gebhart/patrepeval huggingface dataset:
T cells expressing a LMP1-specific chimeric antigen receptor mediate antitumor effects against LMP1-positive nasopharyngeal carcinoma cells in vitro and in vivo (2014)

T cells modified with chimeric antigen receptor are an attractive strategy to treat Epstein-Barr virus (EBV) associated malignancies. The EBV latent membrane protein 1 (LMP1) is a 66-KD integral membrane protein encoded by EBV that consists of transmembrane-spanning loops. Previously, we have identified a functional signal chain variable fragment (scFv) that specifically recognizes LMP1 through phage library screening. Here, we constructed a LMP1 specific chimeric antigen receptor containing anti-LMP1 scFv, the CD28 signalling domain, and the CD3ζ chain (HELA/CAR). We tested its functional ability to target LMP1 positive nasopharyngeal carcinoma cells. HELA/CAR cells were efficiently generated using lentivirus vector encoding the LMP1-specific chimeric antigen receptor to infect activated human CD3+ T cells. The HELA/CAR T cells displayed LMP1 specific cytolytic action and produced IFN-γ and IL-2 in response to nasopharyngeal carcinoma cells overexpressing LMP1. To demonstrate in vivo anti-tumor activity, we tested the HELA/CAR T cells in a xenograft model using an LMP1 overexpressing tumor. Intratumoral injection of anti-LMP1 HELA/CAR-T cells significantly reduced tumor growth in vivo. These results show that targeting LMP1 using HELA/CAR cells could represent an alternative therapeutic approach for patients with EBV-positive cancers.
Cyclooxygenase-2 expression is up-regulated in human pancreatic cancer. (1999)

A large body of evidence suggests that cyclooxygenase-2 (COX-2) is important in gastrointestinal cancer. The purpose of this study was to determine whether COX-2 was expressed in adenocarcinoma of the human pancreas. Quantitative reverse transcription-PCR, immunoblotting, and immunohistochemistry were used to assess the expression of COX-2 in pancreatic tissue. Levels of COX-2 mRNA were increased by >60-fold in pancreatic cancer compared to adjacent nontumorous tissue. COX-2 protein was present in 9 of 10 cases of adenocarcinoma of the pancreas but was undetectable in nontumorous pancreatic tissue. Immunohistochemical analysis showed that COX-2 was expressed in malignant epithelial cells. In cultured human pancreatic cancer cells, levels of COX-2 mRNA and protein were induced by treatment with tumor-promoting phorbol esters. Taken together, these results suggest that COX-2 may be a target for the prevention or treatment of pancreatic cancer.
Size and mechanical stability of norovirus capsids depend on pH: a nanoindentation study (2010)

Norovirus-like particles were imaged using atomic force microscopy. The mechanical stability of the virus-like particles (VLPs) was probed by nanoindentation at pH values ranging from 2 to 10. This range includes pH values of the natural environment during the life cycle of noroviruses. The resistance of VLPs to indentation was constant at acidic and neutral pH. The Young's modulus was of the order of 30 MPa. At basic pH the compliance of the capsid increased along with an increase in diameter. This specific pH-dependent mechanical response of the capsid may be related to mechanisms controlling uptake and release of the RNA during infection. Consecutive indentations with pressures ≤ 300 bar demonstrated the ability of the capsids to fully recover from deformations comparable with the size of the capsid. The capsids can be viewed as nanocontainers with an inbuilt self-repair mechanism. At pH 10 the capsids lost their stability and were irreversibly destroyed after one single indentation.
A New Highly Efficient Ruthenium Metathesis Catalyst This work was supported by the Fonds der Chemischen Industrie. (2002)

Olefin metathesis even at 0°C! A phenyl substituent in the ruthenium catalyst 2 leads to greatly increased initiation rates in different metathesis reactions, for example, the cyclization of 1 to form 3.
In vivo demonstration of increased leukocyte entrapment in retinal microcirculation of diabetic rats. (1998)

Pharmacologically induced and spontaneously diabetic rats showed increased leukocyte entrapment in the living retina in the early stages of diabetes. In light of the damaging potential of leukocytes, accumulation of leukocytes in diabetic retinas from the preretinopathy stage could cause microvascular occlusions and dysfunction, in turn causing diabetic retinopathy.
Protein−Protein Interactions:  Interface Structure, Binding Thermodynamics, and Mutational Analysis (1997)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProtein−Protein Interactions: Interface Structure, Binding Thermodynamics, and Mutational AnalysisWesley E. StitesView Author Information Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, Arkansas 72701-1201 Cite this: Chem. Rev. 1997, 97, 5, 1233–1250Publication Date (Web):August 5, 1997Publication History Received14 November 1996Revised4 March 1997Published online5 August 1997Published inissue 1 August 1997https://pubs.acs.org/doi/10.1021/cr960387hhttps://doi.org/10.1021/cr960387hresearch-articleACS PublicationsCopyright © 1997 American Chemical SocietyRequest reuse permissionsArticle Views6256Altmetric-Citations418LEARN 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 SUBJECTS:Genetics,Hydrophobicity,Interfaces,Monomers,Peptides and proteins Get e-Alerts
Circular dichroic evidence for an ordered sequence of ligand/binding site interactions in the catalytic reaction of the cAMP-dependent protein kinase (1985)

A limiting requirement for substrate specificity of the cAMP-dependent protein kinase is the presence of one or two basic residues located to the N-terminal side of the target substrate serine. Furthermore, circular dichroic (CD) studies have shown that binding of protein substrate involves a series of at least two independent conformational changes in the enzyme, each of which is initiated by a recognition signal on the substrate protein. The present study attempts to elucidate further the complete sequence of enzyme/ligand interactions by using the synthetic substrate peptide Kemptide and analogues differing from it at crucial points in the sequence: the Ala-peptide, where alanine is substituted for the target serine, and D-Ser-Kemptide, where the target serine is in the D rather than the L configuration. Examination of the effects of binding of these substrates on the intrinsic UV CD of the enzyme and the induced CD in the presence of Blue Dextran has revealed a third step in the substrate/enzyme binding interaction. Although sections of the conformational change at the active site are dependent on the basic subsite and the serine hydroxyl group on the peptide, respectively, the complete conformational change requires that the substrate be bound in random coil conformation. Where this does not occur, the kinetics show that the peptide will not act either as substrate or as inhibitor of the enzyme. Further, the interaction between the serine hydroxyl group and an enzyme tyrosine residue, previously observed, appears to be dependent on the correct orientation as well as the mere presence of the target -OH group.(ABSTRACT TRUNCATED AT 250 WORDS)
Spectrum-efficient and scalable elastic optical path network: architecture, benefits, and enabling technologies (2009)

The sustained growth of data traffic volume calls for an introduction of an efficient and scalable transport platform for links of 100 Gb/s and beyond in the future optical network. In this article, after briefly reviewing the existing major technology options, we propose a novel, spectrum- efficient, and scalable optical transport network architecture called SLICE. The SLICE architecture enables sub-wavelength, superwavelength, and multiple-rate data traffic accommodation in a highly spectrum-efficient manner, thereby providing a fractional bandwidth service. Dynamic bandwidth variation of elastic optical paths provides network operators with new business opportunities offering cost-effective and highly available connectivity services through time-dependent bandwidth sharing, energy-efficient network operation, and highly survivable restoration with bandwidth squeezing. We also discuss an optical orthogonal frequency-division multiplexing-based flexible-rate transponder and a bandwidth-variable wavelength cross-connect as the enabling technologies of SLICE concept. Finally, we present the performance evaluation and technical challenges that arise in this new network architecture.
Individualizing pain therapy with opioids: The rational approach based on pharmacogenetics and pharmacokinetics (2010)

Abstract A correct long‐term opioid therapy implies the selection of the appropriate opioid and dose for each patient, but it is well demonstrated that the “clinical” approach alone is not sufficient. To this purpose, the literature is stressing that physicians have to focalize even more their attention both on the pharmacokinetic and pharmacodynamic properties of the opioids and on the differences among patients, including the genetic background. Accurate and fast analytical methods (e.g. Tandem Mass Spectrometry) for detecting plasma opioid concentrations represent a useful tool for clinicians to prevent adverse reactions in selected patients. The detection of polymorphisms of several genes involved in opioid absorption, distribution, metabolism, and elimination are promising to customize pain therapy. The success of the chronic opioid therapy also depends on the other drugs co‐administered, possibly giving origin to drug‐drug interactions; the clinical outcome should be constantly monitored.
Endogenous and exogenous polyamines in support of tumor growth. (1990)

The combination of inhibitors of ornithine decarboxylase and polyamine oxidase and of antibiotics suitable for the (partial) decontamination of the gastrointestinal tract with a polyamine-deficient diet reduced the growth rate of Lewis lung carcinoma by more than 80%. The formation of lung metastases was prevented by 70 to 100%, depending on the treatment. The reduction of tumor growth was accompanied by a decrease of tissue polyamine concentrations, a reduced rate of tumor cell proliferation, and protein synthesis. The comparison of the ornithine decarboxylase inhibitors Eflornithine [D,L-2-(difluoromethyl)ornithine] and (E)-2-(fluoromethyl)dehydroornithine ethylester confirmed the greater in vivo potency of the latter compound. Our method of growth inhibition by systematic polyamine deprivation is not tumor specific, but presumably generally applicable to rapid growth.
Use of the Accelerating Rotarod for Assessment of Motor Performance Decrement Induced by Potential Anticonvulsant Compounds DM Nerve Agent Poisoning (1992)

The accelerating rotarod was used to assess motor performance decrement in rats after administration of candidate anticonvulsant compounds (acetazolamide, amitriptyline, chlordiazepoxide, diazepam, diazepam-lysine, lorazepam, loprazolam, midazolam, phenobarbital and scopolamine) against nerve agent poisoning. All compounds were tested as the commercially available injectable preparation except for diazepam-lysine and loprazolam, which are not FDA approved. A peak effect time, as well as a dose to decrease performance time by 50% from control (PDD50), was determined. The calculated PDD50 (mumol/kg) values and peak effect times were midazolam, 1.16 at 15 min; loprazolam, 1.17 at 15 min; diazepam-lysine, 4.17 at 30 min; lorazepam, 4.98 at 15 min; diazepam, 5.27 at 15 min; phenobarbital, 101.49 at 45 min; chlordiazepoxide, 159.21 at 30 min; scopolamine, amitriptyline and acetazolamide did not demonstrate a performance decrement at any of the doses tested. The PDD50 values were compared with doses which have been utilized against nerve agent-induced convulsions or published ED50 values from standard anticonvulsant screening tests (maximal electroshock [MES] and subcutaneous pentylenetetrazol [scMET]). The results suggest that at anticonvulsant doses against nerve agents, all the benzodiazepines and phenobarbital have the potential to cause a performance decrement, whereas candidate anticonvulsants of the non-benzodiazepine or non-barbiturate type would not be expected to demonstrate this effect on motor performance. It is concluded that compounds such as acetazolamide, amitriptyline and scopolamine offer alternatives to the highly decrementing benzodiazepines and phenobarbital and should be further tested as anticonvulsant candidates against nerve agent intoxication.
Regulation of effector and memory T-cell functions by type I interferon (2011)

Type I interferon (IFN-α/β) is comprised of a family of highly related molecules that exert potent antiviral activity by interfering with virus replication and spread. IFN-α/β secretion is tightly regulated through pathogen sensing pathways that are operative in most somatic cells. However, specialized antigen-presenting plasmacytoid dendritic cells are uniquely equipped with the capacity to secrete extremely high levels of IFN-α/β, suggesting a key role for this cytokine in priming adaptive T-cell responses. Recent studies in both mice and humans have demonstrated a role for IFN-α/β in directly influencing the fate of both CD4(+) and CD8(+) T cells during the initial phases of antigen recognition. As such, IFN-α/β, among other innate cytokines, is considered an important 'third signal' that shapes the effector and memory T-cell pool. Moreover, IFN-α/β also serves as a counter-regulator of T helper type 2 and type 17 responses, which may be important in the treatment of atopy and autoimmunity, and in the development of novel vaccine adjuvants.
Prolactin, the Hormone of Paternity (1999)

Prolactin has long been known to play a significant role in maternal care. When behavioral endocrinologists began to examine the endocrinology of fatherhood, prolactin was also found to be connected with paternal care in fish, birds, and mammals including primates.
Quantitative Analysis of Circulating Mitochondrial DNA in Plasma (2003)

Both particle-associated and free mitochondrial DNA are present in plasma, and their respective concentrations are affected by the process used to harvest plasma from whole blood. These results may have implications in the design of future studies on circulating mitochondrial DNA measured in different disease conditions.
Mammalian Antifertility Agents. IV. Basic 3,4-Dihydronaphthalenes and 1,2,3,4-Tetrahydro-1-naphthols (1967)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMammalian Antifertility Agents. IV. Basic 3,4-Dihydronaphthalenes and 1,2,3,4-Tetrahydro-1-naphtholsDaniel. Lednicer, Stanley C. Lyster, and Gordon W. DuncanCite this: J. Med. Chem. 1967, 10, 1, 78–84Publication Date (Print):January 1, 1967Publication History Published online1 May 2002Published inissue 1 January 1967https://pubs.acs.org/doi/10.1021/jm00313a016https://doi.org/10.1021/jm00313a016research-articleACS PublicationsRequest reuse permissionsArticle Views184Altmetric-Citations57LEARN 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
Structure, expression, and evolution of a gene encoding the precursor of nisin, a small protein antibiotic. (1988)

We have cloned and sequenced a gene (spaN) from Streptococcus lactis ATCC 11454 which encodes the peptide precursor of the small protein antibiotic nisin. The encoded precursor is 57 amino acids long, with a 23-residue leader region and a 34-residue structural region. The structural region contains serines, threonines, and cysteines at exactly the positions required to give mature nisin by a series of post-translational modifications involving dehydration of serines and threonines to dehydro forms, and cross-linking with cysteine residues. S1 mapping revealed a 267-nucleotide transcript of the nisin gene that is expressed during vegetative growth and stationary phase. It has a half-life of 7-10 min. The absence of an identifiable promoter or rho-independent terminator and the detection of two different 5'-ends of the transcript suggested it is a processing product from a larger RNA. This may represent a polycistronic mRNA which may also encode proteins involved in processing the nisin precursor peptide. Open reading frames were found in regions flanking the nisin gene. The one downstream had a ribosome binding site and appeared to be transcribed by read-through from the nisin gene. The one upstream had significant homology to a putative transposase from the Escherichia coli IS2 insertion element. Comparison of gene sequence homologies between nisin and the other lanthionine antibiotics, subtilin and epidermin, indicated that they all evolved from a common ancestor. Corresponding leader peptide sequences showed mediocre amino acid homology, but nearly perfect hydropathic homologies, suggesting a common function. It is proposed that this function includes recognition signals or other information required for post-translational processing.
Neochondrogenesis in free intra-articular, periosteal, and perichondrial autografts in horses (1989)

Periosteal autografts were obtained from the medial aspect of the proximal portion of the tibia, and perichondrial autografts were obtained from the sternum. Using arthroscopic visualization, each autograft was placed as a loose body into 1 tarsocrural joint in 6 young horses (2 to 4 years old). Horses were hand-walked daily, starting the day after surgery, for a total of 6 h/wk for 8 weeks. Eight weeks after autograft implantation, radiographs were taken of each tarsocrural joint and were interpreted with regard to mineralization in the transplanted autografts. Autografts were then surgically removed, and examined macroscopically and microscopically for viability, size, and production of chondroid tissue. All autografts appeared viable and most had evidence of growth. Longest-by-shortest axis value, cross-sectional area, and perimeter were greater in perichondrial autografts than in their periosteal counterparts in 3 horses, but the difference was not significant. Neochondrogenesis was observed in 5 of 6 periosteal grafts and in 1 of 6 perichondrial grafts. Furthermore, the amount of chondroid tissue produced in periosteal autografts was significantly (P less than 0.05) greater than that produced in the 1 perichondrial graft. The chondroid tissue produced by periosteal autografts had morphologic and matrical staining properties similar to those of hyaline cartilage.
Characterization of Lipid Rafts from Medicago truncatula Root Plasma Membranes: A Proteomic Study Reveals the Presence of a Raft-Associated Redox System (2007)

Several studies have provided new insights into the role of sphingolipid/sterol-rich domains so-called lipid rafts of the plasma membrane (PM) from mammalian cells, and more recently from leaves, cell cultures, and seedlings of higher plants. Here we show that lipid raft domains, defined as Triton X-100-insoluble membranes, can also be prepared from Medicago truncatula root PMs. These domains have been extensively characterized by ultrastructural studies as well as by analysis of their content in lipids and proteins. M. truncatula lipid domains are shown to be enriched in sphingolipids and Delta(7)-sterols, with spinasterol as the major compound, but also in steryl glycosides and acyl-steryl glycosides. A large number of proteins (i.e. 270) have been identified. Among them, receptor kinases and proteins related to signaling, cellular trafficking, and cell wall functioning were well represented whereas those involved in transport and metabolism were poorly represented. Evidence is also given for the presence of a complete PM redox system in the lipid rafts.
Sybase SQL Server II: An Administrator's Guide (1996)

From the Publisher:
Sybase SQL Server 11: An Administrator's Guide includes detailed descriptions on how to set up, manage, and maintain both SQL Server 10 and SQL Server 11, and notes system changes affecting migration from earlier versions of SQL Server releases, from data integrity functions to performance and tuning. Both new and experienced SQL Server users can home in on areas that would otherwise prove troublesome, and learn the ropes from practical examples and exercises. The book includes a CD-ROM containing the complete System 11 documentation for SQL Server, Open Client and Open Server, Replication Server, and SQL Server Monitor. Valuable reference material is also available on the World Wide Web as a WebExtra, at http://www.thomson.com/itcp.html.
Inhibitory effects of leptin-related synthetic peptide 116-130 on food intake and body weight gain in female C57BL/6J ob/ob mice may not be mediated by peptide activation of the long isoform of the leptin receptor. (1999)

We recently reported that intraperitoneal administration of leptin-related synthetic peptide 116-130 [LEP-(116-130)] resulted in reduced food intake and significant weight loss in homozygous female C57BL/6J ob/ob mice. In this study, we used two in vitro bioassays to show that the interaction of LEP-(116-130) with the long form of the leptin receptor (OB-Rb), the receptor isoform that is predominantly expressed in the hypothalamus, is not required for the observed in vivo effects of the peptide on energy balance. LEP-(116-130) was unable to compete the binding of alkaline phosphatase-leptin fusion protein to OB-R. Moreover, LEP-(116-130) was unable to activate signal transduction by OB-Rb in vitro. In homozygous female C57BLKS/J-m db/db mice that do not express OB-Rb, intraperitoneal administration of LEP-(116-130) reduced body weight gain and blood glucose levels but not food intake, which further supports a mechanism of action that does not require peptide interaction with OB-Rb.