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Electronic transitions at interfaces between MoO3 layers and organic layers of C60, SubPc, MgPc, and nano-composite layers of SubPc:C60 and MgPc:C60 have been studied by modulated surface photovoltage (SPV) spectroscopy. For all systems, time dependent and modulated SPV signals pointed to dissociation of excitons at the MoO3/organic layer interfaces with a separation of holes towards MoO3. The highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) gaps (EHL) of C60, SubPc, and MgPc and the effective EHL of SubPc:C60 and MgPc:C60 were measured. The offsets between the LUMO (ΔEL) or HOMO (ΔEH) bands were obtained with high precision and amounted to 0.33 or 0.73?eV for SubPc:C60, respectively, and to -0.33 or 0.67?eV for MgPc:C60, respectively. Exponential tails below EHL and most pronounced sub-bandgap transitions were characterized and ascribed to disorder and transitions from HOMO bands to unoccupied defect states. [ABSTRACT FROM AUTHOR]

Callus cell cultures of Arabidopsis thaliana (cv. Columbia) were exposed to parabolic flights in order to assess molecular, short-term responses to altered gravity fields. Using transgenic cell lines, hydrogen peroxide ( H2 O2) and cytosolic Ca2+ were continuously monitored. In parallel, the metabolism of samples was chemically quenched ( RNAlater, Ambion for RNA; acid/base for NADPH, NADP) at typical stages of a parabola [1 g before pull up; end of pull up (1.8 g), end of microgravity (20 s) and end of pull out (1.8 g)]. Cells exhibited an increase in both Ca2+ and H2 O2 with the onset of microgravity, and a decline thereafter. This behaviour was accompanied by a decrease of the NADPH/ NADP redox ratio, indicating Ca2+-dependent activation of a NADPH oxidase. Microarray analyses revealed concomitant expression profiles. At the end of the microgravity phase, 396 transcripts were specifically up-, while 485 were down-regulated. Up-regulation was dominated by Ca2+- and ROS-related gene products. The same material was also used for analysis of phosphopeptides with 2- D SDS PAGE. Relevant spots were identified by liquid chromatography- MS. With the exception of a chaperone ( HSP 70-3), hypergravity (1.8 g) and microgravity modified different sets of proteins. These are partly involved in primary metabolism (glycolysis, gluconeogenesis, citrate cycle) and detoxification of ROS. Taken together, these data show that both gene expression and protein modulation jointly respond within seconds to alterations in the gravity field, with a focus on metabolic adaptation, signalling and control of ROS. [ABSTRACT FROM AUTHOR]

Cu2ZnSn(SxSe1-x)4 (CZTSSe) layers deposited from multi-component nanoparticle inks were characterized by modulated surface photovoltage (SPV) spectroscopy to investigate the effect of annealing conditions. The SPV signals increased strongly with decreasing sulfur content. Band gaps were obtained in terms of SPV onset energy. A diffusion length of above 1 μm was estimated for photo-generated electrons at x = 0.28. The band gap increased with increasing x showing an anomaly in the range of 0.5 < x < 1. The results suggested that an excess of selenium is required for the formation of a photo-active phase reliable for efficient Cu2ZnSn(SxSe1-x)4-based solar cells. [ABSTRACT FROM AUTHOR]

An essential step toward enabling the production of renewable and cost-efficient fuels is an improved understanding of the performance of energy conversion materials. In recent years, there has been growing interest in ternary metal oxides. Particularly, α-SnWO 4 exhibited promising properties for application to photoelectrochemical (PEC) water splitting. However, the number of corresponding studies remains limited, and a deeper understanding of the physical and chemical processes in α-SnWO 4 is necessary. To date, charge-carrier generation, separation, and transfer have not been exhaustively studied for SnWO 4 -based photoelectrodes. All of these processes depend on the phase composition, not only α-SnWO 4 but also on the related phases SnW 3 O 9 and WO 3 , as well as on their spatial distributions resulting from the coating synthesis. In the present work, these processes in different phases of tin tungstate films were investigated by transient surface photovoltage (TSPV) spectroscopy to complement the analysis of the applicability of α-SnWO 4 thin films for practical PEC oxygen evolution. Pure α-SnWO 4 films exhibit higher photoactivities than those of films containing secondary SnW 3 O 9 and WO 3 phases due to the higher recombination of charge carriers when these phases are present.

Optimizing drug candidates for blood-brain barrier (BBB) penetration remains one of the key challenges in drug discovery to finally target brain disorders including neurodegenerative diseases which do not have adequate treatments so far. It has been difficult to establish state-of-the-art stem cell derived in vitro models that mimic physiological barrier properties including a 3D microvasculature in a format that is scalable to screen drugs for BBB penetration. To address this challenge, we established human induced pluripotent stem cell (iPSC)-derived brain endothelial microvessels in a standardized and scalable multi-well plate format. iPSC-derived brain microvascular endothelial cells (BMECs) were supplemented with primary cell conditioned media and grew to microvessels in 10 days. Produced microvessels show typical BBB endothelial protein expression, tight-junctions and polarized localization of efflux transporter. Microvessels exhibited physiological relevant trans-endothelial electrical resistance (TEER), were leak-tight for 10 kDa dextran-Alexa 647 and strongly limited the permeability of sodium fluorescein (NaF). Permeability tests with reference compounds confirmed the suitability of our model as platform to identify potential BBB penetrating anti-inflammatory drugs. The here presented platform recapitulates physiological properties and allows rapid screening of BBB permeable anti-inflammatory compounds that has been suggested as promising substances to cure so far untreatable neurodegenerative diseases., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Hydrogen produced from solar energy has the potential to replace petroleum in the future. To this respect, there is a need in the abandoned and efficient materials that can continuously split water molecules using solar energy. In this report, an ammonium thiomolybdate (ATM: (NH 4 ) 2 Mo 3 S 13 ) is evaluated as a p-type semiconductor film photocathode for hydrogen evolution reaction. The ATM thin films are prepared by spin-coating on fluorine-doped tin oxide substrates, and their structural, morphological, optical, photoelectrical, and photoelectrochemical (PEC) properties are studied. Transient surface photovoltage (TSPV) spectroscopy and spectroscopic ellipsometry indicate the band gap E g = 1.9 eV for the ATM thin films. Furthermore, the photovoltage of the ATM thin films measured by TSPV is correlated to the photocurrents measured by the PEC characterization that can be used to evaluate the material potential for hydrogen generation. The films exhibit a low photocurrent density of 46 μA cm -2 at 0 V RHE . However, its combination with WSe 2 thin-film photocathodes results in a significant increase in photocurrent density up to 4.6 mA cm -2 at 0 V RHE (100 times). The reason for such a strong charge carrier transfer effect for ATM/WSe 2 heterojunction photocathodes is studied by TSPV spectroscopy that allows a comprehensive evaluation of potential photovoltaic materials toward PEC hydrogen production. Furthermore, the photovoltage generated by a WSe 2 thin film is 30 times lower than that of its single crystal, which indicates that the quality of WSe 2 thin films should be improved for faster PEC hydrogen evolution.

Patient satisfaction is an important indicator of health care quality, and it remains an important goal for optimal treatment outcomes to reduce the level of misdiagnoses and inappropriate or absent therapeutic actions. Digital support tools for differential diagnosis to assist clinicians in reaching the correct diagnosis may be helpful, but how the use of these affect patients is not clear. The primary objective of this feasibility study was to investigate patient experience and satisfaction in a primary care setting where general practitioners (GPs) used a visual clinical decision support system (CDSS) compared with standard consultations. Secondary objectives were diagnostic accuracy and length of consultation. Thirty-one patients with a dermatologist-confirmed skin diagnosis were allocated to consult GPs that had been randomized to conduct either standard consultations (SDR, n = 21) or CDSS (n = 16) on two separate study days one week apart. All patients were diagnosed independently by multiple GPs (n = 3-8) in both the SDR and CDSS study arms. Using the CDSS, more patients felt involved in the decision making (P = 0.05). In addition, more patients were exposed to images during the consultations (P = 6.8e-27), and 83% of those that were shown images replied they felt better supported in the consultation. The use of CDSS significantly improved the diagnostic accuracy (34%, P = 0.007), and did not increase the duration of the consultation (median 10 minutes in both arms). This study shows for the first time that compared with standard GP consultations, CDSS assist the GP on skin related diagnoses and improve patient satisfaction and diagnostic accuracy without impacting the duration of the consultations. This is likely to increase correct treatment choices, patient adherence, and overall result in better healthcare outcomes., Competing Interests: EB, KC, HB, and SF declare no competing financial interests. AMS, ADA, and JRZ are employees of LEO Innovation Lab, this does not alter our adherence to PLOS ONE policies on sharing data and materials.

Electronic properties and charge transfer processes were studied in an n-Si(n ++ )/TiO 2 (ALD) system at an amorphous TiO 2 /anatase transition by transient surface photovoltage spectroscopy at constant photon flux. The TiO 2 layers were deposited by atomic layer deposition (ALD) onto highly doped silicon (c-Si(n ++ )), and the phase composition of the TiO 2 layers changed with increasing thickness from amorphous to the anatase polymorph as anatase crystallites started to grow at the surface. Depending on phase composition, the band gap of TiO 2 correlated with the characteristic energy of exponential tails. In most cases, photogenerated electrons were separated toward the back contact. For photogeneration in c-Si(n ++ ), electron back transfer was limited by Auger recombination with holes in the surface space charge region of c-Si(n ++ ), and by electron transfer across the interface, either via exponentially distributed states near the conduction band edge of amorphous TiO 2 or via distance-dependent recombination with holes trapped in anatase. For photogeneration in TiO 2 , electron back transfer was limited by trapping in TiO 2 . Under strong light absorption in amorphous TiO 2 with anatase crystallites on top, electrons were preferentially separated toward the TiO 2 surface.

Conductive metal oxides represent a new category of functional material with vital importance for many modern applications. The present work introduces a new conductive metal oxide V 13 O 16 , which is synthesized via a simplified photoelectrochemical procedure and decorated onto the semiconducting photocatalyst BiVO 4 in controlled mass percentages ranging from 25% to 37%. Owing to its excellent conductivity and good compatibility with oxide materials, the metallic V 13 O 16 -decorated BiVO 4 hybrid catalyst shows a high photocurrent density of 2.2 ± 0.2 mA cm -2 at 1.23 V versus reversible hydrogen electrode (RHE). Both experimental characterization and density functional theory calculations indicate that the superior photocurrent derives from enhanced charge separation and transfer, resulting from ohmic contact at the interface of mixed phases and superior electrical conductivity from V 13 O 16 . A Co-Pi coating on BiVO 4 -V 13 O 16 further increases the photocurrent to 5.0 ± 0.5 mA cm -2 at 1.23 V versus RHE, which is among the highest reported for BiVO 4 -based photoelectrodes. Surface photovoltage and transient photocurrent measurements suggest a charge-transfer model in which photocurrents are enhanced by improved surface passivation, although the barrier at the Co-Pi/electrolyte interface limits the charge transfer., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The proto-oncogenic epidermal growth factor receptor (EGFR) is a tyrosine kinase whose sensitivity to growth factors and signal duration determines cellular behavior. We resolve how EGFR's response to epidermal growth factor (EGF) originates from dynamically established recursive interactions with spatially organized protein tyrosine phosphatases (PTPs). Reciprocal genetic PTP perturbations enabled identification of receptor-like PTPRG/J at the plasma membrane and ER-associated PTPN2 as the major EGFR dephosphorylating activities. Imaging spatial-temporal PTP reactivity revealed that vesicular trafficking establishes a spatially distributed negative feedback with PTPN2 that determines signal duration. On the other hand, single-cell dose-response analysis uncovered a reactive oxygen species-mediated toggle switch between autocatalytically activated monomeric EGFR and the tumor suppressor PTPRG that governs EGFR's sensitivity to EGF. Vesicular recycling of monomeric EGFR unifies the interactions with these PTPs on distinct membrane systems, dynamically generating a network architecture that can sense and respond to time-varying growth factor signals., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Although other nonmotor phenomena representing possible prodromal symptoms of Parkinson's disease have been described in some detail, the occurrence and characteristics of cognitive decline in this early phase of the disease are less well understood. The aim of this review is to summarize the current state of research on cognitive changes in prodromal PD. Only a small number of longitudinal studies have been conducted that examined cognitive function in individuals with a subsequent PD diagnosis. However, when we consider data from at-risk groups, the evidence suggests that cognitive decline may occur in a substantial number of individuals who have the potential for developing PD. In terms of specific cognitive domains, executive function in particular and, less frequently, memory scores are reduced. Prospective longitudinal studies are thus needed to clarify whether cognitive, and specifically executive, decline might be added to the prodromal nonmotor symptom complex that may precede motor manifestations of PD by years and may help to update the risk scores used for early identification of PD. © 2017 International Parkinson and Movement Disorder Society., (© 2017 International Parkinson and Movement Disorder Society.)

Background: In July 2008, the German statutory health insurance introduced a nationwide skin cancer screening program. Before the introduction, eligible physicians had to qualify to perform the screening test and counsel their patients on skin cancer screening. To educate physicians, a curriculum and training materials were developed. Since 2015 a revised curriculum and training materials have been used. The purpose of this paper is to provide information about the curriculum and to evaluate the revised training program., Methods: A total of 573 completed pre- and posttests were analyzed with regard to changes in the identification of skin cancer, diagnostic accuracy, knowledge, and physicians' self-assessed-confidence. For statistical analysis, Mann-Whitney U test, Cohen's d, and chi-square test were used., Results: General practitioners (GPs) diagnosed 7.45 of 12 skin lesions correctly before and 9.26 after the training course (P < 0.001). Compared to GPs, dermatologists' accuracy was higher at pre- and posttest (pre: 10.03, post: 10.21, P = 0.160). The mean of correctly answered questions increased significantly in knowledge on screening and early detection (4.46-5.14, P < 0.001) as well as skin cancer and skin cancer screening (5.51-6.39, P < 0.001)., Conclusion: Participating physicians got a comprehensive understanding of skin cancer screening and counseling through the training and increased their diagnostic skills. In particular, GPs identified and diagnosed significantly more skin lesions correctly after the training compared to before the training, while dermatologists' diagnostic skills were high at both times, before and after., (© 2017 The International Society of Dermatology.)

The measurement of transient surface photovoltage (SPV) signals in a fixed capacitor arrangement over 12 orders of magnitude in time has been demonstrated for a SnO 2 :F/TiO 2 /In 2 S 3 layer system under high vacuum. For this purpose, a high impedance buffer with a bandwidth above 200 MHz and an effective input resistance of 200-700 TΩ has been developed. Fast separation of photo generated charge carriers within ns and very slow relaxation of SPV signals excited with short laser pulses and the measurement of SPV spectra under continuous illumination with a halogen lamp were demonstrated.

Rupture of endosomes and lysosomes is a major cellular stress condition leading to cell death and degeneration. Here, we identified an essential role for the ubiquitin-directed AAA-ATPase, p97, in the clearance of damaged lysosomes by autophagy. Upon damage, p97 translocates to lysosomes and there cooperates with a distinct set of cofactors including UBXD1, PLAA, and the deubiquitinating enzyme YOD1, which we term ELDR components for Endo-Lysosomal Damage Response. Together, they act downstream of K63-linked ubiquitination and p62 recruitment, and selectively remove K48-linked ubiquitin conjugates from a subpopulation of damaged lysosomes to promote autophagosome formation. Lysosomal clearance is also compromised in MEFs harboring a p97 mutation that causes inclusion body myopathy and neurodegeneration, and damaged lysosomes accumulate in affected patient tissue carrying the mutation. Moreover, we show that p97 helps clear late endosomes/lysosomes ruptured by endocytosed tau fibrils. Thus, our data reveal an important mechanism of how p97 maintains lysosomal homeostasis, and implicate the pathway as a modulator of degenerative diseases., (© 2016 The Authors.)

Background: Given the high prevalence of cognitive impairment in Parkinson's disease (PD), cognitive screening is important in clinical practice. The Montreal Cognitive Assessment (MoCA) is a frequently used screening test in PD to detect mild cognitive impairment (PD-MCI) and Parkinson's disease dementia (PD-D). However, the proportion in which the subtests are represented in the MoCA total score does not seem reasonable. We present the development and preliminary evaluation of an empirically based alternative scoring system of the MoCA which aims at increasing the overall diagnostic accuracy., Methods: In study 1, the MoCA was administered to 40 patients with PD without cognitive impairment (PD-N), PD-MCI, or PD-D, as defined by a comprehensive neuropsychological test battery. The new MoCA scoring algorithm was developed by defining Areas under the Curve (AUC) for MoCA subtests in a Receiver Operating Characteristic (ROC) and by weighting the subtests according to their sensitivities and specificities. In study 2, an independent sample of 24 PD patients (PD-N, PD-MCI, or PD-D) was tested with the MoCA. In both studies, diagnostic accuracy of the original and the new scoring procedure was calculated., Results: Diagnostic accuracy increased with the new MoCA scoring algorithm. In study 1, the sensitivity to detect cognitive impairment increased from 62.5% to 92%, while specificity decreased only slightly from 77.7% to 73%; in study 2, sensitivity increased from 68.8% to 81.3%, while specificity stayed stable at 75%., Conclusion: This pilot study demonstrates that the sensitivity of the MoCA can be enhanced substantially by an empirically based weighting procedure and that the proposed scoring algorithm may serve the MoCA's actual purpose as a screening tool in the detection of cognitive dysfunction in PD patients better than the original scoring of the MoCA. Further research with larger sample sizes is necessary to establish efficacy of the alternate scoring system.

The Simbox mission was the first joint space project between Germany and China in November 2011. Eleven-day-old Arabidopsis thaliana wild type semisolid callus cultures were integrated into fully automated plant cultivation containers and exposed to spaceflight conditions within the Simbox hardware on board of the spacecraft Shenzhou 8. The related ground experiment was conducted under similar conditions. The use of an in-flight centrifuge provided a 1 g gravitational field in space. The cells were metabolically quenched after 5 days via RNAlater injection. The impact on the Arabidopsis transcriptome was investigated by means of whole-genome gene expression analysis. The results show a major impact of nonmicrogravity related spaceflight conditions. Genes that were significantly altered in transcript abundance are mainly involved in protein phosphorylation and MAPK cascade-related signaling processes, as well as in the cellular defense and stress responses. In contrast to short-term effects of microgravity (seconds, minutes), this mission identified only minor changes after 5 days of microgravity. These concerned genes coding for proteins involved in the plastid-associated translation machinery, mitochondrial electron transport, and energy production.

The DemTect, a frequently used cognitive screening tool for the German-speaking population, has been proven to be age-, but not education-dependent. To date, scoring routines for persons under and over 60 years of age have been available. In order to describe the age-effect more specifically, the DemTect was administered to persons under 40 (n = 105; median 33 years [18 - 39]) and over 80 years of age [n = 68; median 83 years [80 - 93}). After transformation of the raw scores, which are based on the mean and standard deviation of the respective reference group, an adequate attribution of scores could be achieved and no differences between the groups can be observed in the total score or the subtest scores. The median of the transformed total score was 16 [5 – 18] for the younger and 15 [5 – 18] for the older age group. The new scoring routines supplement the scoring procedures of the DemTect for these age groups., (© Georg Thieme Verlag KG Stuttgart · New York.)