gebhart/patrepeval huggingface dataset:
A cerebral primitive neuroectodermal tumor in a squirrel monkey (Saimiri sciureus) (1999)

An adult squirrel monkey with a history of long-term exposure to microwave radiation was found at necropsy to have a malignant tumor of the right cerebral cortex. Gross examination revealed a mass with expanding borders in the right frontoparietal cortex with compression of the adjacent lateral ventricle. Microscopy revealed a tumor composed of sheets of moderate-sized cells, resembling an oligodendroglioma, with clear cytoplasm and central nuclei interrupted by delicate vasculature. Malignant features were present in the form of marked nuclear pleomorphism, frequent mitotic figures, and focal necrosis. A neuronal cell origin for this tumor was supported by immunohistochemical analysis, which revealed immunopositivity for neurofilament proteins and neuron-specific enolase. Staining for vimentin and glial fibrillary acid protein was negative, except in reactive astrocytes at the tumor margins and adjacent to intra-tumoral blood vessels. Antibody activity against Ki-67 antigen, a marker of rapidly proliferating tumor cells, and p53 oncoprotein was strongly positive, indicative of the aggressive and malignant nature of this tumor. The tumor was diagnosed as a cerebral primitive neuroectodermal tumor.
Neuron-specific enolase concentrations in blood as a prognostic parameter in cerebrovascular diseases. (1994)

The course of plasma NSE levels is seen as a relevant parameter for assessing the prognosis of cerebral hypoxia-ischemia. Additionally, it may prove to be a useful tool for monitoring space-occupying brain infarctions and intracerebral hemorrhages and therefore may contribute to improved therapeutic management of severe cerebrovascular diseases.
ST2 as a Marker for Risk of Therapy-Resistant Graft-versus-Host Disease and Death (2013)

ST2 levels measured at the initiation of therapy for GVHD and during the first month after transplantation improved risk stratification for treatment-resistant GVHD and death without relapse after transplantation. (Funded by the National Institutes of Health.)
Antithrombotic effects of controlled inhibition of factor VIII with a partially inhibitory human monoclonal antibody in a murine vena cava thrombosis model (2002)

The human monoclonal antibody mAb-LE2E9 partially inactivates human factor VIII (FVIII), leaving approximately 10% residual activity. The antithrombotic efficacy of the antibody was evaluated in mouse models of inferior vena cava thrombosis. Thrombi were induced in wild-type mice given either the antibody or saline. No thrombi occurred in any of 8 mice treated with mAb-LE2E9, whereas 6 of 8 control mice developed thrombi (P =.007). Treatment with mAb-LE2E9 did not result in a severe bleeding phenotype: a tail-cutting experiment that resulted in death of C57BL/6 FVIII-deficient (FVIII(-/-)) mice did not cause hemorrhagic death in mice treated with mAb-LE2E9. To evaluate the antithrombotic effect of mAb-LE2E9 in presence of human FVIII, thrombus formation was induced in FVIII(-/-) mice reconstituted intravenously with recombinant human FVIII (rhFVIII) or rhFVIII preincubated with mAb-LE2E9. Only 1 of 9 mice produced a thrombus in the rhFVIII/antibody complex-treated group, compared with 7 of 9 in the control group (P =.015). FVIII(-/-) mice were also reconstituted with rhFVIII and then injected with either mAb-LE2E9 or saline. One of 14 mice in the group treated with the antibody developed a thrombus, compared with 10 of 14 in the control group (P =.001). The thrombi occurring in antibody-treated animals were smaller than in controls (P <.01). All animals survived, and there were no bleeding complications. Thus, the mAb-LE2E9 antibody inhibits thrombosis without causing an overt bleeding tendency.
Application of a human tumor colony-forming assay to new drug screening. (1985)

The applicability of a human tumor colony-forming assay to drug screening was investigated in terms of feasibility, validity, and potential for discovering new antitumor drugs. Feasibility was addressed in a pilot study during which basic methods, appropriate assay quality controls, and a standardized protocol for screening were developed. Considerable variability was noted in the availability and colony growth of different tumor types. The majority of the evaluable experiments utilized breast, colorectal, kidney, lung, melanoma, or ovarian tumors. For many tumor types, little evidence of growth was observed, or only rare specimens formed colonies. Colony-forming efficiencies ranged from 0.05 to 0.11% for the six most useful tumors listed above. A set of quality control measures was developed to address technical problems inherent in the assay. Testing of standard agents in the pilot study established that most of these agents could be detected as active. However, it also identified three assay limitations: compounds requiring systemic metabolic activation are inactive; medium constituents may block the activity of certain antimetabolites; and compounds without therapeutic efficacy may be positive in the assay. The assay categorized nontoxic clinically ineffective agents as true negatives with 97% accuracy. Of 79 compounds which were negative in the current National Cancer Institute prescreen (leukemia P388), 14 were active in the assay. Several demonstrated outstanding in vitro activity and are structurally unrelated to compounds already in development or in clinical trials. A subset of these active compounds were found to lack activity in a P388 in vitro colony-forming assay. This indication of differential cytotoxicity to human tumor cells makes this subset of compounds particularly interesting as antitumor drug leads. The demonstrated sensitivity to most standard agents, discrimination of nontoxic compounds, reproducibility of survival values within assays and between laboratories, and evidence of ability to identify active compounds which were negative in the in vivo prescreen suggest that the human tumor colony-forming assay may be a valuable tool for antitumor drug screening. However, because of technical limitations inherent in the current assay methodology, this must be confined to selected tumor types and limited to screening on a moderate scale.
Structural Requirements for the Activation of Rat Anterior Pituitary Adenylate Cyclase by Growth Hormone–Releasing Factor (GRF): Discovery of (N–Ac–Tyr1,d–Arg2)–GRF(l–29)–NH2as a GRF Antagonist on Membranes* (1985)

The efficacy and potency of 14 GH-releasing factor (GRF) analogs, substituted in position 1 to 7, on adenylate cyclase activation in crude homogenates from rat anterior pituitary were related to those of human pancreatic GRF(1-29)-amide and vasoactive intestinal peptide. Among several D-amino acid substitutions, that in position 2 was the only one to yield a super-agonist [with a Kact (concentration required for half-maximal adenylate cyclase activation) 2 times lower than that of GRF(1-29)-NH2]. By contrast, D-isomer substitution in position 1 and 3 was without effect and D-isomer substitution in position 4, 6, or 7 decreased the affinity of the analog. The N-acetylated analog of GRF was as potent and active as the parent peptide, and the identity of the amino acid in position 2 of (N-Ac-Tyr1)-GRF(1-29)-NH2 proved to be determining for enzyme activation, with D-Phe2 and D-Trp2 derivatives acting as partial agonists and the (N-Ac-Tyr1,D-Arg2) analog being an efficient competitive antagonist of GRF(1-29)-NH2. With use of this antagonist, it was possible to demonstrate that GRF and vasoactive intestinal peptide receptors represent distinct entities in the rat anterior pituitary.
Aggregation of colloidal nanoparticles in polymer matrices (2005)

Colloidal nanoparticles may possess many functional properties, whose nature may be electronic, chemical, biological, mechanical, . It is often advantageous to incorporate them into a matrix material, , a polymer solution or melt, or an elastomer, in order to obtain a 'nanomaterial' with additional properties brought in by the filler particles. One of the basic but nonetheless crucial properties is the mechanical strength of such polymer nanocomposites, whose rheological (or mechanical) properties are usually better than those of the pure matrix. The precise origin of this mechanical reinforcement effect, however, remains unclear. In this context, some recent studies of the structure and mechanical properties of a special type of nanocomposites are reviewed here. In silica-latex systems, a latex film with silica inclusions is formed from a colloidal solution of both components. During drying of the solution, the formation of silica domains can be controlled the physico-chemical properties of the solution. Well-defined silica aggregates embedded in a polymer matrix can be generated, and the mechanical properties of the resulting nanocomposite have been shown to be directly correlated to the average structure. We believe that the fine-tuning of the structure of the filler phase opens new perspectives for systematic studies of the reinforcement effect, , by modifying filler-polymer interfacial properties at fixed structure, or by generating original structures.
Solubilization of selected polycyclic aromatic compounds by nonionic surfactants (2006)

Abstract Solubilization of selected polycyclic aromatic compounds (PAC) by biodegradable nonionic surfactants, Tergitol 15‐S‐ X ( X =7 or 9) and Neodol 25–7, was investigated and correlated with micellar properties of these surfactants. These PAC include dibenzofuran, phenanthrene, acenaphthene, fluoranthene, and 9‐chloroanthracene. Tergitol surfactants are mixtures of secondary ethoxylated alcohols, and Neodol 25–7 is a mixture of similar species but has the alcohol group in the primary position. These surfactants have the same chain length of hydrophobic tails and similar numbers of ethylene oxides. The results show that the Neodol surfactant yields micelles having larger hydrophobic core volume and renders a higher solubilization capacity for the PAC solubilizates in comparison with Tergitol surfactants. In general, aggregation numbers and micellar sizes both increase at elevated temperatures still below the cloud point. The micellewater partition coefficients of these PAC by the nonionic surfactants were well correlated to their octanol‐water partition coefficients. Moreover, an estimated log K ow value of 9‐chloanthracene is 4.78.
Surface Immobilization of Catalytic Beacons Based on Ratiometric Fluorescent DNAzyme Sensors:  A Systematic Study (2007)

DNAzyme-based catalytic beacons have the potential for sensing a large number of relevant analytes. Thus, a systematic investigation of factors affecting their performance when immobilized into gold-coated nanocapillary array membranes (NCAMs) was undertaken. Enzyme immobilization times were varied to determine that as little as 15 min was sufficient for ratiometric detection of Pb2+-specific activity, while immobilization density saturated after 1.5 h. Immobilization of the DNAzymes into NCAMs with 600 nm pore size resulted in higher immobilization efficiency and higher enzymatic activity than that with 200 nm pore size. A poly-T linker length between the tethering thiol and first oligonucleotide, used to extend the DNAzyme above the backfilling mercaptohexanol (MCH) monolayer, had no effect on DNAzyme activity. The backfilling method of immobilization, involving backfilling followed by hybridization, was found most effective for DNAzyme activity compared to immobilization of hybridized DNAzyme complex (a 67% loss of activity) or concurrent enzyme and MCH immobilization (75% loss of activity). The backfilling MCH monolayer provided approximately 3.5 times increase in activity compared to DNAzyme assembled without MCH, and was over 5 times more active than shorter and longer backfilling molecules tested. The immobilized DNAzyme retained its optimized performance at 50 mM NaCl. Finally, the generalized immobilization and ratiometric procedure was employed for a uranyl-specific DNAzyme with 25 +/- 15 times increase in ratio observed. These findings form a firm basis on which practical applications of catalytic beacons can be realized, including sensors for both Pb2+ and UO22+ ions.
Highly Concave Platinum Nanoframes with High‐Index Facets and Enhanced Electrocatalytic Properties (2013)

Deeply excavated: Platinum nanoframes with highly concave {740} facets are synthesized directly by a facile oleylamine-assisted solvothermal method. Because of the unique structure and exposed high-index facets, the as-prepared Pt nanoframes exhibit very high electrocatalytic activity and remarkable stability for the oxygen reduction reaction and the oxidation of methanol and formic acid.
Structural Description of Pressure-Induced Amorphization inZrW2O8 (2007)

ZrW2O8 undergoes a high-pressure amorphization transition above 1.5 GPa to a phase which is recoverable to ambient conditions. Reverse Monte Carlo modeling of neutron and x-ray total scattering data from ZrW2O8 recovered from approximately 4 GPa shows that the large increase in density on pressurizing ZrW2O8 is accommodated within the structure by increased bonding between the WO4 tetrahedra. This increases the tungsten coordination; changes to the ZrO6 octahedral environment are not required. This densified crystal-based model, which contains significant local disorder within a distorted periodic structure, is also in reasonable agreement with x-ray and neutron total scattering data measured in situ at high pressure.
Solution structure of the HIV gp120 C5 Domain (2002)

In HIV the viral envelope protein is processed by a host cell protease to form gp120 and gp41. The C1 and C5 domains of gp120 are thought to directly interact with gp41 but are largely missing from the available X-ray structure. Biophysical studies of the HIV gp120 C5 domain (residues 489-511 of HIV-1 strain HXB2), which corresponds to the carboxy terminal region of gp120, have been undertaken. CD studies of the C5 domain suggest that it is unstructured in aqueous solutions but partially helical in trifluoroethanol/aqueous and hexafluoroisopropanol/aqueous buffers. The solution structure of the C5 peptide in 40% trifluoroethanol/aqueous buffer was determined by NMR spectroscopy. The resulting structure is a turn helix structural motif, consistent with the CD results. Fluorescence titration experiments suggest that HIV C5 forms a 1 : 1 complex with the HIV gp41 ectodomain in the presence of cosolvent with an apparent Kd of approximately 1.0 micro m. The absence of complex formation in the absence of cosolvent indicates that formation of the turn-helix structural motif of C5 is necessary for complex formation. Examination of the C5 structure provides insight into the interaction between gp120 and gp41 and provides a possible target site for future drug therapies designed to disrupt the gp120/gp41 complex. In addition, the C5 structure lends insight into the site of HIV envelope protein maturation by the host enzymes furin and PC7, which provides other possible targets for drug therapies.
Inhibition of 7,12-dimethylbenz(a)anthracene-induced tumors and DNA adduct formation in the mammary glands of female Sprague-Dawley rats by the synthetic organoselenium compound, 1,4-phenylenebis(methylene)selenocyanate. (1992)

We synthesized a novel organoselenium compound, 1,4-phenylenebis(methylene)selenocyanate (XSC), possessing low toxicity by comparison with inorganic Na2SeO3, and several other synthetic organoselenium compounds (K. El-Bayoumy, Cancer Res., 45: 3631-3636, 1985). We tested the effect of XSC treatment during the initiation phase on 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinoma formation. A semipurified high-fat diet containing 80 ppm of XSC (40 ppm as selenium) was fed to 6-wk-old virgin female Sprague-Dawley rats for 2 wk, starting 1 wk before and ending 1 wk after carcinogen treatment. At 7 wk of age, rats were given a single dose of DMBA (5 mg) in 0.2 ml of olive oil by gastric intubation; the experiment was terminated 16 wk later. The development of mammary tumors in those rats that received XSC-supplemented diets was significantly inhibited when compared with the control group (fed the same diet without XSC supplements). This was evident from tumor incidence (percentage of tumor-bearing rats, 88 versus 20) and multiplicity of tumors (mean number of tumors/rats, 3.96 versus 0.28). The finding that XSC acts as a chemopreventive agent in the DMBA mammary tumor model prompted us to examine the effect of dietary XSC on DMBA-DNA binding in both the liver and mammary tissue under conditions identical to those described above for the bioassay. Rats (four/group) were killed 6, 24, 48, and 168 h after [3H]DMBA (5 mg/rat; specific activity, 51.2 mCi/mM) administration. Liver and mammary tissue were obtained and DNA was isolated. Dietary XSC was found to inhibit total DMBA-DNA binding in the mammary tissue, but not in the liver. The most profound effect was observed at early time points, i.e., 24 to 48 h after [3H]DMBA administration. The inhibition in total binding was attributed to a reduction in the formation of the three major adducts derived from bay-region diol-epoxides of DMBA; these were identified as anti-diol-epoxide:deoxyguanosine, syn-diol-epoxide:deoxyadenosine, and anti-diol-epoxide:deoxyadenosine adducts on the basis of their chromatographic characteristics on high-pressure liquid chromatography and on a boronate affinity column. The inhibition of the DMBA-DNA binding in the target tissue provides a plausible explanation for the chemopreventive effect of XSC during the initiation stage of carcinogenesis.
Exact and approximate algorithms for the extension of embedded processor instruction sets (2006)

In embedded computing, cost, power, and performance constraints call for the design of specialized processors, rather than for the use of the existing off-the-shelf solutions. While the design of these application-specific CPUs could be tackled from scratch, a cheaper and more effective option is that of extending the existing processors and toolchains. Extensibility is indeed a feature now offered in real designs, e.g., by processors such as Tensilica Xtensa [T. R. Halfhill, Microprocess Rep., 2003], ARC ARCtangent [T. R. Halfhill, Microprocess Rep., 2000], STMicroelectronics ST200 [P. Faraboschi, G. Brown, J. A. Fisher, G. Desoli, and F. Homewood, Proc. 27th Annu. Int. Symp. Computer Architecture, 2000, p. 203], and MIPS CorExtend [T. R. Halfhill, Microprocess Rep., 2003]. While all these processors provide development environments with simulation capabilities for evaluating efficiently hand-crafted solutions, the tools to identify automatically the best processor configuration for a given application are less common. In particular, solutions to choose specialized instruction-set extensions (ISEs) have been investigated in the past years but are still seldom part of commercial toolchains. This paper provides a formal methodology and a set of algorithms that help address the problem. It proposes exact algorithms to derive optimal ISEs; exact identification of a single ISE is applicable to basic blocks of up to 1500 assembler-like instructions. This paper also introduces approximate methods that can process basic blocks of larger size. Results show that the described algorithms find solutions close to those that a designer would obtain by a detailed study of the application code. Both heuristic and exact algorithms find ISEs able to speed up unextended processors up to 5.0x. State-of-the-art comparisons show that the presented algorithms outperform existing ones by up to 2.6x
Intraocular lens power calculations in patients with extreme myopia (2000)

In eyes with axial lengths longer than or equal to 27.0 mm, current third- and fourth-generation lens calculation formulas have a tendency to over minus patients between -1.0 and -4.0 D. The formulas appear to perform better for plus-power IOL implantation than for minus-power IOL implantation. The use of B-scan ultrasonography to locate posterior pole staphylomas may improve the accuracy of IOL calculations in eyes with extreme myopia.
Assessment of multiple displacement amplification for polymorphism discovery and haplotype determination at a highly polymorphic locus,MC1R (2005)

The identification of common genetic variants such as single nucleotide polymorphisms (SNPs) in the human genome has become central in human population genetics and evolution studies, as well as in the study of the genetic basis of complex traits and diseases. Crucial for the accurate identification of genetic variants is the availability of high quality genomic DNA (gDNA). Since popular sources of gDNA (buccal cells, lymphocytes, hair bulb) often do not yield sufficient quantities of DNA for molecular genetic applications, whole genome amplification methods have recently been introduced to generate a renewable source of double-stranded linear DNA. Here, we assess the fidelity of one method, multiple displacement amplification (MDA), which utilizes bacteriophage Φ29 DNA polymerase to generate amplified DNA from an original source of gDNA, in a representative SNP discovery and genetic association study at the melanocortin 1 receptor (MC1R) locus, a highly polymorphic gene in humans involved in skin and hair pigmentation. We observed that MDA has high fidelity for novel SNP discovery and can be a valuable tool in generating a potentially indefinite source of DNA. However, we observed an allele amplification bias that causes genotype miscalls at heterozygous sites. At loci with multiple polymorphic sites in linkage disequilibrium, such as at MC1R, this bias can create a significant number of heterozygote genotype errors that subsequently misrepresents haplotypes. Hum Mutat 26(2), 1–8, 2005. © 2005 Wiley-Liss, Inc.
Asymmetric Total Synthesis of (+)- and ent-(−)-Yatakemycin and Duocarmycin SA:  Evaluation of Yatakemycin Key Partial Structures and Its Unnatural Enantiomer (2006)

Complementary to studies that provided the first yatakemycin total synthesis resulting in its structure revision and absolute stereochemistry assignment, a second-generation asymmetric total synthesis is disclosed herein. Since the individual yatakemycin subunits are identical to those of duocarmycin SA (alkylation subunit) or CC-1065 (central and right-hand subunits), the studies also provide an improvement in our earlier total synthesis of CC-1065 and, as detailed herein, have been extended to an asymmetric total synthesis of (+)-duocarmycin SA. Further extensions of the studies provided key yatakemycin partial structures and analogues for comparative assessments. This included the definition of the DNA selectivity (adenine central to a five-base-pair AT sequence, e.g., 5'-AAAAA), efficiency, relative rate, and reversibility of ent-(-)-yatakemycin and its comparison with the natural enantiomer (identical selectivity and efficiency), structural characterization of the adenine N3 adduct confirming the nature of the DNA reaction, and comparisons of the cytotoxic activity of the natural product (L1210, IC50 = 5 pM) with those of its unnatural enantiomer (IC50 = 5 pM) and a series of key partial structures including those that probe the role of the C-terminus thiomethyl ester. The only distinguishing features between the enantiomers is that ent-(-)-yatakemycin alkylates DNA at a slower rate (krel = 0.13) and is reversible, whereas (+)-yatakemycin is not. Nonetheless, even ent-(-)-yatakemycin alkylates DNA at a faster rate and with a greater thermodynamic stability than (+)-duocarmycin SA, illustrating the unique characteristics of such "sandwiched" agents.