Transmission XMCD-PEEM imaging of an engineered vertical FEBID cobalt nanowire with a domain wall

Using focused electron-beam-induced deposition, we fabricate a vertical, platinum-coated cobalt nanowire with a controlled three-dimensional structure. The latter is engineered to feature bends along the height: these are used as pinning sites for domain walls, which are obtained at remanence after saturation of the nanostructure in a horizontally applied magnetic field. The presence of domain walls is investigated using x-ray magnetic circular dichroism (XMCD) coupled to photoemission electron microscopy (PEEM). The vertical geometry of our sample combined with the low incidence of the x-ray beam produce an extended wire shadow which we use to recover the wire''s magnetic configuration. In this transmission configuration, the whole sample volume is probed, thus circumventing the limitation of PEEM to surfaces. This article reports on the first study of magnetic nanostructures standing perpendicular to the substrate with XMCD-PEEM. The use of this technique in shadow mode enabled us to confirm the presence of a domain wall without direct imaging of the nanowire

Risk factors for oral mucositis in paediatric oncology patients receiving alkylant chemotherapy

BACKGROUND: We describe the risk indicators for oral mucositis (OM) in paediatric oncology patients hospitalised in the Institut Gustave Roussy (Villejuif-Paris) and treated with alkylant chemotherapy with autologous peripheral blood progenitor cells. METHODS: The sample was selected using PIGAS software. Three groups of subjects received different chemotherapy regimens: A. Melphalan, B. Busulfan and C. other alkylant protocols. The degree of mucositis was recorded by CTC version 2.0 (Common Toxicity Criteria). Descriptive statistics were performed. The association between mucositis and risk indicator variables was tested using a χ(2 )test. The association between case status and covariates was tested using unconditional logistic regression analysis. RESULTS: Of the 337 children enrolled, 241 showed mucositis (group 1) and 96 did not show mucositis (group 2) during alkylant chemotherapy. There was a higher prevalence of male patients in both groups. The three different chemotherapy regimen groups are correlated with the appearance of oral mucositis (χ(2 )= 22.42, p < 0.01). Weight loss was higher in group 1 (χ(2 )= 6.31, p = 0.01). The duration of aplasia was lower in the Busulfan protocol (7.5 days) than in the Melphalan group (9.3 days) or the other regimens (8.6 days). The use of Bufulfan(® )was directly associated with case status (presence of oral mucositis): odds ratio [OR] = 2.1 and confidence interval [95%CI] = 1.3–3.0. Also, occurrences of germinal tumours and secondary bacterial infections were directly linked with case status: [OR] = 1.4 and 1.8, confidence interval [95%CI] = 1.2 – 1.7 and 1.1 – 2.5, respectively. CONCLUSION: The presence of OM was associated with the three different chemotherapy regimens considered; in particularly patients treated with Busulfan had the highest prevalence

Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR

Erratum in : Metabolic and Innate Immune Cues Merge into a Specific Inflammatory Response via the UPR. [Cell. 2019]International audienceInnate immune responses are intricately linked with intracellular metabolism of myeloid cells. Toll-likereceptor (TLR) stimulation shifts intracellular metabolism toward glycolysis, while anti-inflammatorysignals depend on enhanced mitochondrial respiration. How exogenous metabolic signals affect theimmune response is unknown. We demonstrate that TLR-dependent responses of dendritic cells (DC)are exacerbated by a high fatty acid (FA) metabolic environment. FA suppress the TLR-inducedhexokinase activity and perturb tricarboxylic acid cycle metabolism. These metabolic changesenhance mitochondrial reactive oxygen species (mtROS) production and, in turn, the unfolded proteinresponse (UPR) leading to a distinct transcriptomic signature, with IL-23 as hallmark. Interestingly,chemical or genetic suppression of glycolysis was sufficient to induce this specific immune response.Conversely, reducing mtROS production or DC-specific deficiency in XBP1 attenuated IL-23expression and skin inflammation in an IL-23-dependent model of psoriasis. Thus, fine-tuning of innateimmunity depends on optimization of metabolic demands and minimization of mtROS-induced UPR

Identification and thermochemical analysis of high-lignin feedstocks for biofuel and biochemical production

Background - Lignin is a highly abundant biopolymer synthesized by plants as a complex component of plant secondary cell walls. Efforts to utilize lignin-based bioproducts are needed. Results - Herein we identify and characterize the composition and pyrolytic deconstruction characteristics of high-lignin feedstocks. Feedstocks displaying the highest levels of lignin were identified as drupe endocarp biomass arising as agricultural waste from horticultural crops. By performing pyrolysis coupled to gas chromatography-mass spectrometry, we characterized lignin-derived deconstruction products from endocarp biomass and compared these with switchgrass. By comparing individual pyrolytic products, we document higher amounts of acetic acid, 1-hydroxy-2-propanone, acetone and furfural in switchgrass compared to endocarp tissue, which is consistent with high holocellulose relative to lignin. By contrast, greater yields of lignin-based pyrolytic products such as phenol, 2-methoxyphenol, 2-methylphenol, 2-methoxy-4-methylphenol and 4-ethyl-2-methoxyphenol arising from drupe endocarp tissue are documented. Conclusions - Differences in product yield, thermal decomposition rates and molecular species distribution among the feedstocks illustrate the potential of high-lignin endocarp feedstocks to generate valuable chemicals by thermochemical deconstruction

Dose finding and O6-alkylguanine-DNA alkyltransferase study of cisplatin combined with temozolomide in paediatric solid malignancies

Cisplatin may have additive activity with temozolomide due to ablation of the DNA repair protein O6-alkylguanine-DNA alkyltransferase (MGMT). This phase I/II study determined recommended combination doses using the Continual Reassessment Method, toxicities and antitumour activity in paediatric patients, and evaluated MGMT in peripheral blood mononuclear cells (PBMCs) in order to correlate with haematological toxicity. In total, 39 patients with refractory or recurrent solid tumours (median age ∼13 years; 14 pretreated with high-dose chemotherapy, craniospinal irradiation, or having bone marrow involvement) were treated with cisplatin, followed the next day by oral temozolomide for 5 days every 4 weeks at dose levels 80 mg m−2/150 mg m−2 day−1, 80/200, and 100/200, respectively. A total of 38 patients receiving 113 cycles (median 2, range 1–7) were evaluable for toxicity. Dose-limiting toxicity was haematological in all but one case. Treatment-related toxicities were thrombocytopenia, neutropenia, nausea-vomiting, asthenia. Hearing loss was experienced in five patients with prior irradiation to the brain stem or posterior fossa. Partial responses were observed in two malignant glioma, one brain stem glioma, and two neuroblastoma. Median MGMT activity in PBMCs decreased after 5 days of temozolomide treatment: low MGMT activity correlated with increased severity of thrombocytopenia. Cisplatin–temozolomide combinations are well tolerated without additional toxicity to single-agent treatments; the recommended phase II dosage is 80 mg m−2 cisplatin and 150 mg m−2 × 5 temozolomide in heavily treated, and 200 mg m−2 × 5 temozolomide in less-heavily pretreated children