gebhart/patrepeval huggingface dataset:
The location of DNA in complexes of recA protein with double-stranded DNA. A neutron scattering study (1989)

Purified recA protein is found as rodlike homopolymers, and it forms filamentous complexes with double-stranded DNA that are stable in the presence of ATP gamma S, a nonhydrolyzable analogue of ATP. The structure of these filaments has been described in some detail by electron microscopy. Here we confirm the mass per length of 6.5 recA/100 A in solution by small-angle neutron scattering and extend the analysis to homopolymers of recA protein, finding a mass per length of about 7 recA/100 A and a radial mass distribution (cross-sectional radius of gyration) significantly different for the two filaments. The models proposed so far for the structure of the complex have placed the DNA in the center of the filament. Here we verify this assumption using small-angle neutron scattering to locate the DNA in the complexes, exploiting the contrast variation method in D2O/H2O mixtures. Model calculations show that the natural contrast difference between DNA and protein is not sufficient to locate the DNA (which accounts for only 4.7% of the mass in the complex). When deuterated DNA is used, the contrast difference is enhanced, and model calculations and experiment then converge, indicating that the DNA is indeed near the axis of the complex.
Combined adenosine and lidocaine administration limits myocardial reperfusion injury. (1990)

The endogenous compound adenosine may play a role in limiting myocardial ischemia-reperfusion injury through its ability to cause vasodilation, modulate cardiac adrenergic responses, inhibit neutrophil function, or modulate energy supply and demand of the myocardium. The local anesthetic lidocaine has been shown to be protective against myocardial ischemia-reperfusion injury, although its mechanism of action remains unresolved. We hypothesized that administration of exogenous adenosine during reperfusion would limit the size of the infarct that results from a period of ischemia and reperfusion only when the animals are treated with lidocaine. Male, mongrel dogs (13.0-20.0 kg) were anesthetized (30 mg/kg i.v. sodium pentobarbital), and a left thoracotomy was performed. The left circumflex coronary artery (LCx) was isolated and instrumented with an electromagnetic flow probe, a 25-gauge nonobstructing intracoronary catheter, and a critical stenosis. The dogs were allocated randomly to one of four groups: 1) control, n = 13, (saline), 2) adenosine, n = 13, (0.15 mg/kg/ml/min i.c. for the first hour of reperfusion), 3) lidocaine, n = 9, (2.0 mg/kg i.v. given immediately before coronary artery occlusion and just before reperfusion), or 4) adenosine plus lidocaine, n = 11. The LCx was occluded for 90 minutes and reperfused for 6 hours. Regional myocardial blood flow (RMBF) was determined (n = 6 per group) at 80 minutes of occlusion and at 45 minutes of reperfusion with radiolabeled microspheres. RMBF determinations revealed an increase in blood flow to the inner two thirds of the myocardium at 45 minutes of reperfusion only in the presence of the combined treatment. Adenosine treatment alone or lidocaine treatment alone did not affect RMBF. Quantification of infarct size (triphenyltetrazolium method) expressed as a percent of the area at risk revealed a significant limitation of infarct size only in the group treated with both adenosine and lidocaine: control, 47.8 +/- 6.6%; adenosine, 45.0 +/- 3.2%; lidocaine, 46.9 +/- 6.0%; and adenosine and lidocaine, 20.8 +/- 5.6%. Statistical analyses were performed with two-way analysis of variance to account for the two individual drug treatments. The findings show that intracoronary administration of exogenous adenosine, at the dose used, is only effective at limiting myocardial infarct size when administered to lidocaine-treated animals.
Direct Catalytic Synthesis of Enantiopure 5-Substituted Oxazolidinones from Racemic Terminal Epoxides (2005)

A venerable scaffold for asymmetric synthesis and drug development, chiral 5-substituted oxazolidinones are obtained in almost enantiomerically pure form (up to 99.9% ee) starting from racemic terminal epoxides. The salient features of this process include the very simple and convenient experimental protocol and the employment of a readily accessible catalyst and inexpensive, easily handled starting materials. An enantioconvergent approach for the total conversion of racemic epoxide into a single stereoisomeric oxazolidinone is also described.
Production of an interleukin-1 inhibitor by cell line P388D1 murine macrophages stimulated with Haemophilus actinomycetemcomitans lipopolysaccharide (1988)

Murine macrophages of the P388D1 cell line stimulated with lipopolysaccharide (LPS) from Haemophilus actinomycetemcomitans Y4 released an interleukin-1 (IL-1) inhibitor, as well as IL-1. Maximal IL-1 activity in culture supernatants was detected after 24 h of culture. On the other hand, IL-1 inhibitor activity reached a maximum level after 72 h of culture. An IL-1 inhibitor was partially purified from the culture supernatant of P388D1 cells stimulated with Y4 LPS for 72 h by ammonium sulfate precipitation, followed by Sephacryl S-200 gel chromatography. A 160-kilodalton peak inhibitory to IL-1 and a 14-kilodalton peak showing IL-1 activity were separated by Sephacryl S-200 column chromatography. The partially purified IL-1 inhibitor significantly suppressed the proliferation of C3H/HeJ murine thymocytes that had been induced with murine and human IL-1 in the presence of a submitogenic dose of concanavalin A. The IL-1 inhibitor more strongly suppressed human recombinant IL-1 beta than human recombinant IL-1 alpha. This inhibitory activity of the partially purified preparation was unaffected by the presence of trypsin inhibitor and the protease inhibitor aprotinin. The IL-1 inhibitor did not exhibit either IL-2 or IL-2 inhibitor activity. The inhibitor suppressed C3H/HeJ thymocyte proliferation induced by IL-1 in the presence of a saturated concentration of IL-2 instead of a suboptimal concentration of concanavalin A. These results indicate that prolonged culture of Y4 LPS-stimulated murine macrophages releases a specific inhibitor of IL-1.
Correction of genetic disease by making sense from nonsense (1999)

trophin-associated glycoprotein complex. Although gentamicin did not completely restore dystrophin levels, the level produced was sufficient to protect against contraction-induced injury. This presents a significant first step toward the use of these antibiotics in treating a broad class of genetic diseases resulting from nonsense mutations. Although gentamicin promotes translation read-through of the nonsense codon in dystrophin, it may also interfere with nonsense-mediated mRNA decay (6). All eukaryotic cells eliminate mRNAs that encode prematurely terminated products. This may protect cells from the production of nonfunctional or gain-offunction proteins. mRNAs that contain nonsense mutations more than 50 nucleotides upstream of the 3′-most exon-exon junction are selectively degraded by a process that requires protein synthesis. Stabilization of these mRNAs can occur if the ribosome translates through the termination codon (7, 8). The nonsense mutation in the mdx mouse reduces dystrophin mRNA levels to 10‐15% of normal (9). Therefore, the beneficial effects of gentamicin may result from dystrophin mRNA stabilization. It will be important to study dystrophin mRNA levels in the muscle tissues to determine if these drugs exert their action by stabilizing the nonsensecontaining mRNA. This appears likely, because gentamicin restored CFTR mRNA level in a cystic fibrosis (CF) bronchial epithelial cell line carrying a premature stop codon (3).
Change Process for the Session Initiation Protocol (SIP) (2002)

This memo documents a process intended to apply architectural discipline to the future development of the Session Initiation Protocol (SIP). There have been concerns with regards to new SIP proposals. Specifically, that the addition of new SIP features can be damaging towards security and/or greatly increase the complexity of the protocol. The Transport Area directors, along with the SIP and Session Initiation Proposal Investigation (SIPPING) working group chairs, have provided suggestions for SIP modifications and extensions.
Ultra-Subwavelength Two-Dimensional Plasmonic Circuits (2012)

We report electronics regime (GHz) two-dimensional (2D) plasmonic circuits, which locally and nonresonantly interface with electronics, and thus offer to electronics the benefits of their ultrasubwavelength confinement, with up to 440,000-fold mode-area reduction. By shaping the geometry of 2D plasmonic media 80 nm beneath an unpatterned metallic gate, plasmons are routed freely into various types of reflections and interferences, leading to a range of plasmonic circuits, e.g., plasmonic crystals and plasmonic-electromagnetic interferometers, offering new avenues for electronics.
Crystal structure of Zen4 in the apo state reveals a missing conformation of kinesin (2017)

Kinesins hydrolyse ATP to transport intracellular cargoes along microtubules. Kinesin neck linker (NL) functions as the central mechano-chemical coupling element by changing its conformation through the ATPase cycle. Here we report the crystal structure of kinesin-6 Zen4 in a nucleotide-free, apo state, with the NL initial segment (NIS) adopting a backward-docked conformation and the preceding α6 helix partially melted. Single-molecule fluorescence resonance energy transfer (smFRET) analyses indicate the NIS of kinesin-1 undergoes similar conformational changes under tension in the two-head bound (2HB) state, whereas it is largely disordered without tension. The backward-docked structure of NIS is essential for motility of the motor. Our findings reveal a key missing conformation of kinesins, which provides the structural basis of the stable 2HB state and offers a tension-based rationale for an optimal NL length to ensure processivity of the motor.
Rab geranylgeranyl transferase catalyzes the geranylgeranylation of adjacent cysteines in the small GTPases Rab1A, Rab3A, and Rab5A. (1994)

Rab proteins are Ras-related small GTPases that are geranylgeranylated on cysteine residues located at or near their C termini. They differ from other geranylgeranylated small GTPases in several important respects. (i) Most Rab proteins contain two adjacent cysteine residues within one of the following C-terminal sequence motifs: -XXCC, -XCXC, or -CCXX; (ii) a Rab protein that ends in a -XCXC motif has been shown to be geranylgeranylated on both adjacent cysteine residues; and (iii) Rab proteins are substrates of a unique Rab-specific geranylgeranyltransferase. Whether this enzyme catalyzes the geranylgeranylation of both cysteines is unknown. We addressed this question by direct structural analysis of in vitro prenylated proteins. We incubated recombinant Rab geranylgeranyltransferase, Rab escort protein, and [1-3H]geranylgeranyl pyrophosphate with recombinant wild-type Rab1A (-XXCC), Rab3A (-XCXC), or Rab5A (-CCXX) and treated each labeled protein with trypsin. We then analyzed the resulting peptides by HPLC and electrospray mass spectrometry and found that for each protein both C-terminal adjacent cysteines were geranylgeranylated. These results indicate that Rab geranylgeranyltransferase/Rab escort protein catalyzes the geranylgeranylation of both cysteines in Rab proteins with three distinct C-terminal motifs and suggest that other Rab proteins with these motifs may be similarly modified.
The cytokine storm and COVID‐19 (2020)

Coronavirus disease 2019 (COVID-19), which began in Wuhan, China, in December 2019, has caused a large global pandemic and poses a serious threat to public health. More than 4 million cases of COVID-19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been confirmed as of 11 May 2020. SARS-CoV-2 is a highly pathogenic and transmissible coronavirus that primarily spreads through respiratory droplets and close contact. A growing body of clinical data suggests that a cytokine storm is associated with COVID-19 severity and is also a crucial cause of death from COVID-19. In the absence of antivirals and vaccines for COVID-19, there is an urgent need to understand the cytokine storm in COVID-19. Here, we have reviewed the current understanding of the features of SARS-CoV-2 and the pathological features, pathophysiological mechanisms, and treatments of the cytokine storm induced by COVID-19. In addition, we suggest that the identification and treatment of the cytokine storm are important components for rescuing patients with severe COVID-19.
Synthesis and Characterization of Stable Fluorocarbon Nanostructures as Drug Delivery Vehicles for Cytolytic Peptides (2008)

The therapeutic potential of cytolytic peptides is plagued by nonspecificity and enzymatic degradation. We report the first stable incorporation of melittin (a 26 amino acid amphipathic peptide) into an outer lipid monolayer of perfluorocarbon nanoparticles. Melittin binds avidly to the nanoparticles (dissociation constant approximately 3.27 nM) and retains its pore-forming activity after contact-mediated delivery to model bilayer membrane (liposomes) thereby demonstrating the effectiveness of perfluorocarbon nanoparticles as unique nanocarriers for cytolytic peptides.
Toward the structural genomics of complexes: Crystal structure of a PE/PPE protein complex from Mycobacterium tuberculosis (2006)

The developing science called structural genomics has focused to date mainly on high-throughput expression of individual proteins, followed by their purification and structure determination. In contrast, the term structural biology is used to denote the determination of structures, often complexes of several macromolecules, that illuminate aspects of biological function. Here we bridge structural genomics to structural biology with a procedure for determining protein complexes of previously unknown function from any organism with a sequenced genome. From computational genomic analysis, we identify functionally linked proteins and verify their interaction in vitro by coexpression/copurification. We illustrate this procedure by the structural determination of a previously unknown complex between a PE and PPE protein from the Mycobacterium tuberculosis genome, members of protein families that constitute approximately 10% of the coding capacity of this genome. The predicted complex was readily expressed, purified, and crystallized, although we had previously failed in expressing individual PE and PPE proteins on their own. The reason for the failure is clear from the structure, which shows that the PE and PPE proteins mate along an extended apolar interface to form a four-alpha-helical bundle, where two of the alpha-helices are contributed by the PE protein and two by the PPE protein. Our entire procedure for the identification, characterization, and structural determination of protein complexes can be scaled to a genome-wide level.
Fabrication and characterization of individually addressable vertical-cavity surface-emitting laser arrays and integrated VCSEL/PIN detector arrays (2007)

With the emergence of the internet, the demand for high data transmission rates in short haul area networks and fiber-to-the- desktop applications is increasing every year. Densely packed one-dimensional and two-dimensional vertical-cavity surface-emitting laser (VCSEL) arrays offer new possibilities for future short haul parallel optical links, free-space optical interconnects at the chip-to-chip, board-to-board, and on-board level. In this paper, we describe the manufacturing process of individually addressable two-dimensional VCSEL arrays, PIN detector arrays, and integrated VCSEL / PIN detector arrays. We also present measurement results of the fabricated devices and comment on the reliability.
New Reactions Involving Alkaline Treatment of 3-Nitroso-2-oxazolidones. II (1954)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNew Reactions Involving Alkaline Treatment of 3-Nitroso-2-oxazolidones. IIMelvin S. Newman and Walter M. EdwardsCite this: J. Am. Chem. Soc. 1954, 76, 7, 1840–1845Publication Date (Print):April 1, 1954Publication History Published online1 May 2002Published inissue 1 April 1954https://pubs.acs.org/doi/10.1021/ja01636a031https://doi.org/10.1021/ja01636a031research-articleACS PublicationsRequest reuse permissionsArticle Views293Altmetric-Citations16LEARN 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 optionsGet e-Alertsclose Get e-Alerts
Homogeneous pharmacologic and cell-based screens provide diverse strategies in drug discovery: somatostatin antagonists as a case study. (1998)

The development of high throughput, homogeneous pharmacologic and functional assays and their implementation in screening combinatorial libraries has increased the pace of stochastic drug discovery in recent years. New, noninvasive approaches involving radiometric proximity assays, an array of fluorescence-based technologies, and reporter gene constructs in mammalian and nonmammalian systems are providing more options for the selection of specific therapeutic targets. The increasing sophistication of homogeneous assay designs has also served as a springboard to better lead validation in drug discovery initiatives. This review examines these approaches in the context of new drug discovery strategies which combine a growing repertoire of high throughput screening techniques. The utility and importance of cell-based assays vis-a-vis pharmacologic (cell-free) assays is considered with specific reference given to yeast-based functional screens and homogeneous binding methodologies used to search for somatostatin antagonists and other potential growth hormone secretagogues. Also considered is the custom tailoring of specific chemical libraries which provide yet another level of target selectivity. The advantages and shortcomings of these various technologies are discussed in light of emerging trends toward higher throughput and nanoscale formats which are pushing the limits of measurable response at the cellular and molecular level.
Human cutaneous T cell lymphoma and leukemia cell lines produce and respond to T cell growth factor (1981)

Three cell lines of mature T cell origin derived from patients with cutaneous T cell lymphoma-leukemias (CTCL) were found to be constitutive producers of T cell growth factor (L-TCGF). These are the first reported human cell lines which constitutively produce TCGF. Biologically active TCGF could also be eluted from the surface of these cells using an acid glycine buffer under conditions that maintained cell viability, and subcellular fractionation showed that almost all the TCGF activity was associated with the plasma membrane. Over 30 other human hematopoietic cell lines derived from other disorders were unable to produce TCGF even after induction, and their acid eluates did not contain TCGF activity. L-TCGF from CTCL lines had the same biological activity as TCGF obtained from normal leukocytes (N-TCGF) in that they both supported the long-term growth of normal T cells only after the cells were previously activated by antigen or lectin. Both L-TCGF and N-TCGF increased the rate of proliferation of TCGF-independent and TCGF-dependent CTCL cell lines. The same three factor-independent cell lines that released TCGF adsorbed TCGF in a cell-concentration, time-, and temperature-dependent manner. Since the CTCL cell lines produce TCGF, adsorb TCGF, and increase their proliferative rate in response to TCGF or a related molecule, it is suggested that this endogenously produced factor plays a role in maintaining the abnormal proliferation of these cells in culture as permanently growing cell lines independent of exogenous TCGF. However, this does not mean that this is an essential aspect of neoplastic transformation. Since it is unusual to develop these cell lines in the absence of the continuous need for added TCGF, "autostimulation" may be one of the many unusual variant phenotypic properties sometimes associated with neoplastic cells that gives them a selective advantage for in vitro growth.
Molecular and Cellular MR Imaging (2007)

The application of histology and molecular biology in humans is very restricted. Neither can provide a satisfactory noninvasive deep-tissue visualization of molecules or cells in living organisms. The development of molecular and cellular imaging aims to bridge this gap and provide methods that
IL-21 in Synergy with IL-15 or IL-18 Enhances IFN-γ Production in Human NK and T Cells (2003)

NK and T cell-derived IFN-gamma is a key cytokine that stimulates innate immune responses and directs adaptive T cell response toward Th1 type. IL-15, IL-18, and IL-21 have significant roles as activators of NK and T cell functions. We have previously shown that IL-15 and IL-21 induce the expression of IFN-gamma, T-bet, IL-12R beta 2, and IL-18R genes both in NK and T cells. Now we have studied the effect of IL-15, IL-18, and IL-21 on IFN-gamma gene expression in more detail in human NK and T cells. IL-15 clearly activated IFN-gamma mRNA expression and protein production in both cell types. IL-18 and IL-21 enhanced IL-15-induced IFN-gamma gene expression. IL-18 or IL-21 alone induced a modest expression of the IFN-gamma gene but a combination of IL-21 and IL-18 efficiently up-regulated IFN-gamma production. We also show that IL-15 activated the binding of STAT1, STAT3, STAT4, and STAT5 to the regulatory sites of the IFN-gamma gene. Similarly, IL-21 induced the binding of STAT1, STAT3, and STAT4 to these elements. IL-15- and IL-21-induced STAT1 and STAT4 activation was verified by immunoprecipitation with anti-phosphotyrosine Abs followed by Western blotting with anti-STAT1 and anti-STAT4 Abs. IL-18 was not able to induce the binding of STATs to IFN-gamma gene regulatory sites. IL-18, however, activated the binding of NF-kappa B to the IFN-gamma promoter NF-kappa B site. Our results suggest that both IL-15 and IL-21 have an important role in activating the NK cell-associated innate immune response.