gebhart/patrepeval huggingface dataset:
Aflibercept in Epithelial Ovarian Carcinoma (2009)

Angiogenesis is a hallmark of malignant transformation. With improved understanding of angiogenic signaling in both the normal and malignant state, there have been a number of agents developed that target VEGF signaling. These targeted agents can affect downstream VEGF signal transduction via unique mechanisms at different cellular and extracellular locations. The aflibercept, or VEGF-Trap, molecule is the subject of this article. Its molecular structure, pharmacokinetic and pharmacodynamic profile, and preclinical and early clinical data in epithelial ovarian carcinoma is reviewed. For comparison, other anti-angiogenic agents that have been or are currently being studied in epithelial ovarian carcinoma are also summarized. Finally, the anticipated role of aflibercept in the treatment of epithelial ovarian carcinoma is also discussed.
Effects of Molecular Weight on the Structure of Poly(phenylene sulfide) Crystallized at Low Temperatures (1997)

We report a study of the effects of molecular weight on the structure and properties of poly(phenylene sulfide), PPS, crystallized from the rubbery amorphous state at temperatures just above the glass transition. PPS films were characterized using temperature-modulated differential scanning calorimetry (MDSC), small angle X-ray scattering (SAXS), and dynamic mechanical analysis (DMA). For samples crystallized so as to have the same half-time, we find (1) the degree of crystallinity, χc, is not dependent upon molecular weight and (2) as the molecular weight increases, the heat capacity increment at the glass transition increases. These results suggest that lower molecular weight PPS contains a greater fraction of the rigid amorphous phase, probably as a result of formation of taut tie molecules between crystals. It is found from DMA that molecular weight is the determining factor that affects the Young's modulus value at the higher temperature. A lower E‘ is observed for the higher molecular weight material. MDSC data suggest that higher molecular weight PPS has a slower crystallization rate and reorganization rate. The amount of crystals formed during heating is smaller in higher molecular weight PPS, and this may be the explanation for the reduced Young's modulus above Tg.
Evaluation of Protective Effects of Trehalose on Desiccation of Epithelial Cells in Three Dimensional Reconstructed Human Corneal Epithelium (2012)

CLSM and an in vitro cell viability assays could be successfully used for the characterization of 3D-HCE tissue. We demonstrated the protective role of trehalose using reconstructed corneal epithelium (3D-HCE), which mimics HCE and has the potential to become a valuable model in ophthalmic research.
Phylogenetic relationships between Bacillus species and related genera inferred from comparison of 3′ end 16S rDNA and 5′ end 16S–23S ITS nucleotide sequences (2003)

The nucleotide sequences of the 3' end of the 16S rDNA and the 16S-23S internal transcribed spacer (ITS) of 40 Bacillaceae species were determined. These included 21 Bacillus, 9 Paenibacillus, 6 Brevibacillus, 2 Geobacillus, 1 Marinibacillus and 1 Virgibacillus species. Comparative sequence analysis of a 220 bp region covering a highly conserved 150 bp sequence located at the 3' end of the 16S rRNA coding region and a conserved 70 bp sequence located at the 5' end of the 16S-23S ITS of the 40 species and six sequences available in GenBank were used to infer the phylogenetic relationships between all 46 taxa. When a maximal distance (D(max), where D refers to the number of nucleotide substitutions per site) of 0.31 was introduced as a threshold to determine groupings, 10 phylogenetically distinct clusters were revealed. Twenty-six Bacillus species were separated in seven groups (I, II, III, IV, V, VI and X), but Bacillus circulans remained ungrouped. All six Brevibacillus species under study were in Group VII. The nine Paenibacillus species fell into two distinct groups (VIII and IX). Species with D(max) values within 0.05 were considered to be very closely related. These were Bacillus psychrophilus and Bacillus psychrosaccharolyticus in Group II; 'Bacillus maroccanus' and Bacillus simplex in Group II; Bacillus amyloliquefaciens, Bacillus atrophaeus, Bacillus mojavensis and Bacillus subtilis in Group VI; Bacillus fusiformis and Bacillus sphaericus in Group VI; Brevibacillus brevis and Brevibacillus formosus in Group VII; Paenibacillus gordonae and Paenibacillus validus in Group VIII; and Bacillus anthracis, Bacillus cereus, Bacillus mycoides and Bacillus thuringiensis in Group X. The phylogenetic classification presented here is, in general, in agreement with current classifications based on phenotypic and molecular data. Our findings suggest, however, that in some cases, further divisions or, conversely, further groupings might be warranted. Should current classifications be re-examined in the light of our results, D(max) values of 0.31 and 0.05, as exemplified here, may prove useful threshold values for the grouping of Bacillaceae into taxa akin to genera and species, respectively. These D(max) thresholds may also reveal, in a different way, bacterial species for which further characterization might be warranted for proper classification and/or reassignment.
A 900 MHz CMOS LC-oscillator with quadrature outputs (2002)

The local oscillator (LO) in a wireless transceiver satisfies many exacting requirements. A variable frequency enables a phase-locked loop (PLL) to servo the LO to a stable lower frequency reference, or to correct frequency errors from measurements on the received signal. A low phase noise ensures little interference with nearby channels. A large LO voltage-swing means that it can drive a mixer with greater linearity. Finally, in single-sideband applications, the LO must supply precise quadrature phases. Low phase noise mandates use of a high-Q resonator to tune the LO, although most RF resonators are usually not integrable on ICs. Quadrature outputs are usually derived from RC phase-shift of a single-phase LO output, but this is susceptible to component inaccuracy and loss in LO amplitude. The authors present a 900 MHz oscillator circuit implemented in 1 /spl mu/m CMOS that affords modestly low-phase noise, has variable frequency with large output swing, and provides quadrature-phase outputs from two identical coupled oscillators, connected in such a way that they exert a mutual squelch when their relative phase is not in quadrature. The coupled oscillators synchronize to exactly the same frequency, in spite of mismatches in their resonant circuits.
Landfarming of petroleum wastes in a cold dry climate of Tierra del Fuego: (Effects on soil and vegetation) (2000)

Fil: Mendoza, Rodolfo Ernesto. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Parque Centenario. Instituto de Investigaciones en Biociencias Agricolas y Ambientales. Universidad de Buenos Aires. Facultad de Agronomia. Instituto de Investigaciones en Biociencias Agricolas y Ambientales; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro de Ecofisiologia Vegetal (i); Argentina
Site-specific cleavage of left-handed DNA in pBR322 by lambda-tris(diphenylphenanthroline)cobalt(III). (1985)

The chiral complex tris(4,7-diphenyl-1,10-phenanthroline)cobalt(III), lambda-Co(DiP)3(3+), binds to and, with photoactivation, cleaves left-handed DNA helices, thereby providing a unique molecular probe for local DNA conformation. We have mapped the specific left-handed sites where lambda-Co(DiP)3(3+) cleaves in the plasmids pBR322 and pLP32, which is the derivative of pBR322 containing a Z-form d(C-G)16 insert. For pLP32, a primary cleavage is at the insert; for native pBR322, cleavage occurs at four discrete sites: 1.45, 2.3, 3.3, and 4.2 kilobase pairs. These sites correspond to segments of alternating purine-pyrimidines. Moreover, these positions map to the ends of the three distinct coding regions in pBR322: the tetracycline-resistance gene, the origin of replication, and either end of the ampicillin-resistance (beta-lactamase) gene. The locations of these left-handed segments suggest to us that Z-DNA might serve as a conformational punctuation mark to demarcate the ends of genes.
The structural basis for insulin-like growth factor I receptor high affinity binding. (1988)

We have recently identified high and low affinity insulin-like growth factor I (IGF I) binding sites in solubilized human placental membranes and purified the high affinity IGF I receptor by IGF I affinity chromatography (Tollefsen, S. E., Thompson, K., and Petersen, D. J. (1987) J. Biol. Chem. 262, 16461-16469). To define the structural basis for high affinity IGF I binding, we have examined the effect of disulfide bond reduction on the binding parameters of the high affinity IGF I receptor. We find that the disulfide bonds linking the two alpha beta dimers of the IGF I receptor heterotetramer are reduced by incubation at pH 8.75 with 2 mM dithiothreitol (DTT) for 5 min at room temperature. Gel filtration chromatography on a Superose 12 fast protein liquid chromatography column indicates that the alpha beta dimers do not remain associated by noncovalent interactions after reduction. Scatchard plots of IGF I binding to the IGF I receptor incubated at pH 8.75 with or without DTT indicate that the IGF I receptor alpha beta dimers have a 6.1 +/- 1.6 (mean +/- S.D.) times lower affinity than the heterotetramer for IGF I. The total binding capacity of the IGF I receptor treated with DTT is 1.6 +/- 0.3 (mean +/- S.D.) times higher than that of an equal amount of receptor treated without DTT. These results are consistent with a model in which the heterotetramer binds a single IGF I molecule with high affinity, whereas each of the two alpha beta dimers binds an IGF I molecule with lower affinity after dissociation. We conclude that association of two alpha beta dimers is required for formation of an IGF I receptor with high affinity for its ligand.
Pharmacokinetics of recombinant human granulocyte colony-stimulating factor conjugated to polyethylene glycol in rats. (1991)

The pharmacokinetics of recombinant human granulocyte colony-stimulating factor conjugated to polyethylene glycol (PEG-rhG-CSF) and rhG-CSF were studied in male Sprague-Dawley rats. The serum concentration after i.v. administration at a dose of 100 micrograms protein/kg was investigated by a bioassay. The serum rhG-CSF concentration decreased steadily after injection with a terminal half-life of 1.79 h. The PEG-rhG-CSF concentration after injection decreased much more slowly with a half-life of 7.05 h. The slower disappearance of PEG-rhG-CSF resulted in a greater area under the concentration-time curve. The neutrophil count after 100 micrograms of protein/kg of rhG-CSF administration reached a peak 12 h after injection and returned to the control level 48 h after injection. The neutrophil count after 100 micrograms of protein/kg of PEG-rhG-CSF administration was identical to that of rhG-CSF after 12 h but the highest level was maintained for 24 to 72 h after injection and returned to the control level after 168 h. These data indicated that PEG-rhG-CSF administration exerted a sustained biological effect on peripheral blood neutrophils. It is expected that PEG-rhG-CSF may contribute greatly to human G-CSF treatment because it has a prolonged neutrophil-proliferating activity enabling fewer administrations.
A comparison of lycopene and astaxanthin absorption from corn oil and olive oil emulsions (2000)

The effect of different oils on the absorption of carotenoids was investigated in mesenteric lymph duct cannulated rats. Sixteen treatment emulsions containing increasing concentrations of either lycopene (LYC) or astaxanthin (AST) (5, 10, 15, 20 micromol/L) were prepared with olive oil or corn oil and continuously infused into the duodenum of the rat. Absorption of carotenoids into the mesenteric lymph duct was determined. Absorption of LYC and AST from both oils increased with the amount infused into the duodenum. The average recovery of AST in the lymph from the olive oil emulsion was 20% but was decreased to 13% from emulsions containing corn oil. Lycopene was not as well absorbed as AST. The average recovery of LYC was 6% from olive oil emulsions but only 2.5% when infused with corn oil. The LYC used in this study was isolated from tomato paste and was primarily in the all-trans form. We did not observe any significant isomerization of all-trans LYC to 9-cis LYC during absorption. We conclude that the type of oil with which a carotenoid is consumed can influence its absorption.
Roles of matrix metalloproteinases in cancer progression and their pharmacological targeting (2010)

Matrix metalloproteinases (MMPs) consist of a multigene family of zinc-dependent extracellular matrix (ECM) remodeling endopeptidases implicated in pathological processes, such as carcinogenesis. In this regard, their activity plays a pivotal role in tumor growth and the multistep processes of invasion and metastasis, including proteolytic degradation of ECM, alteration of the cell-cell and cell-ECM interactions, migration and angiogenesis. The underlying premise of the current minireview is that MMPs are able to proteolytically process substrates in the extracellular milieu and, in so doing, promote tumor progression. However, certain members of the MMP family exert contradicting roles at different stages during cancer progression, depending among other factors on the tumor stage, tumor site, enzyme localization and substrate profile. MMPs are therefore amenable to therapeutic intervention by synthetic and natural inhibitors, providing perspectives for future studies. Multiple therapeutic agents, called matrix metalloproteinase inhibitors (MMPIs) have been developed to target MMPs, attempting to control their enzymatic activity. Even though clinical trials with these compounds do not show the expected results in most cases, the field of MMPIs is ongoing. This minireview critically evaluates the role of MMPs in relation to cancer progression, and highlights the challenges, as well as future prospects, for the design, development and efficacy of MMPIs.
[125I/127I]IodoHoechst 33342:  Synthesis, DNA Binding, and Biodistribution (1996)

An iodinated analog of the DNA-minor-groove-binding agent Hoechst 33342 has been synthesized and evaluated for DNA binding and tumor targeting. The bis-benzimidazole ring system of the title compound was constructed from the piperazinyl terminus via a Pinner-type cyclization followed by oxidative cyclization of the diamine Schiff base. To synthesize radioiodoHoechst 33342, (trimethylstannyl)Hoechst 33342 was prepared by the same strategy and subjected to mild radioiododestannylation in the presence of lactoperoxidase. After purification by HPLC, the radiochemical was separated in carrier-free form with > 85% radiochemical yield and > 99% chemical and radiochemical purity. Fluorescence spectrometric analysis of the binding of iodoHoechst 33342 to calf thymus DNA gave an equilibrium association constant (Ka) of 2.57 x 10(7) M-1 comparable to the Ka value of Hoechst 33342. Fluorescence microscopy of viable V79 cells demonstrated that the iodinated dye stained the nuclei with avidity similar to that of the noniodinated dye. The biodistribution of [125I]-iodoHoechst 33342 in LS174T tumor-bearing athymic mice 4 h postadministration showed a tumor uptake of 3-4% injected dose per gram (ID/g), tumor/blood ratio of 6-8, and tumor/ nontumor ratios above unity for most organs. A low thyroid uptake (approximately 2% ID/g) indicated that the radiochemical did not deiodinate and was stable in vivo.
Inhibition of Nogo: A key strategy to increase regeneration, plasticity and functional recovery of the lesioned central nervous system (2005)

In the adult central nervous system (CNS) myelin and oligodendrocytes, Nogo-A exerts a growth inhibitory function leading to restricted axonal regeneration. After development of different anti-Nogo-A antibodies and other Nogo-A blocking reagents their application has recently been studied in various in vivo animal models of spinal cord injury and stroke. These studies show that intracerebral application of Nogo-A-inactivating reagents leads to enhanced regeneration and compensatory sprouting, structural reorganization or plasticity, and functional recovery as seen in different behavioural analyses.
Novel Polymeric Materials from Vegetable Oils and Vinyl Monomers: Preparation, Properties, and Applications (2009)

Veggie-based products: Vegetable-oil-based polymeric materials, prepared by free radical, cationic, and olefin metathesis polymerizations, range from soft rubbers to ductile or rigid plastics, and to high-performance biocomposites and nanocomposites. They display a wide range of thermophysical and mechanical properties and may find promising applications as alternatives to petroleum-based polymers.Vegetable oils are considered to be among the most promising renewable raw materials for polymers, because of their ready availability, inherent biodegradability, and their many versatile applications. Research on and development of vegetable oil based polymeric materials, including thermosetting resins, biocomposites, and nanocomposites, have attracted increasing attention in recent years. This Minireview focuses on the latest developments in the preparation, properties, and applications of vegetable oil based polymeric materials obtained by free radical, cationic, and olefin metathesis polymerizations. The novel vegetable oil based polymeric materials obtained range from soft rubbery materials to ductile or rigid plastics and to high-performance biocomposites and nanocomposites. These vegetable oil based polymeric materials display a wide range of thermophysical and mechanical properties and should find useful applications as alternatives to their petroleum-based counterparts.
Acetalated dextran is a chemically and biologically tunable material for particulate immunotherapy (2009)

Materials that combine facile synthesis, simple tuning of degradation rate, processability, and biocompatibility are in high demand for use in biomedical applications. We report on acetalated dextran, a biocompatible material that can be formed into microparticles with degradation rates that are tunable over 2 orders of magnitude depending on the degree and type of acetal modification. Varying the degradation rate produces particles that perform better than poly(lactic-co-glycolic acid) and iron oxide, two commonly studied materials used for particulate immunotherapy, in major histocompatibility complex class I (MHC I) and MHC II presentation assays. Modulating the material properties leads to antigen presentation on MHC I via pathways that are dependent or independent of the transporter associated with antigen processing. To the best of our knowledge, this is the only example of a material that can be tuned to operate on different immunological pathways while maximizing immunological presentation.
Reaktionen von Chloracetaldehyd mit aromatischen Kohlenwasserstoffen, Phenolen und Phenoläthern (1969)

Abstract Durch Kondensation von Chloracetaldehyd mit aromatischen Kohlenwasserstoffen, Phenolen, Phenoläthern bzw. Thiophenoläthern und Umlagerung der Kondensationsprodukte bei erhöhter Temperatur können in einfacher Weise mit z. T. ausgezeichneten Ausbeuten 4.4′‐disubstituierte Stilbene gewonnen werden.
Ex vivo porcine model to measure pH dependence of chemical exchange saturation transfer effect of glycosaminoglycan in the intervertebral disc (2013)

gagCEST is sensitive to pH and enables investigation of the IVD pH status. Iopromide CEST is independent of the local GAG concentration and has the potential for measuring pH in the IVD.
Cytotoxic T lymphocytes do not appear to select for mutations in an immunodominant epitope of simian immunodeficiency virus gag (1992)

Studies to date assessing HIV escape from CTL in vivo have yielded conflicting results. Previous studies have demonstrated that simian immunodeficiency virus of macaques (SIVmac)-infected rhesus monkeys expressing the MHC class I allele Mamu-A*01 reproducibly develop a gag-specific CTL response limited to a 9-amino acid epitope of the SIVmac gag protein (residues 182-190 within peptide 11C). To determine whether CTL have a role in selecting for AIDS virus mutants, we examined mutations in SIVmac proviral DNA encoding this gag CTL epitope in PBL of infected rhesus monkeys. Three Mamu-A*01+ rhesus monkeys were infected with SIVmac and assessed for gag- and peptide 11C-specific CTL responses. This specific CTL response was maintained in two monkeys, but lost in the third animal 2 yr after infection. The generation of proviral gag mutations was then determined by sequencing 500-bp proviral fragments amplified from fresh PBL obtained from the monkeys more than 2.5 yr after infection. Although numerous point mutations were characterized in 131 polymerase chain reaction-generated clones of SIVmac gag, only four mutations within the gag CTL epitope-coding region of the genome were identified. Comparison of synonymous and nonsynonymous nucleotide substitutions in the regions encoding peptide 11C (p11C) and the flanking gag protein indicated a lack of selective pressure for viral mutations in the CTL epitope coding region. Interestingly, a predominant gag mutant encoding a single amino acid change in p11C was found in a monkey which lost its CTL activity. However, even in this setting there was no evidence for selection of mutations in the CTL epitope coding region when compared with the flanking region. Furthermore, synthetic peptides corresponding to all naturally occurring variants in the gag epitope-coding region were recognized by cloned and bulk cultured effector cells of the infected monkeys with persistent CTL. These results indicate that SIVmac gag- and p11C-specific CTL do not select for mutations in the immunodominant epitope-coding region and that the naturally occurring mutants do not appear to escape CTL recognition.
An accuracy center in the ribosome conserved over 2 billion years. (1993)

The accuracy of translation in Escherichia coli is profoundly influenced by three interacting ribosomal proteins, S12, S4, and S5. Mutations at lysine-42 of S12, originally isolated as causing resistance to streptomycin, increase accuracy. Countervailing "ribosomal ambiguity mutations" (ram) in S4 or S5 decrease accuracy. In the eukaryotic ribosome of Saccharomyces cerevisiae, mutations in SUP46 and SUP44, encoding the proteins equivalent to S4 and S5, lead to omnipotent suppression--i.e., to less accurate translation. The evolution of ribosomal protein S12 can be traced, by comparison with archaebacteria and Tetrahymena, to S28 of S. cerevisiae, even though the two proteins share only very limited regions of homology. However, one region that has been conserved contains a lysine residue whose mutation leads to increased accuracy in E. coli. We have introduced into S28 of yeast the same amino acid substitutions that led to the original streptomycin-resistant mutations in E. coli. We find that they have a profound effect on the accuracy of translation and interact with SUP44 and SUP46, just as predicted from the E. coli model. Thus, the interplay of these three proteins to provide the optimal level of accuracy of translation has been conserved during the 2 billion years of evolution that separate E. coli from S. cerevisiae.