gebhart/patrepeval huggingface dataset:
Self‐Cleaving Ribozymes of Hepatitis Delta Virus RNA (1997)

Hepatitis delta virus (HDV) is a small single-stranded RNA satellite of hepatitis B virus. Although it is a human pathogen, it shares a number of features with a subset of the small plant satellite RNA viruses, including self-cleaving sequences in the genomic and antigenomic sequences of the viral RNA. The self-cleaving sequence is critical to viral replication and is thought to function as a ribozyme in vivo to process the products of rolling-circle replication to unit-length molecules. A divalent cation is required for cleavage and while a structural role is implicated for metal ions, a more direct role for a metal ion in catalysis has not yet been proven. A minimal natural ribozyme sequence with proficient in vitro self-cleavage activity is about 85 nucleotides long and adopts a secondary structure with four paired regions (P1-P4). The two pairings that define the 5' and 3' boundaries of the ribozyme, P1 and P2, form an atypical pseudoknot arrangement. This secondary structure places a number of constraints on the possible tertiary folding of the sequence, which together with chemical probing, photo-cross-linking, mutagenesis and computer-assisted modeling provides clues to the three-dimensional structure. The data are consistent with a model in which the cleavage site, located at the 5' end of P1, is in close proximity to three single-stranded regions, consisting of a hairpin loop at the end of P3 and two sequences joining P1 to P4 and P4 to P2. While the natural forms of the HDV ribozymes appear to be prone to misfolding, biochemical and mutagenesis studies from a number of laboratories has allowed the production of trans-acting ribozymes and smaller more active cis-acting ribozymes, both of which will aid in further mechanistic and structural studies of this RNA.
Cytokinetic comparison of thymidine and leucovorin rescue of marrow in humans after exposure to high-dose methotrexate. (1979)

The cytokinetics of marrow recovery were compared in patients receiving a standard exposure to high-dose methotrexate followed by either thymidine rescue, leucovorin rescue at the doses used in most clinical protocols (10 mg/sq m every 6 hr), or leucovorin rescue at a 5-fold higher dose rate (50 mg/sq m every 6 hr). Thymidine rescue initiated a prompt recovery of DNA synthesis, as detected by [3H]deoxycytidine incorporation, and progression of cells through the cell cycle monitored by flow cytometry, even in the presence of methotrexate levels that prevented initiation of rescue by the lower doses of leucovorin. Dose dependency for leucovorin in vivo in humans was suggested by the observation that the higher leucovorin dose rate was successful in initiating recue within the first 24 hr, whereas the lower dose was not. Recovery of DNA synthesis is more rapid and/or complete with thymidine rescue than with either dose of leucovorin. Thymidine rescue was accomplished without requirement for purines over and above those present in plasma. These results suggest that the kinetics of marrow recovery is quite different for thymidine and leucovorin rescue.
Isolation of a Novel Tyrosine Kinase Inhibitor, Lavendustin A, from Streptomyces griseolavendus (1989)

A potent tyrosine kinase inhibitor, lavendustin A [1], has been isolated from a butyl acetate extract of Streptomyces griseolavendus culture filtrate. It inhibits epidermal growth factor receptor-associated tyrosine kinase with an IC50 of 4.4 ng/ml, which is about 50 times more inhibitory than erbstatin. It does not inhibit protein kinase A or C. Its structure, determined by spectral data and total synthesis, is novel, having a tertiary amine in the center with substituted benzyl and phenyl groups. Lavendustin A competes with ATP and is noncompetitive with the peptide. Its structure-activity relationship is discussed.
Cell-homologous genes in the Kaposi's sarcoma-associated rhadinovirus human herpesvirus 8: determinants of its pathogenicity? (1997)

The epidemiology of Kaposi’s sarcoma (KS) among patients with AIDS has suggested that a sexually transmitted infectious agent other than human immunodeficiency virus (HIV) must be involved in its pathogenesis. KS is about 20,000 times more common in patients with AIDS than in the general population of the United States, and other immunosuppressed groups develop KS approximately 600 times more frequently than the healthy population. During the first decade of the AIDS epidemic, about 20% of homosexual and bisexual patients developed KS, in contrast to about 1% of men with hemophilia. Women were more likely to have KS if their partners were bisexual rather than parenterally infected men (4). This led to a broad search by PCR in patients with KS for the presence of viruses known to affect humans, such as cytomegalovirus (53, 57), human herpesvirus 6 (HHV-6) (29), and BK virus (43). Some of these viruses were found frequently in KS biopsy specimens, but none of them was consistently present (25, 30). A new era of KS research began when Y. Chang, P. S. Moore, and their colleagues (14) detected by representational difference analysis (35) two short DNA fragments from a herpesvirus that was distinct from all previously known herpesviruses. Remarkably, more than 90% of KS tissues obtained from patients with AIDS contained the virus. The viral sequences were not present in biopsy specimens from patients without AIDS but were found in 15% of non-KS tissue DNA from patients with AIDS. The new virus, tentatively termed KS-associated herpesvirus or HHV-8, was soon found to be common in all epidemiological forms of KS (24). Viral DNA is consistently present in AIDS-associated KS lesions (1, 36) and in the vast majority of classical European-Mediterranean KS lesions (1, 18), while it is far less frequent in uninvolved skin of patients with KS and in the various biopsy specimens from Caucasian patients without KS and HIV. AIDS-associated African KS specimens (92%) and non-AIDS-associated KS lesions in Uganda (85%) had the virus (16). Based on PCR, the prevalence of HHV-8 appeared to be high in the general population in Uganda, while searches in non-KS tumors and in normal tissues showed that the virus is rarely detectable in Caucasians. While some lymphomas carry other herpesviruses, such as Epstein-Barr virus (EBV) and HHV-6 (22), those specimens did not contain HHV-8 DNA. However, one type of lymphoid tumor, the AIDS-associated body cavity-based lymphoma (BCBL), was positive for HHV-8 DNA by PCR and Southern
Regulation of Rac1 activation by the low density lipoprotein receptor–related protein (2002)

The low density lipoprotein receptor-related protein (LRP-1) binds and mediates the endocytosis of multiple ligands, transports the urokinase-type plasminogen activator receptor (uPAR) and other membrane proteins into endosomes, and binds intracellular adaptor proteins involved in cell signaling. In this paper, we show that in murine embryonic fibroblasts (MEFs) and L929 cells, LRP-1 functions as a major regulator of Rac1 activation, and that this activity depends on uPAR. LRP-1-deficient MEFs demonstrated increased Rac1 activation compared with LRP-1-expressing MEFs, and this property was reversed by expressing the VLDL receptor, a member of the same gene family as LRP-1, with overlapping ligand-binding specificity. Neutralizing the activity of LRP-1 with receptor-associated protein (RAP) increased Rac1 activation and cell migration in MEFs and L929 cells. The same parameters were unaffected by RAP in uPAR-/- MEFs, prepared from uPAR gene knockout embryos, and in uPAR-deficient LM-TK- cells. Untreated uPAR+/+ MEFs demonstrated substantially increased Rac1 activation compared with uPAR-/- MEFs. In addition to Rac1, LRP-1 suppressed activation of extracellular signal-regulated kinase (ERK) in MEFs; however, it was Rac1 (and not ERK) that was responsible for the effects of LRP-1 on MEF migration. Thus, LRP-1 regulates two signaling proteins in the same cell (Rac1 and ERK), both of which may impact on cell migration. In uPAR-negative cells, LRP-1 neutralization does not affect Rac1 activation, and other mechanisms by which LRP-1 may regulate cell migration are not unmasked.
An oncogenic super-enhancer formed through somatic mutation of a noncoding intergenic element (2014)

In certain human cancers, the expression of critical oncogenes is driven from large regulatory elements, called super-enhancers, that recruit much of the cell's transcriptional apparatus and are defined by extensive acetylation of histone H3 lysine 27 (H3K27ac). In a subset of T-cell acute lymphoblastic leukemia (T-ALL) cases, we found that heterozygous somatic mutations are acquired that introduce binding motifs for the MYB transcription factor in a precise noncoding site, which creates a super-enhancer upstream of the TAL1 oncogene. MYB binds to this new site and recruits its H3K27 acetylase-binding partner CBP, as well as core components of a major leukemogenic transcriptional complex that contains RUNX1, GATA-3, and TAL1 itself. Additionally, most endogenous super-enhancers found in T-ALL cells are occupied by MYB and CBP, which suggests a general role for MYB in super-enhancer initiation. Thus, this study identifies a genetic mechanism responsible for the generation of oncogenic super-enhancers in malignant cells.
A Feature-Driven Approach to Automated Class Diagram Construction (2015)

Internetware denotes a type of complex distributed software system, which executes in an open, uncertain and dynamic environment, and adapts itself to changes in the environment. An important problem in the researches of Internetware is how to automatically construct the Internetware application that realizes the new requirements resulted from changes in the environment. In this paper, we focus on the automated construction of an important realization artifact of an Internetware application: the class diagram. A feature-driven approach is taken to automatically construct class diagrams. The approach consists of two components: a feature model utilized to model all the requirements that an Internetware application has to realize in different environments; the transformation rules from this feature model to class diagrams for automated class diagram construction. With this approach, once the requirements specific to an environment is given, the class diagram realizing the requirements can be constructed with the transformation rules automatically. To support the formal specification of the transformation rules, we design a transformation description language TDL4CD. Furthermore, several criteria for checking the validity of transformation rules written in TDL4CD is provided to support the construction of class diagrams. The usability of TDL4CD, as well as the feasibility of automatically constructing a class diagram with transformation rules in TDL4CD are preliminarily evaluated with 2 case studies.
The value of autofluorescence as a diagnostic feature of acute promyelocytic leukemia. (2006)

Autofluorescence is an immunophenotypic characteristic of leukemic blasts in acute promyelocytic leukemia (APL). We examined the fluorescent intensity of isotype controls in 25 cases of APML and 25 controls with acute myeloid leukemia. The fluorescence of the FITC- and PE-conjugated controls was consistently higher in APML. Autofluorescence may therefore represent a helpful diagnostic marker in APML.
Platelet-derived growth factor plays a key role in proliferative vitreoretinopathy. (1999)

These findings show that PDGF makes an important contribution to the development of PVR in this animal model. Furthermore, there is a marked difference between the two receptors for PDGF, and it is the PDGF alpha receptor that is capable of driving events that lead to PVR.
Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas (1995)

Chemotherapy for brain tumours has been limited because of difficulty in achieving adequate exposure to the tumour without systemic toxicity. We have developed a method for local sustained release of chemotherapeutic agents by their incorporation into biodegradable polymers. Implantation of the drug-impregnated polymer at the tumour site allows prolonged local exposure with minimal systemic exposure. We conducted a randomised, placebo-controlled, prospective study to evaluate the effectiveness of biodegradable polymers impregnated with carmustine to treat recurrent malignant gliomas. In 27 medical centres, 222 patients with recurrent malignant brain tumours requiring re-operation were randomly assigned to receive surgically implanted biodegradable polymer discs with or without 3.85% carmustine. Randomisation balanced the treatment groups for all of the prognostic factors examined. Median survival of the 110 patients who received carmustine polymers was 31 weeks compared with 23 weeks for the 112 patients who received only placebo polymers (hazard ratio = 0.67, p = 0.006, after accounting for the effects of prognostic factors). Among patients with glioblastoma, 6-month survival in those treated with carmustine-polymer discs was 50% greater than in those treated with placebo (mortality = 32 of 72 [44%] vs 47 of 73 [64%], p = 0.02). There were no clinically important adverse reactions related to the carmustine polymer, either in the brain or systemically. Interstitial chemotherapy delivered with polymers directly to brain tumours at the time of surgery seems to be a safe and effective treatment for recurrent malignant gliomas.
Cloning and characterization of the Escherichia coli K-12 rfa-2 (rfaC) gene, a gene required for lipopolysaccharide inner core synthesis (1993)

A genetically defined mutation, designated rfa-2, results in altered lipopolysaccharide (LPS) biosynthesis. rfa-2 mutants produce a core-defective LPS that contains lipid A and a single sugar moiety, 2-keto-3-deoxyoctulosonic acid, in the LPS core region. Such LPS core-defective or deep-rough (R) mutant structures were previously designated chemotype Re. Phenotypically, rfa-2 mutants exhibit increased permeability to a number of hydrophilic and hydrophobic agents. By restriction analyses and complementation studies, we clearly defined the rfa-2 gene on a 1,056-bp AluI-DraI fragment. The rfa-2 gene and the flanking rfa locus regions were completely sequenced. Additionally, the location of the rfa-2 gene on the physical map of the Escherichia coli chromosome was determined. The rfa-2 gene encodes a 36,000-dalton polypeptide in an in vivo expression system. N-terminal analysis of the purified rfa-2 gene product confirmed the first 24 amino acid residues as deduced from the nucleotide sequence of the rfa-2 gene coding region. By interspecies complementation, a Salmonella typhimurium rfaC mutant (LPS chemotype Re) is transformed with the E. coli rfa-2+ gene, and the transformant is characterized by wild-type sensitivity to novobiocin (i.e., uninhibited growth at 600 micrograms of novobiocin per ml) and restoration of the ability to synthesize wild-type LPS structures. On the basis of the identity and significant similarity of the rfa-2 gene sequence and its product to the recently defined (D. M. Sirisena, K. A. Brozek, P. R. MacLachlan, K. E. Sanderson, and C. R. H. Raetz, J. Biol. Chem. 267:18874-18884, 1992), the S. typhimurium rfaC gene sequence and its product (heptosyltransferase 1), the E. coli K-12 rfa-2 locus will be designated rfaC.
Synthesis and 13C CP-MAS NMR Characterization of a New Chitosan-Based Polymeric Network (1998)

New chemical hydrogels, potentially suitable for biomedical applications, have been synthesized and characterized by 13C CP-MAS NMR spectroscopy. The polysaccharidic component of these hydrogels is chitosan, while the novel cross-linking agent is diethyl squarate (DES). 1H and 13C NMR spectra of chitosan allow a good characterization of the starting materials. In dried chitosan/DES networks, the structure of the chemical bridges (i.e., of the cross-links), has been investigated by 13C CP-MAS NMR. The spectrum of the cross-linked material appears rather broad and poorly resolved. A large number of weak signals in the 160−190 ppm region is observed, all due to the squarate moiety, but none due to the original diethyl squarate. Squarate may be thought to act both as a bidentate cross-linking agent and as a monodentate substituent. A partial spectral assignment of the CP-MAS spectrum was obtained through a spectral “editing” sequence.
A Microbial Sensor Based on Direct Electron Transfer at Shewanella Sp. Drop‐Coated Screen‐Printed Carbon Electrodes (2009)

Abstract Aerobically grown Shewanella sp. bacterial suspension drop‐coated on a disposable screen‐printed carbon electrode was found to possess electroactivity without the aid of redox mediator. Cyclic voltammetric studies revealed the characteristics of a mixed diffusion adsorption‐controlled electrochemical process for direct electron transfer at the bacteria‐modified electrode. Both FE‐SEM and ATR FT‐IR experiments were carried out to investigate the surface characteristics. The electroanalytical applicability was further demonstrated for electrocatalytic reduction of arsenite, hydrogen peroxide and nitrite. Low cost and very simple manufacturing procedure allow for the proposed bacterial sensor to be applied as disposable devices.
An adaptive array processor with robustness and broad-band capabilities (1984)

A new type of receiving array which adaptively minimizes ouput noise power while simultaneously satisfying certain robustness and/or bandwidth criteria is considered. The resulting array gains are shown to be robust against direction uncertainty in the assumed look direction, against wavefront distortions and against array geometry errors. The robustness property is incorporated directly into the adaption algorithm via constraints. Extensive simulation has established very satisfactory performance of this new algorithm, both as a limited broad-band processor and as a robust narrow-band processor.
Recapitulation of embryonic neuroendocrine differentiation in adult human pancreatic duct cells expressing neurogenin 3 (2002)

Regulatory proteins have been identified in embryonic development of the endocrine pancreas. It is unknown whether these factors can also play a role in the formation of pancreatic endocrine cells from postnatal nonendocrine cells. The present study demonstrates that adult human pancreatic duct cells can be converted into insulin-expressing cells after ectopic, adenovirus-mediated expression of the class B basic helix-loop-helix factor neurogenin 3 (ngn3), which is a critical factor in embryogenesis of the mouse endocrine pancreas. Infection with adenovirus ngn3 (Adngn3) induced gene and/or protein expression of NeuroD/beta2, Pax4, Nkx2.2, Pax6, and Nkx6.1, all known to be essential for beta-cell differentiation in mouse embryos. Expression of ngn3 in adult human duct cells induced Notch ligands Dll1 and Dll4 and neuroendocrine- and beta-cell-specific markers: it increased the percentage of synaptophysin- and insulin-positive cells 15-fold in ngn3-infected versus control cells. Infection with NeuroD/beta2 (a downstream target of ngn3) induced similar effects. These data indicate that the Delta-Notch pathway, which controls embryonic development of the mouse endocrine pancreas, can also operate in adult human duct cells driving them to a neuroendocrine phenotype with the formation of insulin-expressing cells.
Total Synthesis of (−)-Ecklonialactone B (2013)

The total synthesis of (-)-ecklonialactone B as well as the 9,10-dihydro derivative by two different strategies is reported. The catalytic asymmetric Claisen rearrangement of Gosteli-type allyl vinyl ethers delivered elaborated α-keto ester building blocks. Ring-closing metatheses, including a notable diastereotopos-differentiating variant, a B-alkyl Suzuki-Miyaura cross-coupling reaction and a regio- and diastereoselective last-step epoxidation are key contributors.
Enzymatic Synthesis of a Blood Group B-related Pentaglycosylceramide by an α-Galactosyltransferase from Rabbit Bone Marrow (1973)

Abstract An α-galactosyltransferase that catalyzes the biosynthesis in vitro of blood group B-specific pentaglycosylceramide from UDP-[14C]galactose and O-β-galactosyl (1→3)-O-β-(N-acetyl) glucosaminosyl (1←3)-O-β-galactosyl (1→4)-O-β-glucosyl (1 →1) ceramide was detected in homogenates of adult rabbit bone marrow. The enzyme was present in the supernatant solution obtained after homogenization of rabbit bone marrow in the presence of 0.6% Triton X-100 and centrifugation at 100,000 x g. The enzyme was precipitated from the supernatant solution at 0 to 45% saturation with ammonium sulfate. The 14C product of the reaction was isolated, purified, and analyzed for its constituents. It inhibited the hemagglutination reaction of human B-type cells and rabbit erythrocytes against human anti-B serum. The terminal [14C]galactose was cleaved 85% by the action of fig α-galactosidase. The Km values were 1.67 x 10-3 m and 1.43 x 10-4 m for the tetraglycosylceramide (LacTet-cer) and UDP-galactose, respectively.
Differential metabolism of dihomo-γ-linolenic acid and arachidonic acid by cyclo-oxygenase-1 and cyclo-oxygenase-2: implications for cellular synthesis of prostaglandin E1 and prostaglandin E2 (2002)

Prostaglandin (PG) E(1) has been shown to possess anti-inflammatory properties and to modulate vascular reactivity. These activities are sometimes distinct from those of PGE(2), suggesting that endogenously produced PGE(1) may have some beneficial therapeutic effects compared with PGE(2). Increasing the endogenous formation of PGE(1) requires optimization of two separate processes, namely, enrichment of cellular lipids with dihomo-gamma-linolenic acid (20:3 n-6; DGLA) and effective cyclo-oxygenase-dependent oxygenation of substrate DGLA relative to arachidonic acid (AA; 20:4 n-6). DGLA and AA had similar affinities (K(m) values) and maximal reaction rates (V(max)) for cyclo-oxygenase-2 (COX-2), whereas AA was metabolized preferentially by cyclo-oxygenase-1 (COX-1). To overcome the kinetic preference of COX-1 for AA, CP-24879, a mixed Delta(5)/Delta(6) desaturase inhibitor, was used to enhance preferential accumulation of DGLA over AA in cells cultured in the presence of precursor gamma-linolenic acid (18:3 n-6). This protocol was tested in two cell lines and both yielded a DGLA/AA ratio of approx. 2.8 in the total cellular lipids. From the enzyme kinetic data, it was calculated that this ratio should offset the preference of COX-1 for AA over DGLA. PGE(1) synthesis in the DGLA-enriched cells was increased concurrent with a decline in PGE(2) formation. Nevertheless, PGE(1) synthesis was still substantially lower than that of PGE(2). It appears that employing a dietary or a combined dietary/pharmacological paradigm to augment the cellular ratio of DGLA/AA is not an effective route to enhance endogenous synthesis of PGE(1) over PGE(2), at least in cells/tissues where COX-1 predominates over COX-2.
A defective purine nucleotide synthesis pathway in psoriatic patients. (1992)

Purine nucleotide concentrations in skin- and blood-cells of psoriatic patients are abnormal: The increase in the steady state level of cGMP and the decrease in the cAMP concentrations are associated with an enhanced rate of cellular proliferation. Concomitantly we found in the present study decreased ADP and ATP concentrations in blood cells (p less than 0.0001). The change in nucleotide concentrations suggests a defective purine nucleotide synthesis pathway. Stimulation of the Krebs cycle with fumaric acid raises ATP (p less than 0.0001) and most probably cAMP levels and at the same time slows down the purine nucleotide synthesis through end-product inhibition. Both effects can inhibit DNA and protein synthesis activity, which results in inhibition of cellular proliferation. Fumaric acid seems therefore a useful treatment for psoriatic lesions if liver and kidney functions (purine nucleotide and urea cycle) are controlled during treatment.