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On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G_{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G_{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.
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For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion.
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BACKGROUND: Pathologically prolonged bursts of neural activity in the 8-30â¯Hz frequency range in Parkinson's disease have been measured using high power event detector thresholds. NEW METHOD: This study introduces a novel method for determining beta bursts using a power baseline based on spectral activity that overlapped a simulated 1/f spectrum. We used resting state local field potentials from people with Parkinson's disease and a simulated 1/f signal to measure beta burst durations, to demonstrate how tuning parameters (i.e., bandwidth and center frequency) affect burst durations, to compare burst duration distributions with high power threshold methods, and to study the effect of increasing neurostimulation intensities on burst duration. RESULTS: The baseline method captured a broad distribution of resting state beta band burst durations. Mean beta band burst durations were significantly shorter on compared to off neurostimulation (pâ¯=â¯0.0046), and their distribution shifted towards that of the 1/f spectrum during increasing intensities of stimulation. COMPARISON WITH EXISTING METHODS: High power event detection methods, measure duration of higher power bursts and omit portions of the neural signal. The baseline method captured the broadest distribution of burst durations and was more sensitive than high power detection methods in demonstrating the effect of neurostimulation on beta burst duration. CONCLUSIONS: The baseline method captured a broad range of fluctuations in beta band neural activity and demonstrated that subthalamic neurostimulation shortened burst durations in a dose (intensity) dependent manner, suggesting that beta burst duration is a useful control variable for closed loop algorithms.
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Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Ritmo beta , Humanos , Potenciais da Membrana , Doença de Parkinson/terapiaRESUMO
OBJECTIVES: The aim of this study was to estimate the potential effectiveness of an in-vehicle automatic collision notification (ACN) system in reducing all road crash fatalities in South Australia (SA). METHODS: For the years 2008 to 2009, traffic accident reporting system (TARS) data, emergency medical services (EMS) road crash dispatch data, and coroner's reports were matched and examined. This was done to initially determine the extent to which there were differences between the reported time of a fatal road crash in the mass crash data and the time EMS were notified and dispatched. In the subset of fatal crashes where there was a delay, injuries detailed by a forensic pathologist in individual coroner's reports were examined to determine the likelihood of survival had there not been a delay in emergency medical assistance. RESULTS: In 25% (N = 53) of fatalities in SA in the period 2008 to 2009, there was a delay in the notification of the crash event, and hence dispatch of EMS, that exceeded 10 min. In the 2-year crash period, 5 people were likely to have survived through more prompt crash notification enabling quicker emergency medical assistance. Additionally, 3 people potentially would have survived if surgical intervention (or emergency medical assistance to sustain life until surgery) occurred more promptly. CONCLUSIONS: The minimum effectiveness rate of an ACN system in SA with full deployment is likely to be in the range of 2.4 to 3.8% of all road crash fatalities involving all vehicle types and all vulnerable road users (pedestrians, cyclists, and motorcyclists) from 2008 to 2009. Considering only passenger vehicle occupants, the benefit is likely to be 2.6 to 4.6%. These fatality reductions could only have been achieved through earlier notification of each crash and their location to enable a quicker medical response. This might be achievable through a fully deployed in-vehicle ACN system.
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Acidentes de Trânsito/mortalidade , Automóveis , Sistemas de Comunicação entre Serviços de Emergência , Acidentes de Trânsito/estatística & dados numéricos , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Serviços de Saúde Rural , Austrália do Sul/epidemiologia , Fatores de Tempo , Serviços Urbanos de Saúde , Adulto JovemRESUMO
A novel application of age-period-cohort methods are used to explain changes in vehicle based crash rates in New South Wales, Australia over the period 2003-2010. Models are developed using vehicle age, crash period and vehicle cohort to explain changes in the rate of single vehicle driver fatalities and injuries in vehicles less than 13 years of age. Large declines in risk are associated with vehicle cohorts built after about 1996. The decline in risk appears to have accelerated to 12 percent per vehicle cohort year for cohorts since 2004. Within each cohort, the risk of crashing appears to be a minimum at two years of age and increases as the vehicle ages beyond this. Period effects (i.e., other road safety measures) between 2003 and 2010 appear to have contributed to declines of up to about two percent per annum to the driver-fatality single vehicle crash rate, and possibly only negligible improvements to the driver-injury single vehicle crash rate. Vehicle improvements appear to have been responsible for a decline in per-vehicle crash risk of at least three percent per calendar year for both severity levels over the same period. Given the decline in risk associated with more recent vehicle cohorts and the dynamics of fleet turnover, continued declines in per-vehicle crash risk over coming years are almost certain.
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Acidentes de Trânsito/mortalidade , Acidentes de Trânsito/estatística & dados numéricos , Veículos Automotores/estatística & dados numéricos , Segurança , Ferimentos e Lesões/epidemiologia , Estudos de Coortes , Humanos , New South Wales/epidemiologia , Risco , Fatores de TempoRESUMO
This paper presents the head kinematics of a novel ovine model of non-accidental head injury (NAHI) that consists only of a naturalistic oscillating insult. Nine, 7-to-10-day-old anesthetized and ventilated lambs were subjected to manual shaking. Two six-axis motion sensors tracked the position of the head and torso, and a triaxial accelerometer measured head acceleration. Animals experienced 10 episodes of shaking over 30 min, and then remained under anesthesia for 6h until killed by perfusion fixation of the brain. Each shaking episode lasted for 20s resulting in about 40 cycles per episode. Each cycle typically consisted of three impulsive events that corresponded to specific phases of the head's motion; the most substantial of these were interactions typically with the lamb's own torso, and these generated accelerations of 30-70 g. Impulsive loading was not considered severe. Other kinematic parameters recorded included estimates of head power transfer, head-torso flexion, and rate of flexion. Several styles of shaking were also identified across episodes and subjects. Axonal injury, neuronal reaction and albumin extravasation were widely distributed in the hemispheric white matter, brainstem and at the craniocervical junction and to a much greater magnitude in lower body weight lambs that died. This is the first biomechanical description of a large animal model of NAHI in which repetitive naturalistic insults were applied, and that reproduced a spectrum of injury associated with NAHI.
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Traumatismos Craniocerebrais/fisiopatologia , Aceleração , Animais , Fenômenos Biomecânicos , Cabeça/fisiologia , Humanos , Modelos Animais , Movimento , Síndrome do Bebê Sacudido/fisiopatologia , Ovinos , Carneiro Doméstico , Processamento de Sinais Assistido por Computador , Fatores de TempoRESUMO
Pedestrian impact testing is used to provide information to the public about the relative level of protection provided by different vehicles to a struck pedestrian. Autonomous Emergency Braking (AEB) is a relatively new technology that aims to reduce the impact speed of such crashes. It is expected that vehicles with AEB will pose less harm to pedestrians, and that the benefit will come about through reductions in the number of collisions and a change in the severity of impacts that will still occur. In this paper, an integration of the assessment of AEB performance and impact performance is proposed based on average injury risk. Average injury risk is calculated using the result of an impact test and a previously published distribution of real world crash speeds. A second published speed distribution is used that accounts for the effects of AEB, and reduced average risks are implied. This principle allows the effects of AEB systems and secondary safety performance to be integrated into a single measure of safety. The results are used to examine the effect of AEB on Euro NCAP and ANCAP assessments using previously published results on the likely effect of AEB. The results show that, given certain assumptions about AEB performance, the addition of AEB is approximately the equivalent of increasing Euro NCAP test performance by one band, which corresponds to an increase in the score of 25% of the maximum.
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Acidentes de Trânsito , Automóveis , Traumatismos Craniocerebrais/prevenção & controle , Desaceleração , Desenho de Equipamento , Segurança , Humanos , Manequins , Índices de Gravidade do TraumaRESUMO
Non-accidental head injury (NAHI), also termed the "shaken baby syndrome", is a major cause of death and severe neurological dysfunction in children under three years of age, but it is debated whether shaking alone is sufficient to produce brain injury and mortality or whether an additional head impact is required. In an attempt to resolve this question, we used a lamb model of NAHI since these animals have a relatively large gyrencephalic brain and weak neck muscles resembling those of a human infant. Three anaesthetised lambs of lower body weight than others in the experimental group died unexpectedly after being shaken, proving that shaking alone can be lethal. In these lambs, axonal injury, neuronal reaction and albumin extravasation were widely distributed in the hemispheric white matter, brainstem and at the craniocervical junction, and of much greater magnitude than in higher body weight lambs which did not die. Moreover, in the eyes of these shaken lambs, there was damage to retinal inner nuclear layer neurons, mild, patchy ganglion cell axonal injury, widespread Muller glial reaction, and uveal albumin extravasation. This study proved that shaking of a subset of lambs can result in death, without an additional head impact being required.
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Modelos Animais de Doenças , Síndrome do Bebê Sacudido/patologia , Síndrome do Bebê Sacudido/fisiopatologia , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Encéfalo/patologia , Proteínas de Ligação ao Cálcio , Proteínas de Ligação a DNA/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Proteínas dos Microfilamentos , Neurônios/metabolismo , Neurônios/patologia , Retina/patologia , OvinosRESUMO
The motivation for this paper is the high rate of inappropriate child restraint selection in cars that is apparent in published surveys of child restraint use and how the public health messages promoting child restraints might respond. Advice has increasingly been given solely according to the child's weight, while many parents do not know the weight of their children. A common objection to promoting restraint use based on the age of the child is the imprecision of such advice, given the variation in the size of children, but the magnitude of the misclassification such advice would produce has never been estimated. This paper presents a method for estimating the misclassification of children by weight, when advice is posed in terms of age, and applies it to detailed child growth data published by the Centers for Disease Control and Prevention. In Australia, guidelines instructing all parents to promote their children from an infant restraint to a forward-facing child seat at 6 months, and then to a belt-positioning booster at 4 years, would mean that 5% of all children under the age of 6 years would be using a restraint not suited to their weight. Coordination of aged-based advice and the weight ranges chosen for the Australian Standard on child restraints could reduce this level of misclassification to less than 1%. The general method developed may also be applied to other aspects of restraint design that are more directly relevant to good restraint fit.
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Fatores Etários , Peso Corporal , Educação em Saúde , Equipamentos para Lactente/normas , Austrália , Estatura , Criança , Pré-Escolar , Desenho de Equipamento , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Cintos de Segurança/normas , Fatores SexuaisRESUMO
Motor vehicle airbag technology is directed at the reduction of injury to drivers and passengers however a number of researchers have reported cases of injuries caused by airbags. Injuries to tooth surfaces, particularly tooth wear following the deployment of motor vehicle airbags, have never been studied. A review of the literature and clinical experience does not suggest tooth enamel abrasion to be a likely outcome following airbag deployment. This in vitro pilot study was conducted to assess the effect on tooth surfaces following the deployment of motor vehicle airbags, and in particular to attempt to reproduce the injuries claimed in a case report published in the Journal of Forensic Odonto- Stomatology in December 2007. A sample of extracted upper anterior teeth (n = 20) were analyzed using unaided visual observation, photographic and microscopic observation pre- and post- airbag deployment. Teeth were mounted on a fabricated head form (similar to those used in crash test dummies) using dental putty. The tests were performed using a modified airbag test rig with airbags deployed in 5 different positions relative to the head, with respect to distance and angulations. The result of the tests showed no changes to the teeth with unaided observation, macro photography or under the microscope. Tooth wear patterns described in the case report were not observed. Although accurate reproduction of an in vivo situation is not possible, this study has given some insight into the effects of motor vehicle airbag deployment, and suggests that significant tooth wear is an unlikely outcome from airbag deployment.
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Air Bags , Dente/patologia , Air Bags/efeitos adversos , Dente Canino/patologia , Odontologia Legal , Humanos , Incisivo/patologia , Modelos Anatômicos , Fotografia Dentária , Projetos Piloto , Abrasão Dentária/etiologia , Colo do Dente/patologia , Coroa do Dente/patologiaRESUMO
The paper assesses unplanned operational events at the Sellafield nuclear installation, formerly Windscale and Calder Works, in Cumbria, England, over the period 1950-2000 that had, or could have had, radiological implications for members of the general public. A unified system of off-site impact rating has been developed using a site-specific application of the International Nuclear Event Scale (INES) that is applied retrospectively to events since the start of operations at the site in 1950. Published and unpublished sources of information have been used to assemble what the authors believe to be a complete list of events over the period that would now be assessed as INES level 3 or above on the basis of off-site impact. The last such event occurred in 1984. The exercise also demonstrates that it is possible to apply the current INES rating scheme to a wide variety of radiological events.
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Exposição Ambiental , Reatores Nucleares , Liberação Nociva de Radioativos/classificação , Humanos , Centrais Elétricas , Doses de Radiação , Poluentes Radioativos , Estudos Retrospectivos , Medição de Risco , Reino UnidoRESUMO
Can normal-sized bacteria pass through small holes, and if so how? We have found that common, potentially pathogenic, bacteria (which are nominally larger than 0.2 microm) can cross a 0.2 microm nylon membrane. All of the bacteria crossed from the upper membrane surface to the solid medium below the membrane; this ability was highly repeatable and did not depend on the make of membrane used. Bacteria growing below the membrane exhibited normal size and morphology. We suggest that the ability of common bacteria to pass through small holes has important implications in relation to their role as pathogens.
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Fenômenos Fisiológicos Bacterianos , Membranas ArtificiaisRESUMO
During the life cycle of Physarum polycephalum, uninucleate amoebae develop into multinucleate syncytial plasmodia. These two cell types differ greatly in cellular organisation, behaviour and gene expression. Classical genetic analysis has identified the mating-type gene, matA, as the key gene controlling the initiation of plasmodium development, but nothing is known about the molecular events controlled by matA. In order to identify genes involved in regulating plasmodium formation, we constructed a subtracted cDNA library from cells undergoing development. Three genes that have their highest levels of expression during plasmodium development were identified: redA, redB (regulated in development) and mynD (myosin). Both redA and redB are single-copy genes and are not members of gene families. Although redA has no significant sequence similarities to known genes, redB has sequence similarity to invertebrate sarcoplasmic calcium-binding proteins. The mynD gene is closely related to type II myosin heavy-chain genes from many organisms and is one of a family of type II myosin genes in P. polycephalum. Our results indicate that many more red genes remain to be identified, some of which may play key roles in controlling plasmodium formation.
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Genes de Protozoários , Physarum polycephalum/crescimento & desenvolvimento , Physarum polycephalum/genética , Sequência de Aminoácidos , Animais , DNA Complementar/genética , DNA de Protozoário/genética , Regulação da Expressão Gênica no Desenvolvimento , Biblioteca Gênica , Dados de Sequência Molecular , Homologia de Sequência de AminoácidosRESUMO
The level of contamination by antineoplastic agents in drug preparation and administration areas in cancer treatment centers in Canada and the United States was determined. Sampling locations at three cancer treatment centers in Canada and three centers in the United States were selected (biological safety cabinets, countertops, and floors in and adjacent to preparation areas; tabletops, chairs, and floors in administration areas). A solution of sodium hydroxide (0.03 M) was spread over the surface of each area. The surface was wiped with one or two absorbent tissues, which were then stored in plastic screw-top containers. Samples were stored at -40 degrees C before analysis of ifosfamide content (U.S. centers only) and cyclophosphamide content by gas chromatography in tandem with mass spectroscopy-mass spectroscopy and fluorouracil content by reverse-phase high-performance liquid chromatography with ultraviolet-light detection. Measurable amounts of the antineoplastic agents were detected in 75% of the pharmacy samples and 65% of the administration samples. In general, the levels of contamination were higher in the pharmacy areas than in the drug administration areas. The pharmacy area at the site with the highest number of drug preparations had considerably more drug contamination than the other sites. The results were similar for Canadian and U.S. centers. Substantial levels of contamination from three antineoplastic agents were detected on a variety of surfaces in pharmacy drug preparation areas and drug administration areas in six cancer treatment centers in Canada and the United States.
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Antineoplásicos/análise , Institutos de Câncer/normas , Composição de Medicamentos/normas , Contaminação de Equipamentos , Substâncias Perigosas/análise , Serviço de Farmácia Hospitalar/normas , Gestão da Segurança , Antineoplásicos/efeitos adversos , Canadá , Ciclofosfamida/efeitos adversos , Ciclofosfamida/análise , Fluoruracila/efeitos adversos , Fluoruracila/análise , Substâncias Perigosas/efeitos adversos , Humanos , Ifosfamida/efeitos adversos , Ifosfamida/análise , Oncologia/normas , Exposição Ocupacional/prevenção & controle , Estados UnidosRESUMO
A potential complication of lumbo-sacral surgery is the inadvertent tear of the dura mater, which sometimes eludes intra-operative detection. ADCON-L, a bioabsorbable gel used in lumbosacral laminectomies or laminotomies, is a physical barrier to post-operative epidural fibrosis. Three experimental lumbar laminectomy studies were designed to assess in vivo the effects of ADCON-L when applied in presence of dural punctures in a rat model. In the first study, the durotomy was repaired with fibrin sealant, in the second experiment the dural defect was microsurgically sutured, while in a third protocol the durotomy was left unrepaired. In each study, dural healing was assessed respectively at 4, 8, or 12 weeks post-operatively. Blinded anatomical dissection and histopathology were used to compare results between treatments (sham operated control vs. ADCON-L). In the fibrin sealant experiment, an additional treatment group (fibrin sealant used together with ADCON-L) was included. The results of these studies consistently demonstrate that ADCON-L is an effective anti-fibrotic agent, and does not interfere with the normal dural healing processes following a meningeal puncture. The application of the gel may therefore be safe in presence of dural incisions, even when they are not identified during surgery, as demonstrated in these in vivo studies.
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Discotomia , Dura-Máter/cirurgia , Géis/uso terapêutico , Cicatrização/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Espaço Epidural , Fibrose/prevenção & controle , Região Lombossacral , Masculino , Compostos Orgânicos , Ratos , Ratos Sprague-Dawley , Técnicas de SuturaRESUMO
The two-dimensional distribution of population activity in the superior colliculus (SC) during saccadic eye movements in the monkey was estimated using radial basis functions. To make these ensemble activity estimates, cells in the deeper layers of the SC were recorded over much of the rostrocaudal (caudal to 3.8 mm from the rostral tip), mediolateral extent of this structure. The dynamic movement field of each cell was determined at 2-ms intervals around the time of saccades for a wide variety of horizontal and oblique movements. Collicular neurons were divided into partially overlapping dorsal and ventral cell layers on the basis of recorded depth in SC. The pattern of presaccadic activity was used as an additional discriminant to sort the cells in the two layers into separate burst (dorsal) and buildup (ventral) cell classes. Rostrocaudal and medioventral cell location on the colliculus was estimated from the optimal target vector for a cell's visual response rather than from the optimal motor vector. The former technique was more reliable for locating some buildup neurons because it produced locations that compared better with the locations suggested by electrical stimulation. From the movement field data and from the estimates of each cell's anatomic location, a similar algorithm was used to compute the two-dimensional population activity in the two layers of the SC during horizontal and oblique saccades. A subset of the sample of neurons, located near the horizontal meridian of the SC, first was used to compute one-dimensional dynamic population activity estimates for horizontal saccades to allow partial comparison to previous studies. Statistical analyses on the one-dimensional data were limited to saccades of =20 degrees. The analyses indicated that while there was a small rostrally directed shift in the center of gravity of the distributed activity in the buildup cell layer, there was little support for the theory of a systematic rostrally directed spread of the leading edge of the activity. The two-dimensional results extend the previous one-dimensional estimates of collicular activity during saccades. Discharge in the burst layer was invariant in size for all saccade vectors and symmetrically arranged about a center of gravity that did not move during saccades. The size of the active area in the buildup layer grew modestly with saccade amplitude, whereas the distribution of activity was skewed toward the rostral end of the SC for saccades larger than 10 degrees. There was a small, but consistent shift in the center of gravity of the two-dimensional activity that was directed along the horizontal meridian (for horizontal movements) or an oblique meridian (for oblique movements) of the SC. However, the spread of activity during a saccade was as large or larger in the mediolateral direction as it was in the rostral direction. The results indicate that changes in activity occur in an extended zone on the SC, and in all directions but caudal, in the buildup layer during saccades and do not support the idea of a rostrally directed spread of activity as a dynamic control mechanism for saccades. Our results and those of previous investigators of collicular population activity may be limited by stationarity concerns in that the cells used to estimate population activity were recorded in several monkeys over an extended period of time to obtain a sufficient spatial sample.
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Neurônios Motores/fisiologia , Movimentos Sacádicos/fisiologia , Colículos Superiores/citologia , Colículos Superiores/fisiologia , Algoritmos , Animais , Estimulação Elétrica , Eletrofisiologia , Interneurônios/fisiologia , Macaca fascicularis , Macaca mulatta , Masculino , Neurônios Motores/classificação , Neurônios Aferentes/fisiologiaRESUMO
There is significant experimental evidence for bound water in collagen and related polymers. (Pro-Pro-Gly)10 [(PPG)10] is a polymer that forms a collagen-like triple-helical structure in aqueous solution. Like collagen, (PPG)10 adopts a structure in which side chains are mostly exposed to solvent, and the backbone polar groups are limited in their ability to form hydrogen bonds with each other. (PPG)10, like collagen, also has many of its backbone polar groups in positions that inhibit complete solvation in aqueous solution; thus the necessity of bound waters for stabilization of the structure. We have constructed a model for bound waters in (PPG)10, based on an examination of the geometry and steric environment of the backbone polar groups. As will become clear, the number of bound waters is determined by the geometry of the backbone carbonyl groups and the steric crowding surrounding them. In this model, each water forms one hydrogen bond with each of two backbone carbonyls from a glycine and a proline in different monomer chains, thus bridging the two carbonyls. The carbonyls in question are quite sterically crowded by neighboring (PPG)10 atoms and would not be likely to experience complete solvation by bulk solvent in aqueous solution. The bound waters are therefore likely to be present even in solution, since otherwise the unsatisfied hydrogen-bonding potential of the carbonyls would destabilize the structure. Other carbonyls also are sterically crowded and possibly prevented from experiencing full solvation, but are not in a favorable geometry for such bridging hydrogen bonds. The intra- and interchain interactions found in a previous computational study of (PPG)10 without bound waters are not disrupted by the addition of waters.
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Oligopeptídeos/química , Polímeros/química , Conformação Proteica , Modelos Moleculares , ÁguaRESUMO
A rapid method for measuring nicotine concentration in serum and urine is described. Deuterated nicotine is used as an internal standard. Nicotine and deuterated nicotine are extracted using a copolymeric-bonded phase silica column. The extract is analysed by gas chromatography coupled with mass spectrometry (GC/MS) operating in selected ion monitoring mode. The method has a lower limit of detection of approximately 2 micrograms/L and is linear to at least 2000 micrograms/L. Within-run percentage coefficients of variation (% CV) are < 4 in both assays over a nicotine concentration range of 10-2000 micrograms/L. Between-run % CV in the serum assay are 5.4, 5.2, 4.8 and 5.9, respectively, at nicotine concentrations of 10, 15, 25, and 50 micrograms/L. Between-run % CV in the urine assay are 5.9, 4.5, 2.7 and 5.2, respectively, at nicotine concentrations of 100, 250, 500, and 2000 micrograms/L. The absolute recovery of nicotine is 61 +/- 6% (mean +/- SD) over the range of 10-250 micrograms/L. The assay has been used to measure serum nicotine concentrations and 24-h urinary excretion of nicotine to monitor the extent of replacement in subjects receiving transdermal nicotine therapy for smoking cessation.