Disorder-to-order transition of long fibers contained in evaporating sessile drops.

A liquid drop containing a long fiber is a complex system whose configuration is determined by an interplay of elastic stresses in the fiber and capillary forces due to the liquid. We study the morphological evolution of fibers that are much longer than the drop diameter in evaporating sessile drops. After insertion, the fibers are either found in an ordered or disordered state, with increasing disorder for increasing fiber length. Upon evaporation, the order increases, in such a way that the final configuration deposited on the solid surface is either a circle, an ellipse, or 8-shaped. The morphology of the deposit depends on the fiber length and the elastocapillary length, both non-dimensionalized with the characteristic drop size, which we classify in a morphology regime map. The disorder-to-order transition allows depositing ordered fiber structures on solid surfaces even in cases of a strongly disordered state after fiber insertion. Combined with technologies such as inkjet printing, this process could open new avenues to decorate surfaces with filamental structures whose morphology can be controlled by varying the fiber length.

Using personal monitoring data to derive organ doses for medical radiation workers in the Million Person Study-considerations regarding NCRP Commentary no. 30.

The study of low dose and low-dose rate exposure is of central importance in understanding the possible range of health effects from prolonged exposures to radiation. The One Million Person Study of Radiation Workers and Veterans (MPS) of low-dose health effects was designed to evaluate radiation risks among healthy American workers and veterans. The MPS is evaluating low-dose and dose-rate effects, intakes of radioactive elements, cancer and non-cancer outcomes, as well as differences in risks between women and men. Medical radiation workers make up a large group of individuals occupationally exposed to low doses of radiation from external x-ray/gamma exposures. For the MPS, about 100 000 United States medical radiation workers have been selected for study. The approach to the complex dosimetry circumstances for such workers over three to four decades of occupation were initially and broadly described in National Council on Radiation Protection and Measurements (NCRP) Report No. 178. NCRP Commentary No. 30 provides more detail and describes an optimum approach for using personal monitoring data to estimate lung and other organ doses applicable to the cohort and provides specific precautions/considerations applicable to the dosimetry of medical radiation worker organ doses for use in epidemiologic studies. The use of protective aprons creates dosimetric complexity. It is recommended that dose values from dosimeters worn over a protective apron be reduced by a factor of 20 for estimating mean organ doses to tissues located in the torso and that 15% of the marrow should be assumed to remain unshielded for exposure scenarios when aprons are worn. Conversion coefficients relating personal dose equivalent,Hp(10) in mSv, to mean absorbed doses to organs and tissues,DTin mGy, for females and males for six exposure scenarios have been determined and presented for use in the MPS. This Memorandum summarises several key points in NCRP Commentary No. 30.

Morphogenesis of filaments growing in flexible confinements.

Space-saving design is a requirement that is encountered in biological systems and the development of modern technological devices alike. Many living organisms dynamically pack their polymer chains, filaments or membranes inside deformable vesicles or soft tissue-like cell walls, chorions and buds. Surprisingly little is known about morphogenesis due to growth in flexible confinements--perhaps owing to the daunting complexity lying in the nonlinear feedback between packed material and expandable cavity. Here we show by experiments and simulations how geometric and material properties lead to a plethora of morphologies when elastic filaments are growing far beyond the equilibrium size of a flexible thin sheet they are confined in. Depending on friction, sheet flexibility and thickness, we identify four distinct morphological phases emerging from bifurcation and present the corresponding phase diagram. Four order parameters quantifying the transitions between these phases are proposed.

Susceptibility of cat fleas (Siphonaptera: Pulicidae) to fipronil and imidacloprid using adult and larval bioassays.

The monitoring of the susceptibility offleas to insecticides has typically been conducted by exposing adults on treated surfaces. Other methods such as topical applications of insecticides to adults and larval bioassays on treated rearing media have been developed. Unfortunately, baseline responses of susceptible strains of cat flea, Ctenocephalides felis (Bouchè), except for imidacloprid, have not been determined for all on-animal therapies and new classes of chemistry now being used. However, the relationship between adult and larval bioassays of fleas has not been previously investigated. The adult and larval bioassays of fipronil and imidacloprid were compared for both field-collected isolates and laboratory strains. Adult topical bioassays of fipronil and imidacloprid to laboratory strains and field-collected isolates demonstrated that LD50s of fipronil and imidacloprid ranged from 0.11 to 0.40 nanograms per flea and 0.02 to 0.18 nanograms per flea, respectively. Resistance ratios for fipronil and imidacloprid ranged from 0.11 to 2.21. Based on the larval bioassay published for imidacloprid, a larval bioassay was established for fipronil and reported in this article. The ranges of the LC50s of fipronil and imidacloprid in the larval rearing media were 0.07-0.16 and 0.11-0.21 ppm, respectively. Resistance ratios for adult and larval bioassays ranged from 0.11 to 2.2 and 0.58 to 1.75, respectively. Both adult and larval bioassays provided similar patterns for fipronil and imidacloprid. Although the adult bioassays permitted a more precise dosage applied, the larval bioassays allowed for testing isolates without the need to maintain on synthetic or natural hosts.

[Diagnostics and exclusion of hereditary angioedema : a standarized approach for the practice]. / Diagnostik und Ausschluss des hereditären Angioödems : Ein standardisierter Ansatz für die Praxis.

The differentiation between mast cell mediator-mediated and bradykinin-mediated forms of angioedema can be difficult. Bradykinin-mediated hereditary angioedema is a rare autosomal dominant hereditary disease which is characterized by recurrent edema attacks of varying magnitude. The edema occurs in the skin and mucous membranes and can be temporarily disfiguring, very painful and life-threatening by attacks in the laryngeal region. Because of the multitude of differential diagnoses, a final diagnosis is only achieved after an average duration of more than 10 years. The anamnestic and laboratory diagnostic algorithm presented here is designed to assist a simpler differentiation of the various forms of angioedema and to reach the correct diagnosis more quickly.

Fractalkine in human inflammatory cardiomyopathy.

BACKGROUND: Cardiac inflammation is important for the prognosis of patients with inflammatory cardiomyopathy (CMi), but the mechanisms leading to it are not fully elucidated. OBJECTIVE: To study the role of fractalkine (CX3CL1) in chemotactic and adhesive properties of peripheral blood mononuclear cells (PBMCs) in patients with CMi. METHODS AND RESULTS: Patients with enterovirus (EV)-positive CMi, patients with virus-negative CMi, patients with parvovirus B19 (B19) genomes with low intramyocardial inflammation and patients without cardiac inflammation and viral infection in the endomyocardial biopsy (EMB) were enrolled (n=10/group). The expression of CX3CL1 and monocyte chemoattractant protein (MCP-1) in EMBs was significantly increased in EV-positive and virus-negative patients with CMi in contrast to controls and B19-positive patients (EV+ vs controls: CX3CL1-area fraction (AF) % 0.078±0.012 vs 0.009±0.003 p<0.05; MCP-1-AF % 0.093±0.023 vs 0.011±0.009). The receptor (CX3CR1)-mediated chemotaxis was increased twofold in PBMCs in comparison with those of controls. The MCP-1 secretion was 3.1-fold higher in PBMCs from EV-positive patients compared with controls, and this elevation was further increased by CX3CL1 in EV-positive patients. No significant CX3CL1-mediated MCP-1 increase was seen in PBMCs from healthy controls. Moreover, spontaneously beating neonatal rat cardiomyocytes exposed to CX3CL1 exhibited an attenuated positive chronotropic response to ß-adrenergic stimulation with isoproterenol. CONCLUSION: The cardiac and plasma CX3CL1/CX3CR1 system is upregulated in CMi and this affects the functional potential of PBMCs. Moreover, a direct cardiodepressive effect of CX3CL1 in cardiac tissue was demonstrated since neonatal cardiomyocytes exhibited an attenuated positive chronotropic response to ß-adrenergic stimulation.

Spatial steering of deep brain stimulation volumes using a novel lead design.

OBJECTIVE: To investigate steering the volume of activated tissue (VTA) with deep brain stimulation (DBS) using a novel high spatial-resolution lead design. METHODS: We examined the effect of asymmetric current-injection across the DBS-array on the VTA. These predictions were then evaluated acutely in a non-human primate implanted with the DBS-array, using motor side-effect thresholds as the metric for estimating VTA asymmetries. RESULTS: Simulations show the DBS-array, with electrodes arranged together in a cylindrical configuration, can generate field distributions equivalent to commercial DBS leads, and these field distributions can be modulated using field-steering methods. Stimulation with implanted DBS-arrays showed directionally-selective muscle activation, presumably through spread of stimulation fields into portions of the corticospinal tract lying in the internal capsule. CONCLUSIONS: Our computational and experimental studies demonstrate that the DBS-array is capable of spatially selective stimulation. Displacing VTAs away from the lead's axis can be achieved using a single simple and intuitive control parameter. SIGNIFICANCE: Optimal DBS likely requires non-uniform VTAs that may differentially affect a nucleus or fiber pathway. The DBS-array allows positioning VTAs with sub-millimeter precision, which is especially relevant for those patients with DBS leads placed in sub-optimal locations. This may present clinicians with an additional degree of freedom to optimize the DBS therapy.

microRNA122-regulated transgene expression increases specificity of cardiac gene transfer upon intravenous delivery of AAV9 vectors.

Adeno-associated virus (AAV) vectors with capsids of AAV serotype 9 enable an efficient transduction of the heart upon intravenous injection of adult mice but also transduce the liver. The aim of this study was to improve specificity of AAV9 vector-mediated cardiac gene transfer by microRNA (miR)-dependent control of transgene expression. We constructed plasmids and AAV vectors containing target sites (TSs) of liver-specific miR122, miR192 and miR148a in the 3' untranslated region (3'UTR) of a luciferase expression cassette. Luciferase expression was efficiently suppressed in liver cell lines expressing high levels of the corresponding miRs, whereas luciferase expression was unaffected in cardiac myocytes. Intravenous injections of AAV9 vectors bearing three repeats of miR122 TS in the 3'UTR of an enhanced green fluorescent expression (EGFP) expression cassette resulted in the absence of EGFP expression in the liver of adult mice, whereas the control vectors without miR TS displayed significant hepatic EGFP expression. EGFP expression levels in the heart, however, were comparable between miR122-regulated and control vectors. The liver-specific de-targeting in vivo using miR122 was even more efficient than transcriptional targeting with a cardiac cytomegalovirus (CMV)-enhanced myosin light chain (MLC) promoter. These data indicate that miR-regulated targeting is a powerful new tool to further improve cardiospecificity of AAV9 vectors.

Cryptic speciation in the vermilion rockfish (Sebastes miniatus) and the role of bathymetry in the speciation process.

A recent phylogenetic review of the genus Sebastes suggested the existence of a cryptic species of vermilion rockfish (Sebastes miniatus). To evaluate the geographical and bathymetric range of the Type 1 and Type 2 forms reported in that study, cytochrome b sequences were examined from 548 fish. Type 1 fish were found primarily south of Point Conception on reefs deeper than 100 m. Type 2 fish were common range-wide at sites shallower than 100 m. Reproductive isolation between the two types was tested using nine microsatellite loci. Estimates of genetic divergence were made using the fixation index (F(ST)) and correspondence between haplotype and genotype was tested by Bayesian population assignment and multivariate plotting of individual genotypes. Microsatellite analyses gave strong support for the presence of two distinct groups of genotypes. All fish with Type 1 haplotypes and fish with Type 2 haplotypes from < 100 m depth had genotypes unique to their haplotype group. However, most (68%) fish with Type 2 haplotypes from > 100 m depth assigned strongly to the Type 1 genotype group. Morphometric comparisons between the two genotypic groups revealed significant differences at three of the six examined measurements. Differences in both genetics, depth of occurrence, and morphology suggest these are separate species. This observation along with evidence of depth segregation in many recent species pairs led us to hypothesize a speciation model for Sebastes spp. by which the loss or truncation of a depth-related ontogenetic migration can lead to the creation of reproductively isolated populations.

Coxsackievirus B3 and adenovirus infections of cardiac cells are efficiently inhibited by vector-mediated RNA interference targeting their common receptor.

As coxsackievirus B3 (CoxB3) and adenoviruses may cause acute myocarditis and inflammatory cardiomyopathy, isolation of the common coxsackievirus-adenovirus-receptor (CAR) has provided an interesting new target for molecular antiviral therapy. Whereas many viruses show high mutation rates enabling them to develop escape mutants, mutations of their cellular virus receptors are far less likely. We report on antiviral efficacies of CAR gene silencing by short hairpin (sh)RNAs in the cardiac-derived HL-1 cell line and in primary neonatal rat cardiomyocytes (PNCMs). Treatment with shRNA vectors mediating RNA interference against the CAR resulted in almost complete silencing of receptor expression both in HL-1 cells and PNCMs. Whereas CAR was silenced in HL-1 cells as early as 24 h after vector treatment, its downregulation in PNCMs did not become significant before day 6. CAR knockout resulted in inhibition of CoxB3 infections by up to 97% in HL-1 cells and up to 90% in PNCMs. Adenovirus was inhibited by only 75% in HL-1 cells, but up to 92% in PNCMs. We conclude that CAR knockout by shRNA vectors is efficient against CoxB3 and adenovirus in primary cardiac cells, but the efficacy of this approach in vivo may be influenced by cell type-specific silencing kinetics in different tissues.

Highly efficient and specific modulation of cardiac calcium homeostasis by adenovector-derived short hairpin RNA targeting phospholamban.

Impaired function of the phospholamban (PLB)-regulated sarcoplasmic reticulum Ca(2+) pump (SERCA2a) contributes to cardiac dysfunction in heart failure (HF). PLB downregulation may increase SERCA2a activity and improve cardiac function. Small interfering (si)RNAs mediate efficient gene silencing by RNA interference (RNAi). However, their use for in vivo gene therapy is limited by siRNA instability in plasma and tissues, and by low siRNA transfer rates into target cells. To address these problems, we developed an adenoviral vector (AdV) transcribing short hairpin (sh)RNAs against rat PLB and evaluated its potential to silence the PLB gene and to modulate SERCA2a-mediated Ca(2+) sequestration in primary neonatal rat cardiomyocytes (PNCMs). Over a period of 13 days, vector transduction resulted in stable > 99.9% ablation of PLB-mRNA at a multiplicity of infection of 100. PLB protein gradually decreased until day 7 (7+/-2% left), whereas SERCA, Na(+)/Ca(2+) exchanger (NCX1), calsequestrin and troponin I protein remained unchanged. PLB silencing was associated with a marked increase in ATP-dependent oxalate-supported Ca(2+) uptake at 0.34 microM of free Ca(2+), and rapid loss of responsiveness to protein kinase A-dependent stimulation of Ca(2+) uptake was maintained until day 7. In summary, these results indicate that AdV-derived PLB-shRNA mediates highly efficient, specific and stable PLB gene silencing and modulation of active Ca(2+) sequestration in PNCMs. The availability of the new vector now enables employment of RNAi for the treatment of HF in vivo.

Multifunctional flexible parylene-based intracortical microelectrodes.

Delivering drugs directly to the brain tissue opens new approaches to disease treatment and improving neural interfaces. Several approaches using neural prostheses have been made to deliver drugs directly with bypassing the blood-brain barrier (BBB) [1, 2]. In this paper, we propose a new polymer-based flexible microelectrode with drug delivery capability. The probe was fabricated and tested for electrical and fluidic functionality in early stage design. In vivo chronic recording experiments succeeded in demonstrating the in vivo reliability of the probe. Successful in vivo experiments confirm the suitability of the probes as implantable chronic recording devices with robust fluid delivery function.

Development of a Microscale Implantable Neural Interface (MINI) Probe System.

Cortical recording devices hold promise for providing augmented control of neuroprostheses and brain-computer interfaces in patients with severe loss of motor function due to injury or disease. This paper reports on the preliminary in vitro and in vivo results of our microscale implantable neural interface (MINI) probe system. The MINI is designed to use proven components and materials with a modular structure to facilitate ongoing improvements as new technologies become available. This device takes advantage of existing, well-characterized Michigan probe technologies and combines them to form a multichannel, multiprobe cortical assembly. To date, rat, rabbit, and non-human primate models have been implanted to test surgical techniques and in vivo functionality of the MINI. Results demonstrate the ability to form a contained hydrostatic environment surrounding the implanted probes for extended periods and the ability of this device to record electrophysiological signals with high SNRs. This is the first step in the realization of a cortically-controlled neuroprosthesis designed for human applications.

An optical-optical double resonance experiment in LiH molecules: lifetime measurements in the C state.

An optical-optical double resonance sub-Doppler experiment is used to measure short nonradiative lifetimes in the C (1)Sigma(+) state of LiH. These lifetimes are expected to result from the strong electronic interaction between the C (1)Sigma(+) state and the continuum of the A (1)Sigma(+) state and to vary with the vibrational quantum number, from nanoseconds to milliseconds. The experimental setup combines a molecular beam of LiH, a first cw laser beam locked to a given A-X absorption line, and a second cw laser beam scanned over C-A absorption profiles. Analysis of these absorption profiles in terms of Voigt profiles shows that their Lorentzian components significantly vary with the vibrational quantum numbers of the C state. Nonradiative decay rates deduced this way are systematically larger than the calculated ones but their variations are similar. Coherent saturation effects cannot be invoked to explain this discrepancy.

Pulse reflection by photonic barriers.

The time behavior of microwaves undergoing partial reflection by photonic barriers was measured in the time and in the frequency domain. It was observed that for opaque barriers the reflection delay is almost independent of the barrier's length. This result corresponds to the Hartman effect in transmission.

[Aspects of data protection in telemedicine]. / Datenschutzrechtliche Aspekte der Telemedizin.

Telemedical applications like the electronic patient file, the electronic physician's letter and the electronic consultation ("Telekonsil"), the electronic prescription, the electronic patient's card (the "patient smart card") facilitate and improve the processing of sensitive medical data as well as the possibilities for using medical resources in an unusual degree and can thereby substantially contribute to the well-being of the patient. However, improving the quality of medical supply must not lead to a degradation of the patients' rights, in particular their right of self-determination. The introduction and the use of telemedical applications do not change the legal basic conditions for medical data processing. Therefore, a patient-friendly telemedicine must include data protection as well. Data protective telemedicine requires medical secrecy ensuring the patients' rights of information and transparency, correction of false and the up-to-date deletion of information that is no longer necessary, as well as secure data processing. All electronic processing of patients' data must meet the requirements of data security, i.e. the confidentiality, the integrity, the availability of the data at any time and the verifiability of the data processing have to be guaranteed. For this, electronic signatures and encodings have to be used, medical information systems have to be protected effectively against any risks resulting from open networks, particularly the Internet, and data processing has to be monitored. Electronic patient files may be open only to the treating physician and the medical assistants up to the necessary extent, ensuring the possibility of an emergency access. Any access beyond that does require the special consent of the patient. The medical secrecy has to be ensured. The electronic prescription with a documentation of the patient's medication requires the consent of the patient and must protect the rights of the physicians. In particular it has to ensure that the respective physician's prescribing behaviour cannot be stored or become known from a third party. Furthermore it has to protect the pharmacists' right to hide their turnover from other pharmacies. So-called patient smart cards require the consent of the patient. The right of the patient to keep his information secret, must be ensured with access options to the information stored on the smart card. Electronic physician's letters and socalled Telekonsile, i.e. the consultation with professional colleagues who were not involved in the patient's treatment from the beginning, require basically the agreement of the patient--if there cannot be dealt with anonymized data already from the beginning. In emergencies, after adequate consideration and weighing of values and interests, the consent of the patient can be suspected. The adherence to these boundary conditions ensures security and trustworthiness of telemedicine regarding the security of data processing as well as the rights of self-determination of all who are concerned. Data protection is also a contribution for the acceptance of these revolutionary advancements in the medical world.

Update on patient radiation doses at a large tertiary care medical center.

Radiation procedures in diagnostic radiology and nuclear medicine examinations, especially at referral centers, contribute a significant proportion to population dose; hence, there is a presumed detriment. Knowledge of the magnitude of dose from each type of exam is helpful in determining where to implement dose reduction efforts. Additionally, new records of dose data facilitate comparisons with past measurements. In this paper, updated patient exam dose data (frequency and effective dose equivalent) are provided for a large, comprehensive, tertiary care medical center that served more than 340,000 patients in 1997. Patient billing code data were used to study 31 different types of diagnostic exams encompassed in five major categories (angiography, fluoroscopy, radiography, nuclear medicine, and computerized tomography). Organ doses for each radiographic and nuclear medicine exam were estimated using published Monte Carlo conversion factors and appropriate exposure values. Estimates of organ doses were utilized to compute effective dose equivalent (EDE) per ICRP 26 and collective effective dose equivalent. Mean effective dose equivalent was also calculated for each exam category. Total collective effective dose equivalent had decreased from 1988 (2,030 person-Sv) to 1997 (1,817 person-Sv). The largest contributors to collective effective dose equivalent were angiography (768 person-Sv), computerized tomography (447 person-Sv), and nuclear medicine (355 person-Sv). Radiography (150 person-Sv) and fluoroscopy (97 person-Sv) contributed the least to collective effective dose equivalent. Mean effective dose equivalent contributions remained the same, with angiography accounting for the highest component, followed by nuclear medicine, computerized tomography, fluoroscopy, and radiography, respectively. Effective dose equivalent, collective effective dose equivalent, and mean effective dose equivalent values were calculated and tabulated in five major categories. These data provide updated information as to trends in exam and; collective dose from 31 common types of radiologic exams performed at a large medical center, which can be used as an up to date baseline for analyses of trends in U.S. radiation doses due to medical imaging procedures. Although minor changes were observed in comparing the mean effective dose equivalent data to those of a previous study, substantial differences were evident in the collective effective dose equivalent data. This was due primarily to variations in the number of patients examined and changes in technology and practice.

Effects of angiotensin II subtype 1 receptor blockade on cardiac fibrosis and sarcoplasmic reticulum Ca2+ handling in hypertensive transgenic rats overexpressing the Ren2 gene.

OBJECTIVE: We evaluated the effects of angiotensin II subtype 1 (AT1) receptor antagonism on cardiac fibrosis and sarcoplasmic (SR) Ca2+ handling in a transgenic rat model of renin-dependent left ventricular (LV) hypertrophy (LVH). METHODS: Hypertensive transgenic rats overexpressing the Ren2 gene (TGR(mRen2)27) were treated between 10 and 30 weeks of age with the angiotensin II subtype 1 (AT1) receptor antagonist, eprosartan, in an antihypertensive (Ren2-E60, 60 mg/kg per day) and a non-antihypertensive (Ren2-E6, 6 mg/kg per day) dose applied intraperitoneally via osmotic-mini-pumps. They were compared to age-matched Ren2 and Sprague-Dawley (SD) control rats receiving 0.9% NaCl as vehicle via osmotic mini-pumps (Ren2-Vehicle, SD-Vehicle, respectively). RESULTS: Systolic blood pressure (SBP), LV weight, LV end-diastolic pressure (LVEDP), and cardiac fibrosis were elevated in Ren2-Vehicle, while diastolic function (-dP/dt(max)) and sarcoplasmic reticulum (SR) Ca2+ uptake were decreased in Ren2-Vehicle compared to SD-Vehicle (P < 0.05, respectively). SBP was not altered in Ren2-E6, but reduced to normotensive levels in Ren2-E60 compared to Ren2-Vehicle and SD-Vehicle (P < 0.0001). In both Ren2-E6 and Ren2-E60, LV weights were reduced and LVEDP and -dP/dt(max)normalized compared to Ren2-Vehicle (P < 0.05). SR Ca2+ uptake was normalized in both Ren2-E6 and Ren2-E60. Cardiac fibrosis did not change in Ren2-E6, but perivascular LV fibrosis and hydroxyprolin content were reduced in Ren2-E60 compared to Ren2-Vehicle (P < 0.05, respectively). CONCLUSIONS: Normalization of LV SR Ca2+ uptake is an important mechanism by which AT1 receptor antagonism improves LV diastolic dysfunction independent from a reduction of SBP and cardiac fibrosis in the TGR (mRen2)27 model.