Integrated nonlinear structural simulation of composite buildings in fire

The collapse of several tall composite buildings over the last two decades has shown that the performance of tall, composite and complex buildings in fire is a necessary design consideration that ought to go beyond simple code compliance. To this end, several advancements in the field of numerical simulation of both the fire and the thermomechanical response of structures have been made. In isolation, the practical benefit of these advancements is limited, and their true potential is only unlocked when the results of those numerical simulations are integrated. This paper starts by showcasing recent developments in the thermal and thermomechanical analysis of structures using OpenSees. Integration of these developments into a unified simulation environment combining fire simulation, heat transfer, and mechanical analysis is then introduced. Finally, a demonstration example based on the large compartment Cardington test is used to showcase the necessity and efficiency of the developed simulation environment for thermomechanical simulation of composite structures in fire

Multiplex shRNA screening of germ cell development by in vivo transfection of mouse testis

Spermatozoa are one of the few mammalian cell types that cannot be fully derived in vitro, severely limiting the application of modern genomic techniques to study germ cell biology. The current gold standard approach of characterizing single-gene knockout mice is slow as generation of each mutant line can take 6–9 months. Here, we describe an in vivo approach to rapid functional screening of germline genes based on a new nonsurgical, nonviral in vivo transfection method to deliver nucleic acids into testicular germ cells. By coupling multiplex transfection of short hairpin RNA (shRNA) constructs with pooled amplicon sequencing as a readout, we were able to screen many genes for spermatogenesis function in a quick and inexpensive experiment. We transfected nine mouse testes with a pilot pool of RNA interference (RNAi) against well-characterized genes to show that this system is highly reproducible and accurate. With a false negative rate of 18% and a false positive rate of 12%, this method has similar performance as other RNAi screens in the well-described Drosophila model system. In a separate experiment, we screened 26 uncharacterized genes computationally predicted to be essential for spermatogenesis and found numerous candidates for follow-up studies. Finally, as a control experiment, we performed a long-term selection screen in neuronal N2a cells, sampling shRNA frequencies at five sequential time points. By characterizing the effect of both libraries on N2a cells, we show that our screening results from testis are tissue-specific. Our calculations indicate that the current implementation of this approach could be used to screen thousands of protein-coding genes simultaneously in a single mouse testis. The experimental protocols and analysis scripts provided will enable other groups to use this procedure to study diverse aspects of germ cell biology ranging from epigenetics to cell physiology. This approach also has great promise as an applied tool for validating diagnoses made from medical genome sequencing, or designing synthetic biological sequences that can act as potent and highly specific male contraceptives

Analysis of Restrained Composite Perforated Beams during Fire Using a Hybrid Simulation Approach

This paper is concerned with the behavior of restrained perforated beams acting compositely with a profiled slab during a fire. These members are increasingly popular in the construction of long-span floor systems because they provide a structurally and materially efficient design solution and provide space for placement of building services. However, their response during a fire has received little attention from the research community until recently. In the current work, a hybrid simulation-type numerical approach is adopted using a combination of the OpenSEES, ABAQUS, and OpenFresco software. The accuracy of the model is validated using available fire test data whereby the temperatures measured during the experiments are directly applied in the numerical model at various locations. The effect of axial and rotational restraint due to the connections between the beams and columns is also investigated following validation of the model. Furthermore, the hybrid simulation approach is employed to study a number of salient parameters, including load ratios, material grade, and the location of the openings. The variation in axial force during the fire is also examined. Various failure modes were observed during the analysis, including flexural and shear failure, failure of the web-post, concrete crushing, and also a Vierendeel mechanism. The fire resistance of the analyzed beams is compared with the values obtained from the most common design codes. Because of the consideration of restraint forces, which are not included in the design codes, the resistances predicted by the finite-element simulations were more favorable. It was found that the location of the openings along the span and also the boundary conditions had a considerable effect on the time-displacement behavior, axial reactions, and web-post buckling behavior, as well as the fire performance of the perforated beam

Analysis of restrained composite beams exposed to fire using a hybrid simulation approach

Obtaining an accurate simulation of the boundary conditions is very challenging but it is essential in order to represent the true behaviour of the whole structure in fire. In recent years, hybrid simulation has been emerging as an efficient and economical method for simulating realistic boundary conditions in the field of earthquake engineering. This technique can be used to study the load redistribution that may occur in a structural system as a result of locally elevated temperatures. In this paper, the fire-exposed element will be modelled in one analysis (a 3D model) and the rest of the structure in another analysis (a 2D model). This kind of sub-structuring enables the behaviour of the structural system as a whole to be studied. A hybrid simulation (HS) approach is presented and successfully implemented using the OpenFresco and OpenSees software. This approach enables the simulation of the correct restraint provided by the cold structure to the fire affected structural element. The HS analysis of a composite beam is compared with an unrestrained or simply supported version to highlight the difference in behaviour. Finally, the Cardington restrained beam test is modelled to demonstrate the potential of HS technique. Good agreement with the test results highlights that HS approach can be an effective method for studying the behaviour of the whole structural system

Heralded quantum entanglement between two crystals

Quantum networks require the crucial ability to entangle quantum nodes. A prominent example is the quantum repeater which allows overcoming the distance barrier of direct transmission of single photons, provided remote quantum memories can be entangled in a heralded fashion. Here we report the observation of heralded entanglement between two ensembles of rare-earth-ions doped into separate crystals. A heralded single photon is sent through a 50/50 beamsplitter, creating a single-photon entangled state delocalized between two spatial modes. The quantum state of each mode is subsequently mapped onto a crystal, leading to an entangled state consisting of a single collective excitation delocalized between two crystals. This entanglement is revealed by mapping it back to optical modes and by estimating the concurrence of the retrieved light state. Our results highlight the potential of rare-earth-ions doped crystals for entangled quantum nodes and bring quantum networks based on solid-state resources one step closer.Comment: 10 pages, 5 figure

Isatuximab plus pomalidomide and dexamethasone in relapsed/refractory multiple myeloma patients with renal impairment: ICARIA-MM subgroup analysis

The randomized, phase 3 ICARIA-MM study investigated isatuximab (Isa) with pomalidomide and dexamethasone (Pd) versus Pd in patients with relapsed/refractory multiple myeloma and ?2 prior lines. This prespecified subgroup analysis examined efficacy in patients with renal impairment (RI; estimated glomerular filtration rate <60 mL/min/1.73 m²). Isa 10 mg/kg was given intravenously once weekly in cycle 1, and every 2 weeks in subsequent 28-day cycles. Patients received standard doses of Pd. Median progression-free survival (PFS) for patients with RI was 9.5 months with Isa-Pd (n = 55) and 3.7 months with Pd (n = 49; hazard ratio [HR] 0.50; 95% confidence interval [CI], 0.30-0.85). Without RI, median PFS was 12.7 months with Isa-Pd (n = 87) and 7.9 months with Pd (n = 96; HR 0.58; 95% CI, 0.38-0.88). The overall response rate (ORR) with and without RI was higher with Isa-Pd (56 and 68%) than Pd (25 and 43%). Complete renal response rates were 71.9% (23/32) with Isa-Pd and 38.1% (8/21) with Pd; these lasted ?60 days in 31.3% (10/32) and 19.0% (4/21) of patients, respectively. Isa pharmacokinetics were comparable between the subgroups, suggesting no need for dose adjustment in patients with RI. In summary, the addition of Isa to Pd improved PFS, ORR and renal response rates

Different effect of the hyperons Λ\Lambda and Ξ\Xi on the nuclear core

We demonstrate the different effect of strange impurities ($\Lambda$ and $\Xi$) on the static properties of nuclei within the framework of the relativistic mean-field model. Systematic calculations show that the gluelike role of $\Lambda$ hyperon is universal for all $\Lambda$-hypernuclei considered. However, $\Xi^-$ hyperon has the gluelike role only for the protons distribution in nuclei, and for the neutrons distribution $\Xi^-$ hyperon plays a repulsive role. On the other hand, $\Xi^0$ hyperon attracts surrounding neutrons and reveals a repulsive force to the protons. Possible explanations of the above observation are discussed.Comment: 8 pages, 3 figure

Hsp90 governs dispersion and drug resistance of fungal biofilms

Fungal biofilms are a major cause of human mortality and are recalcitrant to most treatments due to intrinsic drug resistance. These complex communities of multiple cell types form on indwelling medical devices and their eradication often requires surgical removal of infected devices. Here we implicate the molecular chaperone Hsp90 as a key regulator of biofilm dispersion and drug resistance. We previously established that in the leading human fungal pathogen, Candida albicans, Hsp90 enables the emergence and maintenance of drug resistance in planktonic conditions by stabilizing the protein phosphatase calcineurin and MAPK Mkc1. Hsp90 also regulates temperature-dependent C. albicans morphogenesis through repression of cAMP-PKA signalling. Here we demonstrate that genetic depletion of Hsp90 reduced C. albicans biofilm growth and maturation in vitro and impaired dispersal of biofilm cells. Further, compromising Hsp90 function in vitro abrogated resistance of C. albicans biofilms to the most widely deployed class of antifungal drugs, the azoles. Depletion of Hsp90 led to reduction of calcineurin and Mkc1 in planktonic but not biofilm conditions, suggesting that Hsp90 regulates drug resistance through different mechanisms in these distinct cellular states. Reduction of Hsp90 levels led to a marked decrease in matrix glucan levels, providing a compelling mechanism through which Hsp90 might regulate biofilm azole resistance. Impairment of Hsp90 function genetically or pharmacologically transformed fluconazole from ineffectual to highly effective in eradicating biofilms in a rat venous catheter infection model. Finally, inhibition of Hsp90 reduced resistance of biofilms of the most lethal mould, Aspergillus fumigatus, to the newest class of antifungals to reach the clinic, the echinocandins. Thus, we establish a novel mechanism regulating biofilm drug resistance and dispersion and that targeting Hsp90 provides a much-needed strategy for improving clinical outcome in the treatment of biofilm infections