Towards fabrication of ordered gallium nanostructures by laser manipulation of neutral atoms: study of self-assembling phenomena

Surface diffusion has an impact on the lateral resolution of nanostructures in bottom-up atom nanofabrication. In this paper we study the effects of the gallium atoms self-assembled on silicon surfaces (100) patterned with trenches at different slopes. These particular substrate morphologies have been made to enable an effective deposition rate variation along the surface. In this way we experimentally mimic the effect of the atomic flux modulation created by standing wave during an atom nanofabrication experiment. Even if we observe self organization of gallium atoms on the surface, we conclude that the nano-islands are not affected by surface diffusion processes and the effective variation of the deposition rate per unit area is the dominant factor affecting the growth differences along the surface. This result demonstrates that the gallium atoms self-organization should not prevent the observation of a periodic nano-patterning created by atom nano-fabrication techniques.Comment: 7 pages, 5 figures, EMRS conference procee

Determining PD-L1 Status in Patients with Triple-Negative Breast Cancer: Lessons Learned from IMpassion130

International audienceAbstract Triple-negative breast cancer (TNBC) accounts for approximately 12% to 17% of all breast cancers and has an aggressive clinical behavior. Increased tumor-infiltrating lymphocyte counts are prognostic for survival in TNBC, making this disease a potential target for cancer immunotherapy (CIT). Research on immunophenotyping of tumor-infiltrating lymphocytes is revealing molecular and structural organization in the tumor microenvironment that may predict patient prognosis. The anti–programmed death-ligand 1 (PD-L1) antibody atezolizumab plus nab-paclitaxel was the first CIT combination to demonstrate progression-free survival benefit and clinically meaningful overall survival benefit in the first-line treatment of metastatic TNBC (mTNBC) in patients with PD-L1–expressing tumor-infiltrating immune cells (IC) in ≥ 1% of the tumor area. This led to its US and EU approval for mTNBC and US approval of the VENTANA PD-L1 (SP142) assay as a companion diagnostic immunohistochemistry (IHC) assay. Subsequently, the anti– programmed death-1 (PD-1) antibody pembrolizumab plus chemotherapy was approved by the FDA for mTNBC based on progression-free survival benefit in patients with a combined positive score ≥10 by its concurrently approved 22C3 companion diagnostic assay. Treatment guidelines now recommend PD-L1 testing for patients with mTNBC, and the testing landscape will likely become increasingly complex as new anti–PD-L1/PD-1 agents and diagnostics are approved for TNBC. Integrating PD-L1 testing into current diagnostic workflows for mTNBC may provide more treatment options for these patients. Therefore, it is critical for medical oncologists and pathologists to understand the available assays and their relevance to therapeutic options to develop an appropriate workflow for IHC testing

Brain Mapping as Helpful Tool in Brain Glioma Surgical Treatment—Toward the “Perfect Surgery”?

Gliomas are the most common primary malignant brain tumours in adults, representing nearly 80%, with poor prognosis in their high-grade forms. Several variables positively affect the prognosis of patients with high-grade glioma: young age, tumour location, radiological features, recurrence, and the opportunity to perform post-operative adjuvant therapy. Low-grade gliomas are slow-growing brain neoplasms of adolescence and young-adulthood, preferentially involving functional areas, particularly the eloquent ones. It has been demonstrated that early surgery and higher extent rate ensure overall longer survival time regardless of tumour grading, but nowadays, functional preservation that is as complete as possible is imperative. To achieve the best surgical results, along with the best functional results, intraoperative mapping and monitoring of brain functions, as well as different anaesthesiology protocols for awake surgery are nowadays being widely adopted. We report on our experience at our institution with 28 patients affected by malignant brain tumours who underwent brain mapping-aided surgical resection of neoplasm: 20 patients underwent awake surgical resection and 8 patients underwent asleep surgical resection. An analysis of the results and a review of the literature has been performed

Influence of hydrofluoric acid treatment on electroless deposition of Au clusters

The morphology of gold nanoparticles (AuNPs) deposited on a (100) silicon wafer by simple immersion in a solution containing a metal salt and hydrofluoric acid (HF) is altered by HF treatment both before and after deposition. The gold clusters are characterized by the presence of flat regions and quasispherical particles consistent with the layer-by-layer or island growth modes, respectively. The cleaning procedure, including HF immersion prior to deposition, affects the predominantly occurring gold structures. Flat regions, which are of a few tens of nanometers long, are present after immersion for 10 s. The three-dimensional (3D) clusters are formed after a cleaning procedure of 4 min, which results in a large amount of spherical particles with a diameter of ≈15 nm and in a small percentage of residual square layers of a few nanometers in length. The samples were also treated with HF after the deposition and we found out a general thickening of flat regions, as revealed by TEM and AFM analysis. This result is in contrast to the coalescence observed in similar experiments performed with Ag. It is suggested that the HF dissolves the silicon oxide layer formed on top of the thin flat clusters and promotes the partial atomic rearrangement of the layered gold atoms, driven by a reduction of the surface energy. The X-ray diffraction investigation indicated changes in the crystalline orientation of the flat regions, which partially lose their initially heteroepitaxial relationship with the substrate. A postdeposition HF treatment for almost 70 s has nearly the same effect of long duration, high temperature annealing. The process presented herein could be beneficial to change the spectral response of nanoparticle arrays and to improve the conversion efficiency of hybrid photovoltaic devices

De novo missense variants in phosphatidylinositol kinase PIP5KIγ underlie a neurodevelopmental syndrome associated with altered phosphoinositide signaling

Phosphoinositides (PIs) are membrane phospholipids produced through the local activity of PI kinases and phosphatases that selectively add or remove phosphate groups from the inositol head group. PIs control membrane composition and play key roles in many cellular processes including actin dynamics, endosomal trafficking, autophagy, and nuclear functions. Mutations in phosphatidylinositol 4,5 bisphosphate [PI(4,5)P2] phosphatases cause a broad spectrum of neurodevelopmental disorders such as Lowe and Joubert syndromes and congenital muscular dystrophy with cataracts and intellectual disability, which are thus associated with increased levels of PI(4,5)P2. Here, we describe a neurodevelopmental disorder associated with an increase in the production of PI(4,5)P2 and with PI-signaling dysfunction. We identified three de novo heterozygous missense variants in PIP5K1C, which encodes an isoform of the phosphatidylinositol 4-phosphate 5-kinase (PIP5KIγ), in nine unrelated children exhibiting intellectual disability, developmental delay, acquired microcephaly, seizures, visual abnormalities, and dysmorphic features. We provide evidence that the PIP5K1C variants result in an increase of the endosomal PI(4,5)P2 pool, giving rise to ectopic recruitment of filamentous actin at early endosomes (EEs) that in turn causes dysfunction in EE trafficking. In addition, we generated an in vivo zebrafish model that recapitulates the disorder we describe with developmental defects affecting the forebrain, including the eyes, as well as craniofacial abnormalities, further demonstrating the pathogenic effect of the PIP5K1C variants. We describe a neurodevelopmental disorder associated with de novo gain-of-function variants in PIP5KIγ kinase. The variants cause perturbed endosomal function resulting from increased production of phosphatidylinositol 4,5 bisphosphate and enhanced association of F-actin at endosomes. Moreover, mutant zebrafish larvae recapitulate the phenotypes observed in affected individuals from our cohort