gebhart/patrepeval huggingface dataset:
Production of human normal adult and fetal hemoglobins in Escherichia coli (1997)

A hemoglobin expression system in Escherichia coli is described. In order to produce authentic human hemoglobin, we need to co-express both methionine aminopeptidase and globin genes under the control of a strong promoter. We have constructed three plasmids, pHE2, pHE4 and pHE7, for the expression of human normal adult hemoglobin and a plasmid, pHE9, for the expression of human fetal hemoglobin, in high yields. The globin genes can be derived from either synthetic genes or human globin cDNAs. The extra amino-terminal methionine residues of the expressed globins can be removed by the co-expressed methionine aminopeptidase. The heme is inserted correctly into the expressed alpha-globin from our expression plasmids. A fraction (approximately 25%) of the heme is not inserted correctly into the expressed beta- or gamma-globin. However, the incorrectly inserted hemes can be converted into the correct conformation by carrying out a simple oxidation-reduction process on the purified hemoglobin molecule. We have investigated the functional properties of the expressed hemoglobins by measuring their oxygen-binding properties and their structural features by obtaining their 1H-NMR spectra. Our results show that authentic human normal adult and fetal hemoglobins can be produced from our expression plasmids in E. coli and in high yields. Our expression system allows us to design and to produce any recombinant hemoglobins needed for our research on the structure-function relationship in hemoglobin.
Glycerol metabolism in the extremely halophilic bacteriumSalinibacter ruber (2004)

Growth of Salinibacter ruber, a red, extremely halophilic bacterium phylogenetically affiliated with the Flavobacterium/Cytophaga branch of the domain Bacteria, is stimulated by glycerol. In contrast to glucose consumption, which starts only after more easily degradable substrates present in yeast extract have been depleted, glycerol is consumed during the earliest growth phases. When U-14C-labeled glycerol was added to the culture, up to 25% of the radioactivity was incorporated by the cells. Glycerol kinase activity was detected only in cells grown in the presence of glycerol (up to 90 nmol mg protein−1 min−1). This enzyme functioned over salt concentrations from 0.6 to 2.8 M KCl. No significant activity of NAD-dependent glycerol dehydrogenase was found. It is suggested that Salinibacter may use glycerol as one of its principal substrates in its habitat, the saltern crystallizer ponds.
A power conditioning system for thermoelectric generator based on interleaved Boost converter with MPPT control (2011)

The thermoelectric generation (TEG) system has its special charactristics of high stablility, low voltage and high current output, which is different from PV modules. The power conditioning system and control schemes used in PV applications cannot be directly applied to TEG applications. A power conditioning system for TEG based on interleaved Boost converter with maximum power point tracking (MPPT) control is investigated in this paper. Since an internal resistance exists inside TEG modules, an improved perturbation and observation (P&O) MPPT control scheme with power limit is proposed to extract maximum power from TEG by matching the load with internal resistance. Since the battery is usually employed as the load for TEG systems, the interleaved Boost converter operates in two different modes for battery charging: before the battery is fully charged, the system outputs the maximum power (MPPT mode); after that, the system outputs constant voltage for floating charge (constant voltage mode). A mode transfer method is proposed to ensure smooth switching between the two above operating modes. A 200W experimental prototype has been built, and the experimental results verify the feasibility and effectiveness of the developed power conditioning system with the proposed control schemes.
Structure and electrocompression of electrodeposited iodine monolayers on gold (111) (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStructure and electrocompression of electrodeposited iodine monolayers on gold (111)B. M. Ocko, G. M. Watson, and Jia WangCite this: J. Phys. Chem. 1994, 98, 3, 897–906Publication Date (Print):January 1, 1994Publication History Published online1 May 2002Published inissue 1 January 1994https://pubs.acs.org/doi/10.1021/j100054a026https://doi.org/10.1021/j100054a026research-articleACS PublicationsRequest reuse permissionsArticle Views568Altmetric-Citations157LEARN 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 InRedditEmail Other access options Get e-Alerts
Muscle miRNAome shows suppression of chronic inflammatory miRNAs with both prednisone and vamorolone (2018)

Corticosteroids are highly prescribed and effective anti-inflammatory drugs but the burden of side effects with chronic use significantly detracts from patient quality of life, particularly in children. Developing safer steroids amenable to long-term use is an important goal for treatment of chronic inflammatory diseases such as Duchenne muscular dystrophy (DMD). We have developed vamorolone (VBP15), a first-in-class dissociative glucocorticoid receptor (GR) ligand that shows the anti-inflammatory efficacy of corticosteroids without key steroid side effects in animal models. miRNAs are increasingly recognized as key regulators of inflammatory responses. To define effects of prednisolone and vamorolone on the muscle miRNAome, we performed a preclinical discovery study in the mdx mouse model of DMD. miRNAs associated with inflammation were highly elevated in mdx muscle. Both vamorolone and prednisolone returned these toward wild-type levels (miR-142-5p, miR-142-3p, miR-146a, miR-301a, miR-324-3p, miR-455-5p, miR-455-3p, miR-497, miR-652). Effects of vamorolone were largely limited to reduction of proinflammatory miRNAs. In contrast, prednisolone activated a separate group of miRNAs associated with steroid side effects and a noncoding RNA cluster homologous to human chromosome 14q32. Effects were validated for inflammatory miRNAs in a second, independent preclinical study. For the anti-inflammatory miRNA signature, bioinformatic analyses showed all of these miRNAs are directly regulated by, or in turn activate, the inflammatory transcription factor NF-κB. Moving forward miR-146a and miR-142 are of particular interest as biomarkers or novel drug targets. These data validate NF-κB signaling as a target of dissociative GR-ligand efficacy in vivo and provide new insight into miRNA signaling in chronic inflammation.
Nodal Signaling in Vertebrate Development (2003)

TGFss signals belonging to the Nodal family set up the embryonic axes, induce mesoderm and endoderm, pattern the nervous system, and determine left-right asymmetry in vertebrates. Nodal signaling activates a canonical TGFss pathway involving activin receptors, Smad2 transcription factors, and FoxH1 coactivators. In addition, Nodal signaling is dependent on coreceptors of the EGF-CFC family and antagonized by the Lefty and Cerberus families of secreted factors. Additional modulators of Nodal signaling include convertases that regulate the generation of the mature signal, and factors such as Arkadia and DRAP1 that regulate the cellular responses to the signal. Complex regulatory cascades and autoregulatory loops coordinate Nodal signaling during early development. Nodals have concentration-dependent roles and can act both locally and at a distance. These studies demonstrate that Nodal signaling is modulated at almost every level to precisely orchestrate tissue patterning during vertebrate embryogenesis.
Induction of geranyl pyrophosphate pyrophosphatase activity by cholesterol‐suppressive isoprenoids (1995)

Abstract Diets supplemented (1 mmol/kg) with thymol, carvacrol, and β‐ionone significantly decreased the serum cholesterol levels of cockerels. These mevalonate‐derived end products of plant secondary metabolism (isoprenoids) had no impact on two cytosolic prenyl alcohol (and ethanol) dehydrogenase activities; each treatment increased microsomal geranyl pyrophosphate pyrophosphatase activity by greater than twofold. The structural diversity of the isoprenoids which suppress cholesterol synthesis may be reconciled by their ability to increase pyrophosphatase activity, thus leading to the production of the endogenous, post‐transcriptional regulator of 3‐hydroxy‐3‐methyglutaryl coenzyme A reductase activity.
Liposome-mediated in vivo E1A gene transfer suppressed dissemination of ovarian cancer cells that overexpress HER-2/neu. (1995)

The HER-2/neu proto-oncogene is frequently amplified or overexpressed in many different types of human cancers, a phenomenon that has been shown to correlate with shorter survival time and lower survival rate in ovarian cancer patients. We previously reported that increased HER-2/neu expression led to more severe malignancy and increased metastatic potential in animal models and that the adenovirus 5 E1A gene repressed HER-2/neu gene expression at transcriptional level and was able to suppress tumor growth when stably transfected into human ovarian cancer SKOV-3 cells which overexpress HER-2/neu. To investigate whether the E1A gene may be used as a therapeutic agent for HER-2/neu-overexpressing human cancers in living hosts, we first developed tumor-bearing mice by injecting SKOV-3 cells that overexpress HER-2/neu intraperitonealy into female nu/nu mice. Five days later, we used cationic liposomes to directly deliver the E1A gene into adenocarcinomas that developed in the peritoneal cavity and on the mesentery of the mice that received the SKOV-3 cell injection. We found that liposome-mediated E1A gene transfer significantly inhibited growth and dissemination of ovarian cancer cells that overexpress HER-2/neu in the treated mice; about 70% of these mice survived at least 365 days, whereas all the control mice that did not receive the gene therapy developed severe tumor symptoms and died within 160 days. The results suggest that liposome-mediated E1A gene transfer may serve as an effective therapy for human ovarian cancers that overexpress HER-2/neu by directly targeting the HER-2/neu oncogene.
The PI3Kδ inhibitor parsaclisib ameliorates pathology and reduces autoantibody formation in preclinical models of systemic lupus erythematosus and Sjӧgren’s syndrome (2021)

Dysregulation of phosphoinositide 3-kinase δ (PI3Kδ) signaling pathway has been implicated in the pathogenesis of inflammatory and autoimmune diseases. Parsaclisib (INCB050465) represents a potent and selective PI3Kδ inhibitor, which is being clinically investigated for treatment of autoimmune hemolytic anemia and hematological malignancies. We characterized the potential of parsaclisib to ameliorate autoimmune mechanisms implicated in the pathophysiology of systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). Spontaneous mouse models of SLE and SS were utilized to elucidate the efficacy of orally administered parsaclisib on autoreactive B-cell-mediated antibody-driven disease. Parsaclisib significantly reduced disease symptoms and pathology in three distinct mouse models of SLE. Parsaclisib effectively preserved renal function as measured by glomerular filtration rate, abrogated histopathological evidence of nephritis, modulated discrete immune cell subsets, and decreased anti-dsDNA antibody level. Furthermore, parsaclisib demonstrated efficacy in two spontaneous mouse models of SS. Oral parsaclisib treatment ameliorated the severity of salivary gland inflammation and reduced circulating levels of autoantibodies. Parsaclisib mediated improvement of salivary gland inflammation coincided with reduced B-cell activating cytokine (BAFF) in saliva. Transcriptomic analysis of kidney and salivary gland tissues revealed a downregulation in inflammatory gene expression consistent with PI3Kδ pathway inhibition. Parsaclisib reduced autoreactive B-cells and autoantibody levels, and significantly improved nephritis and salivary gland inflammation. These data provide the scientific rationale for PI3Kδ inhibition as a therapeutic strategy for treatment of B-cell-mediated antibody-driven autoimmune diseases.
Phenomenology and Law FEELING CRIMINAL IN MACBETH (2012)

Macbeths murder of Duncan is sensible crime, not because it's practical or judicious (it's neither), but because it's born of the senses and experi enced as sensation. This is not to say that Macbeth does not thin him self into the criminal event, but that the thinking he does he does with his body. Macbeth presents criminal thoughts not as ontologically distinct products of the intellect or soul, but as secretions of the senses, properties of active receptive bodies moving through world of things. Focusing on the dagger scene in act 2, scene 1, this essay shows how criminality becomes riela for phenomenological speculation in the play. Macbeth s experience of criminal becoming is characterized by what Bruce Smith calls a relational way of knowing, one in which murderous thoughts are shaped by physical, sensual interaction with the objects of the mate rial world.1 For Macbeth, then, being criminal might more accurately be described as feeling criminal. Criminality is less state of being than a unit of experience, process involving both ideas and things in way that forces us to abandon the mutually exclusive categories of subject and object. Criminality was career-long preoccupation for Shakespeare, and his approach to the topic varied from play to play, from poem to poem, and even within individual plays or poems. Still, one can identify marked tendency in his writing to seek criminality beyond the flesh. In The Rape of Lucrece, it is untimely thought did instigate Tarquin's all too timeless speed (11.43—44) towards the woman he would violate. Richard Duke of Gloucester is from the very outset of Richard III defined as some one whose criminality originates within, at the level of thoughts, someone who is malicious to the core and who understands, moreover, the inner reaches of the selr to be not only source or crime, but also place or concealment: Dive, thoughts, down to my soul (1.1.41), he says as Ciar ence approaches. Angelo, in Measure for Measure, begins the play with
The highly dynamic CRISPR1 system of Streptococcus agalactiae controls the diversity of its mobilome (2012)

Clustered regularly interspaced short palindromic repeats (CRISPR) confer immunity against mobile genetic elements (MGEs) in prokaryotes. Streptococcus agalactiae, a leading cause of neonatal infections contains in its genome two CRISPR/Cas systems. We show that type 1-C CRISPR2 is present in few strains but type 2-A CRISPR1 is ubiquitous. Comparative sequence analysis of the CRISPR1 spacer content of 351 S. agalactiae strains revealed that it is extremely diverse due to the acquisition of new spacers, spacer duplications and spacer deletions that witness the dynamics of this system. The spacer content profile mirrors the S. agalactiae population structure. Transfer of a conjugative transposon targeted by CRISPR1 selected for spacer rearrangements, suggesting that deletions and duplications pre-exist in the population. The comparison of protospacers located within MGE or the core genome and protospacer-associated motif-shuffling demonstrated that the GG motif is sufficient to discriminate self and non-self and for spacer selection and integration. Strikingly more than 40% of the 949 different CRISPR1 spacers identified target MGEs found in S. agalactiae genomes. We thus propose that the S. agalactiae type II-A CRISPR1/Cas system modulates the cohabitation of the species with its mobilome, as such contributing to the diversity of MGEs in the population.
Oil Thickening in the Mack T-7 Engine Test—Fuel Effects and the Influence of Lubricant Additives on Soot Aggregation (1985)

&lt;div class="htmlview paragraph"&gt;For a diesel lubricant to meet the new Mack EO-K/2 specification, it must be effective in preventing excessive viscosity increase during the 150-hour Mack T-7 test. The severity of this test is shown to be highly dependent upon fuel chemistry and injection timing. A comparison of various lubricant formulations in the Mack T-7 engine run with a given fuel suggests that nitrogen-containing succinimide dispersants, dispersant viscosity improvers, and supplemental ash in the form of overbased sulfonate detergents are effective in controlling viscosity increase. Crankcase oil thickening follows a modified form of Brinkman’s equation and can be predicted from measured values of soot particle size and concentration. Basic lubricant additives are shown to prevent particle size growth by adsorption on to the acidic soot surface, thereby interrupting soot aggregation and retarding oil thickening.&lt;/div&gt;
A compact superconducting cyclotron for the production of high intensity protons (1997)

This paper reviews a study of a compact superconducting cyclotron to accelerate 200 microamps of protons to 250 MeV. The basic cyclotron structure is the same as that developed in a previous study of a 250 MeV cancer therapy cyclotron, the chief difference in the study reported here being much higher beam current (x10,000) than in the therapy cyclotron to meet desired specifications for the ‘Driver ’ accelerator of an ISOL type radioactive beam facility. The increase in current is far below (x1/50) the axial space charge limit of the proposed cyclotron, but longitudinal space charge requires changing the extraction system from a single turn to a multi-turn system thereby increasing beam losses. Leading design uncertainties, namely the overall efficiency of the multi-turn extraction system and the distribution of radioactivity generated by lost beam are addressed herein; results indicate reasonable residual activity in the cyclotron from the perspective of customary ‘hands-on ’ maintenance operations.
Paclitaxel Derivatives for Targeted Therapy of Cancer:  Toward the Development of Smart Taxanes (1999)

The pharmacologic efficacy of the promising antitumor agent paclitaxel (Taxol) may be potentially enhanced through derivatization of the drug to a water-soluble tumor-recognizing conjugate. This work reports the design and synthesis of the first tumor-directed derivative of paclitaxel. A 7-amino acid synthetic peptide, BBN[7-13], which binds to the cell surface bombesin/gastrin-releasing peptide (BBN/GRP) receptor, was conjugated to the paclitaxel-2'-hydroxy function by a heterobifunctional poly(ethylene glycol) linker. The resulting conjugate, designated PTXPEGBBN[7-13], was soluble to the upper limit of tested concentrations (250 mg/mL). The conjugate completely retained the receptor binding properties of the attached peptide as compared with those of the unconjugated BBN[7-13]. In experiments with NCI-H1299 human nonsmall cell lung cancer cells, the cytotoxicity of the PTXPEGBBN[7-13] conjugate at a 15 nM dose was enhanced by a factor of 17.3 for 24 h and 10 for 96 h exposure times, relative to paclitaxel. The IC(50) of the conjugate, tested against the same cell line, was lower than the free drug by a factor of 2.5 for both 24 h and 96 h exposures. These results describe, for the first time, the design and synthesis of a soluble tumor-directed paclitaxel prodrug which may establish a new mode for the utilization of this drug in cancer therapy.
Elastin biosynthesis: The missing link in tissue-engineered blood vessels (2006)

Nearly 20 years have passed since Weinberg and Bell attempted to make the first tissue-engineered blood vessels. Following this early attempt, vascular tissue engineering has emerged as one of the most promising approaches to fabricate orderly and mechanically competent vascular substitutes. In elastic and muscular arteries, elastin is a critical structural and regulatory matrix protein and plays an important and dominant role by conferring elasticity to the vessel wall. Elastin also regulates vascular smooth muscle cells activity and phenotype. Despite the great promise that tissue-engineered blood vessels have to offer, little research in the last two decades has addressed the importance of elastin incorporation into these vessels. Although cardiovascular tissue engineering has been reviewed in the past, very little attention has been given to elastin. Thus, this review focuses on the recent advances made towards elastogenesis and the challenges we face in the quest for appropriate functional vascular substitutes.
The First Immunoglobulin-Like Domain of HveC Is Sufficient To Bind Herpes Simplex Virus gD with Full Affinity, While the Third Domain Is Involved in Oligomerization of HveC (1999)

The human herpesvirus entry mediator C (HveC/PRR1) is a member of the immunoglobulin family used as a cellular receptor by the alphaherpesviruses herpes simplex virus (HSV), pseudorabies virus, and bovine herpesvirus type 1. We previously demonstrated direct binding of the purified HveC ectodomain to purified HSV type 1 (HSV-1) and HSV-2 glycoprotein D (gD). Here, using a baculovirus expression system, we constructed and purified truncated forms of the receptor containing one [HveC(143t)], two [HveC(245t)], or all three immunoglobulin-like domains [HveC(346t)] of the extracellular region. All three constructs were equally able to compete with HveC(346t) for gD binding. The variable domain bound to virions and blocked HSV infection as well as HveC(346t). Thus, all of the binding to the receptor occurs within the first immunoglobulin-like domain, or V-domain, of HveC. These data confirm and extend those of Cocchi et al. (F. Cocchi, M. Lopez, L. Menotti, M. Aoubala, P. Dubreuil, and G. Campadelli-Fiume, Proc. Natl. Acad. Sci. USA 95:15700, 1998). Using biosensor analysis, we measured the affinity of binding of gD from HSV strains KOS and rid1 to two forms of HveC. Soluble gDs from the KOS strain of HSV-1 had the same affinity for HveC(346t) and HveC(143t). The mutant gD(rid1t) had an increased affinity for HveC(346t) and HveC(143t) due to a faster rate of complex formation. Interestingly, we found that HveC(346t) was a tetramer in solution, whereas HveC(143t) and HveC(245t) formed dimers, suggesting a role for the third immunoglobulin-like domain of HveC in oligomerization. In addition, the stoichiometry between gD and HveC appeared to be influenced by the level of HveC oligomerization.
Biometric Identity Verification Using Intra-Body Propagation Signal (2007)

We propose to utilize an electromagnetic wave through a human body as biometrics. The electromagnetic wave (intra-body propagation signal) is generated at a relatively shallow depth in the human body through a pair of electrodes pasted on the human skin. The biological tissue of each individual human being is different from that of others, so that the transfer characteristic of the intra-body propagation signal is also different mutually. By using such a difference, it is expected to authenticate personal identification. In addition, liveness detection can be realized simultaneously using the intra-body propagation signal. It is effective on the detection of spoofing using artificial bodies. In this paper, we examine the individual feature in the intra-body propagation signal based on the spectrum analysis. As a result, the verification rate of 58% is obtained using the similarity of the power spectrum especially in the 30-60 MHz sub-band.