gebhart/patrepeval huggingface dataset:
The Translation Start Codon Region Is Sensitive to Antisense PNA Inhibition in Escherichia coli (2003)

Antisense peptide nucleic acids (PNA) can inhibit bacterial gene expression with gene and sequence specificity. Using attached carrier peptides that aid cell permeation, the antisense effects when targeting essential genes are sufficient to prevent growth and even kill bacteria. However, many design uncertainties remain, including the difficult question of target sequence selection. In this study, we synthesized 90 antisense peptide-PNAs to target sequences in a head to tail manner across the entire length of the mRNA encoding beta-lactamase. The results from this scan pointed to the start codon region as most sensitive to inhibition. To confirm and refine the result, a higher-resolution scan was conducted over the start codon region of the beta-lactamase gene and the essential Escherichia coli acpP gene. For both genes, the start codon region, including the Shine-Dalgarno motif, was sensitive, whereas antisense agents targeted outside of this region were largely ineffective. These results are in accord with natural antisense mechanisms, which typically hinder the start codon region, and the sensitivity of this region should hold true for most bacterial genes as well as for other RNase H-independent antisense agents that rely on a steric blocking mechanism. Therefore, although other design parameters are also important, the start codon region in E. coli mRNA is the most reliable target site for antisense PNAs.
Target cell-restricted apoptosis induction by 528scFv-TRAIL fusion protein specific for human EGFR and expressed in Escherichia coli (2010)

We report the preparation and functional characterization of an Escherichia coli-expressed recombinant fusion protein, 528scFv-TRAIL, specific for the human epidermal growth factor receptor (EGFR) and empowered by the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). The 528scFv-TRAIL, expressed as insoluble inclusion bodies in E. coli, was solubilized and then refolded by using a modified stepwise dialysis method. Treatment with 528scFv-TRAIL resulted in the specific binding to the cell surface of EGFR-positive cells with concomitant deployment of the TRAIL moiety to DR-5 receptor in a manner comparable to a commercially available form of recombinant TRAIL (cTRAIL). 528scFv-TRAIL, prepared by either of three refolding processes described herein, showed potent cytotoxic activity against EGFR-positive TFK-1 cell line and was superior to its parental 528scFv; a recombinant variable fragment with single specificity against human EGFR. Narrow variations in the cytotoxic potential of 528scFv-TRAIL were ascribed to manipulation of redox conditions during the refolding process. Together, our findings point to the potential value of 528scFv-TRAIL for treatment of EGFR-expressing cancers. Furthermore, preparation of 528scFv-TRAIL from insoluble aggregates in a prokaryotic cell based expression system by means of in vitro refolding introduces a feasible cost-benefit, time-efficient approach for industrial-scale production.
Characterization of a 1:1 Complex of Unusual Structure in the Binary Phenothiazine: Phenazine System (1983)

Abstract The phase diagram for the binary system phenothiazine and phenazine has been examined and found to demonstrate the existence of a 1:1 phase. Crystals fo this phase are dark red in color and display a visible absorpiton spectrum which seems indicative of a π-molecular donor: acceptor complex. A crystal structure determination has been carried out; space group PC1/c: a = 9.072(2), b = 8.872(2), c = 25.934(5) Å, β = 112.65(2)°, and Z = 4. The crystal structure reverals interactions between the components that differ markedly from those commonly observed for weak π-molecular donor: acceptor complexs. Instead of the infinite stacks of alternating donor and acceptor molecules, the phenothiazine and phenazine molecules are nearly mutually perpedicular. There is an intermolecular hydrogen bond in which the phenothiazine molecule serves as the donor. A center of inversion gives rise to “dimer” in which the two phenazine molecules are stacked swith their mean planes separated by 3.714 Å. Any induced polarizatin resulting from the intermolecular hydrogen bonding in monomer is balanced by summetry in the dimer. Consequenlty, the dimer may be appropriately regarded as the crystallographic packing unit.
An unusual polyanion from Physarum polycephalum that inhibits homologous DNA-polymerase .alpha. in vitro (1989)

From extracts of microplasmodia of Physarum polycephalum and their culture medium, an unusual substance was isolated which inhibited homologous DNA polymerase alpha of this slime mold but not beta-like DNA polymerase and not heterologous DNA polymerases. Analysis, especially NMR spectroscopy, revealed the major component to be an anionic polyester of L-malic acid and the inhibition to be due to poly(L-malate) in binding reversibly to DNA polymerase alpha. The mode of inhibition is competitive with substrate DNA and follows an inhibition constant Ki = 10 ng/mL. Inhibition is reversed in the presence of spermine, spermidine, poly(ethylene imine), and calf thymus histone H1. According to its ester nature, the inhibitor is slightly labile at neutral and instable at acid and alkaline conditions. Its largest size corresponds to a molecular mass of 40-50 kDa, but the bulk of the material after purification has lower molecular masses. The inhibitory activity depends on the polymer size and has a minimal size requirement.
Myocardial Lesion Size After Epicardial Electroporation Catheter Ablation After Subxiphoid Puncture (2014)

Epicardial electroporation ablation after subxiphoid pericardial puncture can create deep, wide, and transmural ventricular myocardial lesions. There is a significant relationship between the amounts of electroporation energy delivered epicardially and lesion size in the absence of major adverse events.
Synthesis of some biologically active agents derived from thieno[2,3-d]pyrimidine derivatives. (1997)

The key compound 1-amino-8-iminocyclopenta[b]thieno[2,3-d]pyrimidine (5g) was prepared by reaction of 2-amino-3-cyano cyclopenta[b]thiophene (1) with triethyl orthoformate followed by cyclization with hydrazine hydrate in ethanol. Refluxing of 1 with triethyl orthoformate in the presence of acetic anhydride gave an unexpected product 2. while reaction with aromatic amines gave the condensation products 4a-c. Reaction of 5g with formic acid, other formate derivatives, ethoxymethylenemalononitrile and ethyl ethoxymethylenecyanoacetate gave the same product cyclopentathieno-[2,3-d]-1,2,4-triazolo[3,2-f]pyrimidine 6. Compound 7 was prepared by different methods. Treatment of 5g with dicarbonyl compounds gave the triazol derivatives 8-11. Reaction of 5g with phenyl isothiocyanate, carbon disulphide and ethyl chloroformate gave the corresponding derivatives 12-14, respectively. Condensation of 5g with some selected aromatic and heterocyclic aldehydes, acetone, N-acetyl isatin and isatin gave the condensation products 15a-e, 16-18, respectively in good yields. Many of the synthesized compounds were tested in vitro for their inhibitory activity against a variety of bacteria such as: Serratia rhodnii, Bacillus cereus, Staphylococcus citreus and Pseudomonas aeruginosa and fungi such as: Aspergillus flavus, Penicillium chrysogenum and Alternaria alternarta. Some compounds showed modest activity.
In vivo activity of ajoene against rodent malaria (1994)

Ajoene (4,5,9-trithiadodeca-1,6,11-triene 9-oxide), a product initially isolated from extracts of garlic (Allium sativum), was tested for its antimalarial activity in vivo in a well-characterized murine model. A single ajoene dose of 50 mg/kg, on the day of infection, suppressed the development of parasitemia; there were no obvious acute toxic effects from the tested dose. The combination of ajoene (50 mg/kg) and chloroquine (4.5 mg/kg), given as a single dose on the day of the infection, completely prevented the subsequent development of parasitemia in treated mice.
Pyridoxylated-Polyhemoglobin Solution: A Low Viscosity Oxygen-Delivering Blood Replacement Fluid with Normal Oncotic Pressure and Long-Term Storage Feasibility (1988)

Stroma-free hemoglobin (P50 = 14 torr, T1/2 = 3 hr, COP = 60 torr @ 15 g%) was pyridoxylated (PP-SFHb P50 = 28 torr) and then cross-linked with glutaraldehyde to yield pyridoxylated-polyhemoglobin (PP-PolyHb). Sephadex G-200 gel chromatography showed 33% to be in the 470-750,000 dalton range, 60% 470,000 MW, and 10% remaining unmodified. PP-PolyHb (14 g%), was iso-oncotic (COP = 25 torr) with plasma, and had a viscosity at 37 degrees C = 3.8 cP. Despite glutaraldehyde crosslinking PP-PolyHb retained some cooperative oxygen binding (Hill coefficient n = 1.88), with a P50 of 20 torr. MetHb levels ranged from 3.1-4.8% in fresh PP-PolyHb solutions. Storage in liquid form was possible at 4 degrees C for up to 12 months, with MetHb forming at 0.6%/month. At 25 degrees C storage was possible for 6 months if lyophilized with 3.0% glucose, after which MetHb levels rose at 9.4%/year. At -20 degrees C, the lyophilized PP-PolyHb could be stored for up to 3 years, with MetHb levels remaining below 6.0%.
Mechanisms for Lithium Insertion in Carbonaceous Materials (1995)

Lithium can be inserted reversibly within most carbonaceous materials. The physical mechanism for this insertion depends on the carbon type. Lithium intercalates in layered carbons such as graphite, and it adsorbs on the surfaces of single carbon layers in nongraphitizable hard carbons. Lithium also appears to reversibly bind near hydrogen atoms in carbonaceous materials containing substantial hydrogen, which are made by heating organic precursors to temperatures near 700°C. Each of these three classes of materials appears suitable for use in advanced lithium batteries.
Gender identification using a general audio classifier (2003)

In the context of content-based multimedia indexing gender identification using speech signal is an important task. Existing techniques are dependent on the quality of the speech signal making them unsuitable for the video indexing problems. In this paper we introduce a novel gender identification approach based on a general audio classifier. The audio classifier models the audio signal by the first order spectrum's statistics in 1s windows and uses a set of neural networks as classifiers. The presented technique shows robustness to adverse audio compression and it is language independent. We show how practical considerations about the speech in audio-visual data, such as the continuity of speech, can further improve the classification results which attain 92%.
Down-regulation of Vascular Endothelial Growth Factor in a Human Colon Carcinoma Cell Line Transfected with an Antisense Expression Vector Specific for c-src (1998)

Vascular endothelial growth factor (VEGF) is implicated in the angiogenesis of human colon cancer. Recent evidence suggests that factors that regulate VEGF expression may partially depend on c-src-mediated signal transduction pathways. The tyrosine kinase activity of Src is activated in most colon tumors and cell lines. We established stable subclones of the human colon adenocarcinoma cell line HT29 in which Src expression and activity are decreased specifically as a result of a transfected antisense expression vector. This study determined whether VEGF expression is decreased in these cell lines and whether the smaller size and reduced growth rate of antisense vector-transfected cell lines in vivo might result, in part, from reduced vascularization of tumors. Northern blot analysis of these cell lines revealed that VEGF mRNA expression was decreased in proportion to the decrease in Src kinase activity. Under hypoxic conditions, cells with decreased Src activity had a <2-fold increase in VEGF expression, whereas parental cells had a >50-fold increase. VEGF protein in the supernatants of cells was also reduced in antisense transfectants compared with that from parental cells. In nude mice, subcutaneous tumors from antisense transfectants showed a significant reduction in vascularity. These results suggest that Src activity regulates the expression of VEGF in colon tumor cells.
Trends in immunoconjugate and ligand-receptor based targeting development for cancer therapy (2007)

Many agents used to treat cancer are toxic to normal tissues. Thus, treatments delivering drug specifically to tumour, while minimising exposure to normal tissue, may be advantageous over non-targeted treatments. The exquisite specificity of the immune system has been used successfully to help develop targeted anticancer agents. The most common (and successful) tissue-specific targeting strategies rely on antibody conjugates, but additional approaches, including targeting through cytokines, peptides and recombinant viruses, have also been used successfully. This review summarises the agents exploiting the immunological principles of target specificity to help maximise delivery to tumour while minimising collateral damage to normal tissues. Such targeted molecules are collectively referred to as immunoconjugates.
Stereoselective Effects of Etomidate Optical Isomers on Gamma-aminobutyric Acid Type A Receptors and Animals (1998)

These data are consistent with the idea that the GABA(A) receptor plays a central role in the actions of etomidate. Etomidate exerts its effects on the receptor by binding directly to a specific site or sites on the protein and allosterically enhancing the apparent affinity of GABA for its receptor.
Cell surface heparan sulfate mediates some adhesive responses to glycosaminoglycan-binding matrices, including fibronectin. (1983)

Proteins with affinities for specific glycosaminoglycans (GAC's) were used as probes for testing the potential of cell surface GAG's to mediate cell adhesive responses to extracellular matrices (ECM). Plasma fibronectin (FN) and proteins that bind hyaluronate (cartilage proteo-glycan core and link proteins) or heparan sulfate (platelet factor 4 [PF4]) were adsorbed to inert substrata to evaluate attachment and spreading of several 3T3 cell lines. Cells failed to attach to hyaluronate-binding substrata. The rates of attachment on PF4 were identical to those on FN; however, PF4 stimulated formation of broad convex lamellae but not tapered cell processes fibers during the spreading response. PF4-mediated responses were blocked by treating the PF4-adsorbed substratum with heparin (but not chondroitin sulfate), or alternatively the cells with Flavobacter heparinum heparinase (but not chondroitinase ABC). Heparinase treatment did not inhibit cell attachment to FN but did inhibit spreading. Cells spread on PF4 or FN contained similar Ca2+-independent cell-substratum adhesions, as revealed by EGTA-mediated retraction of their substratum-bound processes. Microtubular networks reorganized in cells on PF4 but failed to extend into the broadly spread lamellae, where fine microfilament bundles had developed. Stress fibers, common on FN, failed to develop on PF4. These experiments indicate that (a) heparan sulfate proteoglycans are critical mediators of cell adhesion and heparan sulfate-dependent adhesion via PF4 is comparable in some, but not all, ways to FN-mediated adhesion, (b) the uncharacterized and heparan sulfate-independent "cell surface" receptor for FN permits some but not all aspects of adhesion, and (c) physiologically compatible and complete adhesion of fibroblasts requires binding of extracellular matrix FN to both the unidentified "cell surface" receptor and heparan sulfate proteoglycans.
A 750 Mb/s, 12 pJ/b, 6-to-10 GHz CMOS IR-UWB Transmitter With Embedded On-Chip Antenna (2009)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> This paper presents a novel impulse radio based ultra-wideband transmitter. The transmitter is designed in 0.18<formula formulatype="inline"><tex Notation="TeX">$\ \mu$</tex></formula>m CMOS process realizing extremely low complexity and low power. It exploits the 6-to-10 GHz band to generate short duration bi-phase modulated UWB pulses with a center frequency of 8 GHz. No additional RF filtering circuits are required since the pulse generator circuit itself has the functionality of pulse shaping. Generated pulses comply with the FCC spectral emission mask. Measured results show that the transmitter consumes 12 pJ/b to achieve a maximum pulse repetition rate of 750 Mb/s. An optional embedded on-chip antenna and a power amplifier operating in 6–10 GHz band are also designed and investigated as a future low cost solution for very short distance IR-UWB communications. </para>
The V Protein of Simian Virus 5 Inhibits Interferon Signalling by Targeting STAT1 for Proteasome-Mediated Degradation (1999)

To replicate in vivo, viruses must circumvent cellular antiviral defense mechanisms, including those induced by the interferons (IFNs). Here we demonstrate that simian virus 5 (SV5) blocks IFN signalling in human cells by inhibiting the formation of the IFN-stimulated gene factor 3 and gamma-activated factor transcription complexes that are involved in activating IFN-alpha/beta- and IFN-gamma-responsive genes, respectively. SV5 inhibits the formation of these complexes by specifically targeting STAT1, a component common to both transcription complexes, for proteasome-mediated degradation. Expression of the SV5 structural protein V, in the absence of other virus proteins, also inhibited IFN signalling and induced the degradation of STAT1. Following infection with SV5, STAT1 was degraded in the absence of virus protein synthesis and remained undetectable for up to 4 days postinfection. Furthermore, STAT1 was also degraded in IFN-pretreated cells, even though the cells were in an antiviral state. Since pretreatment of cells with IFN delayed but did not prevent virus replication and protein synthesis, these observations suggest that following infection of IFN-pretreated cells, SV5 remains viable within the cells until they eventually go out of the antiviral state.
Surfactant Protein-A and Phosphatidylglycerol Suppress Type IIA Phospholipase A2 Synthesis via Nuclear Factor-κB (2003)

We previously showed that surfactant inhibits the synthesis of type IIA secretory phospholipase A2 (sPLA2-IIA) by alveolar macrophages. These cells have been identified as the main source of this enzyme in an animal model of acute lung injury. The aim of the present study was to identify the surfactant components involved in the inhibition of sPLA2-IIA expression in alveolar macrophages and the signaling pathways that mediate this inhibition. Our results show that various surfactant preparations can inhibit sPLA2-IIA expression in endotoxin-stimulated alveolar macrophages. Both the surfactant protein (SP)-A and the surfactant phospholipid fraction inhibit this expression. The surfactant phospholipid dioleylphosphatidylglycerol (DOPG) abolishes sPLA2-IIA expression, whereas dipalmitoylphosphatidylcholine does not. Chromatographic analysis and confocal microscopy revealed that phosphatidylglycerol was rapidly incorporated and metabolized by alveolar macrophages and that its metabolites accumulate in the cytosol. Nuclear factor-kappaB (NF-kappaB) modulates sPLA2-IIA expression in endotoxin-activated alveolar macrophages, and surfactant preparations, surfactant phospholipid fraction, SP-A, and DOPG indeed suppressed NF-kappaB activation. In summary, our results show that SP-A and DOPG play a role in the surfactant-mediated inhibition of sPLA2-IIA expression in alveolar macrophages and that this inhibition occurs via a downregulation of NF-kappaB activation.
Effect of liposomes containing sodium butyrate conjugated with anti-CD19 monoclonal antibody on in vitro and in vivo growth of malignant lymphoma. (1990)

A differentiation-inducer, sodium butyrate (SB), encapsulated in liposomes conjugated covalently to a monoclonal antibody directed to CD19 antigen, was successfully targeted to human lymphoma cell lines SKLY-18 and Ramos grown in vitro and in vivo in nude mice. Various control liposomes (lacking SB, lacking antibody, containing SB alone, or coupled to irrelevant antibody) were not effective targeters. Growth of tumor cells not expressing the relevant antigen was unaffected by the antibody-SB-liposome complex. Suppression of lymphoma growth in vivo was remarkable, and tumor regression was observed under certain conditions, although changes in morphology were not clearly observed. In view of the practical nonexistence of "tumor-specific" antigens, targeting of differentiation-inducers or growth modifiers, rather than cytotoxic drugs, to tumor cells, as exemplified in these experiments, may provide a useful approach for conversion of highly malignant to less malignant tumors, although the exact mechanism of the growth inhibitory effect on B-cell lymphoma of the anti-CD19 antibody-SB-liposome complex is unknown.
Epidemiology of Poliomyelitis in the United States One Decade after the Last Reported Case of Indigenous Wild Virus-Associated Disease (1992)

Poliomyelitis caused by wild poliovirus has been virtually nonexistent in the United States since 1980, and vaccine-associated paralytic poliomyelitis (VAPP) has emerged as the predominant form of the disease. We reviewed national surveillance data on poliomyelitis for 1960-1989 to assess the changing risks of wild-virus, vaccine-associated, and imported paralytic disease; we also sought to characterize the epidemiology of poliomyelitis for the period 1980-1989. The risk of VAPP has remained exceedingly low but stable since the mid-1960s, with approximately 1 case occurring per 2.5 million doses of oral poliovirus vaccine (OPV) distributed during 1980-1989. Since 1980 no indigenous cases of wild-virus disease, 80 cases of VAPP, and five cases of imported disease have been reported in the United States. Three distinct groups are at risk of vaccine-associated disease: recipients of OPV (usually infants receiving their first dose), persons in contact with OPV recipients (mostly unvaccinated or inadequately vaccinated adults), and immunologically abnormal individuals. Overall, 93% of cases in OPV recipients and 76% of vaccine-associated cases have been related to administration of the first or second dose of OPV. Our findings suggest that adoption of a sequential vaccination schedule (inactivated poliovirus vaccine followed by OPV) would be effective in decreasing the risk of VAPP while retaining the proven public health benefits of OPV.
Delactosed, High Milk Protein Powder. 2. Physical and Functional Properties (1991)

The objective of this research was to examine some physicochemical properties of a novel delactosed, high milk protein powder. Data indicate that the solubility index of the powder was dependent on temperature of mixing. Solubility index decreased (solubility increased) as temperature increased from 25 to WC. Foaming capacity, expressed as percentage overrun, was low at pH 7 and 8 but increased at higher pH, e.g., after 10 min of whipping, overrun increased from 470 to 941% as pH increased from 7 to 10. Foaming increased with time at higher pH but not at lower pH. Particles of the high milk protein powders as examined by scanning electron microscopy were characterized by smooth surface and dents. Particles of skim milk powder prepared in the same spray dryer had a wrinkled surface. Commercial casein products had a structure similar to that of the high milk protein powders.
Summaries of FY13 LANL Experimental Campaigns at the OMEGA Laser Facility (2013)

Abstract not provided.