Opinion on the Importance of Sharing Toxicologic Pathology Data for Educational and/or Scientific Purposes.

Sharing pathology data is critical for educational and scientific purposes. Since most pharmaceutical or (agro)chemical companies outsource nonclinical safety assessment studies to contract research organizations (CROs), the pathology data of those studies are not owned by the investigator but is the legal property of the respective company sponsoring the work. Although some companies have installed policies that govern sharing of pathology data, many companies generally do not allow the external use of data by either the CRO-based study pathologist or the sponsor pathologist.

Magnetic droplet soliton pairs.

We demonstrate magnetic droplet soliton pairs in all-perpendicular spin-torque nano-oscillators (STNOs), where one droplet resides in the STNO free layer (FL) and the other in the reference layer (RL). Typically, theoretical, numerical, and experimental droplet studies have focused on the FL, with any additional dynamics in the RL entirely ignored. Here we show that there is not only significant magnetodynamics in the RL, but the RL itself can host a droplet driven by, and coexisting with, the FL droplet.

European Society of Toxicologic Pathology (Pathology 2.0 Molecular Pathology Special Interest Group): Review of In Situ Hybridization Techniques for Drug Research and Development.

In situ hybridization (ISH) is used for the localization of specific nucleic acid sequences in cells or tissues by complementary binding of a nucleotide probe to a specific target nucleic acid sequence. In the last years, the specificity and sensitivity of ISH assays were improved by innovative techniques like synthetic nucleic acids and tandem oligonucleotide probes combined with signal amplification methods like branched DNA, hybridization chain reaction and tyramide signal amplification. These improvements increased the application spectrum for ISH on formalin-fixed paraffin-embedded tissues.

Spin pumping through nanocrystalline topological insulators.

The topological surface states (TSSs) in topological insulators (TIs) offer exciting prospects for dissipationless spin transport. Common spin-based devices, such as spin valves, rely on trilayer structures in which a non-magnetic layer is sandwiched between two ferromagnetic (FM) layers. The major disadvantage of using high-quality single-crystalline TI films in this context is that a single pair of spin-momentum locked channels spans across the entire film, meaning that only a very small spin current can be pumped from one FM to the other, along the side walls of the film.

Freezing and thawing magnetic droplet solitons.

Magnetic droplets are non-topological magnetodynamical solitons displaying a wide range of complex dynamic phenomena with potential for microwave signal generation. Bubbles, on the other hand, are internally static cylindrical magnetic domains, stabilized by external fields and magnetostatic interactions. In its original theory, the droplet was described as an imminently collapsing bubble stabilized by spin transfer torque and, in its zero-frequency limit, as equivalent to a bubble.

Transition Metal Synthetic Ferrimagnets: Tunable Media for All-Optical Switching Driven by Nanoscale Spin Current.

All-optical switching of magnetization has great potential for use in future ultrafast and energy efficient nanoscale magnetic storage devices. So far, research has been almost exclusively focused on rare-earth based materials, which limits device tunability and scalability. Here, we show that a perpendicularly magnetized synthetic ferrimagnet composed of two distinct transition metal ferromagnetic layers, NiPt and Co, can exhibit helicity independent magnetization switching.

Publication Categories in .

is the official journal of the Society of Toxicologic Pathology (STP), the British Society of Toxicological Pathology, and the European STP (ESTP). publishes articles related to topics in various aspects of toxicologic pathology such as anatomic pathology, clinical pathology, experimental pathology, and biomarker research. Publications include society-endorsed Best Practice/Position and Points to Consider publications and ESTP Expert Workshop articles that are relevant to toxicologic pathology and scientific regulatory processes, Opinion articles under the banner of the STP Toxicologic Pathology Forum, Original Articles, Review Articles (unsolicited/contributed, mini, and invited), Brief Communications, Letters to the Editor, Meeting Reports, and Book Reviews.

Artificial Intelligence in Toxicologic Pathology: Quantitative Evaluation of Compound-Induced Hepatocellular Hypertrophy in Rats.

Digital pathology evolved rapidly, enabling more systematic usage of image analysis and development of artificial intelligence (AI) applications. Here, combined AI models were developed to evaluate hepatocellular hypertrophy in rat liver, using commercial AI-based software on hematoxylin and eosin-stained whole slide images. In a first approach, deep learning-based identification of critical tissue zones (centrilobular, midzonal, and periportal) enabled evaluation of region-specific cell size.

Optically and Microwave-Induced Magnetization Precession in [Co/Pt]/NiFe Exchange Springs.

Microwave and heat-assisted magnetic recordings are two competing technologies that have greatly increased the capacity of hard disk drives. The efficiency of the magnetic recording process can be further improved by employing non-collinear spin structures that combine perpendicular and in-plane magnetic anisotropy. Here, we investigate both microwave and optically excited magnetization dynamics in [Co/Pt]/NiFe exchange spring samples.

Coherent Transfer of Spin Angular Momentum by Evanescent Spin Waves within Antiferromagnetic NiO.

Insulating antiferromagnets have recently emerged as efficient and robust conductors of spin current. Element-specific and phase-resolved x-ray ferromagnetic resonance has been used to probe the injection and transmission of ac spin current through thin epitaxial NiO(001) layers. The spin current is found to be mediated by coherent evanescent spin waves of GHz frequency, rather than propagating magnons of THz frequency, paving the way towards coherent control of the phase and amplitude of spin currents within an antiferromagnetic insulator at room temperature.

Nonclinical Safety Assessment of a Long-Acting Recombinant PEGylated Factor Eight (BAY 94-9027) With a 60 kDa PEG.

BAY 94-9027 (Jivi) is a site-specifically PEGylated human B-domain-deleted (BDD) recombinant factor VIII (FVIII), with a 60 kDa branched PEG molecule attached. The nonclinical safety of BAY 94-9027 was evaluated in a toxicology program that included 2 weeks intravenous (IV) toxicity studies in rats and rabbits, a juvenile toxicity study in rats as well as a 26-week chronic study in rats. Doses of 75, 750, or 2250 IU/kg given every other day for 2 weeks did not elicit any findings related to BAY 94-9027.

Detection of MET mRNA in gastric cancer in situ. Comparison with immunohistochemistry and sandwich immunoassays.

Determination of predictive biomarkers by immunohistochemistry (IHC) relies on antibodies with high selectivity. RNA in situ hybridization (RNA ISH) may be used to confirm IHC and may potentially replace it if suitable antibodies are not available or are insufficiently selective to discriminate closely related protein isoforms. We validated RNA ISH as specificity control for IHC and as a potential alternative method for selecting patients for treatment with MET inhibitors.

Histology and Gadolinium Distribution in the Rodent Brain After the Administration of Cumulative High Doses of Linear and Macrocyclic Gadolinium-Based Contrast Agents.

Objectives: Retrospective studies in patients with primary brain tumors or other central nervous system pathologies as well as postmortem studies have suggested that gadolinium (Gd) deposition occurs in the dentate nucleus (DN) and globus pallidus (GP) after multiple administrations of primarily linear Gd-based contrast agents (GBCAs). However, this deposition has not been associated with any adverse effects or histopathological alterations. The aim of this preclinical study was to systematically examine differences between linear and macrocyclic GBCAs in their potential to induce changes in brain and skin histology including Gd distribution in high spatial resolution.

Resonant x-ray diffraction revealing chemical disorder in sputtered L10 FeNi on Si(0 0 1).

In the search for new rare earth free permanent magnetic materials, FeNi with a L10 structure is a possible candidate. We have synthesized the phase in the thin film form by sputtering onto HF-etched Si(0 0 1) substrates. Monatomic layers of Fe and Ni were alternately deposited on a Cu buffer layer, all of which grew epitaxially on the Si substrates.

Novel Mps1 Kinase Inhibitors with Potent Antitumor Activity.

Monopolar spindle 1 (Mps1) has been shown to function as the key kinase that activates the spindle assembly checkpoint (SAC) to secure proper distribution of chromosomes to daughter cells. Here, we report the structure and functional characterization of two novel selective Mps1 inhibitors, BAY 1161909 and BAY 1217389, derived from structurally distinct chemical classes. BAY 1161909 and BAY 1217389 inhibited Mps1 kinase activity with IC50 values below 10 nmol/L while showing an excellent selectivity profile.

Glomerulonephritis-induced changes in kidney gene expression in rats.

We investigated a glomerulonephritis (GN) model in rats induced by nephrotoxic serum (NTS) which contains antibodies against the glomerular basement membrane (GBM). The anti-GBM GN model in rats is widely used since its biochemical and histopathological characteristics are similar to crescentic nephritis and Goodpasture's disease in humans (Pusey, 2003[2]). Male Wistar Kyoto (WKY) and Sprague-Dawley (SD) rats were dosed once with 1, 2.

Application of a Patient Derived Xenograft Model for Predicative Study of Uterine Fibroid Disease.

Human uterine fibroids, benign tumors derived from the smooth muscle layers of the uterus, impose a major health burden to up to 50% of premenopausal women in their daily life. To improve our understanding of this disease, we developed and characterized a patient-derived xenograft model by subcutaneous transplantation of pieces of human uterine fibroid tissue into three different strains of severe combined immunodeficient mice. Engrafted uterine fibroid tissue preserved the classical morphology with interwoven bundles of smooth muscle cells and an abundant deposition of collagenous matrix, similar to uterine fibroids in situ.

Glomerulonephritis-Induced Changes in Urinary and Kidney MicroRNA Profiles in Rats.

MicroRNAs (miRNAs) regulate gene expression post-transcriptionally and thus are involved in various physiological and pathological states. Due to their stability in biofluids miRNAs have also been proposed as biomarkers (BMs) for tissue injury. We investigated the usefulness of urinary miRNAs for detection of site-specific renal damage in an antiglomerular basement membrane glomerulonephritis (GN) model in rats by comparing GN-induced urinary miRNAs profiles to traditional and newer protein BMs, and to proximal tubular injury-induced urinary miRNA profiles observed previously after cisplatin (Cp) treatment.

Expression analysis of the Pseudomonas aeruginosa AlgZR two-component regulatory system.

Pseudomonas aeruginosa virulence components are subject to complex regulatory control primarily through two-component regulatory systems that allow for sensing and responding to environmental stimuli. In this study, the expression and regulation of the P. aeruginosa AlgZR two-component regulatory system were examined.

Comparison of progestin transcriptional profiles in rat mammary gland using Laser Capture Microdissection and whole tissue-sampling.

Introduction: Investigation of molecular mechanisms by gene expression profiling gains increasingly importance in preclinical safety evaluation. However, assigning expressed genes to specific cell populations is nearly impossible if the investigated RNA originates from whole tissue extracts. In this regard, Laser Capture Microdissection (LCM) can be used to detect changes specific to individual cell types.

The effect of iodinated contrast agent properties on renal kinetics and oxygenation.

Objective: We analyzed renal kinetics and renal oxygenation in rats after administration of several classes and formulations of contrast agents (CAs) with a focus on the influence of osmolality and substance-specific properties.

Materials And Methods: We investigated the renal kinetics of a nonionic, dimeric CA (iodixanol) formulated in 3 different osmolalities (hypo-osmolar, iso-osmolar, low-osmolar) and compared it to nonionic, low-osmolar (iopromide), and ionic, low-osmolar CAs (ioxaglate) using computed tomography for a period of 24 hours. The CAs were administered intravenously at a dosage of 4 g iodine/kg body weight.

D-18F-fluoromethyl tyrosine imaging of bone metastases in a mouse model.

Unlabelled: The presence and localization of metastatic bone lesions is important for the staging of the disease and subsequent treatment decisions. Detecting tumor cells would have additional value over the current indirect bone scintigraphy method for detecting areas of elevated skeletal metabolic activity. d-(18)F-fluoromethyl tyrosine (d-(18)F-FMT) has recently shown good uptake and fast elimination, resulting in good tumor-to-background ratios.