Deep learning based electroencephalography (EEG) signal processing methods are known to suffer from poor test-time generalization due to the changes in data distribution. This becomes a more ...challenging problem when privacy-preserving representation learning is of interest such as in clinical settings. To that end, we propose a multi-source learning architecture where we extract domain-invariant representations from dataset-specific private encoders. Our model utilizes a maximum-mean-discrepancy (MMD) based domain alignment approach to impose domain-invariance for encoded representations, which outperforms state-of-the-art approaches in EEG-based emotion classification. Furthermore, representations learned in our pipeline preserve domain privacy as dataset-specific private encoding alleviates the need for conventional, centralized EEG-based deep neural network training approaches with shared parameters.
Activating hot spot R29S mutations in RAC1, a small GTPase influencing several cellular processes including cell proliferation and cytoskeleton rearrangement, have been reported in up to 9% of ...sun-exposed melanomas. Clinical characteristics and treatment implications of RAC1 mutations in melanoma remain unclear.
We investigated the largest set (n = 64) of RAC1 mutated melanoma patients reported to date, including a retrospective single institution cohort (n = 34) from the University Hospital Essen and a prospective multicentre cohort (n = 30) from the translational study Tissue Registry in Melanoma (TRIM; CA209-578), for patient and tumour characteristics as well as therapy outcomes.
From 3037 sequenced melanoma samples screened RAC1 mutations occurred in ∼2% of samples (64/3037). The most common RAC1 mutation was P29S (95%, 61/64). The majority of tumours had co-occuring MAP kinase mutations (88%, 56/64); mostly activating NRAS (47%, 30/64) mutations, followed by activating BRAF (28%, 18/64) and NF1 (25%, 16/64) mutations. RAC1 mutated melanomas were almost exclusively of cutaneous origin (84%, 54/64) or of unknown primary (MUP, 14%, 9/64). C > T alterations were the most frequent mutation type identified demonstrating a UV-signature for RAC1 mutated melanoma. Most patients with unresectable disease (39) received immune checkpoint inhibitors (ICI) (77%, 30/39). Objective response rate of first-line treatment in patients with stage III/IV disease was 21%; median overall survival was 47.8 months.
RAC1 mutated melanomas are rare, mostly of cutaneous origin and frequently harbour concomitant MAP kinase mutations, particularly in NRAS. Patients with advanced disease benefit from systemic treatment with ICI.
•RAC1 mutations occur in UV-exposed melanoma.•RAC1 mutations frequently co-occur with NRAS mutations.•Solitary RAC1 mutation without co-occurrence of other MAP kinase mutations is rare.•Metastatic RAC1 patients benefit from immune checkpoint inhibition (ICI).
The response of a colloidal dispersion of Ni nanorods to an oscillating magnetic field was characterized by optical transmission measurements as well as small-angle neutron scattering (SANS) ...experiments using the TISANE (Time-dependent SANS experiments) technique. Exposed to a static magnetic field, the scattering intensity of the rod ensemble could be well described by the cylinder form factor using the geometrical particle parameters (length, diameter, orientation distribution) determined by transmission electronmicroscopy and magnetometry. An oscillation of the field vector resulted in a reorientation of the nanorods and a time-dependency of the scattering intensity due to the shape anisotropy of the rods. Analysis of the SANS data revealed that in the range of low frequencies the orientation distribution of the rods is comparable to the static case. With increasing frequency, the rod oscillation was gradually damped due to an increase of the viscous drag. It could be shown that despite of the increased friction in the high frequency range no observable change of the orientation distribution of the ensemble with respect to its symmetry axis occurs.
Time-dependent SANS experiments (TISANE) show that the orientation distribution of Ni nanorod colloids exposed to oscillating magnetic fields is frequency-independent.
As part of ROBDEKON, a 24-ton crawler excavator was equipped with sensors and a digital actuation interface as a technology demonstrator which features autonomy capabilities. The system architecture ...includes algorithms for localization, perception, mapping, planning, and control. The system is capable of tasks like autonomous driving to a target location, excavation of a predefined area to a given depth, and autonomous loading of an autonomously approaching transport vehicle. To ensure safety, collision avoidance based on 360° perception is always active during autonomous operation. This article presents the concept and implementation of the excavator’s autonomy functionality.
Differential diagnosis of hypoglycemia in the non-diabetic adult patient is complex and comprises various diseases, including endogenous hyperinsulinism caused by functional β-cell disorders. The ...latter is also designated as nesidioblastosis or non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS). Clinically, this rare disease presents with unspecific adrenergic and neuroglycopenic symptoms and is, therefore, often overlooked. A combination of careful clinical assessment, oral glucose tolerance testing, 72 h fasting, sectional and functional imaging, and invasive insulin measurements can lead to the correct diagnosis. Due to a lack of a pathophysiological understanding of the condition, conservative treatment options are limited and mostly ineffective. Therefore, nearly all patients currently undergo surgical resection of parts or the entire pancreas. Consequently, apart from faster diagnosis, more elaborate and less invasive treatment options are needed to relieve the patients from the dangerous and devastating symptoms. Based on a case of a 23-year-old man presenting with this disease in our department, we performed an extensive review of the medical literature dealing with this condition and herein presented a comprehensive discussion of this interesting disease, including all aspects from epidemiology to therapy.
Diminished hepatocyte regeneration is a key feature of acute and chronic liver diseases and after extended liver resections, resulting in the inability to maintain or restore a sufficient functional ...liver mass. Therapies to restore hepatocyte regeneration are lacking, making liver transplantation the only curative option for end-stage liver disease. Here, we report on the structure-based development and characterization (nuclear magnetic resonance NMR spectroscopy) of first-in-class small molecule inhibitors of the dual-specificity kinase MKK4 (MKK4i). MKK4i increased liver regeneration upon hepatectomy in murine and porcine models, allowed for survival of pigs in a lethal 85% hepatectomy model, and showed antisteatotic and antifibrotic effects in liver disease mouse models. A first-in-human phase I trial (European Union Drug Regulating Authorities Clinical Trials EudraCT 2021-000193-28) with the clinical candidate HRX215 was conducted and revealed excellent safety and pharmacokinetics. Clinical trials to probe HRX215 for prevention/treatment of liver failure after extensive oncological liver resections or after transplantation of small grafts are warranted.
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•A first-in-class small-molecule-based MKK4 inhibitor was developed (HRX215)•HRX215 increased liver regeneration after hepatectomy in murine and porcine models•HRX215 treatment allowed for survival of pigs in a lethal 85% hepatectomy model•A phase I trial revealed safety and excellent pharmacokinetics of HRX215 in humans
A targeted therapy against the kinase MKK4 was developed (HRX215) and investigated preclinically, as well as in a phase I study in humans. HRX215 boosted liver regeneration, prevented liver failure after extensive hepatectomy in pigs, and holds the promise to prevent liver failure after extensive oncological liver resections or transplantation of small liver grafts in humans.
Monolithic perovskite/silicon tandem solar cells recently surpass the efficiency of silicon single‐junction solar cells. Most tandem cells utilize >250 μm thick, planarized float‐zone (FZ) silicon, ...which is not compatible with commercial production using <200 μm thick Czochralski (CZ) silicon. The perovskite/silicon tandem cells based on industrially relevant 100 μm thick CZ‐silicon without mechanical planarization are demonstrated. The best power conversion efficiency (PCE) of 27.9% is only marginally below the 28.2% reference value obtained on the commonly used front‐side polished FZ‐Si, which are about three times thicker. With both wafer types showing the same median PCE of 27.8%, the thin CZ‐Si‐based devices are preferred for economic reasons. To investigate perspectives for improved current matching and, therefore, further efficiency improvement, optical simulations with planar and textured silicon have been conducted: the perovskite's bandgap needs to be increased by ≈0.02 eV when reducing the silicon thickness from 280 to 100 μm. The need for bandgap enlargement has a strong impact on future tandem developments ensuring photostable compositions with lossless interfaces at bandgaps around or above 1.7 eV.
Lab‐scale perovskite/silicon tandem solar cells are typically fabricated on thick, expensive float‐zone silicon. Herein, tandem cells based on industry‐compatible bottom cells are demonstrated which enable the same high efficiencies of ≈28% as lab‐scale devices. Optical simulations reveal that adjustments of the top cell are required to further improve the efficiency of the industry‐compatible devices.
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