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Abstract An early childhood skull deformity can have long-term health and aesthetic consequences for the growing toddler. Individual helmet therapy aims at a healthy growth of the skull shape, although not every helmet shape guarantees an optimal result. To ensure an optimal fit, a scanning procedure based on a hand-held surface scanner was evaluated. The new helmet orthosis has an inner layer adapted to the shape of the head, which can be exchanged depending on the growth stage without changing the outer layer. In collaboration with surgeons and engineers, a new helmet orthosis concept was developed that is intended to offer improvements in wearing comfort, overall weight, fit and user-friendliness compared to conventional systems. In the course of the development process and in constant exchange with parents, a multi-layer helmet system with generous perforations was created using additive manufacturing processes. The new helmet shape promises easier handling, especially through the closure system. The helmet shape developed in this study is of high quality, especially in terms of fitting accuracy. Unpleasant perspiration is significantly reduced. The integration of the closure as a direct component of the helmet represents a secure closure option.

Multiple thick film samples of the AgcPd1−c solid solution were prepared using physical vapour deposition over a borosilicate glass substrate. This synthesis technique allows continuous variation in stoichiometry, while the distribution of silver or palladium atoms retains the arrangement into an on-average periodic lattice with smoothly varying unit cell parameters. The alloy concentration and geometry were measured over a set of sample points, respectively, via energy-dispersive X-ray spectroscopy and via X-ray diffraction. These results are compared with ab initio total energy and electronic structure calculations based on density functional theory, and using the coherent potential approximation for an effective medium description of disorder. The theoretically acquired lattice parameters appear in qualitative agreement with the measured trends. The numerical study of the Fermi surface also shows a variation in its topological features, which follow the change in silver concentration. These were related to the electrical resistivity of the AgcPd1−c alloy. The theoretically obtained variation exhibits a significant correlation with nonlinear changes in the resistivity as a function of composition. This combined experimental and theoretical study suggests the possibility of using resistivity measurements along concentration gradients as a way to gain some microscopic insight into the electronic structure of an alloy.

Kidney involvement with resulting kidney failure leads to increased mortality in patients with multiple myeloma (MM). Cast nephropathy (CN), in particular, if left untreated, quickly leads to kidney failure requiring dialysis and has a very poor prognosis for the affected patient. The gold standard for diagnosing kidney involvement is a kidney biopsy. However, due to bleeding risk, this cannot be done in every patient. We recently reported that a quotient of urine light chain (LCurine) to glomerular filtration rate (eGFR) is a non-invasive diagnostic tool for patients with kidney involvement in MM. But this quotient has not yet been tested in everyday clinical practice. In this study, our LCurine/eGFR ratio was tested on 67 patients in two centers. Enrollment took place between January 2019 and September 2023. A total of 18 of the 67 patients had CN. With the threshold defined in our initial paper, we were able to show a sensitivity of 100% with a specificity of 85.7% for CN in patients with MM. As a result, the LCurine/eGFR quotient recognizes 100% of all CN and can therefore detect this group, which has a very poor prognosis, without the need for a kidney biopsy.

Abstract In this paper, an electrostatic compliant mechanical amplifier intended for force-compensated displacement amplification in MEMS sensor applications is described. Usually, mechanical transformers that enhance a small input displacement into a large output displacement generate large forces at the input of the transformer. The microsystem proposed here allows for the reduction and compensation of the input stiffness of the amplifier and any mechanical components connected to it while providing a constant amplification ratio at the same time. The amplifying mechanism features bidirectional electrostatic anti-springs enabling the control of the stiffness by applying a constant DC voltage. The electrode design of the anti-springs and its influence on the force-displacement characteristic, the side instability and the maximal displacement are studied through analytical approaches and supported by FEA and by experiments. Based on the derived models, a compliant electromechanical amplifier is developed, featuring an amplification ratio of 50. For this amplifier the initial input stiffness of 422 N/m could be reduced to 6.8 N/m by applying a voltage of 100 V. As an additional application, we show how the amplifier can be used as a mechanical force sensor with tuneable sensitivity, where the forces at the input are transformed into large output displacements. Through experiments, we show how the sensitivity can be adjusted and increased by a factor of 25 by applying a voltage at the anti-springs.

Guiding mechanisms are among the most elementary components of MEMS. Usually, a spring is required to be compliant in only one direction and stiff in all other directions. We introduce triangular springs with a preset tilting angle. The tilting angle lowers the reaction force and implements a constant reaction force. We show the influence of the tilting angle on the reaction force, on the spring stiffness and spring selectivity. Furthermore, we investigate the influence of the different spring geometry parameters on the spring reaction force. We experimentally show tilted triangular springs exhibiting constant force reactions in a large deflection range and a comb-drive actuator guided by tilted triangular springs.

Summary: At the moment of union in fertilization, sperm and oocyte are transcriptionally silent. The ensuing onset of embryonic transcription (embryonic genome activation [EGA]) is critical for development, yet its timing and profile remain elusive in any vertebrate species. We here dissect transcription during EGA by high-resolution single-cell RNA sequencing of precisely synchronized mouse one-cell embryos. This reveals a program of embryonic gene expression (immediate EGA [iEGA]) initiating within 4 h of fertilization. Expression during iEGA produces canonically spliced transcripts, occurs substantially from the maternal genome, and is mostly downregulated at the two-cell stage. Transcribed genes predict regulation by transcription factors (TFs) associated with cancer, including c-Myc. Blocking c-Myc or other predicted regulatory TF activities disrupts iEGA and induces acute developmental arrest. These findings illuminate intracellular mechanisms that regulate the onset of mammalian development and hold promise for the study of cancer.

With the increase in potential uses of terahertz technology, the need for terahertz transceivers with application-oriented adaptive radiation patterns has emerged. Reconfigurable reflectarrays consisting of actuated sub-wavelength reflectors have been successfully used for terahertz beam steering and beamforming. They do not require a complex feeding network and associated electronics, enabling a compact and power-efficient terahertz beam steering system. However, the current reflectarray-based beam steering is accomplished by forming the reflectarray as a grating structure, which is accompanied by the problems such as grating lobes, limited steering range, and discrete steering angles. Here, we configure a MEMS-based reflectarray with the genetic algorithm to eliminate the grating lobes and open up the possibility of customizing its radiation pattern. We used single- and multi-objective optimization to find the optimal height profile of the reflectarray and verified the results by full-wave electromagnetic simulations. We measured the radiation patterns of four reflectarray phantoms, i.e. reflectarrays without the MEMS actuation systems. The measurement results agree well with the calculated ones, with the main beam deviating at most 2° from the target direction. Our work demonstrates how a genetic algorithm is used to shape a reconfigurable terahertz reflectarray to eliminate the grating lobes and tailor some specific featuress in its radiation pattern.

Background: As research examining human-robot interaction moves from the laboratory to the real world, studies seeking to examine how people interact with robots face the question of which robotic platform to employ to collect data in situ. To facilitate the study of a broad range of individuals, from children to clinical populations, across diverse environments, from homes to schools, a robust, reproducible, low-cost and easy-to-use robotic platform is needed. Methods: We describe how a commercially available off-the-shelf robot, Cozmo, can be used to study embodied human-robot interactions in a wide variety of settings, including the user’s home. We describe the steps required to use this affordable and flexible platform for longitudinal human-robot interaction studies. First, we outline the technical specifications and requirements of this platform and accessories. We then show how log files containing detailed data on the human-robot interaction can be collected and extracted. Finally, we detail the types of information that can be retrieved from these data. Results: We present findings from a validation that mapped the behavioural repertoire of the Cozmo robot and introduce an accompanying interactive emotion classification tool to use with this robot. This tool combined with the data extracted from the log files can provide the necessary details to understand the psychological consequences of long-term interactions. Conclusions: This low-cost robotic platform has the potential to provide the field with a variety of valuable new possibilities to study the social cognitive processes underlying human-robot interactions within and beyond the research laboratory, which are user-driven and unconstrained in both time and place.

This paper presents the design, modeling, fabrication and characterization of a passive micromechanical acceleration sensor intended for condition monitoring. The sensor is composed of purely micromechanical components forming a mechanical integrated sensing circuit, which allows to measure, select, store, and digitize the peak value of an imposed acceleration without the need of electrical auxiliary energy. We present micromechanical components arranged in a mechanical integrated sensor circuit. A network model is derived describing the static mechanical properties of the system. As part of the accelerometer, a cascaded mechanical memory is presented in detail which allows to store an acceleration peak value with a resolution of 6 bits, i.e. 64 discrete states. The memory is resettable by an electrostatic actuator. For an electrical read out of the memory, e.g. by RFID, an integrated micromechanical analog-to-digital converter is used.

Abstract Lenalidomide (LEN) maintenance (MT) post autologous stem cell transplantation (ASCT) is standard of care in newly diagnosed multiple myeloma (MM) but has not been compared to other agents in clinical trials. We retrospectively compared bortezomib (BTZ; n = 138) or LEN (n = 183) MT from two subsequent GMMG phase III trials. All patients received three cycles of BTZ-based triplet induction and post-ASCT MT. BTZ MT (1.3 mg/m2 i.v.) was administered every 2 weeks for 2 years. LEN MT included two consolidation cycles (25 mg p.o., days 1–21 of 28 day cycles) followed by 10–15 mg/day for 2 years. The BTZ cohort more frequently received tandem ASCT (91% vs. 33%) due to different tandem ASCT strategies. In the LEN and BTZ cohort, 43% and 46% of patients completed 2 years of MT as intended (p = 0.57). Progression-free survival (PFS; HR = 0.83, p = 0.18) and overall survival (OS; HR = 0.70, p = 0.15) did not differ significantly with LEN vs. BTZ MT. Patients with

The potential of pulsed THz radiation for time-of-flight imaging applications is well recognized. However, advances in this field are currently severely limited by the low average power of ultrafast THz sources. Typically, this results in impractically long acquisition times and a loss in resolution and contrast. These limitations make imaging of the objects in real-life scenarios impossible. Here, conclusively, the potential of state-of-the-art high-average power THz time-domain spectrometer (TDS), driven by a 100-W class, one-box ultrafast oscillator for imaging applications is shown by demonstrating lensless THz imaging in reflection mode of a dielectric sample with low reflectivity. Images obtained with our home-built 20-mW average power THz-TDS system show a significant contrast enhancement compared to a state-ofthe-art commercial THz-TDS with less than 200 μW of average power. Our unique setup even allows us to obtain images of such an object with high-contrast hidden inside a medium-density fiberboard (MDF) box. This opens the door to THz time-of-flight imaging of concealed objects of unknown shape and orientation in various real-life scenarios which were so far impossible to realize.

In this paper, we present different microelectromechanical systems based on electrostatic actuators, and demonstrate their capacity to achieve large and stepwise displacements using a cooperative function of the actuators themselves. To explore this, we introduced micro-stepper actuators to our experimental systems, both with and without a guiding spring mechanism; mechanisms with such guiding springs can be applied to comb-drive and parallel-plate actuators. Our focus was on comparing various guiding spring designs, so as to increase the actuator displacement. In addition, we present systems based on cascaded actuators; these are converted to micromechanical digital-to-analog converters (DAC). With DACs, the number of actuators (and thus the complexity of the digital control) are significantly reduced in comparison to analog stepper-actuators. We also discuss systems that can achieve even larger displacements by using droplet-based bearings placed on an array of aluminum electrodes, rather than guiding springs. By commutating the voltages within these electrode arrays, the droplets follow the activated electrodes, carrying platforms atop themselves as they do so. This process thus introduces new applications for springless large displacement stepper-actuators.

Metastatic dissemination in breast cancer patients occurs early in malignant transformation, raising questions about how disseminated cancer cells (DCC) progress at distant sites. Here, the authors show that DCCs in bone marrow are activated via IL6-trans-signaling and thereby acquire stemness traits relevant for metastasis formation.

Background: We aimed to evaluate the incidence of severe acute respiratory syndrome coronavirus type-2 (SARS-CoV2) vaccine-related hypermetabolic lymphadenopathy (HLA) and evaluate which time point produces the least number of false-positive findings in an 18F-2-Fluor-2-desoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT). Methods: For this retrospective, multi-center imaging study, patients with any form of SARS-CoV2 vaccination prior to an 18F-FDG-PET/CT were included between January 2021 and December 2021. Patients were divided into six groups according to the time point of vaccination prior to their 18F-FDG-PET/CT imaging, e.g., group one (0–6 days) and group six (35–80 days). As the reference standards, the SUVmax of the mediastinal blood pool (MBP) and the SUVmax contralateral reference lymph node (RL) were determined. (A) The absolute SUVmax of HLA, (B) the ratio of SUVmaxHLA/SUVmax mediastinal blood pool (rHLA/MBP), (C) the ratio SUVmax HLA vs. SUVmax contralateral reference lymph node (rHLA/RL), (D) and the incidence of HLA defined as rHLA/MBP > 1.5 were assessed. Results: Group one (days 0–6) showed the highest incidence of HLA 16/23 (70%) and rHLA/MBP (2.58 ± 2.1). All three parameters for HLA reduced statistically significantly in the comparison of Groups 1–3 (days 0–20) versus Groups 4–6 (days 21–80) (p-values < 0.001). Conclusions: If feasible, an FDG PET should be postponed by at least 3 weeks after SARS-CoV2 vaccination, especially if an accurate evaluation of axillary status is required.

Background: The simultaneous occurrence of impaired kidney function and paraproteinemia is common in our constantly aging society. Both can be independent entities; however, renal insufficiency can also be caused by the paraprotein. We assessed all kidney biopsies in patients with monoclonal gammopathy in our clinic over the past 20 years and evaluated the histological results. Methods: Biopsies were systematically performed in nearly all patients with paraproteinemia and impaired kidney function (n = 178). The histological findings were systematically evaluated and correlated with the initial clinical diagnosis. Results: We found cast nephropathy (CN) in n = 66 (37.1%) biopsies, AL amyloidosis in n = 31 (17.4%) biopsies, monoclonal immunoglobulin deposition disease (MIDD) in n = 7 (3.9%) biopsies and other renal diseases (ORDs) in n = 74 (41.6%) biopsies. In the latter group, paraprotein-associated changes were found in 37 of 74 (50%) patients, whereas paraprotein-independent changes were found in the other half. Whereas, in the group of patients with MGUS, the findings were heterogenous, most of the patients with known multiple myeloma (MM) or B-NHL showed malignancy-associated changes in the kidney. The biopsy changed the diagnoses in a significant proportion of the patients: The group of patients with MM grew from 71 to 112 patients, whereas, in the MGUS group, only 31 of 44 patients remained. Conclusion: Kidney biopsies in patients with paraproteinemia and renal impairment show a wide range of findings that can lead to a change in diagnosis.

The performance of micromirrors in terms of their maximum deflection is often limited due to mechanical constraints in the design. To increase the range of achievable deflection angles, we present a novel concept in which a free-lying sphere with a flat side as reflector can be rotated. Due to the large forces needed to move the sphere, multiple electrostatic actuators are used to cooperatively rotate the sphere in iterative steps by impacts and friction. A parameterized system-level model of the configuration is derived, which considers arbitrary multi-contact scenarios and can be used for simulation, analysis, and control design purposes. Due to the complex, indirect relation between the actuator voltages and the sphere motion, model-based numerical optimization is applied to obtain suitable system inputs. This results in rotation sequences, which can be understood as a sequence of motion primitives, thus transforming the continuous time model into an abstract discrete time model. Based on this, we propose a feedback control strategy for trajectory following, considering model uncertainties by a learning scheme. High precision is achieved by an extension controlling the angular change of each rotation step. The suitability of the overall approach is demonstrated in simulation for maximum angles of 40°, achieving angular velocities of approximately 10°/s.

Introduction: Bühler's anastomosis (or Bühler's arcade) is an embryonic relic and represents an arterio-arterial connection between the superior mesenteric artery and the celiac trunk. It can be found as a variety in 1–2% of patients.Case Presentation: We present a case of a patient with metatastatic squamous cell carcinoma of the lung. The patient was in stable disease for 4 years under palliative therapy (most recently second-line therapy with Nevolumab). In 2019, a locally advanced adenocarcinoma of the papilla vateri was diagnosed, additionally. The patient also underwent right hemicolectomy and patch plasty of the celiac trunk and superior mesenteric artery due to colonic ischemia and arteriosclerotic disease with 50–70% stenosis of the superior mesenteric artery several years ago. Due to a complex vascular prehistory, the standardized preoperative imaging was supplemented by two independent vascular reconstructions (a CT angiogram and a reconstruction based on the CT) for the planning of a pylorus-preserving pancreatic head resection and reconstruction according to Traverso-Longmire. In addition, a 3D print was produced. Both, the reconstruction based on the CT scan and the 3D print were created for off-label use as a part of a research project (VIVATOP: Versatile Immersive Virtual and Augmented Tangible OP).Discussion: In the standardized CT scan and in the clinical CT-angiography, there were no obvious surgically relevant anatomical variations. A Bühler anastomosis was detected in a digital, virtual and interactive 3D-reconstruction. In addition, in the 3D print of the abdominal site the anastomosis was seen as well. Intraoperatively, the presence of Bühler's anastomosis was confirmed. This information had a significant impact on the intraoperative approach. Retrospectively, the vessel variant could be surmised in the axial projection of the CT scan, if one knew what to look for.Conclusion: For the conduction of a safe surgical procedure, it is imperative that rare anatomical variations are known preoperatively. Increasing digitalization in surgical and perioperative preparation holds great potential for better planning and improved patient safety. Research and cooperation projects such as the VIVATOP project are instrumental for the development of new visualization techniques, which are able to enhance the understanding of complex anatomical relations.

Objective Measuring the success of molecularly guided therapies is a major challenge in precision oncology trials. A commonly used endpoint is an intra-patient progression-free survival (PFS) ratio, defined as the PFS interval associated with molecularly guided therapy (PFS2) divided by the PFS interval associated with the last prior systemic therapy (PFS1), above 1.3 or, in some studies, above 1.33 or 1.5.Methods To investigate if the concept of PFS ratios is in agreement with actual response evaluations by physicians, we conducted a survey among members of the MASTER (Molecularly Aided Stratification for Tumor Eradication Research) Programme of the German Cancer Consortium who were asked to classify the success of molecularly guided therapies in 194 patients enrolled in the MOSCATO 01 trial based on PFS1 and PFS2 times.Results A comparison of classification profiles revealed three distinct clusters of PFS benefit assessments. Only 29% of assessments were consistent with a PFS ratio threshold of 1.3, whereas the remaining 71% of participants applied a different classification scheme that did not rely on the relation between PFS times alone, but also took into account absolute PFS1 intervals. Based on these community-driven insights, we developed a modified PFS ratio that incorporates the influence of absolute PFS1 intervals on the judgement of clinical benefit by physicians. Application of the modified PFS ratio to outcome data from two recent precision oncology trials, MOSCATO 01 and WINTHER, revealed significantly improved concordance with physician-perceived clinical benefit and identified comparable proportions of patients who benefited from molecularly guided therapies.Conclusions The modified PFS ratio may represent a meaningful clinical endpoint that could aid in the design and interpretation of future precision oncology trials.

For several cancer types, mouse models indicate that metastasis occurs early. Here, the authors show that human melanoma cells disseminate early and illustrate a genetic colonisation signature that evolves in parallel at different sites.

We present the design, fabrication, and experimental characterization of microsystems achieving large and stepwise discrete displacements. The systems consist of electrostatic bending plate actuators linked in a chain with increasing electrode gaps to allow a stepwise system displacement. A derived analytic transfer function permits to evaluate the influence of the system components on both the total and the stepwise system displacement. Based on calculation and simulation results, systems featuring 5, 8, 10, 13, and 16 steps are modeled and fabricated using a dicing-free SOI-fabrication process. During experimental voltage- and time-dependent system characterization, the minimum switching speed of the electrostatic actuators is 1 ms. Based on the guiding spring stiffness and the switching time, step-by-step and collective activations of the microsystems are performed and the system properties are derived. Furthermore, we analyze the influence of the number of steps on the total system displacement and present 16-step systems with a total maximum displacement of 230.7 ± 0.9 µm at 54 V.

We present the design, fabrication, and characterization of a MEMS-based 3-bit Digital-to-Analog Converter (DAC) that allows the generation of large displacements. The DAC consists of electrostatic bending-plate actuators that are connected to a mechanical amplifier (mechAMP), enabling the amplification of the DAC output displacement. Based on a parallel binary-encoded voltage signal, the output displacement of the system can be controlled in an arbitrary order. Considering the system design, we present a simplified analytic model, which was confirmed by FE simulation results. The fabricated systems showed a total stroke of approx. 149.5 ± 0.3 µm and a linear stepwise displacement of 3 bit correlated to 23 ≙ eight defined positions at a control voltage of 60 V. The minimum switching time between two input binary states is 0.1 ms. We present the experimental characterization of the system and the DAC and derive the influence of the mechAMP on the functionality of the DAC. Furthermore, the resonant behavior and the switching speed of the system are analyzed. By changing the electrode activation sequence, 27 defined positions are achieved upgrading the 3-bit systems into a 3-tri-state (33) system.

In recent years, tissue engineering with mechanical stimulation has received considerable attention. In order to manipulate tissue samples, there is a need for electromechanical devices, such as constant-force actuators, with integrated deflection measurement. In this paper, we present an electrostatic constant-force actuator allowing the generation of a constant force and a simultaneous displacement measurement intended for tissue characterization. The system combines a comb drive structure and a constant-force spring system. A theoretical overview of both subsystems, as well as actual measurements of a demonstrator system, are provided. Based on the silicon-on-insulator technology, the fabrication process of a moveable system with an extending measurement tip is shown. Additionally, we compare measurement results with simulations. Our demonstrator reaches a constant-force of 79 ± 2 μN at an operating voltage of 25 V over a displacement range of approximately 40 μm, and the possibility of adjusting the constant-force by changing the voltage is demonstrated.

A 500 años del origen del protestantismo, se plantea la pregunta: ¿Cuál es el significado de la Reforma para hoy? El autor sostiene que la importancia de la Reforma va más allá de una época histórica o de una controversia teológica de su tiempo. Más bien la Reforma es un proceso permanente, un movimiento y un cierto método del quehacer teológico. Remontándose a la teología de la cruz del apóstol Pablo, Martín Lutero, el iniciador de la Reforma, desarrolló un nuevo paradigma de la teología. Es caracterizado por tres aspectos: La cruz como principio epistemológico, la justicia de Dios como contenido esencial del Evangelio, y una ética discursiva de los mandamientos. Este paradigma de la teología posibilita una renovación y una transformación continua de las iglesias y de la teología enfrente de los desafíos contemporáneos como las crisis de la ecología, de la economía, de la justicia social y el aumento de violencia y guerras. La actualidad de la Reforma se demuestra en su nuevo modo de pensar y de actuar, o sea en su potencial crítico a partir del Crucificado y sus perspectivas constructivas para la humanidad y la convivencia a partir de la justicia de Dios.

Gene expression analysis of rare or heterogeneous cell populations such as disseminated cancer cells (DCCs) requires a sensitive method allowing reliable analysis of single cells. Therefore, we developed and explored the feasibility of a quantitative PCR (qPCR) assay to analyze single-cell cDNA pre-amplified using a previously established whole transcriptome amplification (WTA) protocol. We carefully selected and optimized multiple steps of the protocol, e.g. re-amplification of WTA products, quantification of amplified cDNA yields and final qPCR quantification, to identify the most reliable and accurate workflow for quantitation of gene expression of the ERBB2 gene in DCCs. We found that absolute quantification outperforms relative quantification. We then validated the performance of our method on single cells of established breast cancer cell lines displaying distinct levels of HER2 protein. The different protein levels were faithfully reflected by transcript expression across the tested cell lines thereby proving the accuracy of our approach. Finally, we applied our method to breast cancer DCCs of a patient undergoing anti-HER2-directed therapy. Here, we were able to measure ERBB2 expression levels in all HER2-protein-positive DCCs. In summary, we developed a reliable single-cell qPCR assay applicable to measure distinct levels of ERBB2 in DCCs.

It is unclear what regulates gamete reprogramming competence. Here, the authors inject sperm into parthenogenetic embryos, generating viable offspring and show that mouse embryos in the mitotic cell cycle can reprogram sperm for full term development.

With an increasing number of applications of terahertz systems in industrial fields and communications, terahertz beamforming and beam steering techniques are required for high-speed, large-area scanning. As a promising means for beam steering, micro-electro-mechanical system (MEMS)-based reflection gratings have been successfully implemented for terahertz beam control. So far, the diffraction grating efficiency is relatively low due to the limited vertical displacement range of the reflectors. In this paper, we propose a design for a reconfigurable MEMS-based reflection grating consisting of multiple subwavelength reflectors which are driven by 5-bit, high-throw electrostatic actuators. We vary the number of the reflectors per grating period and configure the throw of individual reflectors so that the reflection grating is shaped as a blazed grating to steer the terahertz beam with maximum diffraction grating efficiency. Furthermore, we provide a mathematical model for calculating the radiation pattern of the terahertz wave reflected by general reflection gratings consisting of subwavelength reflectors. The calculated and simulated radiation patterns of the designed grating show that we can steer the angle of the terahertz waves in a range of up to ± 56.4 ∘ with a maximum sidelobe level of −10 dB at frequencies from 0.3 THz to 1 THz.

In this work a non-contact biaxial nanoprobe for surface profile scans of macroscopic objects with 150 nm accuracy is presented. The biaxial nanoprobe oscillates in two directions to overcome the challenges of sticking in contact mode. Two electrostatic actuators drive the nanoprobe while two electrostatic sensors measure the position of the tip ball. The contact behavior between the tip ball and the specimen is determined by the contact stiffness and the contact damping. Dependent on the dominating effect the nanoprobeoperatesat semi- or non-contact mode, respectively. The aims of this paper are the investigation of the contact behavior, the proof of the independent evaluation of the two axes and the check if sticking is safely avoided.

Autonomous sensors are of interest in all cases where a continuous power source is not available or difficult to realize. Besides harvesting of electrical energy for a complex storage system, it is of interest to directly store an event in a non-electrical storage, but in a way that allows a later electrical read-out. Therefore, a miniaturized micromechanical binary counter is presented, which enables counting of threshold events, such as exceeding temperature limits or high mechanical shocks. An electro-mechanical digital-to-analog converter integrated in the binary counter is demonstrated as an option for monolithic electrical read-out of the mechanically stored information.

A growing number of applications in science and industry are currently pushing the development of ultrafast laser technologies that enable high average powers. SESAM modelocked thin disk lasers (TDLs) currently achieve higher pulse energies and average powers than any other ultrafast oscillator technology, making them excellent candidates in this goal. Recently, 275 W of average power with a pulse duration of 583 fs were demonstrated, which represents the highest average power so far demonstrated from an ultrafast oscillator. In terms of pulse energy, TDLs reach more than 40 μJ pulses directly from the oscillator. In addition, another major milestone was recently achieved, with the demonstration of a TDL with nearly bandwidth-limited 96-fs long pulses. The progress achieved in terms of pulse duration of such sources enabled the first measurement of the carrier-envelope offset frequency of a modelocked TDL, which is the first key step towards full stabilization of such a source. We will present the key elements that enabled these latest results, as well as an outlook towards the next scaling steps in average power, pulse energy and pulse duration of such sources. These cutting-edge sources will enable exciting new applications, and open the door to further extending the current performance milestones.

Background/Aim: In contrast to diverticulosis of the colon, jejunal diverticulosis is a rare entity that often becomes clinically relevant only after exacerbations occur. The variety of symptoms and low incidence make this disease a difficult differential diagnosis. Patients and Methods: Data from all patients who were treated in our surgical department for complicated jejunal diverticulitis, that is, gastrointestinal hemorrhage or a diverticula perforation were collected prospectively over a 6-year period (January 2004 to January 2010) and analyzed retrospectively. Results: The median age among the 9 patients was 82 years (range: 54-87). Except for 2 cases (elective operation for a status postjejunal peridiverticulitis and a re-perforation of a diverticula in a patient s/p segment resection with free perforation), the diagnosis could only be confirmed with an exploratory laparotomy. Perforation was observed in 5 patients, one of which was a retroperitoneal perforation. The retroperitoneal perforation was associated with transanal hemorrhage. Hemodynamically relevant transanal hemorrhage requiring transfusion were the reason for an exploratory laparotomy in 2 further cases. In one patient, the hemorrhage was the result of a systemic vasculitis with resultant gastrointestinal involvement. A singular jejunal diverticulum caused an adhesive ileus in one patient. The extent of jejunal diverticulosis varied between a singular diverticulum to complete jejunal involvement. A tangential, transverse excision of the diverticulum was carried out in 3 patients. The indication for segment resection was made in the case of a perforation with associated peritonitis (n=4) as well as the presence of 5 or more diverticula (n=2). Histological analysis revealed chronic pandiverticulitis in all patients. Median operating time amounted to 142 minutes (range: 65-210) and the median in-hospital stay was 12 days (range: 5-45). Lethality was 0%. Major complications included secondary wound closure after s/p repeated lavage and bilateral pleural effusions in one case. Signs of malabsorption as the result of a short bowel syndrome were not observed. Minor complications included protracted intestinal atony in 2 cases and pneumonia in one case. Median follow-up was 6 months (range: 1-18). Conclusion: Complicated jejunal diverticulitis often remains elusive preoperatively due to its unspecific clinical presentation. A definitive diagnosis can often only be made intraoperatively. The resection of all diverticula and/or the complete diverticula-laden segment is the goal in chronic cases. The operative approach chosen (tangential, transverse excision vs segment resection) should be based on the extent of the jejunal diverticulosis as well as the intraoperative findings.

X-ray photoelectron spectroscopy (XPS) is a key method for studying (electro-)chemical changes in metal-ion battery electrode materials. In a recent publication, we pointed out a conflict in binding energy (BE) scale referencing at alkali metal samples, which is manifested in systematic deviations of the BEs up to several eV due to a specific interaction between the highly reactive alkali metal in contact with non-conducting surrounding species. The consequences of this phenomenon for XPS data interpretation are discussed in the present manuscript. Investigations of phenomena at surface-electrolyte interphase regions for a wide range of materials for both lithium and sodium-based applications are explained, ranging from oxide-based cathode materials via alloys and carbon-based anodes including appropriate reference chemicals. Depending on material class and alkaline content, specific solutions are proposed for choosing the correct reference BE to accurately define the BE scale. In conclusion, the different approaches for the use of reference elements, such as aliphatic carbon, implanted noble gas or surface metals, partially lack practicability and can lead to misinterpretation for application in battery materials. Thus, this manuscript provides exemplary alternative solutions.

The importance of micro-electromechanical systems (MEMS) for radio-frequency (RF) applications is rapidly growing. In RF mobile-communication systems, MEMS-based circuits enable a compact implementation, low power consumption and high RF performance, e.g., bulk-acoustic wave filters with low insertion loss and low noise or fast and reliable MEMS switches. However, the cross-hierarchical modelling of micro-electronic and micro-electromechanical constituents together in one multi-physical design process is still not as established as the design of integrated micro-electronic circuits, such as operational amplifiers. To close the gap between micro-electronics and micro-electromechanics, this paper presents an analytical approach towards the linear top-down design of MEMS resonators, based on their electrical specification, by the solution of the mechanical wave equation. In view of the central importance of thermal effects for the performance and stability of MEMS-based RF circuits, the temperature dependence was included in the model; the aim was to study the variations of the RF parameters of the resonators and to enable a temperature dependent MEMS oscillator simulation. The variations of the resonator parameters with respect to the ambient temperature were then verified by RF measurements in a vacuum chamber at temperatures between −35 ∘C and 85 ∘C. The systematic body of data revealed temperature coefficients of the resonant frequency between −26 ppm/K and −20 ppm/K, which are in good agreement with other data from the literature. Based on the MEMS resonator model derived, a MEMS oscillator was designed, simulated, and measured in a vacuum chamber yielding a measured temperature coefficient of the oscillation frequency of −26.3 ppm/K. The difference of the temperature coefficients of frequency of oscillator and resonator turned out to be mainly influenced by the limited Q-factor of the MEMS device. In both studies, the analytical model and the measurement showed very good agreement in terms of temperature dependence and the prediction of fabrication results of the resonators designed. This analytical modelling approach serves therefore as an important step towards the design and simulation of micro-electronics and micro-electromechanics in one uniform design process. Furthermore, temperature dependences of MEMS oscillators can now be studied by simulations instead of time-consuming and complex measurements.

BACKGROUND: Disseminated cancer cells (DCCs) and circulating tumor cells (CTCs) are extremely rare, but comprise the precursors cells of distant metastases or therapy resistant cells. The detailed molecular analysis of these cells may help to identify key events of cancer cell dissemination, metastatic colony formation and systemic therapy escape. METHODOLOGY/PRINCIPAL FINDINGS: Using the Ampli1™ whole genome amplification (WGA) technology and high-resolution oligonucleotide aCGH microarrays we optimized conditions for the analysis of structural copy number changes. The protocol presented here enables reliable detection of numerical genomic alterations as small as 0.1 Mb in a single cell. Analysis of single cells from well-characterized cell lines and single normal cells confirmed the stringent quantitative nature of the amplification and hybridization protocol. Importantly, fixation and staining procedures used to detect DCCs showed no significant impact on the outcome of the analysis, proving the clinical usability of our method. In a proof-of-principle study we tracked the chromosomal changes of single DCCs over a full course of high-dose chemotherapy treatment by isolating and analyzing DCCs of an individual breast cancer patient at four different time points. CONCLUSIONS/SIGNIFICANCE: The protocol enables detailed genome analysis of DCCs and thereby assessment of the clonal evolution during the natural course of the disease and under selection pressures. The results from an exemplary patient provide evidence that DCCs surviving selective therapeutic conditions may be recruited from a pool of genomically less advanced cells, which display a stable subset of specific genomic alterations.

Therapeutic application of mesenchymal stem cells (MSC) requires their extensive in vitro expansion. MSC in culture typically grow to confluence within a few weeks. They show spindle-shaped fibroblastoid morphology and align to each other in characteristic spatial patterns at high cell density. We present an individual cell-based model (IBM) that is able to quantitatively describe the spatio-temporal organization of MSC in culture. Our model substantially improves on previous models by explicitly representing cell podia and their dynamics. It employs podia-generated forces for cell movement and adjusts cell behavior in response to cell density. At the same time, it is simple enough to simulate thousands of cells with reasonable computational effort. Experimental sheep MSC cultures were monitored under standard conditions. Automated image analysis was used to determine the location and orientation of individual cells. Our simulations quantitatively reproduced the observed growth dynamics and cell-cell alignment assuming cell density-dependent proliferation, migration, and morphology. In addition to cell growth on plain substrates our model captured cell alignment on micro-structured surfaces. We propose a specific surface micro-structure that according to our simulations can substantially enlarge cell culture harvest. The 'tool box' of cell migratory behavior newly introduced in this study significantly enhances the bandwidth of IBM. Our approach is capable of accommodating individual cell behavior and collective cell dynamics of a variety of cell types and tissues in computational systems biology.

The balance between maintenance of the stem cell state and terminal differentiation is influenced by the cellular environment. The switching between these states has long been understood as a transition between attractor states of a molecular network. Herein, stochastic fluctuations are either suppressed or can trigger the transition, but they do not actually determine the attractor states.We present a novel mathematical concept in which stem cell and progenitor population dynamics are described as a probabilistic process that arises from cell proliferation and small fluctuations in the state of differentiation. These state fluctuations reflect random transitions between different activation patterns of the underlying regulatory network. Importantly, the associated noise amplitudes are state-dependent and set by the environment. Their variability determines the attractor states, and thus actually governs population dynamics. This model quantitatively reproduces the observed dynamics of differentiation and dedifferentiation in promyelocytic precursor cells.Consequently, state-specific noise modulation by external signals can be instrumental in controlling stem cell and progenitor population dynamics. We propose follow-up experiments for quantifying the imprinting influence of the environment on cellular noise regulation.

Fishes in early developmental stages frequently have morphological features that differ from those of adult stages, and many characters found later in ontogeny are not available in initial stages. Hence, morphological descriptions of early stages are useful to provide information for the identification of eggs and larvae, a knowledge still restricted among Neotropical fishes. We studied the development of Heterocharax macrolepis, a heterocharacine whose adult specimens from the aquarium trade were kept and spawned at around 23-24ºC. A developmental series of 51 specimens was preserved, ranging from 3.2 mm notochord length to 18.6 mm standard length, covering approximately the first 73 days post-hatching. We described the development of main morphological features emphasizing those useful in the identification of H. macrolepislarvae (i.e., appearance of preopercle spine and development of the pseudotympanum). We also compared H. macrolepis with photographs taken of live larval specimens of Gnathocharax steindachneri, recently included in the Heterocharacinae. Both species have a yolk sac with a small rounded projection directed posteroventrally. Although this information is not yet available for all pertinent taxa, the different yolk sac shape in other representatives of the Characiformes may indicate that this peculiar yolk sac represents an additional synapomorphy of the Heterocharacini.