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1.
Plant Physiol ; 187(3): 1117-1130, 2021 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-34618063

RESUMO

Optimizing root system architecture offers a promising approach to developing stress tolerant cultivars in the face of climate change, as root systems are critical for water and nutrient uptake as well as mechanical stability. However, breeding for optimal root system architecture has been hindered by the difficulty in measuring root growth in the field. Here, we describe the RootTracker, a technology that employs impedance touch sensors to monitor in-field root growth over time. Configured in a cylindrical, window shutter-like fashion around a planted seed, 264 electrodes are individually charged multiple times over the course of an experiment. Signature changes in the measured capacitance and resistance readings indicate when a root has touched or grown close to an electrode. Using the RootTracker, we have measured root system dynamics of commercial maize (Zea mays) hybrids growing in both typical Midwest field conditions and under different irrigation regimes. We observed rapid responses of root growth to water deficits and found evidence for a "priming response" in which an early water deficit causes more and deeper roots to grow at later time periods. Genotypic variation among hybrid maize lines in their root growth in response to drought indicated a potential to breed for root systems adapted for different environments. Thus, the RootTracker is able to capture changes in root growth over time in response to environmental perturbations.


Assuntos
Raízes de Plantas/fisiologia , Estresse Fisiológico , Tecnologia/instrumentação , Zea mays/fisiologia , Eletrodos , Meio Ambiente , Raízes de Plantas/crescimento & desenvolvimento , Água/fisiologia , Zea mays/crescimento & desenvolvimento
2.
Plant Physiol ; 171(3): 2028-40, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27208237

RESUMO

Root system architecture (RSA) impacts plant fitness and crop yield by facilitating efficient nutrient and water uptake from the soil. A better understanding of the effects of soil on RSA could improve crop productivity by matching roots to their soil environment. We used x-ray computed tomography to perform a detailed three-dimensional quantification of changes in rice (Oryza sativa) RSA in response to the physical properties of a granular substrate. We characterized the RSA of eight rice cultivars in five different growth substrates and determined that RSA is the result of interactions between genotype and growth environment. We identified cultivar-specific changes in RSA in response to changing growth substrate texture. The cultivar Azucena exhibited low RSA plasticity in all growth substrates, whereas cultivar Bala root depth was a function of soil hardness. Our imaging techniques provide a framework to study RSA in different growth environments, the results of which can be used to improve root traits with agronomic potential.


Assuntos
Oryza/fisiologia , Raízes de Plantas/anatomia & histologia , Raízes de Plantas/fisiologia , Solo/química , Tomografia Computadorizada por Raios X/métodos , Secas , Interação Gene-Ambiente , Genótipo , Oryza/anatomia & histologia , Oryza/genética
3.
J Neuroeng Rehabil ; 11: 105, 2014 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-24981060

RESUMO

BACKGROUND: Functional electrical stimulation (FES) during repetitive practice of everyday tasks can facilitate recovery of upper limb function following stroke. Reduction in impairment is strongly associated with how closely FES assists performance, with advanced iterative learning control (ILC) technology providing precise upper-limb assistance. The aim of this study is to investigate the feasibility of extending ILC technology to control FES of three muscle groups in the upper limb to facilitate functional motor recovery post-stroke. METHODS: Five stroke participants with established hemiplegia undertook eighteen intervention sessions, each of one hour duration. During each session FES was applied to the anterior deltoid, triceps, and wrist/finger extensors to assist performance of functional tasks with real-objects, including closing a drawer and pressing a light switch. Advanced model-based ILC controllers used kinematic data from previous attempts at each task to update the FES applied to each muscle on the subsequent trial. This produced stimulation profiles that facilitated accurate completion of each task while encouraging voluntary effort by the participant. Kinematic data were collected using a Microsoft Kinect, and mechanical arm support was provided by a SaeboMAS. Participants completed Fugl-Meyer and Action Research Arm Test clinical assessments pre- and post-intervention, as well as FES-unassisted tasks during each intervention session. RESULTS: Fugl-Meyer and Action Research Arm Test scores both significantly improved from pre- to post-intervention by 4.4 points. Improvements were also found in FES-unassisted performance, and the amount of arm support required to successfully perform the tasks was reduced. CONCLUSIONS: This feasibility study indicates that technology comprising low-cost hardware fused with advanced FES controllers accurately assists upper limb movement and may reduce upper limb impairments following stroke.


Assuntos
Terapia por Estimulação Elétrica/métodos , Recuperação de Função Fisiológica , Reabilitação do Acidente Vascular Cerebral , Extremidade Superior/fisiopatologia , Adulto , Fenômenos Biomecânicos , Cotovelo/fisiopatologia , Estudos de Viabilidade , Feminino , Hemiplegia/etiologia , Hemiplegia/fisiopatologia , Hemiplegia/reabilitação , Humanos , Masculino , Pessoa de Meia-Idade , Ombro/fisiopatologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/fisiopatologia , Punho/fisiopatologia
4.
Plant J ; 70(1): 5-17, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22449039

RESUMO

Plant development and survival is centered on complex regulatory networks composed of genes, proteins, hormone pathways, metabolites and signaling pathways. The recent advancements in whole genome biology have furthered our understanding of the interactions between these networks. As a result, numerous cell type-specific transcriptome profiles have been generated that have elucidated complex gene regulatory networks occurring at the cellular level, many of which were masked during whole-organ analysis. Modern technologies have also allowed researchers to generate multiple whole-organ metabolite profiles; however, only a limited number have been generated at the level of individual cells. Recent advancements in the isolation of individual cell populations have made cell type-specific metabolite profiles possible, enabling the enhanced detection and quantification of metabolites that were formerly unavailable when considering the whole organ. The comparison of metabolite and transcriptome profiles from the same cells has been a valuable resource to generate predictions regarding specific metabolite activity and function. In this review, we focus on recent studies that demonstrate the value of cell type-specific transcriptional profiles and their comparison with profiles generated from whole organs. Advancements in the isolation of single-cell populations will be highlighted, and the potential application towards generating detailed metabolic profiles will be discussed.


Assuntos
Perfilação da Expressão Gênica , Metabolômica , Plantas/genética , Plantas/metabolismo , Citometria de Fluxo , Redes Reguladoras de Genes , Microdissecção e Captura a Laser , Meristema/citologia , Meristema/genética , Meristema/metabolismo , Raízes de Plantas/citologia , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Brotos de Planta/citologia , Brotos de Planta/genética , Brotos de Planta/metabolismo
5.
Biomolecules ; 13(9)2023 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-37759710

RESUMO

Though originally characterized as an inactive or transcriptionally repressive factor, the NF-κB p50 homodimer has become appreciated as a physiologically relevant driver of specific target gene expression. By virtue of its low affinity for cytoplasmic IκB protein inhibitors, p50 accumulates in the nucleus of resting cells, where it is a binding target for the transcriptional co-activator IκBζ. In this study, we employed X-ray crystallography to analyze the structure of the p50 homodimer on κB DNA from the promoters of human interleukin-6 (IL-6) and neutrophil-gelatinase-associated lipocalin (NGAL) genes, both of which respond to IκBζ. The NF-κB p50 homodimer binds 11-bp on IL-6 κB DNA, while, on NGAL κB DNA, the spacing is 12-bp. This begs the question: what DNA binding mode is preferred by NF-κB p50 homodimer? To address this, we engineered a "Test" κB-like DNA containing the core sequence 5'-GGGGAATTCCCC-3' and determined its X-ray crystal structure in complex with p50. This revealed that, when presented with multiple options, NF-κB p50 homodimer prefers to bind 11-bp, which necessarily imposes asymmetry on the complex despite the symmetry inherent in both the protein and its target DNA, and that the p50 dimerization domain can contact DNA via distinct modes.


Assuntos
Interleucina-6 , Subunidade p50 de NF-kappa B , NF-kappa B , Humanos , Cristalografia por Raios X , DNA , Lipocalina-2 , Raios X , Subunidade p50 de NF-kappa B/química , Subunidade p50 de NF-kappa B/fisiologia
6.
J Neuroeng Rehabil ; 9: 32, 2012 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-22676920

RESUMO

BACKGROUND: Novel stroke rehabilitation techniques that employ electrical stimulation (ES) and robotic technologies are effective in reducing upper limb impairments. ES is most effective when it is applied to support the patients' voluntary effort; however, current systems fail to fully exploit this connection. This study builds on previous work using advanced ES controllers, and aims to investigate the feasibility of Stimulation Assistance through Iterative Learning (SAIL), a novel upper limb stroke rehabilitation system which utilises robotic support, ES, and voluntary effort. METHODS: Five hemiparetic, chronic stroke participants with impaired upper limb function attended 18, 1 hour intervention sessions. Participants completed virtual reality tracking tasks whereby they moved their impaired arm to follow a slowly moving sphere along a specified trajectory. To do this, the participants' arm was supported by a robot. ES, mediated by advanced iterative learning control (ILC) algorithms, was applied to the triceps and anterior deltoid muscles. Each movement was repeated 6 times and ILC adjusted the amount of stimulation applied on each trial to improve accuracy and maximise voluntary effort. Participants completed clinical assessments (Fugl-Meyer, Action Research Arm Test) at baseline and post-intervention, as well as unassisted tracking tasks at the beginning and end of each intervention session. Data were analysed using t-tests and linear regression. RESULTS: From baseline to post-intervention, Fugl-Meyer scores improved, assisted and unassisted tracking performance improved, and the amount of ES required to assist tracking reduced. CONCLUSIONS: The concept of minimising support from ES using ILC algorithms was demonstrated. The positive results are promising with respect to reducing upper limb impairments following stroke, however, a larger study is required to confirm this.


Assuntos
Inteligência Artificial , Estimulação Elétrica/métodos , Transtornos dos Movimentos/etiologia , Transtornos dos Movimentos/reabilitação , Robótica/métodos , Tecnologia Assistiva , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral/complicações , Adulto , Idoso , Algoritmos , Braço/fisiologia , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Movimento/fisiologia , Músculo Esquelético/fisiologia , Paresia/reabilitação , Desempenho Psicomotor/fisiologia , Recuperação de Função Fisiológica , Resultado do Tratamento , Extremidade Superior/fisiologia , Interface Usuário-Computador
7.
Br J Haematol ; 155(2): 190-7, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21848883

RESUMO

Intensive chemotherapy regimens are not feasible in many adults with mantle cell lymphoma (MCL). We sought to build upon our previous experience with a non-intensive regimen, modified R-hyperCVAD chemotherapy (rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone) with maintenance rituximab (MR), by the incorporation of bortezomib (VcR-CVAD) and the extension of MR beyond 2 years. Patients with previously untreated MCL received VcR-CVAD chemotherapy every 21 d for six cycles. Patients achieving at least a partial response to induction chemotherapy received rituximab consolidation (375 mg/m(2) × 4 weekly doses) and MR (375 mg/m(2) every 12 weeks × 20 doses). The primary end points were overall and complete response (CR), and secondary endpoints were progression-free (PFS) and overall survival (OS). Thirty patients were enrolled, with a median age of 61 years. All patients had advanced stage disease, and 60% had medium/high MCL International Prognostic Index risk factors. A CR or unconfirmed CR was achieved in 77% of patients. After a median follow-up of 42 months, the 3-year PFS and OS were 63% and 86%, respectively. The observed 3-year PFS and OS with VcR-CVAD in MCL were comparable to reported outcomes with more intensive regimens. A cooperative group trial (E1405) is attempting to replicate these promising results.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Célula do Manto/tratamento farmacológico , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Anticorpos Monoclonais Murinos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ácidos Borônicos/administração & dosagem , Ácidos Borônicos/efeitos adversos , Bortezomib , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Doenças Hematológicas/induzido quimicamente , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Modelos de Riscos Proporcionais , Inibidores de Proteases/administração & dosagem , Inibidores de Proteases/efeitos adversos , Inibidores de Proteases/farmacologia , Pirazinas/administração & dosagem , Pirazinas/efeitos adversos , Indução de Remissão , Rituximab , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversos
8.
Bioorg Med Chem ; 19(18): 5648-69, 2011 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-21840722

RESUMO

Most nucleosides in solution typically exist in equilibrium between two major sugar pucker forms, N-type and S-type, but bridged nucleosides can be locked into one of these conformations depending on their specific structure. While many groups have researched these bridged nucleosides for the purpose of determining their binding affinity for antisense applications, we opted to look into the potential for biological activity within these conformationally-locked structures. A small library of 2',4'- and 3',4'-bridged nucleoside analogues was synthesized, including a novel 3',4'-carbocyclic bridged system. The synthesized compounds were tested for antibacterial, antitumor, and antiviral activities, leading to the identification of nucleosides possessing such biological activities. To the best of our knowledge, these biologically active compounds represent the first example of 2',4'-bridged nucleosides to demonstrate such properties. The most potent compound, nucleoside 33, exhibited significant antiviral activity against pseudoviruses SF162 (IC(50)=7.0 µM) and HxB2 (IC(50)=2.4 µM). These findings render bridged nucleosides as credible leads for drug discovery in the anti-HIV area of research.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Antivirais/farmacologia , Nucleosídeos/síntese química , Nucleosídeos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Antivirais/síntese química , Antivirais/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Escherichia coli/efeitos dos fármacos , Células HEK293 , HIV-1/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Nucleosídeos/química , Staphylococcus aureus/efeitos dos fármacos , Estereoisomerismo , Relação Estrutura-Atividade
9.
J Cell Biol ; 157(2): 219-29, 2002 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-11940606

RESUMO

Accurate chromosome segregation during cell division requires not only the establishment, but also the precise, regulated release of chromosome cohesion. Chromosome dynamics during meiosis are more complicated, because homologues separate at anaphase I whereas sister chromatids remain attached until anaphase II. How the selective release of chromosome cohesion is regulated during meiosis remains unclear. We show that the aurora-B kinase AIR-2 regulates the selective release of chromosome cohesion during Caenorhabditis elegans meiosis. AIR-2 localizes to subchromosomal regions corresponding to last points of contact between homologues in metaphase I and between sister chromatids in metaphase II. Depletion of AIR-2 by RNA interference (RNAi) prevents chromosome separation at both anaphases, with concomitant prevention of meiotic cohesin REC-8 release from meiotic chromosomes. We show that AIR-2 phosphorylates REC-8 at a major amino acid in vitro. Interestingly, depletion of two PP1 phosphatases, CeGLC-7alpha and CeGLC-7beta, abolishes the restricted localization pattern of AIR-2. In Ceglc-7alpha/beta(RNAi) embryos, AIR-2 is detected on the entire bivalent. Concurrently, chromosomal REC-8 is dramatically reduced and sister chromatids are separated precociously at anaphase I in Ceglc-7alpha/beta(RNAi) embryos. We propose that AIR-2 promotes the release of chromosome cohesion via phosphorylation of REC-8 at specific chromosomal locations and that CeGLC-7alpha/beta, directly or indirectly, antagonize AIR-2 activity.


Assuntos
Caenorhabditis elegans/citologia , Caenorhabditis elegans/enzimologia , Pareamento Cromossômico , Segregação de Cromossomos , Cromossomos/metabolismo , Meiose , Proteínas Serina-Treonina Quinases/metabolismo , Anáfase , Animais , Aurora Quinase B , Aurora Quinases , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Cromossomos/genética , Proteínas de Helminto/metabolismo , Metáfase , Microscopia de Fluorescência , Mutação , Oócitos , Fosfoproteínas Fosfatases/metabolismo , Fosforilação , Proteínas Serina-Treonina Quinases/genética , Transporte Proteico , RNA de Cadeia Dupla/metabolismo , Homologia de Sequência do Ácido Nucleico , Fatores de Tempo
10.
ISA Trans ; 95: 152-163, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31178034

RESUMO

The subject area considered is discrete linear time delay systems operating repetitively on a finite time interval with actuator faults, where the system resets at the end of each operation. Regulation of the dynamics is by iterative learning control and performance goals imposed over finite frequency intervals for the case of uncertainty in the dynamic model. To derive the results, the generalized Kalman-Yakubovich-Popov lemma is used. A simulation based case study is also given to demonstrate the applicability of the new results.

11.
Genetics ; 176(4): 2027-33, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17565963

RESUMO

SYP-3 is a new structural component of the synaptonemal complex (SC) required for the regulation of chromosome synapsis. Both chromosome morphogenesis and nuclear organization are altered throughout the germlines of syp-3 mutants. Here, our analysis of syp-3 mutants provides insights into the relationship between chromosome conformation and the repair of meiotic double-strand breaks (DSBs). Although crossover recombination is severely reduced in syp-3 mutants, the production of viable offspring accompanied by the disappearance of RAD-51 foci suggests that DSBs are being repaired in these synapsis-defective mutants. Our studies indicate that once interhomolog recombination is impaired, both intersister recombination and nonhomologous end-joining pathways may contribute to repair during germline meiosis. Moreover, our studies suggest that the conformation of chromosomes may influence the mode of DSB repair employed during meiosis.


Assuntos
Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Pareamento Cromossômico/genética , Animais , Caenorhabditis elegans/citologia , Troca Genética , Quebras de DNA de Cadeia Dupla , Reparo do DNA , Feminino , Genes de Helmintos , Masculino , Meiose/genética , Mutação , Recombinação Genética , Complexo Sinaptonêmico/genética
12.
Rice (N Y) ; 11(1): 43, 2018 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-30066052

RESUMO

BACKGROUND: Traditional rice (Oryza sativa) varieties are valuable resources for the improvement of drought resistance. qDTY3.2 is a drought-yield quantitative trait locus that was identified in a population derived from the traditional variety Moroberekan and the drought-susceptible variety Swarna. In this study, our aim was to characterize the physiological mechanisms associated with qDTY3.2. Our approach was to phenotype fifteen BC2F3:4 lines for shoot and root drought resistance-related traits as compared to Swarna in the field under well-watered and drought stress conditions. Four BC2F3:4 lines contrasting for yield under drought were selected for detailed characterization of shoot morphology, water use related traits, flowering time and root system architecture in the field as well as in controlled environments (lysimeters in a greenhouse, and gel imaging platform in a growth chamber). RESULTS: Across five field experiments, grain yield correlated significantly with root growth along the soil profile, flowering time, and canopy temperature under drought conditions. The four selected BC2F3:4 lines showed earlier flowering time, reduced distribution of root growth to shallow soil layers which resulted in lower water uptake (between 0 and 30 cm) and drought-induced increased distribution of root growth to deep soil layers (between 30 and 60 cm) as compared to Swarna in the field. Root system architecture phenotypes were confirmed in whole root systems in lysimeters, and corresponded to higher numbers of root tips in a gel imaging platform, highlighting the potential stability of some root traits across different growth stages and systems. CONCLUSIONS: We conclude that earlier flowering time, reduced shallow root growth, and drought-induced increased deep root growth are associated with the presence of qDTY3.2 since these phenotypes were consistently observed in the selected QTL lines with full introgression of qDTY3.2. We hypothesize that the qDTY3.2 associated RSA phenotypes led to better use of water and metabolic resources which, combined with earlier flowering time, improved yield under drought.

13.
Oncotarget ; 8(55): 94711-94725, 2017 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-29212260

RESUMO

Acquired cisplatin resistance is a common feature of tumours following cancer treatment with cisplatin and also of non-small cell lung cancer (H1299) and mesothelioma (P31) cell lines exposed to cisplatin. To elucidate the cellular basis of acquired cisplatin resistance, a comprehensive bioenergetic analysis was undertaken. We demonstrate that cellular oxygen consumption was significantly decreased in cisplatin resistant cells and that the reduction was primarily due to reduced mitochondrial activity as a result of reduced mitochondrial abundance. The differential mitochondrial abundance was supported by data showing reduced sirtuin 1 (SIRT1), peroxisome-proliferator activator receptor-γ co-activator 1-alpha (PGC1α), sirtuin 3 (SIRT3) and mitochondrial transcription factor A (TFAM) protein expression in resistant cells. Consistent with these data we observed increased reactive oxygen species (ROS) production and increased hypoxia inducible factor 1-alpha (HIF1α) stabilization in cisplatin resistant cells when compared to cisplatin sensitive controls. We also observed an increase in AMP kinase subunit α2 (AMPKα2) transcripts and protein expression in resistant H1299 cells. mRNA expression was also reduced for cisplatin resistant H1299 cells in these genes, however the pattern was not consistent in resistant P31 cells. There was very little change in DNA methylation of these genes, suggesting that the cells are not stably reprogrammed epigenetically. Taken together, our data demonstrate reduced oxidative metabolism, reduced mitochondrial abundance, potential for increased glycolytic flux and increased ROS production in acquired cisplatin resistant cells. This suggests that the metabolic changes are a result of reduced SIRT3 expression and increased HIF-1α stabilization.

14.
Clin Cancer Res ; 11(24 Pt 1): 8722-7, 2005 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-16361559

RESUMO

PURPOSE: Rodent models of human breast cancer suggest that the combination of the steroidal aromatase inhibitor exemestane with tamoxifen may have additive activity. Clinical trials combining tamoxifen with letrozole or anastrazole have shown minor pharmacokinetic drug interactions. We did an open-label crossover clinical trial of the effect of exemestane on tamoxifen pharmacokinetics. DESIGN: Thirty-two postmenopausal women who were clinically disease-free following primary treatments for breast cancer receiving tamoxifen for at least 3 months were studied. Blood was collected for pharmacokinetic analysis after at least 4 months of receiving 20 mg tamoxifen daily. Subjects then began 8 weeks of oral exemestane (25 mg daily), followed by another set of blood samples. RESULTS: There were no serious toxicities noted when the two drugs were combined. There was no significant effect of exemestane on the area under the plasma concentration versus time curve (AUC) of tamoxifen at steady state before [3.04 mg h/L; 90% confidence interval (90% CI), 2.71-3.44] and during exemestane treatment (3.05 mg h/L; 90% CI, 2.72-3.41). There were no significant changes in the formation of primary tamoxifen metabolites. Oral clearance of exemestane averaged 602 L/h based on an average plasma exemestane AUC of 41.5 microg h/L (90% CI, 36.7-62.6). Plasma concentrations of estradiol, estrone, and estrone sulfate decreased when exemestane was begun; estradiol concentrations consistently decreased below the limit of quantitation. CONCLUSIONS: There is no pharmacokinetic interaction between tamoxifen and exemestane. No modification in the standard regimen of either drug seems to be indicated if they are used in combination. The combination of the two drugs was well tolerated during the 8-week evaluation period.


Assuntos
Androstadienos/farmacologia , Antineoplásicos Hormonais/farmacocinética , Inibidores da Aromatase/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Tamoxifeno/farmacocinética , Adulto , Idoso , Androstadienos/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/administração & dosagem , Neoplasias da Mama/sangue , Interações Medicamentosas , Estradiol/sangue , Estrona/análogos & derivados , Estrona/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa/sangue , Tamoxifeno/administração & dosagem , Tamoxifeno/uso terapêutico
15.
Artigo em Inglês | MEDLINE | ID: mdl-28210420

RESUMO

This paper continues an initiative conducted by the International Society for Disease Surveillance with funding from the Defense Threat Reduction Agency to connect near-term analytical needs of public health practice with technical expertise from the global research community. The goal is to enhance investigation capabilities of day-to-day population health monitors. A prior paper described the formation of consultancies for requirements analysis and dialogue regarding costs and benefits of sustainable analytic tools. Each funded consultancy targets a use case of near-term concern to practitioners. The consultancy featured here focused on improving predictions of asthma exacerbation risk in demographic and geographic subdivisions of the city of Boston, Massachusetts, USA based on the combination of known risk factors for which evidence is routinely available. A cross-disciplinary group of 28 stakeholders attended the consultancy on March 30-31, 2016 at the Boston Public Health Commission. Known asthma exacerbation risk factors are upper respiratory virus transmission, particularly in school-age children, harsh or extreme weather conditions, and poor air quality. Meteorological subject matter experts described availability and usage of data sources representing these risk factors. Modelers presented multiple analytic approaches including mechanistic models, machine learning approaches, simulation techniques, and hybrids. Health department staff and local partners discussed surveillance operations, constraints, and operational system requirements. Attendees valued the direct exchange of information among public health practitioners, system designers, and modelers. Discussion finalized design of an 8-year de-identified dataset of Boston ED patient records for modeling partners who sign a standard data use agreement.

16.
Curr Opin Biotechnol ; 32: 93-98, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25448235

RESUMO

Root system architecture (RSA) plays a major role in plant fitness, crop performance, and grain yield yet only recently has this role been appreciated. RSA describes the spatial arrangement of root tissue within the soil and is therefore crucial to nutrient and water uptake. Recent studies have identified many of the genetic and environmental factors influencing root growth that contribute to RSA. Some of the identified genes have the potential to limit crop loss caused by environmental extremes and are currently being used to confer drought tolerance. It is hypothesized that manipulating these and other genes that influence RSA will be pivotal for future crop advancements worldwide.


Assuntos
Raízes de Plantas/fisiologia , Produtos Agrícolas , Secas , Aptidão Genética , Solo , Água
17.
IEEE Int Conf Rehabil Robot ; 2013: 6650359, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24187178

RESUMO

Therapies using functional electrical stimulation (FES) in conjunction with practice of everyday tasks have proven effective in facilitating recovery of upper limb function following stroke. The aim of the current study is to develop a multi-channel electrical stimulation system that precisely controls the assistance provided in goal-orientated tasks through use of advanced model-based 'iterative learning control' (ILC) algorithms to facilitate functional motor recovery of the upper limb post-stroke. FES was applied to three muscle groups in the upper limb (the anterior deltoid, triceps and wrist extensors) to assist hemiparetic, chronic stroke participants to perform a series of functional tasks with real objects, including closing a drawer, turning on a light switch and repositioning an object. Position data from the participants' impaired upper limb was collected using a Microsoft Kinect® and was compared to an ideal reference. ILC used data from previous attempts at the task to moderate the FES signals applied to each muscle group on a trial by trial basis to reduce performance error whilst supporting voluntary effort by the participant. The clinical trial is on-going. Preliminary results show improvements in performance accuracy for each muscle group, as well as improvements in clinical outcome measures pre and post 18 training sessions. Thus, the feasibility of applying precisely controlled FES to three muscle groups in the upper limb to facilitate functional reach and grasp movements post stroke has been demonstrated.


Assuntos
Terapia por Estimulação Elétrica/métodos , Paresia/reabilitação , Reabilitação do Acidente Vascular Cerebral , Extremidade Superior/fisiopatologia , Adulto , Algoritmos , Estudos de Viabilidade , Humanos , Aprendizagem , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiologia , Recuperação de Função Fisiológica , Robótica/métodos , Acidente Vascular Cerebral/fisiopatologia , Resultado do Tratamento
18.
PLoS One ; 7(5): e36483, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22606264

RESUMO

Much effort has focused recently on determining the mechanisms that control the allele-specific expression of genes subject to genomic imprinting, yet imprinting regulation is only one aspect of configuring appropriate expression of these genes. Imprinting control mechanisms must interact with those regulating the tissue-specific expression pattern of each imprinted gene in a cluster. Proper expression of the imprinted Delta-like 1 (Dlk1)-Maternally expressed gene 3 (Meg3) gene pair is required for normal fetal development in mammals, yet the mechanisms that control tissue-specific expression of these genes are unknown. We have used a combination of in vivo and in vitro expression assays to localize cis-regulatory elements that may regulate Dlk1 expression in the mouse embryo. A bacterial artificial chromosome transgene encompassing the Dlk1 gene and 77 kb of flanking sequence conferred expression in most endogenous Dlk1-expressing tissues. In combination with previous transgenic data, these experiments localize the majority of Dlk1 cis-regulatory elements to a 41 kb region upstream of the gene. Cross-species sequence conservation was used to further define potential regulatory elements, several of which functioned as enhancers in a luciferase expression assay. Two of these elements were able to drive expression of a lacZ reporter transgene in Dlk1-expressing tissues in the mouse embryo. The sequence proximal to Dlk1 therefore contains at least two discrete regions that may regulate tissue-specificity of Dlk1 expression.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/genética , Elementos Reguladores de Transcrição , Animais , Sequência de Bases , Proteínas de Ligação ao Cálcio , Cromossomos Artificiais Bacterianos/genética , Sequência Conservada , Primers do DNA/genética , Elementos Facilitadores Genéticos , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Impressão Genômica , Óperon Lac , Camundongos , Camundongos Transgênicos , Músculo Esquelético/embriologia , Músculo Esquelético/metabolismo , RNA Longo não Codificante , RNA não Traduzido/genética , Distribuição Tecidual
19.
Artigo em Inglês | MEDLINE | ID: mdl-20698789

RESUMO

PURPOSE: User perceptions are critical, yet often ignored factors in the design and development of rehabilitation technologies. In this article, measures for collection of patient perceptions are developed and applied to a novel upper limb workstation that combines robotic therapy and electrical stimulation (ES). METHOD: Five participants with chronic upper limb hemiplegia post-stroke used a robotic workstation to undertake supported tracking tasks augmented by precisely controlled ES to their triceps muscle. Following a 6 week trial, a purpose designed set of questions was developed and individual interviews were conducted by an independent health psychologist. RESULTS: The simple, quick to administer question set showed that participants had a positive response to the system, and contributed valuable feedback with regard to its usability and effectiveness. Participants want a home-based system targeting their whole arm. CONCLUSION: This article demonstrates the value in assessing user perceptions of a rehabilitation system via a simple question set. While the results of this study have implications for a wider audience, our recommendations are for a qualitative study to develop a generic evaluation tool which could be used across the growing number of devices to provide feedback to enhance future development of any new technology for rehabilitation.


Assuntos
Terapia por Estimulação Elétrica/métodos , Hemiplegia/reabilitação , Satisfação do Paciente , Robótica , Reabilitação do Acidente Vascular Cerebral , Extremidade Superior , Adulto , Idoso , Atitude Frente a Saúde , Feminino , Hemiplegia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Modalidades de Fisioterapia , Acidente Vascular Cerebral/complicações
20.
IEEE Int Conf Rehabil Robot ; 2011: 5975502, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22275698

RESUMO

A novel system has been developed which combines robotic therapy with electrical stimulation (ES) for upper limb stroke rehabilitation. This technology, termed SAIL: Stimulation Assistance through Iterative Learning, employs advanced model-based iterative learning control (ILC) algorithms to precisely assist participant's completion of 3D tracking tasks with their impaired arm. Data is reported from a preliminary study with unimpaired participants, and also from a single hemiparetic stroke participant with reduced upper limb function who has used the system in a clinical trial. All participants completed tasks which involved moving their (impaired) arm to follow an image of a slowing moving sphere along a trajectory. The participants' arm was supported by a robot and ES was applied to the triceps brachii and anterior deltoid muscles. During each task, the same tracking trajectory was repeated 6 times and ILC was used to compute the stimulation signals to be applied on the next iteration. Unimpaired participants took part in a single, one hour training session and the stroke participant undertook 18, 1 hour treatment sessions composed of tracking tasks varying in length, orientation and speed. The results reported describe changes in tracking ability and demonstrate feasibility of the SAIL system for upper limb rehabilitation.


Assuntos
Robótica/instrumentação , Robótica/métodos , Reabilitação do Acidente Vascular Cerebral , Extremidade Superior/fisiologia , Estimulação Elétrica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica
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