gebhart/patrepeval huggingface dataset:
Detection of mitochondria-generated reactive oxygen species in cells using multiple probes and methods: Potentials, pitfalls, and the future (2018)

Reactive oxygen and nitrogen species (ROS/RNS) such as superoxide (O<sub>2</sub><sup>̇̄</sup>), hydrogen peroxide, lipid hydroperoxides, peroxynitrite, and hypochlorous and hypobromous acids play a key role in many pathophysiological processes. Recent studies have focused on mitochondrial ROS as redox signaling species responsible for promoting cell division, modulating and regulating kinases and phosphatases, and activating transcription factors. Many ROS also stimulate cell death and senescence. The extent to which these processes occur is attributed to ROS levels (low or high) in cells. However, the exact nature of ROS remains unknown. Investigators have used redox-active probes that, upon oxidation by ROS, yield products exhibiting fluorescence, chemiluminescence, or bioluminescence. Mitochondria-targeted probes can be used to detect ROS generated in mitochondria. However, because most of these redox-active probes (untargeted and mitochondria-targeted) are oxidized by several ROS species, attributing redox probe oxidation to specific ROS species is difficult. It is conceivable that redox-active probes are oxidized in common one-electron oxidation pathways, resulting in a radical intermediate that either reacts with another oxidant (including oxygen to produce O<sub>2</sub><sup>̇̄</sup>) and forms a stable fluorescent product or reacts with O<sub>2</sub><sup>̇̄</sup> to form a fluorescent marker product. Here, we propose the use of multiple probes and complementary techniques (HPLC, LC-MS, redox blotting, and EPR) and the measurement of intracellular probe uptake and specific marker products to identify specific ROS generated in cells. The low-temperature EPR technique developed to investigate cellular/mitochondrial oxidants can easily be extended to animal and human tissues.
Structural Variants of Human Growth Hormone: Biochemical, Genetic, and Clinical Aspects (1983)

Human growth hormone (hGH) is a mixture of peptides in which the major physiologic component is a single chain polypeptide of 191 residues with a molecular weight of 22,000 ("22K" form). The minor components differ from the 22K form in terms of mass (e.g. the 20K form, a single-chain peptide synthesized by deletion of residues 32-46 of the 22K isomer, and the 45K variant formed by aggregation of the 22K molecule), or of charge (e.g. the more acidic two-chain forms alpha 2 and alpha 3 which are generated by proteolytic deletion of residues 135-140 and 135-146 from the 22K variant). The minor components also differ from the 22K molecule in (a) their metabolic effects; (b) their capacity to bind to antiserum raised against the 22K form in a radioimmunoassay (RIA); and (c) their ability to bind to membrane receptors for the 22K hGH in a radioreceptor assay (RRA). Two genes, N and V, involved in the biosynthesis of hGH, are located on human chromosome 17. Heritable alterations of the N gene may cause deficiency of immunoreactive hGH and growth failure. A pathologic variant of hGH has also been identified which is indistinguishable from the 22K form on RIA, but which has low reactivity on hGH-RRA and low somatomedogenic activity. Several mechanisms to account for this bioinactive variant are discussed.
MEGA6: Molecular Evolutionary Genetics Analysis Version 6.0 (2013)

The Molecular Evolutionary Genetics Analysis (MEGA) software has matured to contain a large collection of methods and tools of computational molecular evolution. Here, we describe new additions that make MEGA a more comprehensive tool for building timetrees of species, pathogens, and gene families using rapid relaxed-clock methods. Methods for estimating divergence times and confidence intervals are implemented to use probability densities for calibration constraints for node-dating and sequence sampling dates for tip-dating analyses. They are supported by new options for tagging sequences with spatiotemporal sampling information, an expanded interactive Node Calibrations Editor, and an extended Tree Explorer to display timetrees. Also added is a Bayesian method for estimating neutral evolutionary probabilities of alleles in a species using multispecies sequence alignments and a machine learning method to test for the autocorrelation of evolutionary rates in phylogenies. The computer memory requirements for the maximum likelihood analysis are reduced significantly through reprogramming, and the graphical user interface has been made more responsive and interactive for very big data sets. These enhancements will improve the user experience, quality of results, and the pace of biological discovery. Natively compiled graphical user interface and command-line versions of MEGA11 are available for Microsoft Windows, Linux, and macOS from www.megasoftware.net.
Role of the Ah Receptor and the Dioxin‐Inducible [Ah] Gene Battery in Toxicity, Cancer, and Signal Transductiona (1993)

1. On the basis of our current knowledge about the evolution of drug-metabolizing enzymes, it appears to be extremely likely that these enzymes play a critical role in maintaining steady-state levels of the ligands involved in ligand-modulated transcription of genes effecting growth, differentiation, homeostasis, and neuroendocrine functions. 2. The original observations about genetic differences in CYP1A1 (cytochrome P1-450) induction by TCDD or benzo[a]pyrene in the mouse have led to an appreciation for a similar polymorphism in the human and the recent cloning of the murine Ah receptor (Ahr) and human Ah receptor nuclear translocator (ARNT) genes. It is most likely that the correlation between genetic differences in human or murine CYP1A1 inducibility by polycyclic hydrocarbons or TCDD and increased risk of cancer will be explained by differences in the AHR gene, leading to enhanced tumor promotion (rather than in the CYP1A1 structural gene). Perhaps the same will be found for birth defects, immunotoxicity, and other forms of toxic damage caused by these environmental chemicals. 3. In a manner similar to that of the phorbol ester tumor promoter, TCDD induces intracellular Ca2+ changes, accumulation of FOS and JUN mRNAs, and large increases in AP-1 transcription factor activity. Interestingly, these early effects of TCDD, and also of benzo[a]pyrene, appear not to require the Ah receptor. 4. Many genes are induced by TCDD, and many others are induced by electrophilic metabolites such as quinones and H2O2; using several mouse experimental systems, we have defined a subset of six of these genes as constituting the [Ah] battery by the sole criterion that a functional CYP1A1 or CYP1A2 enzyme is able to repress the expression of genes that are members of this gene battery.
Run-to-Run Process Control: Literature Review and Extensions (1997)

In the last few years, “Run-to-Run” (R2R) control techniques have been developed and used to control various semiconductor manufacturing processes. These techniques combine response surface, statistical process control, and feedback control techniques. This paper provides a literature review of R2R control methods from a statistical and control engineering point of view. It is shown that self-tuning controllers can provide a valuable control strategy for R2R applications. In this paper we address the single-input-single-output (SISO) case. Two proposed self-tuning controllers compensate not only for the standard case of process shifts, but also in the case a deterministic trend and/or autocorrelation is present in the observed response (i.e., in case there exist process dynamics). In order to reduce the input variance, a control chart is added to the output and acts as a deadband.
High Performance Carbon Nanotube RF Electronics (2008)

Carbon nanotubes-based electronic devices have attracted interest for future high performance RF and digital applications because of their potential to operate at high speed while simultaneously dissipating low power. Recent device modeling and measurements conducted at Northrop Grumman predict, due to their unique one- dimensional (1-D) physics, RF carbon nanotube (CNT)-based field effect transistors (FET) are capable of achieving 100 - 1000x higher linearity than current state-of-the-art semiconductor device technology, while maintaining the same dissipated power. Alternatively, this increased linearity for CNT FETs can also be traded to reduce the power dissipation. Low noise amplifiers based on CNT FETs could reduce power dissipation by 20 - 30 dB without sacrificing linearity. Because these performance advantages result from the unique physics of a one-dimensional conducting channel, the channel need obviously be narrow (~3nm or less) which puts a limit on the maximum transconductance of the device. A theoretical maximum transconductance of 155 muS projected for a single CNT FET is insufficient to source a standard impedance load (e.g. 50Omega). To make a device capable of driving a 50Omega load requires a FET made from thousands of CNTs in parallel.
A Method for Estimating Zero-Flow Pressure and Intracranial Pressure (2012)

Proposed alterations to a procedure for estimating ZFP lead to more accurate and more precise estimates of ICP, thereby offering improved means of estimating it noninvasively. The quality of the estimates is inadequate for many applications, but further work is proposed, which may lead to clinically useful results.
Enterically-transmitted non-A, non-B hepatitis (1990)

More than 50% of acute viral hepatitis occurring in some developing countries appears to be unrelated to infection by HAV or HBV and accumulating evidence suggests that a high proportion of this non-A, non-B hepatitis (NANB) is enterically transmitted. Epidemics or outbreaks of enterically-transmitted NANB (ET-NANB) have been documented in the Soviet Union, Nepal, Burma, Pakistan, India, Borneo, Somalia, Sudan, Ivory Coast, Algeria, and Mexico. These outbreaks primarily affect young to middle-age adults and are often associated with a high mortality rate in infected pregnant women, approaching 20% in most reported epidemics. Several investigators have reported finding 27 to 34 nm virus-like particles (VLPs) in stools of acutely infected cases. Stools containing these small, non-enveloped VLPs have been shown to cause NANB in experimentally infected cynomolgus macaques, African green monkeys, chimpanzees, rhesus monkeys, and Saguinus mystax monkeys (tamarins). Infected primates have been shown to seroconvert to 27-34 nm VLPs recovered from stools of cases occurring in the Soviet Union, India, Nepal, Burma, Pakistan and/or Mexico, suggesting that ET-NANB is caused by one virus or class of serologically related viruses. The morphological features and physicochemical properties of one candidate virus are very similar to those of some human caliciviruses, a group of viruses that is normally associated with outbreaks of severe diarrhoea.
Stereospecific hydrogen loss in the conversion of [2H7]isobutyrate to β-hydroxyisobutyrate in Pseudomonas putida. The stereochemistry of β-hydroxyisobutyrate dehydrogenase (1979)

Ammonium [2H7]isobutyrate was converted by Pseudomonas putida(ATCC 21 244) into a mixture of (2S)β-hydroxy[3-2H2,2′-2H3]isobutyric acid (69%) and (2S,3S)-β-hydroxy[3-2H1,2′-2H3]isobutyric acid (31%). The latter is formed stereospecifically with loss of the 3-pro-R-hydrogen atom, probably via reversible formation of methylmalonic semialdehyde by the enzyme β-hydroxyisobutyrate dehydrogenase.
In vivo restoration of T cell functions by human IL-1 beta or its 163-171 nonapeptide in immunodepressed mice. (1988)

The immunorestorative capacities of human (hu) IL-1 beta or its synthetic fragment 163-171 (VQGEESNDK) were assessed in vivo in mice immunodepressed by aging, sublethal irradiation, or both. Subcutaneous administration of hu rIL-1 beta into immunodepressed animals immediately after carrier (horse red blood cells, HRBC) priming could restore to normal levels Th cell activity. This was measured as the ability of spleen cells from HRBC-primed mice to induce a hapten-specific antibody response in spleen cells from nonimmune mice in vitro stimulated with the hapten-carrier conjugate TNP-HRBC. In parallel, the ability of spleen cells from hu rIL-1 beta-treated immunodepressed animals to produce T cell growth factor activity upon in vitro mitogen stimulation was also increased significantly as compared to that of untreated mice and approached that of immunocompetent controls. The immunorestorative activity of hu rIL-1 beta on Th cell activity and T cell growth factor production could be mimicked by the synthetic nonapeptide 163-171 which, at the doses used, produced in most instances even greater effects than the whole protein. Although the optimal immunorestorative doses of the 163-171 peptide were several orders of magnitude higher than those of hu rIL-1 beta, the complete lack of IL-1-like inflammatory and toxic effects suggests that the synthetic hu IL-1 beta fragment may be successfully used as immunomodulating agent in the therapy of T cell immunodeficiencies.
Influence of Core Fucosylation on the Flexibility of a Biantennary N-Linked Oligosaccharide (1996)

Fluorescence energy transfer was used to study the conformation of each antenna of a complex biantennary oligosaccharide. A core fucosylated biantennary oligosaccharide was converted to a glycosylamine which allowed coupling of a naphthyl donor fluorophore directly to the reducing-end GlcNAc 1. After generating an aldehyde at C-6 of residue 6 or 6' using galactose oxidase, a dansyl ethylenediamine acceptor fluorophore was coupled to either antenna of the oligosaccharide resulting in two donor-acceptor pairs. [Formula: see text] The fluorescence properties of the naphthyl group allowed determination of the end-to-end donor-acceptor distance and antenna flexibility of each isomer by steady-state and time-resolved fluorescence energy transfer at temperatures ranging from 0 to 40 degrees C. Extended (20.6 A) and folded (11.4 A) donor-acceptor distance populations were identified for the isomer containing dansyl attached to Gal 6', whereas only a single extended population (19.7 A) was determined when dansyl was attached to Gal 6. The presence of Fuc 1' had a dramatic effect on the conformation of the 6' antenna. Temperature modulation failed to alter the ratio of extended/folded populations when fucose was present. However, following the removal of fucose, the ratio of the extended/folded populations for 6' exhibited a temperature dependent conformational equilibrium allowing calculation of the enthalpy and entropy of unfolding. These results established a unique conformational property for the 6' antenna of a biantennary oligosaccharide that is influenced by core fucosylation. Comparison of the results obtained for the 6 antenna of biantennary with previous fluorescence energy transfer studies on a triantennary glycopeptide also established conformational differences in this antenna which are dependent on oligosaccharide structure.
Current treatment approaches for chronic myelogenous leukemia. (2001)

Chronic myelogenous leukemia (CML) is a clonal hematopoietic stem cell disorder that progresses through distinct phases characterized by progressive loss of the differentiation of the malignant clone. Over the past 4 decades, it has been established that the Bcr-Abl protein, created as a consequence of a (9:22) chromosomal translocation, is the cause of the disease. Bcr-Abl functions as a constitutively activated tyrosine kinase, and this kinase activity is absolutely required for the transforming function of the Bcr-Abl protein. Thus, a specific inhibitor of the Bcr-Abl tyrosine kinase would be predicted to be an effective and selective therapeutic agent for CML. STI571, an Abl-specific tyrosine kinase inhibitor, has shown remarkable activity in all phases of CML. The clinical features, molecular pathogenesis, and current treatment options of CML are reviewed along with the development of STI571, the phase I clinical results, and the application of this paradigm to other malignancies.
Development of a drug delivery system for the inner ear using poly(amino acid)-based nanoparticles (2014)

PHEA nanoparticles may have utility as a drug carrier into the inner ear in terms of both permeability and safety.
Selectivity in the Interaction of Electron Donor and Acceptor Molecules with Graphene and Single-Walled Carbon Nanotubes (2009)

Interaction of electron donor and acceptor molecules with graphene samples prepared by different methods as well as with single-walled carbon nanotubes (SWNTs) has been investigated by isothermal titration calorimetry (ITC). The ITC interaction energies of the graphene samples and SWNTs with electron acceptor molecules are higher than those with electron donor molecules. Thus, tetracyanoethylene (TCNE) shows the highest interaction energy with both graphene and SWNTs. The interaction energy with acceptor molecules varies with the electron affinity as well as with the charge-transfer transition energy for different aromatics. Metallic SWNTs interact reversibly with electron acceptor molecules, resulting in the opening of a gap.
Cytoplasmically Retargeted HSV1-tk/GFP Reporter Gene Mutants for Optimization of Noninvasive Molecular-Genetic Imaging (2003)

To optimize the sensitivity of imaging HSV1-tk/GFP reporter gene expression, a series of HSV1-tk/GFP mutants was developed with altered nuclear localization and better cellular enzymatic activity, compared to that of the native HSV1-tk/GFP fusion protein (HSV1-tk/GFP). Several modifications of HSV1-tk/GFP reporter gene were performed, including targeted inactivating mutations in the nuclear localization signal (NLS), the addition of a nuclear export signal (NES), a combination of both mutation types, and a truncation of the first 135 bp of the native hsv1-tk coding sequence containing a "cryptic" testicular promoter and the NLS. A recombinant HSV1-tk/GFP protein and a highly sensitive sandwich enzyme-linked immunosorbent assay for HSV1-tk/GFP were developed to quantitate the amount of reporter gene product in different assays to allow normalization of the data. These different mutations resulted in various degrees of nuclear clearance, predominant cytoplasmic distribution, and increased total cellular enzymatic activity of the HSV1-tk/GFP mutants, compared to native HSV1-tk/GFP when expressed at the same levels. This appears to be the result of improved metabolic bioavailability of cytoplasmically retargeted mutant HSV1-tk/GFP enzymes for reaction with the radiolabeled probe (e.g., FIAU). The analysis of enzymatic properties of different HSV1-tk/GFP mutants using FIAU as a substrate revealed no significant differences from that of the native HSV1-tk/GFP. Improved total cellular enzymatic activity of cytoplasmically retargeted HSV1-tk/GFP mutants observed in vitro was confirmed by noninvasive imaging of transduced subcutaneous tumor xenografts bearing these reporters using [(131)I]FIAU and a gamma-camera.
Inhibition of STAT3 signaling induces apoptosis and decreases survivin expression in primary effusion lymphoma (2003)

Despite some exciting new leads in molecular pathogenesis, AIDS-defining primary effusion lymphoma (PEL) remains a fatal malignancy. The lack of substantial progress in the management of PEL demands innovative treatment approaches. Targeting intracellular molecules critical to cell survival is one unexplored strategy for treating PEL. Here we show that inhibition of signal transducer and activator of transcription-3 (STAT3) leads to apoptosis in PEL cells. STAT3 is constitutively phosphorylated in PEL cell lines BC-1, BCBL-1, and VG-1. Transduction of dominant-negative STAT3 and pharmacological STAT3 inhibition caused caspase-dependent cell death. Although STAT3 activation is known to induce expression of Bcl-2 family proteins, PEL cell apoptosis was independent of Bcl-2, Bcl-X(L), or Mcl-1 protein expression. Instead, STAT3 inhibition induced transcriptional repression of survivin, a recently identified inhibitor of apoptosis. Forced overexpression of survivin rescued VG-1 cells from apoptosis induced by STAT3 inhibition. Our findings suggest that activated STAT3 signaling directly contributes to malignant progression of PEL by preventing apoptosis, acting through the prosurvival protein survivin. Since constitutive STAT3 activation and survivin expression have been widely documented in different types of cancers, their linkage may extend to many malignancies and be critical to their pathogenesis.
Antibody gene transfer with adeno‐associated viral vectors as a method for HIV prevention (2017)

Broadly neutralizing antibodies (bNAbs) against human immunodeficiency virus (HIV) show great promise in HIV prevention as they are capable of potently neutralizing a considerable breadth of genetically diverse strains. Passive transfer of monoclonal bNAb proteins can confer protection in animal models of HIV infection at modest concentrations, inspiring efforts to develop an HIV vaccine capable of eliciting bNAb responses. However, these antibodies demonstrate high degrees of somatic mutation and other unique characteristics that may hinder the ability of conventional approaches to consistently and effectively produce bNAb analogs. As an alternative strategy, we and others have proposed vector-mediated gene transfer to generate long-term, systemic production of bNAbs in the absence of immunization. Herein, we review the use of adeno-associated virus (AAV) vectors for delivery of HIV bNAbs and antibody-like proteins and summarize both the advantages and disadvantages of this strategy as a method for HIV prevention.
In Situ Peptide-Modified Supported Lipid Bilayers for Controlled Cell Attachment (2003)

The control of cellular interactions with engineered materials is critical for the development of cell-integrated biochips used in cell-based sensors, “lab-on-a-chip” bioanalytical systems, and artificial neuronal networks, as well as medical implants and functional biomaterial scaffolds for tissue engineering. Supported lipid bilayers offer efficient reduction of nonspecific cell and protein binding and, if selectively functionalized, constitute one attractive approach to surface modification strategies of materials used in such devices. The present work describes the in situ modification of supported lipid bilayers through the coupling of a cysteine-terminated peptide to thiol-reactive maleimido lipids incorporated in the bilayer. The accumulation of peptide at the lipid bilayer interface was monitored by the quartz crystal microbalance technique with dissipation monitoring (QCM-D). Coupling of the peptide could be detected by QCM-D with a high signal-to-noise ratio despite its low molecular weight (2 kDa), primarily because the mass uptake included both peptide and the water associated to it. Lipid bilayers that were modified with the cysteine-terminated IKVAV-containing peptide promoted the binding of anti-IKVAV antibodies, as well as the attachment of PC12 cells, which express a membrane receptor for the IKVAV sequence. Very low nonspecific binding of peptides, proteins, and the cells was observed on nonfunctionalized lipid bilayers. Similarly, IKVAV-functionalized lipid bilayers were resistant to serum protein adsorption as well as the binding of non-IKVAV-specific antibodies. QCM-D and fluorescence recovery after photobleaching revealed that the lipid bilayers persisted under all the experimental conditions used for cell attachment, including staining and fixation. Thus, the described lipid-based surface modification is highly relevant for the development of controlled cell-attachment substrates and can even be applicable for patterning cell attachment because lipid-bilayer formation by vesicle fusion is material-specific.