gebhart/patrepeval huggingface dataset:
Raloxifene- and estradiol-mediated effects on uterus, bone and B lymphocytes in mice (2002)

Raloxifene is a selective estrogen receptor modulator approved for the prevention of osteoporosis in postmenopausal women. It is selective by having estrogen-agonistic effects on bone, vessels and blood lipids while it is antagonistic on mammary and uterine tissue. Our aim was to study the agonistic and antagonistic properties of the raloxifene analogue LY117018 (LY) on uterus, bone, B lymphopoiesis and B cell function. Oophorectomized and sham-operated animals were treated with s.c. injections of equipotent anti-osteoporotic doses of 17beta-estradiol (E2) (0.1 mg/kg) or LY (3 mg/kg) or vehicle as controls. Effects on bone mineral density (BMD) were studied using peripheral quantitative computed tomography, uterine weight was examined, B lymphopoiesis was examined using flow cytometry and B cell function in bone marrow and spleen was studied by the use of an ELISPOT assay. E2 and LY had similar effects on BMD and bone marrow B lymphopoiesis, while LY had a clear antagonistic effect on endogenous estrogen in uterine tissue and no stimulating effect on the frequency of Ig-producing B cells in sham-operated animals. Our results are discussed in the context of estrogen receptor biology, relations between the immune system and bone metabolism and also with respect to the estrogen-mediated effects on rheumatic diseases.
A shortcut to garnet-type fast Li-ion conductors for all-solid state batteries (2015)

Scanning transmission electron microscopy (STEM) images and elemental mapping of cubic c-Li<sub>6.4</sub>Ga<sub>0.2</sub>La<sub>3</sub>Zr<sub>2</sub>O<sub>12</sub> powders (synthesized at 650 °C) indicating the homogeneous distribution of Zr (red), La (green) and Ga (blue) over the nanostructures.
X-ray and Mössbauer spectroscopy studies of the silicon-antimony and bismuth-antimony alloys (1971)

X-ray and Mossbauer spectroscopy were used to investigate two antimony alloys, Bi-Sb and Si-Sb, showing semiconductorsemimetallic transitions or vice versa, depending on the antimony concentration in the host lattice. Resistivity and density measurements were found to be helpful in the analysis of the results. X-ray studies for dislocation-free antimony-doped silicon showed that the lattice constant of the alloy increased as the antimony concentration increased from 18 19 10 to 10 Sb atoms/cc. Rather good agreement was found between theoretical and experimental changes in lattice constant for dislocation-free silicon. Mossbauer studies showed that the isomer shift decreased linearly with increasing antimony concentration, which implies that the s-electron density at the antimony nucleus increases linearly with increasing antimony concentration. The relation between isomer shift and lattice constants is linear. Hence it 1s believed that the electrons in p-orbits are moving away from the nucleus as the antimony concentration increases, and there is an increase in the measurable s-electron density at the nucleus. The resistivity measurements showed that a semiconductor-semimetallic transition occurs between 2.8 and 18 4.Sxl0 Sb atoms/cc. X-ray studies of the Bi-Sb alloys showed similar results as previously reported for most of the compositional range. The lattice constants were found to decrease linearly with
Fibrinogen microspheres as novel drug delivery systems for antitumor drugs. (1986)

Fibrinogen microspheres containing 5-fluorouracil (5-FU) were prepared and evaluated as a novel drug delivery system. The shape of the microspheres was invariably spherical. The average diameters were 3.9 and 1.1 μm and the drug contents in the microspheres were 16.1 and 6.1%, for the microspheres prepared at 90 and 160°C, respectively. Release of the drug from fibrinogen microspheres was slow after the initial burst, and the drug release continued over 5d. These results indicated that the drug-loaded fibrinogen microspheres could be prepared providing a sustained release property in vitro. The antitumor activity of fibrinogen microspheres containing 5-FU was evaluated against Ehrlich ascites carcinoma in mice. The mean survival time of the group receiving the microspheres was larger than that of the control group, though essentially the same as that of the free 5-FU-treated group. Fibrinogen microspheres show good biocompatibility and should be useful as a novel drug carrier in injectable delivery systems for antitumor drugs.
Differential regulation of lambda pL and pR promoters by a cI repressor in a broad-host-range thermoregulated plasmid marker system (1989)

Plasmid systems with unique markers were constructed to assess the fate of recombinant DNA and genetically manipulated bacteria in soil and freshwater model environments. On such constructs the marker gene, xylE (for catechol 2,3-dioxygenase), is expressed from the lambda promoter pL or pR, each of which is controlled by the temperature-sensitive lambda repressor c1857. Combinations of these elements were cloned into the broad-host-range plasmid pKT230 to form pLV1010 (pL-xylE), pLV1011 (pL-xylE-c1857), and pLV1013 (pR-xylE-c1857). The recombinant plasmids were introduced into different gram-negative bacteria. The thermoregulated system of pLV1013 functioned well in a range of species, with xylE induction being readily achieved by elevation of the temperature from 28 to 37 degrees C. There was a difference in the induction of catechol 2,3-dioxygenase activity, depending on whether xylE was expressed from pL (pLV1011) or pR (pLV1013). Our observations on testing the different systems in a number of hosts suggest that genes carried by the DNA of genetically engineered microorganisms may not be expressed in a predictable manner following transfer from the release host to other species.
The Inhibition of Cathepsin S by its Propeptide — Specificity and Mechanism of Action (1997)

The interaction of human recombinant full-length cathepsin S propeptide (amino acids 16-114) with mature cysteine proteinases was studied with respect to selectivity and pH dependence. The inhibitory capacity was tested towards mature human recombinant cathepsin S, purified cathepsin L from rat and Paramecium tetraurelia, rat cathepsin B, human cathepsin H, and papain. The propeptide of cathepsin S strongly inhibited cathepsin S (Ki = 0.27 nM) and the two cathepsin L species (Ki = 0.36 nM) at neutral pH. Papain, and to a minor extent cathepsin H, hydrolyzed the propeptide of cathepsin S, leading to competition with the hydrolysis of the fluorogenic substrates in the respective assays. Cathepsin B activity was nearly unaffected up to micromolar propeptide concentrations in the assay. The inhibition of cathepsin-L-like peptidases was diminished with decreasing pH, probably due to dramatic changes in the conformation of the propeptide. This assumption was supported by far-ultraviolet CD spectroscopy and by the finding of rapid hydrolysis of the cathepsin S propeptide by cathepsin L at pH values less than 5.5.
Antitumor effects elicited by antisense-mediated downregulation of the insulin-like growth factor I receptor (review). (1998)

Antisense-mediated downregulation of the insulin-like growth factor I receptor results in massive apoptosis of tumor cells in vivo, leading to abrogation of tumorigenesis. In addition to the apoptotic effect, antitumor responses are elicited in syngeneic immunocompetent animals, protecting them from subsequent tumor challenge and causing regression of established tumors with no further recurrence. The mechanisms involved in the antitumor responses elicited in the animals following exposure to antisense cells are discussed, focusing on the immunogenicity of the antisense cells as well as the effectors that participate in these responses.
Replication: Regressive Reproduction or Progressive Evolution? (2000)

Increasing numbers of organizations are "replicating" the programs of successful microfinance institutions (MFIs). This approach allows rapid start-up using tested models and systems. These strengths are also weaknesses, though, since the models being replicated usually require substantial modifications to make them appropriate for local conditions. Furthermore, close adherence to "blueprints" is likely to substitute for careful research into the needs and opportunities for the provision of financial services to the poor--and thus the design of appropriate systems. Replication also risks the suppression of innovative ways of providing still better financial services--particularly when promoted by powerful apex funding organizations, as is currently in vogue among donor agencies. Perhaps the most dangerous form of replication is that driven by consultants, lenders, or donors who design or recommend systems they only partly understand, thus giving incomplete or blurred blueprints. Credit is alsoused as a way to attract clients to meetings (where they may be required to participate in other activities, such as family planning, etc.). This "parttime banking" is dangerous, both as a result of the complexity of providing financial services, and because clients come to rely on permanent access to these services.
Phosphorylation of Proteins by Inositol Pyrophosphates (2004)

The inositol pyrophosphates IP7 and IP8 contain highly energetic pyrophosphate bonds. Although implicated in various biologic functions, their molecular sites of action have not been clarified. Using radiolabeled IP7, we detected phosphorylation of multiple eukaryotic proteins. We also observed phosphorylation of endogenous proteins by endogenous IP7 in yeast. Phosphorylation by IP7 is nonenzymatic and may represent a novel intracellular signaling mechanism.
A cell-permeable dominant-negative survivin protein induces apoptosis and sensitizes prostate cancer cells to TNF-α therapy (2010)

The results demonstrate that antagonism of survivin function triggers the apoptosis of prostate and cervical cancer cells grown in 3D culture. It renders cancer cells sensitive to the proapoptotic affects of TNF-α, suggesting that survivin blocks the extrinsic pathway of apoptosis. Combination of the biologically active dNSurR9-C84A protein or other survivin antagonists with TNF-α therapy warrants consideration as an approach to cancer therapy.
Cell-free synthesis of deoxyhypusine. Separation of protein substrate and enzyme and identification of 1,3-diaminopropane as a product of spermidine cleavage. (1988)

The post-translational formation of hypusine (N epsilon-(4-amino-2-hydroxybutyl)lysine) occurs in a precursor of eukaryotic initiation factor 4D by way of two major steps: 1) transfer of the 4-aminobutyl moiety from spermidine to the epsilon-amino group of a specific lysine residue to form an intermediate, deoxyhypusine; 2) hydroxylation of the deoxyhypusine residue to form hypusine. The initial step of this modification, deoxyhypusine synthesis, was studied in fractionated lysates of Chinese hamster ovary cells, untreated, or treated with alpha-difluoromethylornithine (DFMO); the enzyme(s) and the protein substrate (eukaryotic initiation factor 4D precursor) were separated. The enzyme activity was found in the 0-45% ammonium sulfate fraction from both untreated and DFMO-treated cells. The protein substrate was detected in the 45-75% ammonium sulfate fraction from cells depleted of spermidine by treatment with DFMO, but not in any fraction from untreated cells. Upon further purification of the protein substrate by ion exchange chromatography, the requirement for a pyridine nucleotide, notably NAD+, became apparent. Free 1,3-diaminopropane was identified as a spermidine cleavage product formed concurrently with the 4-aminobutyl transfer step of deoxyhypusine synthesis. Compounds structurally related to spermidine, e.g. caldine, N4-benzylspermidine, homospermidine, and a spermine homologue, thermine, as well as 1,7-diaminoheptane, 1,8-diaminooctane, and 1,9-diaminononane caused significant inhibition of deoxyhypusine synthesis presumably due to competition with spermidine. 1,3-Diaminopropane exhibited a potent inhibition of deoxyhypusine formation, probably through a different mechanism.
Halofenate Is a Selective Peroxisome Proliferator–Activated Receptor γ Modulator With Antidiabetic Activity (2006)

Halofenate has been shown previously to lower triglycerides in dyslipidemic subjects. In addition, significant decreases in fasting plasma glucose were observed but only in type 2 diabetic patients. We hypothesized that halofenate might be an insulin sensitizer, and we present data to suggest that halofenate is a selective peroxisome proliferator–activated receptor (PPAR)-γ modulator (SPPARγM). We demonstrate that the circulating form of halofenate, halofenic acid (HA), binds to and selectively modulates PPAR-γ. Reporter assays show that HA is a partial PPAR-γ agonist, which can antagonize the activity of the full agonist rosiglitazone. The data suggest that the partial agonism of HA may be explained in part by effective displacement of corepressors (N-CoR and SMRT) coupled with inefficient recruitment of coactivators (p300, CBP, and TRAP 220). In human preadipocytes, HA displays weak adipogenic activity and antagonizes rosiglitazone-mediated adipogenic differentiation. Moreover, in 3T3-L1 adipocytes, HA selectively modulates the expression of multiple PPAR-γ–responsive genes. Studies in the diabetic ob/ob mouse demonstrate halofenate’s acute antidiabetic properties. Longer-term studies in the obese Zucker (fa/fa) rat demonstrate halofenate’s comparable insulin sensitization to rosiglitazone in the absence of body weight increases. Our data establish halofenate as a novel SPPARγM with promising therapeutic utility with the potential for less weight gain.
Efficacy of interleukin-1 beta against systemic Candida albicans infections in normal and immunosuppressed mice (1989)

Prophylactic treatments with either recombinant human interleukin-1 beta (rHuIL-1 beta) or a muramyl dipeptide analog ([Abu1]MDP) enhanced the resistance of mice to systemic infection with Candida albicans. The optimum treatment regimen in both normal and cyclophosphamide-treated mice was intraperitoneal administration of 100 ng of rHuIL-1 beta or 1.6 mg of [Abu1]MDP per mouse once daily for 3 consecutive days before infection. Neither rHuIL-1 beta nor [Abu1]MDP was efficacious when started after the infection or when given before cyclophosphamide to mice infected subsequently. Continuing to treat after the infection with either drug neither enhanced nor antagonized the efficacy of prophylactic treatments.
ALLOGENEIC MESENCHYMAL STEM CELLS REGENERATE BONE IN A CRITICAL-SIZED CANINE SEGMENTAL DEFECT (2003)

The results of this study demonstrated that allogeneic mesenchymal stem cells loaded on hydroxyapatite-tricalcium phosphate implants enhanced the repair of a critical-sized segmental defect in the canine femur without the use of immunosuppressive therapy. No adverse immune response was detected in this model.
The epidemiology of epilepsy revisited (2003)

Purpose of review Epidemiology is the study of the dynamics of a medical condition in a population. There are many shortcomings in the understanding of the epidemiology of epilepsy mostly caused by methodological problems. These include diagnostic accuracy, case ascertainment, and selection bias. In this article recent progress in this area is discussed and suggestions for future research are made. Recent findings It is generally accepted that in developed countries the incidence is around 50/100 000/year. In resource-poor countries, the incidence is likely to be higher. Prevalence of active epilepsy is in the range of 5-10/1000 in most locations, although it might be higher in some isolates. Age-specific incidence rates have changed, with a decrease in younger age groups and an increase in persons above 60 years. The overall prognosis for seizure control is good and over 70% will enter remission. Epilepsy carries an increased risk of premature death particularly in patients with chronic epilepsy. Sudden unexpected death has been increasingly recognized as a major culprit for this increased mortality. Summary There is geographic variation in the incidence of epileptic syndromes likely to be associated with genetic and environmental factors, although as yet causality has not been fully established. The complete range of aetiologies in the general population is not known. Few predictors of outcome are recognized and it is difficult to prognosticate in any individual case. Knowledge is patchy about the epidemiology of sudden unexpected death in epilepsy. Future epidemiological research needs to address these issues if we are to progress.
Structure, function and diversity of the healthy human microbiome (2012)

Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat's signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81-99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.
Measurement of Type I Interferon Production (2011)

The Basic Protocol in this unit describes measurement of murine interferon (IFN)α/β by intracellular staining for these cytokines and detection by flow cytometry. Alternate protocols detail an enzyme-linked immunoabsorbent assay (ELISA) for IFNα and a biological assay to measure IFN. The FACS assay allows measurement of IFNα/β production by defined cell populations, while ELISA measures secreted IFNα. The bioassay measures functional antiviral activity and is the most sensitive of the assays discussed. These assays therefore provide complementary methods to assess IFN production by murine cells.
Lipid based intramuscular long-acting injectables: Current state of the art (2022)

Long acting injectables (LAI) have received increased research and commercial interest due to their potential for improving treatment effectiveness and adherence for antipsychotic, antiviral and addiction treatments. A range of materials have been used to formulate LAI products, including lipids and polymers. Classic lipid-based LAI, such as oil solutions of antipsychotic drugs, have been widely prescribed to patients. Clinical evidence has shown significantly improved key therapeutic markers such as reduction of relapses in the case of schizophrenia patients. The commercial LAI products can be given either via subcutaneous or intramuscular injection. The main types of lipid-based LAI formulations include oil solutions, lipid-based nanoparticles and lipid based liquid crystal formulations, which are currently clinically available, and oil suspensions and oleogels and which currently have no commercial products available. This review will discuss all relevant aspects related to the development of lipid-based long acting injectables with a special focus on intramuscular (IM) injectables. It aims to provide useful guidance on effective future LAI product design and development. Lipid-based nanoformulations are not discussed in this review as they are thoroughly reviewed in literature elsewhere.
THE 2.3-*ANGSTROMS RESOLUTION STRUCTURE OF THE MALTOSE- OR MALTODEXTRIN-BINDING PROTEIN, A PRIMARY RECEPTOR FOR BACTERIAL ACTIVE TRANSPORT AND CHEMOTAXIS (1990)

The three-dimensional structure of the maltose- or maltodextrin-binding protein (Mr = 40,622) with bound maltose has been obtained by crystallographic analysis at 2.8-A resolution. The structure, which has been partially refined at 2.3 A, is ellipsoidal with overall dimensions of 30 x 40 x 65 A and divided into two distinct globular domains by a deep groove. Although each domain is built from two peptide segments from the amino- and carboxyl-terminal halves, both domains exhibit similar supersecondary structure, consisting of a central beta-pleated sheet flanked on both sides with two or three parallel alpha-helices. The groove, which has a depth of 18 A and a base of about 9 x 18 A, contains the maltodextrin-binding site. We have previously observed the same general features in the well-refined structures of six other periplasmic receptors with specificities for L-arabinose, D-galactose/D-glucose, sulfate, phosphate, leucine/isoleucine/valine, and leucine. The bound maltose is buried in the groove and almost completely inaccessible to the bulk solvent. The groove is heavily populated by polar and aromatic groups many of which are involved in extensive hydrogen-bonding and van der Waals interactions with the maltose. All the disaccharide hydroxyl groups, which form a peripheral polar surface approximately in the plane of the sugar rings, are tied in a total of 11 direct hydrogen bonds with six charged side chains, one Trp side chain, and one peptide backbone NH, and five indirect hydrogen bonds via water molecules. The maltose is wedged between four aromatic side chains. The resulting stacking of these aromatic residues on the faces of the glucosyl units provides a majority of the van der Waals contacts in the complex. The nonreducing glucosyl unit of the maltose is involved in approximately twice as many hydrogen bonds and van der Waals contacts as the glucosyl unit at the reducing end. The binding protein-maltose complex shows the best example of the extensive use of polar and aromatic residues in binding oligosaccharides. The tertiary structure of the maltodextrin-binding protein, along with the results of genetic studies by a number of investigators, has also enabled us for the first time to map the different regions on the surface of the protein involved in the interactions with the membrane-bound protein components necessary for transport of and chemotaxis toward maltodextrins. These sites permit distinction of the "open cleft" (without bound sugar) and closed (with bound sugar) conformations of the binding protein by the chemotactic signal transducer with which the maltodextrin-binding protein interacts.(ABSTRACT TRUNCATED AT 250 WORDS)