gebhart/patrepeval huggingface dataset:
ErbB Receptors: Directing Key Signaling Networks Throughout Life (2004)

The epidermal growth factor (EGF)-related peptides bind the ErbB receptors, inducing the formation of different homo- and heterodimers. Receptor dimerization promotes activation of the intrinsic kinase, leading to phosphorylation of specific tyrosines located in the ErbB's cytoplasmic region. These phosphorylated residues serve as docking sites for a variety of signaling molecules whose recruitment stimulates intracellular signaling cascades, which ultimately control diverse genetic programs. Particular ligand-receptor complexes have essential roles in embryonic development as well as in the adult. Finally, ErbB receptors are being pursued as therapeutic targets because aberrant ErbB activity has been observed in many human cancers. In this review, we discuss these data in more detail, illustrating the importance of tightly regulated ErbB signaling throughout life.
Area efficient layouts of binary trees in grids (2001)

We consider layouts of binary trees into two and three dimensional grids with the objective to minimize the layout's expansion, where expansion is the number of grid nodes divided by the number of tree nodes. A layout is a special case of an embedding, i.e. a one-to-one mapping from tree nodes to grid nodes, such that edges of the tree are assigned to specific paths of grid edges which must not include nodes in the grid assigned to tree nodes. Furthermore, the paths assigned to tree edges in a layout must not overlap with any other such path at any node. 
The results shown include (1) layouts of arbitrarily large complete binary trees into square two-dimensional grids with asymptotic expansion 1.4238 for even height and 1.4194 for odd heights, respectively, (2) layouts for arbitrarily large complete binary trees into square three dimensional grids with two layers with asymptotic expansion 1.2656 for even heights and 1.2207 for odd heights, (3) layouts for arbitrarily large complete binary trees into square three dimensional grids with six layers with asymptotic expansion 1.1719, and (4) layouts for arbitrarily large complete binary trees into three-dimensional grids with all three dimensions of approximately the same size with asymptotic expansion 1.09375. Furthermore, the techniques used for the recursive construction of these techniques may well be applicable in layouts with better expansion bounds of complete binary trees. 
It is also shown that the problem of deciding if an arbitrary binary tree can be laid out in a two dimensional grid with specified dimensions is NP-Complete. No constant upper bound is known on expansion for laying out arbitrary binary trees in two dimensional grids. It is shown that any binary tree can be laid out in area O(n log n) in a two dimensional grid and with area O(n) in a two dimensional extended grid (with added diagonal connections).
Internal regulation of ATP turnover, glycolysis and oxidative phosphorylation in rat hepatocytes (1999)

Previously [Ainscow, E.K. & Brand, M.D. (1999) Eur. J. Biochem. 263, 671-685], top-down control analysis was used to describe the control pattern of energy metabolism in rat hepatocytes. The system was divided into nine reaction blocks (glycogen breakdown, glucose release, glycolysis, lactate production, NADH oxidation, pyruvate oxidation, mitochondrial proton leak, mitochondrial phosphorylation and ATP consumption) linked by five intermediates (intracellular glucose 6-phosphate, pyruvate and ATP levels, cytoplasmic NADH/NAD ratio and mitochondrial membrane potential). The kinetic responses (elasticities) of reaction blocks to intermediates were determined and used to calculate control coefficients. In the present paper, these elasticities and control coefficients are used to quantify the internal regulatory pathways within the cell. Flux control coefficients were partitioned to give partial flux control coefficients. These describe how strongly one block of reactions controls the flux through another via its effects on the concentration of a particular intermediate. Most flux control coefficients were the sum of positive and negative partial effects acting through different intermediates; these partial effects could be large compared to the final control strength. An important result was the breakdown of the way ATP consumption controlled respiration: changes in ATP level were more important than changes in mitochondrial membrane potential in stimulating oxygen consumption when ATP consumption increased. The partial internal response coefficients to changes in each intermediate were also calculated; they describe how steady state concentrations of intermediates are maintained. Increases in mitochondrial membrane potential were opposed mostly by decreased supply, whereas increases in glucose-6-phosphate, NADH/NAD and pyruvate were opposed mostly by increased consumption. Increases in ATP were opposed significantly by both decreased supply and increased consumption.
Serum Peptide Profiling by Magnetic Particle-Assisted, Automated Sample Processing and MALDI-TOF Mass Spectrometry (2004)

Human serum contains a complex array of proteolytically derived peptides (serum peptidome) that may provide a correlate of biological events occurring in the entire organism; for instance, as a diagnostic for solid tumors (Petricoin, E. F.; Ardekani, A. M.; Hitt, B. A.; Levine, P. J.; Fusaro, V. A.; Steinberg, S. M.; Mills, G. B.; Simone, C.; Fishman, D. A.; Kohn, E. C.; Liotta, L. Lancet 2002, 359, 572-577). Here, we describe a novel, automated technology platform for the simultaneous measurement of serum peptides that is simple, scalable, and generates highly reproducible patterns. Peptides are captured and concentrated using reversed-phase (RP) batch processing in a magnetic particle-based format, automated on a liquid handling robot, and followed by a MALDI TOF mass spectrometric readout. The protocol is based on a detailed investigation of serum handling, RP ligand and eluant selection, small-volume robotics design, an optimized spectral acquisition program, and consistent peak extraction plus binning across a study set. The improved sensitivity and resolution allowed detection of 400 polypeptides (0.8-15-kDa range) in a single droplet (approximately 50 microL) of serum, and almost 2000 unique peptides in larger sample sets, which can then be analyzed using common microarray data analysis software. A pilot study indicated that sera from brain tumor patients can be distinguished from controls based on a pattern of 274 peptide masses. This, in turn, served to create a learning algorithm that correctly predicted 96.4% of the samples as either normal or diseased.
Reported gastrointestinal infections in the U.S. Air Force, 2000-2012. (2014)

During 2000-2012, U.S. Air Force Public Health Offices reported 3,429 cases of gastrointestinal infection (GI) diagnosed at Air Force medical treatment facilities. The four most commonly reported specific etiologies of GIs accounted for 86.7% of all GI cases (n=2,972). Salmonellosis accounted for 41.4% (n=1,420) of all cases. The next most commonly reported events were associated with Campylobacter infection, shigellosis, and giardiasis. The majority of GI cases were reported among dependents, most notably among those aged 0-5 years. Campylobacter infections represented a significantly larger proportion of GI reported from locations outside the continental United States (OCONUS) (n=222, 33.7%) compared to continental U.S. (CONUS) locations (n=363, 13.1%). CONUS locations reported higher proportions of salmonellosis, shigellosis, and giardiasis infections compared to OCONUS locations. Annual numbers of reported cases of GI peaked in 2002, declined to much lower numbers during 2004-2007, and then began to climb until the end of the surveillance period.
Matrix metalloproteinase inhibitors in rheumatic diseases (2001)

The rheumatic diseases continue to represent a significant healthcare burden in the 21st century. However, despite the best standard of care and recent therapeutic advances it is still not possible to consistently prevent the progressive joint destruction that leads to chronic disability. In rheumatoid arthritis and osteoarthritis this progressive cartilage and bone destruction is considered to be driven by an excess of the matrix metalloproteinase (MMP) enzymes. Consequently, a great number of potent small molecule MMP inhibitors have been examined. Several MMP inhibitors have entered clinical trials as a result of impressive data in animal models, although only one MMP inhibitor, Ro32-3555 (Trocade), a collagenase selective inhibitor, has been fully tested in the clinic, but it did not prevent progression of joint damage in patients with rheumatoid arthritis. The key stages and challenges associated with the development of an MMP inhibitor in the rheumatic diseases are presented below with particular reference to Trocade. It is concluded that the future success of MMP inhibitors necessitates a greater understanding of the joint destructive process and it is hoped that their development may be accompanied with clearer, more practical, outcome measures to test these drugs for, what remains, an unmet medical need.
Real-time Estimation of Elastic Properties of Formation Rocks Based on Drilling Data by Using an Artificial Neural Network (2013)

Understanding the mechanical properties of formations has its importance in the drilling, production, and management phases of reservoirs. In petroleum engineering, measurements through wire-line logs, which run in the boreholes after the drilling phase, are of the most common methods to estimate mechanical properties of different layers. Elastic rock mechanic measurements from logs are dynamic values and need to be upscaled and calibrated to fit the corresponding pseudo-static measurements that are obtained from cores in the laboratory. As a practical approach to having a continuous profile of these static parameters and surmount the arduousness that confronts by using core samples and laboratory tests, many researchers tried to deploy predictive methods and empirical correlations. However, it will be a great advantage to have a real-time estimation of these static parameters while drilling based on bit and formation rock interaction. Artificial neural networks are powerful tools for estimation of complex functions subjected to availability of large enough data sets that present samples of actual behavior of the function. In this study, artificial neural networks were implemented to estimate in situ rock mechanical properties, including Unconfined Compressive Strength, Young's Modulus of Elasticity, and the ratio of these parameters known as Modulus Ratio, by using operational drilling parameters as inputs. Required data were gathered from drilling reports, logging operations, and core samples from nine wells placed in Ahwaz Oilfield located in south-west Iran. The trained networks showed satisfactory low errors in the testing process and sketched the capability of artificial neural networks in estimation of complex functions. The accuracy of the presented model was then compared with the results of calibrated regional correlations and modified Warren's equation. These correlations are used in the candidate wells to estimate Unconfined Compressive Strength and Young's Modulus of Elasticity. It was observed that the new artificial neural network approach is a competent and accurate method for real-time calculation of static elastic properties of formation rocks. The results of this work could be used for drilling optimization, reducing stability problems, and lithologic boundary detection while drilling.
A Multiepitope Subunit Vaccine Conveys Protection against Extraintestinal PathogenicEscherichia coliin Mice (2010)

Infections due to extraintestinal pathogenic Escherichia coli (ExPEC) are common in humans and animals and include urinary tract infections (from uropathogenic E. coli [UPEC]), septicemia, and wound infections. These infections result in significant morbidity and mortality and in high health care costs. In view of the increasing number of ExPEC infections and the ever-growing antibiotic resistance capability of ExPEC isolates, preventive measures such as an effective vaccine against ExPEC are desirable. An ExPEC vaccine may be cost-effective for select patient groups. Previous vaccine candidates consisted of single target proteins or whole ExPEC cells. Here we describe a subunit vaccine against ExPEC which is based on immunodominant epitopes of the virulence-associated ExPEC proteins FyuA, IroN, ChuA, IreA, Iha, and Usp. Using a novel approach of computer-aided design, two completely artificial genes were created, both encoding eight peptide domains derived from these ExPEC proteins. The recombinant expression of these two genes resulted in a protein vaccine directed against ExPEC but not against commensal E. coli of the gut flora. In mice, the vaccine was highly immunogenic, eliciting both strong humoral and cellular immune responses. Nasal application resulted in high secretory immunoglobulin A (sIgA) production, which was detectable on the mucosal surface of the urogenital tract. Finally, it conveyed protection, as shown by a significant reduction of bacterial load in a mouse model of ExPEC peritonitis. This study provides evidence that a novel vaccine design encompassing distinct epitopes of virulence-associated ExPEC proteins may represent a means for providing a protective and pathogen-specific vaccine.
The inhibition of T cell proliferation in a mixed lymphocyte reaction by Itolizumab (T1h) is associated with reduction in pro inflammatory cytokines and CD6 internalization. (52.27) (2011)

Abstract We have shown previously that the CD6-ALCAM interaction in vitro induced a synergistic co-stimulation of normal human peripheral blood mononuclear cells (PBMCs), defined by Bliss analysis. The use of a CD6 membrane-distal domain (SRCR1)-specific non-depleting monoclonal antibody Itolizumab, inhibited the CD6-ALCAM induced proliferation of PBMCs. This is associated with reduction in pro inflammatory cytokines at the protein and mRNA level. In this study, we show that the antibody inhibits T cell proliferation in a typical mixed lymphocyte reaction wherein the matured dendritic cells over express ALCAM. The inhibition is associated with reduction in CD4 and CD25 surface expression in these T cells. A marked reduction in interferon-γ, tumour necrosis factor-α and IL-17 production is also observed. Using confocal microscopy we show that the receptor CD6 internalization occurs within minutes in T cells in the presence of Itolizumab and is not localized to the immunological synapse. Intriguingly, a deglycosylated antibody showed reduced inhibition of T cells in the mixed lymphocyte reaction. The deglycosylated antibody did not show any difference in binding to HuT 78 cell expressing CD6 as compared to the normal antibody. These results would suggest that the monoclonal antibody Itolizumab also prevents T cell proliferation induced in mixed lymphocyte reactions and there is a role for the Fc region glycosylation of the antibody to elucidate this function.
Pausing of the Restriction Endonuclease EcoRI during Linear Diffusion on DNA (1994)

Linear diffusion is a mechanism to accelerate association rates beyond their three-dimensional diffusional limit. It is employed by the restriction endonuclease EcoRI as well as many other proteins interacting with specific DNA sequences to locate their target sites on the macromolecular substrate. In order to investigate biochemical and biophysical details of the linear diffusion process, we have developed a competitive cleavage assay which allows us to assess with great accuracy the influence of sequence, sequence context, and other structural features on the linear diffusion of EcoRI on DNA. We show here that linear diffusion is not a hopping but a sliding movement in which EcoRI follows the helical pitch of the DNA, because it does not "overlook" any cleavage site. Linear diffusion is slowed when EcoRI encounters sites on the DNA which resemble its recognition site ("star" sites). Pauses of up to 20 s are induced, depending on sequence and orientation of the star site. These data suggest that EcoRI can bind to DNA in two binding modes: one tight, specific, and immobile, leading to DNA cleavage, and another one loose and nonspecific, allowing for linear diffusion. Depending on the similarity between the recognition sequence and the DNA sequence being encountered by EcoRI, there will be a continuous transition between these binding modes. Other proteins bound to the DNA and irregular DNA structures such as bent DNA or a triple helix constitute a barrier that cannot easily be passed by EcoRI.
Fluorescent Probes Used for Detection of Hydrogen Peroxide under Biological Conditions (2015)

Hydrogen peroxide is a well-established precursor of reactive oxygen and nitrogen species that are known to contribute to oxidative stress-the crucial factor responsible for the course of a wide range of phy-sicochemical processes as well as the genesis of various diseases, such as cancer and neurodegenerative disorders. Thus, the development of sensitive and selective methods for the detection and quantitative determination of hydrogen peroxide is of great importance in monitoring the in vivo production of that species and elucidating its biological functions. This review highlights the progress that has been made in the development of fluorescent and luminescent probes (excluding nanoparticles) employed to monitor hydrogen peroxide under biological conditions. Attention was focused on probes developed in the past 10 years.
Environment and Disease Risks (2010)

A new paradigm is needed to assess how a lifetime of exposure to environmental factors affects the risk of developing chronic diseases.
Cordycepin analogues of 2-5A and its derivatives. Chemical synthesis and biological activity. (1983)

Cordycepin (3'-deoxyadenosine) analogues of 2-5A were prepared by dicyclohexylcarbodiimide-induced polymerization of cordycepin 5'-monophosphate. A series of oligomers of the general formula p5'(3'dA)-2'[p5'(3'dA)]n (n = 1-5) was obtained. Cordycepin trimer 5'-monophosphate (n = 2) and cordycepin tetramer 5'-monophosphate (n = 3) were converted to the corresponding 5'-di- and triphosphates via the phosphorimidazolide method. Confirmation of assigned structures was provided through enzyme digestions, 1H and 31P NMR, and comparison with material which was synthesized by a completely independent route. Neither the cordycepin trimer triphosphate, ppp5'(3'dA)-2'p5'(3'dA)2'p5'(3'dA), nor the cordycepin tetramer triphosphate, ppp5'(3'dA)2'p5'(3'dA)2'p5'(3'dA)2'p5'-(3'dA), were inhibitors of translation in cell-free extracts of mouse L-cells programmed with encephalomyocarditis virus. In rabbit reticulocyte lysates, the cordycepin trimer triphosphate was devoid of activity, whereas the cordycepin tetramer triphosphate had approximately 1/100th the activity of 2-5A tetramer triphosphate, ppp5'A2'p5'A2'p5'A2'p5'A. Even though the cordycepin analogues were unable to activate the 2-5A-dependent endoribonuclease, they were able to bind to the endonuclease, thereby antagonizing the translational inhibitory effects of 2-5A. Thus, replacement of the 3'-hydroxyl groups of all the ribose moieties of 2-5A results in an analogue which can bind to the 2-5A-dependent endoribonuclease but is incapable of activating the enzyme. The 3'-hydroxyl groups of 2-5A, therefore, are critical for activation of the 2-5A-dependent endonuclease.
Unique Lipoproteins Secreted by Primary Astrocytes From Wild Type, apoE (−/−), and Human apoE Transgenic Mice (1999)

Composition of central nervous system lipoproteins affects the metabolism of lipoprotein constituents within the brain. The epsilon4 allele of apolipoprotein E (apoE) is a risk factor for Alzheimer's disease via an unknown mechanism(s). As glia are the primary central nervous system cell type that synthesize apoE, we characterized lipoproteins secreted by astrocytes from wild type (WT), apoE (-/-), and apoE transgenic mice expressing human apoE3 or apoE4 in a mouse apoE (-/-) background. Nondenaturing size exclusion chromatography demonstrates that WT, apoE3, and apoE4 astrocytes secrete particles the size of plasma high density lipoprotein (HDL) composed of phospholipid, free cholesterol, and protein, primarily apoE and apoJ. However, the lipid:apoE ratio of particles containing human apoE is significantly lower than WT. ApoE localizes across HDL-like particle sizes. ApoJ localizes to the smallest HDL-like particles. ApoE (-/-) astrocytes secrete little phospholipid or free cholesterol despite comparable apoJ expression, suggesting that apoE is required for normal secretion of astrocyte lipoproteins. Further, particles were not detected in apoE (-/-) samples by electron microscopy. Nondenaturing immunoprecipitation experiments indicate that apoE and apoJ reside predominantly on distinct particles. These studies suggest that apoE expression influences the unique structure of astrocyte lipoproteins, a process further modified by apoE species.
EGFR Inhibition Induces Proinflammatory Cytokines via NOX4 in HNSCC (2013)

The antitumor activity of EGFR inhibitors is reduced by activation of NOX4-mediated proinflammatory pathways in HNSCC.
High critical currents in strained epitaxial YBa2Cu3O7−δ on Si (1990)

Epitaxial YBa2Cu3O7−δ (YBCO) films were grown on Si (100) using an intermediate buffer layer of yttria-stabilized zirconia. Both layers are grown via an entirely in situ process by pulsed laser deposition. All films consist of c-axis oriented grains as measured by x-ray diffraction. Strain results from the large difference in thermal expansion coefficients between Si and YBCO. Thin (&amp;lt;500 Å) YBCO films are unrelaxed and under tensile strain with a distorted unit cell. Rutherford backscattering spectroscopy indicates a high degree of crystalline perfection with a channeling minimum yield for Ba as low as 12%. The normal-state resistivity is 280 μΩ cm at 300 K; the critical temperature Tc (R=0) is 86–88 K with a transition width (ΔTc) of 1 K. Critical current densities of 2×107 A/cm2 at 4.2 K and 2.2×106 A/cm2 at 77 K have been achieved.