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Copper iodide (CuI) is an emerging high-performance p-type, wide-band-gap semiconductor. However, the growth mechanisms of CuI thin films and nanocrystals are currently unclear, as they do not foll...

In this paper, we present a method to obtain explicit, expressive and interpretable gait feature signals from an inertial sensor, mounted on any segment of the lower limbs. The proposed method is invariant to the mounting orientation of the sensor, works without magnetometer information, requires no prior knowledge and can be used in real-time scenarios. Moreover, the constructed signals are robust for a wide variety of changing walking speeds and directions. We investigate the informational content of our three feature signals lying in the human sagittal plane with respect to the gait phase segmentation problem and compare them to other commonly used signals, such as the sagittal angular velocity and the norms of accelerations and angular velocities. To this end, we make use of the filter-based maximum relevance minimum redundancy algorithm, which is a classifier-independent feature selection method. For validating our approach, we consider gait data of twelve healthy subjects walking straight and in curves at self-chosen speeds with inertial sensors attached to either the thigh, shank or foot. Additionally, pressure measuring insoles are used to obtain ground truth toe-off and heel-strike gait events for reference. With those events as the gait phase transitions, the event detection is cast into a classification problem. To support the theoretical findings of the feature selection and ranking, we finally evaluate different choices of feature sets with a simple linear support vector machine classifier in an online fashion and obtain superior segmentation results with our feature signals.

This prospective study evaluated the relationship between fecal markers of intestinal inflammation and cystic fibrosis (CF)-associated abdominal symptoms. These were assessed using the CFAbd-Score, a CF-specific patient-related outcome measure developed and validated, following FDA guidelines.In feces from patients with CF (n = 41) and healthy volunteers (n = 27), concentrations of fecal calprotectin (FC), M2-pyruvate kinase (M2-PK), interleukins IL-1β, IL-6, IL-8, and neutrophilic elastase (NE) were measured. Abdominal symptoms during the 2 preceding weeks were recorded using the CFAbd-Score. This patient-reported outcome measure (PROM) for assessment of the multi-organic abdominal involvement in CF includes 28 items in five domains.Inflammatory parameters FC, IL-1β, M2-PK, and NE in feces, as well as CFAbd-Scores resulted significantly higher in CF patients than in healthy controls (all P 0.01). Furthermore, significant differences between both groups were found for pain-symptoms, disorders of bowel movement, impaired quality of life, as well as disorders of eating and appetite. With 83% sensitivity and 74% specificity, FC was the most reliable measure for CF-related intestinal inflammation, which, in the CFAbd-Score, was associated to significantly higher rates of abdominal pain, as well as to general quality of life items such as gastrointestinal-related impaired sleep and frustration.Using the CFAbd-Score as a CF-specific PROM for identification and quantification of abdominal symptoms revealed that abdominal pain and impaired quality of life are associated with intestinal inflammation in CF.

Background: In Germany, the first case of coronavirus disease 2019 (COVID-19) was registered on 28 January 2020. By February 2021, the third wave of the pandemic began. So far, only few data are available on the SARS-CoV-2 prevalence and the clinical impact of an infection in patients with cystic fibrosis (CF).Methods: From February 2020 until March 2021, we screened 156 CF patients for anti-SARS-CoV-2 IgG antibodies (serology) and the presence of SARS-CoV-2 in deep throat saliva or nasopharyngeal swabs (molecular testing). From patients with confirmed SARS-CoV-2 infection, we recorded symptoms and collected clinical data. Results: In total, 13 patients (8.3%) were tested positive for SARS-CoV-2 infection, most of them during the second and the beginning third wave of the pandemic. Ten positive tested patients described symptoms linked to COVID-19. The most common symptom was cough followed by fatigue and headache. SARS-CoV-2 infection did not impair lung function. No positive tested patient needed to be hospitalized.Conclusions: SARS-CoV-2 infections in patients with CF are not as rare as initially anticipated, as frequent testing revealed. However, infected patients did not experience more severe clinical courses or worse clinical outcome. Our observation is in line with published reports indicating that individuals with CF are not at higher risk for severe COVID-19.

For people with cystic fibrosis, validated patient-reported outcome measures for the assessment of the complex abdominal involvement are lacking. The objective of this study was to examine whether the CFAbd-Score, a novel questionnaire consisting of 28 items, meets the essential requirements (validity and reliability) for a patient-reported outcome measure according to US Food and Drug Administration recommendations. Content validity was assessed by recording the frequencies and severity of symptoms that occurred during the prior 2 weeks in patients with cystic fibrosis (n = 116; aged ≥ 6 years). Comparing the CFAbd-Score results obtained from patients with cystic fibrosis and healthy controls (n = 88), we determined known-groups validity. To explore the structure of the patient-reported outcome measure, a factor analysis was conducted. Internal consistency of the five extracted score domains was assessed using Cronbach’s alpha. For test–retest reliability, a subgroup of patients (n = 43) was reevaluated and intra-class correlation coefficients were determined. The CFAbd-Score differentiated patients with cystic fibrosis from healthy controls with a large effect size (17.3 ± 1.1 vs. 8.0 ± 0.7 points; p

The electronic and optical properties of (InxGa1–x)2O3 alloys are highly tunable, giving rise to a myriad of applications including transparent conductors, transparent electronics, and solar-blind ...

Indium sulfide hyperdoped with vanadium has been predicted to be a promising material to realize an intermediate band (IB) solar cell. Using co-evaporation of the elements we grew In 2 S 3 :V on (111)-oriented $p$ -Si substrates. As transparent top electrode n-ZnO:Al is used to realize heterostructure $pin$ -solar cells. Investigations of structural properties reveal epitaxial growth independent of the vanadium doping content. We further characterize pin-heterostructure solar cells by current-voltage characteristics in the dark and under illumination. We do not observe an increase of short circuit current density for V-doped samples, which indicates that the IB is fully occupied.

Herein, the magnetoelectric (ME) performance of epitaxial multilayer composite films built from nanometer‐thick layers of multiferroic BiFeO3 and ferroelectric BaTiO3 is reviewed. A successful implementation of shadow‐mask pulsed laser deposition considerably reduces the interface and surface roughness of the multilayers. In dependence of double‐layer thickness and the degree of structural perfection, the multilayers show high ME voltage coefficients up to 480 V cm−1 Oe−1 at 300 K and 0 T bias magnetic field. With decreasing double‐layer thickness, an interface‐driven effect critically enhances the ME coupling in this strain and charge-comediated system. Interestingly, the characteristics of temperature and DC magnetic field dependencies of magnetoelectric voltage coefficients change with the transition from the 2D to 3D character of the single layers, i.e., for BiFeO3 layers thicker than 5 nm within the multilayers. These changes are attributed to variations of the contributing ME coupling mechanisms. Furthermore, scanning transmission electron microscopy (STEM) with energy‐dispersive X‐ray (EDX) spectroscopy mapping‐based nanoanalysis indicates that chemical effects at the interfaces play an important role for the ME performance of the BiFeO3-BaTiO3 multilayer thin films.

This paper gives an overview of current research topics at the Institute of Mechanism Theory, Machine Dynamics and Robotics of RWTH Aachen University. A variety of application areas is introduced, including robotic reconstruction, agile production, additive manufacturing and human-robot collaboration. Each topic offers novel and unique contributions to its field of robotics.

Patients after total hip arthroplasty (THA) suffer from lingering musculoskeletal restrictions. Three-dimensional (3D) gait analysis in combination with machine-learning approaches is used to detect these impairments. In this work, features from the 3D gait kinematics, spatio temporal parameters (Set 1) and joint angles (Set 2), of an inertial sensor (IMU) system are proposed as an input for a support vector machine (SVM) model, to differentiate impaired and non-impaired gait. The features were divided into two subsets. The IMU-based features were validated against an optical motion capture (OMC) system by means of 20 patients after THA and a healthy control group of 24 subjects. Then the SVM model was trained on both subsets. The validation of the IMU system-based kinematic features revealed root mean squared errors in the joint kinematics from 0.24&deg, to 1.25&deg, The validity of the spatio-temporal gait parameters (STP) revealed a similarly high accuracy. The SVM models based on IMU data showed an accuracy of 87.2% (Set 1) and 97.0% (Set 2). The current work presents valid IMU-based features, employed in an SVM model for the classification of the gait of patients after THA and a healthy control. The study reveals that the features of Set 2 are more significant concerning the classification problem. The present IMU system proves its potential to provide accurate features for the incorporation in a mobile gait-feedback system for patients after THA.

Objective— Cancer patients are at high risk of developing deep venous thrombosis (DVT) and venous thromboembolism, a leading cause of mortality in this population. However, it is largely unclear how malignant tumors drive the prothrombotic cascade culminating in DVT. Approach and Results— Here, we addressed the pathophysiology of malignant DVT compared with nonmalignant DVT and focused on the role of tumor microvesicles as potential targets to prevent cancer-associated DVT. We show that microvesicles released by pancreatic adenocarcinoma cells (pancreatic tumor–derived microvesicles [pcMV]) boost thrombus formation in a model of flow restriction of the mouse vena cava. This depends on the synergistic activation of coagulation by pcMV and host tissue factor. Unlike nonmalignant DVT, which is initiated and propagated by innate immune cells, thrombosis triggered by pcMV was largely independent of myeloid leukocytes or platelets. Instead, we identified externalization of the phospholipid phosphatidylethanolamine as a major mechanism controlling the prothrombotic activity of pcMV. Disrupting phosphatidylethanolamine-dependent activation of factor X suppressed pcMV-induced DVT without causing changes in hemostasis. Conclusions— Together, we show here that the pathophysiology of pcMV-associated experimental DVT differs markedly from innate immune cell–promoted nonmalignant DVT and is therefore amenable to distinct antithrombotic strategies. Targeting phosphatidylethanolamine on tumor microvesicles could be a new strategy for prevention of cancer-associated DVT without causing bleeding complications.

Abdominal symptoms are a hallmark of Cystic fibrosis (CF). Yet, their association with morphological abnormalities of different abdominal organs is still poorly understood. Aim was therefore to relate these symptoms, assessed with a questionnaire, to findings in abdominal ultrasound (US). In 114 CF patients of all ages, findings in US considering seventeen specific parameters were related to abdominal symptoms compiled with our novel CF-specific 26-modal symptom score (CFAbd-Score). US abnormalities were detected in 95% of the patients. Most frequent findings were pancreatic lipomatosis (88%), liver steatosis (37%), hepatomegaly (31%), and thickened bowel walls (23%). Highest burden of GI-symptoms was clearly associated with pancreatic lipomatosis (p = 0.036). In detail, patients revealing this pathology reported higher rates of abdominal pain (p = 0.018), flatulence (p = 0.006), heartburn (p = 0.04), and reflux of stomach content (p = 0.006). Patients with pancreatic sufficiency had less US-findings (p = 0.033), which in turn was associated with lower rates of abdominal symptoms. The majority of them were carriers of class IV-VI or G551D mutations. Our approach gives new insights regarding the underestimated multi-organ abdominal involvement in CF. The new score can be of high interest e.g. as a complementary tool to assess the gastrointestinal effects of promising novel CF therapeutics.

Novel devices based on orthorhombic κ-Ga2O3 could enable solar blind infrared detection or high-electron mobility transistors with large two-dimensional electron gas densities. Here, we report on the current transport parallel to the growth direction of κ-Ga2O3 layers grown by pulsed-laser deposition on highly conductive Al-doped ZnO back contact layers. Besides ohmic Ti/Al/Au contact layer stacks, vertical Pt/PtOx/κ-Ga2O3 and Pd/PdOx/κ-Ga2O3 Schottky barrier diodes and NiO/κ-Ga2O3 and ZnCo2O4/κ-Ga2O3 pn-heterodiodes are investigated by current–voltage measurements. While a lateral current transport is severely suppressed to less than 10−9Acm−2 due to rotational domains, we record a significant current flow through the ohmic contacts in the vertical direction of >0.1Acm−2. The Schottky barrier diodes and the pn-heterojunctions exhibit rectification ratios of up to seven orders of magnitude. Room temperature current–voltage characteristics of diode ensembles as well as temperature-dependent measurements for selected Pt-based diodes reveal a mean barrier height of ϕBm≈2.1eV and ideality factors down to η≈1.3.

SummaryBackground In current guidelines, 6 hours of fasting is recommended for solids to limit the risk of pulmonary aspiration during anesthesia in children. Ultrasonography has recently been introduced to evaluate gastric volumes in children in the context of preanesthetic fasting. Therefore, in this study, we firstly evaluated the precision of ultrasound assessment of gastric volume in an experimental setting and secondly studied gastric emptying times after a normal breakfast in healthy preschool children using ultrasound. Methods In a preliminary experiment, a pear-shaped elastic balloon was filled and emptied in 50 mL steps from 0 to 500 mL with water. After each step, the balloon antral area was measured using ultrasonography. Thereafter, gastric emptying was examined in healthy preschool children after normal breakfast by sonographic measurements of the gastric antral area in right lateral decubitus position at two consecutive timepoints. Correlation coefficients (Pearson, 95% CI) between the balloon antral area and the balloon volume or gastric antral area and fasting time were calculated and gastric emptying time was extrapolated by linear regression. Data are presented as mean (range). Results In the balloon experiment, the balloon volume correlated significantly with the balloon antral area (63 measurements, r=.96, P

This paper describes the design of a gripper for horticulture product grasping. The design solution has been achieved by means of a systematic approach by evaluating all the possible architecture. The proposed structure is optimized and numerically simulated. Then, a prototype has been built and tested in laboratory. The design process and test results are discussed to show the efficiency of the built prototype with lab tests.

Clinical observations implicate a role of eosinophils in cardiovascular diseases because markers of eosinophil activation are elevated in atherosclerosis and thrombosis. However, their contribution to atherosclerotic plaque formation and arterial thrombosis remains unclear. In these settings, we investigated how eosinophils are recruited and activated through an interplay with platelets. Here, we provide evidence for a central importance of eosinophil-platelet interactions in atherosclerosis and thrombosis. We show that eosinophils support atherosclerotic plaque formation involving enhanced von Willebrand factor exposure on endothelial cells and augmented platelet adhesion. During arterial thrombosis, eosinophils are quickly recruited in an integrin-dependent manner and engage in interactions with platelets leading to eosinophil activation as we show by intravital calcium imaging. These direct interactions induce the formation of eosinophil extracellular traps (EETs), which are present in human thrombi and constitute a substantial part of extracellular traps in murine thrombi. EETs are decorated with the granule protein major basic protein, which causes platelet activation by eosinophils. Consequently, targeting of EETs diminished thrombus formation in vivo, which identifies this approach as a novel antithrombotic concept. Finally, in our clinical analysis of coronary artery thrombi, we identified female patients with stent thrombosis as the population that might derive the greatest benefit from an eosinophil-inhibiting strategy. In summary, eosinophils contribute to atherosclerotic plaque formation and thrombosis through an interplay with platelets, resulting in mutual activation. Therefore, eosinophils are a promising new target in the prevention and therapy of atherosclerosis and thrombosis.

Auslander, die nicht nur kurzfristig fur touristische Zwecke nach Thailand reisen, sondern sich dort langere Zeit aufhalten wollen, benotigen hierfur nach dem Immigration Act B. E. 2522 von 1979 eine Aufenthaltsgenehmigung. Wird in diesem Zeitraum ferner einer Beschaftigung oder geschaftlichen Tatigkeit nachgegangen, ist in fast allen Fallen auch eine Arbeitserlaubnis („Work Permit“) erforderlich (siehe Kap. 4.2).

The German Labour Law regulates the relation between employers and employees and intends to establish social justice on the basis of private law by (labour) contract. In order to provide a fair and just working environment, it creates a balance between the (supposedly) stronger bargaining position of the employer and protection of employee’s rights. The aim is therefore not to provide employers and employees with equal rights but to elevate the employee to a near equal level of rights (and duties) as the “more powerful” employer.

Polymicrobial intra-abdominal infections (IAIs) are clinically prevalent and cause significant morbidity and mortality, especially those involving fungi. Our laboratory developed a mouse model of IAI and demonstrated that intraperitoneal inoculation with Candida albicans or other virulent non-albicans Candida (NAC) species plus Staphylococcus aureus resulted in 70 to 80% mortality in 48 to 72 h due to robust local and systemic inflammation (sepsis). Surprisingly, inoculation with Candida dubliniensis or Candida glabrata with S. aureus resulted in minimal mortality, and rechallenge of these mice with lethal C. albicans/S. aureus (i.e., coninfection) resulted in >90% protection. The purpose of this study was to define requirements for C. dubliniensis/S. aureus-mediated protection and interrogate the mechanism of the protective response. Protection was conferred by C. dubliniensis alone or by killed C. dubliniensis plus live S. aureus. S. aureus alone was not protective, and killed S. aureus compromised C. dubliniensis-induced protection. C. dubliniensis/S. aureus also protected against lethal challenge by NAC plus S. aureus and could protect for a long-term duration (60 days between primary challenge and C. albicans/S. aureus rechallenge). Unexpectedly, mice deficient in T and B cells (Rag-1 knockouts [KO]) survived both the initial C. dubliniensis/S. aureus challenge and the C. albicans/S. aureus rechallenge, indicating that adaptive immunity did not play a role. Similarly, mice depleted of macrophages prior to rechallenge were also protected. In contrast, protection was associated with high numbers of Gr-1hi polymorphonuclear leukocytes (PMNLs) in peritoneal lavage fluid within 4 h of rechallenge, and in vivo depletion of Gr-1+ cells prior to rechallenge abrogated protection. These results suggest that Candida species can induce protection against a lethal C. albicans/S. aureus IAI that is mediated by PMNLs and postulated to be a unique form of trained innate immunity., IMPORTANCE Polymicrobial intra-abdominal infections are clinically devastating infections with high mortality rates, particularly those involving fungal pathogens, including Candida species. Even in patients receiving aggressive antimicrobial therapy, mortality rates remain unacceptably high. There are no available vaccines against IAI, which is complicated by the polymicrobial nature of the infection. IAI leads to lethal systemic inflammation (sepsis), which is difficult to target pharmacologically, as components of the inflammatory response are also needed to control the infection. Our studies demonstrate that prior inoculation with low-virulence Candida species provides strong protection against subsequent lethal infection with C. albicans and S. aureus. Surprisingly, protection is long-lived but not mediated by adaptive (specific) immunity. Instead, protection is dependent on cells of the innate immune system (nonspecific immunity) and provides protection against other virulent Candida species. This discovery implies that a form of trained innate immunity may be clinically effective against polymicrobial IAI.

Introduction. P. aeruginosais the primary cause for pulmonary destruction and premature death in cystic fibrosis (CF). Therefore, prevention of airway colonization with the pathogen, ubiquitously present in water, is essential. Infection of CF patients withP. aeruginosaafter dentist treatment was proven and dental unit waterlines were identified as source, suggesting prophylactic measures. For their almost regular sinonasal involvement, CF patients often require otorhinolaryngological (ORL) attendance. Despite some fields around ORL-procedures with comparable risk for acquisition ofP. aeruginosa, such CF cases have not yet been reported. We present four CF patients, who primarily acquiredP. aeruginosaaround ORL surgery, and one around dentist treatment. Additionally, we discuss risks and preventive strategies for CF patients undergoing ORL-treatment. Perils include contact to pathogen-carriers in waiting rooms, instrumentation, suction, drilling, and flushing fluid, when droplets containing pathogens can be nebulized. Postsurgery mucosal damage and debridement impair sinonasal mucociliary clearance, facilitating pathogen proliferation and infestation. Therefore, sinonasal surgery and dentist treatment of CF patients without chronicP. aeruginosacolonization must be linked to repeated microbiological assessment. Further studies must elaborate whether all CF patients undergoing ORL-surgery require antipseudomonal prophylaxis, including nasal lavages containing antibiotics. Altogether, this underestimated risk requires structured prevention protocols.

Precision is an important feature in modern robotics and manipulation technology. Elevation of the robot's end-effector precision depends on different features as stiffness, tolerance etc. which should be considered during the synthesis and design phase of the manipulator. The focus of this study is on the structural stiffness of parallel kinematic manipulators (PKM) exhibiting actuation redundancy. It is determined how the stiffness depends on physical and geometrical characteristics of the manipulator and how it is possible to take advantage of redundancy to enhance the stiffness of the manipulator. It is shown that redundantly actuated PKM (RA-PKM) with components made of softer and accordingly lighter materials demonstrate comparable stiffness to the non-redundant manipulators which consequently decrease the required energy for moving the dead-load in operation. Based on the model built in this study, optimizations are conducted and manipulators with optimal morphologies for different tasks are introduced. As a case study, RA-PKM of type n-R RPaRs are considered.

Thermoelectric devices that are flexible and optically transparent hold unique promise for future electronics. However, development of invisible thermoelectric elements is hindered by the lack of p-type transparent thermoelectric materials. Here we present the superior room-temperature thermoelectric performance of p-type transparent copper iodide (CuI) thin films. Large Seebeck coefficients and power factors of the obtained CuI thin films are analysed based on a single-band model. The low-thermal conductivity of the CuI films is attributed to a combined effect of the heavy element iodine and strong phonon scattering. Accordingly, we achieve a large thermoelectric figure of merit of ZT=0.21 at 300 K for the CuI films, which is three orders of magnitude higher compared with state-of-the-art p-type transparent materials. A transparent and flexible CuI-based thermoelectric element is demonstrated. Our findings open a path for multifunctional technologies combing transparent electronics, flexible electronics and thermoelectricity., Flexible thermoelectric devices with high optical transparency may enable new applications; however, the lack of a p-type counterpart has hitherto hindered its development. Yang et al., report a transparent p-type thermoelectric based on polycrystalline copper iodide thin film with record performance.

Compared to other fungal pathogens, Cryptococcus neoformans is particularly adept at avoiding detection by innate immune cells. To explore fungal cellular features involved in immune avoidance, we characterized cell surface changes of the C. neoformans rim101Δ mutant, a strain that fails to organize and shield immunogenic epitopes from host detection. These cell surface changes are associated with an exaggerated, detrimental inflammatory response in mouse models of infection. We determined that the disorganized strain rim101Δ cell wall increases macrophage detection in a contact-dependent manner. Using biochemical and microscopy methods, we demonstrated that the rim101Δ strain shows a modest increase in the levels of both cell wall chitin and chitosan but that it shows a more dramatic increase in chito-oligomer exposure, as measured by wheat germ agglutinin staining. We also created a series of mutants with various levels of cell wall wheat germ agglutinin staining, and we demonstrated that the staining intensity correlates with the degree of macrophage activation in response to each strain. To explore the host receptors responsible for recognizing the rim101Δ mutant, we determined that both the MyD88 and CARD9 innate immune signaling proteins are involved. Finally, we characterized the immune response to the rim101Δ mutant in vivo, documenting a dramatic and sustained increase in Th1 and Th17 cytokine responses. These results suggest that the Rim101 transcription factor actively regulates the C. neoformans cell wall to prevent the exposure of immune stimulatory molecules within the host. These studies further explored the ways in which immune cells detect C. neoformans and other fungal pathogens by mechanisms that include sensing N-acetylglucosamine-containing structures, such as chitin and chitosan., IMPORTANCE Infectious microorganisms have developed many ways to avoid recognition by the host immune system. For example, pathogenic fungi alter their cell surfaces to mask immunogenic epitopes. We have created a fungal strain with a targeted mutation in a pH response pathway that is unable to properly organize its cell wall, resulting in a dramatic immune reaction during infection. This mutant cell wall is defective in hiding important cell wall components, such as the chito-oligomers chitin and chitosan. By creating a series of cell wall mutants, we demonstrated that the degree of chito-oligomer exposure correlates with the intensity of innate immune cell activation. This activation requires a combination of host receptors to recognize and respond to these infecting microorganisms. Therefore, these experiments explored host-pathogen interactions that determine the degree of the subsequent inflammatory response and the likely outcome of infection.

The rise in energy consumption and the associated costs instigate financial concerns among industrial energy consumers. For industrial processes addressing heating and cooling as well as material transformation, a wide range of energy efficiency measures have been developed and successfully implemented. In contrast to that, most robot-based operations such as pick-and-place motions or assembly tasks still use inefficient standard concepts causing high-energy consumption and high-energy costs. Thanks to a rather low payload-to-weight ratio of new robot designs, such as parallel kinematic or hybrid robot manipulators, a high potential for energy savings is expected. This article identifies potentials for energy saving concerning industrial consumers by assessing three different robot concepts. Based on a literature review, two existing designs for robots the conventional serial robot and the parallel kinematic robot are analysed and compared with respect to the energy utilised during a typical item placement task. Afterwards, the concept of PARAGRIP, a hybrid of the two presented robot designs is introduced and examined based on simulation regarding its energy consumption. The final results demonstrate significantly different energy consumptions between the robot concepts, identifying potential savings of about 40% in a selected industrial application scenario.

Platelets modulate the process of cancer metastasis. However, current knowledge on the direct interaction of platelets and tumor cells is mostly based on findings obtained in vitro. We addressed the role of the platelet fibrinogen receptor glycoprotein IIb (integrin αIIb) for experimental melanoma metastasis in vivo. Highly metastatic B16-D5 melanoma cells were injected intravenously into GPIIb-deficient (GPIIb-/-) or wildtype (WT) mice. Acute accumulation of tumor cells in the pulmonary vasculature was assessed in real-time by confocal videofluorescence microscopy. Arrest of tumor cells was dramatically reduced in GPIIb-/- mice as compared to WT. Importantly, we found that mainly multicellular aggregates accumulated in the pulmonary circulation of WT, instead B16-D5 aggregates were significantly smaller in GPIIb-/- mice. While pulmonary arrest of melanoma was clearly dependent on GPIIb in this early phase of metastasis, we also addressed tumor progression 10 days after injection. Inversely, and unexpectedly, we found that melanoma metastasis was now increased in GPIIb-/- mice. In contrast, GPIIb did not regulate local melanoma proliferation in a subcutaneous tumor model. Our data suggest that the platelet fibrinogen receptor has a differential role in the modulation of hematogenic melanoma metastasis. While platelets clearly support early steps in pulmonary metastasis via GPIIb-dependent formation of platelet-tumor-aggregates, at a later stage its absence is associated with an accelerated development of melanoma metastases.

Pulsed laser deposition is one of the most flexible growth methods for high-quality epitaxial multifunctional thin films and short-period superlattices. The following examples of current research interest demonstrate the state-of-the art: First, it is shown that the magnetoelectric performance of multiferroic BiFeO3-BaTiO3 (001)-oriented superlattices depends on the crystalline coherence of the different layers at the interfaces. Second, it is exemplified that dielectric-plasmonic superlattices built from the electrically insulating oxide MgO and the metallically conducting nitride TiN are promising metamaterials with hyperbolic dispersion. As a third example, it is demonstrated that LaNiO3- and LaMnO3-based superlattices with (001)-, (011)-, and (111)-out-of-plane orientation and controlled single layer thickness from 2 to 15 atomic monolayers show metal-insulator transitions and tunable gaps, in partial agreement with density functional theory calculations. Underlined by these examples, it is shown that the precise control of an epitaxially coherent, or two-dimensional layer-by-layer growth, named after Jan van der Merwe, is a prerequisite to achieve the desired functionality of oxide-oxide and oxide-nitride superlattices.

In patients with atrial fibrillation, oral anticoagulation with oral thrombin inhibitors (OTIs), in contrast to vitamin K antagonists (VKAs), associates with a modest increase in acute coronary syndromes (ACSs). Whether this observation is causatively linked to OTI treatment and, if so, whether OTI action is the result of a lower antithrombotic efficacy of OTI compared to VKA or reflects a yet undefined prothrombotic activity of OTI remain unclear. We analyzed platelet function in patients receiving OTI or dose-adapted VKA under static and flow conditions. In vivo, we studied arterial thrombosis in OTI-, VKA-, and vehicle-treated mice using carotid ligation and wire injury models. Further, we examined thrombus formation on human atherosclerotic plaque homogenates under arterial shear to address the relevance to human pathology. Under static conditions, aggregation in the presence of ristocetin was increased in OTI-treated blood, whereas platelet reactivity and aggregation to other agonists were only marginally affected. Under flow conditions, firm platelet adhesion and thrombus formation on von Willebrand factor, collagen, and human atherosclerotic plaque were increased in the presence of OTI in comparison to VKA. OTI treatment was associated with increased thrombus formation in injured carotid arteries of mice. Inhibition or ablation of GPIbα-thrombin interactions abolished the effect of OTI on thrombus formation, suggesting a mechanistic role of the platelet receptor GPIbα and its thrombin-binding site. The effect of OTI was also abrogated in the presence of aspirin. In summary, OTI treatment has prothrombotic activity that might contribute to the increase in ACS observed clinically in patients.

This paper describes the design of a gripper for grasping and manipulating horticulture products. The design solution has been achieved by means of a systematic approach, by evaluating all the possible architectures to get an optimal one. The proposed structure is numerically designed and simulated and then a prototype has been built and successfully tested in laboratory.

Spatial object manipulation is subject to various parameters, which can be optimized by means of suitable motion strategies. In addition, corresponding strategies can be adapted to specified handling devices enabling efficient motion design with respect to kinematic and dynamic characteristics of particular manipulators. Further optimization is provided by the application of robot redundancy, whose resolution can be adapted to efficient motion planning. In this context, parallel kinematic systems featuring kinematic redundancy or a redundant actuator concept can be operated with an optimal set of actuator parameters allowing a resource-efficient object manipulation. This contribution is devoted to the conception and modeling of redundantly actuated parallel kinematic manipulators (RA-PKM) in order to realize optimal configuration strategies and motion design. Accordingly, the structure selection and the dimensional synthesis of a translational RA-PKM are presented based on parametric kinematic and dynamic modeling. Corresponding models provide an application-oriented transformation from intuitive CAD design software to technical computing and simulation software. The developed manipulator is suitable for the comparison of different redundant and non-redundant actuator configurations as well as optimal trajectories. Concluding analyses exemplarily refer to a non-redundant 3-arm and a redundant n-arm PRPaR system.

Integrins are critical for platelet adhesion and aggregation during arterial thrombosis and hemostasis. Although the platelet-specific αIIbβ3 integrin is known to be crucial for these processes, the in vivo role of β1 integrins is a matter of debate. Here we demonstrate that mice expressing reduced levels of β1 integrins or an activation-deficient β1 integrin show strongly reduced platelet adhesion to collagen in vitro and in a carotis ligation model in vivo. Interestingly, hypomorphic mice expressing only 3% of β1 integrins on platelets show normal bleeding times despite reduced platelet adhesion. The residual 3% of β1 integrins are able to trigger intracellular signals driving Rac-1-dependent granule release required for platelet aggregation and hemostasis. Our findings support a model, in which platelet β1 integrins serve as an important signaling receptor rather than an adhesion receptor in vivo and therefore promote β1 integrins as a promising and so far clinically unemployed antithrombotic target.

Halide semiconductors stand at the very beginning of semiconductor science and technology. CuI was reported as the first transparent conductor, and the first field effect transistor was made from KBr. Although halogens are frequently used in semiconductor preparation, little use is currently made from halide semiconductors in electronics and photonics. We review past reports on the metal halide semiconductor CuI and related alloys and discuss recent progress with regard to this material including its use in organic electronics and solar cells as well as our own work on fully transparent bipolar heterostructure diodes (p-CuI/n-ZnO) with high rectification of several 107 and ideality factors down to 1.5. γ-CuI(111) thin film on glass (1 × 1 cm2) and IV-characteristics of p-CuI/n-ZnO/a-Al2O3 bipolar heterojunction diode.

We compare key properties of zinc oxide (ZnO)-based junction field-effect transistors (JFETs), metal-semiconductor field-effect transistors (MESFETs), and metal-insulator-semiconductor field-effect transistors (MISFETs) prepared from a common ZnO:Mg thin film. The JFETs are fabricated with a ZnCo2O4-gate, the MESFETs with reactively sputtered Pt-gate and the MISFETs with WO3 as gate insulator. The three FET types are compared with regarding dc characteristics, frequency dependence, and stability at temperatures up to 150°C. All devices can be switched within a similar gate voltage range of less than 3 V, making a direct comparison of the device characteristics possible. Measurements above room temperature show a common shift of the transfer curves to higher gate voltages, which seems to be a distinguishing property of ZnO compared with other semiconductors. All electric measurements show major differences between the devices, which can be attributed to the different gate structures.

Human megakaryocytes (MKs) release trillions of platelets each day into the circulation to maintain normal homeostatic platelet levels. We have previously shown that extracellular sphingosine 1-phosphate (S1P) plays a key role in thrombopoiesis via its receptor S1pr1. In addition to its role as an extracellular mediator, S1P can also function as a second messenger in the intracellular compartment. Although signaling via intracellular S1P is involved in various cellular processes, a role in thrombopoiesis has not been examined. Sphingosine kinases are the key enzymes that produce intracellular S1P. Here we report that sphingosine kinase 2 (Sphk2) is the major messenger RNA species present in MKs. Sphk2 predominantly localizes to the nucleus and is the major source of intracellular S1P in MKs. Loss of Sphk2 significantly reduced intracellular S1P in MKs and downregulated the expression and activity of Src family kinases (SFKs). Loss of Sphk2 and inhibition of SFK activity resulted in defective intravascular proplatelet shedding, the final stage of thrombopoiesis. Correspondingly, mice lacking Sphk2 in the hematopoietic system display thrombocytopenia. Together, our data suggest that Sphk2 provides the source of intracellular S1P that controls thrombopoiesis, which is associated with SFK expression and activity in MKs.

Background & aims Abdominal symptoms (AS) are a hallmark of the multiorgan-disease cystic fibrosis (CF). However, the abdominal involvement in CF is insufficiently understood and, compared to the pulmonary manifestation, still receives little scientific attention. Aims were to assess and quantify AS and to relate them to laboratory parameters, clinical findings, and medical history. Methods A total of 131 patients with CF of all ages were assessed with a new CF-specific questionnaire (JenAbdomen-CF score 1.0) on abdominal pain and non-pain symptoms, disorders of appetite, eating, and bowel movements as well as symptom-related quality of life. Results were metrically dimensioned and related to abdominal manifestations, history of surgery, P. aeruginosa and S. aureus colonization, genotype, liver enzymes, antibiotic therapy, lung function, and nutritional status. Results AS during the preceding 3 months were reported by all of our patients. Most common were lack of appetite (130/131) and loss of taste (119/131) followed by abdominal pain (104/131), flatulence (102/131), and distention (83/131). Significantly increased AS were found in patients with history of rectal prolapse (p = 0.013), distal intestinal obstruction syndrome (p = 0.013), laparotomy (p = 0.022), meconium ileus (p = 0.037), pancreas insufficiency (p = 0.042), or small bowel resection (p = 0.048) as well as in patients who have been intermittently colonized with P. aeruginosa (p = 0.006) compared to patients without history of these events. In contrast, no statistically significant associations were found to CF-associated liver disease, chronic pathogen colonization, lung function, CF-related diabetes, and nutritional status. Conclusion As the complex abdominal involvement in CF is still not fully understood, the assessment of the common AS is of major interest. In this regard, symptom questionnaires like the herein presented are meaningful and practical tools facilitating a wider understanding of the abdominal symptoms in CF. Furthermore, they render to evaluate possible abdominal effects of novel modulators of the underlying cystic fibrosis transmembrane (conductance) regulator (CFTR) defect.

Spatial object manipulation is typically accomplished by parallel kinematic manipulators (PKM), whose number of actuators is equal to the required number of degrees of freedom. In order to improve the performance and reliability of PKM, their basic configuration can be extended by redundant actuators. This paper is devoted to the special case of PKM with both linear and rotational actuation, which can be operated simultaneously. Corresponding manipulators face the problem of coexisting translational and rotational joint space parameters inducing inhomogeneous Jacobian matrices. In this context, power manipulability ellipsoids provide a suitable performance evaluation for PKM featuring different types of redundantly applicable actuators. Accordingly, this research intends to analyze the kinetostatic performance of redundantly actuated PKM and to demonstrate their efficiency in contrast to non-redundant drive configurations. The analyses exemplarily are focused on the translational 3-RPC manipulator, since it can be equipped with both revolute and/or prismatic joint actuation.

‘Legal capacity, nationality, residency and habitual residence are irrelevant for the existence of personal income tax liability in Germany. Residency or habitual residence and nationality are the only criteria to determine the personal income tax liability, i.e.: unlimited, limited, extended unlimited or extended limited.’

Deep venous thrombosis (DVT) is one of the most common cardiovascular diseases, but its pathophysiology remains incompletely understood. Although sterile inflammation has recently been shown to boost coagulation during DVT, the underlying molecular mechanisms are not fully resolved, which could potentially identify new anti-inflammatory approaches to prophylaxis and therapy of DVT. Using a mouse model of venous thrombosis induced by flow reduction in the vena cava inferior, we identified blood-derived high-mobility group box 1 protein (HMGB1), a prototypical mediator of sterile inflammation, to be a master regulator of the prothrombotic cascade involving platelets and myeloid leukocytes fostering occlusive DVT formation. Transfer of platelets into Hmgb1-/- chimeras showed that this cell type is the major source of HMGB1, exposing reduced HMGB1 on their surface upon activation thereby enhancing the recruitment of monocytes. Activated leukocytes in turn support oxidation of HMGB1 unleashing its prothrombotic activity and promoting platelet aggregation. This potentiates the amount of HMGB1 and further nurtures the accumulation and activation of monocytes through receptor for advanced glycation end products (RAGE) and Toll-like receptor 2, leading to local delivery of monocyte-derived tissue factor and cytokines. Moreover, disulfide HMGB1 facilitates formation of prothrombotic neutrophil extracellular traps (NETs) mediated by RAGE, exposing additional HMGB1 on their extracellular DNA strands. Eventually, a vicious circle of coagulation and inflammation is set in motion leading to obstructive DVT formation. Therefore, platelet-derived disulfide HMGB1 is a central mediator of the sterile inflammatory process in venous thrombosis and could be an attractive target for an anti-inflammatory approach for DVT prophylaxis.

Deep vein thrombosis initiation is mediated by cross talk between monocytes, neutrophils, and platelets., Deep vein thrombosis (DVT) is a major cause of cardiovascular death. The sequence of events that promote DVT remains obscure, largely as a result of the lack of an appropriate rodent model. We describe a novel mouse model of DVT which reproduces a frequent trigger and resembles the time course, histological features, and clinical presentation of DVT in humans. We demonstrate by intravital two-photon and epifluorescence microscopy that blood monocytes and neutrophils crawling along and adhering to the venous endothelium provide the initiating stimulus for DVT development. Using conditional mutants and bone marrow chimeras, we show that intravascular activation of the extrinsic pathway of coagulation via tissue factor (TF) derived from myeloid leukocytes causes the extensive intraluminal fibrin formation characteristic of DVT. We demonstrate that thrombus-resident neutrophils are indispensable for subsequent DVT propagation by binding factor XII (FXII) and by supporting its activation through the release of neutrophil extracellular traps (NETs). Correspondingly, neutropenia, genetic ablation of FXII, or disintegration of NETs each confers protection against DVT amplification. Platelets associate with innate immune cells via glycoprotein Ibα and contribute to DVT progression by promoting leukocyte recruitment and stimulating neutrophil-dependent coagulation. Hence, we identified a cross talk between monocytes, neutrophils, and platelets responsible for the initiation and amplification of DVT and for inducing its unique clinical features.

Phosphorus-doped MgxZn1−xO thin films with various Mg content (0.07 ≤ x ≤ 0.28) and up to 0.7 at% P were grown on ZnO(000-1) single crystals by pulsed laser deposition (PLD). In dependence on the dopant concentrations, tensile or compressively strained, in-plane lattice matched, i.e., pseudomorphic growth of the MgZnO:P films was confirmed by high-resolution X-ray diffraction (HR-XRD). All investigated, high-quality MgZnO:P films are n-type, also after post-growth annealing at 850 °C. From the Hall analysis the activation energy of the dominating donors was derived, yielding values of up to 345 meV for high oxygen partial pressure during growth, and shallow donors with an activation energy of about 30 meV for low oxygen pressure. The Hall-mobility of the MgxZn1−xO:P films at a temperature of 65 K was as high as 740 cm2/Vs, and reached values up to 190 cm2/Vs at room temperature, close to the best values reported for bulk ZnO.

Advanced Pulsed Laser Deposition (PLD) processes allow the growth of oxide thin film heterostructures on large area substrates up to 4-inch diameter, with flexible and controlled doping, low dislocation density, and abrupt interfaces. These PLD processes are discussed and their capabilities demonstrated using selected results of structural, electrical, and optical characterization of superconducting (YBa2Cu3O7−δ), semiconducting (ZnO-based), and ferroelectric (BaTiO3-based) and dielectric (wide-gap oxide) thin films and multilayers. Regarding the homogeneity on large area of structure and electrical properties, flexibility of doping, and state-of-the-art electronic and optical performance, the comparably simple PLD processes are now advantageous or at least fully competitive to Metal Organic Chemical Vapor Deposition or Molecular Beam Epitaxy. In particular, the high flexibility connected with high film quality makes PLD a more and more widespread growth technique in oxide research.

Metal-semiconductor field-effect transistors (MESFETs) are widely known from opaque high-speed GaAs or high-power SiC and GaN technology. For the emerging field of transparent electronics, only metal-insulator-semiconductor field-effect transistors (MISFETs) were considered so far. This article reviews the progress of high-performance MESFETs in oxide electronics and reflects the recent advances of this technique towards transparent MESFET circuitry. We discuss design prospects as well as limitations regarding device performance, reliability and stability. The presented ZnO-based MESFETs and inverters have superior properties compared to MISFETs, i.e., high channel mobilities and on/off-ratios, high gain, and low uncertainty level at comparatively low operating voltages. This makes them a promising approach for future low-cost transparent electronics.

Homoepitaxial MgZnO thin films were grown from PLD targets with 1, 2, 4, and 10 wt.% MgO content on ZnO-buffered ZnO(001) substrates. The resulting Mg content of the films was determined from the blue-shift of the excitonic peak in low-temperature photoluminescence spectra. With increasing Mg content a considerable increase of film mosaicity was observed from HR-XRD (002) rocking curves. Triple-axis reciprocal space maps of symmetric (002) and asymmetric (104) reflections show the structural development in terms of tilt and perpendicular and parallel strain. For more than 1% Mg the films exhibit increasing tensile out-of-plane strain. Very high electron mobilities of 200 cm²/Vs at 300 K and 900 cm²/Vs at 65 K were measured in the homoepitaxial MgZnO/ZnO thin films with free electron concentrations around 10 18 and 10 17 cm − 3 , respectively. The homoepitaxial ZnO template film deposited from a melt-grown ZnO single crystal as PLD target shows two orders of magnitude lower carrier concentration due to high compensation.