gebhart/patrepeval huggingface dataset:
Deoxynucleoside [1-thio]triphosphates prevent proofreading during in vitro DNA synthesis. (1981)

The contribution of proofreading to the fidelity of catalysis by DNA polymerases has been determined with deoxyribonucleoside [1-thio]triphosphate substrates. These analogues, which contain a sulfur in place of an oxygen on the alpha phosphorus, are incorporated into DNA by DNA polymerases at rates similar to those of the corresponding unmodified deoxynucleoside triphosphates. The fidelity of DNA synthesis was measured with phi X174 am3 DNA; reversion to wild type occurs most frequently by a single base substitution, a C for a T at position 587. By using avian myeloblastosis virus DNA polymerase and DNA polymerase beta (enzymes without a proofreading 3' leads to 5' exonucleolytic activity), substitution of deoxycytidine thiotriphosphate in the reaction mixture did not alter fidelity. In contrast, with DNA polymerases from E. coli (DNA polymerase I) and bacteriophage T4 (enzymes containing a proofreading activity), fidelity was markedly reduced with deoxycytidine [1-thio]triphosphate. DNA containing phosphorothioate nucleotides is insensitive to hydrolysis by the exonuclease associated with these prokaryotic DNA polymerases. These combined results indicate that the deoxynucleoside [1-thio]triphosphates have normal base-pairing properties; however, once misinserted by a polymerase, they are not excised by proofreading. Proofreading of a C:A mismatch at position 587 is thereby found to contribute 20-fold to the fidelity of E. coli DNA polymerase I and a greater amount to the fidelity of bacteriophage T4 DNA polymerase.
Plac1 is a tumor‐specific antigen capable of eliciting spontaneous antibody responses in human cancer patients (2008)

Immunoselection and tumor evasion constitutes one of the major obstacles in cancer immunotherapy. A potential solution to this problem is the development of polyvalent vaccines, and the identification of more tumor-specific antigens is a prerequisite for the development of cancer vaccines. To identify novel tumor-specific antigens, suppression subtractive hybridization (SSH) was performed to isolate genes differentially expressed in human hepatocellular cancer (HCC) tissues. PLAC1 (PLACenta-specific 1) was one of the genes identified highly expressed in HCC tissues but not in paired noncancerous tissues. Further analyses revealed its expression in several other types of cancer tissues as well as tumor cell lines, but not in normal tissues except for placenta. Among HCC samples tested, 32% (22/69) showed PLAC1 mRNA expression while the protein was detected in 23.3% (7/30). A serological survey revealed that 3.8% (4/101) of HCC patients had anti-PLAC1 antibody response, suggesting the immunogenicity of PLAC1 in HCC patients. PLAC1 represents a new class of tumor associated antigen with restricted expression in placenta and cancer tissues, that may serve as a target for cancer vaccination.
Optimal conditions for Ca-acidic phospholipid-PO4 formation. (1982)

Calcium-acidic phospholipid-phosphate complexes (Ca-PL-PO4) cause hydroxyapatite (HA) deposition in vitro. The acidic phospholipids--phosphatidylserine (PS), phosphatidylinositol (PI), phosphatidylglycerol (PG), and diphosphatidylglycerol (DPG)--all form Ca-PL-PO4 complexes: Nonacidic phospholipids--sphingomyelin (SPL), phosphatidylcholine (PC) and phosphatidylethanolamine (PE)--do not form Ca-PL-PO4 and do not induce hydroxyapatite (HA) deposition in low ionic strength metastable calcium phosphate solution or in synthetic lymph. The extent to which each of the acidic phospholipids reacts with calcium and inorganic phosphate, and the chemical composition of the Ca-PL-PO4 complexes is a function of pH, solution composition, the nature of the phospholipid, and the method of isolation. The addition of inorganic phosphate prior to or in combination with calcium appears to be an absolute requirement for Ca-PL-PO4 formation.
Molecular Analysis of Bacterial Species Associated with Childhood Caries (2002)

Although substantial epidemiologic evidence links Streptococcus mutans to caries, the pathobiology of caries may involve more complex communities of bacterial species. Molecular methods for bacterial identification and enumeration now make it possible to more precisely study the microbiota associated with dental caries. The purpose of this study was to compare the bacteria found in early childhood caries (ECC) to those found in caries-free children by using molecular identification methods. Cloning and sequencing of bacterial 16S ribosomal DNAs from a healthy subject and a subject with ECC were used for identification of novel species or uncultivated phylotypes and species not previously associated with dental caries. Ten novel phylotypes were identified. A number of species or phylotypes that may play a role in health or disease were identified and warrant further investigation. In addition, quantitative measurements for 23 previously known bacterial species or species groups were obtained by a reverse capture checkerboard assay for 30 subjects with caries and 30 healthy controls. Significant differences were observed for nine species: S. sanguinis was associated with health and, in order of decreasing cell numbers, Actinomyces gerencseriae, Bifidobacterium, S. mutans, Veillonella, S. salivarius, S. constellatus, S. parasanguinis, and Lactobacillus fermentum were associated with caries. These data suggest that A. gerencseriae and other Actinomyces species may play an important role in caries initiation and that a novel Bifidobacterium may be a major pathogen in deep caries. Further investigation could lead to the identification of targets for biological interventions in the caries process and thereby contribute to improved prevention of and treatment for this significant public health problem.
Cathepsin B and cysteine proteinase inhibitors in bronchoalveolar lavage fluid of lung cancer patients. (1993)

The enzymatic activity and the concentration of cathepsin B (CB), determined by ELISA, and total inhibitory activity of cysteine proteinase inhibitors (CPIs) were measured in bronchoalveolar lavage fluid (BALF) of lung tumor patients (n = 49). Significantly higher CB activity and concentration was found in BALF from metastasis (n = 15), when compared to squamous cell carcinoma (SCC; n = 15) and small cell lung carcinoma (SCLC; n = 7). Patients with adenocarcinoma (n = 12) also secreted considerably more CB, about 14- and 3.3-fold, compared to SCC and SCLC patients, respectively. However, only tumor patients without inflammation were considered because the comparison of patients with lung tumors (n = 49) and with other non-neoplastic lung diseases (n = 18) showed no differences due to high CB in BALF of patients with inflammatory conditions, present in some patients from both groups. Immunolabeling of tumor BALF proteins revealed CB immunoreactivity at molecular sizes that corresponded to the size of its precursor and mature forms, as well as to complexes with kininogen(s) and low molecular weight CPIs. Stefins A and B, but not cystatins C and S appeared in the complexes with CB.
Mitochondrial Uncoupling and the Reprograming of Intermediary Metabolism in Leukemia Cells (2013)

Nearly 60 years ago Otto Warburg proposed, in a seminal publication, that an irreparable defect in the oxidative capacity of normal cells supported the switch to glycolysis for energy generation and the appearance of the malignant phenotype (Warburg, 1956). Curiously, this phenotype was also observed by Warburg in embryonic tissues, and recent research demonstrated that normal stem cells may indeed rely on aerobic glycolysis - fermenting pyruvate to lactate in the presence of ample oxygen - rather than on the complete oxidation of pyruvate in the Krebs cycle - to generate cellular energy (Folmes et al., 2012). However, it remains to be determined whether this phenotype is causative for neoplastic development, or rather the result of malignant transformation. In addition, in light of mounting evidence demonstrating that cancer cells can carry out electron transport and oxidative phosphorylation, although in some cases predominantly using electrons from non-glucose carbon sources (Bloch-Frankenthal et al., 1965), Warburg's hypothesis needs to be revisited. Lastly, recent evidence suggests that the leukemia bone marrow microenvironment promotes the Warburg phenotype adding another layer of complexity to the study of metabolism in hematological malignancies. In this review we will discuss some of the evidence for alterations in the intermediary metabolism of leukemia cells and present evidence for a concept put forth decades ago by lipid biochemist Feodor Lynen, and acknowledged by Warburg himself, that cancer cell mitochondria uncouple ATP synthesis from electron transport and therefore depend on glycolysis to meet their energy demands (Lynen, 1951; Warburg, 1956).
Built-In Self-Testing RAM: A Practical Alternative (1987)

The article investigates the design of a built-in self-testing RAM as an economical way, in terms of silicon area overhead, to test memories-more economical than the use of external testers. The design of a BIST static RAM is given, along with design decisions, retrospectives on how design could have used the area even more efficiently, and results of implementation. The extra silicon area used by the BIST hardware for 64K static memories is only five percent; for larger memories, it is less. BIST RAM, then, is a practical alternative, especially since testing can be done even during burn-in without the aid of an expensive external tester.
Cleavage of Automodified Poly(ADP-ribose) Polymerase during Apoptosis (1999)

The abundant nuclear enzyme poly(ADP-ribose) polymerase (PARP) synthesizes poly(ADP-ribose) in response to DNA strand breaks. During almost all forms of apoptosis, PARP is cleaved by caspases, suggesting the crucial role of its inactivation. A few studies have also reported a stimulation of PARP during apoptosis. However, the role of PARP stimulation and cleavage during this cell death process remains poorly understood. Here, we measured the stimulation of endogenous poly(ADP-ribose) synthesis during VP-16-induced apoptosis in HL60 cells and found that PARP was cleaved by caspases at the time of its poly(ADP-ribosyl)ation. In vitro experiments showed that PARP cleavage by caspase-7, but not by caspase-3, was stimulated by its automodification by long and branched poly(ADP-ribose). Consistently, caspase-7 exhibited an affinity for poly(ADP-ribose), whereas caspase-3 did not. In addition, caspase-7 was activated and accumulated in the nucleus of HL60 cells in response to the VP-16 treatment. Furthermore, caspase-7 activation was concommitant with PARP cleavage in the caspase-3-deficient cell line MCF-7 in response to staurosporine treatment. These results strongly suggest that, in vivo, it is caspase-7 that is responsible for PARP cleavage and that poly(ADP-ribosyl)ation of PARP accelerates its proteolysis. Cleavage of the active form of caspase substrates could be a general feature of the apoptotic process, ensuring the rapid inactivation of stress signaling proteins.
High genomic variability in the pre‐C region of hepatitis B virus in anti‐HBe, HBV DNA‐positive chronic hepatitis (1990)

Some chronic HBV carriers have circulating HBV DNA despite the presence of anti-HBeAg antibodies. This observation has recently been related to the presence, in the HBV pre-C region, of a translational stop codon that prevents HBeAg synthesis. In the present study, we analyzed, at the nucleotide level, the pre-C/C region of HBV isolated from the sera of 11 anti-HBe, HBV DNA-positive chronic carriers. Nucleotide sequence analysis of 25 independent clones revealed that the pre-C sequence is highly variable, even among clones derived from the same serum sample. Moreover, our data show that HBeAg synthesis can also be prevented by as yet undescribed T-C substitution at position 1815 that eliminates the start codon of the pre-C transcript. These results suggest that the HBV genome contains segments of high variability that have probably been selected during evolution to favor the segregation of functionally advantaged mutants capable of avoiding host immunity.
Interferometer based on four diffraction gratings (1959)

An interferometer based on diffraction gratings, used over their whole area, and designed to overcome some of the disadvantages of the four-mirror Mach-Zehnder arrangement is described. Its theoretical and practical assessment leads to the conclusion that, in comparison with the latter, it is remarkably inexpensive and insensitive to misalinement, though wasteful of light and subject to certain residual optical imperfections.
Synthesis of 2,9-Dichloro-1,10-phenanthroline from N,N′-Annelated Phenanthrolinediones (1990)

Abstract Though the chlorination of an N,N′-annelated phenanthrolinedione, 3,6,7,9-tetrahydro-5H-[1,4]diazepino[1,2,3,4-lmn][1,10]phenanthroline-3,9-dione, gave 2,9-dichloro-1,10-phenanthroline, another dione, 3,5,6,8-tetrahydropyrazino[1,2,3,4-lmn][1,10]phenanthroline-3,8-dione, did not. It demonstrated a simultanous introduction of two chlorine substituents to non-substituted 1,10-phenanthroline via only the former intermediate.
FTIR microspectroscopic study of cell types and potential confounding variables in screening for cervical malignancies (1998)

FTIR microscopy was applied to the analysis of cell types and other variables present in Pap smears to ascertain the limitations of infrared spectroscopy in the diagnosis of cervical cancer and dysplasia. It was found that leukocytes, and in particular lymphocytes, have spectral features in the phosphodiester region (1300-900 cm[-1]) suggestive of what has previously been described as changes indicative of malignancy. Endocervical cells and fibroblasts have similar spectral features to HeLa cells and consequently could also confound diagnosis. The use of ethanol as a fixative and dehydrating agent results in retention of glycogen in cervical cell types and thus minimizes spectral changes in the glycogen region due to sampling technique. Spectra of seminal fluids exhibit strong bands in the phosphodiester/carbohydrate region; however, sperm contamination should be easily detectable by the presence of a distinctive doublet at 981/968 cm(-1). Erythrocyte spectra exhibit a reduction in glycogen band intensity, but can be discerned by a relatively low-intensity nu(s) PO2- band. Endocervical mucin spectra exhibit a reduction in glycogen bands and a very pronounced nu(s) PO2- band, which is similar in intensity to the corresponding band in HeLa cells. Thrombocytes have strong bands in the phosphodiester region, but thrombocytes can be discerned from other cell types by the presence of two small broad bands at 980 and 935 cm(-1). Candida albicans is characterized by strong bands in the polysaccharide region which could potentially obscure diagnostic bands if C. albicans is present in large numbers. Spectra of bacteria common to the female genital tract, in general, also have strong absorptions in the polysaccharide region; however, bacterial contamination is usually minimal and would not be expected to obscure cervical cell spectra. Nylon threads and bristles from cervical sampling implements produce characteristic IR profiles which allow for easy identification. Given the number of potential confounding variables associated with cervical cytology, a multivariate statistical or neural network analysis would appear to be necessary before the implementation of FTIR technology in clinical laboratories.
Ecology-guided prediction of cross-feeding interactions in the human gut microbiome (2021)

Understanding a complex microbial ecosystem such as the human gut microbiome requires information about both microbial species and the metabolites they produce and secrete. These metabolites are exchanged via a large network of cross-feeding interactions, and are crucial for predicting the functional state of the microbiome. However, till date, we only have information for a part of this network, limited by experimental throughput. Here, we propose an ecology-based computational method, GutCP, using which we predict hundreds of new experimentally untested cross-feeding interactions in the human gut microbiome. GutCP utilizes a mechanistic model of the gut microbiome with the explicit exchange of metabolites and their effects on the growth of microbial species. To build GutCP, we combine metagenomic and metabolomic measurements from the gut microbiome with optimization techniques from machine learning. Close to 65% of the cross-feeding interactions predicted by GutCP are supported by evidence from genome annotations, which we provide for experimental testing. Our method has the potential to greatly improve existing models of the human gut microbiome, as well as our ability to predict the metabolic profile of the gut.
New oligomers with isatin. Condensation reactions of thiophene and 2,2′‐bithiophene with isatin (1990)

Abstract A systematic study of the well‐known indophenin reaction between isatin and thiophene was extended to embrace bithiophene. The products of the reactions were isolated and characterized by FT‐IR, UV, 1 H‐NMR, 13 C‐NMR, and GPC. The values of the thus determined molar masses and molar mass distributions differed from the data given in the literature. The reaction conditions – solvent, temperature, and concentration – are of crucial importance for the course of the reaction and the products obtained. New structures suggested for the oligomeric reaction products agree with all the analytical data. The reactions between isatin and thiophene (bithiophene) are explained schematically.
Active immunization with recombinant V antigen from Yersinia pestis protects mice against plague (1995)

The gene encoding V antigen from Yersinia pestis was cloned into the plasmid expression vector pGEX-5X-2. When electroporated into Escherichia coli JM109, the recombinant expressed V antigen as a stable fusion protein with glutathione S-transferase. The glutathione S-transferase-V fusion protein was isolated from recombinant E. coli and cleaved with factor Xa to yield purified V antigen as a stable product. Recombinant V antigen was inoculated intraperitoneally into mice and shown to induce a protective immune response against a subcutaneous challenge with 3.74 x 10(6) CFU of virulent Y. pestis. Protection correlated with the induction of a high titer of serum antibodies and a T-cell response specific for recombinant V antigen. These results indicate that V antigen should be a major component of an improved vaccine for plague.
On the Specificity of the Oxygenation of Unsaturated Fatty Acids Catalyzed by Soybean Lipoxidase (1967)

Abstract The positional and stereochemical specificities of the soybean lipoxidase-catalyzed oxygenation of unsaturated fatty acids have been investigated. It was found that the oxygen function was introduced at position ω6 in all of the fatty acids which reacted. In one case a small amount of the substrate was oxygenated in position ω10. The structural requirement for substrates is the presence of a cis, cis-1,4-pentadiene group with its methylene group located in position ω8. The structure of the hydroperoxy acid formed from 8,11,14-eicosatrienoic acid was 15l-hydroperoxy-8(cis), 11(cis),13(trans)-eicosatrienoic acid. By using sterospecifically tritium-labeled 8,11,14-eicosatrienoic acids, it was found that the removal of hydrogen from the ω8 methylene group is stereospecific. Thus, only the hydrogen of the l configuration is removed by the enzyme during the conversion into 15l-hydroperoxy-8(cis), 11(cis),13(trans)-eicosatrienoic acid. The conversion of [13l-3H, 3-14C]8,11,14-eicosatrienoic acid is accompanied by an isotope effect, suggesting that the hydrogen removal occurs as the initial step of the reaction.
Enhancing the Cell Permeability and Metabolic Stability of Peptidyl Drugs by Reversible Bicyclization (2016)

Therapeutic applications of peptides are currently limited by their proteolytic instability and impermeability to the cell membrane. A general, reversible bicyclization strategy is now reported to increase both the proteolytic stability and cell permeability of peptidyl drugs. A peptide drug is fused with a short cell-penetrating motif and converted into a conformationally constrained bicyclic structure through the formation of a pair of disulfide bonds. The resulting bicyclic peptide has greatly enhanced proteolytic stability as well as cell-permeability. Once inside the cell, the disulfide bonds are reduced to produce a linear, biologically active peptide. This strategy was applied to generate a cell-permeable bicyclic peptidyl inhibitor against the NEMO-IKK interaction.
Novel Strategies for Immortalization of Human Hepatocytes (2001)

Normal somatic cells have a finite life span due in part to their inability to maintain telomere length and chromosome stability. Immortalization strategies based on recent advances in telomere biology and aging research have led to the creation of genetically stable, nontumorigenic immortalized cell lines. Reversible immortalization, using the Cre-lox recombination and excision system, has been developed for the expansion of primary cells for cell based clinical therapies. Immortalized human hepatocyte cell lines with differentiated liver functions would find broad applications in biomedical research, especially for pharmacology and toxicology, artificial liver support, and hepatocyte transplantation. The biological basis of these new immortalization methods and their application to human hepatocytes is reviewed.
Generating iPS Cells from MEFS through Forced Expression of Sox-2, Oct-4, c-Myc, and Klf4 (2008)

Pluripotency can be induced in differentiated murine by viral transduction of Oct4, Sox2, Klf4, and c-Myc (Takahashi and Yamanaka, 2006; Wernig, et al., 2007; Okita, et al., 2007; Maherali, et al., 2007). We have devised a reprogramming strategy in which these four transcription factors are expressed from doxycycline (dox)-inducible lentiviral vectors (Brambrink et al., 2008). Using these inducible constructs, we can derive induced pluripotent stem (iPS) cells from mouse embryonic fibroblasts (MEFs). In this video, we demonstrate the procedure for the generation of inducible lentiviruses that express the four transcription factors and show how to infect MEFs with these viruses in order to produce iPS cells. By using inducible lentiviruses, the expression of the four factors in controlled by the addition of doxycyline to the culture medium. The advantage of this system over the traditional retroviral infection is the ability to turn the genes on and off so that the kinetics of reprogramming and gene expression requirements can be analyzed in detail.
A bacterial analog of the mdr gene of mammalian tumor cells is present in Streptomyces peucetius, the producer of daunorubicin and doxorubicin. (1991)

Sequence analysis of the drrAB locus from Streptomyces peucetius (American Type Culture Collection 29050) reveals the presence of two genes, drrA and drrB, both of which are required for daunorubicin and doxorubicin (Adriamycin) resistance in the heterologous host Streptomyces lividans. The DrrA protein is similar to a large family of ATP-binding transport proteins, including the proteins encoded by the mdr genes from mammalian tumor cells, which confer resistance to daunorubicin, doxorubicin, and some other structurally unrelated chemotherapeutic agents. The DrrB protein shows no significant similarity to other known proteins but is probably very hydrophobic, suggesting that it is located in the bacterial membrane. These two proteins may act jointly to confer daunorubicin and doxorubicin resistance by an analog of the antiport mechanism established for mammalian tumor cells that contain amplified or overexpressed mdr genes. Transcriptional analysis of the drrAB region supports the presence of one transcript containing drrA and drrB and indicates that these genes are expressed only during antibiotic production.