gebhart/patrepeval huggingface dataset:
Paclitaxel chemotherapy: from empiricism to a mechanism-based formulation strategy (2005)

Paclitaxel is an anticancer agent effective for the treatment of breast, ovarian, lung, and head and neck cancer. Because of water insolubility, paclitaxel is formulated with the micelle-forming vehicle Cremophor EL to enhance drug solubility. However, the addition of Cremophor EL results in hypersensitivity reactions, neurotoxicity, and altered pharmacokinetics of paclitaxel. To circumvent these unfavorable effects resulting from the addition of Cremophor EL, efforts have been made to develop new delivery systems for paclitaxel administration. For example, ABI-007 is a Cremophor-free, albumin-stabilized, nanoparticle paclitaxel formulation that was found to have significantly less toxicity than Cremophor-containing paclitaxel in mice. Pharmacokinetic studies indicate that in contrast to Cremophor-containing paclitaxel, ABI-007 displays linear pharmacokinetics over the clinically relevant dose range of 135-300 mg/m(2). In a phase III study conducted in patients with metastatic breast cancer, patients treated with ABI-007 achieved a significantly higher objective response rate and time to progression than those treated with Cremophor-containing paclitaxel. Together these findings suggest that nanoparticle albumin-bound paclitaxel may enable clinicians to administer paclitaxel at higher doses with less toxicity than is seen with Cremophor-containing paclitaxel. The role of this novel paclitaxel formulation in combination therapy with other antineoplastic agents needs to be determined.
Systems for production of calves from cultured bovine embryonic cells (1994)

The development of totipotent bovine embryonic cell cultures has great value in cattle breeding. They provide: (1) a mechanism for making large numbers of clonal offspring by nuclear transfer; (2) an efficient gene transfer system through the use of selectable markers to select transgenic cells; and (3) a mechanism for site-specific gene transfer or deletion by homologous DNA sequence recombination. Bovine embryonic cell cultures have been established from blastocyst inner cell mass (ICM) cells, morulae and the precompaction 16-20-cell stage. All have exhibited similar morphology to mouse embryonic stem (ES) cells, pluripotency on differentiation and proliferation in culture. Culture systems have consisted of microdrop loose suspension short-term cultures or long-term cultures on bovine or murine fibroblast feeder layers, in either a microdrop or a culture dish. The relative merit of culture systems or media requirements for mitosis and prevention of differentiation have not been determined. At present, totipotency is also unknown for cultured cells of the 16-20-cell stage. For cultured ICM cells, totipotency was demonstrated by the birth of four calves from ICM cells cultured 27 days or less in a loose suspension microdrop. Advanced pluripotency and perhaps totipotency was demonstrated in one fetus in a recently reported study where morulae cells cultured in vitro were chimaerized with non-cultured cells. DNA fingerprinting to associate cell lines with offspring and karyotyping to ascertain chromatin normalcy is important in ES cell research. Data pertaining to the use of each are presented.
Human bronchial epithelial cells exposed in vitro to cigarette smoke at the air-liquid interface resemble bronchial epithelium from human smokers (2013)

Organotypic culture of human primary bronchial epithelial cells is a useful in vitro system to study normal biological processes and lung disease mechanisms, to develop new therapies, and to assess the biological perturbations induced by environmental pollutants. Herein, we investigate whether the perturbations induced by cigarette smoke (CS) and observed in the epithelium of smokers' airways are reproducible in this in vitro system (AIR-100 tissue), which has been shown to recapitulate most of the characteristics of the human bronchial epithelium. Human AIR-100 tissues were exposed to mainstream CS for 7, 14, 21, or 28 min at the air-liquid interface, and we investigated various biological endpoints [e.g., gene expression and microRNA profiles, matrix metalloproteinase 1 (MMP-1) release] at multiple postexposure time points (0.5, 2, 4, 24, 48 h). By performing a Gene Set Enrichment Analysis, we observed a significant enrichment of human smokers' bronchial epithelium gene signatures derived from different public transcriptomics datasets in CS-exposed AIR-100 tissue. Comparison of in vitro microRNA profiles with microRNA data from healthy smokers highlighted various highly translatable microRNAs associated with inflammation or with cell cycle processes that are known to be perturbed by CS in lung tissue. We also found a dose-dependent increase of MMP-1 release by AIR-100 tissue 48 h after CS exposure in agreement with the known effect of CS on this collagenase expression in smokers' tissues. In conclusion, a similar biological perturbation than the one observed in vivo in smokers' airway epithelium could be induced after a single CS exposure of a human organotypic bronchial epithelium-like tissue culture.
Spatial Hearing: The Psychophysics of Human Sound Localization by Jens Blauert (1985)

First Page
Fluorescence resonance energy transfer analysis of the structure of the four-way DNA junction (1992)

We have carried out fluorescence resonance energy transfer (FRET) measurements on four-way DNA junctions in order to analyze the global structure and its dependence on the concentration of several types of ions. A knowledge of the structure and its sensitivity to the solution environment is important for a full understanding of recombination events in DNA. The stereochemical arrangement of the four DNA helices that make up the four-way junction was established by a global comparison of the efficiency of FRET between donor and acceptor molecules attached pairwise in all possible permutations to the 5' termini of the duplex arms of the four-way structure. The conclusions are based upon a comparison between a series of many identical DNA molecules which have been labeled on different positions, rather than a determination of a few absolute distances. Details of the FRET analysis are presented; features of the analysis with particular relevance to DNA structures are emphasized. Three methods were employed to determine the efficiency of FRET: (1) enhancement of the acceptor fluorescence, (2) decrease of the donor quantum yield, and (3) shortening of the donor fluorescence lifetime. The FRET results indicate that the arms of the four-way junction are arranged in an antiparallel stacked X-structure when salt is added to the solution. The ion-related conformational change upon addition of salt to a solution originally at low ionic strength progresses in a continuous noncooperative manner as the ionic strength of the solution increases. The mode of ion interaction at the strand exchange site of the junction is discussed.
Degradation of ornithine decarboxylase: exposure of the C-terminal target by a polyamine-inducible inhibitory protein. (1993)

Polyamine-mediated degradation of vertebrate ornithine decarboxylase (ODC) is associated with the production of antizyme, a reversible tightly binding protein inhibitor of ODC activity. The interaction of antizyme with a binding element near the N terminus of ODC is essential but not sufficient for regulation of the enzyme by polyamines (X. Li and P. Coffino, Mol. Cell. Biol. 12:3556-2562, 1992). We now show that a second element present at the C terminus is required for the degradation process. Antizyme caused a conformational change in ODC, which made the C terminus of ODC more accessible. Blocking the C terminus with antibody prevented degradation. Tethering the C terminus by creating a circularly permuted, enzymatically active form of ODC prevented antizyme-mediated degradation. These data elucidate a form of feedback regulation whereby excess polyamines induce destruction of ODC, the enzyme that initiates their biosynthesis.
Granzyme B and perforin can be used as predictive markers of acute rejection in heart transplantation (1994)

We have investigated perforin and granzyme B expression in graft-infiltrating lymphocytes of patients who underwent heart transplantation. Those proteins are commonly present in the cytoplasmic granules of cytotoxic T lymphocytes and are released upon effector-target cell interaction. From 28 patients 103 endomyocardial biopsies were obtained and examined by histology and immunocytochemical analysis using relevant monoclonal antibodies. We found that "high" biopsy histological grades were associated with perforin and granzyme B expression in graft-infiltrating lymphocytes of patients with acute severe rejection crisis. In contrast, these markers were not detected in patients without rejection or during graft stabilization. Interestingly, in patients with mild rejection and "low" histological grades, two groups could be distinguished with a differential expression of the two intracytoplasmic proteins. The presence of perforin and granzyme B-expressing cells was found to be predictive of rapid progression to severe rejection, so that this situation required additional treatment; in contrast, their absence seemed to correlate with a good graft outcome without additional treatment. Moreover, perforin and granzyme B expression seemed to be down-regulated by immunosuppressive drugs, which coincided with graft stabilization. In conclusion, our data suggest that detection of granzyme B and perforin in graft-infiltrating lymphocytes might be helpful for routinely monitoring heart transplant patients.
Biosynthesis of ethers: Unusual or common natural events? (2010)

Ether bonds are found in a wide variety of natural products--mainly secondary metabolites--including lipids, oxiranes, terpenoids, flavonoids, polyketides, and carbohydrate derivatives, to name some representative examples. To furnish such a biodiversity of structures, a large number of different enzymes are involved in several different biosynthetic pathways. Depending on the compound and on the (micro) environment in which the reaction is performed, ethers are produced by very different (enzymatic) reactions, thus providing an impressive display of how Nature has combined evolution and thermodynamics to be able to produce a vast number of compounds. In addition, many of these compounds possess different biological activities of pharmacological interest. Moreover, some of these ethers (i.e., epoxides) have high chemical reactivity, and can be useful starting materials for further synthetic processes. This review aims to provide an overview of the different strategies that are found in Nature for the formation of these "bioethers". Both fundamental and practical insights of the biosynthetic processes will be discussed.
Liposomal Delivery of Nucleic Acids In Vivo (2002)

Optimization of cationic liposomal complexes for in vivo applications and therapeutics is complex involving many distinct components. These components include nucleic acid purification, plasmid design, formulation of the delivery vehicle, administration route and schedule, dosing, detection of gene expression, and others. This review will focus on optimization of these components for use in a variety of in vivo applications. Use of improved liposome formulations for delivery in vivo is valuable for gene therapy and would avoid several problems associated with viral delivery. Delivery of nucleic acids using liposomes is promising as a safe and non-immunogenic approach to gene therapy. Furthermore, gene therapeutics composed of artificial reagents can be standardized and regulated as drugs rather than as biologics. Optimizing all components of the delivery system will allow broad use of liposomal complexes to treat or cure human diseases or disorders.
Pulmonary diffusing capacity as a predictor of performance in competitive swimming. (1989)

Pulmonary diffusing capacity has been noted by many investigators to be higher in championship swimmers than in average swimmers and in the non-swimming population. We measured pulmonary diffusing capacity (DLCO) and other parameters in 22 members of a collegiate swimming team and studied the relationship between pulmonary diffusing capacity and swimming performance. We also investigated change in lung function over a season of training and racing. Results suggested that while most good swimmers had above average diffusing capacities, there was no statistically significant difference in performance between those swimmers with high DLCO (greater than or equal to 110% predicted value) and those with a low DLCO (less than 100% predicted value). It was also determined that there was not a good correlation between performance (measured by either "best time" or "average time") and lung function (DLCO or VC).
Toxicology and biocompatibility of bioglasses (1981)

Evidence for the lack of toxicity of various bioglass formulations has been deduced from studies carried out, both in vivo and in vitro, in several different centers. Recent studies of the authors, described here, include testing of solid bioglass implants in the soft tissues of rats and rabbits for time periods of up to eight weeks. Two new techniques are described for the toxicological testing of particulate biomaterials. These tests, which involve rat peritoneal macrophages in culture and a mouse pulmonary biomaterial embolus model, indicate the biocompatibility of bioglass powders. Thus, the surface activity so critical in bone adhesion is without toxic effect in non-osseous tissues in contact with solid bioglass implants. Should wear occur and produce particulate bioglass, the material should be eliminated without consequence.
Retinal pigment epithelium is protected against apoptosis by alphaB-crystallin. (2002)

alphaB-crystallin may function as a stress-inducible antiapoptotic protein in human RPE and is inducible by oxidative stress, a condition implicated in the pathogenesis of AMD. Overexpression of alphaB-crystallin may be an important mechanism for the RPE to prevent apoptotic cell death in response to cellular stress.
Left Ventricular Endocardial Pacing Improves Resynchronization Therapy in Canine Left Bundle-Branch Hearts (2009)

Data from this acute animal study indicate that the use of an endocardial LV pacing electrode may increase the efficacy of resynchronization therapy as compared with conventional epicardial resynchronization therapy.
Purification and characterization of matrix metalloproteinase 9 from U937 monocytic leukaemia and HT1080 fibrosarcoma cells (1992)

The precursor of matrix metalloproteinase 9 (proMMP-9), also known as '92 kDa progelatinase/type IV procollagenase', was purified from the conditioned medium of U937 monocytic leukaemia and HT1080 fibrosarcoma cell lines stimulated with phorbol 12-myristate 13-acetate. ProMMP-9 in these culture media is non-covalently complexed with the 29 kDa tissue inhibitor of metalloproteinases (TIMP), but free proMMP-9 was separated from the TIMP-proMMP-9 complex by chromatography on Green A Dyematrex gel. The final product was homogeneous on SDS/PAGE, with a molecular mass of 88 kDa without reduction and 92 kDa with reduction. Treatment of proMMP-9 with 4-aminophenylmercuric acetate converted the 88 kDa precursor into 80 kDa and 68 kDa forms. Gelatin-containing zymographic analysis showed zones of lysis associated with all three species. However, only the 68 kDa species was shown to be catalytically active by its ability to bind to alpha 2-macroglobulin. In the presence of an equimolar amount of TIMP, only the 80 kDa species was generated by treatment with 4-aminophenylmercuric acetate, but no enzyme activity was detected. This indicates that TIMP binds to the 80 kDa intermediate and inhibits the generation of the active 68 kDa species. Eight endopeptidases (trypsin, chymotrypsin, plasmin, plasma kallikrein, thrombin, cathepsin G, neutrophil elastase and thermolysin) were tested for their ability to activate proMMP-9. Of them, trypsin was the most effective activator of proMMP-9. Only partial activation (10-30%) was observed with plasmin, cathepsin G and chymotrypsin. The active forms generated by trypsin were identified as 80 kDa, 74 kDa and 66 kDa by their abilities to bind to alpha 2-macroglobulin. In the presence of an equimolar amount of TIMP, proMMP-9 was also converted into the same molecular-mass species by trypsin, but they were not proteolytically active. This suggests activated MMP-9 is inhibited by TIMP. Activated MMP-9 digested gelatin, type-V collagen, reduced carboxymethylated transferrin and, to a lesser extent, type-IV collagen and laminin A chain. The specific activity against gelatin was estimated to be 15,000 units/mg (1 unit = 1 microgram of gelatin degraded/min at 37 degrees C) by titration with alpha 2-macroglobulin. Comparative studies on digestion of gelatin and collagen types IV and V by MMP-9 and MMP-2 indicated that both enzymes degrade these substrates into similar fragments. However, the susceptibilities of laminin, fibronectin and reduced carboxymethylated transferrin to these two MMPs were sufficiently different to indicate differences in substrate specificities between these two closely related proteinases.
Gene Expression Profiles Differentiating Between Breast Cancers Clinically Responsive or Resistant to Letrozole (2009)

To our knowledge, this is the first study to describe genetic covariables and molecular processes discriminating between tumors clinically responsive and resistant to an aromatase inhibitor. The understanding of such molecular phenotypes will be important in optimizing the clinical use of aromatase inhibitors, both in terms of identifying responsive breast cancers and developing new agents to target resistance pathways.
Immaturity associated antigens are lost during induction for T cell lymphoblastic leukemia: Implications for minimal residual disease detection (2010)

Our study strongly argues for expansion of immunophenotyping panels for T-ALL MRD to decrease reliance on immature antigens. This study represents the first demonstration of consistent immunophenotypic shifts in T-ALL.
IgE production by normal human lymphocytes is induced by interleukin 4 and suppressed by interferons gamma and alpha and prostaglandin E2. (1988)

The effect of human recombinant interleukin 4 (IL-4) on antibody production by normal peripheral blood mononuclear cells enriched for B cells was investigated. IL-4 preferentially induced IgE synthesis in vitro. In addition, a low induction of IgG production was observed, whereas IL-4 had no effect on IgA and IgM synthesis. The IL-4-induced IgE production by B cells required T cells and monocytes but was specifically inhibited by an anti-IL-4 antiserum indicating that, although IL-4 acts indirectly, it is responsible for the induction of IgE synthesis. IL-4-induced IgE production was blocked in a dose-dependent way by interferon gamma (IFN-gamma), interferon alpha (IFN-alpha), and prostaglandin E2. IFN-gamma also inhibited IL-4-induced IgG production. These inhibitory effects of IFN-gamma and IFN-alpha on IgE production cannot be attributed to toxic effects since IFN-alpha induced IgM production in the presence of IL-4, whereas IFN-gamma was ineffective in inhibiting IgG production induced by IL-2. IFN-gamma, IFN-alpha, and prostaglandin E2 also inhibited IL-4-induced expression of the low-affinity receptor for the Fc portion of IgE (CD23) on B cells, indicating that there is an association between CD23 expression and IL-4-induced IgE production. This theory was supported by the finding that IL-4-induced IgE production was inhibited by F(ab')2 fragments of an anti-CD23 monoclonal antibody.
enabled, a dosage-sensitive suppressor of mutations in the Drosophila Abl tyrosine kinase, encodes an Abl substrate with SH3 domain-binding properties. (1995)

Genetic screens for dominant second-site mutations that suppress the lethality of Abl mutations in Drosophila identified alleles of only one gene, enabled (ena). We report that the ena protein contains proline-rich motifs and binds to Abl and Src SH3 domains, ena is also a substrate for the Abl kinase; tyrosine phosphorylation of ena is increased when it is coexpressed in cells with human or Drosophila Abl and endogenous ena tyrosine phosphorylation is reduced in Abl mutant animals. Like Abl, ena is expressed at highest levels in the axons of the embryonic nervous system and ena mutant embryos have defects in axonal architecture. We conclude that a critical function of Drosophila Abl is to phosphorylate and negatively regulate ena protein during neural development.
Regulating G Protein Signaling (1996)

Cell biologists have long known that cells can damp down their responses to hormones, neurotransmitters, and other regulators, but exactly how this “desensitization” occurs has been unclear. Now a flurry of work from several labs is revealing how one major group of intracellular communication lines—those using G proteins to transmit signals to the cell interior—achieves this volume control. Researchers have identified a new family of proteins, known as the RGS proteins (for regulators of G protein signaling), that attenuate signaling through those pathways, apparently by binding to one of the three protein subunits that make up a complete G protein. The new findings could lead to a much better understanding of how G protein-signal pathways work—information that could have practical implications as up to 60% of all drugs exert their effects through these pathways.
Anastrozole (1998)

Estrogen manipulation represents an effective treatment for advanced breast cancer in postmenopausal women with estrogen-receptor positive disease. The antiestrogen agent, tamoxifen, is the first choice for advanced breast cancer in postmenopausal women due to its efficacy and lack of significant side effects. As with all cancer treatments, however, cancer may recur after initial treatment with tamoxifen, and the limitations of currently available alternative hormonal therapies in terms of tolerability and convenience of administration underscore the need for new agents. Anastrozole is a new, highly selective, nonsteroidal aromatase inhibitor capable of maximal estrogen depletion with fewer side effects than other hormonal therapies. Anastrozole is administered in a convenient, once-daily oral dosing regimen and does not require steroid replacement therapy. In two multicenter clinical trials, anastrozole was as effective as megestrol acetate for the treatment of advanced breast cancer in postmenopausal women who progressed after tamoxifen therapy, based on objective response rates and time to objective progression of disease. In addition, the drug did not produce the weight gain observed with megestrol acetate therapy. Anastrozole is an effective endocrine agent in the treatment of advanced breast cancer in postmenopausal women.
[Aseptic adenitis in pyoderma gangrenosum]. (1994)

Lymph node involvement has been described in Sneddon-Wilkinson's disease associated with pyoderma gangrenosum. In neutrophilic dermatosis, pulmonary manifestations appear to be the least exceptional of the extra-cutaneous lesions. The pathophysiology has not been elucidated although recent hypotheses suggest that G-CSF could be involved. Corticotherapy is remarkably effective in most cases but thalidomide could be an interesting alternative treatment.