In Vivo Effects of a GHR Synthesis Inhibitor During Prolonged Treatment in Dogs.

The activation of the growth hormone receptor (GHR) is a major determinant of body growth. Defective GHR signaling, as seen in human Laron dwarfism, resulted in low plasma IGF-1 concentrations and limited growth, but also marked absence in the development of breast cancer and type 2 diabetes. In vitro, we identified a small molecule (C#1) that inhibits the translation of GHR mRNA to receptor protein.

How do exhausted parents experience their interactions with their children? A qualitative and participative study.

Introduction: Parental burnout, known as a state of physical and psychological exhaustion, results in an imbalance between the parent's perceived stressors in relation to parenting, and the resources available to the parent to cope with such stressors. The causes and consequences of parental burnout for the parents themselves have been studied from the parents' point of view, but the perception of parents regarding the impact of parental burnout on the parent-child relationship has not yet been documented.

Methods: We conducted a qualitative study through semi-structured interviews with exhausted parents (n=21).

Thermoelectric Limitations of Graphene Nanodevices at Ultrahigh Current Densities.

Graphene is atomically thin, possesses excellent thermal conductivity, and is able to withstand high current densities, making it attractive for many nanoscale applications such as field-effect transistors, interconnects, and thermal management layers. Enabling integration of graphene into such devices requires nanostructuring, which can have a drastic impact on the self-heating properties, in particular at high current densities. Here, we use a combination of scanning thermal microscopy, finite element thermal analysis, and scanning transmission electron microscopy techniques to observe prototype graphene devices in operation and gain a deeper understanding of the role of geometry and interfaces during high current density operation.

Quantum interference enhances the performance of single-molecule transistors.

Quantum effects in nanoscale electronic devices promise to lead to new types of functionality not achievable using classical electronic components. However, quantum behaviour also presents an unresolved challenge facing electronics at the few-nanometre scale: resistive channels start leaking owing to quantum tunnelling. This affects the performance of nanoscale transistors, with direct source-drain tunnelling degrading switching ratios and subthreshold swings, and ultimately limiting operating frequency due to increased static power dissipation.

Connections to the Electrodes Control the Transport Mechanism in Single-Molecule Transistors.

When designing a molecular electronic device for a specific function, it is necessary to control whether the charge-transport mechanism is phase-coherent transmission or particle-like hopping. Here we report a systematic study of charge transport through single zinc-porphyrin molecules embedded in graphene nanogaps to form transistors, and show that the transport mechanism depends on the chemistry of the molecule-electrode interfaces. We show that van der Waals interactions between molecular anchoring groups and graphene yield transport characteristic of Coulomb blockade with incoherent sequential hopping, whereas covalent molecule-electrode amide bonds give intermediately or strongly coupled single-molecule devices that display coherent transmission.

Mental Health Nurses' Social Representations of People Who Experience Mental Illness: A Story of Paradoxes.

Public representations of people who experience mental illness (PEMI) have been well documented within the stigma literature. However, studies about mental health nurses' representations of PEMI are still scarce and characterized by contradictions. Using the theoretical concept of social representation instead of stigma, the current study aims to explore and understand mental health nurses' social representations of PEMI.

WIP1 is a novel specific target for growth hormone action.

DNA damage repair (DDR) is mediated by phosphorylating effectors ATM kinase, CHK2, p53, and γH2AX. We showed earlier that GH suppresses DDR by suppressing pATM, resulting in DNA damage accumulation. Here, we show GH acting through GH receptor (GHR) inducing wild-type p53-inducible phosphatase 1 (WIP1), which dephosphorylated ATM and its effectors in normal human colon cells and three-dimensional human intestinal organoids.

A novel antifolate suppresses growth of FPGS-deficient cells and overcomes methotrexate resistance.

Cancer cells make extensive use of the folate cycle to sustain increased anabolic metabolism. Multiple chemotherapeutic drugs interfere with the folate cycle, including methotrexate and 5-fluorouracil that are commonly applied for the treatment of leukemia and colorectal cancer (CRC), respectively. Despite high success rates, therapy-induced resistance causes relapse at later disease stages.

Phase-Coherent Charge Transport through a Porphyrin Nanoribbon.

Since the early days of quantum mechanics, it has been known that electrons behave simultaneously as particles and waves, and now quantum electronic devices can harness this duality. When devices are shrunk to the molecular scale, it is unclear under what conditions does electron transmission remain phase-coherent, as molecules are usually treated as either scattering or redox centers, without considering the wave-particle duality of the charge carrier. Here, we demonstrate that electron transmission remains phase-coherent in molecular porphyrin nanoribbons connected to graphene electrodes.

Exceptionally clean single-electron transistors from solutions of molecular graphene nanoribbons.

Only single-electron transistors with a certain level of cleanliness, where all states can be properly accessed, can be used for quantum experiments. To reveal their exceptional properties, carbon nanomaterials need to be stripped down to a single element: graphene has been exfoliated into a single sheet, and carbon nanotubes can reveal their vibrational, spin and quantum coherence properties only after being suspended across trenches. Molecular graphene nanoribbons now provide carbon nanostructures with single-atom precision but suffer from poor solubility, similar to carbon nanotubes.

Charge-State Dependent Vibrational Relaxation in a Single-Molecule Junction.

The outcome of an electron-transfer process is determined by the quantum-mechanical interplay between electronic and vibrational degrees of freedom. Nonequilibrium vibrational dynamics are known to direct electron-transfer mechanisms in molecular systems; however, the structural features of a molecule that lead to certain modes being pushed out of equilibrium are not well understood. Herein, we report on electron transport through a porphyrin dimer molecule, weakly coupled to graphene electrodes, that displays sequential tunneling within the Coulomb-blockade regime.

Nanoscale Control of DNA-Linked MoS-Quantum Dot Heterostructures.

The ability to control the assembly of mixed-dimensional heterostructures with nanoscale control is key for the fabrication of novel nanohybrid systems with new functionalities, particularly for optoelectronics applications. Herein we report a strategy to control the assembly of heterostructures and tune their electronic coupling employing DNA as a linker. We functionalized MoS nanosheets (NSs) with biotin-terminated dsDNA employing three different chemical strategies, namely, thiol, maleimide, and aryl diazonium.

Small molecules to regulate the GH/IGF1 axis by inhibiting the growth hormone receptor synthesis.

Growth hormone (GH) and insulin-like growth factor-1 (IGF1) play an important role in mammalian development, cell proliferation and lifespan. Especially in cases of tumor growth there is an urgent need to control the GH/IGF1 axis. In this study we screened a 38,480-compound library, and in two consecutive rounds of analogues selection, we identified active lead compounds based on the following criteria: inhibition the GH receptor (GHR) activity and its downstream effectors Jak2 and STAT5, and inhibition of growth of breast and colon cancer cells.

Healing the Separation in High-Conflict Post-divorce Co-parenting.

Objective: Our research aim is to enrich the conceptualization of high conflict post-divorce co-parenting by understanding the dynamic process involved.

Background: The studied phenomena were explored by linking previous scientific knowledge to practice.

Method: We cross-referenced the previous study results with the experiences reported by eight professionals and tried to answer the following research question: how professionals' experience and previous scientific knowledge contribute to a better understanding of HC post-divorce co-parenting? Individual face to face interviews were conducted and analyzed regarding the qualitative theoretical reasoning of thematic analysis.

Statistical signature of electrobreakdown in graphene nanojunctions.

Controlled electrobreakdown of graphene is important for the fabrication of stable nanometer-size tunnel gaps, large-scale graphene quantum dots, and nanoscale resistive switches, etc. However, owing to the complex thermal, electronic, and electrochemical processes at the nanoscale that dictate the rupture of graphene, it is difficult to generate conclusions from individual devices. We describe here a way to explore the statistical signature of the graphene electrobreakdown process.

Contrast Mechanisms in Secondary Electron e-Beam-Induced Current (SEEBIC) Imaging.

Over the last few years, a new mode for imaging in the scanning transmission electron microscope (STEM) has gained attention as it permits the direct visualization of sample conductivity and electrical connectivity. When the electron beam (e-beam) is focused on the sample in the STEM, secondary electrons (SEs) are generated. If the sample is conductive and electrically connected to an amplifier, the SE current can be measured as a function of the e-beam position.

Mapping Conductance and Switching Behavior of Graphene Devices In Situ.

Graphene is proposed for use in various nanodevice designs, many of which harness emergent quantum properties for device functionality. However, visualization, measurement, and manipulation become nontrivial at nanometer and atomic scales, representing a significant challenge for device fabrication, characterization, and optimization at length scales where quantum effects emerge. Here, proof of principle results at the crossroads between 2D nanoelectronic devices, e-beam-induced modulation, and imaging with secondary electron e-beam induced currents (SEEBIC) is presented.

Imaging Secondary Electron Emission from a Single Atomic Layer.

Graphene-based devices hold promise for a wide range of technological applications. Yet characterizing the structure and the electrical properties of a material that is only one atomic layer thick still poses technical challenges. Recent investigations indicate that secondary-electron electron-beam-induced current (SE-EBIC) imaging can reveal subtle details regarding electrical conductivity and electron transport with high spatial resolution.

Controlling the Entropy of a Single-Molecule Junction.

Single molecules are nanoscale thermodynamic systems with few degrees of freedom. Thus, the knowledge of their entropy can reveal the presence of microscopic electron transfer dynamics that are difficult to observe otherwise. Here, we apply thermocurrent spectroscopy to directly measure the entropy of a single free radical molecule in a magnetic field.

Charge transport through extended molecular wires with strongly correlated electrons.

Electron-electron interactions are at the heart of chemistry and understanding how to control them is crucial for the development of molecular-scale electronic devices. Here, we investigate single-electron tunneling through a redox-active edge-fused porphyrin trimer and demonstrate that its transport behavior is well described by the Hubbard dimer model, providing insights into the role of electron-electron interactions in charge transport. In particular, we empirically determine the molecule's on-site and inter-site electron-electron repulsion energies, which are in good agreement with density functional calculations, and establish the molecular electronic structure within various oxidation states.

Understanding Electrical Conduction and Nanopore Formation During Controlled Breakdown.

Controlled breakdown has recently emerged as a highly appealing technique to fabricate solid-state nanopores for a wide range of biosensing applications. This technique relies on applying an electric field of approximately 0.4-1 V nm across the membrane to induce a current, and eventually, breakdown of the dielectric.

Nanobody-targeted photodynamic therapy for the treatment of feline oral carcinoma: a step towards translation to the veterinary clinic.

Nanobody-targeted photodynamic therapy (NB-PDT) has been developed as a potent and tumor-selective treatment, using nanobodies (NBs) to deliver a photosensitizer (PS) specifically to cancer cells. Upon local light application, reactive oxygen species are formed and consequent cell death occurs. NB-PDT has preclinically shown evident success and we next aim to treat cats with oral squamous cell carcinoma (OSCC), which has very limited therapeutic options and is regarded as a natural model of human head and neck SCC.

A Thermodynamic Approach to Measuring Entropy in a Few-Electron Nanodevice.

The entropy of a system gives a powerful insight into its microscopic degrees of freedom; however, standard experimental ways of measuring entropy through heat capacity are hard to apply to nanoscale systems, as they require the measurement of increasingly small amounts of heat. Two alternative entropy measurement methods have been recently proposed for nanodevices: through charge balance measurements and transport properties. We describe a self-consistent thermodynamic framework for applying thermodynamic relations to few-electron nanodevices-small systems, where fluctuations in particle number are significant, whilst highlighting several ongoing misconceptions.

Graphene nanogaps for the directed assembly of single-nanoparticle devices.

Significant advances in the synthesis of low-dimensional materials with unique and tuneable electrical, optical and magnetic properties has led to an explosion of possibilities for realising hybrid nanomaterial devices with unconventional and desirable characteristics. However, the lack of ability to precisely integrate individual nanoparticles into devices at scale limits their technological application. Here, we report on a graphene nanogap based platform which employs the large electric fields generated around the point-like, atomically sharp nanogap electrodes to capture single nanoparticles from solution at predefined locations.