Single-Crystal Organic Charge-Transfer Interfaces probed using Schottky-Gated Heterostructures

Organic semiconductors based on small conjugated molecules generally behave as insulators when undoped, but the hetero-interfaces of two such materials can show electrical conductivity as large as in a metal. Although charge transfer is commonly invoked to explain the phenomenon, the details of the process and the nature of the interfacial charge carriers remain largely unexplored. Here we use Schottky-gated heterostructures to probe the conducting layer at the interface between rubrene and PDIF-CN2 single crystals. Gate-modulated conductivity measurements demonstrate that interfacial transport is due to electrons, whose mobility exhibits band-like behavior from room temperature to ~ 150 K, and remains as high as ~ 1 cm2V-1s-1 at 30 K for the best devices. The electron density decreases linearly with decreasing temperature, an observation that can be explained quantitatively based on the heterostructure band diagram. These results elucidate the electronic structure of rubrene-PDIF-CN2 interfaces and show the potential of Schottky-gated organic heterostructures for the investigation of transport in molecular semiconductors.Comment: 37 pages, 9 Figures (including supplementary information

Very low bias stress in n-type organic single crystal transistors

Bias stress effects in n-channel organic field-effect transistors (OFETs) are investigated using PDIF-CN2 single-crystal devices with Cytop gate dielectric, both under vacuum and in ambient. We find that the amount of bias stress is very small as compared to all (p-channel) OFETs reported in the literature. Stressing the PDIF-CN2 devices by applying 80 V to the gate for up to a week results in a decrease of the source drain current of only ~1% under vacuum and ~10% in air. This remarkable stability of the devices leads to characteristic time constants, extracted by fitting the data with a stretched exponential - that are \tau ~ 2\cdot10^9 s in air and \tau ~ 5\cdot10^9 s in vacuum - approximately two orders of magnitude larger than the best values reported previously for p-channel OFETs.Comment: Submitted to Applied Physics Letters; 14 pages, 3 figure

CANcer BEhavioural nutrition and exercise feasibility trial (CanBenefit); phase I qualitative interview findings

Background: Older people with lung cancer are often frail and unfit due to their cancer and co-morbidities and may tolerate cancer treatments poorly. Physical activity (PA) and a healthy diet offer quality of life benefit to people with cancer before, during, and post treatment. However, older adults are poorly represented in the clinical trials on which recommendations were made. Objective: To assess the acceptability, usefulness, and practicality of delivering a tailored wellbeing (PA and nutrition) intervention for older adults with lung cancer before, during, and after cancer treatments (chemotherapy and/or immunotherapy). Methods: Semi-structured interviews conducted with nine patients with lung cancer and three patients with mesothelioma, ≥70 years and ten informal carers, and nine Multidisciplinary Team (MDT) members. A topic guide covered the acceptability, usefulness, and practicality of a wellbeing intervention as well as specific feedback on individual components. Data were subjected to thematic analysis. Findings: Four themes were generated: current lack of wellbeing care in clinical work; preferred “can have” dietary and “can do” PA advice; peer support as facilitating factor; and barriers to compliance including patients' psychological and physical issues as well as current cancer pathway and staffing issues. Conclusion: Older adults with lung cancer would welcome a proactive, clear and instructive, wellbeing intervention. Many barriers to compliance exist, particularly before and during cancer treatments due to the psycho-social impact of diagnosis, and the effects of cancer treatment. The intervention must be tailored to individual need and address physical limitations, psychological and social welfare in addition to PA and nutritional advice

Advanced antifouling and antibacterial hydrogels enabled by controlled thermo-responses of a biocompatible polymer composite

To optimally apply antibiotics and antimicrobials, smart wound dressing conferring controlled drug release and preventing adhesions of biological objects is advantageous. Poly(; N; -isopropylacrylamide) (PNIPAAm), a conventional thermo-responsive polymer, and poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC), a typical antifouling polymer, have therefore potential to be fabricated as copolymers to achieve dual functions of thermo-responsiveness and antifouling. Herein, a hydrogel made of PNIPAM-; co; -PMPC was designed and loaded with octenidine, a widely applied antimicrobial agent for wound treatment, to achieve both antifouling and triggered drug release. The thermo-switch of the fabricated hydrogel allowed 25-fold more octenidine release at 37 °C (infected wound temperature) than at 30 °C (normal skin temperature) after 120 minutes, which led to at least a 3 lg reduction of the viable bacteria at 37 °C on artificially infected wounds. Furthermore, we pioneeringly assessed the antifouling property of the material in PBS buffer using single molecule/cell/bacterial force spectroscopy, and revealed that the fabricated hydrogel displayed distinctive antifouling properties against proteins, mammalian cells, and bacteria. This work demonstrated a promising design of a hydrogel applicable for preventing and treating wound infections. The concept of dual-functional materials can be envisaged for other clinical applications related to the prevention of biofilm-associated infections, such as urinary catheters, stents, and dental implants

Hyponatremia and Psychiatric Diseases

Eating disorders, psychotic illnesses, and substance use disorders are some of the more common psychiatric conditions encountered in clinical practice that are associated with hyponatremia. The mechanisms that lead to hyponatremia vary, and at times hyponatremia may be a result of a drug side effect or drug-drug interaction. Additionally, hyponatremia from a non-psychiatric condition may lead to psychiatric symptomatology. Given the potential for hyponatremia to cause significant morbidity and potential mortality, clinicians are urged to consider screening for plasma sodium in patients at risk of hyponatremia, such as patients in the three categories of psychiatric conditions described above. Treatment of hyponatremia consists of various acute interventions, with consideration that treatment of the underlying psychiatric condition may help to diminish or eliminate the frequency of hyponatremic episodes in the long run

Dissecting heterogeneous cell populations across drug and disease conditions with PopAlign

Single-cell measurement techniques can now probe gene expression in heterogeneous cell populations from the human body across a range of environmental and physiological conditions. However, new mathematical and computational methods are required to represent and analyze gene expression changes that occur in complex mixtures of single cells as they respond to signals, drugs, or disease states. Here, we introduce a mathematical modeling platform, PopAlign, that automatically identifies subpopulations of cells within a heterogeneous mixture, and tracks gene expression and cell abundance changes across subpopulations by constructing and comparing probabilistic models. We apply PopAlign to analyze the impact of 42 different immunomodulatory compounds on a heterogeneous population of donor-derived human immune cells as well as patient-specific disease signatures in multiple myeloma. PopAlign scales to comparisons involving tens to hundreds of samples, enabling large-scale studies of natural and engineered cell populations as they respond to drugs, signals or physiological change

pH-responsive silica nanoparticles for the treatment of skin wound infections

Chronic wounds are not only a burden for patients but also challenging for clinic treatment due to biofilm formation. Here, we utilized the phenomenon that chronic wounds possess an elevated local pH of 8.9 and developed pH-sensitive silica nanoparticles (SiNPs) to achieve a targeted drug release on alkaline wounds and optimized drug utility. Chlorhexidine (CHX), a disinfectant and antiseptic, was loaded into SiNPs as the model drug. The loaded CHX displayed a release 4 - 5 fold higher at pH 8.0 and 8.5 than at pH 6.5, 7.0 and 7.4. CHX-SiNPs furthermore exhibited a distinctive antibacterial activity at pH 8.0 and 8.5 against both Gram-negative and -positive bacterial pathogens, while no cytotoxicity was found according to cell viability analysis. The CHX-SiNPs were further formulated into alginate hydrogels to allow ease of use. The antibacterial efficacy of CHX-SiNPs was then studied with artificial wounds on ex vivo human skin. Treatment with CHX-SiNPs enabled nearly a 4-lg reduction of the viable bacterial cells, and the alginate formulated CHX-SiNPs led to almost a 3-lg reduction compared to the negative controls. The obtained results demonstrated that CHX-SiNPs are capable of efficient pH-triggered drug release, leading to high antibacterial efficacy. Moreover, CHX-SiNPs enlighten clinic potential towards the treatment of chronic wound infections. STATEMENT OF SIGNIFICANCE: A platform for controlled drug release at a relatively high pH value i.e., over 8, was established by tuning the physical structures of silica nanoparticles (SiNPs). Incorporation of chlorhexidine, an antimicrobial agent, into the fabricated SiNPs allowed a distinctive inhibition of bacterial growth at alkaline pHs, but not at acidic pHs. The efficacy of the SiNPs loaded with chlorhexidine in treating wound infections was further validated by utilizing ex vivo human skin samples. The presented work demonstrates clinic potential of employing alkaline pH as a non-invasive stimulus to achieve on-demand delivery of antimicrobials through SiNPs, showcasing a valuable approach to treating bacterial infections on chronic wounds

A supramodal representation of the body surface

The ability to accurately localize both tactile and painful sensations on the body is one of the most important functions of the somatosensory system. Most accounts of localization refer to the systematic spatial relation between skin receptors and cortical neurons. The topographic organization of somatosensory neurons in the brain provides a map of the sensory surface. However, systematic distortions in perceptual localization tasks suggest that localizing a somatosensory stimulus involves more than simply identifying specific active neural populations within a somatotopic map. Thus, perceptual localization may depend on both afferent inputs and other unknown factors. In four experiments, we investigated whether localization biases vary according to the specific skin regions and subset of afferent fibers stimulated. We represented localization errors as a ‘perceptual map’ of skin locations. We compared the perceptual maps of stimuli that activate Aβ (innocuous touch), Aδ (pinprick pain), and C fibers (non-painful heat) on both the hairy and glabrous skin of the left hand. Perceptual maps exhibited systematic distortions that strongly depended on the skin region stimulated. We found systematic distal and radial (i.e., towards the thumb) biases in localization of touch, pain, and heat on the hand dorsum. A less consistent proximal bias was found on the palm. These distortions were independent of the population of afferent fibers stimulated, and also independent of the response modality used to report localization. We argue that these biases are likely to have a central origin, and result from a supramodal representation of the body surface

Recombination Monophosphoryl Lipid A-Derived Vacosome for the Development of Preventive Cancer Vaccines

Recently, there has been an increasing interest for utilizing the host immune system to fight against cancer. Moreover, cancer vaccines, which can stimulate the host immune system to respond to cancer in the long term, are being investigated as a promising approach to induce tumor-specific immunity. In this work, we prepared an effective cancer vaccine (denoted as vacosome) by reconstructing the cancer cell membrane, monophosphoryl lipid A as a toll-like receptor 4 agonist, and egg phosphatidylcholine. The vacosome triggered and enhanced bone marrow dendritic cell maturation as well as stimulated the antitumor response against breast cancer 4T1 cells in vitro. Furthermore, an immune memory was established in BALB/c mice after three-time preimmunization with the vacosome. After that, the immunized mice showed inhibited tumor growth and prolonged survival period (longer than 50 days). Overall, our results demonstrate that the vacosome can be a potential candidate for clinical translation as a cancer vaccine.Peer reviewe