gebhart/patrepeval huggingface dataset:
Immunization of Saimiri sciureus Monkeys with a Recombinant Hybrid Protein Derived from the Plasmodium falciparum Antigen Glutamate-Rich Protein and Merozoite Surface Protein 3 Can Induce Partial Protection with Freund and Montanide ISA720 Adjuvants (2005)

The immunogenicity and efficacy of a hybrid recombinant protein derived from the N-terminal end of the glutamate-rich protein (GLURP) and the C-terminal portion of the merozoite surface protein 3 (MSP3) of Plasmodium falciparum was evaluated in Saimiri sciureus monkeys. The GLURP/MSP3 hybrid protein, expressed in Lactococcus lactis, was administered in association with alum, Montanide ISA720, or complete or incomplete Freund adjuvant (CFA/IFA) in groups of five animals each. The three formulations were shown to be immunogenic, but the one with alum was shown to be weak compared to the other two, particularly CFA/IFA, which provided very high antibody titers (enzyme-linked immunosorbent assay titers of >3,000,000 and immunofluorescence antibody test titers of 6,400). After a challenge infection with P. falciparum FUP strain, all five monkeys from the GLURP/MSP3-alum group showed a rapid increase in parasitemia, reaching 10% and were treated early. The two monkeys with the highest antibody titers in group GLURP/MSP3-Montanide ISA720 had a delay in the course of parasitemia and were treated late due to a low hematocrit. In the GLURP/MSP3-CFA/IFA group, parasitemia remained below this threshold in four of the five animals and, after it reached a peak, parasitemia started to decrease and monkeys were treated late. When all animals were grouped according to the outcome, a statistically significant association between high antibody titers and partial protection was observed. The challenge infection boosted the antibody titers, and the importance of this event for vaccine efficacy in areas where this parasite is endemic is discussed. In conclusion, these data suggest that GLURP and MSP3 can induce protection against malaria infection if antibodies are induced at properly high titers.
FDA Approval Summary: Tocilizumab for Treatment of Chimeric Antigen Receptor T Cell-Induced Severe or Life-Threatening Cytokine Release Syndrome (2018)

Severe or life-threatening chimeric antigen receptor (CAR) T cell-induced cytokine release syndrome (CRS) requires urgent treatment to prevent fatal outcomes. In two independent cohorts, the majority of patients with severe or life-threatening CAR T cell-induced CRS responded to treatment with one or two doses of tocilizumab in addition to advanced supportive care. More research is needed to determine the optimal dose and schedule of tocilizumab for treatment of CAR T cell-induced CRS.
Inhibition by perhexiline of oxidative phosphorylation and the beta-oxidation of fatty acids: possible role in pseudoalcoholic liver lesions. (1994)

In an attempt to better understand the mechanisms for pseudoalcoholic liver lesions in human beings, we determined the effects of perhexiline on mitochondrial functions in mice and rats. A first series of studies suggested that protonated perhexiline entered mouse mitochondria along the mitochondrial membrane potential. Release of a proton in the mitochondrial matrix led to uncoupling of oxidative phosphorylation, and accumulation of perhexiline inhibited complexes I and II of the respiratory chain, decreased ATP formation in vitro and decreased the mitochondrial beta-oxidation of long-, medium- and short-chain fatty acids in vitro and in vivo in mice. In cultured rat hepatocytes, exposure for 24 hr to 25 mumol/L perhexiline markedly decreased hepatocellular ATP and cell viability. Exposure to 5 mumol/L perhexiline did not modify ATP and viability but decreased the beta-oxidation of palmitic acid uniformly labeled with carbon 14 by 38%, increased hepatocyte triglyceride levels by 98% and produced microvesicular steatosis after 72 hr of culture. We conclude that perhexiline is concentrated inside mitochondria, where it inhibits both oxidative phosphorylation and the mitochondrial beta-oxidation of fatty acids. These effects may contribute to the development of necrosis, steatosis and possibly certain other pseudoalcoholic liver lesions in human beings.
Antiviral activity of human immunodeficiency virus type 1 protease inhibitors in a single cycle of infection: evidence for a role of protease in the early phase (1994)

The antiviral activities of two substrate-based inhibitors of human immunodeficiency virus type 1 (HIV-1) protease, UK-88,947 and Ro 31-8959, were studied in acute infections. H9 and HeLaCD4-LTR/beta-gal cells were infected either with HIV-1IIIB or a replication-defective virus, HIV-gpt(HXB-2). Both inhibitors were capable of blocking early steps of HIV-1 replication if added to cells prior to infection. Partial inhibition was also obtained by addition of inhibitor at the time of or as late as 15 min after infection. The inhibitors were ineffective if added 30 min postinfection. The inhibitory effects were studied by cDNA analysis with PCR followed by Southern blot hybridization and by infectivity assays allowing quantitation of HIV-1 in a single cycle of replication. When UK-88,947-treated H9 cells were coinfected with HIV-1 and human T-cell leukemia virus type I only the replication of HIV-1 was inhibited, demonstrating viral specificity. Pretreating the infectious virus stocks with the inhibitors also prevented replication, indicating that the inhibitors block the action of the viral protease and not a cellular protease. A panel of primer sets was used to analyze cDNA from cell lysates by PCR amplification at 4 and 18 h postinfection. Four hours after infection, viral specific cDNA was detected with all of the four primer pairs used: R/U5, nef/U3, 5' gag, and long terminal repeat (LTR)/gag. However, after 18 h, only the R/U5 and nef/U3 primer pairs and not the 5' gag or LTR/gag primer pair were able to allow amplification of cDNA. The results suggest a crucial role of HIV-1 protease in the early phase of viral replication. Although it is not clear what early steps are affected by the protease, it is likely that the target is the NC protein, as referred from our previous reports of the in situ cleavage of the nucleocapsid (NC) protein by the viral protease inside lentiviral capsids. The results suggest that it is not the inhibition of initiation and progression of reverse transcription but the stability of full-size unintegrated cDNA which is affected in the presence of protease inhibitors. Alternatively, the cleavage of the NC protein may be required for the proper formation of preintegration complex and/or for its transport to the nucleus.
Excitation of Morphology Dependent Resonances of Microspherical Cavities Using Optical Fibers (1995)

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 Giora Griffel, Stephen Arnold, Dogan Taskent, Ali Serpengüzel, John Connolly, and Nancy Morris, "Excitation of Morphology Dependent Resonances of Microspherical Cavities Using Optical Fibers," Optics & Photonics News 6(12), 21-22 (1995) Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
A Self-Assembled DNA Bipyramid (2007)

Nanometer-scale DNA polyhedra, consisting of 3- or 4-arm branch junctions connected by rigid double-helical edges, can be created by self-assembly protocols that exploit the specificity of base-pairing interactions. The DNA tetrahedron was the first such structure to be made rapidly and in high yield from multiple strands in a single assembly step. Facile and efficient synthesis is a necessary enabling step toward the application of these controllable three-dimensional scaffolds as building blocks for nanofabrication or as functional molecular cages. Herein we demonstrate the single-step assembly of a DNA trigonal bipyramid, demonstrating that more complex, less symmetric polyhedra can also be created by one-step assembly.
Exploiting Proprioception in Virtual-Environment Interaction (1997)

Manipulation in immersive virtual environments is difficult partly because users must do without the haptic contact with real objects they rely on in the real world to orient themselves and the objects they are manipulating. To compensate for this lack, I propose exploiting the one real object every user has in a virtual environment, his body. I present a unified framework for virtual-environment interaction based on proprioception, a person&amp;apos;s sense of the position and orientation of his body and limbs. I describe three forms of body-relative interaction: . Direct manipulation---ways to use body sense to help control manipulation . Physical mnemonics---ways to store/recall information relative to the body . Gestural actions---ways to use body-relative actions to issue commands Automatic scaling is a way to bring objects instantly within reach so that users can manipulate them using proprioceptive cues. Several novel virtual interaction techniques based upon automatic scaling and our proposed framework of proprioception allow a user to interact with a virtual world intuitively, efficiently, precisely, and lazily. Two formal user studies evaluate key aspects of body-relative interaction. The virtual docking study compares the manipulation of objects co-located with one&amp;apos;s hand and the manipulation of objects at a distance. The widget interaction experiment explores the differences between interacting with a widget held in one&amp;apos;s hand and interacting with a widget floating in space. Lessons learned from the integration of body-relative techniques into a real-world system, the Chapel Hill Immersive Modeling Program (CHIMP), are presented and discus...
Environmentally stable picosecond ytterbium fiber laser with a broad tuning range (1998)

We demonstrate a widely tunable passively mode-locked fiber laser operating at a fundamental frequency of 80 MHz with an output power of 90 mW. The laser is capable of generating 5-ps pulses in the region 1010-1064 nm. A strong mode-locking mechanism promoted by frequency-shifted feedback allows us to operate in simultaneous Q-switched and mode-locked regimes and to obtain peak power in excess of 1.2 kW.
Pro-coagulant state resulting from high levels of soluble P-selectin in blood (2000)

The plasma concentration of soluble adhesion receptors is increased under pathological circumstances, but their function remains enigmatic. Soluble P-selectin (sP-sel) is shed from activated platelets and endothelial cells. Mice genetically engineered to express P-selectin without the cytoplasmic tail (DeltaCT) constitutively show a 3- to 4-fold increase of sP-sel in plasma. We observed that the DeltaCT mice formed fibrin very readily. In an ex vivo perfusion chamber, there was more fibrin deposited at the site of platelet thrombus formation than in wild type (WT), whereas no fibrin deposits were detected using P-selectin-deficient blood during the same interval. Similarly, in vivo, the hemorrhage produced by local Shwartzman reaction was smaller in the DeltaCT mice than in WT. In contrast, we previously showed hemorrhage to be more prominent in P-selectin knock-out mice. Infusion of mouse P-sel-Ig chimera produced the same protective effect in WT mice as seen in the DeltaCT mice, indicating that the effect was due to increased levels of sP-sel. Mice infused with P-sel-Ig showed significantly more fibrin deposited on the luminal face of the injured vessels than control mice. Plasma from DeltaCT mice or mice infused with P-sel-Ig contained higher concentration of pro-coagulant microparticles and clotted one minute faster than WT. This pro-coagulant phenotype of DeltaCT mice could be reversed by a 4-day treatment with PSGL-Ig, a P-selectin inhibitor. We propose that sP-sel should no longer be considered only as a marker of inflammation or platelet activation, but also as a direct inducer of pro-coagulant activity associated with vascular and thrombotic diseases.
Ureter metastatic castration-resistant prostate cancer: a case report (2017)

We herein report a rare case of ureteral metastasis in castration resistant prostate cancer.
Localization of the Serine Protease-binding Sites in the Collagen-like Domain of Mannose-binding Protein (2004)

Mutations in the collagen-like domain of serum mannose-binding protein (MBP) interfere with the ability of the protein to initiate complement fixation through the MBP-associated serine proteases (MASPs). The resulting deficiency in the innate immune response leads to susceptibility to infections. Studies have been undertaken to define the region of MBP that interacts with MASPs and to determine how the naturally occurring mutations affect this interaction. Truncated and modified MBPs and synthetic peptides that represent segments of the collagen-like domain of MBP have been used to demonstrate that MASPs bind on the C-terminal side of the hinge region formed by an interruption in the Gly-X-Y repeat pattern of the collagen-like domain. The binding sites for MASP-2 and for MASP-1 and -3 overlap but are not identical. The two most common naturally occurring mutations in MBP result in substitution of acidic amino acids for glycine residues in Gly-X-Y triplets on the N-terminal side of the hinge. Circular dichroism analysis and differential scanning calorimetry demonstrate that the triple helical structure of the collagen-like domain is largely intact in the mutant proteins, but it is more easily unfolded than in wild-type MBP. Thus, the effect of the mutations is to destabilize the collagen-like domain, indirectly disrupting the binding sites for MASPs. In addition, at least one of the mutations has a further effect on the ability of MBP to activate MASPs.
Folate analogs altered in the C9-N10 bridge region: N10-tosylisohomofolic acid and N10-tosylisohomoaminopterin (1978)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFolate analogs altered in the C9-N10 bridge region: N10-tosylisohomofolic acid and N10-tosylisohomoaminopterinM. G. Nair, P. Colleen O'Neal, C. M. Baugh, Roy L. Kisliuk, Y. Gaumont, and Michael RodmanCite this: J. Med. Chem. 1978, 21, 7, 673–677Publication Date (Print):July 1, 1978Publication History Published online1 May 2002Published inissue 1 July 1978https://pubs.acs.org/doi/10.1021/jm00205a015https://doi.org/10.1021/jm00205a015research-articleACS PublicationsRequest reuse permissionsArticle Views90Altmetric-Citations6LEARN 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
Inhibition of human erythroid colony-forming units by gamma interferon can be corrected by recombinant human erythropoietin [see comments] (1991)

Tumor necrosis factor (TNF), interleukin-1 (IL-1), and gamma interferon (gamma IFN) inhibit erythropoiesis in vivo and in vitro, and have been implicated in the pathogenesis of the anemia of chronic disease. Anemia in patients with rheumatoid arthritis and in animals exposed chronically to IL-1 and TNF can be corrected by the administration of recombinant erythropoietin (Epo). We exposed highly purified human erythroid colony-forming units (CFU-E) cultured from peripheral blood burst-forming units-erythroid (BFU-E) and unpurified human marrow CFU-E to recombinant human gamma IFN and showed inhibition of colony formation in vitro. This inhibition was reversed by increased concentrations of Epo. The mechanisms by which this effect occurs are unknown at present. Epo may cause a downregulation of gamma IFN receptor expression on CFU-E or, alternatively, gamma IFN may cause a downregulation of Epo receptor expression. A full understanding of these mechanisms awaits a more complete comprehension of the regulation of erythropoiesis; however, the effect of Epo in vitro is similar to its ability to correct the anemia of chronic disease in vivo.
Sequence-specific modification of mitochondrial DNA using a chimeric zinc finger methylase (2006)

We used engineered zinc finger peptides (ZFPs) to bind selectively to predetermined sequences in human mtDNA. Surprisingly, we found that engineered ZFPs cannot be reliably routed to mitochondria by using only conventional mitochondrial targeting sequences. We here show that addition of a nuclear export signal allows zinc finger chimeric enzymes to be imported into human mitochondria. The selective binding of mitochondria-specific ZFPs to mtDNA was exemplified by targeting the T8993G mutation, which causes two mitochondrial diseases, neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) and also maternally inherited Leigh's syndrome. To develop a system that allows the monitoring of site-specific alteration of mtDNA we combined a ZFP with the easily assayed DNA-modifying activity of hDNMT3a methylase. Expression of the mutation-specific chimeric methylase resulted in the selective methylation of cytosines adjacent to the mutation site. This is a proof of principle that it is possible to target and alter mtDNA in a sequence-specific manner by using zinc finger technology.
Induction of Neoangiogenesis in Ischemic Myocardium by Human Growth Factors (1998)

We believe that the use of FGF-I for myocardial revascularization is in principle a new concept and that it may be particularly suitable for patients with additional peripheral stenoses that cannot be revascularized surgically.
THE WORLD WIDE WEB AND HIGH-ENERGY PHYSICS (1997)

▪ Abstract High-energy physics and the World Wide Web (WWW) share a rich history. The Web, developed at CERN as a collaboration tool and quickly adopted by the Internet community, has become a communications phenomenon. This article reviews early WWW development and its basic technology. I also summarize some significant applications of Web technology, past and present, and discuss prospects for future use.
Deoxyribonucleoside 3‘-O-(2-Thio- and 2-Oxo-“spiro”-4,4-pentamethylene-1,3,2-oxathiaphospholane)s:  Monomers for Stereocontrolled Synthesis of Oligo(deoxyribonucleoside phosphorothioate)s and Chimeric PS/PO Oligonucleotides (1998)

New monomers, 5‘-O-DMT-deoxyribonucleoside 3‘-O-(2-thio-“spiro”-4,4-pentamethylene-1,3,2-oxathiaphospholane)s, were prepared and used for the stereocontrolled synthesis of PS−Oligos via the oxathiaphospholane approach. These monomers and their 2-oxo analogues were used for the synthesis of “chimeric” constructs (PS/PO−Oligos) possessing phosphate and P-stereodefined phosphorothioate internucleotide linkages. The yield of a single coupling step is approximately 92−95%, and resulting oligomers are free of nucleobase- and sugar-phosphorothioate backbone modifications. Thermal dissociation studies showed that for heteroduplexes formed by [RP]-, [SP]-, or [mix]-PS/PO-T10 with dA12, dA30, or poly(dA), for each template, the melting temperatures, as well as free Gibbs' energies of dissociation process, are virtually equal. Stereochemical evidence derived from crystallographic analysis of one of the oxathiaphospholane monomers strongly supports the participation of pentacoordinate intermediates in the mechanism of the oxathiaphospholane ring-opening condensation.
Multicopy Suppression Underpins Metabolic Evolvability (2007)

Our understanding of the origins of new metabolic functions is based upon anecdotal genetic and biochemical evidence. Some auxotrophies can be suppressed by overexpressing substrate-ambiguous enzymes (i.e., those that catalyze the same chemical transformation on different substrates). Other enzymes exhibit weak but detectable catalytic promiscuity in vitro (i.e., they catalyze different transformations on similar substrates). Cells adapt to novel environments through the evolution of these secondary activities, but neither their chemical natures nor their frequencies of occurrence have been characterized en bloc. Here, we systematically identified multifunctional genes within the Escherichia coli genome. We screened 104 single-gene knockout strains and discovered that many (20%) of these auxotrophs were rescued by the overexpression of at least one noncognate E. coli gene. The deleted gene and its suppressor were generally unrelated, suggesting that promiscuity is a product of contingency. This genome-wide survey demonstrates that multifunctional genes are common and illustrates the mechanistic diversity by which their products enhance metabolic robustness and evolvability.
Phase phirst! An improved strong-PSM paradigm (2001)

The remaining difficulties in applying dual exposure dark-field strong-PSM technology can be overcome using the Sidewall Chrome Alternating Aperture (SCAA) mask structure, first proposed in 1992 and now fabricated. With all silica sidewalls covered and all chrome supported, the SCAA mask is largely immune to the phase and amplitude anomalies that cause spacewidth alternation as well as the design, fabrication and cleaning difficulties that plague other structures. Maxwell's equation solvers predict that the optical phase will be essentially independent of aperture size. Chips designed with their fmest features on a pre-defined regular grid can employ generic SCAA mask substrates in which the topography has been pre-patterned using wafer fab techniques. Guaranteed defect-free SCAA mask substrates will be manufactured in large quantity and low cost if the design grids become standardized. Fabricating strong-PSMs using these Phase Phirst mask substrates will prove no more difficult for mask-makers than COG masks, and the reduced MEEF will permit loosened CD specifications, among other advantages. The Phase Phirst Paradigm promises to reduce optical lithography costs —even for ASIC manufactures — and to delay the need for NGL technologies.
A fusion protein containing a lepidopteran-specific toxin from the South Indian red scorpion (Mesobuthus tamulus) and snowdrop lectin shows oral toxicity to target insects (2006)

The ButaIT/GNA recombinant fusion protein is toxic to lepidopteran larvae both when injected and when fed orally, showing the utility of GNA as a carrier to transport potentially toxic peptides and proteins across the insect gut. Although ButaIT has been claimed to be lepidopteran-specific, the fusion protein has more wide-ranging insecticidal activity. Fusion proteins based on plant lectins have potential applications in crop protection, both as exogenously applied treatments and as endogenous products in transgenic plants.
Physical and Chemical Mutagenesis (2003)

Important methods to artificially induce mutations are the use of chemical and physical agents. Most chemical mutagens are alkylating agents and azides. Physical mutagens include electromagnetic radiation, such as gamma rays, X rays, and UV light, and particle radiation, such as fast and thermal neutrons, beta and alpha particles. Mutagenic treatment of seeds is the most convenient and, therefore, the standard method in seed propagated crops. Seeds can be treated in large quantities and are easily handled, stored, and shipped. It is fairly easy to repeat the conditions of mutagenic treatment, pre- and post-treatment, and hence, to obtain reproducible results within practical limits. Besides seed treatment, whole plants, cuttings, tubers, pollen, bulbs, corms, or in vitro plants or tissues can be treated. This chapter is restricted to the commonly applied techniques of mutation induction in seeds by ethyl methanesulfonate (EMS) treatment and by gamma and fast neutron irradiation.