gebhart/patrepeval huggingface dataset:
Single Point Mutations in Either Gene Encoding the Subunits of the Heterooctameric Yeast Phosphofructokinase Abolish Allosteric Inhibition by ATP (2000)

Yeast phosphofructokinase is a heterooctameric enzyme subject to a complex allosteric regulation. A mutation in the PFK1 gene, encoding the larger -subunits, rendering the enzyme insensitive to allosteric inhibition by ATP was found to be caused by an exchange of proline 728 for a leucine residue. By in vitro mutagenesis, we introduced this mutation in either PFK1 or PFK2 and found that the exchange in either subunit drastically reduced the sensitivity of the holoenzyme to ATP inhibition. This was accompanied by a lack of allosteric activation by AMP, fructose 2,6-bisphosphate, or ammonium and an increased resistance to heat inactivation. Yeast cells carrying either one mutation or both in conjunction did not display a strong phenotype when grown on fermentable carbon sources and did not show any significant changes in intermediary metabolites. Growth on non-fermentable carbon sources was clearly impaired. The strain carrying both mutant alleles was more sensitive to Congo Red than the wild-type strain or the single mutants indicating differences in cell wall composition. In addition, we found single pfk null mutants to be less viable than wild type at different storage temperatures and a pfk2 null mutant to be temperature-sensitive for growth at 37 degrees C. The latter mutant was shown to be respiration-dependent for growth on glucose.
Inducible Activation of MyD88 and CD40 in CAR T Cells Results in Controllable and Potent Antitumor Activity in Preclinical Solid Tumor Models (2017)

Adoptive immunotherapy with T cells expressing chimeric antigen receptors (CAR) has had limited success for solid tumors in early-phase clinical studies. We reasoned that introducing into CAR T cells an inducible costimulatory (iCO) molecule consisting of a chemical inducer of dimerization (CID)-binding domain and the MyD88 and CD40 signaling domains would improve and control CAR T-cell activation. In the presence of CID, T cells expressing HER2-CARζ and a MyD88/CD40-based iCO molecule (HER2ζ.iCO T cells) had superior T-cell proliferation, cytokine production, and ability to sequentially kill targets <i>in vitro</i> relative to HER2ζ.iCO T cells without CID and T cells expressing HER2-CAR.CD28ζ. HER2ζ.iCO T cells with CID also significantly improved survival <i>in vivo</i> in two xenograft models. Repeat injections of CID were able to further increase the antitumor activity of HER2ζ.iCO T cells <i>in vivo</i> Thus, expressing MyD88/CD40-based iCO molecules in CAR T cells has the potential to improve the efficacy of CAR T-cell therapy approaches for solid tumors.<b>Significance:</b> Inducible activation of MyD88 and CD40 in CAR T cells with a small-molecule drug not only enhances their effector function, resulting in potent antitumor activity in preclinical solid tumors, but also enables their remote control post infusion. <i>Cancer Discov; 7(11); 1306-19. ©2017 AACR.</i><i>This article is highlighted in the In This Issue feature, p. 1201</i>.
Epithelial Wound Healing Enhanced by Transforming Growth Factor-α and Vaccinia Growth Factor (1987)

Epidermal regeneration following middermal injuries to skin requires both proliferation and migration of keratinocytes. Epidermal growth factor (EGF) stimulates the proliferation of keratinocytes in culture, and topical administration of EGF accelerates epidermal regeneration of partial thickness burns or split-thickness incisions in vivo. Transforming growth factor-alpha (TGF-alpha) and vaccinia growth factor (VGF) have substantial sequence homology with EGF, and all appear to bind to the same receptor protein. Whether TGF-alpha or VGF can affect epidermal wound healing in vivo is not known. The present studies show that topical administration of TGF-alpha or VGF in antibiotic cream to partial thickness burns (second degree) accelerated epidermal regeneration in comparison with untreated or vehicle-treated burns. Low levels of both TGF-alpha and VGF (0.1 microgram per milliliter) appeared to be more effective than EGF in stimulating epidermal regeneration. Regenerated epithelium from burns treated with TGF-alpha or VGF appeared normal histologically. This finding suggests that topical application of selected growth factors may be useful in accelerating healing of partial thickness injuries.
Proofs of Work and Bread Pudding Protocols (1999)

The bread pudding protocol of the present invention represents a novel use of proofs of work and is based upon the same principle as the dish from which it takes its name, namely, that of reuse to minimize waste. Whereas the traditional bread pudding recipe recycles stale bread, our bread pudding protocol recycles the “stale” computations in a POW to perform a separate and useful task, while also maintaining privacy in the task. In one advantageous embodiment of our bread pudding protocol, we consider the computationally intensive operation of minting coins in the MicroMint scheme of Rivest and Shamir and demonstrate how the minting operation can be partitioned into a collection of POWs, which are then used to shift the burden of the minting operation onto a large group of untrusted computational devices. Thus, the computational effort invested in the POWs is recycled to accomplish the minting operation.
Factors Contributing to Medication Noncompliance in Elderly Public Housing Tenants (1986)

A study examined the extent and correlates of noncompliance in 155 predominantly elderly public housing tenants. Data were gathered through in-home interviews; only data from tenants taking prescribed medications on a regularly scheduled basis (n = 140) were analyzed. Noncompliance was significantly (p less than 0.05) associated with taking more than five prescribed medications, an inability to read prescription and auxiliary labels, and difficulty opening flip-off type medication container lids. The results indicate that attempts to reduce the total number of prescription drug products used in these elderly residents by carefully scrutinizing the need for each prescription drug may enhance compliance. Pharmacists could assist in the detection of elderly patients at risk for medication noncompliance (five or more total prescription medications) by assessing the patients' ability to read labels on prescription containers for all new drug additions and refills, and by having them try to open a flip-off container lid.
Insights into the Phosphoregulation of β‐Secretase Sorting Signal by the VHS Domain of GGA1 (2004)

BACE (beta-site amyloid precursor protein cleaving enzyme, beta-secretase) is a type-I membrane protein which functions as an aspartic protease in the production of beta-amyloid peptide, a causative agent of Alzheimer's disease. Its cytoplasmic tail has a characteristic acidic-cluster dileucine motif recognized by the VHS domain of adaptor proteins, GGAs (Golgi-localizing, gamma-adaptin ear homology domain, ARF-interacting). Here we show that BACE is colocalized with GGAs in the trans-Golgi network and peripheral structures, and phosphorylation of a serine residue in the cytoplasmic tail enhances interaction with the VHS domain of GGA1 by about threefold. The X-ray crystal structure of the complex between the GGA1-VHS domain and the BACE C-terminal peptide illustrates a similar recognition mechanism as mannose 6-phosphate receptors except that a glutamine residue closes in to fill the gap created by the shorter BACE peptide. The serine and lysine of the BACE peptide point their side chains towards the solvent. However, phosphorylation of the serine affects the lysine side chain and the peptide backbone, resulting in one additional hydrogen bond and a stronger electrostatic interaction with the VHS domain, hence the reversible increase in affinity.
Disparity in expression of protein kinase C alpha in human glioma versus glioma-derived primary cell lines: therapeutic implications. (1998)

Intracellular signal transduction by the protein kinase C (PKC) family of enzymes plays a critical role in carcinogenesis and cellular growth regulation. Recent studies have suggested that the PKC isoform alpha may be a critical target for antiglioma therapy in humans (G. H. Baltuch et al., Can. J. Neurol. Sci., 22: 264-271, 1995). We studied the expression and subcellular distribution of the PKC alpha isoform in human high- and low-grade gliomas and also in glioma-derived cell lines with immunoblot analyses. Cell lines derived from high-grade gliomas expressed higher levels of PKC alpha than did cell lines derived from low-grade gliomas. In glioblastoma-derived cell lines, PKC alpha was mainly expressed in the soluble (cytosolic) fraction, indicating an inactive state of the enzyme. When analyzed in freshly frozen samples from human gliomas, the expression of PKC alpha was at similar levels in high- and low-grade tumors and was also similar to the levels in normal brain tissue controls. The PKC partial antagonist bryostatin 1, currently undergoing Phase II testing in patients with malignant gliomas, was capable of specifically down-regulating PKC alpha in vitro in glioblastoma-derived cell lines. However, this was not associated with significant growth inhibition. We conclude that the observed overexpression of PKC alpha in glioblastoma-derived cell lines may be an artifact of in vitro growth. Furthermore, we conclude that expression of PKC alpha in glioma-derived cell lines is not essential for cellular growth in vitro because down-regulation of PKC alpha following treatment with bryostatin 1 was not associated with growth inhibition.
Effect of Quaternization of the Glucose Oxidase “Wiring” Redox Polymer on the Maximum Current Densities of Glucose Electrodes (1996)

Redox polymers based on the poly(vinylpyridine) complex of [Os(bpy)2Cl]+/2+ were quaternized with methyl iodide, and the quaternized polymers were used to “wire” glucose oxidase. Quaternization enhanced both the rate of electron transport in cross-linked redox hydrogels containing glucose oxidase and the strength of the electrostatic complex formed between the polycationic redox polymer and the polyanionic glucose oxidase. Quaternization with methyl groups also decreased the number of pyridine rings available for cross-linking by the water soluble cross-linker poly(ethylene glycol) diglycidyl ether. The current densities of glucose electrooxidation increased with the degree of quaternization of the “wires” until one-third of the pyridine rings were quaternized, and the activation energies decreased until one-half of the rings were quaternized.
Multipurpose overhead lines protection algorithm (1999)

A numerical algorithm for multipurpose overhead lines protection, based on one terminal data and derived in the time domain, is presented. The fault location, direction and its nature (arcing or arcless fault) are estimated using the least squares error technique. The faulted phase voltage is modelled as a serial connection of fault resistance and arc voltage, offering more sophisticated line protection. The algorithm can be applied to both the ordinary and high-impedance fault detection, distance protection, intelligent autoreclosure, as well as for directional relaying. The new approach does not require the line zero-sequence resistance as an input datum. The algorithm is derived for the case of most frequent single-phase-to-ground asymmetrical faults. The results of algorithm testing through computer simulation are given. The influence of remote infeed, fault resistance, higher-order harmonics, power system frequency, network topology, line parameters and other factors are investigated and systematically presented.
Fusion of Escherichia coli lacZ to the cytochrome c gene of Saccharomyces cerevisiae. (1981)

Hybrid genes between the Escherichia coli lacZ gene and the iso-1-cytochrome c (CYC1) gene of Saccharomyces cerevisiae were constructed by recombination in vitro. Each of the hybrid genes encodes a chimeric protein with a cytochrome c moiety at the amino terminus and an active beta-galactosidase (beta-D-galactoside galactohydrolase, EC 3.2.1.23) moiety at the carboxy terminus. When these hybrids are introduced into S. cerevisiae on plasmid vectors, they direct synthesis of beta-galactosidase. beta-Galactosidase levels directed by one such plasmid display the pattern of regulation normally seen for cytochrome c (i.e., a reduction of synthesis in cells grown in glucose). This plasmid contains one codon of CYC1 fused to lacZ, and the fused gene is preceded by the 1100 nucleotides that lie upstream from CYC1. An analysis of deletions in the upstream DNA suggests that sequences required for efficient transcription initiation of CYC1 lie within the DNA segment 250--700 base pairs upstream from the start of the CYC1 coding sequence. This region is at least 130 base pairs upstream from the "Hogness box" sequence that precedes the CYC1 coding sequence.
Longitudinal COVID-19 profiling associates IL-1RA and IL-10 with disease severity and RANTES with mild disease (2020)

Together, our data suggest that early intervention to increase expression of CCL5 may prevent patients from developing severe illness. Our data also suggest that measurement of levels of CCL5, as well as IL-1RA and IL-10 in blood individually and in combination, might be useful prognostic biomarkers to guide treatment strategies.
Sleep and Activity Rhythms are Related to Circadian Phase in the Blind (1999)

Changes in sleep and activity rhythms reflect changes in circadian phase.
Identification of Itk/Tsk Src Homology 3 Domain Ligands (1996)

The tyrosine kinase Itk/Tsk is a T cell specific analog of Btk, the tyrosine kinase defective in the human immunodeficiency X-linked agammaglobulinemia and in xid mice. T lymphocytes from Itk-deficient mice are refractory to mitogenic stimuli delivered through the T cell receptor (TCR). To gain insights into the biochemical role of Itk, the binding properties of the Itk SH3 domain were examined. An optimal Itk SH3 binding motif was derived by screening biased phage display libraries; peptides based on this motif bound with high affinity and selectivity to the Itk SH3 domain. Initial studies with T cell lysates indicated that the Itk SH3 domain bound Cbl, Fyn, and other tyrosine phosphoproteins from TCR-stimulated Jurkat cells. Under conditions of increased detergent stringency Sam 68, Wiskott-Aldrich Syndrome protein, and hnRNP-K, but not Cbl and Fyn, were bound to the Itk SH3 domain. By examining the ability of different SH3 domains to interact with deletion variants of Sam 68 and WASP, we demonstrated that the Itk-SH3 domain and the SH3 domains of Src family kinases bind to overlapping but distinct sets of proline-rich regions in Sam 68 and WASP.
Properties of a murine retroviral recombinant of avian acute leukemia virus E26: a murine fibroblast assay for v-ets function (1989)

A replication-defective murine retroviral construct, termed pME26, was generated by inserting avian gag-myb-ets sequences derived from the cloned avian acute leukemia virus E26 into an Abelson murine leukemia virus-derived retroviral vector. ME26 virus can be rescued efficiently from transfected NIH 3T3 cells by replicating murine leukemia viruses. Either pME26-transfected nonproducers or ME26 virus-infected NIH 3T3 cells expressed a 135-kilodalton fusion protein (p135) which was detectable by immunoprecipitation with antiserum directed against avian leukemia virus p27gag, myb or ets oncogene protein, or murine leukemia virus p15gag and was principally localized in the nucleus. NIH 3T3 cells infected with ME26 exhibited morphological alterations and increased proliferation in reduced serum and formed small colonies in agar suspension. Discrete foci could be readily recognized in cells maintained in a defined medium containing 0.03 to 0.1% calf serum. In newborn NFS/N mice, ME26 induced a significantly higher mortality and incidence of erythroid and myeloid leukemias. Analysis of a series of mutants affecting the expression of various portions of p135 indicated that the v-ets gene acts to mitogenically stimulate the proliferation of NIH 3T3 fibroblasts and reduces or abolishes their serum dependence. These properties provide an assay system to study functions of the ets gene family.
Evolution of oligomeric state through geometric coupling of protein interfaces (2012)

Oligomerization plays an important role in the function of many proteins. Thus, understanding, predicting, and, ultimately, engineering oligomerization presents a long-standing interest. From the perspective of structural biology, protein-protein interactions have mainly been analyzed in terms of the biophysical nature and evolution of protein interfaces. Here, our aim is to quantify the importance of the larger structural context of protein interfaces in protein interaction evolution. Specifically, we ask to what extent intersubunit geometry affects oligomerization state. We define a set of structural parameters describing the overall geometry and relative positions of interfaces of homomeric complexes with different oligomeric states. This allows us to quantify the contribution of direct sequence changes in interfaces versus indirect changes outside the interface that affect intersubunit geometry. We find that such indirect, or allosteric mutations affecting intersubunit geometry via indirect mechanisms are as important as interface sequence changes for evolution of oligomeric states.
System-oriented modeling and simulation of biofluidic lab-on-a chip (2005)

This paper presents a schematic-based and system-oriented modeling and simulation framework to enable top-down designs of multifunctional biofluidic lab-on-a-chip systems. An analog hardware description language (Verilog-A) is used to integrate parameterized and closed-form models of elements with different functionalities (e.g., mixing, reaction, injection and separation). Both DC and transient analysis are performed on a practical competitive immunoassay chip to capture the influence of topology, element sizes, material properties and operational parameters on the chip performance. Accuracy (relative error generally less than 5%) and speedup (>100/spl times/) of the schematic-based simulation is obtained by comparison to continuum numerical simulation as well as experimental measurements. A redesign of the original LoC device using our framework to improve bio-analysis efficiency and minimize chip-area has been demonstrated.
Isolation of somatic cell mutants defective in the biosynthesis of phosphatidylethanolamine. (1981)

An in situ autoradiographic assay for CDP-ethanolamine:1,2-sn-diacylglycerol ethanolamine phosphotransferase (EC 2.7.8.1) activity in Chinese hamster ovary cells was developed and used to screen approximately 10,000 individual mutagen-treated colonies attached to filter paper (Esko, J. D., and Raetz, C. R. H. (1978) Proc. Natl. Acad. Sci. U. S. A. 75, 1190-1193). A variant (strain 40.11) was isolated in which the ethanolamine phosphotransferase specific activity in vitro was 6-10-fold less than in the parent, but the level of CDP-choline:1,2-sn-diacylglycerol choline phosphotransferase (EC 2.7.8.2) activity was normal. In extracts, the mutant was also defective in the synthesis of ethanolamine plasmalogen. In vivo, the short term kinetics of labeling with [32P]phosphate or [14C]ethanolamine was correspondingly altered. However, the long tem growth rate and steady state phospholipid compositions of the mutant and parent were quite similar. These results show that the ethanolamine and choline phosphotransferases of Chinese hamster ovary cells are distinct as judged by genetic criteria, while the biosynthesis of phosphatidylethanolamine and its plasmalogen share common enzymatic component(s).
Web page summarization for handheld devices: a natural language approach (2005)

Summarization of web pages is a very interesting topicfrom both academic and commercial point of view.Academically, it is challenging to create a summary of adocument (e.g. a web page) that is highly structured andhas multi-media components in it. From the commercialpoint of view, it is advantageous to summarize web pagesto be viewed in small display devices such as PDAs andcell phones. Summarization not only makes web browsingand navigation easier, but it makes browsing faster ascomplete web pages need not be downloaded beforeviewing. In this paper, a novel combination of naturallanguage and non-natural language based summarizationtechniques have been used to automatically generate anintelligent re-authored display of web pages in real time.
Synthesis of Novel 6,11‐O‐Bridged Bicyclic Ketolides via a Palladium‐Catalyzed Bis‐allylation. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Expression of the Murine Duchenne Muscular Dystrophy Gene in Muscle and Brain (1988)

Complementary DNA clones were isolated that represent the 5' terminal 2.5 kilobases of the murine Duchenne muscular dystrophy (Dmd) messenger RNA (mRNA). Mouse Dmd mRNA was detectable in skeletal and cardiac muscle and at a level approximately 90 percent lower in brain. Dmd mRNA is also present, but at much lower than normal levels, in both the muscle and brain of three different strains of dystrophic mdx mice. The identification of Dmd mRNA in brain raises the possibility of a relation between human Duchenne muscular dystrophy (DMD) gene expression and the mental retardation found in some DMD males. These results also provide evidence that the mdx mutations are allelic variants of mouse Dmd gene mutations.
REFERENCE: Taber's Cyclopedic Medical Dictionary (1993)

REFERENCE: Taber's Cyclopedic Medical Dictionary, 17th ed Edited by Clayton L. Thomas 1993, 2, 590 pp $29.95 hardcover
Speech Act Identification Using Semantic Dependency Graphs with Probabilistic Context-Free Grammars (2016)

We propose an approach for identifying the speech acts of speakers’ utterances in conversational spoken dialogue that involves using semantic dependency graphs with probabilistic context-free grammars (PCFGs). The semantic dependency graph based on the HowNet knowledge base is adopted to model the relationships between words in an utterance parsed by PCFG. Dependency relationships between words within the utterance are extracted by decomposing the semantic dependency graph according to predefined events. The corresponding values of semantic slots are subsequently extracted from the speaker's utterances according to the corresponding identified speech act. The experimental results obtained when using the proposed approach indicated that the accuracy rates of speech act detection and task completion were 95.6% and 77.4% for human-generated transcription (REF) and speech-to-text recognition output (STT), respectively, and the average numbers of turns of each dialogue were 8.3 and 11.8 for REF and STT, respectively. Compared with Bayes classifier, partial pattern tree, and Bayesian-network-based approaches, we obtained 14.1%, 9.2%, and 3% improvements in the accuracy of speech act identification, respectively.