gebhart/patrepeval huggingface dataset:
Pyrene Excimer Fluorescence:  A Spatially Sensitive Probe To Monitor Lipid-Induced Helical Rearrangement of Apolipophorin III (2000)

Manduca sexta apolipophorin III (apoLp-III), an 18-kDa, monomeric, insect hemolymph apolipoprotein, is comprised of five amphipathic alpha-helices arranged as a globular bundle in the lipid-free state. Upon lipid binding, it is postulated that the bundle opens, exposing a continuous hydrophobic surface which becomes available for lipid interaction. To investigate lipid binding-induced helical rearrangements, we exploited the unique fluorescence characteristics of N-(1-pyrene)maleimide. Pyrene is a spatially sensitive extrinsic fluorescent probe, which forms excited-state dimers (excimers) upon close encounter with another pyrene molecule. Cysteine residues were introduced into apoLp-III (which otherwise lacks cysteine) at Asn 40 (helix 2) and/or Leu 90 (helix 3), creating two single-cysteine mutants (N40C-apoLp-III and L90C-apoLp-III) and N40C/L90C-apoLp-III, a double-cysteine mutant, which were labeled with pyrene maleimide. Pyrene-labeled N40C/L90C-apoLp-III, but not the pyrene-labeled single-cysteine mutants, exhibited strong excimer fluorescence in the lipid-free, monomeric state. Guanidine hydrochloride titration and temperature studies revealed a loss in excimer fluorescence, accompanied by a loss in the molar ellipticity of the protein. When apoLp-III interacts with phospholipid vesicles to form disklike complexes, a significant loss in excimer fluorescence was noted, indicating that the helices bearing the pyrene moieties diverge from each other. Pyrene excimer fluorescence was further employed to examine the relative orientation of lipid-bound apoLp-III molecules. Pyrene-labeled N40C- or L90C-apoLp-III displayed no excimer fluorescence in the disk complexes, while complexes prepared with an equal mixture of both single-labeled mutants did emit excimer fluorescence, indicating apoLp-III adopts a preferred nonrandom orientation around the perimeter of the bilayer disk. These studies establish pyrene excimer fluorescence as a useful spectroscopic tool to address intra- and intermolecular interactions of exchangeable apolipoproteins upon binding to lipid.
Cost of Home Canning (1989)

Publication is a cost analysis of estimated costs involved with home canning.
Combating Drug-Resistant Bacteria:  Small Molecule Mimics of Plasmid Incompatibility as Antiplasmid Compounds (2004)

A major mechanism for bacterial resistance to antibiotics is through the acquisition of a plasmid coding for resistance-mediating proteins. Described herein is a strategy to eliminate these plasmids from bacteria, thus resensitizing the bacteria to antibiotics. This approach involves mimicking a natural mechanism for plasmid elimination, known as plasmid incompatibility. The compound apramycin was identified as a tight binder to SLI RNA (Kd = 93 nM), the in vivo target of the plasmid incompatibility determinate RNA I, and footprinting/mutagenesis studies indicate apramycin binds SLI in the important regulatory region that dictates plasmid replication control and incompatibility. In vivo studies demonstrate that this compound causes significant plasmid loss and resensitizes bacteria to conventional antibiotics. The demonstration that a small molecule can mimic incompatibility, cause plasmid elimination, and resensitize bacteria to antibiotics opens up new targets for antibacterial research.
Use of Peptides for the Management of Alzheimer’s Disease: Diagnosis and Inhibition (2018)

Alzheimer's disease (AD) is a form of dementia and the most common progressive neurodegenerative disease (ND). The targeting of amyloid-beta (Aβ) aggregation is one of the most widely used strategies to manage AD, and efforts are being made globally to develop peptide-based compounds for the early diagnosis and treatment of AD. Here, we briefly discuss the use of peptide-based compounds for the early diagnosis and treatment of AD and the use of peptide-based inhibitors targeting various Aβ aggregation checkpoints. In addition, we briefly discuss recent applications of peptide-based inhibitors against various AD targets including amyloid beta, β-site amyloid precursor protein cleaving enzyme 1 (BACE1), Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), tyrosine phosphatase (TP) and potassium channel KV1.3.
Tobacco-specific nitrosamine adducts: studies in laboratory animals and humans. (1993)

This paper describes quantitation of human hemoglobin and DNA adducts of the carcinogenic tobacco-specific nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN). NNK and NNN are believed to be involved in cancers of the lung, esophagus, oral cavity, and pancreas in people who use tobacco products. The adduct dosimetry method employs GC-MS for quantitation of 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) released by mild base hydrolysis of hemoglobin or acid hydrolysis of DNA as a biochemical marker of the pyridyloxobutylation metabolic activation pathway. Approximately 22% of smokers (n = 101) had elevated levels of HPB released from hemoglobin (range, 200-1600 fmole/g Hb). Adduct levels in snuff dippers ranged from 200-1800 fmole/g Hb. HPB levels in nonsmokers were generally below the detection limit. Acid hydrolysis of lung and tracheal DNA obtained at autopsy and analysis for released HPB revealed levels ranging up to 50 fmole/mg DNA in smokers; the adduct was not detected in nonsmokers. These findings are consistent with data generated in studies of adduct formation by NNK in rats. The biological significance of the HPB-releasing DNA pyridyloxobutylation pathway was compared to that of the DNA methylation pathway in the A/J mouse. These studies demonstrated that the persistence of O6-methylguanine in lung DNA is critical for tumorigenesis by NNK and that pyridyloxobutylation enhances both persistence of O6-methylguanine and tumorigenesis by acetoxymethylmethylnitrosamine. In the rat, the relative roles of methylation and pyridyloxobutylation in lung tumorigenesis by NNK are not as clearly defined.(ABSTRACT TRUNCATED AT 250 WORDS)
Tandem Mass Spectrometry (2019)

One of the most important analytical techniques among mass spectrometric methodologies is tandem mass spectrometry (MS/MS). During MS/MS procedure, the ions are fragmented. There are two options that allow for separation of the parent ion from the remaining ions on MS spectrum: separation in space (tandem in space) and separation in time (tandem in time). This chapter discusses most important parameters of mass spectrometers usually used in routine fragmentation of the ions. One of the most important applications of MS/MS in life sciences is peptide sequencing. Peptides, known as relatively big molecules, having numerous covalent bonds of the same energies, can dissociate during fragmentation process, generating complex MS/MS spectra. Sequential Windowed Acquisition of All Theoretical Fragment Ion Mass Spectra (SWATH) was designed for a special type of analyses; the technique is used for simultaneous sequence determination of hundreds of peptides derived from the proteomic samples. SWATH analysis is used in liquid chromatography-MS/MS systems only.
Metabolic Abnormalities Characteristic of Dysmetabolic Syndrome Predict the Development of Transplant Coronary Artery Disease (2001)

These data suggest that insulin resistance plays a role in TXCAD:
Metallic Single-Crystal CoSi Nanowires via Chemical Vapor Deposition of Single-Source Precursor (2006)

We report the synthesis, structural characterization, and electrical transport properties of free-standing single-crystal CoSi nanowires synthesized via a single-source precursor route. Nanowires with diameters of 10-150 nm and lengths of greater than 10 mum were synthesized through the chemical vapor deposition of Co(SiCl(3))(CO)(4) onto silicon substrates that were covered with 1-2 nm thick SiO(2). Transmission electron microscopy confirms the single-crystal structure of the cubic CoSi. X-ray absorption and emission spectroscopy confirm the chemical identity and show the expected metallic nature of CoSi, which is further verified by room-temperature and low-temperature electrical transport measurements of nanowire devices. The average resistivity of CoSi nanowires is found to be about 510 muOmega cm. Our general and rational nanowire synthesis approach will lead to a broad class of silicide nanowires, including those metallic materials that serve as high-quality building blocks for nanoelectronics and magnetic semiconducting Fe(1-x)Co(x)Si suitable for silicon-based spintronics.
Cartilage-Characteristic Matrix Reconstruction by Sequential Addition of Soluble Factors During Expansion of Human Articular Chondrocytes and Their Cultivation in Collagen Sponges (2011)

Dedifferentiation of chondrocytes occurred during cell expansion on plastic, and FI stimulated this dedifferentiation. We found that addition of BIT could trigger chondrocyte redifferentiation and cartilage-characteristic matrix production in the collagen sponges. The presence of FI during cell expansion increased the chondrocyte responsiveness to BIT.
Unrestricted Hybridization of Oligonucleotides to Structure-Free DNA (2006)

The existence of secondary structure in long single-stranded DNA and RNA is a serious obstacle to the practical use of short oligonucleotide probes (<20-mers). Here, we show that replication of a highly structured DNA in the presence of a unique set of dNTP analogues leads to synthesis of daughter DNA with a significantly reduced level of secondary structure. This replicated DNA, composed of 2-aminoadenine, 2-thiothymine, 7-deazaguanine, and cytosine bases, was readily accessible to tiled 8-mer LNA and 15-mer DNA probes, whereas an unmodified version of the same DNA was inaccessible. Importantly, while the base analogues enhanced probe-target stability, they did not significantly reduce the specificity of base pairing. The availability of structure-free DNA targets should facilitate the use of short oligonucleotide probes and promote development of generic oligonucleotide microarrays.
An integrated quantification method to increase the precision, robustness, and resolution of protein measurement in human plasma samples (2015)

We demonstrated that InteQuan is a simple yet robust quantification method for MS-based quantitative proteomics, especially for applications in biomarker research and in routine clinical testing.
The Complete Primary Structure of Protein Kinase C—the Major Phorbol Ester Receptor (1986)

Protein kinase C, the major phorbol ester receptor, was purified from bovine brain and through the use of oligonucleotide probes based on partial amino acid sequence, complementary DNA clones were derived from bovine brain complementary DNA libraries. Thus, the complete amino acid sequence of bovine protein kinase C was determined, revealing a domain structure. At the amino terminal is a cysteine-rich domain with an internal duplication; a putative calcium-binding domain follows, and there is at the carboxyl terminal a domain that shows substantial homology, but not identity, to sequences of other protein kinase.
Boron-loaded macromolecules in experimental physiology: tracing by neutron capture radiography (1984)

The search for suitable methods of attaching the boron isotope 10B to tumour cells in the human body for the treatment of malignant disease has prompted a study of ways of optimising the localisation of 10B in mammalian tissues. Compounds rich in boron, linked to various carriers, have been studied in experimental animals and in systems of cultivated cells. The current experimental prerequisites and results are outlined. The method for 'neutron capture radiography' has significant potential for general application in experimental physiology. The techniques are presented from this viewpoint and compared with other methods for visualisation of macromolecular markers by the use of physical or chemical principles.
Myocardial Reperfusion Injury: Etiology, Mechanisms, and Therapies (2004)

Reperfusion of ischemic myocardium is required for tissue survival; however, reperfusion elicits pathologic consequences. Myocardial reperfusion injury is a multifarious process that is mediated in part by oxygen free radicals, neutrophil-endothelium interactions, apoptosis, and intracellular calcium overload. The oxygen paradox describes the contradictory need to delivery oxygen to ischemic tissue and the resultant reduction of oxygen to form free radicals that are involved in macromolecule oxidation, membrane disfunction, apoptosis, and damaged calcium sequestering ability, which results in hypercontracture. These cell-damaging crises are amplified by the excessive activation of neutrophils, which promote the formation of proinflammatory mediators, oxygen radicals, and the reduction of endothelial nitric oxide formation, leading to increased neutrophil-endothelium interactions and capillary occlusion. Neutrophil action is twofold, however, because it is required for necrotic debris removal after severe ischemia. The oxygen radicals produced by neutrophils, endothelium, and myocytes may also play a role in activating the apoptotic cascade. Although the role of apoptosis in reperfusion injury is controversial, apoptotic cells are found in infarcted tissue. One of the key mediators may be increased inner mitochondrial membrane permeability, resulting in reduced ATP formation, release of cytochrome c, and caspase activation, which is key to promotion of apoptosis. Increased mitochondrial membrane permeability occurs during exposure to supraphysiological calcium concentrations. This occurs because of compensatory Na+/Ca2+ exchange to remove the excess intracellular sodium resulting from decreased Na+/K+ pumping during ischemia and increased Na+/H+ exchange following reperfusion. Supraphysiological calcium elicits hypercontracture and cellular damage. The various therapies being developed to diminish myocardial reperfusion injury involve inhibition of the processes described above as well as others. Although single therapies have shown some promise, the complexity of the response to reperfusion has made dramatic improvement elusive. Effective treatment will most likely require multifaceted antagonism of the numerous pathological cascades initiated by reperfusion.
Targeted Disruption of LDLR Causes Hypercholesterolemia and Atherosclerosis in Yucatan Miniature Pigs (2014)

Recent progress in engineering the genomes of large animals has spurred increased interest in developing better animal models for diseases where current options are inadequate. Here, we report the creation of Yucatan miniature pigs with targeted disruptions of the low-density lipoprotein receptor (LDLR) gene in an effort to provide an improved large animal model of familial hypercholesterolemia and atherosclerosis. Yucatan miniature pigs are well established as translational research models because of similarities to humans in physiology, anatomy, genetics, and size. Using recombinant adeno-associated virus-mediated gene targeting and somatic cell nuclear transfer, male and female LDLR+/- pigs were generated. Subsequent breeding of heterozygotes produced LDLR-/- pigs. When fed a standard swine diet (low fat, no cholesterol), LDLR+/- pigs exhibited a moderate, but consistent increase in total and LDL cholesterol, while LDLR-/- pigs had considerably elevated levels. This severe hypercholesterolemia in homozygote animals resulted in atherosclerotic lesions in the coronary arteries and abdominal aorta that resemble human atherosclerosis. These phenotypes were more severe and developed over a shorter time when fed a diet containing natural sources of fat and cholesterol. LDLR-targeted Yucatan miniature pigs offer several advantages over existing large animal models including size, consistency, availability, and versatility. This new model of cardiovascular disease could be an important resource for developing and testing novel detection and treatment strategies for coronary and aortic atherosclerosis and its complications.
Purification of human brain tissue factor. (1985)

Tissue factor (factor III) is a lipoprotein cofactor which markedly enhances the catalytic effect of coagulation factor VIIa upon factors IX and X. Human tissue factor apoprotein was purified 53,000-fold to homogeneity from brain using acetone delipidation, Triton X-100 extraction, and affinity chromatography upon factor VII-agarose. The purified apoprotein has an apparent molecular weight of 44,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, an amino acid composition similar to bovine brain tissue factor, and an NH2-terminal amino acid sequence of Ser-X-Asn-Thr-Val-Ala-Val-Tyr-X-Tyr-X-Leu-Lys-(Ser)-Lys-Asn-Phe. Optimal relipidation of the tissue factor apoprotein was associated with a 5000-fold enhancement of clotting activity and occurred at a phospholipid/apoprotein (w/w) ratio of greater than 600.
Cloud security is not (just) virtualization security (2009)

Cloud infrastructure commonly relies on virtualization. Customers provide their own VMs, and the cloud provider runs them often without knowledge of the guest OSes or their configurations. However, cloud customers also want effective and efficient security for their VMs. Cloud providers offering security-as-a-service based on VM introspection promise the best of both worlds: efficient centralization and effective protection. Since customers can move images from one cloud to another, an effective solution requires learning what guest OS runs in each VM and securing the guest OS without relying on the guest OS functionality or an initially secure guest VM state.
Continuous Intravenous Vasopressin in Active Upper Gastrointestinal Bleeding (1982)

Sixty patients with active upper gastrointestinal bleeding were randomized to received either continuous intravenous infusions of vasopressin (29 patients) or placebo (31 patients) at a rate of 40 U/h. Six hours after beginning the study, 13 patients in the vasopressin group and 11 in the placebo group] had ceased bleeding (p = 0.46). By 24 hours. 17 patients in the vasopressin group and 14 in the placebo group had stopped bleeding (p = 0.30). Restriction of the analysis to patients bleeding from varices showed no advantage with vasopressin treatment after 6 or 24 hours. No consistent trend favoring use of vasopressin to stop hemorrhage was noted during the 30-month study period. There was little difference between the two groups in the number of patients needing surgery (13 on vasopressin, 18 on placebo; p = 0.30) or the number of deaths (eight on vasopressin, 11 on placebo; p = 0.51); the transfusion requirement was the same. In our patients, a continuous intravenous infusion of vasopressin neither controlled bleeding nor altered outcome.
Feed improvement by energy efficient storage using Pichia anomala inoculated ensiled cereal grain (2010)

Borling, J. 2010. Preservation of moist crimped cereal grain can be achieved as a result of fermentation by lactic acid bacteria. Climatic variations make it difficult under practical farm conditions to harvest the grain at a moisture content (30-45%), suitable to ensure fermentation. Therefore the yeast Pichia anomala J121, previously found to prevent mould spoilage and improve preservation of moist grain in malfunctioning air tight silos, was added to the storage of moist crimped cereal grain in big plastic tubes. Freshly harvested barley was rolled and inoculated with 105 colony-forming units (Cfu) g-1 P. anomala, strain J121. Due to the local weather conditions, harvest was delayed and moisture content in the cereal grain had decreased to only 16-18%. Inoculation of P. anomala was done in 48 tons of barley, packed into three plastic tubes. Three additional sets of plastic tubes were packed with cereal grain without addition of P. anomala. The grain tubes were left closed for 5 months, after which feeding to cattle commenced. The population diversity of lactic acid bacteria (LAB) was very high both in the P. anomala inoculated barley and in the non-inoculated barley. A shift in the dominant LAB over the course of storage to Pediococcus pentosaceus and Lactobacillus paracasei was discernible in inoculated and non-inoculated respectively. The yeast population in the inoculated barley was totally dominated by P. anomala during the entire storage period. In the non-inoculated grain, the yeast population was more diverse, displaying shifts in the dominant species during storage. Pichia burtonii was the dominant species at the last sampling occasion. In the inoculated grain, mould numbers were reduced by approximately two log units, and the number of Enterobacteriaceae was reduced beneath detection limit. Negative effects on animal health or on weight gain were not observed.
A HISTORICAL SURVEY OF NORTH KOREA’S ECONOMIC DEVELOPMENT AND TRADE, 1945-1984 (2002)

Economic reality supersedes political rhetoric, even in the hermit kingdom. North Korea is one of the most secluded countries in the world, and its self-imposed isolation and the resulting dearth of hard data make any systematic study of the nation a challenge. Despite the political and technical constraints, this paper nevertheless attempts to demystify North Korea’s claim of economic self-sufficiency. A longitudinal survey reveals the reasons why the Kim Il Sung regime had to make a major policy compromise by enacting the 1984 joint venture law. This paper shows the gradual evolution of North Korea’s economic stagnation that has since the mid 1980s led to economic openness towards the West.
Inhibitory Mechanism of Serpins:  Loop Insertion Forces Acylation of Plasminogen Activator by Plasminogen Activator Inhibitor-1 (1998)

Serpin inhibitors are believed to form an acyl enzyme intermediate with their target proteinases which is stabilized through insertion of the enzyme-linked part of the reactive center loop (RCL) as strand 4 in beta-sheet A of the inhibitor. To test critically the role and timing of these steps in the reaction of the plasminogen activator inhibitor PAI-1, we blocked the vacant position 4 in beta-sheet A of this serpin with an octapeptide. The peptide-blocked PAI-1 was a substrate for both tissue-type plasminogen activator (tPA) and trypsin and was hydrolyzed at the scissile bond. The reactivity of the peptide-blocked substrate PAI-1 was compared to that of the unmodified inhibitor by rapid acid quenching as well as photometric techniques. With trypsin as target, the limiting rate constants for enzyme acylation were essentially the same with inhibitor and substrate PAI-1 (21-23 s-1), as were also the associated apparent second-order rate constants (2.8-2.9 microM-1 s-1). With tPA, inhibitor and substrate PAI-1 reacted identically to form a tightly bound Michaelis complex (Kd approximately Km approximately 20 nM). The limiting rate constant for acylation of tPA, however, was 57 times faster with inhibitor PAI-1 (3.3 s-1) than with the substrate form (0.059 s-1), resulting in a 5-fold difference in the corresponding second-order rate constants (13 vs 2.5 microM-1 s-1). We attribute the ability of tPA to discriminate between the two PAI-1 forms to exosite bonds that cannot occur with trypsin. The exosite bonds retain specifically the distal part of the PAI-1 RCL in the substrate pocket, which favors a reversal of the acylation step. Acylation of tPA becomes effective only by separating the products of the acylation step. With substrate PAI-1, this depends on passive displacement of bonds, whereas with inhibitor PAI-1, separation is accomplished by loop insertion that pulls tPA from its docking site on PAI-1, resulting in faster acylation than with substrate PAI-1.