Characterization of MSCs expressing islet neogenesis associated protein (INGAP): INGAP secretion and cell survival in vitro and in vivo.

Mesenchymal stem/stromal cells (MSCs) are emerging as a new therapy for diabetes. Here we investigate the properties of MSCs engineered to express Islet Neogenesis Associated Protein (INGAP) previously shown to reverse diabetes in animal models and evaluate their potential for anti-diabetic applications in mice. Mouse bone marrow-derived MSCs retrovirally transduced to co-express INGAP, Firefly Luciferase and EGFP (INGAP-MSCs), were characterized in vitro and implanted intraperitoneally (IP) into non-diabetic and diabetic C57BL/6 mice (Streptozotocin model) and tracked by live bioluminescence imaging (BLI). Distribution and survival of IP injected INGAP-MSCs differed between diabetic and non-diabetic mice, with a rapid clearance of cells in the latter, and a stronger retention (up to 4 weeks) in diabetic mice concurring with homing towards the pancreas. Interestingly, INGAP-MSCs inhibited the progression of hyperglycemia starting at day 3 and lasting for the entire 6 weeks of the study. Pursuing greater retention, we investigated the survival of INGAP-MSCs in hydrogel matrices. When mixed with Matrigel™ and injected subcutaneously into non-diabetic mice, INGAP-MSCs remained in the implant up to 16 weeks. In vitro tests in three matrices (Matrigel™, Type I Collagen and VitroGel®-MSC) demonstrated that INGAP-MSCs survive and secrete INGAP, with best results at the density of 1-2 x 106 cells/mL. However, all matrices induced spontaneous adipogenic differentiation of INGAP-MSCs in vitro and in vivo, which requires further investigation of its potential impact on MSC therapeutic properties. In summary, based on their ability to stop the rise in hyperglycemia in STZ-treated mice, INGAP-MSCs are a promising therapeutic tool against diabetes but require further research to improve cell delivery and survival.

Spatially Dependent in-Gap States Induced by Andreev Tunneling through a Single Electronic State.

By using low-temperature scanning tunneling microscopy and spectroscopy (STM/STS), we observe in-gap states induced by Andreev tunneling through a single impurity state in a low carrier density superconductor (NaAlSi). The energy-symmetric in-gap states appear when the impurity state is located within the superconducting gap. In-gap states can cross the Fermi level, and they show X-shaped spatial variation. We interpret the in-gap states as a consequence of the Andreev tunneling through the impurity state, which involves the formation or breakup of a Cooper pair. Due to the low carrier density in NaAlSi, the in-gap state is tunable by controlling the STM tip-sample distance. Under strong external magnetic fields, the impurity state shows Zeeman splitting when it is located near the Fermi level. Our findings not only demonstrate the Andreev tunneling involving single electronic state but also provide new insights for understanding the spatially dependent in-gap states in low carrier density superconductors.

Asymmetric Metal-Carboxylate Complexes for Synthesis of InGaP Alloyed Quantum Dots with Blue Emission.

Indium phosphide (InP) quantum dots (QDs) have attracted significant interest as next-generation light-emitting materials. However, the synthesis of blue-emitting InP-based QDs has lagged behind that of established green- and red-emitting InP QDs. Herein, we present a strategy to synthesize blue-emitting QDs by forming an InGaP alloy composition. The introduction of asymmetric In-carboxylate and Ga-carboxylate complexes resulted in a balanced synthetic reactivity between In-P and Ga-P, leading to the formation of InGaP alloyed QDs. The resultant In1-xGaxP alloyed QDs exhibited a broad range of photoluminescence (PL) tunability, spanning from 535 nm (InP) to 465 nm (In0.62Ga0.38P), depending on the In/Ga ratio used in the synthesis. In contrast, synthesis with symmetric In-carboxylate and Ga-carboxylate complexes produced a core/shell structure of InP/GaP QDs, which did not exhibit a blue shift of the PL peak with Ga addition. By employing a core/shell structure of In0.62Ga0.38P/ZnS QDs, we achieved a PL quantum yield of 42% at 475 nm. This work highlights the material-processing strategy essential for forming alloyed structures in III-V ternary systems.

Composition, Optical Resonances, and Doping of InP/InGaP Nanowires for Tandem Solar Cells: a Micro-Raman Analysis.

We present a micro-Raman study of InP/InGaP tandem junction photovoltaic nanowires. These nanowires render possible InGaP compositions that cannot be made in thin films due to strain. The micro-Raman spectra acquired along the nanowires reveal the existence of compositional changes in the InGaP alloy associated with the doping sequence. The heavily Zn-doped InxGa1-xP (x is the In molar fraction) side of the tunnel diode is Ga rich, x = 0.25, with respect to the n-type and intrinsic segments of the top cell, which are close to the nominal composition of the NWs (x = 0.35). The p-type end segment is still Ga-rich. Electromagnetic resonances are observed in the tunnel diode. The Raman signal arising from the InGaP side of the tunnel diode is significantly enhanced. This enhancement permits the observation of a Raman mode that can be associated with an LO phonon plasmon coupled mode (LOPCM). This mode has not been previously reported in the literature of InGaP, and it permits the Raman characterization of the tunnel diode. The analysis of this mode and its relation to the LO phonon modes of the alloy, InP-like and GaP-like, allows to establish an apparent one-mode behavior for the phonon plasmon coupling. It indicates that hole plasma couples to the GaP-like LO mode. The LOPCMs are modeled using the Lindhard Mermin formalism for the dielectric function.

A cathodoluminescence study of InP/InGaP axially heterostructured NWs for tandem solar cells.

Axially heterostructured nanowires (NWs) constitute a promising platform for advanced electronic and optoelectronic nanodevices. The presence of different materials in these NWs introduces a mismatch resulting in complex strain distributions susceptible of changing the band gap and carrier mobility. The growth of these NWs presents challenges related to the reservoir effect in the catalysts droplet that affect to the junction abruptness, and the occurrence of undesired lateral growth creating core-shell heterostructures that introduce additional strain. We present herein a cathodoluminescence (CL) analysis on axially heterostructured InP/InGaP NWs with tandem solar cell structure. The CL is complemented with micro Raman, micro photoluminescence (PL), and high resolution transmission electron microscopy measurements. The results reveal the zinc blende structure of the NWs, the presence of a thin InGaP shell around the InP bottom cell, along with its associated strain, and the doping distribution.

Symmetry Breaking and Spin-Orbit Coupling for Individual Vacancy-Induced In-Gap States in MoS2 Monolayers.

Spins confined to point defects in atomically thin semiconductors constitute well-defined atomic-scale quantum systems that are being explored as single-photon emitters and spin qubits. Here, we investigate the in-gap electronic structure of individual sulfur vacancies in molybdenum disulfide (MoS2) monolayers using resonant tunneling scanning probe spectroscopy in the Coulomb blockade regime. Spectroscopic mapping of defect wave functions reveals an interplay of local symmetry breaking by a charge-state-dependent Jahn-Teller lattice distortion that, when combined with strong (≃100 meV) spin-orbit coupling, leads to a locking of an unpaired spin-1/2 magnetic moment to the lattice at low temperature, susceptible to lattice strain. Our results provide new insights into the spin and electronic structure of vacancy-induced in-gap states toward their application as electrically and optically addressable quantum systems.

Structural modifications of INGAP-PP present in HTD4010 peptide potentiate its effect on rat islet gene expression and insulin secretion.

Type 2 diabetes (T2D) is characterized by peripheral insulin resistance and altered insulin secretion due to a progressive loss of ß-cell mass and function. Today, most antidiabetic agents are designed to resolve impaired insulin secretion and/or insulin resistance, and only GLP-1-based formulations contribute to stopping the decline in ß-cell mass. HTD4010, a peptide carrying two modifications of the amino acid sequence of INGAP-PP (N-terminus acetylation and substitution of Asn13 by Ala) showed greater plasma stability and could be a good candidate for proposal as a drug that could improve ß cell mass and function lost in T2D. In the present study, we showed that HTD4010 included in the culture media of normal rat islets at a dose 100 times lower than that used for INGAP-PP was able to modulate, in the same way as the original peptide, both insulin secretion in response to glucose and the expression of key genes related to insular function, insulin and leptin intracellular pathways, neogenesis, apoptosis, and inflammatory response. Our results confirm the positive effect of HTD4010 on ß-cell function and gene expression of factors involved in the maintenance of ß-cell mass. Although new assays in animal models of prediabetes and T2D must be performed to be conclusive, our results are very encouraging, and they suggest that the use of HTD4010 at a dose 100 times lower than that of INGAP-PP could minimize its side effects in a future clinical trial.

Transcriptional signature of islet neogenesis-associated protein peptide-treated rat pancreatic islets reveals induction of novel long non-coding RNAs.

Background: Diabetes mellitus is characterized by chronic hyperglycemia with loss of ß-cell function and mass. An attractive therapeutic approach to treat patients with diabetes in a non-invasive way is to harness the innate regenerative potential of the pancreas. The Islet Neogenesis-Associated Protein pentadecapeptide (INGAP-PP) has been shown to induce ß-cell regeneration and improve their function in rodents. To investigate its possible mechanism of action, we report here the global transcriptional effects induced by the short-term INGAP-PP in vitro treatment of adult rat pancreatic islets. Methods and findings: Rat pancreatic islets were cultured in vitro in the presence of INGAP-PP for 4 days, and RNA-seq was generated from triplicate treated and control islet samples. We performed a de novo rat gene annotation based on the alignment of RNA-seq reads. The list of INGAP-PP-regulated genes was integrated with epigenomic data. Using the new gene annotation generated in this work, we quantified RNA-seq data profiled in INS-1 cells treated with IL1ß, IL1ß+Calcipotriol (a vitamin D agonist) or vehicle, and single-cell RNA-seq data profiled in rat pancreatic islets. We found 1,669 differentially expressed genes by INGAP-PP treatment, including dozens of previously unannotated rat transcripts. Genes differentially expressed by the INGAP-PP treatment included a subset of upregulated transcripts that are associated with vitamin D receptor activation. Supported by epigenomic and single-cell RNA-seq data, we identified 9 previously unannotated long noncoding RNAs (lncRNAs) upregulated by INGAP-PP, some of which are also differentially regulated by IL1ß and vitamin D in ß-cells. These include Ri-lnc1, which is enriched in mature ß-cells. Conclusions: Our results reveal the transcriptional program that could explain the enhancement of INGAP-PP-mediated physiological effects on ß-cell mass and function. We identified novel lncRNAs that are induced by INGAP-PP in rat islets, some of which are selectively expressed in pancreatic ß-cells and downregulated by IL1ß treatment of INS-1 cells. Our results suggest a relevant function for Ri-lnc1 in ß-cells. These findings are expected to provide the basis for a deeper understanding of islet translational results from rodents to humans, with the ultimate goal of designing new therapies for people with diabetes.

High-Q Trampoline Resonators from Strained Crystalline InGaP for Integrated Free-Space Optomechanics.

Nanomechanical resonators realized from tensile-strained materials reach ultralow mechanical dissipation in the kHz to MHz frequency range. Tensile-strained crystalline materials that are compatible with epitaxial growth of heterostructures would thereby at the same time allow realizing monolithic free-space optomechanical devices, which benefit from stability, ultrasmall mode volumes, and scalability. In our work, we demonstrate nanomechanical string and trampoline resonators made from tensile-strained InGaP, which is a crystalline material that is epitaxially grown on an AlGaAs heterostructure. We characterize the mechanical properties of suspended InGaP nanostrings, such as anisotropic stress, yield strength, and intrinsic quality factor. We find that the latter degrades over time. We reach mechanical quality factors surpassing 107 at room temperature with a Q·f product as high as 7 × 1011Hz with trampoline-shaped resonators. The trampoline is patterned with a photonic crystal to engineer its out-of-plane reflectivity, desired for efficient signal transduction of mechanical motion to light.

inGAP-family: Accurate Detection of Meiotic Recombination Loci and Causal Mutations by Filtering Out Artificial Variants due to Genome Complexities.

Accurately identifying DNA polymorphisms can bridge the gap between phenotypes and genotypes and is essential for molecular marker assisted genetic studies. Genome complexities, including large-scale structural variations, bring great challenges to bioinformatic analysis for obtaining high-confidence genomic variants, as sequence differences between non-allelic loci of two or more genomes can be misinterpreted as polymorphisms. It is important to correctly filter out artificial variants to avoid false genotyping or estimation of allele frequencies. Here, we present an efficient and effective framework, inGAP-family, to discover, filter, and visualize DNA polymorphisms and structural variants (SVs) from alignment of short reads. Applying this method to polymorphism detection on real datasets shows that elimination of artificial variants greatly facilitates the precise identification of meiotic recombination points as well as causal mutations in mutant genomes or quantitative trait loci. In addition, inGAP-family provides a user-friendly graphical interface for detecting polymorphisms and SVs, further evaluating predicted variants and identifying mutations related to genotypes. It is accessible at https://sourceforge.net/projects/ingap-family/.

Sub-gap Fano resonances in a topological superconducting wire with on-site Coulomb interactions.

We consider theoretically a 1D-semiconducting wire with strong Rashba interaction in proximity withs-wave superconductor, driven into topological phase by external magnetic field. Additionally, we take into account on-site Coulomb interactions inside the wire. The system is modelled by a tight binding Hamiltonian with Rashba hopping term and induceds-wave superconductivity. Calculations are performed utilizing recursive Green's function method, and Coulomb interactions are treated selfconsistently within Hubbard I approximation. For the Hubbard levels residing withinp-wave superconducting gap, particle-hole symmetric four-resonance structure develops in the density of states, apart from Majorana resonance. One pair of particle-hole symmetric resonances is created by the discrete II-Hubbard levels of the particular site, and the second pair of Hubbard sub-bands originates from recursive summation over the sites of the wire. Quantum interference between both types of pairs of states creates in-gap charge-conjugated Fano resonances with opposite asymmetry factors. We demonstrate that when quantum interference is dominated by two-particle tunneling, the Majorana resonance is strongly diminished, while it is not altered when single-particle tunneling dominates in interference process. We also discuss some consequences for experimental distinction of true Majorana states, and show that on-site Coulomb interactions support the appearance of topological phase.

Low-energy in-gap states of vortices in superconductor-semiconductor heterostructures.

The recent interest in the low-energy states in vortices of semiconductor-superconductor heterostructures are mainly fuelled by the prospects of using Majorana zero modes for quantum computation. The knowledge of low-lying states in the vortex core is essential as they pose a limitation on the topological computation with these states. Recently, the low-energy spectra of clean heterostructures, for superconducting-pairing profiles that vary slowly on the scale of the Fermi wavelength of the semiconductor, have been analytically calculated. In this work, we formulate an alternative method based on perturbation theory to obtain concise analytical formulas to predict the low-energy states including explicit magnetic-field and gap profiles. We provide results for both a topological insulator (with a linear spectrum) as well as for a conventional electron gas (with a quadratic spectrum). We discuss the spectra for a wide range of parameters, including both the size of the vortex and the chemical potential of the semiconductor, and thereby provide a tool to guide future experimental efforts. We compare these findings to numerical results.

Significance Of Nuclear Quantum Effects In Hydrogen Bonded Molecular Chains.

In hydrogen-bonded systems, nuclear quantum effects such as zero-point motion and tunneling can significantly affect their material properties through underlying physical and chemical processes. Presently, direct observation of the influence of nuclear quantum effects on the strength of hydrogen bonds with resulting structural and electronic implications remains elusive, leaving opportunities for deeper understanding to harness their fascinating properties. We studied hydrogen-bonded one-dimensional quinonediimine molecular networks which may adopt two isomeric electronic configurations via proton transfer. Herein, we demonstrate that concerted proton transfer promotes a delocalization of π-electrons along the molecular chain, which enhances the cohesive energy between molecular units, increasing the mechanical stability of the chain and giving rise to distinctive electronic in-gap states localized at the ends. These findings demonstrate the identification of a class of isomeric hydrogen-bonded molecular systems where nuclear quantum effects play a dominant role in establishing their chemical and physical properties. This identification is a step toward the control of mechanical and electronic properties of low-dimensional molecular materials via concerted proton tunneling.

Atomistic investigation of surface characteristics and electronic features at high-purity FeSi(110) presenting interfacial metallicity.

Iron silicide (FeSi) is a fascinating material that has attracted extensive research efforts for decades, notably revealing unusual temperature-dependent electronic and magnetic characteristics, as well as a close resemblance to the Kondo insulators whereby a coherent picture of intrinsic properties and underlying physics remains to be fully developed. For a better understanding of this narrow-gap semiconductor, we prepared and examined FeSi(110) single-crystal surfaces of high quality. Combined insights from low-temperature scanning tunneling microscopy and density functional theory calculations (DFT) indicate an unreconstructed surface termination presenting rows of Fe-Si pairs. Using high-resolution tunneling spectroscopy (STS), we identify a distinct asymmetric electronic gap in the sub-10 K regime on defect-free terraces. Moreover, the STS data reveal a residual density of states in the gap regime whereby two in-gap states are recognized. The principal origin of these features is rationalized with the help of the DFT-calculated band structure. The computational modeling of a (110)-oriented slab notably evidences the existence of interfacial intragap bands accounting for a markedly increased density of states around the Fermi level. These findings support and provide further insight into the emergence of surface metallicity in the low-temperature regime.

Study of the Cross-Influence between III-V and IV Elements Deposited in the Same MOVPE Growth Chamber.

We have deposited Ge, SiGe, SiGeSn, AlAs, GaAs, InGaP and InGaAs based structures in the same metalorganic vapor phase epitaxy (MOVPE) growth chamber, in order to study the effect of the cross influence between groups IV and III-V elements on the growth rate, background doping and morphology. It is shown that by adopting an innovative design of the MOVPE growth chamber and proper growth condition, the IV elements growth rate penalization due to As "carry over" can be eliminated and the background doping level in both IV and III-V semiconductors can be drastically reduced. In the temperature range 748-888 K, Ge and SiGe morphologies do not degrade when the semiconductors are grown in a III-V-contaminated MOVPE growth chamber. Critical morphology aspects have been identified for SiGeSn and III-Vs, when the MOVPE deposition takes place, respectively, in a As or Sn-contaminated MOVPE growth chamber. III-Vs morphologies are influenced by substrate type and orientation. The results are promising in view of the monolithic integration of group-IV with III-V compounds in multi-junction solar cells.

Application of Solidago chilensis and laser improved the repair of burns in diabetic rats.

BACKGROUND: The repair of burns in diabetic patients is a clinical problem. It is relevant to study alternative therapies that can improve the healing process. Our aim was to investigate the effects of Solidago chilensis associated or not with laser on burns in diabetic rats. METHODS: The animals were divided in four groups (n = 30): C- without treatment; S- S. chilensis extract; L-laser irradiated; LS- laser and S. chilensis. In 7, 14 and 21 days samples were collected after the injury to structural, morphometric and molecular analysis. RESULTS: Our results demonstrate the association of S. chilensis and laser reduced the inflammatory infiltrate and favored the angiogenesis. In the groups treated only with laser or with the plant extract showed higher levels of VEGF. The low-level laser therapy (LLLT) promoted higher collagen I and reduction of collagen III. It was also observed higher MMP-2 activation and a decreasing of the active isoform of MMP-9 in the S, L and LS groups. CONCLUSIONS: The treatments improved the repair of burns in diabetic rats, since it reduced the inflammatory infiltrate and favored the collagen organization presenting similar effects in the burn repair of the diabetics.

A new analogue of islet neogenesis associated protein with higher structural and plasma stability.

Islet Neogenesis Associated Protein pentadecapeptide (INGAP-PP) increases ß-cell mass and function in experimental animals. A short clinical trial also yielded promising results. However, HTD4010, a new peptide derived from INGAP-PP, was developed in order to optimize its specific effects by minimizing its side effects. To study and compare the tertiary structure, stability dynamics, and plasma stability of HTD4010, an INGAP-PP analogue. Both peptides were pre-incubated in human, rat and mouse plasma at 37 °C, and their presence was identified and quantified by high performance liquid chromatography at different time-points. GROMACS 2019 package and the Gromos 54A7 force field were used to evaluate overall correlated motion of the peptide molecule during molecular dynamics simulation by essential dynamics. HTD4010 exhibited significantly larger plasma stability than INGAP-PP, and its structural stability was almost 3.36-fold higher than INGAP-PP. These results suggest that HTD4010 may facilitate longer tissue interaction, thereby developing higher potential biological effects. If so, HTD4010 may become a promising therapeutic agent to treat people with diabetes. Communicated by Ramaswamy H. Sarma.

Transition Metal-Hyperdoped InP Semiconductors as Efficient Solar Absorber Materials.

This work explores the possibility of increasing the photovoltaic efficiency of InP semiconductors through a hyperdoping process with transition metals (TM = Ti, V, Cr, Mn). To this end, we investigated the crystal structure, electronic band and optical absorption features of TM-hyperdoped InP (TM@InP), with the formula TMxIn1-xP (x = 0.03), by using accurate ab initio electronic structure calculations. The analysis of the electronic structure shows that TM 3d-orbitals induce new states in the host semiconductor bandgap, leading to improved absorption features that cover the whole range of the sunlight spectrum. The best results are obtained for Cr@InP, which is an excellent candidate as an in-gap band (IGB) absorber material. As a result, the sunlight absorption of the material is considerably improved through new sub-bandgap transitions across the IGB. Our results provide a systematic and overall perspective about the effects of transition metal hyperdoping into the exploitation of new semiconductors as potential key materials for photovoltaic applications.

Understanding the Effect of Catalyst Size on the Epitaxial Growth of Hierarchical Structured InGaP Nanowires.

Understanding the effect of a catalyst on the growth of nanowires is crucial for their controllable synthesis. In this study, we report the growth of InGaP nanowires induced by different-sized Au catalysts by metal-organic chemical vapor deposition. Through electron microscopy characterization, two types of InGaP nanowires are identified, and the difference in catalyst size is shown to cause their different morphological, structural, and compositional characteristics. Furthermore, the influencing mechanism of catalyst size on the formation of hierarchical structures in nanowires is discussed. This study provides an insight for a better understanding of the growth of ternary nanowires, especially the effect of catalyst size, which can be a promising approach to control the ternary nanowire growth, and is therefore beneficial for the design of the corresponding nanowire-based device.

Compositional Varied Core-Shell InGaP Nanowires Grown by Metal-Organic Chemical Vapor Deposition.

In this study, we report the growth of core-shell InGaP nanowires with compositional varied cores/shells using metal-organic chemical vapor deposition. These core-shell InGaP nanowires exhibit Ga-enriched cores attributed to the strong affinity between Au and In, and In-enriched shells due to In-rich vapor ambient. Detailed electron microscopy investigations indicate that the In and Ga concentrations in the nanowire cores and shells varied along the growth direction of InGaP nanowires. It is found that the strain relaxation through Ga diffusion outward and In diffusion inward leads to the decrease of compositional difference between the nanowire core and shell from top to bottom. This study offers a possibility to grow structural complex ternary nanowires that can be used for future applications.