3,717 research outputs found
Discursos históricos de la vida y muerte de Don Antonio de Zuñiga, Comendador de Ribera del Consejo de Guerra de su Magestad y su Capitán General del Reyno de Portugal
Copia digital. Valladolid : Junta de Castilla y León. Consejería de Cultura y Turismo, 2011Colofón con marca tip.Sign.: [calderón]8, A-G8, H7Hojas escritas por ambas cara
Inflation with Non-minimal Gravitational Couplings and Supergravity
We explore in the supergravity context the possibility that a Higgs scalar
may drive inflation via a non-minimal coupling to gravity characterised by a
large dimensionless coupling constant. We find that this scenario is not
compatible with the MSSM, but that adding a singlet field (NMSSM, or a variant
thereof) can very naturally give rise to slow-roll inflation. The inflaton is
necessarily contained in the doublet Higgs sector and occurs in the D-flat
direction of the two Higgs doublets.Comment: 13 pages, 1 figur
Erroma eta Jerusalem
Dialecto : texto en euskera labortanoS. XIX -- Periodo : último euskera modernoEuskalkia : lapurteraXIX. md. -- Aroa : azken euskara modernoaDigitalización. Vitoria-Gasteiz : Fundación Sancho el Sabio, 2008Carton
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Compliant membranes for the development of MEMS dual-backplate capacitive microphone using the SUMMiT V fabrication process.
The objective of this project is the investigation of compliant membranes for the development of a MicroElectrical Mechanical Systems (MEMS) microphone using the Sandia Ultraplanar, Multilevel MEMS Technology (SUMMiT V) fabrication process. The microphone is a dual-backplate capacitive microphone utilizing electrostatic force feedback. The microphone consists of a diaphragm and two porous backplates, one on either side of the diaphragm. This forms a capacitor between the diaphragm and each backplate. As the incident pressure deflects the diaphragm, the value of each capacitor will change, thus resulting in an electrical output. Feedback may be used in this device by applying a voltage between the diaphragm and the backplates to balance the incident pressure keeping the diaphragm stationary. The SUMMiT V fabrication process is unique in that it can meet the fabrication requirements of this project. All five layers of polysilicon are used in the fabrication of this device. The SUMMiT V process has been optimized to provide low-stress mechanical layers that are ideal for the construction of the microphone's diaphragm. The use of chemical mechanical polishing in the SUMMiT V process results in extremely flat structural layers and uniform spacing between the layers, both of which are critical to the successful fabrication of the MEMS microphone. The MEMS capacitive microphone was fabricated at Sandia National Laboratories and post-processed, packaged, and tested at the University of Florida. The microphone demonstrates a flat frequency response, a linear response up to the designed limit, and a sensitivity that is close to the designed value. Future work will focus on characterization of additional devices, extending the frequency response measurements, and investigating the use of other types of interface circuitry
Parasitic Cape honeybee workers, Apis mellifera capensis, evade policing
Relocation of the Cape honeybee, Apis mellifera capensis, by bee-keepers from southern to northern South Africa in 1990 has caused widespread death of managed African honeybee, A. m. scutellata, colonies. Apis mellifera capensis worker bees are able to lay diploid, female eggs without mating by means of automictic thelytoky (meiosis followed by fusion of two meiotic products to restore egg diploidy), whereas workers of other honeybee subspecies are able to lay only haploid, male eggs. The A. m. capensis workers, which are parasitizing and killing A. m. scutellata colonies in northern South Africa, are the asexual offspring of a single, original worker in which the small amount of genetic variation observed is due to crossing over during meiosis (P. Kryger, personal communication). Here we elucidate two principal mechanisms underlying this parasitism. Parasitic A. m. capensis workers activate their ovaries in host colonies that have a queen present (queenright colonies), and they lay eggs that evade being killed by other workers (worker policing)—the normal fate of worker-laid eggs in colonies with a queen. This unique parasitism by workers is an instance in which a society is unable to control the selfish actions of its members
Differences in the Active Endometrial Microbiota across Body Weight and Cancer in Humans and Mice
Obesity is a risk factor for endometrial cancer. The aim of this study was to determine whether actively replicating microbiota in the endometrium differ between obese vs. lean and cancer vs. benign states. We performed 16S rRNA amplicon sequencing on endometrial tissues from lean and obese women with and without endometrial cancer, and lean and obese mice. Results displayed human endometrial microbiota clustered into three community types (R = 0.363, p = 0.001). Lactobacillus was dominant in community type 1 (C1) while community type 2 (C2) had high levels of Proteobacteria and more cancer samples when compared to C1 (p = 0.007) and C3 (p = 0.0002). A significant increase in the prevalence of the C2 community type was observed across body mass index and cancer (χ2 = 14.24, p = 0.0002). The relative abundance of Lactobacillus was lower in cancer samples (p = 0.0043), and an OTU with 100% similarity to Lactobacillus iners was enriched in control samples (p = 0.0029). Mouse endometrial microbiota also clustered into three community types (R = 0.419, p = 0.001) which were not influenced by obesity. In conclusion, obesity and cancer are associated with community type prevalence in the human endometrium, and Lactobacillus abundance is associated with normal uterine histologies in humans and mice
Targeting tumour re-wiring by triple blockade of mTORC1, epidermal growth factor, and oestrogen receptor signalling pathways in endocrine-resistant breast cancer
Background
Endocrine therapies are the mainstay of treatment for oestrogen receptor (ER)-positive (ER+) breast cancer (BC). However, resistance remains problematic largely due to enhanced cross-talk between ER and growth factor pathways, circumventing the need for steroid hormones. Previously, we reported the anti-proliferative effect of everolimus (RAD001-mTORC1 inhibitor) with endocrine therapy in resistance models; however, potential routes of escape from treatment via ERBB2/3 signalling were observed. We hypothesised that combined targeting of three cellular nodes (ER, ERBB, and mTORC1) may provide enhanced long-term clinical utility.
Methods
A panel of ER+ BC cell lines adapted to long-term oestrogen deprivation (LTED) and expressing ESR1wt or ESR1Y537S, modelling acquired resistance to an aromatase-inhibitor (AI), were treated in vitro with a combination of RAD001 and neratinib (pan-ERBB inhibitor) in the presence or absence of oestradiol (E2), tamoxifen (4-OHT), or fulvestrant (ICI182780). End points included proliferation, cell signalling, cell cycle, and effect on ER-mediated transactivation. An in-vivo model of AI resistance was treated with monotherapies and combinations to assess the efficacy in delaying tumour progression. RNA-seq analysis was performed to identify changes in global gene expression as a result of the indicated therapies.
Results
Here, we show RAD001 and neratinib (pan-ERBB inhibitor) caused a concentration-dependent decrease in proliferation, irrespective of the ESR1 mutation status. The combination of either agent with endocrine therapy further reduced proliferation but the maximum effect was observed with a triple combination of RAD001, neratinib, and endocrine therapy. In the absence of oestrogen, RAD001 caused a reduction in ER-mediated transcription in the majority of the cell lines, which associated with a decrease in recruitment of ER to an oestrogen-response element on the TFF1 promoter. Contrastingly, neratinib increased both ER-mediated transactivation and ER recruitment, an effect reduced by the addition of RAD001. In-vivo analysis of an LTED model showed the triple combination of RAD001, neratinib, and fulvestrant was most effective at reducing tumour volume. Gene set enrichment analysis revealed that the addition of neratinib negated the epidermal growth factor (EGF)/EGF receptor feedback loops associated with RAD001.
Conclusions
Our data support the combination of therapies targeting ERBB2/3 and mTORC1 signalling, together with fulvestrant, in patients who relapse on endocrine therapy and retain a functional ER
Expression of Foxp3 in colorectal cancer but not in Treg cells correlates with disease progression in patients with colorectal cancer
Background: Regulatory T cells (Treg) expressing the transcription factor forkhead-box protein P3 (Foxp3) have been identified to counteract anti-tumor immune responses during tumor progression. Besides, Foxp3 presentation by cancer cells itself may also allow them to evade from effector T-cell responses, resulting in a survival benefit of the tumor. For colorectal cancer (CRC) the clinical relevance of Foxp3 has not been evaluated in detail. Therefore the aim of this study was to study its impact in colorectal cancer (CRC).
Methods and Findings: Gene and protein analysis of tumor tissues from patients with CRC was performed to quantify the expression of Foxp3 in tumor infiltrating Treg and colon cancer cells. The results were correlated with clinicopathological parameters and patients overall survival. Serial morphological analysis demonstrated Foxp3 to be expressed in cancer cells. High Foxp3 expression of the cancer cells was associated with poor prognosis compared to patients with low Foxp3 expression. In contrast, low and high Foxp3 level in tumor infiltrating Treg cells demonstrated no significant differences in overall patient survival.
Conclusions: Our findings strongly suggest that Foxp3 expression mediated by cancer cells rather than by Treg cells contribute to disease progression
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