Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 78
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Nature ; 566(7742): 85-88, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30675066

RESUMO

The origin of the supermassive black holes that inhabit the centres of massive galaxies remains unclear1,2. Direct-collapse black holes-remnants of supermassive stars, with masses around 10,000 times that of the Sun-are ideal seed candidates3-6. However, their very existence and their formation environment in the early Universe are still under debate, and their supposed rarity makes modelling their formation difficult7,8. Models have shown that rapid collapse of pre-galactic gas (with a mass infall rate above some critical value) in metal-free haloes is a requirement for the formation of a protostellar core that will then form a supermassive star9,10. Here we report a radiation hydrodynamics simulation of early galaxy formation11,12 that produces metal-free haloes massive enough and with sufficiently high mass infall rates to form supermassive stars. We find that pre-galactic haloes and their associated gas clouds that are exposed to a Lyman-Werner intensity roughly three times the intensity of the background radiation and that undergo at least one period of rapid mass growth early in their evolution are ideal environments for the formation of supermassive stars. The rapid growth induces substantial dynamical heating13,14, amplifying the Lyman-Werner suppression that originates from a group of young galaxies 20 kiloparsecs away. Our results strongly indicate that the dynamics of structure formation, rather than a critical Lyman-Werner flux, is the main driver of the formation of massive black holes in the early Universe. We find that the seeds of massive black holes may be much more common than previously considered in overdense regions of the early Universe, with a co-moving number density up to 10-3 per cubic megaparsec.

2.
Proc Natl Acad Sci U S A ; 119(24): e2109665119, 2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35679347

RESUMO

The information content of crystalline materials becomes astronomical when collective electronic behavior and their fluctuations are taken into account. In the past decade, improvements in source brightness and detector technology at modern X-ray facilities have allowed a dramatically increased fraction of this information to be captured. Now, the primary challenge is to understand and discover scientific principles from big datasets when a comprehensive analysis is beyond human reach. We report the development of an unsupervised machine learning approach, X-ray diffraction (XRD) temperature clustering (X-TEC), that can automatically extract charge density wave order parameters and detect intraunit cell ordering and its fluctuations from a series of high-volume X-ray diffraction measurements taken at multiple temperatures. We benchmark X-TEC with diffraction data on a quasi-skutterudite family of materials, (CaxSr[Formula: see text])3Rh4Sn13, where a quantum critical point is observed as a function of Ca concentration. We apply X-TEC to XRD data on the pyrochlore metal, Cd2Re2O7, to investigate its two much-debated structural phase transitions and uncover the Goldstone mode accompanying them. We demonstrate how unprecedented atomic-scale knowledge can be gained when human researchers connect the X-TEC results to physical principles. Specifically, we extract from the X-TEC-revealed selection rules that the Cd and Re displacements are approximately equal in amplitude but out of phase. This discovery reveals a previously unknown involvement of [Formula: see text] Re, supporting the idea of an electronic origin to the structural order. Our approach can radically transform XRD experiments by allowing in operando data analysis and enabling researchers to refine experiments by discovering interesting regions of phase space on the fly.

3.
BMC Plant Biol ; 23(1): 590, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38008766

RESUMO

BACKGROUND: Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), poses a threat to global wheat production. Deployment of widely effective resistance genes underpins management of this ongoing threat. This study focused on the mapping of stripe rust resistance gene YR63 from a Portuguese hexaploid wheat landrace AUS27955 of the Watkins Collection. RESULTS: YR63 exhibits resistance to a broad spectrum of Pst races from Australia, Africa, Asia, Europe, Middle East and South America. It was mapped to the short arm of chromosome 7B, between two single nucleotide polymorphic (SNP) markers sunCS_YR63 and sunCS_67, positioned at 0.8 and 3.7 Mb, respectively, in the Chinese Spring genome assembly v2.1. We characterised YR63 locus using an integrated approach engaging targeted genotyping-by-sequencing (tGBS), mutagenesis, resistance gene enrichment and sequencing (MutRenSeq), RNA sequencing (RNASeq) and comparative genomic analysis with tetraploid (Zavitan and Svevo) and hexaploid (Chinese Spring) wheat genome references and 10+ hexaploid wheat genomes. YR63 is positioned at a hot spot enriched with multiple nucleotide-binding and leucine rich repeat (NLR) and kinase domain encoding genes, known widely for defence against pests and diseases in plants and animals. Detection of YR63 within these gene clusters is not possible through short-read sequencing due to high homology between members. However, using the sequence of a NLR member we were successful in detecting a closely linked SNP marker for YR63 and validated on a panel of Australian bread wheat, durum and triticale cultivars. CONCLUSIONS: This study highlights YR63 as a valuable source for resistance against Pst in Australia and elsewhere. The closely linked SNP marker will facilitate rapid introgression of YR63 into elite cultivars through marker-assisted selection. The bottleneck of this study reinforces the necessity for a long-read sequencing such as PacBio or Oxford Nanopore based techniques for accurate detection of the underlying resistance gene when it is part of a large gene cluster.


Assuntos
Basidiomycota , Triticum , Mapeamento Cromossômico , Triticum/genética , Resistência à Doença/genética , Austrália , Nucleotídeos , Doenças das Plantas/genética , Basidiomycota/genética
4.
Theor Appl Genet ; 137(1): 1, 2023 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-38071267

RESUMO

KEY MESSAGE: Sr65 in chromosome 1A of Indian wheat landrace Hango-2 is a potentially useful all-stage resistance gene that currently protects wheat from stem rust in Australia, India, Africa and Europe. Stem rust, caused by Puccinia graminis f. sp. tritici (Pgt), threatened global wheat production with the appearance of widely virulent races that included TTKSK and TTRTF. Indian landrace Hango-2 showed resistance to Pgt races in India and Australia. Screening of a Hango-2/Avocet 'S' (AvS) recombinant inbred line population identified two stem rust resistance genes, a novel gene (temporarily named as SrH2) from Hango-2 and Sr26 from AvS. A mapping population segregating for SrH2 alone was developed from two recombinant lines. SrH2 was mapped on the short arm of chromosome 1A, where it was flanked by KASP markers KASP_7944 (proximal) and KASP_12147 (distal). SrH2 was delimited to an interval of 1.8-2.3 Mb on chromosome arm 1AS. The failure to detect candidate genes through MutRenSeq and comparative genomic analysis with the pan-genome dataset indicated the necessity to generate a Hango-2 specific assembly for detecting the gene sequence linked with SrH2 resistance. MutRenSeq however enabled identification of SrH2-linked KASP marker sunCS_265. Markers KASP_12147 and sunCS_265 showed 92% and 85% polymorphism among an Australian cereal cultivar diversity panel and can be used for marker-assisted selection of SrH2 in breeding programs. The effectiveness of SrH2 against Pgt races from Europe, Africa, India, and Australia makes it a valuable resource for breeding stem rust-resistant wheat cultivars. Since no wheat-derived gene was previously located in chromosome arm 1AS, SrH2 represents a new locus and named as SR65.


Assuntos
Basidiomycota , Triticum , Triticum/genética , Mapeamento Cromossômico , Resistência à Doença/genética , Austrália , Melhoramento Vegetal , Doenças das Plantas/genética
5.
EMBO Rep ; 22(11): e54000, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34734669

RESUMO

Open Science calls for transparent science and involvement of various stakeholders. Here are examples of and advice for meaningful stakeholder engagement.


Assuntos
Participação dos Interessados
6.
Phytopathology ; 113(4): 667-677, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36897760

RESUMO

Rust diseases are among the major constraints for wheat production worldwide due to the emergence and spread of highly destructive races of Puccinia. The most common approach to minimize yield losses due to rust is to use cultivars that are genetically resistant. Modern wheat cultivars, landraces, and wild relatives can contain undiscovered resistance genes, which typically encode kinase or nucleotide-binding site leucine rich repeat (NLR) domain containing receptor proteins. Recent research has shown that these genes can provide either resistance in all growth stages (all-stage resistance; ASR) or specially in later growth stages (adult-plant resistance; APR). ASR genes are pathogen and race-specific, meaning can function against selected races of the Puccinia fungus due to the necessity to recognize specific avirulence molecules in the pathogen. APR genes are either pathogen-specific or multipathogen resistant but often race-nonspecific. Prediction of resistance genes through rust infection screening alone remains complex when more than one resistance gene is present. However, breakthroughs during the past half century such as the single-nucleotide polymorphism-based genotyping techniques and resistance gene isolation strategies like mutagenesis, resistance gene enrichment, and sequencing (MutRenSeq), mutagenesis and chromosome sequencing (MutChromSeq), and association genetics combined with RenSeq (AgRenSeq) enables rapid transfer of resistance from source to modern cultivars. There is a strong need for combining multiple genes for better efficacy and longer-lasting resistance. Hence, techniques like gene cassette creation speeds up the gene combination process, but their widespread adoption and commercial use is limited due to their transgenic nature.


Assuntos
Basidiomycota , Triticum , Triticum/genética , Triticum/microbiologia , Resistência à Doença/genética , Doenças das Plantas/microbiologia , Basidiomycota/fisiologia , Fungos
7.
Nat Mater ; 20(2): 250-259, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32895507

RESUMO

Organoids can shed light on the dynamic interplay between complex tissues and rare cell types within a controlled microenvironment. Here, we develop gut organoid cocultures with type-1 innate lymphoid cells (ILC1) to dissect the impact of their accumulation in inflamed intestines. We demonstrate that murine and human ILC1 secrete transforming growth factor ß1, driving expansion of CD44v6+ epithelial crypts. ILC1 additionally express MMP9 and drive gene signatures indicative of extracellular matrix remodelling. We therefore encapsulated human epithelial-mesenchymal intestinal organoids in MMP-sensitive, synthetic hydrogels designed to form efficient networks at low polymer concentrations. Harnessing this defined system, we demonstrate that ILC1 drive matrix softening and stiffening, which we suggest occurs through balanced matrix degradation and deposition. Our platform enabled us to elucidate previously undescribed interactions between ILC1 and their microenvironment, which suggest that they may exacerbate fibrosis and tumour growth when enriched in inflamed patient tissues.


Assuntos
Matriz Extracelular/metabolismo , Mucosa Intestinal/metabolismo , Linfócitos/metabolismo , Organoides/metabolismo , Animais , Feminino , Humanos , Mucosa Intestinal/citologia , Linfócitos/citologia , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Organoides/citologia , Fator de Crescimento Transformador beta1/metabolismo
9.
Proc Natl Acad Sci U S A ; 112(17): 5479-84, 2015 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-25847991

RESUMO

The glucocorticoid receptor (GR) is a member of the nuclear receptor superfamily, which controls programs regulating cell proliferation, differentiation, and apoptosis. We have identified an unexpected role for GR in mitosis. We discovered that specifically modified GR species accumulate at the mitotic spindle during mitosis in a distribution that overlaps with Aurora kinases. We found that Aurora A was required to mediate mitosis-driven GR phosphorylation, but not recruitment of GR to the spindle. GR was necessary for mitotic progression, with increased time to complete mitosis, frequency of mitotic aberrations, and death in mitosis observed following GR knockdown. Complementation studies revealed an essential role for the GR ligand-binding domain, but no clear requirement for ligand binding in regulating chromosome segregation. The GR N-terminal domain, and specifically phosphosites S203 and S211, were not required. Reduced GR expression results in a cell cycle phenotype, with isolated cells from mouse and human subjects showing changes in chromosome content over prolonged passage. Furthermore, GR haploinsufficient mice have an increased incidence of tumor formation, and, strikingly, these tumors are further depleted for GR, implying additional GR loss as a consequence of cell transformation. We identified reduced GR expression in a panel of human liver, lung, prostate, colon, and breast cancers. We therefore reveal an unexpected role for the GR in promoting accurate chromosome segregation during mitosis, which is causally linked to tumorigenesis, making GR an authentic tumor suppressor gene.


Assuntos
Transformação Celular Neoplásica/metabolismo , Segregação de Cromossomos , Regulação Neoplásica da Expressão Gênica , Neoplasias/metabolismo , Receptores de Glucocorticoides/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Humanos , Camundongos , Camundongos Mutantes , Mitose/genética , Neoplasias/genética , Neoplasias/patologia , Estrutura Terciária de Proteína , Receptores de Glucocorticoides/genética , Células Tumorais Cultivadas , Proteínas Supressoras de Tumor/genética
10.
Biochem J ; 473(23): 4271-4288, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27888239

RESUMO

RNA-binding proteins play a central role in cellular metabolism by orchestrating the complex interactions of coding, structural and regulatory RNA species. The SAFB (scaffold attachment factor B) proteins (SAFB1, SAFB2 and SAFB-like transcriptional modulator, SLTM), which are highly conserved evolutionarily, were first identified on the basis of their ability to bind scaffold attachment region DNA elements, but attention has subsequently shifted to their RNA-binding and protein-protein interactions. Initial studies identified the involvement of these proteins in the cellular stress response and other aspects of gene regulation. More recently, the multifunctional capabilities of SAFB proteins have shown that they play crucial roles in DNA repair, processing of mRNA and regulatory RNA, as well as in interaction with chromatin-modifying complexes. With the advent of new techniques for identifying RNA-binding sites, enumeration of individual RNA targets has now begun. This review aims to summarise what is currently known about the functions of SAFB proteins.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a RNA/metabolismo , Animais , Reparo do DNA/genética , Reparo do DNA/fisiologia , Proteínas de Ligação a DNA/genética , Humanos , Proteínas de Ligação à Região de Interação com a Matriz/genética , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , Proteínas Associadas à Matriz Nuclear/genética , Proteínas Associadas à Matriz Nuclear/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo
11.
Proc Natl Acad Sci U S A ; 110(5): 1623-7, 2013 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-23319646

RESUMO

The competition between proximate electronic phases produces a complex phenomenology in strongly correlated systems. In particular, fluctuations associated with periodic charge or spin modulations, known as density waves, may lead to exotic superconductivity in several correlated materials. However, density waves have been difficult to isolate in the presence of chemical disorder, and the suspected causal link between competing density wave orders and high-temperature superconductivity is not understood. Here we used scanning tunneling microscopy to image a previously unknown unidirectional (stripe) charge-density wave (CDW) smoothly interfacing with the familiar tridirectional (triangular) CDW on the surface of the stoichiometric superconductor NbSe(2). Our low-temperature measurements rule out thermal fluctuations and point to local strain as the tuning parameter for this quantum phase transition. We use this quantum interface to resolve two longstanding debates about the anomalous spectroscopic gap and the role of Fermi surface nesting in the CDW phase of NbSe(2). Our results highlight the importance of local strain in governing phase transitions and competing phenomena, and suggest a promising direction of inquiry for resolving similarly longstanding debates in cuprate superconductors and other strongly correlated materials.


Assuntos
Nióbio/química , Transição de Fase , Teoria Quântica , Compostos de Selênio/química , Algoritmos , Cristalização , Condutividade Elétrica , Microscopia de Tunelamento/métodos , Modelos Químicos , Modelos Moleculares , Estrutura Molecular , Temperatura de Transição
12.
Proc Natl Acad Sci U S A ; 110(44): 17774-7, 2013 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-24101464

RESUMO

The energy gap for electronic excitations is one of the most important characteristics of the superconducting state, as it directly reflects the pairing of electrons. In the copper-oxide high-temperature superconductors (HTSCs), a strongly anisotropic energy gap, which vanishes along high-symmetry directions, is a clear manifestation of the d-wave symmetry of the pairing. There is, however, a dramatic change in the form of the gap anisotropy with reduced carrier concentration (underdoping). Although the vanishing of the gap along the diagonal to the square Cu-O bond directions is robust, the doping dependence of the large gap along the Cu-O directions suggests that its origin might be different from pairing. It is thus tempting to associate the large gap with a second-order parameter distinct from superconductivity. We use angle-resolved photoemission spectroscopy to show that the two-gap behavior and the destruction of well-defined electronic excitations are not universal features of HTSCs, and depend sensitively on how the underdoped materials are prepared. Depending on cation substitution, underdoped samples either show two-gap behavior or not. In contrast, many other characteristics of HTSCs, such as the dome-like dependence of on doping, long-lived excitations along the diagonals to the Cu-O bonds, and an energy gap at the Brillouin zone boundary that decreases monotonically with doping while persisting above (the pseudogap), are present in all samples, irrespective of whether they exhibit two-gap behavior or not. Our results imply that universal aspects of high- superconductivity are relatively insensitive to differences in the electronic states along the Cu-O bond directions.


Assuntos
Cobre/química , Condutividade Elétrica , Espectroscopia Fotoeletrônica/métodos , Temperatura , Anisotropia , Modelos Químicos , Difração de Raios X
13.
BMC Biol ; 13: 111, 2015 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-26694817

RESUMO

BACKGROUND: SAFB1 is a RNA binding protein implicated in the regulation of multiple cellular processes such as the regulation of transcription, stress response, DNA repair and RNA processing. To gain further insight into SAFB1 function we used iCLIP and mapped its interaction with RNA on a genome wide level. RESULTS: iCLIP analysis found SAFB1 binding was enriched, specifically in exons, ncRNAs, 3' and 5' untranslated regions. SAFB1 was found to recognise a purine-rich GAAGA motif with the highest frequency and it is therefore likely to bind core AGA, GAA, or AAG motifs. Confirmatory RT-PCR experiments showed that the expression of coding and non-coding genes with SAFB1 cross-link sites was altered by SAFB1 knockdown. For example, we found that the isoform-specific expression of neural cell adhesion molecule (NCAM1) and ASTN2 was influenced by SAFB1 and that the processing of miR-19a from the miR-17-92 cluster was regulated by SAFB1. These data suggest SAFB1 may influence alternative splicing and, using an NCAM1 minigene, we showed that SAFB1 knockdown altered the expression of two of the three NCAM1 alternative spliced isoforms. However, when the AGA, GAA, and AAG motifs were mutated, SAFB1 knockdown no longer mediated a decrease in the NCAM1 9-10 alternative spliced form. To further investigate the association of SAFB1 with splicing we used exon array analysis and found SAFB1 knockdown mediated the statistically significant up- and downregulation of alternative exons. Further analysis using RNAmotifs to investigate the frequency of association between the motif pairs (AGA followed by AGA, GAA or AAG) and alternative spliced exons found there was a highly significant correlation with downregulated exons. Together, our data suggest SAFB1 will play an important physiological role in the central nervous system regulating synaptic function. We found that SAFB1 regulates dendritic spine density in hippocampal neurons and hence provide empirical evidence supporting this conclusion. CONCLUSIONS: iCLIP showed that SAFB1 has previously uncharacterised specific RNA binding properties that help coordinate the isoform-specific expression of coding and non-coding genes. These genes regulate splicing, axonal and synaptic function, and are associated with neuropsychiatric disease, suggesting that SAFB1 is an important regulator of key neuronal processes.


Assuntos
Antígeno CD56/genética , Expressão Gênica , Glicoproteínas/genética , Proteínas de Ligação à Região de Interação com a Matriz/genética , Proteínas do Tecido Nervoso/genética , Proteínas Associadas à Matriz Nuclear/genética , Splicing de RNA , Receptores de Estrogênio/genética , Processamento Alternativo , Antígeno CD56/metabolismo , Regulação para Baixo , Glicoproteínas/metabolismo , Humanos , Proteínas de Ligação à Região de Interação com a Matriz/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas Associadas à Matriz Nuclear/metabolismo , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , Receptores de Estrogênio/metabolismo , Regulação para Cima
14.
Ann Emerg Med ; 65(2): 178-86.e6, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24976534

RESUMO

STUDY OBJECTIVE: We describe the evolution, environment, and psychosocial context of alcoholism from the perspective of chronically homeless, alcohol-dependent, frequent emergency department (ED) attendees. We use their words to explore how homelessness, health care, and other influences have contributed to the cause, progression, and management of their alcoholism. METHODS: We conducted detailed, semistructured, qualitative interviews, using a phenomenological approach with 20 chronically homeless, alcohol-dependent participants who had greater than 4 annual ED visits for 2 consecutive years at Bellevue Hospital in New York City. We used an administrative database and purposive sampling to obtain typical and atypical cases with diverse backgrounds. Interviews were audio recorded and transcribed verbatim. We triangulated interviews, field notes, and medical records. We used ATLAS.ti to code and determine themes, which we reviewed for agreement. We bracketed for researcher bias and maintained an audit trail. RESULTS: Interviews lasted an average of 50 minutes and yielded 800 pages of transcript. Fifty codes emerged, which were clustered into 4 broad themes: alcoholism, homelessness, health care, and the future. The participants' perspectives support a multifactorial process for the evolution of their alcoholism and its bidirectional reinforcing relationship with homelessness. Their self-efficacy and motivation for treatment is eroded by their progressive sense of hopelessness, which provides context for behaviors that reinforce stigma. CONCLUSION: Our study exposes concepts for further exploration in regard to the difficulty in engaging individuals who are incapable of envisioning a future. We hypothesize that a multidisciplinary harm reduction approach that integrates health and social services is achievable and would address their needs more effectively.


Assuntos
Transtornos Relacionados ao Uso de Álcool , Alcoólicos , Serviço Hospitalar de Emergência/estatística & dados numéricos , Pessoas Mal Alojadas , Inquéritos e Questionários , Adulto , Transtornos Relacionados ao Uso de Álcool/etiologia , Transtornos Relacionados ao Uso de Álcool/reabilitação , Feminino , Hospitais Urbanos , Humanos , Entrevistas como Assunto , Masculino , Competência Mental , Pessoa de Meia-Idade , Cidade de Nova Iorque , Pesquisa Qualitativa
15.
Proc Natl Acad Sci U S A ; 108(23): 9346-9, 2011 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-21606341

RESUMO

In order to understand the origin of high-temperature superconductivity in copper oxides, we must understand the normal state from which it emerges. Here, we examine the evolution of the normal state electronic excitations with temperature and carrier concentration in Bi(2)Sr(2)CaCu(2)O(8+δ) using angle-resolved photoemission. In contrast to conventional superconductors, where there is a single temperature scale T(c) separating the normal from the superconducting state, the high-temperature superconductors exhibit two additional temperature scales. One is the pseudogap scale T(∗), below which electronic excitations exhibit an energy gap. The second is the coherence scale T(coh), below which sharp spectral features appear due to increased lifetime of the excitations. We find that T(∗) and T(coh) are strongly doping dependent and cross each other near optimal doping. Thus the highest superconducting T(c) emerges from an unusual normal state that is characterized by coherent excitations with an energy gap.


Assuntos
Fenômenos Químicos , Cobre/química , Temperatura Alta , Condutividade Elétrica , Elétrons , Termodinâmica
16.
Environ Pollut ; 347: 123734, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38458523

RESUMO

Black carbon (BC) and particle number (PN) concentrations are usually high in cities due to traffic emissions. European mitigation policies, including Euro emission standards, have been implemented to curb these emissions. We analyzed BC and PN (particle diameter Dp > 4 nm) concentrations in Stockholm spanning the years 2013-2019 (BC) and 2009-2019 (PN) measured at street canyon and rooftop sites to assess the effectiveness of the implemented policies. Combining these data with inverse dispersion modeling, we estimated BC and PN emission factors (EFBC and EFPN) for the mixed fleet, reflecting real-world driving conditions. The pollutants showed decreasing trends at both sites, but PN concentrations remained high at the canyon site considering the World Health Organization (WHO) recommendations. BC concentrations declined more rapidly than PN concentrations, showing a -9.4% and -4.9% annual decrease at the canyon and -7.2% and -0.5% at the rooftop site in the years 2013-2019. The EFBC and EFPN trends showed that the mitigation strategies for reducing particulate emissions for on-road vehicles were successful over the study period. However, the introduction of biofuels in the vehicle fleet -ethanol and later rapeseed methyl ester (RME)- increased the concentrations of particles with Dp < 10 nm before the adoption of particulate filters in the exhausts. Stricter Euro emission regulations, especially with diesel particulate filters (DPF) in Euro 5, 6, and VI vehicles, led to 66% decrease in EFBC and 55% in EFPN. Real-world EFBC surpassed HBEFA (Handbook Emission Factors for Road Transport) database values by 2.4-4.8 times; however, direct comparisons between real-world and HBEFA EFPN are difficult due to differences in lower cut-off sizes and measurement techniques. Our results underscore the necessity for revising the HBEFA database, updating laboratory testing methods and portable emission measuring systems (PEMS) measurements to account for liquid condensate contributions to PN measurements.


Assuntos
Poluentes Atmosféricos , Emissões de Veículos , Emissões de Veículos/análise , Poluentes Atmosféricos/análise , Material Particulado/análise , Monitoramento Ambiental/métodos , Poeira , Fuligem , Carbono , Veículos Automotores , Tamanho da Partícula
17.
Biofabrication ; 16(4)2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38955197

RESUMO

Plasma cells (PCs) in bone marrow (BM) play an important role in both protective and pathogenic humoral immune responses, e.g. in various malignant and non-malignant diseases such as multiple myeloma, primary and secondary immunodeficiencies and autoimmune diseases. Dedicated microenvironmental niches in the BM provide PCs with biomechanical and soluble factors that support their long-term survival. There is a high need for appropriate and robust model systems to better understand PCs biology, to develop new therapeutic strategies for PCs-related diseases and perform targeted preclinical studies with high predictive value. Most preclinical data have been derived fromin vivostudies in mice, asin vitrostudies of human PCs are limited due to restricted survival and functionality in conventional 2D cultures that do not reflect the unique niche architecture of the BM. We have developed a microphysiological, dynamic 3D BM culture system (BM-MPS) based on human primary tissue (femoral biopsies), mechanically supported by a hydrogel scaffold casing. While a bioinert agarose casing did not support PCs survival, a photo-crosslinked collagen-hyaluronic acid (Col-HA) hydrogel preserved the native BM niche architecture and allowed PCs survivalin vitrofor up to 2 weeks. Further, the Col-HA hydrogel was permissive to lymphocyte migration into the microphysiological system´s circulation. Long-term PCs survival was related to the stable presence in the culture of soluble factors, as APRIL, BAFF, and IL-6. Increasing immunoglobulins concentrations in the medium confirm their functionality over culture time. To the best of our knowledge, this study is the first report of successful long-term maintenance of primary-derived non-malignant PCsin vitro. Our innovative model system is suitable for in-depthin vitrostudies of human PCs regulation and exploration of targeted therapeutic approaches such as CAR-T cell therapy or biologics.


Assuntos
Hidrogéis , Plasmócitos , Humanos , Plasmócitos/citologia , Plasmócitos/metabolismo , Hidrogéis/química , Sobrevivência Celular/efeitos dos fármacos , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Células da Medula Óssea/citologia , Colágeno/química , Medula Óssea/metabolismo , Células Cultivadas , Técnicas de Cultura de Células em Três Dimensões , Modelos Biológicos , Alicerces Teciduais/química , Sefarose/química
18.
Environ Int ; 185: 108510, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38460241

RESUMO

Ultrafine particles (UFP, those with diameters ≤ 100 nm), have been reported to potentially penetrate deeply into the respiratory system, translocate through the alveoli, and affect various organs, potentially correlating with increased mortality. The aim of this study is to assess long-term trends (5-11 years) in mostly urban UFP concentrations based on measurements of particle number size distributions (PNSD). Additionally, concentrations of other pollutants and meteorological variables were evaluated to support the interpretations. PNSD datasets from 12 urban background (UB), 5 traffic (TR), 3 suburban background (SUB) and 1 regional background (RB) sites in 15 European cities and 1 in the USA were evaluated. The non-parametric Theil-Sen's method was used to detect monotonic trends. Meta-analyses were carried out to assess the overall trends and those for different environments. The results showed significant decreases in NO, NO2, BC, CO, and particle concentrations in the Aitken (25-100 nm) and the Accumulation (100-800 nm) modes, suggesting a positive impact of the implementation of EURO 5/V and 6/VI vehicle standards on European air quality. The growing use of Diesel Particle Filters (DPFs) might also have clearly reduced exhaust emissions of BC, PM, and the Aitken and Accumulation mode particles. However, as reported by prior studies, there remains an issue of poor control of Nucleation mode particles (smaller than 25 nm), which are not fully reduced with current DPFs, without emission controls for semi-volatile organic compounds, and might have different origins than road traffic. Thus, contrasting trends for Nucleation mode particles were obtained across the cities studied. This mode also affected the UFP and total PNC trends because of the high proportion of Nucleation mode particles in both concentration ranges. It was also found that the urban temperature increasing trends might have also influenced those of PNC, Nucleation and Aitken modes.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Cidades , Monitoramento Ambiental/métodos , Europa (Continente) , Tamanho da Partícula , Material Particulado/análise , Emissões de Veículos/análise
19.
Appl Opt ; 52(18): 4258-63, 2013 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-23842168

RESUMO

This paper describes frequency-doubled operation of a high-energy chirped-pulse-amplification beamline. Efficient type-I second-harmonic generation was achieved using a 3 mm thick 320 mm aperture KDP crystal. Shots were fired at a range of energies achieving more than 100 J in a subpicosecond, 527 nm laser pulse with a power contrast of 10(14).

20.
Appl Opt ; 52(15): 3597-607, 2013 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-23736246

RESUMO

The commissioning of the Orion laser facility at the Atomic Weapons Establishment (AWE) in the UK has recently been completed. The facility is a twelve beam Nd:glass-based system for studying high energy density physics. It consists of ten frequency-tripled beam-lines operating with nanosecond pulses, synchronized with two beam-lines with subpicosecond pulses, each capable of delivering 500 J to target. One of the short pulse beams has the option of frequency doubling, at reduced aperture, to yield up to 100 J at 527 nm in a subpicosecond pulse with high temporal contrast. An extensive array of target diagnostics is provided. This article describes the laser design and commissioning and presents key performance data of the facility's laser systems.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA