Baseline cytokine profiles of tuberculin-specific CD4 T-cells in non-muscle invasive bladder cancer may predict outcomes of BCG immunotherapy within reach?

Intravesical Bacillus Calmette-Guérin (BCG) immunotherapy preserves the bladder after resection of high-risk non-muscle invasive bladder cancer (NMIBC). About 30% of patients experience treatment failure, which cannot be predicted a priori and carries a high risk of disease progression. We examined the in vitro tuberculin-responsiveness of CD4+ T cells before BCG immunotherapy in 42 patients with high-risk NMIBC. The frequencies and functionalities of cytokine-expressing CD4+ T cells immediately before and after BCG immunotherapy induction were assessed by flow cytometry after overnight tuberculin stimulation. Tuberculin-induced secreted mediators were measured by electrochemiluminescence. We correlated the results with recurrence-free patient survival 6 months after induction. A tuberculin-induced, secreted, IL2 concentration > 250 pg/ml was the best predictor of recurrence-free survival, providing 79% sensitivity, 86% specificity (AUC = 0.852, P = 0.000), and overall correct classification in 78.6% of cases. In 50% of patients later experiencing recurrence, but not in any of the recurrence-free survivors, IL2 secretion was < 120 pg/ml. Other parameters predicting recurrence-free survival included secreted IFNγ (AUC = 0.796, P = 0.002) and the frequencies of TNF-producing (TNF+) CD4+ T cells (AUC = 0.745, P = 0.010). 'Polyfunctional' CD4+ T cells (IFNγ+/IL2+/ TNF+) were significantly associated with recurrence-free survival (AUC = 0.801, P = 0.002). Thus, the amount of IL2 secretion from CD4+ T cells after overnight in vitro incubation with tuberculin predicted the outcome of BCG immunotherapy. As many as half of potential BCG failures could be identified before induction therapy is begun, enabling better choices regarding treatment

Physiological function and catalytic versatility of bacterial multihaem cytochromescinvolved in nitrogen and sulfur cycling

Bacterial MCCs (multihaem cytochromes c) represent widespread respiratory electron-transfer proteins. In addition, some of them convert substrates such as nitrite, hydroxylamine, nitric oxide, hydrazine, sulfite, thiosulfate or hydrogen peroxide. In many cases, only a single function is assigned to a specific MCC in database entries despite the fact that an MCC may accept various substrates, thus making it a multifunctional catalyst that can play diverse physiological roles in bacterial respiration, detoxification and stress defence mechanisms. The present article briefly reviews the structure, function and biogenesis of selected MCCs that catalyse key reactions in the biogeochemical nitrogen and sulfur cycles

Selected human rights indicators in the context of current EU regulation: Towards more social sustainability in the financial and economic system. Part II: Substantial Contribution

In March 2018, the European Commission published its Action Plan on Financing Sustainable Growth. Part of the plan calls for the EU to develop classification systems for environmentally and socially sustainable activities to help direct private sector financing to such activities. This is the second briefing paper of a research project aimed at discussing and developing concepts and indicators for the standardised measurement of socially sustainable activities in alignment with international human rights

Selected human rights indicators in the context of current EU regulation: Towards more social sustainability in the financial and economic system. Part I: Minimum standards

This briefing paper, funded by the German Federal Ministry of Labour and Social Affairs (BMAS), develops 15 central indicators to represent a “minimum standard”. Indicators cover key human rights and key due diligence processes and were drawn from indicator sets widely used in practice; where useful we also suggest refinements of the existing indicators

Essential histidine pairs indicate conserved haem binding in epsilonproteobacterial cytochrome c haem lyases

Bacterial cytochrome c maturation occurs at the outside of the cytoplasmic membrane, requires transport of haem b across the membrane, and depends on membrane-bound cytochrome c haem lyase (CCHL), an enzyme that catalyses covalent attachment of haem b to apocytochrome c. Epsilonproteobacteria such as Wolinella succinogenes use the cytochrome c biogenesis system II and contain unusually large CCHL proteins of about 900 amino acid residues that appear to be fusions of the CcsB and CcsA proteins found in other bacteria. CcsBA-type CCHLs have been proposed to act as haem transporters that contain two haem b coordination sites located at different sides of the membrane and formed by histidine pairs. W. succinogenes cells contain three CcsBA-type CCHL isoenzymes (NrfI, CcsA1 and CcsA2) that are known to differ in their specificity for apocytochromes and apparently recognize different haem c binding motifs such as CX2CH (by CcsA2), CX2CK (by NrfI) and CX15CH (by CcsA1). In this study, conserved histidine residues were individually replaced by alanine in each of the W. succinogenes CCHLs. Characterization of NrfI and CcsA1 variants in W. succinogenes demonstrated that a set of four histidines is essential for maturing the dedicated multihaem cytochromes c NrfA and MccA, respectively. The function of W. succinogenes CcsA2 variants produced in Escherichia coli was also found to depend on each of these four conserved histidine residues. The presence of imidazole in the growth medium of both W. succinogenes and E. coli rescued the cytochrome c biogenesis activity of most histidine variants, albeit to different extents, thereby implying the presence of two functionally distinct histidine pairs in each CCHL. The data support a model in which two conserved haem b binding sites are involved in haem transport catalysed by CcsBA-type CCHLs

C58 on Au(111): a scanning tunneling microscopy study

C58 fullerenes were adsorbed onto room temperature Au(111) surface by low-energy (~6 eV) cluster ion beam deposition under ultrahigh vacuum conditions. The topographic and electronic properties of the deposits were monitored by means of scanning tunnelling microscopy (STM at 4.2 K). Topographic images reveal that at low coverages fullerene cages are pinned by point dislocation defects on the herringbone reconstructed gold terraces (as well as by step edges). At intermediate coverages, pinned monomers, act as nucleation centres for the formation of oligomeric C58 chains and 2D islands. At the largest coverages studied, the surface becomes covered by 3D interlinked C58 cages. STM topographic images of pinned single adsorbates are essentially featureless. The corresponding local densities of states are consistent with strong cage-substrate interactions. Topographic images of [C58]n oligomers show a stripe-like intensity pattern oriented perpendicular to the axis connecting the cage centers. This striped pattern becomes even more pronounced in maps of the local density of states. As supported by density functional theory, DFT calculations, and also by analogous STM images previously obtained for C60 polymers (M. Nakaya et al., J. Nanosci. Nanotechnol. 11, 2829 (2011)), we conclude that these striped orbital patterns are a fingerprint of covalent intercage bonds. For thick C58 films we have derived a band gap of 1.2 eV from scanning tunnelling spectroscopy data, STS, confirming that the outermost C58 layer behaves as a wide band semiconductor

Completion conditions and response behavior in smartphone surveys: A prediction approach using acceleration data

Includes supplementary materials for the online appendix.This study utilizes acceleration data from smartphone sensors to predict motion conditions of smartphone respondents. Specifically, we predict whether respondents are moving or nonmoving on a survey page level to learn about distractions and the situational conditions under which respondents complete smartphone surveys. The predicted motion conditions allow us to (1) estimate the proportion of smartphone respondents who are moving during survey completion and (2) compare the response behavior of moving and nonmoving respondents. Our analytical strategy consists of two steps. First, we use data from a lab experiment that systematically varied motion conditions of smartphone respondents and train a prediction model that is able to accurately infer respondents’ motion conditions based on acceleration data. Second, we use the trained model to predict motion conditions of respondents in two cross-sectional surveys in order to compare response behavior of respondents with different motion conditions in a field setting. Our results indicate that active movement during survey completion is a relatively rare phenomenon, as only about 3%–4% of respondents were predicted as moving in both cross-sectional surveys. When comparing respondents based on their predicted motion conditions, we observe longer completion times of moving respondents. However, we observe little differences when comparing moving and nonmoving respondents with respect to indicators of superficial responding, indicating that moving during survey completion does not pose a severe threat to data quality

Exile Vol. L

47th Year FALL 2003: Title Page 3 Epigraph by Ezra Pound 5 Table of Contents 7 Contributors\u27 Notes 32-33 Editorial Board 34 ART Untitled I by Tricia DiFranco \u2706 10 Untitled I by Derek Mong \u2704 16 Untitled II by Derek Mong \u2704 18 Untitled II by Tricia DiFranco \u2706 21 Andromeda Chained to the Rock of Doom by Matt Messmer \u2706 24 Something Wicked This Way Comes by Matt Messmer \u2706 26 Tony by Erin Saelzler \u2706 30 FICTION Inside by Thomas Kern \u2705 11-15 Dreamer by Sandy Liang \u2707 22-23 POETRY Blackout by Derek Mong \u2704 (Winner of Exile Prize for Poetry) 8-9 Canoeing on the Kalamazoo by Meghan Vesper \u2705 17 Dinner with Daddy by Nicki Bennet \u2704 19 Leaving Behind Yaknapatawpha by Nikki Bennet \u2704 20 Folklore by Derek Mong \u2704 25 Trapped by Sarah Clapp \u2706 27 Blue Ridge Mountains by Meghan Vesper \u2705 28 Grilling on the Back Porch by Meghan Vesper \u2705 29 Communion Cup by Nicki Bennet \u2704 31 SPRING 2004: Title Page 37 Table of Contents 39 Contributors\u27 Notes 85 Editorial Board 86 ART She Will Run by Julianne McCall \u2706 35 Curious George by Geoff Young \u2705 40 Anxious by Tricia DiFranco \u2706 42 Untited by Ashley Meade \u2704 50 Untitled I by Tom Michaels \u2704 52 Moment of Autumn by Gary Weber \u2705 62 Untitled II by Tom Michaels \u2704 64 Jesus Lives by Carol Collins \u2705 76 Untitled by Chris Jessen \u2704 79 Untitled by Gary Weber \u2705 82 Untitled by Pam Arbisi \u2707 84 FICTION The Pilot by Lauryn Dwyer \u2705 43-49 Cigars Are Meant to be Smoked by Melanie Vanderkolk \u2704 53-61 Painting Over by Sarah Broderick \u2706 65-75 POETRY The Fisherman by Beth Clevenstine \u2704 41 When Time Leaves Us by Rachel Wise \u2706 51 Reconstructing the Myth by Rachel Wise \u2706 63 Omission by Molly Graber \u2704 77-78 Here Always by Sarah Broderick \u2706 80-81 Destination Companion by Beth Clevenstine \u2704 83 All submissions are reviewed on an anonymous basis, and all editorial decisions are shared equally among the members of the Editorial Board. The winning submission for the 2003 Exile Poetry Competition was chosen by a faculty member from the English Department -34 Cover Art Florence Mannequin by Harper Leich \u2704 / Back Cover Art Firenze by Harper Leich \u2704 -34 Printed by Printing Arts Press -34 All submissions are reviewed on an anonymous basis, and all editorial decisions are shared equally among the members of the Editorial Board. -86 Printed by Printing Arts Press -86 NOTE: Both the Fall 2003 and Spring 2004 issues of Exile are included in these scans, as they are bound in a single volume. NOTE: The author of the poem Dinner with Daddy (19) is listed as Nicki Bennet in the table of contents and Nikki Bennet on the page where the work is published. Nikki Bennet is consistently credited as the author of the poem Leaving Behind Yaknapatawpha (20), while Nicki Bennet is consistently credited as the author of the poem Communion Cup (31). Only Nikki Bennett is listed in the Contributors\u27 Notes, and also as Co-Editor of the Poetry Board. Winner of Exile Prize for Poetry: Blackout by Derek Mong \u2704 (8-9