gebhart/patrepeval huggingface dataset:
Tethered Epidermal Growth Factor Provides a Survival Advantage to Mesenchymal Stem Cells (2007)

MSC can act as a pluripotent source of reparative cells during injury and therefore have great potential in regenerative medicine and tissue engineering. However, the response of MSC to many growth factors and cytokines is unknown. Many envisioned applications of MSC, such as treating large defects in bone, involve in vivo implantation of MSC attached to a scaffold, a process that creates an acute inflammatory environment that may be hostile to MSC survival. Here, we investigated cellular responses of MSC on a biomaterial surface covalently modified with epidermal growth factor (EGF). We found that surface-tethered EGF promotes both cell spreading and survival more strongly than saturating concentrations of soluble EGF. By sustaining mitogen-activated protein kinase kinase-extracellular-regulated kinase signaling, tethered EGF increases the contact of MSC with an otherwise moderately adhesive synthetic polymer and confers resistance to cell death induced by the proinflammatory cytokine, Fas ligand. We concluded that tethered EGF may offer a protective advantage to MSC in vivo during acute inflammatory reactions to tissue engineering scaffolds. The tethered EGF-modified polymers described here could be used together with structural materials to construct MSC scaffolds for the treatment of hard-tissue lesions, such as large bony defects. Disclosure of potential conflicts of interest is found at the end of this article.
Catalytic Reduction of Biomass-Derived Furanic Compounds with Hydrogen (2013)

Furfural and 5-hydroxymethylfurfural (HMF) are important platform chemicals in biorefinery. Reduction of furfural or HMF with H2 over heterogeneous catalysts is the simplest way to convert the oxygen-rich compounds. However, the process can involve many types of reactions such as hydrogenation of the C═O bond, hydrogenation of the furan ring, C–O hydrogenolysis, rearrangement, C–C dissociation, and polymerization. Hydrogenation reactions are most studied in line with hydrogenations of other α,β-unsaturated aldehydes, and it becomes possible to produce each product selectively: furfuryl alcohol, tetrahydrofurfuryl alcohol, 2,5-bis(hydroxymethyl)furan, or 2,5-bis(hydroxymethyl)tetrahydrofuran. Total reduction of side substituents to give 2-methylfuran or 2,5-dimethylfuran is another well-known reaction. Rearrangement and C–O hydrogenolysis reactions have been recently investigated, and they can give useful products such as cyclopentanone, 1,5-pentanediol, and 1,6-hexanediol. Ongoing studies of the reaction mechanisms are also reviewed.
Neuro-oncology 1999 (1999)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
A 30‐residue fragment of the carp granulin‐1 protein folds into a stack of two β‐hairpins similar to that found in the native protein (1999)

Upon air oxidation, a peptide corresponding to the 30-residue N-terminal subdomain of carp granulin-1 spontaneously formed the disulfide pairing observed in the native protein. Structural characterization using NMR showed the presence of a defined secondary structure within this peptide. The chemical shifts for most of the alphaCH protons of the peptide and the protein are very similar, and the observed NOE contacts of the peptide strongly resemble those in the protein. A structure calculation of the peptide using NOE distance constraints indicates that the peptide fragment adopts the same conformation as formed within the native protein. The 30-residue N-terminal peptide of carp granulin-1 is the first example of an independently folded stack of two beta-hairpins reinforced by two interhairpin disulfide bonds. Two key areas of the structure show a clustering of hydrophobic residues that may account for its exceptional conformational stability.
Palladium-Catalyzed Coupling Reactions of Aryl Chlorides (2002)

Collectively, palladium-catalyzed coupling reactions represent some of the most powerful and versatile tools available to synthetic organic chemists. Their widespread popularity stems in part from the fact that they are generally tolerant to a large number of functional groups, which allows them to be employed in a wide range of applications. However, for many years a major limitation of palladium-catalyzed coupling processes has been the poor reactivity of aryl chlorides, which from the standpoints of cost and availability are more attractive substrates than the corresponding bromides, iodides, and triflates. Traditional palladium/triarylphosphane catalysts are only effective for the coupling of certain activated aryl chlorides (for example, heteroaryl chlorides and substrates that bear electron-withdrawing groups), but not for aryl chlorides in general. Since 1998, major advances have been described by a number of research groups addressing this challenge; catalysts based on bulky, electron-rich phosphanes and carbenes have proved to be particularly mild and versatile. This review summarizes both the seminal early work and the exciting recent developments in the area of palladium-catalyzed couplings of aryl chlorides.
Decline of two Cinnamomum species associated with Phytophthora cinnamomi in Taiwan. (1993)

Yellowing and wilting followed by death of trees were found on Cinnamomum osmophloeum in plantations located at Chia-yi and Hwa-ling farms. Similar symptoms were also observed on trees of C camphora in one plantation in Hua-lien county. All observed diseased trees were associated with Phytophthora cinnamomi causing root rot. All isolates of P. cinnamomi obtained from trees and rhizosphere soils of C. osmophloeum at Chia-yi farm were of A^1 mating type, whereas A^1 and A^2 mating types were isolated from trees and rhizosphere soils at Hwa-ling farm. Two isolates of P. cinnamomi obtained from roots and rhizosphere soils of C camphora were A^1. Isolates of P. cinnamomi isolated from C. osmophloeum or C. camphora were able to cause the disease on tested plants of both C. osmophloeum and C. camphora. The fungus was reisolated from all inoculated plants. P. cinnamomi on C osmophloeum was first documented in the world. P. cinnamomi on C camphora was first reported in Taiwan.
Interleukin 2 gene therapy of colorectal carcinoma with autologous irradiated tumor cells and genetically engineered fibroblasts: a Phase I study. (1999)

The purpose of this study was to determine the safety, toxicity, and antitumor immune response following S.C. immunizations with a mixture of irradiated, autologous tumor cells and autologous fibroblasts that were genetically modified to express the gene for interleukin 2 (IL-2) in patients with colorectal carcinoma. Ten patients were treated with a fixed dose of tumor cells (10(7)) and escalating doses of fibroblasts secreting IL-2 (per 24 h): 100 units (three patients), 200 units (three patients), 400 units (three patients), and 800 units (one patient). Pre- and posttreatment peripheral blood mononuclear cells were evaluated for evidence of antitumor immune responses. Fatigue and/or flu-like symptoms were experienced by seven patients and delayed-type hypersensitivity-like skin reactions were observed at the sites of the second or subsequent vaccinations in five patients. Low frequencies of tumor cytotoxic T-cell precursors (range, 1/190,000-1/1,320,000 peripheral blood mononuclear cells) were detected prior to therapy in four of seven patients. There was a 5-fold increase following treatment in the frequency of tumor cytotoxic T-cell precursors in two of six evaluable patients. Some patients with colorectal cancer have low frequencies of tumor cytotoxic T-cell precursors that may be increased by this well-tolerated form of IL-2 gene therapy, which warrants continued clinical evaluation.
Status Epilepticus (1998)

A patient in status epilepticus has continuous or rapidly repeating seizures. Although the danger of this pattern of seizure activity has been recognized since antiquity, our understanding of the pathophysiology of status epilepticus is incomplete. The frequency of cases in the United States is approximately 102,000 to 152,000 per year, and roughly 55,000 deaths are associated with status epilepticus annually.1 Twelve to 30 percent of adult patients with a new diagnosis of epilepsy first present in status epilepticus.2,3 This review focuses on generalized status epilepticus, which is the most common form of the disorder.1,4 This is a life-threatening . . .
Molecular Cloning of the Rhesus Glycoprotein Hormone α-Subunit Gene (1991)

A rhesus monkey genomic library was screened with a cDNA for the glycoprotein hormone alpha-subunit. Genomic clones hybridizing with exon-specific probes were selected and the DNA sequences were determined for 1.6 kb of 5'-flanking DNA, all four exons, the second and third introns, all exon-intron junctions, and 357 bp of 3'-flanking DNA. Comparison with the 236 bp of 5'-flanking sequence data available for the human alpha gene indicates an overall homology of 95%. Primer extension analysis of rhesus placental and pituitary mRNA demonstrated that transcription initiation is identical to that in the human placenta. The rhesus gene contains an element nearly identical (21/22 bases) to the placental tissue-specific element described for the human alpha gene. The rhesus gene has only one copy of the cAMP-response element (CRE), which is present as a direct repeat in the human gene. The rhesus CRE contains the consensus core sequence TGACG-TCA with the cytosine in the fourth position that is essential for placental expression of the human gene. The 5'-flanking region also has elements highly homologous to the consensus estrogen and progesterone/glucocorticoid response elements, as well as thyrotrope-specific and Pit-1-like binding sites described in rodent genes. The nucleotide sequence of four exons (predicted mRNA) have an aggregate homology of 92.7% with the human sequence. However, a 12-bp insertion to the second exon results in the addition of 4 amino acids to the amino-terminal end of the protein; these are homologous with the proteins of nonprimates but are lacking in the human alpha-subunit. The amino acid sequence of the deduced protein was slightly more homologous with the bovine than the human protein (91.6% vs. 89.6%). Thus, the rhesus glycoprotein alpha-subunit gene codes for a protein whose structure somewhat more closely resembles that of lower species, but the 5'-flanking DNA of the gene has gained the elements necessary for transcription in the placental syncytiotrophoblast which distinguishes the primate placenta from the other species examined.
A cell cycle-regulated inhibitor of cyclin-dependent kinases. (1994)

Cyclin-dependent kinases (Cdks) previously have been shown to drive the major cell cycle transitions in eukaryotic organisms ranging from yeast to humans. We report here the identification of a 28-kDa protein, p28Ick (inhibitor of cyclin-dependent kinase), that binds to and inhibits the kinase activity of preformed Cdk/cyclin complexes from human cells. p28 inhibitory activity fluctuates during the cell cycle with maximal levels in G1 and accumulates in G1- and G0-arrested cells. These results suggest that control of the G1/S transition may be influenced by a family of Cdk inhibitors that include p28Ick and the recently described inhibitors p21Cip1/Waf1/Cap20 and p16Ink4.
The Structure of Tumor Necrosis Factor-α at 2.6 Å Resolution (1989)

The three-dimensional structure of tumor necrosis factor (TNF-a), a protein hormone sgcreted by macrophages, has been determined at 2.6 A resolution by xray crystallography.Phases were determined by multiple isomorphous replacement using data collected from five heavy atom derivatives.The multiple isomorphous replacement phases were further improved by real space symmetry averaging, exploiting the noncrystallographic 3-fold symmetry of the TNF-a trimer.An atomic model corresponding to the known amino acid sequence of TNF-a was readily built into the electron density map calculated with these improved phases.The 17,350-dalton monomer forms an elongated, antiparallel @-pleated sheet sandwich with a "jelly-roll" topology.Three monomers associate intimately about a 3-fold axis of symmetry to form a compact bellshaped trimer.Examination of the model and comparison to known protein structures reveals striking structural homology to several viral coat proteins, particularly satellite tobacco necrosis virus.Locations of residues conserved between TNF-a and lymphotoxin (TNF-@, a related cytokine known to bind to the same receptors as TNF-a) suggest that lymphotoxin, like TNF-a, binds to the receptor as a trimer and that the general site of interaction with the receptor is at the "base" of the trimer.Tumor necrosis factor-a (TNF-a)' is a pluripotent cytokine secreted by macrophages in response to a variety of inflammatory agents, particularly bacterial endotoxin.TNF-a was also isolated as cachectin (1, 2) which has been shown to mediate endotoxin-induced fever (3), shock (4, 5), and cachexia (wasting) ( 6), (and is believed to play a role in the cachectic state induced by many chronic diseases including cancer and AIDS.Th.e cytokine also induces hemorrhagic necrosis of certain transplantable tumors in mice and is specifically cytotoxic to a variety of tumor cells in culture (7, 8).The biological functions of the molecule are mediated by high affinity binding to receptors expressed on many cell types; specific effects of receptor binding include inhibition of triglyceride metabolism in adipocytes (1, 9-11), activation of neutrophils (12,13), and stimulation of proto-oncogenes cmyc and c-fos in fibroblasts (14).TNF-a is encoded in the
Transcriptional silencing of human immunodeficiency virus type 1 long terminal repeat-driven gene expression by the Krüppel-associated box repressor domain targeted to the transactivating response element (1995)

The evolutionarily conserved protein domain, called the Krüppel-associated box (KRAB), present in the amino termini of a large number of Krüppel-type zinc finger proteins is a strong repressor domain. In order to develop novel strategies to control human immunodeficiency virus type 1 (HIV-1) gene expression, we constructed a series of expression vectors expressing the wild-type Tat or Tat transdominant negative mutants fused to the KRAB repressor domain. We found that the KRAB domain tethered to the transactivating response element is able to suppress both basal and Tat-mediated activity of HIV-1 long terminal repeat-driven gene expression. These results suggest that the KRAB repressor domain fused to the Tat transdominant negative mutants can be successfully employed to control HIV-1 gene expression.
Purification, cloning, and functional expression of sucrose:fructan 6-fructosyltransferase, a key enzyme of fructan synthesis in barley. (1995)

Fructans play an important role in assimilate partitioning and possibly in stress tolerance in many plant families. Sucrose:fructan 6-fructosyltransferase (6-SFT), an enzyme catalyzing the formation and extension of beta-2,6-linked fructans typical of grasses, was purified from barley (Hordeum vulgare L.). It occurred in two closely similar isoforms with indistinguishable catalytic properties, both consisting of two subunits with apparent masses of 49 and 23 kDa. Oligonucleotides, designed according to the sequences of tryptic peptides from the large subunit, were used to amplify corresponding sequences from barley cDNA. The main fragment generated was cloned and used to screen a barley cDNA expression library. The longest cDNA obtained was transiently expressed in Nicotiana plumbaginifolia protoplasts and shown to encode a functional 6-SFT. The deduced amino acid sequence of the cDNA comprises both subunits of 6-SFT. It has high similarity to plant invertases and other beta-fructosyl hydrolases but only little to bacterial fructosyltransferases catalyzing the same type of reaction as 6-SFT.
Current Perspectives on Stability of Protein Drug Products during Formulation, Fill and Finish Operations (2008)

Commercialization of protein-based therapeutics is a challenging task in part due to the difficulties in maintaining protein solutions safe and efficacious throughout the drug product development process, storage, transportation and patient administration. Bulk drug substance goes through a series of formulation, fill and finish operations to provide the final dosage form in the desired formulation and container or delivery device. Different process parameters during each of these operations can affect the purity, activity and efficacy of the final product. Common protein degradation pathways and the various physical and chemical factors that can induce such reactions have been extensively studied for years. This review presents an overview of the various formulation-fill-finish operations with a focus on processing steps and conditions that can impact product quality. Various manufacturing operations including bulk freeze-thaw, formulation, filtration, filling, lyophilization, inspection, labeling, packaging, storage, transport and delivery have been reviewed. The article highlights our present day understanding of protein instability issues during biopharmaceutical manufacturing and provides guidance on process considerations that can help alleviate these concerns.
An integrated solid-phase extraction system for sub-picomolar detection (2002)

A microchip structure etched on a glass substrate for packed column solid-phase extraction (SPE) and capillary electrochromatography (CEC) is described. A 200 microm long, octadecylsilane (ODS) packed column was secured using two different approaches: solvent lock or polymer entrapment. The former method was utilized for SPE while the latter approach was applied for CEC. In SPE, the ODS packed chamber gave a detection limit of 70 fM for a nonpolar BODIPY (493/503) dye when concentrated for 3 min at an electroosmotic flow rate of 4.14 nL/min, compared to 30 pM for this detector without the SPE step. SPE beds showed reproducible, linear calibration curves (R(2) = 0.9989) between 1 and 100 pM BODIPY at fixed preconcentration times. Breakthrough curves for the 330 pL (ODS-packed) bed indicated a capacity for BODIPY dye of 8.1 x 10(-14) mmol, or 0.25 mmol dye per liter of bed. The ODS-chamber could also be used to analyze dilute amino acid and peptide solutions. In the CEC format, two neutral dyes (BODIPY and acridine orange) were baseline-separated in an isocratic run with a theoretical plate count of 84 (420 000 plates/m) and a reduced plate height of about 1. A labeled peptide was also analyzed by CEC, using the acidic eluent (84% acetonitrile, and 26% aqueous trifluoroacetic acid (0.05%)) preferred for peptide separations on ODS-coated silica particles.
Identification and characterization of Serpulina hyodysenteriae by restriction enzyme analysis and Southern blot analysis (1994)

Chromosomal DNA restriction enzyme analysis and Southern blot hybridization were used to characterize Serpulina hyodysenteriae strains. When chromosomal DNAs from selected strains (reference serotypes) of S. hyodysenteriae were digested with the restriction endonuclease Sau3A and hybridized with a 1.1-kb S. hyodysenteriae-specific DNA probe, a common 3-kb band was always detected in S. hyodysenteriae strains but was absent from Serpulina innocens strains. When the chromosomal DNA was digested with the restriction endonuclease Asp 700 and hybridized with two S. hyodysenteriae-specific DNA probes (0.75 and 1.1 kb of DNA), distinct hybridization patterns for each S. hyodysenteriae reference strain and the Australian isolate S. hyodysenteriae 5380 were detected. Neither the 1.1-kb nor the 0.75-kb DNA probe hybridized with Asp 700- or Sau3A-digested S. innocens chromosomal DNA. The presence of the 3-kb Sau3A DNA fragment in S. hyodysenteriae reference strains from diverse geographical locations shows that this fragment is conserved among S. hyodysenteriae strains and can be used as a species-specific marker. Restriction endonuclease analysis and Southern blot hybridization with these well-defined DNA probes are reliable and accurate methods for species-specific and strain-specific identification of S. hyodysenteriae.
Fast coordinate descent methods with variable selection for non-negative matrix factorization (2011)

Nonnegative Matrix Factorization (NMF) is an effective dimension reduction method for non-negative dyadic data, and has proven to be useful in many areas, such as text mining, bioinformatics and image processing. NMF is usually formulated as a constrained non-convex optimization problem, and many algorithms have been developed for solving it. Recently, a coordinate descent method, called FastHals, has been proposed to solve least squares NMF and is regarded as one of the state-of-the-art techniques for the problem. In this paper, we first show that FastHals has an inefficiency in that it uses a cyclic coordinate descent scheme and thus, performs unneeded descent steps on unimportant variables. We then present a variable selection scheme that uses the gradient of the objective function to arrive at a new coordinate descent method. Our new method is considerably faster in practice and we show that it has theoretical convergence guarantees. Moreover when the solution is sparse, as is often the case in real applications, our new method benefits by selecting important variables to update more often, thus resulting in higher speed. As an example, on a text dataset RCV1, our method is 7 times faster than FastHals, and more than 15 times faster when the sparsity is increased by adding an L1 penalty. We also develop new coordinate descent methods when error in NMF is measured by KL-divergence by applying the Newton method to solve the one-variable sub-problems. Experiments indicate that our algorithm for minimizing the KL-divergence is faster than the Lee & Seung multiplicative rule by a factor of 10 on the CBCL image dataset.
Anal Carcinoma: A 15-Year Retrospective Analysis (2000)

Cloacogenic and squamous cell carcinoma account for only a small proportion of large bowel cancers. The squamous cell type is the more common type and presents at a younger age in both sexes. The squamous cell type is also more common in males and is associated with human papilloma and HIV infection. Treatment modality and survival is, however, similar in both histologic variants of anal cancer.