gebhart/patrepeval huggingface dataset:
Functions involved in bacteriophage P2-induced host cell lysis and identification of a new tail gene (1994)

Successful completion of the bacteriophage P2 lytic cycle requires phage-induced lysis of its Escherichia coli host, a process that is poorly understood. Genetic analysis of lysis-deficient mutants defined a single locus, gene K, which lies within the largest late transcription unit of P2 and maps between head gene L and tail gene R. We determined and analyzed the DNA sequence of a ca. 2.1-kb EcoRV fragment that spans the entire region from L to R, thus completing the sequence of this operon. This region contains all of the functions necessary for host cell lysis. Sequence analysis revealed five open reading frames, initially designated orf19 through orf23. All of the existing lysis mutants--ts60, am12, am76, and am218--were located in orf21, which must therefore correspond to gene K. The K gene product has extensive amino acid sequence similarity to the product of gene R of bacteriophage lambda, and its exhibits endolysin function. Site-directed mutagenesis and reverse genetics were used to create P2 amber mutants in each of the four other newly identified open reading frames. Both orf19 (gene X) and orf20 (gene Y) encode essential functions, whereas orf22 (lysA) and orf23 (lysB) are nonessential. Gene Y encodes a polypeptide with striking similarities to the family of holin proteins exemplified by gpS of phage lambda, and the Yam mutant displayed the expected properties of a holin mutant. The gene products of lysA and lysB, although nonessential, appear to play a role in the correct timing of lysis, since a lysA amber mutant caused slightly accelerated lysis and a lysB amber mutant slightly delayed lysis of nonpermissive strains. Gene X must encode a tail protein, since lysates from nonpermissive cells infected with the X amber mutant were complemented in vitro by similar lysates of cells infected with P2 head mutants but not with tail mutants.
GLYCEROL DISSIMILATION AND ITS REGULATION IN BACTERIA (1976)

Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and ...Read More
A chimeric humanized single-chain antibody against the type I insulin-like growth factor (IGF) receptor renders breast cancer cells refractory to the mitogenic effects of IGF-I. (2003)

Insulin-like growth factors (IGFs) stimulate breast cancer proliferation, motility, and survival. The type I IGF receptor (IGF1R) mediates the effects of IGF-I. Thus, inhibition of IGF1R activation could inhibit IGF action in breast cancer cells. A single-chain antibody directed against IGF1R (IGF1R scFv-Fc) has been shown to partially inhibit xenograft growth of MCF-7 cells in athymic mice. In this study, we have examined the effects of scFv-Fc on IGF1R signaling in the estrogen receptor-positive (ER+) MCF-7 breast cancer cells in vitro and in vivo. The antibody stimulated IGF1R activation in vitro in MCF-7 cells and was unable to block IGF-I effects. The antibody also stimulated proliferation of MCF-7 cells in monolayer growth assays. To determine how scFv-Fc could stimulate in vitro growth yet inhibit in vivo tumor growth, we examined the effect of scFv-Fc on IGF1R expression. In MCF-7 cells, scFv-Fc down-regulated IGF1R levels after 2 h, and the levels were greatly reduced after 24 h. In contrast, IGF-I treatment over the same time period did not affect IGF1R levels. Twenty-four-h pretreatment of cells with scFv-Fc blocked IGF-I mediated phosphorylation of insulin receptor substrate-1 and subsequent extracellular signal-regulated kinase 1/extracellular signal-regulated kinase 2 and phosphatidylinositol 3'-kinase activation. In contrast, cells treated with 5 nM IGF-I for 24 h still retained the ability to further activate downstream signaling pathways in response to IGF-I. Moreover, pretreatment of MCF-7 cells with scFv-Fc rendered them refractory to further proliferation induced by additional IGF-I. Twenty-four-h pretreatment of cells with scFv-Fc also inhibited IGF-I stimulated anchorage-independent growth. scFv-Fc did not enhance antibody-dependent cell-mediated cytotoxicity. In vivo, treatment of mice bearing MCF-7 xenograft tumors with scFv-Fc resulted in near complete down-regulation of IGF1R. Our data show that scFv-Fc stimulates biochemical activation of IGF1R, then causes receptor down-regulation, making MCF-7 cells refractory to additional IGF-I exposure. These results indicate that such chimeric single-chain antibodies against IGF1R have future potential in breast cancer therapy by causing down-regulation of receptor.
Npa1p is an essential trans-acting factor required for an early step in the assembly of 60S ribosomal subunits in Saccharomyces cerevisiae (2004)

Ribosome biogenesis requires >100 nonribosomal proteins, which are associated with different preribosomal particles. The substrates, the interacting partners, and the timing of action of most of these proteins are largely unknown. To elucidate the functional environment of the putative ATP-dependent RNA helicase Dbp6p from Saccharomyces cerevisiae, which is required for 60S ribosomal subunit assembly, we have previously performed a synthetic lethal screen and thereby revealed a genetic interaction network between Dbp6p, Rpl3p, Nop8p, and the novel Rsa3p. In this report, we extended the characterization of this functional network by performing a synthetic lethal screen with the rsa3 null allele. This screen identified the so far uncharacterized Npa1p (YKL014C). Polysome profile analysis indicates that there is a deficit of 60S ribosomal subunits and an accumulation of halfmer polysomes in the slowly growing npa1-1 mutant. Northern blotting and primer extension analysis shows that the npa1-1 mutation negatively affects processing of all 27S pre-rRNAs and the normal accumulation of both mature 25S and 5.8S rRNAs. In addition, 27SA(2) pre-rRNA is prematurely cleaved at site C(2). Moreover, GFP-tagged Npa1p localizes predominantly to the nucleolus and sediments with large complexes in sucrose gradients, which most likely correspond to pre-60S ribosomal particles. We conclude that Npa1p is required for ribosome biogenesis and operates in the same functional environment of Rsa3p and Dbp6p during early maturation of 60S ribosomal subunits.
Degradation of Epichlorohydrin and Halohydrins by Bacterial Cultures Isolated from Freshwater Sediment (1989)

Three bacterial cultures, the Gram-negative strain AD1 and the Gram-positive strains AD2 and AD3, were isolated from freshwater sediment after enrichment with epichlorohydrin as sole carbon source. In batch cultures of strain AD1 and strain AD3, epichlorohydrin was rapidly degraded to 3-chloro-l,2-propanediol. Crude extracts of strain AD1 contained epoxide hydrolase activity towards epichlorohydrin, epibromohydrin, glycidol and propylene oxide as substrates. In contrast, strain AD2 did not actively convert epichlorohydrin but utilized 3-chloro-l,2-propanediol produced by slow chemical hydrolysis. No epichlorohydrin epoxide hydrolase was found in extracts of this organism. Crude extracts of strains AD1 and AD2 dehalogenated a number of mono- and dihalogenated alcohols and ketones, such as 1,3-dichloro-2-propanol, 3-chloro-l,2-propanediol, l-chloro-2-propanol, l,3-dibromo-2-propanol, chloro-acetone and 1,3-dichloroacetone. Dehalogenation yielded epoxides as products. The results suggest that epichlorohydrin is converted by strain AD1 via 3-chloro-l,2-propanediol and glycidol by the action of an epoxide hydrolase and a dehalogenase, respectively. The same route for dehalogenation proceeds in strain AD2, which, however, is dependent on chemical hydrolysis of epichlorohydrin rather than enzymic conversion.
CD40 and Dendritic Cell Function (2003)

CD40 has emerged as a key signaling pathway for the function of B cells, monocytes, and dendritic cells (DC) in the immune system, and plays a major role in inflammatory pathways of nonhemopoietic cells. CD40 is expressed by monocytes and DC and is up-regulated when DC migrate from the periphery to draining lymph nodes (DLN) in response to microbial challenge. CD154 signaling by MHC-restricted, activated CD4+ T cells induces differentiation of DC, as defined by an increased surface expression of MHC, costimulatory, and adhesion molecules. Thus, CD40 functions in the adaptive immune response as a trigger for the expression of costimulatory molecules for efficient T-cell activation. CD40 ligation of DC also has the capacity to induce high levels of the cytokine IL-12, which polarizes CD4+ T cells toward a T helper 1 (Th1) type, enhances proliferation of CD8+ T cells, and activates NK cells. CD40 may also play an important role in the decision between tolerance and immunity and the generation of regulatory CD4+ T cells that are thought to maintain peripheral self-tolerance in vivo.
Systematic Association Mapping Identifies NELL1 as a Novel IBD Disease Gene (2007)

Crohn disease (CD), a sub-entity of inflammatory bowel disease (IBD), is a complex polygenic disorder. Although recent studies have successfully identified CD-associated genetic variants, these susceptibility loci explain only a fraction of the heritability of the disease. Here, we report on a multi-stage genome-wide scan of 393 German CD cases and 399 controls. Among the 116,161 single-nucleotide polymorphisms tested, an association with the known CD susceptibility gene NOD2, the 5q31 haplotype, and the recently reported CD locus at 5p13.1 was confirmed. In addition, SNP rs1793004 in the gene encoding nel-like 1 precursor (NELL1, chromosome 11p15.1) showed a consistent disease-association in independent German population- and family-based samples (942 cases, 1082 controls, 375 trios). Subsequent fine mapping and replication in an independent sample of 454 French/Canadian CD trios supported the authenticity of the NELL1 association. Further confirmation in a large German ulcerative colitis (UC) sample indicated that NELL1 is a ubiquitous IBD susceptibility locus (combined p<10(-6); OR = 1.66, 95% CI: 1.30-2.11). The novel 5p13.1 locus was also replicated in the French/Canadian sample and in an independent UK CD patient panel (453 cases, 521 controls, combined p<10(-6) for SNP rs1992660). Several associations were replicated in at least one independent sample, point to an involvement of ITGB6 (upstream), GRM8 (downstream), OR5V1 (downstream), PPP3R2 (downstream), NM_152575 (upstream) and HNF4G (intron).
Vitamin B[6], pyridoxal phosphate : chemical, biochemical, and medical aspects (1986)

Partial table of contents: Pyridoxal Phosphate: History and Nomenclature (E. Snell). Conformation and Stereochemistry of Free and Bound Pyridoxal Phosphate and Its Derivatives (M. Palcic, H. Floss). Kinetic and Equilibria Studies with Pyridoxal Phosphate Enzymes (W. Jenkins). Mass Spectra of Pyridoxal and Pyridoxamine Phosphates (G. Tryfiates, R. Smith). Crystal Structure of Vitamin B6 and Derivatives (M. Darriet et al.). Synthesis of Vitamin B6 and Its Analogs: Labeling, Biological Activities, and Characterization by Physical Methods (W. Korytnyk). Biosynthesis of Vitamin B6 (R. Hill, I. Spenser). Chromatographic Analysis of Vitamin B6 and Derivatives (S. Coburn). Determination of Pyridoxal Phosphate and Pyridoxamine Phosphate Using a Chromogenic Substrate (C. Suelter, J. Dombrowski). Radiometric-Microbiological Assay of Vitamin B6 and Derivatives (T. Guilarte). Author Index. Subject Index.
Altered Cytokine Export and Apoptosis in Mice Deficient in Interleukin-1β Converting Enzyme (1995)

The interleukin-1 beta (IL-1 beta) converting enzyme (ICE) processes the inactive IL-1 beta precursor to the proinflammatory cytokine. Adherent monocytes from mice harboring a disrupted ICE gene (ICE-/-) did not export IL-1 beta or interleukin-1 alpha (IL-1 alpha) after stimulation with lipopolysaccharide. Export of tumor necrosis factor-alpha and interleukin-6 (IL-6) from these cells was also diminished. Thymocytes from ICE-/- mice were sensitive to apoptosis induced by dexamethasone or ionizing radiation, but were resistant to apoptosis induced by Fas antibody. Despite this defect in apoptosis, ICE-/- mice proceed normally through development.
Differential Expression of Syndecan-1 Mediates Cationic Nanoparticle Toxicity in Undifferentiated versus Differentiated Normal Human Bronchial Epithelial Cells (2011)

Most in vitro toxicity studies on engineered nanomaterials (ENMs) use transformed rather than primary cells for logistical reasons. However, primary cells may provide a more appropriate connection to in vivo toxicity because these cells maintain their phenotypic fidelity and are also capable of differentiating into lineages that may be differently affected by potentially hazardous ENMs. Few studies to date have focused on the role of cellular differentiation in determining ENM toxicity. We compared the response of undifferentiated and differentiated primary human bronchial epithelial (NHBE) cells to cationic mesoporous silica nanoparticles (MSNPs) that are coated with polyethyleneimine (PEI) since this polymer is known to exert differential cytotoxicity depending on its molecular weight and cationic density. The attachment of cationic PEI polymers to the MSNP surface was used to assess these materials' toxicological potential in undifferentiated and differentiated human bronchial epithelial cells, using a multiparametric assay that screens for an integrated set of sublethal and lethal response outcomes. MSNPs coated with high molecular weight (10 and 25 kD) polymers were more toxic in differentiated cells than particles coated with shorter length polymers. The increased susceptibility of the differentiated cells is in agreement with more abundant expression of a proteoglycan, syndecan-1, which contains copious heparin sulfate side chains. Pretreatment with heparinase to remove the negatively charged sulfates decreased MSNP-PEI binding to the cell surface and lowered the cytotoxic potential of the cationic particles. These data demonstrate the importance of studying cellular differentiation as an important variable in the response of primary cells to toxic ENM properties.
Reduction of interleukin‐17–induced inhibition of chondrocyte proteoglycan synthesis in intact murine articular cartilage by interleukin‐4 (2000)

IL-17 plays a role in the inhibition of chondrocyte PG synthesis. IL-4 and IL-10 have no effect on basal chondrocyte metabolism. However, IL-4-pretreated cartilage is less sensitive to the suppressive effect of IL-1 as well as IL-17. This suggests that IL-4 is protective in T cell-driven cartilage disturbances, probably through reduction of iNOS.
Design and synthesis of novel bicalutamide and enzalutamide derivatives as antiproliferative agents for the treatment of prostate cancer (2016)

Prostate cancer (PC) is one of the major causes of male death worldwide and the development of new and more potent anti-PC compounds is a constant requirement. Among the current treatments, (R)-bicalutamide and enzalutamide are non-steroidal androgen receptor antagonist drugs approved also in the case of castration-resistant forms. Both these drugs present a moderate antiproliferative activity and their use is limited due to the development of resistant mutants of their biological target. Insertion of fluorinated and perfluorinated groups in biologically active compounds is a current trend in medicinal chemistry, applied to improve their efficacy and stability profiles. As a means to obtain such effects, different modifications with perfluoro groups were rationally designed on the bicalutamide and enzalutamide structures, leading to the synthesis of a series of new antiproliferative compounds. Several new analogues displayed improved in vitro activity towards four different prostate cancer cell lines, while maintaining full AR antagonism and therefore representing promising leads for further development. Furthermore, a series of molecular modelling studies were performed on the AR antagonist conformation, providing useful insights on potential protein-ligand interactions.
Mutation detection by denaturing gradient gel electrophoresis (DGGE) (1994)

The molecular analysis of genetic diseases relies on several technical approaches which allow genetic and physical mapping, characterization of the gene structure, expression studies, and identification of disease-causing mutations. Denaturing gradient gel electrophoresis (DGGE) allows the rapid screening for single base changes in enzymatically amplified DNA. The technique is based on the migration of double-stranded DNA molecules through polyacrylamide gels containing linearly increasing concentrations of a denaturing agent. In this review DGGE and the several modifications of the original protocol are presented. Moreover, its applications in human molecular genetics are summarized together with a preliminary comparison with other mutation detection technologies such as chemical cleavage, RNase protection, and single-strand conformation polymorphism.
Open-Loop Digital Predistorter for RF Power Amplifiers Using Dynamic Deviation Reduction-Based Volterra Series (2008)

In this paper, we propose an efficient open-loop digital predistorter (DPD) derived from the dynamic deviation reduction-based Volterra series that allows compensation for both nonlinear distortion and memory effects induced by RF power amplifiers in wireless transmitters. In this approach, the parameters of the predistorter can be directly extracted from an offline system identification process. This eliminates the usual requirement for a closed-loop real-time parameter adaptation, which dramatically reduces the implementation complexity of the system. It is shown that a further reduction in system complexity can be achieved by applying under-sampling theory in the model extraction and utilizing parameter interpolation in the DPD implementation. Experimental results show that by utilizing this technique with only a small number of parameters, nonlinear distortion induced by the PA can be significantly reduced, as evaluated by both adjacent channel power ratio reduction and normalized root mean square error improvement. A comparison with a memoryless polynomial function based predistorter and an analysis of the impact of decresting are also presented.
Case History of the World's First Level 5 Multilateral Completed from a Semisubmersible Rig (1999)

Abstract Multilateral technology has become a catalyst for enabling deepwater development. This challenging environment dictates that functionality and junction integrity are key requirements for multilateral completions. For an injection well in the Voador Field, offshore Brazil, a TAML Level 5 multilateral completion was implemented from a semisubmersible rig to achieve the junction isolation required for this application. It is the intent of this paper to demonstrate that a complex TAML Level 5 multilateral completion can be professionally designed, managed, and implemented from a semisubmersible rig, while saving ten million dollars (US) in costs over conventional technology applied in this region. This will be accomplished by reviewing the operator's deepwater development philosophy, reservoir considerations, design, operational procedures, and overall cost information related to the completion. In addition, details of the challenges faced, problems solved, and lessons learned will be examined on the world's first TAML Level 5 multilateral well completed from a semisubmersible rig, the Petrobras 8-VD #6HP-RJS and #7HPA-RJS dual lateral injection well in the Campos Basin off the coast of Brazil.
Nuclear Magnetic Resonance Spectroscopy. The Effect of Structure on Magnetic Nonequivalence Due to Molecular Asymmetry (1964)

The difference in chemical shift between the methylene protons of a number of compounds related structurally to 1-phenylethyl benzyl ether has been measured. Correlations between structural features of these compounds and the magnitude of the magnetic nonequivalence induced by the center of molecular asymmetry provide a basis for qualitative identification of the most important factors contributing to the chemical-shift difference. Although it is clear that no single factor Completely determines the magnitude of the methylene proton nonequivalence in these ethers, it is suggested that the proximity of the asymmetric center to the benzyl group results in a preferred conformation of the phenyl ring with respect to the methylene protons, and that the principal contribution to the nonequivalence originates in the magnetic anisotropy of the phenyl group.
Triterpenoid total synthesis, I. Synthesis of ambrein and Ambrox® (1990)

Abstract The first total synthesis of (+)‐ambrein ( 1 ), a triterpene alcohol isolated from ambergris, was achieved. Both the enantiomers of ambrox® ( 2 ) were also synthesized.
Awake evoked electromyography recording from the chronically implanted rat (1994)

Investigation of the effects of various factors on nerve regeneration has been compromised by the lack of an accurate and objective technique which can monitor dynamic changes in the status of nerve-muscle innervation over the entire course of regeneration. The approach of evoked electromyography (EEMG) was adopted to obtain temporal and quantitative data during nerve regeneration. Initially, transcutaneous nerve stimulation and percutaneous muscle recording was performed, but the approach was abandoned because of the high interest variability (20% average deviation) and requirement for anesthesia during testing. A new approach using chronically implanted stimulation and recording electrodes was adopted in an attempt to circumvent these problems. Initial acute studies performed in the hindlimb of the anesthetized rat identified stable EEMG recording sites with sciatic nerve stimulation. In a second study conducted in chronically implanted unanesthetized unrestrained animals, EEMG recording from these sites demonstrated remarkable stability with an average interest variability of only 5%. Preliminary results have been obtained with this technique in monitoring the progression of hindlimb reinnervation following crush and transection nerve injuries.
The NSR processor (2002)

The NSR processor is a general-purpose computer structured as a collection of self-timed blocks. These blocks operate concurrently and cooperate by communicating with other blocks using self-timed communication protocols. The blocks that make up the NSR processor correspond to standard synchronous pipeline stages such as instruction fetch, instruction decode, execute, memory interface and register file, but each operates concurrently as a separate self-timed process. In addition to being internally self-timed, the units are decoupled through self-timed first-in first-out (FIFO) queues between each of the units which allows a high degree of overlap in instruction execution. Branches, jumps, and memory accesses are also decoupled through the use of additional FIFO queues which can hide the execution latency of these instructions. A prototype implementation of the NSR processor has been constructed using Actel FPGAs (field programmable gate arrays).< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
1 alpha hydroxycholecalciferol and 25 hydroxycholecalciferol in renal bone disease. (1976)

Four microgrammes of 1-alpha-hydroxycholecalciferol (1-alpha-OH D3) or 200 mug of 25-hydroxycholecalciferol (25-OH D3) were given orally every other day respectively to 10 uraemic patients (8 on chronic haemodialysis) for 1-12 weeks and to 3 patients on chronic haemodialysis for 4-8 weeks. A transilial bone biopsy and serial evaluation of serum immunoreactive PTH (iPTH) calcium phosphate and alkaline phosphatase were performed before and at the end of therapy. Both 1-alpha-OH D3 and 25-OH D3 (the latter at a 50 times higher dose) were able to depress hyperparathyroidism in two-thirds of the cases and to consistently improve the mineralisation defect. In no case did iPTH or the bone histomorphometric parameters return to normal, so that long term evaluation of these two drugs is warranted.