gebhart/patrepeval huggingface dataset:
Hemophilia B with Mutations at Glycine-48 of Factor IX Exhibited Delayed Activation by the Factor VIIa-tissue Factor Complex (2000)

Gly-48 is in the conserved DGDQC sequence (residues 47-51 of human factor IX) of the first EGF (EGF-1)-like domain of factor IX. The importance of the Gly-48 is manifested by two hemophilia B patients; factor IXTainan and factor IXMalmo27, with Gly-48 replaced by arginine (designated IXG48R) and valine (IXG48V), respectively. Both patients were CRM+ exhibiting mild hemophilic episodes with 25% (former) and 19% (latter) normal clotting activities. We characterize both factor IX variants to show the roles of Gly-48 and the conservation of the DGDQC sequence in factor IX. Purified plasma and recombinant factor IX variants exhibited approximately 26%-27% normal factor IX's clotting activities with G48R or G48V mutation. Both variants depicted normal quenching of the intrinsic fluorescence by increasing concentrations of calcium ions and Tb3+, indicating that arginine and valine substitution for Gly-48 did not perturb the calcium site in the EGF-1 domain. Activation of both mutants by factor XIa appeared normal. The reduced clotting activity of factors IXG48R and IXG48V was attributed to the failure of both mutants to cleavage factor X: in the presence of only phospholipids and calcium ions, both mutants showed a 4 to approximately 7-fold elevation in Km, and by adding factor VIIIa to the system, although factor VIIIa potentiated the activation of factor X by the mutants factor IXaG48R and factor IXaG48V, a 2 to approximately 3-fold decrease in the catalytic function was observed with the mutant factor IXa's, despite that they bound factor VIIIa on the phospholipid vesicles with only slightly reduced affinity when compared to wild-type factor IXa. The apparent Kd for factor VIIIa binding was 0.83 nM for normal factor IXa, 1.74 nM for IXaG48R and 1.4 nM for IXaG48V. Strikingly, when interaction with the factor VIIa-TF complex was examined, both mutations were barely activated by the VIIa-TF complex and they also showed abnormal interaction with VIIa-TF in bovine thromboplastin-based PT assays. Taken together, our results suggest that mutations at Gly-48 altered the interaction of factor IX with its extrinsic pathway activator (VIIa-TF complex), its macromolecular substrate (factor X), and its cofactor (factor VIIIa).
Mouse Model of Tracheal Replacement With Electrospun Nanofiber Scaffolds (2019)

Graft stenosis seen in orthotopic tracheal replacement with synthetic tracheal scaffolds can be modeled in mice. The wide array of lineage tracing and transgenic mouse models available will permit future investigation of the cellular and molecular mechanisms underlying TETG stenosis.
Active Replication of Middle East Respiratory Syndrome Coronavirus and Aberrant Induction of Inflammatory Cytokines and Chemokines in Human Macrophages: Implications for Pathogenesis (2013)

Middle East respiratory syndrome coronavirus (MERS-CoV) infection caused severe pneumonia and multiorgan dysfunction and had a higher crude fatality rate (around 50% vs. 10%) than SARS coronavirus (SARS-CoV) infection. To understand the pathogenesis, we studied viral replication, cytokine/chemokine response, and antigen presentation in MERS-CoV-infected human monocyte-derived macrophages (MDMs) versus SARS-CoV-infected MDMs. Only MERS-CoV can replicate in MDMs. Both viruses were unable to significantly stimulate the expression of antiviral cytokines (interferon α [IFN-α] and IFN-β) but induced comparable levels of tumor necrosis factor α and interleukin 6. Notably, MERS-CoV induced significantly higher expression levels of interleukin 12, IFN-γ, and chemokines (IP-10/CXCL-10, MCP-1/CCL-2, MIP-1α/CCL-3, RANTES/CCL-5, and interleukin 8) than SARS-CoV. The expression of major histocompatibility complex class I and costimulatory molecules were significantly higher in MERS-CoV-infected MDMs than in SARS-CoV-infected cells. MERS-CoV replication was validated by immunostaining of infected MDMs and ex vivo lung tissue. We conclusively showed that MERS-CoV can establish a productive infection in human macrophages. The aberrant induction of inflammatory cytokines/chemokines could be important in the disease pathogenesis.
Translational Mini-Review Series on Th17 Cells: Function and regulation of human T helper 17 cells in health and disease (2009)

T helper (Th) cell have a central role in modulating immune responses. While Th1 and Th2 cells have long been known to regulate cellular and humoral immunity, Th17 cells have been identified only recently as a Th lineage that regulates inflammation via production of distinct cytokines such as interleukin (IL)-17. There is growing evidence that Th17 cells are pathological in many human diseases, leading to intense interest in defining their origins, functions and developing strategies to block their pathological effects. The cytokines that regulate Th17 differentiation have been the focus of much debate, due primarily to inconsistent findings from studies in humans. Evidence from human disease suggests that their in vivo development is driven by specialized antigen-presenting cells. Knowledge of how Th17 cells interact with other immune cells is limited, but recent data suggest that Th17 cells may not be subject to strict cellular regulation by T regulatory cells. Notably, Th17 cells and T regulatory cells appear to share common developmental pathways and both cell types retain significant plasticity. Herein, we will discuss the molecular and cellular regulation of Th17 cells with an emphasis on studies in humans.
Preventing Biomolecular Adsorption in Electrowetting-Based Biofluidic Chips (2003)

Electrowetting-on-dielectric (EWOD) is a new method for moving liquids in biofluidic chips through electrical modification of the surface hydrophobicity. EWOD-based devices are reconfigurable, have low power requirements, and can handle neutral and charged analytes, as well as particulates. We show that biomolecular adsorption in EWOD is minimized by limiting the time during which no potential is applied and through choice of solution pH and electrode polarity. The same approach may be useful for controlling biomolecular adsorption in other applications of hydrophobic dielectric materials. These results demonstrate the feasibility of implementing EWOD for fluid actuation in biofluidic chips.
Particle Tracking Microrheology of Complex Fluids (1997)

We present a new method for measuring the linear viscoelastic shear moduli of complex fluids. Using photodiode detection of laser light scattered from a thermally excited colloidal probe sphere, we track its trajectory and extract the moduli using a frequency-dependent Stokes-Einstein equation. Spectra obtained for polyethylene oxide in water are in excellent agreement with those found mechanically and using diffusing wave spectroscopy. Since only minute sample volumes are required, this method is well suited for biomaterials of high purity, as we demonstrate with a concentrated DNA solution.
Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor (1998)

Bone morphogenetic protein (BMP) receptors signal by phosphorylating Smad1, which then associates with Smad4; this complex moves into the nucleus and activates transcription. Here we report the existence of a natural inhibitor of this process, Smad6, a longer version of the previously reported JV15-1. In Xenopus embryos and in mammalian cells, Smad6 specifically blocks signaling by the BMP/Smad1 pathway. Smad6 inhibits BMP/Smad1 signaling without interfering with receptor-mediated phosphorylation of Smad1. Smad6 specifically competes with Smad4 for binding to receptor-activated Smad1, yielding an apparently inactive Smad1-Smad6 complex. Therefore, Smad6 selectively antagonizes BMP-activated Smad1 by acting as a Smad4 decoy.
Thyroxine Analogs. I. Synthesis of 3,5-Diiodo-4-(2'-alkylphenoxy)-DL-phenylalanines1 (1959)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThyroxine Analogs. I. Synthesis of 3,5-Diiodo-4-(2'-alkylphenoxy)-DL-phenylalanines1Nicolas Zenker and Eugene C. JorgensenCite this: J. Am. Chem. Soc. 1959, 81, 17, 4643–4647Publication Date (Print):September 1, 1959Publication History Published online1 May 2002Published inissue 1 September 1959https://doi.org/10.1021/ja01526a049RIGHTS & PERMISSIONSArticle Views48Altmetric-Citations14LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (566 KB) Get e-Alertsclose Get e-Alerts
Monte Carlo modeling of light propagation in highly scattering tissues. II. Comparison with measurements in phantoms (1989)

Measurements of the fluence-depth distributions and of the diffuse reflectance of 633 nm light have been made in liquid media with optical properties similar to soft tissues. The results are compared with predictions of Monte Carlo computer calculations in order to test the adequacy of Monte Carlo modeling of light transport in tissue. Except at extremely high albedo, the experimental data and the Monte Carlo results agree well for the depth dependence of the fluence as a function of incident light beam diameter and optical absorption and scattering, and for the dependence of the diffuse reflectance on the albedo. The absolute experimental values for the fluence must be renormalized by a factor which varies with the albedo in order to match the model values, and the possible sources of this discrepancy are discussed.
37.3: High Performance 2.2″ QCIF Full Color AMOLED Display based on Electrophosphorescence (2002)

Abstract Full color 2.2‐inch Quarter Common Intermediate Format (QCIF) organic EL displays were developed using phosphorescent materials and low temperature poly‐Si (LTPS) technology. These displays exhibited a world record efficiency of 11cd/A at an optimized white CIE coordinate of (0.31, 0.32) with an OLED operating voltage of 6V. The current pixel structure for the 2.2‐inch display allows about 32% aperture ratios and a white peak luminance of over 300cd/m 2 .
Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials (2001)

An analysis of the activity of compounds tested in pre-clinical in vivo and in vitro assays by the National Cancer Institute's Developmental Therapeutics Program was performed. For 39 agents with both xenograft data and Phase II clinical trials results available, in vivo activity in a particular histology in a tumour model did not closely correlate with activity in the same human cancer histology, casting doubt on the correspondence of the pre-clinical models to clinical results. However, for compounds with in vivo activity in at least one-third of tested xenograft models, there was correlation with ultimate activity in at least some Phase II trials. Thus, an efficient means of predicting activity in vivo models remains desirable for compounds with anti-proliferative activity in vitro. For 564 compounds tested in the hollow fibre assay which were also tested against in vivo tumour models, the likelihood of finding xenograft activity in at least one-third of the in vivo models tested rose with increasing intraperitoneal hollow fibre activity, from 8% for all compounds tested to 20% in agents with evidence of response in more than 6 intraperitoneal fibres (P< 0.0001). Intraperitoneal hollow fibre activity was also found to be a better predictor of xenograft activity than either subcutaneous hollow fibre activity or intraperitoneal plus subcutaneous activity combined. Since hollow fibre activity was a useful indicator of potential in vivo response, correlates with hollow fibre activity were examined for 2304 compounds tested in both the NCI 60 cell line in vitro cancer drug screen and hollow fibre assay. A positive correlation was found for histologic selectivity between in vitro and hollow fibre responses. The most striking correlation was between potency in the 60 cell line screen and hollow fibre activity; 56% of compounds with mean 50% growth inhibition below 10(-7.5) M were active in more than 6 intraperitoneal fibres whereas only 4% of compounds with a potency of 10(-4) M achieved the same level of hollow fibre activity (P< 0.0001). Structural parameters of the drugs analysed included compound molecular weight and hydrogen-bonding factors, both of which were found to be predictive of hollow fibre activity.
Prophylactic Tumor Vaccination: Comparison of Effector Mechanisms Initiated by Protein Versus DNA Vaccination (2001)

Clinical success in tumor vaccination frequently does not reach expectation. Since vaccination protocols are quite variable, we used the murine renal cell carcinoma line RENCA transfected with the lacZ gene (RENCA-beta-gal) to compare the efficacy of two different vaccination strategies or their combination and to elaborate on the underlying mechanisms. BALB/c mice were vaccinated either with naked lacZ DNA or with attenuated Salmonella typhimurium transformed with lacZ DNA or with dendritic cells (DC) loaded with the beta-galactosidase protein or mice were vaccinated with both DNA and protein. Although all regimens led to a prolongation of survival time, oral vaccination with transfected S. typhimurium followed by i.v. transfer of protein-loaded DC provided the optimal schedule. In this setting, >50% of mice remained tumor free after challenge with 10 times the lethal tumor dose of RENCA-beta-gal. As explored in transfer experiments, the superior efficacy of combining DNA and protein vaccination is due to the facts that 1) optimal protection depends on both activated CD4(+) and CD8(+) cells and 2) CD8(+) CTL are most strongly activated by vaccination with transformed Salmonella, whereas vaccination with protein-loaded DC is superior for the activation of Th. The latter induced sustained activation of CTL and recruitment of nonadaptive defense mechanisms. The data demonstrate the strength of DNA vaccination, particularly by the oral route, and provide evidence that a combined treatment with protein-loaded DC can significantly increase the therapeutic efficacy.
Inhibition of clostridium scindens and clostridium hiranonis growth by bifidobacterium pseudocatenulatum G4 in simulated colonic pH (2013)

In some patients, increased proportions of deoxycholic acid produced by 7Î±-dehydroxylating in the bile acid pool in the intestines have been associated with the development of cholesterol gallstones. The levels and activities of bile acid 7Î±-dehydroxylating bacteria have been reported to be increased in gallstone patients. In the current study, the ability of Bifidobacterium pseudocatenulatum G4 to survive and tolerate the simulated colonic pH and its inhibitory activity against two 7Î±-dehydroxylating bacteria, Clostridium scindens JCM 10418 and Clostridium hiranonis JCM 10541, was investigated. B. pseudocatenulatum G4 showed antimicrobial activity against the two tested indicator organisms, however, B. pseudocatenulatum G4 showed higher antagonistic activity against C. hiranonis as compared with C. scindens. Also, the effect of three different colonic pH (5.7, 6.2 and 6.8) on Clostridiums and B. pseudocatenulatum G4 growth was studied. Reducing the pH leads to 1-2 log decrease in number of both C. scindens and C. hiranonis. B. pseudocatenulatum G4 showed more inhibitory activity against each one of Clostridiums compared to mix of them and the effect of pH on Clostridium growth was increased by presence of B. pseudocatenulatum G4. The highest reduction in Clostridium growth observed at pH 6.8 followed by pH 6.2 and 5.7. Good tolerance and survival of B. pseudocatenulatum at different levels of pH demonstrating this bacterium as a potential probiotic for human consumption.
Reed-Sternberg Cells and the TNF Family of Receptors/Ligands (1997)

Treatment of cancer with means other than chemo- and radiation therapy becomes more and more important. Through the better understanding of tumor biology approaches towards the cure of cancer interfering with the pathophysiological mechanisms of malignancy can be considered. Hodgkin's disease is a good example for the role of the immune system in cancer. The Reed-Sternberg (RS) cells, malignant cells of Hodgkin's disease (HD), are surrounded by tumor infiltrating lymphocytes (TILs) and still evade immunesurveillance. In this respect the importance of the superfamily of tumor necrosis factor (TNF) receptors and ligands is becoming more and more clear. Ligand-receptor interaction either leads to death or survival signals. Many of these receptors and ligands are expressed by the RS cells and the surrounding lymphocytes. Their expression and function in HD are discussed and future directions for possible therapeutical investigations are proposed.
Expression of Umbelopsis ramanniana DGAT2A in Seed Increases Oil in Soybean (2008)

Oilseeds are the main source of lipids used in both food and biofuels. The growing demand for vegetable oil has focused research toward increasing the amount of this valuable component in oilseed crops. Globally, soybean (Glycine max) is one of the most important oilseed crops grown, contributing about 30% of the vegetable oil used for food, feed, and industrial applications. Breeding efforts in soy have shown that multiple loci contribute to the final content of oil and protein stored in seeds. Genetically, the levels of these two storage products appear to be inversely correlated with an increase in oil coming at the expense of protein and vice versa. One way to overcome the linkage between oil and protein is to introduce a transgene that can specifically modulate one pathway without disrupting the other. We describe the first, to our knowledge, transgenic soy crop with increased oil that shows no major impact on protein content or yield. This was achieved by expressing a codon-optimized version of a diacylglycerol acyltransferase 2A from the soil fungus Umbelopsis (formerly Mortierella) ramanniana in soybean seed during development, resulting in an absolute increase in oil of 1.5% (by weight) in the mature seed.
Peptide‐polymer biotherapeutic synthesis on novel cross‐linked beads with “spatially tunable” and “isolated” functional sites (2008)

Solid phase synthesis of polymer biotherapeutics using conventional polymers suffers from many limitations such as low synthetic yield and purity. The conventional polymers prepared by either pre- or post-functionalization strategies have no control over the point of functionalization. Hence we report a novel cross-linked polymer in which the functional groups are spatially tuned to predefined distance with optimal site isolation. This has been achieved by the design and synthesis of a tetra functional PEG, 3,3'-(PEG)bis(1-(4-vinylphenoxy)propan-2-ol) (bis(VPP)PEG). It has been incorporated at cross-linking of 1-12%, into a polystyrene network by free radical suspension polymerization. In this polymer, the distance between hydroxyl functional groups has been spatially tuned in a predefined manner by varying the length of the cross-linker backbone from ethylene glycol to PEG1000 Da and the loading capacity could be varied from 0.1 to 0.9 mmol/g. The polymer has been characterized by SEM, FTIR, and 13C NMR. The polymer exhibits excellent swelling behavior and high chemical stability. The synthetic efficiency of the polymer was demonstrated by the successful synthesis of three structural classes of PEGylated antimicrobial peptide biotherapeutics and the difficult ACP (65-74) fragment. Thus the "spatially defined" and "site isolated" synthesis within the new polymer offers a novel strategy for synthesis of difficult peptide-polymer bioconjugates. The bioassay studies shows that PEGylation of AMPs significantly reduces their hemolytic potential but the retainment of antibacterial property was dependent both on the peptide sequence and the size of PEG used.
A Practical Bayesian Framework for Backpropagation Networks (1992)

A quantitative and practical Bayesian framework is described for learning of mappings in feedforward networks. The framework makes possible (1) objective comparisons between solutions using alternative network architectures, (2) objective stopping rules for network pruning or growing procedures, (3) objective choice of magnitude and type of weight decay terms or additive regularizers (for penalizing large weights, etc.), (4) a measure of the effective number of well-determined parameters in a model, (5) quantified estimates of the error bars on network parameters and on network output, and (6) objective comparisons with alternative learning and interpolation models such as splines and radial basis functions. The Bayesian "evidence" automatically embodies "Occam's razor," penalizing overflexible and overcomplex models. The Bayesian approach helps detect poor underlying assumptions in learning models. For learning models well matched to a problem, a good correlation between generalization ability and the Bayesian evidence is obtained.
Glucagon carboxyl-terminal derivatives: preparation, purification, and characterization (1982)

Chemical and enzymatic methods have been used to prepare the following series of seven glucagon derivatives modified in the carboxyl-terminal region important for hormone-receptor binding: [des-Asn28,Thr29](homoserine lactone27)glucagon, [des-Asn28,Thr29](homoserine27)glucagon, (S-methyl-Met27)glucagon, [des-Thr29](S-methyl-Met27)-glucagon, [des-Thr29]glucagon,[des-Asn28,Thr29](S-methyl-Met27)glucagon, and [des-Asn28,Thr29]glucagon. The derivatives were isolated in high yield, extensively purified, and chemically characterized. All were found to be full agonists of native glucagon. Binding affinity was evaluated by displacement of mono[125I]iodoglucagon prepared by new methods. Binding and biological activities closely correlated, indicating that most modifications affected the relative binding affinity and relative biological potency of glucagon to a comparable extent. Circular dichroism measured in dilute acid solution resembled that of native glucagon except for [des-Asn28,Thr29]glucagon which displayed increased alpha helicity (25%). All derivatives formed helical structures in 2-chloro-ethanol, although the amount of helicity induced was not closely correlated with biological activity. Binding and biological activities were not affected by removal of Thr-29, though both were reduced 20-fold when Asn-28 was also removed, irrespective of whether homoserine or native methionine remained at the carboxyl terminus. Lactone formation was associated with a further 5-fold reduction in binding affinity but not in activity. Methylation of Met-27 had essentially the same effect as removing the two carboxyl-terminal residues, although the combined effect of both modifications was greater than 100-fold reduction in binding and activity. These findings provide additional insight concerning glucagon structure-function relationships.