gebhart/patrepeval huggingface dataset:
Alzheimer’s Disease and Glaucoma (2013)

Alzheimer's disease (AD) is the most common form of dementia. Intraneuronal neurofibrillary tangles, extracellular Aβ amyloid deposits in the form of amyloid plaques and cerebral amyloid angiopathy, and synaptic and neuronal loss co-exist in the brain parenchyma, with the limbic areas being the most severely affected. The classic clinical findings are personality changes, progressive cognitive dysfunction, and loss of ability to perform activities of daily living. Visual impairment is common and appears related to disease severity, suggesting that visual testing may provide a method of screening and tracking AD changes. Although still not fully understood, research and clinical findings point to a possible common causal relationship between AD and glaucoma. These two chronic neurodegenerative disorders share biological and mechanistic features, among them (1) a strong age-related incidence, (2) retinal ganglion cell degeneration, and (3) extracellular fibrillar deposits in exfoliation syndrome, the most common recognizable cause of glaucoma, suggesting that both diseases may originate from similar misfolding mechanisms. A presentation of common pathogenetic pathways associated with these disorders, including cell death mechanisms, reactive oxygen species (ROS) production, mitochondrial dysfunction and vascular abnormalities, will serve as an initiation point for further exploration.
Enhanced autophagy as a potential mechanism for the improved physiological function by simvastatin in muscular dystrophy (2016)

Autophagy has recently emerged as an important cellular process for the maintenance of skeletal muscle health and function. Excessive autophagy can trigger muscle catabolism, leading to atrophy. In contrast, reduced autophagic flux is a characteristic of several muscle diseases, including Duchenne muscular dystrophy, the most common and severe inherited muscle disorder. Recent evidence demonstrates that enhanced reactive oxygen species (ROS) production by CYBB/NOX2 impairs autophagy in muscles from the dmd/mdx mouse, a genetic model of Duchenne muscular dystrophy. Statins decrease CYBB/NOX2 expression and activity and stimulate autophagy in skeletal muscle. Therefore, we treated dmd/mdx mice with simvastatin and showed decreased CYBB/NOX2-mediated oxidative stress and enhanced autophagy induction. This was accompanied by reduced muscle damage, inflammation and fibrosis, and increased muscle force production. Our data suggest that increased autophagy may be a potential mechanism by which simvastatin improves skeletal muscle health and function in muscular dystrophy.
SNVMix: predicting single nucleotide variants from next-generation sequencing of tumors (2010)

sshah@bccrc.ca SUPPLEMANTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Studies on the biosynthesis of quinones in fungi. Incorporation of 6-methylsalicylic acid into fumigatin and related compounds in Aspergillus fumigatus I.M.I. 89353 (1965)

1. Orsellinic acid has been detected as a metabolite of Aspergillus fumigatus. 2. The other principal aromatic components of the medium are fumigatin and the quinol, fumigatol. Fumigatol has been shown to be dihydrofumigatin after oxidation to the quinone followed by acetylation. 3. (14)C-labelled 6-methylsalicylic acid can be hydroxylated in A. fumigatus to form orsellinic acid and decarboxylated to give m-cresol. 4. (14)C-labelled 6-methylsalicylic acid is incorporated into fumigatin and fumigatol (1.0-1.5%), but the conversion does not occur until about 2-3 days after supplementation of the medium. At this stage of growth, the organism has already synthesized approx. 20 times as much fumigatol as fumigatin and this ratio is reflected in the much lower specific activity of the quinol. 5. Supplementation of the medium with either orsellinic acid or orcinol, in addition to (14)C-labelled 6-methylsalicylic acid, greatly decreases the latter's incorporation into fumigatin. At the same time, the cultures containing these substances are stimulated to produce another quinone with relatively high specific activity. 6. 6-Methylsalicylic acid has not been detected in the medium of normal cultures. The results indicate that 6-methylsalicylic acid itself is not a direct precursor of fumigatin and fumigatol but that it is converted into a true intermediate, probably after hydroxylation to orsellinic acid. 7. Supplementation of the medium with 6-methylsalicylic acid (15-25mg./200ml.) greatly affects the metabolism of A. fumigatus. Growth is inhibited and the synthesis of fumigatol is markedly depressed in these cultures. The inhibitory effects may possibly be related in some way to the production of m-cresol.
Synthesis of Zirconium Complexes That Contain the Diamidophosphine Ligands [(Me3SiNCH2CH2)2PPh]2- or [(RNSiMe2CH2)2PPh]2- (R = t-Bu or 2,6-Me2C6H3) (1998)

A new synthesis of PhP(CH2CH2NH3Cl)2 is reported that involves the addition of 2 equiv of butyllithium to a mixture of PhPH2 and 2 equiv of ClCH2CH2(cyclo-NSiMe2CH2CH2SiMe2). The reaction between PhP(CH2CH2NH3Cl)2 and 4 equiv of butyllithium followed by 2 equiv of Me3SiCl then yielded (Me3SiNHCH2CH2)2PPh (H2[N2P]) quantitatively. Addition of H2[N2P] to Zr(NMe2)4 in pentane gave intermediate [N2P]Zr(NMe2)2 that was converted without purification to white, crystalline [N2P]ZrCl2 in 80% yield overall upon treatment with 2 equiv of Me3SiCl. The alkyl complexes that were prepared include [N2P]Zr(THF)MeCl, [N2P]Zr(i-Bu)Cl, [N2P]ZrMe2, [N2P]Zr(CH2Ph)2, and [N2P]Zr(CH3)(CH2Ph). An X-ray diffraction study showed that the basic structure of [N2P]Zr(CH3)(CH2Ph) is a distorted trigonal bipyramid in which the methyl group is in the apical position trans to phosphorus and the η2-benzyl group is cis to phosphorus. Compounds of the type PhP(CH2SiMe2NHR)2 (R = t-Bu or 2,6-Me2C6H3; H2[R2NPN]) were prepared by treating ClCH2SiMe2Cl with LiNHR to give ClCH2SiMe2NHR followed by a reaction between PhPH2, ClCH2SiMe2NHR, and butyllithium. Zirconium complexes that were prepared include [t-Bu2NPN]ZrMeCl, [Ar2NPN]ZrMeCl, and [Ar2NPN]ZrMe2. An attempted synthesis of [t-Bu2NPN]ZrMe2 led to loss of a tert-butyl group and formation of a dimeric complex containing imido-type bridging nitrogen ligands, as confirmed in an X-ray study. X-ray studies of [t-Bu2NPN]ZrMeCl and [Ar2NPN]ZrMeCl demonstrate that extensive steric crowding exerted by a tert-butyl group in complexes of this type contributes to the inability to form a simple complex such as [PhP(CH2SiMe2N-t-Bu)2]ZrMe2.
Silencing of the Maternally Imprinted Tumor Suppressor ARHI Contributes to Follicular Thyroid Carcinogenesis (2005)

The two most common subtypes of thyroid cancer, follicular thyroid carcinoma (FTC) and papillary thyroid carcinoma, have been extensively studied, but our fundamental understanding of the molecular events in thyroid epithelial oncogenesis is still limited. Unreported data from our previous published global gene expression analysis revealed that the tumor suppressor gene aplysia ras homolog I (ARHI) is frequently underexpressed in FTCs. In this study, we elucidated the frequency and mechanism of ARHI silencing in benign and malignant thyroid neoplasia. We demonstrated that underexpression of ARHI occurs principally in FTCs (P = 0.0018), including its oncocytic variant (11 of 13), even at minimally invasive stage but not classic papillary thyroid carcinoma (two of seven) or follicular adenoma (FA) (three of 14). FTCs show strong allelic imbalance with reduction in copy number/loss of heterozygosity (LOH) in 69%, compared with less than 10% for FAs. In combination with our LOH data, bisulfite sequencing in a subset of samples revealed that FA displays a symmetric methylation pattern, likely representing one unmethylated allele and one presumptively imprinted allele, whereas FTC shows a virtually complete methylation pattern, representing LOH of the nonimprinted allele with only the hypermethylated allele remaining. Furthermore, we showed that pharmacologic inhibition of histone deacetylation but not demethylation could reactivate ARHI expression in the FTC133 FTC cell line. Therefore, our data suggest that silencing of the putative maternally imprinted tumor suppressor gene ARHI, primarily by large genomic deletion in conjunction with hypermethylation of the genomically imprinted allele, serves as a key early event in follicular thyroid carcinogenesis.
Lipid- and receptor-binding regions of apolipoprotein E4 fragments act in concert to cause mitochondrial dysfunction and neurotoxicity (2005)

Apolipoprotein (apo) E4, a 299-aa protein and a major risk factor for Alzheimer's disease, can be cleaved to generate C-terminal-truncated fragments that cause neurotoxicity in vitro and neurodegeneration and behavioral deficits in transgenic mice. To investigate this neurotoxicity, we expressed apoE4 with C- or N-terminal truncations or mutations in transfected Neuro-2a cells. ApoE4 (1-272) was neurotoxic, but full-length apoE4(1-299) and apoE4(1-240) were not, suggesting that the lipid-binding region (amino acids 241-272) mediates the neurotoxicity and that amino acids 273-299 are protective. A quadruple mutation in the lipid-binding region (I250A, F257A, W264R, and V269A) abolished the neurotoxicity of apoE4(1-272), and single mutations in the region of amino acids 273-299 (L279Q, K282A, or Q284A) made full-length apoE4 neurotoxic. Immunofluorescence staining showed that apoE4(1-272) formed filamentous inclusions containing phosphorylated tau in some cells and interacted with mitochondria in others, leading to mitochondrial dysfunction as determined by MitoTracker staining and flow cytometry. ApoE4(241-272) did not cause mitochondrial dysfunction or neurotoxicity, suggesting that the lipid-binding region alone is insufficient for neurotoxicity. Truncation of N-terminal sequences (amino acids 1-170) containing the receptor-binding region (amino acids 135-150) and triple mutations within that region (R142A, K146A, and R147A) abolished the mitochondrial interaction and neurotoxicity of apoE4(1-272). Further analysis showed that the receptor-binding region is required for escape from the secretory pathway and that the lipid-binding region mediates mitochondrial interaction. Thus, the lipid- and receptor-binding regions in apoE4 fragments act together to cause mitochondrial dysfunction and neurotoxicity, which may be important in Alzheimer's disease pathogenesis.
A 2-D Liquid Separations/Mass Mapping Method for Interlysate Comparison of Ovarian Cancers (2002)

A two-dimensional liquid phase separation of proteins from whole cell lysates coupled on-line to an electrospray-ionization time-of-flight (ESI-TOF) mass spectrometer (MS) is used to map the protein content of ovarian surface epithelial cells (OSE) and an ovarian carcinoma-derived cell line (ES2). The two dimensions involve the use of liquid isoelectric focusing as the first phase and nonporous silica reversed-phase HPLC as the second phase of separation. Accurate molecular weight (MW) values are then obtained upon the basis of ESI-TOFMS so that an image of isolectric point (pI) versus MW analogous to 2-D gel electrophoresis is produced. The accurate MW together with the pI fraction and corresponding hydrophobicity (%B) are used to tag each protein so that protein expression can be compared in interlysate studies. Each protein is also identified on the basis of matrix-assisted laser desorption-ionization (MALDI) TOFMS peptide mapping and intact MW so that a standard map is produced against which other cell lines can be compared. Quantitative changes in protein expression are measured in these interlysate comparisons using internal standards in the on-line ESI-TOFMS process. In the ovarian epithelial cell lines under study, it is shown that in the three pI fractions chosen for detailed analysis, over 50 unique proteins can be detected per fraction, of which 40% can be identified from web-based databases. It is also shown that when using an accurate MW to compare proteins in the OSE versus ovarian cancer sample, there are proteins highly expressed in cancer cells but not in normal cells. In addition, many of the proteins in the cancer sample appear to be down-regulated, as compared to the normal cells. This two-dimensional (2-D) liquid/mass mapping method may provide a means of studying proteins in interlysate comparisons not readily available by other methods.
Effects of transformation on fibronectin gene expression using cloned fibronectin cDNA. (1981)

Recombinant plasmids containing cellular fibronectin (CFN) cDNA sequences have been constructed and cloned in Escherichia coli The cloned sequences from one plasmid were shown to be complementary to CFN mRNA by linking this DNA to diazobenzyloxyniethylcellulose, incubating with total mRNA from chick embryo fibroblasts (CEF) under DNA-RNA hybridization conditions, and demonstrating that the RNA which hybridized specifically to the DNA-cellulose was enriched 24-fold in CFN mRNA translational activity.The sequence of this cloned cDNA has been partially determined and has characteristics common to the 3' noncoding regions of other eukaryotic mRNAs.Cloned CFN cDNA was used as a hybridization probe to quantitate CFN mRNA levels in normal and avian sarcoma virus (ASV)-transformed CEF.It was found that CFN mRNA is decreased to 10 to 13% of normal in ASV-transformed CEF.When CEF transformed with ASV mutants temperature-sensitive for transformation were cultured at the permissive temperature and then transferred to the nonpermissive temperature, there was a 10-h lag following which CFN mRNA levels increased to normal over a period of 15 h.The time course of these changes was indentical with that observed for the changes in the pro-a1 and pro-a2 collagen mRNAs but was much slower than the changes in morphology, CAMP levels, and glucose transport that occur in CEF transformed by the same temperature-sensitive ASV mutants.These findings are consistent with the possibility that the levels of the CFN and procollagen mRNAs are coordinately regulated as part of a pleotrophic differentiation program specific for CEF.The slow rise in mRNA levels following temperature shift of CEF infected with temperature-sensitive ASV is consistent with an indirect action of the ASV src gene product on regulation of cellular genes.Transformation of cells in culture with RNA tumor viruses not only results in the expression of viral genetic information but also alters the expression of cellular genes.The work presented here is directed towards understanding the mechanisms by which viral transformation influences cellular gene expression.Cellular fibronectin, the major glycoprotein found on the surface of chick embryo fibroblasts (CEF) and other fibroblasts in culture, constitutes 1 to 3% of total cellular protein (1).The function of fibronectin is primarily adhesive, contributing to both cell-cell and cell-substratum interactions (2-5).
Restriction endonuclease digest patterns of chromosomal DNA from group B -haemolytic streptococci (1991)

Scanning densitometry and computer-assisted numerical analysis were used to examine restriction endonuclease digest patterns (RDPs) of chromosomal DNA from 26 infecting strains and 44 vaginal isolates of group B beta-haemolytic streptococci (GBS). At the 95% similarity level, HindIII RDPs of serotype Ia and III strains clustered into four and three RDP types, respectively. Nine of 10 strains from neonates with early-onset septicaemia belonged to two particular RDP types (Ia-3 and III-3). In contrast, serotype III GBS strains from meningitis cases were not characterised by particular RDP types. Associations between RDPs and certain phenotypic characteristics were also found.
Yeast α Mating Factor Structure-Activity Relationship Derived from Genetically Selected Peptide Agonists and Antagonists of Ste2p (1996)

alpha-Factor, a 13-amino-acid pheromone secreted by haploid alpha cells of Saccharomyces cerevisiae, binds to Ste2p, a seven-transmembrane, G-protein-coupled receptor present on haploid alpha cells, to activate a signal transduction pathway required for conjugation and mating. To determine the structural requirements for alpha-factor activity, we developed a genetic screen to identify from random and semirandom libraries novel peptides that function as agonists or antagonists of Ste2p. The selection scheme was based on autocrine strains constructed to secrete random peptides and respond by growth to those that were either agonists or antagonists of Ste2p. Analysis of a number of peptides obtained by this selection procedure indicates that Trp1, Trp3, Pro8, and Gly9 are important for agonist activity specifically. His2, Leu4, Leu6, Pro10, a hydrophobic residue 12, and an aromatic residue 13 are important for both agonist and antagonist activity. Our results also show that activation of Ste2p can be achieved with novel, unanticipated combinations of amino acids. Finally, the results suggest the utility of this selection scheme for identifying novel ligands for mammalian G-protein-coupled receptors heterologously expressed in S. cerevisiae.
Classless Inter-Domain Routing (CIDR): an Address Assignment and Aggregation Strategy (1993)

This RFC specifies an Internet standards track protocol for the Internet community, and requests discussion and suggestions for improvements.
Improvement of GaInNAs p-i-n photodetector responsivity by antimony incorporation (2007)

Deep-level transient spectra (DLTS) and photoresponsivity were measured for Ga0.90In0.10N0.033As0.967∕GaAs and Ga0.96In0.04N0.028As0.967Sb0.005∕GaAs p-i-n photodetector structures. The GaInNAs and GaInNAsSb layers were grown closely lattice matched to GaAs substrate at 460°C using molecular beam epitaxy. Two hole-trap levels were observed in the DLTS spectra of the GaInNAs sample with activation energies of 0.152 and 0.400eV (labeled as H-1 and H-2 peak, respectively). The lower activation energy is believed to be associated with nitrogen-related defects and the higher activation energy is associated with arsenic antisite defects (AsGa). Following the incorporation of Sb into GaInNAs, the H-1 peak vanished from the DLTS spectra of the GaInNAsSb sample, and the AsGa defect-related DLTS signal was significantly reduced. Analysis of the DLTS data also showed that the trap concentration related to AsGa was reduced from 2.15×1015to2.58×1014cm−3. The DLTS results are in good agreement with the photoresponsivity results, in which the GaInNAsSb sample showed 10× higher photoresponse compared to the GaInNAs sample. This indicates the incorporation of Sb into GaInNAs has effectively improved the p-i-n photodetector device performance.
Preprotein transfer to the Escherichia coli translocase requires the co‐operative binding of SecB and the signal sequence to SecA (1998)

In Escherichia coli, precursor proteins are targeted to the membrane-bound translocase by the cytosolic chaperone SecB. SecB binds to the extreme carboxy-terminus of the SecA ATPase translocase subunit, and this interaction is promoted by preproteins. The mutant SecB proteins, L75Q and E77K, which interfere with preprotein translocation in vivo, are unable to stimulate in vitro translocation. Both mutants bind proOmpA but fail to support the SecA-dependent membrane binding of proOmpA because of a marked reduction in their binding affinities for SecA. The stimulatory effect of preproteins on the interaction between SecB and SecA exclusively involves the signal sequence domain of the preprotein, as it can be mimicked by a synthetic signal peptide and is not observed with a mutant preprotein (delta8proOmpA) bearing a non-functional signal sequence. Delta8proOmpA is not translocated across wild-type membranes, but the translocation defect is suppressed in inner membrane vesicles derived from a prIA4 strain. SecB reduces the translocation of delta8proOmpA into these vesicles and almost completely prevents translocation when, in addition, the SecB binding site on SecA is removed. These data demonstrate that efficient targeting of preproteins by SecB requires both a functional signal sequence and a SecB binding domain on SecA. It is concluded that the SecB-SecA interaction is needed to dissociate the mature preprotein domain from SecB and that binding of the signal sequence domain to SecA is required to ensure efficient transfer of the preprotein to the translocase.
Peptide fragmentation suitable for solid-phase microsequencing. Use of N-bromosuccinimide and BNPS-skatole {3-bromo-3-methyl-2-[(2-nitrophenyl)thio]-3H-indole} (1980)

BNPS-skatole (3-bromo-3-methyl-2-(2-nitrophenyl)thiol-3H-indole) and N-bromosuccinimide have been used to specifically cleave at peptide bonds after amino acids with available C-gamma=C-delta double bonds, i.e. tryptophan, tyrosine and histidine. The resulting C-terminal lactones conveniently attach to amino-glass supports for sequencing with DABITC (4-NN-dimethylaminoazobenzene 4'-isothiocyanate). Also, peptides having such C-termini, i.e. from a chymotryptic digest, can be readily made to react with these reagents and thus be easily attached and sequenced by solid-phase methods.
Hyponatraemia in the newborn (1998)

Hyponatraemia is common in inpatients and this includes newborns in neonatal intensive care units. Surveys from around the world suggest that up to a third of very low birthweight infants are hyponatraemic in the first week after birth and between 25 and 65% thereafter (unpublished data). 1
Chromosome 3p12.3-p14.2 and 3q26.2-q26.32 Are Genomic Markers for Prognosis of Advanced Nasopharyngeal Carcinoma (2009)

The combined microarray technologies suggested novel candidate oncogenes, amplification of GPR160 and SKIL at 3q26.2-q26.32, and deletion of tumor suppressor genes ADAMTS9 and LRIG1 at 3p12.3-p14.2. Altered expression of these genes may be responsible for malignant progression and could be used as potential markers for nasopharyngeal carcinoma.
A frequent pattern mining algorithm for feature extraction of customer reviews (2012)

Online shoppers often have different idea about the same product. They look for the product features that are consistent with their goal. Sometimes a feature might be interesting for one, while it does not make that impression for someone else. Unfortunately, identifying the target product with particular features is a tough task which is not achievable with existing functionality provided by common websites. In this paper, we present a frequent pattern mining algorithm to mine a bunch of reviews and extract product features. Our experimental results indicate that the algorithm outperforms the old pattern mining techniques used by previous researchers.