The detection of individual quanta of light is important for quantum communication, fluorescence lifetime imaging, remote sensing and more. Due to their high detection efficiency, exceptional ...signal-to-noise ratio and fast recovery times, superconducting-nanowire single-photon detectors (SNSPDs) have become a critical component in these applications. However, the operation of conventional SNSPDs requires costly cryocoolers. Here we report the fabrication of two types of high-temperature superconducting nanowires. We observe linear scaling of the photon count rate on the radiation power at the telecommunications wavelength of 1.5 μm and thereby reveal single-photon operation. SNSPDs made from thin flakes of Bi
Sr
CaCu
O
exhibit a single-photon response up to 25 K, and for SNSPDs from La
Sr
CuO
/La
CuO
bilayer films, this response is observed up to 8 K. While the underlying detection mechanism is not fully understood yet, our work expands the family of materials for SNSPD technology beyond the liquid helium temperature limit and suggests that even higher operation temperatures may be reached using other high-temperature superconductors.
As the limits of traditional von Neumann computing come into view, the brain’s ability to communicate vast quantities of information using low-power spikes has become an increasing source of ...inspiration for alternative architectures. Key to the success of these largescale neural networks is a power-efficient spiking element that is scalable and easily interfaced with traditional control electronics. In this work, we present a spiking element fabricated from superconducting nanowires that has pulse energies on the order of ∼10 aJ. We demonstrate that the device reproduces essential characteristics of biological neurons, such as a refractory period and a firing threshold. Through simulations using experimentally measured device parameters, we show how nanowire-based networks may be used for inference in image recognition and that the probabilistic nature of nanowire switching may be exploited for modeling biological processes and for applications that rely on stochasticity.
We developed superconducting nanowire single-photon detectors based on tungsten silicide, which show saturated internal detection efficiency up to a wavelength of 10 μm. These detectors are promising ...for applications in the mid-infrared requiring sub-nanosecond timing, ultra-high gain stability, low dark counts, and high efficiency, such as chemical sensing, LIDAR, dark matter searches, and exoplanet spectroscopy.
The purpose of this article is to report the exposure–response (E–R) relationship of posaconazole oral suspension (POS) for prophylaxis against invasive fungal infections (IFIs), on the basis of the ...US Food and Drug Administration (FDA) clinical pharmacology review of two randomized, active‐controlled clinical studies. Posaconazole average steady state plasma concentrations (Cavg) ranged from 22 to 3,650 ng/ml after administration of POS 200 mg three times daily (t.i.d.). In a double‐blind, randomized clinical trial, the quartile ranges of Cavg with midpoint values of 289, 736, 1,239, and 2,607 ng/ml had clinical failure rates of 44, 21, 18, and 18%, respectively, indicating an inverse association between Cavg and clinical failure rate. There were no significant relationships between Cavg and posaconazole‐related major adverse events. Determining posaconazole concentrations in plasma will aid in assessing the need for either POS dose adjustment (e.g., increasing the POS dose) or switching to another systemic antifungal drug, thereby improving the effectiveness of prophylaxis against IFIs.
Clinical Pharmacology & Therapeutics (2010) 88 1, 115–119. doi: 10.1038/clpt.2010.64
Selective or Multiple Reaction monitoring (SRM/MRM) is a liquid-chromatography (LC)/tandem-mass spectrometry (MS/MS) method that enables the quantitation of specific proteins in a sample by analyzing ...precursor ions and the fragment ions of their selected tryptic peptides. Instrumentation software has advanced to the point that thousands of transitions (pairs of primary and secondary m/z values) can be measured in a triple quadrupole instrument coupled to an LC, by a well-designed scheduling and selection of m/z windows. The design of a good MRM assay relies on the availability of peptide spectra from previous discovery-phase LC–MS/MS studies. The tedious aspect of manually developing and processing MRM assays involving thousands of transitions has spurred to development of software tools to automate this process. Software packages have been developed for project management, assay development, assay validation, data export, peak integration, quality assessment, and biostatistical analysis. No single tool provides a complete end-to-end solution, thus this article reviews the current state and discusses future directions of these software tools in order to enable researchers to combine these tools for a comprehensive targeted proteomics workflow.
Virions are thought to contain all the essential proteins that govern virus egress from the host cell and initiation of replication in the target cell. It has been known for some time that influenza ...virions contain nine viral proteins; however, analyses of other enveloped viruses have revealed that proteins from the host cell can also be detected in virions. To address whether the same is true for influenza virus, we used two complementary mass spectrometry approaches to perform a comprehensive proteomic analysis of purified influenza virus particles. In addition to the aforementioned nine virus-encoded proteins, we detected the presence of 36 host-encoded proteins. These include both cytoplasmic and membrane-bound proteins that can be grouped into several functional categories, such as cytoskeletal proteins, annexins, glycolytic enzymes, and tetraspanins. Interestingly, a significant number of these have also been reported to be present in virions of other virus families. Protease treatment of virions combined with immunoblot analysis was used to verify the presence of the cellular protein and also to determine whether it is located in the core of the influenza virus particle. Immunogold labeling confirmed the presence of membrane-bound host proteins on the influenza virus envelope. The identification of cellular constituents of influenza virions has important implications for understanding the interactions of influenza virus with its host and brings us a step closer to defining the cellular requirements for influenza virus replication. While not all of the host proteins are necessarily incorporated specifically, those that are and are found to have an essential role represent novel targets for antiviral drugs and for attenuation of viruses for vaccine purposes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Increased forest vulnerability is being reflected as more widespread and severe drought-induced decline episodes. In particular, the Mediterranean area is revealing a high susceptibility to phenomena ...of loss in tree vitality across species. Within tree species, oaks (Quercus spp.) are experiencing extensive decline in many countries. However, in the wake of the so-called “oak decline phenomenon”, the attention on these species has generally been limited. In this paper, we review the current available literature on oak-decline cases reported within the Mediterranean Basin, with particular remark for those occurred in Italy and Spain. More specifically our main aims were to: (i) provide an update on the patterns and mechanisms of decline by focusing on tree-ring and wood-anatomical variables; (ii) provide some hints for improving the resistance and resilience of oak stands experiencing decline. Our review reveals that drought is reported as the main driver triggering oak decline within the Mediterranean Basin, although other causes (i.e., increasing temperature, pathogens attack or excessive stand density) could exacerbate decline. In most reported cases, drought induced a substantial reduction of growth and changes in some wood anatomical properties. Indeed, growth decline prior death is also indicated as an early-warning signal of impending death. In ring-porous oak species, declining trees were often characterized by a very low production of latewood and a decrease in lumen area of the widest earlywood vessels, suggesting a potential reduction of hydraulic conductivity. Moreover, hydraulic dysfunction is reported as the main cause of decline. Finally, regarding management actions that should be considered for improving the resilience of declining stands and preserve the species-specific stand composition, it could be useful to shorten the rotation period of coppice stands or promoting their gradual conversion towards high forests, and favoring more drought-resistant species should also be considered. In addition, regeneration prior to regeneration cuts should be improved by anticipating seed dispersal or by planting oak seedlings obtained from local germoplasm.
Electromagnetic fields (EMFs) have been proposed as a tool to ameliorate bone formation and healing. Despite their promising results, however, they have failed to enter routine clinical protocols to ...treat bone conditions where higher bone mass has to be achieved. This is no doubt also due to a fundamental lack of knowledge and understanding on their effects and the optimal settings for attaining the desired therapeutic effects. This review analysed the available in vitro and in vivo studies that assessed the effects of sinusoidal EMFs (SEMFs) on bone and bone cells, comparing the results and investigating possible mechanisms of action by which SEMFs interact with tissues and cells. The effects of SEMFs on bone have not been as thoroughly investigated as pulsed EMFs; however, abundant evidence shows that SEMFs affect the proliferation and differentiation of osteoblastic cells, acting on multiple cellular mechanisms. SEMFs have also proven to increase bone mass in rodents under normal conditions and in osteoporotic animals.
Superconducting nanowires are widely used as sensitive single photon detectors with wide spectral coverage and high timing resolution. We describe a demonstration of an array of dc-biased ...superconducting nanowire single photon detectors read out with a microwave multiplexing circuit. In this design, each individual nanowire is part of a resonant LC circuit where the inductance is dominated by the kinetic inductance of the nanowire. The circuit also contains two parallel plate capacitors, one of them is in parallel with the inductor and the other is coupled to a microwave transmission line that carries the signals to a cryogenic low-noise amplifier. All of the nanowires are connected via resistors to a single dc bias line that enables the nanowires to be current biased close to their critical current. When a photon hits a nanowire, it creates a normal hotspot that produces a voltage pulse across the LC circuit. This pulse rings down at the resonant frequency of the LC circuit over a time period that is fixed by the quality factor. We present measurements of an array of these devices and an evaluation of their performance in terms of frequency and time response.
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