gebhart/patrepeval huggingface dataset:
Clinical-Grade Generation of Active NK Cells from Cord Blood Hematopoietic Progenitor Cells for Immunotherapy Using a Closed-System Culture Process (2011)

Natural killer (NK) cell-based adoptive immunotherapy is a promising treatment approach for many cancers. However, development of protocols that provide large numbers of functional NK cells produced under GMP conditions are required to facilitate clinical studies. In this study, we translated our cytokine-based culture protocol for ex vivo expansion of NK cells from umbilical cord blood (UCB) hematopoietic stem cells into a fully closed, large-scale, cell culture bioprocess. We optimized enrichment of CD34 + cells from cryopreserved UCB units using the CliniMACS system followed by efficient expansion for 14 days in gas-permeable cell culture bags. Thereafter, expanded CD34 + UCB cells could be reproducibly amplified and differentiated into CD56 + CD3 2 NK cell products using bioreactors with a mean expansion of more than 2,000 fold and a purity of .90%. Moreover, expansion in the bioreactor yielded a clinically relevant dose of NK cells (mean: 2610 9 NK cells), which display high expression of activating NK receptors and cytolytic activity against K562. Finally, we established a versatile closed washing procedure resulting in optimal reduction of medium, serum and cytokines used in the cell culture process without changes in phenotype and cytotoxic activity. These results demonstrate that large numbers of UCB stem cell-derived NK cell products for adoptive immunotherapy can be produced in closed, large-scale bioreactors for the use in clinical trials.
Adjuvant effect of docetaxel on the immune responses to influenza A H1N1 vaccine in mice (2012)

Docetaxel has adjuvant effect on the influenza H1N1 vaccine by up-regulation of Th1/Th2 immune responses. Considering its unique vaccine adjuvant property as well as the safe record as an anti-neoplastic agent clinically used in humans during a long period, docetaxel should be further studied for its use in influenza vaccine production.
The Chemistry of the Hydantoins. (1950)

ADVERTISEMENT RETURN TO ISSUEArticleNEXTThe Chemistry of the Hydantoins.Elinor. WareCite this: Chem. Rev. 1950, 46, 3, 403–470Publication Date (Print):June 1, 1950Publication History Published online1 May 2002Published inissue 1 June 1950https://pubs.acs.org/doi/10.1021/cr60145a001https://doi.org/10.1021/cr60145a001research-articleACS PublicationsRequest reuse permissionsArticle Views4215Altmetric-Citations385LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Identification of Small Molecule Activators of BMP Signaling (2013)

Bone Morphogenetic Proteins (BMPs) are morphogens that play a major role in regulating development and homeostasis. Although BMPs are used for the treatment of bone and kidney disorders, their clinical use is limited due to the supra-physiological doses required for therapeutic efficacy causing severe side effects. Because recombinant BMPs are expensive to produce, small molecule activators of BMP signaling would be a cost-effective alternative with the added benefit of being potentially more easily deliverable. Here, we report our efforts to identify small molecule activators of BMP signaling. We have developed a cell-based assay to monitor BMP signaling by stably transfecting a BMP-responsive human cervical carcinoma cell line (C33A) with a reporter construct in which the expression of luciferase is driven by a multimerized BMP-responsive element from the Id1 promoter. A BMP-responsive clone C33A-2D2 was used to screen a bioactive library containing ∼5,600 small molecules. We identified four small molecules of the family of flavonoids all of which induced luciferase activity in a dose-dependent manner and ventralized zebrafish embryos. Two of the identified compounds induced Smad1, 5 phosphorylation (P-Smad), Id1 and Id2 expression in a dose-dependent manner demonstrating that our assays identified small molecule activators of BMP signaling.
Neurotrophic Strategies for Treating Alzheimer's Disease: Lessons from Basic Neurobiology and Animal Modelsa (1993)

Because neurotrophic factors can prevent natural and experimental cases of neural cell death and induce and maintain differentiation, they are especially attractive agents for the treatment of neurodegenerative diseases, such as Alzheimer's disease (AD). The present report argues for the specific role of particular families of trophic factors, such as neurotrophins (e.g., nerve growth factor [NGF]) and neurokines (e.g., ciliary neurotrophic factor [CNTF]), for the promotion of the survival and phenotype of subsets of central nervous system (CNS) neurons vulnerable in AD, such as basal forebrain cholinergic neurons and cortical projection neurons. Although there is ample evidence for the therapeutic role of NGF in experimental or natural injury of cholinergic neurons, not enough progress has been made on trophic models involving cortical neurons. Further understanding of the mechanisms of cell death in AD and elucidation of the transduction cascades of trophic factors will undoubtedly refine our current concepts of a neurotrophic treatment for AD.
Eradication of Therapy-Resistant Human Prostate Tumors Using a Cancer Terminator Virus (2007)

Terminal prostate cancer is refractory to conventional anticancer treatments because of frequent overexpression of antiapoptotic proteins Bcl-2 and/or Bcl-x(L). Adenovirus-mediated delivery of melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24), a secreted cytokine having cancer-selective apoptosis-inducing properties, profoundly inhibits prostate cancer cell growth. However, forced overexpression of Bcl-2 or Bcl-x(L) renders prostate cancer cells resistant to Ad.mda-7. We constructed a conditionally replication-competent adenovirus in which expression of the adenoviral E1A gene, necessary for replication, is driven by the cancer-specific promoter of progression elevated gene-3 (PEG-3) and which simultaneously expresses mda-7/IL-24 in the E3 region of the adenovirus (Ad.PEG-E1A-mda-7), a cancer terminator virus (CTV). This CTV generates large quantities of MDA-7/IL-24 as a function of adenovirus replication uniquely in cancer cells. Infection of Ad.PEG-E1A-mda-7 (CTV) in normal prostate epithelial cells and parental and Bcl-2- or Bcl-x(L)-overexpressing prostate cancer cells confirmed cancer cell-selective adenoviral replication, mda-7/IL-24 expression, growth inhibition, and apoptosis induction. Injecting Ad.PEG-E1A-mda-7 (CTV) into xenografts derived from DU-145-Bcl-x(L) cells in athymic nude mice completely eradicated not only primary tumors but also distant tumors (established in the opposite flank), thereby implementing a cure. These provocative findings advocate potential therapeutic applications of this novel virus for advanced prostate cancer patients with metastatic disease.
Infection of peripheral blood mononuclear cells and cell lines by cell-free human T-cell lymphoma/leukemia virus type I (1992)

Previous studies of in vitro infection by human T-cell lymphoma/leukemia virus type I (HTLV-I) have required cocultivation of target cells with HTLV-I cell lines or vesicular stomatitis virus pseudotypes containing HTLV-I envelope proteins. We report here the development of a cell-free infection assay for HTLV-I. Target cells were incubated with purified, DNase-treated HTLV-I virions for 4 h at 37 degrees C. Target cell DNA was then analyzed for the presence of newly synthesized HTLV-I proviral DNA by the highly sensitive polymerase chain reaction. Using this assay system, we have been able to consistently detect in vitro infection of a variety of cellular targets by different HTLV-I isolates. Optimal infection required the presence of 10 micrograms of DEAE-dextran per ml. The assay was dose dependent with respect to virus input. In general, the amount of proviral DNA detected correlated with the level of HTLV-I receptors present on the surface of the target cells, as measured by fluorochrome-labelled HTLV-I binding. Finally, the specificity of the assay was confirmed by demonstrating that the cell line, L1q, a somatic cell hybrid containing human chromosome 17q, to which the gene for the HTLV-I receptor has been mapped, was susceptible to infection by HTLV-I, while the parental mouse cell line from which it was derived, LMTK-, which lacks human chromosome 17q, was not.
Formation of ursodeoxycholic acid from chenodeoxycholic acid by a 7 beta-hydroxysteroid dehydrogenase-elaborating Eubacterium aerofaciens strain cocultured with 7 alpha-hydroxysteroid dehydrogenase-elaborating organisms (1982)

A gram-positive, anaerobic, chain-forming, rod-shaped anaerobe (isolate G20-7) was isolated from normal human feces. This organism was identified by cellular morphology as well as fermentative and biochemical data as Eubacterium aerofaciens. When isolate G20-7 was grown in the presence of Bacteroides fragilis or Escherichia coli (or another 7 alpha-hydroxysteroid dehydrogenase producer) and chenodeoxycholic acid, ursodeoxycholic acid produced. Time course curves revealed that 3 alpha-hydroxy-7-keto-5 beta-cholanoic acid produced by B. fragilis or E. coli or introduced into the medium as a pure substance was reduced by G20-7 specifically to ursodeoxycholic acid. The addition of glycine- and taurine-conjugated primary bile acids (chenodeoxycholic and cholic acids) and other bile acids to binary cultures of B. fragilis and G20-7 revealed that (i) both conjugates were hydrolyzed to give free bile acids, (ii) ursocholic acid (3 alpha, 7 beta, 12 alpha-trihydroxy-5 beta-cholanoic acid) was produced when conjugated (or free) cholic acid was the substrate, and (iii) the epimerization reaction was at least partially reversible. Corroborating these observations, an NADP-dependent 7 beta-hydroxysteroid dehydrogenase (reacting specifically with 7 beta-OH-groups) was demonstrated in cell-free preparations of isolate G20-7; production of the enzyme was optimal at between 12 and 18 h of growth. This enzyme, when measured in the oxidative direction, was active with ursodeoxycholic acid, ursocholic acid, and the taurine conjugate of ursodeoxycholic acid (but not with chenodeoxycholic, deoxycholic, or cholic acids) and displayed an optimal pH range of 9.8 to 10.2
NF-κB signaling in inflammation (2017)

The transcription factor NF-κB regulates multiple aspects of innate and adaptive immune functions and serves as a pivotal mediator of inflammatory responses. NF-κB induces the expression of various pro-inflammatory genes, including those encoding cytokines and chemokines, and also participates in inflammasome regulation. In addition, NF-κB plays a critical role in regulating the survival, activation and differentiation of innate immune cells and inflammatory T cells. Consequently, deregulated NF-κB activation contributes to the pathogenic processes of various inflammatory diseases. In this review, we will discuss the activation and function of NF-κB in association with inflammatory diseases and highlight the development of therapeutic strategies based on NF-κB inhibition.
Affinity blotting: polyvinyldifluoride (PVDF) is superior to nitrocellulose (1990)

Journal Article Affinity blotting: polyvinyldifluoride (PVDF) is superior to nitrocellulose Get access S Callaghan, S Callaghan Pathol. Dept., Peter MacCallum Cancer Inst., Melbourne, Australia Search for other works by this author on: Oxford Academic Google Scholar R McLachlan R McLachlan Pathol. Dept., Peter MacCallum Cancer Inst., Melbourne, Australia Search for other works by this author on: Oxford Academic Google Scholar Clinical Chemistry, Volume 36, Issue 7, 1 July 1990, Page 1377, https://doi.org/10.1093/clinchem/36.7.1377a Published: 01 July 1990
Cell-free synthesis of human interferon. (1975)

With mRNA prepared from induced human fibroblasts biologically active human interferon was synthesized de novo in a cell-free extract from mouse cells. The identity of the antiviral activity as human interferon was demonstrated by its species and antigenic specificity.
Evaluation of potential carcinogenic properties of Tołpa Peat Preparation in vitro. (1994)

For the evaluation of the potential carcinogenic properties of TPP the Syrian hamster embryo cell transformation test was employed. TPP did not induce morphological cell transformation in these cells.
Liarozole Acts Synergistically with 1 ,25-Dihydroxyvitamin D3 to Inhibit Growth of DU 145 Human Prostate Cancer Cells by Blocking 24-Hydroxylase Activity (1999)

1, 2 D 3 ] inhibits the proliferation of many cancer cells in culture, but not the aggressive human prostate cancer cell line DU 145.We postulated that the 1,25-(OH) 2 D 3 -resistant phenotype in DU 145 cells might result from the high levels of expression of 25-hydroxyvitamin D-24-hydroxylase (24hydroxylase) induced by treatment with 1,25-(OH) 2 D 3 .As this P450 enzyme initiates 1,25-(OH) 2 D 3 catabolism, we presumed that a high level of enzyme induction could limit the effectiveness of the 1,25-(OH) 2 D 3 antiproliferative action.To examine this hypothesis we explored combination therapy with liarozole fumarate (R85,246), an imidazole derivative currently in trials for prostate cancer therapy.As imidizole derivatives are known to inhibit P450 enzymes, we postulated that this drug would inhibit 24-hydroxylase activity, increasing the 1,25-(OH) 2 D 3 half-life, thereby enhancing 1,25-(OH) 2 D 3 antiproliferative effects on DU 145 cells.Cell growth was assessed by measurement of viable cells using the MTS assay.When used alone, neither 1,25-(OH) 2 D 3 (1-10 nM) nor liarozole (1-10 M) inhibited DU 145 cell growth.However, when added together, 1,25-(OH) 2 D 3 (10 nM)/liarozole (1 M) inhibited growth 65% after 4 days of culture.We used a TLC method to assess 24-hydroxylase activity and demonstrated that liarozole (1-100 M) inhibited this P450 enzyme in a dose-dependent manner.Moreover, liarozole treatment caused a significant increase in 1,25-(OH) 2 D 3 half-life from 11 to 31 h.In addition, 1,25-(OH) 2 D 3 can cause homologous up-regulation of the vitamin D receptor (VDR), and in the presence of liarozole, this effect was amplified, thus enhancing 1,25-(OH) 2 D 3 activity.Western blot analyses demonstrated that DU 145 cells treated with 1,25-(OH) 2 D 3 /liarozole showed greater VDR up-regulation than cells treated with either drug alone.In summary, our data demonstrate that liarozole augments the ability of 1,25-(OH) 2 D 3 to inhibit DU 145 cell growth.The mechanism appears to be due to inhibition of 24-hydroxylase activity, leading to increased 1,25-(OH) 2 D 3 half-life and augmentation of homologous up-regulation of VDR.We raise the possibility that combination therapy using 1,25-(OH) 2 D 3 and liarozole or other inhibitors of 24-hydroxylase, both in nontoxic doses, might serve as an effective treatment for prostate cancer.
Critical radius for exchange bias in naturally oxidized Fe nanoparticles (2006)

Details of synthesis and structural characterization of highly crystalline iron oxide nanoparticles are presented together with results on the magnetic investigation as a function of the temperature and applied field. Monodisperse Fe nanoparticles were prepared by thermal decomposition of iron pentacarbonyl in the presence of oleic acid. These iron nanoparticles were readily oxidized on exposure to air. The resulting nanocrystals have been identified as inverse spinels, being $\ensuremath{\gamma}\text{\ensuremath{-}}{\mathrm{Fe}}_{2}{\mathrm{O}}_{3}$ the dominant phase of the small $5\text{\ensuremath{-}}\mathrm{nm}$ iron oxide nanocrystals, whereas the proportion of the ${\mathrm{Fe}}_{3}{\mathrm{O}}_{4}$ component gradually increases on increasing the particle size. The small particles volume resulted in finite-size effects, for instance, the magnetization deviates from the ${T}^{3∕2}$ Bloch's law. At the same time, high field irreversibility and shifted hysteresis loops after field-cooled processes have been detected, and attributed to a low-temperature surface spin-glass layer. Moreover, there is a critical diameter below which the surface spin-glass behavior and exchange bias effect abruptly disappear.
The challenge of developing a herpes simplex virus 2 vaccine (2012)

HSV infections are prevalent worldwide. A vaccine to prevent genital herpes would have a significant impact on this disease. Several vaccines have shown promise in animal models; however, so far these have not been successful in human clinical studies. Prophylactic HSV vaccines to prevent HSV infection or disease have focused primarily on eliciting antibody responses. Potent antibody responses are needed to result in sufficiently high levels of virus-specific antibody in the genital tract. Therapeutic vaccines that reduce recurrences need to induce potent T-cell responses at the site of infection. With the increasing incidence of HSV-1 genital herpes, an effective herpes vaccine should protect against both HSV-1 and HSV-2. Novel HSV vaccines, such as replication-defective or attenuated viruses, have elicited humoral and cellular immune responses in preclinical studies. These vaccines and others hold promise in future clinical studies.
A novel in situ hybridization signal amplification method based on the deposition of biotinylated tyramine. (1995)

For amplification of in situ hybridization (ISH) signals, we describe a method using catalyzed reporter deposition (CARD). This amplification method is based on the deposition of biotinylated tyramine (BT) at the location of the DNA probe. The BT precipitate can then visualized with fluorochrome- or enzyme-labeled avidin. Both for bright-field ISH (BRISH) and for fluorescence ISH (FISH), the detection limit was highly increased. This method is especially suitable for visualization of very weak ISH signals, such as those obtained by ISH using locus-specific DNA probes. Furthermore, CARD amplification of ISH signals (CARD-ISH) is highly sensitive, rapid, flexible, and easy to implement. Successful application of CARD-ISH with locus-specific DNA probes on histological and cytological samples may improve the determination of structural chromosomal aberrations in archival material.
Tunable Heparan Sulfate Mimetics for Modulating Chemokine Activity (2013)

Heparan sulfate (HS) glycosaminoglycans participate in critical biological processes by modulating the activity of a diverse set of protein binding partners. Such proteins include all known members of the chemokine superfamily, which are thought to guide the migration of immune cells through their interactions with HS. Here, we describe an expedient, divergent synthesis to prepare defined HS glycomimetics that recapitulate the overall structure and activity of HS glycosaminoglycans. Our approach uses a core disaccharide precursor to produce a variety of differentially sulfated glycopolymers. We demonstrate that a specific trisulfated mimetic antagonizes the chemotactic activity of the proinflammatory chemokine RANTES with potency similar to that of heparin, without inhibiting serine proteases in the blood coagulation cascade. Our work provides a general strategy for modulating chemokine activity and dissecting the pleiotropic functions of HS/heparin through the presentation of defined sulfation motifs within polymeric scaffolds.
[Therapy experience and pathogeny analysis of intercurrent infection after augmentation mammaplasty]. (2004)

The infection after augmentation mammaplasty will get an effective controlling result if take a timely operative therapy according to the position and character of the intercurrent infection. But some galactophore will shrink after the cure of infection.
Wavelength Tuning of GaAs/AlGaAs Quantum-Well Infrared Photo-detectors by Proton Implantation Induced Intermixing (2000)

Proton implantation induced intermixing was used to tune the quantum well infrared photo-detector (QWIP) response wavelength, which may provide a method of fabricating two-color QWIP devices. Obvious red shift of response wavelength as large as 0.6 µm was observed relative to the reference sample that was annealed without implantation, from 7.7 µm to 8.3 µm. Two response wavelengths for the highest-dose implanted sample were observed in the photo-current spectra. In the highest dose case (5×10 15 H/cm 2 ), the dark current increased by an order of magnitude and peak responsivity decreased by a factor of 3 for the implanted and annealed sample. This has been attributed to the raising of the ground state energy level in the intermixed quantum well and residual damage in the implanted and annealed QWIPs.
Selectivity of small molecule ligands for parallel and anti-parallel DNA G-quadruplex structures (2009)

We report CD, ESI-MS and molecular modelling studies of ligand binding interactions with DNA quadruplex structures derived from the human telomeric repeat sequence (h-Tel) and the proto-oncogenic c-kit promoter sequence. These sequences form anti-parallel (both 2 + 2 and 3 + 1) and parallel conformations, respectively, and demonstrate distinctively different degrees of structural plasticity in binding ligands. With h-Tel, we show that an extended heteroaromatic 1,4-triazole (TRZ), designed to exploit pi-stacking interactions and groove-specific contacts, shows some selectivity for parallel folds, however, the polycyclic fluorinated acridinium cation (RHPS4), which is a similarly potent telomerase inhibitor, shows selectivity for anti-parallel conformations implicating favourable interactions with lateral and diagonal loops. In contrast, the unique c-kit parallel-stranded quadruplex shows none of the structural plasticity of h-Tel with either ligand. We show by quantitative ESI-MS analysis that both sequences are able to bind a ligand on either end of the quadruplex. In the case of h-Tel the two sites have similar affinities, however, in the case of the c-kit quadruplex the affinities of the two sites are different and ligand-dependent. We demonstrate that two different small molecule architectures result in significant differences in selectivity for parallel and anti-parallel quadruplex structures that may guide quadruplex targeted drug-design.
Motion compensated frequency modulated continuous wave 3D coherent imaging ladar with scannerless architecture (2012)

A principal difficulty of long dwell coherent imaging ladar is its extreme sensitivity to target or platform motion. This paper describes a motion compensated frequency modulated continuous wave 3D coherent imaging ladar method that overcomes this motion sensitivity, making it possible to work with nonstatic targets such as human faces, as well as imaging of targets through refractive turbulence. Key features of this method include scannerless imaging and high range resolution. The reduced motion sensitivity is shown with mathematical analysis and demonstration 3D images. Images of static and dynamic targets are provided demonstrating up to 600×800 pixel imaging with millimeter range resolution.