gebhart/patrepeval huggingface dataset:
Evolutionary Origin and Emergence of a Highly Successful Clone of Serotype M1 Group AStreptococcusInvolved Multiple Horizontal Gene Transfer Events (2005)

To better understand the molecular events involved in the origin of new pathogenic bacteria, we studied the evolution of a highly virulent clone of serotype M1 group A Streptococcus (GAS). Genomic, DNA-DNA microarray, and single-nucleotide polymorphism analyses indicated that this clone evolved through a series of horizontal gene transfer events that involved (1) the acquisition of prophages encoding streptococcal pyrogenic exotoxin A and extracellular DNases and (2) the reciprocal recombination of a 36-kb chromosomal region encoding the extracellular toxins NAD + -glycohydrolase (NADase) and streptolysin O (SLO). These gene transfer events were associated with significantly increased production of SLO and NADase. Virtual identity in the 36kb region present in contemporary serotype M1 and M12 isolates suggests that a serotype M12 strain served as the donor of this region. Multiple horizontal gene transfer events were a crucial factor in the evolutionary origin and emergence of a very abundant contemporary clone of serotype M1 GAS.
Detection of Recombinant Protein Based on Reporter Enzyme Activity: Chloramphenicol Acetyltransferase (2003)

Genetic engineering technologies allow the construction of genetic chimeras between the promoter region of a gene of interest and a reporter gene as a means to study the regulation of eukaryotic gene expression at the transcriptional level. The genetic constructs in plasmid form are delivered back into cells to measure the expression of the reporter gene. A good reporter gene product possesses the following characteristics: the enzymatic activity is heat stable and protease resistant, and corresponds well to the strength of the promoter; background and/or interfering enzymatic activities are not present in mammalian cells; and, simple, sensitive, reproducible, and convenient enzymatic or immunological assays of the reporter gene product are available for the assessment of the promoter activity (1). For many applications, the bacterial chloramphenicol acetyltransferase (CAT) satisfies these criteria (2).
Visibility preprocessing for interactive walkthroughs (1991)

The number of polygons comprising interesting architectural models is many more than can be rendered at interactive frame rates. However, due to occlusion by opaque surfaces (e.g., walls), only a small fraction of a typical model is visible from most viewpoints.We describe a method of visibility preprocessing that is efficient and effective for axis-aligned or axial architectural models. A model is subdivided into rectangular cells whose boundaries coincide with major opaque surfaces. Non-opaque portals are identified on cell boundaries, and used to form an adjacency graph connecting the cells of the subdivision. Next, the cell-to-cell visibility is computed for each cell of the subdivision, by linking pairs of cells between which unobstructed sightlines exist.During an interactive walkthrough phase, an observer with a known position and view cone moves through the model. At each frame, the cell containing the observer is identified, and the contents of potentially visible cells are retrieved from storage. The set of potentially visible cells is further reduced by culling it against the observer's view cone, producing the eye-to-cell visibility . The contents of the remaining visible cells are then sent to a graphics pipeline for hidden-surface removal and rendering.Tests on moderately complex 2-D and 3-D axial models reveal substantially reduced rendering loads.
Disposition and metabolic profile of a new antitumor agent: CL 216,942 (bisantrene) in laboratory animals. (1982)

A 14C-labeled antitumor drug, CL 216,942 (bisantrene), was administered iv at doses of 1-20 mg/kg to the monkey, dog, and rat. The serum concentration versus time profiles indicated at least a biphasic disappearance of the drug with long elimination half-lives of about 2-8 days in all three species. Total recoveries in the excreta collected through Day 7 were low (less than 50% of the administered dose), especially in the monkey and dog, with most of the drug found in the feces. Volumes of distribution in the central compartment as well as tissue distribution studies in all three species indicated a rapid uptake and significant concentration of the drug with long elimination half-lives in a deep compartment. The same organs and tissues (heart, liver, kidney, pancreas, spleen, lymph nodes, bone marrow, and most of the highly perfused glands) contained the highest drug concentrations in all three species. Metabolism studies indicated no evidence of significant biologic transformation of the drug in these species. In vitro studies by equilibrium dialysis indicated significant binding of the drug to DNA by intercalation.
Synthesis and antitumor activity of novel 4-demethoxyanthracyclines (1990)

A versatile and efficient synthetic route to 4-demethoxyanthracyclinones has been utilized in the preparation of a number of aglycons having 9-alkyl, 9-(hydroxylalkyl), or 9-carbamoyl substituents. Silver trifluoromethanesulfonate catalyzed coupling of these aglycons with various daunosamine derivatives has yielded a series of novel anthracyclines which have been evaluated as antitumor agents. 9-Alkylanthracyclines 22, 23, 33, and 34 have higher efficacy vs L-1210 leukemia than the parent 4-demethoxydaunorubicin (21), or the natural anthracyclines daunorubicin (1) and doxorubicin (2). 9-(Hydroxyalkyl) derivatives have in most cases high efficacy but are slightly less potent than 21. 9-Methyl analogue 22 has higher efficacy vs P388 leukemia than other anthracyclines tested, while 9-(hydroxymethyl) derivative 37 retains similar efficacy to anthracyclines 1, 2, and 21 but is considerably more potent. The N-substituted 9-carbamoylanthracyclines are devoid of antitumor activity.
Properties of nanostructured hydroxyapatite prepared by a spray drying technique (2004)

In previous studies nano sized hydroxyapatite (HA) particles were prepared by solgel or precipitation methods, in which the products were washed by aqueous or non-aqueous liquids to remove impurities or undesired components. The washing is know to modify the surfaces of the cystalline particles. This study evaluated properties of nano HA materials prepared by a spray drying method in which the HA product was not exposed to any liquid after its formation. The spray drying apparatus consisted of a nozzle that sprayed an acidic calcium phosphate solution in the form of a fine mist into a stream of filtered air flowing through a heated glass column. The water and volatile acid were evaporated by the time the mist reached the end of the column, and the fine particles were collected by an electrostatic precipitator. Powder x ray diffraction patterns suggested the material was amorphous, exhibiting a single broad peak at 30.5° 2θ. However, high resolution transmission electron microscopic analysis showed that the particles, some of which were 5 nm in size, exhibited well ordered HA lattice fringes. Small area diffraction patterns were indicative of HA. Fourier transfer infrared spectroscopy showed patterns of typical of HA with small amounts of HPO4 (2-). The thermodynamic solubility product of the nano HA was 3.3 × 10(-94) compared to 1 × 10(-117) for macro scale crystalline HA. These results showed that a spray drying technique can be used to prepare nanometer sized crystalline HA that have significantly different physicochemical properties than those of its bulk-scale counterpart.
A Critical Review of Trypsin Digestion for LC-MS Based Proteomics (2012)

Proteomics is defined as the large-scale study of proteins in particular for their structures and functions Proteomics increasingly plays an important role in areas like protein interaction studies, biomarker discovery, cancer prevention, drug treatment and disease screening medical diagnostics Proteomics can be performed either in a comprehensive or "shotgun" mode, where proteins are identified in complex mixtures, or as "targeted proteomics" where "selective reaction monitoring" (SRM) is used to choose in advance the proteins to observe, and then measuring them accurately, by optimizing the sample preparation as well as the LC-MS method in accordance to the specific proteins (Mitchell 2010). Whether "MS-based shotgun proteomics" has accomplished anything at all regarding clinically useful results was recently addressed by Peter Mitchell in a feature article (Mitchell 2010), and he states that the field needs to make a further step or even change direction. Referring to discussions with among others John Yates and Matthias Mann, Mitchell addresses the failure in the search for biomarkers as indicators of disease, the difficulties of protein arrays, the uncertainty of quantification in "shotgun proteomics" (due to among others the efficiency of ionization in the mass spectrometers), database shortcomings, the problems of detecting post translational modifications (PTMs), and finally the huge disappointment in the area of drug discovery. The field points in the direction of targeted proteomics, but targeted proteomics will not be the solution to all our questions and comprehensive proteomics will still be needed. In order to get as much information, with as high quality as possible, from a biological sample, both the sample preparation and the final LC-MS analyses need to be optimized. The most important step in the sample preparation for proteomics is the conversion of proteins to peptides and in most cases trypsin is used as enzyme. Trypsin is a protease that specifically cleaves the proteins creating peptides both in the preferred mass range for MS sequencing and with a basic residue at the carboxyl terminus of the peptide, producing information-rich, easily interpretable peptide fragmentation mass spectra. Some other proteases can be used as well, such as Lys-C, which is active in more harsh conditions with 8 M urea, and give larger fragments than trypsin. Asp-N and Glu-C are also highly sequencewww.intechopen.
Polymorphism and Gene Conversion in Mouse α-Globin Haplotypes (1987)

ABSTRACT We have cloned and characterized three distinct α-globin haplotypes obtained from inbred strains of the mouse, Mus domesticus. We report here the complete nucleotide sequence of the six α-globin genes that the haplotypes contain. Our analysis of these genes and those from one other previously described haplotype indicates that recurrent gene conversion events have played a major role in their history. The pattern of nucleotide substitutions suggests that conversions have occurred both within and between haplotypes. Limited segments of coding and noncoding DNA have been involved in these gene conversion events. In two of the haplotypes, the nonallelic genes of each maintain DNA sequence identity over discrete intervals and encode the same α-globin polypeptide. On the other hand, the coding regions of some genes have accumulated replacement changes that result in distinct α-globins. In one instance, these changes appear to reflect positive selection of advantageous mutations.
Enhancement of Immunoprotective Effect of CpG-ODN by Formulation with Polyphosphazenes Against E. coli Septicemia in Neonatal Chickens (2009)

Synthetic oligodeoxynucleotides (ODN) containing CpG motifs (CpG-ODN) have been shown to be effective immunoprotective agents and vaccine adjuvants in a variety of bacterial and protozoan diseases in different animal species. The objective of this study was to investigate the immunoprotective effect of formulated CpG-ODN with polyphosphazene, liposome or oil-in-water emulsion against E. coli infections in neonatal chickens. Eighteen-day-old embryonating eggs were inoculated with 50 microg CpG-ODN or formulated CpG-ODN with polyphophazene, liposome or oil-in-water emulsion. Four days after exposure to formulated CpG-ODN or day-1 post-hatch, 1 x 10(4) or 1 x l0(5) cfu of a virulent isolate of E. coli was inoculated by the subcutaneous route in the neck. Clinical signs, pathology, bacterial isolations from the air sacs, and mortality were observed for eight days following challenge with E. coli. The survival rate of birds following E. coli infection was 0% in groups receiving either non-CpG-ODN or saline. In contrast, birds receiving either CpG-ODN or CpG-ODN formulated with polyphosphazene had significantly higher survival of 55% (P<0.0001). The relative risk of mortality was significantly reduced for birds treated with CpG-ODN formulated in PCPP (0.25), in PCEP (0.33), or unformulated CpG-ODN (0.39) in comparison to the group treated with saline (p<0.01). Although formulation of CpG-ODN with liposomes or oil-in-water emulsion did not increase the immunoprotective effect against E. coli infection, no adverse reactions or poor hatchability were observed in embryos. This is the first time that CpG-ODN formulated with polyphosphazene has been demonstrated to have an immunoprotective effect against an extra cellular bacterial infection in neonatal broiler chickens following in ovo delivery.
Repertoire and Immunofocusing of CD8 T Cell Responses Generated by HIV-1 gag-pol and Expression Library Immunization Vaccines (2004)

Several gene-based vaccine approaches are being tested to drive multivalent cellular immune responses to control HIV-1 viral variants. To compare the utility of these approaches, HLA-A*0201 transgenic mice were genetically immunized with plasmids encoding wild-type (wt) gag-pol, codon-optimized (CO) gag-pol, and an expression library immunization (ELI) vaccine genetically re-engineered to express non-CO fragments of gag and pol fused to ubiquitin for proteasome targeting. Equimolar delivery of each vaccine into HLA-A*0201 transgenic mice generated CD8 T cell responses, with the ELI vaccine producing up to 10-fold higher responses than the wt or CO gag-pol plasmids against cognate and mutant epitopes. All three vaccines generated multivalent CD8 responses against varying numbers of epitopes after priming. However, when the animals were immunized again, the wt and CO gag-pol vaccines boosted only the responses against a subset of epitopes and attenuated the responses against all other Ags including epitopes from clade and drug-resistant viral variants. In contrast, the ELI vaccine boosted CD8 responses against all of the gag-pol Ags and against mutant epitopes from clade and drug-resistant variants. These data suggest that HIV-1 vaccines expressing structurally intact gag and pol proteins drive immunofocused CD8 responses that reduce the repertoire of T cell responses. In contrast, the genetically re-engineered ELI vaccine appears to better maintain the multivalent CD8 responses that may be required to control HIV-1 viral variants.
Noninvasive acceleration measurements to characterize the pharyngeal phase of swallowing (1991)

Swallowing disorder (dysphagia) presents a major problem in the rehabilitation of stroke and head injured patients. In the present investigation, a new technique is developed for noninvasive assessment of the pharyngeal phase of the swallowing mechanism. Acceleration was measured with two ultra-miniature accelerometers placed on the skin over the throat. Simultaneously, the swallow suction pressure was monitored. Swallowing in normal individuals gave rise to a characteristic acceleration pattern which was quite reproducible, and was in phase with the swallow pressure. In dysphagic patients, the acceleration response was either absent or significantly delayed. The accelerometry technique provides a tool for continuing patient assessment and demonstrating the clinical improvements.
The mannose permease of Escherichia coli consists of three different proteins. Amino acid sequence and function in sugar transport, sugar phosphorylation, and penetration of phage lambda DNA. (1987)

The mannose permease of the bacterial phosphotransferase system mediates sugar transport across the cytoplasmic membrane concomitant with sugar phosphorylation. It also functions as a receptor for bacterial chemotaxis and is required for infection of the cell by bacteriophage lambda where it most likely functions as a pore for penetration of lambda DNA. The permease consists of three different subunits, IIIMan, II-PMan, and II-MMan, which are encoded in a single transcriptional unit ptsLPM. The complete amino acid sequence of the subunits is deduced from the nucleotide sequence. IIIMan (35 kDa) is a hydrophilic protein which is transiently phosphorylated and most likely contains the active site for sugar phosphorylation. II-PMan (28 kDa) is very hydrophobic; II-MMan (31 kDa) is moderately hydrophobic. Both are integral membrane proteins and most likely form the transmembrane channel. All three subunits are required for sugar transport and phosphorylation; II-PMan and II-MMan alone are sufficient for penetration of lambda DNA. Truncated forms of II-MMan and II-PMan are described that mediate lambda DNA penetration but have no apparent sugar transport activity. Residual sugar phosphorylation activity is found with the truncated form of II-PMan. No obvious homologies at the level of amino acid sequence could be detected with other bacterial transport proteins.
Identification and characterization of intragenic sequences which repress human immunodeficiency virus structural gene expression (1991)

Examination of the life cycle of the human immunodeficiency virus (HIV) has shown that multiple levels of regulation exist, including some which require the virus-encoded Rev protein. In the absence of Rev, mRNAs encoding the structural proteins remain untranslated, a phenomenon which appears, in part, to be caused by nuclear entrapment of these RNA species. To examine the basis for repression of structural gene mRNA expression, a heterologous assay system was utilized to determine whether regions present within gag and pol contain elements capable of suppressing gene expression when present in cis. Both genes were found to contain cis-acting repressor sequences (CRS) that block gene expression when present within the 3' untranslated portion of a heterologous gene transcript. The element within pol was found to have the strongest repressive effect. While Rev alone was unable to reverse the repression observed with the pol sequence, addition of the env Rev-responsive element (RRE) in cis and Rev in trans did cause reversal of inhibition. Deletion mutagenesis defined a 260-bp element within the 3' portion of pol that contains a potent CRS which functions when present in the sense orientation. The corresponding region in HIV-2 pol was found to contain a functionally similar CRS element. To examine the mechanism of repression, the effects of the CRS elements on both the abundance and subcellular distribution of the mRNAs were examined. Neither was dramatically altered when examined in the context of a heterologous reporter (chloramphenicol acetyltransferase) mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)
An instrument for quantifying meibomian lipid on the lid margin: the Meibometer (1993)

An instrument, the Meibometer, is described for estimating the casual level of meibomian lipid on the human eyelid margins, adapted from a commercially-available instrument used for measurement of skin surface lipid. A loop of plastic tape is pressed onto the everted lower lid margin to lift off a blot of lipid. The resultant change in light transmission of the tape is read by a photometer. Readings are not affected by side (R or L), time of day or lid surface temperature. After cleaning lipid from the lid margins with hexane, the rate of recovery per 10 blinks, as a percentage of the pre-cleaned level, was measured as 33.7 +/- 5.8 (mean +/- SE). This rate of delivery appears to provide enough lipid for complete resurfacing of the preocular tear film with every blink. Over short periods no detectable lipid was delivered in the absence of blinking.
A Sequence within the Cytoplasmic Tail of GpIIb Independently Activates Platelet Aggregation and Thromboxane Synthesis (1998)

All integrin alpha subunits contain a highly conserved KXGFFKR motif in their cytoplasmic domains that plays a crucial role in the regulation of integrin affinity for their ligands. We show that a lipid-modified peptide corresponding to the cytoplasmic region, 989-995, of the platelet integrin subunit glycoprotein GpIIb (alphaIIb), palmitoyl-KVGFFKR (Ppep; 10 microM), but not a similarly modified scrambled peptide (palmitoyl-FKFVRGK), can specifically induce platelet activation and aggregation equivalent to that of strong agonists such as thrombin. Ppep-induced aggregation is also associated with indices of platelet activation including thromboxane A2 (TXA2) synthesis (EC50 = 45 +/- 5 microM), secretion of alpha-granules detected as enhanced surface expression of P-selectin (EC50 = 52 +/- 8 microM), and conformational changes in GpIIb/IIIa measured by the monoclonal antibody, PAC-1 (EC50 = 3.7 +/- 1 microM). The TXA2 receptor antagonist, SQ29548, PGE1, and the ADP scavenger, apyrase, differentially inhibit the aggregation response and TXA2 synthesis in response to Ppep. Similarly, GpIIb/IIIa antagonists (RO-449883 and integrelin), which inhibit aggregation by greater than 90%, have little effect on peptide-induced TXA2 synthesis, suggesting that this event is independent of fibrinogen binding to GpIIb/IIIa. Alanine-stepping of the Ppep sequence identifies GFFK(991-994) as the critical residues in all peptide-mediated events. We conclude that this peptide can imitate the cytoplasmic domain of GpIIb and initiate parallel but independent signaling pathways, one leading to ligand binding and platelet aggregation and the other to intracellular signaling events such as TXA2 synthesis and secretion.
Expression Systems and Processes for rDNA Products (1991)

This paper addresses concerns of recombinant microorganism processing including genetic and nongenetic problems. The nongenetic problems discussed include physiological concerns (medium effects, nonoxidative product formation in an aerobic environment, oxygen supply limitations), and product instabilities. The impact of these effects on the host growth and product formation will be shown to be both significant and varied thereby necessitating individual study.
COMPONENT SKILL COMPARISONS ACROSS READING LEVEL AND PROCESSING DEMAND (1990)

Abstract A comparative componential skill analysis across both reading proficiency levels (comprehension‐disabled and non‐disabled) and processing demand conditions [high (erred sentences) and low (control sentences)] was completed using a total of 60 (N = 60) adolescents, consisting of 25 comprehension‐disabled readers (n = 25) and 35 non disabled readers (n = 35). Dependent variables included seven eye movement measures obtained while readers parsed a series of 20 independent, single sentences, half of which contained either a semantic anomaly or syntactic ambiguity. Covariates in this multiple regression analysis included nine component skill indexes related to reading (word coding, sequencing, spatial ability, attention, STM, and four oral and written receptive linguistic skills). Variance contribution models per eye movement measure, across reading proficiency groups and processing demand conditions were derived using simple and then stepwise multiple regression procedures. It was predicted that significant variance contribution models would be found only for disabled readers, especially under the high‐demand processing condition; the skill components of sequencing, spatial ability, and semantic and syntactic linguistic capacities were expected to be significant predictors. Especially sensitive eye movement measures were predicted to include saccade length and regression indices of correction. Results generally supported these predictions, with the notable exception that no component skill models were derived for the high‐demand processing condition within the disabled group. Findings were discussed as supporting Kennedy's (1983) hypothesis regarding the possibility of “spatial maps” (p. 243) acting as lexical re‐access cues under high demand processing conditions. Directions for future componential skill analyses were also discussed.