Part surface roughness on laser sintering and milling of maraging steel 300

International audienceThe additive manufacturing of metal parts provides new opportunities to freely design of molds with conformal cooling channels, which enhances the productivity of injected plastic parts. In contrast to this manufacturing process, the surface quality of laser sintering parts is limiting the application of such technology on mold manufacturing. This work intends to investigate the surface roughness of maraging steel 300 samples produced by direct metal laser sintering (DMLS) and post-processed with end milling. Based on a set of experiments, combining different laser sintering build directions and milling process the measurement of the resulting surface roughness expresses how these process parameters impact on the final surface quality

ABCG2, a novel antigen to sort luminal progenitors of BRCA1- breast cancer cells.

International audienceINTRODUCTION: Tumor-initiating cells (TICs), aka "cancer stem cells", are believed to fuel tumors and to sustain therapy resistance and systemic metastasis. Breast cancer is the first human carcinoma in which a subpopulation of cells displaying a specific CD44+/CD24-/low/ESA+ antigenic phenotype was found to have TIC properties. However, CD44+/CD24-/low/ESA+ is not a universal marker phenotype of TICs in all breast cancer subtypes. The aim of this study was to identify novel antigens with which to isolate the TIC population of the basal-A/basal-like breast cancer cell lines. METHODS: We used polychromatic flow-cytometry to characterize the cell surface of several breast cancer cell lines that may represent different tumor molecular subtypes. We next used fluorescence-activated cell sorting to isolate the cell subpopulations of interest from the cell lines. Finally, we explored the stem-like and tumorigenic properties of the sorted cell subpopulations using complementary in vitro and in vivo approaches: mammosphere formation assays, soft-agar colony assays, and tumorigenic assays in NOD/SCID mice. RESULTS: The CD44+/CD24+ subpopulation of the BRCA1-mutated basal-A/basal-like cell line HCC1937 is enriched in several stemness markers, including the ABCG2 transporter (i.e., the CD338 antigen). Consistently, CD338-expressing cells were also enriched in CD24 expression, suggesting that coexpression of these two antigenic markers may segregate TICs in this cell line. In support of ABCG2 expression in TICs, culturing of HCC1937 cells in ultra-low adherent conditions to enrich them in precursor/stem-cells resulted in an increase in CD338-expressing cells. Furthermore, CD338-expressing cells, unlike their CD338-negative counterparts, displayed stemness and transformation potential, as assessed in mammosphere and colony formation assays. Lastly, CD338-expressing cells cultured in ultra-low adherent conditions maintained the expression of CD326/EpCAM and CD49f/α6-integrin, which is a combination of antigens previously assigned to luminal progenitors. CONCLUSION: Collectively, our data suggest that CD338 expression is specific to the tumor-initiating luminal progenitor subpopulation of BRCA1-mutated cells and is a novel antigen with which to sort this subpopulation

Therapeutic Blockade of LIGHT Interaction With Herpesvirus Entry Mediator and Lymphotoxin β Receptor Attenuates In Vivo Cytotoxic Allogeneic Responses.

BACKGROUND: Tumor necrosis factor/tumor necrosis factor receptor superfamily members conform a group of molecular interaction pathways of essential relevance during the process of T-cell activation and differentiation toward effector cells and particularly for the maintenance phase of the immune response. Specific blockade of these interacting pathways, such as CD40-CD40L, contributes to modulate the deleterious outcome of allogeneic immune responses. We postulated that antagonizing the interaction of LIGHT expression on activated T cells with its receptors, herpesvirus entry mediator and lymphotoxin β receptor, may decrease T cell-mediated allogeneic responses. METHODS: A flow cytometry competition assay was designed to identify anti-LIGHT monoclonal antibodies capable to prevent the interaction of mouse LIGHT with its receptors expressed on transfected cells. An antibody with the desired specificity was evaluated in a short-term in vivo allogeneic cytotoxic assay and tested for its ability to detect endogenous mouse LIGHT. RESULTS: We provide evidence for the first time that in mice, as previously described in humans, LIGHT protein is rapidly and transiently expressed after T-cell activation, and this expression was stronger on CD8 T cells than on CD4 T cells. Two anti-LIGHT antibodies prevented interactions of mouse LIGHT with its two known receptors, herpesvirus entry mediator and lymphotoxin β receptor. In vivo administration of anti-LIGHT antibody (clone 10F12) ameliorated host antidonor short-term cytotoxic response in wild type B6 mice, although to a lesser extent than that observed in LIGHT-deficient mice. CONCLUSION: The therapeutic targeting of LIGHT may contribute to achieve a better control of cytotoxic responses refractory to current immunosuppressive drugs in transplantation

Molecular mechanisms underlying resveratrol effect on renal osmoprotection: modulation of COX-2 expression

Resveratrol (RSV) is a polyphenol naturally present in several plants. Nowadays it is sold as an over-the-counter dietarysupplement due to its antioxidant, anti-inflammatory and antitumoral effects. Paradoxically, it has been documented that RSVmay also present pro-oxidizing and pro-proliferative effects. In fact, some studies suggest that RSV treatment can result inopposite effects depending on the cell type, its concentration, or the treatment time. Particularly in renal tissue, animal injurymodels described RSV beneficial effects, while studies with chronic intake of RSV observed nephrotoxicity. Hence, RSVeffects on renal tissue are still controversial. Due to the urinary concentrating mechanism, renal medullary interstitium presentsan elevated osmolality that can abruptly change depending on the hydric state of the body, reaching values up to 800-1200mOsm/kg H2O. To survive in this environment, renal cells activate protective pathways. We have demonstrated that renalepithelial cell line MDCK undergoes an adaptive process during the first 24h of hyperosmolarity, in which the transcription ofthe osmoprotective gene cyclooxygenase 2 (COX-2) is activated, among others. After 48h these cells are already adapted andbegin to differentiate, acquiring a polarized epithelium morphology. In this work we evaluate RSV effect on adaption anddifferentiation mechanisms, focusing particularly on COX-2 role. To do this, MDCK cells were pretreated with differentconcentrations of RSV (1, 5, 10, 25 µM) and cultured in hyperosmolar medium (~512 mOsm/kg H2O) for 24 and 48h. Cellswere harvested to obtain cell number and viability. Cell cycle, immunofluorescence (IF), western blot and RT-PCR analysiswere performed. We found that RSV significantly decreased cell number in a concentration-dependent manner at 24 and 48h.Cell cycle analysis revealed that RSV increased S-phase and Sub-G0 cell population. In addition, treated cells did not reachtypical epithelium morphology. COX-2 mRNA and protein levels were surprisingly upregulated by RSV at 24 and 48h, andIF revealed an accumulation of the protein in cytoplasmic granules. To investigate the pathways leading to this upregulation,we indirectly evaluated TonEBP, NF-κB and ERK1/2 pathways, which are activated by hyperosmolarity; and SIRT1implication, a target of RSV. TonEBP target genes mRNA did not show any significant change under RSV treatment, whileNF-κB target gene mRNA presented an increase similar to that of COX-2 mRNA. Moreover, NF-κB IF revealed an increasein its nuclear localization. Regarding ERK1/2, treatment with ERK1/2 selective inhibitor (U0126) completely blocked COX2 protein expression. These results suggest that in renal cells RSV pretreatment decreased cell number and impeded typicalcell morphology acquisition; but it increased COX-2 expression, possibly through NF-κB and ERK1/2 activation.Fil: Erjavec, Luciana Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Biología Celular y Molecular; ArgentinaFil: Parra, Leandro Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Biología Celular y Molecular; ArgentinaFil: Morel Gómez, Emanuel Dario. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Biología Celular y Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Lampropulos, T.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Biología Celular y Molecular; ArgentinaFil: Casali, Cecilia Irene. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Biología Celular y Molecular; ArgentinaFil: Fernandez, Maria del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Biología Celular y Molecular; ArgentinaLVII Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research and XVI Annual Meeting of the Argentinean Society for General MicrobiologyVirtualArgentinaSociedad Argentina de Investigación Bioquímica y Biología MolecularAsociación Civil de Microbiología Genera

XBP-1 regulation of arachidonic acid and glicerolipids metabolism in renal epithelial cells under osmotic stress

Hyperosmolarity is a key controversial signal for renal cells. Under physiological conditions, it induces renal celldifferentiation and maturation of urine concentrating system. However, abrupt changes in environmental osmolarity may also induce cell stress that can lead to death. To adapt and survive in such adverse conditions, renal cells implement differentosmoprotective mechanisms that includes both the upregulation of cyclooxygenase-2 (COX-2) expression and prostaglandins(PGs) synthesis from arachidonic acid (AA), and a coordinated increase in phospholipids (PL) and triacylglycerides (TAG)biosynthesis. We previously shown that hyperosmolarity induces ER stress and activates the unfolded protein response (UPR)in Madyn Darby Canine Kidney Cells (MDCK) through IRE1α-XBP1s pathway, and that XBP1s modulates lipid synthesisregulating lipogenic enzymes expression. In the present work we evaluated how XBP1s modulates phospholipase A2(PLA2)/COX-2/PGs pathway and its relationship with lipid synthesis induction under osmotic stress. MDCK cells weresubjected to hyperosmolarity (298-512 mOsm/kg H2O) for different periods of time (0, 12, 24 and 48 h) and treated withdifferent PLA2 (cPLA2, iPLA2 and sPLA2) and IRE1α inhibitors. RT-PCR studies showed that hyperosmolarity increasedcPLA2 expression at 24 and 48 h but did not upregulate iPLA2 expression. Inhibition of cPLA2 but not iPLA2 nor sPLA2prevented hyperosmolarity-induced lipid synthesis and lipid droplets accumulation. Furthermore, IRE1α RNase activityinhibition was accompanied by a decrease in cPLA2 and COX-2 but not in iPLA2 expression evaluated by RT-PCR. Instead,western blot analysis showed a significant increase in COX-2 protein levels when xbp1 (u) splicing was blocked by IRE1αinhibitor. Our findings suggest that the UPR modulates glycerolipids metabolism under osmotic stress by regulatingcPLA2/COX-2/PGs axis.Fil: Parra, Leandro Gastón. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Biología Celular y Molecular; ArgentinaFil: Casali, Cecilia Irene. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Biología Celular y Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Erjavec, Luciana Cecilia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Biología Celular y Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Morel Gómez, Emanuel Dario. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Biología Celular y Molecular; ArgentinaFil: Setton, Clara Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Fernandez, Maria del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Biología Celular y Molecular; ArgentinaLVII Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research and XVI Annual Meeting of the Argentinean Society for General MicrobiologyVirtualArgentinaSociedad Argentina de Investigación Bioquímica y Biología MolecularAsociación Civil de Microbiología Genera

Probing RS scenarios of flavour at LHC via leptonic channels

We study a purely leptonic signature of the Randall-Sundrum scenario with Standard Model fields in the bulk at LHC: the contribution from the exchange of Kaluza-Klein (KK) excitations of gauge bosons to the clear Drell-Yan reaction. We show that this contribution is detectable (even with the low luminosities of the LHC initial regime) for KK masses around the TeV scale and for sufficiently large lepton couplings to KK gauge bosons. Such large couplings can be compatible with ElectroWeak precision data on the Zff coupling in the framework of the custodial O(3) symmetry recently proposed, for specific configurations of lepton localizations (along the extra dimension). These configurations can simultaneously reproduce the correct lepton masses, while generating acceptably small Flavour Changing Neutral Current (FCNC) effects. This LHC phenomenological analysis is realistic in the sense that it is based on fermion localizations which reproduce all the quark/lepton masses plus mixing angles and respect FCNC constraints in both the hadron and lepton sectors.Comment: 15 pages, 6 Figures, Latex fil

Epilepsia y Variables. Departamento de Neurología, Hospital de Clínicas del año 2016 al 2018

En el mundo hay unos 50 millones de personas con epilepsia. En países de ingresos bajos y medianos sugieren una proporción mucho mayor, entre 7 y 14 por 1000 personas. Las poblaciones pobres y las que viven en situaciones de vulnerabilidad, en particular en los países de ingresos bajos y medianos, soportan una carga desproporcionadamente alta; lo que supone una amenaza para la salud pública y el desarrollo económico y social. 1 Por el que el propósito de estudio fue conocer la característica epidemiológica de esta población. Se analizaron 281 fichas de pacientes con epilepsia, en un periodo de dos años, comprendidos entre 16 y 91 años. Resultados: 51.9% corresponde al sexo masculino y el 48.1% al femenino. El 63,34% presentó crisis focal. El 59,2 de los casos de epilepsia, se acompañan de trastornos psiquiátricos. Solo el 5% ha afirmado haber padecido algún efecto adverso a la medicación. Se desconoce la causa de epilepsia en un 58,58%. Dentro las causas de epilepsia secundaria; el Accidente Cerebro Vascular (ACV) se encuentra en un 22.4%. Llamativamente el 30.2% de los pacientes no cuenta con estudio de imagen de encéfalo. El 41.93% presentó crisis con el tratamiento, pero el 50% de los pacientes realiza tratamiento de forma irregular. El 53,73% presentaba tratamiento con un único fármaco anticonvulsivante, siendo la Carbamacepina la más utilizada. Conclusión: La Epilepsia tiene una alta prevalencia dentro de los desórdenes neurológicos. Afecta al sexo masculino de forma más importante, siendo la crisis focal la más frecuente. La baja asociación con trastornos psiquiátricos encontrados; nos obliga a hacer hincapié a ser más exhaustivos en la búsqueda de estos. En un alto porcentaje se desconoce la causa. Las causas más frecuentes de epilepsia secundaria fueron ACV y Traumatismo de Cráneo. Un porcentaje considerable continúan con crisis por incumpliendo del tratamiento. La Carbamacepina, el Ácido Valproico y la Fenitoína son los más utilizados, debidos a los costos y accesibilidad de los mismos, se deben establecer esfuerzos para proponer estrategias de intervención, para facilitar el seguimiento de los pacientes y que estos se puedan también beneficiar de nuevos fármacos anticonvulsivantes

A new benchmark T8-9 brown dwarf and a couple of new mid-T dwarfs from the UKIDSS DR5+ LAS

Benchmark brown dwarfs are those objects for which fiducial constraints are available, including effective temperature, parallax, age, metallicity. We searched for new cool brown dwarfs in 186 sq.deg. of the new area covered by the data release DR5+ of the UKIDSS Large Area Survey. Follow-up optical and near-infrared broad-band photometry, and methane imaging of four promising candidates, revealed three objects with distinct methane absorption, typical of mid- to late-T dwarfs, and one possibly T4 dwarf. The latest-type object, classified as T8-9, shares its large proper motion with Ross 458 (BD+13o2618), an active M0.5 binary which is 102" away, forming a hierarchical low-mass star+brown dwarf system. Ross 458C has an absolute J-band magnitude of 16.4, and seems overluminous, particularly in the K band, compared to similar field brown dwarfs. We estimate the age of the system to be less than 1 Gyr, and its mass to be as low as 14 Jupiter masses for the age of 1 Gyr. At 11.4 pc, this new late T benchmark dwarf is a promising target to constrain the evolutionary and atmospheric models of very low-mass brown dwarfs. We present proper motion measurements for our targets and for 13 known brown dwarfs. Two brown dwarfs have velocities typical of the thick disk and may be old brown dwarfs.Comment: 15 pages, 10 figures and 6 tables. Accepted by MNRAS. Uses mn2e.cls and aas_macr

VLTI status update: a decade of operations and beyond

We present the latest update of the European Southern Observatory's Very Large Telescope interferometer (VLTI). The operations of VLTI have greatly improved in the past years: reduction of the execution time; better offering of telescopes configurations; improvements on AMBER limiting magnitudes; study of polarization effects and control for single mode fibres; fringe tracking real time data, etc. We present some of these improvements and also quantify the operational improvements using a performance metric. We take the opportunity of the first decade of operations to reflect on the VLTI community which is analyzed quantitatively and qualitatively. Finally, we present briefly the preparatory work for the arrival of the second generation instruments GRAVITY and MATISSE.Comment: 10 pages, 7 figures, Proceedings of the SPIE, 9146-1