Multi-stage emplacement of the Götemar Pluton, SE Sweden: new evidence inferred from field observations and microfabric analysis, including cathodoluminescence microscopy

The emplacement of the Mesoproterozoic Götemar Pluton into Paleoproterozoic granitoid host rocks of the Transscandinavian Igneous Belt is re-examined by microfabric analysis, including cathodoluminescence microscopy. Field data on the pluton-host rock system are used to strengthen the model. The Götemar Pluton, situated on the Baltic Shield of SE Sweden, is a horizontally zoned tabular structure that was constructed by the intrusion of successive pulses of magma with different crystal/melt ratios, at an estimated crustal depth of 4–8 km. Initial pluton formation involved magma ascent along a vertical dike, which was arrested at a mechanical discontinuity within the granitoid host rocks; this led to the formation of an initial sill. Subsequent sill stacking and their constant inflation resulted in deformation and reheating of existing magma bodies, which also raised the pluton roof. This multi-stage emplacement scenario is indicated by complex dike relationships and the occurrence of several generations of quartz (Si-metasomatism). The sills were charged by different domains of a heterogeneous magma chamber with varying crystal/melt ratios. Ascent or emplacement of magma with a high crystal/melt ratio is indicated by syn-magmatic deformation of phenocrysts. Complex crystallization fabrics (e.g. oscillatory growth zoning caused by high crystal defect density, overgrowth and replacement features, resorbed and corroded crystal cores, rapakivi structure) are mostly related to processes within the main chamber, that is repeated magma mixing or water influx

Microoptomechanical pumps assembled and driven by holographic optical vortex arrays

Beams of light with helical wavefronts can be focused into ring-like optical traps known as optical vortices. The orbital angular momentum carried by photons in helical modes can be transferred to trapped mesoscopic objects and thereby coupled to a surrounding fluid. We demonstrate that arrays of optical vortices created with the holographic optical tweezer technique can assemble colloidal spheres into dynamically reconfigurable microoptomechanical pumps assembled by optical gradient forces and actuated by photon orbital angular momentum.Comment: 4 pages, 3 figures, submitted to Optics Expres

Vacuum Deployment and Testing of a 4-Quadrant Scalable Inflatable Solar Sail System

Solar sails reflect photons streaming from the sun and transfer momentum to the sail. The thrust, though small, is continuous and acts for the life of the mission without the need for propellant. Recent advances in materials and ultra-low mass gossamer structures have enabled a host of useful missions utilizing solar sail propulsion. The team of L'Garde, Jet Propulsion Laboratories, Ball Aerospace, and Langley Research Center, under the direction of the NASA In-Space Propulsion office, has been developing a scalable solar sail configuration to address NASA s future space propulsion needs. The baseline design currently in development and testing was optimized around the 1 AU solar sentinel mission. Featuring inflatably deployed sub-T(sub g), rigidized beam components, the 10,000 sq m sail and support structure weighs only 47.5 kg, including margin, yielding an areal density of 4.8 g/sq m. Striped sail architecture, net/membrane sail design, and L'Garde's conical boom deployment technique allows scalability without high mass penalties. This same structural concept can be scaled to meet and exceed the requirements of a number of other useful NASA missions. This paper discusses the interim accomplishments of phase 3 of a 3-phase NASA program to advance the technology readiness level (TRL) of the solar sail system from 3 toward a technology readiness level of 6 in 2005. Under earlier phases of the program many test articles have been fabricated and tested successfully. Most notably an unprecedented 4-quadrant 10 m solar sail ground test article was fabricated, subjected to launch environment tests, and was successfully deployed under simulated space conditions at NASA Plum Brook s 30m vacuum facility. Phase 2 of the program has seen much development and testing of this design validating assumptions, mass estimates, and predicted mission scalability. Under Phase 3 a much larger 20 m square test article including subscale vane has been fabricated and tested. A 20 m system ambient deployment has been successfully conducted after enduring Delta-2 launch environment testing. The program will culminate in a vacuum deployment of a 20 m subscale test article at the NASA Glenn s Plum Brook 30 m vacuum test facility to bring the TRL level as close to 6 as possible in 1 g. This focused program will pave the way for a flight experiment of this highly efficient space propulsion technology

Electromagnetic trapping of chiral molecules: orientational effects of the irradiating beam

The photonic interaction generally responsible for the electromagnetic trapping of molecules is forward-Rayleigh scattering, a process that is mediated by transition electric dipoles connecting the ground electronic state and virtual excited states. Higher order electric and magnetic multipole contributions to the scattering amplitude are usually negligible. However, on consideration of chiral discrimination effects (in which an input light of left-handed circular polarization can present different observables compared to right-handed polarization, or molecules of opposite enantiomeric form respond differently to a set circular polarization), the mechanism must be extended to specifically accommodate transition magnetic dipoles. Moreover, it is important to account for the fact that chiral molecules are necessarily non-spherical, so that their interactions with a laser beam will have an orientational dependence. Using quantum electrodynamics, this article quantifies the extent of the energetic discrimination that arises when chiral molecules are optically trapped, placing particular emphasis on the orientational effects of the trapping beam. An in-depth description of the intricate ensemble-weighted method used to incorporate the latter is presented. It is thus shown that, when a mixture of molecular enantiomers is irradiated by a continuous beam of circularly polarized light, a difference arises in the relative rates of migration of each enantiomer in and out of the most intense regions of the beam. In consequence, optical trapping can be used as a means of achieving enantiomer separation

First-in-Man Phase I Trial of the Selective MET Inhibitor Tepotinib in Patients with Advanced Solid Tumors.

PurposeTepotinib is an oral, potent, highly selective MET inhibitor. This first-in-man phase I trial investigated the MTD of tepotinib to determine the recommended phase II dose (RP2D).Patients and methodsPatients received tepotinib orally according to one of three dose escalation regimens (R) on a 21-day cycle: R1, 30-400 mg once daily for 14 days; R2, 30-315 mg once daily 3 times/week; or R3, 300-1,400 mg once daily. After two cycles, treatment could continue in patients with stable disease until disease progression or unacceptable toxicity. The primary endpoint was incidence of dose-limiting toxicity (DLT) and treatment-emergent adverse events (TEAE). Secondary endpoints included safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor effects.ResultsOne hundred and forty-nine patients received tepotinib (R1: n = 42; R2: n = 45; R3: n = 62). Although six patients reported DLTs [one patient in R1 (115 mg), three patients in R2 (60, 100, 130 mg), two patients in R3 (1,000, 1,400 mg)], the MTD was not reached at the highest tested dose of 1,400 mg daily. The RP2D of tepotinib was established as 500 mg once daily, supported by translational modeling data as sufficient to achieve ≥95% MET inhibition in ≥90% of patients. Treatment-related TEAEs were mostly grade 1 or 2 fatigue, peripheral edema, decreased appetite, nausea, vomiting, and lipase increase. The best overall response in R3 was partial response in two patients, both with MET overexpression.ConclusionsTepotinib was well tolerated with clinical activity in MET-dysregulated tumors. The RP2D of tepotinib was established as 500 mg once daily. MET abnormalities can drive tumorigenesis. This first-in-man trial demonstrated that the potent, highly selective MET inhibitor tepotinib can reduce or stabilize tumor burden and is well tolerated at doses up to 1,400 mg once daily. An RP2D of 500 mg once daily, as determined from translational modeling and simulation integrating human population pharmacokinetic and pharmacodynamic data in tumor biopsies, is being used in ongoing clinical trials

The too-much precision effect: When and why precise anchors backfire with experts

All data and materials have been made publicly available via the Open Science Framework and can be accessed at https://osf.io/b8zft/.</p

Analysis of Epithelial Growth Factor-Receptor (EGFR) Phosphorylation in Uterine Smooth Muscle Tumors

Uterine fibroids are the commonest uterine benign tumors. A potential mechanism of malignant transformation from leiomyomas to leiomyosarcomas has beendescribed. Tyrosine phosphorylation is a key mechanism that controls biological functions, such as proliferation and cell differentiation. The aim of the current study was to evaluate the phosphorylation of epithelial growth factor-receptor (EGFR) in normal myometrium, uterine myomas and uterine leiomyosarcomas. Formalin-fixed paraffin-embedded tissue samples from normal myometrium, leiomyomas and leiomyosarcomas were studied. Samples were immunohistochemically (IHC) assessed using the anti-EGFR phosphorylation of Y845 (pEGFR-Y845) and anti-pEGFR-Y1173 phosphorylation-specific antibodies. IHC staining was evaluated using a semiquantitative score. The expression of pEGFR-Y845 was significantly upregulated in leiomyosarcomas (p < 0.001) compared to leiomyomas and normal myometrium. In contrast, pEGFR-Y1173 did not differ significantly between the three groups of the study. Correlation analysis revealed an overall positive correlation between pEGFR Y845 and mucin 1 (MUC1). Further subgroup analysis within the tumoral group (myomas and leiomyosarcomas) revealed an additional negative correlation between pEGFR Y845 and galectin-3 (gal-3) staining. On the contrary no significant correlation was noted within the non-tumoral group. An upregulated EGFR phosphorylation of Y845 in leiomyosarcomas compared to leiomyomas implicates EGFR activation at this special receptor site. Due to these pEGFR-Y845 variations, it can be postulated that MUC1 interacts with it, whereas gal-3 seems to be cleaved from Y845 phosphorylated EGFR. Further research on this field could focus on differences in EGFR pathways as a potentially advantageous diagnostic tool for investigation of benign and malignant signal transduction processes

DEFENS - Drug Exposure Feedback and Education for Nurses’ Safety: study protocol for a randomized controlled trial

Abstract Background Three decades of research findings have documented the health effects of handling hazardous drugs. Oncology nurses are vulnerable due to frequent administration of antineoplastics, low adherence to equipment use, reported barriers to use, and perceived low risk of health effects. No interventions have been tested in a controlled, multi-site trial to increase nurses’ use of protective equipment when handling hazardous drugs. The Drug Exposure Feedback and Education for Nurses’ Safety (DEFENS) study will compare the efficacy of education (control) versus an audit and feedback intervention (treatment) on nurses’ self-reported use of personal protective equipment when handling hazardous drugs. The treatment intervention will include tailored messages based on nurses’ reported barriers to protective equipment use. Methods/Design The DEFENS Study is a cluster randomized controlled trial. We are enrolling cancer centers and will recruit nurse participants in April 2015. Eligible cancer centers employ at least 20 eligible registered nurses in the chemotherapy infusion setting and have on-site phlebotomy resources. Eligible participants are nurses who work at least 0.40 full-time equivalent hours in the chemotherapy infusion setting and have not received an antineoplastic drug for a health problem in the past year. An encrypted, user-authenticated website will administer surveys and deliver control and treatment interventions. The primary endpoint is the change in score on nurses’ reports of the Revised Hazardous Drug Handling Questionnaire between baseline and approximately 18 months later. A baseline survey is completed after informed consent and is repeated 18 months later. Nurses in all sites who experience a drug spill will also report incidents as they occur; these reports inform the treatment intervention. Plasma will be obtained at baseline, approximately 18 months later (the primary endpoint), and with drug spill occurrences to measure hazardous drugs levels and to inform the treatment intervention. Potential mediators include knowledge of hazardous drug handling and perceived risk of drug exposure. We will examine whether personal factors and organizational factors moderate the intervention effects. Trial registration Clinicaltrials.gov NCT02283164 , registered 31 October 2014.http://deepblue.lib.umich.edu/bitstream/2027.42/111045/1/13063_2015_Article_674.pd

Decidual Macrophages Are Significantly Increased in Spontaneous Miscarriages and Over-Express FasL

Decidual macrophages (DM) are the second most abundant population in the fetal-maternal interface. Their role has been so far identified as being local immuno-modulators favoring the maternal tolerance to the fetus. Herein we investigated tissue samples from 11 cases of spontaneous miscarriages and from 9 cases of elective terminations of pregnancy. Using immunohistochemistry and dual immunofluorescence we have demonstrated that in spontaneous miscarriages the DM are significantly increased. Additionally, we noted a significant up-regulation of macrophage FasL expression. Our results further support a dual role for DM during pregnancy and miscarriages. We hypothesize that the baseline DM population in normal pregnancy is in line with an M2 phenotype supporting the ongoing gestation. In contrast, during spontaneous miscarriages, the increased FasL-expressing population could be a part of an M1 phenotype participating in Fas/FasL-related apoptosis. Our results highlight a new aspect of macrophage biology in pregnancy physiology and pathophysiology. Further studies with larger samples are needed to verify the current results and evaluate their clinical impact