gebhart/patrepeval huggingface dataset:
Synthesis and Evaluation of Novel Thymidine Analogs as Antitumor and Antiviral Agents (1996)

Two series of thymidine analogs with a hydroxyalkylammonium(amine) moiety have been synthesized and evaluated for antitumor and antiviral activities. The hydroxyalkylammonium-(amine) group was introduced at the 5' position of the 2'-deoxyribose residue of thymidine or at a corresponding position in acyclic thymidine analogs. In order to increase the lipophilicity of these compounds and potentially enable them to cross the cell membrane, the free hydroxy group also was esterified with a long hydrocarbon chain. The hexadecanoyl analogs (compounds 1c, 1d, 7c, and 7d) showed moderate antitumor cytotoxicity against SV-28 and KB cell lines (IC50 approximately 20 microM). Compound 1d showed moderate anti-HIV activity (EC50 = 6.8 microM), while compound 5 showed weak anti-HIV activity (EC50 = 55 microM). None of the compounds showed antiherpes simplex virus activity.
The Mitochondrial Genome in Embryo Technologies (2003)

The mammalian mitochondrial genome encodes for 37 genes which are involved in a broad range of cellular functions. The mitochondrial DNA (mtDNA) molecule is commonly assumed to be inherited through oocyte cytoplasm in a clonal manner, and apparently species-specific mechanisms have evolved to eliminate the contribution of sperm mitochondria after natural fertilization. However, recent evidence for paternal mtDNA inheritance in embryos and offspring questions the general validity of this model, particularly in the context of assisted reproduction and embryo biotechnology. In addition to normal mt DNA haplotype variation, oocytes and spermatozoa show remarkable differences in mtDNA content and may be affected by inherited or acquired mtDNA aberrations. All these parameters have been correlated with gamete quality and reproductive success rates. Nuclear transfer (NT) technology provides experimental models for studying interactions between nuclear and mitochondrial genomes. Recent studies demonstrated (i) a significant effect of mtDNA haplotype or other maternal cytoplasmic factors on the efficiency of NT; (ii) phenotypic differences between transmitochondrial clones pointing to functionally relevant nuclear-cytoplasmic interactions; and (iii) neutral or non-neutral selection of mtDNA haplotypes in heteroplasmic conditions. Mitochondria form a dynamic reticulum, enabling complementation of mitochondrial components and possibly mixing of different mtDNA populations in heteroplasmic individuals. Future directions of research on mtDNA in the context of reproductive biotechnology range from the elimination of adverse effects of artificial heteroplasmy, e.g. created by ooplasm transfer, to engineering of optimized constellations of nuclear and cytoplasmic genes for the production of superior livestock.
The Maize Low-Phytic Acid Mutant lpa2 Is Caused by Mutation in an Inositol Phosphate Kinase Gene (2003)

Reduced phytic acid content in seeds is a desired goal for genetic improvement in several crops. Low-phytic acid mutants have been used in genetic breeding, but it is not known what genes are responsible for the low-phytic acid phenotype. Using a reverse genetics approach, we found that the maize (Zea mays) low-phytic acid lpa2 mutant is caused by mutation in an inositol phosphate kinase gene. The maize inositol phosphate kinase (ZmIpk) gene was identified through sequence comparison with human and Arabidopsis Ins(1,3,4)P(3) 5/6-kinase genes. The purified recombinant ZmIpk protein has kinase activity on several inositol polyphosphates, including Ins(1,3,4)P(3), Ins(3,5,6)P(3), Ins(3,4,5,6)P(4), and Ins(1,2,5,6)P(4). The ZmIpk mRNA is expressed in the embryo, the organ where phytic acid accumulates in maize seeds. The ZmIpk Mutator insertion mutants were identified from a Mutator F(2) family. In the ZmIpk Mu insertion mutants, seed phytic acid content is reduced approximately 30%, and inorganic phosphate is increased about 3-fold. The mutants also accumulate myo-inositol and inositol phosphates as in the lpa2 mutant. Allelic tests showed that the ZmIpk Mu insertion mutants are allelic to the lpa2. Southern-blot analysis, cloning, and sequencing of the ZmIpk gene from lpa2 revealed that the lpa2-1 allele is caused by the genomic sequence rearrangement in the ZmIpk locus and the lpa2-2 allele has a nucleotide mutation that generated a stop codon in the N-terminal region of the ZmIpk open reading frame. These results provide evidence that ZmIpk is one of the kinases responsible for phytic acid biosynthesis in developing maize seeds.
The importance of 3‘‐phosphoadenosine 5‘‐phosphosulfate (PAPS) in the regulation of sulfation (1997)

Sulfation is the transfer of a sulfate group from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to a substrate that is catalyzed by a family of sulfotransferase enzymes. Many different endogenous and xenobiotic molecules are substrates for the sulfotransferases; sulfation affects many different physiological processes, including: 1) deactivation and bioactivation of xenobiotics, 2) inactivation of hormones and catecholamines, 3) structure and function of macromolecules, and 4) elimination of end products of catabolism. PAPS is the obligate cosubstrate that is synthesized in tissues to make available an "activated form" of sulfate for the sulfation reaction. PAPS participation in the reaction is dependent on its availability, which in turn is dependent on its synthesis, degradation, and ultimately its utilization in the sulfation reaction itself. PAPS synthesis is dependent on the availability of sulfate and on the activity of the two enzymes of its synthesis, ATP-sulfurylase and APS-kinase. Although the kinetic properties of these two enzymes are well described, their in vivo regulation is not fully understood. Sulfation is a high-affinity, low-capacity enzymatic process in which the entire liver content of PAPS can be consumed in less than 2 min. ATP-sulfurylase and APS-kinase can rapidly synthesize additional PAPS. The low capacity of sulfation in rats is due to the limited availability of sulfate, whereas in mice the sulfotransferases appear to limit sulfation capacity. Sulfation rates are not readily enhanced, but they can be decreased. 2,6-Dichloro-4-nitrophenol inhibits phenolsulfotransferases, but not hydroxysteroid-sulfotransferases. However, the sulfation of phenols and hydroxysteroids can be decreased by factors that decrease sulfate availability such as a low-sulfate diet, other xenobiotics that are sulfated, and molybdate, which inhibits sulfate intestinal absorption, renal reabsorption, and sulfate incorporation into PAPS.
Functional organization and nucleotide sequence of virulence Region‐2 on the large virulence plasmid in Shigella flexneri 2a (1989)

The 7 kb virulence Region-2 of the large (virulence) plasmid in Shigella flexneri 2a encodes several proteins required for invasion of intestinal epithelial cells. Insertion and deletion mutagenesis, DNA subcloning and SDS-polyacrylamide gel electrophoresis of proteins synthesized in minicells demonstrated five genes in this region. They encode 24, 18, 62 (IpaB), 41 (IpaC) and 37 (IpaD)-kiloDalton (kD) proteins. Complementation of Tn5-induced mutations in Region-2 with the above plasmid constructs indicated that Region-2 consists of two operons and that the three Ipa proteins are essential for the virulence phenotype. The transcriptional organization determined by Northern blotting, S1 nuclease protection and the effect of Tn5 insertions on expression of the Ipa proteins revealed that Region-2 has three promoters that transcribe RNAs of 4.0, 4.5 and 7.5 kb. The 4.0 kb RNA was the transcript for the operon encoding the 24, 18 kD, IpaB and C proteins and the 4.5 kb RNA for the ipaD gene. In addition, the full-length RNA of 7.5 kb which covers Region-2 supplemented full expression of the Ipa proteins. The 7663 nucleotides of Region-2 were determined to confirm the five open reading frames encoding 23,655, 17,755, 62,168, 41,077 and 36,660 Dalton proteins, respectively, and their regulatory sequences.
The Use of Transcriptional Profiling to Improve Personalized Diagnosis and Management of Cutaneous T-cell Lymphoma (CTCL) (2015)

This study, combined with other gene expression analyses, prepares the foundation for the development of personalized molecular approach toward diagnosis and treatment of CTCL.
Fine-Grained Robust Prosody Transfer for Single-Speaker Neural Text-To-Speech (2019)

We present a neural text-to-speech system for fine-grained prosody transfer from one speaker to another. Conventional approaches for end-to-end prosody transfer typically use either fixed-dimensional or variable-length prosody embedding via a secondary attention to encode the reference signal. However, when trained on a single-speaker dataset, the conventional prosody transfer systems are not robust enough to speaker variability, especially in the case of a reference signal coming from an unseen speaker. Therefore, we propose decoupling of the reference signal alignment from the overall system. For this purpose, we pre-compute phoneme-level time stamps and use them to aggregate prosodic features per phoneme, injecting them into a sequence-to-sequence text-to-speech system. We incorporate a variational auto-encoder to further enhance the latent representation of prosody embeddings. We show that our proposed approach is significantly more stable and achieves reliable prosody transplantation from an unseen speaker. We also propose a solution to the use case in which the transcription of the reference signal is absent. We evaluate all our proposed methods using both objective and subjective listening tests.
Serial angiography in an elastase-induced aneurysm model in rabbits: evidence for progressive aneurysm enlargement after creation. (2001)

Elastase incubation and vessel ligation results in patent aneurysmally dilated arterial segments at the origin of the right CCA in rabbits. These aneurysms show progressive increases in diameter over time, finally stabilizing at approximately 1 month. Our data, which show early progressive aneurysm enlargement, suggest that this model may be used for the study of systemic therapies aimed at diminishing aneurysm rest regrowth and also indicate that embolization of these model aneurysms should be delayed at least 21 days after aneurysm creation.
Speech and language in the laboratory, school, and clinic (1978)

This book reports the proceedings of a May 1976 conference entitled Implications of Basic Speech and Language Research for the School and Clinic, the sixth conference in the Communicating by Language series, sponsored by the Growth and Development Branch of the National Institute of Child Health and Human Development. Although the National Institutes of Health are traditionally associated with fundamental research, there has been growing public pressure for improvement in the communication of relevant laboratory research to the teacher and clinician. This conference brought together some of the country's foremost researchers and clinicians in an effort to examine both the present state of research in speech and language and how communication of that research to those concerned with its practical application might be improved.The book proceeds from the more physical problems of speech perception and production to the more cognitive problems of language meaning and memory. A summary of current knowledge about each topic is presented by a basic researcher, followed by a discussion from the clinician's point of view. The topics include all aspects of language processing in both adults and children, including physiological and acoustic aspects of the speech signal, perceptual processing and memory for speech and language, and processing syntactic and semantic information in sentence comprehension and lexical memory. A final paper reflects on selected themes of the conference and summarizes what the participants learned about the relation of basic research to areas of application.
Potential inhibitors of S-adenosylmethionine-dependent methyltransferases. 5. Role of the asymmetric sulfonium pole in the enzymic binding of S-adenosyl-L-methionine (1976)

The configuration at the asymmetric sulfonium pole of S-adenosyl-L-methionine (SAM) necessary for optimal enzymatic binding and methyl donation has been elucidated in this study. For the transmethylations catalyzed by catechol O-methyltransferase, phenylethanolamine N-methyltransferase, histamine N-methyltransferase, and hydroxyindole O-methyltransferase, it was demonstrated that only the natural (-) enantiomer of SAM was active as a methyl donor. The corresponding (+)-SAM, which was prepared by enzymatic resolution of synthetic (+/-)-SAM, was shown to be inactive as a methyl donor in these enzymatic reactions. The (+)-SAM was found, however, to be a potent inhibitor of each of these enzyme-catalyzed transmethylations. These results suggest that the (+) enantiomer offers a nonproductive configuration for the methyl-transfer reaction itself; however, this configuration fails to hamper enzymatic binding. These results are discussed relative to the geometric requirements necessary for the methyl-transfer reaction and the requirements for enzymatic binding.
Mutational Analysis of Endonuclease V from Thermotoga maritima (2002)

Endonuclease V nicks damaged DNA at the second phosphodiester bond 3' to inosine, uracil, mismatched bases, or abasic (AP) sites. Alanine scanning mutagenesis was performed in nine conserved positions of Thermotoga maritima endonuclease V to identify amino acid residues involved in recognition or endonucleolytic cleavage of these diverse substrates. Alanine substitution at D43, E89, and D110 either abolishes or substantially reduces inosine cleavage activity. These three mutants gain binding affinity for binding to double-stranded or single-stranded inosine substrates in the absence of a metal ion, suggesting that these residues may be involved in coordinating catalytic metal ion(s). Y80A, H116A, and, to a lesser extent, R88A demonstrate reduced affinities for double-stranded or single-stranded inosine substrates or nicked products. The lack of tight binding to a nicked inosine product accounts for the increased rate of turnover of inosine substrate since the product release is less rate-limiting. Y80A, R88A, and H116A fail to cleave AP site substrates. Their activities toward uracil substrates are in the following order: H116A > R88A > Y80A. These residues may play a role in substrate recognition. K139A maintains wild-type binding affinity for binding to double-stranded and single-stranded inosine substrate, but fails to cleave AP site and uracil substrate efficiently, suggesting that K139 may play a role in facilitating non-inosine substrate cleavage.
The role of interferon-γ in the pathogenesis of acute intra-abdominal sepsis (2010)

Several studies indicate that IFN-γ facilitates systemic inflammation during endotoxin-induced shock. However, the pathobiology of IFN-γ in clinically relevant models of septic shock, such as CLP, is not well understood. In this study, the role of IFN-γ in the pathogenesis of CLP-induced septic shock was evaluated by examining IFN-γ production at the tissue and cellular levels. The impact of IFN-γ neutralization on systemic inflammation, bacterial clearance, and survival was also determined. Following CLP, concentrations of IFN-γ in plasma and peritoneal lavage fluid were low in comparison with concentrations of IL-6 and MIP-2, as was IFN-γ mRNA expression in liver and spleen. The overall percentage of IFN-γ+ splenocytes was <5% after CLP and not statistically different from control mice. Intracellular IFN-γ was present in a large proportion of peritoneal exudate cells after CLP, primarily in infiltrating myeloid cells and NK cells. i.p. myeloid cell activation was decreased in IFN-γKO mice, and plasma concentrations of IL-6 and MIP-2 were significantly lower in IFN-γKO mice and in mice treated with anti-IFN-γ compared with controls, but bacterial clearance was not affected. IFN-γKO mice were resistant to CLP-induced mortality when treated with systemic antibiotics. However, neutralization of IFN-γ with blocking antibodies did not improve survival significantly. These studies show that IFN-γ facilitates the proinflammatory response during CLP-induced septic shock. However, neutralization of IFN-γ did not improve survival uniformly.
Aberrant proteolysis of the β‐amyloid precursor protein in familial Alzheimer's disease lymphoblastoid cells (1993)

Lymphoblastoid cells from patients with early-onset and late-onset familial Alzheimer's disease showed increased expressions of beta-amyloid precursor mRNA and protein as well as interleukin-1 and alpha 1-antichymotrypsin protein. Early-onset and late-onset familial Alzheimer's disease cells had greater production of 16-kDa beta-amyloid C-terminal preamyloid peptides than did normal cells. A pulse-chase experiment indicated that aberrant processing of this peptide resulted in its abnormal accumulation. Furthermore, the peptide prepared from early-onset familial Alzheimer's disease cells using formic acid could be separated into four discrete fragments. The N-terminal amino acid sequencing of each fragment indicated that the 16-kDa peptide was generated by cleavage, principally at the 30 amino acids N-terminal to beta-amyloid. Both the enhanced synthesis and aberrant processing of the beta-amyloid precursor protein, therefore, are basic processes associated with familial Alzheimer's disease lymphoblastoid cells.
Superconducting Through-Silicon Vias for Quantum Integrated Circuits (2017)

We describe a microfabrication process for superconducting through-silicon vias appropriate for use in superconducting qubit quantum processors. With a sloped-wall via geometry, we can use non-conformal metal deposition methods such as electron-beam evaporation and sputtering, which reliably deposit high quality superconducting films. Via superconductivity is validated by demonstrating zero via-to-via resistance below the critical temperature of aluminum.
Making and Breaking Peptide Bonds: Protein Engineering Using Sortase (2011)

Sortases are a class of bacterial enzymes that possess transpeptidase activity. It is their ability to site-specifically break a peptide bond and then reform a new bond with an incoming nucleophile that makes sortase an attractive tool for protein engineering. This technique has been adopted for a range of applications, from chemistry-based to cell biology and technology. In this Minireview we provide a brief overview of the biology of sortase enzymes and current applications in protein engineering. We identify areas that lend themselves to further innovation and that suggest new applications.
T Cell Epitopes of a Lipocalin Allergen Colocalize with the Conserved Regions of the Molecule (1999)

In this study we characterized the human T cell-reactive sites of the major cow dander allergen, Bos d 2, a member of the lipocalin protein family. We showed that Bos d 2 contains only a limited number of epitopes. This is in contrast to many other allergens, which usually contain multiple T cell epitopes throughout the molecule. The epitopes of Bos d 2 were primarily concentrated in the conserved regions of the molecule. One of the epitopes was recognized by all the cow-asthmatic individuals regardless of their HLA phenotype. Computer-predicted T cell epitopes on Bos d 2, other lipocalin allergens, and human endogenous lipocalins were situated in similar locations on these molecules and corresponded to experimentally identified epitopes on Bos d 2. The results suggest that human endogenous lipocalins could be involved in the modulation of immune responses against exogenous lipocalin allergens. In addition, our findings are likely to facilitate the development of new forms of immunotherapy against allergies induced by the important group of lipocalin allergens.
Effect of glucose on the cultivation of mammalian cells. (1987)

Most of the glucose consumed by mammalian cells cultivated in vitro is converted to lactate. The glucose consumption rate appears to be affected by glucose concentration. In a batch cultivation of cells the glucose concentration can be manipulated at a low level by programmed feeding of glucose. In such a culture the specific consumption rate of glucose and the fraction of glucose converted to lactate can be reduced. This reduced conversion rate of glucose to lactate appears to coincide with an increased oxygen uptake rate. A possible consequence of such programmed feeding of glucose is the increased oxidation of glutamine and the concurrent increased production of ammonium. For the cultivation of hybridoma cells high concentrations of ammonium and lactate can be growth inhibitory. It is suggested that the identification of the optimum cultivation conditions is necessary if such a programmed feeding is to be used to increase cell concentration and medium utilization efficiency.
Conservative Mutations in the Immunosuppressive Region of the Bovine Leukemia Virus Transmembrane Protein Affect Fusion but Not Infectivity in Vivo (1998)

Many retroviruses, including bovine leukemia virus (BLV), contain a highly conserved region located about 40 amino acids downstream from the fusion peptide within the sequence of the external domain of the transmembrane (TM) protein. This region is notably thought to be involved in the presentation of the NH2-terminal peptide to allow cell fusion. By using hydrophobic cluster analysis and by analogy with the influenza A hemagglutinin structures, the core of the TM structure including this particular region was predicted to consist, in the BLV and other retroviral envelope proteins, of an alpha-helix followed by a loop region, both docked against a subsequent alpha-helix that forms a triple-stranded coiled coil. The loop region could undergo, as in hemagglutinin, a major refolding into an alpha-helix integrating the coiled coil structure and putting the fusion peptide to one tip of the molecule. Based on this model, we have identified amino acids that may be essential to the BLV TM structure, and a series of mutations were introduced in the BLV env gene of an infectious molecular clone. A first series of mutations was designed to disturb the coiled coil structure (substitutions with proline residues), whereas others would maintain the general TM structure. When expressed by Semliki Forest virus recombinants, all the mutated envelope proteins were stable and efficiently synthesized in baby hamster kidney cells. Both proline-substituted and conservative mutants were strongly affected in their capacity to fuse to CC81 indicator cells. In addition, it appeared that the integrity of the TM coiled coil structure is essential for envelope protein multimerization, as analyzed by metrizamide gradient centrifugation. Finally, to gain insight into the role of this coiled coil in the infectious potential of BLV in vivo, the mutated TM genes were introduced in an infectious and pathogenic molecular clone and injected into sheep. It appeared that only the conservative mutations (A60V and A64S) allowed maintenance of viral infectivity in vivo. Since these mutations destroyed the ability to induce syncytia, we conclude that efficient fusion capacity of the recombinant envelopes is not a prerequisite for the infectious potential of BLV in vivo. Viral propagation of these mutants was strongly affected in some of the infected sheep. However, the proviral loads within half of the infected animals (2 out of 2 for A60V and 1 out of 4 for A64S) were close to the wild-type levels. In these sheep, it thus appears that the A60V and A64S mutants propagate efficiently despite being unable to induce syncytia in cell culture.