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On November 7, 2023, voters of Central Harlem in New York City elected Dr. Yusef Salaam to the City Council. Jeffery C. Mays, Yusef Salaam Is Declared Winner of Harlem [...]

In the past decade, state statutes on the expungement and sealing of criminal history records have multiplied and expanded, thanks to bipartisan legislative action. In 2019-2022 alone, almost every state [...]

While roughly a tenth of the size of the US Air Force, the French Air and Space Force (FASF) is considered by some to be the Air Force's most near-peer [...]

Prosecution offices have been referred to as black boxes from which data cannot be extracted or seen. In an era of criminal justice reform, this perception promotes distrust and contributes [...]

Purpose of Review: To investigate the state of patch testing regarding necessity, cost, and value. Recent Findings: Comprehensive patch testing may cost between $500–2500 for patients in the United States but more transparency is needed regarding associated fees which may be substantially higher. Reimbursement for patch test allergens is decreasing which is a possible threat to patient care. Summary: Contact dermatitis is a common, morbid, and costly disease to patients. Patch testing, regarded as the gold standard of diagnosing allergic contact dermatitis (ACD), is necessary to differentiate ACD from other inflammatory dermatoses or in cases where contact dermatitis may complicate other skin diseases. Occupational contact dermatitis may carry additional costs related to lost productivity and job switching. Patch testing is overall associated with decreased costs for patients with dermatitis. Costs of emergency room visits or potentially unnecessary systemic medications for dermatitis patients often outweigh the costs of patch testing.

Insurance agents play a role in advising small businesses and guiding them to mitigate workers' compensation losses and improve employee health and safety. In today's dynamic marketplace, small businesses face [...]

The industrial robot with extended workspace offers an alternative concept for machining of large CFRP components. Due to their serial kinematics, robots have a good ratio of mounting space to workspace and provide high flexibility in the production line. Although the machining with industrial robots of thin aerospace shell components has already been successful, the next step for the growing utilization of robots in the scope of machining is increasing their robustness against process forces and their application in more demanding machining tasks.

Revealing traffic behavior from GPS data is a possibility to create a current and detailed data basis for city and traffic planning. Currently, traffic planning is mostly done by surveys or simulations, which may be costly, slow and not flexible enough. The concept of semantic trajectories has become relevant in recent years. Enriching GPS trip data with additional data helps to gain more insights into traffic behavior and can even reveal trip purposes of the drivers. This paper introduces a combination of a data-driven city segmentation with semantic trajectories. We show that enriching GPS trip data with additional information and analyzing the destination areas of these trajectories in detail helps to understand the journey and to reveal possible trip purposes. Multiple data sources are used, such as Points of Interest (POI), OD-points and whole trajectories of cars, vans and trucks. A fully automated clustering approach is introduced, which results in an interpretable city segmentation. The results are added to the trajectories before they are clustered. As a result, trajectories are clustered into four groups which can be interpreted as differences in the travel purpose as well as the start and end point of the trips. The method is demonstrated for the city of Frankfurt am Main, with trajectories, that either start, end, or pass through the city. By comparing the segmented city area with land-use maps and by interpreting a random sample of the clustered GPS trajectories, the plausibility of results is discussed.

Foundation models (FMs) currently dominate news headlines. They employ advanced deep learning architectures to extract structural information autonomously from vast datasets through self-supervision. The resulting rich representations of complex systems and dynamics can be applied to many downstream applications. Therefore, advances in FMs can find uses in electric power grids, challenged by the energy transition and climate change. This paper calls for the development of FMs for electric grids. We highlight their strengths and weaknesses amidst the challenges of a changing grid. It is argued that FMs learning from diverse grid data and topologies, which we call grid foundation models (GridFMs), could unlock transformative capabilities, pioneering a new approach to leveraging AI to redefine how we manage complexity and uncertainty in the electric grid. Finally, we discuss a practical implementation pathway and road map of a GridFM-v0, a first GridFM for power flow applications based on graph neural networks, and explore how various downstream use cases will benefit from this model and future GridFMs.

We report here the orchestration of molecular ion networking (MoIN) and a set of computationally assisted structural elucidation approaches in the discovery and assignment of a new class of rearranged 4,5-seco-abietane diterpenoids including serra A (1), which possesses an unusual 6/6/5/5 fused-ring skeleton system, together with two previously unreported diterpenoids serras B–C (2–3) and five known compounds were isolated from Isodon serra(I. serra). The structures were elucidated by spectroscopic analysis in conjunction with computationally assisted structure elucidation tools. In silico, serras A–C (1–3) bind well to PXR, suggesting their potential role in reducing inflammation. The results of serra A (1) with hPXR demonstrated agonist activity with an EC50value of 15 μM. Serra A (1), graciliflorin F (4), gerardianin C (5), 11,12,15-trihydroxy-8,11,13-abietatrien-7-one (6), rabdosin D (7), and 15-hydroxysalprionin (8) exhibited promising anti-inflammatory activities in lipopolysaccharide (LPS)-induced RAW 267.4 cells, and their inhibition rates on NO production were more than 65% at 10 μM.

The emerging field of synthetic morphogenesis implements synthetic biology tools to investigate the minimal cellular processes sufficient for orchestrating key developmental events. As the field continues to grow, there is a need for new tools that enable scientists to uncover nuances in the molecular mechanisms driving cell fate patterning that emerge during morphogenesis. Here, we present a platform that combines cell engineering with biomaterial design to potentiate artificial signaling in pluripotent stem cells (PSCs). This platform, referred to as PSC-MATRIX, extends the use of programmable biomaterials to PSCs competent to activate morphogen production through orthogonal signaling, giving rise to the opportunity to probe developmental events by initiating morphogenetic programs in a spatially constrained manner through non-native signaling channels. We show that the PSC-MATRIX platform enables temporal and spatial control of transgene expression in response to bulk, soluble inputs in synthetic Notch (synNotch)-engineered human PSCs for an extended culture of up to 11 days. Furthermore, we used PSC-MATRIX to regulate multiple differentiation events via material-mediated artificial signaling in engineered PSCs using the orthogonal ligand green fluorescent protein, highlighting the potential of this platform for probing and guiding fate acquisition. Overall, this platform offers a synthetic approach to interrogate the molecular mechanisms driving PSC differentiation that could be applied to a variety of differentiation protocols.

Reactive carbonyl species (RCS) induce a fundamental form of biological stress that has driven the evolution of diverse mechanisms for minimizing its impact on organismal health. The complications that accompany uncontrolled hyperglycemia exemplify the health implications when RCS stress exceeds the body’s capacity to prevent the excessive formation of advanced glycation end-products. Presented here is a novel quantitative NMR (qNMR) technique for evaluating scavengers of the prominent sugar-derived carbonyl methylglyoxal (MGO). This tool was employed to screen the chemical diversity of marine macroalgae extracts, with a focus on species that have a history of consumption by the World’s healthiest populations and are subject to global scale aquacultural production. Fucus vesiculosusdemonstrated the highest capacity for inhibiting glycation and scavenging MGO. Additionally, the Chondrus cripsus, Gracilaria vermiculophyla,and Gracilaria tikvahiaeextracts had a high capacity for scavenging MGO, representing the first report of this activity. This new qNMR methodology presented is highly applicable for screening extracts and compounds from diverse sources, and the results highlight the potential of macroalgae extracts to be employed as RCS and AGE targeting therapeutics and food additives.

"[We] spent a lot of time [...] overcoming the stigma. And, you know, you run the risk, if you will, of looking soft on crime in certain circles. But that's [...]

The killing of George Floyd by police was a tragic and disturbing event that is a call to action for those in the criminal justice system. As protests and outrage [...]

The impact of the pandemic has hit every aspect of the criminal justice system. It forced all members of the system to adjust on the fly and adopt methods that [...]

The analysis and reuse of measured process data are enablers for sustainable and resilient manufacturing in the future. Maintaining high measurement data quality is vital for maximising the usage and value of the data at hand. To ensure this data quality, the data management must be applied consequently throughout the complete Data Life-Cycle (DLC) and adhere to the FAIR guiding principles. In the two research consortia NFDI4Ing and the Cluster of Excellence “Internet of Production,” we investigate approaches to increase the measurement of data quality by integrating the FAIR guiding principles in all data management activities of the DLC. To facilitate the uptake of the FAIR guiding principles, we underline the significance of FAIR data for the reuse of high-quality data. Second, we are introducing a harmonised DLC to streamline data management activities. Third, we concisely review current trends and best practices in FAIR-aware data management and give suggestions for implementing the FAIR guiding principles.

The use of neuroimaging allows the ophthalmologist to identify structural lesions in the orbit or along the neuroaxis that allow for more accurate diagnosis and treatment of patients with neuro-ophthalmic diseases. The primary imaging tools include computed tomography (CT) and magnetic resonance imaging (MRI), both of which can be used to evaluate the brain, spinal cord and canal, and orbits. Neurovascular structures, both arterial and venous, also can be imaged in high resolution with modern CT and MR angiography and CT and MR venography. In many cases, invasive procedures such as catheter angiography can be avoided with these studies, and angiography is often reserved for confirmation of vascular lesions combined with endovascular treatment. In this article, we illustrate how the evaluation of patients presenting with neuro-ophthalmic diseases involving the afferent and efferent visual pathways can be optimized with the use of appropriate diagnostic imaging studies. The complementary value of ophthalmic imaging is also demonstrated, and the advantages and disadvantages of both CT and MRI as well as their use in longitudinal patient follow up is demonstrated.

Optic disc drusen (ODD) are calcified, acellular bodies, seen in the optic nerve head of up to 2% of the population. Although seldomly affecting visual acuity, visual field defects are common, and severe, ischemic complications causing irreversible vision loss are known to occur. Different treatment strategies for ODD have been explored, but so far without success. This review focuses on the unique, calcified property of ODD, describing what we know about ODD pathogenesis and previously tried treatment strategies. In this context, we discuss current knowledge about calcium and pathological calcifications, including intracranial and ocular calcifications. We also explore some of the obstacles that must be addressed to develop a therapy centred on the concept of calcification, should calcification be identified as a pathogenic factor contributing to vision loss.

TRIM7 is a ubiquitin E3 ligase with key regulatory functions, mediating viral infection, tumor biology, innate immunity, and cellular processes, such as autophagy and ferroptosis. It contains a PRYSPRY domain that specifically recognizes degron sequences containing C-terminal glutamine. Ligands that bind to the TRIM7 PRYSPRY domain may have applications in the treatment of viral infections, as modulators of inflammation, and in the design of a new class of PROTACs (PROteolysis TArgeting Chimeras) that mediate the selective degradation of therapeutically relevant proteins (POIs). Here, we developed an assay toolbox for the comprehensive evaluation of TRIM7 ligands. Using TRIM7 degron sequences together with a structure-based design, we developed the first series of peptidomimetic ligands with low micromolar affinity. The terminal carboxylate moiety was required for ligand activity but prevented cell penetration. A prodrug strategy using an ethyl ester resulted in enhanced permeability, which was evaluated using confocal imaging.

Perovskite nanocrystals (PNCs) bear a huge potential for widespread applications, such as color conversion, X-ray scintillators, and active laser media. However, the poor intrinsic stability and high susceptibility to environmental stimuli including moisture and oxygen have become bottlenecks of PNC materials for commercialization. Appropriate barrier material design can efficiently improve the stability of the PNCs. Particularly, the strategy for packaging PNCs in organosilicon matrixes can integrate the advantages of inorganic-oxide-based and polymer-based encapsulation routes. However, the inert long-carbon-chain ligands (e.g., oleic acid, oleylamine) used in the current ligand systems for silicon-based encapsulation are detrimental to the cross-linking of the organosilicon matrix, resulting in performance deficiencies in the nanocrystal films, such as low transparency and large surface roughness. Herein, we propose a dual-organosilicon ligand system consisting of (3-aminopropyl)triethoxysilane (APTES) and (3-aminopropyl)triethoxysilane with pentanedioic anhydride (APTES-PA), to replace the inert long-carbon-chain ligands for improving the performance of organosilicon-coated PNC films. As a result, strongly fluorescent PNC films prepared by a facile solution-casting method demonstrate high transparency and reduced surface roughness while maintaining high stability in various harsh environments. The optimized PNC films were eventually applied in an X-ray imaging system as scintillators, showing a high spatial resolution above 20 lp/mm. By designing this promising dual organosilicon ligand system for PNC films, our work highlights the crucial influence of the molecular structure of the capping ligands on the optical performance of the PNC film.

This article explores the role of prosecutors in the criminal justice system, specifically in relation to conviction review. It emphasizes the importance of prosecutors in upholding justice and protecting the innocent. The article discusses the establishment of Conviction Review Units (CRUs) in prosecutor offices across the United States, which aim to review claims of innocence and correct wrongful convictions. It also addresses the evolving definition of exoneration and the considerations involved in creating a CRU or conviction review process. The article highlights the need for a standardized intake process, the involvement of outside sources for input, and the importance of conducting retroactive reviews for systemic errors. It also discusses the Colorado Justice Review Project, which used DNA analysis to review felony cases and led to the exoneration of one individual. The article provides guidance on conducting reinvestigations, working with defense counsel, communicating with victims, and handling inconclusive results or ethical breaches. The ultimate goal is to prevent future errors and achieve justice in every case. [Extracted from the article]

Technology is expanding, evolving, and improving at an explosive rate. Society, including law enforcement, is struggling to keep pace with these seemingly daily developments. This paper addresses facial recognition technology [...]

You don't have to walk far in downtown Bellingham to see a 'coming soon' sign in a storefront window. A major project, the renovation of Cornwall Avenue's former JC Penney [...]

They represent the future of business in Whatcom County--bright, ambitious and dedicated to building something greater, not just for themselves, but for everyone around them. The 2018 winners of the [...]

as police departments across the United States embrace the use of police body-worn cameras (BWCs), the cameras inevitably will capture a great deal of evidentiary material that will be useful [...]

Manzamine-A is a marine-derived alkaloid that has demonstrated antimalarial and antiproliferative properties and is an emerging drug lead compound as a possible intervention in certain cancers. This compound has been found to modulate SIX1gene expression, a target that is critical for the proliferation and survival of cells via various developmental pathways. As yet, little research has focused on manzamine-A and how its use may affect tissue systems including bone. Here we hypothesized that manzamine-A, through its interaction with SIX1, would alter precursor cells that give rise to the bone cell responsible for remodeling: the osteoclast. We further hypothesized reduced effects in differentiated osteoclasts, as these cells are generally not mitotic. We interrogated the effects of manzamine-A on preosteoclasts and osteoclasts. qrtPCR, MTS cell viability, Caspase 3/7, and TRAP staining were used as a functional assay. Preosteoclasts show responsiveness to manzamine-A treatment exhibited by decreases in cell viability and an increase in apoptosis. Osteoclasts also proved to be affected by manzamine-A but only at higher concentrations where apoptosis was increased and activation was reduced. In summary, our presented results suggest manzamine-A may have significant effects on bone development and health through multiple cell targets, previously shown in the osteoblast cell lineage, the cell responsible for mineralized tissue formation, and here in the osteoclast, the cell responsible for the removal of mineralized tissue and renewal via precipitation of bone remodeling.

A persistent challenge for lithium-ion batteries (LIBs) is operation under extreme environments, where temperatures can exceed −40 and 60 °C. At the same time, a growing number of high-impact applications require batteries that demonstrate longevity and high performance during low- and high-temperature operation, such as vehicle electrification, polar expeditions, and satellites/spacecraft. The discovery of novel electrolytes is therefore critical for developing next-generation energy storage solutions to widen operational capabilities beyond current technologies. Though trade-offs exist for targeting either low- or high-temperature performance, solutions that address both operational domains simultaneously are still sparse. In this Perspective, we highlight recent advancements in electrolyte formulations that enable a wide operating temperature window beyond −20 and 60 °C. Emerging research in fluorinated electrolytes, liquefied gas electrolytes, ionic liquids, and even aqueous chemistries offers a unique approach to overcoming this trade-off between low- and high-temperature operation of LIBs. The works highlighted in this Perspective present an exciting direction in the energy storage field that provides potential electrochemical solutions where engineering solutions may become exhausted.

The urgent need for new classes of orally available, safe, and effective antivirals─covering a breadth of emerging viruses─is evidenced by the loss of life and economic challenges created by the HIV-1 and SARS-CoV-2 pandemics. As frontline interventions, small-molecule antivirals can be deployed prophylactically or postinfection to control the initial spread of outbreaks by reducing transmissibility and symptom severity. Natural products have an impressive track record of success as prototypic antivirals and continue to provide new drugs through synthesis, medicinal chemistry, and optimization decades after discovery. Here, we demonstrate an approach using computational analysis typically used for rational drug design to identify and develop natural product-inspired antivirals. This was done with the goal of identifying natural product prototypes to aid the effort of progressing toward safe, effective, and affordable broad-spectrum inhibitors of Betacoronavirusreplication by targeting the highly conserved RNA 2′-O-methyltransferase (2′-O-MTase). Machaeriols RS-1 (7) and RS-2 (8) were identified using a previously outlined informatics approach to first screen for natural product prototypes, followed by in silico-guided synthesis. Both molecules are based on a rare natural product group. The machaeriols (3–6), isolated from the genus Machaerium, endemic to Amazonia, inhibited the SARS-CoV-2 2′-O-MTase more potently than the positive control, Sinefungin (2), and in silicomodeling suggests distinct molecular interactions. This report highlights the potential of computationally driven screening to leverage natural product libraries and improve the efficiency of isolation or synthetic analog development.

Cobalt polypyridyl complexes stand out as efficient catalysts for electrochemical proton reduction, but investigations into their operating mechanisms, with broad-reaching implications in catalyst design, have been limited. Herein, we investigate the catalytic activity of a cobalt(II) polypyridyl complex bearing a pendant pyridyl base with a series of organic acids spanning 20 pKaunits in acetonitrile. Structural analysis, as well as electrochemical studies, reveals that the Co(III) hydride intermediate is formed through reduction of the Co(II) catalyst followed by direct metal protonation in the initial EC step despite the presence of the pendant base, which is commonly thought of as a more kinetically accessible protonation site. Protonation of the pendant base occurs after the Co(III) hydride intermediate is further reduced in the overall ECEC pathway. Additionally, when the acid used is sufficiently strong, the Co(II) catalyst can be protonated, and the Co(III) hydride can react directly with acid to release H2. With thorough mechanistic understanding, the appropriate electroanalytical methods were identified to extract rate constants for the elementary steps over a range of conditions. Thermodynamic square schemes relating catalytic intermediates proposed in the three electrocatalytic HER mechanisms were constructed. These findings reveal a full description of the HER electrocatalysis mediated by this molecular system and provide insights into strategies to improve synthetic fuel-forming catalysts operative through metal hydride intermediates.

Nuclear magnetic resonance (NMR) spectroscopy is an indispensable tool for structure analysis. Students traditionally learn to interpret NMR spectra by using correlation tables to connect substructural units to their respective signals. This activity presents a successfully implemented classroom exercise in which students discover for themselves the pattern underlying the chemical shift correlation. To accomplish this goal, students analyze sets of NMR data selected to highlight paradigms of molecular structure on chemical shift, including the effects of electronegative elements, double bonds, and aromatic systems as well as cumulative effects. This approach improved students’ abilities to interpret spectra and use correlation tables.

Identifying research gaps and priorities is paramount to advance sustainability science and contribute to a sustainable future. This editorial contributes to this effort by contemplating the sustainability science research agenda and aligning it with recent changes in global dynamics. Drawing on consultations with the editorial board members of the Sustainability Science journal and a review of relevant literature, we identified 12 key research topics. These topics are interpreted within a strategic framework encompassing three key themes: (1) goals that drive sustainability science, (2) approaches to attain these goals, and (3) tools to advance sustainability science research. In so doing, this editorial emphasizes a sustainable development agenda extending beyond 2030, fostering equity and justice, and tackling issues related to power dynamics and geopolitical conflicts. It underscores the significance of research approaches to attaining sustainability goals, in particular, theorizing, co-production of knowledge and action, attaining clarity in conceptual descriptions, and developing systems-oriented analytical frameworks. Additionally, it highlights the value of place-based approaches, learning from significant systemic shocks, and nurturing inner transformations. It also underlines the need to explore emerging technologies and data-intensive methodologies as a tool to address sustainability concerns. The systematic contemplation of the sustainability science research agenda presented in this editorial piece aims to invoke further discussion among researchers and practitioners about a fresh and relevant agenda that promotes the sustainable integration of nature and society.

Als Prinzip für die Herstellung und Legitimation sozialer Ordnung gilt Meritokratie entweder als normativer Maßstab moderner Gesellschaften oder als eine von der Empirie sozialer Ungleichheiten laufend widerlegte Ideologie. Der Beitrag wählt einen anderen Ausgangspunkt und widmet sich den Herausforderungen der konkreten Umsetzung des abstrakten Leistungsprinzips. Anhand von Berufungsakten zu 145 Berufungsverfahren aus der zweiten Hälfte des 20. Jahrhunderts wird ein spezifisches Problem rekonstruiert: Meritokratie ist in Berufungsverfahren nicht das einzige Prinzip zur Herstellung und Legitimation sozialer Ordnung. Die Besetzung von Professuren ist nicht nur an der Bestenauslese, sondern auch an der sozialen Passung von Kandidatinnen und Kandidaten orientiert. In der Praxis entsteht so das Ordnungsproblem, die Orientierung an Leistung mit der Orientierung an sozialer Passung zu vereinbaren. Der Beitrag zeigt, erstens, dass dieses Problem überhaupt erst entsteht, als das meritokratische Prinzip in den 1970er-Jahren so verbindlich wird, dass Leistungszuschreibungen die alleingültige Rechtfertigung für Berufungsentscheidungen sind. Zweitens wird herausgearbeitet, wie Gutachterinnen und Gutachter und Kommissionen mit diesem Ordnungsproblem umgehen und die meritokratische Bestenauslese in Berufungsverfahren mit der sozialen Passung von Kandidatinnen und Kandidaten vereinbaren. Der Beitrag trägt zu einem differenzierteren Verständnis des Leistungsprinzips bei, indem er praktische Probleme bei der konkreten Umsetzung des meritokratischen Prinzips beleuchtet.

Shock-breakout emission is light that arises when a shockwave, generated by the core-collapse explosion of a massive star, passes through its outer envelope. Hitherto, the earliest detection of such a signal was at several hours after the explosion1, although a few others had been reported2–7. The temporal evolution of early light curves should provide insights into the shock propagation, including explosion asymmetry and environment in the vicinity, but this has been hampered by the lack of multiwavelength observations. Here we report the instant multiband observations of a type II supernova (SN 2023ixf) in the galaxy M101 (at a distance of 6.85 ± 0.15 Mpc; ref. 8), beginning at about 1.4 h after the explosion. The exploding star was a red supergiant with a radius of about 440 solar radii. The light curves evolved rapidly, on timescales of 1−2 h, and appeared unusually fainter and redder than predicted by the models9–11within the first few hours, which we attribute to an optically thick dust shell before it was disrupted by the shockwave. We infer that the breakout and perhaps the distribution of the surrounding dust were not spherically symmetric.

Wichtige neue Erkenntnisse zur Diagnostik und Therapie des Typ-2-Diabetes werden aufgezeigt. Der Schwerpunkt liegt dabei auf der medikamentösen Therapie gemäß aktuellen nationalen und internationalen Leitlinien. Bei Patienten mit kardiovaskulärer Vorerkrankung wird basierend auf den Daten aus Endpunktstudien der Einstieg in die medikamentöse Therapie mit einem SGLT-2-Inhibitor (SGLT: Natrium-Glukose-Kotransporter [„sodium glucose linked transporter“]) oder GLP-1-Rezeptor-Agonisten (GLP: glukagonähnliches [„glucagon-like“] Peptid) mit Nachweis einer Überlegenheit in Endpunktstudien empfohlen. Insbesondere bei den inkretinbasierten Therapien schreitet die Entwicklung weiter voran. Der duale GLP-1-/GIP-Rezeptor-Agonist (GIP: glukoseabhängiges insulinotropes Peptid) Tirzepatid ist der erste zugelassene Vertreter einer neuen Generation von Designermolekülen, die ihre Wirkung kalkuliert über mehrere Rezeptoren vermitteln und so nicht nur auf die diabetische Stoffwechsellage, sondern auch auf Adipositas und andere Komorbiditäten günstige Effekte erzielen können. Eine Neuerung in der Insulintherapie ist die nur 1‑mal wöchentliche Gabe von Basalinsulin, was für viele Patienten mit Typ-2-Diabetes eine Alternative zur bisherigen täglichen Injektion sein kann. Im Hinblick auf eine Erhöhung der Therapiesicherheit und eine stabilere Stoffwechsellage gewinnt die kontinuierliche Glukosemessung auch bei Typ-2-Diabetes zunehmend an Bedeutung. Die Zukunft wird zeigen, ob AID-Systeme (AID: automatische Insulindosierung) auch in der Therapie des Typ-2-Diabetes einen relevanten Stellenwert erlangen werden.

Schlieren imaging is an optical technique to observe the flow of transparent media, such as air or water, without any particle seeding. However, conventional frame-based techniques require both high spatial and temporal resolution cameras, which impose bright illumination and expensive computation limitations. Event cameras offer potential advantages (high dynamic range, high temporal resolution, and data efficiency) to overcome such limitations due to their bio-inspired sensing principle. This article presents a novel technique for perceiving air convection using events and frames by providing the first theoretical analysis that connects event data and schlieren. We formulate the problem as a variational optimization one combining the linearized event generation model with a physically-motivated parameterization that estimates the temporal derivative of the air density. The experiments with accurately aligned frame- and event camera data reveal that the proposed method enables event cameras to obtain on par results with existing frame-based optical flow techniques. Moreover, the proposed method works under dark conditions where frame-based schlieren fails, and also enables slow-motion analysis by leveraging the event camera's advantages. Our work pioneers and opens a new stack of event camera applications, as we publish the source code as well as the first schlieren dataset with high-quality frame and event data.

Zusammenfassung: Hintergrund: Die chronische Harnretention aufgrund eines hyposensitiven und hypokontraktilen Detrusors ist schwer therapierbar. Konservative, wie etwa medikamentöse Therapieansätze, verbessern die Detrusorfunktion oftmals nur unwesentlich. Im fortgeschrittenen Stadium verbleibt die Katheterversorgung der Harnblase vielfach als letzte Option. Ziel der Arbeit ist es zu prüfen, inwieweit die temporäre Niederdruckableitung der Harnblase Einfluss auf die Sensorik und die Motorik des Detrusors nimmt. Patienten und Methoden: Ausgehend von urodynamischen Daten wurden insgesamt 31 Patienten im Alter von durchschnittlich 54 (18–87) Jahren retrospektiv untersucht. Alle Patienten wiesen objektiv eine überhöhte Harnblasenkapazität, verminderte Detrusorsensitivität, -kontraktilität und Restharnbildung auf. Nach Ausschluss relevanter Begleitpathologien erfolgte die kontinuierliche Ableitung der Blase mittels suprapubischen Katheters. Nach durchschnittlich 13,1 (6–40) Wochen Dauerableitung wurde eine erneute Urodynamik durchgeführt. Ergebnisse: Nach Dauerableitung zeigten sich urodynamische Veränderungen sowohl bei Blasenfüllung als auch bei Miktion. Die Patienten gaben nach Dauerableitung den ersten Harndrang durchschnittlich früher (281,77 ml) als vor Kathetereinlage (306,92 ml) an (p<0,05). Die maximale Blasenkapazität reduzierte sich im Durchschnitt von 691,84 auf 496,87 ml. Die Compliance des Detrusors betrug initial 65,6 ml/cmH2O und reduzierte sich im Beobachtungszeitraum auf durchschnittlich 51,8 ml/cmH2O. In der Miktionsphase zeigte sich eine Reduktion der Restharnbildung um im Mittel 227,2 ml. Die maximale Harnstrahlstärke nach Dauerableitung betrug im Durchschnitt 9,4 ml/s bei unwesentlich gesteigertem Detrusordruck von 23,6 cmH2O. Schlussfolgerung: Nach temporärer Dauerableitung der hypokontraktilen und hyposensitiven Harnblase ergeben sich in der vorliegenden Untersuchung deutliche funktionelle Veränderungen. Die Reduktion der überhöhten maximalen Blasenkapazität sowie der Rückgang der Restharnmenge sind Hinweise auf eine Rehabilitationstendenz. Anhand der vorliegenden Daten kann die konsequente Niederdruckableitung der Harnblase als nichtinvasives Behandlungskonzept diskutiert werden. Zukünftig gilt es, anhand funktioneller und struktureller Analysen zu prüfen, inwiefern Blasenentleerungsstörungen in Abhängigkeit von Alter und Begleiterkrankungen reversibel sind.

ObjectiveThe hallmark oncogene MYC drives the progression of most tumours, but direct inhibition of MYC by a small-molecule drug has not reached clinical testing. MYC is a transcription factor that depends on several binding partners to function. We therefore explored the possibility of targeting MYC via its interactome in pancreatic ductal adenocarcinoma (PDAC).DesignTo identify the most suitable targets among all MYC binding partners, we constructed a targeted shRNA library and performed screens in cultured PDAC cells and tumours in mice.ResultsUnexpectedly, many MYC binding partners were found to be important for cultured PDAC cells but dispensable in vivo. However, some were also essential for tumours in their natural environment and, among these, the ATPases RUVBL1 and RUVBL2 ranked first. Degradation of RUVBL1 by the auxin-degron system led to the arrest of cultured PDAC cells but not untransformed cells and to complete tumour regression in mice, which was preceded by immune cell infiltration. Mechanistically, RUVBL1 was required for MYC to establish oncogenic and immunoevasive gene expression identifying the RUVBL1/2 complex as a druggable vulnerability in MYC-driven cancer.ConclusionOne implication of our study is that PDAC cell dependencies are strongly influenced by the environment, so genetic screens should be performed in vitro and in vivo. Moreover, the auxin-degron system can be applied in a PDAC model, allowing target validation in living mice. Finally, by revealing the nuclear functions of the RUVBL1/2 complex, our study presents a pharmaceutical strategy to render pancreatic cancers potentially susceptible to immunotherapy.