Plasmonic modulator with >170 GHz bandwidth demonstrated at 100 GBd NRZ.

We demonstrate a plasmonic Mach-Zehnder (MZ) modulator with a flat frequency response exceeding 170 GHz. The modulator comprises two phase modulators exploiting the Pockels effect of an organic electro-optic material in plasmonic slot waveguides. We further show modulation at 100 GBd NRZ and 60 GBd PAM-4. The electrical drive signals were generated using a 100 GSa/s digital to analog converter (DAC). The high-speed and small-scale devices are relevant for next-generation optical interconnects.

Prospective validation of a novel renal activity index of lupus nephritis.

Objectives The renal activity index for lupus (RAIL) score was developed in children with lupus nephritis as a weighted sum of six urine biomarkers (UBMs) (neutrophil gelatinase-associated lipocalin, monocyte chemotactic protein 1, ceruloplasmin, adiponectin, hemopexin and kidney injury molecule 1) measured in a random urine sample. We aimed at prospectively validating the RAIL in adults with lupus nephritis. Methods Urine from 79 adults was collected at the time of kidney biopsy to assay the RAIL UBMs. Using receiver operating characteristic curve analysis, we evaluated the accuracy of the RAIL to discriminate high lupus nephritis activity status (National Institutes of Health activity index (NIH-AI) score >10), from low/moderate lupus nephritis activity status (NIH-AI score ≤10). Results In this mixed racial cohort, high lupus nephritis activity was present in 15 patients (19%), and 71% had proliferative lupus nephritis. Use of the identical RAIL algorithm developed in children resulted in only fair prediction of lupus nephritis activity status of adults (area under the receiver operating characteristic curve (AUC) 0.62). Alternative weightings of the six RAIL UBMs as suggested by logistic regression yielded excellent accuracy to predict lupus nephritis activity status (AUC 0.88). Accuracy of the model did not improve with adjustment of the UBMs for urine creatinine or albumin, and was little influenced by concurrent kidney damage. Conclusions The RAIL UBMs provide excellent prediction of lupus nephritis activity in adults. Age adaption of the RAIL is warranted to optimize its discriminative validity to predict high lupus nephritis activity status non-invasively.

Plasmonic phased array feeder enabling ultra-fast beam steering at millimeter waves.

In this paper, we demonstrate an integrated microwave phoneeded for beamtonics phased array antenna feeder at 60 GHz with a record-low footprint. Our design is based on ultra-compact plasmonic phase modulators (active area <2.5µm2) that not only provide small size but also ultra-fast tuning speed. In our design, the integrated circuit footprint is in fact only limited by the contact pads of the electrodes and by the optical feeding waveguides. Using the high speed of the plasmonic modulators, we demonstrate beam steering with less than 1 ns reconfiguration time, i.e. the beam direction is reconfigured in-between 1 GBd transmitted symbols.

High speed plasmonic modulator array enabling dense optical interconnect solutions.

Plasmonic modulators might pave the way for a new generation of compact low-power high-speed optoelectronic devices. We introduce an extremely compact transmitter based on plasmonic Mach-Zehnder modulators offering a capacity of 4 × 36 Gbit/s on a footprint that is only limited by the size of the high-speed contact pads. The transmitter array is contacted through a multicore fiber with a channel spacing of 50 µm.

Plasmonic-organic hybrid (POH) modulators for OOK and BPSK signaling at 40 Gbit/s.

We report on high-speed plasmonic-organic hybrid Mach-Zehnder modulators comprising ultra-compact phase shifters with lengths as small as 19 µm. Choosing an optimum phase shifter length of 29 µm, we demonstrate 40 Gbit/s on-off keying (OOK) modulation with direct detection and a BER < 6 × 10(-4). Furthermore, we report on a 29 µm long binary-phase shift keying (BPSK) modulator and show that it operates error-free (BER < 1 × 10(-10)) at data rates up to 40 Gbit/s and with an energy consumption of 70 fJ/bit.

The function of plakophilin 1 in desmosome assembly and actin filament organization.

Plakophilin 1, a member of the armadillo multigene family, is a protein with dual localization in the nucleus and in desmosomes. To elucidate its role in desmosome assembly and regulation, we have analyzed its localization and binding partners in vivo. When overexpressed in HaCaT keratinocytes, plakophilin 1 localized to the nucleus and to desmosomes, and dramatically enhanced the recruitment of desmosomal proteins to the plasma membrane. This effect was mediated by plakophilin 1's head domain, which interacted with desmoglein 1, desmoplakin, and keratins in the yeast two-hybrid system. Overexpression of the armadillo repeat domain induced a striking dominant negative phenotype with the formation of filopodia and long cellular protrusions, where plakophilin 1 colocalized with actin filaments. This phenotype was strictly dependent on a conserved motif in the center of the armadillo repeat domain. Our results demonstrate that plakophilin 1 contains two functionally distinct domains: the head domain, which could play a role in organizing the desmosomal plaque in suprabasal cells, and the armadillo repeat domain, which might be involved in regulating the dynamics of the actin cytoskeleton.

Microwave plasmonic mixer in a transparent fibre-wireless link.

To cope with the high bandwidth requirements of wireless applications1, carrier frequencies are shifting towards the millimetre-wave and terahertz bands2-5. Conversely, data is normally transported to remote wireless antennas by optical fibres. Therefore, full transparency and flexibility to switch between optical and wireless domains would be desirable6,7. Here, we demonstrate for the first time a direct wireless-to-optical receiver in a transparent optical link. We successfully transmit 20 and 10 Gbit/s over wireless distances of 1 and 5 m at a carrier frequency of 60 GHz, respectively. Key to the breakthrough was a plasmonic mixer directly mapping the wireless information onto optical signals. The plasmonic scheme with its subwavelength feature and pronounced field confinement provides a built-in field enhancement of up to 90'000 over the incident field in an ultra-compact and CMOS compatible structure. The plasmonic mixer is not limited by electronic speed and thus compatible with future terahertz technologies.

Direct interaction of the 170 kDa isoform of synaptojanin 1 with clathrin and with the clathrin adaptor AP-2.

Synaptojanin 1, a polyphosphoinositide phosphatase, is expressed as two major alternatively spliced isoforms of 145 kDa (SJ145) and 170 kDa (SJ170) [1] [2], which are thought to have pleiotropic roles in endocytosis, signaling and actin function [3] [4] [5]. SJ145 is highly enriched in nerve terminals where it participates in clathrin-dependent synaptic vesicle recycling [1] [5]. SJ170, which differs from SJ145 by the presence of a carboxy-terminal extension, is the predominant isoform in developing neurons and is expressed in a variety of tissues [2]. The carboxy-terminal domain unique to SJ170 was previously shown to bind Eps15 [6], a protein involved in receptor-mediated endocytosis. Here, we show that the same domain also binds clathrin and the clathrin adaptor AP-2. These interactions occur both in vitro and in vivo and are direct. Binding of AP-2 is mediated by the ear domain of its alpha-adaptin subunit and binding of clathrin by the amino-terminal domain of its heavy chain. Overexpression in chinese hamster ovary (CHO) cells of full-length SJ170 or its unique carboxy-terminal region caused mislocalization of Eps15, AP-2 and clathrin, as well as inhibition of clathrin-dependent transferrin uptake. These findings suggest a close association of SJ170 with the clathrin coat and provide new evidence for its physiological role in the regulation of clathrin coat dynamics.

Accuracy of electronic apex locators in comparison to actual length--an in vivo study.

OBJECTIVES: The measurement precision of four electronic apex locators (Root ZX, Morita, Tokyo, Japan; Endy, Loser, Leverkusen, Germany; Justy II, Hager-Werken, Duisburg, Germany; Endox Lysis, Milan, Italy) was examined in the present in vivo study. METHODS: The root canal length of 40 single-rooted and multi-rooted teeth was determined with the four devices prior to tooth extraction. To determine the actual root canal length, the apical third was longitudinally sectioned, the root canal instrument was positioned and the apex was examined using a microscope. RESULTS: The average measurement deviation (+/-SD) in relation to the apical constriction was 0.3 mm (+/-0.6) for the Root ZX, 0.7 mm (+/-1.0) for the Endy, 0.2 mm (+/-0.7) for the Justy II and 1.3 mm (+/-1.7) for the Endox. The limit of +/-0.5 mm from the apical constriction was attained by the Root ZX in 78%, by the Endy in 67%, by the Justy II in 80% and by Endox in 31% of all measurements. CONCLUSIONS: The latest generation of apex locaters provide the clinician with an accurate and useful adjunct for the determination of root canal length.

Synaptojanin 1: localization on coated endocytic intermediates in nerve terminals and interaction of its 170 kDa isoform with Eps15.

Synaptojanin 1 is an inositol 5-phosphatase with a putative role in clathrin-mediated endocytosis. Goal of this study was to provide new evidence for this hypothesis. We show that synaptojanin 1 is concentrated at clathrin-coated endocytic intermediates in nerve terminals. Furthermore, we report that synaptojanin-170, an alternatively spliced isoform of synaptojanin 1, binds Eps15, a clathrin coat-associated protein. Binding is mediated by the COOH-terminal region of synaptojanin-170 which we show here to be poorly conserved from rat to humans, but to contain in both species three asparagine-proline-phenylalanine (NPF) repeats. This motif has been found to be the core of the binding site for the EH domains of Eps15. Together with previous data, our results suggest that synaptojanin 1 can be recruited to clathrin-coated pits via a multiplicity of interactions.

Structure-activity relationships for inhibition of type 1 and 2 human 5 alpha-reductase and human adrenal 3 beta-hydroxy-delta 5-steroid dehydrogenase/3-keto-delta 5-steroid isomerase by 6-azaandrost-4-en-3-ones: optimization of the C17 substituent.

A variety of C17 amide-substituted 6-azaandrost-4-en-3-ones were prepared and tested versus human type 1 and 2 steroid 5 alpha-reductase (5AR) and human adrenal 3 beta-hydroxy-delta 5-steroid dehydrogenase/3-keto-delta 5-steroid isomerase (3BHSD) in order to optimize potency versus both isozymes of 5AR and selectivity versus 3BHSD. Two series of potent and selective C17 amides were discovered, 2,5-disubstituted anilides and (arylcycloalkyl)amides. Compounds from each series with picomolar IC50's versus human type 2 5AR and low nanomolar to picomolar IC50's versus human type 1 5AR possessing 100-500-fold selectivity versus 3BHSD were identified. A conformational model to predict 3BHSD potency was developed which could rationalize 3BHSD potency within three different series of compounds. Evaluation of some optimal compounds from this series in a chronic castrated rat model of 5AR inhibitor induced prostate involution, and pharmacokinetic measurements identified compounds (9, 12, 16, and 29) with good in vivo efficacy and half-life in the dog. An intact rat model of in vivo selectivity for 5AR versus 3BHSD inhibition was also developed. Dual inhibitors of both human 5AR's may show advantages over type 2 selective 5AR inhibitors, such as finasteride (1), in the treatment of disease states which depend upon dihydrotestosterone.

6-Azasteroids: structure-activity relationships for inhibition of type 1 and 2 human 5 alpha-reductase and human adrenal 3 beta-hydroxy-delta 5-steroid dehydrogenase/3-keto-delta 5-steroid isomerase.

6-Azaandrost-4-en-3-ones were synthesized and tested versus human type 1 and 2 steroid 5 alpha-reductase (5AR) and human adrenal 3 beta-hydroxy-delta 5-steroid dehydrogenase/3-keto-delta 5-steroid isomerase (3BHSD) to explore the structure-activity relationship of this novel series in order to optimize potency versus both isozymes of 5AR and selectivity versus 3BHSD. Compounds with picomolar IC50's versus human type 2 5AR and low nanomolar Ki's versus human type 1 5AR with 100-fold selectivity versus 3BHSD were identified (70). Preliminary in vivo evaluation of some optimal compounds from this series in a chronic castrated rat model of 5AR inhibitor-induced prostate involution and dog pharmacokinetic measurements identified a series of 17 beta-[N-(diphenylmethyl)carbamoyl]-6-azaandrost-4-en-3-ones (compounds 54, 66, and 67) with good in vivo efficacy and half-life in the dog. Inhibitors with, at the minimum, low nanomolar potency toward both human 5AR's and selectivity versus 3BHSD may show advantages over previously known 5AR inhibitors in the treatment of disease states which depend upon dihydrotestosterone, such as benign prostatic hyperplasia.

Investigation of the beta 2-agonist properties of dilevalol: metabolic effects of intravenous infusion.

We describe two studies which investigate the beta 2-agonist properties of dilevalol. We have previously demonstrated, by giving an infusion of terbutaline to human volunteers, that beta 2-stimulation causes a rise in plasma glucose and a fall in plasma potassium. These metabolic effects can be prevented by prior beta-blockade. We now show that infusion of dilevalol produces similar, but quantitatively smaller, metabolic effects at a dose which also produces clinically significant beta-blockade, as judged by a fall in exercise heart rate. This adds support to the claim that dilevalol is a non-selective beta-blocker with selective beta 2-agonist activity.

A metabolic assessment of the beta 1 selectivity of bisoprolol.

Twelve healthy volunteers were given single oral doses of bisoprolol 5 mg, 10 mg and 20 mg and atenolol 50 mg and 100 mg in a randomised, placebo-controlled study. The effects of these drugs on beta 2-stimulated hypokalaemia and hyperglycaemia (produced by intravenous terbutaline infusion) were studied. Comparable beta-blockade was achieved with bisoprolol 20 mg, and atenolol 50 mg and 100 mg as measured by attenuation of exercise heart rate. Measurements of areas under or over the curve (AUC and AOC) of hypokalaemic or hyperglycaemic response to terbutaline infusion showed that bisoprolol (10 mg and 20 mg) and atenolol (50 mg and 100 mg) were significantly less beta 1 selective than 5 mg bisoprolol. Furthermore, there was a trend towards decreasing beta 1 selectivity with increasing doses of bisoprolol. Bisoprolol, an effective once daily antihypertensive and antianginal treatment, has comparable beta 1 selectivity to atenolol as measured by metabolic response. At a dose of 5 mg, bisoprolol has a measurable impact on beta 1 receptors but minimal effect on beta 2 receptors.

Root substance removal with Er:YAG laser radiation at different parameters using a new delivery system.

BACKGROUND: The recently introduced Er:YAG laser radiation appears to be a promising alternative in treating dental hard tissue due to its thermo-mechanical ablation properties and the lack of thermal side effects. The present in vitro study attempted to evaluate the use of Er:YAG laser radiation in combination with a specially developed delivery system in removing calculus from root surfaces. METHODS: Fifty extracted anterior teeth, premolars and molars, were divided into 2 groups of 25 each with (group A) and without (group B) subgingival calculus. Source of radiation was an Er:YAG laser device with a wavelength of 2.94 microm, in the infrared optical spectrum, a pulse duration of 250 ns, and a pulse repetition rate of 15 pps. In each group, 6 teeth were irradiated with 300 laser pulses either at 60 mJ, 80 mJ, 100 mJ, or 150 mJ. The samples were continually moved linearly using a computer numeric controlled device. The volumetric evaluation of root substance removal was performed with a 3-dimensional laser scanning system (100,000 surface points per sample, accuracy: 5 microm) and special image analyzing software. A scanning electron microscopic (SEM) observation was performed to assess the laser induced ultrastructural changes on the root surfaces. Statistical analysis was carried out with ANOVA followed by the Scheff*e test and with regression analysis according to Pearson-Bravais at a level of significance of 5% (P <0.05). RESULTS: The linear measurement of substance removal on calculus samples (group A) revealed average depths between 174.38 (+/-16.13) microm and 501.85 (+/-111.01) microm. Defect depths on the teeth without calculus (group B) ranged from 37.78 (+/-14.03) microm to 484.44 (+/-80.63) microm. The SEM observation of laser-treated root surfaces revealed no signs of thermal damage; e.g., melting, fusion, or cracking. CONCLUSIONS: The results of the present study showed that a substance removal with Er:YAG laser radiation at lower energy densities is comparable, in effect, to that after conventional root surface instrumentation with curets. The results seem to indicate that calculus removal can be selectively done using lower radiation energies. Considering the favorable results of the SEM investigation, the use of the Er:YAG laser in periodontal therapy may be possible in the future.

Bactericidal effects of 2.94 microns Er:YAG-laser radiation in dental root canals.

The purpose of this study was to investigate the antimicrobial properties of Er:YAG-laser radiation in dental root canals. The root canals of 90 freshly extracted anterior teeth were enlarged mechanically, sterilized, and randomly divided into subgroups of 10 samples. The root canals were inoculated with Escherichia coli or Staphylococcus aureus for 2 h. The laser treatment groups were exposed for either 15 or 60 s to Er:YAG-laser radiation (pulse energy: 50 mJ; 15 pps). Additionally, for each bacterial strain, one sample group was rinsed with a NaOCl solution (1.25%), and one was left untreated as control. After irradiation or irrigation, the number of bacteria was evaluated using the surface spread plate technique. In the case of S. aureus, the primary bacterial load (control group) of the root canals was reduced to 0.15% after 15 s and 0.06% after 60 s of laser treatment. In the E. coli group, the number of bacteria was diminished to 0.13%, with the shorter radiation time and to 0.034% after 60 s of radiation. Irrigating the root canals with NaOCl, a reduction of the number of bacteria to 0.033% for S. aureus and to 0.020% for E. coli could be obtained. As the results confirm, Er:YAG-laser radiation exerts very effective antimicrobial properties in dental root canals, depending on the time of radiation.

Polishing and coating of dental ceramic materials with 308 nm XeCl excimer laser radiation.

OBJECTIVES: The polishing and coating of ceramic surfaces is recommended in order to improve the physical properties of dental ceramics. Conventional methods for the surface treatment of dental ceramic materials are not capable of creating a smooth surface without microcracks. The special radiation characteristics of XeCl excimer laser light indicate that it must be possible to treat ceramic surfaces in order to produce a polished finish. The aim of this study was to investigate the efficacy of XeCl excimer laser radiation for the polishing and coating of dental ceramics. METHODS: Samples (n = 64) of four different dental ceramic materials were irradiated with 308 nm XeCl excimer laser radiation at varying energy densities per laser pulse of 1.57, 3.14, and 6.28 J cm-2. In detail, the subjects for irradiation were samples of Ivoclar-Empress (leucite-reinforced feldspathic ceramic), In-Ceram Spinell (double crystalline spinell ceramic), In-Ceram Alumina (alumina oxide; continous interpenetrating phase composite ceramic) and Vita-Mark II (feldspathic ceramic). The roughness (Ra) of the laser-treated ceramic surfaces was measured using a profilometer. In addition, SEM and AFM investigations of the changes in surface structure were conducted. The changes in surface roughness due to laser treatment were analyzed for their statistical significance using ANOVA with the Scheffé test at a level of significance of 0.05% (p < 0.05). Depending on the type of ceramic material and the energy density of the radiation, varying reductions of the surface roughness were obtained. In general, minimum values of the roughness were measured on samples irradiated with maximum energy density of radiation. RESULTS: The lowest roughness value was obtained for the specimen of In-Ceram Spinell: 1.30 (+/- 0.19) microns. The mean value for minimal roughness of Ivoclar-Empress was 1.92 (+/- 0.35) microns, that for In-Ceram Alumina was 2.04 (+/- 0.49) microns, and that for Vita-Mark II was 2.72 (+/- 0.40) microns. Ultrastructural examination of laser-treated ceramics in part demonstrated both extensive fusion and inhomogeneous surfaces with blistering and the formation of microcracks. SIGNIFICANCE: It is concluded that the physical roughness of dental ceramic surfaces can be significantly reduced by 308 nm excimer laser irradiation. Nevertheless, the laser-treated surface was in no case completely fused and the formation of microcracks and blistering was observed. Therefore, after using an XeCl excimer laser for finishing dental ceramic alloys, further polishing of the laser-treated ceramic surfaces will be needed.

Relative maxillary retrusion as a natural consequence of aging: combining skeletal and soft-tissue changes into an integrated model of midfacial aging.

The contribution of maxillary retrusion to the formation of the nasolabial fold is evaluated in the present study. Clinical observation of patients from the craniofacial unit with concomitant maxillary retrusion revealed prominent signs of midfacial aging: specifically these individuals displayed a prominent nasolabial fold at an early age. This observation led to the hypothesis that relative maxillary retrusion occurs as a normal feature of the aging process. Retrusion of the lower facial skeleton below the soft tissue of the nasolabial fold causes the nasolabial fold to appear more prominent. To test this hypothesis, computed tomographic data were assembled retrospectively and included both males and females, young and old. The age range of the males (n = 14) was 18 to 24 years (young) and 43 to 57 years (old); the age range of the females (n = 14) was 15 to 30 years (young) and 43 to 57 years (old). All individuals had complete upper dentition and had no bony facial injury. Computed tomographic data were reconstructed into three-dimensional images, and a technique was developed to create a standardized lateral view which eliminated rotational variance. Analysis of anterior-posterior changes showed that there is a tendency for the lower maxillary skeleton at pyriform to become retrusive with age relative to the upper face in individuals with complete dentition. Findings were very significant for both males and females (p = 0.0001 and p = 0.002, respectively). In both groups, a slight increase in vertical maxillary dimension was noted, consistent with previous studies. It is suggested that relative maxillary retrusion is a factor in the development of the nasolabial fold. The skeletal features of normal midfacial aging can be combined with the soft-tissue features such as ptosis and atrophy into an integrated model of midfacial aging. A model such as this has significance regarding both the timing and choice of procedure used to restore the aging midface.

[Value and limitations of coronary artery imaging with the MRI navigator technique. Comparison with coronary angiography results in 37 patients]. / Intérêt et limites actuelles de l'imagerie des artères coronaires avec la technique d'IRM du navigateur. Comparaison avec les données coronaro-angiographiques chez 37 patients.

The introduction of a non-invasive method of imaging the coronary arteries would be a great advance in daily cardiological practice. The authors report their experience of imaging the coronary arteries with 1 Tesla MRI using the "navigator technique". Twenty-five sections 1.2 mm thick, focused on the proximal left coronary artery, were acquired with a 512 matrix, without injecting contrast during normal respiration with a tolerance on the portion of the right diaphragmatic cupola of 5 mm. Analysis of the coronary segments included in the field of view was performed on native sections after curve reconstruction and on targetedMIP series. A comparison of the results with respect to conventional coronary angiography showed a relatively limited visualisation of the proximal coronary segments because, in addition to the impossibility of carrying out the investigation in 24% of cases (faulty cardiac or respiratory synchronisation, poor signal/noise ratio), only 93% of the left main coronary and 75% of the proximal left anterior descending arteries could be visualised. In the analyzable segments, the diagnostic performances were modest with a global sensitivity of 60.8% and specificity of 91%. With the exception of the left main coronary artery, the sensitivities observed did not make MRI of the coronary arteries a rival to conventional coronary angiography. These limited performances may be explained by the lack of rapidity of the sequences of acquisition compared to the rapid motion of the structures under investigation whose dimensions are 5 to 10 times smaller than their amplitude of excursion. Technical developments are regularly accomplished in this domain, especially 3rd generation sequences in apnoea with injection of contrast media. At present, despite some results reported in the literature, angio-MRI of the coronary arteries cannot be used reliably to guide clinical decisions in coronary artery disease with the exception of some situations like congenital abnormalities of the coronary arteries, non-invasive follow-up of coronary aneurysms or analysis of the left main coronary artery.

A technique for three-dimensional cephalometric analysis as an aid in evaluating changes in the craniofacial skeleton.

A technique is presented for creating a standardized view for use in three-dimensional cephalometry. Three-dimensional cephalometric analysis has become a valuable tool in the assessment of skeletal remodeling, contour changes, and changes in proportion that occur with aging. Computer-assisted tomographic data can be used in either coronal or axial sections; the present study was performed with axially acquired data that was processed in several steps to achieve a standardized position of the facial skeleton for further evaluation. This technique may be a useful adjunct to standard cephalometrics to evaluate the craniofacial skeleton.