gebhart/patrepeval huggingface dataset:
The Basis for the Distinct Biological Activities of Vascular Endothelial Growth Factor Receptor–1 Ligands (2013)

Vascular endothelial growth factors (VEGFs) regulate blood and lymphatic vessel development through VEGF receptors (VEGFRs). The VEGFR immunoglobulin homology domain 2 (D2) is critical for ligand binding, and D3 provides additional interaction sites. VEGF-B and placenta growth factor (PlGF) bind to VEGFR-1 with high affinity, but only PlGF is angiogenic in most tissues. We show that VEGF-B, unlike other VEGFs, did not require D3 interactions for high-affinity binding. VEGF-B with a PlGF-derived L1 loop (B-L1P) stimulated VEGFR-1 activity, whereas PlGF with a VEGF-B-derived L1 loop (P-L1B) did not. Unlike P-L1B and VEGF-B, B-L1P and PlGF were also angiogenic in mouse skeletal muscle. Furthermore, B-L1P also bound to VEGFR-2 and activated downstream signaling. These results establish a role for L1-mediated D3 interactions in VEGFR activation in endothelial cells and indicate that VEGF-B is a high-affinity VEGFR-1 ligand that, unlike PlGF, cannot efficiently induce signaling downstream of VEGFR-1.
Mechanisms of resistance to anti-Pd-1 therapy in metastatic cutaneous melanoma (2018)

The appearance of modulators immune synapse in clinical practice has become a revolution in metastatic skin melanoma treatment. However, blockade PD-1 allows to achieve objective response in only 30–40 % of patients. Recently, many mechanisms of primary resistance of melanoma to immunotherapy studied, they related both to the characteristics of the tumor and the tumor microenvironment. The response to anti-PD-1 therapy usually is durable, but acquired resistance emerges in 25 % of patients, who had an objective response to this treatment. This review will describe the main mechanisms of resistance to anti-PD-1 therapy in metastatic skin melanoma and possible ways of their overcoming.
Leucine Deprivation Increases Hepatic Insulin Sensitivity via GCN2/mTOR/S6K1 and AMPK Pathways (2011)

This study describes mechanisms underlying increased hepatic insulin sensitivity under leucine deprivation. Furthermore, we demonstrate a novel function for GCN2 in the regulation of insulin sensitivity. These observations provide a rationale for short-term dietary restriction of leucine for the treatment of insulin resistance and associated metabolic diseases.
Modulation of transcription factor--DNA interactions by anticancer drugs. (1994)

Anticancer drugs which bind DNA can alter the mechanism of gene transcription regulation. In this paper, we report examples of the ability of DNA-interacting drugs to alter the specific DNA binding and function of well-characterized transcription factors to their consensus DNA sequences. In particular, we have examined the effects of major groove binders such as methylating agents, chloroethylating agents and nitrogen mustards, and also minor groove binders such as distamycin derivatives. The results support the view that alterations of the DNA binding of transcription factors caused by the DNA-interacting agents may play an important role in the antitumor effects of these agents. Work is needed to obtain more highly DNA sequence-specific binders which can act as selective modulators of the transcription of genes involved in the malignant properties of cancer cells.
Avian VEGF-C: cloning, embryonic expression pattern and stimulation of the differentiation of VEGFR2-expressing endothelial cell precursors (1998)

VEGF-C is a recently discovered secreted polypeptide related to the angiogenic mitogen VEGF. We have isolated the quail VEGF-C cDNA and shown that its protein product is secreted from transfected cells and interacts with the avian VEGFR3 and VEGFR2. In situ hybridization shows that quail VEGF-C mRNA is strongly expressed in regions destined to be rich in lymphatic vessels, particularly the mesenteries, mesocardium and myotome, in the region surrounding the jugular veins, and in the kidney. These expression sites are similar to those observed in the mouse embryo (E. Kukk, A. Lymboussaki, S. Taira, A. Kaipainen, M. Jeltsch, V. Joukov and K. Alitalo, 1996, Development 122, 3829-3837). We have observed VEGFR3-positive endothelial cells in proximity to most of the VEGF-C-expressing sites, suggesting functional relationships between this receptor-ligand couple. The comparison of the VEGF and VEGFR2 knockout phenotypes had suggested the existence of another ligand for VEGFR2. We therefore investigated the effect of VEGF-C on VEGFR2-positive cells isolated from the posterior mesoderm of gastrulating embryos. We have recently shown that VEGF binding triggers endothelial differentiation of these cells, whereas hemopoietic differentiation appears to be mediated by binding of a so far unidentified VEGFR2 ligand. We show here that VEGF-C also triggers endothelial differentiation of these cells, presumably via VEGFR2. These results indicate that VEGF and VEGF-C can act in a redundant manner via VEGFR2. In conclusion, VEGF-C appears to act during two different developmental phases, one early in posterior mesodermal VEGFR2-positive endothelial cell precursors which are negative for VEGFR3 and one later in regions rich in lymphatic vessels at a time when endothelial cells express both VEGFR2 and VEGFR3.
Contemporary polymer chemistry (1981)

I. SYNTHESIS AND REACTIONS OF POLYMERS. 1. The Scope of Polymer Chemistry. 2. Condensation and Other Step-Type Polymerizations. 3. Free-Radical Polymerization. 4. Ionic and Coordination Polymerization. 5. Photolytic, Radiation, and Electrolytic Polymerization. 6. Polmerization of Cyclic Organic Compounds. 7. Reactions of Synthetic Polymers. 8. Biological Polymers and Their Reactions. 9. Inorganic Elements in Polymers. II. THERMODYNAMICS AND KINETICS OF POLYMERIZATION. 10. Polymerization and Depolymerization Equilibria. 11. Kinetics of Condensation (Step-Growth) Polymerization. 12. Kinetics of Free-Radical Polymerization. 13. Kinetics of Ionic Polymerization. III. PHYSICAL CHARACTERIZATION OF POLYMERS. 14. Determination of Absolute Molecular Weights. 15. Secondary Methods for Molecular Weight Determination. 16. Thermodynamics of Solutions of High Polymers. 17. Morphology, Glass Transitions, and Polymer Crystallinity. 18. Conformational Analysis of Polymers. 19. X-Ray Diffraction by Polymers. IV. FABRICATION AND TESTING OF POLYMERS. 20. Fabrication of Polymers. 21. Testing of Polymers. V. MOLECULAR STRUCTURE, PROPERTIES, AND USES. 22. General Structure-Property Relationships. 23. Electroactive Polymers. 24. Biomedical Applications of Synthetic Polymers. VI. APPENDICES. I. Polymer Nomenclature. II. Properties and Uses of Selected Polymers. III. References to Topics not Discussed in this Book. Author Index. Subject Index.
Recombinant Activated Factor VII for the Rapid Correction of Coagulopathy in Nonhemophilic Neurosurgical Patients (2003)

The use of rFVIIa for the urgent surgical treatment of coagulopathic patients is quite promising. Further studies, including randomized, prospective trials using rFVIIa to address issues such as optimal dosing, efficacy, surgical indications, cost-effectiveness, morbidity, and mortality are needed.
Nucleotide sequence of β-lactamase regulatory genes from staphylococcal plasmid p1258 (1991)

Journal Article Nucleotide sequence of β-lactamase regulatory genes from staphylococcal plasmid p1258 Get access Pei-Zhi Wang, Pei-Zhi Wang Departments of Plasmid Biology and Applied Genetics, The Public Health Research Institute of the City of New York, Inc.,455 First Avenue, New York, NY 10016, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Steven J. Projan, Steven J. Projan Departments of Plasmid Biology and Applied Genetics, The Public Health Research Institute of the City of New York, Inc.,455 First Avenue, New York, NY 10016, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard P. Novick Richard P. Novick Departments of Plasmid Biology and Applied Genetics, The Public Health Research Institute of the City of New York, Inc.,455 First Avenue, New York, NY 10016, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Nucleic Acids Research, Volume 19, Issue 14, 25 July 1991, Page 4000, https://doi.org/10.1093/nar/19.14.4000 Published: 25 July 1991 Article history Accepted: 02 May 1991 Published: 25 July 1991
A study of dielectric covered mono-conical antenna for broadband and small-sized application (2004)

This paper presented the fundamental characteristics of the dielectric covered mono-conical antenna, followed by its principal radiation property obtained both analytically and experimentally. The multi angled configuration for constructing a slim or low profile antenna and the resistive loaded configuration for compactness were also investigated. In conclusion, our study suggested that this kind of antenna holds sufficient potential as a small-sized antenna for ultra-wideband communications.
Maximum-Likeliho od Seauence Estimation of Digital Sequences i&he Presence of Intersymbol Interference (1972)

A maximum-likelihood sequence estimator for a digital pulse-amplitude-modulated sequence in the presence of finite intersymbol interference and white Gaussian noise is developed. The structure cbm- prises a sampled linear filter, called a whitened matched filter, and a recursive nonlinear processor, called the Viterbi algorithm. The outputs of the whitened matched filter, sampled once for each input symbol, are shown to form a set of suillcient statistics for estimation of the input sequence, a fact that makes obvious some earlier results on optimum linear processors. The Viterbi algorithm is easier to implement than earlier optimum nonlinear processors and its performance can be straight- forwardly and accurately estimated. It is shown that performance (by whatever criterion) is effectively as good as could be attained by any receiver structure and in many cases is as good as if intersymbol inter- ference were absent. Finally, a simplified but effectively optimum algorithm suitable for the most popular partial-response schemes is described.
Gravity and magnetics studies in the Vrancea Zone of Romania (1996)

The paper presents a method of computing the gravity gradient tensor resulting from a system of right rectangular prisms into 3-D model for the Vrancea zone (Galati - Focsani - Vrancioaia - Tg. Secuiesc profile).
Nucleoside analogs. I. A synthesis of 1,3‐dihydroxy‐2‐(6‐substituted‐9‐purinyl)cyclohexane (1969)

Abstract Biologically active 1,3‐dihydroxy‐2‐(6‐substituted‐9‐purinyl)cyclohexanes (VI‐X) were prepared by a reaction between trans ‐2‐amino‐1,3‐cyclohexanediol (I) and 4,6‐dichloro‐5‐amino‐pyrimidine (II), followed by cyclization and nucleophilic substitution. Compounds VI and VII showed a weak inhibitory effect against Xanthomonas oryzae , a pathogenic bacteria of leaf blight of rice plant.
Immunomodulatory and immunotherapeutic properties of recombinant gamma-interferon and recombinant tumor necrosis factor in mice. (1987)

These studies were designed to examine the immunodulatory and immunotherapeutic properties of recombinant murine interferon gamma (rM IFN-gamma) and recombinant human tumor necrosis factor (rH TNF). We report that rM IFN-gamma activated murine natural killer cells and macrophages in a dose-dependent manner in vivo. The rM IFN-gamma, which demonstrated a bell-shaped therapeutic response curve, must be administered at specific doses and schedules to produce optimal therapeutic activity. Optimal activity was observed after i.v. administration of 50,000 U/animal rM IFN-gamma three times per week. In contrast, rH TNF produced its major therapeutic activity in the treatment of metastatic disease after i.v. but not i.p. administration. The therapeutic effects of rH TNF were as great in these in vivo systems as those of rM IFN-gamma. Furthermore, rH TNF had additive therapeutic activity when administered in conjunction with suboptimal doses of rM IFN-gamma. Unlike rM IFN-gamma, rH TNF did not activate natural killer cells in vivo or in vitro but did augment in vivo and in vitro macrophage tumoricidal activity. It also had synergistic cytostatic properties with rM IFN-gamma for some murine tumor cell lines in vitro. High levels of rH TNF were readily detected in the serum with a half-life of approximately 30 min after i.v. administration. In contrast, only minimal serum TNF activity occurred after i.p. administration, suggesting that i.v. administration may more efficiently facilitate systemic therapeutic activity. In summary, rH TNF and rM IFN-gamma have therapeutic activity for metastatic disease as individual agents and additive therapeutic activity when used in combination. Furthermore, it appears that in addition to therapeutic potential as cytostatic agents, the immunomodulatory properties of rH TNF have a role in its therapeutic properties.
Aliovalent Substitutions in Olivine Lithium Iron Phosphate and Impact on Structure and Properties (2009)

Abstract Lithium transition metal phosphate olivines are enabling a new generation of high power, thermally stable, long‐life rechargeable lithium batteries that may prove instrumental in the worldwide effort to develop cleaner and more sustainable energy. Nanoscale (&lt;100 nm) derivatives of the olivine family LiMPO 4 (M = Fe, Mn, Co, Ni) are being adopted in applications ranging in size scale from hybrid and plug‐in hybrid electric vehicles to utilities‐scale power regulation. Following the previous paradigm set with intercalation oxides, most studies have focused on the pure ordered compounds and isovalent substitutions. In contrast, even the possibility for, and role of, aliovalent doping has been widely debated. Here, critical tests of plausible defect compensation mechanisms using compositions designed to accommodate Mg 2+ , Al 3+ , Zr 4+ , Nb 5+ ions on the M1 and/or M2 sites of LiFePO 4 with appropriate charge‐compensating defects are carried out, and conclusive crystallographic evidence for lattice doping, e.g., up to at least 12 atomic percent added Zr, is obtained. Structural and electrochemical analyses show that doping can reduce the lithium miscibility gap, increase phase transformation kinetics during cycling, and expand Li diffusion channels in the structure. Aliovalent modifications may be effective for introducing controlled atomic disorder into the ordered olivine structure to improve battery performance.
Fabricating neuromast-inspired gel structures for membrane-based hair cell sensing (2012)

Recent research has shown that a new class of mechanical sensor, assembled from biomolecules and which features an artificial cell membrane as the sensing element, can be used to mimic basic hair cell mechanotransduction in vertebrates. The work presented in this paper is motivated by the need to increase sensor performance and stability by refining the methods used to fabricate and connect lipid-encapsulated hydrogels. Inspired by superficial neuromasts found on fish, three hydrogel materials are compared for their ability to be readily shaped into neuromast-inspired geometries and enable lipid bilayer formation using self-assembly at an oil/water interface. Agarose, polyethylene glycol (PEG, 6kg/mole), and hydroxyethyl methacrylate (HEMA) gel materials are compared. The results of this initial study determined that UV-curable gel materials such as PEG and HEMA enable more accurate shaping of the gel-needed for developing a sensor that uses a gel material both for mechanical support and membrane formation-compared to agarose. However, the lower hydrophobicity of agarose and PEG materials provide a more fluid, water-like environment for membrane formation-unlike HEMA. In working toward a neuromast-inspired design, a final experiment demonstrates that a bilayer can also be formed directly between two lipid-covered PEG surfaces. These initial results suggest that candidate gel materials with a low hydrophobicity, high fluidity, and a low modulus can be used to provide membrane support.
Metabolism of Alzheimer beta-amyloid precursor protein: regulation by protein kinase A in intact cells and in a cell-free system. (1996)

Various compounds that affect signal transduction regulate the relative utilization of alternative processing pathways for the beta-amyloid precursor protein (beta APP) in intact cells, increasing the production of nonamyloidogenic soluble beta APP (s beta APP) and decreasing that of amyloidogenic beta-amyloid peptide. In a recent study directed toward elucidating the mechanisms underlying phorbol ester-stimulated s beta APP secretion from cells, it was demonstrated that protein kinase C increases the formation from the trans-Golgi network (TGN) of beta APP-containing secretory vesicles. Here we present evidence that forskolin increases s beta APP production from intact PC12 cells, and protein kinase A stimulates formation from the TGN of beta APP-containing vesicles. Although protein kinase A and protein kinase C converge at the level of formation from the TGN of beta APP-containing vesicles, additional evidence indicates that the regulatory mechanisms involved are distinct.
Intrinsic excitability measures track antiepileptic drug action and uncover increasing/decreasing excitability over the wake/sleep cycle (2015)

Pathological changes in excitability of cortical tissue commonly underlie the initiation and spread of seizure activity in patients suffering from epilepsy. Accordingly, monitoring excitability and controlling its degree using antiepileptic drugs (AEDs) is of prime importance for clinical care and treatment. To date, adequate measures of excitability and action of AEDs have been difficult to identify. Recent insights into ongoing cortical activity have identified global levels of phase synchronization as measures that characterize normal levels of excitability and quantify any deviation therefrom. Here, we explore the usefulness of these intrinsic measures to quantify cortical excitability in humans. First, we observe a correlation of such markers with stimulation-evoked responses suggesting them to be viable excitability measures based on ongoing activity. Second, we report a significant covariation with the level of AED load and a wake-dependent modulation. Our results indicate that excitability in epileptic networks is effectively reduced by AEDs and suggest the proposed markers as useful candidates to quantify excitability in routine clinical conditions overcoming the limitations of electrical or magnetic stimulation. The wake-dependent time course of these metrics suggests a homeostatic role of sleep, to rebalance cortical excitability.
Comparison of Commercially Available Target Enrichment Methods for Next-Generation Sequencing (2013)

Isolating high-priority segments of genomes greatly enhances the efficiency of next-generation sequencing (NGS) by allowing researchers to focus on their regions of interest. For the 2010-11 DNA Sequencing Research Group (DSRG) study, we compared outcomes from two leading companies, Agilent Technologies (Santa Clara, CA, USA) and Roche NimbleGen (Madison, WI, USA), which offer custom-targeted genomic enrichment methods. Both companies were provided with the same genomic sample and challenged to capture identical genomic locations for DNA NGS. The target region totaled 3.5 Mb and included 31 individual genes and a 2-Mb contiguous interval. Each company was asked to design its best assay, perform the capture in replicates, and return the captured material to the DSRG-participating laboratories. Sequencing was performed in two different laboratories on Genome Analyzer IIx systems (Illumina, San Diego, CA, USA). Sequencing data were analyzed for sensitivity, specificity, and coverage of the desired regions. The success of the enrichment was highly dependent on the design of the capture probes. Overall, coverage variability was higher for the Agilent samples. As variant discovery is the ultimate goal for a typical targeted sequencing project, we compared samples for their ability to sequence single-nucleotide polymorphisms (SNPs) as a test of the ability to capture both chromosomes from the sample. In the targeted regions, we detected 2546 SNPs with the NimbleGen samples and 2071 with Agilent's. When limited to the regions that both companies included as baits, the number of SNPs was ∼1000 for each, with Agilent and NimbleGen finding a small number of unique SNPs not found by the other.
Phase II Trial of Cetuximab in Patients With Refractory Colorectal Cancer That Expresses the Epidermal Growth Factor Receptor (2004)

Cetuximab on this once-weekly schedule has modest activity and is well-tolerated as a single agent in patients with chemotherapy-refractory colorectal cancer whose tumors express the epidermal growth factor receptor. Further studies of cetuximab will evaluate the use of cetuximab in conjunction with first-line and adjuvant treatments for this disease.
Introduction to the issue on high-efficiency light-emitting diodes (2002)

Since their inception in the 1960s, light-emitting diodes (LEDs) have enjoyed sustained rapid development in terms of efficiency, available emission spectrum, higher power, higher speed, and application methods. These improvements, coupled with the inherent properties of solid-state devices-ruggedness, low-voltage operation, high reliability, and low cost-have catapulted LEDs into a wide range of applications, from telecommunications, to solid-state lighting, to displays. In each case, LEDs are increasingly replacing the conventional technologies. Even more exciting is the fact that progress in LED technology in each of these areas is continuing at very rapid rate, ensuring that LEDs will continue to see accelerated growth in new and emerging markets, and will find use in applications that would have been considered impossible just a few years ago. Indeed, in this special issue, Watt-class visible-spectrum LEDs are presented for the first time. Here we have 9 invited and 13 contributed papers that give a comprehensive cross-sectional view of the current state-of-the-art in LED technology. The papers are grouped into four main areas: communications, solid-state lighting, ultraviolet emitters, and organic LEDs.
Analysis and Design of Short Block OFDM Spreading Matrices for Use on Multipath Fading Channels (2005)

We consider the use of block spreading in a multicarrier system to gain diversity advantage when employed over multipath fading channels. The main idea is to split the full set of subcarriers into smaller blocks and spread the data symbols across these blocks via unitary spreading matrices in order to gain multipath diversity across each block at the receiver. We pose the problem of designing the spreading matrix as a finite dimensional optimization problem in which the asymptotic error is minimized. This formulation allows us to find explicit solutions for the optimal spreading matrices. The performance is validated for the uncoded channel as well as for the coded channel employing turbo-iterative decoding. We further demonstrate that suboptimal linear complexity equalization strategies for spread orthogonal frequency division multiplexing (OFDM) do not gain any diversity advantage over traditional diagonal OFDM.