gebhart/patrepeval huggingface dataset:
Presence of Simian Virus 40 DNA Sequences in Human Lymphoid and Hematopoietic Malignancies and Their Relationship to Aberrant Promoter Methylation of Multiple Genes (2004)

The simian polyoma virus SV40 has been detected in specific human tumors including non-Hodgkin's lymphomas, although a causative role for the virus has not been convincingly demonstrated. Aberrant methylation of CpG islands in promoter regions is a frequent method of silencing tumor suppressor genes (TSGs) in cancers and may be induced by oncogenic viruses. We investigated the relationship between the presence of SV40 or EBV DNA sequences and the methylation profiles for 10 TSGs in 90 cases of non-Hodgkin's lymphomas/leukemias and 56 control tissues. SV40 sequences were present in 33/90 (37%) non-Hodgkin's lymphomas/leukemias, and EBV was present in 11/42 (26%) of non-Hodgkin's lymphomas. We found a highly significant correlation between the presence of SV40 and methylation of seven genes (P values, 0.006 to <0.0001). In lymphomas, there was no relationship between EBV and methylation. Oncogenic viruses and methylation were rarely present in control tissues. We investigated methylation of the same 10 TSGs in peripheral blood mononuclear cells (PBMC) from a healthy volunteer infected with EBV or EBV and SV40. Promoter methylation of CDH1 and CDH13 were noted in dual SV40- and EBV-infected PBMC, and these two genes were also highly significantly correlated to the presence of SV40 sequences in tumors. SV40 infection also resulted in appearance of the lymphoma/leukemia-specific marker, methylated SHP1. Methylation was completely absent in uninfected and EBV-infected PBMC. Our results demonstrate that the presence of SV40 in hematological malignancies is associated with promoter methylation of TSGs and that in all probability, the virus plays a role in tumor pathogenesis.
Biologically Active Fibronectin Fragments Stimulate Release of MCP-1 and Catabolic Cytokines from Murine Retinal Pigment Epithelium (2009)

Fnfs stimulate the release of proinflammatory cytokines, matrix metalloproteinases, and monocyte chemoattractant protein from murine RPE cells. This observation indicated that Fnfs could contribute to ocular abnormalities by promoting inflammation, catabolism, and monocyte chemoattraction.
Relevance feedback: a power tool for interactive content-based image retrieval (1998)

Content-based image retrieval (CBIR) has become one of the most active research areas in the past few years. Many visual feature representations have been explored and many systems built. While these research efforts establish the basis of CBIR, the usefulness of the proposed approaches is limited. Specifically, these efforts have relatively ignored two distinct characteristics of CBIR systems: (1) the gap between high-level concepts and low-level features, and (2) the subjectivity of human perception of visual content. This paper proposes a relevance feedback based interactive retrieval approach, which effectively takes into account the above two characteristics in CBIR. During the retrieval process, the user's high-level query and perception subjectivity are captured by dynamically updated weights based on the user's feedback. The experimental results over more than 70000 images show that the proposed approach greatly reduces the user's effort of composing a query, and captures the user's information need more precisely.
Int6/eIF3e Is Essential for Proliferation and Survival of Human Glioblastoma Cells (2014)

Glioblastomas (GBM) are very aggressive and malignant brain tumors, with frequent relapses despite an appropriate treatment combining surgery, chemotherapy and radiotherapy. In GBM, hypoxia is a characteristic feature and activation of Hypoxia Inducible Factors (HIF-1α and HIF-2α) has been associated with resistance to anti-cancer therapeutics. Int6, also named eIF3e, is the "e" subunit of the translation initiation factor eIF3, and was identified as novel regulator of HIF-2α. Eukaryotic initiation factors (eIFs) are key factors regulating total protein synthesis, which controls cell growth, size and proliferation. The functional significance of Int6 and the effect of Int6/EIF3E gene silencing on human brain GBM has not yet been described and its role on the HIFs is unknown in glioma cells. In the present study, we show that Int6/eIF3e suppression affects cell proliferation, cell cycle and apoptosis of various GBM cells. We highlight that Int6 inhibition induces a diminution of proliferation through cell cycle arrest and increased apoptosis. Surprisingly, these phenotypes are independent of global cell translation inhibition and are accompanied by decreased HIF expression when Int6 is silenced. In conclusion, we demonstrate here that Int6/eIF3e is essential for proliferation and survival of GBM cells, presumably through modulation of the HIFs.
Asfotase alfa: Enzyme replacement for the treatment of bone diseasein hypophosphatasia (2016)

Hypophosphatasia (HPP) is a rare disease caused by loss-of-function mutations in the tissue-nonspecific alkaline phosphatase (TNAP, TNSALP) gene. HPP causes a multisystemic syndrome with a predominant bone phenotype. The clinical spectrum ranges from high lethality in early onset (<6 months) HPP to mild late-onset syndromes. HPP management so far has been only supportive. Subcutaneous asfotase alfa, a first-in-class bone-targeted human TNAP enzyme replacement therapy, is the first compound to be approved for long-term treatment of bone manifestations in pediatric-onset HPP. In noncomparative clinical trials (treatment up to 7 years), this treatment was associated with skeletal, respiratory and functional improvement in perinatal, infantile and childhood-onset HPP. Compared with age-matched historical controls, patients with life-threatening perinatal and infantile HPP treated with asfotase alfa had substantially improved bone mineralization, survival and ventilation-free survival. In childhood HPP, asfotase alfa improved growth, gross motor function, strength and agility and decreased pain. The compound was well tolerated and most adverse events were of mild to moderate intensity. To date, data and experience concerning its efficacy and safety in long-term treatment are not yet available. Further studies to evaluate risks and benefits of enzyme replacement therapy with asfotase alfa in adults are in progress and are also strongly needed.
The Structure and Receptor Binding Properties of the 1918 Influenza Hemagglutinin (2004)

The 1918 influenza pandemic resulted in about 20 million deaths. This enormous impact, coupled with renewed interest in emerging infections, makes characterization of the virus involved a priority. Receptor binding, the initial event in virus infection, is a major determinant of virus transmissibility that, for influenza viruses, is mediated by the hemagglutinin (HA) membrane glycoprotein. We have determined the crystal structures of the HA from the 1918 virus and two closely related HAs in complex with receptor analogs. They explain how the 1918 HA, while retaining receptor binding site amino acids characteristic of an avian precursor HA, is able to bind human receptors and how, as a consequence, the virus was able to spread in the human population.
The Repressor Protein, Bm3R1, Mediates an Adaptive Response to Toxic Fatty Acids in Bacillus megaterium (1998)

Bm3R1 is a helix-turn-helix transcriptional repressor from Bacillus megaterium whose binding to DNA is inhibited by fatty acids and a wide range of compounds that modulate lipid metabolism. The inactivation of Bm3R1/DNA binding activity results in the activation of transcription of the operon encoding a fatty acid hydroxylase, cytochrome P450 102. The metabolic role of this operon is unknown. It is possible that it is involved in the synthesis of modified fatty acids as part of normal cellular metabolism or may represent a protective mechanism by which B. megaterium detoxifies harmful foreign lipids. In this report we demonstrate that polyunsaturated fatty acids (PUFA) activate the transcription of the CYP102 operon. These PUFA are the most potent activators of the CYP102 operon observed to date, and we show that their effects are due to binding directly to Bm3R1. In addition, cultures that have been treated with the CYP102 inducer, nafenopin, are protected against PUFA toxicity. Resistance to PUFA toxicity is also seen in a Bm3R1-deficient strain that constitutively expresses CYP102. The resistant phenotype of this Bm3R1 mutant strain is reversed by specific chemical inactivation of CYP102. These data demonstrate that Bm3R1 can act as a direct sensor of toxic fatty acids and, in addition, provide the first direct evidence of fatty acids binding to a prokaryotic transcription factor.
TCR ITAM multiplicity is required for the generation of follicular helper T-cells (2015)

The T-cell antigen receptor (TCR) complex contains 10 copies of a di-tyrosine Immunoreceptor-Tyrosine-based-Activation-Motif (ITAM) that initiates TCR signalling by recruiting protein tyrosine kinases. ITAM multiplicity amplifies TCR signals, but the importance of this capability for T-cell responses remains undefined. Most TCR ITAMs (6 of 10) are contributed by the CD3ζ subunits. We generated 'knock-in' mice that express non-signalling CD3ζ chains in lieu of wild-type CD3ζ. Here we demonstrate that ITAM multiplicity is important for the development of innate-like T-cells and follicular helper T-cells, events that are known to require strong/sustained TCR-ligand interactions, but is not essential for 'general' T-cell responses including proliferation and cytokine production or for the generation of a diverse antigen-reactive TCR repertoire.
Enhancement of antitumor immune response in glioma models in mice by genetically modified dendritic cells pulsed with Semliki Forest virus—mediated complementary DNA (2001)

Therapy with DCs that have been pulsed with SFV-mediated tumor cDNA may be an excellent procedure for the development of new cancer vaccines.
Bisthiazolidines: A Substrate-Mimicking Scaffold as an Inhibitor of the NDM-1 Carbapenemase (2015)

Pathogenic Gram-negative bacteria resistant to almost all β-lactam antibiotics are a major public health threat. Zn(II)-dependent or metallo-β-lactamases (MBLs) produced by these bacteria inactivate most β-lactam antibiotics, including the carbapenems, which are "last line therapies" for life-threatening Gram-negative infections. NDM-1 is a carbapenemase belonging to the MBL family that is rapidly spreading worldwide. Regrettably, inhibitors of MBLs are not yet developed. Here we present the bisthiazolidine (BTZ) scaffold as a structure with some features of β-lactam substrates, which can be modified with metal-binding groups to target the MBL active site. Inspired by known interactions of MBLs with β-lactams, we designed four BTZs that behave as in vitro NDM-1 inhibitors with Ki values in the low micromolar range (from 7 ± 1 to 19 ± 3 μM). NMR spectroscopy demonstrated that they inhibit hydrolysis of imipenem in NDM-1-producing Escherichia coli. In vitro time kill cell-based assays against a variety of bacterial strains harboring blaNDM-1 including Acinetobacter baumannii show that the compounds restore the antibacterial activity of imipenem. A crystal structure of the most potent heterocycle (L-CS319) in complex with NDM-1 at 1.9 Å resolution identified both structural determinants for inhibitor binding and opportunities for further improvements in potency.
Activation of CAAT Enhancer-binding Protein δ (C/EBPδ) by Interleukin-1 Negatively Influences Apolipoprotein C-III Expression (1997)

Tissue-specific transcription of the apolipoprotein C-III (apoC-III) gene is mainly regulated by synergistic interactions between the liver-enriched transcription factor HNF-4, which binds to the proximal promoter, and ubiquitous factors, which bind to the upstream enhancer region. Here we show that apoC-III expression in HepG2 cells is negatively regulated in response to interleukin-1 (IL-1), and this inhibition is mainly due to transcriptional repression. CAAT enhancer-binding protein delta (C/EBPdelta) was found to be the main mediator of IL-1-induced suppression. Analysis of the apoC-III promoter revealed two IL-1 response elements. The first is located in the proximal promoter region D and the second in the distal enhancer region I. Proximal element D is a high affinity binding site for C/EBPdelta, while the enhancer element I is not directly recognized by this transcription factor. Functional analysis of different combinations of homologous and heterologous promoter constructs revealed that indirect interaction of C/EBPdelta with site I, in the context of the full promoter, leads to repression. C/EBPdelta is activated by phosphorylation during IL-1-induced signal transduction pathway. This modification is important for both DNA binding activity and indirect transrepression of the apoC-III promoter.
The Battery: Not Yet a Terminal Case (2002)

It seems inevitable that fuel cells will soon take over many of the jobs that batteries now do (see p.
 1222), and increasingly photovoltaic cells and even clockwork are muscling in on their territory. But the chemists and materials scientists who work in the field say they still have a few tricks up their sleeves. Complex ceramic electrodes and solid electrolytes made from conducting polymers may keep rivals at bay for years yet.
Calcium phosphate precipitation on the surface of HA‐G‐Ti composite under physiologic conditions (1994)

Hydroxyapatite-glass-titanium (HA-G-Ti) functionally gradient composite plates bound face-to-face by nylon wire were soaked in a simulated body fluid. The gap between the plates was filled with the precipitates after soaking for 6 months, and a tight chemical bond was formed between them. Field emission-type (FE) scanning electron microscopy (SEM) and transmission electron microscopy observations revealed that the growth rate and morphology of the precipitates differed widely from the outside portion to the inside one on the surface region of the composite plates. In the portion relatively near the outside, the mutually bonded portion, needle-like precipitates with preferred orientation to the c-axis were markedly observed. From the results of Fourier transform infrared spectroscopy and energy dispersive x-ray microanalysis, it was found that the precipitates were Ca-deficient carbonate apatite with low crystallinity. On the other hand, HA-G-Ti composite rods were implanted in the femur of beagle dogs for 3 months. FE-SEM observations demonstrated that needle-like precipitates were deposited on both the surfaces of the composite and bone at the portion having a narrow gap, about 0.1-0.2 mm between them prepared deliberately before implantation. It was found that both the morphologies and the composition of the precipitates in vivo were similar to those in vitro. It is concluded that the HA particles on the surface of the composite act as nucleation sites for precipitation in physiologic environments, whereas the glass matrix is independent to it.
The Relation of Free Sulfhydryl Groups to Chromatographic Heterogeneity and Polymerization of Bovine Plasma Albumin* (1962)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Relation of Free Sulfhydryl Groups to Chromatographic Heterogeneity and Polymerization of Bovine Plasma Albumin*Robert W. Hartley, Jr., Elbert A. Peterson, and Herbert A. SoberCite this: Biochemistry 1962, 1, 1, 60–68Publication Date (Print):January 1, 1962Publication History Published online1 May 2002Published inissue 1 January 1962https://pubs.acs.org/doi/10.1021/bi00907a010https://doi.org/10.1021/bi00907a010research-articleACS PublicationsRequest reuse permissionsArticle Views99Altmetric-Citations69LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Functional interactions within 23S rRNA involving the peptidyltransferase center (1992)

A molecular genetic approach has been employed to investigate functional interactions within 23S rRNA. Each of the three base substitutions at guanine 2032 has been made. The 2032A mutation confers resistance to the antibiotics chloramphenicol and clindamycin, which interact with the 23S rRNA peptidyltransferase loop. All three base substitutions at position 2032 produce an erythromycin-hypersensitive phenotype. The 2032 substitutions were compared with and combined with a 12-bp deletion mutation in domain II and point mutations at positions 2057 and 2058 in the peptidyltransferase region of domain V that also confer antibiotic resistance. Both the domain II deletion and the 2057A mutation relieve the hypersensitive effect of the 2032A mutation, producing an erythromycin-resistant phenotype; in addition, the combination of the 2032A and 2057A mutations confers a higher level of chloramphenicol resistance than either mutation alone. 23S rRNAs containing mutations at position 2058 that confer clindamycin and erythromycin resistance become deleterious to cell growth when combined with the 2032A mutation and, additionally, confer hypersensitivity to erythromycin and sensitivity to clindamycin and chloramphenicol. Introduction of the domain II deletion into these double-mutation constructs gives rise to erythromycin resistance. The results are interpreted as indicating that position 2032 interacts with the peptidyltransferase loop and that there is a functional connection between domains II and V.
The pathogenicity of Haemophilus influenzae (1984)

SUMMARY Problems about the pathogenicity of an organism can be classified as: (1) clinical and epidemiological—what diseases does it cause or take part in, and when? (2) research (with prophylactic and therapeutic implications)—how does it do so? Category (1) answers for Haemophilus influenzae began in 1892, with Pfeiffer's claim that it was the cause of influenza; but the true picture of the range of pathogenic activities of this species became clear in the period 1930-1960. Category (2) answers have in general been more recent, and are still far from complete (as is the case with most pathogens); but a fascinating array of contributions has appeared in the past few years.
N-Tosyl-l-phenylalanine Chloromethyl Ketone, a Serine Protease Inhibitor, Identifies Glutamate 398 at the Coenzyme-Binding Site of Human Aldehyde Dehydrogenase. Evidence for a Second “Naked Anion” at the Active Site (1998)

Human aldehyde dehydrogenase isozymes were inactivated by N-tosyl-L-phenylalanine chloromethyl ketone (TPCK), an inhibitor of chymotrypsin. The inactivation was a first-order process that followed saturation kinetics. NAD and chloral when used together protected against inactivation. In steady-state kinetics, TPCK produced only slope effects versus varied NAD, both slope and intercept effects versus varied glycolaldehyde were produced, indicating that TPCK reacted with the same enzyme form with which NAD reacted. Ki values from steady-state kinetics and saturation kinetics were comparable. Use of [3H]-labeled TPCK showed that inactivation was associated with the incorporation of two molecules of TPCK per molecule of enzyme. The label incorporation occurred into a single tryptic peptide and also into a single chymotryptic peptide of the E1 isozyme. Purification of labeled peptides, followed by sequencing, demonstrated that E398 of aldehyde dehydrogenase was labeled. Reaction of a haloketone, TPCK, with a carboxyl group of E398 indicates that E398 occurs as a "naked anion" within the molecule. This paper constitutes identification of the second (after E268) "naked anion" at the active site of aldehyde dehydrogenase.
Continuum robots - a state of the art (2003)

Like the human limbs which inspired them most robots are discrete mechanisms with rigid links connected by single degree of freedom joints. In contrast, 'continuum' and 'serpentine' robot mechanisms move by bending through a series of continuous arcs producing motion which resembles that of biological tentacles or snakes. This paper provides a single reference to the expanding technology of continuum robot mechanisms. It defines the fundamental difference between discrete, serpentine and continuum robot devices, presents the 'state of the art' of continuum robots, outlines their areas of application, and introduces some control issues. Finally, some conclusions regarding the continued development of these devices are made.
Analysis of SARS-CoV-2-controlled autophagy reveals spermidine, MK-2206, and niclosamide as putative antiviral therapeutics (2020)

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses an acute threat to public health and the world economy, especially because no approved specific drugs or vaccines are available. Pharmacological modulation of metabolism-dependent cellular pathways such as autophagy reduced propagation of highly pathogenic Middle East respiratory syndrome (MERS)-CoV. Here we show that SARS-CoV-2 infection limits autophagy by interfering with multiple metabolic pathways and that compound-driven interventions aimed at autophagy induction reduce SARS-CoV-2 propagation in vitro . In-depth analyses of autophagy signaling and metabolomics indicate that SARS-CoV-2 reduces glycolysis and protein translation by limiting activation of AMP-protein activated kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1). Infection also downregulates autophagy-inducing spermidine, and facilitates AKT1/SKP2-dependent degradation of autophagy-initiating Beclin-1 (BECN1). Targeting of these pathways by exogenous administration of spermidine, AKT inhibitor MK-2206, and the Beclin-1 stabilizing, antihelminthic drug niclosamide inhibited SARS-CoV-2 propagation by 85, 88, and &gt;99%, respectively. In sum, SARS-CoV-2 infection causally diminishes autophagy. A clinically approved and well-tolerated autophagy-inducing compound shows potential for evaluation as a treatment against SARS-CoV-2.
A repair system for 8-Oxo-7,8-dihydrodeoxyguanine (1992)

Active oxygen species can damage DNA and may play a role in aging and carcinogenesis. We have tested MutY glycosylase for activity on undamaged mispairs as well as mispairs formed with the oxidatively damaged substrates, 8-oxo-7,8-dihydrodeoxyguanine (GO) or 8-oxo-7,8-dihydrodeoxyadenine (AO). MutY acts as a glycosylase on four of the heteroduplexes tested, A/G, A/GO, A/C, and A/AO, removing the undamaged adenine from each substrate. Genetic data suggest that the primary substrate for MutY glycosylase in vivo is the A/GO mispair. We present biochemical evidence demonstrating that MutY glycosylase is an important part of a repair system that includes the MutM and MutT proteins. The GO repair system is dedicated to the repair of the oxidatively damaged guanine and the mutations it can induce.
Effects of long-term organophosphate exposures on neurological symptoms, vibration sense and tremor amongst South African farm workers (1998)

Strong evidence was found for an association between symptom outcomes and past organophosphate poisoning and between symptom outcomes and current spray activity. In contrast to symptoms, there was no association between either past poisoning or current spray activity and vibration sense or tremor outcome. Long-term organophosphate exposure did not appear to predict symptoms, vibration sense, or tremor outcome.