0D/2D Heterostructures Vertical Single Electron Transistor

Mixed-dimensional heterostructures formed by the stacking of 2D materials with nanostructures of distinct dimensionality constitute a new class of nanomaterials that offers multifunctionality that goes beyond those of single dimensional systems. An unexplored architecture of single electron transistor (SET) is developed that employs heterostructures made of nanoclusters (0D) grown on a 2D molybdenum disulfide (MoS₂) channel. Combining the large Coulomb energy of the nanoclusters with the electronic capabilities of the 2D layer, the concept of 0D–2D vertical SET is unveiled. The MoS₂ underneath serves both as a charge tunable channel interconnecting the electrode, and as bottom electrode for each v-SET cell. In addition, its atomic thickness makes it thinner than the Debye screening length, providing electric field transparency functionality that allows for an efficient electric back gate control of the nanoclusters charge state. The Coulomb diamond pattern characteristics of SET are reported, with specific doping dependent nonlinear features arising from the 0D/2D geometry that are elucidated by theoretical modeling. These results hold promise for multifunctional single electron device taking advantage of the versatility of the 2D materials library, with as example envisioned spintronics applications while coupling quantum dots to magnetic 2D material, or to ferroelectric layers for neuromorphic devices.     

Sparsity Driven People Localization with a Heterogeneous Network of Cameras

This paper addresses the problem of localizing people in low and high density crowds with a network of heterogeneous cameras. The problem is recast as a linear inverse problem. It relies on deducing the discretized occupancy vector of people on the ground, from the noisy binary silhouettes observed as foreground pixels in each camera. This inverse problem is regularized by imposing a sparse occupancy vector, i.e., made of few non-zero elements, while a particular dictionary of silhouettes linearly maps these non-empty grid locations to the multiple silhouettes viewed by the cameras network. The proposed framework is (i) generic to any scene of people, i.e., people are located in low and high density crowds, (ii) scalable to any number of cameras and already working with a single camera, (iii) unconstrained by the scene surface to be monitored, and (iv) versatile with respect to the camera??s geometry, e.g., planar or omnidirectional. Qualitative and quantitative results are presented on the APIDIS and the PETS 2009 Benchmark datasets. The proposed algorithm successfully detects people occluding each other given severely degraded extracted features, while outperforming state-of-the-art people localization techniques.     

Tumor Suppressive Role of miR-342-5p in Human Chondrosarcoma Cells and 3D Organoids

Chondrosarcomas are malignant bone tumors. Their abundant cartilage-like extracellular matrix and their hypoxic microenvironment contribute to their resistance to chemotherapy and radiotherapy, and no effective therapy is currently available. MicroRNAs (miRNAs) may be an interesting alternative in the development of therapeutic options. Here, for the first time in chondrosarcoma cells, we carried out high-throughput functional screening using impedancemetry, and identified five miRNAs with potential antiproliferative or chemosensitive effects on SW1353 chondrosarcoma cells. The cytotoxic effects of miR-342-5p and miR-491-5p were confirmed on three chondrosarcoma cell lines, using functional validation under normoxia and hypoxia. Both miRNAs induced apoptosis and miR-342-5p also induced autophagy. Western blots and luciferase reporter assays identified for the first time Bcl-2 as a direct target of miR-342-5p, and also Bcl-xL as a direct target of both miR-342-5p and miR-491-5p in chondrosarcoma cells. MiR-491-5p also inhibited EGFR expression. Finally, only miR-342-5p induced cell death on a relevant 3D chondrosarcoma organoid model under hypoxia that mimics the in vivo microenvironment. Altogether, our results revealed the tumor suppressive activity of miR-342-5p, and to a lesser extent of miR-491-5p, on chondrosarcoma lines. Through this study, we also confirmed the potential of Bcl-2 family members as therapeutic targets in chondrosarcomas.     

Evolution of interleukin-15 for higher E. coli expression and solubility

Directed evolution was used to generate IL-15 mutants with increased solubility and cytoplasmic over-expression in Escherichia coli. A protein solubility selection method was used in which the IL-15 gene was expressed as an N-terminal fusion to chloramphenicol acetyltransferase (CAT) as reporter protein. Clones that grew in the presence of high concentrations of chloramphenicol were then screened by ELISA to assay the binding activity of the IL-15-CAT fusion to the IL-15Rα Sushi domain. Two variants of IL-15, M38 and M253, containing five mutations and one mutation respectively, were selected with a dramatic improvement in solubility; the soluble concentration in cell culture was 12- to 18-fold higher, respectively, than for WT IL-15. Characterization of their binding to IL-15Rα and their ability to stimulate the T-cell growth response showed that M38 binds as strongly as native IL-15 to IL-15Rα and acts as an effective agonist of IL-15.     

Nanoscale coordination polymers exhibiting luminescence properties and NMR relaxivity

This article presents the first example of ultra-small (3-4 nm) magneto-luminescent cyano-bridged coordination polymer nanoparticles Ln0.33(3+)Gdx3+/[Mo(CN)8]3- (Ln=Eu (x=0.34), Tb (x=0.35)) enwrapped by a natural biocompatible polymer chitosan. The aqueous colloidal solutions of these nanoparticles present a luminescence characteristic of the corresponding lanthanides (5D0→7F0-4 (Eu3+) or the 5D4→7F6-2 (Tb3+)) under UV excitation and a green luminescence of the chitosan shell under excitation in the visible region. Magnetic Resonance Imaging (MRI) efficiency, i.e. the nuclear relaxivity, measurements performed for Ln0.33(3+)Gdx3+/[Mo(CN)8]3- nanoparticles show r1p and r2p relaxivities slightly higher than or comparable to the ones of the commercial paramagnetic compounds Gd-DTPA? or Omniscan? indicating that our samples may potentially be considered as a positive contrast agent for MRI. The in vitro studies performed on these nanoparticles show that they maybe internalized into human cancer and normal cells and well detected by fluorescence at the single cell level. They present high stability even at low pH and lack of cytotoxicity both in human cancer and normal cells.     

Highly Insensitive/Reactive Thermite Prepared from Cr2O3 Nanoparticles

Thermites prepared from nanoparticles are currently the subject of growing interest due to their increased performances compared to classical micrometer‐sized thermites. Here, we studied the combustion behavior of energetic composite composed of Al and chromium (III) oxide (Cr₂O₃) as function of the oxide particle size. Homogeneous composites were prepared by mixing Al nanoparticles (Φ≈50 nm) with Cr₂O₃ micro‐ and nanoparticles (Φ≈20 nm), respectively, in hexane solution. The dried Cr₂O₃/Al composite powders were ignited by using a CO₂ laser beam. The use of nanosized Cr₂O₃ particles incontestably improves the energetic performances of the Al/Cr₂O₃ thermite since the ignition delay time was shortened by a factor 3.5 (16±2 vs 54±4 ms) and the combustion rate (340±10 mm s⁻¹) was significantly accelerated in contrast to those reported until now. Interestingly, the sensitivity to friction of the Al‐based thermites formulated from Cr₂O₃ is two orders of magnitude lower than the thermite prepared from other metal oxide nanoparticles (MnO₂, WO₃). Finally, our study shows that the decrease of Cr₂O₃ particle size has an interesting and beneficial effect on the energetic properties of Cr₂O₃/Al thermites and appears as an alternative to tune the properties of these energetic materials.     

Net Shape Fins for Compact Heat Exchanger Produced by Cold Spray

This work explores the manufacturability of pyramidal fin arrays produced using the cold spray process. Near-net shaped pyramidal fin arrays of various sizes and fin densities were manufactured using masks made of commercially available steel wire mesh. The feedstock powders used to produce the fins are characterized using scanning electron microscopy. Obstruction of the masks was investigated. The standoff distances between the substrate, mesh, and nozzle were empirically determined. Fin array characterization was performed using digital microscopy. The fin arrays’ heat transfer performance was assessed experimentally for a range of Reynolds number relevant to the application sought. The fins produced using the cold spray process outperform traditional straight (rectangular) fins at the same fin density and it is hypothesized that this is due to increased fluid mixing and turbulence.     

Advanced Spectroscopy and APBS Modeling for Determination of the Role of His190 and Trp103 in Mouse Thymidylate Synthase Interaction with Selected dUMP Analogues

A homo-dimeric enzyme, thymidylate synthase (TS), has been a long-standing molecular target in chemotherapy. To further elucidate properties and interactions with ligands of wild-type mouse thymidylate synthase (mTS) and its two single mutants, H190A and W103G, spectroscopic and theoretical investigations have been employed. In these mutants, histidine at position 190 and tryptophan at position 103 are substituted with alanine and glycine, respectively. Several emission-based spectroscopy methods used in the paper demonstrate an especially important role for Trp 103 in TS ligands binding. In addition, the Advanced Poisson–Boltzmann Solver (APBS) results show considerable differences in the distribution of electrostatic potential around Trp 103, as compared to distributions observed for all remaining Trp residues in the mTS family of structures. Together, spectroscopic and APBS results reveal a possible interplay between Trp 103 and His190, which contributes to a reduction in enzymatic activity in the case of H190A mutation. Comparison of electrostatic potential for mTS complexes, and their mutants, with the substrate, dUMP, and inhibitors, FdUMP and N4-OH-dCMP, suggests its weaker influence on the enzyme–ligand interactions in N4OH-dCMP-mTS compared to dUMP-mTS and FdUMP-mTS complexes. This difference may be crucial for the explanation of the ”abortive reaction” inhibitory mechanism of N4OH-dCMP towards TS. In addition, based on structural analyses and the H190A mutant capacity to form a denaturation-resistant complex with N4-OH-dCMP in the mTHF-dependent reaction, His190 is apparently responsible for a strong preference of the enzyme active center for the anti rotamer of the imino inhibitor form.     

Plocabulin,a Novel Tubulin Inhibitor,Has Potent Antitumour Activity in Patient-Derived Xenograft Models of Soft Tissue Sarcoma

A clinically relevant subset of patients with soft tissue sarcoma presents with either locally advanced or upfront metastatic disease, or will develop distant metastases over time, despite successful treatment of their primary tumour. The currently available systemic agents to treat such advanced cases only provide modest disease control and are not active in all histological subtypes. Thus, there is an unmet need for novel and more efficacious agents to improve the outcome of this rare disease. In the current preclinical in vivo study, we evaluated plocabulin, a novel tubulin inhibitor, in five distinct histological subtypes of soft tissue sarcoma: dedifferentiated liposarcoma, leiomyosarcoma, undifferentiated sarcoma, intimal sarcoma and CIC-rearranged sarcoma. The efficacy was tested in seven patient-derived xenograft models, which were generated by the engraftment of tumour fragments from patients directly into nude mice. The treatment lasted 22 days, and the efficacy of the drug was assessed and compared to the doxorubicin and vehicle groups by volumetric analysis, histopathology and immunohistochemistry. We observed tumour volume control in all the tested histological subtypes. Additionally, in three sarcoma subtypes, extensive central necrosis, associated with significant tumour regression, was seen. This histological response is explained by the drug’s vascular-disruptive properties, reflected by a decreased total vascular area in the xenografts. Our results demonstrate the in vivo efficacy of plocabulin in the preclinical models of soft tissue sarcoma and corroborate the findings of our previous study, which demonstrated similar vascular-disruptive effects in gastrointestinal stromal tumours—another subtype of soft tissue sarcoma. Our data provide a convincing rationale for further clinical exploration of plocabulin in soft tissue sarcomas.