Der Freiberger Dom: Architektur als Sprache

Das Lehr-Lern-Projekt beinhaltet die Ableitung und Erprobung von Handlungsempfehlungen und Werkzeugen für interdisziplinäre Praxis- und Forschungsprojekte anhand einer Projektarbeit, welche auf die Erstellung einer Besucher-App für den Freiberger Dom zielt

Novel Approaches to research and discover Urban History

Photographs and plans are an essential source for historical research (Münster, Kamposiori, Friedrichs, & Kröber, 2018) and key objects in Digital Humanities (Kwastek, 2014). Numerous digital image archives, containing vast numbers of photographs, have been set up in the context of digitization projects. These extensive repositories of image media are still difficult to search. It is not easy to identify sources relevant for research, analyze and contextualize them, or compare them with the historical original. The eHumanities research group HistStadt4D, funded by the German Federal Ministry of Education and Research (BMBF) until July 2020 consists of 14 people – including 4 post-doctoral and 5 PhD researchers. Since a focal interest is to comprehensively investigate how to enhance accessibility of large scale image repositories, researchers and research approaches originate from the humanities, geoand information technologies as well as from educational and information studies. In contrast to adjacent projects dealing primarily with large scale linked text data as the Venice Time Machine project (“The Venice Time Machine,” 2017), sources addressed by the junior group are primarily historical photographs and plans. Historical media and their contextual information are being transferred into a 4D – 3D spatial and temporal scaled - model to support research and education on urban history. Content will be made accessible in two ways; via a 4D browser and a location-dependent augmented-reality representation. The prototype database consists of about 200,000 digitized historical photographs and plans of Dresden from the Deutsche Fotothek (“Deutsche Fotothek,”)

Respiratory adverse effects of opioids for breathlessness: a systematic review and meta-analysis

Background: Previous studies have shown that opioids can reduce chronic breathlessness in advanced disease. However, physicians remain reluctant to prescribe opioids for these patients, commonly due to fear of respiratory adverse effects. Aim: To systematically review reported respiratory adverse effects of opioids in patients with advanced disease and chronic breathlessness. Methods: Pubmed, Embase, Cochrane central register of controlled trials, CINAHL, ClinicalTrials.gov and the reference lists of relevant systematic reviews were searched. Two independent researchers screened against predefined inclusion criteria and extracted data. Meta-analysis was conducted where possible. Results: We included 63 out of 1990 articles, describing 67 studies. Meta-analysis showed an increase in partial pressure of carbon dioxide (0.27 kPa; 95% CI 0.08 to 0.45) and no significant change in partial pressure of oxygen and oxygen saturation (both p>0.05). Non-serious respiratory depression (definition variable/not stated) was described in 4/1064 patients. One cancer patient pre-treated with morphine for pain needed temporary respiratory support following nebulized morphine for breathlessness (single case study). Conclusions: We found no evidence of significant or clinically relevant respiratory adverse effects of opioids for chronic breathlessness. Heterogeneity of design and study population, and low study quality are limitations. Larger studies designed to detect respiratory adverse effects are needed

Contemporary human H3N2 influenza A viruses require a low threshold of suitable glycan receptors for efficient infection

Recent human H3N2 influenza A viruses have evolved to employ elongated glycans terminating in α2,6-linked sialic acid as their receptors. These glycans are displayed in low abundancies by (humanized) Madin-Darby Canine Kidney cells, which are commonly employed to propagate influenza A virus, resulting in low or no viral propagation. Here, we examined whether the overexpression of the glycosyltransferases β-1,3-N-acetylglucosaminyltransferase and β-1,4-galactosyltransferase 1, which are responsible for the elongation of poly-N-acetyllactosamines (LacNAcs), would result in improved A/H3N2 propagation. Stable overexpression of β-1,3-N-acetylglucosaminyltransferase and β-1,4-galactosyltransferase 1 in Madin-Darby Canine Kidney and "humanized" Madin-Darby Canine Kidney cells was achieved by lentiviral integration and subsequent antibiotic selection and confirmed by qPCR and protein mass spectrometry experiments. Flow cytometry and glycan mass spectrometry experiments using the β-1,3-N-acetylglucosaminyltransferase and/or β-1,4-galactosyltransferase 1 knock-in cells demonstrated increased binding of viral hemagglutinins and the presence of a larger number of LacNAc repeating units, especially on "humanized" Madin-Darby Canine Kidney-β-1,3-N-acetylglucosaminyltransferase cells. An increase in the number of glycan receptors did, however, not result in a greater infection efficiency of recent human H3N2 viruses. Based on these results, we propose that H3N2 influenza A viruses require a low number of suitable glycan receptors to infect cells and that an increase in the glycan receptor display above this threshold does not result in improved infection efficiency.</p

Mitochondrial respiration - an important therapeutic target in melanoma

The importance of mitochondria as oxygen sensors as well as producers of ATP and reactive oxygen species (ROS) has recently become a focal point of cancer research. However, in the case of melanoma, little information is available to what extent cellular bioenergetics processes contribute to the progression of the disease and related to it, whether oxidative phosphorylation (OXPHOS) has a prominent role in advanced melanoma. In this study we demonstrate that compared to melanocytes, metastatic melanoma cells have elevated levels of OXPHOS. Furthermore, treating metastatic melanoma cells with the drug, Elesclomol, which induces cancer cell apoptosis through oxidative stress, we document by way of stable isotope labeling with amino acids in cell culture (SILAC) that proteins participating in OXPHOS are downregulated. We also provide evidence that melanoma cells with high levels of glycolysis are more resistant to Elesclomol. We further show that Elesclomol upregulates hypoxia inducible factor 1-α (HIF-1α), and that prolonged exposure of melanoma cells to this drug leads to selection of melanoma cells with high levels of glycolysis. Taken together, our findings suggest that molecular targeting of OXPHOS may have efficacy for advanced melanoma. © 2012 Barbi de Moura et al

Contemporary human H3N2 influenza a viruses require a low threshold of suitable glycan receptors for efficient infection

Recent human H3N2 influenza A viruses (IAV) have evolved to employ elongated glycans terminating in α2,6-linked sialic acid as their receptors. These glycans are displayed in low abundancies by (humanized) Madin-Darby Canine Kidney cells (MDCK and hCK) which are commonly employed to propagate IAV, resulting in low or no viral propagation. Here, we examined whether the overexpression of the glycosyltransferases B3GNT2 and B4GALT1, which are responsible for the elongation of poly-N-acetyllactosamines (LacNAc), would result in improved A/H3N2 propagation. Stable overexpression of B3GNT2 and B4GALT1 in MDCK and hCK cells was achieved by lentiviral integration and subsequent antibiotic selection and confirmed by qPCR and protein mass spectrometry experiments. Flow cytometry and glycan mass spectrometry experiments using the B3GNT2 and/or B4GALT1 knock-in cells demonstrated increased binding of viral hemagglutinins and the presence of a larger number of LacNAc repeating units, especially on hCK-B3GNT2 cells. An increase in the number of glycan receptors did, however, not result in a greater infection efficiency of recent human H3N2 viruses. Based on these results, we propose that H3N2 IAVs require a low number of suitable glycan receptors to infect cells and that an increase in the glycan receptor display above this threshold does not result in improved infection efficiency

Short-chain fructo-oligosaccharides supplementation to suckling piglets : assessment of pre- and post-weaning performance and gut health

Farmers face difficulties in redeeming their investment in larger litter sizes since this comes with larger litter heterogenicity, lower litter resilience and risk of higher mortality. Dietary oligosaccharides, given to the sow, proved beneficial for the offspring's performance. However, giving oligosaccharides to the suckling piglet is poorly explored. Therefore, this field trial studied the effect of dietary short-chain fructo-oligosaccharides (scFOS; 1g/day; drenched) supplementation to low (LBW, lower quartile), normal (NBW, two intermediate quartiles) and high (HBW, upper quartile) birth weight piglets from birth until 7 or 21 days of age. Performance parameters, gut microbiome and short-chain fatty acids profile of feces and digesta were assessed at birth (d 0), d 7, weaning (d 21.5) and 2 weeks post-weaning (d 36.5). Additional parameters reflecting gut health (intestinal integrity and morphology, mucosal immune system) were analysed at d 36.5. Most parameters changed with age or differed with the piglet's birth weight. Drenching with scFOS increased body weight by 1 kg in NBW suckling piglets and reduced the post-weaning mortality rate by a 100%. No clear difference in the IgG level, the microbiota composition and fermentative activity between the treatment groups was observed. Additionnally, intestinal integrity, determined by measuring intestinal permeability and regenerative capacity, was similar between the treatment groups. Also, intestinal architecture (villus lenght, crypt depth) was not affected by scFOS supplementation. The density of intra-epithelial lymphocytes and the expression profiles (real-time qPCR) for immune system-related genes (IL-10, IL-1ss, IL-6, TNF alpha and IFN gamma) were used to assess mucosal immunity. Only IFN gamma expression, was upregulated in piglets that received scFOS for 7 days. The improved body weight and the reduced post-weaning mortality seen in piglets supplemented with scFOS support the view that scFOS positively impact piglet's health and resilience. However, the modes of action for these effects are not yet fully elucidated and its potential to improve other performance parameters needs further investigation

Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen–specific CD8+ T cell dysfunction in melanoma patients

The paradoxical coexistence of spontaneous tumor antigen–specific immune responses with progressive disease in cancer patients furthers the need to dissect the molecular pathways involved in tumor-induced T cell dysfunction. In patients with advanced melanoma, we have previously shown that the cancer-germline antigen NY-ESO-1 stimulates spontaneous NY-ESO-1–specific CD8+ T cells that up-regulate PD-1 expression. We also observed that PD-1 regulates NY-ESO-1–specific CD8+ T cell expansion upon chronic antigen stimulation. In the present study, we show that a fraction of PD-1+ NY-ESO-1–specific CD8+ T cells in patients with advanced melanoma up-regulates Tim-3 expression and that Tim-3+PD-1+ NY-ESO-1–specific CD8+ T cells are more dysfunctional than Tim-3−PD-1+ and Tim-3−PD-1− NY-ESO-1–specific CD8+ T cells, producing less IFN-γ, TNF, and IL-2. Tim-3–Tim-3L blockade enhanced cytokine production by NY-ESO-1–specific CD8+ T cells upon short ex vivo stimulation with cognate peptide, thus enhancing their functional capacity. In addition, Tim-3–Tim-3L blockade enhanced cytokine production and proliferation of NY-ESO-1–specific CD8+ T cells upon prolonged antigen stimulation and acted in synergy with PD-1–PD-L1 blockade. Collectively, our findings support the use of Tim-3–Tim-3L blockade together with PD-1–PD-L1 blockade to reverse tumor-induced T cell exhaustion/dysfunction in patients with advanced melanoma

CD56dim CD16− Natural Killer Cell Profiling in Melanoma Patients Receiving a Cancer Vaccine and Interferon-α

Natural killer (NK) cells are innate cytotoxic and immunoregulatory lymphocytes that have a central role in anti-tumor immunity and play a critical role in mediating cellular immunity in advanced cancer immunotherapies, such as dendritic cell (DC) vaccines. Our group recently tested a novel recombinant adenovirus-transduced autologous DC-based vaccine that simultaneously induces T cell responses against three melanoma-associated antigens for advanced melanoma patients. Here, we examine the impact of this vaccine as well as the subsequent systemic delivery of high-dose interferon-α2b (HDI) on the circulatory NK cell profile in melanoma patients. At baseline, patient NK cells, particularly those isolated from high-risk patients with no measurable disease, showed altered distribution of CD56dim CD16+ and CD56dim CD16− NK cell subsets, as well as elevated serum levels of immune suppressive MICA, TN5E/CD73 and tactile/CD96, and perforin. Surprisingly, patient NK cells displayed a higher level of activation than those from healthy donors as measured by elevated CD69, NKp44 and CCR7 levels, and enhanced K562 killing. Elevated cytolytic ability strongly correlated with increased representation of CD56dim CD16+ NK cells and amplified CD69 expression on CD56dim CD16+ NK cells. While intradermal DC immunizations did not significantly impact circulatory NK cell activation and distribution profiles, subsequent HDI injections enhanced CD56bright CD16− NK cell numbers when compared to patients that did not receive HDI. Phenotypic analysis of tumor-infiltrating NK cells showed that CD56dim CD16− NK cells are the dominant subset in melanoma tumors. NanoString transcriptomic analysis of melanomas resected at baseline indicated that there was a trend of increased CD56dim NK cell gene signature expression in patients with better clinical response. These data indicate that melanoma patient blood NK cells display elevated activation levels, that intra-dermal DC immunizations did not effectively promote systemic NK cell responses, that systemic HDI administration can modulate NK cell subset distributions and suggest that CD56dim CD16− NK cells are a unique non-cytolytic subset in melanoma patients that may associate with better patient outcome

The Vehicle, Spring 1981

Vol. 22, No. 2 Table of Contents Old Farmers at the Arcade CafeJohn Stockmanpage 4 ConfettiCathy Georgepage 6 Ode to a Corned Beef SandwichJeff Bennettpage 6 The Ice on Kirschner\u27s CreekScott Fishelpage 7 Love Poem to LindaJohn Stockmanpage 7 Grandfather\u27s PortraitJames Marshpage 8 The MassageKathleen Alakspage 9 A Driving ForceSandy Youngpage 10 King DandelionNancy Siebenpage 12 One Afternoon - Contemplating HouseworkKelli Sanderpage 13 Tent WallsAndy Sudkamppage 14 The SentinelElise Hempelpage 16 Daddy\u27s AftershaveJeff Bennettpage 16 The WeddingChris Goerlichpage 17 UntitledCarol Hansenpage 17 Treasures in the YardScott Fishelpage 18 Hitchhiker\u27s BootsAndy Sudkamppage 20 The RaffleLaura Henrypage 21 A Walk at NightJudi Jinespage 24 Morning in the DumpJeff Bennettpage 24 In Praise of Chocolate Ice CreamJohn Stockmanpage 25 Summer on the Isle of PalmsElisabeth Cristpage 26 The WaveHerbert S. Demminpage 27 RememberingJohn Kleinsteiberpage 27 PotatoJohn Stockmanpage 28 Late ShowChris Goerlichpage 30 Love in Him - JoeDebbie Klinnertpage 31 ShoeScott Fishelpage 35 The DrinkerBob Huntpage 36 The WidowGeorge Ndu Igbudupage 37 ElectricityScott Fishelpage 37 Hatchet JackB.L. Davidsonpage 39 Walking Home LateJohn Stockmanpage 41 NovemberCindy Hubbarttpage 41 On the BusLaura Henrypage 42 HaikuJames Marshpage 43 SpillwayGloria Rhoadspage 43 Art Cover design by Linda Fraembs PhotographRobin Scholzpage 3 PhotographRobin Scholzpage 5 PhotographMichelle Glassmeyerpage 15 PhotographRobert Schinaglpage 19 PhotographTom Robertspage 38 PhotographRobert Schinaglpage 44https://thekeep.eiu.edu/vehicle/1039/thumbnail.jp