gebhart/patrepeval huggingface dataset:
Nanosize and Vitality:  TiO2 Nanotube Diameter Directs Cell Fate (2007)

We generated, on titanium surfaces, self-assembled layers of vertically oriented TiO2 nanotubes with defined diameters between 15 and 100 nm and show that adhesion, spreading, growth, and differentiation of mesenchymal stem cells are critically dependent on the tube diameter. A spacing less than 30 nm with a maximum at 15 nm provided an effective length scale for accelerated integrin clustering/focal contact formation and strongly enhances cellular activities compared to smooth TiO2 surfaces. Cell adhesion and spreading were severely impaired on nanotube layers with a tube diameter larger than 50 nm, resulting in dramatically reduced cellular activity and a high extent of programmed cell death. Thus, on a TiO2 nanotube surface, a lateral spacing geometry with openings of 30-50 nm represents a critical borderline for cell fate.
Leukocyte subpopulations elicited by a nontumorigenic variant of B16 melanoma: their role in direct rejection of the melanoma and in prevention of tumorigenesis in Winn assays. (1982)

The mechanisms by which various leukocyte subpopulations elicited by an immunogenic, nontumorigenic subclone (C3471) of B16 melanoma caused rejection of the tumorigenic parental melanoma (B559), were investigated. Leukocytes from C3471-immune mice were co-injected with B559 tumor cells in Winn assays into normal syngeneic recipients. Tumor formation by B559 cells was prevented when C3471-immune (a) unfractionated peritoneal leukocytes, or (b) glass-adherent peritoneal cells (90% macrophages), or (c) nylon wool purified nonadherent cells (95% Thy-1.2+) were used in the Winn assays. If the C3471-immunized mice were treated with antithymocyte serum before harvest of their peritoneal cells, none of these leukocyte populations were effective in the Winn assay. However, macrophages from these immunologically compromised donors regained their tumoricidal activity after incubation in vitro with T lymphocytes from untreated C3471-immune donors; similarly, C3471-immune lymphocytes rendered normal resident peritoneal macrophages tumoricidal in Winn assays. When C3471-immunized mice were irradiated or treated with antithymocyte serum before direct challenge with B559 cells, melanomas developed, thus providing additional evidence for the need for intact T cell function to establish immunity against the melanoma. Furthermore, when Winn assay recipients were treated with antithymocyte serum, neither C3471-immune macrophages nor T cells were able to prevent tumor formation. These findings indicate that antithymocyte serum-sensitive (Thy-1.2+) lymphocytes are necessary both for the generation of tumoricidal leukocytes in C3471-immunized mice, and for the rejection of B559 melanoma by demonstrably tumoricidal macrophages in Winn assay recipients. In addition, long-lasting immunity developed in 50% of the normal mice that had received both C3471-immune peritoneal cells and B559 tumor cells, as manifested by their capacity to reject a second challenge with B559 cells 40-60 d later.
Sustained Dystrophin Expression Induced by Peptide-conjugated Morpholino Oligomers in the Muscles of mdx Mice (2020)

Cell-penetrating peptides (CPPs), containing arginine (R), 6-aminohexanoic acid (X), and/or β-alanine (B) conjugated to phosphorodiamidate morpholino oligomers (PMOs), enhance their delivery in cell culture. In this study, the potency, functional biodistribution, and toxicity of these conjugates were evaluated in vivo, in EGFP-654 transgenic mice that ubiquitously express the aberrantly spliced EGFP-654 pre-mRNA reporter. Correct splicing and enhanced green fluorescence protein (EGFP) upregulation serve as a positive readout for peptide-PMO (PPMO) entry into cells and access to EGFP-654 pre-mRNA in the nucleus. Intraperitoneal injections of a series of PPMOs, A-N (12 mg/kg), administered once a day for four successive days resulted in splicing correction in numerous tissues. PPMO-B was highly potent in the heart, diaphragm, and quadriceps, which are key muscles in the treatment of Duchenne muscular dystrophy. We therefore investigated PPMO M23D-B, designed to force skipping of stop-codon containing dystrophin exon 23, in an mdx mouse model of the disease. Systemic delivery of M23D-B yielded persistent exon 23 skipping, yielding high and sustained dystrophin protein expression in body-wide muscles, including cardiac muscle, without detectable toxicity. The rescued dystrophin reduced serum creatinine kinase to near-wild-type levels, indicating improvement in muscle integrity. This is the first report of oligonucleotide-mediated exon skipping and dystrophin protein induction in the heart of treated animals.
517. Improving CAR T Cell Efficacy for Solid Tumors By Nanogel-Based Delivery of Immunomodulatory Proteins (2015)

Adoptive T cell therapies utilizing T lymphocytes transduced to stably express an anti-CD19 chimeric antigen receptor (CAR) have shown remarkable success against refractory B cell malignancies in multiple clinical trials. Studies are underway to adapt this technology towards the treatment of solid tumors, however, the immunosuppressive tumor microenvironment of many solid tumors may represent a significant barrier to CAR T cell efficacy. In this study, we investigate a means to enhance CAR T cell function by loading them with nanogel “backpacks” containing the T and NK cell stimulatory molecule IL-15N72D:IL-15RaSu/Fc superagonist complex (IL-15sa, also referred to as ALT-803 and currently in clinical trials). The IL15sa nanogel is a crosslinked, protein-polyethylene glycol (PEG) complex that breaks down slowly under physiological conditions allowing for pseudoautocrine stimulation of the CAR T cells with the IL15sa cargo. The effects of IL15sa nanogel loading on CAR T cell function were tested in a glioblastoma multiforme tumor model. Human T lymphocytes were lentivirally-transduced with a CAR targeting the epidermal growth factor variant III (EGFRvIII) antigen, as is currently being tested in early human clinical trials. EGFRvIII is expressed in up to 30% of glioblastoma multiforme cells but not on normal cells. EGFRvIII CAR T cells were loaded with a fluorophore-labeled IL15sa nanogel and examined in vitro for nanogel breakdown and effects on CAR T cell functions. The nanogel was detected on labeled cells for up to five days. Nanogels loaded with either control or IL-15sa did not alter antigen-specific cytolytic activity of EGFRvIII CAR T cells towards glioblastoma target cells. EGFRvIII CAR T cells loaded with control nanogel proliferated with the same kinetics as non-loaded CAR T cells upon co-culture with EGFRvIII+ glioblastoma targets. In contrast, IL15sa nanogel loaded CAR T cells had increased proliferation upon co-culture with antigenbearing targets. Additionally, IL15sa nanogel loaded EGFRvIII CAR T cells proliferated more with repeated stimulation of EGFRvIII-expressing glioblastoma cells. Studies are currently underway to test the efficacy of IL15sa nanogel-loaded EGFRvIII CAR T cells in vivo using a xenogeneic murine model of glioblastoma. These results indicate that nanogel loading of T cells can be a viable way of delivering immunostimulatory agents with CAR T cells. Nanogel loading of immune-modulating or tumoricidal drugs coupled to CAR T cells represents a novel platform for enhancing T cell function, and potentially for delivering systemically toxic drugs, into a specific and hostile tumor microenvironment.
YC-1, a novel activator of platelet guanylate cyclase (1994)

YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole] inhibited the aggregation of and ATP release from washed rabbit platelets induced by arachidonic acid (AA), collagen, U46619, platelet-activating factor (PAF), and thrombin in a concentration-dependent manner. YC-1 also disaggregated the clumped platelets caused by these inducers. The thromboxane B2 formation caused by collagen, PAF, and thrombin was inhibited by concentrations of YC-1 that did not affect formation of thromboxane B2 and prostaglandin D2 caused by AA. YC-1 suppressed the increase of intracellular Ca2+ concentration and generation of inositol 1,4,5-trisphosphate caused by these five aggregation inducers. Both the cAMP and cGMP contents of platelets were increased by YC-1 in a concentration- and time-dependent manner. Like sodium nitroprusside, YC-1 potentiated formation of cAMP caused by prostaglandin E1 but not that by 3-isobutyl-1-methylxanthine. Adenylate cyclase and cAMP phosphodiesterase activities were not altered by YC-1. Activity of cGMP phosphodiesterase was unaffected by YC-1. Activities of guanylate cyclase in platelet homogenate and cytosolic fraction were activated by YC-1, whereas particulate guanylate cyclase activity was unaffected. The antiplatelet effect of sodium nitroprusside but not that of YC-1 was blocked by hemoglobin and potentiated by superoxide dismutase. After intraperitoneal administration for 30 minutes, YC-1 prolonged the tail bleeding time of conscious mice. These data indicate that YC-1 is a direct soluble guanylate cyclase activator in rabbit platelets. It may also possess antithrombotic potential in vivo.
Phylogeny of the Ammonia-Producing Ruminal Bacteria Peptostreptococcus anaerobius, Clostridium sticklandii, and Clostridium aminophilum sp. nov. (1993)

In previous studies, gram-positive bacteria which grew rapidly with peptides or an amino acid as the sole energy source were isolated from bovine rumina. Three isolates, strains C, FT (T = type strain), and SR, were considered to be ecologically important since they produced up to 20-fold more ammonia than other ammonia-producing ruminal bacteria. On the basis of phenotypic criteria, the taxonomic position of these new isolates was uncertain. In this study, the 16S rRNA sequences of these isolates and related bacteria were determined to establish the phylogenetic positions of the organisms. The sequences of strains C, FT, and SR and reference strains of Peptostreptococcus anaerobius, Clostridium sticklandii, Clostridium coccoides, Clostridium aminovalericum, Acetomaculum ruminis, Clostridium leptum, Clostridium lituseburense, Clostridium acidiurici, and Clostridium barkeri were determined by using a modified Sanger dideoxy chain termination method. Strain C, a large coccus purported to belong to the genus Peptostreptococcus, was closely related to P. anaerobius, with a level of sequence similarity of 99.6%. Strain SR, a heat-resistant, short, rod-shaped organism, was closely related to C. sticklandii, with a level of sequence similarity of 99.9%. However, strain FT, a heat-resistant, pleomorphic, rod-shaped organism, was only distantly related to some clostridial species and P. anaerobius. On the basis of the sequence data, it was clear that strain FT warranted designation as a separate species. The closest known relative of strain FT was C. coccoides (level of similarity, only 90.6%). Additional strains that are phenotypically similar to strain FT were isolated in this study.(ABSTRACT TRUNCATED AT 250 WORDS)
Nitric Oxide Synthesis in Murine Peritoneal Macrophages by Fungal .BETA.-Glucans. (1997)

Fungal beta-glucans have abilities to induce NO (nitric oxide) synthesis by macrophages in vivo, and the intensity of NO synthesis significantly varied dependent on the structure of beta-glucans. The molecular mechanism of NO synthesis by beta-glucans, however, has not been clarified in detail. To determine beta-glucan-mediated NO production, we used various beta-glucans (SPG-OH, GRN; Grifolan, SSG, OL-2, ZYM; zymosan A and ZYC; zymocel), which could enhance NO synthesis in vivo, and stimulated peritoneal macrophages (MPs) in vitro in the presence of interferon-gamma (IFN-gamma). Using recombinant cytokines, a minimum concentration of the cytokines for NO induction was about 20 mg/ml in the presence of IFN-gamma under the experimental conditions. Of beta-glucans tested, only SPG-OH and GRN produced high concentrations of IL-6 in the culture supernatants. SSG also induced NO synthesis in vitro, but concentrations of inflammatory cytokines were low even in the presence of IFN-gamma. In addition, there are some beta-glucans which could induce NO synthesis in vivo but not in vitro (OL-2, ZYM, ZYC). These findings suggested that NO productivity of beta-glucans in vivo is regulated by several mechanisms.
Symbolic planning and control of robot motion [Grand Challenges of Robotics] (2007)

In this paper, different research trends that use symbolic techniques for robot motion planning and control are illustrated. As it often happens in new research areas, contributions to this topic started at about the same time by different groups with different emphasis, approaches, and notation. This article tries to describe a framework in which many of the current methods and ideas can be placed and to provide a coherent picture of what the authors want to do, what have they got so far, and what the main missing pieces are. Generally speaking, the aim of symbolic control as is envisioned in this article is to enable the usage of methods of formal logic, languages, and automata theory for solving effectively complex planning problems for robots and teams of robots. The results presented in this article can be divided in two groups: top-down approaches, whereby formal logic tools are employed on rather abstract models of robots; and bottom up approaches, whose aim is to provide means by which such abstractions are possible and effective. The two ends do not quite tie as yet, and much work remains to be done in both directions to obtain generally applicable methods. However, the prospects of symbolic control of robots are definitely promising, and the challenging nature of problems to be solved warrants for the interest of a wide community of researchers
An Open Rectifier Potassium Channel with Two Pore Domains in Tandem Cloned from Rat Cerebellum (1998)

Tandem pore domain K+ channels represent a new family of ion channels involved in the control of background membrane conductances. We report the structural and functional properties of a TWIK-related acid-sensitive K+ channel (rTASK), a new member of this family cloned from rat cerebellum. The salient features of the primary amino acid sequence include four putative transmembrane domains and, unlike other cloned tandem pore domain channels, a PDZ (postsynaptic density protein, disk-large, zo-1) binding sequence at the C terminal. rTASK has distant overall homology to a putative Caenorhabditis elegans K+ channel and to the mammalian clones TREK-1 and TWIK-1. rTASK expression is most abundant in rat heart, lung, and brain. When exogenously expressed in Xenopus oocytes, rTASK currents activate instantaneously, are noninactivating, and are not gated by voltage. Because rTASK currents satisfy the Goldman-Hodgkin-Katz current equation for an open channel, rTASK can be classified an open rectifier. Activation of protein kinase A produces inhibition of rTASK, whereas activation of protein kinase C has no effect. rTASK currents were inhibited by extracellular acidity. rTASK currents also were inhibited by Zn2+ (IC50 = 175 microM), the local anesthetic bupivacaine (IC50 = 68 microM), and the anti-convulsant phenytoin ( approximately 50% inhibition at 200 microM). By demonstrating open rectification and open probability independent of voltage, we have established that rTASK is a baseline potassium channel.
Chemical Stabilisation of Collagen as a Biomimetic (2003)

Collagen is the most abundant protein in animals and because of its high mechanical strength and good resistance to degradation has been utilized in a wide range of products in industry whilst its low antigenicity has resulted in its widespread use in medicine. Collagen products can be purified from fibres, molecules reconstituted as fibres or from specific recombinant polypeptides with preferred properties. A common feature of all these biomaterials is the need for stable chemical cross-linking to control the mechanical properties and the residence time in the body, and to some extent the immunogenicity of the device. This can be achieved by a number of different cross-linking agents that react with specific amino acid residues on the collagen molecule imparting individual biochemical, thermal and mechanical characteristics to the biomaterial. In this review we have summarised the major techniques for testing these characteristics and the mechanisms involved in the variety of cross-linking reactions to achieve particular properties.
Acetyl hypofluorite as a taming carrier of elemental fluorine for novel electrophilic fluorination of activated aromatic rings (1981)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAcetyl hypofluorite as a taming carrier of elemental fluorine for novel electrophilic fluorination of activated aromatic ringsOri Lerman, Yitzhak Tor, and Shlomo RozenCite this: J. Org. Chem. 1981, 46, 22, 4629–4631Publication Date (Print):October 1, 1981Publication History Published online1 May 2002Published inissue 1 October 1981https://pubs.acs.org/doi/10.1021/jo00335a083https://doi.org/10.1021/jo00335a083research-articleACS PublicationsRequest reuse permissionsArticle Views523Altmetric-Citations39LEARN 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
Inducible expression of Bcl‐XL restricts apoptosis resistance to the antibody secretion phase in hybridoma cultures (2002)

B-cell hybridomas are widely used to produce monoclonal antibodies via large-scale cell culture. Unfortunately, these cells are highly sensitive to apoptotic death under conditions of nutrient deprivation observed at the plateau phase of batch cultures. Previous work has indicated that constitutive high-level expression of antiapoptotic genes in hybridoma cells could delay apoptosis, resulting in higher cell densities and prolonged viability. However, the constitutive high-level expression of antiapoptotic genes has been shown to have detrimental effects on genomic stability of other types of cultured cells. Inducible gene expression may be used to avoid this problem. In the present study, we first constructed an expression vector in which the promoter of a mammalian metallothionein (MT) gene drives the expression of bcl-XL in response to metal exposure. The vector was then used to exogenously control the expression of bcl-XL in D5 hybridoma cells. Our data show that stably transfected D5 cells (4G1.D9) expressed high levels of Bcl-X(L) following overnight exposure to ZnSO(4) concentrations (50 to 100 microM) that did not affect control cells. The level of Bcl-X(L) expressed after ZnSO(4) induction was sufficient to prevent apoptosis experimentally induced by cycloheximide and allowed 4G1.D9 cells to grow at higher densities and remain viable for prolonged periods in suboptimal culture conditions. The use of inducible bcl-XL expression permits extension of the viability of cultured B-cell hybridomas during the antibody secretion phase without the adverse genetic effects associated with constitutive long-term bcl-XL expression.
Heat Shock Protein as Molecular Targets for Breast Cancer Therapeutics (2011)

Recent advances in the understanding of the molecular mechanisms involved in the breast cancer development and progression have led to the identification of numerous novel molecular targets. Among these, heat shock proteins (HSPs) are being emerging molecular target due to its diverse function in cancer cells. HSPs are highly conserved molecular chaperone that are synthesized by cell in response to various stress conditions. Mammalian HSPs have been classified into several families according to their molecular weight: HSP100, HSP90, HSP72, and small molecular HSPs (including HSP27). They are essential proteins that play a key role in cell survival through the cytoprotective mechanisms. In addition, HSPs are often overexpressed in a rage of cancers including breast cancer, and its overexpression seems to be associated with poor clinical outcomes. Also, HSP90 play a role in facilitating transformation by stabilizing the mutated and overexpressed oncoproteins found in breast cancer cell. Pharmacological targeting of HSP is therefore indicated and in the case of HSP90, numerous inhibitory drugs are undergoing clinical trial for treatment of breast cancer and other cancers. In this review, we describe the roles of HSPs in cancer cell and introduce the HSPs inhibitor as molecular target in cancer therapy and its recent clinical trials in breast cancer.
The Shape Transition of Gold Nanorods (1998)

We report a revised synthetic procedure based on an electrochemical method for preparing an aqueous solution containing suspended Au nanorods. The mean aspect ratios of the Au nanorods can be experimentally adjusted between 1 and 7. The evolution of the longitudinal surface plasmon bands shows an eminently sensitive dependence on the aspect ratios of the nanorods. Their dependence is accordingly described by classical-electrostatic-model predictions. The shape transition of the nanorod particles has been studied by varying some key influencing factors such as the wavelength, the laser fluence, and matrix effects. The nanorods were exposed to laser lines at 532 and 1064 nm, frequencies which correspond closely to the short- and long-axis plasmon resonances, respectively. A photon-induced shape transition process was evidenced, and the corresponding rod-to-sphere conversion contributed by a photoannealing process was observed in both cases. Meanwhile, we observed a new type of “φ-shaped” Au nanostructure in the case of 1064-nm irradiation, which possibly represents the early stage of the shape transition and indicates that the starting location of the atomic-scale restructuring is at the centroid of the Au nanorod. The results of laser fluence-dependence measurements state that an efficient shape transition occurs via a multiphoton process. We also demonstrate the fabrication of the Au nanorod@silica nanostructures for preliminary studies of the matrix effects. As a result of the higher rigidity of the thin-silica-coating layer, the associated shape transition requires higher energy and proceeds less efficiently as compared with the cases for the micelle-stabilized Au nanorods.