Open quantum systems can have exceptional points (EPs), degeneracies where both eigenvalues and eigenvectors coalesce. Recently, it has been proposed and demonstrated that EPs can enhance the ...performance of sensors in terms of amplification of a detected signal. However, typically amplification of signals also increases the system noise, and it has not yet been shown that an EP sensor can have improved signal-to-noise performance. We develop a quantum noise theory to calculate the signal-to-noise performance of an EP sensor. We use the quantum Fisher information to extract a lower bound for the signal-to-noise ratio (SNR) and show that parametrically improved SNR is possible. Finally, we construct a specific experimental protocol for sensing using an EP amplifier near its lasing threshold and heterodyne signal detection that achieves the optimal scaling predicted by the Fisher bound. Our results can be generalized to higher order EPs for any bosonic non-Hermitian system with linear interactions.
Why are globe-spanning environmental problems on the rise and
what can be done about them? Christopher Stone presents a concise
and balanced overview of the risks, from climate change and ozone
...depletion to deforestation and biodiversity loss. Exploring the
institutional framework, Stone shows why global problems do not
always benefit from "global solutions," how environmental diplomacy
has to account for the growing tensions between rich and poor
nations, and why even checking population growth would not heal the
planet. Stone's latest work, at once theoretical and realistic, is
a major contribution to our understanding of one of humanity's
greatest challenges.
Electrospray ionization mass spectrometry (ESI-MS) is a ubiquitously used analytical method applied across multiple departments in biopharma, ranging from early research discovery to process ...development. Accurate, efficient, and consistent protein MS spectral deconvolution across multiple instrument and detector platforms (time-of-flight, Orbitrap, Fourier-transform ion cyclotron resonance) is essential. When proteins are ionized during the ESI process, a distribution of consecutive multiply charged ions are observed on the m/z scale, either positive M + nH n+ or negative M – nH n− depending on the ionization polarity. The manual calculation of the neutral molecular weight (MW) of single proteins measured by ESI-MS is simple; however, algorithmic deconvolution is required for more complex protein mixtures to derive accurate MWs. Multiple deconvolution algorithms have evolved over the past two decades, all of which have their advantages and disadvantages, in terms of speed, user-input parameters (or ideally lack thereof), and whether they perform optimally on proteins analyzed under denatured or native-MS and solution conditions. Herein, we describe the utility of a parsimonious deconvolution algorithm (explaining the observed spectra with a minimum number of masses) to process a wide range of highly diverse biopharma relevant and research grade proteins and complexes (PEG-GCSF; an IgG1k; IgG1- and IgG2-biotin covalent conjugates; the membrane protein complex AqpZ; a highly polydisperse empty MSP1D1 nanodisc and the tetradecameric chaperone protein complex GroEL) analyzed under native-MS, denaturing LC-MS, and positive and negative modes of ionization, using multiple instruments and therefore multiple data formats. The implementation of a comb filter and peak sharpening option is also demonstrated to be highly effective for deconvolution of highly polydisperse and enhanced separation of a low level lysine glycation post-translational modification (+162.1 Da), partially processed heavy chain lysine residues (+128.1 Da), and loss of N-acetylglucosamine (GlcNAc; −203.1 Da).
On February 28, 2020, public health officials in the Seattle area were informed of a Covid-19 infection at a long-term care facility. An investigation identified 167 infected persons associated with ...the facility, including residents, health care personnel, and visitors; more than a third of the 101 residents identified died.
Genetically modified T cells expressing chimeric antigen receptors (CARs) demonstrate robust responses against lineage restricted, non-essential targets in hematologic cancers. However, in solid ...tumors, the full potential of CAR T cell therapy is limited by the availability of cell surface antigens with sufficient cancer-specific expression. The majority of CAR targets have been normal self-antigens on dispensable hematopoietic tissues or overexpressed shared antigens. Here, we established that abnormal self-antigens can serve as targets for tumor rejection. We developed a CAR that recognized cancer-associated Tn glycoform of MUC1, a neoantigen expressed in a variety of cancers. Anti-Tn-MUC1 CAR T cells demonstrated target-specific cytotoxicity and successfully controlled tumor growth in xenograft models of T cell leukemia and pancreatic cancer. These findings demonstrate the therapeutic efficacy of CAR T cells directed against Tn-MUC1 and present aberrantly glycosylated antigens as a novel class of targets for tumor therapy with engineered T cells.
•Cancer cells of many tissues express an abnormal glycoform of MUC1, Tn-MUC1•Normal human tissue does not express detectable Tn-MUC1 on the cellular surface•CAR T cells are engineered to target Tn-MUC1 lyse tumor cells in vitro and in vivo•Abnormal glycoform epitopes are valid clinical targets for CAR T cells
Posey and colleagues developed a CAR T cell therapy to break immune tolerance to solid tumors by targeting an aberrantly glycosylated, cancer-specific glycoprotein in multiple cancer histotypes and demonstrated efficacy and safety in tumors as diverse as leukemia and pancreatic cancer.
IgE, mast cells, basophils, and eosinophils Stone, Kelly D., MD, PhD; Prussin, Calman, MD; Metcalfe, Dean D., MD
Journal of allergy and clinical immunology,
02/2010, Letnik:
125, Številka:
2
Journal Article
Recenzirano
Odprti dostop
IgE, mast cells, basophils, and eosinophils are essential components of allergic inflammation. Antigen-specific IgE production, with subsequent fixation of IgE to FcϵRI receptors on mast cells and ...basophils, is central to the initiation and propagation of immediate hypersensitivity reactions. Mast cells, basophils, and eosinophils are central effector cells in allergic inflammation, as well as in innate and adaptive immunity. This review highlights what is known about these components and their roles in disease pathogenesis.
The summer of 2003 was probably the hottest in Europe since at latest ad 1500, and unusually large numbers of heat-related deaths were reported in France, Germany and Italy. It is an ill-posed ...question whether the 2003 heatwave was caused, in a simple deterministic sense, by a modification of the external influences on climate-for example, increasing concentrations of greenhouse gases in the atmosphere-because almost any such weather event might have occurred by chance in an unmodified climate. However, it is possible to estimate by how much human activities may have increased the risk of the occurrence of such a heatwave. Here we use this conceptual framework to estimate the contribution of human-induced increases in atmospheric concentrations of greenhouse gases and other pollutants to the risk of the occurrence of unusually high mean summer temperatures throughout a large region of continental Europe. Using a threshold for mean summer temperature that was exceeded in 2003, but in no other year since the start of the instrumental record in 1851, we estimate it is very likely (confidence level >90%) that human influence has at least doubled the risk of a heatwave exceeding this threshold magnitude.
PDF
