gebhart/patrepeval huggingface dataset:
Radioimmunotherapy of B-Cell Lymphoma with [131I]Anti-B1 (Anti-CD20) Antibody (1993)

Radioimmunotherapy with [131I]anti-B1 antibody is a promising new treatment for lymphoma.
Identification and characterization of a human agonist cytotoxic T-lymphocyte epitope of human prostate-specific antigen. (2002)

One potential target of vaccine therapy for human prostate cancer is the prostate-specific antigen (PSA). One strategy to enhance the immunogenicity of a self-antigen such as PSA is to develop agonist epitopes that are potentially more immunogenic. The studies described here report the design and analysis of an agonist epitope designated PSA-3A ("A" for agonist) of the PSA-3 CTL epitope. Studies demonstrate that when compared with the native PSA-3 epitope, the PSA-3A agonist demonstrates enhanced binding to the MHC class I A2 allele as well as enhanced stability of the peptide-MHC complex. T-cell lines generated with either the PSA-3 or the PSA-3A peptide showed higher levels of lysis of targets pulsed with the PSA-3A peptide than those targets pulsed with the PSA-3 peptide; this was observed when both the concentration of peptide and the ratio of effector to target cells were titrated. T cells stimulated with dendritic cells (DCs) pulsed with PSA-3A peptide produced higher levels of IFN-gamma than did DCs pulsed with PSA-3 peptide; however, no increase in apoptosis was seen in T cells stimulated with the PSA-3A agonist compared with those stimulated with PSA-3. Human T-cell lines generated with the PSA-3A agonist had the ability to lyse human prostate carcinoma cells expressing native PSA in an MHC-restricted manner. Recombinant vaccinia viruses were also constructed that contained the entire PSA transgene with and without the single amino acid change that constitutes the PSA-3A epitope; DCs infected with the recombinant vector containing the agonist amino acid change within the entire PSA gene (designated rV-PSA-3A) were more effective than DCs infected with the rV-PSA vector in enhancing IFN-gamma production by T cells. Finally, the PSA-3A agonist was shown to induce higher levels of T-cell activation, compared with the PSA-3 peptide, in an in vivo model using HLA-A2.1/K(b) transgenic mice. These studies thus demonstrate the potential use of the PSA-3A agonist epitope in both peptide- and vector-mediated immunotherapy protocols for prostate cancer.
Human sperm sex selection (1994)

Journal Article Human sperm sex selection: The safety of sperm selection by flow cytometry Get access Lawrence A. Johnson, Lawrence A. Johnson 1US Department of Agriculture, Agncultural Research Service, Germplasm & Gamete Physiology LaboratoryBettsville, MD 20705 Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph D. Schulman Joseph D. Schulman 2Genetics &IVF InstituteFairfax, VA 22031, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Human Reproduction, Volume 9, Issue 5, 1 May 1994, Pages 758–759, https://doi.org/10.1093/oxfordjournals.humrep.a138591 Published: 01 May 1994
Genomic Organization of the HumanKAI1Metastasis-Suppressor Gene (1997)

Decreased expression of the human KAI1 metastasis-suppressor gene is involved in the progression of human prostatic cancer and possibly lung and breast cancer. To evaluate the frequency of mutation and allelic loss during the progression of human cancer, as well as to determine the regulatory mechanism for the expression of the KAI1 gene in normal and cancerous tissues, we characterized the 5'-promoter region, exon/intron organization, and transcription initiation site of the human KAI1 gene. About 80 kb of DNA was identified as the human KAI1 gene, which contains 8 kb of 5'-region, 10 exons, 9 introns, and 8 kb of DNA following exon 10. The coding region starts in exon 3 and ends in exon 10. The size of intron 1 is 29 kb, which almost equals the sizes of all other introns combined. A CpG island is present in the 5'-promoter region and extends to exon 1 and intron 1. The promoter region has no TATA or CCAAT box but has many putative binding motifs for various transcription factors, including nine Sp1 sites and five AP2 sites. These results suggest a diverse regulatory mechanism for the expression of the KAI1 gene in human tissues. The transcription initiation site of the KAI1 gene is located 181 bp upstream of the first nucleotide of the translation initiation codon. Comparisons of gene structures between KAI1 and seven other members of the transmembrane 4 superfamily revealed that the splicing sites relative to the different structural domains of the predicted proteins are well conserved, suggesting that these genes are evolutionarily related and that they arose through gene duplication and divergent evolution.
Pyrimidine Derivatives. I. Synthesis of a New Series of Sulfanilamides having Dialkylamino Groups in the Pyrimidine Nucleus (1965)

The synthesis of a number of sulfonamides having dialkylamino groups in the pyrimidine nucleus was described. Among these new compounds, N1-(6-chloro-2-dialkylamino-4-pyrimidyl)sulfanilamide were found to possess notable antibacterial activities.
Protein‐tyrosine kinases: Potential targets for anticancer drug development (1994)

Protein-tyrosine kinases (PTKs) were originally discovered over a decade ago as the dominant transforming components of certain tumor viruses. Since then these enzymes have become recognized as important intracellular mediators of a variety of mitogenic signaling pathways, including those associated with several growth factor receptors. The strong correlation of aberrant or over-expressed PTKs with a number of proliferative diseases has raised the possibility that PTK inhibitors may afford new approaches toward anticancer therapeutics. To address this possibility, potent and specific PTK inhibitors are needed both as pharmacological probes to study PTK-dependent signaling and as potential antiproliferative agents in their own right. De novo design of PTK inhibitors is hampered by a lack of three dimensional information regarding PTKs or the interaction of inhibitors with the enzymes. Motifs for the design of new inhibitors are therefore frequently derived by modification of structural them identified in natural-product screens. Exemplary of this process is the Laboratory of Medicinal Chemistry's program to develop PTK inhibitors based on pharmacophores present in three natural-product PTK inhibitors: lavendustin A, erbstatin and piceatannol. As summarized in this report, such efforts have led to new inhibitors with increased potency and interkinase selectivity. Whether PTK inhibitors will ultimately prove to be useful as antiproliferative therapeutics remains an open question whose answer will be heavily reliant on a cooperative partnership among natural-product and medicinal chemists, pharmacologists and clinicians.
Elimination of smooth muscle cells in experimental restenosis: targeting of fibroblast growth factor receptors. (1992)

Factors in plasma and platelets do not fully account for the proliferation of smooth muscle cells in vascular injury, implying that additional factors are involved. Recently, we and others have observed that vascular injury regulates basic fibroblast growth factor, suggesting a further role for this pleiotropic factor. We report here that injury of rat arteries leads to an increase in fibroblast growth factor receptors in vascular smooth muscle cells. This up-regulation makes smooth muscle cells susceptible, in vitro and in vivo, to the lethal effects of a conjugate of basic fibroblast growth factor with the ribosome inactivator saporin. Saporin alone has no effect, whereas the conjugate kills proliferating, but not quiescent, smooth muscle cells in vitro. In vivo, one to three doses inhibit neointimal proliferation but have no apparent effect on the uninjured artery. Thus, the up-regulation of fibroblast growth factor receptors in vascular injury suggests new therapeutic possibilities for such refractory conditions as restenosis following balloon angioplasty.
Induction of Epstein-Barr virus lytic cycle by tumor-promoting and non-tumor-promoting phorbol esters requires active protein kinase C (1991)

Exposure to the tiglian 12-O-tetradecanoylphorbol-13-acetate (TPA) represents one of the most efficient and widely used protocols for inducing Epstein-Barr virus (EBV)-infected cells from latent into lytic cycle. Since TPA is both a potent tumor promoter and a potent activator of the cellular protein kinase C (PKC), we sought to determine whether either of these activities was closely linked to EBV lytic cycle induction. A panel of TPA structural analogs, encompassing tiglians with different spectra of biological activities, was assayed on a number of EBV-positive B-lymphoid cell lines. Lytic cycle induction correlated with the capacity to activate PKC, not with tumor promoter status; some nonpromoting tiglians were as efficient as TPA in inducing lytic cycle antigen expression. We then sought more direct evidence for an involvement of PKC in the induction process. In initial experiments, 1-(5-isoquinolinyl sulphonyl)-2-methylpiperazine (H-7), the best available pharmacological inhibitor of PKC, completely blocked the induction of the lytic cycle by TPA and its active analogs. This is consistent with, but does not prove, a requirement for active PKC in the induction process, since H-7 targets PKC preferentially but also has some effects on other kinases. We therefore turned to the synthetic pseudosubstrate peptide PKC(19-36) as a means of specific PKC inhibition and to the closely related but inactive peptide PKC(19-Ser-25-36) as a control. Using the technique of scrape loading to deliver the peptides into cells of an adherent EBV-positive target line, we found that the pseudosubstrate peptide PKC(19-36) completely and specifically blocked tiglian-induced entry of the cells into the lytic cycle. The evidence both from TPA analogs and from enzyme inhibition studies therefore indicates that the pathway linking TPA treatment to lytic cycle induction involves active PKC. Interestingly, inhibition of PKC had no effect upon the spontaneous entry into lytic cycle which occurs in naturally productive cell lines, suggesting that spontaneous entry is signalled by another route.
Next generation products for wound management (2002)

This review attempts to clarify the developments of novel types of 'bioactive' dressings as well as tissue-engineered 'skin substitutes'. This is an evolving field, where emerging products try to find their own particular clinical or commercial niche. The importance of controlled clinical studies to test the effectiveness of these products is stressed. Considerations to be taken into account, both for novel dressing types and for skin substitutes include ease of use, patient satisfaction and cost-effectiveness.
Picture coding using pseudo-random noise (1962)

In order to transmit television pictures over a digital channel, it is necessary to send a binary code which represents the intensity level at each point in the picture. For good picture quality using standard PCM transmission, at least six bits are required at each sample point, since the eye is very sensitive to the small intensity steps introduced by quantization. However, by simply adding some noise to the signal before it is quantized and subtracting the same noise at the receiver, the quantization steps can be broken up and the source rate reduced to three bits per sample. Pseudo-random number generators can be synchronized at the transmitter and receiver to provide the identical "noise" which makes the process possible. Thus, with the addition of only a small amount of equipment, the efficiency of a PCM channel can be doubled.
Ubiquitination and Proteolysis of Cancer-Derived Smad4 Mutants by SCFSkp2 (2004)

Smad4/DPC4, a common signal transducer in transforming growth factor beta (TGF-beta) signaling, is frequently inactivated in human cancer. Although the ubiquitin-proteasome pathway has been established as one mechanism of inactivating Smad4 in cancer, the specific ubiquitin E3 ligase for ubiquitination-mediated proteolysis of Smad4 cancer mutants remains unclear. In this report, we identified the SCFSkp2 complex as candidate Smad4-interacting proteins in an antibody array-based screen and further elucidated the functions of SCFSkp2 in mediating the metabolic instability of cancer-derived Smad4 mutants. We found that Skp2, the F-box component of SCFSkp2, physically interacted with Smad4 at the physiological levels. Several cancer-derived unstable mutants exhibited significantly increased binding to Skp2, which led to their increased ubiquitination and accelerated proteolysis. These results suggest an important role for the SCFSkp2 complex in switching cancer mutants of Smad4 to undergo polyubiquitination-dependent degradation.
Ultrasensitive Proteome Profiling for 100 Living Cells by Direct Cell Injection, Online Digestion and Nano-LC-MS/MS Analysis (2015)

Single-cell proteome analysis has always been an exciting goal because it provides crucial information about cellular heterogeneity and dynamic change. Here we presented an integrated proteome analysis device (iPAD) for 100 living cells (iPAD-100) that might be suitable for single-cell analysis. Once cells were cultured, the iPAD-100 could be applied to inject 100 living cells, to transform the living cells into peptides, and to produce protein identification results with total automation. Due to the major obstacle for detection limit of mass spectrometry, we applied the iPAD-100 to analyze the proteome of 100 cells. In total, 813 proteins were identified in a DLD-cell proteome by three duplicate runs. Gene Ontology analysis revealed that proteins from different cellular compartments were well-represented, including membrane proteins. The iPAD-100 greatly simplified the sampling process, reduced sample loss, and prevented contamination. As a result, proteins whose copy numbers were lower than 1000 were identified from 100-cell samples with the iPAD-100, showing that a detection limit of 200 zmol was achieved. With increased sensitivity of mass spectrometry, the iPAD-100 may be able to reveal bountiful proteome information from a single cell in the near future.
cDNA cloning and expression of a metalloproteinase inhibitor related to tissue inhibitor of metalloproteinases. (1990)

The purification and characterization of a metalloproteinase inhibitor (MI) from bovine aortic endothelial cells, and the demonstration that it is related to, but distinct from, tissue inhibitor of metalloproteinase (TIMP), have previously been reported [De Clerck, Y. A., Yean, T.-D., Ratzkin, B. J., Lu, H.S. & Langley, K. E. (1989) J. Biol. Chem. 264, 17445-17453]. The cDNA cloning of the bovine MI and its human homolog is now reported. The bovine cDNA cloning used probes designed on the basis of NH2-terminal amino acid sequence of bovine MI. The human cDNA cloning in turn used probes representing parts of the bovine cDNA nucleotide sequence. Both cDNAs encode leader sequences of 26 amino acids and mature protein sequences of 194 amino acids. The amino acid sequences of the mature proteins are 94% identical. The human MI cDNA was expressed in Escherichia coli, and a preparation containing anticollagenase activity was recovered. The amino acid sequence of mature human MI is 38% identical to the sequence for human TIMP, and the 12 cysteines in MI and TIMP are aligned almost identically. Thus MI and TIMP comprise an inhibitor family.
SURGERY OF EXPERIMENTAL LESION OF SPINAL CORD EQUIVALENT TO CRUSH INJURY OF FRACTURE DISLOCATION OF SPINAL COLUMN (1911)

<h3>PREFATORY REMARKS</h3> In two former papers I have dwelt at length on the mechanical considerations of injury to the spinal cord in cases of fracture dislocation of the spinal column.<sup>1, 2</sup> In this communication, therefore, I shall limit myself to the discussion of the experimental work in which I have been engaged for the past year in the laboratories of the University of Pennsylvania. I would accentuate the fact that this is a preliminary report and that I am fully aware of the amount of control experimentation necessary before an<i>ex cathedra</i>statement can be made as to applicability of this work in the human subject. <h3>MEASUREMENT OF IMPACT ON SPINAL CORD IN SPINAL FRACTURE DISLOCATION</h3> In order to arrive at an adequate concept as to the amount of impact a spinal cord could receive and yet recover its function, I designed an instrument whereby a given weight could
Mitogenic Influence of Human R-Spondin1 on the Intestinal Epithelium (2005)

Several described growth factors influence the proliferation and regeneration of the intestinal epithelium. Using a transgenic mouse model, we identified a human gene, R-spondin1, with potent and specific proliferative effects on intestinal crypt cells. Human R-spondin1 (hRSpo1) is a thrombospondin domain-containing protein expressed in enteroendocrine cells as well as in epithelial cells in various tissues. Upon injection into mice, the protein induced rapid onset of crypt cell proliferation involving beta-catenin stabilization, possibly by a process that is distinct from the canonical Wnt-mediated signaling pathway. The protein also displayed efficacy in a model of chemotherapy-induced intestinal mucositis and may have therapeutic application in gastrointestinal diseases.
The Influence of Antisense Oligonucleotide Length on Dystrophin Exon Skipping (2006)

Antisense oligonucleotides (AOs) can be used to redirect dystrophin pre-messenger RNA (mRNA) processing, to remove selected exons from the mature dystrophin mRNA, to overcome nonsense mutations, and/or restore the reading frame. Redundancy within the dystrophin protein allows some domains to be removed without seriously compromising function. One of the challenges for splicing blockade is to design AOs that efficiently remove targeted exons across the dystrophin pre-mRNA. AOs are initially designed to anneal to the more obvious motifs implicated in the splicing process, such as acceptor or donor splice sites and in silico predicted exonic splicing enhancers. The AOs are evaluated for their ability to induce targeted exon skipping after transfection into cultured myoblasts. Although no single motif has been implicated in the consistent induction of exon skipping, the length of the AO has emerged as an important parameter in designing compounds that redirect dystrophin pre-mRNA processing. We present data from in vitro studies in murine and human cells showing that appropriately designed AOs of 25-31 nucleotides are generally more effective at inducing exon skipping than shorter counterparts. However, there appears to be an upper limit in optimal length, which may have to be established on a case-by-case basis.
Sex chromosome systems of European noterid beetles (Coleoptera, Adephaga: Noteridae) (1992)

Abstract The karyotypes and sex chromosome systems of the four European species of noterid beetles are described. Chromosome preparations were made from the mid-gut and testes of adult beetles by acetic acid spreading. Canthydrus diophthalmus was found to have a chromosome compliment of 2n = 16 + XX/XY. A multiple sex chromosome system was common to the three species of Noterus investigated (2n = 18 + X1X1X2X2/X1X2Y). The behaviour of Noterus sex chromosomes during early meiosis was examined and is discussed, along with the occurrence of multiple sex chromosome systems in other Adephaga.
Hybridization kinetics of double-stranded DNA probes for rapid molecular analysis (2009)

This study reports the hybridization kinetics of double-stranded DNA probes for rapid molecular analysis. Molecular binding schemes based on double-stranded DNA probes have been developed for quantitative detection of various biomolecules, such as nucleic acids and DNA binding proteins recently. The thermodynamic competition between the target and the competitor in binding to the probe provides a highly specific mechanism for molecular detection. The kinetics of the double-stranded DNA probe, on the other hand, represent another key aspect toward its general applicability for a wide set of biomedical applications. Herein we report a systematic investigation of the kinetics of double-stranded DNA probes. The signal-to-background ratio and assay time of the double-stranded DNA probes are optimized at a high ionic strength (over 100 mM NaCl). Both the donor probe and the quencher probe sequences are shown to be important in the hybridization kinetics. A long sticky end of the probe is able to dramatically accelerate the kinetics of the assay. To provide a quantitative description of the kinetics, a two-stage binding model is developed to describe the major features of the kinetics of the assay. The sensitivity of the kinetic model and the dominant affinity constants are studied. The study provides a general guideline for the design of the probes for reducing the total assay time. With an appropriate design of the probes, the assay can be finished within minutes at room temperature.
Restoration of Superhydrophobicity in Crushed Polymer Films by Treatment with Water: Self‐Healing and Recovery of Damaged Topographic Features Aided by an Unlikely Source (2013)

The crushing of superhydrophobic polymer multilayers destroys micro/nanoscale topographic features critical for the maintenance of superhydrophobicity. We demonstrate that these surface features can be recovered, and that superhydrophobicity can be fully restored, by treatment of damaged films with liquid water. These polymer-based films can also sustain other forms of severe abuse without loss of superhydrophobicity. This combination of features addresses several important practical issues associated with the durability of artificial superhydrophobic surfaces.
[125I]deoxycytidine used in a rapid, sensitive, and specific assay for herpes simplex virus type 1 thymidine kinase (1977)

[125I]deoxycytidine was a good substrate for herpes simplex virus type 1 thymidine kinase (TK), whereas [125I]deoxycytidine was a very poor substrate for cellular TK. Simple, sensitive, and specific assays for viral TK could be carried out in vivo and in vitro even in the presence of cell TK. Autoradiographic detection of incorporated [125I]deoxycytidine provided a rapid and simple method for detection of and screening for viral TK in infected as well as viral TK-transformed cells.
Immunolocalization of basic fibroblast growth factor and platelet-derived growth factor-A during adjuvant arthritis in the Lewis rat. (1994)

A prerequisite in defining the role of a growth factor in a disease is knowledge of its expression kinetics during the natural course of the disease. We, therefore, used immunohistochemical and immunoblot analyses to examine tissue distribution of basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF-A) during the development of destructive arthropathy in the rat adjuvant arthritis model. In normal joints, bFGF was primarily localized in endothelial cells. In inflamed joints, increased staining for bFGF was found in the invading panni, hyperplastic synovium, and thickened periosteum where bFGF was also co-localized with two cell proliferation markers. Staining for bFGF began to increase at the onset of arthritis (days 11 to 13), reached peak level on days 17 to 24, and gradually declined afterward. In contrast, PDGF-A staining did not change until day 17 and the increased staining was restricted to areas of newly formed bone. The district temporal and spatial distribution pattern of these two growth factors during the destructive arthropathy strongly suggests that they play different roles during arthritis. Although PDGF-A seems to be exclusively related to osteogenesis, bFGF may have a more extensive impact on synovial proliferation and bone destruction as well as bone formation.