Nanoscale layering of antiferromagnetic and superconducting phases in Rb2Fe4Se5

We studied phase separation in a single-crystalline antiferromagnetic superconductor Rb2Fe4Se5 (RFS) using a combination of scattering-type scanning near-field optical microscopy (s-SNOM) and low-energy muon spin rotation (LE-\mu SR). We demonstrate that the antiferromagnetic and superconducting phases segregate into nanometer-thick layers perpendicular to the iron-selenide planes, while the characteristic in-plane size of the metallic domains reaches 10 \mu m. By means of LE-\mu SR we further show that in a 40-nm thick surface layer the ordered antiferromagnetic moment is drastically reduced, while the volume fraction of the paramagnetic phase is significantly enhanced over its bulk value. Self-organization into a quasiregular heterostructure indicates an intimate connection between the modulated superconducting and antiferromagnetic phases.Comment: 5 pages, 2 figures. Updated version published in Phys. Rev. Lett. on 5 July 201

Sub-wavelength surface IR imaging of soft-condensed matter

Outlined here is a technique for sub-wavelength infrared surface imaging performed using a phase matched optical parametric oscillator laser and an atomic force microscope as the detection mechanism. The technique uses a novel surface excitation illumination approach to perform simultaneously chemical mapping and AFM topography imaging with an image resolution of 200 nm. This method was demonstrated by imaging polystyrene micro-structures

Mapping electron beam injected trapped charge with scattering scanning near-field optical microscopy

Scattering scanning near-field optical microscopy (s-SNOM) has been demonstrated as a valuable tool for mapping the optical and optoelectronic properties of materials with nanoscale resolution. Here we report experimental evidence that trapped electric charges injected by an electron beam at the surface of dielectric samples affect the sample-dipole interaction, which has direct impact on the s-SNOM image content. Nanoscale mapping of the surface trapped charge holds significant potential for the precise tailoring of the electrostatic properties of dielectric and semiconductive samples, such as hydroxyapatite, which has particular importance with respect to biomedical applications. The methodology developed here is highly relevant to semiconductor device fabrication as well

Infrared nanoscopy of Dirac plasmons at the graphene-SiO2 interface

We report on infrared (IR) nanoscopy of 2D plasmon excitations of Dirac fermions in graphene. This is achieved by confining mid-IR radiation at the apex of a nanoscale tip: an approach yielding two orders of magnitude increase in the value of in-plane component of incident wavevector q compared to free space propagation. At these high wavevectors, the Dirac plasmon is found to dramatically enhance the near-field interaction with mid-IR surface phonons of SiO2 substrate. Our data augmented by detailed modeling establish graphene as a new medium supporting plasmonic effects that can be controlled by gate voltage.Comment: 12 pages, 4 figure

OTX015 (MK-8628), a novel BET inhibitor, exhibits antitumor activity in non-small cell and small cell lung cancer models harboring different oncogenic mutations.

Inhibitors targeting epigenetic control points of oncogenes offer a potential mean of blocking tumor progression in small cell and non-small cell lung carcinomas (SCLC, NSCLC). OTX015 (MK-8628) is a BET inhibitor selectively blocking BRD2/3/4. OTX015 was evaluated in a panel of NSCLC or SCLC models harboring different oncogenic mutations. Cell proliferation inhibition and cell cycle arrest were seen in sensitive NSCLC cells. MYC and MYCN were downregulated at both the mRNA and protein levels. In addition, OTX015-treatment significantly downregulated various stemness cell markers, including NANOG, Musashi-1, CD113 and EpCAM in H3122-tumors in vivo. Conversely, in SCLC models, weak antitumor activity was observed with OTX015, both in vitro and in vivo. No predictive biomarkers of OTX015 activity were identified in a large panel of candidate genes known to be affected by BET inhibition. In NSCLC models, OTX015 was equally active in both EML4-ALK positive and negative cell lines, whereas in SCLC models the presence of functional RB1 protein, which controls cell progression at G1, may be related to the final biological outcome of OTX015. Gene expression profiling in NSCLC and SCLC cell lines showed that OTX015 affects important genes and pathways with a very high overlapping between both sensitive and resistant cell lines. These data support the rationale for the OTX015 Phase Ib (NCT02259114) in solid tumors, where NSCLC patients with rearranged ALK gene or KRAS-positive mutations are currently being treated

Factors predicting efficacy of oxaliplatin in combination with 5-fluorouracil (5-FU) ± folinic acid in a compassionate-use cohort of 481 5-FU-resistant advanced colorectal cancer patients

A statistical analysis was performed on the patient data collected from two compassionate-use programmes using oxaliplatin (Eloxatin®) + 5-fluorouracil (5-FU) ± folinic acid (FA), to identify predictive factors for oxaliplatin-based salvage treatment in patients with 5-FU-resistant advanced colorectal cancer (ACRC). 481 5-FU-resistant ACRC patients, most with performance status ≤ 2, ≥ 3 involved sites, and ≥ 2 prior lines of chemotherapy, received oxaliplatin + 5-FU ± FA. Prognostic factors associated with overall response rate (ORR), time to progression (TTP) and overall survival (OS) were identified using univariate and multivariate logistic and/or Cox proportional hazards analyses. The ORR was 16% (95% CI: 13–20), the median TTP was 4.2 months (95% CI: 3.4–4.6), and the median OS was 9.6 months (95% CI: 8.6–10.6). The multivariate analysis indicated poor (≥ 2 WHO) performance status (PS), a large number of prior chemotherapy regimens (≥ 3), a low baseline haemoglobin level (< 10 g/dl), and a triweekly (vs biweekly) treatment administration schedule as significantly associated (P< 0.05) with a lower ORR. Sex (male), number of organs involved (≥3) and alkaline phosphatase (AP) level (≥ 2 × the upper limit of normal) were associated (P< 0.05) with shorter TTP. Poor PS, a large number of organs involved, and elevated AP were independently and significantly correlated with shorter OS. Our analysis identified a relationship between efficacy results of oxaliplatin + 5-FU ± FA treatment in 5-FU-resistant ACRC patients and baseline prognostic factors related to PS, extent of disease and number of prior regimens. © 2001 Cancer Research Campaign http://www.bjcancer.co

Prognostic value of clinicopathological parameters in head and neck squamous cell carcinoma: a prospective analysis.

The prognostic weight of histological and biological factors was compared with that of known clinical prognostic factors in a population of 108 consecutive previously untreated patients with head and neck squamous cell carcinoma. Parameters studied were: tumour vascularisation, mitotic index, histological differentiation, nuclear grade, keratinisation, desmoplasia, growth pattern, inflammation, tumour emboli in peripheral vessels, keratins 6, 13, 19 immunohistochemical expression, cytofluorometric ploidy and S-phase. In multivariate analysis (Cox), only age and nodal status had a significant impact on the overall survival, whereas T stage was the only significant factor associated with locoregional failure. The cumulative incidence of metastases was correlated not only with age, T and N stage, but also with histological differentiation. All the other histological and biological factors studied failed to provide further prognostic information. These findings may help to select patients with high metastatic risk

Advances in Xenotransplantation: Evaluation of αGal-KO Porcine Livers and Lungs Using Normothermic Machine Perfusion in a Collaborative Perfusion Hub

Recently, initial clinical experience has been gained with the xenotransplantation of pig organs such as heart and kidney into terminally ill human patients in an effort to overcoming organ shortage. Here, we investigated the use of normothermic machine perfusion (NMP) to advance xenotransplantation research and develop bridging therapies for acute organ failure such as the use of pig livers as a liver dialysis system. We simultaneously analyzed livers and lungs from genetically modified pigs, carrying a knock-out of the GGTA1 gene, which is essential for xenoreactive αGal-KO-epitopes, by applying clinically established normothermic perfusion systems, solutions and human blood. Experiments involved perfusing organs with cell-free solutions as well as human erythrocyte concentrates for up to six hours, analyzing organ quality using invasive and non-invasive methods, and the isolation and analysis of immune cells from the perfusate. The results obtained show stable flow characteristics with physiological perfusion and oxygenation levels of the organs, and a largely intact organ architecture, confirmed by histological sections before and after perfusion. Overall, this study demonstrates the feasibility of normothermic machine perfusion of xenogeneic organs by an interdisciplinary team, thus paving the way for clinical applications of porcine xenografts involving NMP

Manual versus automatic bladder wall thickness measurements: a method comparison study

Purpose To compare repeatability and agreement of conventional ultrasound bladder wall thickness (BWT) measurements with automatically obtained BWT measurements by the BVM 6500 device. Methods Adult patients with lower urinary tract symptoms, urinary incontinence, or postvoid residual urine were urodynamically assessed. During two subsequent cystometry sessions the infusion pump was temporarily stopped at 150 and 250 ml bladder filling to measure BWT with conventional ultrasound and the BVM 6500 device. For each method and each bladder filling, repeatability and variation was assessed by the method of Bland and Altman. Results Fifty unselected patients (30 men, 20 women) aged 21–86 years (median 62.5 years) were prospectively evaluated. Invalid BWT measurements were encountered in 2.1–14% of patients when using the BVM 6500 versus 0% with conventional ultrasound (significant only during the second measurement at 150 ml bladder filling). Mean difference in BWT values between the measurements of one technique was -0.1 to +0.01 mm. Measurement variation between replicate measurements was smaller for conventional ultrasound and the smallest for 250 ml bladder filling. Mean difference between the two techniques was 0.11–0.23 mm and did not differ significantly. The BVM 6500 device was not able to correctly measure BWTs above 4 mm. Conclusions Both BWT measurements are repeatable and agree with each other. However, conventional ultrasound measurements have a smaller measurement variance, can measure BWT in all patients, and BWTs above 4 mm