RESUMO
Power system reliability is sensitive to climate-driven variations in both energy demand and water availability, yet the combined effect of these impacts is rarely evaluated. Here we show that combined climate change impacts on loads and hydropower generation may have a transformative effect on the nature and seasonality of power shortfall risk in the U.S. Pacific Northwest. Under climate change, potential shortfall events occur more readily, but are significantly less severe in nature. A seasonal reversal in shortfall risk occurs: winter shortfalls are eradicated due to reduced building heating demands, while summer shortfalls multiply as increased peak loads for day-time cooling coincide with impaired hydropower generation. Many of these summer shortfalls go unregistered when climate change impacts on loads and hydropower dispatch are analyzed in isolation-highlighting an important role of compound events.
RESUMO
Human peripheral blood γδ T cells expressing the Vγ9Vδ2 T cell receptor are activated by microbial or endogenous pyrophosphate antigens and indirectly by nitrogen-containing bisphosphonates. Apart from proliferation, such phosphoantigens induce proinflammatory cytokine production including TNF-α and IFN-γ and trigger cytotoxic effector function. Neutrophil granulocytes are known to modulate T cell activation. The neutrophil serine proteases proteinase 3, elastase and cathepsin G have multiple potential targets and promote microbial killing. In this study, we investigated the effect of the three serine proteases on the in vitro proliferation and effector functions of γδ T cells cultured in serum-free medium. All three proteases inhibited the proliferative activity, suppressed the cytokine production and decreased the cytotoxicity of γδ T cells. Further studies indicated that proteolytic cleavage of IL-2 and modulation of butyrophilin 3A1 (CD277) expression might contribute to the overall inhibition.
Assuntos
Ativação Linfocitária/imunologia , Neutrófilos/enzimologia , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Serina Proteases/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Antígenos CD/metabolismo , Butirofilinas , Proliferação de Células/efeitos dos fármacos , Citocinas/biossíntese , Citotoxicidade Imunológica/efeitos dos fármacos , Humanos , Imunofenotipagem , Interleucina-2/metabolismo , Interleucina-2/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Receptores de Interleucina-2/metabolismo , Serina Proteases/farmacologia , Subpopulações de Linfócitos T/efeitos dos fármacosRESUMO
Natural killer (NK) cells are innate immune cells involved in antiviral defence and tumour surveillance. To fulfil these tasks, NK cells make use of two major effector functions, cytokine and chemokine release and cytotoxicity. In addition, NK cells proliferate in response to cytokines such as IL-2. NK cells possess a large array of activating and inhibitory receptors and their activation demands a complex crosstalk between those receptors. The signalling pathways leading to NK-cell activation are a field of intensive research. The first clue for signal specificity was provided by studies showing that a pathway leading to NF-κB activation selectively induces cytokine release, but is dispensable for cytotoxicity. Here, we demonstrate that in human NK cells caspase activity is required for the upregulation of select activation markers and IFN-γ and TNF production, but not for cytotoxicity. Interestingly, caspases have previously been linked in T cells to the same mechanism of NF-κB induction that is active in NK cells. Moreover, we provide evidence that caspases are involved in IL-2-induced proliferation. Thus, our data provide the basis for a novel approach using caspase inhibitors to generate cytotoxic NK cells, while simultaneously suppressing cytokine release.
Assuntos
Caspases/metabolismo , Proliferação de Células , Citocinas/metabolismo , Células Matadoras Naturais/metabolismo , Clorometilcetonas de Aminoácidos/farmacologia , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Inibidores de Caspase , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Inibidores de Cisteína Proteinase/farmacologia , Ativação Enzimática/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Antígenos HLA-DR/metabolismo , Humanos , Interferon gama/metabolismo , Interleucina-2/farmacologia , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Células K562 , Células Matadoras Naturais/citologia , Células Matadoras Naturais/efeitos dos fármacos , Lectinas Tipo C/metabolismo , Fatores de Tempo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Twenty one of 118 irrigation water wells in the shallow (25-30 m thick) Mississippi River Valley alluvial aquifer in the Bayou Bartholomew watershed, southeastern Arkansas had arsenic (As) concentrations (<0.5 to 77 microg/L) exceeding 10 microg/L. Sediment and groundwater samples were collected and analyzed from the sites of the highest, median, and lowest concentrations of As in groundwater in the alluvial aquifers located at Jefferson County, Arkansas. A traditional five-step sequential extraction was performed to differentiate the exchangeable, carbonate, amorphous Fe and Mn oxide, organic, and hot HNO(3)-leachable fraction of As and other compounds in sediments. The Chao reagent (0.25 M hydroxylamine hydrochloride in 0.25 M HCl) removes amorphous Fe and Mn oxides and oxyhydroxides (present as coatings on grains and amorphous minerals) by reductive dissolution and is a measure of reducible Fe and Mn in sediments. The hot HNO(3) extraction removes mostly crystalline metal oxides and all other labile forms of As. Significant total As (20%) is complexed with amorphous Fe and Mn oxides in sediments. Arsenic abundance is not significant in carbonates or organic matter. Significant (40-70 microg/kg) exchangeable As is only present at shallow depth (0-1 m below ground surface). Arsenic is positively correlated to Fe extracted by Chao reagent (r=0.83) and hot HNO(3) (r=0.85). Arsenic extracted by Chao reagent decreases significantly with depth as compared to As extracted by hot HNO(3). Fe (II)/Fe (the ratio of Fe concentration in the extracts of Chao reagent and hot HNO(3)) is positively correlated (r=0.76) to As extracted from Chao reagent. Although Fe (II)/Fe increases with depth, the relative abundance of reducible Fe decreases noticeably with depth. The amount of reducible Fe, as well as As complexed to amorphous Fe and Mn oxides and oxyhydroxides decreases with depth. Possible explanations for the decrease in reducible Fe and its complexed As with depth include historic flushing of As and Fe from hydrous ferric oxides (HFO) by microbially-mediated reductive dissolution and aging of HFO to crystalline phases. Hydrogeochemical data suggests that the groundwater in the area falls in the mildly reducing (suboxic) to relatively highly reducing (anoxic) zone, and points to reductive dissolution of HFO as the dominant As release mechanism. Spatial variability of gypsum solubility and simultaneous SO(4)(2-) reduction with co-precipitation of As and sulfide is an important limiting process controlling the concentration of As in groundwater in the area.
Assuntos
Arsênio/análise , Monitoramento Ambiental , Sedimentos Geológicos/análise , Rios , Poluentes Químicos da Água/análise , Áreas Alagadas , Arkansas , Substâncias Húmicas/análise , Modelos Teóricos , Oxirredução , Solubilidade , Abastecimento de Água/análise , Abastecimento de Água/normasRESUMO
A 56-year-old man developed a nasal field defect in his left eye 3 months after a traumatic accident. An examination showed a posterior subcapsular cataract in the left eye with no neurologic deficits. Humphrey 24-2 visual field testing revealed a nasal hemianopsia in the left eye. After cataract extraction and intraocular lens implantation, the patient's visual field returned to normal. This case shows that a cataract can present with a localized visual field deficit, which may be corrected by cataract extraction.
Assuntos
Catarata/diagnóstico , Traumatismos Oculares/diagnóstico , Hemianopsia/diagnóstico , Cristalino/lesões , Extração de Catarata , Humanos , Implante de Lente Intraocular , Masculino , Pessoa de Meia-Idade , Campos VisuaisRESUMO
True exfoliation or lamellar delamination of the lens capsule is a rare disorder in which the lens capsule is thickened and the superficial portion of the lens capsule splits from the deeper layer and extends into the anterior chamber. The pathogenesis of this disorder is not clear, but intense infrared radiation has been thought to be the main causative factor. We describe a patient with a history of heat exposure who had a cataract and was found to have bilateral delamination of the anterior lens capsule. Findings from light microscopy and scanning and transmission electron microscopy demonstrated a lamellar separation of the anterior portion of the lens capsule, confirming the diagnosis of true exfoliation.
Assuntos
Síndrome de Exfoliação/patologia , Cápsula do Cristalino/patologia , Doenças do Cristalino/patologia , Idoso , Idoso de 80 Anos ou mais , Extração de Catarata , Feminino , Humanos , Cápsula do Cristalino/ultraestrutura , Acuidade VisualRESUMO
Two patients with symptomatic fast/slow pathway double responses were evaluated with electrophysiology studies. Chronic palpitations were resistant or worsened by medical therapy. No reentry tachycardias were induced. A nonreentrant paroxysmal supraventricular tachycardia was documented. Radiofrequency ablation of the slow pathway was safely and successfully performed. Patients remain asymptomatic for 16-18 months. Ablation of the slow pathway for this substrate is a viable option.
Assuntos
Ablação por Cateter , Eletrocardiografia , Taquicardia por Reentrada no Nó Atrioventricular/cirurgia , Taquicardia Paroxística/cirurgia , Adulto , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/cirurgia , Nó Atrioventricular/fisiopatologia , Nó Atrioventricular/cirurgia , Estimulação Cardíaca Artificial , Eletrocardiografia Ambulatorial , Feminino , Seguimentos , Humanos , Taquicardia por Reentrada no Nó Atrioventricular/diagnóstico , Taquicardia por Reentrada no Nó Atrioventricular/fisiopatologia , Taquicardia Paroxística/diagnóstico , Taquicardia Paroxística/fisiopatologia , Resultado do TratamentoRESUMO
Motor imagery is a dynamic state in which an individual mentally simulates the performance of a specific motor action or motor task. Recent behavioural and neuroimaging evidence suggests that the same neurocognitive networks control real and imagined movements. This hypothesis was tested by investigating whether motor asymmetries related to cerebral dominance also occurred for imagined movements. Fifty subjects performed the visually guided pointing task of Sirigu et al. [Sirigu, A., Duhamel, J., Cohen, L., Pillon, B., Dubois, B. and Agid, Y., The mental representation of hand movements after parietal cortex damage. Science, 1996, 273, 1564-1567.] using their dominant and non-dominant hands. Analysis of group data indicated that both real and imagined movement conformed to Fitts' law. Analysis of individual data indicated that asymmetries arising from motor dominance in real movements also occurred for imagined movements. However, the relative slowing and error associated with the non-dominant hand was greater for imagined movements than for real movements. These asymmetries support the hypothesis that real and imagined movements are represented within the same neurocognitive networks but suggest that asymmetries in performance related to handedness are greater for imagined movements. In addition, while the visually guided pointing task provides a useful test of the ability to make imagined movements, asymmetries in the speed and reliability of imagined performance are significantly greater than those for real performance.
Assuntos
Córtex Cerebral/fisiologia , Lateralidade Funcional , Imaginação/fisiologia , Destreza Motora , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora , Análise e Desempenho de Tarefas , Fatores de TempoAssuntos
Humanos , Feminino , Gravidez , Anormalidades Congênitas , Desenvolvimento Fetal , Feto , Complicações na Gravidez , Gravidez MúltiplaRESUMO
Although pleural and pericardial effusions are common and may rarely be the initial manifestation of disease, there are few reports of SLE diagnosed in a cytopathology laboratory. We describe an unusual case of SLE in a 75-year-old man who presented with cardiac tamponade. Cytologic examination of the pericardial fluid revealed numerous LE cells and led to the diagnosis of SLE. This case illustrates the importance of careful evaluation of a serous effusion for LE cells in patients of either gender and of any age.
Assuntos
Tamponamento Cardíaco/patologia , Lúpus Eritematoso Sistêmico/patologia , Derrame Pericárdico/citologia , Idoso , Tamponamento Cardíaco/complicações , Humanos , Lúpus Eritematoso Sistêmico/complicações , MasculinoRESUMO
This paper reports the results of a study that explored the relationship between fatal crashes and conflict rates at mid-block on 14 locations in Delhi, India. All locations had a mix of motorized and non-motorized traffic. The sites were selected to represent low, medium and high fatality rates. The analysis was done in two stages. The first stage used recent 3-year statistics along the entire street. The second stage focused on each fatal crash for mid-block segments on those streets. Peak-hour traffic at 14 selected locations was videotaped. Trained observers recorded traffic compositions at mid-block, average space mean speeds by mode and conflicts by type, reactor mode and cause mode. After converting raw conflict counts to rates, site ranking went from high to low conflict rate sites. The studies showed a weak crash-conflict association. Conflict data for various sites were compared for different combinations of conflicts. The comparison revealed that the presence of only a few non-motorized modes is enough to cause conflicts between motorized vehicles and on-road non-motorized vehicles. The study did not provide a conclusive relationship between mid-block conflicts and fatal crash sites. However, the conflict study provided useful insights into the interaction between different traffic entities in the traffic streams of 14 sites. An important conclusion of this study is that a traffic-planning emphasis on studying conflict rates may not result in reducing fatality rates on urban roads along mid-block segments.
Assuntos
Acidentes de Trânsito/mortalidade , Prevenção de Acidentes , Acidentes de Trânsito/prevenção & controle , Acidentes de Trânsito/estatística & dados numéricos , Planejamento Ambiental , Humanos , ÍndiaAssuntos
Traumatismos Craniocerebrais/enfermagem , Emergências/enfermagem , Corpos Estranhos/enfermagem , Ferimentos Penetrantes/enfermagem , Adulto , Traumatismos Craniocerebrais/diagnóstico por imagem , Traumatismos Craniocerebrais/cirurgia , Corpos Estranhos/diagnóstico por imagem , Corpos Estranhos/cirurgia , Humanos , Masculino , Radiografia , Ferimentos Penetrantes/diagnóstico por imagem , Ferimentos Penetrantes/cirurgiaRESUMO
Tonic immobility in chickens was influenced by a variety of drugs that act on the adrenergic neurochemical system of the body. Alpha 1 agonists such as methoxamine and phenylephrine produced decreases in the duration of immobility, although the former compound also caused a significant increase in the immobility response at high dosages. Alpha 2 agonists such as clonidine, naphazoline, and guanfacine enhanced the duration of immobility, but clonidine also produced an apparent reversal of this effect at high dosages. Subsequent experiments examined more fully the biphasic effects by methoxamine and clonidine on tonic immobility through interactions with alpha antagonists. Yohimbine, an alpha 2 blocker, attenuated the duration of immobility, either alone or in conjunction with various dosages of methoxamine. Prazosin, an alpha 1 blocker, had no direct effect on tonic immobility, but potentiated the duration of the response when given in conjunction with various dosages of methoxamine. When these antagonists were given in conjunction with clonidine, yohimbine reduced immobility durations, while prazosin had no apparent effect on this response. These results are discussed in terms of the relative contributions of the alpha 1 and alpha 2 adrenoceptors to the duration of the immobility response.
Assuntos
Agonistas alfa-Adrenérgicos/farmacologia , Antagonistas Adrenérgicos alfa/farmacologia , Comportamento Animal/fisiologia , Animais , Galinhas , Clonidina/farmacologia , Guanfacina , Guanidinas/farmacologia , Metoxamina/farmacologia , Nafazolina/farmacologia , Fenilacetatos/farmacologia , Fenilefrina/farmacologia , Prazosina/farmacologia , Restrição Física , Fatores de Tempo , Ioimbina/farmacologiaRESUMO
Groups of young chickens were injected with various dosages of several alpha-adrenergic antagonists and tested for the effects of these drugs on tonic immobility. Yohimbine, a very potent alpha2 antagonist, produced a significant decrease in the duration of tonic immobility at doses of 1 mg/kg, while prazosin, a potent alpha1 antagonist, had no apparent effect on immobility duration. Phentolamine, a on-specific alpha antagonist, produced a significant decrease in the duration of immobility at doses of 0.1 mg/kg, but had no effect at higher or lower doses. These results support the involvement of the alpha-adrenergic system with the duration of the tonic immobility reflex, but at the same time they also suggest that alpha2 receptors are more closely involved with the immobility response than alpha1 receptors. However, none of these drugs had any apparent effect on the initial susceptibility of subjects to the immobility reflex, as measured by the number of inductions required to produce tonic immobility.
Assuntos
Antagonistas Adrenérgicos alfa/farmacologia , Atividade Motora/efeitos dos fármacos , Animais , Galinhas , Relação Dose-Resposta a Droga , Fentolamina/farmacologia , Prazosina/farmacologia , Ioimbina/farmacologiaRESUMO
A method was developed for determining methyl and propyl p-hydroxybenzoates (methyl and propyl parabens) in comminuted meats. The parabens were extracted from the meat sample with acetonitrile. After filtering, the extract was analyzed by reverse phase high pressure liquid chromatography, using a 254 nm absorbance detector. Samples of bologna, chicken roll, and chopped ham were fortified with approximately 100, 200, and 400 ppm of each paraben. Average recoveries were 92% for methyl paraben and 94% for propyl paraben.