gebhart/patrepeval huggingface dataset:
Short Pyrimidine Stretches Containing Mixed Base PNAs Are Versatile Tools to Induce Translation Elongation Arrest and Truncated Protein Synthesis (2003)

Recently, we showed that antisense peptide nucleic acids (PNA) containing a short pyrimidine stretch (C(4)TC(3)) invade Ha-ras mRNA hairpin structures to form highly stable duplex and triplex complexes that contribute to the arrest of translation elongation. The antisense PNA targeted to codon 74 of Ha-ras was designed to bind in antiparallel configuration (the N-terminal of the PNA faces the 3'-end of target mRNA), as PNA/RNA duplexes are most stable in this configuration. In order to show that different sequences in the coding region could be targeted successfully with antisense PNAs, we extended our study to three other purine-rich targets. We show that the tridecamer PNA (targeted to codon 149) containing a CTC(3)T pyrimidine stretch forms with the complementary oligoribonucleotide (ORN) a stable (PNA)(2)/ORN triplex at neutral pH (T(m) = 50 degrees C) and arrests Ha-ras mRNA translation elongation. Interestingly, the thermal stability of triplexes formed with PNAs designed to bind to the complementary ORN in a parallel orientation (the N-terminal of the PNA faces the 5'-end of target) was higher than that formed with antiparallel oriented PNAs (T(m) = 58 degrees C). Because parallel and antiparallel PNAs form stable triplexes with target sequence, they act as translation elongation blockers. These duplex-forming and partly triplex-forming PNAs targeted to Ha-ras mRNA also arrested translation elongation at specific polypurine sites contained in the mRNA coding for HIV-integrase protein. Furthermore, the tridecamer PNA containing the C(3)TC(4) motif was more active than a bis-PNA in which the Hoogsteen recognizing strand was linked to the Watson-Crick recognizing strand by a flexible linker. Pyrimidine-rich, short PNAs that form very stable duplexes with target Ha-ras mRNA inhibit translation by a mechanism that does not involve ribosome elongation arrest, whereas PNAs forming duplex and triplex structures arrest ribosome elongation. The remarkable efficacy of the tridecamer PNAs in arresting translation elongation of HIV-1 integrase mRNA is explained by their ability to form stable triplexes at neutral pH with short purine sequences.
Isolation of a human anti-haemophilic factor IX cDNA clone using a unique 52-base synthetic oligonucleotide probe deduced from the amino acid sequence of bovine factor IX (1983)

A unique 52mer oligonucleotide deduced from the amino acid sequence of bovine Factor IX was synthesized and used as a probe to screen a human liver cDNA bank. The Factor IX clone isolated shows 5 differences in nucleotide and deduced amino acid sequence as compared to a previously isolated clone. In addition, precisely one codon has been deleted.Images
Beneficial Read-Through of aUSH1CNonsense Mutation by Designed Aminoglycoside NB30 in the Retina (2010)

Purpose.: The human Usher syndrome (USH) is the most frequent cause of inherited combined deaf-blindness. USH is clinically and genetically heterogeneous, assigned to three clinical types. The most severe type is USH1, characterized by profound inner ear defects and retinitis pigmentosa. Thus far, no effective treatment for the ophthalmic component of USH exists. The p.R31X nonsense mutation in USH1C leads to a disease causing premature termination of gene translation. Here, we investigated the capability of the novel synthetic aminoglycoside NB30 for the translational read-through of the USH1C-p.R31X nonsense mutation as a retinal therapy option. Methods.: Read-through of p.R31X by three commercial, clinically applied aminoglycosides and the synthetic derivative NB30 was validated in vitro, in cell culture, and in retinal explants. Restoration of harmonin functions was monitored in GST pull-downs (scaffold function) and by F-actin bundling analysis in HEK293T cells. Biocompatibility of aminoglycosides was determined in retinal explants by TUNEL assays. Results.: In vitro translation and analyses of transfected HEK293T cells revealed a dose-dependent read-through by all aminoglycosides. In addition, gentamicin, paromomycin, and NB30 induced read-through of p.R31X in mouse retinal explants. The read-through of p.R31X restored harmonin protein function. In contrast to all commercial aminoglycosides NB30 showed good biocompatibility. Conclusions.: Commercial aminoglycosides and NB30 induced significant read-through of the USH1C-p.R31X nonsense mutation. However, the observed read-through efficiency, along with its significantly reduced toxicity and good biocompatibility, indicate that the novel derivate NB30 represents a better choice than commercial aminoglycosides in a read-through therapy of USH1C and other ocular diseases.
Molecular Biology of the Cell (2007)

For nearly a quarter century Molecular Biology of the Cell has been the leading cell biology textbook. This tradition continues with the new Fifth Edition, which has been completely revised and updated to describe our current, rapidly advancing understanding of cell biology. To list but a few examples, a large amount of new material is presented on epigenetics; stem cells; RNAi; comparative genomics; the latest cancer therapies; apoptosis (now its own separate chapter); and cell cycle control and the mechanics of M phase (now integrated into one chapter). The hallmark features of Molecular Biology of the Cell have been retained, such as its consistent and comprehensive art program, clear concept headings, and succinct section summaries. Additionally, in response to extensive feedback from readers, the Fifth Edition now includes several new features. It is now more portable. Chapters 1-20 are printed and Chapters 21-25, covering multicellular systems, are provided as&nbsp;PDF files on the free Media DVD-ROM which accompanies the book.* And for the first time, Molecular Biology of the Cell now contains end-of-chapter questions. These problems, written by John Wilson and Tim Hunt, emphasize a quantitative approach and the art of reasoning from experiments, and they will help students review and extend their knowledge derived from reading the textbook. The Media DVD-ROM, which is packaged with every copy of the book, contains PowerPoint® presentations with all of the figures, tables and micrographs from the text (available as JPEGs too). Also included is the Media Player, which plays over 125 movies—animations, videos, and molecular models—all with voice-over narration. A new reader-friendly feature is the integration of media codes throughout the text that link directly to relevant videos and animations. The Media DVD-ROM holds the multicellular systems chapters (21-25) of the text as well. By skillfully extracting the fundamental concepts from this enormous and ever-growing field, the authors tell the story of cell biology, and thereby create a coherent framework through which readers may approach and enjoy this subject that is so central to all of biology. * There is also a reference edition of Molecular Biology of the Cell, Fifth Edition (ISBN 978-0-8153-4111-6) that contains Chapters 1-25 entirely in printed format.
Antiproliferative effect of exemestane in lung cancer cells (2009)

Our findings suggest an antiproliferative effect of exemestane on NSCLC cell lines. Exemestane may be more effective in cells with higher aromatase levels. Further studies are needed to assess the activity of exemestane in NSCLC.
Fiber‐Based Wearable Electronics: A Review of Materials, Fabrication, Devices, and Applications (2014)

Fiber-based structures are highly desirable for wearable electronics that are expected to be light-weight, long-lasting, flexible, and conformable. Many fibrous structures have been manufactured by well-established lost-effective textile processing technologies, normally at ambient conditions. The advancement of nanotechnology has made it feasible to build electronic devices directly on the surface or inside of single fibers, which have typical thickness of several to tens microns. However, imparting electronic functions to porous, highly deformable and three-dimensional fiber assemblies and maintaining them during wear represent great challenges from both views of fundamental understanding and practical implementation. This article attempts to critically review the current state-of-arts with respect to materials, fabrication techniques, and structural design of devices as well as applications of the fiber-based wearable electronic products. In addition, this review elaborates the performance requirements of the fiber-based wearable electronic products, especially regarding the correlation among materials, fiber/textile structures and electronic as well as mechanical functionalities of fiber-based electronic devices. Finally, discussions will be presented regarding to limitations of current materials, fabrication techniques, devices concerning manufacturability and performance as well as scientific understanding that must be improved prior to their wide adoption.
The susceptibility sequence to rheumatoid arthritis is a cross-reactive B cell epitope shared by the Escherichia coli heat shock protein dnaJ and the histocompatibility leukocyte antigen DRB10401 molecule. (1992)

Immunological responses to bacterial heat shock proteins have been implicated in the pathogenesis of arthritis in animals and humans. The predicted amino acid sequence of dnaJ, a heat shock protein from Escherichia coli, contains an 11-amino acid segment that is homologous to the third hypervariable region of the human histocompatibility antigen (HLA) DRB10401 (formerly known as HLA Dw4), the part of the molecule that carries susceptibility to rheumatoid arthritis. To test the biological significance of this finding, we expressed and purified recombinant dnaJ (rdnaJ), and determined its immunologic cross-reactivity with HLA DRB10401. A rabbit antipeptide antiserum raised against the sequence of the third hypervariable region of HLA DRB10401 specifically bound to 'dnaJ, thus confirming that a similar sequence is expressed on the bacterial protein. Of greater consequence, an antiserum to the 'dnaJ protein recognized not only a peptide from the third hypervariable region of HLA DRB10401, but also the intact HLA DRB10401 polypeptide. Furthermore, the antibody to 'dnaJ reacted with HLA DRB10401 homozygous B lymphoblasts, but not with HLA DRB11501, DRB10101, DRB10301, and DRB10701 (formerly known as HLA Dw2, DR 1, DR 3, and DR 7, in the same order) homozygous cells. These results demonstrate that exposure to a bacterial heat shock protein can elicit antibodies against the rheumatoid arthritis susceptibility sequence in the third hypervariable region of HLA DRB10401.
Parthenogenetic activation of mouse oocytes in vitro with ethanol and benzyl alcohol (1983)

Abstract Treatment in vitro of ovulated mouse oocytes for 5–10 min with 4.5–8.6% ethanol or 0.24–0.4% benzyl alcohol was found to induce parthenogenetic activation. Suppression of the second polar body with cytochalasin D and subsequent culture in vitro gave a high yield of parthenogenetic morulae and blastocysts (up to 85% overall). Fifty percent of transferred diploid parthenogenones implanted, 14% developed into egg cylinders, and 8% formed somites and developed as far as the forelimb‐bud stage.
Position Paper Role of Technology Design Rules in Design Automation (1983)

Today when VLSI is the major concern of Design Automation system designers, we must remember that size and complexity are not the only problems. This is a time of rapidly changing and evolving semiconductor process technologies, and advancements in this area make the realization of VLSI possible. The Design Automation community must recognize the severity of the problems associated with this changing technology environment and be able to respond quickly to them.Technology-dependent factors influence every phase of the design process.A formal set of technology design rules, integrated with Design Automation tools can provide a basis for supporting ever-changing technologies.
Maintenance of the hydrophobic face of the diphtheria toxin amphipathic transmembrane helix 1 is essential for the efficient delivery of the catalytic domain to the cytosol of target cells (1994)

The transmembrane (T) domain of diphtheria toxin (DT) comprises nine alpha-helices and has been shown to play an essential role in the efficient delivery of the catalytic (C) domain of DT across the eukaryotic cell membrane and into the cytosol. We have demonstrated recently that the first three amphipathic helixes of the T domain, although not necessary for either channel formation or receptor binding, are required for the efficient transmembrane delivery of the C domain. In the present study, we have performed a detailed structure-function analysis of T domain helix 1 (TH1) of the DT-related fusion protein DAB389IL-2. We performed exchange and site-directed mutagenesis of TH1 and the resulting mutant fusion toxins were analyzed by gel electrophoresis and tested for their efficiencies in the delivery of the C domain to the cell cytosol. We demonstrate that the overall charge distribution and hydrophobicity of amino acids in the amphipathic helix TH1, rather than a specific amino acid sequence, are critical for the function of this helix. The insertion of a charged residue in the hydrophobic face of TH1 abolishes cytotoxic activity, whereas replacement of a hydrophobic residue by a charged amino acid in the hydrophilic face of the helix has little, if any, effect on cytotoxic activity. In addition, we have identified Ser220 by site-directed mutagenesis as a residue that appears to be critical for correct folding of the fusion toxin. Mutations in this position result in fusion proteins that are extremely sensitive to proteolytic attack.
Generation of tumoricidal cytotoxic T lymphocytes from healthy donors after in vitro stimulation with a replication‐incompetent vaccinia virus encoding MART‐1/Melan‐A 27‐35 epitope (1997)

Active specific immunotherapy targeting tumor-associated antigens (TAA) requires reagents of high immunogenicity and safety. To address this issue, we constructed a recombinant vaccinia virus carrying a minigene insert encoding the HLA-A2.1-restricted MART-1/Melan-A27-35 melanoma TAA (rVV-M). To facilitate the entry of the antigenic epitope into the endoplasmic reticulum, a sequence coding for adenovirus E3/19K leader peptide was added. This rVV-M was made replication-incompetent by treatment with psoralen and UV light. Infection with rVV-M rendered HLA-A2.1 EBV-transformed lymphoblastoid cells sensitive to the cytotoxic effects of HLA-class-I-restricted, MART-1/Melan-A27-35-specific cytotoxic T lymphocytes (CTL). The capacity of rVV-M to generate HLA-A2.1-restricted MART-1/Melan A-specific CTL was demonstrated from tumor-infiltrating-lymphocyte (TIL) cultures and from healthy donors' peripheral-blood mononuclear cells (PBMC). MART-1/Melan-A27-35-specific CTL were generated from TIL after 2 weekly stimulation courses. Infection with rVV-M elicited a higher CTL response than addition of exogenous peptide, whereas, when a similar protocol was used to stimulate PBMC of healthy donors, significant and specific cytotoxic activity could be observed only upon rVV-M infection but not upon exogenous peptide addition. All CTL generated upon rVV-M stimulation were also able to efficiently kill melanoma cell lines expressing both MART-1/Melan-A and HLA-A2.1. In addition, TNF-α production could be induced in rVV-M-stimulated CTL upon co-culture with COS-7 cells transiently transfected with MART-1/Melan-A and HLA-A2.1 genes. This safe and highly immunogenic reagent could be of use in TAA-targeted clinical immunotherapy. Int. J. Cancer 71:491-496, 1997. © 1997 Wiley-Liss Inc.
Imaging of cells by autofluorescence: a new tool in the probing of biopharmaceutical effects at the intracellular level (1998)

The success of biopharmaceuticals relies on the ability to have reliable probes to interpret their mechanisms of action in situ at the intracellular level in terms of cell organelles and microcompartments. One of the most effective probes is the endogenous coenzyme NAD(P)H and its fluorescence transients obtained by the microinjection or perfusion of metabolic intermediates and modifiers, in the presence of drugs and inhibitors. The approach in fluorescence microtopography and microspectrofluorimetry is based on the premise that natural cell fluorescence (autofluorescence) holds a decisively greater potential in unravelling intracellular physiopathological processes than extrinsic fluorescence or artificial pseudocolouring. The mounting as a detector of a cooled charge-coupled device camera or alternatively of a non-cooled camera in conjunction with an image intensifier or an investigator (i.e. frame scan accumulator) to enhance sensitivity makes possible the detection of the low-quantum-yield NAD(P)H fluorescence at a level comparable to images previously obtained with high-quantum-yield fluorochromes. The modulation of mitochondrial autofluorescence by rotenone, carbonyl cyanide p-trifluoromethoxyphenylhydrazone and oligomycin, and of cytoplasmic and nuclear autofluorescence by glucose and iodacetamide in CV-1 kidney epithelial cells, Ehrlich-Lettre hypotetraploid CCL77 cells and Saccharomyces cerevisiae, provides examples of the usefulness of fluorescence imaging in the study of biopharmaceuticals. The method goes beyond NAD(P)H to the multiplicity of extrinsic and intrinsic probes already available or in development.
Selective wordline voltage boosting for caches to manage yield under process variations (2009)

One of the most important hurdles of technology scaling is process variations, i.e., variations in device characteristics. Process variations cause large fluctuations in performance and power consumption in the manufactured chips. In addition, these fluctuations cause reductions in the chip yields. In this work, we present an analysis of a representative high-performance processor architecture and show that the caches have the highest probability of causing yield losses under process variations. We then propose a novel selective wordline voltage boosting mechanism that aims at reducing the latency of the cache lines that are affected by process variations. We show that our approach can eliminate over 80% of the yield losses under medium level of variations, while incurring less than 1% per-access energy overhead on average and less than 4.5% area overhead.
Stability analysis of CO2 control of ventilation (1990)

A theoretical analysis of the CO2 control of the respiratory system is presented using both analytic and simulation techniques. A stability index (SI) is obtained by linearizing a dynamic first-order model with a time delay. Analytically, SI values greater than unity predict an unstable response to a disturbance. Because the first-order model is reduced from a higher-order physiological model, SI can be algebraically related to physiological parameters. This relationship shows that SI increases with a decrease in system tissue volume, metabolic rate, or inspired CO2 partial pressure; SI decreases with a decrease in time delay, cardiac output, controller gain, or controller intercept. Analytically, SI distinguishes stable from unstable domains. By simulations of the nonlinear first-order model, three domains are obtained: an unstable domain (sustained oscillations, SI greater than 1.1), an underdamped stable domain (transient oscillations, 0.3 less than SI less than 1.1), and an overdamped stable domain (no oscillations, 0 less than SI less than 0.3). With this classification, disturbances such as change of state (e.g., from awake to asleep) or sigh may produce transient oscillations if the system becomes underdamped even though stable. Potential applications of this work include quantitative distinction of the physiological factors in control disorders associated with short-term periodicities (e.g., Cheyne-Stokes breathing, sleep apnea, breathing at altitude).
Impaired meal stimulated glucagon-like peptide 2 response in ileal resected short bowel patients with intestinal failure (1999)

Identification of GLP-2 as a tissue specific intestinal growth factor and demonstration of an impaired meal stimulated GLP-2 response in short bowel patients raises the possibility that GLP-2 administration may constitute a new therapeutic strategy, enhancing jejunal adaptation in ileum resected short bowel patients with intestinal failure.
Spectral karyotype (SKY) analysis of human prostate carcinoma cell lines (2003)

The present study provides a comprehensive karyotypic analysis of a large number of prostate carcinoma cell lines, and offers a valuable resource for future investigations.
A non-invasive computer vision system for reliable eye tracking (2000)

Knowing what the user is attending to and what they are looking at is essential for creating attentive user interfaces. Towards this end, we are building a reliable, real-time, non-invasive eye tracker using computer vision. Our system can robustly locate and track eyes without any calibration, and estimate the user's focus of attention. We have built several higher-level processes on top of this tracking system and have done some user studies to test the viability of our approach.
Ceramides as modulators of cellular and whole-body metabolism (2011)

Nearly all stress stimuli (e.g., inflammatory cytokines, glucocorticoids, chemotherapeutics, etc.) induce sphingolipid synthesis, leading to the accumulation of ceramides and ceramide metabolites. While the role of these lipids in the regulation of cell growth and death has been studied extensively, recent studies suggest that a primary consequence of ceramide accumulation is an alteration in metabolism. In both cell-autonomous systems and complex organisms, ceramides modify intracellular signaling pathways to slow anabolism, ensuring that catabolism ensues. These ceramide actions have important implications for diseases associated with obesity, such as diabetes and cardiovascular disease.
GPCR-GIP networks: a first step in the discovery of new therapeutic drugs? (2004)

G protein-coupled receptors (GPCRs) are transmembrane molecules that, on interaction with G proteins upon ligand binding, can associate with a large variety of transmembrane or soluble proteins, termed 'GPCR-interacting proteins' (GIPs). Some special transmembrane GIPs are themselves GPCRs that form homo- or heterodimers, while other transmembrane GIPs are ionic channels, ionotropic receptors and single transmembrane proteins that control GPCR pharmacology and trafficking. Most soluble GIPs interact with the C-termini of GPCRs and often physically link GPCRs to large protein networks, called 'receptosomes', that include ionic channels, protein kinases, small G proteins, cytoskeletal proteins and adhesion molecules. Here, we review the nature and functions of some of these networks, such as the glutamate and serotonin receptosomes, and focus on the fine-tuning of GPCR signaling by GIPs. Finally, we discuss the possibilities for developing new therapeutic drugs capable of modulating GPCR signaling by disrupting or reinforcing specific GPCR-GIP interactions.