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1.
Curr Biol ; 32(21): 4645-4659.e3, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36283410

RESUMO

During development, animals can maintain behavioral output even as underlying circuitry structurally remodels. After hatching, C. elegans undergoes substantial motor neuron expansion and synapse rewiring while the animal continuously moves with an undulatory pattern. To understand how the circuit transitions from its juvenile to mature configuration without interrupting functional output, we reconstructed the C. elegans motor circuit by electron microscopy across larval development. We observed the following: First, embryonic motor neurons transiently interact with the developing post-embryonic motor neurons prior to remodeling of their juvenile wiring. Second, post-embryonic neurons initiate synapse development with their future partners as their neurites navigate through the juvenile nerve cords. Third, embryonic and post-embryonic neurons sequentially build structural machinery needed for the adult circuit before the embryonic neurons relinquish their roles to post-embryonic neurons. Fourth, this transition is repeated region by region along the body in an anterior-to-posterior sequence, following the birth order of neurons. Through this orchestrated and programmed rewiring, the motor circuit gradually transforms from asymmetric to symmetric wiring. These maturation strategies support the continuous maintenance of motor patterns as the juvenile circuit develops into the adult configuration.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Caenorhabditis elegans/fisiologia , Neurônios Motores/fisiologia , Sinapses/fisiologia , Neuritos , Proteínas de Caenorhabditis elegans/genética
2.
Am J Cardiol ; 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36270826

RESUMO

Adverse cardiac events after laparoscopic bariatric surgery are rare, yet preoperative cardiology evaluation and testing remain common, resulting in the overuse of cardiac testing in low-risk patients. Our objective was to assess the frequency of, and factors associated with, overuse of preoperative cardiac testing in patients at low cardiac risk before laparoscopic bariatric surgery. We retrospectively reviewed data from 1,094 adult patients who underwent laparoscopic bariatric surgery at our institution from January 1, 2015, through December 31, 2019. The cardiac risk was determined using the Revised Cardiac Risk Index (RCRI) and the National Surgical Quality Improvement Program Myocardial Infarction and Cardiac Arrest (NSQIP MICA) risk model. Multivariate logistic regression was used to evaluate risk factors associated with the overuse of cardiac testing in low-risk patients. Overall, 1,059 patients (96.8%) were estimated to be at low cardiac risk by the RCRI, and 1,094 (100%) were at low cardiac risk by NSQIP MICA. A total of 587 patients (51.8%) were referred to cardiology for preoperative evaluation, and 643 patients (56.7%) underwent one or more preoperative cardiac tests. Factors associated with overuse of preoperative cardiac testing in low-risk patients included preoperative cardiology referral (adjusted odds ratio 37.2, 95% confidence interval 25.3 to 54.7) and patient age (adjusted odds ratio 1.05, 95% confidence interval 1.03 to 1.07). Overuse of preoperative cardiac testing was common in patients at low cardiac risk before laparoscopic bariatric surgery. Preoperative referral to cardiology was the most significant risk factor associated with the overuse of preoperative cardiac testing. Application of risk models such as the RCRI or NSQIP MICA at the time of bariatric program enrollment may reduce unnecessary preoperative cardiac testing in low-risk patients.

3.
Nat Commun ; 13(1): 4061, 2022 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-35831316

RESUMO

Most lncRNAs display species-specific expression patterns suggesting that animal models of cancer may only incompletely recapitulate the regulatory crosstalk between lncRNAs and oncogenic pathways in humans. Among these pathways, Sonic Hedgehog (SHH) signaling is aberrantly activated in several human cancer entities. We unravel that aberrant expression of the primate-specific lncRNA HedgeHog Interacting Protein-AntiSense 1 (HHIP-AS1) is a hallmark of SHH-driven tumors including medulloblastoma and atypical teratoid/rhabdoid tumors. HHIP-AS1 is actively transcribed from a bidirectional promoter shared with SHH regulator HHIP. Knockdown of HHIP-AS1 induces mitotic spindle deregulation impairing tumorigenicity in vitro and in vivo. Mechanistically, HHIP-AS1 binds directly to the mRNA of cytoplasmic dynein 1 intermediate chain 2 (DYNC1I2) and attenuates its degradation by hsa-miR-425-5p. We uncover that neither HHIP-AS1 nor the corresponding regulatory element in DYNC1I2 are evolutionary conserved in mice. Taken together, we discover an lncRNA-mediated mechanism that enables the pro-mitotic effects of SHH pathway activation in human tumors.


Assuntos
Neoplasias Cerebelares , Meduloblastoma , MicroRNAs , RNA Longo não Codificante , Animais , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Cerebelares/genética , Dineínas/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Humanos , Meduloblastoma/genética , Glicoproteínas de Membrana/metabolismo , Camundongos , MicroRNAs/genética , RNA Longo não Codificante/genética
4.
Am J Infect Control ; 50(2): 203-213, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34182069

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to over 170?million cases worldwide with over 33.2?million cases and 594,000 deaths in the US alone as of May 31st, 2021. The pandemic has also created severe shortages of personal protective equipment, particularly of filtering facepiece respirators (FFRs). The Centers for Disease Control and Prevention (CDC) has issued recommendations to help conserve FFRs, as well as crisis standards, including four criteria required for decontamination of the traditionally single use respirators. This review is designed to provide an overview of the current literature on vaporized hydrogen peroxide (vHP), hydrogen peroxide gas plasma (HPGP), and aerosolized hydrogen peroxide (aHP) with respect to each of the four CDC decontamination criteria. METHODS: PubMed and Medrxiv were queried for relevant articles. All articles underwent a title and abstract screen as well as subsequent full text screen by two blinded reviewers if indicated. RESULTS: Searches yielded 195 papers, of which, 79 were found to be relevant. Of those, 23 papers presented unique findings and 8 additional articles and technical papers were added to provide a comprehensive review. Overall, while there are potential concerns for all 3 decontamination methods, we found that vHP has the most evidence supporting its use in FFR decontamination consistent with CDC recommendation. CONCLUSIONS: Future research is recommended to evaluate biological inactivation and real world fit failures after FFR reuse.


Assuntos
COVID-19 , Peróxido de Hidrogênio , Descontaminação , Reutilização de Equipamento , Humanos , SARS-CoV-2 , Ventiladores Mecânicos
5.
Nature ; 596(7871): 257-261, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34349261

RESUMO

An animal's nervous system changes as its body grows from birth to adulthood and its behaviours mature1-8. The form and extent of circuit remodelling across the connectome is unknown3,9-15. Here we used serial-section electron microscopy to reconstruct the full brain of eight isogenic Caenorhabditis elegans individuals across postnatal stages to investigate how it changes with age. The overall geometry of the brain is preserved from birth to adulthood, but substantial changes in chemical synaptic connectivity emerge on this consistent scaffold. Comparing connectomes between individuals reveals substantial differences in connectivity that make each brain partly unique. Comparing connectomes across maturation reveals consistent wiring changes between different neurons. These changes alter the strength of existing connections and create new connections. Collective changes in the network alter information processing. During development, the central decision-making circuitry is maintained, whereas sensory and motor pathways substantially remodel. With age, the brain becomes progressively more feedforward and discernibly modular. Thus developmental connectomics reveals principles that underlie brain maturation.


Assuntos
Encéfalo/citologia , Encéfalo/crescimento & desenvolvimento , Caenorhabditis elegans/citologia , Conectoma , Modelos Neurológicos , Vias Neurais , Sinapses/fisiologia , Envelhecimento/metabolismo , Animais , Encéfalo/anatomia & histologia , Encéfalo/ultraestrutura , Caenorhabditis elegans/anatomia & histologia , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/ultraestrutura , Individualidade , Interneurônios/citologia , Microscopia Eletrônica , Neurônios/citologia , Comportamento Estereotipado
6.
J Acquir Immune Defic Syndr ; 88(1): 86-95, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34397746

RESUMO

BACKGROUND: With the highest rates of HIV/AIDS in the United States, Black Americans are still underrepresented in HIV medical research. SETTING: BRAAVE (NCT03631732) is a randomized, phase 3b, multicenter, open-label US study. METHODS: Adults identifying as Black or African American and virologically suppressed on 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus third agent were randomized (2:1) to switch to open-label bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) once daily or stay on baseline regimen (SBR) for 24 weeks, after which SBR had delayed switch to B/F/TAF. Resistance to non-NRTIs, protease inhibitors, and/or NRTIs was permitted; integrase strand transfer inhibitor resistance was exclusionary. Primary endpoint was proportion of participants with HIV-1 RNA ≥50 copies/mL at week 24 (snapshot algorithm; noninferiority margin of 6%). RESULTS: Of 558 screened, 495 were randomized/treated (B/F/TAF n = 330; SBR n = 165). Overall, 32% were ciswomen, 2% transwomen, and 10% had an M184V/I mutation. At week 24, 0.6% on B/F/TAF vs 1.8% on SBR had HIV-1 RNA ≥50 copies/mL (difference -1.2%; 95% confidence interval -4.8% to 0.9%), demonstrating noninferiority of B/F/TAF vs SBR. Proportions with HIV-1 RNA <50 copies/mL at week 24 were 96% B/F/TAF and 95% SBR and remained high at week 48. No participant had treatment-emergent resistance to study drug. Treatments were well tolerated. Study drug-related adverse events, mostly grade 1, occurred in 10% of participants on B/F/TAF through week 48 and led to discontinuation in 9 participants through week 48. CONCLUSIONS: For Black Americans with HIV, switching to B/F/TAF was noninferior to continuing a variety of regimens, including those with pre-existing NRTI mutations.


Assuntos
Alanina/uso terapêutico , Amidas/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Emtricitabina/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Piperazinas/uso terapêutico , Piridonas/uso terapêutico , Tenofovir/análogos & derivados , Adenina/uso terapêutico , Adolescente , Adulto , Afro-Americanos , Idoso , Combinação de Medicamentos , Feminino , Infecções por HIV/etnologia , Soropositividade para HIV , HIV-1/genética , HIV-1/isolamento & purificação , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , RNA/uso terapêutico , Tenofovir/uso terapêutico , Estados Unidos/epidemiologia , Carga Viral/efeitos dos fármacos
7.
Neuroimage ; 243: 118530, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34464739

RESUMO

The first phase of the Human Connectome Project pioneered advances in MRI technology for mapping the macroscopic structural connections of the living human brain through the engineering of a whole-body human MRI scanner equipped with maximum gradient strength of 300 mT/m, the highest ever achieved for human imaging. While this instrument has made important contributions to the understanding of macroscale connectional topology, it has also demonstrated the potential of dedicated high-gradient performance scanners to provide unparalleled in vivo assessment of neural tissue microstructure. Building on the initial groundwork laid by the original Connectome scanner, we have now embarked on an international, multi-site effort to build the next-generation human 3T Connectome scanner (Connectome 2.0) optimized for the study of neural tissue microstructure and connectional anatomy across multiple length scales. In order to maximize the resolution of this in vivo microscope for studies of the living human brain, we will push the diffusion resolution limit to unprecedented levels by (1) nearly doubling the current maximum gradient strength from 300 mT/m to 500 mT/m and tripling the maximum slew rate from 200 T/m/s to 600 T/m/s through the design of a one-of-a-kind head gradient coil optimized to minimize peripheral nerve stimulation; (2) developing high-sensitivity multi-channel radiofrequency receive coils for in vivo and ex vivo human brain imaging; (3) incorporating dynamic field monitoring to minimize image distortions and artifacts; (4) developing new pulse sequences to integrate the strongest diffusion encoding and highest spatial resolution ever achieved in the living human brain; and (5) calibrating the measurements obtained from this next-generation instrument through systematic validation of diffusion microstructural metrics in high-fidelity phantoms and ex vivo brain tissue at progressively finer scales with accompanying diffusion simulations in histology-based micro-geometries. We envision creating the ultimate diffusion MRI instrument capable of capturing the complex multi-scale organization of the living human brain - from the microscopic scale needed to probe cellular geometry, heterogeneity and plasticity, to the mesoscopic scale for quantifying the distinctions in cortical structure and connectivity that define cyto- and myeloarchitectonic boundaries, to improvements in estimates of macroscopic connectivity.


Assuntos
Conectoma/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Masculino , Neuroimagem/métodos , Imagens de Fantasmas
8.
Dev Neurobiol ; 81(5): 746-757, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33977655

RESUMO

Dendritic spines are membranous protrusions that receive essentially all excitatory inputs in most mammalian neurons. Spines, with a bulbous head connected to the dendrite by a thin neck, have a variety of morphologies that likely impact their functional properties. Nevertheless, the question of whether spines belong to distinct morphological subtypes is still open. Addressing this quantitatively requires clear identification and measurements of spine necks. Recent advances in electron microscopy enable large-scale systematic reconstructions of spines with nanometer precision in 3D. Analyzing ultrastructural reconstructions from mouse neocortical neurons with computer vision algorithms, we demonstrate that the vast majority of spine structures can be rigorously separated into heads and necks, enabling morphological measurements of spine necks. We then used a database of spine morphological parameters to explore the potential existence of different spine classes. Without exception, our analysis revealed unimodal distributions of individual morphological parameters of spine heads and necks, without evidence for subtypes of spines. The postsynaptic density size was strongly correlated with the spine head volume. The spine neck diameter, but not the neck length, was also correlated with the head volume. Spines with larger head volumes often had a spine apparatus and pairs of spines in a post-synaptic cell contacted by the same axon had similar head volumes. Our data reveal a lack of morphological subtypes of spines and indicate that the spine neck length and head volume must be independently regulated. These results have repercussions for our understanding of the function of dendritic spines in neuronal circuits.


Assuntos
Espinhas Dendríticas , Neurônios , Animais , Axônios/ultraestrutura , Dendritos/fisiologia , Espinhas Dendríticas/fisiologia , Mamíferos , Camundongos , Microscopia Eletrônica , Neurônios/fisiologia , Sinapses
9.
Comput Vis ECCV ; 12363: 103-120, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33345257

RESUMO

For large-scale vision tasks in biomedical images, the labeled data is often limited to train effective deep models. Active learning is a common solution, where a query suggestion method selects representative unlabeled samples for annotation, and the new labels are used to improve the base model. However, most query suggestion models optimize their learnable parameters only on the limited labeled data and consequently become less effective for the more challenging unlabeled data. To tackle this, we propose a two-stream active query suggestion approach. In addition to the supervised feature extractor, we introduce an unsupervised one optimized on all raw images to capture diverse image features, which can later be improved by fine-tuning on new labels. As a use case, we build an end-to-end active learning framework with our query suggestion method for 3D synapse detection and mitochondria segmentation in connectomics. With the framework, we curate, to our best knowledge, the largest connectomics dataset with dense synapses and mitochondria annotation. On this new dataset, our method outperforms previous state-of-the-art methods by 3.1% for synapse and 3.8% for mitochondria in terms of region-of-interest proposal accuracy. We also apply our method to image classification, where it outperforms previous approaches on CIFAR-10 under the same limited annotation budget. The project page is https://zudi-lin.github.io/projects/#two_stream_active.

10.
Brachytherapy ; 19(6): 827-836, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32811761

RESUMO

Image-guided adaptive brachytherapy (IGABT) has been shown to improve local/regional control and survival for cervix cancer patients while reducing morbidity. However, the technique is complex involving several conceptual, methodological, and technical innovations compared to conventional brachytherapy. The delivery of high-quality IGABT which will translate into improved outcomes is therefore critically dependent on effective education and training of all health professionals involved in the brachytherapy treatment process. This paper reviews the (GEC)-ESTRO/EMBRACE initiatives for education and training to promote the dissemination and implementation of IGABT for cervix cancer worldwide. The new skills required in different health professionals for successful implementation of IGABT are described. The achievements and challenges of current educational strategies for disseminating IGABT are discussed. Innovations to improve the effectiveness of current and future educational strategies are explored.


Assuntos
Braquiterapia/métodos , Radioterapia (Especialidade)/educação , Neoplasias do Colo do Útero/radioterapia , Competência Clínica , Feminino , Humanos , Internacionalidade , Imageamento por Ressonância Magnética , Radioterapia Guiada por Imagem
11.
Data Brief ; 28: 104794, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31871969

RESUMO

This article contains data on structural characterization of the [C2Mim][NTf2] in bulk and in nano-confined environment obtained using MD simulations. These data supplement those presented in the paper "Insights from Molecular Dynamics Simulations on Structural Organization and Diffusive Dynamics of an Ionic Liquid at Solid and Vacuum Interfaces" [1], where force fields with three different charge methods and three charge scaling factors were used for the analysis of the IL in the bulk, at the interface with the vacuum and the IL film in the contact with a hydroxylated alumina surface. Here, we present details on the construction of the model systems in an extended detailed methods section. Furthermore, for best parametrization, structural and dynamic properties of IL in different environment are studied with certain features presented herein.

12.
Radiother Oncol ; 141: 123-129, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31495516

RESUMO

PURPOSE: Recent evidence from EMBRACE shows that around 16% patients with locally advanced cervical cancer (LACC) have residual tumor in distal parametrium (DP) and pelvic wall disease (LPW) after concurrent radio-chemotherapy (CCRT). Adequate target coverage with standard brachytherapy approaches represents a challenge. Therefore, we modified the Vienna I applicator with an add-on cap allowing for additional oblique needles into the DP/LPW (Vienna II). We report here the feasibility and clinical outcomes using Vienna II applicator in LACC patients treated in 2 institutions. METHODS AND MATERIALS: 69 patients with residual disease in DP/LPW after CCRT were accrued. FIGO (2009) stage was 26% IIB, 52% III, 15% IVA, 7% IVB (para-aortic nodes). At diagnosis 91% had disease involving DP/LPW. After CCRT, patients underwent image guided adaptive brachytherapy (IGABT) using Vienna II applicator. IGABT details, acute complications, dose volume parameters and clinical outcome variables were compiled and analyzed. RESULTS: Residual DP/LPW disease at BT was found in 90% patients. Median total number of needles were 7 [3-15], oblique 4 [1-7]. Manageable intraoperative utero-vaginal complications occurred in 8 patients and manageable arterial bleeding in 6 patients during removal. Mean distance between tandem and outer contour of CTVHR was 38 mm and mean CTVHR (±SD) volume was 69 ±â€¯32 cm3. The mean D90 CTVHR was 86 ±â€¯7 Gy (EQD2) and mean (±SD) D2cm3 (Gy, EQD2) 86 ±â€¯12, 68 ±â€¯7, 68 ±â€¯9 for bladder, rectum and sigmoid respectively. Actuarial LC, PFS, OS at 3/5 years was 76/72%, 56/50%, 62/54% and G3-4 late toxicities (n = 23) were observed in 14 patients (20%). CONCLUSIONS: IGABT using Vienna II applicator allows for appropriate target coverage in tumors extending into DP/LPW at the time of BT. Clinical use is feasible and results in good local control, DFS and OS with moderate rate of acute and late ≥G3 toxicity.


Assuntos
Braquiterapia/instrumentação , Braquiterapia/métodos , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Estudos de Viabilidade , Feminino , Humanos , Imagem por Ressonância Magnética Intervencionista , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Neoplasia Residual , Pelve/diagnóstico por imagem , Pelve/patologia , Peritônio/diagnóstico por imagem , Peritônio/patologia , Radiografia Intervencionista , Dosagem Radioterapêutica , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Neoplasias do Colo do Útero/diagnóstico por imagem , Adulto Jovem
13.
Cell Rep ; 27(10): 2799-2808.e3, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31167127

RESUMO

Reciprocal communication between neurons and oligodendrocytes is essential for the generation and localization of myelin, a critical feature of the CNS. In the neocortex, individual oligodendrocytes can myelinate multiple axons; however, the neuronal origin of the myelinated axons has remained undefined and, while largely assumed to be from excitatory pyramidal neurons, it also includes inhibitory interneurons. This raises the question of whether individual oligodendrocytes display bias for the class of neurons that they myelinate. Here, we find that different classes of cortical interneurons show distinct patterns of myelin distribution starting from the onset of myelination, suggesting that oligodendrocytes can recognize the class identity of individual types of interneurons that they target. Notably, we show that some oligodendrocytes disproportionately myelinate the axons of inhibitory interneurons, whereas others primarily target excitatory axons or show no bias. These results point toward very specific interactions between oligodendrocytes and neurons and raise the interesting question of why myelination is differentially directed toward different neuron types.


Assuntos
Axônios/metabolismo , Bainha de Mielina/fisiologia , Neocórtex/fisiologia , Oligodendroglia/metabolismo , Animais , Axônios/fisiologia , Axônios/ultraestrutura , Feminino , Interneurônios/citologia , Interneurônios/metabolismo , Interneurônios/fisiologia , Interneurônios/ultraestrutura , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Bainha de Mielina/metabolismo , Neocórtex/metabolismo , Neocórtex/ultraestrutura , Inibição Neural , Oligodendroglia/citologia , Oligodendroglia/fisiologia , Oligodendroglia/ultraestrutura , Células Piramidais/metabolismo , Software
14.
PLoS One ; 14(6): e0218326, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31242218

RESUMO

The origin of the tin used for the production of bronze in the Eurasian Bronze Age is still one of the mysteries in prehistoric archaeology. In the past, numerous studies were carried out on archaeological bronze and tin objects with the aim of determining the sources of tin, but all failed to find suitable fingerprints. In this paper we investigate a set of 27 tin ingots from well-known sites in the eastern Mediterranean Sea (Mochlos, Uluburun, Hishuley Carmel, Kfar Samir south, Haifa) that had been the subject of previous archaeological and archaeometallurgical research. By using a combined approach of tin and lead isotopes together with trace elements it is possible to narrow down the potential sources of tin for the first time. The strongly radiogenic composition of lead in the tin ingots from Israel allows the calculation of a geological model age of the parental tin ores of 291 ± 17 Ma. This theoretical formation age excludes Anatolian, central Asian and Egyptian tin deposits as tin sources since they formed either much earlier or later. On the other hand, European tin deposits of the Variscan orogeny agree well with this time span so that an origin from European deposits is suggested. With the help of the tin isotope composition and the trace elements of the objects it is further possible to exclude many tin resources from the European continent and, considering the current state of knowledge and the available data, to conclude that Cornish tin mines are the most likely suppliers for the 13th-12th centuries tin ingots from Israel. Even though a different provenance seems to be suggested for the tin from Mochlos and Uluburun by the actual data, these findings are of great importance for the archaeological interpretation of the trade routes and the circulation of tin during the Late Bronze Age. They demonstrate that the trade networks between the eastern Mediterranean and some place in the east that are assumed for the first half of the 2nd millennium BCE (as indicated by textual evidence from Kültepe/Kanes and Mari) did not exist in the same way towards the last quarter of the millennium.


Assuntos
Isótopos/química , Estanho/química , Grécia , História Antiga , Mar Mediterrâneo , Microscopia Eletrônica de Varredura
15.
J Colloid Interface Sci ; 553: 350-363, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31220709

RESUMO

HYPOTHESIS: A reliable modelling approach is required for simultaneous characterisation of static and dynamic properties of bulk and interfacial ionic liquids (ILs). This is a prerequisite for a successful investigation of experimentally inaccessible, yet important properties, including those that change significantly with the distance from both vacuum and solid interfaces. SIMULATIONS: We perform molecular dynamics simulations of bulk [C2Mim][NTf2], and thick IL films in contact with vacuum and hydroxylated sapphire surface, using the charge methods CHelpG, RESP-HF and RESP-B3LYP with charge scaling factors 1.0, 0.9 and 0.85. FINDINGS: By determining and employing appropriate system sizes and simulations lengths, and by benchmarking against self-diffusion coefficients, surface tension, X-ray reflectivity, and structural data, we identify RESP-HF/0.9 as the best non-polarizable force field for this IL. We use this optimal parametrisation to predict novel physical properties of confined IL films. First we fully characterise the internal configurations and orientations of IL molecules relative to, and as a function of the distance from the solid and vacuum interfaces. Second, we evaluate densities together with mobilities in-plane and normal to the interfaces and find that strong correlations between the IL's stratification and diffusive transport in the interfacial layers persist for several nanometres deep into IL films.

17.
Micromachines (Basel) ; 10(5)2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31075891

RESUMO

Metallic implants were the only option for both medical and dental applications for decades. However, it has been reported that patients with metal implants can show allergic reactions. Consequently, technical ceramics have become an accessible material alternative due to their combination of biocompatibility and mechanical properties. Despite the recent developments in ductile mode machining, the micro-grinding of bioceramics can cause insufficient surface and subsurface integrity due to the inherent hardness and brittleness of these materials. This work aims to determine the influence on the surface and subsurface damage (SSD) of zirconia-based ceramics ground with diamond wheels of 10 mm diameter with a diamond grain size (dg) of 75 µm within eight grinding operations using a variation of the machining parameters, i.e., peripheral speed (vc), feed speed (vf), and depth of cut (ae). In this regard, dental thread structures were machined on fully sintered zirconia (ZrO2), alumina toughened zirconia (ATZ), and zirconia toughened alumina (ZTA) bioceramics. The ground workpieces were analysed through a scanning electron microscope (SEM), X-ray diffraction (XRD), and white light interferometry (WLI) to evaluate the microstructure, residual stresses, and surface roughness, respectively. Moreover, the grinding processes were monitored through forces measurement. Based on the machining parameters tested, the results showed that low peripheral speed (vc) and low depth of cut (ae) were the main conditions investigated to achieve the optimum surface integrity and the desired low grinding forces. Finally, the methodology proposed to investigate the surface integrity of the ground workpieces was helpful to understand the zirconia-based ceramics response under micro-grinding processes, as well as to set further machining parameters for dental implant threads.

18.
Clin Liver Dis ; 23(2): 345-361, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30947881

RESUMO

Liver diseases during pregnancy pose a unique clinical challenge because they can affect the lives of both the mother and unborn child. Although severe liver disease is rare, pregnancy-related liver disease affects approximately 3% of pregnancies and can be fatal. Timely recognition and diagnosis are essential in order to institute appropriate management strategies. This article provides an overview of liver diseases during pregnancy and is divided into 2 sections: (1) liver diseases specific to pregnancy, and (2) preexisting or coincident liver diseases during pregnancy.


Assuntos
Hipertensão Induzida pela Gravidez/diagnóstico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Hepatopatias/diagnóstico , Hepatopatias/terapia , Colestase Intra-Hepática/sangue , Colestase Intra-Hepática/diagnóstico , Colestase Intra-Hepática/tratamento farmacológico , Fígado Gorduroso/diagnóstico , Feminino , Hepatite B/diagnóstico , Hepatite B/terapia , Hepatite B/transmissão , Hepatite C/diagnóstico , Hepatite C/terapia , Hepatite C/transmissão , Hepatite Autoimune/tratamento farmacológico , Humanos , Hiperêmese Gravídica/sangue , Hipertensão Induzida pela Gravidez/terapia , Cirrose Hepática/complicações , Cirrose Hepática/terapia , Hepatopatias/sangue , Testes de Função Hepática , Transplante de Fígado , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/diagnóstico , Complicações na Gravidez/tratamento farmacológico
19.
Angew Chem Int Ed Engl ; 58(3): 741-745, 2019 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-30467935

RESUMO

Supported ionic liquid phase (SILP) catalysis enables a highly efficient, Ru-based, homogeneously catalyzed water-gas shift reaction (WGSR) between 100 °C and 150 °C. The active Ru-complexes have been found to exist in imidazolium chloride melts under operating conditions in a dynamic equilibrium, which is dominated by the [Ru(CO)3 Cl3 ]- complex. Herein we present state-of-the-art theoretical calculations to elucidate the reaction mechanism in more detail. We show that the mechanism includes the intermediate formation and degradation of hydrogen chloride, which effectively reduces the high barrier for the formation of the requisite dihydrogen complex. The hypothesis that the rate-limiting step involves water is supported by using D2 O in continuous catalytic WGSR experiments. The resulting mechanism constitutes a highly competitive alternative to earlier reported generic routes involving nucleophilic addition of hydroxide in the gas phase and in solution.

20.
J Cell Mol Med ; 23(1): 670-679, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30460772

RESUMO

Testicular germ cell tumours (GCTs) mostly affect young men at age 17-40. Although high cure rates can be achieved by orchiectomy and chemotherapy, GCTs can still be a lethal threat to young patients with metastases or therapy resistance. Thus, alternative treatment options are needed. Based on studies utilising GCT cell lines, the histone deacetylase inhibitor romidepsin is a promising therapeutic option, showing high toxicity at very low doses towards cisplatin-resistant GCT cells, but not fibroblasts or Sertoli cells. In this study, we extended our analysis of the molecular effects of romidepsin to deepen our understanding of the underlying mechanisms. Patients will benefit from these analyses, since detailed knowledge of the romidepsin effects allows for a better risk and side-effect assessment. We screened for changes in histone acetylation of specific lysine residues and analysed changes in the DNA methylation landscape after romidepsin treatment of the GCT cell lines TCam-2, 2102EP, NCCIT and JAR, while human fibroblasts were used as controls. In addition, we focused on the role of the dehydrogenase/reductase DHRS2, which was strongly up-regulated in romidepsin treated cells, by generating DHRS2-deficient TCam-2 cells using CRISPR/Cas9 gene editing. We show that DHRS2 is dispensable for up-regulation of romidepsin effectors (GADD45B, DUSP1, ZFP36, ATF3, FOS, CDKN1A, ID2) but contributes to induction of cell cycle arrest. Finally, we show that a combinatory treatment of romidepsin plus the gluccocorticoid dexamethasone further boosts expression of the romidepsin effectors and reduces viability of GCT cells more strongly than under single agent treatment. Thus, romidepsin and dexamethasone might represent a new combinatorial approach for treatment of GCT.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carbonil Redutase (NADPH)/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Depsipeptídeos/farmacologia , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/farmacologia , Dexametasona/farmacologia , Inibidores de Histona Desacetilases/farmacologia , Humanos , Neoplasias Embrionárias de Células Germinativas/metabolismo , Neoplasias Testiculares/metabolismo , Regulação para Cima/efeitos dos fármacos
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