gebhart/patrepeval huggingface dataset:
The Money or the Principle? (2000)

Christel Lane and Reinhard Bachmann (eds), Trust within and Between Organizations , Oxford: Oxford University Press 1998, £45.00, xiii+334 pp. Patrick Maclagan, Management and Morality. A Developmental Perspective , London: Sage, £45.00, paper £14.99, vii+212 pp. Trust seems a useful test-case for business morality. According to Fukuyama it is the opposite of contractual relations, as it is ‘based on commonly shared norms . . . about deep “value” questions like the nature of God or justice, but it may also encompass secular norms, like professional standards and codes of behaviour.’ (Fukuyama 1995: 26).
Functional Characterization of the Prodomain of Interleukin1β-converting Enzyme (1996)

Interleukin-1beta-converting enzyme (ICE) has been identified as the main protease responsible for maturation of the prodomain of interleukin-1beta. Recently, it was shown to belong to a larger gene family, members of which play an important role in programmed cell death. A common feature of the ICE family proteases is the presence of a prodomain that has been hypothesized to keep the enzyme in an inactive form. Expression analysis in yeast revealed autocatalytic degradation of p45ICE, but not of p30ICE lacking a prodomain. We further demonstrate that p45ICE, in which the critical cysteine has been mutated, is still able to dimerize in vivo. Dimerization requires the prodomain and occurs prior to autoprocessing. These results provide evidence for a regulatory role of the prodomain of ICE.
Antibody-Mediated Clearance of Alphavirus Infection From Neurons (1991)

Humoral immunity is important for protection against viral infection and neutralization of extracellular virus, but clearance of virus from infected tissues is thought to be mediated solely by cellular immunity. However, in a SCID mouse model of persistent alphavirus encephalomyelitis, adoptive transfer of hyperimmune serum resulted in clearance of infectious virus and viral RNA from the nervous system, whereas adoptive transfer of sensitized T lymphocytes had no effect on viral replication. Three monoclonal antibodies to two different epitopes on the E2 envelope glycoprotein mediated viral clearance. Treatment of alphavirus-infected primary cultured rat neurons with these monoclonal antibodies to E2 resulted in decreased viral protein synthesis, followed by gradual termination of mature infectious virion production. Thus, antibody can mediate clearance of alphavirus infection from neurons by restricting viral gene expression.
Interleukin-15:Interleukin-15 receptor scaffold for creation of multivalent targeted immune molecules (2010)

Human interleukin-15 (hIL-15) and its receptor α (hIL-15Rα) are co-expressed in antigen presenting cells allowing trans-presentation of the cytokine to immune effector cells. We exploited the high-affinity interactions between hIL-15 and the extracellular hIL-15Rα sushi domain (hIL-15RαSu) to create a functional scaffold for the design of multispecific fusion protein complexes. Using single-chain T cell receptors (scTCRs) as recognition domains linked to the IL-15:IL-15Rα scaffold, we generated both bivalent and bispecific complexes. In these fusions, the scTCR domains retain the antigen-binding activity and the hIL-15 domain exhibits receptor binding and biological activity. As expected, bivalent scTCR fusions exhibited improved antigen binding due to increased avidity, whereas fusions comprising two different scTCR domains were capable of binding two cognate peptide/MHC complexes. Bispecific molecules containing scTCR and scCD8αβ domains also exhibit enhanced binding to peptide/MHC complexes, demonstrating that the IL-15:IL-15Rα scaffold displays flexibility necessary to support multi-domain interactions with a given target. Surprisingly, functional heterodimeric molecules could be formed by co-expressing the TCR α and β chains separately as fusions to the hIL-15 and hIL-15RαSu domains. Together, these properties indicate that the hIL-15 and hIL-15RαSu domains can be used as versatile, functional scaffold for generating novel targeted immune molecules.
B cell epitopes on infliximab identified by oligopeptide microarray with unprocessed patient sera (2015)

Our data shall contribute to a knowledge-based recommendation for a potentially necessary therapy switch from infliximab to another type of TNF-alpha-blocker. The characterization of immunogenic epitopes on therapeutic monoclonal antibodies using unprocessed patient sera shall lead to direct translational aspects for the development of less immunogenic therapeutic antibodies. Patients benefit from less adverse events and longer lasting drug effects.
An antibody produced in tobacco expressing a hybrid β-1,4-galactosyltransferase is essentially devoid of plant carbohydrate epitopes (2006)

N-glycosylation of a mAb may have a major impact on its therapeutic merits. Here, we demonstrate that expression of a hybrid enzyme (called xylGalT), consisting of the N-terminal domain of Arabidopsis thaliana xylosyltransferase and the catalytic domain of human beta-1,4-galactosyltransferase I (GalT), in tobacco causes a sharp reduction of N-glycans with potentially immunogenic core-bound xylose (Xyl) and fucose (Fuc) residues as shown by Western blot and MALDI-TOF MS analysis. A radioallergosorbent test inhibition assay with proteins purified from leaves of WT and these transgenic tobacco plants using sera from allergic patients suggests a significant reduction of potential immunogenicity of xylGalT proteins. A mAb purified from leaves of plants expressing xylGalT displayed an N-glycan profile that featured high levels of galactose, undetectable xylose, and a trace of fucose. Hence, a transgenic plant expressing the hybrid GalT might yield more effective and safer monoclonals for therapeutic purposes than WT plants and even transgenic plants expressing the unchanged GalT.
Electrostatically optimized Ras-binding Ral guanine dissociation stimulator mutants increase the rate of association by stabilizing the encounter complex (2004)

Association of two proteins can be described as a two-step process, with the formation of an encounter complex followed by desolvation and establishment of a tight complex. Here, by using the computer algorithm PARE, we designed a set of mutants of the Ras effector protein Ral guanine nucleotide dissociation stimulator (RalGDS) with optimized electrostatic steering. The fastest binding RalGDS mutant, M26K,D47K,E54K, binds Ras 14-fold faster and 25-fold tighter compared with WT. A linear correlation was found between the calculated and experimental data, with a correlation coefficient of 0.97 and a slope of 0.65 for the 24 mutants produced. The data suggest that increased electrostatic steering specifically stabilizes the encounter complex and transition state. This conclusion is backed up by Phi analysis of the encounter complex and transition state of the RalGDS(M26K,D47K,E54K)/Ras complex, with both values being close to 1. Upon further formation of the final complex, the increased Coulombic interactions are probably counterbalanced by the cost of desolvation of charges, keeping the dissociation rate constant almost unchanged. This mechanism is also reflected by the mutual compensation of enthalpy and entropy changes quantified by isothermal titration calorimetry. The binding constants of the faster binding RalGDS mutants toward Ras are similar to those of Raf, the most prominent Ras effector, suggesting that the design methodology may be used to switch between signal transduction pathways.
Propionibacterium acnes, a resident of lipid-rich human skin, produces a 33 kDa extracellular lipase encoded by gehA (1997)

Five independent clones of the Propionibacterium acnes P-37 lipase gene (gehA) were obtained in Escherichia coli, and the gene was localized to a 2.75 kb Xhol fragment by subcloning. The five clones were shown to contain the same gene by Southern blotting with a DIG-labelled probe to gehA. The nucleotide sequence of gehA was determined, and shown to contain a single ORF of 1017 kb, encoding a protein of 339 amino acids. The predicted molecular mass was 36 kDa. A 33 kDa (PAGE) radiolabelled polypeptide was detected from E. coli minicell preparations harbouring gehA, which could correspond to GehA after cleavage of the putative 26 amino acid residue signal peptide. gehA was overexpressed in E. coli under the control of the bacteriophage T7 promoter, and the corresponding polypeptide was found to be present in insoluble aggregates. Active lipase was produced when the overexpressing strain was incubated at a reduced temperature in the presence of sucrose. Purification of lipase from P. acnes culture supernatant fluids confirmed the production of a 33 kDa (PAGE) lipase.
Automated shimming at 1.5 t using echo‐planar image frequency maps (1995)

Using echo-planar imaging, we developed an automated image-based procedure to shim the static (B0) field. Our method uses the rapid acquisition capability of echo-planar imaging to collect the required frequency data rapidly, rendering the shim data acquisition time negligible in comparison with the total study time. We address image distortion issues involved in echo-planar imaging acquisition of the data and formulate analytic methods for arriving at an optimal shim for the NMR imaging experiment in a single iteration. We investigated the use of cost functions other than least-squares (Chebychev, high-order numeric) and found that choice between the cost functions we tested was irrelevant to resultant image quality, at least when used in conjunction with low-order shims. With appropriate integration, the method has become routine practice for investigators at our laboratory.
Home monitoring of transcutaneous oxygen tension in the early detection of hypoxaemia in infants and young children. (1991)

Twenty three patients (age range 0.5-40 months) with recurrent cyanotic episodes underwent physiological recordings, including transcutaneous oxygen tension (TcPO2) from a monitor modified for use at home (Kontron 821S). Of 69 episodes in which the arterial oxygen saturation (SaO2, Nellcor N200) was less than or equal to 80% for greater than or equal to 20 seconds and/or central cyanosis was present, the TcPO2 monitor alarmed (less than or equal to 20 mmHg or 2.67 kPa) in every episode. The pulse oximeter identified hypoxaemia in 62 out of 69 episodes, failing in seven episodes due to signal loss from movement artefact. In only seven of 69 episodes was there an accompanying apnoeic pause (greater than or equal to 20 seconds), and heart rate fell to less than or equal to 80 beats/minute in only five of 28 episodes in which an electrocardiogram was recorded. In 32 episodes in which SaO2 fell to less than or equal to 60%, the TcPO2 monitor alarmed after a median time interval of 16 seconds (maximum time interval 30 seconds). The TcPO2 monitor was then used in an uncontrolled trial at home in 350 patients at increased risk of sudden death and/or hypoxaemia. Indications for monitoring included apparent life threatening events or cyanotic episodes (n = 163), prematurity and prematurity related disorders (n = 86), and sudden unexpected death in one or more siblings (n = 122). The TcPO2 monitor detected cyanotic episodes at home in 81 patients, 52 of whom received vigorous stimulation and/or mouth to mouth resuscitation. Twenty one of these 52 patients had further hypoxaemic episodes documented in hospital with pulse oximetry. In 30 patients, the TcPo2 monitor also identified the gradual development of hypoxaemia, as confirmed by pulse oximetry. Twenty of these needed additional inspired oxygen and six subsequently needed ventilatory support in hospital. This TcPo2 monitor is a reliable detector of both sudden and gradual onset hypoxaemia and is able to be used by parents in the home.
Survey and taxonomy of IP address lookup algorithms (2001)

Due to the rapid growth of traffic in the Internet, backbone links of several gigabits per second are commonly deployed. To handle gigabit-per-second traffic rates, the backbone routers must be able to forward millions of packets per second on each of their ports. Fast IP address lookup in the routers, which uses the packet's destination address to determine for each packet the next hop, is therefore crucial to achieve the packet forwarding rates required. IP address lookup is difficult because it requires a longest matching prefix search. In the last couple of years, various algorithms for high-performance IP address lookup have been proposed. We present a survey of state-of-the-art IP address lookup algorithms and compare their performance in terms of lookup speed, scalability, and update overhead.
Histone Deacetylase Inhibitors Trigger a G2 Checkpoint in Normal Cells That Is Defective in Tumor Cells (2000)

Important aspects of cell cycle regulation are the checkpoints, which respond to a variety of cellular stresses to inhibit cell cycle progression and act as protective mechanisms to ensure genomic integrity. An increasing number of tumor suppressors are being demonstrated to have roles in checkpoint mechanisms, implying that checkpoint dysfunction is likely to be a common feature of cancers. Here we report that histone deacetylase inhibitors, in particular azelaic bishydroxamic acid, triggers a G2 phase cell cycle checkpoint response in normal human cells, and this checkpoint is defective in a range of tumor cell lines. Loss of this G2 checkpoint results in the tumor cells undergoing an aberrant mitosis resulting in fractured multinuclei and micronuclei and eventually cell death. This histone deacetylase inhibitor-sensitive checkpoint appears to be distinct from G2/M checkpoints activated by genotoxins and microtubule poisons and may be the human homologue of a yeast G2 checkpoint, which responds to aberrant histone acetylation states. Azelaic bishydroxamic acid may represent a new class of anticancer drugs with selective toxicity based on its ability to target a dysfunctional checkpoint mechanism in tumor cells.
Evaluation of the β-CARBA™ test, a colorimetric test for the rapid detection of carbapenemase activity in Gram-negative bacilli (2017)

Despite lack of specificity towards non-KPC Ambler class A and OXA-48-like carbapenemases, the β-CARBA™ test could complete the existing panel of tests available for the confirmation of carbapenemases in Gram-negatives.
Immunodeficient Mouse Models: An Overview (2009)

The development and use of an increasing number and variety of naturally, transgenic, induced mutant, and genetically engineered immunodeficient mouse and mouse/human hybrids models have been imperative for understanding the gene-driven cellular and molecular mechanisms and pathophysiological manifestations (phenotypes) of immune disorders that are similar to mice and humans. Much more effort is needed to develop new system models to promote the integration of thousands of genes and their variants that are likely to affect the outcome of microbial infections, immune deficiency and autoimmunity. This article provides an update on characteristics and applications of most commonly used inbred and new hybrid strains of naturally immunodeficiency, knockout and transgenic mouse models, and a short discussion on how innovative technologies and databases presently available can be used for devising new models to better understand the human immune system and diseases that affect it.
The der(11)-encoded MLL/AF-4 fusion transcript is consistently detected in t(4;11)(q21;q23)-containing acute lymphoblastic leukemia (1994)

The t(4;11)(q21;q23) is the most common translocation involving band 11q23 and is found predominantly in acute lymphoblastic leukemias (ALLs) of infants. Recent studies have shown that this translocation involves the MLL gene on chromosome 11 and the AF-4 gene on chromosome 4. Using oligonucleotide primers derived from these genes, we established reverse transcription-polymerase chain reaction (RT-PCR) assays for the detection of the fusion transcripts from both the der(11) and der(4) chromosomes. Using these assays we analyzed 23 pediatric cases of t(4;11) containing ALL. RT-PCR analysis for the der(11)-derived MLL/AF-4 fusion transcript resulted in its detection in every case at a sensitivity of greater than 1 leukemic cell in 10(5) cells. Sequence analysis of MLL/AF-4 PCR products demonstrated fusion mRNAs resulting from breaks in MLL introns 6, 7, or 8, with alternative splicing to one of three exons in the AF-4 gene. In contrast, analysis for the der(4)-derived transcript resulted in the detection of this chimeric mRNA in only 84% of the cases analyzed. These data suggest that the critical chimeric gene product involved in the establishment of the leukemic clone is derived from the der(11) chromosome. Moreover, these data demonstrate the utility of the RT-PCR assay for the der(11)-encoded message both for diagnosing t(4;11)-containing leukemia and for monitoring patients for minimal residual disease.
Comprehensive Proteomic Analysis of Human Cervical−Vaginal Fluid (2007)

Cervical-vaginal fluid (CVF) is a potential rich source of biomarkers for enhancing our understanding of human parturition and pathologic conditions affecting pregnancy. In this study, we performed a comprehensive survey of the CVF proteome in pregnancy utilizing multidimensional liquid chromatography (2D-LC) coupled with mass spectrometry and gel-electrophoresis-based protein separation and identification. In total, 150 unique proteins were identified using multiple protein identification algorithms. Metabolism (32%) and immune response-related (22%) proteins are the major functional categories represented in the CVF proteome. A comparison of the CVF, serum, and amniotic fluid proteomes showed that 77 proteins are unique to CVF, while 56 and 17 CVF proteins also occur in serum and amniotic fluid, respectively. This data set provides a foundation for evaluation of these proteins as potential CVF biomarkers for noninvasive diagnosis of pregnancy-related disorders.
A Comparison of Base-calling Algorithms for Illumina Sequencing Technology (2015)

Recent advances in next-generation sequencing technology have yielded increasing cost-effectiveness and higher throughput produced per run, in turn, greatly influencing the analysis of DNA sequences. Among the various sequencing technologies, Illumina is by far the most widely used platform. However, the Illumina sequencing platform suffers from several imperfections that can be attributed to the chemical processes inherent to the sequencing-by-synthesis technology. With the enormous amounts of reads produced, statistical methodologies and computationally efficient algorithms are required to improve the accuracy and speed of base-calling. Over the past few years, several papers have proposed methods to model the various imperfections, giving rise to accurate and/or efficient base-calling algorithms. In this article, we provide a comprehensive comparison of the performance of recently developed base-callers and we present a general statistical model that unifies a large majority of these base-callers.
Polyethyleneimine Coating Enhances the Cellular Uptake of Mesoporous Silica Nanoparticles and Allows Safe Delivery of siRNA and DNA Constructs (2009)

Surface-functionalized mesoporous silica nanoparticles (MSNP) can be used as an efficient and safe carrier for bioactive molecules. In order to make the MSNP a more efficient delivery system, we modified the surface of the particles by a functional group that enhances cellular uptake and allows nucleic acid delivery in addition to traditional drug delivery. Noncovalent attachment of polyethyleneimine (PEI) polymers to the surface not only increases MSNP cellular uptake but also generates a cationic surface to which DNA and siRNA constructs could be attached. While efficient for intracellular delivery of these nucleic acids, the 25 kD PEI polymer unfortunately changes the safety profile of the MSNP that is otherwise very safe. By experimenting with several different polymer molecular weights, it was possible to retain high cellular uptake and transfection efficiency while reducing or even eliminating cationic MSNP cytotoxicity. The particles coated with the 10 kD PEI polymer were particularly efficient for transducing HEPA-1 cells with a siRNA construct that was capable of knocking down GFP expression. Similarly, transfection of a GFP plasmid induced effective expression of the fluorescent protein in >70% cells in the population. These outcomes were quantitatively assessed by confocal microscopy and flow cytometry. We also demonstrated that the enhanced cellular uptake of the nontoxic cationic MSNP enhances the delivery of the hydrophobic anticancer drug, paclitaxel, to pancreatic cancer cells. In summary, we demonstrate that, by a careful selection of PEI size, it is possible to construct cationic MSNP that are capable of nucleotide and enhanced drug delivery with minimal or no cytotoxicity. This novel use of a cationic MSNP extends its therapeutic use potential.
Studies on the Subsite Specificity of Rat Nardilysin (N-Arginine Dibasic Convertase) (2000)

The subsite specificity of rat nardilysin was investigated using fluorogenic substrates of the type 2-aminobenzoyl-GGX(1)X(2)RKX(3)GQ-ethylenediamine-2,4- dinitrophenyl, where P(2), P(2)', and P(3) residues were varied. (The nomenclature of Schechter and Berger (Schechter, I., and Berger, A. (1967) Biochem. Biophys. Res. Commun. 27, 157-162) is used where cleavage of a peptide occurs between the P(1) and P(1)' residues, and adjacent residues are designated P(2), P(3), P(2)', P(3)', etc.) There was little effect on K(m) among different residues at any of these positions. In contrast, residues at each position affected k(cat), with P(2) residues having the greatest effect. The S(3), S(2), and S(2)' subsites differed in their amino acid preference. Tryptophan and serine, which produced poor substrates at the P(2) position, were among the best P(2)' residues. The specificity at P(3) was generally opposite that of P(2). Residues at P(2), and to a lesser extent at P(3), influenced the cleavage site. At the P(2) position, His, Phe, Tyr, Asn, or Trp produced cleavage at the amino side of the first basic residue. In contrast, a P(2) Ile or Val produced cleavage between the dibasic pair. Other residues produced intermediate effects. The pH dependence for substrate binding showed that the enzyme prefers to bind a protonated histidine. A comparison of the effect of arginine or lysine at the P(1)' or P(1) position showed that there is a tendency to cleave on the amino side of arginine and that this cleavage produces the highest k(cat) values.
Control optimization of spherical modal liquid crystal lenses (1999)

Liquid crystal modal lenses are switchable lenses with a continuous phase variation across the lens. A critical issue for such lenses is the minimization of phase aberrations. In this paper we present results of a simulation of control signals that have a range of harmonics. Experimental results using optimal sinusoidal and rectangular voltages are presented. A lack of uniqueness in the specification of the control voltage parameters is explained. The influence of a variable duty cycle of the control voltage on an adaptive lens is investigated. Finally we present experimental results showing a liquid crystal lens varying its focal length.