Business Plays a Key Role in Shaping Regulation

The relationship between business ethics and regulation is complex. The role of MNCs in shaping regulation is growing. MNCs in emerging economies need to take an active approach in shaping their regulatory environments.York's Knowledge Mobilization Unit provides services and funding for faculty, graduate students, and community organizations seeking to maximize the impact of academic research and expertise on public policy, social programming, and professional practice. It is supported by SSHRC and CIHR grants, and by the Office of the Vice-President Research & Innovation. [email protected] www.researchimpact.c

Inhibitors of dihydroorotate dehydrogenase cooperate with molnupiravir and N4-hydroxycytidine to suppress SARS-CoV-2 replication

Funding Information: We thank Thorsten Wolff, Daniel Bourquain, Jessica Schulz, and Christian Mache from the Robert-Koch Institute and Martin Beer from the Friedrich Loeffler Institute (FLI) for providing isolates of SARS-CoV-2 variants. We thank Anna Kraft and Gabriele Czerwinski (both FLI) for support in the preparation of samples for pathology, and Catherine Hambly (University of Aberdeen) for help with daily energy expenditure measurements. We would like to thank Cathrin Bierwirth (University Medical Center Göttingen), Isabell Schulz, Anne-Kathrin Donner, and Frank-Thorben Peters for excellent technician assistance and Jasmin Fertey and Alexandra Rockstroh for providing the virus stocks for the mice experiment (Fraunhofer Institute IZI Leipzig). We acknowledge support by the Open Access Publication Funds of the Göttingen University. KMS was a member of the Göttingen Graduate School GGNB during this work. This work was funded by the COVID-19 Forschungsnetzwerk Niedersachsen (COFONI) to MD, by the Federal Ministry of Education and Research Germany ( Bundesministerium für Bildung und Forschung; BMBF ; OrganSARS , 01KI2058 ) to SP and TM, and by a grant of the Max Planck Foundation to DG. Declaration of interests AS, HK, EP, and DV are employees of Immunic AG and own shares and/or stock-options of the parent company of Immunic AG, Immunic Inc. Some of the Immunic AG employees also hold patents for the Immunic compounds described in this manuscript (WO2012/001,148, WO03006425). KMS, AD, and MD are employees of University Medical Center Göttingen, which has signed a License Agreement with Immunic AG covering the combination of DHODH inhibitors and nucleoside analogs to treat viral infections, including COVID-19 (inventors: MD, KMS, and AD). The other authors declare no conflict of interest.Peer reviewedPublisher PD

Influence of Ocean Acidification on a Natural Winter-to-Summer Plankton Succession : First Insights from a Long-Term Mesocosm Study Draw Attention to Periods of Low Nutrient Concentrations

Every year, the oceans absorb about 30% of anthropogenic carbon dioxide (CO2) leading to a re-equilibration of the marine carbonate system and decreasing seawater pH. Today, there is increasing awareness that these changes-summarized by the term ocean acidification (OA)-could differentially affect the competitive ability of marine organisms, thereby provoking a restructuring of marine ecosystems and biogeochemical element cycles. In winter 2013, we deployed ten pelagic mesocosms in the Gullmar Fjord at the Swedish west coast in order to study the effect of OA on plankton ecology and biogeochemistry under close to natural conditions. Five of the ten mesocosms were left unperturbed and served as controls (similar to 380 mu atm pCO(2)), whereas the others were enriched with CO2-saturated water to simulate realistic end-of-the-century carbonate chemistry conditions (mu 760 mu atm pCO(2)). We ran the experiment for 113 days which allowed us to study the influence of high CO2 on an entire winter-to-summer plankton succession and to investigate the potential of some plankton organisms for evolutionary adaptation to OA in their natural environment. This paper is the first in a PLOS collection and provides a detailed overview on the experimental design, important events, and the key complexities of such a "long-term mesocosm" approach. Furthermore, we analyzed whether simulated end-of-the-century carbonate chemistry conditions could lead to a significant restructuring of the plankton community in the course of the succession. At the level of detail analyzed in this overview paper we found that CO2-induced differences in plankton community composition were non-detectable during most of the succession except for a period where a phytoplankton bloom was fueled by remineralized nutrients. These results indicate: (1) Long-term studies with pelagic ecosystems are necessary to uncover OA-sensitive stages of succession. (2) Plankton communities fueled by regenerated nutrients may be more responsive to changing carbonate chemistry than those having access to high inorganic nutrient concentrations and may deserve particular attention in future studies.Peer reviewe

Lead-free Solders for Ribbon Interconnection of Crystalline Silicon PERC Solar Cells with Infrared Soldering

We report about the analysis of Pb-free, low-temperature solders for the ribbon-interconnection of PERC solar cells with an industrial infrared stringer. Five solders (SnPb, SnBi-A, SnBi-B, SnBiAg and a proprietary lead-free, low-temperature (PLFLT) alloy) are characterized with differential scanning calorimetry to determine the melting and solidification temperature. It is found that SnBi-B, SnBiAg, and the PLFLT composition melt in a temperature range between 137 C to 171 C instead of a single temperature. Solidification occurs at a 3K to 11K lower temperature (undercooling). Mono-crystalline silicon PERC cells are contacted using an industrial stringer. The microstructure of the solder bonds is investigated with scanning electron microscopy. For the SnBi-A-solder, large and brittle Bi-phases are identified. The SnBi-B, SnBiAg and PLFLT solder show a finer grain structure. The added Ag in SnBiAg forms an intermetallic compound of Ag3Sn close to the Cu-core of the ribbon. The peel strength of the connected solar cells with the Pb-free solders is on average 1Nmm\u1000001 or slightly higher. Some bonds show low adhesion. The observed fracture mode is mainly failure at the busbar metallization to solar cell irrespective of the solder type. However, the occasionally observed solder residues on the metallization clearly reveal brittle fracture for the Pb-free solders, which is not observed for SnPb. First reliability tests show similar degradation of 1% to 2% for all solders

High efficiency of antiviral CD4(+) killer T cells.

The destruction of infected cells by cytotxic T lymphocytes (CTL) is integral to the effective control of viral and bacterial diseases, and CTL function at large has long been regarded as a distinctive property of the CD8(+)T cell subset. In contrast, and despite their first description more than three decades ago, the precise contribution of cytotoxic CD4(+)T cells to the resolution of infectious diseases has remained a matter of debate. In particular, the CTL activity of pathogen-specific CD4(+) "helper" T cells constitutes a single trait among a diverse array of other T cell functionalities, and overall appears considerably weaker than the cytolytic capacity of CD8(+) effector T cells. Here, using an in vivo CTL assay, we report that cytotoxic CD4(+)T cells are readily generated against both viral and bacterial pathogens, and that the efficiency of MHC-II-restricted CD4(+)T cell killing adjusted for effector:target cell ratios, precise specificities and functional avidities is comparable in magnitude to that of CD8(+)T cells. In fact, the only difference between specific CD4(+) and CD8(+)T cells pertains to the slightly delayed killing kinetics of the former demonstrating that potent CTL function is a cardinal property of both antiviral CD8(+) and CD4(+)T cells

Lobar lung transplantation from deceased donors: A systematic review

AIM To systematically review reports on deceased-donor-lobar lung transplantation (ddLLTx) and uniformly describe size matching using the donor-to-recipient predicted-total lung-capacity (pTLC) ratio. METHODS We set out to systematically review reports on ddLLTx and uniformly describe size matching using the donor-to-recipient pTLC ratio and to summarize reported one-year survival data of ddLLTx and conventional-LTx. We searched in PubMed, CINAHL via EBSCO, Cochrane Database of Systematic Reviews via Wiley (CDSR), Database of Abstracts of Reviews of Effects via Wiley (DARE), Cochrane Central Register of Controlled Trials via Wiley (CENTRAL), Scopus (which includes EMBASE abstracts), and Web of Science for original reports on ddLLTx. RESULTS Nine observational cohort studies reporting on 301 ddLLTx met our inclusion criteria for systematic review of size matching, and eight for describing one-year-survival. The ddLLTx-group was often characterized by high acuity; however there was heterogeneity in transplant indications and pre-operative characteristics between studies. Data to calculate the pTLC ratio was available for 242 ddLLTx (80%). The mean pTLCratio before lobar resection was 1.25 ± 0.3 and the transplanted pTLCratio after lobar resection was 0.76 ± 0.2. One-year survival in the ddLLTx-group ranged from 50%-100%, compared to 72%-88% in the conventional-LTx group. In the largest study ddLLTx (n = 138) was associated with a lower one-year-survival compared to conventional-LTx (n = 539) (65.1% vs 84.1%, P < 0.001). CONCLUSION Further investigations of optimal donor-to-recipient size matching parameters for ddLLTx could improve outcomes of this important surgical option

Aging boosts antiviral CD8+T cell memory through improved engagement of diversified recall response determinants.

The determinants of protective CD8+ memory T cell (CD8+TM) immunity remain incompletely defined and may in fact constitute an evolving agency as aging CD8+TM progressively acquire enhanced rather than impaired recall capacities. Here, we show that old as compared to young antiviral CD8+TM more effectively harness disparate molecular processes (cytokine signaling, trafficking, effector functions, and co-stimulation/inhibition) that in concert confer greater secondary reactivity. The relative reliance on these pathways is contingent on the nature of the secondary challenge (greater for chronic than acute viral infections) and over time, aging CD8+TM re-establish a dependence on the same accessory signals required for effective priming of naïve CD8+T cells in the first place. Thus, our findings reveal a temporal regulation of complementary recall response determinants that is consistent with the recently proposed "rebound model" according to which aging CD8+TM properties are gradually aligned with those of naïve CD8+T cells; our identification of a broadly diversified collection of immunomodulatory targets may further provide a foundation for the potential therapeutic "tuning" of CD8+TM immunity

Kinetics of concurrent CD4⁺ and CD8⁺CTL activities directed against the same LCMV determinant.

<p><b>A.,</b> frequencies of GP₆₇-specific CD8⁺ and CD4⁺T cells in spleens of LCMV d8 mice. The EC₅₀ values listed above the bar diagrams are taken from ref. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060420#pone.0060420-Homann2" target="_blank">[19]</a> and are not significantly different. <b>B.,</b> experimental design: B cells were purified from naïve B6, B6.b2m^−/− (“class I ko”) and B6.IA^b−/− (“class II ko”) donors to >98% purity, coated with GP₆₇ peptide (class I and II ko B cells) or left uncoated (B6 B cells), differentially labeled with CFSE, mixed at a ratio of 1∶1∶1 and transferred (3×8×10⁶ B cells) into B6.CD45.1-congenic recipients infected with LCMV eight days earlier. The experimental design assures that target cells sensitized with the same peptide (GP₆₇) are recognized either by specific CD8⁺T cells (class II ko B cells) or specific CD4⁺T cells (class I ko B cells), but no target cells are recognized by both T cell populations. <b>C.,</b> kinetics of GP₆₇-specific CD8⁺ (black) and CD4⁺ (gray) T cell killing determined by sequential blood draws and non-linear regression analysis as detailed above (SEM, n = 3 mice; asterisks indicate significantly increased killing by GP₆₇-specific CD8⁺ as compared to CD4⁺T cells at 1 h and 2 h after target cell transfer).</p