gebhart/patrepeval huggingface dataset:
A fold-back single-chain diabody format enhances the bioactivity of an anti-monkey CD3 recombinant diphtheria toxin-based immunotoxin (2007)

T-cell depleting anti-CD3 immunotoxins have utility in non-human primate models of transplantation tolerance and autoimmune disease therapy. We recently reported that an affinity matured single-chain (scFv) anti-monkey CD3 antibody, C207, had increased binding to T-cells and increased bioactivity in a diphtheria toxin (DT)-based biscFv immunotoxin compared with the parental antibody, FN18. However, FN18 scFvs and their mutant derivatives such as C207 did not exhibit robust bivalent character in the biscFv format. We now report that C207 in a diabody format exhibits a 7-fold increase in binding to T-cells over scFv (C207) indicating considerable divalent character for the diabody. This construct was formed by reducing the V(L)/V(H) linker to five residues and was secreted from Pichia pastoris as the non-covalent dimer. An immunotoxin based on this diabody format was secreted as a non-covalent dimer but was devoid of bioactivity and failed to bind T-cells, suggesting steric hindrance from the two large closely positioned truncated DT moieties. We constructed a single-chain diabody immunotoxin by fusing to the truncated DT C-terminus L1-VL-L1-VH-L2-VL-L1-VH where L1 is a five-residue linker and L2 is the longer (G4S)3 linker permitting interactions between the distal and proximal VL/VH domains. This 'fold-back' immunotoxin was secreted predominantly as the monomer and exhibited a 5- to 7-fold increase in bioactivity over DT390biscFv(C207) and depleted monkey T-cells in vivo.
The P190, P210, and P230 Forms of the BCR/ABL Oncogene Induce a Similar Chronic Myeloid Leukemia–like Syndrome in Mice but Have Different Lymphoid Leukemogenic Activity (1999)

The product of the Philadelphia chromosome (Ph) translocation, the BCR/ABL oncogene, exists in three principal forms (P190, P210, and P230 BCR/ABL) that are found in distinct forms of Ph-positive leukemia, suggesting the three proteins have different leukemogenic activity. We have directly compared the tyrosine kinase activity, in vitro transformation properties, and in vivo leukemogenic activity of the P190, P210, and P230 forms of BCR/ABL. P230 exhibited lower intrinsic tyrosine kinase activity than P210 and P190. Although all three oncogenes transformed both myeloid (32D cl3) and lymphoid (Ba/F3) interleukin (IL)-3-dependent cell lines to become independent of IL-3 for survival and growth, their ability to stimulate proliferation of Ba/F3 lymphoid cells differed and correlated directly with tyrosine kinase activity. In a murine bone marrow transduction/transplantation model, the three forms of BCR/ABL were equally potent in the induction of a chronic myeloid leukemia (CML)-like myeloproliferative syndrome in recipient mice when 5-fluorouracil (5-FU)-treated donors were used. Analysis of proviral integration showed the CML-like disease to be polyclonal and to involve multiple myeloid and B lymphoid lineages, implicating a primitive multipotential target cell. Secondary transplantation revealed that only certain minor clones gave rise to day 12 spleen colonies and induced disease in secondary recipients, suggesting heterogeneity among the target cell population. In contrast, when marrow from non- 5-FU-treated donors was used, a mixture of CML-like disease, B lymphoid acute leukemia, and macrophage tumors was observed in recipients. P190 BCR/ABL induced lymphoid leukemia with shorter latency than P210 or P230. The lymphoid leukemias and macrophage tumors had provirus integration patterns that were oligo- or monoclonal and limited to the tumor cells, suggesting a lineage-restricted target cell with a requirement for additional events in addition to BCR/ABL transduction for full malignant transformation. These results do not support the hypothesis that P230 BCR/ABL induces a distinct and less aggressive form of CML in humans, and suggest that the rarity of P190 BCR/ABL in human CML may reflect infrequent BCR intron 1 breakpoints during the genesis of the Ph chromosome in stem cells, rather than intrinsic differences in myeloid leukemogenicity between P190 and P210.
The sintered microsphere matrix for bone tissue engineering: In vitro osteoconductivity studies (2002)

A tissue engineering approach has been used to design three-dimensional synthetic matrices for bone repair. The osteoconductivity and degradation profile of a novel polymeric bone-graft substitute was evaluated in an in vitro setting. Using the copolymer poly(lactide-co-glycolide) [PLAGA], a sintering technique based on microsphere technology was used to fabricate three-dimensional porous scaffolds for bone regeneration. Osteoblasts and fibroblasts were seeded onto a 50:50 PLAGA scaffold. Morphologic evaluation through scanning electron microscopy demonstrated that both cell types attached and spread over the scaffold. Cells migrated through the matrix using cytoplasmic extensions to bridge the structure. Cross-sectional images indicated that cellular proliferation had penetrated into the matrix approximately 700 microm from the surface. Examination of the surfaces of cell/matrix constructs demonstrated that cellular proliferation had encompassed the pores of the matrix by 14 days of cell culture. With the aim of optimizing polymer composition and polymer molecular weight, a degradation study was conducted utilizing the matrix. The results demonstrate that degradation of the sintered matrix is dependent on molecular weight, copolymer ratio, and pore volume. From this data, it was determined that 75:25 PLAGA with an initial molecular weight of 100,000 has an optimal degradation profile. These studies show that the sintered microsphere matrix has an osteoconductive structure capable of functioning as a cellular scaffold with a degradation profile suitable for bone regeneration.
Proteins Associated with Adaptation of Cultured Tobacco Cells to NaCl (1985)

Cultured tobacco cells (Nicotiana tabacum L. cv Wisconsin 38) adapted to grow in medium containing high levels of NaCl or polyethylene glycol (PEG) produce several new or enhanced polypeptide bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The intensities of some of the polypeptide bands (molecular weights of 58, 37, 35.5, 34, 26, 21, 19.5, and 18 kilodaltons) increase with increasing levels of NaCl adaptation, while the intensities of other polypeptide bands (54, 52, 17.5, and 16.5 kilodaltons) are reduced. Enhanced levels of 43- and 26-kilodalton polypeptides are present in both NaCl and PEG-induced water stress adapted cells but are not detectable in unadapted cells. In addition, PEG adapted cells have enhanced levels of 29-, 17.5-, 16.5-, and 11-kilodalton polypeptides and reduced levels of 58-, 54-, 52-, 37-, 35.5-, 34-, 21-, 19.5-, and 18-kilodalton polypeptide bands.Synthesis of 26-kilodalton polypeptide(s) occurs at two different periods during culture growth of NaCl adapted cells. Unadapted cells also incorporate (35)S into a 26-kilodalton polypeptide during the later stage of culture growth beginning at midlog phase. The 26-kilodalton polypeptides from adapted and unadapted cells have similar partial proteolysis peptide maps and are immunologically cross-reactive. During adaptation to NaCl, unadapted cells synthesize and accumulate a major 26-kilodalton polypeptide, and the beginning of synthesis corresponds to the period of osmotic adjustment and culture growth. From our results, we suggest an involvement of the 26-kilodalton polypeptide in the adaptation of cultured tobacco cells to NaCl and water stress.
New forms of democracy (1986)

New Forms of Democracy explores the idea of extending democracy to new domains, a question which no single text addresses broadly. It therefore contributes to the continuing debate about this central concept of political and social theory. At a time when some vitality appears to be going out of the traditional Western liberal democracies (with fewer people joining parties and voting at elections) new growth points for political activity are simultaneously appearing. The book considers increasing the scope of democracy and applying it to the private sphere, the workplace, bureaucracies, and to military and foreign policy. It investigates new methods by which the democratic process could be conducted. This includes a discussion of electoral systems and an assessment of the possibilities of discovering popular preferences using new technological developments - such as direct democracy through mass electronic communications networks. The extent to which these ideas and proposals can be practically applied is also discussed. New Forms of Democracy draws on examples from many countries. It is critically concerned with examining new initiatives from below as well as new developments in formal political and policy agendas. In short, in spanning both theoretical and empirical questions, this book offers a unique account of the possibilities for democracy in the twentieth century.
Monovalent Interactions of Galectin-1 (2010)

Galectin-1, a β-galactoside binding lectin involved in immunoregulation and cancer, binds natural and many synthetic multivalent glycoconjugates with an apparent glycoside cluster effect, that is, affinity above and beyond what would be expected from the concentration of the determinant sugar. Here we have analyzed the mechanism of such cluster effects in solution at physiological concentration using a fluorescence anisotropy assay with a novel fluorescent high-affinity galectin-1 binding probe. The interaction of native dimeric and monomeric mutants of rat and human galectin-1 with mono- and divalent small molecules, fetuin, asialofetuin, and human serum glycoproteins was analyzed. Surprisingly, high-affinity binding did not depend much on the dimeric state of galectin-1 and thus is due mainly to monomeric interactions of a single carbohydrate recognition domain. The mechanism for this is unknown, but one possibility includes additional interactions that high-affinity ligands make with an extended binding site on the carbohydrate recognition domain. It follows that such weak additional interactions must be important for the biological function of galectin-1 and also for the design of galectin-1 inhibitors.
Coronary laser angioplasty (1994)

With the widespread growth of percutaneous transluminal coronary angioplasty (PTCA), the realization of limitations of balloon angioplasty stimulated the development of alternative revascularization approaches such as laser angioplasty. PTCA is best suited for the treatment of discrete atherosclerotic stenoses, with lower success rates and more difficult application in patients with diffuse atherosclerotic disease or total occlusions [1-3]. Moreover, despite an initially high primary success rate, coronary angioplasty is still plagued by a restenosis rate as high as 57% [4]. The potential advantages of laser angioplasty address the limitations of PTCA. In contrast to balloon angioplasty where the plaque material is compressed or displaced, laser angioplasty ablates the plaque material [5]. This bulk removal of plaque material could improve acute procedural success rates, decrease complication rates, treat "untreatable" lesions, and decrease restenosis rates. Because laser energy can vaporize atherosclerotic plaque, there may be no requirement for a preexisting channel, and therefore laser angioplasty may have a high success rate for the treatment of coronary occlusions. In its best embodiment, laser angioplasty offers the potential for passing a fiberoptic catheter through the entire length of the coronary circulation to vaporize all atherosclerotic plaque along the arterial wall. This applicability for the treatment of diffuse atherosclerotic disease would offer treatment opportunities currently unavailable with conventional bypass surgery or angioplasty.
Targeted delivery of tissue factor to the ED-B domain of fibronectin, a marker of angiogenesis, mediates the infarction of solid tumors in mice. (2001)

The selective thrombosis of tumor blood vessels, leading to the starvation and subsequent death of tumor cells, is an attractive anticancer strategy. Here we report that a fusion protein, consisting of an antibody fragment specific for the oncofoetal ED-B domain of fibronectin fused to the extracellular domain of tissue factor, selectively targets tumor blood vessels in vivo. Furthermore, this fusion protein mediates the complete and selective infarction of three different types of solid tumors in mice. At the highest doses administered, complete tumor eradication was observed in 30% of the mice treated without apparent side effects. These results are of therapeutic relevance because the ED-B domain of fibronectin, a naturally occurring marker of angiogenesis identical in mouse and man, is expressed in the majority of aggressive solid tumors but is undetectable in normal vessels and tissues.
Total Knee Arthroplasty in the Valgus Knee (2002)

The valgus knee presents a unique set of problems that must be addressed during total knee arthroplasty. Both bone and soft-tissue deformities complicate restoration of proper alignment, positioning of components, and attainment of joint stability. The variables that may need to be addressed include lateral femoral condyle or tibial plateau deficiencies secondary to developmental abnormalities, and/or wear; primary or acquired contracture of the lateral capsular and ligamentous structures; and, occasionally, laxity of the medial collateral ligament. Understanding the specific pathologic anatomy associated with the valgus knee is a prerequisite to selecting the proper surgical method to optimize component position and restore soft-tissue balance.
PRIMERSELECT (1997)

The polymerase chain reaction (PCR) has proven to be one of the most useful tools available to the modern molecular biology laboratory. One of the more important aspects of successful PCR is the proper design of primers. Because PCR is fairly robust, you may have had success designing primers manually. Failures designing primers are usually caused by primer duplexing or false priming sites in the sequence template that may not be obvious to the eye. For these cases, the use of primer software can greatly improve experimental results. Good software can evaluate more accurate (and complex) thermodynamic models than traditional GC content alone. Because you improve accuracy in free energy and melting temperature prediction as well as accuracy evaluating primer duplexing you can greatly refine primer design from the manual level. Using the computer’s ability to perform more complex sequence and mathematical analysis allows you to start with better primers and finish with higher yield products of greater accuracy.
Performance Testing of Suspension Plasma Sprayed Thermal Barrier Coatings Produced with Varied Suspension Parameters (2015)

Suspension plasma spraying has become an emerging technology for the production of thermal barrier coatings for the gas turbine industry. Presently, though commercial systems for coating production are available, coatings remain in the development stage. Suitable suspension parameters for coating production remain an outstanding question and the influence of suspension properties on the final coatings is not well known. For this study, a number of suspensions were produced with varied solid loadings, powder size distributions and solvents. Suspensions were sprayed onto superalloy substrates coated with high velocity air fuel (HVAF) -sprayed bond coats. Plasma spray parameters were selected to generate columnar structures based on previous experiments and were maintained at constant to discover the influence of the suspension behavior on coating microstructures. Testing of the produced thermal barrier coating (TBC) systems has included thermal cyclic fatigue testing and thermal conductivity analysis. Pore size distribution has been characterized by mercury infiltration porosimetry. Results show a strong influence of suspension viscosity and surface tension on the microstructure of the produced coatings.
Single-vector inducible lentiviral RNAi system for oncology target validation (2009)

The use of RNA interference (RNAi) has enabled loss-of-function studies in mammalian cancer cells and has hence become critical for identifying and validating cancer drug targets. Current transient siRNA and stable shRNA systems, however, have limited utility in accurately assessing the cancer dependency due to their short-lived effects and limited in vivo utility, respectively. In this study, a single-vector lentiviral, Tet-inducible shRNA system (pLKO-Tet-On) was generated to allow for the rapid generation of multiple stable cell lines with regulatable shRNA expression. We demonstrate the advantages and versatility of this system by targeting two polycomb group proteins, Bmi-1 and Mel-18, in a number of cancer cell lines. Our data show that pLKO-Tet-On-mediated knockdown is tightly regulated by the inducer tetracycline and its derivative, doxycycline, in a concentration- and time-dependent manner. Furthermore, target gene expression is fully restored upon withdrawal of the inducing agent. An additional, 17 distinct gene products have been targeted by inducible shRNAs with robust regulation in all cases. Importantly, we functionally validate the ability of the pLKO-Tet-On vector to reversibly silence targeted transcripts in vivo. The versatile and robust inducible lentiviral RNAi system reported herein can therefore serve as a powerful tool to rapidly reveal tumor cell dependence.
Genipin‐crosslinked gelatin microspheres as a drug carrier for intramuscular administration: In vitro and in vivo studies (2003)

Gelatin microspheres have been widely evaluated as a drug carrier. Nevertheless, gelatin dissolves rather rapidly in aqueous environments, making the use of the polymer difficult for the production of long-term delivery systems. This adverse aspect requires the use of a crosslinking agent in forming nonsoluble networks in microspheres. However, the use of crosslinking agents such as formaldehyde and glutaraldehyde can lead to toxic side effects owing to residual crosslinkers. In an attempt to overcome this problem, a naturally occurring crosslinking agent (genipin) was used to crosslink gelatin microspheres as a biodegradable drug-delivery system for intramuscular administration. Glutaraldehyde was used as a control. In the in vitro study, the morphology, dynamic swelling, and antienzymatic degradation of test microspheres were evaluated. In the in vivo study, the biocompatibility and degradability of test microspheres were implanted in the skeletal muscle of a rat model via intramuscular injection. The results obtained in the study suggested that crosslinking of gelatin microspheres with glutaraldehyde or genipin may produce distinct crosslinking structures. The water transport mechanism in both the glutaraldehyde- and genipin-crosslinked gelatin microspheres exhibit anomalous behavior ranging from Fickian to Case-II extremes. The increase of the swelling diameter for the genipin-crosslinked microspheres was significantly less than that observed for the glutaraldehyde-crosslinked microspheres. In the animal study, it was found that the degree in inflammatory reaction for tissues implanted with the genipin-crosslinked microspheres was significantly less than that implanted with the glutaraldehyde-crosslinked microspheres. Additionally, the degradation rate of the genipin-crosslinked microspheres was significantly slower than their glutaraldehyde-crosslinked counterparts. These results indicated that the genipin-crosslinked gelatin microspheres may be used as a long-acting drug carrier for intramuscular administration.
Document Cards: A Top Trumps Visualization for Documents (2009)

Finding suitable, less space consuming views for a document's main content is crucial to provide convenient access to large document collections on display devices of different size. We present a novel compact visualization which represents the document's key semantic as a mixture of images and important key terms, similar to cards in a top trumps game. The key terms are extracted using an advanced text mining approach based on a fully automatic document structure extraction. The images and their captions are extracted using a graphical heuristic and the captions are used for a semi-semantic image weighting. Furthermore, we use the image color histogram for classification and show at least one representative from each non-empty image class. The approach is demonstrated for the IEEE InfoVis publications of a complete year. The method can easily be applied to other publication collections and sets of documents which contain images.
Methoxy-Substituted 3-Formyl-2-phenylindoles Inhibit Tubulin Polymerization (1998)

The aim of this study was the identification of the essential structural elements in the 12-formyl-5,6-dihydroindolo[2, 1-a]isoquinoline system required for the inhibition of tubulin polymerization which is understood to be the predominant mode of action of this class of cytostatics. Since 2-phenylindole forms the main fragment of this tetracycle, it was used as the basic structure and modified with respect to the number and positions of the oxygen functions in the aromatic rings. Further modifications related to the nitrogen, which was both replaced by oxygen and sulfur and alkylated. All derivatives were tested for cytostatic activity in human breast cancer cells (MDA-MB 231, MCF-7) and inhibition of tubulin polymerization. The spectrum of activity ranged from inactive to IC50 values of 35 nM (cell growth inhibition) and 1.5 microM (tubulin polymerization), respectively, for the most active derivative 3e (3-formyl-6-methoxy-2-(4-methoxyphenyl)indole). Although the correlation between antiproliferative activity and inhibition of tubulin polymerization was not very pronounced, all of the potent cytostatic agents in this study disrupted microtubule assembly completely at the standard concentration of 40 microM. By fluorescence microscopy it was demonstrated that the derivative 3e degrades the cytoskeleton in a similar fashion as colchicine does leading to the condensation of the microtubules around the nucleus after treatment. The comparison between hydroxy and methoxy derivatives revealed a striking difference between the 2-phenylindole derivatives and the indoloisoquinolines. In the 2-phenylindole series, the methoxy compounds were much more effective than the free phenols, whereas in the tetracyclic system the effect of the hydroxy derivatives exceeded that of the methylated compounds by 1 order of magnitude. Preliminary studies on the binding mode showed that both the 2-phenylindole derivatives and the indoloisoquinolines bind to the colchicine site on tubulin.
Interleukin 8 (NAP-1) and related chemotactic cytokines (1991)

Neutrophil activation and the effects of interleukin-8/neutrophil-activating peptide 1, M. Baggiolini et al NMR and X-ray analysis of the three dimensional structure of interleukin-8, G.M. Clore et al regulation of IL-8 production and the characteristics of the receptors for IL-8, N. Mukaida and K. Matsushima generation of NAP-1 and related peptides in psoriasis and other inflammatory skin diseases, J.M. Schroder generation and properties of neutrophil-activating peptide 2, A. Walz structural, regulatory and functional studies of the GRO gene and protein, R. Sager et al macrophage inflammatory proteins 1 and 2 - an overview, B. Sherry et al monocyte chemoattractant protein-1 - structure and function, T. Yoshimura and E.J. Leonard.