A Lacustrine Paleoenvironment Recorded at Vera RubinRidge, Gale Crater: Overview of the Sedimentology and Stratigraphy Observed by the Mars ScienceLaboratory Curiosity Rover

For ~500 Martian solar days (sols), the Mars Science Laboratory team explored Vera Rubin ridge (VRR), a topographic feature on the northwest slope of Aeolis Mons. Here we review the sedimentary facies and stratigraphy observed during sols 1,800–2,300, covering more than 100 m of stratigraphic thickness. Curiosity's traverse includes two transects across the ridge, which enables investigation of lateral variability over a distance of ~300 m. Three informally named stratigraphic members of the Murray formation are described: Blunts Point, Pettegrove Point, and Jura, with the latter two exposed on VRR. The Blunts Point member, exposed just below the ridge, is characterized by a recessive, fine‐grained facies that exhibits extensive planar lamination and is crosscut by abundant curvi‐planar veins. The Pettegrove Point member is more resistant, fine‐grained, thinly planar laminated, and contains a higher abundance of diagenetic concretions. Conformable above the Pettegrove Point member is the Jura member, which is also fine‐grained and parallel stratified, but is marked by a distinct step in topography, which coincides with localized meter‐scale inclined strata, a thinly and thickly laminated facies, and occasional crystal molds. All members record low‐energy lacustrine deposition, consistent with prior observations of the Murray formation. Uncommon outcrops of low‐angle stratification suggest possible subaqueous currents, and steeply inclined beds may be the result of slumping. Collectively, the rocks exposed at VRR provide additional evidence for a long‐lived lacustrine environment (in excess of 106 years via comparison to terrestrial records of sedimentation), which extends our understanding of the duration of habitable conditions in Gale crater

Lixiviação de metolachlor e diuron em coluna de latossolo amarelo, em condições de laboratório.

Coinfection with HIV adversely impacts every stage of hepatitis C (HCV) infection. Liver damage in HCV infection results from host antiviral responses rather than direct viral pathogenesis. Despite depressed cellular immunity, coinfected patients show accelerated hepatic fibrosis compared with HCV monoinfected patients. This paradox is poorly understood. T-regulatory (Treg) cells (CD4+ and FOXP3+) are hypothesized to limit hepatic damage in HCV. Our hypothesis was that reduced frequency of hepatic Treg in HIV/HCV coinfection compared with HCV monoinfection may explain poorer outcomes. We quantified FOXP3+, CD4+, CD8+ and CD20+ cells in liver biopsies of 35 male subjects matched by age and ISHAK fibrosis score, 12 HIV monoinfected, 11 HCV monoinfected and 12 HIV/HCV coinfected. Cell counts were performed using indirect immunohistochemical staining and light microscopy. HIV/HCV coinfected subjects had fewer hepatic FOXP3+ (P = 0.031) and CD4+ cells (P = 0.001) than HCV monoinfected subjects. Coinfected subjects had more hepatic CD8+ cells compared with HCV monoinfected (P = 0.023), and a lower ratio of FOXP3+ to CD8+ cells (0.08 vs 0.27, P < 0.001). Multivariate analysis showed number of CD4+ cells controlled for differences in number of FOXP3+ cells. Fewer hepatic FOXP3+ and CD4+ cells in HIV/HCV coinfection compared with HCV monoinfection suggests lower Treg activity, driven by an overall loss of CD4+ cells. Higher number of CD8+ cells in HIV/HCV coinfection suggests higher cytotoxic activity. This may explain poorer outcomes in HIV/HCV coinfected patients and suggests a potential mechanism by which highly active antiretroviral therapy may benefit these patients

Future therapeutic targets in rheumatoid arthritis?

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent joint inflammation. Without adequate treatment, patients with RA will develop joint deformity and progressive functional impairment. With the implementation of treat-to-target strategies and availability of biologic therapies, the outcomes for patients with RA have significantly improved. However, the unmet need in the treatment of RA remains high as some patients do not respond sufficiently to the currently available agents, remission is not always achieved and refractory disease is not uncommon. With better understanding of the pathophysiology of RA, new therapeutic approaches are emerging. Apart from more selective Janus kinase inhibition, there is a great interest in the granulocyte macrophage-colony stimulating factor pathway, Bruton's tyrosine kinase pathway, phosphoinositide-3-kinase pathway, neural stimulation and dendritic cell-based therapeutics. In this review, we will discuss the therapeutic potential of these novel approaches

Swimming against the tide: A case study of an integrated social studies department

A recent trend in developed countries&rsquo; school curricula has been the transition from disciplinary to generic forms of knowledge, resulting in an emphasis on interdisciplinary organisation and more active forms of learning. Subject specialists are increasingly expected to demonstrate how their subject interconnects and equips pupils with key life skills. Such a change requires a major cultural shift and has been controversial, particularly in Scotland where Curriculum for Excellence, the latest curriculum reform, has seen this debate re-emerge. A detailed empirical case study of one secondary school Social Studies department that has already negotiated these shifts is presented. The case study provides insights into how school and department structures and cultures conducive to a more integrated approach have been developed. Leadership, increased opportunities for teachers to exercise greater autonomy in their work, sources of impetus and support for innovation, and the co-construction of meaning through dialogue are important themes in this process. This case study connects with current policy and provides an insight into strategies that other schools might employ when seeking to embed integrative practices. The department is identified as a significant locus for innovation and one which appears to challenge the norm

Apšvietimas kaip architektūros modernumo simbolis

The paper is designed to reveal the aesthetics of artificial lighting and its influence on the architecture of the 20th century. The main topics discussed are electric lighting, which appeard in our history at the end of the 19th century, and the technical development of lighting till the middle of the 20th century. Connections of artificial lighting with visual arts, its influence on advertisement, building architecture and the whole city are analysed. An idea is proposed that although lighting by nature was purely functional, very soon it acquired symbolic ambitions to represent architecture. In modern times architects understood that lighting was both a technological development and a symbol of a new era, when there appeared an independent field of creation - lighting architecture. Santrauka Straipsnyje nagrinėjama dirbtinio apšvietimo estetika ir jos įtaka XX a. architektūrai. Išryškinta XIX a. pabaigoje atsiradusio elektrinio apšvietimo svarba ir atskleista apšvietimo techninė raida iki XX a. vidurio. Nagrinėjamos dirbtinio apšvietimo sąsajos su vizualiaisiais menais, apšvietimo įtaka reklamai, pastatų architektūrai bei visam miestui. Straipsnyje keliama idėja, kad nors apšvietimo prigimtis pradžioje buvo grynai funkcionali, ji greitai įgavo simbolinių ambicijų – reprezentuoti architektūrą. Architektai į apšvietimą žvelgė ne tik kaip į technologinę pažangą, tai buvo naują erą ženklinantis simbolis, erą, kurioje atsiranda didelės įtakos visoms kūrybinėms idėjoms turinti nauja savarankiška kūrybos sritis – šviesos architektūra. First Published Online: 22 May 2013 Reikšminiai žodžiai: meninis, dirbtinis, elektrinis apšvietimas, stiklo, šviesos architektūra, modernumas

Pancreatic (pro)enzymes treatment suppresses BXPC-3 pancreatic Cancer Stem Cell subpopulation and impairs tumour engrafting

Cancer stem cells (CSCs) subpopulation within the tumour is responsible for metastasis and cancer relapse. Here we investigate in vitro and in vivo the effects of a pancreatic (pro)enzyme mixture composed of Chymotrypsinogen and Trypsinogen (PRP) on CSCs derived from a human pancreatic cell line, BxPC3. Exposure of pancreatic CSCs spheres to PRP resulted in a significant decrease of ALDEFLUOR and specific pancreatic CSC markers (CD 326, CD 44 and CxCR4) signal tested by flow cytometry, further CSCs markers expression was also analyzed by western and immunofluorescence assays. PRP also inhibits primary and secondary sphere formation. Three RT2 Profiler PCR Arrays were used to study gene expression regulation after PRP treatment and resulted in, (i) epithelialmesenchymal transition (EMT) inhibition; (ii) CSCs related genes suppression; (iii) enhanced expression of tumour suppressor genes; (iv) downregulation of migration and metastasis genes and (v) regulation of MAP Kinase Signalling Pathway. Finally, in vivo anti-tumor xenograft studies demonstrated high anti-tumour efficacy of PRP against tumours induced by BxPC3 human pancreatic CSCs. PRP impaired engrafting of pancreatic CSC’s tumours in nude mice and displayed an antigrowth effect toward initiated xenografts. We concluded that (pro)enzymes treatment is a valuable strategy to suppress the CSC population in solid pancreatic tumours

Neutralising antibodies after COVID-19 vaccination in UK haemodialysis patients

Vaccination against COVID-19 induces highly protective immune responses in most people. As some countries switch from suppression to acceptance of transmission of SARS-CoV-2 within a largely vaccinated adult population, vulnerable patient groups that have not mounted adequate immune responses to vaccination might experience significant morbidity and mortality. There is an urgent need to identify such patient groups and to optimise medical advice and vaccination strategies for them

Evidence for a Diagenetic Origin of Vera Rubin Ridge, Gale Crater, Mars: Summary and Synthesis of <i>Curiosity's</i> Exploration Campaign

This paper provides an overview of the Curiosity rover's exploration at Vera Rubin ridge and summarizes the science results. Vera Rubin ridge (VRR) is a distinct geomorphic feature on lower Aeolis Mons (informally known as Mt. Sharp) that was identified in orbital data based on its distinct texture, topographic expression, and association with a hematite spectral signature. Curiosity conducted extensive remote sensing observations, acquired data on dozens of contact science targets, and drilled three outcrop samples from the ridge, as well as one outcrop sample immediately below the ridge. Our observations indicate that strata composing VRR were deposited in a predominantly lacustrine setting and are part of the Murray formation. The rocks within the ridge are chemically in family with underlying Murray formation strata. Red hematite is dispersed throughout much of the VRR bedrock, and this is the source of the orbital spectral detection. Gray hematite is also present in isolated, gray‐colored patches concentrated towards the upper elevations of VRR, and these gray patches also contain small, dark Fe‐rich nodules. We propose that VRR formed when diagenetic event(s) preferentially hardened rocks, which were subsequently eroded into a ridge by wind. Diagenesis also led to enhanced crystallization and/or cementation that deepened the ferric‐related spectral absorptions on the ridge, which helped make them readily distinguishable from orbit. Results add to existing evidence of protracted aqueous environments at Gale crater and give new insight into how diagenesis shaped Mars’ rock record

High density of FOXP3-positive T cells infiltrating colorectal cancers with microsatellite instability

High-level microsatellite instability (MSI-H) in colorectal cancer accounts for about 12% of colorectal cancers and is typically associated with a dense infiltration with cytotoxic CD8-positive lymphocytes. The role of regulatory T cells that may interfere with the host's antitumoural immune response in MSI-H colorectal cancers has not been analysed yet. Using an antibody directed against the regulatory T-cell marker transcription factor forkhead box P3 (FOXP3), regulatory T cells were examined in 70 colorectal cancers with known MSI status (MSI-H, n=37; microsatellite stable, n=33). In MSI-H colorectal cancers, we found a significantly higher intraepithelial infiltration with FOXP3-positive cells (median: 8.5 cells per 0.25 mm2 vs 3.1 cells per 0.25 mm2 in microsatellite stable, P<0.001), and a significantly elevated ratio of intraepithelial to stromal infiltration (0.05 vs 0.01 in microsatellite stable, P<0.001). CD8-positive cell counts were related positively to the number of FOXP3-positive cells (Spearman's ρ=0.56 and 0.55, respectively). Our results show that the elevated number of CD8-positive lymphocytes found in MSI-H colorectal cancers is paralleled by an enhanced infiltration with CD8-negative FOXP3-positive cells. These data suggest that FOXP3-positive cells may play a role in the regulation of the immune response directed against MSI-H colorectal cancers at the primary tumour site