gebhart/patrepeval huggingface dataset:
Selective control of physiological responses by temporally-patterned electrical stimulation of the canine vagus nerve (2011)

Vagus nerve stimulation (VNS) is effective for treating epilepsy and depression, and has emerging indications for anxiety and heart failure. However, stimulation-evoked side effects remain a challenge for long-term compliance. We investigated the feasibility of reducing VNS side effects by using a temporally-modified stimulation pattern. In 4 anesthetized canines, we measured changes in both the heart rate and evoked laryngeal muscle activity. Compared to baseline, we found that a 5% duty cycle (measured by the number of pulses per second of stimulation) could still evoke a 21% reduction in heart rate; whereas compared to continuous stimulation (3 mA, 300 μs pulsewidth, 20 Hz) the same 5% duty cycle reduced the evoked laryngeal muscle activity by 90%. The results of this study indicate that temporally-patterned stimulation may provide an effective tool for optimizing VNS therapy.
Anti-human immunodeficiency virus type 1 activity of an anti-CD4 immunoconjugate containing pokeweed antiviral protein (1993)

The ability of an alpha CD4-pokeweed antiviral protein (PAP) immunoconjugate to inhibit replication of human immunodeficiency virus type 1 (HIV-1) was evaluated in vitro with 22 clinical HIV-1 strains obtained from four seropositive asymptomatic individuals, three patients with AIDS-related complex, and four patients with AIDS. Fifteen isolates were from zidovudine-untreated individuals, whereas seven isolates were obtained after 24 to 104 weeks of therapy with zidovudine, alone or alternating with zalcitabine. Mean zidovudine 50% inhibitory concentrations (IC50s) were 126 nM (range, 1 to 607 nM) for isolates from zidovudine-untreated individuals and 2,498 nM (range, 14 to 6,497 nM) for strains from patients treated with antiretroviral agents. Mean alpha CD4-PAP IC50s were 48 x 10(-3) nM (range, 0.02 x 10(-3) to 212 x 10(-3) nM) for isolates from zidovudine-untreated individuals, and 16 x 10(-3) nM (range, 2 x 10(-3) to 28 x 10(-3) nM) for isolates from treated patients. Overall, higher concentrations of alpha CD4-PAP were necessary to inhibit HIV-1 strains from untreated individuals at more advanced stages of disease. Seventeen isolates were susceptible to zidovudine (mean IC50, 117 nM), and five were resistant to zidovudine (mean IC50, 3,724 nM). Mean alpha CD4-PAP IC50s were 43 x 10(-3) nM for zidovudine-susceptible isolates and 19 x 10(-3) nM for isolates resistant to zidovudine. All HIV-1 strains had IC50s greater than 0.5 nM for unconjugated PAP, the alpha CD19-PAP immunoconjugate, and monoclonal antibody alpha CD4. At concentrations as high as 5,000 nM, alphaCD4-PAP did not inhibit colony formation by normal bone marrow progenitor cells(BFU-E, CFU-GM , and CFU-GEMM) or myeloid cell lines (KG-1 and HL-60) and did not decrease cell viabilities of T-cell (Jurkat) or B-cell (FL-112 and Raji) precursor lines. Overall, alphaCD4-PAP demonstrated more potent anti-HIV-1 activity than zidovudine and inhibited replication of zidovudine-susceptible and zidovudine-resistant viruses at concentrations that were not toxic to lymphohematopoietic cell populations.
[Effect of prolonged hypokinesia on PO2 dynamics in the brain tissues of rats in orthostatic and antiorthostatic tests]. (1977)

Variations of PO2 in rat brain tissues were assessed polarographically during orthostatic tests. Prolonged hypokinesia (up to 100 days) did not induce significant changes of PO2 in rats at rest. During orthostatic tests PO2 of control rats changed insignificantly. Prolonged hypokinesia led to more marked changes of PO2 in rats exposed to an orthostatic test. Changes in the cerebral oxygenation of hypokinetic rats were varying and inadequate, differing appreciably from the cerebral oxygenation of control animals.
Small Molecule Inhibition of the TNF Family Cytokine CD40 Ligand through a Subunit Fracture Mechanism (2011)

BIO8898 is one of several synthetic organic molecules that have recently been reported to inhibit receptor binding and function of the constitutively trimeric tumor necrosis factor (TNF) family cytokine CD40 ligand (CD40L, aka CD154). Small molecule inhibitors of protein-protein interfaces are relatively rare, and their discovery is often very challenging. Therefore, to understand how BIO8898 achieves this feat, we characterized its mechanism of action using biochemical assays and X-ray crystallography. BIO8898 inhibited soluble CD40L binding to CD40-Ig with a potency of IC(50) = 25 μM and inhibited CD40L-dependent apoptosis in a cellular assay. A co-crystal structure of BIO8898 with CD40L revealed that one inhibitor molecule binds per protein trimer. Surprisingly, the compound binds not at the surface of the protein but by intercalating deeply between two subunits of the homotrimeric cytokine, disrupting a constitutive protein-protein interface and breaking the protein's 3-fold symmetry. The compound forms several hydrogen bonds with the protein, within an otherwise hydrophobic binding pocket. In addition to the translational splitting of the trimer, binding of BIO8898 was accompanied by additional local and longer-range conformational perturbations of the protein, both in the core and in a surface loop. Binding of BIO8898 is reversible, and the resulting complex is stable and does not lead to detectable dissociation of the protein trimer. Our results suggest that a set of core aromatic residues that are conserved across a subset of TNF family cytokines might represent a generic hot-spot for the induced-fit binding of trimer-disrupting small molecules.
The Condensed Protocols from Molecular Cloning: A Laboratory Manual (2006)

1. Using Plasmid Vectors in Molecular Cloning 2. Bacteriophage bb and Its Vectors 3. Working with Bacteriophage M13 Vectors 4. Working with High-capacity Vectors 5. Gel Electrophoresis of DNA and Pulsed-field Agarose Gel Electrophoresis 6. Preparation and Analysis of Eukaryotic Genomic DNA 7. Extraction, Purification, and Analysis of mRNA from Eukaryotic Cells 8. In Vitro Amplification of DNA by the Polymerase Chain Reaction 9. Preparation of Radiolabeled DNA and RNA Probes 10. Working with Synthetic Oligonucleotide Probes 11. Preparation of cDNA Libraries and Gene Identification 12. DNA Sequencing 13. Mutagenesis 14. Screening Expression Libraries 15. Expression of Cloned Genes in Escherichia coli 16. Introducing Cloned Genes into Cultured Mammalian Cells 17. Analysis of Gene Expression in Mammalian Cells 18. Protein Interaction Technologies Appendices Index
Frequent loss of heterozygosity on 6q at the mannose 6-phosphate/insulin-like growth factor II receptor locus in human hepatocellular tumors. (1995)

The mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGFIIr) is required for the activation of transforming growth factor beta, and previously we have found its expression to be significantly reduced in both rat and human hepatocellular carcinomas (HCCs). Therefore, we have postulated that loss of the M6P/IGFIIr gene may be mechanistically involved in liver carcinogenesis. Using the polymerase chain reaction, we utilized two polymorphisms in the 3' untranslated region of the M6P/IGFIIr gene to screen non-cirrhotic, hepatitis virus negative patients with hepatocellular tumors for LOH. Twenty-two of 36 (61%) patients were informative (heterozygous), and 14/22 (64%) liver tumors had LOH; 11/16 (69%) carcinomas, 1/3 (33%) fibrolamellar tumors and 2/3 (67%) adenomas. This is the first report of LOH at the M6P/IGFIIr locus in human hepatocellular tumors, and the presence of LOH in adenomas suggests that allelic loss may be an early event in the etiology of HCCs. These results support the hypothesis that the M6P/IGFIIr gene may function as a tumor suppressor gene in the liver.
A linear prognostic score based on the ratio of interleukin-6 to interleukin-10 predicts outcomes in COVID-19 (2020)

Funding was received from the Elaine Galwey Research Fellowship, American Thoracic Society, National Institutes of Health and the Parker B Francis Research Opportunity Award.
N-Amination of Pyrrole and Indole Heterocycles with Monochloramine (NH2Cl) (2004)

A survey of several electrophilic ammonia reagents for the N-amination of indole- and pyrrole-containing heterocycles revealed that monochloramine (NH(2)Cl) is an excellent reagent for this transformation. Pyrroles and indoles containing a variety of substitution were aminated on nitrogen with isolated yields ranging from 45% to 97%.
Stability of DNA Origami Nanoarrays in Cell Lysate (2011)

Scaffolded DNA origami, a method to create self-assembled nanostructures with spatially addressable features, has recently been used to develop water-soluble molecular chips for label-free RNA detection, platforms for deterministic protein positioning, and single molecule reaction observatories. These applications highlight the possibility of exploiting the unique properties and biocompatibility of DNA nanostructures in live, cellular systems. Herein, we assembled several DNA origami nanostructures of differing shape, size and probes, and investigated their interaction with lysate obtained from various normal and cancerous cell lines. We separated and analyzed the origami-lysate mixtures using agarose gel electrophoresis and recovered the DNA structures for functional assay and subsequent microscopic examination. Our results demonstrate that DNA origami nanostructures are stable in cell lysate and can be easily separated from lysate mixtures, in contrast to natural, single- and double-stranded DNA. Atomic force microscope (AFM) and transmission electron microscope (TEM) images show that the DNA origami structures are fully intact after separation from cell lysates and hybridize to their targets, verifying the superior structural integrity and functionality of self-assembled DNA origami nanostructures relative to conventional oligonucleotides. The stability and functionality of DNA origami structures in cell lysate validate their use for biological applications, for example, as programmable molecular rafts or disease detection platforms.
Closing the Gaps on Human Chromosome 19 Revealed Genes With a High Density of Repetitive Tandemly Arrayed Elements (2004)

The reported human genome sequence includes about 400 gaps of unknown sequence that were not found in the bacterial artificial chromosome (BAC) and cosmid libraries used for sequencing of the genome. These missing sequences correspond to approximately 1% of euchromatic regions of the human genome. Gap filling is a laborious process because it relies on analysis of random clones of numerous genomic BAC or cosmid libraries. In this work we demonstrate that closing the gaps can be accelerated by a selective recombinational capture of missing chromosomal segments in yeast. The use of both methodologies allowed us to close the four remaining gaps on the human chromosome 19. Analysis of the gap sequences revealed that they contain several abnormalities that could result in instability of the sequences in microbe hosts, including large blocks of micro- and minisatellites and a high density of Alu repeats. Sequencing of the gap regions, in both BAC and YAC forms, allowed us to generate a complete sequence of four genes, including the neuronal cell signaling gene SCK1/SLI. The SCK1/SLI gene contains a record number of minisatellites, most of which are polymorphic and transmitted through meiosis following a Mendelian inheritance. In conclusion, the use of the alternative recombinational cloning system in yeast may greatly accelerate work on closing the remaining gaps in the human genome (as well as in other complex genomes) to achieve the goal of annotation of all human genes.
Reception of Teletext Under Multipath Conditions (1979)

Information for data broadcasting services such as Teletext is transmitted as digital signals inserted in the vertical interval of the television video waveform. The specifications for these signals are drawn very carefully to ensure compatibility with the existing television system. This paper examines some of these specifications such as data rate and waveform shape, which must be selected to maintain the spectral energy within the television bandwidth. Using computer simulation, the transmitted signal and encoded teletext data (as defined in Broadcast Teletext Specifications') will be examined for different multipath conditions. For all these experiments, echoes have been generated and evaluated at the baseband, ignoring system amplitude and group delay characteristics. These, in general, will have additional influence on decoding reliability.
Nucleotide sequence of cDNA coding for saporin‐6, a type‐1 ribosome‐inactivating protein from Saponaria officinalis (1989)

We have isolated and sequenced partial cDNA clones that encode SO-6, a ribosome-inactivating protein from Saponaria officinalis. A cDNA library was constructed from the leaves of this plant and screened with synthetic oligonucleotide probes representing various portions of the protein. The deduced amino acid sequence shows the signal peptide and a coding region virtually accounting for the entire amino acid sequence of SO-6. The sequence reveals regions of similarity to other ribosome-inactivating proteins, especially in a region of the molecule where critical amino acid residues might participate in the active site.
Genetic and dietary regulation of lipid droplet expansion in Caenorhabditis elegans (2010)

Dietary fat accumulates in lipid droplets or endolysosomal compartments that undergo selective expansion under normal or pathophysiological conditions. We find that genetic defects in a peroxisomal beta-oxidation pathway cause size expansion in lipid droplets that are distinct from the lysosome-related organelles in Caenorhabditis elegans. Expansion of lipid droplets is accompanied by an increase in triglycerides (TAG) that are resistant to fasting- or TAG lipase-triggered lipolysis. Nevertheless, in mutant animals, a diet poor in vaccenic acid reduced the TAG level and lipid droplet size. Our results implicate peroxisomal dysfunction in pathologic lipid droplet expansion in animals and illustrate how dietary factors modulate the phenotype of such genetic defects.
Molecular cloning and adhesive properties of murine platelet/endothelial cell adhesion molecule 1. (1993)

We describe the isolation and characterization of a functional murine platelet/endothelial cell adhesion molecule (PECAM) 1 cDNA clone from a mouse lung library. At the nucleotide level, the coding sequence of murine PECAM-1 is 73% identical to human PECAM-1, and at the amino acid level, the sequence is 79% homologous to its human counterpart. Southern hybridization reveals that one copy of the gene exists in the mouse genome; Northern hybridization reveals a single mRNA species in mouse lung tissue. COS-7 and mouse L cells transfected with murine PECAM-1 expressed a 130-kDa glycoprotein on their surfaces that reacted with anti-murine PECAM-1 monoclonal antibody and comigrated on SDS/PAGE with human PECAM-1. Stable L-cell transfectants aggregate with each other in a PECAM-dependent, homophilic manner.
Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions (1999)

Poly(ADP-ribosyl)ation is a post-translational modification of proteins. During this process, molecules of ADP-ribose are added successively on to acceptor proteins to form branched polymers. This modification is transient but very extensive in vivo, as polymer chains can reach more than 200 units on protein acceptors. The existence of the poly(ADP-ribose) polymer was first reported nearly 40 years ago. Since then, the importance of poly(ADP-ribose) synthesis has been established in many cellular processes. However, a clear and unified picture of the physiological role of poly(ADP-ribosyl)ation still remains to be established. The total dependence of poly(ADP-ribose) synthesis on DNA strand breaks strongly suggests that this post-translational modification is involved in the metabolism of nucleic acids. This view is also supported by the identification of direct protein-protein interactions involving poly(ADP-ribose) polymerase (113 kDa PARP), an enzyme catalysing the formation of poly(ADP-ribose), and key effectors of DNA repair, replication and transcription reactions. The presence of PARP in these multiprotein complexes, in addition to the actual poly(ADP-ribosyl)ation of some components of these complexes, clearly supports an important role for poly(ADP-ribosyl)ation reactions in DNA transactions. Accordingly, inhibition of poly(ADP-ribose) synthesis by any of several approaches and the analysis of PARP-deficient cells has revealed that the absence of poly(ADP-ribosyl)ation strongly affects DNA metabolism, most notably DNA repair. The recent identification of new poly(ADP-ribosyl)ating enzymes with distinct (non-standard) structures in eukaryotes and archaea has revealed a novel level of complexity in the regulation of poly(ADP-ribose) metabolism.
Tumor Necrosis Factor α-induced Inflammation Is Increased but Apoptosis Is Inhibited by Common Food Additive Carrageenan (2010)

Tumor necrosis factor (TNF)-α, a homotrimeric, pleiotropic cytokine, is secreted in response to inflammatory stimuli in diseases such as rheumatoid arthritis and inflammatory bowel disease. TNF-α mediates both apoptosis and inflammation, stimulating an inflammatory cascade through the non-canonical pathway of NF-κB activation, leading to increased nuclear RelB and p52. In contrast, the common food additive carrageenan (CGN) stimulates inflammation through both the canonical and non-canonical pathways of NF-κB activation and utilizes the adaptor molecule BCL10 (B-cell leukemia/lymphoma 10). In a series of experiments, colonic epithelial cells and mouse embryonic fibroblasts were treated with TNF-α and carrageenan in order to simulate the possible effects of exposure to dietary CGN in the setting of a TNF-α-mediated inflammatory disease process. A marked increase in secretion of IL-8 occurred, attributable to synergistic effects on phosphorylated NF-κB-inducing kinase (NIK) in the non-canonical pathway. TNF-α induced the ubiquitination of TRAF2 (TNF receptor-associated factor 2), which interacts with NIK, and CGN induced phosphorylation of BCL10, leading to increased NIK phosphorylation. These results suggest that TNF-α and CGN in combination act to increase NIK phosphorylation, thereby increasing activation of the non-canonical pathway of NF-κB activation. In contrast, the apoptotic effects of TNF-α, including activation of caspase-8 and PARP-1 (poly(ADP-ribose) polymerase 1) fragmentation, were markedly reduced in the presence of CGN, and CGN caused reduced expression of Fas. These findings demonstrate that exposure to CGN drives TNF-α-stimulated cells toward inflammation rather than toward apoptotic cell death and suggest that CGN exposure may compromise the effectiveness of anti-TNF-α therapy.
Discrepant sensitivity of thromboplastin reagents to clotting factor levels explored by the prothrombin time in patients on stable oral anticoagulant treatment: impact on the international normalized ratio system. (2002)

The discrepant sensitivity to factor VII, X and V levels of the two thromboplastin reagents explored in this study prevents INR calibration with commercially available calibrator plasmas and is responsible for a significant variability in INR values even under optimal conditions of INR calibration.
Double-Gate Nanowire Field Effect Transistor for a Biosensor (2010)

A silicon nanowire field effect transistor (FET) straddled by the double-gate was demonstrated for biosensor application. The separated double-gates, G1 (primary) and G2 (secondary), allow independent voltage control to modulate channel potential. Therefore, the detection sensitivity was enhanced by the use of G2. By applying weakly positive bias to G2, the sensing window was significantly broadened compared to the case of employing G1 only, which is nominally used in conventional nanowire FET-based biosensors. The charge effect arising from biomolecules was also analyzed. Double-gate nanowire FET can pave the way for an electrically working biosensor without a labeling process.
5-Fluorouracil spares hemopoietic stem cells responsible for long-term repopulation. (1990)

The long-term immunohemopoietic reconstituting ability of bone marrow, treated with a single administration of 5-fluorouracil (5-FU), was measured to determine whether 5-FU caused any deleterious effect upon primitive stem cells (PSCs). Cells from 5-FU-treated marrow donors were mixed in four different proportions of total marrow contents with untreated competitor marrow containing genetically distinguishable hemoglobin (Hb) and glucosephosphate isomerase (GPI) transplantation markers. These cell mixtures were introduced into lethally irradiated hosts. The functional ability of the donor cell population was assessed by measuring the percentage of donor type Hb and GPI found in the host's circulating erythrocytes and lymphocytes, respectively. Bone marrow from mice treated with 5-FU 1, 5, and 8 days prior to transplantation produced circulating lymphoid and erythroid cells as well as equal fractions of untreated fresh marrow when surveyed approximately 90 days after transplantation. Normal reconstitutive ability was thus maintained despite a tenfold reduction in marrow cell numbers when donor mice had been treated with 5-FU 5 days prior to transplantation. Donor marrow treated with 5-FU 15 days prior to transplantation had slightly decreased repopulating ability in one of two experiments. A second round of repopulation was stimulated subsequent to the initial 90-day screening by giving hosts a sublethal (500 rad) dose of irradiation. After 3-4 months, Hb and GPI parameters were the same as preirradiation values. Thus, the radioresistance of 5-FU treated PSCs remains comparable to that of fresh marrow, and their relative repopulating ability was not comprised by the additional stress of sublethal irradiation. After both rounds of repopulation the myeloid and lymphoid pathways were repopulated equally well by PSCs surviving 5-FU treatment. Repopulation of both pathways to the same extent suggests a common precursor as the proliferative agent. These results indicate that the PSCs were unaffected after a single treatment with 5-FU, although they were concentrated tenfold.
Myostatin, a transforming growth factor-? superfamily member, is expressed in heart muscle and is upregulated in cardiomyocytes after infarct (1999)

Myostatin is a secreted growth and differentiating factor (GDF-8) that belongs to the transforming growth factor-beta (TGF-beta) superfamily. Targeted disruption of the myostatin gene in mice and a mutation in the third exon of the myostatin gene in double-muscled Belgian Blue cattle breed result in skeletal muscle hyperplasia. Hence, myostatin has been shown to be involved in the regulation of skeletal muscle mass in both mice and cattle. Previous published reports utilizing Northern hybridization had shown that myostatin expression was seen exclusively in skeletal muscle. A significantly lower level of myostatin mRNA was also reported in adipose tissue. Using a sensitive reverse transcription-polymerase chain reaction (RT-PCR) technique and Western blotting with anti-myostatin antibodies, we show that myostatin mRNA and protein are not restricted to skeletal muscle. We also show that myostatin expression is detected in the muscle of both fetal and adult hearts. Sequence analysis reveals that the Belgian Blue heart myostatin cDNA sequence contains an 11 nucleotide deletion in the third exon that causes a frameshift that eliminates virtually all of the mature, active region of the protein. Anti-myostatin immunostaining on heart sections also demonstrates that myostatin protein is localized in Purkinje fibers and cardiomyocytes in heart tissue. Furthermore, following myocardial infarction, myostatin expression is upregulated in the cardiomyocytes surrounding the infarct area. Given that myostatin is expressed in fetal and adult hearts and that myostatin expression is upregulated in cardiomyocytes after the infarction, myostatin could play an important role in cardiac development and physiology.