An ultra-compact low temperature scanning probe microscope for magnetic fields above 30 T

We present the design of a highly compact High Field Scanning Probe Microscope (HF-SPM) for operation at cryogenic temperatures in an extremely high magnetic field, provided by a water-cooled Bitter magnet able to reach 38 T. The HF-SPM is 14 mm in diameter: an Attocube nano-positioner controls the coarse approach of a piezo resistive AFM cantilever to a scanned sample. The Bitter magnet constitutes an extreme environment for SPM due to the high level of vibrational noise; the Bitter magnet noise at frequencies up to 300 kHz is characterized and noise mitigation methods are described. The performance of the HF-SPM is demonstrated by topographic imaging and noise measurements at up to 30 T. Additionally, the use of the SPM as a three-dimensional dilatometer for magnetostriction measurements is demonstrated via measurements on a magnetically frustrated spinel sample.Comment: 6 pages, 5 figure

Isolation and function of a human endothelial cell C1q receptor

It has been shown previously that cultured human venous and arterial endothelial cells (EC) bind C1q in a time- and dose-dependent manner. Cultured human endothelial cells express an average number of 5.2 × 105 binding sites/cell. In the present study the putative receptor for C1q (C1qR) was isolated from the membranes of 1–5 × 109 human umbilical cord EC by affinity chromatography on C1q–Sepharose. During isolation, C1qR was detected by its capacity to inhibit the lysis of EAC1q in C1q-deficient serum. The eluate from C1q–Sepharose was concentrated, dialysed and subjected to QAE-A50 chromatography and subsequently to gel filtration on HPLC–TSK 3000. C1qR filtered at an apparent molecular weight of 60 kDa. Purified C1qR exhibited an apparent molecular weight of 55–62 kDa in the unreduced state and a molecular weight of 64–68 kDa in reduced form. Two IgM monoclonal antibodies (mAb) D3 and D5 were raised following immunization of mice with purified receptor preparations. Both monoclonal antibodies increased the binding of 125I-C1q to endothelial cells but F(ab')2 anti-C1qR mAb inhibited the binding of a125I-C1q to EC in a dosedependent manner. The D3 mAb recognized a band of 54–60 kDa in Western blots of membranes of human EC and polymorphonuclear leukocytes. Previously, the authors showed that C1q induces the binding of IgM-containing immune complexes to EC. Therefore, it was hypothesized that during a primary immune response generation of IgM-IC may occur, resulting in binding and activation of C1, dissociation of activated C1 by C1 inhibitor and subsequent interaction of IgM-IC bearing C1q with EC–C1qR

Denitrification in an oligotrophic estuary: a delayed sink for riverine nitrate

Estuaries are often seen as natural filters of riverine nitrate, but knowledge of this nitrogen sink in oligotrophic systems is limited. We measured spring and summer dinitrogen production (denitrification, anammox) in muddy and non-permeable sandy sediments of an oligotrophic estuary in the northern Baltic Sea, to estimate its function in mitigating the riverine nitrate load. Both sediment types had similar denitrification rates, and no anammox was detected. In spring at high nitrate loading, denitrification was limited by likely low availability of labile organic carbon. In summer, the average denitrification rate was similar to 138 mu mol N m(-2) d(-1). The corresponding estuarine nitrogen removal for August was similar to 1.2 t, of which similar to 93% was removed by coupled nitrification-denitrification. Particulate matter in the estuary was mainly phytoplankton derived (> 70% in surface waters) and likely based on the riverine nitrate which was not removed by direct denitrification due to water column stratification. Subsequently settling particles served as a link be tween the otherwise uncoupled nitrate in surface waters and benthic nitrogen removal. We suggest that the riverine nitrate brought into the oligotrophic estuary during the spring flood is gradually, and with a time delay, removed by benthic denitrification after being temporarily ` trapped' in phytoplankton particulate matter. The oligotrophic system is not likely to face eutrophication from increasing nitrogen loading due to phosphorus limitation. In response, coupled nitrification-denitrification rates are likely to stay constant, which might increase the future export of nitrate to the open sea and decrease the estuary's function as a nitrogen sink relative to the load.Peer reviewe

On the Neutral Gas Content and Environment of NGC 3109 and the Antlia Dwarf Galaxy

As part of a continuing survey of nearby galaxies, we have mapped the neutral gas content of the low surface brightness, Magellanic-type galaxy NGC 3109 --- and its environment, including the Antlia dwarf galaxy --- at unprecedented velocity resolution and brightness sensitivity. The HI mass of NGC 3109 is measured to be (3.8 +/- 0.5) x 10^8 Msun. A substantial warp in the disk of NGC 3109 is detected in the HI emission image in the form of an extended low surface brightness feature. We report a positive detection in HI of the nearby Antlia dwarf galaxy, and measure its total neutral gas mass to be (6.8 +/- 1.4) x 10^5 Msun. We show the warp in NGC 3109 to lie at exactly the same radial velocity as the gas in the Antlia dwarf galaxy and speculate that Antlia disturbed the disk of NGC 3109 during a mild encounter ~1 Gyr in the past. HI data for a further eight galaxies detected in the background are presented.Comment: Accepted for publication in A

Abundance Gradients and the Formation of the Milky Way

In this paper we adopt a chemical evolution model, which is an improved version of the Chiappini, Matteucci and Gratton (1997) model, assuming two main accretion episodes for the formation of the Galaxy. The present model takes into account in more detail than previously the halo density distribution and explores the effects of a threshold density in the star formation process, during both the halo and disk phases. In the comparison between model predictions and available data, we have focused our attention on abundance gradients as well as gas, stellar and star formation rate distributions along the disk. We suggest that the mechanism for the formation of the halo leaves detectable imprints on the chemical properties of the outer regions of the disk, whereas the evolution of the halo and the inner disk are almost completely disentangled. This is due to the fact that the halo and disk densities are comparable at large Galactocentric distances and therefore the gas lost from the halo can substantially contribute to building up the outer disk. We also show that the existence of a threshold density for the star formation rate, both in the halo and disk phase, is necessary to reproduce the majority of observational data in the solar vicinity and in the whole disk. Moreover, we predict that the abundance gradients along the Galactic disk must have increased with time and that the average [alpha/Fe] ratio in stars (halo plus disk) slightly decrease going from 4 to 10 Kpcs from the Galactic center. We also show that the same ratios increase substantially towards the outermost disk regions and the expected scatter in the stellar ages decreases, because the outermost regions are dominated by halo stars.Comment: 41 pages (including the figures), To be published in Ap

Recurrent Pneumonia Due to an Appendiceal Mucinous Cystadenocarcinoma: A Rare Presentation of a Rare Malignancy

Mucinous cystadenocarcinoma of the appendix is a rare malignancy. This is a report of a 74-year-old man who presented with recurrent pneumonia which turned out to be a postobstructive pneumonia complicating a large mucinous cystadenocarcinoma of the appendix with massive retroperitoneal and intrathoracic extension. Mucinous cystadenocarcinoma of the appendix is a low-grade malignancy characterized by expansive growth due to progressive accumulation of mucinous fluid produced by the cancer cells. The tendency of this tumor to expand massively is well demonstrated by this case. The unusual retroperitoneal location of appendix in this patient probably allowed the tumor to expand massively in the retroperitoneal space and the thoracic cavity. In addition to computed tomography, [18F]fluorodeoxyglucose positron emission tomography (18F-FDG PET) was used as an ancillary method for staging in this patient. The value of 18F-FDG PET in the diagnosis of mucinous cystadenocarcinoma of the appendix has not been determined yet, but it might be promising. The most common presentation of this tumor is abdominal pain or a palpable ileocoecal mass. To the knowledge of the authors, this is the first report of an appendiceal mucinous cystadenocarcinoma with expansion into the thoracic cavity presenting with recurrent pneumonia

Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of >2 years of follow-up.

BackgroundNovel second-line treatments are needed for patients with advanced urothelial cancer (UC). Interim analysis of the phase III KEYNOTE-045 study showed a superior overall survival (OS) benefit of pembrolizumab, a programmed death 1 inhibitor, versus chemotherapy in patients with advanced UC that progressed on platinum-based chemotherapy. Here we report the long-term safety and efficacy outcomes of KEYNOTE-045.Patients and methodsAdult patients with histologically/cytologically confirmed UC whose disease progressed after first-line, platinum-containing chemotherapy were enrolled. Patients were randomly assigned 1 : 1 to receive pembrolizumab [200 mg every 3 weeks (Q3W)] or investigator's choice of paclitaxel (175 mg/m2 Q3W), docetaxel (75 mg/m2 Q3W), or vinflunine (320 mg/m2 Q3W). Primary end points were OS and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central radiology review (BICR). A key secondary end point was objective response rate per RECIST v1.1 by BICR.ResultsA total of 542 patients were enrolled (pembrolizumab, n = 270; chemotherapy, n = 272). Median follow-up as of 26 October 2017 was 27.7 months. Median 1- and 2-year OS rates were higher with pembrolizumab (44.2% and 26.9%, respectively) than chemotherapy (29.8% and 14.3%, respectively). PFS rates did not differ between treatment arms; however, 1- and 2-year PFS rates were higher with pembrolizumab. The objective response rate was also higher with pembrolizumab (21.1% versus 11.0%). Median duration of response to pembrolizumab was not reached (range 1.6+ to 30.0+ months) versus chemotherapy (4.4 months; range 1.4+ to 29.9+ months). Pembrolizumab had lower rates of any grade (62.0% versus 90.6%) and grade ≥3 (16.5% versus 50.2%) treatment-related adverse events than chemotherapy.ConclusionsLong-term results (>2 years' follow-up) were consistent with those of previously reported analyses, demonstrating continued clinical benefit of pembrolizumab over chemotherapy for efficacy and safety for treatment of locally advanced/metastatic, platinum-refractory UC.Trial registrationClinicalTrials.gov: NCT02256436

Participant music listening behaviours in interactive multimedia music instruction

While emerging technologies such as interactive multimedia are increasingly being employed in computerised music instruction, understanding of participant music listening behaviours in interactive multimedia music instruction is currently very limited. With the aim of elucidating music listening behaviour, the central concern of this work is to identify and explain participant interactions with the audio components of interactive multimedia music instruction. The investigation employs a novel documentation procedure, which extends the application of digital audio recording technology, to provide a finely calibrated analysis of the audio activity of a sample of 20 undergraduate music education majors during individual sessions with two commercially-available interactive multimedia music instruction programs. Graphically-based Sound Activity Profiles, which the researcher developed specifically for the current investigation, characterise and summarise participant interactions with audio components, while an analysis of questionnaire responses and follow-up interview transcripts provides supplementary information that further explains participants' music listening behaviours. The results of the investigation show that music listening behaviours during the study sessions were highly variable. While extensive participant interaction with music examples occasionally reflected attentive music listening behaviours, many study sessions were characterised by brief, fragmentary music excerpts and lengthy periods of silence. Participants spent as little as five percent of their session time listening to music and as much as 88 percent of the session time in silence. A substantial number of the study cohort frequently interrupted the music examples they had activated. Participants' perceptions of the extent of their interaction with music examples were frequently inaccurate, as subjects often substantially overestimated the amount of session time they had spent listening to music. The study findings suggest that many interactive multimedia music instruction participants would benefit from interventions that elicit more extensive and prolonged interaction with music examples. Accordingly, recommendations include a call for research to develop and test software designs that incorporate automated monitoring of session audio activity so that dynamic on-screen information about music listening behaviour can be provided to interactive multimedia music instruction participants. Such information may encourage participants to modify inappropriate music listening behaviours

Search for the evidence of endocrine disruption in the aquatic environment; Lessons to be learned from joint biological and chemical monitoring in the European project COMPREHEND

Between January 1999 and December 2001, the European Community project COMPREHEND was performed. The overall aim of COMPREHEND was to assess endocrine disruption in the aquatic environment in Europe, consequent to effluent discharge, with emphasis on estrogenic activity. COMPREHEND demonstrated the widespread occurrence of estrogenic effluents across Europe and presented evidence of impacts on a range of wild fish species. Using a variety of bioassays in combination with chemical analytical methods, estrogenic steroids of human origin from domestic wastewater effluents were identified as the most pervasive problem, although alkylphenols may be important estrogenic components of some industrial effluents. New tools have been developed for the identification of estrogenic effluents, and recommendations are made for the improvement of existing techniques. We have shown that individual fish within natural populations may be feminized to varying degrees, but it has not been possible to show, using traditional fish population parameters, that the survival of fish populations is threatened. However, laboratory-based fish life-cycle studies demonstrate the sensitivity of fish to estrogen (and androgen) exposure and how this might lead to complex (and potentially damaging) genetic changes at the population level. New approaches to this problem, utilizing recent advances made in the field of molecular and population genetics, are recommended. Finally, a study of estrogenic and androgenic activity of waste waters during the treatment process has shown that some of the existing wastewater treatment technologies have the potential to eliminate or minimize the hormonal activity of the final effluen