Simultaneous path weak-measurements in neutron interferometry.

The statistical properties of the detection events constituting the interference fringes at the output of an interferometer are well-known. Nevertheless, there is still no unified view of what is happening to a quantum system inside an interferometer. Strong measurements of path operators destroy the interference effect.

Triggered Superradiance and Spin Inversion Storage in a Hybrid Quantum System.

We study the superradiant emission of an inverted spin ensemble strongly coupled to a superconducting cavity. After fast inversion, we detune the spins from the cavity and store the inversion for tens of milliseconds, during which the remaining transverse spin components disappear. Switching back on resonance enables us to study the onset of superradiance.

The VEGFR/PDGFR tyrosine kinase inhibitor, ABT-869, blocks necroptosis by targeting RIPK1 kinase.

Necroptosis is a mode of programmed, lytic cell death that is executed by the mixed lineage kinase domain-like (MLKL) pseudokinase following activation by the upstream kinases, receptor-interacting serine/threonine protein kinase (RIPK)-1 and RIPK3. Dysregulated necroptosis has been implicated in the pathophysiology of many human diseases, including inflammatory and degenerative conditions, infectious diseases and cancers, provoking interest in pharmacological targeting of the pathway. To identify small molecules impacting on the necroptotic machinery, we performed a phenotypic screen using a mouse cell line expressing an MLKL mutant that kills cells in the absence of upstream death or pathogen detector receptor activation.

Quantum causality emerging in a delayed-choice quantum Cheshire Cat experiment with neutrons.

We report an experiment with neutrons in a silicon perfect crystal interferometer, that realizes a quantum Cheshire Cat in a delayed choice setting. In our setup the quantum Cheshire Cat is established by spatially separating the particle and its property (i.e.

Electrochemically Initiated Synthesis of Methanesulfonic Acid.

The direct sulfonation of methane to methanesulfonic acid was achieved in an electrochemical reactor without adding peroxide initiators. The synthesis proceeds only from oleum and methane. This is possible due to in situ formation of an initiating species from the electrolyte at a boron-doped diamond anode.

The Lck inhibitor, AMG-47a, blocks necroptosis and implicates RIPK1 in signalling downstream of MLKL.

Necroptosis is a form of caspase-independent programmed cell death that arises from disruption of cell membranes by the mixed lineage kinase domain-like (MLKL) pseudokinase after its activation by the upstream kinases, receptor interacting protein kinase (RIPK)-1 and RIPK3, within a complex known as the necrosome. Dysregulated necroptosis has been implicated in numerous inflammatory pathologies. As such, new small molecule necroptosis inhibitors are of great interest, particularly ones that operate downstream of MLKL activation, where the pathway is less well defined.

In Situ Synchrotron X-ray Diffraction Studies of the Mechanochemical Synthesis of ZnS from its Elements.

Invited for the cover of this issue is Claudia Weidenthaler and co-workers at the Max-Planck-Institut für Kohlenforschung, Shenzhen University and Deutsches Elektronen Synchrotron. The image depicts the X-ray diffraction results showing the formation of ZnS and the subsequent phase transition from the hexagonal to the cubic modification. Read the full text of the article at 10.

In Situ Synchrotron X-ray Diffraction Studies of the Mechanochemical Synthesis of ZnS from its Elements.

Mechanochemistry, as a synthesis tool for inorganic materials, became an ever-growing field in material chemistry. The direct energy transfer by collision of the educts with the milling media gives the possibility to design environmental-friendly reactions. Nevertheless, the underlying process of energy transfer and hence the kinetics of mechanosynthesis remain unclear.

Potent Inhibition of Necroptosis by Simultaneously Targeting Multiple Effectors of the Pathway.

Necroptosis is an inflammatory form of programmed cell death that has been implicated in various human diseases. Compound is a more potent analogue of the published compound and inhibits necroptosis in human and murine cells at nanomolar concentrations. Several target engagement strategies were employed, including cellular thermal shift assays (CETSA) and diazirine-mediated photoaffinity labeling via a bifunctional photoaffinity probe derived from compound .

Enhanced Molecular Spin-Photon Coupling at Superconducting Nanoconstrictions.

We combine top-down and bottom-up nanolithography to optimize the coupling of small molecular spin ensembles to 1.4 GHz on-chip superconducting resonators. Nanoscopic constrictions, fabricated with a focused ion beam at the central transmission line, locally concentrate the microwave magnetic field.

Viral MLKL Homologs Subvert Necroptotic Cell Death by Sequestering Cellular RIPK3.

Necroptotic cell death has been implicated in many human pathologies and is thought to have evolved as an innate immunity mechanism. The pathway relies on two key effectors: the kinase receptor-interacting protein kinase 3 (RIPK3) and the terminal effector, the pseudokinase mixed-lineage kinase-domain-like (MLKL). We identify proteins with high sequence similarity to the pseudokinase domain of MLKL in poxvirus genomes.

Conformational switching of the pseudokinase domain promotes human MLKL tetramerization and cell death by necroptosis.

Necroptotic cell death is mediated by the most terminal known effector of the pathway, MLKL. Precisely how phosphorylation of the MLKL pseudokinase domain activation loop by the upstream kinase, RIPK3, induces unmasking of the N-terminal executioner four-helix bundle (4HB) domain of MLKL, higher-order assemblies, and permeabilization of plasma membranes remains poorly understood. Here, we reveal the existence of a basal monomeric MLKL conformer present in human cells prior to exposure to a necroptotic stimulus.

Structure-Guided Rescaffolding of Selective Antagonists of BCL-XL.

Because of the promise of BCL-2 antagonists in combating chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL), interest in additional selective antagonists of antiapoptotic proteins has grown. Beginning with a series of selective, potent BCL-XL antagonists containing an undesirable hydrazone functionality, in silico design and X-ray crystallography were utilized to develop alternative scaffolds that retained the selectivity and potency of the starting compounds.

Discovery of potent and selective benzothiazole hydrazone inhibitors of Bcl-XL.

Developing potent molecules that inhibit Bcl-2 family mediated apoptosis affords opportunities to treat cancers via reactivation of the cell death machinery. We describe the hit-to-lead development of selective Bcl-XL inhibitors originating from a high-throughput screening campaign. Small structural changes to the hit compound increased binding affinity more than 300-fold (to IC50 < 20 nM).

Characterization of the novel broad-spectrum kinase inhibitor CTx-0294885 as an affinity reagent for mass spectrometry-based kinome profiling.

Kinase enrichment utilizing broad-spectrum kinase inhibitors enables the identification of large proportions of the expressed kinome by mass spectrometry. However, the existing inhibitors are still inadequate in covering the entire kinome. Here, we identified a novel bisanilino pyrimidine, CTx-0294885, exhibiting inhibitory activity against a broad range of kinases in vitro, and further developed it into a Sepharose-supported kinase capture reagent.

Structure-guided design of a selective BCL-X(L) inhibitor.

The prosurvival BCL-2 family protein BCL-X(L) is often overexpressed in solid tumors and renders malignant tumor cells resistant to anticancer therapeutics. Enhancing apoptotic responses by inhibiting BCL-X(L) will most likely have widespread utility in cancer treatment and, instead of inhibiting multiple prosurvival BCL-2 family members, a BCL-X(L)-selective inhibitor would be expected to minimize the toxicity to normal tissues. We describe the use of a high-throughput screen to discover a new series of small molecules targeting BCL-X(L) and their structure-guided development by medicinal chemistry.

Effect of differences in tendon properties on functionality of the passive stay apparatus in horses.

Objective: To determine the effect of differences in structural and mechanical tendon properties on functionality of the passive stay apparatus in horses.

Sample: 5 forelimbs each from nondwarf Friesians, dwarf Friesians, and ponies.

Procedures: Harvested forelimbs were loaded to test the passive stay apparatus.

Quinazoline sulfonamides as dual binders of the proteins B-cell lymphoma 2 and B-cell lymphoma extra long with potent proapoptotic cell-based activity.

ABT-737 and ABT-263 are potent inhibitors of the BH3 antiapoptotic proteins, Bcl-x(L) and Bcl-2. This class of putative anticancer agents invariantly contains an acylsulfonamide core. We have designed and synthesized a series of novel quinazoline-based inhibitors of Bcl-2 and Bcl-x(L) that contain a heterocyclic alternative to the acylsulfonamide.

Diagnostic and analytical performance of a screening panel for allergy.

Worldwide, allergic diseases are increasing in prevalence and incidence. Early assessment of the immunoglobulin E (IgE) sensitisation status has a major impact on clinical outcome and selection of therapeutic options. Recently, a number of new IgE-detecting test systems have entered the market, including screening tests allowing identification of a wide spectrum of sensitising allergens.

The equine hind limb is actively stabilized during standing.

Horses spend much of their life standing, and they are believed to be able to keep their limbs straight without muscular effort. We tested the hypothesis that the stifle (knee) and hock (tarsal) joints could be stabilized merely with the help of a passive lock mechanism whereby the patella is secured behind a hook, formed by the medial femoral trochlea. In anaesthetized animals and isolated limbs the stifle and hock flex readily under compression.

Sex difference in target seeking behavior of developing cremaster muscles and the resulting first visible sign of somatic sexual differentiation in marsupial mammals.

Cremaster muscles are present in both male and female developing and adult marsupial mammals. They are complex structures and composed of several distinct bundles of striated muscle fibers provided with: (1) a distinct and extensive innervation; (2) a distinct blood vascular supply; (3) a distinct tendineous origin on the anterosuperior iliac spine; and (4) distinct target structures. The muscles thus seem to be separate anatomical entities and not a part of one or more of the layers of the ventral abdominal wall musculature.

Bilateral cryptorchidism in a dog with persistent cranial testis suspensory ligaments and inverted gubernacula: report of a case with implications for understanding normal and aberrant testis descent.

The genital system of a dog with bilateral intra-abdominal testes is described. External virilisation was normal except for an empty scrotum. Internally there was a prostate of normal macroscopic and histological appearances and, bilaterally, a fully developed male genital tract.

Nerve supply of the proximal sesamoid bone in the horse.

In chronical proximal sesamoid bone lameness it is difficult to localise the exact site of pain. A specific diagnostic analgesia is not available because of a deficiency of detailed information about the nerve supply to the proximal sesamoid bones and surrounding area. A macroscopic study of the nerve distribution to the proximal sesamoid bones of 10 foals and 5 adult horses revealed that these bones are innervated by two branches, in this study called the medial and lateral sesamoidean nerve, respectively, originating from the medial and lateral palmar nerve.

Over-expression of cellular oncogenes in cystadenocarcinomas of the ovary.

A complex analysis of oncogene over-expression in ovarian cystadenocarcinomas of 20 patients was performed. Radioactively labelled cDNAs were synthesized from total cellular RNA from tumor cells and hybridized to dot blot filters. On each filter more than 20 different plasmids containing cloned oncogene fragments were immobilized.

[Acarex test and acarosan effect in house dust mite allergy in 2 year follow-up].

Clinical investigations of the effect of the acaricide product Acarosan shows in a large collective of patients beneficial results, whereby the patients are examined up to three months after sanitation. The remaining patients of this study are followed up one and two years after sanitation in open clinical trials. Without exception Acarex test values decrease highly significant after three months, indicating the effective elimination of the house dust mites by Acarosan treatment and consequently the reduction of the allergen containing excreta.