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Several stilbenoid compounds having structural similarity to the combretastatin group of natural products and characterized by the incorporation of two nitrogen-bearing groups (amine, nitro, serinamide) have been prepared by chemical synthesis and evaluated in terms of biochemical and biological activity. The 2',3'-diamino B-ring analogue 17 demonstrated remarkable cytotoxicity against selected hu

Vorinostat is a histone deacetylase inhibitor that changes gene expression and protein activity. On the basis of the clinical benefit reported in patients with malignant pleural mesothelioma treated in a phase 1 study of vorinostat, we designed this phase 3 trial to investigate whether vorinostat given as a second-line or third-line therapy improved patients' overall survival.

Fluorescence microscopy is introduced as a low cost quality control process for nanoimprint lithography. To depict imprinted structures down to 1 mum lateral size and to detect residues down to 100 nm lateral size, the standard printable polymer mr-18000 is labelled with less than 0.1 wt.% fluorescent dye. Three different types of stamps are used to determine the dependence of the shape and size o

Approximately 25% of eukaryotic proteins possessing homology to at least two trans membrane domains are predicted to be embedded in biological membranes. Nevertheless, this group of proteins is not usually well represented in proteome-wide experiments due to their refractory nature. Here we present a quantitative mass spectrometry-based comparison of membrane protein expression in cerebellar granu

The identification of novel, non-purine based inhibitors of xanthine oxidase is described. After a high-throughput screening campaign, an NMR based counterscreen was used to distinguish actives, which interact with XO in a reversible manner, from assay artefacts. This approach identified pyrimidone 1 as a reversible and competitive inhibitor with good lead-like properties. A hit to lead campaign g

Objectives The study was designed to assess the ability of computer-simulated electrocardiography parameters to predict clinical outcomes and to risk-stratify patients with long QT syndrome type 1 (LQT1). Background Although attempts have been made to correlate mutation-specific ion channel dysfunction with patient phenotype in long QT syndrome, these have been largely unsuccessful. Systems-level

Despite recent progress within the field of immuno-oncology, immune suppression in the tumor microenvironment, defective antigen presentation, and low levels of tumor-specific T cells are key limitations of current cancer immunotherapies. CD40-targeting immunotherapies hold promises for addressing these limitations across solid tumors. Here, we describe ATOR-4066, a bispecific antibody that target

Dynamic Resource Management (DRM) facilitates the real-time adjustment of resources allocated to a job during its execution. Recently, DRM has gained interest due to its potential to contribute to sustainable HPC by enhancing energy efficiency and increasing throughput for HPC system providers and users. Implementing DRM requires comprehensive changes and coordination across the entire HPC softwar

Agentic AI — the new paradigm for creating autonomous systems capable of perceiving, reasoning, learning, and acting towards goals using large language models (LLMs) with minimal human oversight — offers transformative potential but also poses systemic risks that the EU AI Act only partially addresses. These agents can evolve unpredictably, interact with other agents, and operate beyond meaningful

Patients with chronic lymphocytic leukemia (CLL) have an impaired response to vaccination, which calls for improved vaccination strategies. This study aimed to evaluate antibody persistence 5 years after pneumococcal vaccination and response to revaccination. Seventy-four CLL patients and 31 controls, all primary immunized with 13-valent conjugated pneumococcal vaccine (PCV13) or 23-valent polysac

Despite significant progress in oncology research, pancreatic cancer remains inherently difficult to treat, and the mechanisms underlying therapeutic resistance remain unresolved. Decorin (DCN), a member of the family of small leucine-rich proteoglycans, has emerged as a versatile actor in various malignant diseases. The aim of this study was to further explore the potential clinical significance

Background: It is unclear whether the two device-aided therapies (DATs: deep brain stimulation [DBS] and levodopa–carbidopa intestinal gel [LCIG]) affect personality in patients with Parkinson’s disease (PD). Objective: This retrospective study aims to explore if patients with PD and their close relatives experience any changes in the patient’s personality following the start of DAT. Methods: In t

Background General adiposity, assessed by body mass index (BMI), is a well-established cancer risk factor. This study compared waist circumference (WC), a measure of abdominal adiposity, with BMI as a risk factor for obesity-related cancers, and assessed whether WC provides additional information beyond BMI. Methods We analyzed data from 339 190 individuals in a pooled Swedish cohort with baseline

The globular cluster M15 was observed on three occasions with the High Resolution Camera on- board Chandra in 2001 in order to investigate the X- ray source population in the cluster centre. After subtraction of the two bright central sources, four faint sources were identified within 50 arcsec of the core. One of these sources is probably the planetary nebula K648, making this the first positive

Type 2 diabetes mellitus (T2DM) is a major disease affecting nearly 280 million people worldwide. Whilst the pathophysiological mechanisms leading to disease are poorly understood, dysfunction of the insulin-producing pancreatic beta-cells is key event for disease development. Monitoring the gene expression profiles of pancreatic beta-cells under several genetic or chemical perturbations has shed

The construction, operation and maintenance of transportation infrastructure require energy and materials which impact the environment. Large infrastructure projects thus use resources intensively and leave a significant environmental footprint. To demonstrate and support the sustainability of such large-scale projects, life cycle assessment (LCA) has become a common tool to evaluate environmental

The power take-off (PTO) system and control laws for wave energy converters (WECs) are crucial for system performance. Determining optimal PTO parameters based on different sea states is key for formulating control laws, identifying optimal WEC locations, and optimizing wave-to-wire performance. This study focuses on an oscillating water column (OWC) type WEC developed by Waves4Power using a buoy

Estrogen influences T cell development and enhances infection resistance in females, but its immunological effects during gender-affirming hormone therapy (GAHT) remain poorly understood. Here, we characterize immune adaptations in male rhesus macaques (RMs) treated with 17β-estradiol (E2) or placebo over 7 months. E2 therapy suppressed endogenous testosterone production, induced female physical t

A role of the immune system in Parkinson’s disease (PD) progression has long been suspected due to the increased frequency of activated glial cells and infiltrating T cells in the substantia nigra. It was previously reported that PD donors have increased T cell responses towards PINK1 and α-synuclein (α-syn), two Lewy body-associated proteins. Further, T cell reactivity towards α-syn was highest c