Human organoids with an autologous tissue-resident immune compartment.

The intimate relationship between the epithelium and immune system is crucial for maintaining tissue homeostasis, with perturbations therein linked to autoimmune disease and cancer. Whereas stem cell-derived organoids are powerful models of epithelial function, they lack tissue-resident immune cells that are essential for capturing organ-level processes. We describe human intestinal immuno-organoids (IIOs), formed through self-organization of epithelial organoids and autologous tissue-resident memory T (T) cells, a portion of which integrate within the epithelium and continuously survey the barrier.

T-FINDER: A highly sensitive, pan-HLA platform for functional T cell receptor and ligand discovery.

Effective, unbiased, high-throughput methods to functionally identify both class II and class I HLA-presented T cell epitopes and their cognate T cell receptors (TCRs) are essential for and prerequisite to diagnostic and therapeutic applications, yet remain underdeveloped. Here, we present T-FINDER [T cell Functional Identification and (Neo)-antigen Discovery of Epitopes and Receptors], a system to rapidly deconvolute CD4 and CD8 TCRs and targets physiologically processed and presented by an individual's unmanipulated, complete human leukocyte antigen (HLA) haplotype. Combining a highly sensitive TCR signaling reporter with an antigen processing system to overcome previously undescribed limitations to target expression, T-FINDER both robustly identifies unknown peptide:HLA ligands from antigen libraries and rapidly screens and functionally validates the specificity of large TCR libraries against known or predicted targets.

H3K27M neoepitope vaccination in diffuse midline glioma induces B and T cell responses across diverse HLA loci of a recovered patient.

H3K27M, a driver mutation with T and B cell neoepitope characteristics, defines an aggressive subtype of diffuse glioma with poor survival. We functionally dissect the immune response of one patient treated with an H3K27M peptide vaccine who subsequently entered complete remission. The vaccine robustly expanded class II human leukocyte antigen (HLA)-restricted peripheral H3K27M-specific T cells.

High-Precision Determination of g Factors and Masses of ^{20}Ne^{9+} and ^{22}Ne^{9+}.

We present the measurements of individual bound electron g factors of ^{20}Ne^{9+} and ^{22}Ne^{9+} on the relative level of 0.1 parts per billion. The comparison with theory represents the most stringent test of bound-state QED in strong electric fields.

Analysis of off-tumour toxicities of T-cell-engaging bispecific antibodies via donor-matched intestinal organoids and tumouroids.

Predicting the toxicity of cancer immunotherapies preclinically is challenging because models of tumours and healthy organs do not typically fully recapitulate the expression of relevant human antigens. Here we show that patient-derived intestinal organoids and tumouroids supplemented with immune cells can be used to study the on-target off-tumour toxicities of T-cell-engaging bispecific antibodies (TCBs), and to capture clinical toxicities not predicted by conventional tissue-based models as well as inter-patient variabilities in TCB responses. We analysed the mechanisms of T-cell-mediated damage of neoplastic and donor-matched healthy epithelia at a single-cell resolution using multiplexed immunofluorescence.

Observation of a Low-Lying Metastable Electronic State in Highly Charged Lead by Penning-Trap Mass Spectrometry.

Highly charged ions (HCIs) offer many opportunities for next-generation clock research due to the vast landscape of available electronic transitions in different charge states. The development of extreme ultraviolet frequency combs has enabled the search for clock transitions based on shorter wavelengths in HCIs. However, without initial knowledge of the energy of the clock states, these narrow transitions are difficult to be probed by lasers.

Localization of Sesquiterpene Lactones Biosynthesis in Flowers of Taxa.

is a valuable plant with high demand on the pharmaceutical and cosmetic market due to the presence of helenalin (H) and 11α, 13-dihydrohelenalin (DH) sesquiterpene lactones (SLs), with many applications and anti-inflammatory, anti-tumor, analgesic and other properties. Despite the great importance of these compounds for the protection of the plant and their medicinal value, the content of these lactones and the profile of the compounds present within individual elements of florets and flower heads have not been studied so far, and attempts to localize these compounds in flower tissues have also not been conducted. The three studied taxa synthesize SLs only in the aerial parts of plants, and the highest content of these substances was found in cv.

High-precision mass measurement of doubly magic Pb.

The absolute atomic mass of Pb has been determined with a fractional uncertainty of by measuring the cyclotron-frequency ratio of Pb to Xe with the high-precision Penning-trap mass spectrometer Pentatrap and computing the binding energies and of the missing 41 and 26 atomic electrons, respectively, with the fully relativistic multi-configuration Dirac-Hartree-Fock (MCDHF) method. has been measured with a relative precision of . and have been computed with an uncertainty of 9.

Fast silicon carbide MOSFET based high-voltage push-pull switch for charge state separation of highly charged ions with a Bradbury-Nielsen gate.

In this paper, we report on the development of a fast high-voltage switch, which is based on two enhancement mode N-channel silicon carbide metal-oxide-semiconductor field-effect transistors in push-pull configuration. The switch is capable of switching high voltages up to 600 V on capacitive loads with rise and fall times on the order of 10 ns and pulse widths ≥20 ns. Using this switch, it was demonstrated that, from the charge state distribution of bunches of highly charged ions ejected from an electron beam ion trap with a specific kinetic energy, single charge states can be separated by fast switching of the high voltage applied to a Bradbury-Nielsen Gate with a resolving power of about 100.

A digital feedback system for advanced ion manipulation techniques in Penning traps.

The possibility of applying active feedback to a single ion in a Penning trap using a fully digital system is demonstrated. Previously realized feedback systems rely on analog circuits that are susceptible to environmental fluctuations and long term drifts, as well as being limited to the specific task they were designed for. The presented system is implemented using a field-programmable gate array (FPGA)-based platform (STEMlab), offering greater flexibility, higher temporal stability, and the possibility for highly dynamic variation of feedback parameters.

Direct Q-Value Determination of the β^{-} Decay of ^{187}Re.

The cyclotron frequency ratio of ^{187}Os^{29+} to ^{187}Re^{29+} ions was measured with the Penning-trap mass spectrometer PENTATRAP. The achieved result of R=1.000 000 013 882(5) is to date the most precise such measurement performed on ions.

Targeting RIOK2 ATPase activity leads to decreased protein synthesis and cell death in acute myeloid leukemia.

Novel therapies for the treatment of acute myeloid leukemia (AML) are urgently needed, because current treatments do not cure most patients with AML. We report a domain-focused, kinome-wide CRISPR-Cas9 screening that identified protein kinase targets for the treatment of AML, which led to the identification of Rio-kinase 2 (RIOK2) as a potential novel target. Loss of RIOK2 led to a decrease in protein synthesis and to ribosomal instability followed by apoptosis in leukemic cells, but not in fibroblasts.

Detection of metastable electronic states by Penning trap mass spectrometry.

State-of-the-art optical clocks achieve precisions of 10 or better using ensembles of atoms in optical lattices or individual ions in radio-frequency traps. Promising candidates for use in atomic clocks are highly charged ions (HCIs) and nuclear transitions, which are largely insensitive to external perturbations and reach wavelengths beyond the optical range that are accessible to frequency combs. However, insufficiently accurate atomic structure calculations hinder the identification of suitable transitions in HCIs.

Mass-Difference Measurements on Heavy Nuclides with an eV/c^{2} Accuracy in the PENTATRAP Spectrometer.

First ever measurements of the ratios of free cyclotron frequencies of heavy, highly charged ions with Z>50 with relative uncertainties close to 10^{-11} are presented. Such accurate measurements have become realistic due to the construction of the novel cryogenic multi-Penning-trap mass spectrometer PENTATRAP. Based on the measured frequency ratios, the mass differences of five pairs of stable xenon isotopes, ranging from ^{126}Xe to ^{134}Xe, have been determined.

Production of highly charged ions of rare species by laser-induced desorption inside an electron beam ion trap.

This paper reports on the development and testing of a novel, highly efficient technique for the injection of very rare species into electron beam ion traps (EBITs) for the production of highly charged ions (HCI). It relies on in-trap laser-induced desorption of atoms from a sample brought very close to the electron beam resulting in a very high capture efficiency in the EBIT. We have demonstrated a steady production of HCI of the stable isotope Ho from samples of only 10 atoms (∼300 pg) in charge states up to 45+.

Small bowel protection in IMRT for rectal cancer : A dosimetric study on supine vs. prone position.

Background: This treatment planning study analyzes dose coverage and dose to organs at risk (OAR) in intensity-modulated radiotherapy (IMRT) of rectal cancer and compares prone vs. supine positioning as well as the effect of dose optimization for the small bowel (SB) by additional dose constraints in the inverse planning process.

Patients And Methods: Based on the CT datasets of ten male patients in both prone and supine position, a total of four different IMRT plans were created for each patient.

Oil Secretory System in Vegetative Organs of Three Arnica Taxa: Essential Oil Synthesis, Distribution and Accumulation.

Arnica, a genus including the medicinal species A. montana, in its Arbo variety, and A. chamissonis, is among the plants richest in essential oils used as pharmaceutical materials.

Naphthalene glucoside and other phenolics from the shoot and callus cultures of Drosophyllum lusitanicum.

The callus and, for the first time established, shoot cultures of Drosophyllum lusitanicum Link. (Droseraceae) yielded new naphthalene glucoside-5-hydroxy-4-methoxy-2-naphthalenecarboxylic acid 5-O-beta-glucoside (drosophylloside) and 5-hydroxy-4-methoxy-2-naphthalenecarboxylic acid methyl ester besides other phenolics like naphthalenes-5-hydroxy-4-methoxy-2-naphthalenecarboxylic acid (ancistronaphthoic acid B), hydroplumbagin 4-O-glucoside, naphthoquinones-plumbagin and 3-chloroplumbagin, C-glycosylflavones- vitexin, isovitexin, orientin and isoorientin. The pattern of phenolics found supports affinity of Drosophyllum to the families-Droseraceae, Ancistrocladaceae and Dioncophyllaceae.

Peripheral and axial bone mass in Austrian free climbers.

The present investigation was carried out in healthy white adult males to determine the effects of exercise, in the form of free climbing, on peripheral and axial bone mass. 13 men who have been regularly engaging in alpine free climbing for a mean period of nine years and, for training purposes, have been performing additional muscle building exercises (4.5 h +/- 1 SEM per week) and 12 age matched controls were included in the study.