The defect emission from h-BN at 1.55 eV is interesting as it enables optical readout of spins. It is necessary to identify the nature of the relevant point defects for its controlled introduction. However, it is challenging to engineer point defects in h-BN without changing the local atomic structure. Here, we controllably introduce boron vacancies in h-BN using an ultrahigh spatial resolution and low-energy He⁺ ion beam. By optimizing the He⁺ ion irradiation conditions, we control the quantity and location of defects spatially and along the depth of h-BN to achieve a robust photoluminescence emission at 1.55 eV from 10 K to room temperature. We show that as-generated defects activate an additional Raman mode at 1295 cm^-1. Electron energy loss spectroscopy confirms introduction of boron vacancies without modification of the local h-BN crystal structure. Our results provide a deterministic strategy to create scalable boron vacancy emitters in h-BN for quantum photonics.

Objective: To determine whether passive leg movement (PLM) in critically ill patients increases oxygen consumption (VO2), and, if so, the relative contributions of increases in cardiac index (CI) and oxygen extraction (O2ER). Design: Prospective, controlled study. Setting: Multidisciplinary department of intensive care in a university hospital. Patients: Sixteen ICU patients undergoing PLM as part of their standard management were divided into two groups according to the presence of cardiac disease and /or cardiac dysfunction. Outcome measures: VO2, CI oxygen extraction. Intervention: Complete hemodynamic data were obtained before and 5 minutes after starting PLM. Results: For the whole group, VO2 increased from 123±23 to 143±34 ml/min.m2 (p<0.05). In the eight patients with cardiac dysfunction, the increase in VO2 was met by an increase in O2ER (from 37.2±7.3 to 41.1±7.1 %, p<0.01) without a significant increase in CI (from 2.44±0.56 to 2.52±0.65 l/min/m2, p=ns). In the eight patients without cardiac dysfunction, the increase in VO2 was met by an increase of CI (from 3.88±0.90 to 4.36±1.00 l/min/m2, p<0.01) without a significant increase in O2ER (from 26.4±7.3 to 27.2±7.9 %, p=ns). Conclusions: Simple maneuvers like PLM can influence the hemodynamic status of ICU patients. The study of the relation between CI and O2 ER may be helpful to assess the hemodynamic response to nursing or physical therapy procedures.

Floating gate memory (FGM), composed of van der Waals (vdW) junctions with an atomically thin floating layer for charge storage, is widely employed to develop logic-in memories and in-sensor computing devices. Most research efforts of FGM are spent on achieving long-term charge storage and fast reading/writing for flash and random-access memory. However, dynamic modulation of memory time via a tunneling barrier and vdW interfaces, which is critical for synaptic computing and machine vision, is still lacking. Here, a van der Waals short-term memory with tunable memory windows and retention times from milliseconds to thousands of seconds is reported, which is approximately exponentially proportional to the thickness h-BN (hexagonal boron nitride) barrier. The specific h-BN barrier with fruitful gap states provides charge release channels for trapped charges, making the vdW device switchable between positive photoconductance and negative photoconductance with a broadband light from IR to UV range. The dynamic short-term memory with tunable photo response highlights the design strategy of novel vdW memory vis interface engineering for further intelligent information storage and optoelectronic detection.

Dobutamine infusion has been proposed to increase splanchnic blood flow in septic conditions, but its' effects on liver blood flow and metabolism have not been well defined. We investigated the effects of dobutamine on liver blood flow, metabolism, and pathology in a canine hyperdynamic endotoxic shock model. Twenty-one dogs were anesthetized and paralyzed. After the administration of 2 mg/kg endotoxin, normal saline was infused to restore the pulmonary artery-occluded pressure to 10 mmHg. The dogs were then randomized to receive fluids either alone (n = 7) or combined with a dobutamine infusion at a rate of 5 (n = 7) or 10 microg/kg per min (n = 7). After initial fluid resuscitation, cardiac index (CI) increased from 152+/-48 to 386+/-97 mL/kg per min (P < 0.01) and then slightly decreased with time in the control group, but further increased to 458+/-54 mL/kg per min (P< 0.05) and remained elevated in the group treated with 5 microg/kg per min of dobutamine. Portal vein and hepatic arterial blood flows followed a similar course and increased with fluid resuscitation. Both decreased with time in the control group, but further increased in the dobutamine-treated animals. Liver oxygen delivery (DO2liv) increased with fluids from 2.2+/-2.4 to 3.8+/-1.9 mL/kg per min (P < 0.01) and further increased in the dobutamine-treated animals to 4.1+/-1.2 mL/kg per min. This was associated with an increase in liver oxygen uptake from 1.6+/-1.6 to 2.9+/-1.1 mL/kg per min with fluid resuscitation and a further increase to 4.3+/-1.5 mL/kg per min with dobutamine administration. Lactate consumption and hepatic vein oxygen saturation increased with initial fluid resuscitation and then decreased with time in the control group, but not in the dobutamine-treated animals. Increasing the dose of dobutamine to 10 microg/kg per min did not alter this response. At the end of the experiment, liver tissue samples were obtained for microscopic studies. The histological lesions seen in the control group were unaffected by dobutamine. In conclusion, dobutamine increases liver blood flow and metabolism, but does not affect microscopic findings in this hyperdynamic endotoxic shock model.

Summary: Background: Angiogenesis is a promising novel therapeutic strategy to provide new venues for blood flow in patients with severe ischaemic heart and peripheral vascular diseases. Among several stimulators, the vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2, basic FGF) have been most widely studied. Methods: Preclinical animal studies suggested the strong therapeutic potentials of VEGF, and such positive effects have also been confirmed in a limited number of phase I clinical trials. However, some animal studies suggest the existence of a considerable risk associated with angiogenic therapy. Results: VEGF is strongly expressed in human atherosclerotic plaques, it promotes atherosclerosis in animal models, and there is evidence indicating that the plaque growth is dependent on the formation of new blood vessels. Therefore, for a convincing demonstration of the safety and efficacy of VEGF gene therapy, the clinical effects need to be evaluated in larger randomized, double-blinded clinical trials. Conclusions: Further understanding of the mechanisms of activity of angiogenic growth factors and the formation of blood vessels is required, and improved gene transfer methods are necessary to introduce therapeutic angiogenesis in clinical practice. Zusammenfassung: Grundlagen: Die Angiogenese ist eine vielversprechende neue therapeutische Strategie bei Patienten mit Myokardischämie und peripheren Gefäßerkrankungen. Unter den verschiedensten Stimulatoren sind der Vascular Endothelial Growth Factor (VEGF) und der Fibroblast Growth Factor-2 (FGF-2, basic FGF) am besten erforscht. Methodik: Vorklinische Tierversuche lassen ein großes therapeutisches Potential erwarten, und diese positiven Effekte werden von einer begrenzten Zahl von Phase-I-Studien bestätigt. Einige der experimentellen Studien lassen erhebliche Risiken in Verbindung mit einer angiogenetischen Therapie vermuten. Ergebnisse: VEGF wird von humanen atherosklerotischen Plaques verstärkt gebildet, fördert Atherosklerose am Tiermodell, und es gibt Anzeichen, daß das Plaquewachstum von der Bildung neuer Blutgefäße abhängig ist. Daher sollten die klinischen Effekte, um die Sicherheit und Effizienz einer VEGF-Gentherapie zu zeigen, in großen, randomisierten, doppelblinden, klinischen Studien evaluiert werden. Schlußfolgerungen: Um eine therapeutische Angiogenese in der klinischen Praxis anwenden zu können, ist ein genaueres Verständnis der Mechanismen der Aktivität von angiogenetischen Wachstumsfaktoren und der Bildung von Blutgefäßen und die Verbesserung der Gentransfermethoden nötig.

The final common pathway involved in the cardiovascular alterations of septic shock is incompletely defined. The opening of KATP channels is associated with vasorelaxation and alterations in cardiac contractility. This event may be triggered during septic shock by increased nitric oxide (NO) production, by a decreased intracellular content of ATP, or by a change in the transmembrane electrical potential. In the present study, we assessed the effects of glibenclamide, an agent that blocks the opening of KATP channels in vitro, on the contractile response of rat aortic rings to norepinephrine, and in vivo in anesthetized dogs, with or without exposure to Escherichia coli endotoxin. In vitro, glibenclamide decreased the contractile response to norepinephrine in the presence of endotoxin, provided that the endothelium was intact. In vivo, administration of 0.15 mg/kg increased systemic vascular resistance (SVR) in the absence of endotoxin only, and increased myocardial performance. A higher dose of 1 mg/kg increased SVR and decreased myocardial performance, both during endotoxic shock and in control conditions. Renal and mesenteric blood flows decreased, but the respective fractional flows were unchanged. Oxygen delivery decreased in both experimental conditions, but oxygen consumption decreased only in control conditions. The in vitro observations suggest that the opening of KATP channels is involved in the regulation of vascular tone during endotoxemia, via an endothelium-dependent mechanism. As different effects of glibenclamide were observed in vivo, the importance of the opening of KATP channels in endotoxic shock may be limited.

Treatment of the acute respiratory distress syndrome includes both supportive measures and correction of the underlying cause. Various pharmacological interventions have been proposed to limit the severity of lung injury and enhance the healing process, including exogenous surfactant, inhaled vasodilators (mainly nitric oxide), corticosteroids, prostaglandin E1, antioxidants (N-acetylcysteine), ketoconazole and other substances. Some of these interventions are administered via the airways, for example inhaled nitric oxide or liquid ventilation with perfluorocarbons. Some have beneficial effects on surrogate end-points such as pulmonary gas exchange. However, in large prospective trials none of these pharmacological approaches have resulted in significantly improved survival in acute respiratory distress syndrome patients.

Magnetically directable materials containing iron oxide nanoparticles (IONPs) have been utilized for a variety of medical applications, including localized drug delivery. Regenerated silk fibroin (RSF) has also been used in numerous regenerative medicine and drug delivery applications, given its biocompatibility and tunable properties. In this work, we explored the hypothesis that chemically conjugating IONPs to RSF to anchor the IONPs to silk microparticles would provide better magnetic guidance than nonconjugated IONPs untethered to silk microparticles. IONPs were fabricated using a coprecipitation method and conjugated with glutathione (GSH) prior to mixing with RSF. IONPs incorporated into RSF were mixed with potassium phosphate buffer to fabricate microparticles. IONPs with and without GSH were characterized for particle size, shape, morphology, GSH conjugation efficiency, and composition. Silk iron microparticles (SIMPs) were also characterized for particle size, shape, and composition and tested for stability, degradation properties, magnetic movability, and cytotoxicity. IONPs demonstrated a uniform size distribution and spherical morphology. Conjugation of IONPs with GSH was verified through changes in the X-ray photoelectron spectroscopy (XPS) and Fourier-transform infrared spectroscopy (FTIR) spectra. IONPs and RSF were able to be chemically conjugated and fabricated into SIMPs, which demonstrated a spherical and porous morphology. FTIR revealed an increased β-sheet content in SIMPs, suggesting that the IONPs may be inducing conformational changes in the silk fibroin. SIMPs showed stability up to 4 weeks in ultrapure water and rapid enzymatic degradation within 24 h. SIMPs were able to be moved magnetically through solution and through a hydrogel and were not cytotoxic.

The charge carriers in a material can, under special circumstances, behave as a viscous fluid. In this work, we investigated such behavior by using scanning tunneling potentiometry to probe the nanometer-scale flow of electron fluids in graphene as they pass through channels defined by smooth and tunable in-plane p-n junction barriers. We observed that as the sample temperature and channel widths are increased, the electron fluid flow undergoes a Knudsen-to-Gurzhi transition from the ballistic to the viscous regime characterized by a channel conductance that exceeds the ballistic limit, as well as suppressed charge accumulation against the barriers. Our results are well modeled by finite element simulations of two-dimensional viscous current flow, and they illustrate how Fermi liquid flow evolves with carrier density, channel width, and temperature.