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1.
Proc Natl Acad Sci U S A ; 119(42): e2205772119, 2022 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-36215503

RESUMO

The power grid is going through significant changes with the introduction of renewable energy sources and the incorporation of smart grid technologies. These rapid advancements necessitate new models and analyses to keep up with the various emergent phenomena they induce. A major prerequisite of such work is the acquisition of well-constructed and accurate network datasets for the power grid infrastructure. In this paper, we propose a robust, scalable framework to synthesize power distribution networks that resemble their physical counterparts for a given region. We use openly available information about interdependent road and building infrastructures to construct the networks. In contrast to prior work based on network statistics, we incorporate engineering and economic constraints to create the networks. Additionally, we provide a framework to create ensembles of power distribution networks to generate multiple possible instances of the network for a given region. The comprehensive dataset consists of nodes with attributes, such as geocoordinates; type of node (residence, transformer, or substation); and edges with attributes, such as geometry, type of line (feeder lines, primary or secondary), and line parameters. For validation, we provide detailed comparisons of the generated networks with actual distribution networks. The generated datasets represent realistic test systems (as compared with standard test cases published by Institute of Electrical and Electronics Engineers (IEEE)) that can be used by network scientists to analyze complex events in power grids and to perform detailed sensitivity and statistical analyses over ensembles of networks.


Assuntos
Fontes de Energia Elétrica
2.
Scand J Rheumatol ; 53(3): 207-216, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38505972

RESUMO

OBJECTIVE: Immunoglobulin G (IgG) autoantibodies in systemic lupus erythematosus (SLE) are considered pathogenic, whereas immunoglobulin M (IgM) autoantibodies may have protective effects. The aim of this study was to identify whether IgG/IgM autoantibody ratios differ between patients with incomplete systemic lupus erythematosus (iSLE), patients with SLE, and healthy controls (HCs), and whether IgG/IgM autoantibody ratios relate to progression from iSLE to SLE. METHOD: This prospective cohort study included 34 iSLE patients, 41 SLE patients, and 11 HCs. IgG and IgM anti-dsDNA, anti-Ro52, and anti-Ro60 were measured by fluoro-enzyme immunoassay in serum samples obtained at baseline in all groups and in follow-up samples of up to 5 years for iSLE patients. Correlations between IgG/IgM autoantibody ratios, interferon signature, and clinical parameters were also assessed. RESULTS: At baseline, IgG anti-dsDNA, anti-Ro52, anti-Ro60, and IgM anti-dsDNA were elevated in iSLE and SLE patients. IgG/IgM anti-dsDNA and anti-Ro52 ratios were similar between groups, while IgG/IgM anti-Ro60 ratios were significantly elevated in iSLE and SLE patients compared to HCs. IgG/IgM autoantibody ratios were not correlated with interferon signature or clinical parameters. IgG/IgM ratios at baseline were similar and remained relatively stable during a median follow-up of 18 months in non-progressors and six iSLE patients who progressed to SLE. CONCLUSION: IgG anti-dsDNA, anti-Ro52, anti-Ro60, and IgM anti-dsDNA were elevated in iSLE and SLE patients, which was not apparent from the respective IgG/IgM ratios only. IgG/IgM autoantibody ratios remained relatively stable over up to 5 years in iSLE non-progressors and six patients who progressed to SLE.


Assuntos
Autoanticorpos , Lúpus Eritematoso Sistêmico , Humanos , Imunoglobulina M , Imunoglobulina G , Estudos Prospectivos , Interferons
3.
Chaos ; 33(2): 023118, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36859214

RESUMO

Mathematical models rooted in network representations are becoming increasingly more common for capturing a broad range of phenomena. Boolean networks (BNs) represent a mathematical abstraction suited for establishing general theory applicable to such systems. A key thread in BN research is developing theory that connects the structure of the network and the local rules to phase space properties or so-called structure-to-function theory. While most theory for BNs has been developed for the synchronous case, the focus of this work is on asynchronously updated BNs (ABNs) which are natural to consider from the point of view of applications to real systems where perfect synchrony is uncommon. A central question in this regard is sensitivity of dynamics of ABNs with respect to perturbations to the asynchronous update scheme. Macauley & Mortveit [Nonlinearity 22, 421-436 (2009)] showed that the periodic orbits are structurally invariant under toric equivalence of the update sequences. In this paper and under the same equivalence of the update scheme, the authors (i) extend that result to the entire phase space, (ii) establish a Lipschitz continuity result for sequences of maximal transient paths, and (iii) establish that within a toric equivalence class the maximal transient length may at most take on two distinct values. In addition, the proofs offer insight into the general asynchronous phase space of Boolean networks.

4.
Bull Math Biol ; 81(5): 1442-1460, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30656504

RESUMO

We present mathematical techniques for exhaustive studies of long-term dynamics of asynchronous biological system models. Specifically, we extend the notion of [Formula: see text]-equivalence developed for graph dynamical systems to support systematic analysis of all possible attractor configurations that can be generated when varying the asynchronous update order (Macauley and Mortveit in Nonlinearity 22(2):421, 2009). We extend earlier work by Veliz-Cuba and Stigler (J Comput Biol 18(6):783-794, 2011), Goles et al. (Bull Math Biol 75(6):939-966, 2013), and others by comparing long-term dynamics up to topological conjugation: rather than comparing the exact states and their transitions on attractors, we only compare the attractor structures. In general, obtaining this information is computationally intractable. Here, we adapt and apply combinatorial theory for dynamical systems from Macauley and Mortveit (Proc Am Math Soc 136(12):4157-4165, 2008. https://doi.org/10.1090/S0002-9939-09-09884-0 ; 2009; Electron J Comb 18:197, 2011a; Discret Contin Dyn Syst 4(6):1533-1541, 2011b. https://doi.org/10.3934/dcdss.2011.4.1533 ; Theor Comput Sci 504:26-37, 2013. https://doi.org/10.1016/j.tcs.2012.09.015 ; in: Isokawa T, Imai K, Matsui N, Peper F, Umeo H (eds) Cellular automata and discrete complex systems, 2014. https://doi.org/10.1007/978-3-319-18812-6_6 ) to develop computational methods that greatly reduce this computational cost. We give a detailed algorithm and apply it to (i) the lac operon model for Escherichia coli proposed by Veliz-Cuba and Stigler (2011), and (ii) the regulatory network involved in the control of the cell cycle and cell differentiation in the Caenorhabditis elegans vulva precursor cells proposed by Weinstein et al. (BMC Bioinform 16(1):1, 2015). In both cases, we uncover all possible limit cycle structures for these networks under sequential updates. Specifically, for the lac operon model, rather than examining all [Formula: see text] sequential update orders, we demonstrate that it is sufficient to consider 344 representative update orders, and, more notably, that these 344 representatives give rise to 4 distinct attractor structures. A similar analysis performed for the C. elegans model demonstrates that it has precisely 125 distinct attractor structures. We conclude with observations on the variety and distribution of the models' attractor structures and use the results to discuss their robustness.


Assuntos
Modelos Biológicos , Algoritmos , Animais , Caenorhabditis elegans/citologia , Pontos de Checagem do Ciclo Celular , Diferenciação Celular , Escherichia coli/genética , Escherichia coli/metabolismo , Óperon Lac , Conceitos Matemáticos , Software , Biologia de Sistemas
5.
Environ Sci Technol ; 52(11): 6508-6517, 2018 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-29733209

RESUMO

Integrated buffer zones (IBZs) represent a novel form of edge-of-field technology in Northwest Europe. Contrary to the common riparian buffer strips, IBZs collect tile drainage water from agricultural fields by combining a ditch-like pond (POND), where soil particles can settle, and a flow-through filter bed (FILTERBED) planted with Alnus glutinosa (L.), a European alder (black alder). The first experimental IBZ facility was constructed and thoroughly tested in Denmark for its capability to retain various nitrogen (N) and phosphorus (P) species within the first three years after construction. We calculated the water and nutrient budget for the total IBZ and for the two compartments, POND and FILTERBED, separately. Furthermore, a tracer experiment using sodium bromide was conducted in order to trace the water flow and estimate the hydraulic residence time in the FILTERBEDs. The monthly average removal efficiency amounted to 10-67% for total N and 31-69% for total P, with performance being highest during the warm season. Accordingly, we suggest that IBZs may be a valuable modification of dry buffer strips in order to mitigate the adverse impacts of high nutrient loading from agricultural fields on the aquatic environment.


Assuntos
Nitrogênio , Fósforo , Agricultura , Dinamarca , Europa (Continente)
6.
Br J Dermatol ; 173(3): 641-50, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26149498

RESUMO

Tumour necrosis factor (TNF)-α, a proinflammatory cytokine central to many autoimmune diseases, has been implicated in the depigmentation process in vitiligo. We review its role in vitiligo by exploring its pro- and anti-inflammatory properties and examine the effects of blocking its actions with TNF-α antagonist therapeutics in reports available in the literature. We found that TNF-α inhibition halts disease progression in patients with progressive vitiligo but that, paradoxically, treatment can be associated with de novo vitiligo development in some patients when used for other autoimmune conditions, particularly when using adalimumab and infliximab. These studies reinforce the importance of stating appropriate outcomes measures, as most pilot trials propose to measure repigmentation, whereas halting depigmentation is commonly overlooked as a measure of success. We conclude that TNF-α inhibition has proven useful for patients with progressive vitiligo, where TNF-α inhibition is able to quash cytotoxic T-cell-mediated melanocyte destruction. However, a lingering concern for initiating de novo disease will likely prevent more widespread application of TNF inhibitors to treat vitiligo.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Vitiligo/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais/uso terapêutico , Ensaios Clínicos como Assunto , Progressão da Doença , Feminino , Previsões , Humanos , Masculino , Melanócitos/efeitos dos fármacos , Pessoa de Meia-Idade , Linfócitos T/efeitos dos fármacos
7.
Rapid Commun Mass Spectrom ; 29(5): 424-30, 2015 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26349464

RESUMO

RATIONALE: Neonicotinoids are widely used insecticides which have been shown to affect the memory and learning abilities of honey bees, and are suspected to play a part in the unexplainable, large-scale loss of honey bee colonies. Fast methods, such as ambient mass spectrometry (MS), for their analysis from a variety of matrices are necessary to control the use of forbidden products and study the spreading of insecticides in nature. METHODS: The feasibilities of two ambient MS methods, desorption electrospray ionization (DESI) and desorption atmospheric pressure photoionization (DAPPI), for the analysis of five most used neonicotinoid compounds, thiacloprid, acetamiprid, clothianidin, imidacloprid and thiamethoxam, were tested. In addition, DAPPI was used to analyze fresh rose leaves treated with commercially available thiacloprid insecticide and dried and powdered turnip rape flowers, which had been collected from a field treated with thiacloprid-containing insecticide. RESULTS: DAPPI was found to be more sensitive than DESI, with 2-11 times better signal-to-noise ratios, and limits of detection at 0.4-5.0 fmol for the standard compounds. DAPPI was able to detect thiacloprid from the rose leaves even 2.5 months after the treatment and from the turnip rape flower samples collected from a field. The analysis of plant material by DAPPI did not require extraction or other sample preparation. CONCLUSIONS: DAPPI was found to be suitable for the fast and direct qualitative analysis of thiacloprid neonicotinoid from plant samples. It shows promise as a fast tool for screening of forbidden insecticides, or studying the distribution of insecticides in nature.


Assuntos
Flores/química , Inseticidas/análise , Folhas de Planta/química , Piridinas/análise , Espectrometria de Massas por Ionização por Electrospray/métodos , Compostos de Enxofre/análise , Brassica napus/química , Limite de Detecção , Rosa/química
8.
Occup Environ Med ; 72(6): 385-93, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25209848

RESUMO

OBJECTIVES: Numerous environmental contaminants have been linked to adverse reproductive health outcomes. However, the complex correlation structure of exposures and multiple testing issues limit the interpretation of existing evidence. Our objective was to identify, from a large set of contaminant exposures, exposure profiles associated with biomarkers of male reproductive function. METHODS: In this cross-sectional study (n=602), male partners of pregnant women were enrolled between 2002 and 2004 during antenatal care visits in Greenland, Poland and Ukraine. Fifteen contaminants were detected in more than 70% of blood samples, including metabolites of di(2-ethylhexyl) and diisononyl phthalates (DEHP, DiNP), perfluoroalkyl acids, metals and organochlorines. Twenty-two reproductive biomarkers were assessed, including serum levels of reproductive hormones, markers of semen quality, sperm chromatin integrity, epididymal and accessory sex gland function, and Y:X chromosome ratio. We evaluated multipollutant models with sparse partial least squares (sPLS) regression, a simultaneous dimension reduction and variable selection approach which accommodates joint modelling of correlated exposures. RESULTS: Of the over 300 exposure-outcome associations tested in sPLS models, we detected 10 associations encompassing 8 outcomes. Several associations were notably consistent in direction across the three study populations: positive associations between mercury and inhibin B, and between cadmium and testosterone; and inverse associations between DiNP metabolites and testosterone, between polychlorinated biphenyl-153 and progressive sperm motility, and between a DEHP metabolite and neutral α-glucosidase, a marker of epididymal function. CONCLUSIONS: This global assessment of a mixture of environmental contaminants provides further indications that some organochlorines and phthalates adversely affect some parameters of male reproductive health.


Assuntos
Exposição Ambiental/efeitos adversos , Poluentes Ambientais , Hormônios Gonadais/sangue , Hidrocarbonetos Clorados , Metais , Ácidos Ftálicos , Reprodução/efeitos dos fármacos , Análise do Sêmen , Adulto , Biomarcadores/sangue , Estudos Transversais , Poluentes Ambientais/sangue , Poluentes Ambientais/toxicidade , Groenlândia , Humanos , Hidrocarbonetos Clorados/sangue , Hidrocarbonetos Clorados/toxicidade , Masculino , Metais/sangue , Metais/toxicidade , Ácidos Ftálicos/sangue , Ácidos Ftálicos/toxicidade , Polônia , Análise de Regressão , Motilidade dos Espermatozoides/efeitos dos fármacos , Ucrânia , Adulto Jovem
9.
Nucleic Acids Res ; 41(16): e158, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23861444

RESUMO

Here, we report the investigation of microsatellite instability (MSI) in human cells with a newly developed reporter system based on fluorescence. We composed a vector into which microsatellites of different lengths and nucleotide composition can be introduced between a functional copy of the fluorescent protein mCherry and an out-of-frame copy of EGFP; in vivo frameshifting will lead to EGFP expression, which can be quantified by fluorescence activated cell sorting (FACS). Via targeted recombineering, single copy reporters were introduced in HEK293 and MCF-7 cells. We found predominantly -1 and +1 base pair frameshifts, the levels of which are kept in tune by mismatch repair. We show that tract length and composition greatly influences MSI. In contrast, a tracts' potential to form a G-quadruplex structure, its strand orientation or its transcriptional status is not affecting MSI. We further validated the functionality of the reporter system for screening microsatellite mutagenicity of compounds and for identifying modifiers of MSI: using a retroviral miRNA expression library, we identified miR-21, which targets MSH2, as a miRNA that induces MSI when overexpressed. Our data also provide proof of principle for the strategy of combining fluorescent reporters with next-generation sequencing technology to identify genetic factors in specific pathways.


Assuntos
Genes Reporter , Instabilidade de Microssatélites , Linhagem Celular , Separação Celular , Citometria de Fluxo , Corantes Fluorescentes , Quadruplex G , Proteínas de Fluorescência Verde/análise , Proteínas de Fluorescência Verde/genética , Humanos , Proteínas Luminescentes/análise , Proteínas Luminescentes/genética , MicroRNAs/metabolismo , Transcrição Gênica , Proteína Vermelha Fluorescente
10.
Artigo em Inglês | MEDLINE | ID: mdl-26348126

RESUMO

The paradox of secondary metabolites, toxic defence compounds produced by plants, in nectar and fruits is well known. Deterrence of feeding by nectarivorous and frugivorous birds is better understood than the effect of these chemicals on the digestive performance of birds. Digestive parameters such as transit time and sugar assimilation are important in assessing nutrient utilization and deterrence may be related to post-ingestive effects involving these parameters. Nectar and many fruits contain mainly sugars and water, and avian consumers compensate for low sugar content in their diet by increasing food intake: this may also increase their intake of secondary metabolites. We investigated how the alkaloid nicotine, naturally present in nectar of Nicotiana species, influences compensatory feeding and digestive performance of nectar-feeding birds. High nicotine concentration negatively affected compensatory feeding and apparent assimilation efficiency of white-bellied sunbirds Cinnyris talatala and Cape white-eyes Zosterops virens; but nicotine slowed gut transit time only in the latter species. In contrast, food intake and digestive performance of dark-capped bulbuls Pycnonotus tricolor was unaffected by nicotine up to a concentration of 50µM. Bulbuls are primarily frugivorous; hence, they are more exposed to secondary metabolites than sunbirds and possibly white-eyes. Because their diet is richer in toxins, frugivorous birds may have evolved more efficient detoxification strategies than those of specialist nectar-feeding birds.


Assuntos
Digestão/efeitos dos fármacos , Tolerância a Medicamentos , Trato Gastrointestinal/efeitos dos fármacos , Absorção Intestinal/efeitos dos fármacos , Nicotina/toxicidade , Agonistas Nicotínicos/toxicidade , Passeriformes/fisiologia , Animais , Sacarose Alimentar/administração & dosagem , Sacarose Alimentar/análise , Sacarose Alimentar/metabolismo , Digestão/fisiologia , Ingestão de Energia/efeitos dos fármacos , Fezes/química , Comportamento Alimentar/efeitos dos fármacos , Fármacos Gastrointestinais/toxicidade , Trato Gastrointestinal/fisiologia , Trânsito Gastrointestinal/efeitos dos fármacos , Inativação Metabólica , Néctar de Plantas/efeitos adversos , Néctar de Plantas/química , África do Sul , Especificidade da Espécie , Toxicocinética
11.
Brain Behav Immun ; 42: 22-32, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24998196

RESUMO

High-fat diet (HFD)-induced obesity is reaching worldwide proportions. In addition to causing obesity, HFDs also induce a variety of health disorders, which includes cognitive decline. Hippocampal function may be particularly vulnerable to the negative consequences of HFD, and it is suspected that 'primed' neuroinflammatory processes may mediate this response. To examine the link between diet, hippocampal function and neuroinflammation, male Wistar rats were fed a medium or HFD. Hippocampal memory function was measured using contextual pre-exposure fear conditioning (CPE-FC). Rats fed a HFD demonstrated impaired memory, an effect that was augmented with longer duration of HFD consumption. HFD-induced memory impairments were linked to potentiated levels of interleukin-1 beta (IL-1ß) protein in the hippocampus 2h after the foot-shock that occurs during CPE-FC. Central IL-1 receptor antagonism, with intracisterna magna (ICM) administration of hIL-1RA prior to the foot-shock prevented the diet-induced memory disruption, suggesting a critical role for IL-1ß in this phenomenon. Additionally, obese animals whose diet regimen was reversed from HFD back to standard chow recovered memory function and did not demonstrate a foot-shock-induced hippocampal IL-1ß increase. Interestingly, dietary reversal neutralized the negative impact of HFD on memory and IL-1ß, yet animals maintained physiological evidence of obesity (increased body mass and serum leptin), indicating that dietary components, not body mass, may mediate the negative effects on memory.


Assuntos
Condicionamento Psicológico/fisiologia , Dieta Hiperlipídica , Hipocampo/metabolismo , Interleucina-1beta/metabolismo , Transtornos da Memória/etiologia , Memória/fisiologia , Receptores de Interleucina-1/antagonistas & inibidores , Animais , Condicionamento Psicológico/efeitos dos fármacos , Medo , Hipocampo/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Transtornos da Memória/metabolismo , Ratos , Ratos Wistar , Receptores de Interleucina-1/metabolismo
12.
Nucleic Acids Res ; 40(20): 10263-73, 2012 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-22941639

RESUMO

UVA (320-400 nm) represents the main spectral component of solar UV radiation, induces pre-mutagenic DNA lesions and is classified as Class I carcinogen. Recently, discussion arose whether UVA induces DNA double-strand breaks (dsbs). Only few reports link the induction of dsbs to UVA exposure and the underlying mechanisms are poorly understood. Using the Comet-assay and γH2AX as markers for dsb formation, we demonstrate the dose-dependent dsb induction by UVA in G(1)-synchronized human keratinocytes (HaCaT) and primary human skin fibroblasts. The number of γH2AX foci increases when a UVA dose is applied in fractions (split dose), with a 2-h recovery period between fractions. The presence of the anti-oxidant Naringin reduces dsb formation significantly. Using an FPG-modified Comet-assay as well as warm and cold repair incubation, we show that dsbs arise partially during repair of bi-stranded, oxidative, clustered DNA lesions. We also demonstrate that on stretched chromatin fibres, 8-oxo-G and abasic sites occur in clusters. This suggests a replication-independent formation of UVA-induced dsbs through clustered single-strand breaks via locally generated reactive oxygen species. Since UVA is the main component of solar UV exposure and is used for artificial UV exposure, our results shine new light on the aetiology of skin cancer.


Assuntos
Quebras de DNA de Cadeia Dupla , Raios Ultravioleta , Células Cultivadas , Cromatina/química , Cromatina/efeitos da radiação , Ensaio Cometa , Dano ao DNA , Reparo do DNA , Sequestradores de Radicais Livres/farmacologia , Histonas/análise , Histonas/metabolismo , Humanos , Oxirredução , Fosforilação , Espécies Reativas de Oxigênio/metabolismo , Pele/efeitos da radiação
13.
Sci Total Environ ; 947: 174195, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38964409

RESUMO

Numerous new lakes have been established during the last few decades. Lakes established on former agricultural soils often have high legacy phosphorus (P)-content, which constitutes a risk for potential internal P-loading after the lake is formed. In this study, we compared the P release and sediment P-pools from 31 new lakes and 31 natural lakes, to assess their similarities and differences. A suite of other sediment characteristics was identified and compared for both natural and new lakes; catchment characteristics of the new lakes also were analyzed. P release from the sediment of new lakes was significantly lower than from natural lakes (13.2 mg P m-2 d-1) compared to new lakes (6.9 mg P m-2 d-1). The P release was found to be low when molar Fe:P ratios were above 10. A significant correlation was found between the content of mobile-P (loosely adsorbed P, iron-bound P, and leachable organic P) and TP in the sediment, irrespective of lake type. The composition of the mobile P-pool also differed, with the new non-excavated lakes showing a higher proportion of RP-BD; both new lake types had significantly (p = 0.021) lower proportions of nrP, compared to natural lakes in the uppermost 10 cm sediment. In addition, variance in P release and mobile-P content of new lakes could be explained in terms of the land use of the catchments. Most sediment characteristics of new lakes established without topsoil excavation reached the average levels of natural Danish lakes with respect to density, organic content and P content within 20-30 years, while excavated lakes showed no such tendencies.

14.
PNAS Nexus ; 3(3): pgae080, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38505694

RESUMO

The ongoing Russian aggression against Ukraine has forced over eight million people to migrate out of Ukraine. Understanding the dynamics of forced migration is essential for policy-making and for delivering humanitarian assistance. Existing work is hindered by a reliance on observational data which is only available well after the fact. In this work, we study the efficacy of a data-driven agent-based framework motivated by social and behavioral theory in predicting outflow of migrants as a result of conflict events during the initial phase of the Ukraine war. We discuss policy use cases for the proposed framework by demonstrating how it can leverage refugee demographic details to answer pressing policy questions. We also show how to incorporate conflict forecast scenarios to predict future conflict-induced migration flows. Detailed future migration estimates across various conflict scenarios can both help to reduce policymaker uncertainty and improve allocation and staging of limited humanitarian resources in crisis settings.

15.
Diabet Med ; 30(5): 590-5, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23320544

RESUMO

AIMS: Consumption of a high-fat diet has been demonstrated to promote endothelial dysfunction, possibly through an increase in lipid peroxidation and decrease in serum nitric oxide. The present study was designed to investigate whether consumption of a hamburger cooked with a polyphenol-rich spice mixture will reduce postprandial lipid oxidation and endothelial dysfunction in men with Type 2 diabetes. METHODS: Twenty-two subjects consumed burgers cooked with salt only (control burger) or with salt and spice mix (spice burger) in randomized order. The postprandial concentration of urinary malondialdehyde and nitrate/nitrite as well as the peripheral arterial tonometry score were determined. RESULTS: Eighteen subjects completed the study. Postprandial serum glucose, insulin and triglyceride concentrations were similar in all subjects after control burger or spice burger consumption. Urine malondialdehyde excretion in mmol/g creatinine was reduced by 31% (P < 0.001) after consuming the spice burger compared with the control burger. Two hours after consumption of the burgers, the peripheral arterial tonometry score was significantly different between control burger consumption (-9.7 ± 21.5%) and spice burger consumption (+18.0 ± 42.4%) (P = 0.025). Mean urinary nitrate/nitrite concentrations in urine collected during the 6 h after consumption of the control burger was 9.09 ± 5.7 mmol/g creatinine, but 12.37 ± 7.00 mmol/g creatinine after the spice burger (P = 0.053). CONCLUSION: Adding a spice mix to hamburger meat prior to cooking resulted in a reduction in urinary malondialdehyde, an increase in urinary nitrate/nitrite and improvement of postprandial endothelial dysfunction in men with Type 2 diabetes. Therefore, cooking a hamburger with a polyphenol-rich spice mixture may lead to potential cardiovascular benefits in patients with Type 2 diabetes mellitus.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Dieta Hiperlipídica/efeitos adversos , Endotélio Vascular/fisiopatologia , Carne , Polifenóis/farmacologia , Período Pós-Prandial , Especiarias , Animais , Bovinos , Culinária , Diabetes Mellitus Tipo 2/sangue , Humanos , Masculino , Malondialdeído/urina , Carne/efeitos adversos , Pessoa de Meia-Idade , Nitratos/metabolismo , Óxido Nítrico/sangue , Nitritos/metabolismo , Estresse Oxidativo
16.
Chem Soc Rev ; 41(12): 4444-56, 2012 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-22491328

RESUMO

Small molecule modulators of biological function can be discovered by the screening of compound libraries. However, it became apparent that some human disease related targets could not be addressed by the libraries commonly used which typically are comprised of large numbers of structurally similar compounds. The last decade has seen a paradigm shift in library construction, with particular emphasis now being placed on increasing a library's structural, and thus functional diversity, rather than only its size. Diversity-oriented synthesis (DOS) aims to generate such structural diversity efficiently. This tutorial review has been written to introduce the subject to a broad audience and recent achievements in both the preparation and the screening of structurally diverse compound collections against so-called 'undruggable' targets are highlighted.


Assuntos
Bioquímica/métodos , Descoberta de Drogas/métodos , Modelos Biológicos , Bibliotecas de Moléculas Pequenas , Animais , Humanos , Camundongos , Modelos Moleculares , Preparações Farmacêuticas/química , Proteínas/química
17.
Front Psychol ; 14: 986289, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37359865

RESUMO

There is little significant work at the intersection of mathematical and computational epidemiology and detailed psychological processes, representations, and mechanisms. This is true despite general agreement in the scientific community and the general public that human behavior in its seemingly infinite variation and heterogeneity, susceptibility to bias, context, and habit is an integral if not fundamental component of what drives the dynamics of infectious disease. The COVID-19 pandemic serves as a close and poignant reminder. We offer a 10-year prospectus of kinds that centers around an unprecedented scientific approach: the integration of detailed psychological models into rigorous mathematical and computational epidemiological frameworks in a way that pushes the boundaries of both psychological science and population models of behavior.

18.
Chemistry ; 18(21): 6548-54, 2012 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-22511395

RESUMO

Carbohydrate microarrays are an emerging tool for the high-throughput screening of carbohydrate-protein interactions that represent the basis of many biologically and medicinally relevant processes. The crucial step in the preparation of carbohydrate arrays is the attachment of carbohydrate probes to the surface. We examined the Diels-Alder reaction with inverse-electron-demand (DARinv) as an irreversible, chemoselective ligation reaction for that purpose. After having shown the efficiency of the DARinv in solution, we prepared a series of carbohydrate-dienophile conjugates that were printed onto tetrazine-modified glass slides. Binding experiments with fluorescently labeled lectins proved successful and homogeneous immobilization was achieved by the DARinv. For immobilization of nonfunctionalized reducing oligosaccharides we developed a bifunctional chemoselective linker that enabled the attachment of a dienophile tag to the oligosaccharides through oxime ligation. The conjugates obtained were successfully immobilized on glass slides. The presented strategies for the immobilization of both synthetic carbohydrate derivatives and unprotected reducing oligosaccharides facilitate the preparation of high-quality carbohydrate microarrays by means of the chemoselective DARinv. This concept can be readily adapted for the preparation of other biomolecule arrays.


Assuntos
Oligossacarídeos/síntese química , Elétrons , Análise em Microsséries , Estrutura Molecular , Oligossacarídeos/química
19.
Org Biomol Chem ; 10(37): 7545-51, 2012 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-22890306

RESUMO

Macrocyclic compounds represent a structural class with exceptional potential for biological activity; however, they have historically been underrepresented in screening collections and synthetic libraries. In this article we report the development of a highly step-efficient strategy for the diversity-oriented synthesis of complex macrocyclic architectures, using a modular approach based on the two-directional synthesis of bifunctional linear precursors and their subsequent combination in a two-directional macrocyclisation process. In this proof of principle study, the synthesis of 14 such compounds was achieved. Cheminformatic analysis of the compounds produced suggests that they reside in biologically relevant regions of chemical space and the compounds were screened for activity against two cancer cell lines.


Assuntos
Antineoplásicos/farmacologia , Compostos Macrocíclicos/farmacologia , Amidas/síntese química , Amidas/química , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Ciclização , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Compostos Macrocíclicos/síntese química , Compostos Macrocíclicos/química , Maleimidas/síntese química , Maleimidas/química , Modelos Moleculares , Estrutura Molecular , Relação Estrutura-Atividade
20.
J Environ Qual ; 41(2): 304-13, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22370392

RESUMO

Phosphorus loss from bank erosion was studied in the catchment of River Odense, a lowland Danish river basin, with the aim of testing the hypothesis of whether stream banks act as major diffuse phosphorus (P) sources at catchment scale. Furthermore, the study aimed at analyzing the impact of different factors influencing bank erosion and P loss such as stream order, anthropogenic disturbances, width of uncultivated buffer strips, and the vegetation of buffer strips. A random stratified procedure in geographical information system (GIS) was used to select two replicate stream reaches covering different stream orders, channelized vs. naturally meandering channels, width of uncultivated buffer strips (≤ 2 m and ≥ 10 m), and buffer strips with different vegetation types. Thirty-six 100-m stream reaches with 180 bank plots and a total of 3000 erosion pins were established in autumn 2006, and readings were conducted during a 3-yr period (2006-2009). The results show that neither stream size nor stream disturbance measured as channelization of channel or the width of uncultivated buffer strip had any significant ( < 0.05) influence on bank erosion and P losses during each of the 3 yr studied. In buffer strips with natural trees bank erosion was significantly ( < 0.05) lower than in buffer strips dominated by grass and herbs. Gross and net P input from bank erosion amounted to 13.8 to 16.5 and 2.4 to 6.3 t P, respectively, in the River Odense catchment during the three study years. The net P input from bank erosion equaled 17 to 29% of the annual total P export and 21 to 62% of the annual export of P from diffuse sources from the River Odense catchment. Most of the exported total P was found to be bioavailable (71.7%) based on a P speciation of monthly suspended sediment samples collected at the outlet of the river basin. The results found in this study have a great importance for managers working with P mitigation and modeling at catchment scale.


Assuntos
Fósforo/análise , Rios/química , Poluentes Químicos da Água/análise , Água/química , Dinamarca , Plantas , Fatores de Tempo
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