gebhart/patrepeval huggingface dataset:
A mechanism of DNA transposition. (1981)

Bacteriophage Mu and many other transposable elements undergo transposition by a process that involves replication of the element. We describe here a mechanism by which such integrative replication may take place. We hve examined electron microscopically the DNA structures generated in host cells after Mu induction and have deduced the following steps in the transposition process, (i) Association. A protein-mediated association is brought about between the transposable element and the target DNA. (ii) Attachment. One end of the element is nicked and attached to a site that undergoes a double-stranded cleavage. (iii) Roll-in replication. While one strand of the target DNA is linked to the nicked strand of the element, the complementary strand of the target DNA is used as a primer for replication into the element such that the replicating DNA is threaded through the replication complex. (iv) Roll-in termination. When the distal end of the element arrives at the replication complex, replication is terminated. The roll-in replication mechanism can also explain laying down of tandem repeats--i.e., amplification of circular DNA sequences.
Die Durchführung wertanalytischer Untersuchungen (1985)

Eine Besonderheit der Wertanalyse ist das systematische Vorgehen nach einem festgelegten Arbeitsplan. Der Zweck dieses Kapitels besteht darin, Ihnen die Vorgehensweise der Wertanalytiker im Detail zu erläutern, und nach Durcharbeiten dieser Lerneinheit sollten Sie insbesondere
Pharmacologically regulated Fas-mediated death of adoptively transferred T cells in a nonhuman primate model (2003)

Conditional suicide genes derived from pathogens have been developed to confer drug sensitivity and enhance safety of cell therapy, but this approach is limited by immune responses to the transgene product. We examined a strategy to regulate survival of transferred cells based on induction of apoptosis through oligomerization of a modified human Fas receptor by a bivalent drug (AP1903). Three macaques (Macaca nemestrina) received autologous T cells retrovirally engineered to express a Fas suicide-construct (LV'VFas). High levels of transduced cells were present in blood following cell transfer, but LV'VFas(+) cells declined rapidly after AP1903 administration. A small fraction of LV'VFas(+) cells resisted elimination by AP1903, in part due to insufficient levels of transgene expression in resting T cells, because reactivation of these cells in vitro enhanced sensitivity to AP1903. An immune response to the transgene product was observed, but epitope mapping indicated the response was directed to discrete components of human LV'VFas that were variant with the corresponding macaque sequences. These data demonstrate that chemically induced dimerization can be used to regulate survival of adoptively transferred T cells in vivo.
Electric potential probes - new directions in the remote sensing of the human body (2001)

In this paper we describe a new approach to the detection of human body electrical activity which has been made possible by recent advances in ultra-low-noise, ultra-high-input-impedance probes. As we demonstrate, these probes, which do not require a real current conducting path in order to operate, can be used non-invasively both on and off body. We present remarkable new data showing the application of these probes to the remote, off-body, sensing of the electrical activity of the heart at distances of up to 1 m from the body and to high-resolution electrocardiograms. We suggest that in the future such probes may form the basis of a radically new technology for measuring the dynamics of the human body as well as in non-contact, imaging systems for pre-emptive and diagnostic medicine.
Functional analysis of regulatory sequences controllingPR‐1 gene expression in Arabidopsis (1998)

The Arabidopsis PR-1 gene is one of a suite of genes induced co-ordinately during the onset of systemic acquired resistance (SAR), a plant defense pathway triggered by pathogen infection or exogenous application of chemicals such as salicylic acid (SA) and 2,6-dichloroisonicotinic acid (INA). We have characterized cis-acting regulatory elements in the PR-1 promoter involved in INA induction using deletion analysis, linker-scanning mutagenesis, and in vivo footprinting. Compared to promoter fragments of 815 bp or longer (which show greater than 10-fold inducibility after INA treatment), induction of a 698 bp long promoter fragment is reduced by half and promoter fragments of 621 bp or shorter have lost all inducibility. Additionally, two 10-bp linker-scanning mutations centered at 640 bp and 610 bp upstream from the transcription initiation site are each sufficient to abolish chemical inducibility of a GUS reporter fusion. The -640 linker-scanning mutation encompasses a region highly homologous to recognition sites for transcription factors of the basic leucine zipper class, while the -610 linker-scanning mutation contains a sequence similar to a consensus recognition site for the transcription factor NF-kappa B. Furthermore, several inducible in vivo footprints located at or nearby these motifs demonstrate significant and highly reproducible changes in DNA accessibility following SAR induction. This in vivo signature of protein-DNA interactions after INA induction is tightly correlated with the functionally important regions of the promoter identified by mutation analysis.
Visible-ultraviolet vibronic emission of silica nanoparticles (2014)

We report the study of the visible-ultraviolet emission properties and the structural features of silica nanoparticles prepared through a laboratory sol-gel technique. Atomic force microscopy, Raman and Infrared investigations highlighted the 10 nm size, purity and porosity of the obtained nanoparticles. By using time resolved photoluminescence techniques in air and in a vacuum we were able to single out two contributions in the visible emission: the first, stable in both atmospheres, is a typical fast blue band centered around 2.8 eV; the second, only observed in a vacuum around the 3.0-3.5 eV range, is a vibrational progression with two phonon modes at 1370 cm(-1) and 360 cm(-1). By fully characterizing the spectroscopic features of this structured emission, we determine its vibronic properties and clarify the different origins with respect to the blue luminescent defect.
Increased cardiac IL-18 mRNA, pro-IL-18 and plasma IL-18 after myocardial infarction in the mouse; a potential role in cardiac dysfunction (2003)

After MI in the mouse, increased production of cardiac IL-18 mRNA and pro-IL-18, as well as circulating IL-18 occurs. Since IL-18 also reduced myocardial contractility, we suggest that IL-18 may be involved in the pathogenesis of contractile dysfunction following MI.
Infectious RNA transcribed from an engineered full-length cDNA template of the genome of a pestivirus (1996)

Infectious RNA was transcribed for the first time from a full-length cDNA template of the plus-strand RNA genome of a pestivirus. The genome of the C strain, which is a vaccine strain of classical swine fever virus, was sequenced and used to synthesize the template. The cDNA sequence of the C strain was found to be 12,311 nucleotides in length and contained one large open reading frame encoding a polyprotein of 3,898 amino acids. Although there were mostly only small differences between the sequence of the C strain and the published sequences of strains Alfort and Brescia, there was one notable insertion of 13 nucleotides, TTTTCTTTTTTTT, in the 3' noncoding region of the C strain. Furthermore, we showed that the sequences at the 5' and 3' termini of the C strain are highly conserved among pestiviruses. We found that the infectivity of the in vitro transcripts of DNA copies pPRKflc-113 and pPRKflc-133 depended on the correctness of the nucleotide sequence. The in vitro transcripts of pPRKflc-133 were infectious, whereas those of pPRKflc-113 were not. In fact, only 5 amino acids among the complete amino acid sequence determined this difference in infectivity. However, virus FLc-133, which was generated from pPRKflc-133, cannot be differentiated from native C-strain virus. Therefore, we exchanged the region encoding the antigenic N-terminal half of envelope protein E2 in pPRKflc-133 with the equivalent region of strain Brescia. The resulting hybrid virus, FLc-h6, could be differentiated from the C strain and from FLc-133 with monoclonal antibodies directed against envelope proteins Erns and E2 of strain Brescia and the C strain. To be suitable for further vaccine development, viruses generated from pPRKflc-133 should grow at least as well as native C-strain virus. In fact, we found that FLc-133, hybrid virus FLc-h6, and the C strain grew equally well. We concluded that pPRKflc-133 is an excellent tool for developing a classical swine fever marker vaccine and may prove valuable for studying the replication, virulence, cell and host tropism, and pathogenesis of classical swine fever virus.
Probing the normal and autoimmune B cell repertoire with Epstein-Barr virus. Frequency of B cells producing monoreactive high affinity autoantibodies in patients with Hashimoto's disease and systemic lupus erythematosus. (1988)

The frequency of cell precursors producing Ig of different classes and Ag-binding activities were determined, using EBV-infection and limiting dilution assays, in healthy subjects and patients with autoimmune disease. A large proportion of circulating B cells from healthy subjects were committed to the production of IgM antibodies that were polyreactive and bound a variety of self- and exogenous Ag, i.e., IgG Fc fragment, ssDNA, thyroglobulin, thyroid microsomal Ag, insulin, and tetanus toxoid. Similar frequencies of these polyreactive antibody-producing cells were found in patients with Hashimoto's disease and SLE. In contrast, significantly higher frequencies of cell precursors producing monoreactive IgG autoantibodies to thyroid Ag (thyroglobulin and thyroid microsomal Ag) and ssDNA were found in Hashimoto's disease and SLE patients, respectively. Calculation of the Kd revealed that monoclonal polyreactive antibodies were in general low affinity (Kd, 10(-3) to 10(-7) mol/liter), whereas monoclonal monoreactive autoantibodies were high affinity (Kd, 10(-9) to 10(-11) mol/liter). The detected frequency and high affinity of the monoreactive autoantibodies in Hashimoto's disease and SLE patients were comparable to those of anti-tetanus toxoid and anti-insulin IgG mAb produced by B cell clones from vaccinated healthy subjects and insulin-treated patients with insulin-dependent diabetes mellitus, respectively. These findings support the hypothesis that the autoimmune B cell repertoire in patients with organ-specific and systemic autoimmunity is shaped by Ag-driven responses rather than merely reflecting a polyclonal B cell activation.
Effects of Dextranation on the Pharmacokinetics of Short Peptides. A PET Study on mEGF (1999)

The effects of dextranation on the biodistribution of mouse epidermal growth factor (mEGF, 6 kDa) were assessed. By reductive amination, mEGF was coupled to 13 and 46 kDa dextran. The two dextranated conjugates and free mEGF were labeled with the positron-emitting nuclide (76)Br (T(1/2) = 16 h). After intravenous administration to Sprague Dawley rats, the radioactivity biodistribution was evaluated by positron emission tomography (PET) and by measurements of dissected tissues. The dextranation prolonged the retention time in blood, especially when the dextran chain was long. [(76)Br]mEGF-dextran conjugates were shown to have significantly, more than 5 times, lower kidney accumulation than the nonconjugated [(76)Br]mEGF. In conclusion, dextranation affects the biodistribution of mEGF in vivo giving a prolonged circulation time, a decreased uptake in kidney, and an increased spleen accumulation.
The Formation of a Department: Theatre at William and Mary 1926-1963 (2014)

From the foundation of the dramatic club in 1926 to the establishment of an independent academic Department of Theatre and Speech in 1963, the William and Mary Theatre experienced many changes as it grew from an extracurricular pursuit into a degree-granting program. Developments in facilities, curriculum, and local theatrical activity all contributed to shaping the organization of the department. This investigation uses information from faculty memoirs, course catalogs, departmental reports to presidents, and news publications to argue that many external factors influenced the particular way in which this department manifested. This work is intended to contribute to a broader literature of histories chronicling the ways in which new disciplines and departments can become integrated into higher education institutions. Conclusions propose that forthcoming changes to William and Mary’s curriculum and physical campus could again change the face of theatrical education at the college.
All Solid-state Lithium Secondary Batteries Using High Lithium Ion Conducting Li2S–P2S5 Glass-Ceramics (2002)

Abstract All solid-state cells of In/LiCoO2 using the 80Li2S·20P2S5 (mol%) glass-ceramics with high ambient temperature conductivity of about 10−3 S cm−1 as a solid electrolyte were fabricated, and the cell performance was investigated. Although an irreversible capacity was observed at the 1st cycle, the solid-state cell exhibited excellent cycling performances with the reversible charge-discharge capacities of about 100 mAh g−1 even after 200 cycles.
Reduced intracellular ionic strength as the initial trigger for activation of endothelial volume-regulated anion channels (1999)

Most mammalian cell types, including endothelial cells, respond to cell swelling by activating a Cl- current termed ICl,swell, but it is not known how the physical stimulus of cell swelling is transferred to the channels underlying ICl,swell. We have investigated the precise relation between cell volume and ICl,swell in endothelial cells by performing whole-cell current recordings while continuously monitoring cell thickness (Tc) as a measure for cell volume. The time course of Tc was accurately predicted by a theoretical model that describes volume changes of patch-clamped cells in response to changes in the extracellular osmolality (OSMo). This model also predicts significant changes in intracellular ionic strength (Gammai) when OSMo is altered. Under all experimental conditions ICl,swell closely followed the changes in Gammai, whereas ICl,swell and cell volume were often found to change independently. These results do not support the hypothesis that Gammai regulates the volume set point for activation of ICl,swell. Instead, they are in complete agreement with a model in which a decrease of Gammai rather than an increase in cell volume is the initial trigger for activation of ICl,swell.
Atomic Structure of Acetylcholinesterase from Torpedo californica : A Prototypic Acetylcholine-Binding Protein (1991)

The three-dimensional structure of acetylcholinesterase from Torpedo californica electric organ has been determined by x-ray analysis to 2.8 angstrom resolution. The form crystallized is the glycolipid-anchored homodimer that was purified subsequent to solubilization with a bacterial phosphatidylinositol-specific phospholipase C. The enzyme monomer is an alpha/beta protein that contains 537 amino acids. It consists of a 12-stranded mixed beta sheet surrounded by 14 alpha helices and bears a striking resemblance to several hydrolase structures including dienelactone hydrolase, serine carboxypeptidase-II, three neutral lipases, and haloalkane dehalogenase. The active site is unusual because it contains Glu, not Asp, in the Ser-His-acid catalytic triad and because the relation of the triad to the rest of the protein approximates a mirror image of that seen in the serine proteases. Furthermore, the active site lies near the bottom of a deep and narrow gorge that reaches halfway into the protein. Modeling of acetylcholine binding to the enzyme suggests that the quaternary ammonium ion is bound not to a negatively charged "anionic" site, but rather to some of the 14 aromatic residues that line the gorge.
PAINS in the Assay: Chemical Mechanisms of Assay Interference and Promiscuous Enzymatic Inhibition Observed during a Sulfhydryl-Scavenging HTS (2015)

Significant resources in early drug discovery are spent unknowingly pursuing artifacts and promiscuous bioactive compounds, while understanding the chemical basis for these adverse behaviors often goes unexplored in pursuit of lead compounds. Nearly all the hits from our recent sulfhydryl-scavenging high-throughput screen (HTS) targeting the histone acetyltransferase Rtt109 were such compounds. Herein, we characterize the chemical basis for assay interference and promiscuous enzymatic inhibition for several prominent chemotypes identified by this HTS, including some pan-assay interference compounds (PAINS). Protein mass spectrometry and ALARM NMR confirmed these compounds react covalently with cysteines on multiple proteins. Unfortunately, compounds containing these chemotypes have been published as screening actives in reputable journals and even touted as chemical probes or preclinical candidates. Our detailed characterization and identification of such thiol-reactive chemotypes should accelerate triage of nuisance compounds, guide screening library design, and prevent follow-up on undesirable chemical matter.
Autoantibodies in lung cancer: possibilities for early detection and subsequent cure (2007)

Measurement of an autoantibody response to one or more tumour-associated antigens in an optimised panel assay may provide a sensitive and specific blood test to aid the early detection of lung cancer.
Effective remote modeling in large-scale distributed simulation and visualization environments (1997)

A Distributed Interactive Simulation provides the illusion of a single, coherent virtual world to a group of users located at different machines connected by a network. Users expect to see a consistent world view, to interact closely with one another and with other simulation entities in the virtual world, and to be shielded from the application's distributed nature. Networked virtual environments are used for multiplayer video games, military and industrial training, and collaborative engineering. Network bandwidth, network latency, and host processing power limit the achievable size and detail of future simulations.
This thesis describes network protocols and algorithms to support remote modeling, allowing a host to model and render remote entities in large-scale distributed simulations. These techniques require fewer network resources and support more entity types than previous approaches. The Position History-Based Dead Reckoning (PHBDR) protocol provides accurate remote position modeling and minimizes dependencies on network performance and entity representation. PHBDR is a foundation for three protocols: (1) Axis Point Protocol: Models entity orientation by tracking the position of points in the entity's local coordinate system. (2) Multiple-Detail Channels: Protocol architecture for modeling entity structural change at different levels of detail depending on locally available computational and network resources. (3) Projection Aggregation Entities: Protocol for bundling information from entities dynamically grouped by their type and location.
This thesis shows that a simple, efficient protocol can provide smooth, accurate remote position modeling and that it can be applied recursively to support entity orientation, structure, and aggregation at multiple levels of detail; these protocols offer performance and costs that are competitive with more complex and application-specific approaches, while providing simpler analyses of behavior by exploiting this recursive structure. In support of this claim, this thesis shows that: (1) PHBDR is a simple, efficient protocol that provides smooth and accurate remote modeling for a broad range of entities and explicitly recognizes network latency. (2) PHBDR is still smooth and accurate when used to model entity orientation, entity structure at multiple levels of detail, and entity aggregations. (3) The recursive protocol structuring provides better network performance and reduced software complexity when compared with the application-specific approaches deployed in previous systems.
Population pharmacokinetics of liposomal irinotecan in patients with cancer and exposure–safety analyses in patients with metastatic pancreatic cancer (2021)

Liposomal irinotecan is a liposomal formulation of irinotecan, which prolongs circulation of irinotecan and its active metabolite SN-38. A population pharmacokinetic (PK) model was developed based on data from seven studies (N = 440). Adequacy of the model was assessed using multiple methods, including visual predictive check. Associations between PK exposure and the incidence of diarrhea (grade ≥3) and neutropenia adverse events (AEs) (grade ≥3) at first event in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) were investigated using logistic regression based on data from two studies (the phase III NAPOLI-1 [N = 260] and phase I/II NCT02551991 [N = 56] trials). The PKs of total irinotecan was described by a two-compartment model with first-order elimination, with SN-38 formed directly by a first-order constant from the central compartment of irinotecan or after using a transit compartment. Clearance was 17.9 L/week (0.107 L/h) and 19,800 L/week (118 L/h) for total irinotecan and SN-38, respectively. The UGT1A1*28 7/7 homozygous genotype had no significant impact on SN-38 clearance. Model evaluation was satisfactory for both irinotecan and SN-38. The incidence of diarrhea (grade ≥3) at first event was significantly higher with increasing average concentrations of total irinotecan and SN-38; there was no significant association between an increased risk of neutropenia AEs (grade ≥3) at first event and average SN-38 concentrations. In summary, the PKs of total irinotecan and SN-38 after administration of liposomal irinotecan were well-described by the model. The UGT1A1*28 status had no significant impact on the PKs of liposomal irinotecan.
The Effect of GH-Releasing Peptide-2 (GHRP-2 or KP 102) on GH Secretion from Primary Cultured Ovine Pituitary Cells Can be Abolished by a Specific GH-Releasing Factor (GRF) Receptor Antagonist (1994)

A newly synthesised GH-releasing peptide, KP 102 (also named GHRP-2), was studied in an in vitro perifusion system of primary cultured ovine anterior pituitary cells. Application of KP 102 to the perifusion medium caused a dose-dependent increase in GH secretion. Dose-response relationships indicated that KP 102 had similar potency to GRF and was 10-fold more potent than earlier generations of GH-releasing peptide (GHRP-6 and GHRP-1) tested in same system. The response to a second application of KP 102 given within 1 h of initial application was significantly lower than the response to the first application. When KP 102 (or GRF) was applied first and then GRF (or KP 102) given 1 h later, the second response was not attenuated. When GRF and KP 102 were coadministered, an additive effect on release of GH was obtained. The effect of maximal dose of KP 102 (100 nM) on GH release was totally abolished by [Ac-Tyr1,D-Arg2] GRF 1-29 (1 microM) which is believed to be a specific antagonist for the GRF receptor. Blockade of Ca2+ channels by Cd2+ (2 mM) diminished the basal GH secretion and abolished the increase in GH release in response to KP 102 (100 nM). These data suggest that the action of KP 102 is blocked by a GRF receptor antagonist and therefore acts through a different receptor to that employed by earlier generations of GH-releasing peptides. GH release in response to KP 102 involves an increase in Ca2+ influx and there is no cross-desensitization between KP 102 and GRF responses.