New meanings from old buildings

The three modest house projects described here are by three fellow travellers — the two authors and David Lea — interested in the Organic side of Modernism. Conversational partners who have worked together in various capacities over many years, they share a common conviction about ‘working with the given

Ca 2+ signalling in urethral interstitial cells of Cajal

Interstitial cells of Cajal (ICC) in the urethra have been proposed as specialized pacemakers that are involved in the generation of urethral tone and therefore the maintenance of urinary continence. Recent studies on freshly dispersed ICC from the urethra of rabbits have demonstrated that pacemaker activity in urethra ICC is characterized by spontaneous transient depolarizations (STDs) under current clamp and spontaneous transient inward currents (STICs) under voltage clamp. When these events were simultaneously recorded with changes in intracellular Ca 2+ (using a Nipkow spinning disk confocal microscope) they were found to be associated with global Ca 2+ oscillations. In this short review we will consider some of these recent findings regarding the contribution of intracellular Ca 2+ stores and Ca 2+ influx to the generation of pacemaker activity in urethral ICC with particular emphasis on the contribution of reverse Na + /Ca 2+ exchange (NCX)

Aprotinin reduces cardiac troponin I release and inhibits apoptosis of polymorphonuclear cells during off-pump coronary artery bypass surgery

Objectives: In addition to blood-sparing effects, aprotinin may have cardioprotective and anti-inflammatory effects during cardiopulmonary bypass-assisted cardiac surgery. In this study, the authors examined whether aprotinin had cardioprotective and/or anti-inflammatory effects in patients undergoing off-pump coronary artery bypass grafting. Design: A prospective randomized clinical trial. Setting: University hospital. Participants: Fifty patients were randomized to control (n = 25) or aprotinin treatment (n = 25) groups. Interventions: Aprotinin was given as a loading dose (2 x 10(6) KIU) followed by a continuous infusion at 5 x 10(5) KIU/h until skin closure. Measurements and Main Results: Blood samples for cardiac troponin I; interleukin-6, interleukin-8, and interleukin-10; tumor necrosis factor a; and elastase were taken after anesthesia induction, completion of revascularization, and 6 hours, 12 hours, and 24 hours after revascularization. Blood samples were taken to assess for apoptosis in polymorphonuclear cells. Baseline plasma levels for cardiac troponin I did not differ between groups but were significantly lower in aprotinin-treated patients at the time of revascularization (P = 0.03) and 6 hours (p = 0.004) and 24 hours (p = 0.03) later. Aprotinin significantly reduced apoptosis in polymorphonuclear cells compared with control-treated patients (p = 0.04). There were no differences in plasma cytokine or elastase levels between groups. Conclusions: The authors conclude that aprotinin reduces perioperative cardiac troponin I release and attenuates apoptosis in polymorphonuclear cells but has no significant effects on plasma cytokine levels in patients undergoing off-pump coronary artery bypass graft surgery

Analytical modeling of axial flux PM machines with eccentricities

© 2017 IOS Press and the authors. All rights reserved. In this paper, an analytical quasi three-dimensional method is used to model an axial flux permanent magnet (AFPM) machine with various eccentricities. AFPM machines (AFPMMs) have various advantages but they are sensitive to geometrical imperfections for manufacturing aspect. The main aim of this paper is to propose a general analytical model to analyze the AFPMMs with various types of eccentricities. The radial and tangential magnetic flux densities in the air gap under healthy condition are obtained via combination of Maxwell's equations and Schwarz-Christoffel (SC) mapping firstly. Next, in order to investigate the eccentricities, equations for air gap length and radii are deduced. The back electromotive force (EMF) is calculated and compared with those from healthy condition and finite element (FE) analysis, respectively. The results show that the analytical predictions agree well with the FE results. Moreover, using this method has a significantly less time consuming than the 3D FM simulation process, which is a great advantage of this method. Finally, the analytical model is verified via experimental results

Recovery of a Medieval Brucella melitensis genome using shotgun metagenomics

ABSTRACT Shotgun metagenomics provides a powerful assumption-free approach to the recovery of pathogen genomes from contemporary and historical material. We sequenced the metagenome of a calcified nodule from the skeleton of a 14th-century middle-aged male excavated from the medieval Sardinian settlement of Geridu. We obtained 6.5-fold coverage of a Brucella melitensis genome. Sequence reads from this genome showed signatures typical of ancient or aged DNA. Despite the relatively low coverage, we were able to use information from single-nucleotide polymorphisms to place the medieval pathogen genome within a clade of B. melitensis strains that included the well-studied Ether strain and two other recent Italian isolates. We confirmed this placement using information from deletions and IS711 insertions. We conclude that metagenomics stands ready to document past and present infections, shedding light on the emergence, evolution, and spread of microbial pathogens

Contribution of K v 2.1 channels to the delayed rectifier current in freshly dispersed smooth muscle cells from rabbit urethra

We have characterized the native voltage-dependent K + (K v ) current in rabbit urethral smooth muscle cells (RUSMC) and compared its pharmacological and biophysical properties with K v 2.1 and K v 2.2 channels cloned from the rabbit urethra and stably expressed in HEK 293 cells (HEK Kv2.1 and HEK Kv2.2 ). RUSMC were perfused with Hanks' solution at 37°C and studied using the patch clamp technique with K + -rich pipette solutions. Cells were bathed in 100 nM penitrem A (Pen A) to block large conductance Ca 2+ -activated K + (BK) currents and depolarized to +40 mV for 500 ms to evoke K v currents. These were unaffected by margatoxin, κ-dendrotoxin or α-dendrotoxin (100 nM, n=3-5), but were blocked by stromatoxin-1 (ScTx, IC 50 ~130 nM), consistent with the idea that the currents were carried through K v 2 channels. RNA was detected for K v 2.1 K v 2.2 and the silent subunit K v 9.3 in urethral smooth muscle. Immunocytochemistry showed membrane staining for both K v 2 subtypes and K v 9.3 in isolated RUSMC. HEK Kv2.1 and HEK Kv2.2 currents were blocked in a concentration dependent manner by ScTx with estimated IC 50 values of ~150 nM (K v 2.1, n=5) and 70 nM (K v 2.2, n=6). The mean V 1/2 of inactivation of the USMC K v current was – 56±3 mV (n=9). This was similar to the HEK Kv2.1 current (–55 ± 3 mV, n=13) but significantly different from the HEK Kv2.2 currents (-30 ± 3 mV, n=11). Action potentials (AP) evoked from RUSMC studied under current clamp mode were unaffected by ScTx. However when ScTx was applied in the presence of Pen A, the AP duration was significantly prolonged. Similarly, ScTx increased the amplitude of spontaneous contractions threefold, but only after Pen A application. These data suggest that K v 2.1 channels contribute significantly to the K v current in RUSMC

How to develop, externally validate, and update multinomial prediction models

Multinomial prediction models (MPMs) have a range of potential applications across healthcare where the primary outcome of interest has multiple nominal or ordinal categories. However, the application of MPMs is scarce, which may be due to the added methodological complexities that they bring. This article provides a guide of how to develop, externally validate, and update MPMs. Using a previously developed and validated MPM for treatment outcomes in rheumatoid arthritis as an example, we outline guidance and recommendations for producing a clinical prediction model using multinomial logistic regression. This article is intended to supplement existing general guidance on prediction model research. This guide is split into three parts: 1) Outcome definition and variable selection, 2) Model development, and 3) Model evaluation (including performance assessment, internal and external validation, and model recalibration). We outline how to evaluate and interpret the predictive performance of MPMs. R code is provided. We recommend the application of MPMs in clinical settings where the prediction of a nominal polytomous outcome is of interest. Future methodological research could focus on MPM-specific considerations for variable selection and sample size criteria for external validation

Experimental investigation of aminoacetonitrile formation through the Strecker synthesis in astrophysical-like conditions: reactivity of methanimine (CH2NH), ammonia (NH3), and hydrogen cyanide (HCN)

International audienceAstronomy & Astrophysics Experimental investigation of aminoacetonitrile formation through the Strecker synthesis in astrophysical-like conditions: reactivity of methanimine (CH 2 NH), ammonia (NH 3), and hydrogen cyanide (HCN) ABSTRACT Context. Studing chemical reactivity in astrophysical environments is an important means for improving our understanding of the origin of the organic matter in molecular clouds, in protoplanetary disks, and possibly, as a final destination, in our solar system. Laboratory simulations of the reactivity of ice analogs provide important insight into the reactivity in these environments. Here, we use these experimental simulations to investigate the Strecker synthesis leading to the formation of aminoacetonitrile in astrophysical-like conditions. The aminoacetonitrile is an interesting compound because it was detected in SgrB2, hence could be a precursor of the smallest amino acid molecule, glycine, in astrophysical environments. Aims. We present the first experimental investigation of the formation of aminoacetonitrile NH 2 CH 2 CN from the thermal processing of ices including methanimine (CH 2 NH), ammonia (NH 3), and hydrogen cyanide (HCN) in interstellar-like conditions without VUV photons or particules. Methods. We use Fourier Transform InfraRed (FTIR) spectroscopy to monitor the ice evolution during its warming. Infrared spec-troscopy and mass spectroscopy are then used to identify the aminoacetonitrile formation. Results. We demonstrate that methanimine can react with − CN during the warming of ice analogs containing at 20 K methanimine, ammonia, and [NH + 4 − CN] salt. During the ice warming, this reaction leads to the formation of poly(methylene-imine) polymers. The polymer length depend on the initial ratio of mass contained in methanimine to that in the [NH + 4 − CN] salt. In a methanimine excess, long polymers are formed. As the methanimine is progressively diluted in the [NH + 4 − CN] salt, the polymer length decreases until the aminoacetonitrile formation at 135 K. Therefore, these results demonstrate that aminoacetonitrile can be formed through the second step of the Strecker synthesis in astrophysical-like conditions