gebhart/patrepeval huggingface dataset:
Isolation and Characterization of a Novel Protein (X-ORF Product) from SIV and HIV-2 (1988)

A protein designated p14 was purified from a simian immunodeficiency virus (SIVMne) and was shown by amino acid sequence analysis to be nearly identical to the predicted translational product of a unique open reading frame (X-ORF) in the nucleotide sequences of SIVmac and human immunodeficiency virus type 2 (HIV-2). Thus the X-ORF is proven to be a new retroviral gene. The p14 is present in SIVMne in molar amounts equivalent to those of the gag proteins. This is the first example of a retrovirus that contains a substantial quantity of a viral protein that is not a product of the gag, pro, pol, or env genes. SIV p14 and its homolog in HIV-2 may function as nucleic acid binding proteins since purified p14 binds to single-stranded nucleic acids in vitro. Antisera to the purified protein detected p14 in SIVMne, SIVmac, and a homologous protein (16 kilodaltons) in HIV-2 but did not react with HIV-1. Diagnostic procedures based on this novel protein will distinguish between HIV-1 and HIV-2.
"CD3low" human thymocyte populations can readily be triggered via the CD2 and/or CD28 activation pathways whereas the CD3 pathway remains nonfunctional. (1990)

We have investigated the role of the CD2 and the CD28 Ag-independent pathways of activation on CD3low thymocytes. We previously showed that anti-CD28 mAb synergized with anti-CD2 mAb directed against epitopes T11.1 and T11.2, in the activation of purified resting T cells or unseparated thymocytes. Proliferation induced via CD2 plus CD28 was mediated via an IL-2-dependent pathway and was not affected by prior modulation of the CD3-TCR complex. Here, we show that a subset of CD3low thymocytes, although unresponsive to CD3 activation, can be activated to proliferate through the CD2 or the CD28 pathways, in the presence of exogenous IL-2. The mitogenic combination of mAb to CD2 and CD28 induces a proliferation of thymocytes which, in absence of exogenous lymphokines, is restricted to the more mature intrathymic subpopulation, CD1a-. However, CD3low thymocytes can also be triggered through the CD2 plus CD28 activation pathways but require at least addition of exogenous IL-2 to proliferate. This study demonstrates that a fraction of immature CD3low thymocytes possesses functional CD2 and CD28 surface molecules at a time when CD3 is not yet functional.
Membrane Microdomain Disassembly Inhibits MRSA Antibiotic Resistance (2017)

A number of bacterial cell processes are confined functional membrane microdomains (FMMs), structurally and functionally similar to lipid rafts of eukaryotic cells. How bacteria organize these intricate platforms and what their biological significance is remain important questions. Using the pathogen methicillin-resistant Staphylococcus aureus (MRSA), we show here that membrane-carotenoid interaction with the scaffold protein flotillin leads to FMM formation, which can be visualized using super-resolution array tomography. These membrane platforms accumulate multimeric protein complexes, for which flotillin facilitates efficient oligomerization. One of these proteins is PBP2a, responsible for penicillin resistance in MRSA. Flotillin mutants are defective in PBP2a oligomerization. Perturbation of FMM assembly using available drugs interferes with PBP2a oligomerization and disables MRSA penicillin resistance in vitro and in vivo, resulting in MRSA infections that are susceptible to penicillin treatment. Our study demonstrates that bacteria possess sophisticated cell organization programs and defines alternative therapies to fight multidrug-resistant pathogens using conventional antibiotics.
Optimisation of the 10-23 DNAzyme-substrate pairing interactions enhanced RNA cleavage activity at purine-cytosine target sites (2003)

The 10-23 RNA cleaving DNAzyme has been shown to cleave any purine-pyrimidine (RY) junction under simulated physiological conditions. In this study, we systematically examine the DNAzymes relative activity against different RY combinations in order to determine the hierarchy of substrate core dinucleotide sequence susceptibility. The reactivity of each substrate dinucleotide compared in the same background sequence with the appropriately matched DNAzyme was found to follow the scheme AU = GU >> or = GC >> AC. The relatively poor activity of the DNAzyme against AC and GC containing substrates was found to be improved substantially by modifications to the binding domain which subtly weaken its interaction with the substrate core. The most effective modification resulting in rate enhancement of up to 200-fold, was achieved by substitution of deoxyguanine with deoxyinosine such that the base pair interaction with the RNA substrates core C is reduced from three hydrogen bonds to two. The increased cleavage activity generated by this modification could be important for application of the 10-23 DNAzyme particularly when the target site core is an AC dinucleotide.
Lesion Size Estimator of Cardiac Radiofrequency Ablation at Different Common Locations With Different Tip Temperatures (2004)

Finite element method (FEM) analysis has become a common method to analyze the lesion formation during temperature-controlled radiofrequency (RF) cardiac ablation. We present a process of FEM modeling a system including blood, myocardium, and an ablation catheter with a thermistor embedded at the tip. The simulation used a simple proportional-integral (PI) controller to control the entire process operated in temperature-controlled mode. Several factors affect the lesion size such as target temperature, blood flow rate, and application time. We simulated the time response of RF ablation at different locations by using different target temperatures. The applied sites were divided into two groups each with a different convective heat transfer coefficient. The first group was high-flow such as the atrioventricular (AV) node and the atrial aspect of the AV annulus, and the other was low-flow such as beneath the valve or inside the coronary sinus. Results showed the change of lesion depth and lesion width with time, under different conditions. We collected data for all conditions and used it to create a database. We implemented a user-interface, the lesion size estimator, where the user enters set temperature and location. Based on the database, the software estimated lesion dimensions during different applied durations. This software could be used as a first-step predictor to help the electrophysiologist choose treatment parameters.
A generalization of weighted subspace fitting to full-rank models (2001)

The idea of subspace fitting provides a popular framework for different applications of parameter estimation and system identification. Previously, some algorithms have been suggested based on similar ideas, for a sensor array processing problem where the underlying data model is not low rank. We show that two of these algorithms (DSPE and DISPARE) fail to give consistent estimates and introduce a general class of subspace fitting-like algorithms for consistent estimation of parameters from a possibly full-rank data model. The asymptotic performance is analyzed, and an optimally weighted algorithm is derived. The result gives a lower bound on the estimation performance for any estimator based on a low-rank approximation of the linear space spanned by the sample data. We show that in general, for full-rank data models, no subspace-based method can reach the Cramer-Rao lower bound (CRB).
Large Scale Outbreak of Yersinia pseudotuberculosis Serotype 5a Infection at Noheji-machi in Aomori Prefecture (1993)

In June 1991, there were large scale outbreaks of Yersinia pseudotuberculosis at 4 primary schools and 1 junior highschool in Noheji-machi in Aomori Prefecture. A total of 732 patients (725 pupils and school children, 7 teachers and personnel) were affected and 134 were hospitalized. Sex ratio of incidence was 1.1: 1.0 without appreciable difference. Clinicalsymptoms (478 patients) were represented frequently by pyrexia (86.4%), eruption (73.8%), abdominal pain (66.7%), vomitingnausea (63.4%), etc., and were characterized by a strawberry tongue, pharyngeal redness, membranous desquamation of the fingers and arthralgia during convalescence.Yersinia pseudotuberculosis was isolated from 27 (81.8%) of 33 patients stool specimens, 1 waste water specimen and 2 (11.7%) of 17 cooking employees' stool specimens.The isolates were confirmed serotype 5a, and positive for calcium-dependency and autoagglutination, and harboring 40-50 megadalton virulent plasmid. Restrictive endonuclease digestive pattern of pasmid proved to be identical.In many cases, patients' serum antibody titer showed a significant increase ratio to the isolated strain.In term of drug susceptibility, all the strains were sensitive to cefem, penicillin and aminoglycoside series and resistant to macrolide and sulfa series.The infectious source was limited to the school feeding, but the responsible food remained unknown. Mean latency and exposure day were presumed to be 6.5 days and May 30, respectively.
Characterization of an ATP Translocase Identified in the Destructive Plant Pathogen “ Candidatus Liberibacter asiaticus” (2009)

ATP/ADP translocases transport ATP across a lipid bilayer, which is normally impermeable to this molecule due to its size and charge. These transport proteins appear to be unique to mitochondria, plant plastids, and obligate intracellular bacteria. All bacterial ATP/ADP translocases characterized thus far have been found in endosymbionts of protozoa or pathogens of higher-order animals, including humans. A putative ATP/ADP translocase was uncovered during the genomic sequencing of the intracellular plant pathogen "Candidatus Liberibacter asiaticus," the causal agent of citrus huanglongbing. Bioinformatic analysis of the protein revealed 12 transmembrane helices and predicted an isoelectric point of 9.4, both of which are characteristic of this family of proteins. The "Ca. Liberibacter asiaticus" gene (nttA) encoding the translocase was subsequently expressed in Escherichia coli and shown to enable E. coli to import ATP directly into the cell. Competition assays with the heterologous E. coli system demonstrated that the translocase was highly specific for ATP and ADP but that other nucleotides, if present in high concentrations, could also be taken up and/or block the ability of the translocase to import ATP. In addition, a protein homologous to NttA was identified in "Ca. Liberibacter solanacearum," the bacterium associated with potato zebra chip disease. This is the first reported characterization of an ATP translocase from "Ca. Liberibacter asiaticus," indicating that some intracellular bacteria of plants also have the potential to import ATP directly from their environment.
Peripherin, a New Member of the Intermediate Filament Protein Family (1983)

Peripherin, a Triton-insoluble protein, whose distribution was found to be restricted to neurons in the rodent and human peripheral nervous system, was characterized by its electrophoretic features (isoelectric point: 5.6; molecular weight: 56,000 daltons) and by its peptidic map after limited proteolysis. Comparative peptide analysis of the 70,000-dalton subunit of neurofilaments (70K NFP), vimentin and peripherin, was performed by two different methods; limited proteolysis with Staphylococcus aureus V8 protease yields a different peptidic map for each protein; treatment with N-chlorosuccinimide, which cleaves preferentially at tryptophan residues, yields only two peptides from each protein: the size of the two fragments indicates that these proteins possess a single tryptophan residue located in the central part of the molecule. A rabbit antiserum raised against mouse peripherin decorated an intracellular filamentous network in mouse neuroblastoma NIE 115 cell line. The IgG fraction of the antiserum recognizes peripherin and the smallest subunit of the neurofilament triplet (70K NFP)--but not vimentin--whereas a monoclonal anti-70K NFP recognizes only the 70K NFP. Moreover, peripherin displays the common antigenic determinant shared by all intermediate filament proteins. Hence, we propose that peripherin represents a new member of the intermediate filament protein family, and might belong to the neurofilament class.
Respiratory Syncytial Virus Induces Selective Production of the Chemokine RANTES by Upper Airway Epithelial Cells (1997)

The presence of histamine and eosinophil cationic protein in nasopharyngeal secretions of infants with respiratory syncytial virus (RSV)-induced bronchiolitis implies the activation of basophil and eosinophil leukocytes, but the specific mechanism of their recruitment has not been elucidated. Chemokines are potent and selective leukocyte chemotactic molecules that are also expressed by airway epithelial cells. Therefore, the pattern of chemokines produced in response to RSV infection was investigated in primary cultures of human nose- and adenoid-derived epithelial cells. Interleukin-8, growth-related peptide-alpha, and monocyte chemotactic protein-1 were constitutively released by uninfected epithelial cells and were not further enhanced by infection with RSV. RANTES (regulated upon activation, normal T cell-expressed and -secreted), which was present in negligible concentrations in uninfected cultures, was strongly induced by RSV infection, in a dose- and time-dependent manner. Through the release of RANTES, epithelial cells may control the selective concentration and activation of basophils and eosinophils in RSV-infected airway mucosa.
Improved Methods of Retroviral Vector Transduction and Production for Gene Therapy (1994)

To facilitate clinical applications of retroviral-mediated human gene transfer, retroviral vectors must be of high titer and free of detectable replication-competent retroviruses. The purpose of this study was to optimize methods of retroviral vector production and transduction. Studies were conducted using 22 retroviral vector producer cell lines. Inactivation of retroviral vectors was greater at 37 degrees C than at 32 degrees C. A 5- to 15-fold increase of vectors was produced at 32 degrees C compared to 37 degrees C; the vector increase at 34 degrees C was intermediate. For example, PA317/G1Na.40 grew to a titer of 1.8 x 10(7) cfu/ml at 32 degrees C, compared to 5.0 x 10(5) cfu/ml at 37 degrees C. The production of retroviral vectors was scalable achieving similar results in flasks, roller bottles, or a CellCube Bioreactor. Retroviral vectors were concentrated 15-24 times with vector recovery ranging from 91 to 96% in a Pellicon tangential flow filtration system. Retroviral supernatants were successfully lyophilized. The combination of glucose or sorbitol with gelatin resulted in recovery rates of 64-83%. In studies on transduction by retroviral vectors, centrifugation of vector supernatants onto target cells significantly increased transduction efficiency as measured by vector titration for G418 resistance, fluorescence-activated cell sorting (FACS), and polymerase chain reaction (PCR) analyses. The combination of the above methods has significantly increased the growth and transduction by this vector system.
Transcription of Click‐Linked DNA in Human Cells (2014)

Click DNA ligation promises an alternative to the current enzymatic approaches for DNA assembly, with the ultimate goal of using efficient chemical reactions for the total chemical synthesis and assembly of genes and genomes. Such an approach would enable the incorporation of various chemically modified bases throughout long stretches of DNA, a feat not possible with current polymerase-based methods. An unequivocal requirement for this approach is the biocompatibility of the resulting triazole-linked DNA. The correct function of this unnatural DNA linker in human cells is demonstrated here by using a click-linked gene encoding the fluorescent protein mCherry. Reverse transcription of mRNA isolated from these cells and subsequent sequencing of the mCherry cDNA shows error-free transcription. Nucleotide excision repair (NER) is shown to not play a role in the observed biocompatibility by using a NER-deficient human cell line. This is the first example of a non-natural DNA linker being functional in a eukaryotic cell.
Circulating Interleukin-1 and Tumor Necrosis Factor in Septic Shock and Experimental Endotoxin Fever (1990)

Interleukins (IL) -1 beta and -1 alpha and tumor necrosis factor (TNF-alpha) were measured by radioimmunoassay in plasma samples from 44 healthy individuals, 15 patients in septic shock, and 6 volunteers infused with endotoxin. Plasma IL-1 alpha levels were low (40 pg/ml) or undetectable in all situations. In 67% of the healthy subjects, plasma IL-1 beta levels were less than 70 pg/ml. Septic patients had higher plasma IL-1 beta levels (120 +/- 17 pg/ml, P = .001); those of surviving patients were higher than those of patients who died (P = .05). Plasma TNF-alpha concentrations in septic individuals were elevated (119 +/- 30 pg/ml) and correlated with severity of illness (r = .73, P = .003), but no correlation was observed between plasma IL-1 beta and TNF-alpha concentrations in individual samples. Infusion of endotoxin caused a twofold elevation of IL-1 beta, from a baseline of 35 +/- 5 pg/ml to a maximum of 69 +/- 27 pg/ml at 180 min (P less than .05). Peak TNF-alpha levels after endotoxin infusion were 15 times higher than IL-1 beta levels, were attained more rapidly (90 min), and as with the septic patients, did not correlate with IL-1 beta levels. These data support the concept that plasma IL-1 beta and TNF-alpha concentrations are regulated independently and are associated with different clinical outcomes.
PEGylated Protein Drugs: Basic Science and Clinical Applications (2009)

PEGylation technology and key applications are introduced by this topical volume. Basic physical and chemical properties of PEG as basis for altering/improving in vivo behaviour of PEG-conjugates such
Impulse response measurement using Golay codes (2005)

This paper describes a digital processing technique for measuring the impulse response of a system. The method utilizes "complementary" codes as described by Golay in 1961 and has been employed by designers of radar, communications and other equipment. This paper discusses the implementation of the technique in a device that measures the impulse response of audio bandwidth systems. The paper begins by describing the general problem of impulse response measurement using digital methods. This leads to a "unit pulse" response sequence that completely characterizes a bandlimited, linear and time-invariant system. Next, Schroeder's (1979) method of probing the system with pseudo-random noise and correlating the result to obtain an estimate of this response is discussed. Our method is a variation on this scheme wherein the system is probed twice using sequences chosen from among the Golay codes. These codes have the remarkable property that their autocorrelation functions have complementary side-lobes. Finally, the response of a speaker/microphone pair is measured using the proposed method.
Cytokine Detection and Modulation in Acute Graft vs. Host Disease in Mice (1993)

A murine model for acute lethal graft vs. host disease (GVHD) was used to study the role that a number of cytokines play in the development of lethal GVHD. In this study we focused on the role of IL-1, IL-2, IL-4, IL-6, IFN-gamma and TNF-alpha. Lethally irradiated (C57BL x CBA)F1 mice were reconstituted either with 10(7) allogeneic BALB/c spleen cells or with a similar number of syngeneic cells, as a control. A significant rise in serum levels of IL-6, TNF-alpha and IFN-gamma levels was found in allogeneically reconstituted mice. This is in contrast to the syngeneic control group in which no rise was seen. Serum IL-2 and IL-4 levels were below the detection limit. In the supernatant of Con A stimulated spleen cells from allogeneically reconstituted mice IL-6, IFN-gamma and TNF-alpha concentrations were increased. The expression of mRNA for cytokines as detected by reverse transcription PCR was studied in spleen cells. In the allogeneic reconstituted mice the mRNA expression of IL-1alpha, IL-2, IL-6, IFN-gamma and TNF-alpha displayed faster kinetics compared with that in syngeneic reconstituted mice. The effect of treatment with recombinant cytokines, antibodies to cytokines and to cytokine receptors on the development of GVHD was investigated. Administration of recombinant IL-2 to allogeneically reconstituted mice strongly increased the morbidity and mortality whereas injection of IL-1alpha and TNF-alpha did not influence survival. Administration of antibodies against IL-2 or the IL-2 receptor decreased the morbidity and mortality. Anti-IL-6, anti-IFN-gamma, and anti-TNF-alpha mAB, on the other hand, did not affect the morbidity and mortality of GVHD. The results of this study suggest successive waves of cytokine-secreting cell populations consistent with the induction of an inflammatory response in the development of acute GVH disease.
The preparation and properties of novel reversible polymer‐protein conjugates 2‐ω‐Methoxypolyethylene (5000) glycoxymethylene‐3‐methylmaleyl conjugates of plasminogen activators (1987)

The preparation of a reagent capable of reversibly attaching polyethylene glycol to proteins and the use of this material in modifying the plasminogen activators urokinase- and tissue-type plasminogen activator are described. The characterisation and the reversible nature of these protein-polymer conjugates are discussed, and some of the in vitro properties of these modified enzymes are explored.
Role of IL-15, IL-2, and their receptors in the development of T cell alveolitis in pulmonary sarcoidosis (1996)

Recent data suggest that the newly discovered cytokine IL-15 cooperates with IL-2 in driving T cell-mediated immune responses. The aim of this study was to determine the role of IL-15 in the regulatory networks leading to the development of T cell alveolitis in the lung of patients with sarcoidosis. We demonstrated that alveolar macrophages (AMs) isolated from the bronchoalveolar lavage of patients with active sarcoidosis expressed IL-15 mRNA and membrane and cytoplasmic IL-15, while AMs from healthy subjects and patients with inactive sarcoidosis did not. Pulmonary CD4+ T cells from sarcoid patients were equipped with the IL-2R subunits, which are able to bind IL-15, i.e., the IL-2R beta/IL-2R gamma complex, and proliferated in response to IL-15. Interestingly, the T cell proliferation elicited by IL-15 was comparable with that determined by IL-2. Following the addition of graded amounts of IL-15, IL-2-pulsed T cells showed a significant increase in their stimulation. TNF-alpha up-regulated the IL-15-mediated proliferative response of bronchoalveolar lavage T lymphocytes. Following the block of the IL-2R beta- and gamma-chains with specific mAbs, the stimulatory activity of IL-15 was abolished. The evaluation of the IL-2R on sarcoid AMs demonstrated the constitutive expression of alpha- and gamma-chain mRNA and proteins. Taken together, these findings demonstrate that IL-15 triggers the growth of sarcoid T cells through the IL-2R beta/IL-2R-gamma complex and raise the possibility that AMs may deliver proliferative signals for the development of the T cell alveolitis. Modulation of IL-2R on AMs could represent a critical variable in regulating local inflammatory responses.