gebhart/patrepeval huggingface dataset:
Predicting antibody complementarity determining region structures without classification (2011)

Antibodies are used extensively in medical and biological research. Their complementarity determining regions (CDRs) define the majority of their antigen binding functionality. CDR structures have been intensively studied and classified (canonical structures). Here we show that CDR structure prediction is no different from the standard loop structure prediction problem and predict them without classification. FREAD, a successful database loop prediction technique, is able to produce accurate predictions for all CDR loops (0.81, 0.42, 0.96, 0.98, 0.88 and 2.25 Å RMSD for CDR-L1 to CDR-H3). In order to overcome the relatively poor predictions of CDR-H3, we developed two variants of FREAD, one focused on sequence similarity (FREAD-S) and another which includes contact information (ConFREAD). Both of the methods improve accuracy for CDR-H3 to 1.34 Å and 1.23 Å respectively. The FREAD variants are also tested on homology models and compared to RosettaAntibody (CDR-H3 prediction on models: 1.98 and 2.62 Å for ConFREAD and RosettaAntibody respectively). CDRs are known to change their structural conformations upon binding the antigen. Traditional CDR classifications are based on sequence similarity and do not account for such environment changes. Using a set of antigen-free and antigen-bound structures, we compared our FREAD variants. ConFREAD which includes contact information successfully discriminates the bound and unbound CDR structures and achieves an accuracy of 1.35 Å for bound structures of CDR-H3.
Subjugation of dominant immunogenic determinants within a chimeric peptide (1992)

The mechanism of immunodominance was investigated using chimeric peptides from mouse myelin basic protein consisting of the immunodominant I-Au-restricted Ac1-11, attached by a peptide bond to I-Eu-restricted 35-47. Our results indicate that this chimeric peptide and certain of its derivatives were excellent immunogens both in vitro and in vivo. Notably, on immunization with Ac1-11:35-47 or Ac1-11 (Ala4):35-47, the proliferative T cell responses to each of its component peptides were almost completely "subjugated" in favor of neo-determinants that are I-Eu restricted. Furthermore, each of 11 hybridomas derived after immunization with Ac1-11:35-47 had specificity for junctional neo-determinants and none could be stimulated to produce interleukin-2 from Ac1-11 or 35-47. Subjugation of the immunogenicity of the original determinants occurred regardless of their dominance when separate. It did not appear to result from non-availability of the original determinants because the chimeric peptide was able to induce neonatal tolerance to each of its constituents. These results indicate that in an overlapping multideterminant array, the dominant determinant is unpredictable from historical data about any of the components. Determinant choice, at any stage of processing, may be governed by competitive aspects of determinant capture in an environment where all components--antigen, major histocompatibility complex and T cell receptor--are available.
Fentanyl versus dexmedetomidine effect on agitation after sevoflurane anaesthesia (2007)

Sixty ASA physical status I and II children aged 3 - 6 years were included in this study. After inhalation induction with sevoflurane, patients were randomly assigned to receive either Saline (group 1, n=20), fentanyl 1 mic /kg IV (group II, n=20) or dexmedetomidine 0.3mic/kg IV (group III, n=20)10 minutes before discontinuation of anesthetics. There was no significant difference (p>0.05) between the three groups regarding age, weight, duration of anesthesia, duration of surgery, time to eye opening, modified Aldrete recovery scores and post operative complication. The time of first postoperative analgesic dose was significantly shorter in group I compared with other two groups. The incidence of agitation was significantly higher in group I compared with other two groups, the incidence of agitation was 40% in Group I, 15% in Group II and 20% in Group III. In conclusion, the dose of fentanyl 1 mic/kg iv or dexmedetomidine 0.3mic/kg iv that is administered 10 minutes before the termination of anesthesia reduces the postoperative agitation in children with no adverse effects.
Level of HLA antigens in locoregional metastases and clinical course of the disease in patients with melanoma. (1988)

Immunohistochemical staining with monoclonal antibodies showed marked variations in the percentage of melanoma cells stained by anti-HLA Class I and anti-HLA Class II monoclonal antibodies among 48 locoregional metastases removed from 39 patients with malignant melanoma. On the other hand there was limited variation in the percentage of melanoma cells stained by anti-HLA antibodies in autologous locoregional metastases removed from 8 of 9 patients. In the remaining patient marked differences were found in the percentage of melanoma cells stained by anti-HLA Class I antibodies in the two parts of the lymph node metastasis analyzed. Therefore this patient was not included in additional analyses to correlate the level of expression of HLA antigens with the clinical course of the disease. In all the lesions tested the percentage of melanoma cells stained by anti-HLA Class II antibodies was lower than or equal to but never higher than that stained by anti-HLA Class I antibodies. According to the level of expression of HLA Class I and Class II antigens the 38 patients could be divided into three groups: Pattern A included lesions with more than 50% of tumor cells stained by anti-HLA Class I antibodies (mean, 86.1; median, 85) and 50% or less by anti-HLA Class II antibodies (mean, 10.5; median, 5); Pattern B included lesions with 50% or less tumor cells stained by anti-HLA Class I antibodies (mean, 14.9; median, 5) and by anti-HLA Class II antibodies (mean, 4.1; median, 1); Pattern C included lesions with more than 50% tumor cells stained by anti-HLA Class I antibodies (mean, 88.8; median, 92) and by anti-HLA Class II antibodies (mean, 70.0; median, 70). The survival of 21 patients with Pattern A was significantly longer than those of 13 and 4 patients with Patterns B and C, respectively. No difference in the survival of patients in the latter two groups was found. These results suggest that HLA antigens play a role in the biology of melanoma and that analysis of the level of HLA antigens in locoregional metastases of patients with melanoma may provide clinically useful information.
Degenerate Ground State in a MesoscopicYBa2Cu3O7−xGrain Boundary Josephson Junction (2001)

We have measured the current-phase relationship I(varphi) of symmetric 45 degrees YBa2Cu3O7-x grain boundary Josephson junctions. Substantial deviations of the Josephson current from conventional tunnel-junction behavior have been observed: (i) The critical current exhibits, as a function of temperature T, a local minimum at a temperature T*. (ii) At T approximately T*, the first harmonic of I(phi) changes sign. (iii) For T<T*, the second harmonic of I(phi) is comparable to the first harmonic, and (iv) the ground state of the junction becomes degenerate. The results are in good agreement with a microscopic model of Josephson junctions between d-wave superconductors.
Measurements of CO, CO_2, OH, and H_2O in room-temperature and combustion gases by use of a broadly current-tuned multisection InGaAsP diode laser (1999)

A new laser technology that achieves nearly 100-nm quasi-continuous tuning with only injection-current control in a four-section grating-coupler sampled-reflector laser was used to detect CO and CO(2) simultaneously in room-temperature gas mixtures. The same grating-coupler sampled-reflector laser was used to perform in situ measurements of CO, H(2)O, and OH in the exhaust gases of a CH(4)-air flame. This laser is being evaluated for inclusion in a multispecies combustion-emissions exhaust-analysis sensor, and its operational characteristics as they have an impact on gas sensing are described. Preliminary results suggest that this single laser can be used to replace multilaser sensor configurations for some combustion-emissions monitoring applications.
IFI16 in Human Prostate Cancer (2007)

Increased expression of IFI16 protein (encoded by the IFI16 gene) in normal human prostate epithelial cells is associated with cellular senescence-associated cell growth arrest. Consistent with a role for IFI16 protein in cellular senescence, the expression of IFI16 protein is either very low or not detectable in human prostate cancer cell lines. We now report that treatment of DU-145 and LNCaP prostate cancer cell lines with histone deacetylase inhibitor trichostatin A (TSA) or CGK1026 resulted in transcriptional activation of the IFI16 gene. The induction of IFI16 protein in LNCaP cells was dependent on the duration of TSA treatment. Furthermore, TSA treatment of LNCaP cells up-regulated the expression of Janus-activated kinase 1 protein kinase and modulated the transcription of certain IFN-activatable genes. However, overexpression of exogenous Janus-activated kinase 1 protein in LNCaP cells and treatment of cells with IFNs (alpha and gamma) did not increase the expression of IFI16. Instead, the transcriptional activation of IFI16 gene by TSA treatment of LNCaP cells was dependent on transcriptional activation by c-Jun/activator protein-1 transcription factor. Importantly, increased expression of IFI16 in LNCaP cells was associated with decreases in the expression of androgen receptor and apoptosis of cells. Conversely, knockdown of IFI16 expression in TSA-treated LNCaP cells increased androgen receptor protein levels with concomitant decreases in apoptosis. Together, our observations provide support for the idea that histone deacetylase-dependent transcriptional silencing of the IFI16 gene in prostate epithelial cells contributes to the development of prostate cancer.
Compensation schemes and performance analysis of IQ imbalances in OFDM receivers (2005)

The implementation of orthogonal frequency division multiplexing (OFDM)-based physical layers suffers from the effect of In-phase and Quadrature-phase (IQ) imbalances in the front-end analog processing. The IQ imbalances can severely limit the achievable operating signal-to-noise ratio (SNR) at the receiver and, consequently, the supported constellation sizes and data rates. In this paper, the effect of IQ imbalances on OFDM receivers is studied, and system-level algorithms to
Dot or pointillistic method for improvement in results of hypertrophic scarring in the argon laser treatment of portwine hemangiomas (1987)

In an attempt to limit scarring, 51 patients have been treated over a period of 2 years with the argon laser in a dot or pointillistic fashion. One- to 2-mm dots are blanched at intervals of 1-2 mm with minimal power, and the interspaces are filled in at 12 weeks. Scar-prone areas of the face such as the upper lip, nasolabial fold, nose, and lower lip have been successfully treated with minimal scarring and good fading. Lesions of the trunk and extremity have also been successfully treated.
Studies on cardiotonic agents. VII. Potent cardiotonic agent KF15232 with myofibrillar Ca2+ sensitizing effect. (1991)

A series of novel 4,5-dihydro-5-methyl-6-(2 or 4-substituted 7-quinazolinyl)-3(2H)-pyridazinones was synthesized and examined for cardiotonic activity in anesthetized dogs. The 4-substituted aminoquinazolines generally showed potent and long-lasting inotropic activity. Fall in the activity was observed on the introduction of substituent at the 2-position of the quinazoline ring. The 3-substituted 4 (3H)-quinazolinimines generally exhibited weak activity. Ca2+ sensitizing effect of the 4-substituted amino derivatives was also examined in chemically skinned fiber from papillary muscle of guinea pig. The alkylamino derivatives exhibited small sensitizing effect, while the benzylamino derivatives exhibited large effect. Among them, KF15232 (Ix) was found to have the most potent cardiotonic and Ca2+ sensitizing activities.
Cellular senescence in the aging and diseased kidney (2017)

The program of cellular senescence is involved in both the G1 and G2 phase of the cell cycle, limiting G1/S and G2/M progression respectively, and resulting in prolonged cell cycle arrest. Cellular senescence is involved in normal wound healing. However, multiple organs display increased senescent cell numbers both during natural aging and after injury, suggesting that senescent cells can have beneficial as well as detrimental effects in organismal aging and disease. Also in the kidney, senescent cells accumulate in various compartments with advancing age and renal disease. In experimental studies, forced apoptosis induction through the clearance of senescent cells leads to better preservation of kidney function during aging. Recent groundbreaking studies demonstrate that senescent cell depletion through INK-ATTAC transgene-mediated or cell-penetrating FOXO4-DRI peptide induced forced apoptosis, reduced age-associated damage and dysfunction in multiple organs, in particular the kidney, and increased performance and lifespan. Senescence is also involved in oncology and therapeutic depletion of senescent cells by senolytic drugs has been studied in experimental and human cancers. Although studies with senolytic drugs in models of kidney injury are lacking, their dose limiting side effects on other organs suggest that targeted delivery might be needed for successful application of senolytic drugs for treatment of kidney disease. In this review, we discuss (i) current understanding of the mechanisms and associated pathways of senescence, (ii) evidence of senescence occurrence and causality with organ injury, and (iii) therapeutic strategies for senescence depletion (senotherapy) including targeting, all in the context of renal aging and disease.
A purine nucleoside hydrolase from Trypanosoma gambiense, purification and properties. (1975)

A purine nucleoside hydrolase from Trypanosoma gambiense was purified 160-fold. Preferred substrates of the reaction were adenosine, inosine and guanosine with a maximum of activity at pH 5.4. Competitive inhibitors of the adenosine hydrolysis were dimethylallyl adenosine, 6-methylmercaptopurine riboside, tubercidin, formycin B, 6-mercaptopurine riboside and deoxyadenosine. A metabolic scheme of adenosine nomophosphate salvage synthesis is discussed.
Differential chemotactic activities of sensory neuropeptides for human peripheral blood mononuclear cells (1997)

We studied the chemotactic effects of calcitonin gene-related peptide, vasoactive intestinal peptide, substance P (SP), and secretoneurin on PBMC and PBL using micropore filter assays. All four peptides induced migration of PBMC, whereas only calcitonin gene-related peptide, vasoactive intestinal peptide, and SP were chemotactic for PBL. Secretoneurin, known to induce monocyte chemotaxis, was unable to affect lymphocyte migration. Effects of SP on PBL were characterized by checkerboard analyses and represented true chemotaxis. Both T and B cells responded chemotactically to SP, the functional activity of SP residing in its C-terminal amino acid sequence. Involvement of neurokinin (NK) receptors was supported by inhibition of SP-induced migration of PBL with an NK1 receptor antagonist and induction of migration with [Sar9, Met(O2)11]SP and [PyrGlu6, Pro9]SP(6-11), two specific agonists for NK1 receptors, but not with [beta-Ala8]NK A(4-10), an agonist for NK2 receptors. PBL chemotaxis to SP was abolished by inhibition of tyrosin kinase but not by that of protein kinase C. Preincubation of PBL with pertussis or cholera toxin inhibited SP chemotaxis, indicating that in PBL, NK receptors for chemotaxis probably are coupled with G protein and involve a tyrosin kinase signaling pathway. We conclude that, together with calcitonin gene-related peptide and vasoactive intestinal peptide, SP is a lymphocyte chemoattractant, whereas secretoneurin, which is coreleased from sensory nerve endings, is not.
A Stable Bovine Papillomavirus Hybrid Plasmid That Expresses a Dominant Selective Trait (1983)

We describe a bovine papillomavirus hybrid plasmid containing the neomycin resistance gene from Tn5 inserted into a mammalian cell transcriptional unit. This plasmid is maintained as a stable extrachromosomal element (20 to 100 copies per diploid genome) in mouse cells selected either for the transformed phenotype or for resistance to the aminoglycoside G418. Cells selected for G418 resistance initially display a flat, nontransformed phenotype before exhibiting the gross morphological characteristics of transformation. The delay in the appearance of the transformed phenotype indicated that some intracellular event or series of events subsequent to the establishment of transcriptionally active bovine papillomavirus 1 hybrid plasmid is required for the manifestation of the transformed phenotype.
Immune response and persistence of the porcine reproductive and respiratory syndrome virus in infected pigs and farm units (1994)

The kinetics of the serum antibody response to porcine reproductive and respiratory syndrome (PRRS) virus and the persistence of the virus after infection were determined in experimentally and naturally infected pigs. In an experimental study, four specific pathogen free (SPF) sows were infected with a French strain of PRRS virus at 90 days of gestation, and their piglets (the test piglets) were monitored for 29 weeks from birth. In one litter, antibodies against PRRS virus were absent before the piglets had ingested colostrum. Four days after birth, passive antibodies were present in the serum of these piglets, but they had disappeared by three weeks (just before weaning) when clinical signs were observed in a minority of the pigs. In a second litter, most of the piglets had no detectable antibodies until they were four weeks old, and clinical signs were observed during their second week of life. By eight weeks, antibodies were detected in all the pigs, and they persisted until observations ceased at 29 weeks. Two groups of three SPF pigs were placed in direct contact with the test piglets when they were four weeks old and a group of five SPF pigs was placed in indirect contact when they were 13 weeks old. The first two groups showed clinical signs and seroconverted but the third group did not. At 22 weeks old, two of the test piglets were subjected to movement stress and were given exogenous corticosteroids, after which the in-contact SPF pigs developed clinical signs and seroconverted.(ABSTRACT TRUNCATED AT 250 WORDS)
20-Methyl-4-azacholanthrene (1940)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT20-Methyl-4-azacholanthreneLouis F. Fieser and E. B. HershbergCite this: J. Am. Chem. Soc. 1940, 62, 7, 1640–1645Publication Date (Print):July 6, 1940Publication History Published online1 May 2002Published inissue 6 July 1940https://pubs.acs.org/doi/10.1021/ja01864a002https://doi.org/10.1021/ja01864a002research-articleACS PublicationsRequest reuse permissionsArticle Views445Altmetric-Citations24LEARN 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
Molecular Characterization of CD40 Signaling Intermediates (2001)

Signal transduction through the CD40 receptor is initiated by binding of its trimeric ligand and propagated by interactions of tumor necrosis factor receptor-associated factor (TRAF) proteins with the multimerized CD40 cytoplasmic domain. Using defined multimeric constructs of the CD40 cytoplasmic domain expressed as either soluble or myristoylated proteins, we have addressed the extent of receptor multimerization needed to initiate signal transduction and identified components of CD40 signaling complexes. Signal transduction in human embryonic kidney 293 cells, measured by nuclear factor kappaB activation, was observed in cells expressing soluble trimeric CD40 cytoplasmic domain and to a lesser extent in cells expressing dimeric CD40 cytoplasmic domain. Nuclear factor kappaB activation was strongest in cells expressing myristoylated trimeric CD40 cytoplasmic domain. Signal transduction through trimeric CD40 cytoplasmic domains with various point mutations in the TRAF binding sites was similar to signal transduction through analogous full-length receptors. Transiently expressed soluble trimeric CD40 cytoplasmic domain was isolated as complexes that contained TRAF2, TRAF3, TRAF5, TRAF6, and the inhibitor of apoptosis protein (c-IAP1). Association of c-IAP1 with the CD40 cytoplasmic domain complex was indirect and dependent on the presence of an intact TRAF1/2/3 binding site. These results suggest that extracellular ligation of CD40 can be bypassed and that soluble trimerized CD40 complexes can be isolated and used to identify components that link CD40 with signaling pathways.
Role of the Amino Latch of Staphylococcal α-Hemolysin in Pore Formation (2005)

Staphylococcal alpha-hemolysin (alphaHL) is a beta barrel pore-forming toxin that is secreted by the bacterium as a water-soluble monomeric protein. Upon binding to susceptible cells, alphaHL assembles via an inactive prepore to form a water-filled homoheptameric transmembrane pore. The N terminus of alphaHL, which in the crystal structure of the fully assembled pore forms a latch between adjacent subunits, has been thought to play a vital role in the prepore to pore conversion. For example, the deletion of two N-terminal residues produced a completely inactive protein that was arrested in assembly at the prepore stage. In the present study, we have re-examined assembly with a comprehensive set of truncation mutants. Surprisingly, we found that after truncation of up to 17 amino acids, the ability of alphaHL to form functional pores was diminished, but still substantial. We then discovered that the mutation Ser(217) --> Asn, which was present in our original set of truncations but not in the new ones, promotes complete inactivation upon truncation of the N terminus. Therefore, the N terminus of alphaHL cannot be critical for the prepore to pore transformation as previously thought. Residue 217 is involved in the assembly process and must interact indirectly with the distant N terminus during the last step in pore formation. In addition, we provide evidence that an intact N terminus prevents the premature oligomerization of alphaHL monomers in solution.
Blood Nucleoside and Nucleotide Studies in Mental Disease (1972)

The generally accepted (Waelsch and Weil-Malherbe, 1964) reduction in the rate of glucose utilization in cases of severe depression could not be confirmed with specifically determined blood glucose in patients given diets high in carbohydrate for three or four days before testing (Herzberg, Coppen and Marks, 1968; Hansen, 1969). Nevertheless, in numerical agreement with previous findings with older methods for blood sugar determination (Henneman, Altschule and Gonz, 1954; Balter and Efron, 1965), depression as a symptom in psychosis correlated highly with elevation of non-glucose carbohydrate concentrations as determined by the colorimetric anthrone method. It was found that elevated whole blood uridine diphosphate glucose (UDPG), enzymatically determined, correlated with depression in psychosis (Hansen, 1969).