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Since the advent of monolayered 2D transition metal carbide and nitrides (MXenes) in 2011, the number of different monolayer systems and the study thereof have been on the rise. Mo

ISG15 is a type I interferon (IFN)-inducible gene encoding a protein with pleiotropic functions, acting both as a soluble molecule and as a protein modifier. Surprisingly, and despite the antiviral functions of ISG15 described in mice, humans born with inactivating mutations of ISG15 do not present with any overt viral phenotype, but are highly susceptible to environmental mycobacteria and have autoinflammatory disease presentations. In vitro, ISG15 deficiency also leads to persistently high levels of type I IFN-stimulated gene expression and to increased resistance to all viruses tested to date. This suggests that ISG15 deficiency increases antiviral responses in humans, in stark contrast to expectations based on mouse experiments. We discuss here the roles of each of the forms of ISG15 in health and disease, as well as the differences between species.

TiO2 nanotubes (NTs) synthesized by electrochemical anodization are discussed as very promising anodes for lithium ion batteries, owing to their high structural stability, high surface area, safety, and low production cost. However, their poor electronic conductivity and low Li+ ion diffusivity are the main drawbacks that prevent them from achieving high electrochemical performance. Herein, we report the fabrication of a novel ternary carbon nanotubes (CNTs)@TiO2/CoO nanotubes composite by a two-step synthesis method. The preparation includes an initial anodic fabrication of well-ordered TiO2/CoO NTs from a Ti-Co alloy, followed by growing of CNTs horizontally on the top of the oxide films using a simple spray pyrolysis technique. The unique 1D structure of such a hybrid nanostructure with the inclusion of CNTs demonstrates significantly enhanced areal capacity and rate performances compared to pure TiO2 and TiO2/CoO NTs, without CNTs tested under identical conditions. The findings reveal that CNTs provide a highly conductive network that improves Li+ ion diffusivity, promoting a strongly favored lithium insertion into the TiO2/CoO NT framework, and hence resulting in high capacity and an extremely reproducible high rate capability.

TiO2 nanotubes (NTs) synthesized by electrochemical anodization are discussed as very promising anodes for lithium ion batteries, owing to their high structural stability, high surface area, safety, and low production cost. However, their poor electronic conductivity and low Li+ ion diffusivity are the main drawbacks that prevent them from achieving high electrochemical performance. Herein, we report the fabrication of a novel ternary carbon nanotubes (CNTs)@TiO2/CoO nanotubes composite by a two-step synthesis method. The preparation includes an initial anodic fabrication of well-ordered TiO2/CoO NTs from a Ti-Co alloy, followed by growing of CNTs horizontally on the top of the oxide films using a simple spray pyrolysis technique. The unique 1D structure of such a hybrid nanostructure with the inclusion of CNTs demonstrates significantly enhanced areal capacity and rate performances compared to pure TiO2 and TiO2/CoO NTs, without CNTs tested under identical conditions. The findings reveal that CNTs provide a highly conductive network that improves Li+ ion diffusivity, promoting a strongly favored lithium insertion into the TiO2/CoO NT framework, and hence resulting in high capacity and an extremely reproducible high rate capability.

ISG15 is an interferon (IFN)-α/β-induced ubiquitin-like protein. It exists as a free molecule, intracellularly and extracellularly, and conjugated to target proteins. Studies in mice have demonstrated a role for Isg15 in antiviral immunity. By contrast, human ISG15 was shown to have critical immune functions, but not in antiviral immunity. Namely, free extracellular ISG15 is crucial in IFN-γ-dependent antimycobacterial immunity, while free intracellular ISG15 is crucial for USP18-mediated downregulation of IFN-α/β signalling. Here we describe ISG15-deficient patients who display no enhanced susceptibility to viruses in vivo, in stark contrast to Isg15-deficient mice. Furthermore, fibroblasts derived from ISG15-deficient patients display enhanced antiviral protection, and expression of ISG15 attenuates viral resistance to WT control levels. The species-specific gain-of-function in antiviral immunity observed in ISG15 deficiency is explained by the requirement of ISG15 to sustain USP18 levels in humans, a mechanism not operating in mice., ISG15 is a ubiquitin-like protein which has important immune-related functions in mice and humans. Here the authors demonstrate that, unlike in mice, human ISG15 stabilizes UPS18 and that ISG15-deficient human cells are more resistant to viral infection.

Meuwissen and collaborators define a novel genetic cause of pseudo-TORCH syndrome, which resembles the sequelae of congenital infection and represents a novel type I interferonopathy., Pseudo-TORCH syndrome (PTS) is characterized by microcephaly, enlarged ventricles, cerebral calcification, and, occasionally, by systemic features at birth resembling the sequelae of congenital infection but in the absence of an infectious agent. Genetic defects resulting in activation of type 1 interferon (IFN) responses have been documented to cause Aicardi-Goutières syndrome, which is a cause of PTS. Ubiquitin-specific peptidase 18 (USP18) is a key negative regulator of type I IFN signaling. In this study, we identified loss-of-function recessive mutations of USP18 in five PTS patients from two unrelated families. Ex vivo brain autopsy material demonstrated innate immune inflammation with calcification and polymicrogyria. In vitro, patient fibroblasts displayed severely enhanced IFN-induced inflammation, which was completely rescued by lentiviral transduction of USP18. These findings add USP18 deficiency to the list of genetic disorders collectively termed type I interferonopathies. Moreover, USP18 deficiency represents the first genetic disorder of PTS caused by dysregulation of the response to type I IFNs. Therapeutically, this places USP18 as a promising target not only for genetic but also acquired IFN-mediated CNS disorders.

Paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) is an episodic movement disorder with autosomal-dominant inheritance and high penetrance, but the causative genetic mutation is unknown. We have now identified four truncating mutations involving the gene PRRT2 in the vast majority (24/25) of well-characterized families with PKD/IC. PRRT2 truncating mutations were also detected in 28 of 78 additional families. PRRT2 encodes a proline-rich transmembrane protein of unknown function that has been reported to interact with the t-SNARE, SNAP25. PRRT2 localizes to axons but not to dendritic processes in primary neuronal culture, and mutants associated with PKD/IC lead to dramatically reduced PRRT2 levels, leading ultimately to neuronal hyperexcitability that manifests in vivo as PKD/IC.

A key feature of my research is to develop a transmission electron microscope (TEM) into an atomic-scale nano-chemistry laboratory to fabricate, modify and characterize samples so that crucial structure property studies and synthesis studies can be conducted in high spatial resolution and high temporal resolution. In this presentation I will show a variety of electron beam driven reactions and electron beam engineering techniques in which we can fabricate and manipulate nano-materials. I will also show how one can structure and look at structure-property relationship of graphene devices, both fabricated and examined in-situ in a TEM.

Since it was first isolated in 2004, monolayer graphene has been studied for its unique optical, electrical, and thermal properties. Recently, interest is growing in the rich physics of twisted bilayer graphene, especially with optical tools such as Raman spectroscopy[1]. In this work, we study the micro-Raman spectra of bi- and tri-layer graphene islands, and develop methods to classify features of these spectra. Graphene islands were grown on monolayer graphene via the CVD method[2], and then transferred to a Si/SiO2 substrate. Micro-Raman hyperspectral maps were taken from bi- and tri- layer islands with a wide variety of shapes and sizes. Using homemade code we fit the spectra from each pixel in the maps and extract the peak parameters for all of the major graphene Raman features. These pixels define a coordinate manifold, with the peak parameters building a hyperdimensional space over these coordinates. Principal Component Analysis was used to find the vectors where the spectra vary most widely, and data clusters were identified along these principal vectors. These clusters were further decomposed using this method iteratively. When all reasonable clusters are identified, the clusters can be remapped to the individual islands, allowing one to classify distinct regions on the islands with similar spectral features. Correlations between the peak parameters can be extracted from each cluster, and then fitted to determine the relationships between them. These relationships reflect the unique physics of the few-layer graphene system, such as biaxial strain or doping level. By classifying regions with similar behavior, we can determine how this physics is influenced by the geometry of the system. Acknowledgement: This work was supported by: NSF ECCS-1509786 References: [1]Ado Jorio, Luiz Gustavo Cançado, Raman spectroscopy of twisted bilayer graphene, Solid State Communications, Volumes 175–176, December 2013, Pages 3-12, ISSN 0038-1098, http://dx.doi.org/10.1016/j.ssc.2013.08.008. [2]Huy Q. Ta, David J. Perello, Dinh Loc Duong, Gang Hee Han, Sandeep Gorantla, Van Luan Nguyen, Alicja Bachmatiuk, Slava V. Rotkin, Young Hee Lee, and Mark H. Rümmeli, Stranski–Krastanov and Volmer–Weber CVD Growth Regimes To Control the Stacking Order in Bilayer Graphene, Nano Letters 2016 16 (10), 6403-6410, DOI: 10.1021/acs.nanolett.6b02826 Figure 1

OBJECTIVE: The Low Molecular Weight Fraction of 5% human serum Albumin (LMWF-5A) is being investigated as a treatment for knee pain from osteoarthritis. METHODS: This was a multicenter randomized, vehicle-controlled, double-blind, parallel study designed to evaluate the safety and efficacy of two doses of an intra-articular injection of LMWF-5A. Patients with symptomatic knee osteoarthritis were randomized 1∶1∶1∶1 to receive a single 4 mL or 10 mL intra-articular knee injection of either LMWF-5A or vehicle control (saline). The primary efficacy endpoint was the difference between treatment groups in the Western Ontario and McMaster Universities (WOMAC) pain change from baseline over 12 weeks. Safety was examined as the incidence and severity of adverse events (AEs). RESULTS: A total of 329 patients were randomized and received treatment. LMWF-5A resulted in a significant decrease in pain at 12 weeks compared to vehicle control (-0.93 vs -0.72; estimated difference from control: -0.25, p = 0.004); an injection volume effect was not observed (p = 0.64). The effect of LMWF-5A on pain was even more pronounced in patients with severe knee OA (Kellgren Lawrence Grade IV): the estimated difference from control was -0.42 (p = 0.02). Adverse events were generally mild and were similar in patients who received vehicle control (47%) and LMWF-5A (41%). CONCLUSIONS: This clinical trial demonstrated that LMWF-5A is safe and effective at providing relief for the pain of moderate to severe OA of the knee over 12 weeks when administered by intra-articular injection into the knee. TRIAL REGISTRATION: ClinicalTrials.gov NCT01839331.

ISG15 is an interferon (IFN)- α / β -inducible protein that exists as a free molecule and conjugated to target proteins (ISGylation). In vivo studies in mice have demonstrated a critical role for ISG15 in antiviral immunity. By contrast, in humans, ISG15 has been shown to have critical functions, but not in antiviral immunity. Extracellular ISG15 is essential in IFN- γ -dependent antimycobacterial immunity, and intracellular ISG15 is essential for the USP18-mediated downregulation of IFN- α / β signaling. We describe ISG15-deficient patients, who, unlike Isg15-deficient mice, display no enhanced susceptibility to viruses in vivo . On the contrary, patients fibroblasts displayed enhanced antiviral protection and transduction of ISG15 restored viral replication to control levels. Difference in antiviral immunity in absence of ISG15 in humans vs. mice is mechanistically explained by ISG15 stabilizing USP18 in humans but not in mice. Thus, ISG15-deficient individuals present with gain-of-function in antiviral immunity at the expense of increased susceptibility to mycobacteria and auto-immunity.

Real-time quantitative polymerase chain reaction (qPCR) depends on precise temperature control of the sample during cycling. In the current study, we investigated how temperature variation in plate-based qPCR instruments influences qPCR results. Temperature variation was measured by amplicon melting analysis as a convenient means to assess well-to-well differences. Multiple technical replicates of several SYBR Green I-based qPCR assays allowed correlation of relative well temperature to quantification cycle. We found that inadequate template denaturation results in an inverse correlation and requires increasing the denaturation temperature, adding a DNA destabilizing agent, or pretreating with a restriction enzyme. In contrast, inadequate primer annealing results in a direct correlation and requires lowering the annealing temperature. Significant correlations were found in 18 of 25 assays. The critical nature of temperature-dependent effects was shown in a blinded study of 29 patients for the diagnosis of Prader-Willy and Angelman syndromes, where eight diagnoses were incorrect unless temperature-dependent effects were controlled. A method to detect temperature-dependent effects by pairwise comparisons of replicates in routine experiments is presented and applied. Systematic temperature errors in qPCR instruments can be recognized and their effects eliminated when high precision is required in quantitative genetic diagnostics and critical complementary DNA analyses.

Mc 2009. Microscopy Conference, Graz, Austria. 30 August - 4 September 2009. First Joint Meeting Of Dreiländertagung And Multinational Congress On Microscopy.

Mc 2009. Microscopy Conference, Graz, Austria. 30 August - 4 September 2009. First Joint Meeting Of Dreiländertagung And Multinational Congress On Microscopy.