gebhart/patrepeval huggingface dataset:
Drug Redeployment to Kill Leukemia and Lymphoma Cells by Disrupting SCD1-Mediated Synthesis of Monounsaturated Fatty Acids (2015)

The redeployed drug combination of bezafibrate and medroxyprogesterone acetate (designated BaP) has potent in vivo anticancer activity in acute myelogenous leukemia (AML) and endemic Burkitt lymphoma (eBL) patients; however, its mechanism-of-action is unclear. Given that elevated fatty acid biosynthesis is a hallmark of many cancers and that these drugs can affect lipid metabolism, we hypothesized that BaP exerts anticancer effects by disrupting lipogenesis. We applied mass spectrometry-based lipidomics and gene and protein expression measurements of key lipogenic enzymes [acetyl CoA carboxylase 1 (ACC1), fatty acid synthase (FASN), and stearoyl CoA desaturase 1 (SCD1)] to AML and eBL cell lines treated with BaP. BaP treatment decreased fatty acid and phospholipid biosynthesis from (13)C D-glucose. The proportion of phospholipid species with saturated and monounsaturated acyl chains was also decreased after treatment, whereas those with polyunsaturated chains increased. BaP decreased SCD1 protein levels in each cell line (0.46- to 0.62-fold; P < 0.023) and decreased FASN protein levels across all cell lines (0.87-fold decrease; P = 1.7 × 10(-4)). Changes to ACC1 protein levels were mostly insignificant. Supplementation with the SCD1 enzymatic product, oleate, rescued AML and e-BL cells from BaP cell killing and decreased levels of BaP-induced reactive oxygen species, whereas supplementation with the SCD1 substrate (and FASN product), palmitate, did not rescue cells. In conclusion, these data suggest that the critical anticancer actions of BaP are decreases in SCD1 levels and monounsaturated fatty acid synthesis. To our knowledge, this is the first time that clinically available antileukemic and antilymphoma drugs targeting SCD1 have been reported.
Application of High Performance Anion Exchange Chromatography to the Study of Carbohydrate Changes in Barley During Malting (2000)

The determination of the carbohydrate composition of barley during its transformation into malt was performed using high performance anion-exchange chromatography coupled with pulsed amperometric detection. Two sets of conditions were developed to analyse arabinose, glucose, xylose, fructose and sucrose on the hand, and maltose, maltotriose, maltotetraose, isomaltose, isomaltotriose and β-glucan degradation products on the other hand. A sizeable increase in the arabinose, xylose, glucose, cellobiose, maltose, isomaltose and maltotriose concentrations was observed. The sucrose and isomaltotriose contents decreased at the beginning of germination and then increased. Fructose showed little augmentation. The β-glucan oligomers showed modifications depending heavily on the variety. The modifications in the β-glucan oligomers content did not increase or decrease regularly during the germination process for each variety. This could be explained by the degradation of these residues to produce glucose and lower molecular weight residues. Moreover high molecular weight carbohydrates could be resynthesised from simpler carbohydrates.
Induction of Mucosal Immunity by Inactivated Poliovirus Vaccine Is Dependent on Previous Mucosal Contact with Live Virus (1999)

The inactivated poliovirus vaccine (IPV) is used for protection against poliomyelitis in The Netherlands. It is not clear, however, whether IPV vaccination can lead to priming of the mucosal immune system and the induction of IgA. It has been demonstrated that IPV vaccination is able to induce strong memory IgA responses in the serum of persons who have been naturally exposed to wild-type poliovirus. This has led to the hypothesis that IPV vaccination is able to induce poliovirus-specific IgA at mucosal sites in persons who have been previously primed with live poliovirus at mucosal sites. To test this hypothesis, the kinetics of the IgA response in serum and saliva after IPV vaccination were examined in persons previously vaccinated with oral poliovirus vaccine (OPV) or IPV. ELISA and enzyme-linked immunospot assays were used for the detection of poliovirus-specific IgA responses. In addition, B cell populations were separated on the basis of the expression of mucosal (alpha4beta7 integrin) and peripheral homing receptors (L-selectin). Parenteral IPV vaccination was able to boost systemic and mucosal IgA responses in previously OPV-vaccinated persons only. None of the previously vaccinated IPV recipients responded with the production of IgA in saliva. In agreement with this finding, a large percentage of the poliovirus-specific IgA-producing lymphocytes detected in previous OPV recipients expressed the alpha4beta7 integrin. It is concluded that IPV vaccination alone is insufficient to induce a mucosal IgA response against poliovirus. In mucosally (OPV-) primed individuals, however, booster vaccination with IPV leads to a strong mucosal IgA response.
A quantitative model for subcutaneous abscess formation in mice. (1980)

The purpose of this experiment was to develop an experimental model of s.c. encapsulated abscesses in which abscess formation could be assessed by quantitative measurements. Inocula were composed of bacterial broth cultures, autoclaved mouse caecal contents or both in combination. These inocula were injected s.c. on the flank in 2 strains of mice. Large encapsulated abscesses formed in all recipients by Day 4 when the inoculum contained either B. fragilis or S. aureus combined with caecal contents. Bacterial concentrations per ml of pus at Day 6 were 10(10.1+/-0.02) for B. fragilis and 10(8.4+/-0.1) for S. aureus. Spontaneous external drainage began by 10--15 days, and complete healing of the lesion occurred by 4--6 weeks. The typical histological pattern consisted of a collagen capsule surrounding a rim of neutrophils, enclosing a central area of necrotic cells and fibre from the inoculum. The cross-sectional areas of the capsule, the neutrophil band and the entire abscess were measured in a reproducible manner by planimetry, and abscess volumes were calculated. Values for these measurements varied with different inocula and different times after inoculation, but were highly consistent for a specified time and inoculum.
Variability of Strap Tension in Brace Treatment for Adolescent Idiopathic Scoliosis (1999)

If strap tension affects the biomechanical actions of the brace, these results indicate that regular brace strap tension adjustments are needed and raise questions about the efficacy of nighttime bracing to correct spinal deformities.
The Oncogenic Activity of Cyclin E Is Not Confined to Cdk2 Activation Alone but Relies on Several Other, Distinct Functions of the Protein (2002)

We have previously shown that cyclin E can malignantly transform primary rat embryo fibroblasts in cooperation with constitutively active Ha-Ras. In addition, we demonstrated that high level cyclin E expression potentiates the development of methyl-nitroso-urea-induced T-cell lymphomas in mice. To further investigate the mechanism underlying cyclin E-mediated malignant transformation, we have performed a mutational analysis of cyclin E function. Here we show that cyclin E mutants defective to form an active kinase complex with Cdk2 are unable to drive cells from G(1) into S phase but can still malignantly transform rat embryo fibroblasts in cooperation with Ha-Ras. In addition, Cdk2 activation is not a prerequisite for the ability of cyclin E to rescue yeast triple cln mutations. We also find that the oncogenic properties of cyclin E did not entirely correspond with its ability to interact with the negative cell cycle regulator p27(Kip1) or the pocket protein p130. These findings suggest that the oncogenic activity of cyclin E does not exclusively rely on its ability as a positive regulator of G(1) progression. Rather, we propose that cyclin E harbors other functions, independent of Cdk2 activation and p27(Kip1) binding, that contribute significantly to its oncogenic activity.
phzO , a Gene for Biosynthesis of 2-Hydroxylated Phenazine Compounds in Pseudomonas aureofaciens 30-84 (2001)

Certain strains of root-colonizing fluorescent Pseudomonas spp. produce phenazines, a class of antifungal metabolites that can provide protection against various soilborne root pathogens. Despite the fact that the phenazine biosynthetic locus is highly conserved among fluorescent Pseudomonas spp., individual strains differ in the range of phenazine compounds they produce. This study focuses on the ability of Pseudomonas aureofaciens 30-84 to produce 2-hydroxyphenazine-1-carboxylic acid (2-OH-PCA) and 2-hydroxyphenazine from the common phenazine metabolite phenazine-1-carboxylic acid (PCA). P. aureofaciens 30-84 contains a novel gene located downstream from the core phenazine operon that encodes a 55-kDa aromatic monooxygenase responsible for the hydroxylation of PCA to produce 2-OH-PCA. Knowledge of the genes responsible for phenazine product specificity could ultimately reveal ways to manipulate organisms to produce multiple phenazines or novel phenazines not previously described.
53BP1 Regulates DSB Repair Using Rif1 to Control 5′ End Resection (2013)

The choice between double-strand break (DSB) repair by either homology-directed repair (HDR) or nonhomologous end joining (NHEJ) is tightly regulated. Defects in this regulation can induce genome instability and cancer. 53BP1 is critical for the control of DSB repair, promoting NHEJ, and inhibiting the 5' end resection needed for HDR. Using dysfunctional telomeres and genome-wide DSBs, we identify Rif1 as the main factor used by 53BP1 to impair 5' end resection. Rif1 inhibits resection involving CtIP, BLM, and Exo1; limits accumulation of BRCA1/BARD1 complexes at sites of DNA damage; and defines one of the mechanisms by which 53BP1 causes chromosomal abnormalities in Brca1-deficient cells. These data establish Rif1 as an important contributor to the control of DSB repair by 53BP1.
Delayed Gastric Emptying After Palliative Gastrojejunostomy for Carcinoma of the Pancreas (1987)

Fifty-seven patients with carcinoma of the pancreas underwent gastrojejunostomy (GJ) alone or in conjunction with biliary bypass. The mortality rate for GJ alone was 18%; for the combined biliary and duodenal bypass operation it was 5%. Fifteen patients (26%) had delayed gastric emptying (DGE) postoperatively for periods extending from nine to 31 days (average, 16 days); five patients (33%) died. Eight (57%) of 14 patients with preoperative duodenal obstruction and five (42%) of 12 patients with retrocolic GJ experienced DGE postoperatively. Stomal diameter in the patients with DGE averaged 6.5 cm, and 8.4 cm was the average in those without DGE. We conclude that DGE is a frequent and serious problem after GJ for patients with unresectable pancreatic cancer.
The claudin gene family: expression in normal and neoplastic tissues (2006)

Our study confirms previously known CLDN gene expression patterns and identifies new ones, which may have applications in the detection, prognosis and therapy of several human cancers. In particular we identify several malignancies that express CLDN3 and CLDN4. These cancers may represent ideal candidates for a novel therapy being developed based on CPE, a toxin that specifically binds claudin-3 and claudin-4.
Design of Cyclic Peptides That Bind Protein Surfaces with Antibody-Like Affinity (2007)

There is a pressing need for new molecular tools to target protein surfaces with high affinity and specificity. Here, we describe cyclic messenger RNA display with a trillion-member covalent peptide macrocycle library. Using this library, we have designed a number of high-affinity, redox-insensitive, cyclic peptides that target the signaling protein G alpha i1. In addition to cyclization, our library construction took advantage of an expanded genetic code, utilizing nonsense suppression to insert N-methylphenylalanine as a 21st amino acid. The designed macrocycles exhibit several intriguing features. First, the core motif seen in all of the selected variants is the same and shares an identical context with respect to the macrocyclic scaffold, consistent with the idea that selection simultaneously optimizes both the cyclization chemistry and the structural placement of the binding epitope. Second, detailed characterization of one molecule, cyclic G alpha i binding peptide (cycGiBP), demonstrates substantially enhanced proteolytic stability relative to that of the parent linear molecule. Third and perhaps most important, the cycGiBP peptide binds the target with very high affinity ( K i approximately 2.1 nM), similar to those of many of the best monoclonal antibodies and higher than that of the betagamma heterodimer, an endogenous G alpha i1 ligand. Overall the work provides a general route to design novel, low-molecular-weight, high-affinity ligands that target protein surfaces.
Nanopatterning with Microdomains of Block Copolymers using Reactive-Ion Etching Selectivity (2002)

Block copolymers are known to generate nanoscale microdomains by microphase separation, if they are annealed at a temperature lower than their order-disorder transition temperatures. We attempted to transfer the microdomains onto substrates by only using the reactive-ion etching (RIE) method, which is widely used in semiconductor manufacturing processes. Block copolymers consisting of an aromatic polymer and an acrylic polymer were used since there is a large difference in the dry-etch resistance, in that only the acrylic polymer was selectively etched by RIE. Furthermore, nanometer-scale dot patterns can be easily obtained on the substrates by the continuous RIE process. Dot patterns of arbitrary diameters could be transferred to silicon wafers, glass substrates and so forth using these materials and processes.
Cu-Catalyzed N- and O-Arylation of 2-, 3-, and 4-Hydroxypyridines and Hydroxyquinolines (2007)

With use of Cu-based catalysts, 2- and 4-hydroxypyridines were N-arylated in modest to excellent yields. In the case of 2-hydroxypyridine, the use of 4,7-dimethoxy-1,10-phenanthroline, 3, expanded the scope of previous literature reports to include the use of N-containing heteroaryl halides, and 2-substituted aryl halides. In addition, by using a copper catalyst based on 2,2,6,6-tetramethylheptane-3,5-dione, 4, the first N-arylations of 4-hydroxypyridines and O-arylations of 3-hydroxypyridines with aryl bromides and iodides have been accomplished. [reaction: see text].
Bim-mediated deletion of antigen-specific CD8+ T cells in patients unable to control HBV infection (2008)

HBV-specific CD8(+) T cells are critical for a successful immune response to HBV infection. They are markedly diminished in number in patients who fail to control the virus, but the mechanisms resulting in their depletion remain ill defined. Here, we dissected the defective HBV-specific CD8(+) T cell response associated with chronic HBV infection by gene expression profiling. We found that HBV-specific CD8(+) T cells from patients with different clinical outcomes could be distinguished by their patterns of gene expression. Microarray analysis revealed that overlapping clusters of functionally related apoptotic genes were upregulated in HBV-specific CD8(+) T cells from patients with chronic compared with resolved infection. Further analysis confirmed that levels of the proapoptotic protein Bcl2-interacting mediator (Bim) were upregulated in HBV-specific CD8(+) T cells from patients with chronic HBV infection. Blocking Bim-mediated apoptosis enhanced recovery of HBV-specific CD8(+) T cells both in culture and directly ex vivo. Consistent with evidence that Bim mediates apoptosis of CD8(+) T cells expressing low levels of CD127 (IL-7R), the few surviving HBV-specific CD8(+) T cells were CD127(hi )and had elevated levels of the antiapoptotic protein Mcl1, suggesting they were amenable to IL-7-mediated rescue from apoptosis. We therefore postulate that Bim-mediated attrition of HBV-specific CD8(+) T cells contributes to the inability of these cell populations to persist and control viral replication.
Construction of Mutant Genes for a Non‐Toxic Verotoxin 2 Variant (VT2vp1) of Escherichia coli and Characterization of Purified Mutant Toxins (1994)

The gene encoding a Verotoxin 2 variant, VTvp1, was mutated by oligonucleotide-directed site-specific mutagenesis. Among 6 mutant toxins encoded by the mutated genes, E167Q-R170L (glutamic acid at position 167 and arginine at position 170 from N-terminus of the A subunit were replaced by glutamine and leucine, respectively) was found to have markedly decreased activities; inhibition of protein synthesis, Vero cell cytotoxicity and mouse lethality of the purified E167Q-R170L were 1/1,900, 1/125,000 and 1/2,000, respectively, of those of the purified wild-type VT2vp1. Since the antigenic property of the E167Q-R170L was demonstrated to be similar to that of the wild-type VT2vp1 by Ouchterlony double gel diffusion test and by neutralization test of Vero cell cytotoxicity of the VT2vp1, a possibility to use the mutant VT2vp1, E167Q-R170L, as a toxoid is discussed.
Larger amygdala but no change in hippocampal volume in 10-year-old children exposed to maternal depressive symptomatology since birth (2011)

Maternal separation and poor maternal care in animals have been shown to have important effects on the developing hippocampus and amygdala. In humans, children exposed to abuse/maltreatment or orphanage rearing do not present changes in hippocampal volumes. However, children reared in orphanages present enlarged amygdala volumes, suggesting that the amygdala may be particularly sensitive to severely disturbed (i.e., discontinous, neglectful) care in infancy. Maternal depressive symptomatology has been associated with reductions in overall sensitivity to the infant, and with an increased rate of withdrawn, disengaged behaviors. To determine if poor maternal care associated with maternal depressive symptomatology has a similar pattern of association to the volumes of the hippocampus and amygdala in children, as is the case for severely disturbed infant care (orphanage rearing), we measured hippocampal and amygdala volumes as well as stress hormone (glucocorticoid) levels in children exposed (n = 17) or not (n = 21) to maternal depressive symptomatology since birth. Results revealed no group difference in hippocampal volumes, but larger left and right amygdala volumes and increased levels of glucocorticoids in the children of mothers presenting depressive symptomatology since birth. Moreover, a significant positive correlation was observed between mothers' mean depressive scores and amygdala volumes in their children. The results of this study suggest that amygdala volume in human children may represent an early marker of biological sensitivity to quality of maternal care.
A novel multifunctionally labelled DNA probe bearing an intercalator and a fluorophore (1994)

A 15-mer DNA labelled with a novel multifunctional fluorescent agent bearing acridine and fluorescein moieties is synthesized and the intensity of fluorescein-based fluorescence detected by the excitation of acridine is shown to be strongly affected by the DNA's secondary structure.
Nod1 Detects a Unique Muropeptide from Gram-Negative Bacterial Peptidoglycan (2003)

Although the role of Toll-like receptors in extracellular bacterial sensing has been investigated intensively, intracellular detection of bacteria through Nod molecules remains largely uncharacterized. Here, we show that human Nod1 specifically detects a unique diaminopimelate-containing N-acetylglucosamine-N-acetylmuramic acid (GlcNAc-MurNAc) tripeptide motif found in Gram-negative bacterial peptidoglycan, resulting in activation of the transcription factor NF-kappaB pathway. Moreover, we show that in epithelial cells (which represent the first line of defense against invasive pathogens), Nod1is indispensable for intracellular Gram-negative bacterial sensing.
UPA, a universal protein array system for quantitative detection of protein-protein, protein-DNA, protein-RNA and protein-ligand interactions (2000)

Protein-protein interactions have been widely used to study gene expression pathways and may be considered as a new approach to drug discovery. Here I report the development of a universal protein array (UPA) system that provides a sensitive, quantitative, multi-purpose, effective and easy technology to determine not only specific protein-protein interactions, but also specific interactions of proteins with DNA, RNA, ligands and other small chemicals. (i) Since purified proteins are used, the results can be easily interpreted. (ii) UPA can be used multiple times for different targets, making it economically affordable for most laboratories, hospitals and biotechnology companies. (iii) Unlike DNA chips or DNA microarrays, no additional instrumentation is required. (iv) Since the UPA uses active proteins (without denaturation and renaturation), it is more sensitive compared with most existing methods. (v) Because the UPA can analyze hundreds (even thousands on a protein microarray) of proteins in a single experiment, it is a very effective method to screen proteins as drug targets in cancer and other human diseases.
Counting linear extensions is #P-complete (1991)

We show that the problem of counting the number of linear extensions of a given partially ordered set is #P-complete. This settles a long-standing open question and contrssts with recent results giving randomized polynomial-time algorit hms for estimating the number of linear extensions. One consequence is that computing the volume of a rational polyhedron is strongly #P-hard.
DETECTION OF CYTOKINES AT THE CARTILAGE/PANNUS JUNCTION IN PATIENTS WITH RHEUMATOID ARTHRITIS: IMPLICATIONS FOR THE ROLE OF CYTOKINES IN CARTILAGE DESTRUCTION AND REPAIR (1992)

Cytokine release at the cartilage/pannus junction (CPJ) may be involved in cartilage destruction and tissue repair in rheumatoid arthritis (RA). Tissue samples of CPJ from 12 RA patients were examined for the presence of cytokines using immunohistochemical techniques with immunoaffinity purified F(ab')2 antibodies raised against recombinant human cytokines. Twenty-four areas of distinct CPJ at which a discrete junction between cartilage and overlying pannus exists were observed. In all specimens, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha. IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor (TGF)-beta 1 were detected in cells in pannus particularly along the surface of cartilage and at the site of cartilage erosion. Double immunofluorescence staining showed that most cytokine containing cells also labelled with a macrophage marker (CD68). About 50% of blood vessel endothelial cells stained for GM-CSF. Twelve areas of diffuse fibroblastic CPJ, at which an indistinct margin is seen between cartilage and pannus were examined. At this site, TGF-beta 1 was the only cytokine detected in fibroblast-like cells. None of these cytokines were detected in synovial tissue at the normal synovium/cartilage junction. Chondrocytes from all 11 normal specimens as well as those from RA patients stained for IL-1 alpha, TNF-alpha, IL-6, GM-CSF and TGF-beta 1, especially those close to subchondral bone. However, IL-1 beta, interferon-gamma and lymphotoxin were not detected in either the normal synovium/cartilage junction or rheumatoid CPJ.(ABSTRACT TRUNCATED AT 250 WORDS)