Analyzing quantum jumps of one and two atoms strongly coupled to an optical cavity

We induce quantum jumps between the hyperfine ground states of one and two Cesium atoms, strongly coupled to the mode of a high-finesse optical resonator, and analyze the resulting random telegraph signals. We identify experimental parameters to deduce the atomic spin state nondestructively from the stream of photons transmitted through the cavity, achieving a compromise between a good signal-to-noise ratio and minimal measurement-induced perturbations. In order to extract optimum information about the spin dynamics from the photon count signal, a Bayesian update formalism is employed, which yields time-dependent probabilities for the atoms to be in either hyperfine state. We discuss the effect of super-Poissonian photon number distributions caused by atomic motion.Comment: 12 pages, 13 figure

Side-by-side analysis of five clinically tested anti-EpCAM monoclonal antibodies

Background: Epithelial cell adhesion molecule (EpCAM) is frequently and highly expressed on human carcinomas. The emerging role of EpCAM as a signalling receptor and activator of the wnt pathway, and its expression on tumor-initiating cells, further add to its attractiveness as target for immunotherapy of cancer. Thus far, five conventional monoclonal IgG antibodies have been tested in cancer patients. These are murine IgG2a edrecolomab and its murine/human chimeric IgG1 antibody version, and humanized, human-engineered and fully human IgG1 antibodies 3622W94, ING-1, and adecatumumab (MT201), respectively. Here we compared all anti-EpCAM antibodies in an attempt to explain differences in clinical activity and safety. Methods: We recombinantly produced all antibodies but murine edrecolomab and investigated them for binding affinity, EpCAM epitope recognition, ADCC and CDC, and inhibition of breast cancer cell proliferation. Results: ING-1 and 3622W94 bound to EpCAM with much higher affinity than adecatumumab and edrecolomab. Edrecolomab, ING-1, and 3622W94 all recognized epitopes in the exon 2-encoded N-terminal domain of EpCAM, while adecatumumab recognized a more membrane proximal epitope encoded by exon 5. All antibodies induced lysis of EpCAM-expressing cancer cell lines by both ADCC and CDC with potencies that correlated with their binding affinities. The chimeric version of edrecolomab with a human Fc gamma 1 domain was much more potent in ADCC than the murine IgG2a version. Only adecatumumab showed a significant inhibition of MCF-7 breast cancer cell proliferation in the absence of complement and immune cells. Conclusion: A moderate binding affinity and recognition of a distinct domain of EpCAM may best explain why adecatumumab showed a larger therapeutic window in cancer patients than the two high-affinity IgG1 antibodies ING-1 and 3622W94, both of which caused acute pancreatitis

A longitudinal study of olfactory dysfunction and parosmia in mild COVID-19 cases

Background: COVID-19-related olfactory dysfunction (OD) can persist long after patients recover from acute infection, yet few studies have investigated the long-term progression of this complication. Moreover, existing studies are focused on hyposmia/anosmia but parosmia is becoming an increasingly recognized long-term symptom. Methods: We completed a longitudinal study about OD in individuals with mild cases of COVID-19. Participants completed a questionnaire and Brief Smell Identification Test (BSIT) one week, one month and one year after diagnosis. At one-year, participants completed an additional survey about parosmia. Results: We obtained questionnaires and psychophysical olfactory testing information from participants at one week (n=45), one month (n=38), and one year (n=33) post COVID-19 diagnosis. At one-year, 15.2% of participants had persistent OD and 66.7% of participants reported experiencing parosmia at some point following COVID-19 diagnosis. The mean onset of parosmia was 1.3 weeks (SD: 1.9 weeks) after diagnosis, although two patients reported delayed onset (>4 weeks after diagnosis). Eight patients (24.2%) reported ongoing parosmia one year after diagnosis. Of the patients whose parosmia resolved, the mean duration of symptoms was 7.2 weeks (SD: 7.3 weeks). Conclusion: Decreased sense of smell associated with COVID-19 infection has received significant recognition in both the media and in the medical literature. Symptoms of OD and parosmia were common in our patients with COVID-19. Hyposmia, anosmia, and parosmia, all decrease quality of life, necessitating continued research to understand the pathogenesis, course of symptoms, and possible treatment for these complications

COVID-19 related olfactory dysfunction prevalence and natural history in ambulatory patients

Background: Evidence regarding prevalence of COVID-19 related Olfactory dysfunction (OD) among ambulatory patients is highly variable due to heterogeneity in study population and measurement methods. Relatively few studies have longitudinally investigated OD in ambulatory patients with objective methods. Methods: We performed a longitudinal study to investigate OD among COVID-19 ambulatory patients compared to symptomatic controls who test negative. Out of 81 patients enrolled, 45 COVID-19 positive patients and an age- and sex-matched symptomatic control group completed the BSIT and a questionnaire about smell, taste and nasal symptoms. These were repeated at 1 month for all COVID-19 positive patients, and again at 3 months for those who exhibited persistent OD. Analysis was performed by mixed-effects linear and logistic regression. Results: 46.7% of COVID-19 patients compared to 3.8% of symptomatic controls exhibited OD at 1-week post diagnosis (p<0.001). At 1 month, 16.7%, (6 of 36), of COVID-19 patients had persistent OD. Mean improvement in BSIT score in COVID-19 patients between 1-week BSIT and 1 month follow-up was 2.0 (95% CI 1.00 – 3.00, p<0.001). OD did not correlate with nasal congestion (r= −0.25, 95% CI, −0.52 to 0.06, p=0.12). Conclusions: Ambulatory COVID-19 patients exhibited OD significantly more frequently than symptomatic controls. Most patients regained normal olfaction by 1 month. The BSIT is a simple validated and objective test to investigate the prevalence of OD in ambulatory patients. OD did not correlate with nasal congestion which suggests a congestion-independent mechanism of OD

Highly Efficient Elimination of Colorectal Tumor-Initiating Cells by an EpCAM/CD3-Bispecific Antibody Engaging Human T Cells

With their resistance to genotoxic and anti-proliferative drugs and potential to grow tumors and metastases from very few cells, cancer stem or tumor-initiating cells (TICs) are a severe limitation for the treatment of cancer by conventional therapies. Here, we explored whether human T cells that are redirected via an EpCAM/CD3-bispecific antibody called MT110 can lyse colorectal TICs and prevent tumor growth from TICs. MT110 recognizes EpCAM, a cell adhesion molecule expressed on TICs from diverse human carcinoma, which was recently shown to promote tumor growth through engagement of elements of the wnt pathway. MT110 was highly potent in mediating complete redirected lysis of KRAS-, PI3 kinase- and BRAF-mutated colorectal TICs, as demonstrated in a soft agar assay. In immunodeficient mice, MT110 prevented growth of tumors from a 5,000-fold excess of a minimally tumorigenic TIC dose. T cells engaged by MT110 may provide a potent therapeutic means to eradicate TICs and bulk tumor cells derived thereof

Sponge spicules as blueprints for the biofabrication of inorganic–organic composites and biomaterials

While most forms of multicellular life have developed a calcium-based skeleton, a few specialized organisms complement their body plan with silica. However, of all recent animals, only sponges (phylum Porifera) are able to polymerize silica enzymatically mediated in order to generate massive siliceous skeletal elements (spicules) during a unique reaction, at ambient temperature and pressure. During this biomineralization process (i.e., biosilicification) hydrated, amorphous silica is deposited within highly specialized sponge cells, ultimately resulting in structures that range in size from micrometers to meters. Spicules lend structural stability to the sponge body, deter predators, and transmit light similar to optic fibers. This peculiar phenomenon has been comprehensively studied in recent years and in several approaches, the molecular background was explored to create tools that might be employed for novel bioinspired biotechnological and biomedical applications. Thus, it was discovered that spiculogenesis is mediated by the enzyme silicatein and starts intracellularly. The resulting silica nanoparticles fuse and subsequently form concentric lamellar layers around a central protein filament, consisting of silicatein and the scaffold protein silintaphin-1. Once the growing spicule is extruded into the extracellular space, it obtains final size and shape. Again, this process is mediated by silicatein and silintaphin-1, in combination with other molecules such as galectin and collagen. The molecular toolbox generated so far allows the fabrication of novel micro- and nanostructured composites, contributing to the economical and sustainable synthesis of biomaterials with unique characteristics. In this context, first bioinspired approaches implement recombinant silicatein and silintaphin-1 for applications in the field of biomedicine (biosilica-mediated regeneration of tooth and bone defects) or micro-optics (in vitro synthesis of light waveguides) with promising results

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Analysis on the influence of grain size and grain layer thickness on the sorption kinetics of grained Wood at low relative humidity with the use of water vapour sorption experiments

Water vapour sorption (WVS) experiments on grained Norway spruce wood (Picea abies) at low relative humidities were carried out to test the influence of grain size and grain layer thickness on the sorption kinetics. Samples were compared under identical climatic conditions (i.e. humidity and temperature), and the kinetic behaviour was analysed with selected modelling approaches existing in the literature. Both, grain size and grain layer thickness influenced the initial kinetics, with the latter showing a larger impact. This confirms the notion of a transport limited initial mass increase with diffusion of water vapour/H2O-molecules to the sorption sites being a possible candidate. In contrast, the long-time behaviour was only slightly affected, supporting the concept of a relaxation and reorganisation dominated long-time behaviour. An analysis on the WVS kinetics of cut and grained wood with comparable sample material has further shown a very similar behaviour, which allows to draw some conclusions for cut wood. Regarding the modelling approaches, the parallel exponential kinetics model provided the best fitting results as the predictive models could not properly capture the split-up for a variation in grain size or grain layer thickness.(VLID)4655693Version of recor