Influence of personalized extended interval dosing on the natalizumab wearing-off effect - a sub-study of the NEXT-MS trial.

BACKGROUND AND OBJECTIVES: Wearing-off symptoms during natalizumab treatment in multiple sclerosis are characterized by an increase of MS-related symptoms prior to natalizumab administration. The influence of extended interval dosing (EID) on wearing-off symptoms are important to consider, as this might cause hesitancy in initiating or continuing EID. METHODS: Participants of the NEXT-MS trial, in which treatment intervals are adjusted based on drug concentrations, were divided into two groups: an extended group containing participants with at least one week of additional interval extension, and a group with a fixed interval during the trial (range 4-7 weeks). Changes in the occurrence, frequency, onset, and severity of wearing-off symptoms were evaluated. RESULTS: 255 participants were included (extended group n = 171, fixed group n = 84). The odds on occurrence of wearing-off symptoms in the extended group did not increase after extending the treatment interval. Additional analyses for frequency, onset, and severity of wearing-off symptoms showed no changes over time. Mean decrease in natalizumab drug concentration did not influence the frequency of wearing-off symptoms. DISCUSSION: Wearing-off symptoms were not reinforced by further extending the natalizumab interval. Wearing-off symptoms might increase in a minority of patients after EID, although our data support the view that wearing-off symptoms appear to be unrelated to the decrease in natalizumab trough drug concentrations.

Cross-sectional and longitudinal correlations between the Arm Function in Multiple Sclerosis Questionnaire (AMSQ) and other outcome measures in multiple sclerosis.

BACKGROUND: The Arm Function in Multiple Sclerosis Questionnaire (AMSQ) is the first validated disease specific patient-reported outcome measure (PROM) designed to assess upper extremity function in patients with multiple sclerosis (MS). OBJECTIVE: To determine correlations between the AMSQ and established physician- and performance based outcome measures. METHODS: In a cross-sectional cohort of 533 patients correlations between the AMSQ and the Expanded Disability Status Scale (EDSS), its functional systems, the 9-Hole Peg Test (9-HPT) and the Timed-25 Foot Walk (T25FW) were determined. Subgroup analyses were performed as well. Also, correlations were determined in 110 of 533 patients with available longitudinal data. RESULTS: Strongest correlations were found in the cross-sectional cohort between the AMSQ and the EDSS (ß 0.60, p<.001), the 9-HPT dominant hand (ß 0.52, p<.001) and 9-HPT non-dominant hand (ß 0.46, p<.001), the Pyramidal (ß 0.57 p<.001) and the Cerebellar functional system (ß 0.54, p<.001) of the EDSS. CONCLUSION: The moderate correlations between the AMSQ and several established physician- and performance based outcome measures underline that the AMSQ, an easily at long-distance administrable PROM, could be considered as a reliable outcome measure for the monitoring of MS in daily practice. Additional research is needed to support these findings.

Responder rates to fampridine differ between clinical subgroups of MS patients and patient reported outcome influences treatment decision making.

BACKGROUND: Fampridine is an effective treatment to improve ambulation for some multiple sclerosis (MS) patients. Remarkable discrepancies exist between responder rates in clinical trials and the proportion of patients continuing treatment in clinical practice. This may be related to clinical phenotypes of MS patients, and the influence of patient reported outcome (PRO) on treatment decision making. OBJECTIVE: To analyse responder rates to fampridine on ambulation and upper extremity function (UEF) and the influence on treatment decision making in different clinical subgroups in a real-world setting. METHODS: MS patients with ambulatory impairment treated with fampridine were included. Patients were subdivided based on disease duration, clinical phenotype, Expanded Disability Status Scale (EDSS), baseline walking speed, and presence of UEF impairment. Ambulatory response was assessed with the Timed 25-Foot Walk (T25FW, responder defined as ≥20% improvement) and with the MS Walking Scale (MSWS, responder defined as ≥8 points improvement) as a PRO. For patients also reporting impaired UEF, the Arm Function in MS Questionnaire (AMSQ, responder defined as ≥15 improvement) was the PRO of choice. Decision on treatment continuation was based on improvement of T25FW, MSWS and the clinicians' overall impression for improvement. RESULTS: In total 344 patients were included of which 75.3% continued treatment. More patients with a relapsing clinical phenotype continued treatment vs patients with a progressive phenotype (83.6 vs 68.6%, p < 0.01). A positive linear trend was found between severity of walking disability, as determined by baseline walking speed, and T25FW response (p < 0.01), while there was an inverse linear association between walking disability and MSWS response (p = 0.03). However, the proportion of patients continuing treatment was similar between subgroups of baseline walking speed. Impaired UEF was reported by 183 (66.5%) patients, of which 64 (39.3%) were AMSQ responders. Patients responding on AMSQ compared to non-responders, were also more frequently MSWS responders (82.8 vs 65.3%, p = 0.02), while response on T25FW was similar, and continued treatment more often (85.9 vs 70.7%, p = 0.04). This suggests an influence of PRO on treatment decision making. CONCLUSION: Responder rates and treatment continuation of fampridine differed between clinical subgroups of MS. PROs influenced treatment decision making of fampridine in clinical practice, particularly in patients with mild ambulatory impairment or those reporting UEF impairment. To some extent, these findings explain discrepancies found between clinical trials and clinical practice, and support the importance of subgroup analyses and incorporation of PROs in clinical trials. For clinical practice, using PROs to assess patients experience in conjunction with performance measures helps in treatment decision making.

Adultos con influenza, evolución clínica, costos y grupos relacionados por el diagnóstico, resultados de 4 años. Clínica Dávila. Santiago de Chile / Adults patients with influenza, clinical evolution, cost and diagnosis related groups, four years results. Clinica Dávila, Santiago, Chile

Resumen Introducción: En 2009 la Influenza A H1N1pdm09 provocó en Chile 12.258 casos y 155 muertes. Objetivo: Analizar en adultos egresados de Clínica Dávila con influenza, en 2009, 2010, 2012 y 2014, soporte ventilatorio, costo de hospitalización, Grupos Relacionados por el Diagnóstico (GRD) y letalidad. Material y Método: Estudio descriptivo retrospectivo usando la ficha médica electrónica. Resultados: Egresaron 115.673 adultos, 338 (0,29%) con diagnóstico de Influenza, edad 56,5 ± 22 años, 59% mujeres, letalidad 4%. Hubo 3 grupos, Grupo 1: sin ningún soporte ventilatorio, 295 pacientes, edad 63 ± 20, estadía 6,6 ± 6,9 días, costo promedio de hospitalización $2.885.261, mediana peso GRD 0,41 (p25 = 0,38 y p75 = 0,62), letalidad 1,01% (3 pacientes). Grupo 2: Ventilación mecánica no invasiva (VMNI), 23 casos, edad 77,1 ± 13, letalidad 22% (5 casos), estadía 16,8 ± 12,4, costo $9.245.242, GRD 0,79 (p25 = 0,62 y p75=1,03). Grupo 3: Intubación y ventilación mecánica invasiva (VMI), 20 pacientes, edad 56,4 ± 15, estadía 36,9 ± 41,4, costo $38.681.099, GRD 5,86 (p25 = 5,82 y p75 = 5,86) y letalidad 30% (6 pacientes). Los GRD grupo VMI versus grupo VMNI y ningún soporte fueron diferentes (p < 0,0001 y p < 0,0001 respectivamente). La letalidad por influenza el 2014 fue de 8,5%, mientras que en los años 2012, 2010 y 2009 fue 1,5%, 3% y 2,5% respectivamente. La mediana de edad el año 2009 fue 37,5 años, menor que la de los otros años (p < 0,0001). Conclusiones: En 2009 los pacientes fueron más jóvenes, la necesidad de soporte ventilatorio provocó un peso GRD, estadía, costo y letalidad mayores que aquellos que no lo requirieron.

Introduction: In 2009 Influenza A H1N1pdm09 caused in Chile 12,258 cases and 155 deaths. Objective: To analyze ventilatory support, cost of hospitalization, Diagnosis Related Groups (DRG) and lethality in adults patients with influenza discharged from our institution, during 2009, 2010, 2012 and 2014. Patients and Method: Retrospective descriptive study using electronic medical records. Results: 115,673 adults were discharged, 338 (0.29%) with diagnosis of Influenza, age 56.5 ± 22 yr.o., 59% women, lethality 4%. There were 3 groups, Group 1: without any ventilatory support, 295 patients, age 63 ± 20, stay 6.6 ± 6.9 days, average cost of hospitalization 2,885,261 clp, medium weight DRG 0.41 (p25 = 0.38) andp75 = 0.62), lethality 1.01% (3 patients). Group 2: Non-invasive mechanical ventilation (NIMV), 23 cases, age 77.1 ± 13, lethality 22% (5 cases), stay 16.8 ± 12.4, cost 9,245,242 clp, DRG 0.79 (p25 = 0.62 and p75 = 1.03). Group 3: Intubation and invasive mechanical ventilation (IMV), 20 patients, age 56.4 ± 15, stay 36.9 ± 41.4, cost 38.681.099 clp, DRG 5.86 (p25 = 5.82 and p75 = 5,86) and lethality 30% (6 patients). The DRG group VMI versus group VMNI and no support were different (p < 0.0001 and p < 0.0001 respectively). The lethality for influenza in 2014 was 8.5%, while in 2012, 2010 and 2009 it was 1.5%, 3% and 2.5% respectively. The median age in 2009 was 37.5 yr.o significantly minor, than the other years (p < 0.0001). Conclusions: In 2009 the patients were younger, the need for ventilatory support led to a higher DRG weight, stay, cost and lethality than those who did not require it.

[A severe stroke following carotid sinus massage]. / Een ernstig herseninfarct na carotismassage.

BACKGROUND: Carotid sinus massage is a widely used method for diagnosis and treatment of supraventricular tachycardia and carotid sinus hypersensitivity. Complications, mostly neurological, can occur but are rare. Carotid stenosis is a risk factor for complications. Hearing a carotid bruit on auscultation indicates stenosis, and is a contraindication for performing carotid sinus massage. However, the sensitivity of auscultation is insufficient. CASE DESCRIPTION: A 71-year-old man with a history of hypertension and hypercholesterolemia presented to the cardiology accident and emergency department with palpitations. A supraventricular tachycardia was found on examination, for which carotid sinus massage was performed. The patient developed severe aphasia and right-sided hemiparesis caused by an extensive stroke, and died a few days later. CONCLUSION: The chance of complications following carotid sinus massage is slight; however, this type of complication can have severe consequences. Safer alternative methods may be used for patients with supraventricular tachycardia. In older patients with vascular risk factors, more extensive diagnostic investigations for carotid stenosis should be considered in the diagnostic workup for carotid sinus hypersensitivity.

Biosolid and alum effects on runoff losses during turfgrass establishment.

Large, volume-based rates of composted biosolids (CB) enhance turfgrass establishment and soil properties, but nonpoint-source runoff losses could occur during production and after transplanting of sod. The objective was to evaluate runoff losses of N, P, sediment, and organic C during establishment of sprigs or transplanted sod of Tifway bermudagrass (Cynodon dactylon L. Pers. X C. transvaalensis Burtt-Davey) with and without CB and aluminum sulfate (Alum). Four treatments comprised Tifway sprigged in a sandy loam soil with and without incorporation of 0.25 m(3) CB m(-3) soil and Alum. In four additional treatments, sod transplanted from Tifway grown with and without CB was established with and without a surface spray of Alum. During early establishment, CB incorporated in soil before sprigging reduced runoff loss of sediment and total N to amounts comparable to transplanted sod. In contrast, mean runoff losses of total dissolved P and soluble-reactive P (SRP) were more than 50% greater for CB-amended sod than for fertilizer-grown sod or Tifway sprigged in soil with or without CB. Yet, the surface spray of Alum reduced runoff loss from sod more than 88% for SRP and 41% for dissolved organic C. Both surface sprays and incorporation of Alum effectively reduced SRP runoff loss from CB, soil, and turfgrass sources during turfgrass establishment.

Assessment of a turfgrass sod best management practice on water quality in a suburban watershed.

The disposal of manure on agricultural land has caused water quality concerns in many rural watersheds, sometimes requiring state environmental agencies to conduct total maximum daily load (TMDL) assessments of stream nutrients, such as nitrogen (N) and phosphorus (P). A best management practice (BMP) has been developed in response to a TMDL that mandates a 50% reduction of annual P load to the North Bosque River (NBR) in central Texas. This BMP exports composted dairy manure P through turfgrass sod from the NBR watershed to urban watersheds. The manure-grown sod releases P slowly and would not require additional P fertilizer for up to 20 years in the receiving watershed. This would eliminate P application to the sod and improve the water quality of urban streams. The soil and water assessment tool (SWAT) was used to model a typical suburban watershed that would receive the sod grown with composted dairy manure to assess water quality changes due to this BMP. The SWAT model was calibrated to simulate historical flow and estimated sediment and nutrient loading to Mary's Creek near Fort Worth, Texas. The total P stream loading to Mary's Creek was lower when manure-grown sod was transplanted instead of sod grown with inorganic fertilizers. Flow, sediment and total N yield were the same for both cases at the watershed outlet. The SWAT simulations indicated that the turfgrass BMP can be used effectively to import manure P into an urban watershed and reduce in-stream P levels when compared to sod grown with inorganic fertilizers.

Runoff water quality from turfgrass established using volume-based composted municipal biosolids applications.

Municipal programs for turfgrass establishment recommend large volume-based application rates of composted municipal biosolids (CMB). This study compared runoff water quality among combinations of two common turfgrass establishment practices and two CMB sources. Bryan- or Austin-CMB were incorporated into 5 cm of soil at a rate of 12.5 or 25% by volume (v/v) on an 8.5% slope. Tifway bermudagrass [Cynodon dactylon (L.) Pers. x C. transvaalensis Burtt-Davy, var. Tifway] sprigs were planted and established; sod, produced at a separate site using either CMB amendment at the 25% v/v rate, was transplanted to the runoff plots on the same day. A mature stand of bermudagrass was used as a control. Runoff water was collected after each of eight natural rain events during the sampling period. Total runoff water loss (mm) was similar for the CMB-amended sprigged and transplanted sod stands. The concentration of total dissolved P (TDP) in runoff water was greatest from the transplanted sod in the first seven rain events (4.1 to 7.5 mg L(-1)). The concentration of TDP in runoff water was similar at both the 12.5 and 25% v/v incorporation rates. Regression analysis indicated Mehlich-3-extractable soil test P concentrations in soil amended with CMB were positively correlated to concentration and mass loss of dissolved P in runoff. At similar application rates, dissolved P loss in runoff water was reduced by incorporating CMB into the soil on site rather than transplanting sod produced with CMB.

Assessment of manure phosphorus export through turfgrass sod production in Erath County, Texas.

A best management practice (BMP) for exporting manure phosphorus (P) in turfgrass sod from the North Bosque River (NBR) watershed in central Texas was assessed using a geographic information system (GIS). The NBR watershed has a mandate to reduce the total annual P load to the NBR by 50% as a result of total maximum daily load regulation. Since dairy waste applications to fields are identified as the major nonpoint source of P to the river, innovative BMPs, such as export of manure P in turfgrass, will be needed to achieve the 50% reduction. However, methods are needed to evaluate the feasibility of these innovative management practices prior to their implementation. A geospatial database of suitable turfgrass production sites was developed for Erath County using GIS. Erath County largely encompasses the upper portion of the NBR watershed. Information from field experiments, production practices, and ground-truthing was used to search, analyze, and verify a geospatial database developed from national and regional sources. The integration and analyses of large databases supports the search by turf producers for sites suitable for turfgrass sod production in Erath County. In addition, GIS enables researchers and regulators to estimate manure P exports and reduced P loading due to implementation of the manure export BMP on a county scale. Under optimal conditions 198,000 kg manure P yr(-1) could be used and 114,840 kg manure P yr(-1) exported from the NBR watershed through implementation of a system using dairy manure to produce turfgrass sod. This is the equivalent of the manure P applied from 10,032 dairy cows yr(-1) and exported from 5808 dairy cows yr(-1). Application of GIS to large-scale planning and decision-making transcends traditional field-scale applications in precision agriculture.

Runoff losses of phosphorus and nitrogen imported in sod or composted manure for turf establishment.

Nutrient loading on impaired watersheds can be reduced through export of sod grown with manure and export of composted manure for turf production on other watersheds. Effects of the sod and manure exports on receiving watersheds were evaluated through monitoring of total dissolved phosphorus (TDP) and N concentrations and losses in runoff from establishing turf. Three replications of seven treatments were established on an 8.5% slope of a Booneville soil (loamy-skeletal, mixed, superactive Pachic Argicryolls). Three treatments comprised imported 'Tifway' bermudagrass [Cynodon dactylon (L.) Pers. x C. transvaalensis Burtt-Davy) sod grown with composted dairy manure (382 or 191 kg P ha(-1)) or fertilizer (50 kg P ha(-1)). Three treatments were sprigged with Tifway and top-dressed with either composted manure (92 or 184 kg P ha(-1)) or fertilizer (100 kg P ha(-1)). The control was established bermudagrass [Cynodon dactylon (L.) Pers. var. Guymon]. During eight fall rain events, mean TDP concentration in runoff (7.8 mg L(-1)) from sprigged Tifway top-dressed with manure (84 kg P ha(-1)) was 1.6 times greater than sod imported with 129 kg manure P ha(-1). During the first fall event, mass losses of TDP (232 mg m(-2)) and total Kjeldahl nitrogen (TKN) (317 mg m(-2)) from sprigged treatments top-dressed with manure or fertilizer were nearly three times greater than manure-grown sod. Percentages of manure P lost as TDP in runoff from imported sod were 33% of percentages lost from sprigged treatments top-dressed with manure. Sod grown with manure P rates of 190 kg P ha(-1) can be imported without increasing runoff losses of TDP compared with conventional fertilization of establishing turfgrass.

The use of vegetation to remediate soil freshly contaminated by recalcitrant contaminants.

The use of vegetation to remediate soil contaminated by recalcitrant hydrocarbons was tested under field conditions. Specifically, an evaluation was made of the effectiveness of deep rooting grasses, Johnsongrass and Canadian wild rye in the dissipation of TNT and PBB's in the soils freshly contaminated to an initial concentration of 10.17+/-1.35 for TNT and 9.87+/-1.23 mg/kg for PBB. The experiment used 72 (1.5m long and 0.1m diameter) column lysimeters with four treatments: Johnsongrass; wild rye grass; a rotation of Johnsongrass and wild rye grass; and unplanted fallow conditions. In the laboratory, immunoassay test procedures determined the TNT and PBB concentrations in the soil, leachate, herbage and root samples. The root characteristics such as total root length, rooting density, and root surface area were quantified to a depth of 1.5m. Changes in microbial biomass were assessed for both rhizosphere soil and the bulk soil during the 2-year study. The largest and most rapid loss in soil chemical concentration was for TNT, which decreased to less than 250 microg/kg, the detection limit, by 93 days after germination. The PBB was at or near the detection limit of 500 microg/kg by 185 days after germination. There was no perceptible difference in contaminant concentration in the soil between the vegetation treatments and/or with depth.

Response of turf and quality of water runoff to manure and fertilizer.

Manure applications can benefit turfgrass production and unused nutrients in manure residues can be exported through sod harvests. Yet, nutrients near the soil surface could be transported in surface runoff. Our research objective was to evaluate responses of bermudagrass [Cynodon dactylon (L.) Pers. var. Guymon] turf and volumes and P and N concentrations of surface runoff after fertilizer or composted manure applications. Three replications of five treatments were established on a Boonville fine sandy loam (fine, smectitic, thermic Vertic Albaqualf) that was excavated to create an 8.5% slope. Manure rates of 50 and 100 kg P ha(-1) at the start of two monitoring periods were compared with P fertilizer rates of 25 and 50 kg ha(-1) and an unfertilized control. Compared with initial soil tests, nitrate concentrations decreased and P concentrations increased after two manure or fertilizer applications and eight rain events over the two monitoring periods. The fertilizer sources of P and N produced 19% more dry weight and 21% larger N concentrations in grass clippings than manure sources. Yet, runoff volumes were similar between manure and fertilizer sources of P. Dissolved P concentration (30 mg L(-1)) in runoff during a rain event 3 d after application of 50 kg P ha(-1) was five times greater for fertilizer than for manure P. Observations during both monitoring periods indicated that total P and N losses in runoff were no greater for composted manure than for fertilizer sources of P at relatively large P rates on a steep slope of turfgrass.

The use of box lysimeters with freshly contaminated soils to study the phytoremediation of recalcitrant organic contaminants.

The potential for phytoremediation of soil contaminated by trinitrotoluene (TNT) and 2,2',5,5'-tetrabromobiphenyl (PBB was used as a surrogate for PCBs) was examined in a 2-year study using box lysimeters under field conditions. The treatments were a warm season grass, Johnson grass, and a cool season grass, Canadian wildrye, and a rotation of Johnson grass and wildrye plus a fallow condition. The experiment was conducted using 12 large (1.50 m x 1.50 m x 0.75 m), in-ground, box lysimeters filled with a Weswood silt-loam soil freshly spiked with the TNT and PBB compounds to a concentration of 10 mg kg(-1) for each chemical. The lysimeters were sheltered to permit controlled applications of water. A total of five sampling rounds were conducted where soil, herbage, and leachate samples were collected for laboratory analysis. TNT and PBB concentrations were determined using the U.S. EPA approved immunoassay test procedures. In the soil, TNT concentrations dropped below the detection limit of 0.25 mg kg(-1) by day 92 and PBB concentrations dropped below the detection limit of 0.50 mg kg(-1) by day 184. There were no significant differences in chemical concentrations among any of the vegetated or fallow treatments at a significance level of alpha < 0.05. However, PBB soil concentrations rebounded above the 0.50 mg kg(-1) level by day 720 for all treatments. No detectable concentrations of TNT or PBB were found in any of the herbage samples or in the leachate.

Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na(+) channel cell surface expression.

The epithelial Na(+) channel (ENaC) plays an essential role in the regulation of whole body Na(+) balance and blood pressure. The cell surface expression of this channel, a complex of three subunits (alpha, beta and gamma ENaC), has been shown to be regulated by hormones such as aldosterone and vasopressin and by intracellular signaling, including ubiquitylation and/or phosphorylation. However, the molecular mechanisms involving phosphorylation in the regulation of ENaC are unclear. Here we show by expression studies in Xenopus laevis oocytes that the aldosterone-induced Sgk1 kinase interacts with the ubiquitin protein ligase Nedd4-2 in a PY motif-dependent manner and phosphorylates Nedd4-2 on Ser444 and, to a lesser extent, Ser338. Such phosphorylation reduces the interaction between Nedd4-2 and ENaC, leading to elevated ENaC cell surface expression. These data show that phosphorylation of an enzyme involved in the ubiquitylation cascade (Nedd4-2) controls cell surface density of ENaC and propose a paradigm for the control of ion channels. Moreover, they suggest a novel and complete signaling cascade for aldosterone-dependent regulation of ENaC.

Plant contamination by organic pollutants in phytoremediation.

Phytoremediation is a remediation technique that involves plant uptake, transformation, accumulation, and/or volatilization of soil- and aqueous-phase contaminants or by the stimulation of microbial cometabolic activity in the rhizosphere of the plant. Even when the principal mechanism is by stimulation of bacteria, any resultant plant contamination cannot be overlooked. For the purpose of modeling, a two-compartment plant model has been developed. The model divides the plant into the shoot compartment (which can be harvested) and the root compartment (into which contaminants can accumulate). Numerical experiments were conducted to investigate model behavior and to determine important parameters affecting plant contamination. Johnsongrass [Sorghum halepense (L.) Pers.] was used to evaluate the model behavior. The contaminants TNT (2,4,6,-trinitrotoluene) and chrysene were selected on the basis of their contrasting aqueous-phase solubilities. The results indicate that plant contamination and soil remediation by plants depend on soil properties such as soil organic carbon content, the physicochemical properties of the contaminants such as the octanol-water partition coefficient, and plant properties. The most important factor affecting plant contamination is bioavailability. As bioavailability increased, the concentrations in root and shoot compartments were predicted to increase. Microbial activities and plant contamination are closely related, which suggests that plants and microorganisms can have complementary roles in phytoremediation.

Thermal unbinding of highly oriented phospholipid membranes.

We present a temperature dependent x-ray reflectivity study of highly oriented, fully hydrated multilamellar phospholipid membranes. Both the specular and diffuse (nonspecular) x-ray reflectivity were measured for dimyristoyl-sn-glycero-phosphocholine (DMPC) and oleoyl-palmitoyl-sn-glycero-phosphocholine (POPC) on silicon substrates in excess water. In this configuration the repeat distance as well as the fluctuation spectra can be determined as a function of temperature. Both model systems studied exhibit a discontinuous unbinding transition from a substrate bound, multilamellar state to a state of freely dispersed bilayers in water. In the unbound phase a single membrane remains on the substrate.

Thermal denaturing of bacteriorhodopsin by X-Ray scattering from oriented purple membranes.

We present a temperature-dependent x-ray diffraction study of thin films of purple membranes (PMs) with the native membrane protein bacteriorhodopsin (BR). The high degree of alignment with respect to the silicon substrates allows for the application of modern interface-sensitive scattering techniques. Here we focus on the structural changes of BR in PMs at the thermal denaturing transition. A partial unfolding of the helices is observed rather than the complete unfolding process known from helix to coil transitions. While BR remains threaded into the lipid bilayer in the denatured state, changes in the short-range lateral structures are associated with the partial unfolding of the transmembrane helices.

Investigation of Structure and Growth of Self-Assembled Polyelectrolyte Layers by X-ray and Neutron Scattering under Grazing Angles.

The structure of self-assembled polyelectrolyte thin films on float glass has been investigated by interface sensitive X-ray and neutron scattering methods. Special emphazis was given to the adsorption process of poly (ethylene imine) and polystyrole sulfonate as an important model system which is often used as a basis for subsequent multilayer buildup. From complementary X-ray and neutron reflectivity data, the vertical film density profile was derived for various growth parameters, including kinetic effects of different adsorption times. In addition to specular reflectivity, we have for the first time employed nonspecular X-ray scattering to study lateral structure parameters in self-assembled polyelectrolyte films. Furthermore, the technique of time-resolved in situ X-ray reflectivity during film growth has been demonstrated and is discussed in view of its future potential. Copyright 2000 Academic Press.

Grazing incidence X-ray diffraction of highly aligned phospholipid membranes containing the antimicrobial peptide magainin 2.

We present the first study of grazing incidence X-ray diffraction on a model system of phospholipid membranes and antimicrobial peptides. For this purpose, highly oriented multilamellar samples have been prepared on solid substrates. By this technique, the short-range order of the lipid chains in the fluid L(alpha) phase can be investigated quantitatively, including not only the mean distance between acyl chains, but also the associated correlation length. The short-range order in lecithin is found to be severely affected by the amphiphilic peptide magainin 2.

Specular and diffuse scattering of highly aligned phospholipid membranes.

We present a quantitative study of specular and diffuse (non-specular) x-ray and neutron reflectivity from highly aligned phospholipid membranes deposited on solid substrates. The height-height correlation function could be obtained from the diffuse scattering without further model assumptions. The results differ significantly from the linear theory of smectic elasticity. We argue that the diffuse scattering is dominated by static liquid-crystalline defects, rather than thermal fluctuations.