gebhart/patrepeval huggingface dataset:
Mutations of ATIC and ADSL affect purinosome assembly in cultured skin fibroblasts from patients with AICA-ribosiduria and ADSL deficiency (2011)

The purinosome is a multienzyme complex composed by the enzymes active in de novo purine synthesis (DNPS) that cells transiently assemble in their cytosol upon depletion or increased demand of purines. The process of purinosome formation has thus far been demonstrated and studied only in human epithelial cervical cancer cells (HeLa) and human liver carcinoma cells (C3A) transiently expressing recombinant fluorescently labeled DNPS proteins. Using parallel immunolabeling of various DNPS enzymes and confocal fluorescent microscopy, we proved purinosome assembly in HeLa, human hepatocellular liver carcinoma cell line (HepG2), sarcoma osteogenic cells (Saos-2), human embryonic kidney cells (HEK293), human skin fibroblasts (SF) and primary human keratinocytes (KC) cultured in purine-depleted media. Using the identical approach, we proved in cultured skin fibroblasts from patients with AICA-ribosiduria and ADSL deficiency that various mutations of ATIC and ADSL destabilize to various degrees of purinosome assembly and found that the ability to form purinosomes correlates with clinical phenotypes of individual ADSL patients. Our results thus shown that the assembly of functional purinosomes is fully dependent on the presence of structurally unaffected ATIC and ADSL complexes and presumably also on the presence of all the other DNPS proteins. The results also corroborate the hypothesis that the phenotypic severity of ADSL deficiency is mainly determined by structural stability and residual catalytic capacity of the corresponding mutant ADSL protein complexes, as this is prerequisite for the formation and stability of the purinosome and at least partial channeling of succinylaminoimidazolecarboxamide riboside-ADSL enzyme substrates-through the DNPS pathway.
A leukemic stem cell with intrinsic drug efflux capacity in acute myeloid leukemia (2001)

The hematopoietic stem cell underlying acute myeloid leukemia (AML) is controversial. Flow cytometry and the DNA-binding dye Hoechst 33342 were previously used to identify a distinct subset of murine hematopoietic stem cells, termed the side population (SP), which rapidly expels Hoechst dye and can reconstitute the bone marrow of lethally irradiated mice. Here, the prevalence and pathogenic role of SP cells in human AML were investigated. Such cells were found in the bone marrow of more than 80% of 61 patients and had a predominant CD34(low/-) immunophenotype. Importantly, they carried cytogenetic markers of AML in all 11 cases of active disease examined and in 2 out of 5 cases in complete hematological remission. Comparison of daunorubicin and mitoxantrone fluorescence emission profiles revealed significantly higher drug efflux from leukemic SP cells than from non-SP cells. Three of 28 SP cell transplants generated overt AML-like disease in nonobese diabetic--severe combined immunodeficient mice. Low but persistent numbers of leukemic SP cells were detected by molecular and immunological assays in half of the remaining mice. Taken together, these findings indicate that SP cells are frequently involved in human AML and may be a target for leukemic transformation. They also suggest a mechanism by which SP cells could escape the effects of cytostatic drugs and might eventually contribute to leukemia relapse. (Blood. 2001;98:1166-1173)
Anti-tumor and cell cycle responses in KB cells treated with a chimeric anti-EGFR monoclonal antibody in combination with cisplatin (1996)

Overexpression of the epidermal growth factor receptor (EGFR) has been found to correlate with a poor prognosis for many cancers. The EGFR appears to play an important role in regulating cell growth during tumorigenesis and blockade of the EGFR/ligand interaction may be a means of inducing cell cytotoxicity, terminal differentiation, or apoptosis. In this report, we show that the growth of well-established xenografts of the human epidermoid carcinoma cell line KB could be significantly inhibited by the combination of cisplatin plus C225, a chimeric anti-EGFR monoclonal antibody, whereas the individual treatments had no effect on tumor growth. Substantive changes in the protein expression levels of the EGFR as well as several important cell cycle regulatory proteins were found in cells treated with the combination. In addition, cisplatin plus C225 inhibited the overall phosphorylation patterns including EGFR activation. These in vitro data suggest a mechanism of action for the in vivo therapeutic effects of C225 plus cisplatin.
Effect of comonomer hydrophilicity and ionization on the lower critical solution temperature of N-isopropylacrylamide copolymers (1993)

Differential scanning calorimetry (DSC) was performed on aqueous solutions of polyCZVisopropylacrylamide-co-butyl methacrylate-co-X), with X being hydrophilic, hydrophobic, cationic, or anionic comonomers, to elucidate the mechanism of temperature-induced phase separation and the effect of comonomer content, hydrophilicity, and charge on the lower critical solution temperature (LCST). The endothermic heat of phase separation, which is related to the breaking of hydrogen bonds between water molecules surrounding hydrophobic moieties on the polymer, was a linear, decreasing function of the LCST. This suggests that the hydrophobic interactions between polymer side groups, which are the major driving force for phase separation, are enhanced at elevated temperatures due to a decrease in the structuring of water around hydrophobic side groups. It is concluded that the changes in LCST caused by the incorporation of comonomers are due to changes in overall hydrophilicity of the polymer and are not due to a direct influence of comonomer hydrophilicity or charge on the structuring of water around hydrophobic groups.
CONTRIBUTION OF ANTI-GAL TO PRIMATE AND HUMAN IgG BINDING TO PORCINE ENDOTHELIAL CELLS (1995)

Department of Microbiology and Immunology, Medical College of Pennsylvania, Philadelphia, Pennsylvania; Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis; and Laboratory for Transplantation Immunology, Department of Cardiothoracic Surgery, Stanford University Medical Center, Stanford, California
Coupling Reagents in Peptide Synthesis (1972)

The chemistry and scope of application of a series of reagents and reactions used for the formation of peptide bonds are discussed. They include: unsaturated ethers, dicyclohexylcarbodiimide, cyanamide, ketenimines, ketenes, ynamines, 1,2-oxazolium salts, EEDQ, acyloxyphosphonium salts, triphenylphosphite and imidazole, oxidation-reduction condensation, copper complexes, and silicon tetrachloride. 1. Unsaturated Ethers 1.1. α-Chlorovinyl Ethyl Ether, α,α-Dichlorodiethyl Ether, and Dichloromethyl Methyl Ether 1.2. Ethoxyacetylene 2. Dicyclohexylcarbodiimide 2.1. Dicyclohexylcarbodiimide and Additives 2.2. Complexes of DCC-Pentachlorophenol and DCC-Pentafluorophenol 3. Cyanamide 4. Ketenimines and Ketenes 5. Ynamines 6. 1,2-Oxazolium Salts 7. EEDQ 8. Acyloxyphosphonium Ions 9. Triphenylphosphite and Imidazole 10. Oxidation-Reduction Condensation 11. Copper(II) Complexes 12. Silicon Tetrachloride
Noncovalent and Nonspecific Molecular Interactions of Polymers with Multiwalled Carbon Nanotubes (2005)

Polymer composites containing variable amounts of multiwalled carbon nanotubes (MWNTs) have been prepared using solution dispersion and melt-shear mixing. Various polymer composites with 1 wt % MWNTs have been found to dissolve homogeneously in organic solvents. The amount of polymer coated or wrapped MWNTs dissolved in the solution was quantified using UV−vis absorbance at 500 nm and the concentration ratio of [MWNTs]solution/[MWNTs]composite was close to 1. A nonspecific polymer adsorption through multiple-weak molecular interactions of CH groups with MWNTs in the composites has been identified through FTIR spectroscopy. The composites of polybutadiene with different wt % of MWNTs showed slight changes in the CH bending vibrations, indicating the presence of intermolecular CH−π interactions. The dissolution of various polymer composites containing low concentration of MWNTs in organic solvents was attributed to polymer coating on the MWNTs via noncovalent and nonspecific CH−π interactions. The dissolution of MWNTs in organic solvents using common polymers used in this study indicates that the coating or wrapping is a general phenomenon occurring between polymers and carbon nanotubes.
Structure-activity relationships for the induction of differentiation of HL-60 human acute promyelocytic leukemia cells by anthracyclines. (1982)

Marcellomycin, a newly developed anthracycline antibiotic with antineoplastic activity, was tested as an inducer of differentiation of the human promyelocytic leukemia cell line HL-60 in vitro. The percentage of cells reducing nitro blue tetrazolium, an indication of a stimulus-induced respiratory burst typical of mature phagocytes, was used as a functional measure of the extent of differentiation. Marcellomycin was a potent inducer of maturation, with 95% of the cells expressing a terminally differentiated state after 10 days of exposure to a concentration of 40 nM anthracycline. Cells exposed to marcellomycin exhibited a 35-fold increase in their total superoxide anion-generating capacity, an 80% increase in acid phosphatase activity, and a loss of myeloperoxidase and chloroacetate esterase activities. In addition, marcellomycin-treated cells stained negatively for alpha-naphthyl acetate esterase. These findings provided evidence for the granulocytic nature of the mature cells. In contrast, marcellomycin was not an effective inducer of differentiation of Friend murine erythroleukemia cells. Studies on the relationship between structure and the ability to induce differentiation of HL-60 leukemia cells demonstrated that removal from the marcellomycin molecule of the terminal 2-deoxyfucose (musettamycin) or its substitution by cinerulose (aclacinomycin A) did not alter differentiation-inducing capacity. However, removal of the carbomethoxy group from the C-10 position of marcellomycin substantially reduced its potency as an initiator of maturation, and removal of the two terminal 2-deoxyfucose moieties (pyrromycin) decreased both potency and the maximal percentage of differentiated cells produced in the population. The monosaccharide anthracyclines Adriamycin and carminomycin were completely inactive as inducers of HL-60 leukemia cell maturation. The results suggest that certain anthracyclines would be reasonable candidate drugs to use in a clinical trial aimed at reducing the leukemic stem cell burden through maturation rather than through cytodestruction.
β2 Adrenergic Receptor Activation (2002)

In many rhodopsin-like G-protein-coupled receptors, agonist binding to a cluster of aromatic residues in TM6 may promote receptor activation by altering the configuration of the TM6 Pro-kink and by the subsequent movement of the cytoplasmic end of TM6 away from TM3. We hypothesized that the highly conserved Cys(6.47), in the vicinity of the conserved Pro(6.50), modulates the configuration of the aromatic cluster and the TM6 Pro-kink through specific interactions in its different rotamer configurations. In the beta(2) adrenergic receptor, mutation of Cys(6.47) to Thr, which in an alpha-helix has a different rotamer distribution from Cys and Ser, produced a constitutively active receptor, whereas the Ser mutant was similar to wild-type receptor. Use of the biased Monte Carlo technique of Conformational Memories showed that the rotamer changes among Cys/Ser/Thr(6.47), Trp(6.48), and Phe(6.52) are highly correlated, representing a rotamer "toggle switch" that may modulate the TM6 Pro-kink. Differential modulation of the accessibility of Cys(6.47) and an engineered Cys(6.52) in wild type and a constitutively active background provides experimental support for the association of this rotamer switch with receptor activation.
Molecular Basis of RNA Recognition by the Embryonic Polarity Determinant MEX-5 (2007)

Embryonic development requires maternal proteins and RNA. In Caenorhabditis elegans, a gradient of CCCH tandem zinc finger (TZF) proteins coordinates axis polarization and germline differentiation. These proteins govern expression from maternal mRNAs by an unknown mechanism. Here we show that the TZF protein MEX-5, a primary anterior determinant, is an RNA-binding protein that recognizes linear RNA sequences with high affinity but low specificity. The minimal binding site is a tract of six or more uridines within a 9-13-nucleotide window. This sequence is remarkably abundant in the 3'-untranslated region of C. elegans transcripts, demonstrating that MEX-5 alone cannot specify mRNA target selection. In contrast, human TZF homologs tristetraprolin and ERF-2 bind with high specificity to UUAUUUAUU elements. We show that mutation of a single amino acid in each MEX-5 zinc finger confers tristetraprolin-like specificity to this protein. We propose that divergence of this discriminator residue modulates the RNA-binding specificity in this protein class. This residue is variable in nematode TZF proteins, but is invariant in other metazoans. Therefore, the divergence of TZF proteins and their critical role in early development is likely a nematode-specific adaptation.
Structure and energetics of a non-proline cis-peptidyl linkage in a proline-202 .fwdarw. alanine carbonic anhydrase II variant (1993)

The crystal structure of a human carbonic anhydrase II (CAII) variant, cis-proline-202-->alanine (P202A), has been determined at 1.7-A resolution, indicating that the wild-type geometry, including the cis-peptidyl linkage, is retained upon substitution of proline by alanine. The CO2 hydrase activity and affinity for sulfonamide inhibitors of P202A CAII are virtually identical to those of wild type. However, the substitution of cis-alanine for cis-proline decreases the stability of the folded state by approximately 5 kcal mol-1 relative to both the unfolded state and an equilibrium intermediate in guanidine hydrochloride-induced denaturation. This destabilization can be attributed mainly to the less favorable cis/trans equilibrium of Xaa-alanine bonds compared to Xaa-proline bonds in the denatured state although other factors, including increased conformational entropy of the denatured state and decreased packing interactions in the native state, also contribute to the observed destabilization. The high catalytic activity of P202A CAII illustrates that unfavorable local conformations are nonetheless endured to satisfy the precise structural requirements of catalysis and ligand binding in the CAII active site.
Characterization of GMP-140 (P-selectin) as a circulating plasma protein. (1992)

GMP-140 is a 140-kD granule membrane protein, found in the alpha granules of platelets and the Weibel-Palade bodies of endothelial cells, that is surface expressed on cell activation and mediates neutrophil attachment. Cloning data for GMP-140 from an endothelial library predict a soluble form of the protein, the transcription message for which is also found in platelets. In this study, we report the detection by enzyme-linked immunosorbent assay of soluble GMP-140 in plasma centrifuged for 3 h at 100,000 g (to remove platelet microparticles) and confirm its identity by purification from plasma. Plasma concentrations were found to be 0.251 +/- 0.043 micrograms/ml (means +/- SD, n = 10) in normal male controls and 0.175 +/- 0.063 micrograms/ml (means +/- SD, n = 10) in normal female controls. The purified protein had an identical molecular mass (nonreduced) to platelet membrane GMP-140 (approximately 3 kD lower, reduced) and was immunoblotted by polyclonal anti-GMP-140, and the anti-GMP-140 monoclonal antibodies AK4 and AK6. Analytical gel filtration studies indicated that the plasma GMP-140 eluted as a monomer whereas detergent-free, platelet membrane GMP-140 eluted as a tetramer consistent with plasma GMP-140 lacking a transmembrane domain. Purified plasma GMP-140 bound to the same neutrophil receptor as the membrane-bound form, and when immobilized on plastic, bound neutrophils equivalently to immobilized platelet membrane GMP-140. Since it has been shown that fluid-phase GMP-140 is antiinflammatory and downregulates CD18-dependent neutrophil adhesion and respiratory burst, its presence in plasma may be of major importance in preventing the inadvertent activation of neutrophils in the circulation.
Structure, solvation, and acid–base property in ionic liquids (2010)

Ionic liquids (ILs) are expected to have specific properties as solvents for chemical reactions in view of solution chemistry. Among physicochemical properties, liquid structure, acid–base, and electron-pair donating and accepting abilities of solvent play a crucial role in ion-solvation and acid–base, metal-ion complexation, and electrochemical reactions. Various types of ILs have been developed, and among others, the bis(trifluoromethanesulfonyl)amide (TFSA – )-based ILs are extensively used. TFSA – is a flexible molecule to give two stable conformers, cis (C1) and trans (C2), which are present in equilibrium in the liquid state. The conformational equilibrium shifts upon solvation to the metal ion. This is quantitatively studied to obtain thermodynamic parameters of conformational change from C2 to C1 in the bulk and in the solvation sphere of the lithium ion. On the other hand, with ethylammonium nitrate (EAN), a typical protic IL, it is revealed that the ammonium group is hydrogen-bonded with three nitrate ions to form a heterogeneous liquid structure. The solvent acid–base property of EAN and acid dissociation reaction in EAN have been quantitatively revealed, and the results will be discussed in comparison with those in normal molecular solvents.
Backcalculation of Layer Moduli from Nondestructive Pavement Deflection Data Using the Expert System Approach (1989)

None of the existing backcalculation procedures is guaranteed to give a reasonable, effective elastic layer modulus for every deflection basin measured. The differences of results among various backcalculation programs are magnified by the differences of distinct analysts using the same program but applying different input parameters. A more experienced analyst often may obtain better results. Some of the difficulties, such as the deviation of pavement material properties from the linear elastic, isotropic, and homogeneous assumptions, the uncertainty of input parameters (for example, the deflection measurement), and the limitation of basin matching techniques, may only be dealt with by informed engineering judgement. A knowledge-based expert system approach as described in this paper may be used to generate more consistent and better estimations of in situ pavement material properties by combining numerical computations with a pavement expert's knowledge and judgement. A knowledge base which serves as an intelligent pre- and postprocessor to the backcalculation program is developed. The knowledge base may be revised easily as better understanding emerges.
Emerging virus diseases: can we ever expect the unexpected? (2012)

Emerging virus diseases are a major threat to human and veterinary public health. With new examples occurring approximately one each year, the majority are viruses originating from an animal host. Of the many factors responsible, changes to local ecosystems that perturb the balance between pathogen and principal host species is one of the major drivers, together with increasing urbanization of mankind and changes in human behavior. Many emerging viruses have RNA genomes and as such are capable of rapid mutation and selection of new variants in the face of environmental changes in host numbers and available target species. This review summarizes recent work on aspects of virus emergence and the current understanding of the molecular and immunological basis whereby viruses may cross between species and become established in new ecological niches. Emergence is hard to predict, although mathematical modeling and spatial epidemiology have done much to improve the prediction of where emergence may occur. However, much needs to be done to ensure adequate surveillance is maintained of animal species known to present the greatest risk thus increasing general alertness among physicians, veterinarians and those responsible for formulating public health policy.
EBSeq: an empirical Bayes hierarchical model for inference in RNA-seq experiments (2013)

Supplementary data are available at Bioinformatics online.
Layered Patterning of Hepatocytes in Co-Culture Systems using Microfabricated Stencils (2010)

Microfabrication and micropatterning techniques in tissue engineering offer great potential for creating and controlling microenvironments in which cell behavior can be observed. Here we present a novel approach to generate layered patterning of hepatocytes on micropatterned fibroblast feeder layers using microfabricated polydimethylsiloxane (PDMS) stencils. We fabricated PDMS stencils to pattern circular holes with diameters of 500 microm. Hepatocytes were co-cultured with 3T3-J2 fibroblasts in two types of patterns to evaluate and characterize the cellular interactions in the co-culture systems. Results of this study demonstrated uniform intracellular albumin staining and E-cadherin expression, increased liver-specific functions, and active glycogen synthesis in the hepatocytes when the heterotypic interface between hepatocytes and fibroblasts was increased by the layered patterning technique. This patterning technique can be a useful experimental tool for applications in basic science, drug screening, and tissue engineering, as well as in the design of bioartificial liver devices.
Retinoic acid stimulates neurite outgrowth in the amphibian spinal cord. (1991)

There is increasing evidence that retinoic acid (RA), a vitamin A metabolite, plays a role in the development of the nervous system. Here we specifically test this notion by examining the effect of RA on neurite outgrowth from explanted segments of the axolotl spinal cord. We show that there is a threshold concentration in the region of 0.1-1 nM above which neurite outgrowth is stimulated 4-5 fold. Retinol, by contrast, only stimulated the migration of glial cells from the explants. Using HPLC we demonstrate that RA and retinol are present endogenously in the axolotl spinal cord. In addition, we have identified by immunocytochemistry with antipeptide antibodies the cells of the spinal cord that contain the binding proteins for RA (cellular RA-binding protein; CRABP) and retinol (cellular retinol-binding protein; CRBP). CRABP is found in the axons and CRBP is found in the ependyma and glial cells. These results provide strong evidence for a role for RA in the developing nervous system, and we propose a specific hypothesis involving CRBP, CRABP, retinol, and RA in the control of axon outgrowth in the spinal cord.
Dysphagia Bedside Screening for Acute-Stroke Patients (2007)

The GUSS offers a quick and reliable method to identify stroke patients with dysphagia and aspiration risk. Such a graded assessment considers the pathophysiology of voluntary swallowing in a more differentiated fashion and provides less discomfort for those patients who can continue with their oral feeding routine for semisolid food while refraining from drinking fluids.