gebhart/patrepeval huggingface dataset:
Sparged Animal Cell Bioreactors: Mechanism of Cell Damage and Pluronic F‐68 Protection (1990)

Pluronic F-68 is a widely used protective agent in sparged animal cell bioreactors. In this study, the attachment-independent Spodoptera frugiperda Sf9 insect cell line was used to explore the mechanism of this protective effect and the nature of cell damage in sparged bioreactors. First, bubble incorporation via cavitation or vortexing was induced by increasing the agitation rate in a surface-aerated bioreactor; insect cells were rapidly killed under these conditions of the absence of polyols. Supplementing the medium with 0.2% (w/v) Pluronic F-68, however, fully protected the cells. Next, cell growth was compared in two airlift bioreactors with similar geometry but different sparger design; one of these bioreactors consisted of a thin membrane distributor, while the other consisted of a porous stainless steel distributor. The flow rates and bubble sizes were comparable in the two bioreactors. Supplementing the medium with 0.2% (w/v) Pluronic F-68 provided full protection to cells growing in the bioreactor with the membrane distributor but provided essentially no protection in the bioreactor with the stainless steel distributor. These results strongly suggest that cell damage can occur in the vicinity of the gas distributor. In addition, these results demonstrate that bubble size and gas flow rate are not the only important considerations of cell damage in sparged bioreactors. A model of cell death in sparged bioreactors is presented.
Histologic Investigation of Hyperphonated Canine Vocal Cords (1988)

Vocal cord injury and its effect on the larynx are topics of considerable importance, yet a clear understanding of acute vocal cord injury from excessive phonation remains elusive. The inability to develop an animal model for vocal abuse has hampered research in this area. This project describes the development of a canine model for acute vocal cord injury from excessive phonation. The method of phonation consisted of a humidified, temperature-controlled, constant flow of air delivered subglottally by an external compressor. A small group of dogs underwent phonation for 2 and 4 hours. Vocal cord injury is described using histologic techniques. Damage to the vocal cords, other than hemorrhage (rare in dogs) and edema, proved to be too elusive for routine microscopy. Scanning and transmission electron microscopy showed extensive surface damage with destruction and loss of the surface microridges and premature desquamation of the vocal cord squamous epithelium. Injury extended to the lamina propria, where the collagen fibers were detached from the basement membrane.
Gene regulation by tetracyclines (2003)

The Tet repressor protein (TetR) regulates transcription of a family of tetracycline (tc) resistance determinants in Gram-negative bacteria. The resistance protein TetA, a membrane-spanning H+-[tc.M]+ antiporter, must be sensitively regulated because its expression is harmful in the absence of tc, yet it has to be expressed before the drugs' concentration reaches cytoplasmic levels inhibitory for protein synthesis. Consequently, TetR shows highly specific tetO binding to reduce basal expression and high affinity to tc to ensure sensitive induction. Tc can cross biological membranes by diffusion enabling this inducer to penetrate the majority of cells. These regulatory and pharmacological properties are the basis for application of TetR to selectively control the expression of single genes in lower and higher eukaryotes. TetR can be used for that purpose in some organisms without further modifications. In mammals and in a large variety of other organisms, however, eukaryotic transcriptional activator or repressor domains are fused to TetR to turn it into an efficient regulator. Mechanistic understanding and the ability to engineer and screen for mutants with specific properties allow tailoring of the DNA recognition specificity, the response to inducer tc and the dimerization specificity of TetR-based eukaryotic regulators. This review provides an overview of the TetR properties as they evolved in bacteria, the functional modifications necessary to transform it into a convenient, specific and efficient regulator for use in eukaryotes and how the interplay between structure--function studies in bacteria and specific requirements of particular applications in eukaryotes have made it a versatile and highly adaptable regulatory system.
Transcription Control by E1A and MAP Kinase Pathway via Sur2 Mediator Subunit (2002)

Sur2 is a metazoan Mediator subunit that interacts with the adenovirus E1A protein and functions in a mitogen-activated protein kinase pathway required for vulva development in Caenorhabditis elegans. We generated sur2-/- embryonic stem cells to analyze its function as a mammalian Mediator component. Our results show that Sur2 forms a subcomplex of the Mediator with two other subunits, TRAP/Med100 and 95. Knock-out of Sur2 prevents activation by E1A-CR3 and the mitogen-activated protein kinase-regulated ETS transcription factor Elk-1, but not by multiple other transcription factors. These results imply that specific activation domains stimulate transcription by binding to distinct Mediator subunits. Activation by E1A and Elk-1 requires recruitment of Mediator to a promoter by binding to its Sur2 subunit.
A locus on chromosome 9p confers susceptibility to ALS and frontotemporal dementia (2006)

A locus on chromosome 9p21.3-p13.3 is linked to ALS-FTD.
Active transport of maltose in Escherichia coli K12. Role of the periplasmic maltose-binding protein and evidence for a substrate recognition site in the cytoplasmic membrane. (1982)

The active transport of maltose in Escherichia coli requires the products of five genes. These include a water-soluble periplasmic maltose-binding protein, three cytoplasmic membrane proteins, and an outer membrane protein. In order to evaluate the role of the maltose-binding protein in active transport, a nonpolar internal deletion of the structural gene for the maltose-binding protein was constructed. A strain which contains this deletion is unable to grow on maltose at an external concentration of 25 mM, even when the remaining components of the transport system are synthesized constitutively. This demonstrates that the periplasmic maltose-binding protein is essential for detectable translocation of maltose across the cytoplasmic membrane. Mal+ revertants of the deletion strain were obtained. In one of these strains, the remaining components of the maltose transport system gained the ability to translocate maltose across the membrane independently of the periplasmic binding protein. Maltose transport in this revertant strain is specific for maltose; it is not inhibited by other alpha and beta glucosides and galactosides. In contrast to the wild type, transport activity in the Mal+ revertant strain is retained by spheroplasts. The cytoplasmic membrane components of the maltose transport system in the revertant appear to form a substrate recognition site. It is likely that this site exists in wild type cells but is available only to substrate molecules that are bound to the maltose-binding protein. A model for the operation of the transport system is presented. In this model, the substrate recognition site in the cytoplasmic membrane is exposed to alternate sides of the membrane.
R707, a fully human antibody directed against CC-chemokine receptor 7, attenuates xenogeneic acute graft-versus-host disease (2019)

Acute graft-versus-host disease (aGVHD) remains a barrier to the success of allogeneic hematopoietic stem cell transplantation (HSCT). Previously, we demonstrated that CC-chemokine receptor 7 (CCR7) is critical for aGVHD pathogenesis but dispensable for beneficial graft-versus-leukemia responses. As a result, we evaluated a fully human anti-CCR7-blocking antibody as a new approach to prevent aGVHD in preclinical models. Here we report that antibody R707 is able to block human CCR7 signaling and function in vitro in response to its 2 natural ligands. The antibody was less active against the murine orthologue, however, and failed to substantially limit aGVHD in a standard murine allogeneic HSCT model. Nevertheless, R707 significantly reduced xenogeneic aGVHD induced by human peripheral blood mononuclear cells (PBMCs). R707 limited CD4<sup>+</sup> and in particular CD8<sup>+</sup> T cell expansion during the period of antibody administration. These effects were transient, however, and T cell numbers recovered after antibody cessation. R707 did not substantially impair the antitumor potential of the PBMC inoculum as antibody-treated mice retained their capacity to reject a human acute myeloid leukemia cell line. Collectively, these data indicate for the first time that an antibody directed against CCR7 might represent a viable new approach for aGVHD prevention.
3-Dimensional structure of membrane-bound coagulation factor VIII: modeling of the factor VIII heterodimer within a 3-dimensional density map derived by electron crystallography (2002)

Despite recent studies, the organization of coagulation factor VIII (FVIII) on a phospholipid (PL) membrane is not known in detail. Thus, 2-dimensional (2D) crystals of human FVIII lacking the B domain were prepared for electron microscopy onto negatively charged PL monolayers. The 3-dimensional (3D) density map of the PL-bound FVIII protein was calculated at 1.5 nm. Existing atomic data and models for FVIII domains were fitted unambiguously within the 3D density map of the molecule. FVIII domains arrangement followed a compact spiral organization with the A3 domains in close association with the C1 and C2 domains near the PL surface. Viewed toward the membrane the A domains' heterotrimer is oriented side-on with the pseudo-3-fold axis almost parallel to the PL surface and A1 fully covering C1. The C2 domain is partially overlapped by the A2 domain of an adjacent molecule in the 2D crystal, favoring close packing. Viewed parallel to the membrane, C2 is slightly inclined to the PL surface covering an area of 12 nm(2). Four C2 loops are embedded within the lipid monolayer at about 0.7 to 1.0 nm depth. C1 forms almost a right angle with C2, its long axis nearly parallel to the membrane. The proposed structure for membrane-bound FVIII results from modeling of the FVIII domains within a 3D density map obtained from electron crystallography and accords with the main biochemical and structural information known to date. A model is proposed for FVIIIa and factor IXa assembly within the membrane-bound factor X-activating complex. (Blood. 2002;99:1215-1223)
Dynamic Adaptive Streaming over HTTP from Multiple Content Distribution Servers (2011)

Dynamic adaptive streaming over HTTP (DASH\footnote{In this paper, we use DASH as a general acronym, which does not represent 3GPP- DASH/MPEG-DASH standards.}) is attractive. It reuses popular web servers rather than relying on expensive streaming server. It takes the benefits of router and firewall optimizations for HTTP traffic. It promises to automatically adapt to bandwidth dynamics to provide smooth playback experience with best achievable visual quality. In this paper, we study a new architecture for DASH, i.e. DASH from multiple content distribution servers with scalable coded video. We take the advantage of content distribution network (CDN) architecture to offer even better DASH experience. In our scheme, users request one video program simultaneously from more than one CDN servers over HTTP. To optimize resource allocation among different servers, we propose a collaborative multi-scale scheduling algorithm (CMSS) which can effectively: 1) mitigate web server load and automatically balance loads among servers; 2) adapt to bandwidth dynamics of each server; 3) optimize aggregated streaming quality. We implemented a prototype of our algorithm and deployed it on PlanetLab open platform. Measurement results verify the effectiveness of CMSS.
Erythropoietin administration after myocardial infarction in mice attenuates ischemic cardiomyopathy associated with enhanced homing of bone marrow‐derived progenitor cells via the CXCR‐4/SDF‐1 axis (2008)

Mobilization of bone marrow-derived stem cells (BMCs) was shown to have protective effects after myocardial infarction (MI). However, the classical mobilizing agent, granulocyte-colony stimulating factor (G-CSF) relapsed after revealing an impaired homing capacity. In the search for superior cytokines, erythropoietin (EPO) appears to be a promising agent. Therefore, we analyzed in a murine model of surgically induced MI the influence of EPO treatment on survival and functional parameters as well as BMC mobilization, homing, and effect on resident cardiac stem cells (CSCs). Human EPO was injected intraperitoneally after ligation of the left anterior descendens (LAD) for 3 days with a total dose of 5000 IU/kg 6 and 30 days after MI, and pressure volume relationships were investigated in vivo. Cardiac tissues were analyzed by histology. To show the effect on BMCs and CSCs, FACS analyses were performed. Homing factors were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and ELISA. EPO-treated animals showed a significant improvement of survival post-MI (62 vs. 36%). At days 6 and 30, all hemodynamic parameters associated with attenuated remodeling, enhanced neovascularization, and diminished apoptotic cells in the peri-infarct area were improved. BMC subpopulations (CD31(+), c-kit(+), and Sca-1(+) cells) were mobilized, and homing of Sca-1(+) and CXCR4(+) BMCs toward an SDF-1 gradient into the ischemic myocardium was enhanced. However, there was no beneficial effect on CSCs. We have shown that EPO application after MI shows cardioprotective effects. This may be explained by mobilization of BMCs, which are homing via the CXCR-4/SDF-1 axis. However, EPO has no beneficial effects on resident CSCs. Therefore, new treatment regimes using EPO together with other agents may combine complementary beneficial effects preventing ischemic cardiomyopathy.
Methods for Anomeric Carbon-Linked and Fused Sugar Amino Acid Synthesis:  The Gateway to Artificial Glycopeptides (2000)

Having solved over the last 30 years or so the majority of the problems associated with the stereocontrolled synthesis of natural O-oligosaccharides and O-glycoconjugates with a substantial beneficial effect on glycobiology, in recent times organic chemists have been focusing more interest upon the development of synthetic procedures for unnatural carbon-linked analogues. Various synthetic procedures to C-glycosyl amino acids have been developed to date.
Selective Optical Recognition and Quantification of Parts Per Million Levels of Cr6+ in Aqueous and Organic Media by Immobilized Polypyridyl Complexes on Glass (2008)

Selective optical sensing of parts per million levels of Cr(6+) in water under acidic conditions with robust, osmium-chromophore-based monolayers is demonstrated. The sensor system can be reset by washing with water at neutral pH and can be readily monitored by UV/vis spectroscopy.
A pilot study of intralymphatic interleukin-2. I. Cytotoxic and surface marker changes of peripheral blood lymphocytes. (1990)

Patients with metastatic solid tumors were treated with six escalating doses of weekly intralymphatically injected recombinant interleukin 2 (i.l. IL-2). Nine patients completed the treatment and were evaluated for immunologic features of their peripheral blood lymphocytes (PBLs). The patients' PBL counts increased 4 days after the first i.l. IL-2 injection. The cell counts remained higher than baseline in week 6 prior to the last i.l. IL-2 injection. However, the PBL number decreased below baseline 1 day after the sixth injection, and recovered to normal levels after 3 days more. Natural killer (NK) activity showed similar changes when calculated as total activity per ml of blood. In vitro 1 h treatment of PBLs with IL-2 greatly enhanced NK cytotoxicity. The enhancement was only slight in the first week of i.l. IL-2 treatment, but was significantly greater on day 35 (7 days after dose 5) and day 39 (4 days after dose 6). In contrast, the increase was similar to the baseline on day 36, the day after the sixth injection. No lymphokine-activated killer activity was detected in the patients' PBLs with or without short-term in vitro IL-2 treatment. Besides the NK cytotoxic function, lymphoid subpopulations were evaluated numerically for total T cells (CD3/OKT3), T-cell subsets (CD4/OKT4 and CD8/OKT8), B cells (OKB7), NK cells (CD56/NKH1/Leu19, CD16/Leu11), and monocytes/NK cells (CD11b/OKM1). The activation markers (HLA-DR, CD25/Tac, and CD38/OKT10/Leu17) were also included. Intralymphatic IL-2 treatment had no effect on the PBL surface marker expression in the first week of treatment. However, by week 6, the percentages of cell populations expressing the NK-associated antigens CD56, CD16, and CD11b were significantly increased. In contrast, the percentage of CD3-positive T cells showed no change or a marginal decrease. Prior to and after i.l. IL-2 treatment, the CD56-positive cells in the PBLs were predominantly CD16 positive and CD3 negative. The i.l. IL-2 treatment did not induce PBL proliferation, or changes in the expression of CD25 (Tac), HLA-DR, CD38, CD4, CD8, CD57, or OKB7 in the patients' PBL. These results indicate that i.l. IL-2 treatment does affect the total number of PBLs, the cells expressing NK activity, and NK-associated surface markers.
Novel insight into molecular mechanism of endotoxin shock: biochemical analysis of LPS receptor signaling in a cell-free system targeting NF-κB and regulation of cytokine production/action through β2 integrin in vivo (1996)

Lipopolysaccharide (LPS), a constituent of gram-negative bacteria cell wall, plays an essential role in the pathogenesis of septic shock by generating endogenous mediators such as cytokines, nitrous oxide, superoxide anions, and lipid mediators. In vitro, LPS induces the transcription of a set of genes involved in inflammatory reactions by activating several types of transcription factors, particularly nuclear factor-kappaB (NF-kappaB). An analysis of NF-kappaB activation using a cell-free system demonstated that two pathways converge to activate NF-kappaB; one is staurosporine-sensitive, the other is staurosporine-insensitive and tyrosine kinase-dependent. Furthermore, the latter pathway culminates in IkappaBalpha phosphorylation at serine/threonine residues in its carboxyl-terminal acidic region with dissociation of IkappaBalpha from NF-kappaB, thereby activating NF-kappaB. The requirement for the phosphorylation at this site was confirmed by the specific inhibition of NF-kappaB activation in a cell-free system by the synthetic peptide corresponding to this site. The in vivo administration of an anti-CD18 antibody prevented elevation of plasma tumor necrosis factor (TNF) levels and acute lethality induced by injection of a low dose of LPS into Propionibacterium acnes-primed rabbits or by the administration of a single high dose of LPS into animals. Anti-CD18 also prevented acute lethality induced by one of the main mediators of endotoxin shock, TNF-alpha. Furthermore, an antibody to a ligand for CD18, intercellular adhesion molecule-1, also prevented TNF-induced shock as well as endotoxin shock in rabbits. These observations suggest that the interaction between leukoytes and endothelium through beta2- integrin adhesion molecules may be of primary importance in mediating LPS signals in vivo.
ANDROGEN THERAPY IN THE HUMAN FEMALE (1941)

THE THERAPEUTIC USE of androgens for gynecologic disorders is the outgrowth of the obser-vations by biochemists, physiologists and clini-cians concerning the presence and role of the normally occurring androgens in the female. Koch and Gal-lagher identified substances in the testicles of bulls and David and Laqueur separated an androgenic com-pound called testosterone from the same source. Later it was produced synthetically by Butenandt and. Rusicka. Koch reported the presence of 4 androgenic substances in the human urine but could not isolate testosterone. One of these four androgens was androsterone which Butenandt and Tscherning were able to crystallize. Later, the Callows identified androsterone and dehydroandrosterone in the urine of normal women. They found androgens even in puberty, though in small amounts varying from 1.1 to 3 international units. Gallagher et al. stated that normal young women excrete 2,6 i.u. of androgen daily in the urine and men excrete 40 to 56 i.u. Only traces were found before puberty. Koch sug-gested that the adrenal probably was the source of the androgens in the female. Hill believes that the ovaries may secrete male hormone as he was able to show that ovaries transplanted to the ears of cas-trated mice stimulated the seminal vesicles and prostate. He believed that the temperature of the environment played a part.
Inter-Platform comparability of microarrays in acute lymphoblastic leukemia (2004)

Interarray comparisons such as this one will further enhance the ability to integrate data from several generations of microarray experiments and will help to break down barriers to the assimilation of existing datasets into a comprehensive data pool.
Induction of Potent Antitumor CTL Responses by Recombinant Vaccinia Encoding a Melan-A Peptide Analogue (2000)

There is considerable interest in the development of vaccination strategies that would elicit strong tumor-specific CTL responses in cancer patients. One strategy consists of using recombinant viruses encoding amino acid sequences corresponding to natural CTL-defined peptide from tumor Ags as immunogens. However, studies with synthetic tumor antigenic peptides have demonstrated that introduction of single amino acid substitutions may dramatically increase their immunogenicity. In this study we have used a well-defined human melanoma tumor Ag system to test the possibility of translating the immunological potency of synthetic tumor antigenic peptide analogues into recombinant vaccinia viruses carrying constructs with the appropriate nucleotide substitutions. Our results indicate that the use of a mutated minigene construct directing the expression of a modified melanoma tumor Ag leads to improved Ag recognition and, more importantly, to enhanced immunogenicity. Thus, recombinant vaccinia viruses containing mutated minigene sequences may lead to new strategies for the induction of strong tumor-specific CTL responses in cancer patients.
Oncolytic Poxviruses (2014)

Current standard treatments of cancer can prolong survival of many cancer patients but usually do not effectively cure the disease. Oncolytic virotherapy is an emerging therapeutic for the treatment of cancer that exploits replication-competent viruses to selectively infect and destroy cancerous cells while sparing normal cells and tissues. Clinical and/or preclinical studies on oncolytic viruses have revealed that the candidate viruses being tested in trials are remarkably safe and offer potential for treating many classes of currently incurable cancers. Among these candidates are vaccinia and myxoma viruses, which belong to the family Poxviridae and possess promising oncolytic features. This article describes poxviruses that are being developed for oncolytic virotherapy and summarizes the outcomes of both clinical and preclinical studies. Additionally, studies demonstrating superior efficacy when poxvirus oncolytic virotherapy is combined with conventional therapies are described.