gebhart/patrepeval huggingface dataset:
Effect of in vitro Mutations in a Vaccinia Virus Early Promoter Region Monitored by Herpes Simplex Virus Thymidine Kinase Expression in Recombinant Vaccinia Virus (1987)

The location of a promoter (PF) in the HindIII F region of the vaccinia virus genome was mapped by introducing deletions into this region of the DNA. Modified promoters were fused to the herpes simplex virus (HSV) thymidine kinase (TK) gene in plasmids facilitating the construction of recombinant vaccinia viruses, and promoter function was monitored by the ability of such plasmids to rescue TK+ vaccinia viruses from cells infected with TK- virus. Deletions from the 3' end of the promoter region produced mutants for which function was either not inhibited or abolished, allowing the 3' promoter boundary to be defined to within 13 nucleotides. As indicated by the presence of the PF transcript in early RNA and the kinetics of HSV TK expression in recombinant vaccinia viruses, transcription from PF occurred primarily at early times during infection. The major transcript was initiated at a site within 20 nucleotides of the 3' end of the promoter and nine bases upstream of the probable translation initiation codon. In one mutant for which a small but reproducible increase in promoter function was detected, the transcription start site was deleted. Nevertheless, transcription still appeared to begin at the equivalent position with respect to the promoter, despite the altered nucleotide sequence. The location of the start site for the PF transcript indicated that the HSV TK gene, inserted at the BamHI site following the promoter, was preceded by an initiation codon which could potentially attenuate expression of the inserted gene. Conversion of this ATG codon to TAG did not significantly improve HSV TK expression.
Role of heme oxygenase‐1 protein in the neuroprotective effects of cyclopentenone prostaglandin derivatives under oxidative stress (2003)

Previously we found that some cyclopenteone prostaglandin derivatives (PGs), referred to as neurite outgrowth-promoting PGs (NEPPs), have dual biological activities of promoting neurite outgrowth and preventing neuronal death [Satoh et al. (2000) J. Neurochem., 75, 1092-1102; Satoh et al. (2001) J. Neurochem., 77, 50-62; Satoh et al. (2002) In Kikuchi, II. (ed.), Strategenic Medical Science Against Brain Attack. Springer-Verlag, Tokyo, pp. 78-93]. To investigate possible cellular mechanisms of the neuroprotective effects, we performed oligo hybridization-based DNA array analysis with mRNA isolated from HT22, a cell line that originated from a mouse hippocampal neuron. Several transcripts up-regulated by NEPP11 were identified. Because heme oxygenase 1 (HO-1) mRNA was the most prominently induced and was earlier reported to protect neuronal and non-neuronal cells against oxidative stress, we focused on it as a possible candidate responsible for the neuroprotective effects. We found NEPP11 to induce HO-1 protein (32 kDa) in HT22 cells in both the presence and the absence of glutamate, whereas non-neuroprotective prostaglandins (PGs) Delta12-PGJ2 or PGA2 did not. Overexpression of HO-1-green fluorescence protein (GFP) fusion protein significantly protected HT22 cells against oxidative glutamate toxicity, whereas that of GFP alone did not. Furthermore, biliverdin and bilirubin, products of HO-1 enzymatic activity on heme, protected HT22 cells from oxidative glutamate toxicity. These results, together with our previous results, suggest that NEPP11 activates the expression of HO-1 and that HO-1 produces biliverdin and bilirubin, which result in the inhibition of neuronal death induced by oxidative stress. NEPP11 is the first molecular probe reported to have a neuroprotective action through induction of HO-1 in neuronal cells.
De Novo Design of Antimicrobial Polymers, Foldamers, and Small Molecules: From Discovery to Practical Applications (2009)

Antimicrobial peptides (AMPs) provide protection against a variety of pathogenic bacteria and are, therefore, an important part of the innate immune system. Over the past decade, there has been considerable interest in developing AMPs as intravenously administered antibiotics. However, despite extensive efforts in the pharmaceutical and biotechnology industry, it has proven difficult to achieve this goal. While researchers have solved some relatively simple problems such as susceptibility to proteolysis, more severe problems have included the expense of the materials, toxicity, poor efficacy, and limited tissue distribution. In this Account, we describe our efforts to design and synthesize "foldamers"-- short sequence-specific oligomers based on arylamide and beta-amino acid backbones, which fold into well-defined secondary structures-- that could act as antimicrobial agents. We reasoned that small "foldamers" would be less expensive to produce than peptides, and might have better tissue distribution. It should be easier to fine-tune the structures and activities of these molecules to minimize toxicity. Because the activities of many AMPs depends primarily on their overall physicochemical properties rather than the fine details of their precise amino acid sequences, we have designed and synthesized very small "coarse-grained" molecules, which are far simpler than naturally produced AMPs. The molecular design of these foldamers epitomizes the positively charged amphiphilic structures believed to be responsible for the activity of AMPs. The designed oligomers show greater activity than the parent peptides. They have also provided leads for novel small molecule therapeutics that show excellent potency in animal models for multidrug resistant bacterial infections. In addition, such molecules can serve as relatively simple experimental systems for investigations aimed at understanding the mechanism of action for this class of antimicrobial agents. The foldamers' specificity for bacterial membranes relative to mammalian membranes appears to arise from differences in membrane composition and physical properties between these cell types. Furthermore, because experimental coarse-graining provided such outstanding results, we developed computational coarse-grained models to enable molecular dynamic simulations of these molecules with phospholipid membranes. These simulations allow investigation of larger systems for longer times than conventional molecular dynamics simulations, allowing us to investigate how physiologically relevant surface concentrations of AMP mimics affect the bilayer structure and properties. Finally, we apply the principles discovered through this work to the design of inexpensive antimicrobial polymers and materials.
Sugar Crystallization, Equilibrium Moisture Content and Crystallization of Amorphous Sucrose and Glucose (1956)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSugar Crystallization, Equilibrium Moisture Content and Crystallization of Amorphous Sucrose and GlucoseBenjamin Makower and W. B. DyeCite this: J. Agric. Food Chem. 1956, 4, 1, 72–77Publication Date (Print):January 1, 1956Publication History Published online1 May 2002Published inissue 1 January 1956https://pubs.acs.org/doi/10.1021/jf60059a010https://doi.org/10.1021/jf60059a010research-articleACS PublicationsRequest reuse permissionsArticle Views2815Altmetric-Citations188LEARN 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
Widespread Distribution of the 14‐3‐3 Protein in Vertebrate Brains and Bovine Tissues: Correlation with the Distributions of Calcium‐Dependent Protein Kinases (1991)

A highly specific antiserum was prepared against bovine brain 14-3-3 protein, a protein kinase-dependent activator of tyrosine and tryptophan hydroxylases. The immunoassay using this antiserum proved the presence of 14-3-3 protein in various bovine tissues and in brains of various vertebrate species. The quantitative analysis indicated that the tissue distribution of 14-3-3 protein is more closely related to the known distributions of the Ca2(+)-dependent protein kinases, i.e., Ca2+/calmodulin- and Ca2+/phospholipid-dependent protein kinases, rather than those of tyrosine and tryptophan hydroxylases. This result, together with the available data on this protein, suggests potential roles of the 14-3-3 protein in more diverse kinase-mediated processes than the predicted role in monoamine synthesis.
The Unique Domain as the Site on Lyn Kinase for Its Constitutive Association with the High Affinity Receptor for IgE (1997)

Aggregation of the high affinity receptor for IgE (FcepsilonRI) leads to the phosphorylation of tyrosines on the beta and gamma chains of the receptor by the Src family kinase Lyn. We have studied the interaction between Lyn and the FcepsilonRI in vivo using a transfection-based approach. FcepsilonRI were stably transfected into Chinese hamster ovary cells. The small amount of endogenous Src family kinase was sufficient to phosphorylate receptor tyrosines upon extensive aggregation of FcepsilonRI but not after addition of dimers of IgE. Upon stable co-transfection of Lyn kinase into the cells, dimers were now able to stimulate receptor phosphorylation and the response to more extensive aggregation was enhanced. In contrast, co-transfection with catalytically inactive Lyn inhibited the aggregation-induced phosphorylation by the endogenous kinase, and a quantitatively similar inhibition was observed in cells transfected with the SH4-containing unique domain of Lyn. Consistent with the results of others using alternative approaches, our additional studies using a yeast two-hybrid system detected a direct interaction between intact Lyn or its unique domain and the C-terminal cytoplasmic domain of the beta chain but not with the receptor's other cytoplasmic domains.
Human Immunodeficiency Virus Type 1 Pathobiology Studied in Humanized BALB/c-Rag2 −/− γ c −/− Mice (2006)

The specificity of human immunodeficiency virus type 1 (HIV-1) for human cells precludes virus infection in most mammalian species and limits the utility of small animal models for studies of disease pathogenesis, therapy, and vaccine development. One way to overcome this limitation is by human cell xenotransplantation in immune-deficient mice. However, this has proved inadequate, as engraftment of human immune cells is limited (both functionally and quantitatively) following transplantation of mature human lymphocytes or fetal thymus/liver. To this end, a human immune system was generated from umbilical cord blood-derived CD34(+) hematopoietic stem cells in BALB/c-Rag2(-/-)gamma(c)(-/-) mice. Intrapartum busulfan administration followed by irradiation of newborn pups resulted in uniform engraftment characterized by human T-cell development in thymus, B-cell maturation in bone marrow, lymph node development, immunoglobulin M (IgM)/IgG production, and humoral immune responses following ActHIB vaccination. Infection of reconstituted mice by CCR5-coreceptor utilizing HIV-1(ADA) and subtype C 1157 viral strains elicited productive viral replication and lymphadenopathy in a dose-dependent fashion. We conclude that humanized BALB/c-Rag2(-/-)gamma(c)(-/-) mice represent a unique and valuable resource for HIV-1 pathobiology studies.
Induction of Aldose Reductase Gene Expression in LEC Rats during the Development of the Hereditary Hepatitis and Hepatoma (1996)

We examined age-related changes in the protein and the mRNA expression of aldose reductase in livers of Long-Evans with a cinnamon-like color (LEC) rats, which develop hereditary hepatitis and hepatoma with aging, using Long-Evans with an agouti color rats as controls. The levels of the protein and mRNA of aldose reductase increased after 20 weeks, at the stage of acute hepatitis, and were maintained at 60 weeks of age, while those of aldehyde reductase seemed to be constant at all ages. The expression of aldose reductase was marked in cancerous lesions in hepatoma-bearing LEC rat liver compared to uninvolved surrounding tissues. These results indicated that elevation of aldose reductase accompanied hepatocarcinogenesis and may be related to the acquisition of immortality of the cancer cells through detoxifying cytotoxic aldehyde compounds.
Delta9-tetrahydrocannabinol induces apoptosis in macrophages and lymphocytes: involvement of Bcl-2 and caspase-1. (1998)

Apoptosis is programed cell death characterized by certain cellular changes and regulated by various gene products including Bcl-2 and caspase-1. The marijuana cannabinoid, Delta9tetrahydrocannabinol (THC), has been reported to suppress in culture the proliferation of splenocytes and increase the release of IL-1 from macrophages; however, the mechanisms of these effects remain unclear. Because cannabinoids have also been reported to induce apoptosis and because the release of IL-1 and suppression of lymphoproliferation are related to apoptosis, we tested for the induction of apoptosis by THC in murine immune cell cultures. Splenocytes cultured with Con A for up to 24 hr showed evidence of DNA fragmentation determined by gel electrophoresis, terminal deoxynucleotide transferase-mediated dUTP-fluorescein nick end labeling and 3H-thymidine labeling and THC (15-30 microM) treatment increased fragmentation under these conditions. Resident peritoneal macrophages cultured with lipopolysaccharides showed no obvious fragmentation unless they were also treated with THC. Time course studies examining DNA fragmentation and cell membrane integrity (assessed by dye exclusion) showed that fragmentation preceded membrane damage indicating that THC induced apoptosis rather than cell necrosis. In addition, THC treatment of splenocytes resulted in a decrease of Bcl-2 mRNA and protein as measured by Northern and Western blotting, respectively, and the drug induced apoptosis was blocked by the caspase inhibitor, Ac-Tyr-Val-Ala-L-aspartic acid aldehyde. These data suggest that THC treatment of cultured immune cells induces apoptosis through the regulation of Bcl-2 and caspase activity.
Costimulatory requirements of murine Th1 clones. The role of accessory cell-derived signals in responses to anti-CD3 antibody. (1990)

We examined the role of accessory cell-derived signals in promoting growth and lymphokine production by murine Th1 clones. Five of six Th1 clones failed to proliferate to immobilized anti-CD3 antibody despite producing IL-2 and IFN-gamma. These clones became unresponsive to Ag after exposure to anti-CD3. With the addition of irradiated splenic accessory cells (SAC), Th1 clones proliferated to anti-CD3 and produced greater amounts of IL-2 and IFN-gamma. High doses of plate-bound anti-CD3 completely inhibited responses of these clones to IL-2 and diminished the growth-promoting activity of SAC. The costimulatory effects of SAC on growth of Th1 clones were also seen in the presence of exogenous IL-2, indicating that enhanced IL-2 production alone was not responsible for the costimulatory effect. Delivery of the costimulatory signal from SAC required their close proximity to the T cells. The costimulatory activity of SAC was not reproduced by the addition of IL-1, IL-6, or IL-1 plus IL-6. IL-7 induced weak proliferation of Th1 clones, but did not synergize with plate-bound anti-CD3. Our results suggest a model in which SAC-derived costimulatory signals regulate growth of Th1 cells primarily at the level of cell cycle progression rather than at the level of IL-2 production.
Overexpression of IL-10 in atopic dermatitis. Contrasting cytokine patterns with delayed-type hypersensitivity reactions. (1995)

The skin lesions of patients with atopic dermatitis provide a model to study immunoregulation in human allergy. To determine the local cytokine pattern of cells present (both endogenous and recruited) at the site of disease, we extracted RNA from skin biopsy specimens from patients with atopic dermatitis, allergic contract dermatitis, and positive tuberculin reactions and used PCR to assay for cytokine mRNA. cDNAs were normalized to the intensity of the CD3 delta PCR product as a marker of T cell mRNA. We found overexpression of IL-10 mRNA in atopic dermatitis lesions, in comparison with allergic contact dermatitis lesions and tuberculin reactions. In contrast, IL-4 mRNA was most strongly expressed in allergic contact dermatitis lesions and IFN-gamma mRNA was the predominant cytokine in tuberculin reactions. Using an anti-IL-10 mAb with immunoperoxidase, we localized IL-10 protein to large mononuclear cells in the dermal infiltrate of atopic lesions. After immunomagnetic sorting of mononuclear cell populations from PBMC of atopic dermatitis subjects, IL-10 mRNA as measured by PCR was found to be strongly expressed in CD14+ cells. Spontaneous release of IL-10 from PBMC-derived adherent cells was greater in atopic dermatitis donors than normal controls. We therefore renormalized skin biopsy cDNA according to the level of beta-actin PCR product, as a marker of total cellular mRNA, and found by PCR that IL-10 was nevertheless greatest in atopic dermatitis subjects. We conclude that the relative overexpression of IL-10 in atopic dermatitis greatest in atopic dermatitis subjects. We conclude that the relative overexpression of IL-10 in atopic dermatitis may contribute to the up-regulation of humoral responses and the down-regulation of Th1 responses.
Systemic delivery of siRNA via targeted nanoparticles in patients with cancer: Results from a first-in-class phase I clinical trial. (2010)

3022 Background: Systemically delivered small interfering RNA (siRNA) would allow targeting oncogenic molecules beyond current approaches. We report on the first siRNA trial with a targeted nanoparticle delivery system. Methods: Open-label, dose- escalation trial in pts with solid refractory cancers receiving 4 i.v. infusions (30 min) on d 1, 3, 8, and 10 of 21-d cycles. CALAA-01 nanoparticles consisted of a cyclodextrin-based polymer, transferrin protein (hTf) targeting ligand, polyethylene glycol (PEG) for stability, and siRNA against ribonucleotide reductase M2 (RRM2). The 70 nm particles were designed to minimize renal clearance and allow tumor vasculature permeation with binding to tumor hTf receptors (TfR). Primary endpoints (safety, MTD determination) were based on the first cycle. Results: 15 pts accrued to 5 dose levels (3, 9, 18, 24, 30 mg/m2), median age 62 (range 53-85). Most common histologies: GI (4), melanoma (3). Dose escalation progressed with no DLTs. Most common treatment-related AEs: fatigue (47%), fever/chills (33%), allergic (33%), constipation (33%), nausea/vomiting (20%), all g1-2. 1 pt had g3 anemia and 2 pts had g2 thrombocytopenia, all shortly after CALAA-01 infusions with rapid recovery. 1 pt had possibly-related sinus bradycardia (g2). No objective tumor responses were seen; 1 pt at highest dose had stable metastatic melanoma for 4 mo, a change from prior course. Biopsies in 3 pts (melanoma) showed particles in tumors. At 30 mg/m2 RRM2 knockdown (mRNA and protein) was seen with confirmation of mechanism by specific cleavage sequence (RACE-PCR). TfR was not downregulated in cancer cells. Conclusions: Systemic delivery of siRNA via targeted nanoparticles is safe and can induce specific, siRNA-mediated gene silencing. This approach could be expanded to any currently undruggable cancer therapy target. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Calando Calando Calando Calando
Effects of androgen withdrawal on the stem cell composition of the Shionogi carcinoma. (1990)

The parent Shionogi mouse mammary carcinoma is androgen dependent but cells that survive hormone withdrawal progress and give rise to an androgen-independent tumor. To determine whether renewed growth might be attributed to the persistence or partial recovery of an androgenic stimulus, we compared the amount of dihydrotestosterone and nuclear androgen receptor in parent and recurrent tumors. The whole tissue concentration of dihydrotestosterone in the parent tumor before castration was 1.40 +/- 0.46 (SE) as compared with 0.22 +/- 0.10 pmol/mg of DNA in the recurrent tumor. The initial concentration of nuclear androgen receptor in the parent was 0.65 +/- 0.12 pmol/mg of DNA; this was reduced to zero within 24 h after castration. Also in keeping with the androgen independence, no receptor was detected in the nuclear fraction of the recurrent carcinoma. In an attempt to relate malignant potential to nonhormonal factors associated with progression, we compared the proportions of androgen-dependent and -independent tumorigenic (stem) cells in parent and recurrent tumors using an in vivo limiting dilution assay. The difference observed, i.e., one stem cell per 4000 tumor cells in the parent versus one stem cell per 200 tumor cells in the recurrent carcinoma, was consistent with a marked enrichment of stem cells in the latter. The proportion of androgen-independent stem cells was also determined by assaying tumor takes in female hosts. The difference, i.e., one stem cell per 370,000 tumor cells in the parent versus one stem cell per 800 tumor cells in the recurrent carcinoma, demonstrated a striking 500-fold increase in androgen-independent stem cells resulting from androgen withdrawal. Unexpectedly, no enrichment of androgen-independent stem cells was evident in regressing parent tumors; rather, the proportion of such cells was very small, i.e., one androgen-independent stem cell per 2,200,000 regressing parent cells. This finding implies that the androgen-independent state of cells which survive androgen withdrawal may result from the ability of a small number of initially androgen-dependent stem cells to adapt to an altered hormone environment.
Laterally confined graphene nanosheets and graphene/SnO2 composites as high-rate anode materials for lithium-ion batteries (2010)

High-rate anode materials for lithium-ion batteries are desirable for applications that require high power density. We demonstrate the advantageous rate capability of few-layered graphene nanosheets, with widths of 100–200 nm, over micro-scale graphene nanosheets. Possible reasons for the better performance of the former include their smaller size and better conductivity than the latter. Combination of SnO2 nanoparticles with graphene was used to further improve the gravimetric capacities of the electrode at high charge-discharge rates. Furthermore, the volumetric capacity of the composites was substantially enhanced compared to pristine graphene due to the higher density of the composites.