gebhart/patrepeval huggingface dataset:
The effect of sample size and species characteristics on performance of different species distribution modeling methods (2006)

Species distribution models should provide conservation practioners with estimates of the spatial distributions of species requiring attention. These species are often rare and have limited known occurrences, posing challenges for creating accurate species distribution models. We tested four modeling methods (Bioclim, Domain, GARP, and Maxent) across 18 species with different levels of ecological specialization using six different sample size treatments and three different evaluation measures. Our assessment revealed that Maxent was the most capable of the four modeling methods in producing useful results with sample sizes as small as 5, 10 and 25 occurrences. The other methods compensated reasonably well (Domain and GARP) to poorly (Bioclim) when presented with datasets of small sample sizes. We show that multiple evaluation measures are necessary to determine accuracy of models produced with presence‐only data. Further, we found that accuracy of models is greater for species with small geographic ranges and limited environmental tolerance, ecological characteristics of many rare species. Our results indicate that reasonable models can be made for some rare species, a result that should encourage conservationists to add distribution modeling to their toolbox.
The cytokine activity of HMGB1 (2005)

High mobility group box 1 (HMGB1) is a highly conserved, ubiquitous protein present in the nuclei and cytoplasm of nearly all cell types. We recently discovered that HMGB1 is secreted into the extracellular milieu and acts as a proinflammatory cytokine. Administration of HMGB1 to normal animals causes inflammatory responses, including fever, weight loss and anorexia, acute lung injury, epithelial barrier dysfunction, arthritis, and death. Anti-HMGB1 treatment, with antibodies or specific antagonists, rescues mice from lethal endotoxemia or sepsis and ameliorates the severity of collagen-induced arthritis and endotoxin-induced lung injury. Here, we give an abridged review of the cytokine activity of HMGB1, its secretion and release into the extracellular milieu, the putative signal transduction pathways, including interaction with cell-surface receptors and intracellular signaling, and its role in several inflammatory diseases. Finally, the therapeutic potential of blocking HMGB1 in the treatment of inflammatory diseases is discussed.
Ursolic acid nanoparticles inhibit cervical cancer growth in vitro and in vivo via apoptosis induction (2017)

Cervical cancer is a cause of cancer death, making it one of the most common causes of death among women globally. Previously, a variety of studies have revealed the molecular mechanisms by which cervical cancer develops. However, there are still limitations in treatment for cervical cancer. Ursolic acid is a naturally derived pentacyclic triterpene acid, exhibiting broad anticancer effects. Nanoparticulate drug delivery systems have been known to better the bioavailability of drugs on intranasal administration compared with only drug solutions. Administration of ursolic acid nanoparticles is thought to be sufficient to lead to considerable suppression of cervical cancer progression. We loaded gold-ursolic acid into poly(DL-lactide-co-glycolide) nanoparticles to cervical cancer cell lines due to the properties of ursolic acid in altering cellular processes and the easier absorbance of nanoparticles. In addition, in this study, ursolic acid nanoparticles were administered to cervical cancer cells to find effective treatments for cervical cancer inhibition. In the present study, ELISA, western blotting, flow cytometry and immunohistochemistry assays were carried out to calculate the molecular mechanism by which ursolic acid nanoparticles modulated cervical cancer progression. Data indicated that ursolic acid nanoparticles, indeed, significantly suppress cervial cancer cell proliferation, invasion and migration compared to the control group, and apoptosis was induced by ursolic acid nanoparticles in cervical cancer cells through activating caspases, p53 and suppressing anti-apoptosis-related signals. Furthermore, tumor size was reduced by treatment of ursolic acid nanoparticles in in vivo experiments. In conclusion, this study suggests that ursolic acid nanoparticles inhibited cervical cancer cell proliferation via apoptosis induction, which could be a potential target for future therapeutic strategy clinically.
Studies of Passive Immunotherapy for Infections of Respiratory Syncytial Virus in the Respiratory Tract of a Primate Model (1985)

Journal Article Studies of Passive Immunotherapy for Infections of Respiratory Syncytial Virus in the Respiratory Tract of a Primate Model Get access Val G. Hemming, Val G. Hemming Search for other works by this author on: Oxford Academic PubMed Google Scholar Gregory A. Prince, Gregory A. Prince Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert L. Horswood, Robert L. Horswood Search for other works by this author on: Oxford Academic PubMed Google Scholar William T. London, William T. London Search for other works by this author on: Oxford Academic PubMed Google Scholar Brian R. Murphy, Brian R. Murphy Search for other works by this author on: Oxford Academic PubMed Google Scholar Edward E. Walsh, Edward E. Walsh Search for other works by this author on: Oxford Academic PubMed Google Scholar Gerald W. Fischer, Gerald W. Fischer Search for other works by this author on: Oxford Academic PubMed Google Scholar Leonard E. Weisman, Leonard E. Weisman Search for other works by this author on: Oxford Academic PubMed Google Scholar Patricia A. Baron, Patricia A. Baron Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert M. Chanock Robert M. Chanock Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 152, Issue 5, November 1985, Pages 1083–1087, https://doi.org/10.1093/infdis/152.5.1083 Published: 01 November 1985 Article history Received: 11 March 1985 Revision received: 20 May 1985 Published: 01 November 1985
ChemInform Abstract: 14‐METHYL STEROIDS. PART 1. SYNTHESIS AND CRYSTAL STRUCTURE OF 3‐METHOXY‐14‐METHYL‐14β‐ESTRA‐1,3,5(10)‐TRIEN‐15‐ONE (1979)

Abstract Aus dem Östratrienon (I) wird über die Derivate (II) und (III) das Oxoacetal (IV) dargestellt, das mit MeI in Gegenwart von NaNH 2 zu dem 14β‐Methylderivat (V) methylieit wird, aus dem durch LiAlH 4 ‐Reduktion die Titelverbindung (VI) (kristallisiert in der Raumgruppe P2 1 2 1 2 1 mit Z=4) erhalten wird.
A Rule-Based System for Optimizing Combinational Logic (1985)

SOCRATES is a rule-based expert system that optimizes combinational logic for a specific target technology. The system performs substitutions of equivalent gate configurations, thereby reducing the overall area of the implementation and improving the speed of the design. A control mechanism uses various backup strategies to choose the rules applied to the circuit. Users can easily extend the library of transformation rules through a rule generation module that automatically encodes rules and inserts them into the knowledge base. Timing constraints placed on the circuit can be modified to allow the designer to explore a large design space in a matter of minutes. Implementations generated by the system are comparable in area and speed to circuits designed by experts.
Synthesis of constrained helical peptides by thioether ligation: application to analogs of gp41 (2005)

We present a straightforward and high yielding method to synthesize constrained helical peptides via thioether ligation; this method represents an attractive alternative to the formation of lactam bridge constraints to induce helicity in peptides.
β Amyloid peptide (Aβ 42 ) is internalized via the G‐protein‐coupled receptor FPRL1 and forms fibrillar aggregates in macrophages 1 (2001)

The 42 amino acid form of beta amyloid (Abeta42) plays a pivotal role in neurotoxicity and the activation of mononuclear phagocytes in Alzheimer's disease (AD). Our recent study revealed that FPRL1, a G-protein-coupled receptor, mediates the chemotactic and activating effect of Abeta42 on mononuclear phagocytes (monocytes and microglia), suggesting that FPRL1 may be involved in the proinflammatory responses in AD. We investigated the role of FPRL1 in cellular uptake and the subsequent fibrillar formation of Abeta42 by using fluorescence confocal microscopy. We found that upon incubation with macrophages or HEK293 cells genetically engineered to express FPRL1, Abeta42 associated with FPRL1 and the Abeta42/FPRL1 complexes were rapidly internalized into the cytoplasmic compartment. The maximal internalization of Abeta42/FPRL1 complexes occurred by 30 min after incubation. Removal of free Abeta42 from culture supernatants at 30 min resulted in a progressive recycling of FPRL1 to the cell surface and degradation of the internalized Abeta42. However, persistent exposure of the cells to Abeta42 over 24 h resulted in retention of Abeta42/FPRL1 complexes in the cytoplasmic compartment and the formation of Congo red positive fibrils in macrophages but not in HEK 293 cell transfected with FPRL1. These results suggest that besides mediating the proinflammatory activity of Abeta42, FPRL1 is also involved in the internalization of Abeta42, which culminates in the formation of fibrils only in macrophages.
The Kinetics of Formation and Biological Activity of Native and Hybrid Molecules of Human Follicle-stimulating Hormone (1974)

Abstract A rat testes tubule tissue receptor assay was utilized to study the kinetics of combination of the hormone-specific β subunit of human follicle-stimulating hormone (hFSH) with the α subunits of hFSH, human luteinizing hormone (hLH), bovine luteinizing hormone (bLH), and human chorionic gonadotropin (hCG). In this competitive protein-binding assay, 125I-hFSH is the radioligand and FSH activity is measured by the ability of the test substance to inhibit uptake of the radioligand by the rat testes tubule receptors. Rate data for combination of subunits were analyzed for quality of fit to first or second order integrated rate equations by nonlinear regression analysis. The time course for the appearance of FSH activity upon incubation of the various subunit combinations was neither clearly first or second order, although each simple mechanism could be fitted to the experimental data. We conclude that at least one kinetically distinguishable state follows formation of the initial α/β subunit complex and that this complex has a binding affinity for its receptors in rat testes tubules which is much less than those of subsequent states. Hybrid molecules of bLH-α/hFSH-β, hLH-α/hFSH-β, and hCG-α/hFSH-β were formed at differing rates, but each was more rapid than the combination always gous hFSH-α/hFSH-β pair. Maximum combination always occurred by 1440 min of incubation. Hybrid molecules formed after this time were tested for FSH activity by the in vitro rat testes tubule receptor assay and results compared with FSH activity as measured by a classical in vivo bioassay. The in vitro activity of hFSH-α/hFSH-β, hLH-α/hFSH-β and hCG-α/hFSH-β hybrid molecules was from 2 to 4 times greater than their activity as measured in vivo. The in vitro activity of these hybrids was similar to that of intact hFSH, but the activity of the hybrid molecules in vivo was less than that of intact hFSH. Of particular interest were the properties of the hybrid molecule formed between bLH-α/hFSH-β. This combinant had an in vitro activity which was 2.8 times greater than that of purified hFSH. The activity of the bLH-α/hFSH-β hybrid as measured by the in vivo bioassay, however, was only 0.14 times the activity of purified hFSH. The ratio of activity in vitro to in vivo for this artificial FSH molecule was 19.8. It is suggested that the bLH-α/hFSH-β hybrid has a greater affinity than native hFSH for receptors in rat testes tubules, but that expression of in vivo biological activity is depressed probably because of factors related to its more rapid clearance from the circulation.
Nondisposable materials, chronic inflammation, and adjuvant action (2003)

Why inflammatory responses become chronic and how adjuvants work remain unanswered. Macrophage-lineage cells are key components of chronic inflammatory reactions and in the actions of immunologic adjuvants. One explanation for the increased numbers of macrophages long term at sites of chronic inflammation could be enhanced cell survival or even local proliferation. The evidence supporting a unifying hypothesis for one way in which this macrophage survival and proliferation may be promoted is presented. Many materials, often particulate, of which macrophages have difficulty disposing, can promote monocyte/macrophage survival and even proliferation. Materials active in this regard and which can initiate chronic inflammatory reactions include oxidized low-density lipoprotein, inflammatory microcrystals (calcium phosphate, monosodium urate, talc, calcium pyrophosphate), amyloidogenic peptides (amyloid beta and prion protein), and joint implant biomaterials. Additional, similar materials, which have been shown to have adjuvant activity (alum, oil-in-water emulsions, heat-killed bacteria, CpG oligonucleotides, methylated bovine serum albumin, silica), induce similar responses. Cell proliferation can be striking, following uptake of some of the materials, when macrophage-colony stimulating factor is included at low concentrations, which normally promote mainly survival. It is proposed that if such responses were occurring in vivo, there would be a shift in the normal balance between cell survival and cell death, which maintains steady-state, macrophage-lineage numbers in tissues. Thus, there would be more cells in an inflammatory lesion or at a site of adjuvant action with the potential, following activation and/or differentiation, to perpetuate inflammatory or antigen-specific, immune responses, respectively.
Detection of wild-type EGFR amplification and EGFRvIII mutation in CSF-derived extracellular vesicles of glioblastoma patients (2017)

Our results demonstrate CSF-derived EVs contain RNA signatures reflective of the underlying molecular genetic status of GBMs in terms of wtEGFR expression and EGFRvIII status. The high specificity of the CSF-derived EV diagnostic test gives us an accurate determination of positive EGFRvIII tumor status and is essentially a less invasive "liquid biopsy" that might direct mutation-specific therapies for GBMs.
Molecular mimicry and lyme borreliosis: A shared antigenic determinant between Borrelia burgdorferi and human tissue (1989)

The pathogenesis of chronic manifestations in Lyme borreliosis, a disease induced by Borrelia burgdorferi, is at present unresolved. By testing monoclonal antibodies directed against various borrelia antigens, we found an antigenic determinant shared by the 41 kDa flagella protein and human tissue, especially prominent on myelinated fibers of human peripheral nerve, on nerve cells and axons of the central nervous system, as well as on certain epithelial cells (including joint synovia) and on heart muscle cells. Immune reactions against such a shared antigen could play a pathogenetic role in chronic organ manifestations of Lyme borreliosis.
Induction of Virus-Specific Antibody Production by Lamina Propria Lymphocytes following Intramuscular Inoculation with Rotavirus (1995)

The relative capacities of intramuscular (im) or oral inoculation of mice with live or inactivated rotavirus to induce a virus-specific humoral immune response in gut-associated lymphoid tissues (GALT) was evaluated. At 4-5 weeks after oral inoculation with live virus, virus-specific IgA was detectable in serum, intestinal contents, and GALT organ culture. Five weeks after im inoculation with live or inactivated virus, virus-specific IgA was detected in GALT organ culture at levels approximately 10-fold less than those found after oral inoculation with live virus. Therefore, neither replication of virus in small intestinal epithelial cells nor presentation of virus at the intestinal mucosal surface was necessary for the induction of virus-specific antibodies by GALT. Possible mechanisms by which im inoculation of virus induces production of virus-specific antibodies by GALT are discussed.
Triptolide: A novel therapeutic strategy for colorectal cancer (2011)

Dudeja, Vikas MD; Beyer, Georg; Banerjee, Sulagna PhD; Chugh, Rohit MD; Sangwan, Veena PhD; Isharwal, Sumit MD; Vickers, Selwyn M. MD, FACS; Saluja, Ashok PhD Author Information
Induction of Type 3 Iodothyronine Deiodinase by Nerve Injury in the Rat Peripheral Nervous System (2001)

Thyroid hormones are essential for the development and repair of the peripheral nervous system. The type 2 deiodinase, which is responsible for the activation of T(4) into T(3), is induced in injured sciatic nerve. To obtain information on the type 3 deiodinase (D3) responsible for the degradation of thyroid hormones, we looked for its expression (mRNA and activity) in the sciatic nerve after injury. D3 was undetectable in the intact sciatic nerve of adult rats, but was rapidly and highly increased in the distal and proximal segments after nerve lesion. After cryolesion, D3 up-regulation disappeared after 3 d in the proximal segment, whereas it was sustained for 10 d in the distal segment, then declined to reach basal levels after 28 d, when functional recovery was completed. After a transsection preventing the nerve regeneration, up-regulation of D3 persisted up to 28 d at high levels in the distal segment. D3 was expressed in peripheral connective sheaths and in the internal endoneural compartment. D3 mRNA was inducible by 12-O-tetradecanoylphorbol-13-acetate in cultured fibroblasts or Schwann cells. In conclusion, induction of D3 in the peripheral nervous system after injury may play an important role during the regeneration process by adjusting intracellular T(3) levels.
Positron emission tomography with [18F]fluorodeoxyglucose to evaluate neutrophil kinetics during acute lung injury (2004)

We measured neutrophil glucose uptake with positron emission tomographic imaging and [18F]fluorodeoxyglucose ([18F]FDG-PET) in anesthetized dogs after intravenous oleic acid-induced acute lung injury (ALI; OA group, n = 6) or after low-dose intravenous endotoxin (known to activate neutrophils without causing lung injury) followed by OA (Etx + OA group, n = 7). The following two other groups were studied as controls: one that received no intervention (n = 5) and a group treated with Etx only (n = 6). PET imaging was performed 1.5 h after initiating experimental interventions. The rate of [3H]deoxyglucose ([3H]DG) uptake was also measured in vitro in cells recovered from bronchoalveolar lavage (BAL) performed after PET imaging. Circulating neutrophil counts fell significantly in animals treated with Etx but not in the other two groups. The rate of [18F]FDG uptake, measured by the influx constant Ki, was significantly elevated (P < 0.05) in both Etx-treated groups (7.9 +/- 2.6 x 10(-3) ml blood x ml lung(-1) x min(-1) in the Etx group, 9.3 +/- 4.8 x 10(-3) ml blood x ml lung(-1) x min(-1) in the Etx + OA group) but not in the group treated only with OA (3.4 +/- 0.8 x 10-3 ml blood x ml lung(-1) x min(-1)) when compared with the normal control (1.6 +/- 0.4 x 10(-3) ml blood x ml lung(-1) x min(-1)). [3H]DG uptake was increased (73 +/- 7%) in BAL neutrophils recovered from the Etx + OA group (P < 0.05) but not in the OA group. Ki and [3H]DG uptake rates were linearly correlated (R2 = 0.65). We conclude that the rate of [18F]FDG uptake in the lungs during ALI reflects the state of neutrophil activation. [18F]FDG-PET imaging can detect pulmonary sequestration of activated neutrophils, despite the absence of alveolar neutrophilia. Thus [18F]FDG-PET imaging may be a useful tool to study neutrophil kinetics during ALI.
Signaling activity of transforming growth factor beta type II receptors lacking specific domains in the cytoplasmic region. (1993)

The transforming growth factor beta (TGF-beta) type II receptor (T beta R-II) is a transmembrane serine/threonine kinase that contains two inserts in the kinase region and a serine/threonine-rich C-terminal extension. T beta R-II is required for TGF-beta binding to the type I receptor, with which it forms a heteromeric receptor complex, and its kinase activity is required for signaling by this complex. We investigated the role of various cytoplasmic regions in T beta R-II by altering or deleting these regions and determining the signaling activity of the resulting products in cell lines made resistant to TGF-beta by inactivation of the endogenous T beta R-II. TGF-beta binding to receptor I and responsiveness to TGF-beta in these cells can be restored by transfection of wild-type T beta R-II. Using this system, we show that the kinase insert 1 and the C-terminal tail of T beta R-II, in contrast to the corresponding regions in most tyrosine kinase receptors, are not essential to specify ligand-induced responses. Insert 2 is necessary to support the catalytic activity of the receptor kinase, and its deletion yields a receptor that is unable to mediate any of the responses tested. However, substitution of this insert with insert 2 from the activin receptor, ActR-IIB, does not diminish the ability of T beta R-II to elicit these responses. A truncated T beta R-II lacking the cytoplasmic domain still binds TGF-beta, supports ligand binding to receptor I, and forms a complex with this receptor. However, TGF-beta binding to receptor I facilitated by this truncated T beta R-II fails to inhibit cell proliferation, activate extracellular matrix protein production, or activate transcription from a promoter containing TGF-beta-responsive elements. We conclude that the transcriptional and antiproliferative responses to TGF-beta require both components of a heteromeric receptor complex that differs from tyrosine kinase receptors in its mode of signaling.
Transcription of the human colony-stimulating factor-1 receptor gene is regulated by separate tissue-specific promoters (1992)

Receptors for macrophage colony-stimulating factor (CSF-1R) are expressed not only by monocytes, macrophages, and their progenitors, but also by placental trophoblasts during fetal development. In monocytes, CSF-1R gene transcripts originate at multiple sites immediately upstream of the gene's coding sequences, whereas in placental cells the transcripts include an additional noncoding exon, located 26 kb upstream near the 3′ end of the B-type platelet-derived growth factor (PDGF) receptor gene. Physically distinct CSF-1R transcription origins suggest separate promoter usage by the two cell types. To identify regulatory elements of these promoters, we fused CSF- 1R genomic sequences to bacterial reporter genes and introduced the resulting constructs into human cell lines and mouse fibroblasts. A 775- bp genomic fragment containing CSF-1R placental transcription origins and adjacent upstream sequences mediated reporter gene expression in BeWo choriocarcinoma cells and mouse NIH-3T3 fibroblasts, but not in myeloid or lymphoid cells. By contrast, a 550-bp genomic fragment containing CSF-1R monocyte transcription origins and 5′ flanking sequences directed gene expression in U-937 human myeloid cells, but not in the other cell types. Thus, nucleotide sequences of fewer than 1,000-bp upstream of the two independent CSF-1R transcription origins contain the minimal promoter elements needed to program appropriate tissue-specific expression of reporter genes.