gebhart/patrepeval huggingface dataset:
The only proposed T-cell epitope derived from the TEL-AML1 translocation is not naturally processed (2011)

Adoptive therapy with T-cell receptor (TCR)-engineered T cells is a promising approach in cancer treatment. While usage of T cells specific for tumor-associated antigens (TAAs) can lead to serious side effects because of autoimmunity, targeting true tumor-specific mutations, such as the products of translocations in leukemias, should reduce such a risk. A potentially ideal target might be the chimeric protein TEL-AML1, which results from the chromosomal translocation 12;21 and represents the most common fusion gene in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Within the fusion region of TEL-AML1, a single epitope has been described by reverse immunology as immunogenic in HLA-A*0201 restriction settings. As a potential source of TCRs specific for this TEL-AML1 epitope, we have used mice expressing a human TCR-αβ repertoire and human MHC class I. Surprisingly, we have found that, although a specific functional CD8(+) T-cell response against this peptide could be evoked, the described epitope was in fact not endogenously processed. Analyses done with a potent antigen-presenting cell line, as well as with purified human proteasomes, support the conclusion that this peptide cannot be proposed as a potential target in immunotherapy of ALL in HLA-A*0201-restricted fashion.
Mobile-assisted localization in wireless sensor networks (2005)

The localization problem is to determine an assignment of coordinates to nodes in a wireless ad-hoc or sensor network that is consistent with measured pairwise node distances. Most previously proposed solutions to this problem assume that the nodes can obtain pairwise distances to other nearby nodes using some ranging technology. However, for a variety of reasons that include obstructions and lack of reliable omnidirectional ranging, this distance information is hard to obtain in practice. Even when pairwise distances between nearby nodes are known, there may not be enough information to solve the problem uniquely. This paper describes MAL, a mobile-assisted localization method which employs a mobile user to assist in measuring distances between node pairs until these distance constraints form a "globally rigid'* structure that guarantees a unique localization. We derive the required constraints on the mobile's movement and the minimum number of measurements it must collect; these constraints depend on the number of nodes visible to the mobile in a given region. We show how to guide the mobile's movement to gather a sufficient number of distance samples for node localization. We use simulations and measurements from an indoor deployment using the Cricket location system to investigate the performance of MAL, finding in real-world experiments that MAL's median pairwise distance error is less than 1.5% of the true node distance.
Monoclonal Antibodies to Human Progesterone Receptor: Characterization by Biochemical and Immunohistochemical Techniques* (1987)

Progesterone receptor (PR) from a human endometrial carcinoma (EnCa 101) grown in nude mice consists of two hormone-binding proteins with mol wt around 116,000 and 85,000. To generate monoclonal antibodies against this receptor, PR was partially purified from EnCa 101 and used to immunize Robertsonian mice. Immune mouse spleens were fused with HL-1 Friendly myeloma-653 cells, and hybridomas were screened by solid phase dot-blot assay and double antibody precipitation. Seven stable hybridomas were obtained, designated hPRa 1-7. Subisotyping revealed that hPRa 1 and 6 were immunoglobulin G2b, while the remainder were immunoglobulin G1. Ultracentrifugation in high salt sucrose gradients showed that six of the seven antibodies effected a shift of [3H]progestin-labeled PR from EnCa 101; only hPRa 4 was ineffective in this regard. Protein blots of EnCa 101 cytosols and DEAE eluates revealed that hPRa 1, 3, 4, 5, and 7 recognized both PR proteins equally. hPRa 2 recognized principally the 116,000 mol wt PR protein; it recognized the lower mol wt PR protein very poorly if at all, whereas hPRa 6 recognized only the 116,000 mol wt protein. Interestingly, the latter was consistently detected as a closely migrating triplet. Immunolocalization of PR by hPRa 1-7 in tissue sections was confined to nuclei of target tissues and varied in intensity: hPRa 7 greater than 3 = 5 greater than 6 = 2 greater than 1 greater than 4. In proliferative phase uterus, the intensity of staining was ranked: endometrial gland nuclei (3+) greater than myometrial cell nuclei (2-3+) greater than endometrial stromal cell nuclei (0-1+). Thus, seven monoclonal antibodies directed against human PR have been prepared, and their suitability for the study of PR by biochemical and immunohistochemical techniques has been demonstrated.
CD38 ligation in human B cell progenitors triggers tyrosine phosphorylation of CD19 and association of CD19 with lyn and phosphatidylinositol 3-kinase (1997)

CD38 is a 45-kDa transmembrane glycoprotein highly expressed in lymphoid progenitors. Ligation of CD38 with specific Abs inhibits growth and induces apoptosis in human immature B cells. CD38 ligation also triggers tyrosine phosphorylation of syk, c-cbl, and phospholipase C-gamma and activates phosphatidylinositol 3-kinase (PI3-K). In the present study, we investigated whether the cell surface membrane molecules used in B cell receptor-mediated signaling, such as Ig alpha, Ig beta, and CD19, could be involved in the CD38-mediated signaling cascade. In the B cell receptor-negative immature B cell lines RS4;11, 380, and REH, Ig alpha and Ig beta were expressed exclusively in the cytoplasm and were not tyrosine phosphorylated after CD38 ligation. By contrast, CD19 was markedly tyrosine phosphorylated and was associated with lyn and PI3-K. PI3-K activation appears to be directly linked to the growth-arresting effects of CD38 ligation, which are reduced by PI3-K inhibitors. Ligation of either CD38 or CD19 resulted in a similar pattern of protein tyrosine phosphorylation; both signaling pathways caused tyrosine phosphorylation of c-cbl. Levels of CD38 surface expression were not affected by prolonged incubation with anti-CD19 Ab, while CD19 expression markedly decreased. These results indicate that CD19 is a major component of the CD38 signaling cascade in B cell precursors, serving as a cell surface membrane docking site for cytoplasmic kinases. CD38 and CD19 are not physically linked, but activate an overlapping set of kinases in human immature B cells.
Targeted mutation of the CREB gene: compensation within the CREB/ATF family of transcription factors. (1994)

The cAMP response element binding protein (CREB) has been implicated as a key regulator in the transcriptional control of many genes. To assess the functional importance of CREB in vivo and its role in development, we used gene targeting to generate mice with a disruption of the CREB gene. Homozygous mutant mice appeared healthy and exhibited no impairment of growth or development. In this report we demonstrate that CREB and two other members of the CREB/ATF family, cAMP response element modulation protein (CREM) and activating transcription factor 1 (ATF1), appear to form a unique subgroup within this extensive class of transcription factors. Examination of CREM mRNA and protein levels in CREB mutant mice demonstrated overexpression of CREM in all tissues examined, but no change in ATF1 levels. These data demonstrate that CREB is not the sole mediator of cAMP-dependent transcriptional regulation and probably acts in concert with a specific subset of cAMP response element-binding proteins to transduce the cAMP signal and, in its absence, these same proteins can compensate for CREB function in vivo.
CDC55, a Saccharomyces cerevisiae gene involved in cellular morphogenesis: identification, characterization, and homology to the B subunit of mammalian type 2A protein phosphatase. (1991)

Microscopic screening of a collection of cold-sensitive mutants of Saccharomyces cerevisiae led to the identification of a new gene, CDC55, which appears to be involved in the morphogenetic events of the cell cycle. CDC55 maps between CDC43 and CHC1 on the left arm of chromosome VII. At restrictive temperature, the original cdc55 mutant produces abnormally elongated buds and displays a delay or partial block of septation and/or cell separation. A cdc55 deletion mutant displays a cold-sensitive phenotype like that of the original isolate. Sequencing of CDC55 revealed that it encodes a protein of about 60 kDa, as confirmed by Western immunoblots using Cdc55p-specific antibodies. This protein has greater than 50% sequence identity to the B subunits of rabbit skeletal muscle type 2A protein phosphatase; the latter sequences were obtained by analysis of peptides derived from the purified protein, a polymerase chain reaction product, and cDNA clones. An extragenic suppressor of the cdc55 mutation lies in BEM2, a gene previously identified on the basis of an apparent role in bud emergence.
Particle Motion in a Macroscale, Multiwavelength Acoustic Field (2014)

Particle motion due to ultrasonic acoustic radiation in a macroscale, multiwavelength acoustic chamber is investigated and compared with available theories. Primary acoustic radiation force theory has been extensively developed to predict single particle motion in a microscale, single-node acoustic chamber/channel. There is a need to investigate the applicability of this theory to macroscale, multiwavelength acoustic channels utilizing the acoustic radiation force for separating polydispersed particles. A particle-tracking velocimetry (PTV) approach for measuring individual particle motion is developed specifically to track particles as they densify at an acoustic pressure node. Particle motion is tracked over the lifetime of their motion to a node. Good agreement between the experimental and theoretical results is observed in the early stages of particle motion, where particles can be considered individually. Only in the densified region of the acoustic pressure node is there some mismatch with theory. The acoustic energy density of the acoustic chamber, a parameter intrinsically associated with the system by the theory, is also determined experimentally for different conditions and shown to be constant for all investigated system settings. The investigation demonstrates the capability of available theory in predicting the motion of polydispersed particles in macroscale, multiwavelength acoustic chambers.
A comb-sampling method for enhanced mass analysis in linear electrostatic ion traps (2011)

In this paper an algorithm for extracting spectral information from signals containing a series of narrow periodic impulses is presented. Such signals can typically be acquired by pickup detectors from the image-charge of ion bunches oscillating in a linear electrostatic ion trap, where frequency analysis provides a scheme for high-resolution mass spectrometry. To provide an improved technique for such frequency analysis, we introduce the CHIMERA algorithm (Comb-sampling for High-resolution IMpulse-train frequency ExtRAaction). This algorithm utilizes a comb function to generate frequency coefficients, rather than using sinusoids via a Fourier transform, since the comb provides a superior match to the data. This new technique is developed theoretically, applied to synthetic data, and then used to perform high resolution mass spectrometry on real data from an ion trap. If the ions are generated at a localized point in time and space, and the data is simultaneously acquired with multiple pickup rings, the method is shown to be a significant improvement on Fourier analysis. The mass spectra generated typically have an order of magnitude higher resolution compared with that obtained from fundamental Fourier frequencies, and are absent of large contributions from harmonic frequency components.
Structure-Based Strategies for Drug Design and Discovery (1992)

Most drugs have been discovered in random screens or by exploiting information about macromolecular receptors. One source of this information is in the structures of critical proteins and nucleic acids. The structure-based approach to design couples this information with specialized computer programs to propose novel enzyme inhibitors and other therapeutic agents. Iterated design cycles have produced compounds now in clinical trials. The combination of molecular structure determination and computation is emerging as an important tool for drug development. These ideas will be applied to acquired immunodeficiency syndrome (AIDS) and bacterial drug resistance.
Highly Luminescent Colloidal Nanoplates of Perovskite Cesium Lead Halide and Their Oriented Assemblies (2015)

Anisotropic colloidal quasi-two-dimensional nanoplates (NPLs) hold great promise as functional materials due to their combination of low dimensional optoelectronic properties and versatility through colloidal synthesis. Recently, lead-halide perovskites have emerged as important optoelectronic materials with excellent efficiencies in photovoltaic and light-emitting applications. Here we report the synthesis of quantum confined all inorganic cesium lead halide nanoplates in the perovskite crystal structure that are also highly luminescent (PLQY 84%). The controllable self-assembly of nanoplates either into stacked columnar phases or crystallographic-oriented thin-sheet structures is demonstrated. The broad accessible emission range, high native quantum yields, and ease of self-assembly make perovskite NPLs an ideal platform for fundamental optoelectronic studies and the investigation of future devices.
<title>Inhomogenous polarization in scanning optical microscopy</title> (2000)

Polarization control and analysis have proven to be a powerful tool both in conventional and confocal microscopies, but most of these approaches have used homogeneously polarized pupils. Other groups have had varying levels of success producing beams with spatially inhomogeneous polarization. In this paper, we describe the generation and focusing properties of such beams and their application to scanning laser microscopy. We specifically consider microscopy using the lowest-order azimuthally polarized beam.
Large offspring syndrome in cattle and sheep (1998)

Bovine and ovine embryos exposed to a variety of unusual environments prior to the blastocyst stage have resulted in the development of unusually large offspring which can also exhibit a number of organ defects. In these animals, the increased incidence of difficult parturition and of fetal and neonatal losses has limited the large-scale use of in vitro embryo production technologies commonly used in humans and other species. Four different situations have been identified that result in the syndrome: in vitro embryo culture, asynchronous embryo transfer into an advanced uterine environment, nuclear transfer and maternal exposure to excessively high urea diets. However, programming of the syndrome by all of these situations is unpredictable and not all of the symptoms described have been observed universally. Neither the environmental factors inducing the large offspring syndrome nor the mechanisms of perturbation occurring in the early embryo and manifesting themselves in the fetus have been identified.
Reversal of hyperglycemia in diabetic rats by portal vein transplantation of islet-like cells generated from bone marrow mesenchymal stem cells (2007)

Rat BM-MSCs could be transdifferentiated into islet-like cells in vitro. Portal vein transplantation of islet-like cells could alleviate the hyperglycemia of diabetic rats.
Preparation and Characterization of Dendrimer Monolayers and Dendrimer−Alkanethiol Mixed Monolayers Adsorbed to Gold (1998)

Single-component monolayers of dendrimers and two-component monolayers consisting of dendrimers and n-alkanethiols immobilized on Au substrates are described. Single-component monolayers are prepared by exposing an Au substrate to ethanolic solutions of amine- or hydroxy-terminated polyamidoamine (PAMAM) dendrimers. The resulting monolayers are highly stable and nearly close-packed for dendrimer generations ranging from 4 to 8 (G4−G8). Electrochemical ac-impedance measurements indicate that the dendrimer surface is very porous toward the electroactive redox couple Fe(CN)63-/4-. Ferrocene-terminated dendrimer monolayers have also been investigated. Exposure of higher-generation dendrimer monolayers to ethanolic solutions of hexadecanethiol (C16SH) results in a dramatic compression of the dendrimers, and causes them to reorient on the surface from an oblate to prolate configuration. The dendrimers originally present on the surface do not desorb as a consequence of this configurational change. Comparison of the extent of adsorption of C16SH in different media (vapor-phase N2, hexane, and ethanol) shows that solvation of the dendrimers is the primary driving force for the structural change. Finally, the reactivity and stability of the dendrimer monolayers is investigated by on-surface functionalization of the dendrimer monolayer with 4-(trifluoromethyl)benzoyl chloride. The physical and chemical properties of the single- and two-component monolayers are evaluated by using reflection infrared spectroscopy, ellipsometry, contact-angle measurements, ac-impedance spectroscopy, cyclic voltammetry, and surface acoustic wave (SAW)-based analyte-dosing experiments.
Alphaviral cytotoxicity and its implication in vector development (2004)

A great variety of viruses have been engineered to serve as expression vectors. Among them, the alphaviruses Semliki Forest virus and Sindbis virus represent promising tools for heterologous gene expression in a wide variety of host cells. Several applications have already been described in neurobiological studies, in gene therapy, for vaccine development and in cancer therapy. Both viruses trigger stress pathways in the cells they infect, sometimes culminating in the death of the host. This inherent property is either an advantage or a drawback, depending on the type of application. This review covers the development and applications of alphavirus vectors and, as our work has been mainly with Semliki Forest virus, we have focused on this virus with special emphasis on how the understanding of Semliki Forest virus cytotoxicity enables it to be manipulated and used.
Ras-Raf Signaling Needs Prohibitin (2005)

Prohibitin has been connected to diverse cellular functions including cell cycle control, senescence, apoptosis and stabilization of mitochondrial proteins. By employing a loss of function approach using siRNAs we have demonstrated an unexpected role of PHB in the activation of Raf/MEK/ERK pathway by active Ras and in modulating epithelial cell adhesion and migration. PHB directly interacts with C-Raf and is required for the displacement of 14-3-3 from C-Raf by active Ras to facilitate plasma membrane localization and activation. Further, the adherent complex proteins cadherin and beta-catenin were localized to plasma membrane suggesting stabilized adherent junctions in PHB silenced cells. Our findings demonstrated a function of PHB in the control of a central signaling pathway involved in cell growth and malignant transformation.
The gene SCL is expressed during early hematopoiesis and encodes a differentiation-related DNA-binding motif. (1989)

We have identified the human gene, SCL. We discovered this gene because of its involvement in a chromosomal translocation associated with the occurrence of a stem cell leukemia manifesting myeloid and lymphoid differentiation capabilities. Here we report the sequence of a cDNA for the normal SCL transcript, as well as for an aberrant fusion transcript produced in the leukemic cells. Although different at their 3' untranslated regions, both cDNAs predict a protein with primary amino acid sequence homology to the previously described amphipathic helix-loop-helix DNA binding and dimerization motif of the Ly1-1, myc, MyoD, immunoglobulin enhancer binding, daughterless, and achaete-scute families of genes. For these cDNAs, at least two different 5' ends are predicted, both of which retain this putative DNA binding domain and predict proteins in the range of 20-30 kDa. SCL mRNA is observed in "early" hematopoietic tissues. Taken together, these studies lead to the speculation that SCL plays a role in differentiation and/or commitment events during hematopoiesis.
Does phosphorylation of the cap‐binding protein eIF4E play a role in translation initiation? (2002)

Eukaryotic initiation factor 4E (eIF4E) plays an important role in mRNA translation by binding the 5'-cap structure of the mRNA and facilitating the recruitment to the mRNA of other translation factors and the 40S ribosomal subunit. eIF4E can interact either with the scaffold protein eIF4G or with repressor proteins termed eIF4E-binding proteins (4E-BPs). High levels of expression can disrupt cellular growth control and are associated with human cancers. A fraction of the cellular eIF4E is found in the nucleus where it may play a role in the transport of certain mRNAs to the cytoplasm. eIF4E undergoes regulated phosphorylation (at Ser209) by members of the Mnk group of kinases, which are activated by multiple MAP kinases (hence Mnk = MAP-kinase signal integrating kinase). The functional significance of its phosphorylation has been the subject of considerable interest. Recent genetic studies in Drosophila point to a key role for phosphorylation of eIF4E in growth and viability. Initial structural data suggested that phosphorylation of Ser209 might allow formation of a salt bridge with a basic residue (Lys159) that would clamp eIF4E onto the mRNA and increase its affinity for ligand. However, more recent structural data place Ser209 too far away from Lys159 to form such an interaction, and biophysical studies indicate that phosphorylation actually decreases the affinity of eIF4E for cap or capped RNA. The implications of these studies are discussed in the light of other, in vitro and in vivo, investigations designed to address the role of eIF4E phosphorylation in mRNA translation or its control.
Stereoselective Synthesis of Polysubstituted Tetrahydropyrans by Radical Cyclization of Epoxides using a Transition‐Metal Radical Source (2005)

Abstract Epoxyalkyl propargyl ethers 3a – f and allyl epoxyalkyl ethers 6a – c smoothly undergo radical cyclization reactions using a titanium( III ) species (Cp 2 TiCl) as the radical initiator to form polysubstituted tetrahydropyrans 4a – f and 7a – c in good yields and with high diastreoselectivity. The titanium( III ) species was prepared in situ from commercially available titanocene dichloride and Zn dust in THF. On the other hand, the epoxyalkyl propargyl ethers 3g and 3h furnished the spirocyclic ethers 4g and 4h , respectively, on radical cyclization reaction as the sole products. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2006)
Multivalent Peptidomimetic Conjugates: A Versatile Platform for Modulating Androgen Receptor Activity (2012)

We introduce a family of multivalent peptidomimetic conjugates that modulate the activity of the androgen receptor (AR). Bioactive ethisterone ligands were conjugated to a set of sequence-specific peptoid oligomers. Certain multivalent peptoid conjugates enhance AR-mediated transcriptional activation. We identify a linear and a cyclic conjugate that exhibit potent anti-proliferative activity in LNCaP-abl cells, a model of therapy-resistant prostate cancer. The linear conjugate blocks AR action by competing for ligand binding. In contrast, the cyclic conjugate is active despite its inability to compete against endogenous ligand for binding to AR in vitro, suggesting a non-competitive mode of action. These results establish a versatile platform to design competitive and non-competitive AR modulators with potential therapeutic significance.