Discovering The Real Impact of COVID-19 on Entrepreneurship

- More than 70% of start-ups have had to terminate full-time employee contracts since the start of the COVID-19 pandemic; - Many entrepreneurial businesses have pivoted to meet new needs for goods or services borne out of the crisis; - The way entrepreneurial business models and approaches are affected by the pandemic will have an impact on how entrepreneurship is perceived as a job choice in the future

The StarScan plate measuring machine: overview and calibrations

The StarScan machine at the U.S. Naval Observatory (USNO) completed measuring photographic astrograph plates to allow determination of proper motions for the USNO CCD Astrograph Catalog (UCAC) program. All applicable 1940 AGK2 plates, about 2200 Hamburg Zone Astrograph plates, 900 Black Birch (USNO Twin Astrograph) plates, and 300 Lick Astrograph plates have been measured. StarScan comprises of a CCD camera, telecentric lens, air-bearing granite table, stepper motor screws, and Heidenhain scales to operate in a step-stare mode. The repeatability of StarScan measures is about 0.2 micrometer. The CCD mapping as well as the global table coordinate system has been calibrated using a special dot calibration plate and the overall accuracy of StarScan x,y data is derived to be 0.5 micrometer. Application to real photographic plate data shows that position information of at least 0.65 micrometer accuracy can be extracted from course grain 103a-type emulsion astrometric plates. Transformations between "direct" and "reverse" measures of fine grain emulsion plate measures are obtained on the 0.3 micrometer level per well exposed stellar image and coordinate, which is at the limit of the StarScan machine.Comment: 24 pages, 8 figures, accepted for PAS

Intracellular Nanoparticle Coating Stability Determines Nanoparticle Diagnostics Efficacy and Cell Functionality

n/

Testicular sarcoidosis

We describe a very unusual form of sarcoidosis of the testis, mimicking malignancy at initial presentation. Genitourinary sarcoidosis is rare and this case report emphasizes the importance of meticulous analysis of the patient’s clinical history combined with imaging findings and specific pathological criteria to diagnose this granulomatous disorder

GDP/GTP exchange factor MADD drives activation and recruitment of secretory Rab GTPases to Weibel-Palade bodies.

von Willebrand factor (VWF) is an essential hemostatic protein that is synthesized and secreted by endothelial cells and stored in Weibel-Palade bodies (WPBs). The secretory Rab GTPases Rab27A, Rab3B, and Rab3D have been linked with WPB trafficking and secretion. How these Rabs are activated and recruited to WPBs remains elusive. In this study, we identified MAP kinase-activating death domain (MADD) as the guanine nucleotide exchange factor for Rab27A and both Rab3 isoforms in primary human endothelial cells. Rab activity assays revealed a reduction in Rab27A, Rab3B, and Rab3D activation upon MADD silencing. Rab activation, but not binding, was dependent on the differentially expressed in normal and neoplastic cells (DENN) domain of MADD, indicating the potential existence of 2 Rab interaction modules. Furthermore, immunofluorescent analysis showed that Rab27A, Rab3B, and Rab3D recruitment to WPBs was dramatically decreased upon MADD knockdown, revealing that MADD drives Rab membrane targeting. Artificial mistargeting of MADD using a TOMM70 tag abolished Rab27A localization to WPB membranes in a DENN domain-dependent manner, indicating that normal MADD localization in the cytosol is crucial. Activation of Rab3B and Rab3D was reduced upon Rab27A silencing, suggesting that activation of these Rabs is enhanced through previous activation of Rab27A by MADD. MADD silencing did not affect WPB morphology, but it did reduce VWF intracellular content. Furthermore, MADD-depleted cells exhibited decreased histamine-evoked VWF release, similar to Rab27A-depleted cells. In conclusion, MADD acts as a master regulator of VWF secretion by coordinating the activation and membrane targeting of secretory Rabs to WPBs

Repercussion of megakaryocyte-specific Gata1 Loss on megakaryopoiesis and the hematopoietic precursor compartment

During hematopoiesis, transcriptional programs are essential for the commitment and differentiation of progenitors into the different blood lineages. GATA1 is a transcription factor expressed in several hematopoietic lineages and essential for proper erythropoiesis and megakaryopoiesis. Megakaryocyte-specific genes, such as GP1BA, are known to be directly regulated by GATA1. Mutations in GATA1 can lead to dyserythropoietic anemia and pseudo gray-platelet syndrome. Selective loss of Gata1 expression in adult mice results in macrothrombocytopenia with platelet dysfunction, characterized by an excess of immature megakaryocytes. To specifically analyze the impact of Gata1 loss in mature committed megakaryocytes, we generated Gata1-Lox|Pf4-Cre mice (Gata1cKOMK). Consistent with previous findings, Gata1cKOMK mice are macrothrombocytopenic with platelet dysfunction. Supporting this notion we demonstrate that Gata1 regulates directly the transcription of Syk, a tyrosine kinase that functions downstream of Clec2 and GPVI receptors in megakaryocytes and platelets. Furthermore, we show that Gata1cKOMK mice display an additional aberrant megakaryocyte differentiation stage. Interestingly, these mice present a misbalance of the multipotent progenitor compartment and the erythroid lineage, which translates into compensatory stress erythropoiesis and splenomegaly. Despite the severe thrombocytopenia, Gata1cKOMK mice display a mild reduction of TPO plasma levels, and Gata1cK-OMK megakaryocytes show a mild increase in Pf4 mRNA levels; such a misbalance might be behind the general hematopoietic defects observed, affecting locally normal TPO and Pf4 levels at hematopoietic stem cell niches. © 2016 Meinders et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

On the variation of the fine-structure constant: Very high resolution spectrum of QSO HE 0515-4414

We present a detailed analysis of a very high resolution (R\approx 112,000) spectrum of the quasar HE 0515-4414 obtained using the High Accuracy Radial velocity Planet Searcher (HARPS) mounted on the ESO 3.6 m telescope at the La Silla observatory. The HARPS spectrum, of very high wavelength calibration accuracy (better than 1 m\AA), is used to search for possible systematic inaccuracies in the wavelength calibration of the UV Echelle Spectrograph (UVES) mounted on the ESO Very Large Telescope (VLT). We have carried out cross-correlation analysis between the Th-Ar lamp spectra obtained with HARPS and UVES. The shift between the two spectra has a dispersion around zero of \sigma\simeq 1 m\AA. This is well within the wavelength calibration accuracy of UVES (i.e \sigma\simeq 4 m\AA). We show that the uncertainties in the wavelength calibration induce an error of about, \Delta\alpha/\alpha\le 10^{-6}, in the determination of the variation of the fine-structure constant. Thus, the results of non-evolving \Delta\alpha/\alpha reported in the literature based on UVES/VLT data should not be heavily influenced by problems related to wavelength calibration uncertainties. Our higher resolution spectrum of the z_{abs}=1.1508 damped Lyman-\alpha system toward HE 0515-4414 reveals more components compared to the UVES spectrum. Using the Voigt profile decomposition that simultaneously fits the high resolution HARPS data and the higher signal-to-noise ratio UVES data, we obtain, \Delta\alpha/\alpha=(0.05\pm0.24)x10^{-5} at z_{abs}=1.1508. This result is consistent with the earlier measurement for this system using the UVES spectrum alone.Comment: 14 pages, 13 figures, Accepted in A&