gebhart/patrepeval huggingface dataset:
Comparative Arterial Antithrombotic Activity of Clopidogrel and Acetyl Salicylic Acid in the Pig (1992)

We investigated the comparative antithrombotic properties of clopidogrel, an analogue of ticlopidine, and aspirin, using the Folts' model on femoral arteries in 22 pigs. On each animal, clopidogrel or aspirin were used to treat the thrombotic process on the left femoral artery and to prevent this process on the right femoral artery. Sequentially: an injury and stenosis were carried out on the left femoral artery; the thrombotic process was monitored with a Doppler during a 30-min observation period for cyclic flow reductions or permanent cessation of flow; after the first cyclic flow reduction occurred, clopidogrel (5 mg kg-1) or aspirin (2.5, 5, 100 mg kg-1) were injected intravenously; if cyclic flow reductions were abolished, epinephrine (0.4 micrograms kg-1 min-1) was injected to try to restore cyclic flow reductions and/or permanent cessation of flow; then injury and stenosis were applied on the right femoral artery. Before and after injection of clopidogrel or aspirin, ear immersion bleeding times and ex-vivo platelet aggregation were performed. Clopidogrel (n = 7) abolished cyclic flow reductions were efficiently prevented, even for two injuries. Basal bleeding time (5 min 28) was lengthened (> 15 min, 30 min after clopidogrel and remained prolonged even after 24 h). ADP-induced platelet aggregation was inhibited (more than 78%). Comparatively, aspirin had a moderate and no dose-dependent effect. Aspirin 2.5 mg kg-1 (n = 6) abolished cyclic flow reductions in 2 animals, CFR reoccurred spontaneously in one animal and epinephrine restored it in a second animal.(ABSTRACT TRUNCATED AT 250 WORDS)
In Search of Biomarkers for Idiopathic Scoliosis:LeptinandBMP4Functional Polymorphisms (2015)

Idiopathic scoliosis (IS) is the most common spinal disorder in children and adolescents. The current consensus on IS maintains that it has a multifactorial etiology with genetic predisposition factors. In the present study the association of two functional polymorphisms of leptin (rs7799039) and BMP4 (rs4898820) with susceptibility to IS and curve severity was investigated in a Bulgarian population sample. The molecular detection of the genotypes was performed by amplification followed by restriction technology. The statistical analysis was performed by Pearson's chi-squared test. This case-control study revealed no statistically significant association between the functional polymorphisms of leptin and BMP4 and susceptibility to IS or curve progression (p > 0.05). On the basis of these results the examined polymorphic variants of leptin and BMP4 could not be considered as genetic variants with predisposition effect or as risk factors for the progression of the curve. In addition, these results do not exclude a synergistic effect of the promoter polymorphisms of leptin and BMP4 in the etiology and pathogenesis of IS. The identification of molecular markers for IS could be useful for early detection and prognosis of the risk for a rapid progression of the curve. That would permit early stage treatment of the patient with the least invasive procedures.
Toward a live microbial microbicide for HIV: Commensal bacteria secreting an HIV fusion inhibitor peptide (2005)

Most HIV transmission occurs on the mucosal surfaces of the gastrointestinal and cervicovaginal tracts, both of which are normally coated by a biofilm of nonpathogenic commensal bacteria. We propose to genetically engineer such naturally occurring bacteria to protect against HIV infection by secreting antiviral peptides. Here we describe the development and characterization of Nissle 1917, a highly colonizing probiotic strain of Escherichia coli, secreting HIV-gp41-hemolysin A hybrid peptides that block HIV fusion and entry into target cells. By using an appropriate combination of cis- and transacting secretory and regulatory signals, micromolar secretion levels of the anti-HIV peptides were achieved. The genetically engineered Nissle 1917 were capable of colonizing mice for periods of weeks to months, predominantly in the colon and cecum, with lower concentrations of bacteria present in the rectum, vagina, and small intestine. Histological and immunocytochemical examination of the colon revealed bacterial growth and peptide secretion throughout the luminal mucosa and in association with epithelial surfaces. The use of genetically engineered live microbes as anti-HIV microbicides has important potential advantages in economy, efficacy, and durability.
Self-Organization Schemes towards Thermodynamic Stable Bulk Heterojunction Morphologies: A Perspective on Future Fabrication Strategies of Polymer Photovoltaic Architectures (2013)

Research efforts to improve our understanding of electronic polymers are developing fast because of their promising advantages over silicon in photovoltaic solar cells. A major challenge in the development of polymer photovoltaic devices is the viable fabrication strategies of stable bulk heterojunction architecture that will retain functionality during the expected lifetime of the device. Block copolymer self-assembly strategies have attracted particular attention as a scalable means toward thermodynamically stable microstructures that combine the ideal geometrical characteristics of a bulk heterojunction with the fortuitous combination of properties of the constituent blocks. Two primary routes that have been proposed in the literature involve the coassembly of block copolymers in which one domain is a hole conductor with the electron-conducting filler (such as fullerene derivatives) or the self-assembly of block copolymers in which the respective blocks function as hole and electron conductor. Either way has proven difficult because of the combination of synthetic challenges as well as the missing understanding of the complex governing parameters that control structure formation in semiconducting block copolymer blends. This paper summarizes important findings relating to structure formation of block copolymer and block copolymer/nanoparticle blend assembly that should provide a foundation for the future design of block copolymer-based photovoltaic systems.
Synthesis and thermal properties of polyurethane–polysiloxane crosslinked polymer networks (2003)

Abstract Polysiloxane–polyurethane crosslinked polymer networks (PSI–PU) were synthesized in solution by polymerization of oligosiloxanes containing γ‐hydroxy propyl groups with polymethane polyphenyl polyisocyanate. Polyether‐based polyurethane and polyester‐based polyurethane were also prepared by a “one‐shot” method. Their thermal properties were studied by thermogravimetric analysis. It was observed that the thermal stability of PSI–PU was better than that of polyether‐based polyurethane and polyester‐based polyurethane, and an inert atmosphere had no effect on decomposition of polyurethanes below 350°C. It was found that polyurethane–polysiloxane crosslinked polymer networks decomposed slower in oxygen than in nitrogen in the temperature range of 350–550°C. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 310–315, 2003
Longitudinal Velocity and Road Slope Estimation in Hybrid/Electric Vehicles - Development and evaluation of an adaptive Kalman filter (2013)

An accurate and efficient method of velocity and slope estimation is presented in this thesis. An adaptive Kalman filter is proposed to deal with the over-slip wheel, which is a challenging problem during velocity estimation. The research object of this work is the hybrid/electric vehicles with electric motors.\nIn the adaptive Kalman filter, we control the gain matrix directly based on the over-slip flag. If all of the four wheels over-slip at the same time, the velocity results are replaced by the integration of acceleration. To reduce the integration error, the longitudinal acceleration is modified by road slope estimation results. The slope estimation is based on typical Kalman filter and the observation variable is velocity estimation result. Then, the over-slip criterion and wheel speed selection method are involved aiming to estimate velocity accurately when all the four wheels are over-slip. Besides the wheel speed and pre-estimation of velocity, the wheel torque, provided by electric motor, is also used to find out the over-slip wheels. Nevertheless, some abnormal measurements that cannot be detected by the over-slip criteria affect the accuracy of the estimation. Thus wheel speed selection is put forward to reduce the influence of measurements error as well as the calculation quantity. After selection, only one wheel speed is selected as the observation variable of Kalman filter. At last, the algorithm is verified on both high and low friction road
Radical Grafting of Tetrafluoroethylene and Vinylidene Fluoride Telomers onto Silica Bearing Vinyl Groups (2011)

Radical addition of ω-iodofluorinated telomers was used to modify silica (S50) nanoparticles bearing vinyl groups. These iodo terminated derivatives were either commercially available tetrafluoroethylene telomers, CnF2n+1I with n = 4 or 6, or vinylidene fluoride telomers, CnF2n+1[VDF]mI with m = 6 and 23. These latters were synthesized by radical telomerization of VDF with CnF2n+1I initiated by bis(4-tert-butylcyclohexyl) peroxydicarbonate in high yields (>85%). The resulting nanohybrids were characterized by solid state NMR spectroscopy, elemental analyses and thermogravimetry. A covalent grafting between double bonds and fluorinated iodotelomers was noted. The covering density of fluorinated chains was assessed and reported with respect to fluorinated chain lengths. These nanohybrids exhibited a high thermostability (higher than 400 °C under air), losing less than 10% by weight at 700 °C, and a low surface tension, γs, from around 15 mN·m–1 to about 44 mN·m–1 for silica.
Type 1 Neurofibromatosis Gene: Identification of a Large Transcript Disrupted in Three NF1 Patients (1990)

Von Recklinghausen neurofibromatosis (NF1) is a common autosomal dominant disorder characterized by abnormalities in multiple tissues derived from the neural crest. No reliable cellular phenotypic marker has been identified, which has hampered direct efforts to identify the gene. The chromosome location of the NF1 gene has been previously mapped genetically to 17q11.2, and data from two NF1 patients with balanced translocations in this region have further narrowed the candidate interval. The use of chromosome jumping and yeast artificial chromosome technology has now led to the identification of a large (approximately 13 kilobases) ubiquitously expressed transcript (denoted NF1LT) from this region that is definitely interrupted by one and most likely by both translocations. Previously identified candidate genes, which failed to show abnormalities in NF1 patients, are apparently located within introns of NF1LT, on the antisense strand. A new mutation patient with NF1 has been identified with a de novo 0.5-kilobase insertion in the NF1LT gene. These observations, together with the high spontaneous mutation rate of NF1 (which is consistent with a large locus), suggest that NF1LT represents the elusive NF1 gene.
Metallophthalocyanine dimers incorporating five-atom covalent bridges (1985)

Metal-free copper and cobalt(II) binuclear phthalocyanines, in which the two phthalocyanine nuclci are covalently linked through five-atom bridges, have been prepared and characterized. Some new metal-free, copper, cobalt(II), and zinc 2,9,16,23-tetraalkoxyphthalocyanines, some of which are extremely soluble in organic solvents, are described.
Modulated barrier photodiode: A new majority-carrier photodetector (1981)

A new majority-carrier photodetector, called a modulated barrier photodiode (MBP), grown by molecular beam epitaxy has been developed. In sharp contrast to a bipolar phototransistor, the optical gain of MBP increases with decreasing incident power. An optical gain of 1000 at 1.5 nW incident power and a fall time of 600 psec have been obtained. In addition to the application for uses as a detector in an optical communication system, the device points to the feasibility of realizing a solid-state triode.
A novel ion-implanted amorphous silicon programmable element (1987)

A novel Ion-Implanted Programmable Element (IPEL) suitable for integration with VLSI technology has been developed. The device operation is based on the electrical properties of a metal/amorphous silicon/single crystal silicon structure made by heavy-dose ion-implantation into a contact to a single crystal silicon. The initial resistance of the amorphous silicon is very high (> 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">15</sup> Ω×cm) and is dielectric strength is in the 1 MV/cm range. Its resistance drops over 6 orders of magnitude after switching and the device is transformed irreversibely into its conductive state.
Molecular and Supramolecular Structural Studies on Significant Repetitive Sequences of Resilin (2009)

Resilin is a member of the family of elastomeric proteins and is found in specialised regions of the cuticle of most insects, and provides low stiffness, high strain and efficient energy storage. It is best known for its role in insect flight and the remarkable jumping ability of fleas and spittle bugs. In common with other elastomeric proteins, the recently identified Drosophila melanogaster proresilin shows glycine-rich repetitive sequences; in particular the N- and C-terminal regions of the protein are dominated by 18 repeats of a 15-residue sequence (SDTYGAPGGGNGGRP) and eleven repeats of a 13-residue sequence (GYSGGRPGGQDLG), respectively. We synthesised and analysed the molecular and supramolecular structure of some polypeptides with sequences belonging to the glycine-rich repeated domain of D. melanogaster resilin. The conformational studies performed by CD, FTIR and NMR spectroscopies pointed to the coexistence of two main conformational features, such as folded beta-turns and (quasi)extended structures (e.g., poly-L-proline II conformation) in common with other elastomeric proteins; this suggests an elasticity mechanism for resilin common to other elastomeric proteins. Our data show that also in the case of resilin, repetitive sequences are characterised by autonomous structures almost independent of the remaining parts of the molecule as already extensively found for elastin. From a supramolecular point of view, a great tendency to aggregate in fibrous structures is observed, particularly for the resilin- inspired polypeptide (PGGGN)(10). This is encouraging for the development of resilin-based biomaterials for the production of biocompatible medical devices, as well as high performing elastic materials.
[Iron deficiency anaemia due to a matriptase-2 mutation]. (2010)

A 36-year old female patient who had had iron deficiency anaemia since her childhood showed no clear response to oral iron treatment. Elevated serum hepcidin levels were found after excluding other causes of iron deficiency. This is in contrast to what is expected in iron deficiency anaemia and indicates a primary defect in hepcidin regulation. Indeed, in the search for a defect in genes coding for hepcidin-regulating proteins the patient was found to be compound heterozygous for two different mutations in the TMPRSS6 gene. This leads to a dysfunctional matriptase-2 protein for which the gene codes. Consequently, liver cells cannot inhibit hepcidin production in the presence of low serum iron levels. High hepcidin levels result in less iron being absorbed from the bowel than is necessary for erythropoiesis. Therefore, patients with matriptase-2 deficiency respond poorly to oral iron treatment and have to be treated with intravenous iron.
Changing the Paradigm for the Treatment and Development of New Therapies for FSGS (2016)

Focal segmental glomerulosclerosis (FSGS) is a renal pathology finding that represents a constellation of rare kidney diseases, which manifest as proteinuria, edema nephrotic syndrome, hypertension, and increased risk for kidney failure. Therapeutic options for FSGS are reviewed displaying the expected efficacy from 25 to 69% depending on specific therapy, patient characteristics, cost, and common side effects. This variability in treatment response is likely caused, in part, by the heterogeneity in the etiology and active molecular mechanisms of FSGS. Clinical trials in FSGS have been scant in number and slow to recruit, which may stem, in part, from reliance on classic clinical trial design paradigms. Traditional clinical trial designs based on the "learn and confirm" paradigm may not be appropriate for rare diseases, such as FSGS. Future drug development and testing will require novel approaches to trial designs that have the capacity to enrich study populations and adapt the trial in a planned way to gain efficiencies in trial completion timelines. A clinical trial simulation is provided that compares a classical and more modern design to determine the maximum tolerated dose in FSGS.
B61, a ligand for the Eck receptor protein-tyrosine kinase, exhibits neurotrophic activity in cultures of rat spinal cord neurons (1996)

Although the Eph subfamily represents the largest group of receptor protein-tyrosine kinases, the biological roles of the Eph-related receptors and their ligands are not well understood. B61 has been identified recently by receptor affinity chromatography as a ligand for the Eph-related receptor Eck (Bartley et al.: Nature 368:558-560, 1994). Here we show that Eck immunoreactivity is localized in areas of the embryonic rat spinal cord that are rich in axons, suggesting that Eck plays a role in this region of the developing nervous system. To examine the biological function of Eck, monolayer cultures of dissociated cells from embryonic rat spinal cord were treated with soluble B61. With an ED50 of approximately 10 ng/ml, B61 treatment improved the survival of the overall neuronal population. Furthermore, in the presence of B61 neurites were longer and more elaborated. B61 similarly affected survival and neurite length in cultures enriched in motor neurons. These neurotrophic effects of B61 were not observed in the presence of anti-Eck antibodies, indicating that these effects are likely to be mediated by the Eck receptor.
Integrated dipole antennas on silicon substrates for intra-chip communication (2003)

To study the feasibility of integrating the antennas in integrated circuits, short linear, meander, and zigzag dipole antennas were implemented on silicon wafers using processing steps compatible with the silicon IC technology. The axial length of the antennas is 2 mm and the width of the metal liner is 10 /spl mu/m. From phase delay measurements, it is shown that EM waves predominantly travel through the silicon substrate. The transmission gain (received power/available transmitted power) dependence on distance is greater than expected. Meander dipole antennas have 3-5 dB higher gains than the other antennas. The input impedances of these antennas can be modeled well using lumped elements. This paper demonstrated that wireless communication within silicon ICs is possible.
Adaptive resistance to anti-PD1 therapy by Tim-3 upregulation is mediated by the PI3K-Akt pathway in head and neck cancer (2016)

Programmed Death 1 (PD-1) and T cell Ig and mucin domain-3 protein (Tim-3) are immune checkpoint receptors that are expressed on tumor-infiltrating lymphocytes (TIL) in tumor-bearing mice and humans. As anti-PD-1 single agent response rates are only <20% in head and neck squamous cell carcinoma (HNSCC) patients, it is important to understand how multiple inhibitory checkpoint receptors maintain suppressed cellular immunity. One such receptor, Tim-3, activates downstream proliferative pathways through Akt/S6, and is highly expressed in dysfunctional TIL. We observed that PD-1 and Tim-3 co-expression was associated with a more exhausted phenotype, with the highest PD-1 levels on TIL co-expressing Tim-3. Dampened Akt/S6 phosphorylation in these PD-1<sup>+</sup>Tim-3<sup>+</sup> TIL, when the PD-1 pathway was ligated, suggested that signaling cross-talk could lead to escape through Tim-3 expression. Indeed, PD-1 blockade of human HNSCC TIL led to further Tim-3 upregulation, supporting a circuit of compensatory signaling and potentially permitting escape from anti-PD-1 blockade in the tumor microenvironment. Also, in a murine HNC tumor model that is partially responsive to anti-PD-1 therapy, Tim-3 was upregulated in TIL from persistently growing tumors. Significant antitumor activity was observed after sequential addition of anti-Tim-3 mAb to overcome adaptive resistance to anti-PD-1 mAb. This increased Tim-3-mediated escape of exhausted TIL from PD-1 inhibition that was mediated by phospho-inositol-3 kinase (PI3K)/Akt complex downstream of TCR signaling but not cytokine-mediated pathways. Taken together, we conclude that during PD-1 blockade, TIL upregulate Tim-3 in a PI3K/Akt-dependent manner, providing further support for dual targeting of these molecules for more effective cancer immunotherapy.
A SCHEME FOR ADAPTIVE BIASING IN IMPORTANCE SAMPLING (1998)

This paper considers simulation of large networks. The quantities of interest, such as system failure, blocking or cell loss probability, are dependent on observations of rare events. For evaluation of such systems, previous work have shown that simulation with a speed-up technique called importance sampling is an efficient means, provided that a good biasing of the simulation parameters exists. This paper addresses the unsolved problem of parameter biasing in large networks with well balanced resources. A new algorithm for adaptive biasing of the simulation parameters is introduced. In addition, a flexible framework for modelling of both traffic and dependability aspects of the network is described. As a feasibility demonstration, the applicability of the proposed simulation framework is demonstrated by evaluation of time blocking probabilities in a network example. This network has traffic classes with different quality of service requirements, different capacity requirements, altern...
Noise sensitivity in frequency-resolved optical-gating measurements of ultrashort pulses (1995)

Frequency-resolved optical gating (FROG), a technique for measuring ultrashort laser pulses, involves producing a spectrogram of the pulse and then retrieving the pulse intensity and phase with an iterative algorithm. We study how several types of noise—multiplicative, additive, and quantization—affect pulse retrieval. We define a convergence criterion and find that the algorithm converges to a reasonable pulse field, even in the presence of 10% noise. Specifically, with appropriate filtering, 1% rms retrieval error is achieved for 10% multiplicative noise, 10% additive noise, and as few as 8 bits of resolution. For additive and multiplicative noise the retrieval errors decrease roughly as the square root of the amount of noise. In addition, the background induced in the wings of the pulse by additive noise is equal to the amount of additive noise on the trace. Thus the dynamic range of the measured intensity and phase is limited by a noise floor equal to the amount of additive noise on the trace. We also find that, for best results, a region of zero intensity should surround the nonzero region of the trace. Consequently, in the presence of additive noise, baseline subtraction is important. We also find that Fourier low-pass filtering improves pulse retrieval without introducing significant distortion, especially in high-noise cases. We show that the field errors in the temporal and the spectral domains are equal. Overall, the algorithm performs well because the measured trace contains N2 data points for a pulse that has only 2N degrees of freedom; FROG has built in redundancy.