gebhart/patrepeval huggingface dataset:
Inhibition of protein synthesis by antagonists of calmodulin in Ehrlich ascites tumor cells (1991)

Several recent publications indicate that Ca2+ is required for protein synthesis in mammalian cells, including the Ehrlich ascites tumor cell. The present communication examines whether the effects of Ca2+ might be mediated through calmodulin or a related protein. Four calmodulin antagonists belonging to different chemical categories were used to provide evidence of calmodulin involvement. Three of the antagonists inhibited protein synthesis in intact cells; 50% inhibitory concentrations were 10 microM calmidazolium, 12 microM N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W7) and 17.5 microM trifluoperazine (TFP). Initiation was preferentially inhibited as indicated by an increase in the 80S monomers accompanied by a significant disaggregation of polyribosomes. All the antagonists also inhibited protein synthesis initiation in the cell-free protein-synthesizing system; 50% inhibitory concentrations for compound 48/80, calmidazolium, TFP, and W7 were 10 microM, 125 microM, 300 microM and 500 microM, respectively. A weak analogue of W7 inhibited only 20% at 1000 microM. Inhibition in the cell-free system was reversed by the addition of exogenous calmodulin in all four cases. The levels of 43S complexes were significantly elevated with all four antagonists, indicating a block in the utilization of 43S complexes. The similarity of the effects of four distinct classes of antagonists and their ready reversal by exogenous calmodulin leads us to suggest that there may be a role for calmodulin or a very similar calcium-binding protein in protein synthesis.
IL-12 induces the production of IFN-gamma by neonatal human CD4 T cells. (1993)

A major difference between "naive" and "memory" or "effector" Th cells is the spectrum of cytokines that they are capable of producing. After stimulation naive cells produce only IL-2, whereas memory cells produce several cytokines including IFN-gamma and IL-4. Using umbilical cord blood-derived CD4 T cells as a source of naive T cells, we first report that these cells are capable of producing large amounts of IFN-gamma when cultured with low concentrations of IL-12. The response is time- and dose-dependent, and it is observed at the protein and mRNA levels. IL-12 also induces neonatal CD4 T cells to produce lymphotoxin but not IL-2, TNF-alpha, or IL-4. The production of IFN-gamma by IL-12-stimulated neonatal T cells is associated with a small but significant T cell activation evidenced by DNA synthesis and by the expression of the activation markers CD25, CD71, and HLA-DR; moreover, it is inhibited by hydrocortisone, cyclosporin A, and transforming growth factor-beta. The response to IL-12 is enhanced and is much more rapid when CD4 T cells are cultured in the presence of accessory cells or of exogenous IL-1, IL-2, or TNF-alpha. Using a three-step culture system, we next show that IL-12 induces the maturation of resting naive CD4 T cells into cells producing both IL-2 and IFN-gamma but not IL-4 upon stimulation with PMA and ionomycin. Endogenously produced IFN-gamma plays a role in this IL-12-induced T cell maturation, as shown by the inhibitory effect of neutralizing IFN-gamma antibodies. Finally, we show that IL-12 supports the production of IFN-gamma during primary stimulation of neonatal T cells via the CD3/TCR complex by means of either immobilized anti-CD3 mAb or superantigen-coated (Staphylococcus enterotoxin B) fixed L cell transfectants expressing HLA-DR. It is suggested that IL-12 is involved in the selection of Th1 type immune responses.
Human Bocaviruses Are Highly Diverse, Dispersed, Recombination Prone, and Prevalent in Enteric Infections (2010)

A new species of parvovirus, tentatively named human bocavirus 4 (HBoV4), was genetically characterized. Among 641 feces samples obtained from children and adults, the most commonly detected bocavirus species were, in descending order, HBoV2, HBoV3, HBoV4, and HBoV1, with an HBoV2 prevalence of 21% and 26% in Nigerian and Tunisian children, respectively. HBoV3 or HBoV4 species were found in 12 of 192 patients with non-polio acute flaccid paralysis in Tunisia and Nigeria and 0 of 96 healthy Tunisian contacts (P = .01). Evidence of extensive recombination at the NP1 and VP1 gene boundary between and within bocavirus species was found. The high degree of genetic diversity seen among the human bocaviruses found in feces specimens, relative to the highly homogeneous HBoV1, suggest that this worldwide-distributed respiratory pathogen may have recently evolved from an enteric bocavirus after acquiring an expanded tropism favoring the respiratory tract. Elucidating the possible role of the newly identified enteric bocaviruses in human diseases, including acute flaccid paralysis and diarrhea, will require further epidemiological studies.
Microstrip Yagi array antenna for mobile satellite vehicle application (1991)

A novel antenna structure formed by combining the Yagi-Uda array concept and the microstrip radiator technique is discussed. This antenna, called the microstrip Yagi array, has been developed for the mobile satellite (MSAT) system as a low-profile, low-cost, and mechanically steered medium-gain land-vehicle antenna. With the antenna's active patches (driven elements) and parasitic patches (reflector and director elements) located on the same horizontal plane, the main beam of the array can be tilted, by the effect of mutual coupling, in the elevation direction providing optimal coverage for users in the continental United States. Because the parasitic patches are not connected to any of the lossy RF power distributing circuit the antenna is an efficient radiating system. With the complete monopulse beamforming and power distributing circuits etched on a single thin stripline board underneath the microstrip Yagi array, the overall L-band antenna system has achieved a very low profile for vehicle rooftop mounting, as well as a low manufacturing cost. Experimental results demonstrate the performance of this antenna.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Nasal obstruction as a risk factor for sleep apnoea syndrome (2000)

Nasal obstruction has frequently been mentioned as a possible risk factor in obstructive sleep apnoea syndrome (OSAS). Over a 2-yr period, 541 unselected consecutive snorers referred for suspected breathing disorders during sleep were included to undergo posterior rhinomanometry. In addition cephalometric landmarks and body mass index (BMI) were obtained. Polysomnography was used to determine the number of abnormal respiratory events that occurred during sleep. OSAS was defined as 15 episodes, or more, of apnoea or hypopnoea per hour of sleep (AHI). Of the 541 consecutive snorers 528 underwent nasal resistance measurement by posterior rhinomanometry (failure rate: 2.4%). Patients with OSAS (259 patients) had higher nasal resistance than patients without OSAS (2.6+/-1.6 hPa x L x s(-1) versus 2.2+/-1.0 hPa x L x s(-1), respectively, p&lt;0.005). A stepwise multiple regression analysis showed that BMI, male sex, nasal resistance, and cephalometric parameters were contributing factors to the AHI. The r2-value of the multiple regression analysis was 0.183. Nasal resistance contributed 2.3% of the variance (p&lt;0.0001), whereas mandibular plane-hyoid distance, BMI, male sex and age contributed 6.2%, 4.6%, 3% and 1.3% of the variance, respectively. To conclude, daytime nasal obstruction is an independent risk factor for OSAS.
Simultaneous switching, noise, and reliability analyses of VLSI core logic (2003)

Summary form only given. The rapid advances in process technology have brought many new challenges to IC design. Interconnects are becoming one of the most significant factors in determining the performance of the design. With increased design complexity and reduced feature size, interconnects become more resistive, have more coupling, and cover longer distances on the chip. With the increase in operating frequencies, inductive effects also influence chip performance. Therefore, in order to produce high performance and reliable designs, the interactions in the operation of the devices in terms of the design and the interconnects, including signal lines, power distribution and clock networks, should be correctly modeled and clearly understood early in the design cycle. In this paper, we focus on voltage drop or voltage variations in power and ground buses and delay and crosstalk noise in signal interconnects. We show by theory and by examples that some of the recently published results and some of the techniques followed in industry for dealing with these problems could produce misleading (or erroneous) results. We first show the relationship between switching and timing to reliability and noise analysis, and derive fast input independent techniques to produce tight bounds on worst-case voltage variations and worst-case current flows in the power bus and on crosstalk noise and delay variations in the signal lines. The techniques we develop are also applicable to the estimation of substrate noise and to maximum leakage currents.
High-Affinity, Protective Antibodies to the Binding Domain of Botulinum Neurotoxin Type A (2001)

Monoclonal antibodies (MAbs) were prepared against the putative binding domain of botulinum neurotoxin A (BoNT/A), a nontoxic 50-kDa fragment. Initially, all fusion products were screened against the holotoxin BoNT/A and against the binding fragment, BoNT/A H(C). Eleven neutralizing hybridomas were cloned, and their specific binding to BoNT/A H(C) was demonstrated by surface plasmon resonance, with dissociation constants ranging from 0.9 to <0.06 nM. Epitope mapping by real-time surface plasmon resonance showed that the antibodies bound to at least two distinct regions of the BoNT/A H(C) fragment. These MAbs will be useful tools for studying BoNT/A interactions with its receptor, and they have potential diagnostic and therapeutic applications.
Deletion of a Cation Transporter Promotes Lysis in Streptococcus pneumoniae (2011)

ABSTRACT Streptococcus pneumoniae is a significant human pathogen which causes respiratory and serious invasive diseases. Mg 2+ is essential for life, and its concentration varies throughout the human body. Magnesium uptake plays an important role in the virulence of many bacterial pathogens. To study the Mg 2+ uptake of S. pneumoniae strain D39, a mutant was generated in SPD1383, a P-type ATPase with homology to the Salmonella Mg 2+ transporter MgtA, which has also been shown to be a Ca 2+ exporter in strain TIGR4. Under low-Ca 2+ conditions, mutation led to a growth defect in complex medium and the gene was nearly essential for growth under low-Mg 2+ conditions. Addition of Mg 2+ restored the normal growth of the mutant in all cases, but the addition of other divalent cations had no effect. Addition of Ca 2+ , Mn 2+ , and Zn 2+ in the presence of high Mg 2+ concentrations inhibited restoration of growth. The mutant was unable to proliferate in blood, which was also alleviated by the addition of Mg 2+ . The protein was located in the membrane and produced in various S. pneumoniae strains and pathogenic streptococcal species. Surprisingly, mutation of the gene led to an elevated toxicity for endothelial cells. This was caused by an increased amount of pneumolysin in the medium, mediated by elevated lysis of the mutant. Thus, in this study, we uncovered a role for SPD1383 in Mg 2+ uptake and hypothesize that the protein is a Mg 2+/ Ca 2+ antiporter. Furthermore, a disturbance in Mg 2+ homeostasis seems to promote lysis of S. pneumoniae .
Intraoperative Assessment of the Stunned versus Infarcted Myocardium with the Simultaneous Use of Transesophageal Echocardiography and the Measurement of Myocardial pH: Two Case Studies (1994)

The ability to differentiate intraoperatively between myocardial stunning, which is reversible, and irreversible myocardial infarction has major implications because it provides a rational approach to the use or withholding of ventricular assist devices in patients with severe postcardiotomy ventricular dysfunction. Two illustrative cases are presented.
A truncated glucoamylase gene fusion for heterologous protein secretion from Aspergillus niger (1993)

The secreted yield of hen egg-white lysozyme (HEWL) from the filamentous fungus Aspergillus niger was increased 10–20-fold by constructing a novel gene fusion. The cDNA sequence encoding mature HEWL was fused in frame to part of the native A. niger gene encoding glucoamylase (glaA), separated by a proteolytic cleavage site for in vivo processing. Using this construct, peak secreted HEWL yields of 1 g/l were obtained in A. niger shake flask cultures compared to about 50 mg/l when using an expression cassette lacking any glaA coding sequence. The portion of glaA used in the gene fusion encoded the first 498 amino acids of glucoamylase (G498) and comprised its secretion signal, the catalytic domain and most of the O-glycosylated linker region which, in the entire glucoamylase molecule, spatially separates and links the catalytic and starch-binding domains.
Searching and mining trillions of time series subsequences under dynamic time warping (2012)

Most time series data mining algorithms use similarity search as a core subroutine, and thus the time taken for similarity search is <i>the</i> bottleneck for virtually all time series data mining algorithms. The difficulty of scaling search to large datasets largely explains why most academic work on time series data mining has plateaued at considering a few millions of time series objects, while much of industry and science sits on billions of time series objects waiting to be explored. In this work we show that by using a combination of four novel ideas we can search and mine truly massive time series for the first time. We demonstrate the following extremely unintuitive fact; in large datasets we can exactly search under DTW much more quickly than the current state-of-the-art <i>Euclidean distance</i> search algorithms. We demonstrate our work on the largest set of time series experiments ever attempted. In particular, the largest dataset we consider is larger than the combined size of all of the time series datasets considered in all data mining papers ever published. We show that our ideas allow us to solve higher-level time series data mining problem such as motif discovery and clustering at scales that would otherwise be untenable. In addition to mining massive datasets, we will show that our ideas also have implications for real-time monitoring of data streams, allowing us to handle much faster arrival rates and/or use cheaper and lower powered devices than are currently possible.
Protection of Mice from Fatal Herpes Simplex Virus Type 1 Infection by Adoptive Transfer of Cloned Virus-specific and H-2-restricted Cytotoxic T Lymphocytes (1983)

A cloned culture of secondary anti-herpes simplex virus (anti-HSV) cytotoxic T lymphocytes (CTL) generated in vitro when adoptively transferred to intact or cyclophosphamide (CP) pretreated syngeneic mice protected the recipients from death following intraperitoneal infection with HSV-1. This in vivo protective effect conferred by anti-HSV CTL was virus-specific and H-2K/D-restricted. Twenty-four h after HSV-1 infection of BALB/c mice (intact or CP-pretreated) relatively high levels of serum interferon-gamma were observed in the recipients of syngeneic anti-HSV CTL and this event may explain, at least in part, the CTL-mediated protective effect.
Whisker based mobile robot navigation (2002)

In this paper we describe the design and implementation of a unique proportional whisker sensor and our general behaviour based software architecture. The architecture for behaviour based agents is used to realise purposive mobile robot navigation in a cluttered indoor environment. The whisker was developed specifically to meet the requirements of high speed and close wall following. We also discuss the specific architecture we have constructed.
Chloroplast Derived Antibodies, Biopharmaceuticals and Edible Vaccines (2004)

This chapter contains sections titled: Introduction Expression of Therapeutic and Human Proteins in Plants The Transgenic Chloroplast System Chloroplast-derived Human Antibodies Chloroplast-derived Biopharmaceuticals Human Serum Albumin Human Insulin-like Growth Factor-1 Human Interferon (IFNα2b) Anti-Microbial Peptides (AMPs): MSI-99 Chloroplast-derived Vaccine Antigens Cholera Toxin B Subunit (CTB) 2Bacillus anthracis Protective Antigen 3Yersinia pestis F1∼V Fusion Antigen Canine Parvovirus (CPV) VP2 Protein Advances in Purification Strategies for Biopharmaceuticals Conclusion Acknowledgements References
Mechanism of lysosome rupture by dipeptides (1995)

Low concentrations of some neutral dipeptides, such as L-Ala-L-Ala, rapidly disrupt rat liver lysosomes. The phenomenon has been attributed to an osmotic imbalance generated by the production of amino acids in the lysosome by lysosomal dipeptidase activity. This hypothesis is challenged by testing several pairs of dipeptides available in both D- and L-forms and a range of dipeptides whose susceptibility to lysosomal dipeptidase activity is known. A good correlation was found between the lytic ability of dipeptides and their capacity to cross the lysosome membrane and be hydrolysed by lysosomal dipeptidase. The osmotic-imbalance hypothesis is critically evaluated in the light of the results and of recent information concerning the carrier-mediated transport of amino acids and dipeptides across the lysosome membrane. It is concluded that intralysosomal generation of amino acids remains the most plausible explanation of the lytic activity of dipeptides, and that the dipeptide porter(s) in the lysosome membrane must have higher Km than the amino acid porters.
Construction and characterization of a single-chain catalytic antibody. (1991)

The antigen-binding (Fab) fragment of the catalytic monoclonal antibody NPN43C9 has recently been cloned by using bacteriophage lambda. By inserting the variable regions of this Fab coding sequence into a (NH2)-VL-linker-VH-(COOH) construct (where VL and VH represent the heavy and light chain variable regions), we have assembled a recombinant gene encoding a catalytic single-chain antigen-binding protein. This protein has been expressed in Escherichia coli and exhibits the same catalytic parameters as the parent monoclonal antibody NPN43C9. Single-chain forms of catalytic antibodies may prove valuable for structural and site-directed mutagenesis studies as well as for large-scale applications of catalytic antibodies.
Binding of influenza A virus NS1 protein to dsRNA in vitro (1992)

The non-structural protein NS1 of influenza A virus exhibits two modes of RNA-binding activity. One is sequence-specific binding to minus-sense virus RNA with either a 5'- or 3'-terminal common sequence as reported previously. The other was identified as binding to dsRNA and this activity did not show sequence specificity. The affinity of binding to dsRNA was much higher than that to ssRNA. A short miniature virion RNA forming a panhandle structure by pairing between the 5'- and 3'-terminal common sequences bound NS1 with higher affinity and stability than did a dsRNA of similar sequence and length.
Proteominer facilitates high‐throughput proteomic analysis of low abundance proteins in the cartilage secretome (LB39) (2014)

Proteomics is increasingly used for biomarker identification. We have developed high‐throughput mass spectrometric (MS) methods to identify proteins in the secretome of articular cartilage explants, which we are utilizing as an in vitro model of joint inflammation. However, the identification of lower abundance proteins of potentially higher biological significance in this model is hampered by the presence of highly abundant glycoproteins in the secretome. Development of protein depletion techniques that allow the identification of low abundance proteins is important for novel biomarker discovery, especially in the context of identifying pathophysiologically relevant biomarkers of joint inflammation and cartilage degradation. Proteominer protein enrichment kits decrease the dynamic range of complex biological samples, allowing improved analytical coverage of the proteome. The objective of this study was to apply high‐throughput MS techniques following proteominer enrichment to expand the range of proteins that can be identified in the secretome of cartilage exposed to proinflammatory cytokines such as IL‐1β. Explant cultures were established in DMEM + 2% Pen/Strep, using metacarpophalangeal joints of horses. Explants were either untreated controls or treated with 10 ng/ml IL‐1β. After incubating for 6 days at 37⁰C in a humidified environment (95% air, 5% CO 2 ) proteins in culture supernatants were concentrated ~24 fold using Centriplus YM‐3 and Centricon‐3 (3000 MWCO) centrifugal filter units. Concentrated samples were processed with a Small Capacity Proteominer™ Protein Enrichment Kit (Bio‐Rad). After elution, samples were reduced, alkylated, acetone precipitated and trypsin digested overnight, before digested peptides were applied to C18 spin columns, followed by nanoLC‐MS/MS analysis on an amaZon speed ETD. Extracellular matrix proteins identified in untreated control secretome included cartilage oligomeric matrix protein (COMP), fibromodulin and fibronectin. Macrophage migration inhibitory factor (MIF), serum amyloid A protein (SAA) and Heat shock 70 kDa protein 1‐like (HSP70) were identified in explants exposed to IL‐1β. Identification of new low abundance proteins in this model will facilitate a greater understanding of inflammatory processes occurring within cartilage. Grant Funding Source : Supported by Biotechnology and Biological Sciences Research Council (BBSRC) (Contract grant number: BB/G018030/1) and the European Commission Framework 7 program (EU FP7; HEALTH.2012.2.4.5–2, project number 305815).
Active site-blocked factor IXa prevents intravascular thrombus formation in the coronary vasculature without inhibiting extravascular coagulation in a canine thrombosis model. (1991)

To assess the contribution of Factor IX/IXa, to intravascular thrombosis, a canine coronary thrombosis model was studied. Thrombus formation was initiated by applying current to a needle in the circumflex coronary artery. When 50% occlusion of the vessel developed, the current was stopped and animals received an intravenous bolus of either saline, bovine glutamyl-glycyl-arginyl-Factor IXa (IXai), a competitive inhibitor of Factor IXa assembly into the intrinsic Factor X activation complex, bovine Factor IX, or heparin. Animals receiving saline or Factor IX developed coronary occlusion due to a fibrin/platelet thrombus in 70 +/- 11 min. In contrast, infusion of IXai prevented thrombus formation completely (greater than 180 min) at doses of 460 and 300 micrograms/kg, and partially blocked thrombus formation at 150 micrograms/kg. IXai attenuated the accumulation of 125I-fibrinogen/fibrin at the site of the thrombus by approximately 67% (P less than 0.001) and resulted in approximately 26% decrease in serotonin release from platelets in coronary sinus (P less than 0.05). Hemostatic variables in animals receiving IXai, remained within normal limits. Animals given heparin in a concentration sufficient to prevent occlusive thrombosis had markedly increased bleeding, whereas heparin levels that maintained extravascular hemostasis did not prevent intracoronary thrombosis. This suggests that Factor IX/IXa can contribute to thrombus formation, and that inhibition of IXa participation in the clotting mechanism blocks intravascular thrombosis without impairing extravascular hemostasis.
Iron-induced hypophosphatemia (2017)

Diagnosis of iron-induced hypophosphatemia requires clinical suspicion. Treatment is guided by the severity of hypophosphatemia, and most patients will require oral or intravenous phosphate substitution. Future treatment options could involve therapeutic anti-FGF23 antibody (KRN23). Prevention and correction of vitamin D deficiency represents a supportive treatment option.