gebhart/patrepeval huggingface dataset:
Retroelements and the human genome: New perspectives on an old relation (2004)

Retroelements constitute a large portion of our genomes. One class of these elements, the human endogenous retroviruses (HERVs), is comprised of remnants of ancient exogenous retroviruses that have gained access to the germ line. After integration, most proviruses have been the subject of numerous amplifications and have suffered extensive deletions and mutations. Nevertheless, HERV-derived transcripts and proteins have been detected in healthy and diseased human tissues, and HERV-K, the youngest, most conserved family, is able to form virus-like particles. Although it is generally accepted that the integration of retroelements can cause significant harm by disrupting or disregulating essential genes, the role of HERV expression in the etiology of malignancies and autoimmune and neurologic diseases remains controversial. In recent years, striking evidence has accumulated indicating that some proviral sequences and HERV proteins might even serve the needs of the host and are therefore under positive selection. The remarkable progress in the analysis of host genomes has brought to light the significant impact of HERVs and other retroelements on genetic variation, genome evolution, and gene regulation.
Augmenting Weak Semantic Cognitive Maps with an “Abstractness” Dimension (2013)

The emergent consensus on dimensional models of sentiment, appraisal, emotions, and values is on the semantics of the principal dimensions, typically interpreted as valence, arousal, and dominance. The notion of weak semantic maps was introduced recently as distribution of representations in abstract spaces that are not derived from human judgments, psychometrics, or any other a priori information about their semantics. Instead, they are defined entirely by binary semantic relations among representations, such as synonymy and antonymy. An interesting question concerns the ability of the antonymy-based semantic maps to capture all "universal" semantic dimensions. The present work shows that those narrow weak semantic maps are not complete in this sense and can be augmented with other semantic relations. Specifically, including hyponym-hypernym relations yields a new semantic dimension of the map labeled here "abstractness" (or ontological generality) that is not reducible to any dimensions represented by antonym pairs or to traditional affective space dimensions. It is expected that including other semantic relations (e.g., meronymy/holonymy) will also result in the addition of new semantic dimensions to the map. These findings have broad implications for automated quantitative evaluation of the meaning of text and may shed light on the nature of human subjective experience.
Forster Transfer Recovery Reveals That Phospholamban Exchanges Slowly From Pentamers but Rapidly From the SERCA Regulatory Complex (2007)

Phospholamban (PLB) or the sarcoplasmic reticulum Ca2+-ATPase (SERCA) were fused to cyan fluorescent protein (CFP) and coexpressed with PLB fused to yellow fluorescent protein (YFP). The expressed fluorescently tagged proteins were imaged using epifluorescence and total internal reflection fluorescence microscopy. YFP fluorescence was selectively bleached by a focused laser beam. CFP fluorescence at the targeted site increased after YFP photobleaching, indicating fluorescence resonance energy transfer between CFP-SERCA/CFP-PLB and YFP-PLB. The increased donor fluorescence relaxed back toward baseline as a result of donor diffusion and exchange of bleached YFP-PLB for unbleached YFP-PLB, which restored fluorescence resonance energy transfer. Requenching of CFP donors, termed Förster transfer recovery (FTR), was quantified as an index of the rate of PLB subunit exchange from the PLB:SERCA and PLB:PLB membrane complexes. PLB subunit exchange from the PLB:SERCA regulatory complex was rapid, showing diffusion-limited FTR (tau=1.4 second). Conversely, PLB:PLB oligomeric complexes were found to be stable on a much longer time scale. Despite free lateral diffusion in the membrane, they showed no FTR over 80 seconds. Mutation of PLB position 40 from isoleucine to alanine (I40A-PLB) did not abolish PLB:PLB energy transfer, but destabilization of the PLB:PLB complex was apparent from an increased FTR rate (tau=8.4 seconds). Oligomers of I40A-PLB were stabilized by oxidative crosslinking of transmembrane cysteines with diamide. We conclude that PLB exchanges rapidly from its regulatory complex with the SERCA pump, whereas subunit exchange from the PLB oligomeric complex is slow and does not occur on the time scale of the cardiac cycle.
Plasma atrial natriuretic peptide is unstable under most storage conditions. (1992)

These findings raise disturbing questions about the interpretation of the substantial literature on ANP.
Apollon modulates chemosensitivity in human esophageal squamous cell carcinoma (2014)

Patients with esophageal squamous cell carcinoma (ESCC) are often diagnosed with advanced diseases that respond poorly to chemotherapy. Here we reported that Apollon, a membrane-associated inhibitor of apoptosis protein, was overexpressed in ESCC cell lines and clinical ESCC tissues, and Apollon overexpression clinically correlated with poor response to chemotherapy (P = 0.001), and short overall survival (P = 0.021). Apollon knockdown increased cisplatin/docetaxel-induced apoptosis, mitochondrial dysfunction and cytochrome c release in two ESCC cell lines. Apollon knockdown potentiated cisplatin/docetaxel-induced long-term cell growth inhibition, and enhanced chemosensitivity of ESCC cells to cisplatin/docetaxel in xenograft tumor models. Apollon knockdown also enhanced cisplatin/docetaxel-induced activation of caspase-8 (extrinsic pathway) and caspase-9 (intrinsic pathway) in ESCC cells and xenograft tumor models. Mechanism studies revealed that the effect of Apollon on chemosensitivity is mainly mediated by Smac. Apollon expression strongly and negatively correlated with Smac expression in clinical ESCC tissues (P = 0.001). Apollon targeted Smac for degradation in ESCC cells. The effect of Apollon on chemosensitivity was reversed by Smac knockdown in ESCC cells. Taken together, our data show association of Apollon expression with chemotherapeutic response in ESCC, and provide a strong rationale for combining Apollon antagonism with chemotherapy to treat ESCC.
mRNA: Detection by In Situ and Northern Hybridization (2003)

In situ hybridization histochemistry (ISHH), first described in 1969 by Gall and Pardue and John et al. (,) and northern hybridization, first described by Alwine et al. (), have become very powerful and now quite well established techniques in many research areas, including that of receptor research. Such applications include 1. direct assessment of the presence, distribution, and modulation of specific RNA species under different physiological conditions (,); 2. molecular investigations of potential mRNA splice variants and region-specific heterogeneity in multimeric-receptor subunit expression (,); 3. indirect identification of receptor-expression to add credence to the existence of that receptor when highly selective ligands are unavailable for receptor binding site localization studies (); and 4. investigation of molecular changes in pathological states and the possible modes of action of drugs used to treat such conditions (, , ).
Crucial role of the connecting region joining the two functional domains of yeast tryptophan synthetase. (1987)

We constructed a hybrid plasmid expressing yeast tryptophan synthetase in Escherichia coli. Several deletion variants lacking the A or B domains of this polypeptide (recognized by their homology to the alpha and beta subunits of prokaryotic tryptophan synthetase) showed no enzymatic activity and failed to substitute for the corresponding E. coli subunits. To examine the role of a presumed interdomain connecting region in the yeast enzyme, we constructed a variant lacking 18 amino acids in that region. The variant polypeptide was completely inactive. Replacing 14 of the 18 missing amino acids with a segment having a different sequence partially restored activity. A spontaneous revertant was characterized and shown to have a duplication of 16 amino acid residues in this region; the activity of the duplication polypeptide was better than that of the 14-residue replacement. If confirmed by additional studies, our finding that the length of the connecting region is more critical than its sequence has implications for understanding the origin of gene fusions during evolution as well as for designing artificial fusions.
Targeting of Multiple Signaling Pathways by the Hsp90 Inhibitor SNX-2112 in EGFR Resistance Models as a Single Agent or in Combination With Erlotinib (2009)

Inhibition of Hsp90 has emerged as a therapeutic strategy to target NSCLC subtypes, which are refractory to epidermal growth factor receptor (EGFR) inhibitor-based treatment. We report on a novel small molecule inhibitor of Hsp90, SNX-2112, and an orally bioavailable prodrug analog, SNX-5422. In cellular models of wild-type or mutant EGFR (L858R and T790M mutations), SNX-2112 alone and in combination with erlotinib inhibited EGF activation of pAKT(473) and pSTAT3(705). pERK1/2 and pS6 were also potently inhibited by similar treatments. SNX-2112 reduced EGF cross-talk and activation of the c-Met receptor by causing c-Met degradation. In NCI-H1975 xenograft models, SNX-5422 showed activity as a single agent and in combination with erlotinib resulted in prolonged animal survival at reduced compound concentrations relative to either compound alone. These results support the advanced evaluation of SNX-5422 as a treatment for non-small cell lung cancer (NSCLC), especially in cases where the cancer is driven by c-Met amplification or mutated EGFR forms that are resistant to EGFR inhibitors.
Effects of monoclonal anti-lymphocyte antibodies in vivo in monkeys and humans. (1983)

The safety and efficacy in vivo of three rat monoclonal anti-lymphocyte antibodies has been tested in cynomolgus monkeys. One IgM antibody, CAMPATH 1, was found to cause rapid but transient lymphopenia associated with consumption of complement. Two other antibodies with the same specificity, YTH 34.5 (IgG2a) and YTH 86.1 (IgG2c), had little effect. No acute or chronic toxic effects were associated with administration of any of the antibodies. CAMPATH 1 was used in a Phase I clinical trial for immunotherapy of two patients with terminal malignant lymphoid disease. It had no detectable toxic effects although it caused disappearance of circulating lymphocytes and consumption of complement. An inadequate rate of synthesis of complement components was a limitation to therapy in these patients with very large tumour burden, but might not be a major problem if antibody therapy were used at an earlier stage of the disease. CAMPATH 1 may also be useful as an immunosuppressive agent.
A default mode of brain function (2001)

A baseline or control state is fundamental to the understanding of most complex systems. Defining a baseline state in the human brain, arguably our most complex system, poses a particular challenge. Many suspect that left unconstrained, its activity will vary unpredictably. Despite this prediction we identify a baseline state of the normal adult human brain in terms of the brain oxygen extraction fraction or OEF. The OEF is defined as the ratio of oxygen used by the brain to oxygen delivered by flowing blood and is remarkably uniform in the awake but resting state (e.g., lying quietly with eyes closed). Local deviations in the OEF represent the physiological basis of signals of changes in neuronal activity obtained with functional MRI during a wide variety of human behaviors. We used quantitative metabolic and circulatory measurements from positron-emission tomography to obtain the OEF regionally throughout the brain. Areas of activation were conspicuous by their absence. All significant deviations from the mean hemisphere OEF were increases, signifying deactivations, and resided almost exclusively in the visual system. Defining the baseline state of an area in this manner attaches meaning to a group of areas that consistently exhibit decreases from this baseline, during a wide variety of goal-directed behaviors monitored with positron-emission tomography and functional MRI. These decreases suggest the existence of an organized, baseline default mode of brain function that is suspended during specific goal-directed behaviors.
[Antiepileptic effects of nimodipine on penicillin-induced seizures in rats]. (1997)

Injecting penicillin (PNC) intraperitoneally in Wistar rats, we observed their epileptic behaviour and electroencephalographys. The results showed that nimodipine (NIM), a calcium antagonist, could inhibit the seizures and epileptic discharges significantly. No epileptic action was noted while NIM was injected before PNC. It supports our consideration of NIM as a new sort of nonsedative anticonvulsant in clinical practice.
T Cells Genetically Modified to Express an Anti–B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Poor-Prognosis Relapsed Multiple Myeloma (2018)

Purpose Therapies with novel mechanisms of action are needed for multiple myeloma (MM). T cells can be genetically modified to express chimeric antigen receptors (CARs), which are artificial proteins that target T cells to antigens. B-cell maturation antigen (BCMA) is expressed by normal and malignant plasma cells but not normal essential cells. We conducted the first-in-humans clinical trial, to our knowledge, of T cells expressing a CAR targeting BCMA (CAR-BCMA). Patients and Methods Sixteen patients received 9 × 10<sup>6</sup> CAR-BCMA T cells/kg at the highest dose level of the trial; we are reporting results of these 16 patients. The patients had a median of 9.5 prior lines of MM therapy. Sixty-three percent of patients had MM refractory to the last treatment regimen before protocol enrollment. T cells were transduced with a γ-retroviral vector encoding CAR-BCMA. Patients received CAR-BCMA T cells after a conditioning chemotherapy regimen of cyclophosphamide and fludarabine. Results The overall response rate was 81%, with 63% very good partial response or complete response. Median event-free survival was 31 weeks. Responses included eradication of extensive bone marrow myeloma and resolution of soft-tissue plasmacytomas. All 11 patients who obtained an anti-MM response of partial response or better and had MM evaluable for minimal residual disease obtained bone marrow minimal residual disease-negative status. High peak blood CAR<sup>+</sup> cell levels were associated with anti-MM responses. Cytokine-release syndrome toxicities were severe in some cases but were reversible. Blood CAR-BCMA T cells were predominantly highly differentiated CD8<sup>+</sup> T cells 6 to 9 days after infusion. BCMA antigen loss from MM was observed. Conclusion CAR-BCMA T cells had substantial activity against heavily treated relapsed/refractory MM. Our results should encourage additional development of CAR T-cell therapies for MM.
Binding of Chemically-Modified Oligonucleotides to the Double-Stranded Stem of an RNA Hairpin (1999)

We monitored the binding of triplex-forming oligopyrimidines to the double-stranded stem of the RNA hairpin responsible for the gag-pol frameshift in HIV-1. Whereas the substitution of 5, propynyl-C for C had a limited effect, the use of a Peptide Nucleic Acid 12mer led to a drastic reduction in the stability of the oligomer/RNA complex.
Where Polyelectrolyte Multilayers and Polyelectrolyte Complexes Meet (2006)

We summarize existing knowledge and present some new results on the relationship between polyelectrolyte multilayer (PEM) growth and phase behavior of polyelectrolyte complexes (PECs) in solution. Detailed understanding of competition between surface and solution as applied to PEMs requires selective labeling of polymers and/or the application of techniques that allow chemically specific monitoring of film components, such as in-situ ATR−FTIR spectroscopy. The trends observed with multilayers directly follow from the properties of PECs in solution. Effects of a number of parameters, such as the type of interacting polyelectrolyte chains, the ratio of their lengths, and ionic strength and pH of deposition solutions, on the likelihood of the multilayer stability or erosion are considered. Polycations with high density of primary amino groups and polyanions with SO3- or SO4- groups show the strongest interpolyelectrolyte binding, resulting in inhibited chain exchange within PECs and/or PEMs. With weakly bound polyelectrolyte pairspolycations containing quaternary ammonium groups and carboxylate polyanionswater-soluble PECs are easily formed, often resulting in erosion of PEMs. For the latter case, we report a full phase diagram of polycation/polyanion/NaCl aqueous mixtures and show how ionic strength can be used to tune the deposition of PEMs at surfaces. In addition, we present that the phase behavior of PECs in solution also controls pH response of PEMs at surfaces. Better knowledge of the relationships between the PEMs and PECs allows rational prediction and control of deposition of a wide range of weak or permanently charged polyelectrolytes at surfaces.
Mammalian Target of Rapamycin, a Molecular Target in Squamous Cell Carcinomas of the Head and Neck (2005)

Emerging knowledge on how the dysregulated function of signaling networks contributes to the malignant growth of squamous cell carcinoma of the head and neck (HNSCC) can now be exploited to identify novel mechanism-based anticancer treatments. In this regard, we have observed that persistent activation of the serine/threonine kinase Akt is a frequent event in HNSCC, and that blockade of its upstream kinase, 3'-phosphoinositide-dependent kinase 1, potently inhibits tumor cell growth. Akt promotes cell proliferation by its ability to coordinate mitogenic signaling with energy- and nutrient-sensing pathways that control protein synthesis through the atypical serine/threonine kinase, mammalian target of rapamycin (mTOR). This kinase, in turn, phosphorylates key eukaryotic translation regulators, including p70-S6 kinase and the eukaryotic translation initiation factor, 4E binding protein 1. Indeed, we show here that aberrant accumulation of the phosphorylated active form of S6, the most downstream target of the Akt-mTOR-p70-S6 kinase pathway, is a frequent event in clinical specimens from patients with HNSCC and their derived cell lines. Of interest, this enhanced level of the phosphorylated active form of S6 was rapidly reduced in HNSCC cell lines and HNSCC xenograft models at clinically relevant doses of rapamycin, which specifically inhibits mTOR. Furthermore, we observed that rapamycin displays a potent antitumor effect in vivo, as it inhibits DNA synthesis and induces the apoptotic death of HNSCC cells, ultimately resulting in tumor regression. These findings identify the Akt-mTOR pathway as a potential therapeutic target for HNSCC, and may provide the rationale for the early clinical evaluation of rapamycin and its analogues in patients with HNSCC.
Seafloor Monitoring for Synthetic-Based Mud Discharged in the Western Gulf of Mexico (1995)

Abstract Synthetic-based muds have been used to simultaneously improve drilling and environmental performance. The fate and effects of synthetic-based mud discharges in the marine environment have been issues of concern with the drilling industry and governmental agencies. Most of the environmental data on synthetic-based muds have been generated under laboratory conditions. This study uses field-collected data to investigate the fate and effects of a polyalphaolefin synthetic-based drilling fluid. The first well drilled in the Gulf of Mexico using synthetic-based mud was completed in June 1992. Approximately 441 bbl of cuttings and 354 bbl of synthetic-based mud were discharged over a 9-day period. Three sampling trips have been made to the discharge location to collect sediment samples for chemical and biological analysis over a 2-year period. The sediment samples were analyzed for content of organic compounds and barium. On the third trip, infaunal samples were also taken. Information collected from the chemical and biological analysis is documented and compared to similar field studies performed on oil-based and water-based muds. Sampling techniques and analytical protocols are described to facilitate future studies. Two years after discharges of synthetic-based cuttings were completed, an area within 50 m of the discharge point continued to exhibit alterations in the benthic community not normally associated with water-based mud discharges. However, the study indicates that polyalphaolefin synthetic-based mud exhibits significant improvements over oil-based mud in terms of removal of organic contamination and minimization of adverse effects on the benthic community.
High-Performance Liquid Chromatography−Electrospray Ionization Mass Spectrometry of Single- and Double-Stranded Nucleic Acids Using Monolithic Capillary Columns (2000)

Monolithic capillary columns were prepared by copolymerization of styrene and divinylbenzene inside a 200-microm i.d. fused silica capillary using a mixture of tetrahydrofuran and decanol as porogen. With gradients of acetonitrile in 100 mM triethylammonium acetate, the synthesized columns allowed the rapid and highly efficient separation of single-stranded oligodeoxynucleotides and double-stranded DNA fragments by ion-pair reversed-phase high-performance liquid chromatography (IP-RP-HPLC). Compared with capillary columns packed with micropellicular, octadecylated poly-(styrene/divinylbenzene) particles, an improvement in column performance of approximately 40% was obtained, enabling the analysis of an 18-mer oligodeoxynucleotide with a column efficiency of more than 190000 plates per meter. The chromatographic separation system was on-line-coupled to electrospray ionization mass spectrometry (ESI-MS). To improve the mass spectrometric detectabilities, 25 mM triethylammonium bicarbonate was utilized as an ion-pair reagent at the cost of only little reduction in separation performance and acetonitrile was added postcolumn as the sheath liquid through the triaxial electrospray probe. High-quality mass spectra of femtomole amounts of 3-mer to 80-mer oligodeoxynucleotides were recorded showing very little cation adduction. Double-stranded DNA fragments ranging in size from 51 to 587 base pairs were separated and detected by IP-RP-HPLC-ESI-MS. Accurate mass determination by deconvolution of the mass spectra was feasible for DNA fragments up to the 267-mer with a molecular mass of 165 019, whereas the spectra of longer fragments were too complex for deconvolution because of incomplete separation due to overloading of the column. Finally, on-line IP-RP-HPLC tandem MS was applied to the sequencing of short oligodeoxynucleotides.
New video coding standard for the 1990s (1990)

The growth of a conversational audio-visual service such as videoconferencing depends on an ability to provide a complete system at a price the customer can afford. Video compression technology can play a significant role by drastically reducing transmission costs. The paper outlines progress in establishing a new standard, H.261, for video coding bit rates between 64 kbit/s and 2 Mbit/s.
Cooper Pair Box Coupled to a Current-Biased Josephson Junction (2002)

We study the dynamics of a quantum superconducting circuit which consists of a Josephson charge qubit, coupled capacitively to a current biased Josephson junction. Under certain conditions, the eigenstates of the qubit and the junction become entangled. We obtain the time evolution of these states in the limit of weak coupling. Rabi oscillations occur, as a result of the spontaneous emission and re-absorption of a single oscillation quantum in the junction. We discuss a possible way to experimentally determine the quantum state of the junction and hence observe the Rabi oscillations.