gebhart/patrepeval huggingface dataset:
Multivalent Recognition of Peptides by Modular Self-Assembled Receptors (2009)

Developing nontraditional approaches to the synthesis and characterization of multivalent compounds is critical to our efforts to study and interface with biological systems and to build new noncovalent materials. This paper demonstrates a biomimetic approach to the construction of discrete, modular, multivalent receptors via molecular self-assembly in aqueous solution. Scaffolds presenting 1-3 viologen groups recruit a respective 1-3 copies of the synthetic host, cucurbit[8]uril, in a noncooperative manner and with a consistent equilibrium association constant (K(a)) value of 2 x 10(6) M(-1) per binding site. The assembled mono-, di-, and trivalent receptors bind to their cognate target peptides containing 1-3 Trp residues with K(a) values in the range 1.7 x 10(4)-4.7 x 10(6) M(-1) and in predetermined mono- or multivalent binding modes with 31-280-fold enhancements in affinity and additive enthalpies due to multivalency. The extent of valency was determined directly by measuring the visible charge-transfer absorptivity due to the viologen-indole pair. The predictable behavior of this system and its ease of synthesis and analysis make it well suited to serve as a model for multivalent binding and for the multivalent recognition of peptides by design.
Methylation-sensitive, single-strand conformation analysis (MS-SSCA): A rapid method to screen for and analyze methylation (1999)

We have developed methylation-sensitive, single-strand conformation analysis (MS-SSCA) as a method of screening for methylation changes. Bisulfite modification converts cytosines to thymines, but methylated cytosines remain unchanged. This modification creates sequence differences between methylated and unmethylated samples, which can be resolved by SSCA. SSCA is 70-95% efficient at detecting single base changes in a fragment. As bisulfite modification of methylated DNA would typically involve several base changes in a fragment, the efficiency of detecting methylation using MS-SSCA could approach 100%. We applied this method to analyze the BRCA1 promoter CpG island in breast cancer samples. About 20% of sporadic breast cancers are hypermethylated at the BRCA1 promoter CpG island. MS-SSCA rapidly detected those tumors that had previously been shown to be methylated by Southern blotting. The variant bands detected by SSCA were analyzed by sequencing and shown to be methylated. MS-SSCA is a simple method for screening large numbers of samples for methylation and can accelerate genomic sequencing, as all bands can be isolated and sequenced directly.
Co‐expression of tenascin and fibronectin in epithelial and stromal cells of benign lesions and ductal carcinomas in the human breast (1997)

Tenascin (TN)-C and fibronectin (FN), which are glycoproteins of the extracellular matrix (ECM), are up-regulated in cancer tissues, including breast cancer. For assessment of their involvement in cancer invasion, it is important to know which cells are responsible for their production and secretion. The distribution of cells expressing TN and FN mRNAs in benign and malignant human breast tissues was therefore analysed by in situ hybridization, using digoxigenin-labelled cRNA probes, in addition to demonstrating the proteins immunohistochemically. Both mRNAs were expressed in epithelial cancer as well as in stromal cells in a large fraction of the tumours, with co-expression in individual cells. In cancers with intraductal components and/or those consisting of large nests, the mRNAs were more often expressed in the cancer than in the stromal cells. In scirrhous carcinomas, in contrast, the stromal cells were almost always positive for TN and FN mRNAs, while the cancer cells only rarely exhibited TN or FN expression. In benign lesions including adenosis, fibroadenoma and intraductal papilloma, the expression patterns also varied. These findings indicate that TN and FN co-expressed by cancer cells and stromal cells are probably involved in the intraductal extension and early invasion of cancer cells and in the remodelling of cancer stroma. © 1997 John Wiley & Sons, Ltd.
IL-2 addiction: withdrawal of growth factor activates a suicide program in dependent T cells. (1986)

IL-2-dependent T effector cells usually die when deprived of growth factor. Cell death (as measured by plasma membrane breakdown) requires protein synthesis because it is inhibited by cycloheximide or emetine. When the DNA in several IL-2-dependent cell lines was examined following removal of IL-2, it was found that extensive chromatin cleavage precedes plasma membrane breakdown by several hours. The DNA fragments observed were not randomly generated but consisted of oligonucleosomes. This suggests that IL-2 deprivation led to activation of an endonuclease with specificity for linker DNA. DNA fragmentation, like cell death, did not occur in the presence of protein synthesis inhibitors. The protein(s) synthesized in response to IL-2 deprivation may, therefore, be the endonuclease or its activator; none of the IL-2-dependent T cells examined contain detectable endogenous endonuclease prior to IL-2 removal. DNA fragments were also found in vivo in lymph node cells draining a site of antigen administration. These results suggest that one aspect of the termination of immune responses involves activation of a cell suicide program in the expanded effector T cell clones. In this program an endonuclease is activated and chromatin is cleaved; as a result macromolecular synthesis begins to wind down so that repair synthesis stops; within a few hours, the cell lyses.
Coadministration of a 9-Valent Human Papillomavirus Vaccine With Meningococcal and Tdap Vaccines (2015)

Concomitant administration of 9vHPV vaccine with MCV4/Tdap was generally well tolerated and did not interfere with the antibody response to any of these vaccines. This strategy would minimize the number of visits required to deliver each vaccine individually.
Opioid Antagonist Modulation of Ischaemia-Induced Ventricular Arrhythmias: A Peripheral Mechanism (1999)

Ventricular arrhythmias are an important cause of death after myocardial ischaemia. Animal studies have generated conflicting data on the potentiating or attenuating effects of opioid agonists and antagonists on cardiac rhythm during acute myocardial ischaemia and coronary artery reperfusion. Whether these effects of opioid antagonists are mediated by central or peripheral nervous system mechanisms remains unclear. We examined (a) the effects of peripheral opioid receptor blockade on ischaemia-induced arrhythmia by using methylnaltrexone (MNTX), a novel quaternary derivative of naltrexone (NTX) that does not cross the blood-brain barrier, and (b) whether MNTX would modulate morphine effects during acute coronary artery ligation and reperfusion in the rabbit. The incidence and severity of cardiac arrhythmias were assessed during 40 min of coronary artery occlusion and reperfusion and summarised in an arrhythmia score (AS). MNTX reduced the incidence of ventricular fibrillation (VF) and arrhythmia score during coronary artery occlusion when compared with vehicle (p < 0.05). Naltrexone reduced the incidence of VF (p < 0.05). Although morphine alone had no significant effects, its coadministration blunted the antiarrhythmic properties of MNTX. The data suggest that blockade of opiate receptors outside the central nervous system may protect against ischaemia-induced arrhythmias.
Preterm Labor Associated With Subclinical Amniotic Fluid Infection and With Bacterial Vaginosis (1986)

Maternal genital infection, particularly subclinical amniotic fluid infection, may cause preterm labor and a premature delivery. The prevalence of subclinical amniotic fluid infection was studied in 54 consecutive afebrile women in preterm labor with singleton gestations and intact fetal membranes. Microorganisms were recovered from the amniotic fluid by transabdominal amniocentesis in 13 (24%) of 54 patients. Bacteria or Candida albicans were recovered from six (11%), and genital mycoplasmas from seven (13%). Compared with women with sterile amniotic fluid, patients whose amniotic fluid contained bacteria or Candida organisms had a shorter interval from onset of preterm labor until delivery (0.6 versus 34.3 days, P less than .01), were less responsive to tocolytic therapy (0 versus 81% success rate, P less than .005), and more frequently developed subsequent intrapartum fever (83 versus 2.4%, P less than .005). In contrast, women whose amniotic fluid contained genital mycoplasmas did not differ in these parameters from those with sterile fluid. Also compared was cervical-vaginal infection among these patients in preterm labor with matched control subjects without preterm labor. In this analysis, bacterial vaginosis was identified in 43% of patients with and 14% of women without preterm labor (P = .02), yielding a relative risk of preterm labor for patients with bacterial vaginosis of 3.8. These data underscore the importance of amniotic fluid bacterial infections in preterm labor and premature delivery, and suggest that bacterial vaginosis is associated with prematurity.
Cardenolide analogues. 11. Improved method for the use of Fétizon's reagent in the synthesis of cardiac glycosides. (1981)

An improved procedure has been developed for preparing glycosides of cardenolide genins. The method uses specially prepared Fétizon's reagent as catalyst, combined, in most cases, with mercuric cyanide and mercuric bromide. In the presence of this catalyst, genins react readily, at room temperature, with per-acetylated 1-bromo-sugars to give the acetylated glycosides in high yield with little or no side reaction. The reaction proceeds almost to completion in 30 to 60 min. The free glycoside is obtained by mild deacetylation using triethylamine/methanol/water (20:20:1) at room temperature for 72 h. Proof of structure was obtained using chemical ionization mass spectrometry, NMR spectroscopy and comparison of physical constants with published data. The compounds were tested for inotropic activity using the isolated guinea pig atrium.
The Structure and Energetics of Helix Formation by Short Templated Peptides in Aqueous Solution. 2. Characterization of the Helical Structure of Ac-Hel1-Ala6-OH (1996)

Analysis of NOE cross-peaks in 1H NMR ROESY spectra of Ac-Hel1-Ala6-OH in water and in water−trifluoroethanol mixtures demonstrates that the template Ac-Hel1 initiates an α-helix in a linked hexa-Ala peptide. Other NMR parameters and circular dichroism spectra are consistent with the presence of an α-helix, frayed at the C-terminus. Effects of NaCl, urea, temperature, and trifluoroethanol on the stability of a short alanine helix are reported.
Increased stratum corneum serine protease activity in acute eczematous atopic skin (2009)

We report increased serine protease activities in acute eczematous AD, especially in deeper layers of the SC, including SC tryptase-like enzyme, plasmin, urokinase and leucocyte elastase activities. These elevations in protease activities were associated with impaired barrier function, irritation, and reduced skin capacitance. Increased SC cohesion was apparent despite elevated TEWL during tape stripping, which would indicate reduced SC thickness in acute eczematous lesions of AD. Indeed, this was observed using an estimate of SC thickness.
Abstract 1764: Inhibition of R-spondin (RSPO) signaling reduces the growth of multiple human tumors (2014)

Abstract Deregulation of the canonical Wnt/beta-catenin signaling pathway has long been associated with cancer. Intracellular components of this pathway, including Axin, APC, and beta-catenin are frequently mutated in a range of human tumors. The identity of specific extracellular ligands that contribute to human cancer development through this signaling axis has remained unclear. Molecular characterization of the secreted beta-catenin signaling activities produced by minimally passaged human tumor xenograft models identified RSPO family members produced by multiple tumor types including ovarian, pancreatic, colon, breast and non-small cell lung cancer. In human tumor xenograft models that had RSPO overexpression, in some instances due to genomic translocation, anti-RSPO treatment markedly inhibited tumor growth. In addition, striking combination activity with standard of care chemotherapy agents resulted in regression of established tumors. These results highlight the potential for therapeutic intervention with this newly appreciated signaling axis. Citation Format: Austin Gurney, Fumiko Axelrod, Chris Bond, Jennifer Cain, Cecile Chartier, Marcus Fischer, May Ji, Chris Murriel, Janak Raval, Jalpa Shah, Min Wang, Wan-Ching Yen, Ann Kapoun, John Lewicki, Timothy Hoey. Inhibition of R-spondin (RSPO) signaling reduces the growth of multiple human tumors. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1764. doi:10.1158/1538-7445.AM2014-1764
Selenocysteine (1996)

Selenocysteine is recognized as the 21st amino acid in ribosome-mediated protein synthesis and its specific incorporation is directed by the UGA codon. Unique tRNAs that have complementary UCA anticodons are aminoacylated with serine, the seryl-tRNA is converted to selenocysteyl-tRNA and the latter binds specifically to a special elongation factor and is delivered to the ribosome. Recognition elements within the mRNAs are essential for translation of UGA as selenocysteine. A reactive oxygen-labile compound, selenophosphate, is the selenium donor required for synthesis of selenocysteyl-tRNA. Selenophosphate synthetase, which forms selenophosphate from selenide and ATP, is found in various prokaryotes, eukaryotes, and archaebacteria. The distribution and properties of selenocysteine-containing enzymes and proteins that have been discovered to date are discussed. Artificial selenoenzymes such as selenosubtilisin have been produced by chemical modification. Genetic engineering techniques also have been used to replace cysteine residues in proteins with selenocysteine. The mechanistic roles of selenocysteine residues in the glutathione peroxidase family of enzymes, the 5′ deiodinases, formate dehydrogenases, glycine reductase, and a few hydrogenases are discussed. In some cases a marked decrease in catalytic activity of an enzyme is observed when a selenocysteine residue is replaced with cysteine. This substitution caused complete loss of glycine reductase selenoprotein A activity.
Identification of H2N3 influenza A viruses from swine in the United States (2007)

Although viruses of each of the 16 influenza A HA subtypes are potential human pathogens, only viruses of the H1, H2, and H3 subtype are known to have been successfully established in humans. H2 influenza viruses have been absent from human circulation since 1968, and as such they pose a substantial human pandemic risk. In this report, we isolate and characterize genetically similar avian/swine virus reassortant H2N3 influenza A viruses isolated from diseased swine from two farms in the United States. These viruses contained leucine at position 226 of the H2 protein, which has been associated with increased binding affinity to the mammalian alpha2,6Gal-linked sialic acid virus receptor. Correspondingly, the H2N3 viruses were able to cause disease in experimentally infected swine and mice without prior adaptation. In addition, the swine H2N3 virus was infectious and highly transmissible in swine and ferrets. Taken together, these findings suggest that the H2N3 virus has undergone some adaptation to the mammalian host and that their spread should be very closely monitored.
Connections between transcriptional activators, silencers, and telomeres as revealed by functional analysis of a yeast DNA-binding protein. (1988)

General regulatory factor I (GRFI) is a yeast protein that binds in vitro to specific DNA sequences at diverse genetic elements. A strategy was pursued to test whether GRFI functions in vivo at the sequences bound by the factor in vitro. Matches to a consensus sequence for GRFI binding were found in a variety of locations: upstream activating sequences (UASs), silencers, telomeres, and transcribed regions. All occurrences of the consensus sequence bound both crude and purified GRFI in vitro. All binding sites for GRFI, regardless of origin, provided UAS function in test plasmids. Also, GRFI binding sites specifically stimulated transcription in a yeast in vitro system, indicating that GRFI can function as a positive transcription factor. The stimulatory effect of GRFI binding sites at UASs for the PYK1 and ENO1 genes is significantly enhanced by flanking DNA elements. By contrast, regulatory sequences that flank the GRFI binding site at HMR E convert this region to a transcriptional silencer.
A 256K dual port memory (1985)

This paper will describe a 64K×4 DRAM and a 256×4 serial readout memory with an access time of 35ns developed to provide graphic data pickup from any location. The ×4 DRAM port affords independent write capability for each bit in the word.
Engineering Encodable Lanthanide-Binding Tags into Loop Regions of Proteins (2010)

Lanthanide-binding tags (LBTs) are valuable tools for investigation of protein structure, function, and dynamics by NMR spectroscopy, X-ray crystallography, and luminescence studies. We have inserted LBTs into three different loop positions (denoted L, R, and S) of the model protein interleukin-1β (IL1β) and varied the length of the spacer between the LBT and the protein (denoted 1−3). Luminescence studies demonstrate that all nine constructs bind Tb3+ tightly in the low nanomolar range. No significant change in the fusion protein occurs from insertion of the LBT, as shown by two X-ray crystallographic structures of the IL1β-S1 and IL1β-L3 constructs and for the remaining constructs by comparing the 1H−15N heteronuclear single-quantum coherence NMR spectra with that of the wild-type IL1β. Additionally, binding of LBT-loop IL1β proteins to their native binding partner in vitro remains unaltered. X-ray crystallographic phasing was successful using only the signal from the bound lanthanide. Large residual dipolar couplings (RDCs) could be determined by NMR spectroscopy for all LBT-loop constructs and revealed that the LBT-2 series were rigidly incorporated into the interleukin-1β structure. The paramagnetic NMR spectra of loop-LBT mutant IL1β-R2 were assigned and the Δχ tensor components were calculated on the basis of RDCs and pseudocontact shifts. A structural model of the IL1β-R2 construct was calculated using the paramagnetic restraints. The current data provide support that encodable LBTs serve as versatile biophysical tags when inserted into loop regions of proteins of known structure or predicted via homology modeling.
Fast multiplierless approximations of the DCT with the lifting scheme (2001)

We present the design, implementation, and application of several families of fast multiplierless approximations of the discrete cosine transform (DCT) with the lifting scheme called the binDCT. These binDCT families are derived from Chen's (1977) and Loeffler's (1989) plane rotation-based factorizations of the DCT matrix, respectively, and the design approach can also be applied to a DCT of arbitrary size. Two design approaches are presented. In the first method, an optimization program is defined, and the multiplierless transform is obtained by approximating its solution with dyadic values. In the second method, a general lifting-based scaled DCT structure is obtained, and the analytical values of all lifting parameters are derived, enabling dyadic approximations with different accuracies. Therefore, the binDCT can be tuned to cover the gap between the Walsh-Hadamard transform and the DCT. The corresponding two-dimensional (2-D) binDCT allows a 16-bit implementation, enables lossless compression, and maintains satisfactory compatibility with the floating-point DCT. The performance of the binDCT in JPEG, H.263+, and lossless compression is also demonstrated.
Interact (2015)

Interact is a mobile virtual assistant that uses multimodal dialog to enable an interactive concierge experience over multiple application domains including hotel, restaurants, events, and TV search. Interact demonstrates how multi- modal interaction combined with conversational dialog en- ables a richer and more natural user experience. This demonstration will highlight incremental recognition and under- standing, multimodal speech and gesture input, context track- ing over multiple simultaneous domains, and the use of multimodal interface techniques to enable disambiguation of erors and online personalization.
The graft-versus-leukemia (GVL) phenomenon: is GVL separable from GVHD? (1990)

Graft-versus-leukemia (GVL) is a major component of the overall beneficial effects of allogeneic bone marrow transplantation (BMT) in the treatment of leukemia. Although several clinical trials have suggested a direct relationship between GVL effects and acute and chronic graft-versus-host disease (GVHD), it is not yet known whether GVL can be separated from GVHD. However, several investigations in murine models of human leukemia indicate that the two may be at least partially separable. Moreover, analysis of clinical data from the International Bone Marrow Transplant Registry suggest that allogeneic BMT may be more advantageous than syngeneic BMT, regardless of the GVHD. Likewise, T lymphocyte depletion is associated with an increased incidence of relapse, independently of GVHD. Recent investigations in murine leukemia suggest that GVL-like effects may be inducible following syngeneic BMT by recombinant cytokines with no overt GVHD. Taken together, current data in experimental animals and man suggest that GVL may be at least partially separable from GVHD. Hence, further understanding of effector and target cells of GVL as well as our ability to induce antitumor effector cells, especially those that are MHC nonrestricted, may lead to new approaches for potentiating anti-tumor effector mechanisms without inducing severe, clinically overt GVHD. Successful attempts in these directions may also lead to improved results following autologous BMT as a result of activation of GVL-like effects by recombinant cytokines that are capable of activating effector cells with anti-leukemic activity in vivo, such as recombinant human IL2, alpha interferon or perhaps a synergistic combination of factors.