Liquid phase epitaxy and optical investigation of KYb(WO4)2 thin layers

In recent years, Yb3+ has attracted much attention as an activating ion because of its small quantum defect for laser emission from 2F5/2 to 2F7/2 at ~1.03 µm [1], which provides high efficiency and reduced heat generation. Of high practical interest is the thin-disk laser concept [2], which possesses a tremendous advantage over rod lasers because of its axial-cooling approach and consequent weak thermal lensing and good beam quality.\ud A promising material for Yb3+ thin-disk lasers is KYb(WO4)2 (KYbW) [3]. It can be grown from high-temperature solutions [4]. Nevertheless, the growth of high-quality, single-crystalline layers with thickness in the range of the absorption length of ~13 µm at 981 nm has as yet not been reported. A suitable substrate material is KY(WO4)2 (KYW), but the relatively large differences in the thermal expansion coefficients between KYW and KYbW along the [100], [001], and especially [010] directions [5] favor low temperatures for the hetero-epitaxial growth.\ud For the first time, we demonstrate liquid phase epitaxy (LPE) of KYbW layers. The layers were grown at start temperatures as low as 520°C, which is favorable in order to decrease the thermal stresses due to the differences in the thermal expansion coefficients of substrate and layer. Moreover, the choice of [010]-oriented substrates bypasses the large difference in the thermal expansion coefficient along the [010] direction. KY1-xYbx(WO4)2 layers with varying x = 0.03-1.00 were grown by LPE. The chloride solvent consisted of the eutectic composition [6] 24.4 mol.% KCl, 30.4 mol.% NaCl, and 42.2 mol.% CsCl. The growth temperature spanned the range from 580 to 500°C and the cooling rate was 0.67-1.00 Kh-1. Crack-free, transparent KYbW layers were grown on (010) substrates.\ud Spectroscopic investigations have shown that the lifetime of ~250 µs measured in our LPE-grown KYbW layers is dominated by radiative decay and is very similar to that measured in top-seeded-solution-grown bulk samples [4]. Fast energy migration among the Yb3+ ions and energy transfer to small amounts of Tm3+ and Er3+ ions present in the YbCl3 reagent lead to visible upconversion luminescence in the layers under 981-nm excitation.\ud \ud [1] T.Y. Fan, IEEE J. Quantum Electron. 29, 1457 (1993).\ud [2] A. Giesen, H. Hügel, A. Voss, K. Wittig, U. Brauch, H. Opower, Appl. Phys. B 58, 365 (1994).\ud [3] P. Klopp, U. Griebner, V. Petrov, X. Mateos, M.A. Bursukova, M.C. Pujol, R. Solé, J. Gavaldà, M. Aguiló, F. Güell, J. Massons, T. Kirilov, F. Díaz, Appl. Phys. B 74, 185 (2002).\ud [4] M.C. Pujol, M.A. Bursukova, F. Güell, X. Mateos, R. Solé, J. Gavaldà, M. Aguiló, J. Massons, F. Díaz, P. Klopp, U. Griebner, V. Petrov, Phys. Rev. B 65, 165121 (2002).\ud [5] M.C. Pujol, X. Mateos, R. Solé, J. Massons, J. Gavaldà, F. Díaz, M. Aguiló, Mater. Sci. Forum 378-381, 710 (2001).\ud [6] D. Ehrentraut, M. Pollnau, S. Kück, Appl. Phys. B 75, 59 (2002)

The biology of cytotoxic cell granule exocytosis pathway: granzymes have evolved to induce cell death and inflammation

The granule exocytosis pathway of cytotoxic lymphocytes (Tc and NK cells) is critical for control of tumor development and viral infections. Granule-associated perforin and granzymes are key components in Tc cell-mediated function(s). On the basis of studies that showed granzymes A, B, C, K and M, to induce apoptosis in vitro, all granzymes were thought to also induce cell death in vivo. This review summarizes our present understanding of the biological processes elicited by purified granzyme A and granzyme as well as the processes induced by the more physiologically relevant cytotoxic cells secreting these proteases. The combined evidence supports the concept that the granule secretion pathway is not mono-specific but rather poly-functional including induction of pro-inflammatory cytokines, besides their widely appreciated apoptotic properties

Independent genomic polymorphisms in the PknH serine threonine kinase locus during evolution of the Mycobacterium tuberculosis Complex affect virulence and host preference

Species belonging to the Mycobacterium tuberculosis Complex (MTBC) show more than 99% genetic identity but exhibit distinct host preference and virulence. The molecular genetic changes that underly host specificity and infection phenotype within MTBC members have not been fully elucidated. Here, we analysed RD900 genomic region across MTBC members using whole genome sequences from 60 different MTBC strains so as to determine its role in the context of MTBC evolutionary history. The RD900 region comprises two homologous genes, pknH1 and pknH2, encoding a serine/threonine protein kinase PknH flanking the tbd2 gene. Our analysis revealed that RD900 has been independently lost in different MTBC lineages and different strains, resulting in the generation of a single pknH gene. Importantly, all the analysed M. bovis and M. caprae strains carry a conserved deletion within a proline rich-region of pknH, independent of the presence or absence of RD900. We hypothesized that deletion of pknH proline rich-region in M. bovis may affect PknH function, having a potential role in its virulence and evolutionary adaptation. To explore this hypothesis, we constructed two M. bovis ‘knock-in’ strains containing the M. tuberculosis pknH gene. Evaluation of their virulence phenotype in mice revealed a reduced virulence of both M. bovis knock-in strains compared to the wild type, suggesting that PknH plays an important role in the differential virulence phenotype of M. bovis vs M. tuberculosis

Novel intravesical bacterial immunotherapy induces rejection of BCG-unresponsive established bladder tumors

Background Intravesical BCG is the gold-standard therapy for non-muscle invasive bladder cancer (NMIBC); however, it still fails in a significant proportion of patients, so improved treatment options are urgently needed. Methods Here, we compared BCG antitumoral efficacy with another live attenuated mycobacteria, MTBVAC, in an orthotopic mouse model of bladder cancer (BC). We aimed to identify both bacterial and host immunological factors to understand the antitumoral mechanisms behind effective bacterial immunotherapy for BC. Results We found that the expression of the BCG-absent proteins ESAT6/CFP10 by MTBVAC was determinant in mediating bladder colonization by the bacteria, which correlated with augmented antitumoral efficacy. We further analyzed the mechanism of action of bacterial immunotherapy and found that it critically relied on the adaptive cytotoxic response. MTBVAC enhanced both tumor antigen-specific CD4 + and CD8 + T-cell responses, in a process dependent on stimulation of type 1 conventional dendritic cells. Importantly, improved intravesical bacterial immunotherapy using MBTVAC induced eradication of fully established bladder tumors, both as a monotherapy and specially in combination with the immune checkpoint inhibitor antiprogrammed cell death ligand 1 (anti PD-L1). Conclusion These results contribute to the understanding of the mechanisms behind successful bacterial immunotherapy against BC and characterize a novel therapeutic approach for BCG-unresponsive NMIBC cases. © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ

Proteomics insights into the Burkholderia cenocepacia phosphorus stress response

The Burkholderia cepacia complex is a group of Burkholderia species that are opportunistic pathogens causing high mortality rates in patients with cystic fibrosis. An environmental stress often encountered by these soil‐dwelling and pathogenic bacteria is phosphorus limitation, an essential element for cellular processes. Here, we describe cellular and extracellular proteins differentially regulated between phosphate‐deplete (0 mM, no added phosphate) and phosphate‐replete (1 mM) growth conditions using a comparative proteomics (LC–MS/MS) approach. We observed a total of 128 and 65 unique proteins were downregulated and upregulated respectively, in the B. cenocepacia proteome. Of those downregulated proteins, many have functions in amino acid transport/metabolism. We have identified 24 upregulated proteins that are directly/indirectly involved in inorganic phosphate or organic phosphorus acquisition. Also, proteins involved in virulence and antimicrobial resistance were differentially regulated, suggesting B. cenocepacia experiences a dramatic shift in metabolism under these stress conditions. Overall, this study provides a baseline for further research into the biology of Burkholderia in response to phosphorus stress

Search for physics beyond the standard model in events with τ leptons, jets, and large transverse momentum imbalance in pp collisions at [Formula: see text].

A search for physics beyond the standard model is performed with events having one or more hadronically decaying τ leptons, highly energetic jets, and large transverse momentum imbalance. The data sample corresponds to an integrated luminosity of 4.98 fb-1 of proton-proton collisions at [Formula: see text] collected with the CMS detector at the LHC in 2011. The number of observed events is consistent with predictions for standard model processes. Lower limits on the mass of the gluino in supersymmetric models are determined

Simultaneous measurement of the ratio B(t->Wb)/B(t->Wq) and the top quark pair production cross section with the D0 detector at sqrt(s)=1.96 TeV

We present the first simultaneous measurement of the ratio of branching fractions, R=B(t->Wb)/B(t->Wq), with q being a d, s, or b quark, and the top quark pair production cross section sigma_ttbar in the lepton plus jets channel using 0.9 fb-1 of ppbar collision data at sqrt(s)=1.96 TeV collected with the D0 detector. We extract R and sigma_ttbar by analyzing samples of events with 0, 1 and >= 2 identified b jets. We measure R = 0.97 +0.09-0.08 (stat+syst) and sigma_ttbar = 8.18 +0.90-0.84 (stat+syst)} +/-0.50 (lumi) pb, in agreement with the standard model prediction.Comment: submitted to Phys.Rev.Letter