gebhart/patrepeval huggingface dataset:
Effects of hunger and prey traces on the search activity of the predatory beetle Notiophilus biguttatus (1989)

Abstract The locomotory behaviour of the predatory beetle Notiophilus biguttatus F. was examined as a function of three experimental factors: prey traces left in the environment, gut contents and daily food ration. Prey traces led to an increase in the frequency of runs and stops. The size of this effect depended on gut contents. Maximum‐likelihood analysis showed that the activity pattern could be described as a mixture of two kinds of activity, one of them presumably reflecting search behaviour. This enabled a quantification of the experimental results in terms of the frequency with which the beetle exibited search behaviour. Résumé Comportement de prospection du carabe , Notiophilus biguttatus Cet article décrit l'influence de trois paramètres liés à la densité des proies sur le comportement locomoteur de N. biguttatus. Les trois paramètres testés expérimentalement ont été: les traces laissées dans l'habitat par une proie invisible, le contenu de l'estomac, et la ration alimentaire quotidienne du carabe. Les résultats indiquent que le conditionnement de l'habitat par les traces augmente le nombre de périodes d'activité, mais diminue en même temps leur durée, si bien que la durée totale reste constante. La réplétion de l'estomac réduit l'effet des traces (ou conditionnement) de l'habitat. L'analyse de la probabilité maximale a montré que le modèle éthologique peut être décrit au mieux comme un mélange de deux types d'activités, l'une d'entre elles correspondant vraisemblablement au comportement de prospection. Il est ainsi possible de quantifier les résultats expérimentaux en termes de fréquence du comportement de prospection.
Reactive oxygen species in cancer (2010)

Elevated rates of reactive oxygen species (ROS) have been detected in almost all cancers, where they promote many aspects of tumour development and progression. However, tumour cells also express increased levels of antioxidant proteins to detoxify from ROS, suggesting that a delicate balance of intracellular ROS levels is required for cancer cell function. Further, the radical generated, the location of its generation, as well as the local concentration is important for the cellular functions of ROS in cancer. A challenge for novel therapeutic strategies will be the fine tuning of intracellular ROS signalling to effectively deprive cells from ROS-induced tumour promoting events, towards tipping the balance to ROS-induced apoptotic signalling. Alternatively, therapeutic antioxidants may prevent early events in tumour development, where ROS are important. However, to effectively target cancer cells specific ROS-sensing signalling pathways that mediate the diverse stress-regulated cellular functions need to be identified. This review discusses the generation of ROS within tumour cells, their detoxification, their cellular effects, as well as the major signalling cascades they utilize, but also provides an outlook on their modulation in therapeutics.
Experimental and Computational Studies into an ATPH‐Promoted exo‐Selective IMDA Reaction: A Short Total Synthesis of Δ9‐THC (2010)

Reversal of fortune: The inherent cis stereoselectivity of an intramolecular Diels–Alder reaction is reversed through promotion with aluminum tris(2,6-diphenylphenoxide) (ATPH), allowing a total synthesis of the natural product Δ9-tetrahydrocannabinol (see scheme). Computational studies predict the experimental findings and shed light on the stereocontrolling influences at play in these Diels–Alder reactions. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Replication-incompetent influenza A viruses that stably express a foreign gene (2011)

A biologically contained influenza A virus that stably expresses a foreign gene can be effectively traced, used to generate a novel multivalent vaccine and have its replication easily assessed, all while satisfying safety concerns regarding pathogenicity or reversion. This study generated a PB2-knockout (PB2-KO) influenza virus that harboured the GFP reporter gene in the coding region of its PB2 viral RNA (vRNA). Replication of the PB2-KO virus was restricted to a cell line stably expressing the PB2 protein. The GFP gene-encoding PB2 vRNA was stably incorporated into progeny viruses during replication in PB2-expressing cells. The GFP gene was expressed in virus-infected cells with no evidence of recombination between the recombinant PB2 vRNA and the PB2 protein mRNA. Furthermore, other reporter genes and the haemagglutinin and neuraminidase genes of different virus strains were accommodated by the PB2-KO virus. Finally, the PB2-KO virus was used to establish an improved assay to screen neutralizing antibodies against influenza viruses by using reporter gene expression as an indicator of virus infection rather than by observing cytopathic effect. These results indicate that the PB2-KO virus has the potential to be a valuable tool for basic and applied influenza virus research.
Epigenetic status of argininosuccinate synthetase and argininosuccinate lyase modulates autophagy and cell death in glioblastoma (2013)

Arginine deprivation, either by nutritional starvation or exposure to ADI-PEG20, induces adaptive transcriptional upregulation of ASS1 and ASL in glioblastoma multiforme ex vivo cultures and cell lines. This adaptive transcriptional upregulation is blocked by neoplasia-specific CpG island methylation in either gene, causing arginine auxotrophy and cell death. In cells with methylated ASS1 or ASL CpG islands, ADI-PEG20 initially induces a protective autophagic response, but abrogation of this by chloroquine accelerates and potentiates cytotoxicity. Concomitant methylation in the CpG islands of both ASS1 and ASL, observed in a subset of cases, confers hypersensitivity to ADI-PEG20. Cancer stem cells positive for CD133 and methylation in the ASL CpG island retain sensitivity to ADI-PEG20. Our results show for the first time that epigenetic changes occur in both of the two key genes of arginine biosynthesis in human cancer and confer sensitivity to therapeutic arginine deprivation. We demonstrate that methylation status of the CpG islands, rather than expression levels per se of the genes, predicts sensitivity to arginine deprivation. Our results suggest a novel therapeutic strategy for this invariably fatal central nervous system neoplasm for which we have identified robust biomarkers and which overcomes the limitations to conventional chemotherapy imposed by the blood/brain barrier.
Gene Delivery to Mammalian Cells (2003)

Whether to assess the function of new genes identified from the Human Genome Project or to apply gene therapy successfully, it is often necessary to deliver genes to specific cells. In Gene Delivery to Mammalian Cells, highly experienced researchers describe in great detail methods that have proven most useful in delivering genes to mammalian cells. Volume 2: Viral Gene Transfer Techniques details procedures for delivering genes to cells in vitro and in vivo, including the use of lentiviral vectors, adenovirus, adeno-associated viruses, alphavirus, herpes simplex virus, baculovirus, and retrovirus. Many of these techniques have only been in practice for a few years and are still being refined and updated. Some are being used not only in basic science, but also in gene therapy applications. Each protocol contains step-by-step instructions, along with background notes, equipment and reagent lists, and tips on troubleshooting and avoiding known pitfalls. Introductory chapters review the delivery methods presented, discussing their advantages and disadvantages, how they have been used successfully for gene delivery, and the future of their technology. An accompanying volume, Volume 1: Nonviral Gene Transfer Techniques, focuses on gene delivery by a variety of chemical and physical methods. Comprehensive and cutting-edge, Gene Delivery to Mammalian Cells, volumes 1 and 2, offers biomedical specialists in industry and academia an unrivaled collection of reliable methods for the chemical, physical, and viral delivery of genes to mammalian cells, all prepared to save laboratory time and ensure experimental success
Pathophysiology of septic shock and implications for therapy. (1993)

Current knowledge about the pathophysiology of septic shock is reviewed, and biotechnology-based therapies under development are discussed. Patients with septic shock begin their clinical course with leukocytosis, fever, tachycardia, tachypnea, and organ hypoperfusion; shock ensues as immunologic and vasoactive mediators produce hypotension. There are many metabolic and cardiovascular responses, and single- or multiple-organ failure is common. Patients may experience adult respiratory distress syndrome. A multitude of endogenous and exogenous factors have been linked to the pathophysiology of sepsis and septic shock, including (1) endotoxin from gram-negative bacteria, (2) peptidoglycan and exotoxins from gram-negative bacteria, (3) endotoxin-binding proteins and receptors, (4) bactericidal proteases, (5) exotoxins from gram-positive bacteria, (6) acute-phase proteins and proteases, (7) cytokines, (8) arachidonic acid metabolites, (9) complement, (10) beta-endorphin, (11) histamine, (12) stimulation of intrinsic and extrinsic coagulation pathways and proteases, and (13) endothelium-derived factors and adhesion molecules. Molecular entities and strategies under development to combat septic shock include monoclonal antibodies to endotoxin, active immunization with lipid-A analogues, bactericidal permeability-increasing protein, interleukin inhibitors, and inhibitors of tumor necrosis factor-alpha. Successful treatment of septic shock will probably require a combination of agents, including antimicrobials. An ideal goal for biotechnology in the area of septic shock is to prevent invading pathogens from overstimulating the host's immune system and to systematically eliminate those pathogens. Biotechnology is opening new avenues to the treatment of septic shock.
Phylogenetic relationships of Nocardiopsis species based on partial gyrB and 16S rRNA gene sequences (2008)

Partial nucleotide sequences of the gyrB gene were determined for members of the genus Nocardiopsis and subjected to phylogenetic analysis. Interspecies DNA similarity values of partial gyrB gene sequences ranged from 79.9 to 99.7% among the Nocardiopsis species. The average similarity of the gyrB gene (87.7%) was significantly less than that of the 16S rRNA gene (96.65%), indicating a high discriminatory power of the gyrB gene. The topology of neighbor-joining, maximum likelihood and maximum parsimony phylogenetic trees based on nucleic acid sequences and protein sequences of gyrB gene were reconstructed. Compared with the 16S rRNA gene dendrogram, the gyrB gene provided more information for understanding the genetic relationships among Nocardiopsis species. Using the information derived from 16S rRNA and gyrB genes, a more comprehensive understanding of the evolutionary history of Nocardiopsis species was obtained.
Screening of Transgenic Plants by Amplification of Unknown Genomic DNA Flanking T-DNA (1999)

For the screening of transfer DNA (T-DNA) integration in transgenic plant material, we developed a method based on specific amplification of genomic plant DNA flanking T-DNA borders. This approach is possible because the length of the region flanking T-DNA extremity on a restriction fragment is specific to the integration locus. We have modified an adaptor ligation PCR technique developed for amplification of unknown DNA flanking known sequence. The PCR patterns obtained were specific and reproducible for different plants from a given transgenic line. Furthermore, the number of PCR products obtained could be considered a good estimation of the T-DNA copy number. When compared to Southern blot analysis, the PCR results give valuable complementary information about the complexity of the T-DNA integration pattern and also about the integrity of the T-DNA borders. We describe the applications of this approach to populations of transgenic Arabidopsis thaliana plants.
Single-Nucleotide Polymorphism Identification Assays Using a Thermostable DNA Polymerase and Delayed Extraction MALDI-TOF Mass Spectrometry (1997)

We report a simple method, the PinPoint assay, for detecting and identifying single-base variations (polymorphisms) at specific locations within DNA sequences. An oligonucleotide primer is annealed to the target DNA immediately upstream of the polymorphic site and is extended by a single base in the presence of all four dideoxynucleotide triphosphates and a thermostable DNA polymerase. The extension products are desalted, concentrated, and subjected to delayed-extraction MALDI-TOF mass spectrometry. The base at the polymorphic site is identified by the mass added onto the primer. Heterozygous targets produce two mass-resolved species that represent the addition of both bases complementary to those at the polymorphic site. The assay is suitable for double-stranded PCR products without purification or strand separation. More than one primer can be simultaneously extended and then mass-analyzed. The mass spectrometric method thus shows promise for high-volume diagnostic or genotyping applications.
The metric properties of a novel non‐motor symptoms scale for Parkinson's disease: Results from an international pilot study (2007)

Non-motor symptoms (NMS) in Parkinson's disease (PD) are common, significantly reduce quality of life and at present there is no validated clinical tool to assess the progress or potential response to treatment of NMS. A new 30-item scale for the assessment of NMS in PD (NMSS) was developed. NMSS contains nine dimensions: cardiovascular, sleep/fatigue, mood/cognition, perceptual problems, attention/memory, gastrointestinal, urinary, sexual function, and miscellany. The metric attributes of this instrument were analyzed. Data from 242 patients mean age 67.2 +/- 11 years, duration of disease 6.4 +/- 6 years, and 57.3% male across all stages of PD were collected from the centers in Europe, USA, and Japan. The mean NMSS score was 56.5 +/- 40.7, (range: 0-243) and only one declared no NMS. The scale provided 99.2% complete data for the analysis with the total score being free of floor and ceiling effect. Satisfactory scaling assumptions (multitrait scaling success rate >95% for all domains except miscellany) and internal consistency were reported for most of the domains (mean alpha, 0.61). Factor analysis supported the a prori nine domain structure (63% of the variance) while a small test-retest study showed satisfactory reproducibility (ICC > 0.80) for all domains except cardiovascular (ICC = 0.45). In terms of validity, the scale showed modest association with indicators of motor symptom severity and disease progression but a high correlation with other measures of NMS (NMSQuest) and health-related quality of life measure (PDQ-8) (both, rS = 0.70). In conclusion, NMSS can be used to assess the frequency and severity of NMS in PD patients across all stages in conjunction with the recently validated non-motor questionnaire.
Second Cancers after Hodgkin's Disease in Childhood (1996)

The treatment of Hodgkin's disease is a model of successful therapy for childhood cancer, with cure rates of over 90 percent expected from chemotherapy regimens and low-dose radiation (15 to 25 Gy) to involved regions.1 The current therapy evolved to minimize previously recognized late effects of treatment, such as growth retardation and secondary malignant tumors. In this issue of the Journal, Bhatia et al.,2 representing the Late Effects Study Group, report that second cancers developed 18 times more often in patients who received treatment for Hodgkin's disease before the age of 16 years than would be expected in the general . . .
Accelerated chemical synthesis of peptides and small proteins (1999)

The chemical synthesis of peptides and small proteins is a powerful complementary strategy to recombinant protein overexpression and is widely used in structural biology, immunology, protein engineering, and biomedical research. Despite considerable improvements in the fidelity of peptide chain assembly, side-chain protection, and postsynthesis analysis, a limiting factor in accessing polypeptides containing greater than 50 residues remains the time taken for chain assembly. The ultimate goal of this work is to establish highly efficient chemical procedures that achieve chain-assembly rates of approximately 10-15 residues per hour, thus underpinning the rapid chemical synthesis of long polypeptides and proteins, including cytokines, growth factors, protein domains, and small enzymes. Here we report Boc chemistry that employs O-(7-azabenzotriazol-1-yl)-N,N, N',N'-tetramethyluronium hexafluorophosphate (HATU)/dimethyl sulfoxide in situ neutralization as the coupling agent and incorporates a protected amino acid residue every 5 min to produce peptides of good quality. This rapid coupling chemistry was successfully demonstrated by synthesizing several small to medium peptides, including the "difficult" C-terminal sequence of HIV-1 proteinase (residues 81-99); fragment 65-74 of the acyl carrier protein; conotoxin PnIA(A10L), a potent neuronal nicotinic receptor antagonist; and the pro-inflammatory chemotactic protein CP10, an 88-residue protein, by means of native chemical ligation. The benefits of this approach include enhanced ability to identify and characterize "difficult couplings," rapid access to peptides for biological and structure-activity studies, and accelerated synthesis of tailored large peptide segments (<50 residues) for use in chemoselective ligation methods.
Surface Modification To Reduce Nonspecific Binding of Quantum Dots in Live Cell Assays (2005)

Nonspecific binding is a frequently encountered problem with fluorescent labeling of tissue cultures when labeled with quantum dots. In these studies various cell lines were examined for nonspecific binding. Evidence suggests that nonspecific binding is related to cell type and may be significantly reduced by functionalizing quantum dots with poly(ethylene glycol) ligands (PEG). The length of PEG required to give a significant reduction in nonspecific binding may be as short as 12-14 ethylene glycol units.
Recombinant human interferon-γ. Differences in glycosylation and proteolytic processing lead to heterogeneity in batch culture (1990)

Recombinant human interferon-gamma (Hu-IFN-gamma) produced by Chinese-hamster ovary (CHO) cells was analysed by immunoprecipitation and SDS/PAGE. Up to twelve molecular-mass variants were secreted by this cell line. Three variants were recovered after enzymic removal of all N-linked oligosaccharides or when glycosylation was inhibited by tunicamycin. The presence of three polypeptide forms rather than a single form suggested that proteolytic cleavage had occurred at two sites in both the glycosylated and non-glycosylated forms. Proteolytically cleaved IFN-gamma was more prevalent in cell lysates than in the secreted glycoprotein. In common with naturally produced IFN-gamma, both fully glycosylated IFN-gamma (asparagine residues 28 and 100 occupied) and partially glycosylated product (thought to be substituted at position Asn28) were secreted. This was deduced from the Mr of the glycosylated products and the relative amounts of sialic acid expressed by each variant. In contrast with naturally produced IFN-gamma, non-glycosylated IFN-gamma was also secreted by the transfected CHO cells. When the cells were grown in batch culture in serum-free medium under pH and dissolved-oxygen control, the proportion of non-glycosylated IFN-gamma increased from 3 to 5% after 3 h, to 30% of the total IFN-gamma present after 195 h. This change in the proportion of glycosylated protein produced was not seen when metabolically labelled IFN-gamma was incubated for 96 h with cell-free supernatant from actively growing CHO cells. This implied that an alteration in intracellular glycosylation was occurring rather than a degradation of oligosaccharide side chains after secretion. The decrease in IFN-gamma glycosylation was independent of the glucose concentration in the culture medium, but could be related to specific growth and IFN-gamma production rates, as these declined steadily after 50 h of culture, in line with the increased production of non-glycosylated IFN-gamma.
Expression of Rgmc, the murine ortholog of hemojuvelin gene, is modulated by development and inflammation, but not by iron status or erythropoietin (2004)

Mutations of hepcidin (HAMP) and hemo-juvelin (HJV) genes have been recently demonstrated to result in juvenile hemochromatosis. Expression of HAMP is regulated by iron status or infection, whereas regulation of HJV is yet unknown. Using quantitative real-time polymerase chain reaction, we compared expression of Hamp and Rgmc (the murine ortholog of HJV) in livers of mice treated with iron, erythropoietin, or lipopolysaccharide (LPS), as well as during fetal and postnatal development. Iron overload increased Hamp expression without effect on Rgmc mRNA. Erythropoietin decreased Hamp mRNA, but Rgmc expression was unchanged. Hamp mRNA level decreased after birth by 4 orders of magnitude, without significant changes in Rgmc expression. Administration of LPS elevated Hamp mRNA levels, while markedly decreasing hepatic Rgmc mRNA levels (to approximately 5% after 6 hours). The responses of Hamp and Rgmc were quite different and suggested that human HJV expression could be modulated by inflammation.
Changes in regional cerebral blood flow on recovery from depression (1995)

We have previously described focal abnormalities of regional cerebral blood flow (rCBF) in the left dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex and angular gyrus in 40 patients with major depression. We now report on the patterns of change in rCBF in a subgroup of 25 of the same patients who were rescanned following clinical remission of depression. Fifteen patients were scanned when optimally matched for drug treatment (4) or drug free on both occasions (11). The other 10 patients were fully recovered but could not be matched for drug status for clinical and ethical reasons. In a paired comparison of the same patients when ill and following recovery it was evident that remission was associated with a significant increase in rCBF in the left DLPFC and medial prefrontal cortex including anterior cingulate. Increases in rCBF in the angular gyrus were not seen when the comparison of depressed and recovered scans was matched for medication. The previously described relationship between clinical symptoms and brain perfusion in the depressed state was no longer present in the recovered state; this supports the hypothesis of state relatedness. Thus, recovery from depression is associated with increases in rCBF in the same areas in which focal decreases in rCBF are described in the depressed state in comparison with normal controls.