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1.
Adv Mater ; 33(24): e2100340, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33960013

RESUMO

Despite important breakthroughs in bottom-up synthetic biology, a major challenge still remains the construction of free-standing, macroscopic, and robust materials from protocell building blocks that are stable in water and capable of emergent behaviors. Herein, a new floating mold technique for the fabrication of millimeter- to centimeter-sized protocellular materials (PCMs) of any shape that overcomes most of the current challenges in prototissue engineering is reported. Significantly, this technique also allows for the generation of 2D periodic arrays of PCMs that display an emergent non-equilibrium spatiotemporal sensing behavior. These arrays are capable of collectively translating the information provided by the external environment and are encoded in the form of propagating reaction-diffusion fronts into a readable dynamic signal output. Overall, the methodology opens up a route to the fabrication of macroscopic and robust tissue-like materials with emergent behaviors, providing a new paradigm of bottom-up synthetic biology and biomimetic materials science.

2.
Nature ; 590(7846): 428-432, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33568809

RESUMO

The atmospheric concentration of trichlorofluoromethane (CFC-11) has been in decline since the production of ozone-depleting substances was phased out under the Montreal Protocol1,2. Since 2013, the concentration decline of CFC-11 slowed unexpectedly owing to increasing emissions, probably from unreported production, which, if sustained, would delay the recovery of the stratospheric ozone layer1-12. Here we report an accelerated decline in the global mean CFC-11 concentration during 2019 and 2020, derived from atmospheric concentration measurements at remote sites around the world. We find that global CFC-11 emissions decreased by 18 ± 6 gigagrams per year (26 ± 9 per cent; one standard deviation) from 2018 to 2019, to a 2019 value (52 ± 10 gigagrams per year) that is similar to the 2008-2012 mean. The decline in global emissions suggests a substantial decrease in unreported CFC-11 production. If the sharp decline in unexpected global emissions and unreported production is sustained, any associated future ozone depletion is likely to be limited, despite an increase in the CFC-11 bank (the amount of CFC-11 produced, but not yet emitted) by 90 to 725 gigagrams by the beginning of 2020.

3.
J Marital Fam Ther ; 2020 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-33161620

RESUMO

Common factors proponents have suggested the need for principle-based meta-models to explain how various factors interact with each other to produce change. The therapeutic pyramid is a common factors meta-model that outlines how therapeutic skills and techniques, the therapeutic alliance, and a therapist's way of being interactive to produce therapeutic change. Skills and techniques occupy the smallest top portion of the pyramid, with the therapeutic alliance in the middle and a therapist's way of being forming the foundation of the pyramid. The success of any layer rests on the quality of the immediately underlying layer. This study illustrates the broad applicability of common factors meta-models by applying the therapeutic pyramid to couples therapy, family therapy, training and supervision, and professional ethics.

4.
Adv Biosyst ; 4(11): e2000101, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33166084

RESUMO

The extent to which biologic payloads can be effectively delivered to cells is a limiting factor in the development of new therapies. Limitations arise from the lack of pharmacokinetic stability of biologics in vivo. Encapsulating biologics in a protective delivery vector has the potential to improve delivery profile and enhance performance. Coacervate microdroplets are developed as cell-mimetic materials with established potential for the stabilization of biological molecules, such as proteins and nucleic acids. Here, the development of biodegradable coacervate microvectors (comprising synthetically modified amylose polymers) is presented, for the delivery of biologic payloads to cells. Amylose-based coacervate microdroplets are stable under physiological conditions (e.g., temperature and ionic strength), are noncytotoxic owing to their biopolymeric structure, spontaneously interacted with the cell membrane, and are able to deliver and release proteinaceous payloads beyond the plasma membrane. In particular, myoglobin, an oxygen storage and antioxidant protein, is successfully delivered into human mesenchymal stem cells (hMSCs) within 24 h. Furthermore, coacervate microvectors are implemented for the delivery of human bone morphogenetic protein 2 growth factor, inducing differentiation of hMSCs into osteoprogenitor cells. This study demonstrates the potential of coacervate microdroplets as delivery microvectors for biomedical research and the development of new therapies.

5.
Equine Vet J ; 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33131087

RESUMO

BACKGROUND: Routine equine odontoplasty is performed by both Veterinary Surgeons and Equine Dental Technicians. The production of aerosolised particulates from motorised equipment has been well documented in human orthodontics but has yet to be investigated in the veterinary industry. OBJECTIVES: To assess the size, quantity and composition of particulates produced during routine motorised odontoplasty and to model their deposition in the human respiratory tree. STUDY DESIGN: Analytic observational study. METHODS: Fifteen-minute routine motorised odontoplasties were performed on cadaver heads with monitoring equipment placed 30 cm away from the oral cavity to simulate the position of the operator's face. For quantitative analysis, an active air sampling photometric monitor was used to detect the concentration of fully respirable (<4.25 µm) particles produced. The use of water and non-water-cooled equipment and 2 different types of face mask (standard surgical and FFP3) were compared. An 8-stage Marple Personal Cascade Impactor modelled the deposition of the particulates in relation to the human respiratory tree. Qualitative analysis of these particulates was performed using scanning electron microscopy and energy dispersive x-ray spectroscopy. RESULTS: Motorised odontoplasty created aerosolised particulates that could reach all levels of the human respiratory tree. These particulates were composed mostly of calcium and phosphate, although traces of metals were found. The concentration of fully respirable particulates exceeded the recommended exposure limits set by the Health and Safety Executive. The use of an FFP-3 face mask significantly reduced the level of inhaled particulates. MAIN LIMITATIONS: This was a simulated experiment. It does not take into account the variety of environments in which routine treatment takes place. CONCLUSIONS: There are possible health risks in performing a large amount of routine motorised dentistry due to inhalation of aerosolised particulates. The use of an adequate face mask lowers exposure levels to within acceptable limits and, therefore, should be worn.

6.
Yearb Med Inform ; 29(1): 235-242, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32823322

RESUMO

OBJECTIVES: Conduct a survey of the literature for advancements in cancer informatics over the last three years in three specific areas where there has been unprecedented growth: 1) digital health; 2) machine learning; and 3) precision oncology. We also highlight the ethical implications and future opportunities within each area. METHODS: A search was conducted over a three-year period in two electronic databases (PubMed, Google Scholar) to identify peer-reviewed articles and conference proceedings. Search terms included variations of the following: neoplasms[MeSH], informatics[MeSH], cancer, oncology, clinical cancer informatics, medical cancer informatics. The search returned too many articles for practical review (23,994 from PubMed and 23,100 from Google Scholar). Thus, we conducted searches of key PubMed-indexed informatics journals and proceedings. We further limited our search to manuscripts that demonstrated a clear focus on clinical or translational cancer informatics. Manuscripts were then selected based on their methodological rigor, scientific impact, innovation, and contribution towards cancer informatics as a field or on their impact on cancer care and research. RESULTS: Key developments and opportunities in cancer informatics research in the areas of digital health, machine learning, and precision oncology were summarized. CONCLUSION: While there are numerous innovations in the field of cancer informatics to advance prevention and clinical care, considerable challenges remain related to data sharing and privacy, digital accessibility, and algorithm biases and interpretation. The implementation and application of these findings in cancer care necessitates further consideration and research.

7.
ANZ J Surg ; 90(9): 1553-1557, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32594617

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has created a global pandemic. Surgical care has been impacted, with concerns raised around surgical safety, especially in terms of laparoscopic versus open surgery. Due to potential aerosol transmission of SARS-CoV-2, precautions during aerosol-generating procedures and production of surgical plume are paramount for the safety of surgical teams. METHODS: A rapid review methodology was used with evidence sourced from PubMed, Departments of Health, surgical colleges and other health authorities. From this, a working group of expert surgeons developed recommendations for surgical safety in the current environment. RESULTS: Pre-operative testing of surgical patients with reverse transcription-polymerase chain reaction does not guarantee lack of infectivity due to a demonstrated false-negative rate of up to 30%. All bodily tissues and fluids should therefore be treated as a potential source of COVID-19 infection during operative management. Caution must be taken, especially when using an energy source that produces surgical plumes, and an appropriate capture device should also be used. Limiting the use of such devices or using lower energy devices is desirable. To reduce perceived risks association with desufflation of pneumoperitoneum during laparoscopic surgery, an appropriate suction irrigator system, attached to a high-efficiency particulate air filter, should be used. Additionally, appropriate use of personal protective equipment by the surgical team is necessary during high-risk aerosol-generating procedures. CONCLUSIONS: As a result of the rapid review, evidence-based guidance has been produced to support safe surgical practice.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Transmissão de Doença Infecciosa/prevenção & controle , Pandemias , Equipamento de Proteção Individual/provisão & distribuição , Pneumonia Viral/epidemiologia , Procedimentos Cirúrgicos Operatórios/normas , Infecções por Coronavirus/transmissão , Humanos , Pneumonia Viral/transmissão
9.
Microb Genom ; 6(5)2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32375974

RESUMO

Mobile genetic elements (MGEs) are key factors responsible for dissemination of virulence determinants and antimicrobial-resistance genes amongst pathogenic bacteria. Conjugative MGEs are notable for their high gene loads donated per transfer event, broad host ranges and phylogenetic ubiquity amongst prokaryotes, with the subclass of chromosomally inserted integrative and conjugative elements (ICEs) being particularly abundant. The focus on a small number of model systems has biased the study of ICEs towards those conferring readily selectable phenotypes to host cells, whereas the identification and characterization of integrated cryptic elements remains challenging. Even though antimicrobial resistance and horizontally acquired virulence genes are major factors aggravating neisserial infection, conjugative MGEs of Neisseria gonorrhoeae and Neisseria meningitidis remain poorly characterized. Using a phenotype-independent approach based on atypical distributions of DNA uptake sequences (DUSs) in MGEs relative to the chromosomal background, we have identified two groups of chromosomally integrated conjugative elements in Neisseria: one found almost exclusively in pathogenic species possibly deriving from the genus Kingella, the other belonging to a group of Neisseria mucosa-like commensals. The former element appears to enable transfer of traditionally gonococcal-specific loci such as the virulence-associated toxin-antitoxin system fitAB to N. meningitidis chromosomes, whilst the circular form of the latter possesses a unique attachment site (attP) sequence seemingly adapted to exploit DUS motifs as chromosomal integration sites. In addition to validating the use of DUS distributions in Neisseriaceae MGE identification, the >170 identified ICE sequences provide a valuable resource for future studies of ICE evolution and host adaptation.

10.
Brief Bioinform ; 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32026945

RESUMO

MOTIVATION: Although gene set enrichment analysis has become an integral part of high-throughput gene expression data analysis, the assessment of enrichment methods remains rudimentary and ad hoc. In the absence of suitable gold standards, evaluations are commonly restricted to selected datasets and biological reasoning on the relevance of resulting enriched gene sets. RESULTS: We develop an extensible framework for reproducible benchmarking of enrichment methods based on defined criteria for applicability, gene set prioritization and detection of relevant processes. This framework incorporates a curated compendium of 75 expression datasets investigating 42 human diseases. The compendium features microarray and RNA-seq measurements, and each dataset is associated with a precompiled GO/KEGG relevance ranking for the corresponding disease under investigation. We perform a comprehensive assessment of 10 major enrichment methods, identifying significant differences in runtime and applicability to RNA-seq data, fraction of enriched gene sets depending on the null hypothesis tested and recovery of the predefined relevance rankings. We make practical recommendations on how methods originally developed for microarray data can efficiently be applied to RNA-seq data, how to interpret results depending on the type of gene set test conducted and which methods are best suited to effectively prioritize gene sets with high phenotype relevance. AVAILABILITY: http://bioconductor.org/packages/GSEABenchmarkeR. CONTACT: ludwig.geistlinger@sph.cuny.edu.

11.
Nat Commun ; 11(1): 333, 2020 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949145

RESUMO

Cutaneous malignant melanoma is an aggressive cancer of melanocytes with a strong propensity to metastasize. We posit that melanoma cells acquire metastatic capability by adopting an embryonic-like phenotype, and that a lineage approach would uncover metastatic melanoma biology. Using a genetically engineered mouse model to generate a rich melanoblast transcriptome dataset, we identify melanoblast-specific genes whose expression contribute to metastatic competence and derive a 43-gene signature that predicts patient survival. We identify a melanoblast gene, KDELR3, whose loss impairs experimental metastasis. In contrast, KDELR1 deficiency enhances metastasis, providing the first example of different disease etiologies within the KDELR-family of retrograde transporters. We show that KDELR3 regulates the metastasis suppressor, KAI1, and report an interaction with the E3 ubiquitin-protein ligase gp78, a regulator of KAI1 degradation. Our work demonstrates that the melanoblast transcriptome can be mined to uncover targetable pathways for melanoma therapy.


Assuntos
Perfilação da Expressão Gênica , Melanoma/genética , Melanoma/metabolismo , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Transcriptoma , Animais , Linhagem Celular Tumoral , Retículo Endoplasmático , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Proteína Kangai-1/genética , Proteína Kangai-1/metabolismo , Pulmão/patologia , Melanócitos/metabolismo , Melanoma/patologia , Camundongos , Camundongos Endogâmicos C57BL , Metástase Neoplásica/genética , Segunda Neoplasia Primária/patologia , Fenótipo , Receptores de Peptídeos/genética , Receptores de Peptídeos/metabolismo , Neoplasias Cutâneas/patologia , Ubiquitina-Proteína Ligases/metabolismo
12.
J Marital Fam Ther ; 46(1): 110-123, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30561122

RESUMO

The purpose of this constructivist grounded theory study was to develop a deeper understanding of the relational system of married couples and God. We interviewed nine marital couples from Christian denominations that reported having a strong relationship with each other and with God together. We used constructivist grounded theory techniques presented by Charmaz (2006) and analyzed emergent categories of behaviors, emotions, and cognitions to construct a theory and model of Christian marital couples and their shared relationship with God. We then compared and contrasted the results and theory to existing literature on attachment theory and theorized a shared attachment to God. We applied the theological concept of kinship covenant to the results in order to organize and situate the theory into a Christian framework. Finally, we discuss clinical, pastoral, and future research implications.


Assuntos
Relações Interpessoais , Apego ao Objeto , Religião e Psicologia , Cônjuges/psicologia , Adulto , Cristianismo , Feminino , Teoria Fundamentada , Humanos , Masculino , Pesquisa Qualitativa
13.
F1000Res ; 9: 1493, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33564398

RESUMO

Gene symbols are recognizable identifiers for gene names but are unstable and error-prone due to aliasing, manual entry, and unintentional conversion by spreadsheets to date format. Official gene symbol resources such as HUGO Gene Nomenclature Committee (HGNC) for human genes and the Mouse Genome Informatics project (MGI) for mouse genes provide authoritative sources of valid, aliased, and outdated symbols, but lack a programmatic interface and correction of symbols converted by spreadsheets. We present HGNChelper, an R package that identifies known aliases and outdated gene symbols based on the HGNC human and MGI mouse gene symbol databases, in addition to common mislabeling introduced by spreadsheets, and provides corrections where possible. HGNChelper identified invalid gene symbols in the most recent Molecular Signatures Database (mSigDB 7.0) and in platform annotation files of the Gene Expression Omnibus, with prevalence ranging from ~3% in recent platforms to 30-40% in the earliest platforms from 2002-03. HGNChelper is installable from CRAN.


Assuntos
Bases de Dados de Compostos Químicos , Bases de Dados Genéticas , Animais , Expressão Gênica , Humanos , Camundongos
14.
Science ; 365(6453): 587-590, 2019 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-31395782

RESUMO

In 2017, western Canadian wildfires injected smoke into the stratosphere that was detectable by satellites for more than 8 months. The smoke plume rose from 12 to 23 kilometers within 2 months owing to solar heating of black carbon, extending the lifetime and latitudinal spread. Comparisons of model simulations to the rate of observed lofting indicate that 2% of the smoke mass was black carbon. The observed smoke lifetime in the stratosphere was 40% shorter than calculated with a standard model that does not consider photochemical loss of organic carbon. Photochemistry is represented by using an empirical ozone-organics reaction probability that matches the observed smoke decay. The observed rapid plume rise, latitudinal spread, and photochemical reactions provide new insights into potential global climate impacts from nuclear war.


Assuntos
Fumaça , Ozônio Estratosférico/análise , Incêndios Florestais , Canadá
15.
Sci Rep ; 9(1): 10887, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31350438

RESUMO

Introducing hierarchical pore structure to microporous materials such as metal-organic frameworks (MOFs) can be beneficial for reactions where the rate of reaction is limited by low rates of diffusion or high pressure drop. This advantageous pore structure can be obtained by defect formation, mostly via post-synthetic acid etching, which has been studied extensively on water-stable MOFs. Here we show that a water-unstable HKUST-1 MOF can also be modified in a corresponding manner by using phosphoric acid as a size-selective etching agent and a mixture of dimethyl sulfoxide and methanol as a dilute solvent. Interestingly, we demonstrate that the etching process which is time- and acidity- dependent, can result in formation of defective HKUST-1 with extra interconnected hexagonal macropores without compromising on the bulk crystallinity. These findings suggest an intelligent scalable synthetic method for formation of hierarchical porosity in MOFs that are prone to hydrolysis, for improved molecular accessibility and diffusion for catalysis.

16.
ANZ J Surg ; 89(12): 1582-1586, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31334600

RESUMO

BACKGROUND: This retrospective, population-based cohort study aims to determine if differences in the regional distribution of procedures or variation in regional mortality contributes to the variable pancreaticoduodenectomy (PD) mortality between Australian states and territories. METHODS: De-identified procedural data from public hospitals between 1 July 2005 and 30 June 2015 from the Australian Institute of Health and Welfare were analysed. The regional distribution of procedures and variation in perioperative mortality rate (POMR) were investigated in New South Wales (NSW), Victoria and Queensland (QLD) using logistic regression analysis. RESULTS: NSW performed the highest proportion of city-based procedures (93.8%) while QLD performed the highest proportion of regional procedures (15.3%). QLD demonstrated the lowest city mortality (1.9%) and lowest POMR overall (2.0%). City, regional and state-wide mortality was highest in NSW (5.0%, 8.4% and 5.3%). No significant difference in POMR was demonstrated between regional and city hospitals in each of the states (P = 0.46) or across all states (P = 0.50). CONCLUSION: This study demonstrates comparable regional PD distribution across Australia. The difference in PD POMR between city and regional areas was not found to be statistically significant. NSW exhibited the highest city, regional and overall PD POMR, potentially warranting further investigation.


Assuntos
Hospitais Públicos/estatística & dados numéricos , Pancreatopatias/mortalidade , Pancreaticoduodenectomia/mortalidade , Programas Médicos Regionais/estatística & dados numéricos , Adulto , Austrália , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Pancreatopatias/patologia , Pancreatopatias/cirurgia , Estudos Retrospectivos
17.
Fam Process ; 58(3): 629-640, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31334848

RESUMO

The common factors paradigm in couple and family therapy has gained popularity over the past several decades, leading many therapists to refer to themselves as common factors family therapists. Despite this, no consensus exists on what it means to be a common factors family therapist, or if such a designation even makes sense given that the common factors paradigm is not a model. Synthesizing the existing common factors literature, a case is made for the designation "common factors informed family therapist," and the following six core principles are outlined that characterize this designation: (1) sees overlap among theories; (2) passionate about theory, not a theory; (3) client centered; (4) monitors hope and the therapeutic alliance; (5) views clients as people rather than objects; and (6) prioritizes healing over therapy. Each of the concepts is discussed in depth, and clinical implications are provided.


Assuntos
Terapia Familiar , Família/psicologia , Terapia Familiar/métodos , Humanos , Modelos Psicológicos , Psicoterapia Centrada na Pessoa/métodos , Relações Profissional-Paciente , Teoria Psicológica
18.
F1000Res ; 8: 752, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31249680

RESUMO

Motivation: The Bioconductor project, a large collection of open source software for the comprehension of large-scale biological data, continues to grow with new packages added each week, motivating the development of software tools focused on exposing package metadata to developers and users. The resulting BiocPkgTools package facilitates access to extensive metadata in computable form covering the Bioconductor package ecosystem, facilitating downstream applications such as custom reporting, data and text mining of Bioconductor package text descriptions, graph analytics over package dependencies, and custom search approaches. Results: The BiocPkgTools package has been incorporated into the Bioconductor project, installs using standard procedures, and runs on any system supporting R. It provides functions to load detailed package metadata, longitudinal package download statistics, package dependencies, and Bioconductor build reports, all in "tidy data" form. BiocPkgTools can convert from tidy data structures to graph structures, enabling graph-based analytics and visualization. An end-user-friendly graphical package explorer aids in task-centric package discovery. Full documentation and example use cases are included. Availability: The BiocPkgTools software and complete documentation are available from Bioconductor ( https://bioconductor.org/packages/BiocPkgTools).


Assuntos
Mineração de Dados , Software , Metadados
19.
F1000Res ; 8: 21, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30828438

RESUMO

Bioconductor's SummarizedExperiment class unites numerical assay quantifications with sample- and experiment-level metadata.  SummarizedExperiment is the standard Bioconductor class for assays that produce matrix-like data, used by over 200 packages.  We describe the restfulSE package, a deployment of  this data model that supports remote storage.  We illustrate use of SummarizedExperiment with remote HDF5 and Google BigQuery back ends, with two applications in cancer genomics.  Our intent is to allow the use of familiar and semantically meaningful programmatic idioms to query genomic data, while abstracting the remote interface from end users and developers.


Assuntos
Genômica , Software , Genoma
20.
Angew Chem Int Ed Engl ; 58(18): 5891-5896, 2019 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-30786125

RESUMO

The azafullerene Tb2 @C79 N is found to be a single-molecule magnet with a high 100-s blocking temperature of magnetization of 24 K and large coercivity. Tb magnetic moments with an easy-axis single-ion magnetic anisotropy are strongly coupled by the unpaired spin of the single-electron Tb-Tb bond. Relaxation of magnetization in Tb2 @C79 N below 15 K proceeds via quantum tunneling of magnetization with the characteristic time τQTM =16 462±1230 s. At higher temperature, relaxation follows the Orbach mechanism with a barrier of 757±4 K, corresponding to the excited states, in which one of the Tb spins is flipped.

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