gebhart/patrepeval huggingface dataset:
Essential Role of Fcγ Receptors in Anti-Type II Collagen Antibody-Induced Arthritis (2003)

Anti-type II collagen (anti-CII) Ab is a well-known autoantibody observed in patients with rheumatoid arthritis. Injection of anti-CII Ab and LPS induces arthritis in mice in which anti-CII Ab as well as inflammatory cytokines, IL-1beta and TNF-alpha, play critical roles. We investigated the involvement of IgG FcRs (FcgammaRs) in this arthritis model. BALB/c mice injected with the F(ab')(2) of anti-CII Ab showed no signs of arthritis. Arthritis development was not observed in FcRgamma(-/-) mice and was partially suppressed in FcgammaRIII(-/-) mice despite the binding of anti-CII Ab and C3 to cartilage surface. Surprisingly, BALB/c mice lacking FcgammaRIIB, which is known as an inhibitory FcgammaR, developed arthritis with no exacerbation in arthritis score compared with wild-type (WT) mice, and only slight exacerbation was observed in the histopathological analysis. In contrast, aged FcgammaRIIB(-/-) BALB/c mice developed arthritis without LPS injection, suggesting an augmented susceptibility to arthritis in aged FcgammaRIIB(-/-) mice. No significant difference was observed among BALB/c-WT, -FcRgamma(-/-), and -FcgammaRIIB(-/-) mice on cytokine production induced by anti-CII Ab and LPS injection. Severe arthritis developed in BALB/c-WT and -FcgammaRIIB(-/-) mice, but not in BALB/c-FcRgamma(-/-) mice, after the injection of anti-CII Ab and inflammatory cytokines. These results suggest that the reason behind the nondevelopment of arthritis in FcRgamma(-/-) BALB/c mice is not due to a disorder in transient cytokine production, but to an irregularity downstream of cytokine production.
Identification and characterization of four PAX8 rare sequence variants (p.T225M, p.L233L, p.G336S and p.A439A) in patients with congenital hypothyroidism and dysgenetic thyroid glands (2007)

We report the occurrence of two nonsynonymous substitutions, one recently reported (p.T225M) and one novel (p.G336S), and two novel synonymous substitutions (p.L233L and p.A439A) in the PAX8 gene. p.T225M and p.G336S are rare sequence variants or may act by inhibiting an unknown particular function. Our study also confirms the very low prevalence of PAX8 mutations in thyroid dysgenesis.
Complement Activation and Hemodynamic Changes Following Intravenous Administration of Phosphorothioate Oligonucleotides in the Monkey (1994)

Rapid intravenous infusion of GEM 91, a 25-mer phosphorothioate oligonucleotide complementary to the gag site of HIV, in the monkey produces transient decreases in peripheral total WBC and neutrophil counts, hemoconcentration, and a brief increase followed by a prolonged decrease in arterial blood pressure. These changes are preceded by and are likely mediated by activation of C5 complement. These effects are dose and infusion rate dependent and can be avoided by administering GEM 91 by slow intravenous infusion. Similar hemodynamic effects are produced with rapid intravenous infusion of other phosphorothioate oligonucleotides varying in length from 20- to 33-mer, and are, therefore, not sequence specific but a property of this chemical structure.
Abstract 3637: MM-302, a HER2-targeted liposomal doxorubicin, shows binding/uptake and efficacy in HER2 2+ cells and xenograft models (2011)

Abstract Introduction: MM-302 is an ErbB2/HER2-targeted liposomal doxorubicin formulation designed to target doxorubicin to HER2-overexpressing cancer cells while limiting uptake into non-target cells. The characterization of the binding and uptake of MM-302 as a function of HER2 surface levels on various cell lines and in tumor models will help determine the minimum HER2 receptor levels required for MM-302 patient selection. Methods: Cellular models included 16+ established human tumor cell lines as well as 4T1 murine breast cancer and HeLa human cervical cancer cells engineered to overexpress HER2 from 1E05-1E06 receptors/cell. Cells were incubated with MM-302, untargeted liposomes or free doxorubicin and binding/uptake was measured by HPLC or flow cytometry. In vivo efficacy was determined in select mouse xenograft models. Tumors were mechanically and enzymatically dissociated, followed by flow cytometry to quantify the uptake of targeted and untargeted liposomes into HER2-expressing tumor cells, macrophages and other cell types. Results: Binding and uptake of MM-302 increased with rising HER2 surface levels in cells of common parental origin (4T1, HeLa), with significant uptake into cells with &amp;gt;2E05 HER2/cell. Further, total cell binding/uptake of MM-302 also increased with rising HER2 expression across a panel of 16+ cell lines. There was negligible uptake of untargeted liposomes under all conditions that showed no dependence on HER2 expression. Improved anti-tumor efficacy of MM-302 was observed in BT474-M3 and NCI-N87 mouse xenograft models relative to untargeted liposomal doxorubicin and free doxorubicin. Further, using disaggregated tumors, the relationship between HER2 expression and MM-302 uptake was confirmed in vivo in both models. Conclusions: Our studies identified a HER2 threshold for uptake of MM-302 of approximately 2E05 receptors/cell, and suggest a role for MM-302 not only in HER2 3+ cancers, but also in HER2 2+ cancers as well. The ability to treat HER2 2+ tumors offers an exciting opportunity to serve a major unmet clinical need. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3637. doi:10.1158/1538-7445.AM2011-3637
Automatic 3D Intersubject Registration of MR Volumetric Data in Standardized Talairach Space (1994)

We present a fully automatic registration method to map volumetric data into stereotaxic space that yields results comparable with those of manually based techniques. The method requires no manual identification of points or contours and therefore does not suffer the drawbacks involved in user intervention such as reproducibility and interobserver variability.
Investigation Of Colon Specificity Of Novel Polysaccharideokra Mucilage-Film Coated With Enteric Materials (2012)

￻Okra polysaccharide as a microbially triggered material and also as the carrier to colon was previously developed and reported. The release profiles of the reported method revealed that okra mucilage, when used as a matrix tablet, does not protect the drug from being released in the upper parts of the gastro intestinal tract. In the present work the tablets were prepared with okra mucilage and coated with enteric materials to retard the drug release in the upper GI tract. Okra polysaccharide was isolated from Abelmoschus esculentus and used for tablet formulation with ibuprofen as model drug. The matrix tablets of okra polysaccharide were prepared by wet granulation method using ibuprofen as a model drug. These prepared matrix tablets were coated with enteric materials by pan coating technique. The in vitro release profile was performed with and without rat cecal content, revealed that the enteric coated formulations completely protected the drug from being released in the upper parts of the gastro intestinal tract. Among the enteric coated tablets, the 3% double layer coated tablets exhibited zero in vitro release profiles at 2 nd and 5 th hours. Hence, this tablet was subjected for further pharmacokinetic estimations and was compared with control tablet. At 5.5 h the ibuprofen appeared first in the blood; this showed the tablet was intact throughout the upper GI. The Tmax and AUC estimates showed that the drug was released from the tablet to colon by bacterial degradation of mucilage.
A PCIe DMA engine to support the virtualization of 40 Gbps FPGA-accelerated network appliances (2015)

Network Function Virtualization (NFV) allows creating specialized network appliances out of general-purpose computing equipment (servers, storage, and switches). In this paper we present a PCIe DMA engine that allows boosting the performance of virtual network appliances by using FPGA accelerators. Two key technologies are demonstrated, SR-IOV and PCI Passthrough. Using these two technologies, a single FPGA board can accelerate several virtual software appliances. The final goal is, in an NFV scenario, to substitute conventional Ethernet NICs by networking FPGA boards (such as NetFPGA SUME). The advantage of this approach is that FPGAs can very efficiently implement many networking tasks, thus boosting the performance of virtual networking appliances. The SR-IOV capable PCIe DMA engine presented in this work, as well as its associated driver, are key elements in achieving this goal of using FPGA networking boards instead of conventional NICs. Both DMA engine and driver are open source, and target the Xilinx 7-Series and UltraScale PCIe Gen3 endpoint. The design has been tested on a NetFPGA SUME board, offering transfer rates reaching 50 Gb/s for bulk transmissions. By taking advantage of SR-IOV and PCI Passthrough technologies, our DMA engine provides transfers rate well above 40 Gb/s for data transmissions from the FPGA to a virtual machine. We have also identified the bottlenecks in the use of virtualized FPGA accelerators caused by reductions in the maximum read request size and maximum payload PCIe parameters. Finally, the DMA engine presented in this paper is a very compact design, using just 2% of a Xilinx Virtex-7 XC7VX690T device.
Reconciling Economic and Non-Economic Perspectives on Media Policy: Transcending the “Marketplace of Ideas” (1992)

A long-standing division in positions on media policy reflects differences in faith regarding the efficacy of market versus government processes for achieving important communications policy objectives. The debate over content diversity between the advocates of market solutions and those who are critical of them reveals that the standard arguments of both camps rest on differences in assumptions that have not been subjected to careful analysis. Furthermore, analysts in each camp have failed to acknowledge or incorporate into their own analyses the other camp's legitimate insights. The result is a flawed policy dialogue that shows no signs of iterating toward a consensus or of making much progress toward an improved understanding of the requirements for effective communications policy. This failure reflects, in part, limitations in the constructs implied by the “marketplace of ideas” metaphor that has guided much of the thinking by both camps and the ways these constructs have been employed. New metaphors are needed to guide an expanded research agenda designed to assist in the development of more effective communications policy.
The biosynthesis of 4-hydroxycoumarin and dicoumarol by Aspergillus fumigatus Fresenius (1970)

A strain of Aspergillus fumigatus Fresenius, isolated from spoiled hay, converts melilotic acid (o-hydroxyphenylpropionic acid) and o-coumaric acid into 4-hydroxycoumarin and dicoumarol. The sequence is shown to be melilotic acid (I) [Formula: see text] coumaric acid (IV) [Formula: see text] beta-hydroxymelilotic acid (II) [Formula: see text] beta-oxomelilotic acid (III) [Formula: see text] 4-hydroxycoumarin (VI), on the basis of (1) studies on the formation of postulated intermediates, (2) experiments with isotopically labelled materials and (3) sequential enzyme induction. In the presence of semicarbazide, o-coumaraldehyde is formed from o-coumaric acid: there is no evidence, however, that this lies on the normal metabolic pathway.
Catalytic Enantioselective Reduction of Ketones by a Chiral Gallium Complex and Catecholborane (1999)

A catalytically active version of Noyori's famous BINAL reagent Li[AlH(OEt)(BINOL dianion)] is formed by the combination of LiGaH<sub>4</sub> , monothiobinaphthol (MTB), and catecholborane. With this mixture unsymmetrical ketones can be reduced in high enantioselectively. Un=unsaturated unit; R=alkyl.
[Effect of endurance training on the compositions of fiber types and myosin light chains in muscles under disuse atrophy]. (1992)

The effects of endurance training on the compositions of fiber types (Type I and Type II) and myosin light chains (MLC) of the muscle under disuse atrophy (soleus) were studied. The hindlimbs of adult Wistar rats were immobilized on the ankle joint in an extended position for 2 weeks. The rats were then trained by a treadmill for 0, 1, 2, 4, and 8 weeks after the release from fixation. The wet weight and cross sectional area of soleus muscle significantly decreased, and a significant decrease in the percentage of slow type of MLC was also observed. In the running group, the weight and area recovered more rapidly than those of the control. The compositions of fiber types and MLC were not significantly different between the control and running groups. Type II fiber appears to have a compensatory function of Type I fiber. These results suggested that endurance training would promote the recovery from malfunction in muscle atrophy induced by disuse.
High-Throughput Multilocus Sequence Typing: Bringing Molecular Typing to the Next Level (2012)

Multilocus sequence typing (MLST) is a widely used system for typing microorganisms by sequence analysis of housekeeping genes. The main advantage of MLST in comparison to other typing techniques is the unambiguity and transferability of sequence data. However, a main disadvantage is the high cost of DNA sequencing. Here we introduce a high-throughput MLST (HiMLST) method that employs next-generation sequencing (NGS) technology (Roche 454), to generate large quantities of high-quality MLST data at low costs. The HiMLST protocol consists of two steps. In the first step MLST target genes are amplified by PCR in multi-well plates. During this PCR the amplicons of each bacterial isolate are provided with a unique DNA barcode, the multiplex identifier (MID). In the second step all amplicons are pooled and sequenced in a single NGS-run. The MLST profile of each individual isolate can be retrieved easily using its unique MID. With HiMLST we have profiled 575 isolates of Legionella pneumophila, Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus pneumoniae in mixed species HiMLST experiments. In conclusion, the introduction of HiMLST paves the way for a broad employment of the MLST as a high-quality and cost-effective method for typing microbial species.
Mismatched dNTP incorporation by DNA polymerase β does not proceed via globally different conformational pathways† (2008)

Understanding how DNA polymerases control fidelity requires elucidation of the mechanisms of matched and mismatched dNTP incorporations. Little is known about the latter because mismatched complexes do not crystallize readily. In this report, we employed small-angle X-ray scattering (SAXS) and structural modeling to probe the conformations of different intermediate states of mammalian DNA polymerase beta (Pol beta) in its wild-type and an error-prone variant, I260Q. Our structural results indicate that the mismatched ternary complex lies in-between the open and the closed forms, but more closely resembles the open form for WT and the closed form for I260Q. On the basis of molecular modeling, this over-stabilization of mismatched ternary complex of I260Q is likely caused by formation of a hydrogen bonding network between the side chains of Gln(260), Tyr(296), Glu(295) and Arg(258), freeing up Asp(192) to coordinate MgdNTP. These results argue against recent reports suggesting that mismatched dNTP incorporations follow a conformational path distinctly different from that of matched dNTP incorporation, or that its conformational closing is a major contributor to fidelity.
Flanking Duplications and Deletions Associated With P-Induced Male Recombination in Drosophila (1996)

We studied P element-induced recombination in germline mitotic cells by examining the structure of the recombinant chromosomes. We found that most recombinants retain a mobile P element at the site of the recombination, usually with either a deletion or a duplication immediately adjacent to the P end at which the crossover occurred. The sizes of these deletions and duplications ranged from a few base pairs to well over 100 kb. These structures fit the "hybrid element insertion" (HEI) model of male recombination in which the two P-element copies on sister chromatids combine to form a "hybrid element" whose termini insert into a nearby position on the homologue. The data suggest that P-induced recombination can be used as an efficient means of generating flanking deletions in the vicinity of existing P elements. These deletions are easily screened using distant flanking markers, and they can be chosen to extend in a given direction depending on which reciprocal recombinant type is selected. Furthermore, the retention of a mobile P element allows one to extend the deletion or generate additional variability at the site by subsequent rounds of recombination.
Auto- and cross-induction within the mammalian epidermal growth factor-related peptide family. (1994)

Several polypeptide growth factors related to epidermal growth factor (EGF) have been identified recently, including transforming growth factor-alpha (TGF-alpha), amphiregulin (AR), heparin-binding EGF-like growth factor (HB-EGF), and betacellulin (BTC). These peptides all bind to the EGF receptor (EGFr). In an effort to understand redundancy within this peptide family and interactions among these related peptides, we compared the biological activities of EGF, TGF-alpha, AR, and HB-EGF in an EGF-responsive, nontransformed intestinal epithelial line (RIE-1) and also determined the effect of individual EGF-related peptides on the expression of related family members in these cells. TGF-alpha, AR, HB-EGF, and EGF were equipotent in stimulating [3H]thymidine incorporation by RIE-1 cells and bound the EGFr with equivalent affinity. Each EGF-related peptide induced the mRNA expression of the remaining family members, including BTC. HB-EGF and AR mRNAs were induced rapidly (within 30 min) and to a greater extent than TGF-alpha and BTC mRNAs, suggesting heterogeneity in the molecular mechanisms for induction. This same pattern was observed for all EGF-related peptides tested. A similar pattern of mRNA induction was observed in secondary cultures of human keratinocytes and in LIM1215 colon adenocarcinoma cells. Nuclear run-on analysis showed that induction of AR and HB-EGF is, at least in part, regulated at the level of gene transcription. Concurrent treatment with HB-EGF and cycloheximide resulted in superinduction of HB-EGF and AR, suggesting that these peptides are immediate early genes in RIE-1 cells. Our results demonstrate an equivalent biological response to EGF-related peptides in RIE-1 cells and further indicate that extensive auto-induction and cross-induction occur within the EGF-related peptide family in several EGF-responsive epithelial cell types.
Human-machine interfaces for minimally invasive surgery (2002)

Increasing numbers of surgical procedures are performed using minimally invasive techniques, in which trauma to external tissue is minimized. Unfortunately, reduced access reduces dexterity, limits perception, increases strain and the likelihood of error, and lengthens procedure time. Surgical technology must improve the interface between task requirements and human abilities. This paper describes three projects to evaluate and improve the human interface in laparoscopic surgery, or minimally invasive surgery of the abdomen: (a) measurement of movement trajectories under different visual conditions to determine the effect of viewing geometry, (b) the development of virtual environments for training, and (c) the development of haptic interfaces and control algorithms for teleoperative surgery.
Identification of Complin, a Novel Complement Inhibitor that Targets Complement Proteins Factor B and C2 (2010)

Complement factor B (fB) is a key constituent of the alternative pathway (AP). Its central role in causing inflammation and tissue injury through activation of the AP urges the need for its therapeutic targeting. In the current study, we have screened phage-displayed random peptide libraries against fB and identified a novel cyclic hendecapeptide that inhibits activation of fB and the AP. Structure-activity studies revealed that: 1) the cysteine-constrained structure of the peptide is essential for its activity; 2) Ile5, Arg6, Leu7, and Tyr8 contribute significantly to its inhibitory activity; and 3) retro-inverso modification of the peptide results in loss of its activity. Binding studies performed using surface plasmon resonance suggested that the peptide has two binding sites on fB, which are located on the Ba and Bb fragments. Studies on the mechanism of inhibition revealed that the peptide does not block the interaction of fB with the activated form of C3, thereby suggesting that the peptide inhibits fB activation primarily by inhibiting its cleavage by factor D. The peptide showed a weak effect on preformed C3 and C5 convertases. Like inhibition of fB cleavage, the peptide also inhibited C2 cleavage by activated C1s and activation of the classical as well as lectin pathways. Based on its inhibitory activities, we named the peptide Complin.
Inhibition of monoamine oxidase by substituted hydrazines (1972)

1. The initial rate of inhibition of monoamine oxidase by phenethylhydrazine was shown to be similar, in pH-dependence and kinetic properties, to the oxidation of that compound by monoamine oxidase. 2. The time-course of irreversible inhibition of monoamine oxidase by phenethylhydrazine lags behind that of reversible inhibition. 3. Hydralzine was shown to be a reversible competitive inhibitor of monoamine oxidase, but phenylhydrazine is an irreversible inhibitor. Inhibition by the latter compound is not affected by the absence of oxygen, and the presence of substrate exerts no protective action. 4. Hydrazine does not inhibit monoamine oxidase unless a substrate and oxygen are present. 5. Phenethylidenehydrazine was found to be a time-dependent inhibitor of monoamine oxidase and the rate of inhibition was hindered by increasing oxygen concentration. 6. A mechanism for the inhibition of the enzyme by phenethylhydrazine is proposed in which the product of oxidation of this compound is a potent reversible inhibitor and an irreversible inhibitor of the enzyme. A computer simulation of such a mechanism predicts time-courses of inhibition that are in reasonable agreement with those observed experimentally.
Effects of screw configuration on indomethacin dissolution behavior in Eudragit E PO (2011)

Abstract This experimental study examines the evolution of the extent of dissolution of the active pharmaceutical ingredient (API) indomethacin (INM) into the polymer excipient Eudragit E PO (E PO) on four screw configurations processed in an APV 15 mm corotating twin screw extruder. The screws were pulled out and quenched by water, which allowed for quick access to the processed stream carcass. Polarized light microscopy (PLM), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FT‐IR), were employed to investigate the evolution of INM's dissolution into the molten excipient along the extrusion direction. The FT‐IR results show that kneading blocks accelerate the complete dissolution process. The unique capability of fully filled kneading blocks in mixing and melting associated with the dissolution of API into polymeric excipient matrix was discussed. © 2011 Wiley Periodicals, Inc. Adv Polym Techn 31: 331–342, 2012; View this article online at wileyonlinelibrary.com . DOI 10.1002/adv.20256