Publications by authors named "Lill J"

Molecular characterization of tumors is essential to identify predictive biomarkers that inform treatment decisions and improve precision immunotherapy development and administration. However, challenges such as the heterogeneity of tumors and patient responses, limited efficacy of current biomarkers, and the predominant reliance on single-omics data, have hindered advances in accurately predicting treatment outcomes. Standard therapy generally applies a "one size fits all" approach, which not only provides ineffective or limited responses, but also an increased risk of off-target toxicities and acceleration of resistance mechanisms or adverse effects.

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Based on the success of cancer immunotherapy, personalized cancer vaccines have emerged as a leading oncology treatment. Antigen presentation on MHC class I (MHC-I) is crucial for the adaptive immune response to cancer cells, necessitating highly predictive computational methods to model this phenomenon. Here, we introduce HLApollo, a transformer-based model for peptide-MHC-I (pMHC-I) presentation prediction, leveraging the language of peptides, MHC, and source proteins.

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In this study, a new design for a 1D gas-phase Raman spectrometer is presented, utilizing two dedicated tracks to image different properties of the measured signal onto a single charge-coupled device (CCD) chip. Two possible configurations are shown: a polarization-separation configuration, which separates the detected Raman signal into s- and p-polarized shares; and a dual-resolution configuration, which captures all process-relevant species in a range of approximately 515-4650 cm on one track and the highly resolved nitrogen spectrum on the other. This new spectrometer design offers several advantages when compared to traditional polarization-separation/dual-resolution systems, which often use switchable filters or two different spectrometers in tandem to achieve comparable measurements.

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  • * Wnt signaling is often altered in colorectal cancer, and ATF6 serves as a novel facilitator in this process.
  • * Targeting ATF6 could present a new therapeutic strategy for treating colorectal cancer.
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The transition toward a carbon-neutral society based on renewable energies goes hand in hand with the availability of energy-efficient technologies. Magnetocaloric cooling is a very promising refrigeration technology to fulfill this role regarding cryogenic gas liquefaction. However, the current reliance on highly resource critical, heavy rare-earth-based compounds as magnetocaloric material makes global usage unsustainable.

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  • For our immune system to fight cancer, special blood cells need to move from the bloodstream into the tumors and find their way to specific areas within the tumor.
  • These cells then work together and interact with other important cells to help either fight the cancer or not, depending on how they interact.
  • Understanding how these cells and chemical signals (called chemokines) guide each other can help us discover better ways to treat cancer and understand how the immune system works against it.
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Once every 13 or 17 years within eastern North American deciduous forests, billions of periodical cicadas concurrently emerge from the soil and briefly satiate a diverse array of naive consumers, offering a rare opportunity to assess the cascading impacts of an ecosystem-wide resource pulse on a complex food web. We quantified the effects of the 2021 Brood X emergence and report that more than 80 bird species opportunistically switched their foraging to include cicadas, releasing herbivorous insects from predation and essentially doubling both caterpillar densities and accumulated herbivory levels on host oak trees. These short-lived but massive emergence events help us to understand how resource pulses can rewire interaction webs and disrupt energy flows in ecosystems, with potentially long-lasting effects.

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  • A survey by the Therapeutic Product Immunogenicity community explored immunogenicity risk assessment strategies used by participants before clinical development, spanning 5 years and focusing on in silico algorithms and in vitro assays.
  • Key findings showed a trend towards using advanced tools like high-throughput in silico algorithms, human immune cell-based assays, and proteomics for effective risk assessments.
  • Participants also indicated that these tools not only supported early development phases but also informed clinical strategies and improved bioanalysis efficiency.
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To compare efficacy outcomes for all approved and investigational first-line (1L) treatment regimens for locally advanced or metastatic urothelial carcinoma (la/mUC) with standard of care (SOC), a network meta-analysis (NMA) was conducted. A systematic literature review (SLR) identified phase 2 and 3 randomized trials investigating 1L treatment regimens in la/mUC published January 2001-September 2021. Three networks were formed based on cisplatin (cis) eligibility: cis-eligible/mixed (cis-eligible patients and mixed populations of cis-eligible/ineligible patients), cis-ineligible (strict; exclusively cis-ineligible patients), and cis-ineligible (wide; including studies with investigator's choice of carbo).

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Transcriptional enhanced associate domain family members 1 to 4 (TEADs) are a family of four transcription factors and the major transcriptional effectors of the Hippo pathway. In order to activate transcription, TEADs rely on interactions with other proteins, such as the transcriptional effectors Yes-associated protein and transcriptional co-activator with PDZ-binding motif. Nuclear protein interactions involving TEADs influence the transcriptional regulation of genes involved in cell growth, tissue homeostasis, and tumorigenesis.

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  • The COVID-19 pandemic has created a significant need for affordable and effective treatments, especially as the search for alternative therapies continues even with vaccine availability.
  • Research tested herbal teas, specifically those made from perilla and sage, and found that they have strong antiviral effects against SARS-CoV-2, performing comparably to some existing treatments.
  • Key compounds like caffeic acid and perilla aldehyde were identified in these teas, and the study suggests they work by activating certain protective mechanisms in the body, indicating potential for herbal remedies in managing COVID-19.
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All holometabolous insects undergo a pupal life stage, a transformative period during which the insects are immobile and thus particularly vulnerable to both natural enemies and harmful abiotic conditions. For multivoltine species like the silver-spotted skipper [Epargyreus clarus (Cramer) (Lepidoptera: Hesperiidae)], which produces both diapausing and nondiapausing generations throughout much of its range, both the duration of the pupal stage and the ecological challenges faced by pupae can differ among generations. We conducted a set of field experiments to investigate the seasonal and annual variation in pupal mortality for E.

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Tertiary lymphoid structures (TLS) are lymph node-like immune cell clusters that emerge during chronic inflammation in non-lymphoid organs like the kidney, but their origin remains not well understood. Here we show, using conditional deletion strategies of the canonical Notch signaling mediator Rbpj, that loss of endothelial Notch signaling in adult mice induces the spontaneous formation of bona fide TLS in the kidney, liver and lung, based on molecular, cellular and structural criteria. These TLS form in a stereotypical manner around parenchymal arteries, while secondary lymphoid structures remained largely unchanged.

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Multicolumn Countercurrent Solvent Gradient Purification (MCSGP) is a continuous chromatography technique used to maximize purification yields compared to traditional batch purification methods. Here we apply MCSGP for the reversed phase purification of a N-acetylgalactosamine (GalNAc)-cluster-conjugated DNA-LNA gapmer oligonucleotide therapeutic using a twin-column chromatography system. Based on a batch process as a starting point, MCSGP was designed, optimized and compared with the batch process regarding process performance and scale-up requirements.

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  • The cancer-associated fibroblast marker podoplanin (PDPN) is linked to poor outcomes in cancer, making it a potential target for therapies.
  • Despite its significance, the fundamental roles of PDPN and its interactions remain unclear, hindering drug development efforts.
  • Recent research has identified CD177 as a new binding partner for PDPN, revealing its influence on cell signaling and potential to act as a functional antagonist in cancer-associated fibroblasts.
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A stimulus preference assessment (SPA) is a fundamental tool used by practitioners to predict stimuli that function as reinforcers. The Behavior Analyst Certification Board (BACB) requires that all certified behavior analysts and behavioral technicians be trained in SPA methodology (BACB, 2017). SPA procedures are used by nearly 9 out of 10 behavior analysts in the field (Graff & Karsten, 2012).

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The ubiquitin conjugating enzyme UBE2W catalyzes non-canonical ubiquitination on the N-termini of proteins, although its substrate repertoire remains unclear. To identify endogenous N-terminally-ubiquitinated substrates, we discover four monoclonal antibodies that selectively recognize tryptic peptides with an N-terminal diglycine remnant, corresponding to sites of N-terminal ubiquitination. Importantly, these antibodies do not recognize isopeptide-linked diglycine (ubiquitin) modifications on lysine.

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Introduction: Pioneering technologies such as proteomics have helped fuel the biotechnology and pharmaceutical industry with the discovery of novel targets and an intricate understanding of the activity of therapeutics and their various activities in vitro and in vivo. The field of proteomics is undergoing an inflection point, where new sensitive technologies are allowing intricate biological pathways to be better understood, and novel biochemical tools are pivoting us into a new era of chemical proteomics and biomarker discovery. In this review, we describe these areas of innovation, and discuss where the fields are headed in terms of fueling biotechnological and pharmacological research and discuss current gaps in the proteomic technology landscape.

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Utilizing the molecular beam epitaxy technique, a nanoscale thin-film magnet of -axis-oriented SmCo and SmCo phases is stabilized. While typically in the prototype Sm(Co, Fe, Cu, Zr) pinning-type magnets, an ordered nanocomposite is formed by complex thermal treatments, here, a one-step approach to induce controlled phase separation in a binary Sm-Co system is shown. A detailed analysis of the extended X-ray absorption fine structure confirmed the coexistence of SmCo and SmCo phases with 65% SmCo and 35% SmCo.

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Advances in several key technologies, including MHC peptidomics, have helped fuel our understanding of basic immune regulatory mechanisms and the identification of T cell receptor targets for the development of immunotherapeutics. Isolating and accurately quantifying MHC-bound peptides from cells and tissues enables characterization of dynamic changes in the ligandome due to cellular perturbations. However, the current multistep analytical process is challenging, and improvements in throughput and reproducibility would enable rapid characterization of multiple conditions in parallel.

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All nucleated mammalian cells express major histocompatibility complex (MHC) proteins that present peptides on cell surfaces for immune surveillance. These MHC-presented peptides (pMHC) are necessary for directing T-cell responses against cells harboring non-self antigens derived from pathogens or from somatic mutations. Alterations in tumor-specific antigen repertoires - particularly novel MHC presentation of mutation-bearing peptides (neoantigens) - can be potent targets of anti-tumor immune responses.

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  • Enterohaemorrhagic E. coli can cause severe epidemics with high mortality rates due to its ability to produce shiga toxin, leading to kidney damage and hemolytic uremic syndrome.
  • The study focused on how tissue-resident macrophages in the kidneys react during this disease, demonstrating that their activation contributes to inflammation and disease severity through the production of TNFα.
  • By depleting macrophages, researchers found reduced inflammation and neutrophil recruitment, indicating that targeting these macrophages could be a potential therapy to lessen kidney damage caused by the infection.
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Inflammasomes sense a number of pathogen and host damage signals to initiate a signaling cascade that triggers inflammatory cell death, termed pyroptosis. The inflammatory caspases (1/4/5/11) are the key effectors of this process through cleavage and activation of the pore-forming protein gasdermin D. Caspase-1 also activates proinflammatory interleukins, IL-1β and IL-18, via proteolysis.

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Patients with chronic lymphocytic leukemia (CLL) typically suffer from frequent and severe bacterial infections. Although it is well known that neutrophils are critical innate immune cells facilitating the early defense, the underlying phenotypical and functional changes in neutrophils during CLL remain largely elusive. Using a murine adoptive transfer model of CLL, we demonstrate aggravated bacterial burden in CLL-bearing mice upon a urinary tract infection with uropathogenic Escherichia coli.

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