gebhart/patrepeval huggingface dataset:
Synthetic Biology Parts for the Storage of Increased Genetic Information in Cells (2017)

To bestow cells with novel forms and functions, the goal of synthetic biology, we have developed the unnatural nucleoside triphosphates dNaMTP and dTPT3TP, which form an unnatural base pair (UBP) and expand the genetic alphabet. While the UBP may be retained in the DNA of a living cell, its retention is sequence-dependent. We now report a steady-state kinetic characterization of the rate with which the Klenow fragment of E. coli DNA polymerase I synthesizes the UBP and its mispairs in a variety of sequence contexts. Correct UBP synthesis is as efficient as for a natural base pair, except in one sequence context, and in vitro performance is correlated with in vivo performance. The data elucidate the determinants of efficient UBP synthesis, show that the dNaM-dTPT3 UBP is the first generally recognized natural-like base pair, and importantly, demonstrate that dNaMTP and dTPT3TP are well optimized and standardized parts for the expansion of the genetic alphabet.
Time-of-Flight Mass Spectrometer with Improved Resolution (1955)

A new type of ion gun is described which greatly improves the resolution of a nonmagnetic time-of-flight mass spectrometer. The focusing action of this gun is discussed and analyzed mathematically. The validity of the analysis and the practicability of the gun are demonstrated by the spectra obtained. The spectrometer is capable of measuring the relative abundance of adjacent masses well beyond 100 amu.
A Donor−Acceptor Conducting Copolymer with a Very Low Band Gap and High Intrinsic Conductivity (1998)

Conducting polymers with very small band gaps have been prepared by the electrochemical copolymerization of 4-dicyanomethylene-4H-cyclopenta[2,1-b;3,4-b‘]dithiophene (1) with 3,4-ethylenedioxythiophene (2). Strong evidence that the materials formed are true copolymers rather than polymer blends is obtained from Raman spectroscopy and cyclic voltammetry. Both of these techniques also show that the copolymer composition can be controlled by varying the polymerization potential, with the ratio of 1:2 in the copolymer increasing with increasing potential. In situ conductivity measurements as a function of potential clearly show that the copolymers have significantly higher intrinsic conductivities than either homopolymer. Band gaps estimated from these intrinsic conductivities range from 0.33 to <0.16 eV. Band gaps for the 3,4-ethylenedioxythiophene-rich copolymers are too low to be accurately estimated but appear to be close to zero. Cyclic voltammograms are consistent with such low band gaps.
Elastic Torque and the Levitation of Metal Wires by a Nematic Liquid Crystal (2004)

Anisotropic particles suspended in a nematic liquid crystal disturb the alignment of the liquid crystal molecules and experience small forces that depend on the particles' orientation. We have measured these forces using magnetic nanowires. The torque on a wire and its orientation-dependent repulsion from a flat surface are quantitatively consistent with theoretical predictions based on the elastic properties of the liquid crystal. These forces can also be used to manipulate submicrometer-scale particles. We show that controlled spatial variations in the liquid crystal's alignment convert the torque on a wire to a translational force that levitates the wire to a specified height.
FastSpeech 2: Fast and High-Quality End-to-End Text to Speech (2020)

Non-autoregressive text to speech (TTS) models such as FastSpeech can synthesize speech significantly faster than previous autoregressive models with comparable quality. The training of FastSpeech model relies on an autoregressive teacher model for duration prediction (to provide more information as input) and knowledge distillation (to simplify the data distribution in output), which can ease the one-to-many mapping problem (i.e., multiple speech variations correspond to the same text) in TTS. However, FastSpeech has several disadvantages: 1) the teacher-student distillation pipeline is complicated and time-consuming, 2) the duration extracted from the teacher model is not accurate enough, and the target mel-spectrograms distilled from teacher model suffer from information loss due to data simplification, both of which limit the voice quality. In this paper, we propose FastSpeech 2, which addresses the issues in FastSpeech and better solves the one-to-many mapping problem in TTS by 1) directly training the model with ground-truth target instead of the simplified output from teacher, and 2) introducing more variation information of speech (e.g., pitch, energy and more accurate duration) as conditional inputs. Specifically, we extract duration, pitch and energy from speech waveform and directly take them as conditional inputs in training and use predicted values in inference. We further design FastSpeech 2s, which is the first attempt to directly generate speech waveform from text in parallel, enjoying the benefit of fully end-to-end inference. Experimental results show that 1) FastSpeech 2 achieves a 3x training speed-up over FastSpeech, and FastSpeech 2s enjoys even faster inference speed; 2) FastSpeech 2 and 2s outperform FastSpeech in voice quality, and FastSpeech 2 can even surpass autoregressive models. Audio samples are available at https://speechresearch.github.io/fastspeech2/.
The Keynesian Revolution (1950)

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Economics and Social Science, 1944.
Longitudinal Analysis of the Humoral Immune Response to Human Immunodeficiency Virus Type 1 (HIV-1) gp160 Epitopes in Rapidly Progressing and Nonprogressing HIV-1-Infected Subjects (1993)

Antibody response to conserved human immunodeficiency virus type 1 (HIV-1)IIIB gp160 epitopes was longitudinally examined in HIV-1-infected persons. Twelve hundred individuals were evaluated, and sequential sera from 25 rapidly progressing (RP) and 30 nonprogressing (NP) subjects collected over an average of 4 years were examined. Initial sera from the RP group contained greater reactivity to a gp120 epitope defined by peptide 503-528 than did sera from the NP group (P < .001). Reactivity declined with sequential sera for the RP group, paralleling disease progression. Conversely, antibody recognition to this site developed in 23% of the NP group with time. However, 60% of the NP group never developed a response to this epitope. This suggests sequential examination of antibody response to an epitope within the gp120 carboxyl-terminus may have prognostic significance. No association between antibodies directed against the gp160 epitopes and in vitro neutralizing activity against HIV-1IIIB was observed.
Increased interleukin-8 concentrations in the pulmonary edema fluid of patients with acute respiratory distress syndrome from sepsis (1996)

The high concentrations of IL-8 in pulmonary edema fluid, coupled with the relatively low concentrations of IL-8 in the plasma, suggest that the lung was the primary source of IL-8 in the patients with ARDS. The markedly increased concentrations of IL-8 in the pulmonary edema fluid of patients with ARDS from sepsis suggests that this group of patients may be particularly suitable for potential trials directed at inhibiting the activity of this important chemokine.
The gene encoding proopiomelanocortin in the dog. (1991)

The regulation of the synthesis of ACTH in the dog is of interest for studies of the physiology of the pituitary-adrenocortical axis as well as for studies of the pathogenesis of pituitary-dependent hyperadrenocorticism. Despite this broad interest the nucleotide sequence encoding ACTH and its precursor proopiomelanocortin (POMC) is not known, nor is it clear whether there are differences in POMC mRNA from the anterior lobe or the intermediate lobe of the normal pituitary or from pituitary tumours causing ACTH excess. Following the preparation of a cDNA library from the canine intermediate lobe of the pituitary gland, the part of the mRNA that is translated into the proopiomelanocortin prohormone was amplified using a polymerase chain reaction. Sequence analysis revealed the highest homology with the porcine mRNA sequence. Translation in a single reading frame revealed highly homologous areas in the amino-terminal, carboxy-terminal, and ACTH part of the prohormone, whereas a high diversity was noticed at the sequence preceding ACTH and the beginning of beta-lipotropin. Northern blot analysis disclosed the presence of a POMC mRNA of approximately 1300 nucleotides. There were no size differences between the anterior lobe, intermediate lobe, and pituitary tumour derived POMC mRNA. The highest expression levels of POMC mRNA as related to the expression of the gene encoding glyceraldehyde-3-phosphate dehydrogenase were found in the intermediate lobe of the canine pituitary gland. It is concluded that excessive production of ACTH by pituitary tumours is not caused by relatively high expression levels or alterations in the size of mRNA.
Antibiotic susceptibility testing in less than 30 min using direct single-cell imaging (2017)

The emergence and spread of antibiotic-resistant bacteria are aggravated by incorrect prescription and use of antibiotics. A core problem is that there is no sufficiently fast diagnostic test to guide correct antibiotic prescription at the point of care. Here, we investigate if it is possible to develop a point-of-care susceptibility test for urinary tract infection, a disease that 100 million women suffer from annually and that exhibits widespread antibiotic resistance. We capture bacterial cells directly from samples with low bacterial counts (10<sup>4</sup> cfu/mL) using a custom-designed microfluidic chip and monitor their individual growth rates using microscopy. By averaging the growth rate response to an antibiotic over many individual cells, we can push the detection time to the biological response time of the bacteria. We find that it is possible to detect changes in growth rate in response to each of nine antibiotics that are used to treat urinary tract infections in minutes. In a test of 49 clinical uropathogenic <i>Escherichia coli</i> (UPEC) isolates, all were correctly classified as susceptible or resistant to ciprofloxacin in less than 10 min. The total time for antibiotic susceptibility testing, from loading of sample to diagnostic readout, is less than 30 min, which allows the development of a point-of-care test that can guide correct treatment of urinary tract infection.
The structure of scientific collaboration networks (2001)

The structure of scientific collaboration networks is investigated. Two scientists are considered connected if they have authored a paper together and explicit networks of such connections are constructed by using data drawn from a number of databases, including MEDLINE (biomedical research), the Los Alamos e-Print Archive (physics), and NCSTRL (computer science). I show that these collaboration networks form "small worlds," in which randomly chosen pairs of scientists are typically separated by only a short path of intermediate acquaintances. I further give results for mean and distribution of numbers of collaborators of authors, demonstrate the presence of clustering in the networks, and highlight a number of apparent differences in the patterns of collaboration between the fields studied.
Multiple roles for platelet GPIIb/IIIa and alphavbeta3 integrins in tumor growth, angiogenesis, and metastasis. (2002)

In vivo tumor cells interact with a variety of host cells such as endothelial cells and platelets, and these interactions are mediated by integrins GPIIb/IIIa and alphavbeta3. We used chimeric (c) 7E3 Fab (ReoPro) and murine (m) 7E3 F(ab')(2) to elucidate the role of these integrins in angiogenesis, tumor growth, and metastasis. These antibodies are potent inhibitors of GPIIb/IIIa and alphavbeta3. c7E3 Fab inhibited alphavbeta3-mediated human umbilical vein endothelial (HUVEC) and melanoma cell adhesion, migration, invasion, and basic fibroblast growth factor stimulated proliferation of HUVECs (IC(50) values range from 0.15 to 5 microg/ml for different assays). In an in vitro angiogenesis assay, c7E3 Fab inhibited basic fibroblast growth factor and platelet-stimulated capillary formation of HUVECs (IC(50) = 10 microg/ml and 15 microg/ml, respectively), demonstrating that endothelial alphavbeta3 is important for sprouting, and platelet-stimulated sprouting is mediated by GPIIb/IIIa. In an experimental metastasis assay, a single pretreatment of human melanoma cells with c7E3 Fab (2.5 microg/ml) inhibited lung colonization of the tumor cells in severe combined immunodeficient mice. In vivo, m7E3 F(ab')(2) partially inhibited growth of human melanoma tumors in nude mice compared with control-treated animals. These data suggest that tumor cell-expressed integrins are important but not the only component involved in tumor growth. Because c7E3 Fab and m7E3 F(ab')(2) do not cross-react with murine integrins, this inhibition of metastasis and tumor growth is attributable to direct blockade of human tumor alphavbeta3 integrins. m7E3 F(ab')(2) completely blocked tumor formation and growth of human melanoma tumors growing in nude rats. In this xenograft model, m7E3 F(ab')(2) simultaneously binds to both human tumor and host platelet GPIIb/IIIa and endothelial alphavbeta3 integrins, thus participating as an antiangiogenic and an antitumor agent. Collectively, these results indicate that combined blockade of GPIIb/IIIa and alphavbeta3 affords significant antiangiogenic and antitumor benefit.
Improvement of Yersinia frederiksenii phytase performance by a single amino acid substitution (2009)

A new phytase (APPA) with optimum pH 2.5--substantially lower than that of most of microbial phytases (pH 4.5-6.0)--was cloned from Yersinia frederiksenii and heterologously expressed in Escherichia coli. Containing the highly conserved motifs typical of histidine acid phosphatases, APPA has the highest identity (84%) to the Yersinia intermedia phytase (optimal pH 4.5), a member of histidine acid phosphatase family. Based on sequence alignment and molecular modeling of APPA and related phytases, APPA has only one divergent residue, Ser51, in close proximity to the catalytic site. To understand the acidic adaptation of APPA, five mutants (S51A, S51T, S51D, S51K, and S51I) were constructed by site-directed mutagenesis, expressed in E. coli, purified, and characterized. Mutants S51T and S51I exhibited a shift in the optimal pH from 2.5 to 4.5 and 5.0, respectively, confirming the role of Ser51 in defining the optimal pH. Thus, a previously unrecognized factor other than electrostatics--presumably the side-chain structure near the active site--contributes to the optimal pH for APPA activity. Compared with wild-type APPA, mutant S51T showed higher specific activity, greater activity over pH 2.0-5.5, and increased thermal and acid stability. These properties make S51T a better candidate than the wild-type APPA for use in animal feed.
Theophylline synergizes with chlorambucil in inducing apoptosis of B- chronic lymphocytic leukemia cells (1996)

We tested the effects of theophylline, a phosphodiesterase inhibitor inducing intracellular accumulation of cyclic adenosine monophosphate (cAMP), on malignant B cells from 15 patients with B-chronic lymphocytic leukemia (B-CLL). We observed a large increase in apoptotic cell numbers (mean, 90% v 20% in medium alone) in the presence of theophylline (100 micrograms/mL) or chlorambucil (10 mumol/L) after 72 hours of incubation. Maximal apoptosis (90%) was reached after 36 hours when the two drugs were used together at fourfold lower concentrations, indicating a synergistic effect; no effect was observed with normal B cells, suggesting that the combination might have therapeutic interest. Chlorambucil induced intracellular Ca+2 influx, pointing to the involvement of two signaling pathways that might explain its synergy with theophylline through their effects on oncogenes. The expression of bcl-2 protein, a proto-oncogene inhibiting apoptosis, decreased after incubation with the drugs, while c-myc, recently described as having a potent role in apoptosis, was overexpressed. For p53 we observed an overexpression in the presence of chlorambucil or both theophylline-chlorambucil and a decrease after theophylline incubation. Chlorambucil- and theophylline-induced apoptosis was partially inhibited by interleukin-4 (IL-4), which also abrogated the effects on oncogene expression. These results provide insight into the mechanisms underlying B-CLL apoptosis and suggest that the theophylline-chlorambucil combination may be of therapeutic value in this setting.
A Different Kind of Kaleidoscope (1997)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text DOUGLAS S. GOODMAN, "A Different Kind of Kaleidoscope," Optics & Photonics News 8(3), 50-51 (1997) Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
Interaction of human osteoblasts with bioinert and bioactive ceramic substrates (2005)

The objective of this study was to compare adhesion, replication, and differentiation of human osteoblasts (OPC1 cell line) on two different ceramic substrates: a bioinert alumina (A1(2)O(3)), and a bioactive hydroxyapatite (HAp). Scanning electron microscopy (SEM) and confocal scanning microscopy were used to assess production and distribution of specific osteoblast proteins. Cells grew readily on HAp and alumina. On alumina and HAp, OPC1 cells produced distinctive cell-to-cell and cell-to-scaffold filopodia and microextensions. OPC1 cells proliferated faster on HAp than on alumina substrates. Adhesion was further assessed by observing production of the protein vinculin. On alumina, vinculin was detected throughout the cytoplasm, with some peripheral punctate regions. On HAp, OPC1 cells developed few punctate peripheral regions of vinculin; rather, the protein was strongly localized within the cytoplasm. Finally, we measured accumulation of the marker osteopontin (OPN). OPN was first detectable on day 5 and increased through day 11 of culture on alumina. OPC1 cells on HAp produced substantial amounts of OPN beginning at day 5, with apparent secretion from the cells by culture day 11. These results suggest that the function of osteoblasts is strongly affected by the properties of ceramic surfaces, and rapid attachment of osteoblasts may result in earlier differentiation on HAp than on alumina.
Spectroscopic and Magnetic Studies of Human Ceruloplasmin:  Identification of a Redox-Inactive Reduced Type 1 Copper Site (1998)

Ceruloplasmin is unique among the multicopper oxidases in that in addition to the usual copper stoichiometry of one Type 1 copper site and a Type 2/Type 3 trinuclear copper cluster, it contains two other Type 1 sites. This assignment of copper sites, based on copper quantitation, sequence alignment, and crystallography, is difficult to reconcile with the observed spectroscopy. Furthermore, some chemical or spectroscopic differences in ceruloplasmin have been reported depending on the method of purification. We have studied the resting (as isolated by a fast, one-step procedure) and peroxide-oxidized forms of human ceruloplasmin. Using a combination of X-ray absorption spectroscopy, a chemical assay, magnetic susceptibility, electron paramagnetic resonance spectroscopy, and absorption spectroscopy, we have determined that peroxide-oxidized ceruloplasmin contains one permanently reduced Type 1 site. This site is shown to have a reduction potential of approximately 1.0 V. Thus, one of the additional Type 1 sites in ceruloplasmin cannot be catalytically relevant in the form of the enzyme studied. Furthermore, the resting form of the enzyme contains an additional reducing equivalent, which is distributed among the remaining five copper sites as expected from their relative potentials. This may indicate that the resting form of ceruloplasmin in plasma under aerobic conditions is a four-electron oxidized form, which is consistent with its function in the four-electron reduction of dioxygen to water.
Estrogen Induces Expression of c-fosand c-mycProtooncogenes in Rat Uterus (1988)

Estrogen stimulates DNA synthesis and cell proliferation in the luminal and glandular epithelia of rodent uterus. We tested the hypothesis that the mitogenic effect of estrogen occurs via activation of the expression of cellular proto-oncogenes by measuring the rate of transcription of 20 proto-oncogenes (abl, bas, erb-A, erb-B, ets, fms, fos, fps/fes, mos, myb, myc, N-myc, raf, Ha-ras, Ki-ras, N-ras, rel, sis, src, and B-lym) in the uterus of ovariectomized rats before and after injection of estrogen. c-onc transcriptional activity was monitored both by an in vitro transcription assay on isolated nuclei (run-on) and by analysis of mature mRNA. c-fos and c-myc proto-oncogenes were found to respond to estrogen with increased expression: c-fos within 30 min, with a first, sharp peak at 2 h and c-myc within 1.5 h, with a first, broad peak at 4-6 h. DNA synthesis start to increase in the uterus 13 h after estrogen injection and show a first peak at 24 h. In the liver and muscle of the same animals there is neither elevation of c-fos and c-myc expression nor increase of DNA synthesis. The kinetics of the induction by estrogen of c-fos gene expression in the uterus parallels the rate of formation of active nuclear estrogen-receptor complex. Furthermore, the ability of estrogen to induce c-fos mRNA was not abolished by the protein synthesis inhibitor cycloheximide.(ABSTRACT TRUNCATED AT 250 WORDS)
Inorganic Mimics of Ribonucleases and Ribozymes:  From Random Cleavage to Sequence-Specific Chemistry to Catalytic Antisense Drugs (1998)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInorganic Mimics of Ribonucleases and Ribozymes: From Random Cleavage to Sequence-Specific Chemistry to Catalytic Antisense DrugsBobby N. Trawick, Andrew T. Daniher, and James K. BashkinView Author Information Department of Chemistry, Washington University, St. Louis, Missouri 63130 Cite this: Chem. Rev. 1998, 98, 3, 939–960Publication Date (Web):April 15, 1998Publication History Received29 July 1997Revised2 January 1998Published online15 April 1998Published inissue 7 May 1998https://doi.org/10.1021/cr960422kCopyright © 1998 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views1136Altmetric-Citations225LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit Read OnlinePDF (585 KB) Get e-AlertsSUBJECTS:Catalysts,Crystal cleavage,Genetics,Metals,Peptides and proteins Get e-Alerts