Energy dissipation in sheared wet granular assemblies

Energy dissipation in sheared dry and wet granulates is considered in the presence of an externally applied confining pressure. Discrete element simulations reveal that for sufficiently small confining pressures, the energy dissipation is dominated by the effects related to the presence of cohesive forces between the particles. The residual resistance against shear can be quantitatively explained by a combination of two effects arising in a wet granulate: (i) enhanced friction at particle contacts in the presence of attractive capillary forces and (ii) energy dissipation due to the rupture and reformation of liquid bridges. Coulomb friction at grain contacts gives rise to an energy dissipation which grows linearly with increasing confining pressure for both dry and wet granulates. Because of a lower Coulomb friction coefficient in the case of wet grains, as the confining pressure increases the energy dissipation for dry systems is faster than for wet ones

Novel Schizophrenia Risk Gene TCF4 Influences Verbal Learning and Memory Functioning in Schizophrenia Patients

Background: Recently, a role of the transcription factor 4 (TCF4) gene in schizophrenia has been reported in a large genome-wide association study. It has been hypothesized that TCF4 affects normal brain development and TCF4 has been related to different forms of neurodevelopmental disorders. Schizophrenia patients exhibit strong impairments of verbal declarative memory (VDM) functions. Thus, we hypothesized that the disease-associated C allele of the rs9960767 polymorphism of the TCF4 gene led to impaired VDM functioning in schizophrenia patients. Method: The TCF4 variant was genotyped in 401 schizophrenia patients. VDM functioning was measured using the Rey Auditory Verbal Learning Test (RAVLT). Results: Carriers of the C allele were less impaired in recognition compared to those carrying the AA genotype (13.76 vs. 13.06; p = 0.049). Moreover, a trend toward higher scores in patients with the risk allele was found for delayed recall (10.24 vs. 9.41; p = 0.088). The TCF4 genotype did not influence intelligence or RAVLT immediate recall or total verbal learning. Conclusion: VDM function is influenced by the TCF4 gene in schizophrenia patients. However, the elevated risk for schizophrenia is not conferred by TCF4-mediated VDM impairment. Copyright (C) 2011 S. Karger AG, Base

Excavación arqueológica y prospección geomagnética en el sector norte del yacimiento de la Edad del Cobre de Valencina de la Concepción (Sevilla). Campaña de 2017

In 2017, excavations of the Valencina Nord Project began in the northern sector of this large mega-site of ca. 200 ha during the Middle Chalcolithic. In the first campaign, geophysical survey at the NW sector, in direction of the Los Pozos ravine was prioritized, and it is possible to propose that three of the ditch systems identified in 2014 continue westward, the outermost with the ditches 5, 14, 6 and 7, a second system with ditches 11 and 12, and the third, which cuts these last two ditches, with a single ditch 10 of larger dimensions. On the other hand, it was documented that the settlement continues outside the outermost ditch 5 in sector 4 at Cerro del Mármol, and ascends northwards towards Cerro de la Cabeza in sector 5. The excavation focused on an area with multiple pit structures excavated in the ground according to geophysics, while grid 4 included part of the great ditch 10. The structures that have begun to be excavated in grid 3 and 4 show a good correlation with the geophysical data. A novel aspect is the identification of a first fragment of Bell Beaker pottery in the excavation of Cerro de la Cabeza and several Early Bronze Age ceramics that extend the Middle Chalcolithic phase detected in survey during 2014, supported by two radiocarbon dates in our excavations. These data suggest that the settlement, which probably reduced its dimensions during the Late Chalcolithic, had a minimum extension of 27 ha, and presents the largest Bell Beaker pottery set in the Iberian Peninsula, tripling in number of fragments to Zambujal.En 2017 comenzaron las excavaciones del Proyecto Valencina Nord en el sector septentrional de este gran poblado de ca. 200 ha durante el Calcolítico Medio. En la primera campaña se priorizó la prospección geofísica en el sector noroeste, en dirección hacia el barranco de Los Pozos, pudiéndose proponer que tres de los sistemas de fosos identificados en 2014 continúan hacia el oeste, el más exterior con los fosos 5, 14, 6 y 7, un segundo sistema con los fosos 11 y 12 y el tercero, que corta estos dos últimos fosos, con un único foso 10 de mayores dimensiones. Por otra parte, se documentó que el poblado continúa por fuera del foso más exterior 5 en el sector 4 del Cerro del Mármol, y asciende en dirección norte hacia el Cerro de la Cabeza en el sector 5. La excavación se centró en un área con múltiples estructuras excavadas en el suelo según la geofísica, a la vez que el corte 4 incluía parte del gran foso 10. Las estructuras que han comenzado a excavarse en los cortes 3 y 4 muestran una buena correlación con los datos geofísicos. Un aspecto novedoso es la identificación de un primer fragmento de cerámica campaniforme en la excavación del Cerro de la Cabeza y varias cerámicas del Bronce Antiguo que amplían la fase del Calcolítico Medio detectada en la prospección superficial durante 2014 y también apuntan dos dataciones de carbono 14 de nuestras excavaciones. Estos datos sugieren que el poblado, el cual redujo probablemente sus dimensiones durante el Calcolítico Final, tenía entonces una extensión mínima de 27 ha, presentando el conjunto de cerámica campaniforme más grande de la Península Ibérica, triplicando en número de fragmentos a Zambujal

EL POBLADO DE LA EDAD DEL COBRE DE VALENCINA DE LA CONCEPCIÓN (SEVILLA): NUEVOS DATOS SOBRE SUS RECINTOS Y ESPACIOS DOMÉSTICOS. CAMPAÑA DE 2018

The second excavation campaign during 2018 in the northern sector of the site of Valencina de la Concepción has documented four Chalcolithic huts with an oval floor plan, semi-excavated in the subsoil, which should have adobe walls, of which the biggest one, UC 447/448, is 6 m long by 3 m wide. Moreover, the largest identified ditch, No. 10, was drilled, which has a V-section, 11 m wide in grid 4 and a maximum depth of 8,50 m according to the drillings made. The main occupation of the sector corresponds to the Middle Chalcolithic, although there are structures assignable to the Early Chalcolithic and more specific occupation of the early Bell-Beakers, Early- Middle Bronze Age and transition from the Late Bronze Age to the Early Iron Age. Otherwise, the geomagnetic surveys of 2018 have covered 14 ha and made it possible to identify a fifth possible enclosure with two parallel ditches, which at least are surrounding the North, Northwest and West sides of the settlement. La segunda campaña de excavación durante 2018 en el sector norte del yacimiento de Valencina de la Concepción ha documentado cuatro cabañas calcolíticas de planta oval, semi-excavadas en el subsuelo, que debían tener paredes de adobes, de las cuales, la de mayores dimensiones, UC 447/448, tiene 6 m de longitud por 3 m de ancho. Por otra parte, se sondeó el foso más grande identificado, el n.º 10, que presenta sección en V, 11 m de ancho en el corte 4 y 8,50 m de profundidad máxima según las perforaciones realizadas. La ocupación principal del sector corresponde al Calcolítico Medio, aunque hay estructuras asignables al Calcolítico Inicial y ocupación más puntual de inicios del Campaniforme, Bronce Antiguo-Medio y transición del Bronce Final al Hierro Inicial. Por otra parte, las prospecciones geomagnéticas de 2018 han abarcado 14 ha y permitido identificar un quinto posible recinto con dos fosos paralelos, los cuales al menos están rodeando el norte, noroeste y oeste del yacimiento.&nbsp

In situ multiple sulfur isotope analysis by SIMS of pyrite, chalcopyrite, pyrrhotite, and pentlandite to refine magmatic ore genetic models

With growing interest in the application of in situ multiple sulfur isotope analysis to a variety of mineral systems, we report here the development of a suite of sulfur isotope standards for distribution relevant to magmatic, magmatic-hydrothermal, and hydrothermal ore systems. These materials include Sierra pyrite (FeS2), Nifty-b chalcopyrite (CuFeS2), Alexo pyrrhotite (Fe(1 −x)S), and VMSO pentlandite ((Fe,Ni)9S8) that have been chemically characterized by electron microprobe analysis, isotopically characterized for δ33S, δ34S, and δ36S by fluorination gas-source mass spectrometry, and tested for homogeneity at the micro-scale by secondary ion mass spectrometry. Beam-sample interaction as a function of crystallographic orientation is determined to have no effect on δ34S and Δ33S isotopic measurements of pentlandite. These new findings provided the basis for a case study on the genesis of the Long-Victor nickel-sulfide deposit located in the world class Kambalda nickel camp in the southern Kalgoorlie Terrane of Western Australia. Results demonstrate that precise multiple sulfur isotope analyses from magmatic pentlandite, pyrrhotite and chalcopyrite can better constrain genetic models related to ore-forming processes. Data indicate that pentlandite, pyrrhotite and chalcopyrite are in isotopic equilibrium and display similar Δ33S values + 0.2‰.This isotopic equilibrium unequivocally fingerprints the isotopic signature of the magmatic assemblage. The three sulfide phases show slightly variable δ34S values (δ34Schalcopyrite = 2.9 ± 0.3‰, δ34Spentlandite = 3.1 ± 0.2‰, and δ34Spyrrhotite = 3.9 ± 0.5‰), which are indicative of natural fractionation. Careful in situ multiple sulfur isotope analysis of multiple sulfide phases is able to capture the subtle isotopic variability of the magmatic sulfide assemblage, which may help resolve the nature of the ore-forming process. Hence, this SIMS-based approach discriminates the magmatic sulfur isotope signature from that recorded in metamorphic- and alteration-related sulfides, which may not be resolved during bulk rock fluorination analysis. The results indicate that, unlike the giant dunite-hosted komatiite systems that thermo-mechanically assimilated volcanogenic massive sulfides proximal to vents and display negative Δ33S values, the Kambalda ores formed in relatively distal environments assimilating abyssal sulfidic shales

Systems-pharmacology dissection of a drug synergy in imatinib-resistant CML

Occurrence of the BCR-ABL[superscript T315I] gatekeeper mutation is among the most pressing challenges in the therapy of chronic myeloid leukemia (CML). Several BCR-ABL inhibitors have multiple targets and pleiotropic effects that could be exploited for their synergistic potential. Testing combinations of such kinase inhibitors identified a strong synergy between danusertib and bosutinib that exclusively affected CML cells harboring BCR-ABL[superscript T315I]. To elucidate the underlying mechanisms, we applied a systems-level approach comprising phosphoproteomics, transcriptomics and chemical proteomics. Data integration revealed that both compounds targeted Mapk pathways downstream of BCR-ABL, resulting in impaired activity of c-Myc. Using pharmacological validation, we assessed that the relative contributions of danusertib and bosutinib could be mimicked individually by Mapk inhibitors and collectively by downregulation of c-Myc through Brd4 inhibition. Thus, integration of genome- and proteome-wide technologies enabled the elucidation of the mechanism by which a new drug synergy targets the dependency of BCR-ABL[superscript T315I] CML cells on c-Myc through nonobvious off targets

Recent advances in gastrointestinal oncology - updates and insights from the 2009 annual meeting of the American Society of Clinical Oncology

We have reviewed the pivotal presentations related to gastrointestinal malignancies from 2009 annual meeting of the American Society of Clinical Oncology with the theme of "personalizing cancer care". We have discussed the scientific findings and the impact on practice guidelines and ongoing clinical trials. Adding trastuzumab to chemotherapy improved the survival of patients with advanced gastric cancer overexpressing human epidermal growth factor receptor 2. Gemcitabine plus cisplatin has become a new standard for first-line treatment of advanced biliary cancer. Octreotide LAR significantly lengthened median time to tumor progression compared with placebo in patients with metastatic neuroendocrine tumors of the midgut. Addition of oxaliplatin to fluoropyrimidines for preoperative chemoradiotherapy in patients with stage II or III rectal cancer did not improve local tumor response but increased toxicities. Bevacizumab did not provide additional benefit to chemotherapy in adjuvant chemotherapy for stage II or III colon cancer. In patients with resected stage II colon cancer, recurrence score estimated by multigene RT-PCR assay has been shown to provide additional risk stratification. In stage IV colorectal cancer, data have supported the routine use of prophylactic skin treatment in patients receiving antibody against epidermal growth factor receptor, and the use of upfront chemotherapy as initial management in patients with synchronous metastasis without obstruction or bleeding from the primary site