Influence of the powders phase composition and sintering atmosphere on the structure and magnetic properties of Mn-Zn ferrites

The magnetic properties of Mn-Zn ferrites depend strongly on the microstructure, chemical and phase composition. In this paper the effect of synthesis and sintering conditions on the structure, phase composition and properties of Mn-Zn ferrites is investigated. The specimens for the study were obtained by pressureless sintering. The magnetic properties were measured on a B-H analyzer. The structure was investigated by XRD and SEM. Materials with an average grain size of 2.2 μm were obtained by sintering at a temperature of 1265 °C. It was found that an increase in the synthesis temperature from 700 to 1000 °C promotes the growth of the initial magnetic permeability of these materials from 1100 to 1370. The rapid cooling of the powders synthesized at 1000 °C allows maintaining a high content of the spinel phase. In the structure of materials obtained by sintering powders with initially high spinel content at 1300 °C, grains of abnormally large size are formed. This leads to an increase in the initial permeability, magnetic induction at Hm = 1200 A/m, f = 10 kHz and magnetic losses at high frequencies (up to 500 kHz). A material with fine-grained structure was obtained by using air at the heating stage of pressureless sintering. This contributed to the reduction of magnetic losses without a significant decrease in Bm

Different skeletal protein toolkits achieve similar structure and performance in the tropical coral Stylophora pistillata and the temperate Oculina patagonica

Stony corals (order: Scleractinia) differ in growth form and structure. While stony corals have gained the ability to form their aragonite skeleton once in their evolution, the suite of proteins involved in skeletogenesis is different for different coral species. This led to the conclusion that the organic portion of their skeleton can undergo rapid evolutionary changes by independently evolving new biomineralization-related proteins. Here, we used liquid chromatography-tandem mass spectrometry to sequence skeletogenic proteins extracted from the encrusting temperate coral Oculina patagonica. We compare it to the previously published skeletal proteome of the branching subtropical corals Stylophora pistillata as both are regarded as highly resilient to environmental changes. We further characterized the skeletal organic matrix (OM) composition of both taxa and tested their effects on the mineral formation using a series of overgrowth experiments on calcite seeds. We found that each species utilizes a different set of proteins containing different amino acid compositions and achieve a different morphology modification capacity on calcite overgrowth. Our results further support the hypothesis that the different coral taxa utilize a species-specific protein set comprised of independent gene co-option to construct their own unique organic matrix framework. While the protein set differs between species, the specific predicted roles of the whole set appear to underline similar functional roles. They include assisting in forming the extracellular matrix, nucleation of the mineral and cell signaling. Nevertheless, the different composition might be the reason for the varying organization of the mineral growth in the presence of a particular skeletal OM, ultimately forming their distinct morphologies

Strong Coupling of Localized Surface Plasmons to Excitons in Light-Harvesting Complexes

Gold nanostructure arrays exhibit surface plasmon resonances that split after attaching light harvesting complexes 1 and 2 (LH1 and LH2) from purple bacteria. The splitting is attributed to strong coupling between the localized surface plasmon resonances and excitons in the light-harvesting complexes. Wild-type and mutant LH1 and LH2 from Rhodobacter sphaeroides containing different carotenoids yield different splitting energies, demonstrating that the coupling mechanism is sensitive to the electronic states in the light harvesting complexes. Plasmon-exciton coupling models reveal different coupling strengths depending on the molecular organization and the protein coverage, consistent with strong coupling. Strong coupling was also observed for self-assembling polypeptide maquettes that contain only chlorins. However, it is not observed for monolayers of bacteriochlorophyll, indicating that strong plasmon-exciton coupling is sensitive to the specific presentation of the pigment molecules

Tumour kinome re-wiring governs resistance to palbociclib in oestrogen receptor positive breast cancers, highlighting new therapeutic modalities.

Combination of CDK4/6 inhibitors and endocrine therapy improves clinical outcome in advanced oestrogen receptor (ER)-positive breast cancer, however relapse is inevitable. Here, we show in model systems that other than loss of RB1 few gene-copy number (CN) alterations are associated with irreversible-resistance to endocrine therapy and subsequent secondary resistance to palbociclib. Resistance to palbociclib occurred as a result of tumour cell re-wiring leading to increased expression of EGFR, MAPK, CDK4, CDK2, CDK7, CCNE1 and CCNE2. Resistance altered the ER genome wide-binding pattern, leading to decreased expression of 'classical' oestrogen-regulated genes and was accompanied by reduced sensitivity to fulvestrant and tamoxifen. Persistent CDK4 blockade decreased phosphorylation of tuberous sclerosis complex 2 (TSC2) enhancing EGFR signalling, leading to the re-wiring of ER. Kinome-knockdown confirmed dependency on ERBB-signalling and G2/M-checkpoint proteins such as WEE1, together with the cell cycle master regulator, CDK7. Noteworthy, sensitivity to CDK7 inhibition was associated with loss of ER and RB1 CN. Overall, we show that resistance to CDK4/6 inhibitors is dependent on kinase re-wiring and the redeployment of signalling cascades previously associated with endocrine resistance and highlights new therapeutic networks that can be exploited upon relapse after CDK4/6 inhibition

Caracterização fenotípica de suínos crioulos da região Centro-Sul do Paraná, Brasil

This research aimed to phenotypically characterize 55 pigs from traditional communities, called Faxinal With each pig, 24 variables were measured: 8 qualitative morphological, 16 quantitative / zoometric and 5 zoometric indices were determined. According to the frequency tables of the qualitative variables, it was observed that most pigs showed similarities to the morphological patterns observed in the Brazilian breeds Moura, Piau and Canastra. For the data of the zoometric variables and the zoometric indices, descriptive statistical analysis and variance analysis were applied using two different sources of variation: sex and Faxinal. There was a great morphological variability of the studied creole pigs, with the highest values of the variation coefficients observed for croup length and width, live weight and snout length. According to the averages obtained, the pigs were classified as elliptical, mesocephalic, longilinous, concavilinous. Significant differences between Faxinal were observed for croup width, body length, snout and croup, croup height and interorbital distance and cephalic, facial and pelvic indices. Significant differences between sexes were observed for withers height, snout length, shin girth and interorbital distance. There was significant between Faxinal *sex interaction for some zoometric variables, but not for the indexes. For body measurements, the correlations were high and significant, with the thoracic perimeter, abdominal perimeter and body length being the characteristics that best correlated with live weight. Cranial measurements (lengths of snout, ear and head and interorbital distance) were moderate to low.  To infer the population structure, a statistical model was applied based on a bayesian approach according to the Structure Harvest software. It was possible to identify three phenotypic groupings, corroborating the results of qualitative variables. Genetic characterization studies should be carried out in these populations to serve as a basis for defining strategic actions for conservation and sustainable use of these genetic resources.Para caracterizar fenotípicamente a 55 cerdos de las comunidades tradicionales Faxinal, se midieron 24 variables: 8 morfológicas cualitativas, 16 cuantitativas / zoométricas y se determinaron 5 índices zoométricos. En la mayoría de los cerdos mostraron similitudes con los patrones morfológicos observados en las razas brasileñas Moura, Piau y Canastra. Para los datos de las variables zoométricas y los índices zoométricos se aplicó análisis descriptivo y estadístico de varianza. Hubo gran variabilidad morfológica de los cerdos criollos estudiados, observándose los valores más altos de los coeficientes de variación para largo y ancho de rabadilla, peso vivo y largo de hocico. De los promedios obtenidos, los cerdos se clasificaron en elipométricos, mesocefálicos, alargados, concavilinos. Se observaron diferencias significativas entre Faxinal para el ancho de la rabadilla, la longitud del cuerpo, el hocico y la rabadilla, la altura de la rabadilla y la distancia interorbital, y para los índices cefálico, facial y pélvico. Se observaron diferencias significativas entre sexos para la altura a la cruz, la longitud del hocico, el perímetro de la espinilla y la distancia interorbital. Hubo una interacción significativa del sexo Faxinal * para algunas variables zoométricas. Para las medidas corporales, las correlaciones fueron altas y significativas, siendo el perímetro torácico, el perímetro abdominal y la longitud corporal los que mejor se correlacionaron con el peso vivo. Las medidas craneales (longitud del hocico, oreja y cabeza y distancia interorbital) fueron de moderadas a bajas. Para inferir la estructura de la población se aplicó un modelo estadístico basado en un enfoque bayesiano según el software Structure Harvester. Fue posible identificar tres grupos fenotípicos, corroborando los resultados de las variables cualitativas. Se deben realizar estudios de caracterización genética en estas poblaciones que sirvan de base para definir acciones estratégicas para programas de conservación y uso sostenible de estos recursos genéticos.Esta pesquisa teve como objetivo caracterizar fenotipicamente 55 suínos provenientes de comunidades tradicionais, chamadas de Faxinal. Em cada suíno foram mensuradas 24 variáveis: 8 morfológicas qualitativas, 16 quantitativa / zoométrica e determinado 5 índices zoométricos.  De acordo com as tabelas de frequência das variáveis qualitativas, observou-se que a maioria dos suínos apresentaram semelhanças aos padrões morfológicos observados nas raças brasileiras Moura, Piau e Canastra.   Para os dados das variáveis zoométricas e os índices zoométricos foram aplicados a análise estatística descritiva e a de variância. Verificou-se grande variabilidade morfológica dos suínos crioulos estudados, sendo os maiores valores dos coeficientes de variação observados para comprimento e largura da garupa, peso vivo e comprimento de focinho.  Através das médias obtidas os suínos foram classificados como elipométricos, mesocefálicos, longilíneos, concavilíneos. Foram observadas diferenças significativas entre Faxinal para largura de garupa, comprimento do corpo, focinho e garupa, altura da garupa e distância interorbital, e dos índices cefálico, facial e pélvico.   As diferenças significativas entre sexo foram observadas para altura da cernelha, comprimento do focinho, perímetro da canela e distância interorbital. Verificou-se interação significativa de Faxinal*sexo para algumas variáveis zoométricas.  Para as medidas corporais as correlações foram altas e significativas, sendo o perímetro torácico, o perímetro abdominal e o comprimento do corpo as que melhor se correlacionaram com o peso vivo. Já as medidas cranianas (comprimento do focinho, orelha e cabeça e a distância interorbital) foram de moderadas a baixas. Para inferir a estrutura populacional foi aplicado um modelo estatístico baseado em uma abordagem bayesiana de acordo com o software Structure Harvester. Foi possível identificar três agrupamentos fenotípicos, corroborando com os resultados das variáveis qualitativas.  Estudos de caracterização genética deverão ser realizados nestas populações para que sirvam de base na definição de ações estratégicas para programas de conservação e uso sustentável desses recursos genéticos

RANK signaling increases after anti-HER2 therapy contributing to the emergence of resistance in HER2-positive breast cancer

Background: Around 15-20% of primary breast cancers are characterized by HER2 protein overexpression and/or HER2 gene amplification. Despite the successful development of anti-HER2 drugs, intrinsic and acquired resistance represents a major hurdle. This study was performed to analyze the RANK pathway contribution in HER2-positive breast cancer and anti-HER2 therapy resistance. Methods: RANK and RANKL protein expression was assessed in samples from HER2-positive breast cancer patients resistant to anti-HER2 therapy and treatment-naive patients. RANK and RANKL gene expression was analyzed in paired samples from patients treated with neoadjuvant dual HER2-blockade (lapatinib and trastuzumab) from the SOLTI-1114 PAMELA trial. Additionally, HER2-positive breast cancer cell lines were used to modulate RANK expression and analyze in vitro the contribution of RANK signaling to anti-HER2 resistance and downstream signaling. Results: RANK and RANKL proteins are more frequently detected in HER2-positive tumors that have acquired resistance to anti-HER2 therapies than in treatment-naive ones. RANK (but not RANKL) gene expression increased after dual anti-HER2 neoadjuvant therapy in the cohort from the SOLTI-1114 PAMELA trial. Results in HER2-positive breast cancer cell lines recapitulate the clinical observations, with increased RANK expression observed after short-term treatment with the HER2 inhibitor lapatinib or dual anti-HER2 therapy and in lapatinib-resistant cells. After RANKL stimulation, lapatinib-resistant cells show increased NF-κB activation compared to their sensitive counterparts, confirming the enhanced functionality of the RANK pathway in anti-HER2-resistant breast cancer. Overactivation of the RANK signaling pathway enhances ERK and NF-κB signaling and increases lapatinib resistance in different HER2-positive breast cancer cell lines, whereas RANK loss sensitizes lapatinib-resistant cells to the drug. Our results indicate that ErbB signaling is required for RANK/RANKL-driven activation of ERK in several HER2-positive cell lines. In contrast, lapatinib is not able to counteract the NF-κB activation elicited after RANKL treatment in RANK-overexpressing cells. Finally, we show that RANK binds to HER2 in breast cancer cells and that enhanced RANK pathway activation alters HER2 phosphorylation status. Conclusions: Our data support a physical and functional link between RANK and HER2 signaling in breast cancer and demonstrate that increased RANK signaling may contribute to the development of lapatinib resistance through NF-κB activation. Whether HER2-positive breast cancer patients with tumoral RANK expression might benefit from dual HER2 and RANK inhibition therapy remains to be elucidated

Scientific challenges of convective-scale numerical weather prediction

Numerical weather prediction (NWP) models are increasing in resolution and becoming capable of explicitly representing individual convective storms. Is this increase in resolution leading to better forecasts? Unfortunately, we do not have sufficient theoretical understanding about this weather regime to make full use of these NWPs. After extensive efforts over the course of a decade, convective–scale weather forecasts with horizontal grid spacings of 1–5 km are now operational at national weather services around the world, accompanied by ensemble prediction systems (EPSs). However, though already operational, the capacity of forecasts for this scale is still to be fully exploited by overcoming the fundamental difficulty in prediction: the fully three–dimensional and turbulent nature of the atmosphere. The prediction of this scale is totally different from that of the synoptic scale (103 km) with slowly–evolving semi–geostrophic dynamics and relatively long predictability on the order of a few days. Even theoretically, very little is understood about the convective scale compared to our extensive knowledge of the synoptic-scale weather regime as a partial–differential equation system, as well as in terms of the fluid mechanics, predictability, uncertainties, and stochasticity. Furthermore, there is a requirement for a drastic modification of data assimilation methodologies, physics (e.g., microphysics), parameterizations, as well as the numerics for use at the convective scale. We need to focus on more fundamental theoretical issues: the Liouville principle and Bayesian probability for probabilistic forecasts; and more fundamental turbulence research to provide robust numerics for the full variety of turbulent flows. The present essay reviews those basic theoretical challenges as comprehensibly as possible. The breadth of the problems that we face is a challenge in itself: an attempt to reduce these into a single critical agenda should be avoided

A synthetic biological quantum optical system

In strong plasmon–exciton coupling, a surface plasmon mode is coupled to an array of localized emitters to yield new hybrid light–matter states (plexcitons), whose properties may in principle be controlled via modification of the arrangement of emitters. We show that plasmon modes are strongly coupled to synthetic light-harvesting maquette proteins, and that the coupling can be controlled via alteration of the protein structure. For maquettes with a single chlorin binding site, the exciton energy (2.06 ± 0.07 eV) is close to the expected energy of the Qy transition. However, for maquettes containing two chlorin binding sites that are collinear in the field direction, an exciton energy of 2.20 ± 0.01 eV is obtained, intermediate between the energies of the Qx and Qy transitions of the chlorin. This observation is attributed to strong coupling of the LSPR to an H-dimer state not observed under weak coupling