Search

Aminoglycosides (AGs) in combination with β-lactams play an important role in antimicrobial therapy in severe infections. Pan-resistance to clinically relevant AGs increasingly arises from the production of 16S rRNA methylases (RMTases) that are mostly encoded by plasmids in Gram-negative bacteria. The recent emergence and spread of isolates encoding RMTases is worrisome, considering that they often co-produce extended-spectrum β-lactamases (ESBLs) or carbapenemases. Our study aimed to retrospectively analyze and characterize the association of carbapenem- and aminoglycoside-resistant clinical isolates in Switzerland during a 3.5-year period between January 2017 and June 2020. A total of 103 pan-aminoglycoside- and carbapenem-resistant clinical isolates were recovered at the NARA (Swiss National Reference Center for Emerging Antibiotic Resistance) during the 2017-2020 period. Carbapenemase and RMTase determinants were identified by PCR and sequencing. The characterization of plasmids bearing resistance determinants was performed by a mating-out assay followed by PCR-based replicon typing (PBRT). Clonality of the isolates was investigated by multilocus sequence typing (MLST). Over the 991

Recently lithium niobate on insulator (LNOI) has emerged as a promising platform for photonic integrated circuits (PICs) owing to the material’s high second order nonlinearity, a large transparency window and high piezo electric coefficients. Published results on LNOI range from efficient electro-optic modulators [1] to broadband supercontinua [2] – [4] . However, lithium niobate has a comparably high sensitivity towards optical damage processes such as photorefractive damage [5] , [6] . Their exact mechanisms are not yet fully understood and the impact on the long-term stability of LNOI devices has not yet been examined. Here, we present long-term measurements showing that during 400 hours of continuous irradiation with a mode-locked laser the supercontinuum spectrum remains stable.

We demonstrate that lithium niobate integrated photonics allows for reliable nonlinear applications under continuous femtosecond laser irradiation. Over >100 hours, a stable octave-spanning supercontinuum plus second-harmonic generation allows for direct self-referencing of a frequency comb.

Optical frequency combs have become a very powerful tool in metrology and beyond thanks to their ability to link radio frequencies with optical frequencies via a process known as self-referencing. Typical self-referencing is accomplished in two steps: the generation of an octave-spanning supercontinuum spectrum and the frequency-doubling of one part of that spectrum. Traditionally, these two steps have been performed by two separate optical components. With the advent of photonic integrated circuits, the combination of these two steps has become possible in a single small and monolithic chip. One photonic integrated circuit platform very well suited for on-chip self-referencing is lithium niobate on insulator - a platform characterised by high second and third order nonlinearities. Here we show that combining a lithium niobate on insulator waveguide with a silicon photodiode results in a very compact and direct low-noise path towards self-referencing of mode-locked lasers. Using digital servo electronics the resulting frequency comb is fully stabilized. Its high degree of stability is verified with an independent out-of-loop measurement and is quantified to be 6.8 mHz. Furthermore, we show that the spectrum generated inside the lithium niobate waveguide remains stable over many hours.

The paper describes the fabrication of a silicon carbide piezoresistive pressure sensors intended for operating temperatures of up to 600°C. The different fabrication aspects, such as the metallization scheme, the etching of a 300μm deep cavity, and the bonding to a silicon carbide back plate are discussed in detail.

In future space missions for Universe and Earth Observation, scientific return could be optimized using MOEMS devices. Large micromirror arrays (MMA) are used for designing new generation of instruments. In Universe Observation, multi-object spectrographs (MOS) are powerful tools for space and ground-based telescopes for the study of the formation and evolution of galaxies. This technique requires a programmable slit mask for astronomical object selection; 2D micromirror arrays are perfectly suited for this task. In Earth Observation, removing dynamically the straylight at the entrance of spectrographs could be obtained by using a Smart Slit, composed of a 1D micro-mirror array as a gating device. We are currently engaged in a European development of micro-mirror arrays, called MIRA, exhibiting remarkable performances in terms of surface quality as well as ability to work at cryogenic temperatures. MMA with 100 × 200 μm2 single-crystal silicon micromirrors were successfully designed, fabricated and tested down to 162 K. In order to fill large focal planes (mosaicing of several chips), we are currently developing large micromirror arrays to be integrated with their electronics. 1D and 2D arrays are built on wafer with Through Wafer Vias in order to allow routing of the device on wafer backside, foreseeing integration with dedicated ASICs. The yield of these devices as well as contrast enhancement have been successfully implemented.

In the context of xenotransplantation, in ischemia/reperfusion injury as well as in cardiovascular research, the study of the fascinating interplay between endothelial cells (EC) and the plasma cascade systems often requires in vitro models. Blood vessels are hardly reproducible with standard flat-bed culture systems and flow-plate assays are limited in their low surface-to-volume ratio which impedes the study of the anticoagulant properties of the endothelial cells. According to the 3R regulations (reduce, replace and refine animal experimentation) we developed a closed circuit microfluidic in vitro system in which endothelial cells are cultured in 3D round section microchannels and subjected to physiological, pulsatile flow. In this study, a 3D monolayer of porcine aortic EC was perfused with human serum to mimic a xenotransplantation setting. Complement as well as EC activation was assessed in the presence or absence of complement inhibitors showing the versatility of the model for drug testing. Complement activation products as well as E-selectin expression were detected and visualized in situ by high resolution confocal microscopy. Furthermore, porcine pro-inflammatory cytokines as well as soluble complement components in the recirculating fluid phase were detected after human serum perfusion providing a better overview of the artificial vascular environment.

We have designed, fabricated and tested narrow-band Fabry-Perot filters in the infrared using gold porous mirrors and a silicon spacer layer. The filter peaks at 10 μm and 15 μm have approximately 10% transmission and a 1.5% linewidth. A Fabry-Perot structure with plane metal layers having a similar linewidth would have a transmission of only 0.2%. Thus, for the same linewidth we have improved the transmission by a factor of 50. Apart from the optical enhancements, these filters also have the advantage that they can be made inexpensively in a standard silicon MEMS technology and that their resonances can be finely tuned through post processing.

Acute vascular rejection (AVR), in particular microvascular thrombosis, is an important barrier to successful pig-to-primate xenotransplantation. Here, we report the generation of pigs with decreased tissue factor (TF) levels induced by small interfering (si)RNA-mediated gene silencing. Porcine fibroblasts were transfected with TF-targeting small hairpin (sh)RNA and used for somatic cell nuclear transfer. Offspring were analyzed for siRNA, TF mRNA and TF protein level. Functionality of TF downregulation was investigated by a whole blood clotting test and a flow chamber assay. TF siRNA was expressed in all twelve liveborn piglets. TF mRNA expression was reduced by 94.1 ± 4.7% in TF knockdown (TFkd) fibroblasts compared to wild-type (WT). TF protein expression in PAEC stimulated with 50 ng/mL TNF-α was significantly lower in TFkd pigs (mean fluorescence intensity TFkd: 7136 ± 136 vs. WT: 13 038 ± 1672). TF downregulation significantly increased clotting time (TFkd: 73.3 ± 8.8 min, WT: 45.8 ± 7.7 min, p

Many studies in the field of cell-based cartilage repair have focused on identifying markers associated with the differentiation status of human articular chondrocytes (HAC) that could predict their chondrogenic potency. A previous study from our group showed a correlation between the expression of S100 protein in HAC and their chondrogenic potential. The aims of the current study were to clarify which S100 proteins are associated with HAC differentiation status and to provide an S100-based assay for measuring HAC chondrogenic potential. The expression patterns of S100A1 and S100B were investigated in cartilage and in HAC cultured under conditions promoting dedifferentiation (monolayer culture) or redifferentiation (pellet culture or BMP4 treatment in monolayer culture), using characterized antibodies specifically recognizing S100A1 and S100B, by immunohistochemistry, immunocytochemistry, Western blot, and gene expression analysis. S100A1 and S100B were expressed homogeneously in all cartilage zones, and decreased during dedifferentiation. S100A1, but not S100B, was re-expressed in pellets and co-localized with collagen II. Gene expression analysis revealed concomitant modulation of S100A1, S100B, collagen type II, and aggrecan: down-regulation during monolayer culture and up-regulation upon BMP4 treatment. These results strongly support an association of S100A1, and to a lesser extent S100B, with the HAC differentiated phenotype. To facilitate their potential application, we established an S100A1/B-based flow cytometry assay for accurate assessment of HAC differentiation status. We propose S100A1 and S100B expression as a marker to develop potency assays for cartilage regeneration cell therapies, and as a redifferentiation readout in monolayer cultures aiming to investigate stimuli for chondrogenic induction.

Purpose Cytokines play an important role in cell signaling in inflammatory and repair processes, also within the posterior segment of the eye. These molecules are thus implicated in the pathophysiology of several vitreoretinal diseases. In the present study, we compared vitreal cytokine profiles in patients with idiopathic epiretinal membranes (ERMs) and idiopathic full-thickness macular holes (MHs) without epiretinal membranes. Methods Native vitreal humor was collected during elective pars plana vitrectomy for the treatment of macular pathologies (group 1: ERM; group 2: MH) from patients without any other ocular or systemic disease. The concentrations of 43 chemokines and cytokines were measured in parallel by multiplex beads analysis. Intergroup comparisons were conducted using the Mann-Whitney U test and Bonferroni's correction, at a level of significance of P < 0.0012. Results Vitreal samples from 31 patients with ERMs (group 1) and from 30 with MHs (group 2) were analyzed. For 12 of the tested cytokines (GM-CSF, MCP-1, MIF, CCL15, CCL20, CCL17, CX3CL1, CXCL10, CXCL16, and TGF-β-1, -2, and -3), no intergroup differences were revealed; for the other 31, the concentrations were higher in the ERM than in the MH group (P < 0.0012 in each case). Conclusions The vitreal levels of 72% of the tested cytokines were higher in ERM than in MH. This indicates that even in the absence of clinical markers, activation of inflammatory and profibrotic mechanisms is implicated in the progression of ERMs. Although frequently used as such in the past, eyes with ERMs should be considered with caution as a healthy control group.

Structural variability and flexibility are crucial factors for biomolecular function. Here we have reduced the invasiness and enhanced the spatial resolution of atomic force microscopy (AFM) to visualize, for the first time, different structural conformations of the two polynucleotide strands in the DNA double helix, for single molecules under near-physiological conditions. This is achieved by identifying and tracking the anomalous resonance behavior of nanoscale AFM cantilevers in the immediate vicinity of the sample.

This paper presents a new fabrication technology for conducting AFM cantilevers with integrated AlN-based piezoelectric actuators. A major effort has been done for the process integration of a high quality AlN layer onto the Si cantilever together with a high wear resistance, PtSi-based conducting tip. Functional AFM devices have been successfully tested in tapping mode imaging experiments. Such type of cantilevers are of great interest for dynamic AFM applications especially for tapping or dithering mode AFMs as well as for using the piezoelectric structures as an integrated position sensor.

We report on the development of a pneumatically coupled graphene membrane system, comprising of two circular cavities connected by a narrow trench. Both cavities and the trench are covered by a thin few-layer graphene membrane to form a sealed dumbbell-shaped chamber. Local electrodes at the bottom of each cavity allow for actuation of each membrane separately, enabling electrical control and manipulation of the gas flow inside the channel. Using laser interferometry, we measure the displacement of each drum at atmospheric pressure as a function of the frequency of the electrostatic driving force and provide a proof-of-principle of using graphene membranes to pump attolitre quantities of gases at the nanoscale.

For patterning organic resists, optical and electron beam lithography are the most established methods; however, at resolutions below 30 nanometers, inherent problems result from unwanted exposure of the resist in nearby areas. We present a scanning probe lithography method based on the local desorption of a glassy organic resist by a heatable probe. We demonstrate patterning at a half pitch down to 15 nanometers without proximity corrections and with throughputs approaching those of Gaussian electron beam lithography at similar resolution. These patterns can be transferred to other substrates, and material can be removed in successive steps in order to fabricate complex three-dimensional structures.

Introduction Data acquisition is still one of the important challenges to be met in clinical settings. This is even more critic in settings with high cognitive workloads, such as emergency room (ER). Observations in these settings are difficult to realize without biases and there is little means to trace fine acquisition activities done in natural environments, using pen and papers. This study is based on the usage of a digital pen and paper (DPP) technology for the acquisition of triage information by nurses in ER. The DPP technology has been used to ease acquisition using a natural mechanism; it also minimizes the external influence of observation during acquisition activities. The aim of this study is to determine whether data recorded by the DPP technology allows explaining how ER triage nurses use the triage forms in real working conditions. Methodology The chief physicians of the ER service wanted to have answers about three main concerns pertaining to the triage process: (1) the average time spent during the triage process; (2) the sequence in which the fields of the forms were filled and; (3) the contribution of objective measurements, such as vital signs, to the triage emergency level and decisions. In order to answer these questions, detailed log data recorded by the DPP during form filling as been analyzed and allowed to built several representations of the triage process. In addition, we completed this analysis with ethnographical-like observations. Results For seven consecutive days, 1183 triage forms have been recorded in the ER for all patients admitted. Among them, 954 forms have been digitalized and 906 forms have been considered as valid and complete. Based on this set of data, the median duration of the triage process is 143 s. There are no converging habits in filling the forms and the sequence of filling fields present a high variability. The emphasis of the objective measurements in the decisional process is rather low, as vital signs are recorded in less than 17% of the cases. Conclusion The DPP technology is an original approach to study data acquisition processes in unbiased conditions. The technical raw data recorded by the DPP allows building the time series of all activities on the paper, therefore letting to constructing several representations of the process. However, the technology is not able to provide information about the context of use, for example interruptions of the form filling processes due to calls or other activities. Therefore, it is necessary to complete these analyses with qualitative approaches such as observational studies and interviews. Noticeably, as a result of this study, the head physicians of ER have redesigned the triage form to enforce the use of objective measurements and ease the data acquisition process.

In this work we describe the design, fabrication, and testing of a mass-balanced planar x/y-scanner designed for parallel-probe data storage applications. The scanner is actuated by comb drives, whose finger shape is improved using finite-element analysis to increase the force output. A mass-balancing concept is used for in-plane shock resistance; in the out-of-plane direction passive shock resistance is achieved using 1:40 aspect-ratio springs that are fabricated by deep reactive ion etching through the full thickness of a [email protected] wafer. A prototype device is presented and its performance is reported.

A microelectromechanical system actuator based on thermophoretic, or Knudson, forces is proposed using analytical calculations. It can potentially execute scanning or spinning motions of a body that is not mechanically attached to the reference substrate. For a silicon device of 100-mum diameter, it is calculated that it can be levitated at a distance of about 0.5 mum from a substrate and that it can execute scanning motion and use quasi-springs by laterally acting thermal forces. In this way, an engine with spinning motion of a floating body having a diameter of 200 mum with up to 5 kHz can be achieved.

Ultrahigh storage densities can be achieved by using a thermomechanical scanning-probe-based data-storage approach to write, read back, and erase data in very thin polymer films. High data rates are achieved by parallel operation of large two-dimensional arrays of cantilevers that can be batch fabricated by silicon-surface micromachining techniques. The very high precision required to navigate the storage medium relative to the array of probes is achieved by microelectromechanical system (MEMS)- based x and y actuators. The ultrahigh storage densities offered by probe-storage devices pose a significant challenge in terms of both control design for nanoscale positioning and read-channel design for reliable signal detection. Moreover, the high parallelism necessitates new dataflow architectures to ensure high performance and reliability of the system. In this paper, we present a small-scale prototype system of a storage device that we built based on scanning-probe technology. Experimental results of multiple sectors, recorded using multiple levers at 840 Gb/in2 and read back without errors, demonstrate the functionality of the prototype system. This is the first time a scanning-probe recording technology has reached this level of technical maturity, demonstrating the joint operation of all building blocks of a storage device.

Currently, the broad market introduction of shape memory alloy (SMA) microactuators and sensors is hampered by technological barriers, since batch fabrication methods common to electronics industry are not available. The present study intends to overcome these barriers by introducing a wafer scale transfer process that allows the selective transfer of heat-treated and micromachined shape memory alloy (SMA) film or foil microactuators to randomly selected receiving sites on a target substrate. The technology relies on a temporary adhesive bonding layer between SMA film/foil and an auxiliary substrate, which can be removed by laser ablation. The transfer technology was tested for microactuators of a cold-rolled NiTi foil of 20 μm thickness, which were heat-treated in free-standing condition, then micromachined on an auxiliary substrate of glass, and finally selectively transferred to different target substrates of a polymer. For demonstration, the new technology was used for batch-fabrication of SMA-actuated polymer microvalves.

We have developed a generic cost-efficient CMOS-compatible heterogeneous device integration method at wafer-scale level. This method enables the distribution of devices from one to numerous wafers using selective transfer technology. We have applied this method for the distribution of atomic force microscopy (AFM) cantilevers and successfully demonstrated the population of multiple wafers from one source wafer. The distribution function has been designed such as to populate 42 wafers with only one source wafer. This CMOS back-end-of-the-line compatible method is particularly suitable for microelectromechanical systems and integrated circuits. Electrical interconnects are compatible with this technology. We present the concept, the selective transfer method, including a laser ablation technique used for the transfer, as well as the process and results of the application for AFM cantilever distribution.

The Fermi surface topology of the layered superconducting charge density wave compound ZrTe3is investigated by angle resolved photoelectron spectroscopy and density functional theory. The Fermi surface is dominated by bands originating from two perpendicular systems of quasi one-dimensional chains. Nesting and opening of a pseudogap at temperatures as high as 250 K are signatures of a Peierls transition in one of these chains. The nesting properties are also studied for high pressure simulated crystal structure.

Spark assisted chemical engraving (SACE) is an unconventional micro-machining technology for glass processing based on electrochemical discharges. SACE gravity-feed drilling is discussed and the material removal rate, quality and geometrical dimensions of drilled micro-holes in glass as a function of the drilling depth are characterized optically. Depending on the machining voltage and drilling depth, four different kinds of micro-hole qualities are obtained from holes with well-defined sharp contours to holes affected by thermal cracks. Based on these results a qualitative model for SACE machining by gravity-feed is given.

SUMMARY Comparative aminoacid sequence studies were done on chymotryptic peptides from the Fc fragments of IgG1, IgG2, IgG4a and IgG4b human myeloma proteins. Eleven peptides were positioned within the Fc fragments of IgG4 proteins. While leucine was present at position 309 of the Fc fragment of the IgG4a protein, it was absent from the Fc fragment of the IgG4b protein.

We describe a planar microelectromechanical systems (MEMS)-based x/y nanopositioner designed for parallel-probe storage applications. The nanopositioner is actuated electromagnetically and has x/y motion capabilities of plusmn60 mum. The mechanical components are fabricated from a single-crystal silicon wafer using a deep-trench-etching process. To render the system robust against vibration, we utilize a mass-balancing concept that makes the system stiff against linear shock, but still compliant for actuation, and therefore results in low power consumption. We present details of the finite-element model used to design the device as well as experimental results for the frequency response, actuation, and vibration-rejection properties of the nanopositioner

An integrated position sensor for a dual-axis electromagnetic tilting mirror is presented. This tilting mirror is composed of a silicon based mirror directly assembled on a silicon membrane supported by flexible beams. The position sensors are constituted by 4 Wheatstone bridges of piezoresistors which are fabricated by doping locally the flexible beams. A permanent magnet is attached to the membrane and the scanner is mounted above planar coils deposited on a ceramic substrate to achieve electromagnetic actuation. The performances of the piezoresistive sensors are evaluated by measuring the output signal of the piezoresistors as a function of the tilt of the mirror and the temperature. White light interferometry was performed for all measurement to measure the exact tilt angle. The minimum detectable angle with such sensors was 30µrad (around 13bits) in the range of the minimum resolution of the interferometer. The tilt reproducibility was 0.0186%, obtained by measuring the tilt after repeated actuations with a coil current of 50mA during 30 min and the stability over time was 0.05% in 1h without actuation. The maximum measured tilt angle was 6° (mechanical) limited by nonlinearity of the MEMS system.

Au tournant des années soixante, Gaëtan Picon s'éloigne d'André Malraux pour affirmer ses propres valeurs. Quittant la critique littéraire pour la critique d'art, il opère une conversion qui, inscrite dans un contexte de mainmise formaliste, intervient en réponse à son questionnement esthétique., At the start of the '60s, Gaëtan Picon distances himself from André Malraux in order to assert his own values. Leaving literary criticism for art criticism, he effects a conversion which, in the context of formalist dominance, is a form of response to aesthetic questioning.

Spark-assisted chemical engraving (SACE) is an unconventional micro-machining technology particularly suited for glass processing, taking advantage of electrochemical discharges. This technology distinguishes itself by its simplicity and flexibility, the possibility of machining high aspect ratio structures, the excellent surface qualities and the non-utilization of expensive clean room facilities. As the process is a serial one, the material removal rate becomes an important issue. It is shown that, by adequate tool vibration, it is possible to improve the mean material removal rate in gravity-feed drilling by a factor of 2. Micro-holes in glass with a depth of 300 µm are drilled in less than 10 s.

Multiple scattering theory based on a cluster model is used to simulate full hemispherical X-ray photoelectron diffraction measurements on a 1T-TaS2(0001) surface. Key points to determine the surface termination are discussed. As the commonly applied single scattering simulations do not give satisfying results, a multiple scattering approach has to be used to accurately simulate the full hemispherical photoelectron diffraction patterns. Differences and similarities between calculations of Ta and S terminated surfaces are presented along with experimental results at room temperature using both, the single and the multiple scattering approaches. We find that the surface is S terminated and that the quantitative difference between the calculations for both terminations permits to show the limits of the single scattering approach for solving surface termination problems. Moreover, by generalizing the results obtained using the multiple scattering approach, we discuss the application of this method to other similar systems

The thermomechanical scanning-probe-based data storage concept, internally known as the ''millipede'' project, combines ultrahigh density, small form factor, and high data rates. Ultrahigh storage densities of more than 1 Tb/in^2 can be achieved by using local-probe techniques to write, read back, and erase data in very thin polymer films. In this paper special focus is given to the crucial role of the polymer storage medium in thermomechanical probe storage systems. High data rates are achieved by parallel operation of large 2D arrays with thousands micro/nanomechanical cantilevers/tips that can be batch-fabricated by silicon surface-micromachining techniques. The very high precision required to navigate the probe tips over the storage medium is achieved by MEMS-based x/y actuators that position the large arrays of probe tips for parallel write/read/erase operations. The inherent parallelism, the ultrahigh areal densities and the small form factor may open up new perspectives and opportunities for application in areas beyond those envisaged today.

Full hemispherical X-ray photoelectron diffraction (XPD) experiments have been performed to investigate at the atomic level ultrathin epitaxial c-axis oriented PbTiO3 (PTO) films grown on Nb-doped SrTiO3 substrates. Comparison between experiment and theory allows us to identify a preferential ferroelectric polarization state in a 60 Å -thick PTO film. Multiple scattering theory based on a cluster-model [ Phys. Rev. B 63, 075404 (2001)] is used to simulate the experiments., This project has been supported by the Swiss National Science Foundation through the National Center of Competence in Research “Materials with Novel Electronic Properties-MaNEP”, and in part by the Office of Science, Materials Sciences Division, of the U.S. Department of Energy under Contract No. DE-AC03-76SF00098.

We successfully fabricated single-crystal silicon cantilevers with spring constants as low as 10−5 N m−1 for use in magnetic resonance force microscopy applications. The fabricated ultra-thin silicon cantilevers had thicknesses ranging from 200 to 400 nm, lengths ranging from 340 to 450 µm and a width of 5 µm. We characterized their force sensitivity in the vacuum range from ambient pressure to 10−3 Pa and the temperature range from 15 to 300 K. A minimum value is observed for the internal friction, Q−1, at 160 K, which corresponds to an activation peak due to phonon scattering by atomic-scale defects. The best force sensitivity was achieved at 20 K, where it was increased by a factor of 10 as compared to that observed at room temperature.

ObjectivesThis article proposes a model for dimensions involved in user evaluation of clinical information systems (CIS). The model links the dimensions in traditional CIS evaluation and the dimensions from the human–computer interaction (HCI) perspective.Proposed methodIn this article, variables are defined as the properties measured in an evaluation, and dimensions are defined as the factors contributing to the values of the measured variables. The proposed model is based on a two-step methodology with: (1) a general review of information systems (IS) evaluations to highlight studied variables, existing models and frameworks, and (2) a review of HCI literature to provide the theoretical basis to key dimensions of user evaluation.ResultsThe review of literature led to the identification of eight key variables, among which satisfaction, acceptance, and success were found to be the most referenced.DiscussionAmong those variables, IS acceptance is a relevant candidate to reflect user evaluation of CIS. While their goals are similar, the fields of traditional CIS evaluation, and HCI are not closely connected. Combining those two fields allows for the development of an integrated model which provides a model for summative and comprehensive user evaluation of CIS. All dimensions identified in existing studies can be linked to this model and such an integrated model could provide a new perspective to compare investigations of different CIS systems.

Summary Objectives: To evaluate the efficiency and acceptance of digital pen and paper technology for real-time clinical data acquisition. Methods: A prospective interventional unblinded study involving consecutive patients in two clinical settings during a defined time-frame was proposed. The first trial was designed as a stress test to evaluate acceptance in a workload-intensive environment. Acceptance was assessed using observations and a satisfaction questionnaire. The second trial was intended to determine the reliability of data acquisition in a controlled environment. Reliability was assessed by comparing the performance of the digital pen against scanner analysis and a double human blinded acquisition. Results: Overall, users were satisfied with the use of the digital pen (median 3 on a Likert-scale (–5, 5)). Without any specific user training, successful data acquisition was greater than 80%. Use of this technology required less adaptation than standard computer devices, and was easy to learn and use. Ergonomic problems shaded the perception of the technology by inducing an increased cognitive load. Digitalized data was missing either because of a bug or due to lack of data validation. The reliability obtained with the digital pen was significantly lower to that obtained with the scanner. Conclusions: Natural technology such as the digital pen proved to be a good tool in stressful clinical environments without interfering with the normal workload or increasing the time for data acquisition. However, in order to improve quality of data acquisition, designing acquisition forms specifically for the use of digital pens is of paramount importance.

We have developed a robust, CMOS back end of the line (BEOL) compatible, wafer-scale device transfer, and interconnect method for batch fabricating systems on chip that are especially suitable for MEMS or VLSI-MEMS applications. We have applied this method to transfer arrays of 4096 free-standing cantilevers with good cantilever flatness control and high-density vertical electrical interconnects to the receiver wafer (typically CMOS). Such an array is used in a highly parallel, scanning-probe-based data-storage system, which we internally call "millipede." A very high-integration density has been achieved, even for wafer-scale transfer, thanks to the interlocking nature of the interconnect structure, which provides easy alignment with an accuracy of 2 /spl mu/m. The typical integration density is 100 cantilevers/mm/sup 2/ and 300 electrical interconnects/mm/sup 2/. Note that only the cantilevers, not a chip with cantilevers, are transferred and, unlike flip-chip technology, our method preserves the device orientation, which is crucial for MEMS applications, where often the MEMS device should have access to its environment (in our case, the cantilever tips are in contact with the storage medium). After device transfer, the system is mechanically and electrically stable up to at least 500/spl deg/C, allowing post-transfer wafer processing.

The transition metal dichalcogenide 1 T - TaS 2 is a layered material exhibiting charge density waves. Based on angle-resolved photoemission experiments mapping spectral weight at the Fermi surface and density functional theory calculations we discuss possible mechanisms involved with the creation of charge density waves. At first the flat parts of the elliptically shaped Fermi surface appear to play an important role via Fermi surface nesting. A closer analysis of the charge density wave induced new Brillouin zones and the possible energy balance between elastic deformation energy and electronic energy points to a more complicated scenario.

Ultrahigh storage areal densities can be achieved by using thermomechanical local-probe techniques to write, read back, and erase data in the form of nanometer-scale indentations in thin polymer films. This paper presents single-probe experimental results in which large data sets were recorded at 641 Gbit/in/sup 2/ and read back with raw bit-error rates better than 10/sup -4/. (d,k) modulation coding is used to mitigate the effect of partial erasing, occurring when subsequent indentations are spaced too closely together, and to increase the effective areal density. The physical indentation profile, the sensitivity of the probe in readback mode, and noise sources that affect data detection are also discussed. Quantitative measurements of the partial erasing effect in both the on-track and cross-track directions are reported.

We perform angle-resolved photoemission spectroscopy on 1T-TaS2 and 1T-TaSe2 using synchrotron radiation. We observe a characteristic splitting of the chalcogen p-derived valence bands along high symmetry directions. Density functional theory calculation and group theory strongly suggest that this splitting is due to spin–orbit interaction along one direction, and to symmetry along the other direction. We note that, according to the Kramers degeneracy, the spin–orbit interaction leaves every state doubly degenerate. Furthermore, this study allows us to identify a mixing between bands with Ta 5d and Se 4p character, possibly relevant for the different temperature behaviours of the two compounds.

We describe a cantilever device for a novel time-of-flight scanning force microscopy (TOF-SFM) concept. The cantilever device consists of a switchable cantilever (SC), a microfabricated extraction electrode, and an Interlocking microstage. It allows quasi-simultaneous topographical and chemical imaging of a sample surface to be performed in the same way as with conventional scanning probe techniques. This is achieved by the micromachined SC with a bimorph actuator that provides a reasonable switching speed. Secondly, a short tip-electrode distance to minimize the ion extraction voltage can be realized by the help of the Interlock type assembling. The measured SC tip deflection is -100 µm at 35 mW, corresponding to an estimated heater temperature of ∼ 250 °C. The maximum switching speed between the two modes is ∼ 50 ms, and the sensitivity ΔR/R of an integrated piezoresistive deflection sensor is ∼ 6.7 × 10-7/nm. The tip-electrode distance is only 10 mm. The TOF-SFM system is currently being integrated in an ultra-high-vacuum system to perform first experiments.

We present the fabrication of thermomechanical cantilevers with nanometer-sized heaters used for data-storage application as implemented in the large two-dimensional cantilever array, known as the Millipede concept. Our goal is to explore how the power consumption of these cantilevers for the thermomechanical writing and reading process can be reduced by reducing the size of the heater structure. Such data are crucial for predicting the power consumption and data rate of storage devices using state-of-the-art CMOS manufacturing technology to achieve its associated minimum feature sizes. We describe the fabrication process and critical issues in connection with a complex device process that merges mix and match e-beam/optical lithography with the micro/nano electromechanical system (M/NEMS) fabrication technique. Fabricated cantilevers typically have a thickness of 100 nm, heater structures with lateral dimensions down to 180 nm, and critical feature alignment in the 50 nm range. We also present first experiments with such cantilevers, which highlight the scaling of the heater energy for the writing process provided by a nanometer-sized thermal constriction.

In thermomechanical data writing, a resistively-heated atomic force microscope (AFM) cantilever tip forms indentations in a thin polymer film. The same cantilever operates as a thermal proximity sensor to detect the presence of previously written data bits. This paper uses recent progress in thermal analysis of the writing and reading modes to develop new cantilever designs for increased speed, sensitivity, and reduced power consumption in both writing and reading operation. Measurements of cantilever electrical resistance during heating reveals physical limits of cantilever writing and reading, and verifies a finite-difference thermal and electrical simulation of cantilever operation. This work proposes two new cantilever designs that correspond to fabrication technology benchmarks. Simulations predict that the proposed cantilevers have a higher data rate and are more sensitive than the present cantilever. The various cantilever designs offer single-bit writing times of 0.2 /spl mu/s-25 /spl mu/s for driving voltages of 2-25 V. The thermal reading /spl Delta/R/R sensitivity is as high as 4/spl times/10/sup -4/ per vertical nm in near steady-state operation.

Present a new scanning-probe-based data-storage concept called the "millipede" that combines ultrahigh density, terabit capacity, small form factor, and high data rate. Ultrahigh storage density has been demonstrated by a new thermomechanical local-probe technique to store, read back, and erase data in very thin polymer films. With this new technique, nanometer-sized bit indentations and pitch sizes have been made by a single cantilever/tip into thin polymer layers, resulting in a data storage densities of up to 1 Tb/in/sup 2/. High data rates are achieved by parallel operation of large two-dimensional (2-D) atomic force microscope (AFM) arrays that have been batch-fabricated by silicon surface-micromachining techniques. The very large-scale integration (VLSI) of micro/nanomechanical devices (cantilevers/tips) on a single chip leads to the largest and densest 2-D array of 32/spl times/32 (1024) AFM cantilevers with integrated write/read/erase storage functionality ever built. Time-multiplexed electronics control the functional storage cycles for parallel operation of the millipede array chip. Initial areal densities of 100-200 Gb/in/sup 2/ have been achieved with the 32/spl times/32 array chip.

This paper reports on the latest developments in the manufacturing of high aspect ratio silicon-based gratings used for X-ray phase contrast imaging (XPCI). Grating-based XPCI provides, in one measurement, unique information about the absorption coefficient, the index of refraction and the microscopic structure of a sample at hard X-ray frequencies. For this reason, XPCI can potentially overcome the limitations of classical absorption-based radiography, notably for weakly absorbing materials. New micro-fabrication processes were developed to manufacture full set of large area and high aspect ratio X-ray gratings with few defects. The complementarity of XPCI with conventional absorption-based radiography was experimentally demonstrated.

This paper reports on wafer scale fabrication of MEMS rubidium (Rb) vapor cells used for spectroscopic measurements in miniaturized atomic clocks. The cell filling process is based on pipetting minute amounts of dissolved rubidium azide (RbN3) into cavities etched in a silicon wafer, hermetic sealing of the cavities by anodic bonding of glass caps, and in situ UV decomposition of the RbN3 into Rb and N2. All relevant elements required for operation such as resistive heaters, temperature sensors, and coils are integrated onto the vapor cell using planar technology. Experiments showed short term frequency stability below 10-10 at 1 second integration time.

Many studies in the field of cell-based cartilage repair have focused on identifying markers associated with the differentiation status of human articular chondrocytes (HAC) that could predict their chondrogenic potency. A previous study from our group showed a correlation between the expression of S100 protein in HAC and their chondrogenic potential. The aims of the current study were to clarify which S100 proteins are associated with HAC differentiation status and to provide an S100-based assay for measuring HAC chondrogenic potential. The expression patterns of S100A1 and S100B were investigated in cartilage and in HAC cultured under conditions promoting dedifferentiation (monolayer culture) or redifferentiation (pellet culture or BMP4 treatment in monolayer culture), using characterized antibodies specifically recognizing S100A1 and S100B, by immunohistochemistry, immunocytochemistry, Western blot, and gene expression analysis. S100A1 and S100B were expressed homogeneously in all cartilage zones, and decreased during dedifferentiation. S100A1, but not S100B, was re-expressed in pellets and co-localized with collagen II. Gene expression analysis revealed concomitant modulation of S100A1, S100B, collagen type II, and aggrecan: down-regulation during monolayer culture and up-regulation upon BMP4 treatment. These results strongly support an association of S100A1, and to a lesser extent S100B, with the HAC differentiated phenotype. To facilitate their potential application, we established an S100A1/B-based flow cytometry assay for accurate assessment of HAC differentiation status. We propose S100A1 and S100B expression as a marker to develop potency assays for cartilage regeneration cell therapies, and as a redifferentiation readout in monolayer cultures aiming to investigate stimuli for chondrogenic induction.

Scanning probe microscopy (SPM) is a well-established technique for surface analysis, but batch-fabricated, low-cost probes still remain a challenging issue. The design and fabrication of entirely photoplastic probes for scanning force microscopy (SFM) have been developed and used for imaging DNA molecules. Using a polymer for the cantilever facilitates the realization of mechanical properties that are difficult to achieve with classical silicon technology. Single lever and cassettes of multiple single-lever probes are presented. The probes are made of an epoxy-based photoresist, which can be structured by standard photolithography and molding techniques. The fabrication process is a simple batch process in which the integrated tips and the levers are defined in one photolithography step. Imaging soft, condensed matter with photoplastic levers, which uses laser beam deflection sensing, exhibits a resolution that compares well with that of commercially available silicon cantilevers. A similar fabrication technique was also developed to fabricate photoplastic tips for scanning near-field optical microscopy (SNOM) that are to be attached to optical fibers. This technique allows optical apertures to be integrated at the end of the well-defined tip directly by probe fabrication, without the need for any post-processing for the aperture formation. Simple fabrication, as well as topographical and optical imaging with such probes, demonstrate the potential of photoplastic-based probes for AFM and SNOM applications.

We report on the 3D integration and interconnect of top-emitting VCSEL and photodiode (PD) arrays on a CMOS substrate. This technology represents a radically new way to increase the I/O bandwidth of processors and enables a path beyond 10Tb/s I/Os by using a high level of integration of opto-electrical devices (OED) directly on the processor. The integration process developed includes an OED placement of better than [email protected], OED thinning down to [email protected], and an interconnect technology with copper vias into the planarization polymer. Although the process is fully compatible with the back-end-of-line of CMOS, the experiments performed were done on dummy CMOS wafers. The opto-electrical characterization performed revealed a minimal impact of the integration process on the OED performance, demonstrating the high potential of the concept.

We report on a new atomic force microscope (AFM)-based data storage concept called the “Millipede” that has a potentially ultrahigh density, terabit capacity, small form factor, and high data rate. Its potential for ultrahigh storage density has been demonstrated by a new thermomechanical local-probe technique to store and read back data in very thin polymer films. With this new technique, 30–40-nm-sized bit indentations of similar pitch size have been made by a single cantilever/tip in a thin (50-nm) polymethylmethacrylate (PMMA) layer, resulting in a data storage density of 400–500 Gb/in. 2 High data rates are achieved by parallel operation of large two-dimensional (2D) AFM arrays that have been batch-fabricated by silicon surface-micromachining techniques. The very large scale integration (VLSI) of micro/nanomechanical devices (cantilevers/tips) on a single chip leads to the largest and densest 2D array of 32 × 32 (1024) AFM cantilevers with integrated write/read storage functionality ever built. Time-multiplexed electronics control the write/read storage cycles for parallel operation of the Millipede array chip. Initial areal densities of 100–200 Gb/in. 2 have been achieved with the 32 × 32 array chip, which has potential for further improvements. In addition to data storage in polymers or other media, and not excluding magnetics, we envision areas in nanoscale science and technology such as lithography, high-speed/large-scale imaging, molecular and atomic manipulation, and many others in which Millipede may open up new perspectives and opportunities.