Detection of biomolecular binding by fourier-transform SPR

Journal ArticleSurface plasmon resonance (SPR) is a widely used label-free detection technique that has many applications in drug discovery, pharmacokinetics, systems biology and food science. The SPR technique measures the dynamics of a biomolecular interaction at a surface, yielding kinetic association and dissociation constants. Present SPR systems measure the step response of the interaction in time domain hence are subject to time-varying noise disturbances and drifts that limit the minimum-detectable mass changes. This paper presents a new synchronous SPR technique that measures the biomolecular interaction not in time domain, but in frequency domain with a high degree of rejection to uncorrelated spurious signals. The new technique was implemented using a PDMS microfluidic chemical signal modulator chip connected to a set of on-chip functionalized Au SPR sensing sites. Preliminary experimental spectral data for a model system of carbonic anhydrase binding demonstrates the feasibility of the new spectral technique

Mechanisms of degassing at Nevado del Ruiz volcano, Colombia

Author Posting. © Geological Society, 2003. This article is posted here by permission of Geological Society for personal use, not for redistribution. The definitive version was published in Journal of the Geological Society 160 (2003): 507-521, doi:10.1144/0016-764902-028.Nevado del Ruiz volcano is an andesite stratovolcano located in the northern Andes of Colombia. The volcano erupted on 11 September 1985, 13 November 1985, and 1 September 1989. The last two eruptions emitted juvenile solid material. This paper examines the volatile and light lithophile trace element contents of melt inclusions and matrix glasses from this juvenile material, and proposes a model for degassing within the volcano. Major element distributions in the glasses show two evolutionary trends, with subsidiary points that lie between the two trends. The data suggest the existence of two separate magmas, which have interacted, mingled, and mixed during their ascent and eruption. Water contents in melt inclusions, as determined by secondary ionization mass spectrometric analysis, are generally low, averaging between 1.6 and 3.3 wt.%. Halogen concentrations in the glasses range from 400 to 1200 ppm for fluorine and from 1100 to 1500 ppm for chlorine. Sulphur contents are low, not exceeding 500 ppm, with most glasses containing <200 ppm. Lithium concentrations range from 20 to 40 ppm, beryllium from 1.5 to 2 ppm, and boron exhibits high variability from 30 to 100 ppm. The only significant difference between melt inclusions and matrix glasses is for water, with matrix glasses having significantly lower concentrations (<0.5 wt.%) than the melt inclusions. The generally elevated concentrations of boron in the magma may be a consequence of enrichment in the source region of the magma, i.e. by subduction of altered oceanic crust and/or sediments. Yet the large degree of boron heterogeneity in both melt inclusions and matrix glasses necessitates subsequent addition of boron at shallower depths as well, by the assimilation of crustal sedimentary rocks or by interaction with hydrothermal fluids. Evidence for pre-eruptive magma emplacement at shallow levels is provided by (1) anhydrous mineral assemblages of plagioclase and pyroxene, (2) high silica contents of glasses, and (3) low water contents in melt inclusions. When combined, these observations suggest a period of magma residence at shallow depths, probably <3 km beneath the summit of the volcano. A multistage model of magma transport and degassing involves alternating periods of magma ascent and magma ponding. Initially, volatile-bearing magma ascends from depths of 9–15 km, driven by buoyancy. During decompression, the magma loses gas, particularly CO2 and sulphur. The magma eventually ponds at its neutral buoyancy level. At this point, the gas-saturated magma cools and crystallizes, thereby liberating gas under isobaric conditions. As a result, CO2 is depleted from the magma whereas H2O and SiO2 are enriched. The H2O enrichment is caused by its increased solubility in the magma as CO2 is degassed, whereas SiO2 is enriched by fractional crystallization. The density of the magma decreases as the level of dissolved H2O increases, eventually causing the magma to become buoyant once more and to continue its ascent, either to erupt or to freeze at shallow depths.This work was funded with grants to J.S. by the Natural Sciences and Engineering Research Council of Canada and by the Fonds pour la formation de chercheurs et l’aide a` la recherche (Que´bec)

A multidisciplinary stroke clinic for outpatient care of veterans with cerebrovascular disease

Background: Managing cerebrovascular risk factors is complex and difficult. The objective of this program evaluation was to assess the effectiveness of an outpatient Multidisciplinary Stroke Clinic model for the clinical management of veterans with cerebrovascular disease or cerebrovascular risk factors. Methods: The Multidisciplinary Stroke Clinic provided care to veterans with cerebrovascular disease during a one-half day clinic visit with interdisciplinary evaluations and feedback from nursing, health psychology, rehabilitation medicine, internal medicine, and neurology. We conducted a program evaluation of the clinic by assessing clinical care outcomes, patient satisfaction, provider satisfaction, and costs. Results: We evaluated the care and outcomes of the first consecutive 162 patients who were cared for in the clinic. Patients had as many as six clinic visits. Systolic and diastolic blood pressure decreased: 137.2 ± 22.0 mm Hg versus 128.6 ± 19.8 mm Hg, P = 0.007 and 77.9 ± 14.8 mm Hg versus 72.0 ± 10.2 mm Hg, P = 0.004, respectively as did low-density lipoprotein (LDL)-cholesterol (101.9 ± 23.1 mg/dL versus 80.6 ± 25.0 mg/dL, P = 0.001). All patients had at least one major change recommended in their care management. Both patients and providers reported high satisfaction levels with the clinic. Veterans with stroke who were cared for in the clinic had similar or lower costs than veterans with stroke who were cared for elsewhere. Conclusion: A Multidisciplinary Stroke Clinic model provides incremental improvement in quality of care for complex patients with cerebrovascular disease at costs that are comparable to usual post-stroke care

Coronaridine congeners attenuate fentanyl seeking during prolonged abstinence

Background: The prevalence of opioid use disorder (OUD) has reached epidemic proportions with a record-breaking number of overdose deaths. Over 70% of the record-breaking number of overdose deaths are caused by synthetic opioids, including fentanyl. Fentanyl is commonly administered intravenously or by inhalation (smoking/vaping), which results in rapid drug bioavailability in the brain. There is a current need to identify a novel pharmacologic therapy to treat OUD, and there is increasing evidence to support the use of novel compounds referred to as coronaridine congeners to treat OUD and other psychiatric illnesses. In preclinical models, coronaridine congeners have been shown to decrease self-administration of drugs of abuse and induce antidepressant and anxiolytic effects. Here we used a preclinical fentanyl vapor self-administration model and fast-scan cyclic voltammetry (FSCV) to study the anti-addictive effects of two coronaridine congeners, 18-methoxycoronaridine (18-MC) and catharanthine (Cath).Methods: C57BL/6J mice were trained to self-administer vaporized fentanyl (5 mg/mL) or vehicle in airtight operant chambers. Mice self-administered vapor for 1 hour per day for 10 days (sessions were conducted for 5 consecutive days, followed by 2 days off). Chambers were equipped with two nosepokes, one active and one inactive. A successful response in the active nosepoke resulted in a vapor delivery that coincided with the presentation of a cue light, followed by a 1-minute timeout period. Mice learned to self-administer vapor with 3-second vapor deliveries for the first 3 days of training, which was then reduced to 1.5-second vapor deliveries the remaining 7 days. After training, mice were returned to their home cages for a forced abstinence period. Cue-induced drug seeking tests were conducted on abstinence days (AD) 20 and 25. During cue-induced seeking tests, successful responses in the active nosepoke resulted in presentation of the drug-associated cue, but no vapor was delivered (i.e. extinction conditions). Cue-induced drug seeking tests were conducted using a crossover design where half of subjects received coronaridine treatment (18-MC or Cath), while the other half received vehicle (ddH2O), on AD20. On AD25, subjects received the opposite treatment compared to AD20. Mice were injected (i.p.) with either vehicle or coronaridine treatment 1 hour before seeking tests. To examine the molecular mechanism of coronaridine congeners, FSCV was conducted on dopaminergic pre-synaptic terminals in the nucleus accumbens (NAc) neurons to measure dopamine (DA) release in the presence of 18-MC and Cath with or without nicotinic acetylcholine receptor antagonists.Results: We found that both 18-MC and Cath significantly reduced fentanylseeking during prolonged abstinence with no effect on mice that had previously self-administered vehicle. Furthermore, FSCV revealed that 18-MC and Cath significantly reduced DA release onto NAc neurons.Conclusion: In this study, we report that both 18-MC and Cath decrease fentanyl seeking during prolonged abstinence. DA release is important for opioid-related behaviors, and we found that 18-MC and Cath reduce DA release in the NAc, a mechanism that may underlie the effect of coronaridine congeners on fentanyl seeking. Together, these results provide evidence that coronaridine congeners may be promising novel compounds for the pharmacotherapeutic treatment of OUD

Efeito do tratamento com aminoetoxivinilglicina (AVG) na queda pré-colheita e na maturação dos frutos em macieiras

ABSTRACTApple trees cultivars Gala and Fuji were sprayed four weeks before commercial harvest with aminoethoxyvinilglycine (AVG), at doses of 0, 125, or 250 mg L-1, and assessed for preharvest fruit drop, fruit growth, and maturation on tree. In 'Gala', 64 days after AVG spraying, fruit drop for control treatment was 85%, and AVG (at 125 and 250 mg L-1) reduced it to 10%. In 'Fuji', 64 days after AVG spraying, fruit drop for control was 6%, while treatments with AVG (at 125 and 250 mg L-1) increased fruit drop to 10%. AVG was a powerful retardant of fruit maturation for 'Gala' but not for 'Fuji'. In 'Gala', the most affected attribute was the skin background color, followed, in decreasing order, by soluble solids content, the starch index, skin red color, the flesh firmness, and titratable acidity. In 'Gala', only flesh firmness retention was improved by increasing AVG dose from 125 mg L-1 to 250 mg L-1. The AVG at 250 mg L-1 inhibited "Gala" late fruit growth but not 'Fuji'. __________________________________________________________________________________ RESUMOMacieiras, das cultivares Gala e Fuji, foram pulverizadas quatro semanas antes do início da colheita comercial dos frutos com aminoetoxivinilglicina (AVG), nas concentrações de 0; 125 ou 250 mg L-1, e avaliadas quanto à queda de frutos na pré-colheita, o crescimento e maturação dos frutos. Na cultivar Gala, 64 dias após a pulverização com AVG, a queda pré-colheita no tratamento-controle era de 85%, mas os tratamentos com AVG (125 e 250 mg L-1) reduziram esta queda para 10%. Na cultivar Fuji, 64 dias após a pulverização com AVG, a queda de frutos no tratamento-controle era de 6%, e os tratamentos com AVG (125 e 250 mg L-1) aumentaram esta queda para 10%. Tratamentos com AVG retardaram substancialmente a maturação dos frutos da cultivar Gala, mas não da 'Fuji'. Na cultivar Gala, o atributo mais afetado foi a cor de fundo da casca, seguido, em ordem decrescente, pelo conteúdo de sólidos solúveis totais, índice de iodo-amido, cor vermelha da casca, firmeza de polpa e acidez titulável. Na cultivar Gala, apenas a retenção de firmeza de polpa foi significativamente aumentada com o aumento na concentração de AVG de 125 mg L-1 para 250 mg L-1. A concentração de 250 mg L-1 inibiu o crescimento final de frutos na cultivar Gala, mas não na 'Fuji'

Providers’ Perspectives on Troublesome Overusers of Medical Services

The purpose of this study was to better understand providers’ perspectives of and experiences with frequent users of medical services. Focus group interviews were con¬ducted with physicians in San Diego, California, and Omaha, Nebraska. Indicators of problematic patient overuse of medical services were identified as well as the common physician experience of overuse that is troublesome and problematic. Qualitative data analysis revealed that physicians did not consider patient overuse, by itself, to be problematic. Overuse became problematic and troublesome when patient behavior violated the physician-patient relationship of trust. All participants described a distinct negative physiological reaction to these patients

SIMS chlorine isotope analyses in melt inclusions from arc settings

International audienceThe relative contribution of volatiles from altered oceanic crust, serpentinized mantle, and subducted sediments on the composition of primary arc magmas is poorly constrained. We measured the chlorine stable isotope composition in olivine-hosted melt inclusions in order to provide a first order constraint on the δ37Cl values of primary magmas, since melt inclusions are not or only little affected by near surface processes. Chlorine isotope analyses were obtained with a CAMECA IMS 1280-HR at the University of Lausanne. A series of six Cl-bearing glass standards with δ37Cl values of − 1.1 to + 1.7‰, SiO2 between 50 and 76 wt% and Cl concentration between 0.15 and 3.25 wt% were used for calibration. We determined that SiO2, Al2O3 and K2O in glasses are primarily responsible for the observed variations in instrumental mass fractionation.We obtained a δ37Cl reproducibility on the standard glasses typically better than 0.3‰ (2SD) and a total uncertainty, corresponding to the propagated error of SIMS and Pyro-IRMS uncertainty, of 0.4‰ (2SD). Melt inclusions from Lesser Antilles, Vanuatu and Aeolian arcs display ranges of δ37Cl values from − 1.9 to + 0.6‰, − 1.7 to + 0.4‰ and − 3.4 to − 1.4‰ respectively. Combined with Cl/K2O ratios, these data suggest that Cl addition mainly originates from serpentinites (lithospheric serpentinites or serpentinized mantle wedge) in the Lesser Antilles and Vanuatu arcs. In contrast, Cl added to the mantle wedge beneath the Aeolian Islands may record a higher proportion of fluids derived from the subducting sediments. The observed differences of δ37Cl values in melt inclusions from the Lesser Antilles and Vanuatu arcs and the Aeolian Islands may directly reflect the different subduction geometries present