Repeatable Perovskite Solar Cells through Fully Automated Spin-Coating and Quenching.

Enhancing reproducibility, repeatability, as well as facilitating transferability between laboratories will accelerate the progress in many material domains, wherein perovskite-based optoelectronics are a prime use case. This study presents fully automated perovskite thin film processing using a commercial spin-coating robot in an inert atmosphere. We successfully apply this novel processing method to antisolvent quenching.

IL-1R Mediated Activation of Renal Sensory Nerves in DOCA-Salt Hypertension.

Background: Clinical trials of renal denervation for the treatment of hypertension have shown a variety of off-target improvements in conditions associated with sympathetic overactivity. This may be due to the ablation of sympathoexcitatory afferent renal nerves, which are overactive under conditions of renal inflammation. Renal IL (interleukin)-1β is elevated in the deoxycorticosterone acetate-salt model of hypertension, and its activity may be responsible for the elevation in afferent renal nerve activity and arterial pressure.

Targeting the aryl hydrocarbon receptor (AhR) with BAY 2416964: a selective small molecule inhibitor for cancer immunotherapy.

Background: The metabolism of tryptophan to kynurenines (KYN) by indoleamine-2,3-dioxygenase or tryptophan-2,3-dioxygenase is a key pathway of constitutive and adaptive tumor immune resistance. The immunosuppressive effects of KYN in the tumor microenvironment are predominantly mediated by the aryl hydrocarbon receptor (AhR), a cytosolic transcription factor that broadly suppresses immune cell function. Inhibition of AhR thus offers an antitumor therapy opportunity via restoration of immune system functions.

Renal denervation: recent developments in clinical and preclinical research.

Purpose Of Review: Renal denervation represents a new dimension to hypertension treatment, with multiple device manufacturers seeking premarket FDA approval currently. Interest in the efficacy and safety of the treatment has spurred compelling mechanistic studies into the function of renal nerves and downstream impacts of denervation.

Recent Findings: A trial of the ultrasound Paradise Catheter system (RADIANCE II) found a 6.

Evaluation of machine learning algorithms for noninvasive intracranial pressure estimation using near infrared spectroscopy as a covariate.

Background: Intracranial pressure (ICP) is a vital parameter that is continuously monitored in patients with severe brain injury and imminent intracranial hypertension.

Objective: To estimate intracranial pressure without intracranial probes based on transcutaneous near infrared spectroscopy (NIRS).

Methods: We developed machine learning based approaches for noninvasive intracranial pressure (ICP) estimation using signals from transcutaneous near infrared spectroscopy (NIRS) as well as other cardiovascular and artificial ventilation parameters.

Amorphous nickel hydroxide shell tailors local chemical environment on platinum surface for alkaline hydrogen evolution reaction.

In analogy to natural enzymes, an elaborated design of catalytic systems with a specifically tailored local chemical environment could substantially improve reaction kinetics, effectively combat catalyst poisoning effect and boost catalyst lifetime under unfavourable reaction conditions. Here we report a unique design of 'Ni(OH)-clothed Pt-tetrapods' with an amorphous Ni(OH) shell as a water dissociation catalyst and a proton conductive encapsulation layer to isolate the Pt core from bulk alkaline electrolyte while ensuring efficient proton supply to the active Pt sites. This design creates a favourable local chemical environment to result in acidic-like hydrogen evolution reaction kinetics with a lowest Tafel slope of 27 mV per decade and a record-high specific activity and mass activity in alkaline electrolyte.

Genetic Ablation of the Nutrient Sensor Ogt in Endocrine Progenitors Is Dispensable for β-Cell Development but Essential for Maintenance of β-Cell Mass.

Previously we utilized a murine model to demonstrate that Ogt deletion in pancreatic progenitors (OgtKO) causes pancreatic hypoplasia, partly mediated by a reduction in the Pdx1-expressing pancreatic progenitor pool. Here, we continue to explore the role of Ogt in pancreas development by deletion of Ogt in the endocrine progenitors (OgtKO). At birth OgtKO, were normoglycemic and had comparable pancreas weight and α-cell, and β-cell mass to littermate controls.

Sharp Signals of Boson Clouds in Black Hole Binary Inspirals.

Gravitational waves (GWs) are an exciting new probe of physics beyond the standard models of gravity and particle physics. One interesting possibility is provided by the so-called "gravitational atom," wherein a superradiant instability spontaneously forms a cloud of ultralight bosons around a rotating black hole. The presence of these boson clouds affects the dynamics of black hole binary inspirals and their associated GW signals.

ICU Cockpit: a platform for collecting multimodal waveform data, AI-based computational disease modeling and real-time decision support in the intensive care unit.

ICU Cockpit: a secure, fast, and scalable platform for collecting multimodal waveform data, online and historical data visualization, and online validation of algorithms in the intensive care unit. We present a network of software services that continuously stream waveforms from ICU beds to databases and a web-based user interface. Machine learning algorithms process the data streams and send outputs to the user interface.

p38 MAPK signaling in M1 macrophages results in selective elimination of M2 macrophages by MEK inhibition.

M2 macrophages promote tumor progression and therapy resistance, whereas proimmunogenic M1 macrophages can contribute to the efficacy of cytostatic and immunotherapeutic strategies. The abundance of M2 macrophages in the immune infiltrate of many cancer types has prompted the search for strategies to target and eliminate this subset. From our prior experiments in syngeneic mouse tumor models, we learned that pharmacological inhibition of mitogen-activated protein kinase kinase (MEK) did not merely result in tumor cell death, but also in the modulation of the tumor immune infiltrate.

Placental mTOR complex 1 regulates fetal programming of obesity and insulin resistance in mice.

Fetal growth restriction, or low birth weight, is a strong determinant for eventual obesity and type 2 diabetes. Clinical studies suggest placental mechanistic target of rapamycin (mTOR) signaling regulates fetal birth weight and the metabolic health trajectory of the offspring. In the current study, we used a genetic model with loss of placental mTOR function (mTOR-KOPlacenta) to test the direct role of mTOR signaling on birth weight and metabolic health in the adult offspring.

Photon versus carbon ion irradiation: immunomodulatory effects exerted on murine tumor cell lines.

While for photon radiation hypofractionation has been reported to induce enhanced immunomodulatory effects, little is known about the immunomodulatory potential of carbon ion radiotherapy (CIRT). We thus compared the radio-immunogenic effects of photon and carbon ion irradiation on two murine cancer cell lines of different tumor entities. We first calculated the biological equivalent doses of carbon ions corresponding to photon doses of 1, 3, 5, and 10 Gy of the murine breast cancer cell line EO771 and the OVA-expressing pancreatic cancer cell line PDA30364/OVA by clonogenic survival assays.

Timed Ang2-Targeted Therapy Identifies the Angiopoietin-Tie Pathway as Key Regulator of Fatal Lymphogenous Metastasis.

Recent clinical and preclinical advances have highlighted the existence of a previously hypothesized lymphogenous route of metastasis. However, due to a lack of suitable preclinical modeling tools, its contribution to long-term disease outcome and relevance for therapy remain controversial. Here, we established a genetically engineered mouse model (GEMM) fragment-based tumor model uniquely sustaining a functional network of intratumoral lymphatics that facilitates seeding of fatal peripheral metastases.

Targeting immune-checkpoint inhibitor resistance mechanisms by MEK inhibitor and agonist anti-CD40 antibody combination therapy.

The widespread application of immune-checkpoint blockade (ICB) has resulted in unprecedented response rates in patients with immunogenic cancers, such as melanoma and lung cancer. However, sub-groups of patients with these indications do not respond to ICB, and the same applies to patients with other cancer types. Mechanisms of resistance to ICB include low tumor immunogenicity associated with low T cell infiltration ('cold' tumors), suppression of anti-tumor immunity by immunosuppressive cells in the tumor microenvironment (TME), lack of antigen-presentation and immune escape (e.

Proimmunogenic impact of MEK inhibition synergizes with agonist anti-CD40 immunostimulatory antibodies in tumor therapy.

Cancer types with lower mutational load and a non-permissive tumor microenvironment are intrinsically resistant to immune checkpoint blockade. While the combination of cytostatic drugs and immunostimulatory antibodies constitutes an attractive concept for overcoming this refractoriness, suppression of immune cell function by cytostatic drugs may limit therapeutic efficacy. Here we show that targeted inhibition of mitogen-activated protein kinase (MAPK) kinase (MEK) does not impair dendritic cell-mediated T cell priming and activation.

Role of nutrient-driven O-GlcNAc-post-translational modification in pancreatic exocrine and endocrine islet development.

Although the developing pancreas is exquisitely sensitive to nutrient supply , it is not entirely clear how nutrient-driven post-translational modification of proteins impacts the pancreas during development. We hypothesized that the nutrient-sensing enzyme O-GlcNAc transferase (Ogt), which catalyzes an O-GlcNAc-modification onto key target proteins, integrates nutrient-signaling networks to regulate cell survival and development. In this study, we investigated the heretofore unknown role of Ogt in exocrine and endocrine islet development.

Radiation-induced alterations in immunogenicity of a murine pancreatic ductal adenocarcinoma cell line.

Pancreatic ductal adenocarcinoma (PDA) is highlighted by resistance to radiotherapy with the possible exception of hypofractionated irradiation. As single photon doses were reported to increase immunogenicity, we investigated dose-dependent irradiation effects on clonogenic survival, expression of immunologically relevant cell surface molecules and susceptibility to cytotoxic T cell (CTL) mediated killing using a murine PDA cell line. Clonogenicity decreased in a dose-responsive manner showing enhanced radioresistance at single photon doses below 5 Gy.

In Situ Transmission Electron Microscopy for Energy Materials and Devices.

Energy devices such as rechargeable batteries, fuel cells, and solar cells are central to powering a renewable, mobile, and electrified future. To advance these devices requires a fundamental understanding of the complex chemical reactions, material transformations, and charge flow that are associated with energy conversion processes. Analytical in situ transmission electron microscopy (TEM) offers a powerful tool for directly visualizing these complex processes at the atomic scale in real time and in operando.

JAK/STAT inhibition with ruxolitinib enhances oncolytic virotherapy in non-small cell lung cancer models.

The concept of using viruses to treat cancer has now shown proof of concept in several recent clinical trials, leading to the first FDA approval of virotherapy for melanoma last year. Vesicular stomatitis virus (VSV) is a promising oncolytic virus that has inhibitory effects on a number of cancer types including non-small cell lung cancer. One of the major mechanisms of resistance to VSV infection is the type I interferon (IFN) response, leading to the development of VSV expressing IFNβ which will lead to resistance of viral replication in normal cells which have intact IFN signaling but allow replication in cancer cells with defective IFNβ signaling.

Fetal undernutrition, placental insufficiency, and pancreatic β-cell development programming in utero.

The prevalence of obesity and type 2 (T2D) diabetes is a major health concern in the United States and around the world. T2D is a complex disease characterized by pancreatic β-cell failure in association with obesity and insulin resistance in peripheral tissues. Although several genes associated with T2D have been identified, it is speculated that genetic variants account for only <10% of the risk for this disease.

Optimized dendritic cell vaccination induces potent CD8 T cell responses and anti-tumor effects in transgenic mouse melanoma models.

Despite melanoma immunogenicity and remarkable therapeutic effects of negative immune checkpoint inhibitors, a significant fraction of patients does not respond to current treatments. This could be due to limitations in tumor immunogenicity and profound immunosuppression in the melanoma microenvironment. Moreover, insufficient tumor antigen processing and presentation by dendritic cells (DC) may hamper the development of tumor-specific T cells.

Targeted afferent renal denervation reduces arterial pressure but not renal inflammation in established DOCA-salt hypertension in the rat.

Recent preclinical studies show renal denervation (RDNx) may be an effective treatment for hypertension; however, the mechanism remains unknown. We have recently reported total RDNx (TRDNx) and afferent-selective RDNx (ARDNx) similarly attenuated the development of deoxycorticosterone acetate (DOCA)-salt hypertension. Whereas TRDNx abolished renal inflammation, ARDNx had a minimal effect despite an identical antihypertensive effect.

Serine racemase is expressed in islets and contributes to the regulation of glucose homeostasis.

NMDA receptors (NMDARs) have recently been discovered as functional regulators of pancreatic β-cell insulin secretion. While these excitatory receptor channels have been extensively studied in the brain for their role in synaptic plasticity and development, little is known about how they work in β-cells. In neuronal cells, NMDAR activation requires the simultaneous binding of glutamate and a rate-limiting co-agonist, such as D-serine.

New Target for Cosmic Axion Searches.

Future cosmic microwave background experiments have the potential to probe the density of relativistic species at the subpercent level. This sensitivity allows light thermal relics to be detected up to arbitrarily high decoupling temperatures. Conversely, the absence of a detection would require extra light species never to have been in equilibrium with the Standard Model.

[Fatal electric accident due to adverse error situation].

Despite wearing high-impedance shoes, a young male died while trying to connect a garden pump (230 V). The cause of death could easily be determined on the basis of testimonies of eye-witnesses and an electric mark on the body. Histological and electron microscopic examinations showed metallisation of the electric mark (pure iron).