Multiphoton-pumped UV-Vis transient absorption spectroscopy of 2D materials: basic concepts and recent applications.

2D materials are considered a key element in the development of next-generation electronics (nanoelectronics) due to their extreme thickness in the nanometer range and unique physical properties. The ultrafast dynamics of photoexcited carriers in such materials are strongly influenced by their interfaces, since the thickness of 2D materials is much smaller than the typical depth of light penetration into their bulk counterparts and the mean free path of photoexcited carriers. The resulting collisions of photoexcited carriers with interfacial potential barriers of 2D materials in the presence of a strong laser field significantly alter the overall dynamics of photoexcitation, allowing laser light to be directly absorbed by carriers in the conduction/valence band through the inverse bremsstrahlung mechanism.

Characterization of charge-carrier dynamics at the BiSe/MgFinterface by multiphoton pumped UV-Vis transient absorption spectroscopy.

Separate relaxation dynamics of electrons and holes in experiments on optical pumping-probing of semiconductors is rarely observed due to their overlap. Here we report the separate relaxation dynamics of long-lived (∼200s) holes observed at room temperature in a 10 nm thick film of the 3D topological insulator (TI) BiSecoated with a 10 nm thick MgFlayer using transient absorption spectroscopy in the UV-Vis region. The ultraslow hole dynamics was observed by applying resonant pumping of massless Dirac fermions and bound valence electrons in BiSeat a certain wavelength sufficient for their multiphoton photoemission and subsequent trapping at the BiSe/MgFinterface.

Two-photon IR pumped UV-Vis transient absorption spectroscopy of Dirac fermions in the topological insulator BiSe.

It is often taken for granted that in pump-probe experiments on the topological insulator (TI) BiSeusing IR pumping with a commercial Ti:sapphire laser [∼800 nm (1.55 eV photon energy)], the electrons are excited in the one-photon absorption regime, even when pumped with absorbed fluences in the mJ cmrange. Here, using UV-Vis transient absorption (TA) spectroscopy, we show that even at low-power Infrared (IR) pumping with absorbed fluences in theJ cmrange, the TA spectra of the TI BiSeextend across a part of the UV and the entire visible region.

Coherent surface-to-bulk vibrational coupling in the 2D topologically trivial insulator BiSe monitored by ultrafast transient absorption spectroscopy.

Ultrafast carrier relaxation in the 2D topological insulator (TI) BiSe [gapped Dirac surface states (SS)] and how it inherits ultrafast relaxation in the 3D TI BiSe (gapless Dirac SS) remains a challenge for developing new optoelectronic devices based on these materials. Here ultrashort (~ 100 fs) pumping pulses of ~ 340 nm wavelength (~ 3.65 eV photon energy) were applied to study ultrafast electron relaxation in the 2D TI BiSe films with a thickness of 2 and 5 quintuple layers (~ 2 and ~ 5 nm, respectively) using transient absorption (TA) spectroscopy in the ultraviolet-visible spectral region (1.

Dynamic Opening of a Gap in Dirac Surface States of the Thin-Film 3D Topological Insulator BiSe Driven by the Dynamic Rashba Effect.

Optical control of Dirac surface states (SS) in topological insulators (TI) remains one of the most challenging problems governing their potential applications in novel electronic and spintronic devices. Here, using visible-range transient absorption spectroscopy exploiting ∼340 nm (∼3.65 eV) pumping, we provide evidence for dynamic opening of a gap in the Dirac SS of the thin-film 3D TI BiSe, which has been induced by the dynamic Rashba effect occurring in the film bulk with increasing optical pumping power (photoexcited carrier density).

Klotho Protein and Cardio-Vascular System.

Klotho protein affects a number of metabolic pathways essential for pathogenesis of cardio-vascular diseases and their prevention. It inhibits lipid peroxidation and inflammation, as well as prevents endothelial injury and calcification of blood vessels. Klotho decreases rigidity of blood vessels and suppresses development of the heart fibrosis.

Systemic Klotho therapy protects against insulitis and enhances beta-cell mass in NOD mice.

The levels of the anti-aging protein α-Klotho, in its soluble form (s-Klotho), are depressed in the circulation of patients with type 1 diabetes (T1D) or type 2 diabetes (T2D). Gene transfer experiments have suggested a protective role for β-cell specific expression of α-Klotho in murine models of T1D and T1D, but these approaches are not easily translatable to clinical therapy. It is unknown whether systemic s-Klotho protein treatment ameliorates disease in T1D, which is characterized by autoimmune destruction of β cells.

Lymphatic vessels identified in failed corneal transplants with neovascularisation.

Background: Corneal transplant failure with neovascularisation is a leading indication for full-thickness grafts in patients. Lymphangiogenesis is implicated in the pathology of graft failure, and here we systematically evaluate failed human corneal transplants with neovascularisation for the presence of lymphatic vessels.

Methods: Nine failed grafts with neovascularisation, based on H&E staining with subsequent immunoperoxidase staining for CD31, a blood vessel marker, were selected.

The anti-aging protein Klotho is induced by GABA therapy and exerts protective and stimulatory effects on pancreatic beta cells.

Systemic gamma-aminobutyric acid (GABA) therapy prevents or ameliorates type 1 diabetes (T1D), by suppressing autoimmune responses and stimulating pancreatic beta cells. In beta cells, it increases insulin secretion, prevents apoptosis, and induces regeneration. It is unclear how GABA mediates these effects.

Nonlinear optical observation of coherent acoustic Dirac plasmons in thin-film topological insulators.

Low-energy collective electronic excitations exhibiting sound-like linear dispersion have been intensively studied both experimentally and theoretically for a long time. However, coherent acoustic plasmon modes appearing in time-domain measurements are rarely observed due to Landau damping by the single-particle continua. Here we report on the observation of coherent acoustic Dirac plasmon (CADP) modes excited in indirectly (electrostatically) opposite-surface coupled films of the topological insulator BiSe.

Neuropilin-1 is a receptor for extracellular miRNA and AGO2/miRNA complexes and mediates the internalization of miRNAs that modulate cell function.

Extracellular miRNAs are increasingly studied as markers for specific diseases. They are released in biological fluids in a remarkably stable form, and may play a role in intercellular communication. They are thought to be protected against degradation by either encapsulation within microparticles, or by binding to proteins (mostly AGO2).

Effect of Mn doping on ultrafast carrier dynamics in thin films of the topological insulator Bi2Se3.

Transient reflectivity (TR) measured at laser photon energy 1.51 eV from the indirectly intersurface-coupled topological insulator Bi2-x Mn x Se3 films (12 nm thick) revealed a strong dependence of the rise-time and initial decay-time constants on photoexcited carrier density and Mn content. In undoped samples (x  =  0), these time constants are exclusively governed by electron-electron and electron-phonon scattering, respectively, whereas in films with x  =  0.

Immunological GABAergic interactions and therapeutic applications in autoimmune diseases.

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain. However, it is also produced in other sites; notably by pancreatic β cells and immune cells. The function of GABA in the immune system is at an early stage of study, but it exerts inhibitory effects that are relevant to autoimmune diseases.

Thickness tunable quantum interference between surface phonon and Dirac plasmon states in thin films of the topological insulator Bi₂Se₃.

We report on a >100-fold enhancement of Raman responses from Bi2Se3 thin films if laser photon energy switches from 2.33 eV (532 nm) to 1.58 eV (785 nm), which is due to direct optical coupling to Dirac surface states (SS) at the resonance energy of ∼1.

GABA protects pancreatic beta cells against apoptosis by increasing SIRT1 expression and activity.

We have previously shown that GABA protects pancreatic islet cells against apoptosis and exerts anti-inflammatory effects. Notably, GABA inhibited the activation of NF-κB in both islet cells and lymphocytes. NF-κB activation is detrimental to beta cells by promoting apoptosis.

GABA protects human islet cells against the deleterious effects of immunosuppressive drugs and exerts immunoinhibitory effects alone.

Background: We recently found that γ-aminobutyric acid (GABA) protects mouse islet β cells. It prevented autoimmune type 1 diabetes in mice, induced islet β-cell regeneration, and exerted immunoinhibitory effects. However, it is not known whether GABA would be equally active on human islet and immune cells.

Neuropilins are multifunctional coreceptors involved in tumor initiation, growth, metastasis and immunity.

The neuropilins (Nrps) are multifunctional proteins involved in development, immunity and cancer. Neuropilin-1 (Nrp1), or its homologue neuropilin-2 (Nrp2), are coreceptors that enhance responses to several growth factors (GFs) and other mediators. Nrps are coreceptors for the class 3 semaphorins (SEMA3), involved in axonal guidance, and several members of the vascular endothelial growth factor (VEGF) family.

Neuropilin-1 is expressed by breast cancer stem-like cells and is linked to NF-κB activation and tumor sphere formation.

Cancer stem cells (CSCs) initiate tumors and have a high resistance to conventional cancer therapy. Tranilast is an orally active drug of low toxicity that exerts inhibitory effects on breast CSCs. This appears to depend on its aryl hydrocarbon receptor (AHR) agonistic activity, but this receptor has diverse functions and it is unclear how CSCs are inhibited.

Immunity against a therapeutic xenoprotein/Fc construct delivered by gene transfer is reduced through binding to the inhibitory receptor FcγRIIb.

Background: Therapeutic xenoproteins are immunogenic and can induce neutralizing antibodies. When delivered by intramuscular injection of a plasmid vector, this mimics classical DNA vaccination. To demonstrate this, we chose Exendin-4 (Ex4), which is a glucagon-like peptide-1 mimetic xenoprotein in clinical use for treating type 2 diabetes.

GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes.

Type 1 diabetes (T1D) is an autoimmune disease characterized by insulitis and islet β-cell loss. Thus, an effective therapy may require β-cell restoration and immune suppression. Currently, there is no treatment that can achieve both goals efficiently.

Neuropilin-1 exerts co-receptor function for TGF-beta-1 on the membrane of cancer cells and enhances responses to both latent and active TGF-beta.

Neuropilin (Nrp)-1 and Nrp-2 are multifunctional proteins frequently expressed by cancer cells and contribute to tumor progression by mechanisms that are not well understood. They are co-receptors for vascular endothelial growth factor and class 3 semaphorins, but recently we found that Nrp1 also binds latent and active transforming growth factor (TGF)-β1, and activates the latent form latency-associated peptide (LAP)-TGF-β1. Here, we report that Nrp1 has affinity for TGF-β receptors TβRI and TβRII, the signaling TGF-β receptors, as well as TβRIII (betaglycan), as determined in binding assays, pull down assays and confocal microscopy.

Breast cancer stem-like cells are inhibited by a non-toxic aryl hydrocarbon receptor agonist.

Background: Cancer stem cells (CSCs) have increased resistance to cancer chemotherapy. They can be enriched as drug-surviving CSCs (D-CSCs) by growth with chemotherapeutic drugs, and/or by sorting of cells expressing CSC markers such as aldehyde dehydrogenase-1 (ALDH). CSCs form colonies in agar, mammospheres in low-adherence cultures, and tumors following xenotransplantation in Scid mice.

Neuropilin-1 is a receptor for transforming growth factor beta-1, activates its latent form, and promotes regulatory T cell activity.

Neuropilin-1 (Nrp1) is a multifunctional protein, identified principally as a receptor for the class 3 semaphorins and members of the vascular endothelial growth factor (VEGF) family, but it is capable of other interactions. It is a marker of regulatory T cells (Tr), which often carry Nrp1 and latency-associated peptide (LAP)-TGF-beta1 (the latent form). The signaling TGF-beta1 receptors bind only active TGF-beta1, and we hypothesized that Nrp1 binds the latent form.

In vivo expression of GLP-1/IgG-Fc fusion protein enhances beta-cell mass and protects against streptozotocin-induced diabetes.

Glucagon-like peptide 1 (GLP-1) and its analogue exendin-4 (Ex4) have displayed potent glucose homeostasis-modulating characteristics in type 2 diabetes (T2D). However, there are few reports of effectiveness in type 1 diabetes (T1D) therapy, where there is massive loss of beta cells. We previously described a novel GLP-1 analogue consisting of the fusion of active GLP-1 and IgG heavy chain constant regions (GLP-1/IgG-Fc), and showed that in vivo expression of the protein, via electroporation-enhanced intramuscular plasmid-based gene transfer, normalized blood glucose levels in T2D-prone db/db mice.