuertes asimetrías de costos entre los oferentes a causa de consideraciones logísticas. Ciertas unidades pueden ser atractivas para una firma y no para otra, de acuerdo a dichas consideraciones, y lo contrario puede suceder en otras unidades a licitar. Este tipo de licitación aparece en la provisión de Internet en las escuelas de Buenos Aires, la capital de Argentina. En 2008, la ciudad de Buenos Aires debía licitar la conexión de Internet para sus 709 escuelas públicas. En este trabajo mostramos cómo fue diseñada la licitación para realizar la adjudicación minimizando el gasto de la ciudad destinado a este fin. En nuestro diseño, cada firma debe dar un precio general por el servicio mensual a ser brindado en cada escuela, descuentos por volumen en bandas prefijadas de antemano y el listado de escuelas en las que le interesa brindar el servicio. La licitación multi-unidades logística resultante se puede interpretar como una licitación combinatorial. Se implementó un modelo de programación lineal entera para obtener el conjunto de ofertas más conveniente para el estado.De acuerdo con los análisis presentados en este trabajo, se puede estimar que la ciudad de Buenos Aires obtuvo ahorros cercanos al 20% por implementar este nuevo modelo de licitación en lugar del formato de licitación originalmente propuesto.Fil: Bonomo, Flavia. Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Investigaciones Matematicas;Fil: Catalán, J.. Universidad de Chile. Fac. de Cs. Físicas y Matemáticas; Chile;Fil: Duran, Guillermo Alfredo. Universidad de Buenos Aires. Facultad de Cs.exactas y Naturales. Instituto de Calculo; Argentina;Fil: Epstein, R.. Universidad de Chile. Fac. de Cs. Físicas y Matemáticas; Chile;Fil: Jawtuschenko, Alexis Boris. Consejo Nacional de Invest.cientif.y Tecnicas. Oficina de Coordinacion Administrativa Ciudad Universitaria. Instituto de Investigaciones Matematicas;Fil: Marenco, Nelida Silvia. Universidad Nacional de General Sarmiento. Instituto de Ciencias; Argentina

Transient Anomalous Diffusion MRI in Excised Mouse Spinal Cord: Comparison Among Different Diffusion Metrics and Validation With Histology

Neural tissue is a hierarchical multiscale system with intracellular and extracellular diffusion compartments at different length scales. The normal diffusion of bulk water in tissues is not able to detect the specific features of a complex system, providing nonlocal, diffusion measurement averaged on a 10-20 mm length scale. Being able to probe tissues with sub-micrometric diffusion length and quantify new local parameters, transient anomalous diffusion (tAD) would dramatically increase the diagnostic potential of diffusion MRI (DMRI) in detecting collective and sub-micro architectural changes of human tissues due to pathological damage. In DMRI, the use of tAD parameters quantified using specific DMRI acquisition protocols and their interpretation has often aroused skepticism. Although the derived formulas may accurately fit experimental diffusion-weighted data, the relationships between the postulated dynamical feature and the underlying geometrical structure remains elusive, or at most only suggestive. This work aimed to elucidate and validate the image contrast and information that can be obtained using the tAD model in white matter (WM) through a direct comparison between different diffusion metrics and histology. Towards this goal, we compared tAD metrics extracted from pure subdiffusion (a-imaging) and superpseudodiffusion (g-imaging) in excised mouse spinal cord WM, together with T2 and T2  relaxometry, conventional (normal diffusion-based) diffusion tensor imaging (DTI) and q-space imaging (QSI), with morphologic measures obtained by optical microscopy, to determine which structural and topological characteristics of myelinated axons influenced tAD contrast. Axon diameter (AxDiam), the standard deviation of diameters (SDax:diam), axonal density (AxDens) and effective local density (ELD) were extracted from optical images in several WM tracts. Among all the diffusion parameters obtained at 9.4 T, g-metrics confirmed a strong dependence on magnetic in-homogeneities quantified by R2  = 1/T2  and showed the strongest associations with AxDiam and ELD. On the other hand, a-metrics showed strong associations with SDax:diam and was significantly related to AxDens, suggesting its ability to quantify local heterogeneity degree in neural tissue. These results elucidate the biophysical mechanism underpinning tAD parameters and show the clinical potential of tAD-imaging, considering that both physiologic and pathologic neurodegeneration translate into alterations of WM morphometry and topology

Promising Tools in Prostate Cancer Research:Selective Non-Steroidal Cytochrome P450 17A1 Inhibitors

Cytochrome P450 17A1 (CYP17A1) is an important target in the treatment of prostate cancer because it produces androgens required for tumour growth. The FDA has approved only one CYP17A1 inhibitor, abiraterone, which contains a steroidal scaffold similar to the endogenous CYP17A1 substrates. Abiraterone is structurally similar to the substrates of other cytochrome P450 enzymes involved in steroidogenesis, and interference can pose a liability in terms of side effects. Using non-steroidal scaffolds is expected to enable the design of compounds that interact more selectively with CYP17A1. Therefore, we combined a structure-based virtual screening approach with density functional theory (DFT) calculations to suggest non-steroidal compounds selective for CYP17A1. In vitro assays demonstrated that two such compounds selectively inhibited CYP17A1 17α-hydroxylase and 17,20-lyase activities with IC(50) values in the nanomolar range, without affinity for the major drug-metabolizing CYP2D6 and CYP3A4 enzymes and CYP21A2, with the latter result confirmed in human H295R cells

Cytogenetic responses of Allium cepa L. after exposure to contaminated pond waters

Biomarkers may refer to certain changes in living cells induced by environmental contaminants. To assess these, plants act as excellent systems for genetic tests as they are sensitive to pollutants. Therefore, the present study aimed to evaluate a coastal pond (Brazil) used for fishing and recreation, but also affected by several environmental impacts. Three sampling stations were established around the pond to collect water during the rainy and a post-rainy period. The A. cepa test was conducted using seeds exposed to water samples and controls. Slides of root meristems were prepared using the Feulgen method and analyzed to calculate the mitotic index, the rate of chromosomal aberrations and the frequency of micronuclei. Statistical analysis was performed using ANOVA followed by the Tukey or Bonferroni test (p <0.05). The results showed significant changes in the mitotic index, chromosomal aberrations and frequency of micronuclei when compared to the negative control. Among the aberrations observed, C-metaphase, chromosomal breaks, nuclear buds and chromosomal losses showed significant values. In addition, it was observed that the rate of chromosomal aberrations during the rainy period was superior to that in the post-rainy period. These results may be associated with the presence of potentially toxic compounds such as aluminum and cadmium, although the pond presents a good water quality index. Therefore, we suggest a combination of more sensitive methods, such as the Allium cepa test, with traditional systems of surveillance and monitoring of aquatic environments.(Respostas citogenéticas de Allium cepa L. após exposição às águas contaminada de uma lagoa). Biomarcadores podem se referir a certas mudanças em células vivas por contaminantes ambientais. Para a avaliação destes, as plantas atuam como ótimos sistemas testes genéticos sensíveis aos poluentes. Portanto, o presente estudo teve como objetivo avaliar uma lagoa utilizada para a pesca e recreação, mas também submetida a vários impactos ambientais. Foram definidas três estações amostrais ao longo da lagoa para a coleta de água durante períodos de chuva e pós-chuva. O teste do A. cepa foi realizado por meio de sementes expostas às amostras de água e controles. Lâminas dos meristemas das raízes foram montadas pelo método de Feulgen e analisadas para calcular o índice mitótico, a frequência de aberrações cromossômicas e a frequência de micronúcleos.  Análise estatística foi realizada utilizando ANOVA seguida de Tukey e teste de Bonferroni (p <0.05). Os resultados demonstraram alterações significativas nos índices mitótico, de aberrações cromossómicas e na frequência de micronúcleos quando comparado ao controle negativo. Entre as aberrações observadas, C-metáfase, quebras cromossômicas, brotos nucleares e perdas cromossômicas apresentaram valores significativos. Além disso, observou-se que a taxa de aberrações cromossómicas durante o período de chuva foi superior ao período pós-chuva. Estes resultados podem estar associados à presença de compostos potencialmente tóxicos, tais como o alumínio e cádmio que foram quantificados em estudo pretérito, embora a lagoa apresente índice de qualidade de água de boa / regular. Portanto, sugerimos a combinação de métodos mais sensíveis, tais como teste de Allium cepa, aos tradicionais métodos de fiscalização e monitoramento de ambientes aquáticos

identifying allosteric networks to fight antibiotics resistance

The rise of multi-drug resistance in bacterial pathogens is one of the grand challenges facing medical science. A major concern is the speed of development of β-lactamase-mediated resistance in Gram-negative species, thus putting at risk the efficacy of the most recently approved antibiotics and inhibitors, including carbapenems and avibactam, respectively. New strategies to overcome resistance are urgently required, which will ultimately be facilitated by a deeper understanding of the mechanisms that regulate the function of β-lactamases such as the Klebsiella Pneumoniae carbapenemases (KPCs). Using enhanced sampling computational methods together with site-directed mutagenesis, we report the identification of two “hydrophobic networks” in the KPC-2 enzyme, the integrity of which has been found to be essential for protein stability and corresponding resistance. Present throughout the structure, these networks are responsible for the structural integrity and allosteric signaling. Disruption of the networks leads to a loss of the KPC-2 mediated resistance phenotype, resulting in restored susceptibility to different classes of β-lactam antibiotics including carbapenems and cephalosporins. The ”hydrophobic networks” were found to be highly conserved among class-A β-lactamases, which implies their suitability for exploitation as a potential target for therapeutic intervention

AN INTEGRATED CALCAREOUS PLANKTON BIOSTRATIGRAPHIC SCHEME AND BIOCHRONOLOGY FOR THE MEDITERRANEAN MIDDLE MIOCENE

The relative position of 30 main bioevents  pertaining to calcareous nannofossils and planktonic foraminifera was identified in the time interval between 13.75 Ma and 10.50 Ma, based on the quantitative study of the those microfossils in three Mediterranean sections spanning the late Langhian – lower Tortonian stratigraphic interval. The events were correlated  to the astronomic target curve using a cyclostratigraphic approach, resulting in a very detailed biostratigraphic and biochronologic subdivision of the interval. The zonal scheme proposed by Fornaciari et al. (1996) was adopted for the calcareous nannofossils, but three subzones were identified in the MMN7 Zone. For the planktonic foraminifera reference is made to the zonal scheme recently proposed by Foresi et al. (1998), slightly modified in order to increase its biostratigraphic resolution. The age of all the zonal boundaries is reported.&nbsp

HIGH RESOLUTION CALCAREOUS PLANKTON BIOSTRATIGRAPHY OF THE SERRAVALLIAN SUCCESSION OF THE TREMITI ISLANDS (ADRIATIC SEA, ITALY)

The planktonic foraminifer and calcareous nannofossil content of two Middle Miocene sections of the Tremiti Islands (Southern Adriatic Sea) have been studied. The two sections are composed of marly limestones rich in calcareous plankton which show cyclic alternations of indurated (higher carbonate content) whitish and less indurated grey or reddish beds. The two sections represent a succession with a total thickness of 38 m. Samples have been collected at a mean spacing of 10-15 cm; qualitative analyses were performed on one sample per meter but quantitative analyses were made for each sample. The abundance fluctuations of several marker species proved to be a very useful tool to correlate the two sections. The astronomical calibration of the sedimentary cycles provided absolute ages for all the recognised calcareous plankton bioevents.&nbsp