gebhart/patrepeval huggingface dataset:
Substrate‐dependent negative selection in plants using a bacterial cytosine deaminase gene (1993)

Summary The inability of many higher eukaryotes to convert 5‐fluorocytosine to cytotoxic 5‐fluorouracil presents the possibility of using the bacterial cytosine deaminase codA gene for negative selection. In transformed plant callus, expression of codA results in cell death on 5‐fluorocytosine. In transgenic tobacco and Lotus japonicus plants the substrate‐dependent negative marker segregates as a single dominant gene, and on 5‐fluorocytosine CodA + seedlings stop growing at the early seedling stage. Positive selection of CodA + tobacco on the pyrimidine biosynthetic inhibitor N ‐(phosphonacetyl)‐l‐aspartate was obtained, by pyrimidine salvage from external cytosine. Activity of cytosine deaminase was determined by conversion of labelled cytosine to uracil followed by separation in thin layer chromatography. The codA marker therefore provides substrate‐dependent negative and positive selection, together with cytosine deaminase reporter activity.
Adhesive Forces Between Aromatic Molecules and Graphene (2014)

Adhesive forces were investigated in a computational study for the complexes of graphene with each of the four adsorbates, benzene, anthracene, pyrene, and tetracene, by using the DFT method B3LYP and the semiempirical method DFTB, together with empirical dispersion corrections. The four aromatic molecules differ in size and flexibility. Whereas the adhesion energy (for complete separation) is independent of the way an adsorbed molecule is separated from graphene, the maximum adhesive forces depend strongly on the way the adsorbate is lifted. We investigated, therefore, four lifting modes: in rigid vertical lifting, all atoms of the adsorbate are pull-off points; in flexible central lifting, the pull-off points are in the middle of the adsorbate; in both rigid and flexible terminal lifting, the pull-off points are at one end and the adsorbate is regarded as being either rigid or flexible. For the systems investigated, we find that, for both the adhesion energies and the maximum adhesive forces, the DFTB results are at most 10% lower than the corresponding DFT results. For small or rigid molecules like benzene and pyrene, there is no significant difference between rigid vertical and flexible central lifting. For a flexible molecule like tetracene, the difference of the maximum adhesive force can be up to 70%. Terminal lifting consists of two subprocesses. For the second subprocess, both the adhesion energy and the maximum adhesive force are essentially unchanged across all four adsorbates; for the first subprocess, however, we find a pronounced size dependence of the adhesion energy.
Solid Phase Peptide Synthesis by Oxidation-Reduction Condensation. Synthesis of Adrenocorticotropin(1–24) by Chain Elongation at the Carboxyl End on Solid Support (1976)

Abstract Solid phase peptide synthesis by oxidation-reduction condensation via fragment condensation at the carboxyl end was established by a new monitoring method based on high pressure liquid chromatography. The merit of the method was demonstrated through the synthesis of ACTH (1–24). A resin–tetracosapeptide with quantitative amino acid ratios was easily prepared by coupling 6 fragments of 1–2, 3–7, 8–10, 11–14, 15–19, and 20–24 sequences. ACTH (1–24) with a full activity was obtained in 25% yield from the initial resin-dipeptide by hydrogen fluoride treatment and purification with carboxymethyl-cellulose chromatography.
Pharmacokinetic and Pharmacodynamic Effects of Clonazepam in Children With Epilepsy Treated With Valproate: A Preliminary Study (2002)

The authors report the use of the quantitative pharmaco-EEG (QPEEG) technique to study the pharmacokinetics (PK) and pharmacodynamics (PD) of clonazepam (CZP) in four epileptic children who suffered uncontrolled seizures despite long-term valproate (VPA) therapy. After a single dose of CZP (0.05 mg/kg, PO), blood samples were collected at 0, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 8.0, 12.0, and 24.0 hours. CZP and VPA concentrations were measured by HPLC or GC assay, respectively. At each blood collection time point, EEG signals (60 s) were recorded for brain electrical activity mapping, and the power percentage average (PPA) of each frequency band was calculated. The relationship between drug concentrations and their corresponding PPA of each frequency band was analyzed. VPA steady-state drug concentrations (Css) were within the therapeutic range and not affected by CZP. The peak concentration (Cmax) of CZP and the time intervals from dosing to Cmax (Tmax) were 20.9 ng/mL to 113.8 ng/mL and 1 hour to 1.5 hours, respectively. There was no significant correlation between VPA concentrations and the PPA of any of the EEG frequency bands. CZP blood concentrations showed significant correlation with PPA in 3 of the 4 patients. Our results suggested CZP could affect fast wave activities in proportion to CZP blood concentrations. We propose that QPEEG is a promising technique to study the PK and PD of selected anti-epileptic drugs.
Nicotinic binding in rat brain: autoradiographic comparison of [3H]acetylcholine, [3H]nicotine, and [125I]-alpha-bungarotoxin (1985)

Three radioligands have been commonly used to label putative nicotinic cholinoceptors in the mammalian central nervous system: the agonists [3H]nicotine and [3H]acetylcholine ([3H]ACh--in the presence of atropine to block muscarinic receptors), and the snake venom extract, [125I]-alpha-bungarotoxin([125I]BTX), which acts as a nicotinic antagonist at the neuromuscular junction. Binding studies employing brain homogenates indicate that the regional distributions of both [3H]nicotine and [3H]ACh differ from that of [125I]BTX. The possible relationship between brain sites bound by [3H]nicotine and [3H]ACh has not been examined directly. We have used the technique of autoradiography to produce detailed maps of [3H]nicotine, [3H]ACh, and [125I]BTX labeling; near-adjacent tissue sections were compared at many levels of the rat brain. The maps of high affinity agonist labeling are strikingly concordant, with highest densities in the interpeduncular nucleus, most thalamic nuclei, superior colliculus, medial habenula, presubiculum, cerebral cortex (layers I and III/IV), and the substantia nigra pars compacta/ventral tegmental area. The pattern of [125I]BTX binding is strikingly different, the only notable overlap with agonist binding being the cerebral cortex (layer I) and superior colliculus. [125I]BTX binding is also dense in the inferior colliculus, cerebral cortex (layer VI), hypothalamus, and hippocampus, but is virtually absent in thalamus. Various lines of evidence suggest that the high affinity agonist-binding sites in brain correspond to nicotinic cholinergic receptors similar to those found at autonomic ganglia; BTX-binding sites may also serve as receptors for nicotine and are possibly related to neuromuscular nicotinic cholinoceptors.
In vitrobiotransformation of imatinib by the tumor expressed CYP1A1 and CYP1B1 (2008)

The main objective of the study was to examine the biotransformation of the anticancer drug imatinib in target cells by incubating it with oxidoreductases expressed in tumor cells. The second objective was to obtain an in silico prediction of the potential activity of imatinib metabolites. An in vitro enzyme kinetic study was performed with cDNA expressed human oxidoreductases and LC-MS/MS analysis. The kinetic parameters (Km and Vmax) were determined for six metabolites. A molecular modeling approach was used to dock these metabolites to the target Abl or Bcr-Abl kinases. CYP3A4 isozyme showed the broadest metabolic capacity, whereas CYP1A1, CYP1B1 and FMO3 isozymes biotransformed imatinib with a high intrinsic clearance. The predicted binding modes for the metabolites to Abl were comparable to that of the parent drug, suggesting potential activity. These findings indicate that CYP1A1 and CYP1B1, which are known to be overexpressed in a wide range of tumors, are involved in the biotransformation of imatinib. They could play a role in imatinib disposition in the targeted stem, progenitor and differentiated cancer cells, with a possible contribution of the metabolites toward the activity of the drug.
Respiratory Syncytial Virus (RSV) G Glycoprotein Is Not Necessary for Vaccine-Enhanced Disease Induced by Immunization with Formalin-Inactivated RSV (2004)

Following respiratory syncytial virus (RSV) challenge, mice immunized with RSV G or with formalin-inactivated RSV (FI-RSV) exhibit severe disease associated with type 2 cytokine production and pulmonary eosinophilia. This has led to the proposal that the presence of RSV G is the factor in FI-RSV that induces disease-enhancing T-cell responses. Therefore, we evaluated the role of RSV G and its immunodominant region in the induction of aberrant immune responses during FI-RSV immunization. BALB/c mice were immunized with FI preparations of wild-type (wt) RSV or recombinant RSV (rRSV) containing deletions of (i) the entire G gene, (ii) the region of the G gene encoding amino acids 187 to 197 of the immunodominant region, or (iii) the entire SH gene. After challenge, illness, RSV titers, cytokine levels, and pulmonary eosinophilia were measured. Peak RSV titers postchallenge were significantly greater in mice immunized with FI preparations of the deletion viruses than in those immunized with FI-rRSV wt, suggesting that the absence of G or SH in FI-RSV reduced its protective efficacy. Deletion of G or its epitope did not reduce illness, cytokine production, or eosinophilia relative to that in mice immunized with FI-rRSV wt. While cytokine levels and eosinophilia were similar, illness was reduced in mice immunized with SH-deleted FI-RSV. These data suggest that G-specific immune responses may be important for vaccine-induced protection and are not solely the basis for FI-RSV vaccine-enhanced illness. These data suggest that the method of RSV antigen delivery, rather than the protein composition, influences the phenotype of the induced immune responses and that RSV G should not necessarily be excluded from potential vaccine strategies.
In Vivo Imaging of Histone Deacetylases (HDACs) in the Central Nervous System and Major Peripheral Organs (2014)

Epigenetic enzymes are now targeted to treat the underlying gene expression dysregulation that contribute to disease pathogenesis. Histone deacetylases (HDACs) have shown broad potential in treatments against cancer and emerging data supports their targeting in the context of cardiovascular disease and central nervous system dysfunction. Development of a molecular agent for non-invasive imaging to elucidate the distribution and functional roles of HDACs in humans will accelerate medical research and drug discovery in this domain. Herein, we describe the synthesis and validation of an HDAC imaging agent, [(11)C]6. Our imaging results demonstrate that this probe has high specificity, good selectivity, and appropriate kinetics and distribution for imaging HDACs in the brain, heart, kidney, pancreas, and spleen. Our findings support the translational potential for [(11)C]6 for human epigenetic imaging.
Blood—Brain Barrier Breakdown Involves Four Distinct Stages of Vascular Damage in Various Models of Experimental Focal Cerebral Ischemia (2014)

Ischemic stroke not only impairs neuronal function but also affects the cerebral vasculature as indicated by loss of blood-brain barrier (BBB) integrity. Therefore, therapeutical recanalization includes an enhanced risk for hemorrhagic transformation and bleeding, traditionally attributed to a 'reperfusion injury'. To investigate the mechanisms underlying ischemia-/reperfusion-related BBB opening, we applied multiple immunofluorescence labeling and electron microscopy in a rat model of thromboembolic stroke as well as mouse models of permanent and transient focal cerebral ischemia. In these models, areas exhibiting BBB breakdown were identified by extravasation of intravenously administered fluorescein isothiocyanate (FITC)-albumin. After 24 hours, expression of markers for tight and adherens junctions in areas of FITC-albumin leakage consistently remained unaltered in the applied models. However, lectin staining with isolectin B4 indicated structural alterations in the endothelium, which were confirmed by electron microscopy. While ultrastructural alterations in endothelial cells did not differ between the applied models including the reperfusion scenario, we regularly identified vascular alterations, which we propose to reflect four distinct stages of BBB breakdown with ultimate loss of endothelial cells. Therefore, our data strongly suggest that ischemia-related BBB failure is predominantly caused by endothelial degeneration. Thus, protecting endothelial cells may represent a promising therapeutical approach in addition to the established recanalizing strategies.
Comorbidity of body dysmorphic disorder and eating disorders: Severity of psychopathology and body image disturbance (2005)

Eating disorders appear relatively common in individuals with BDD. BDD subjects with a comorbid eating disorder differed on several demographic variables, had greater comorbidity and body image disturbance, and had received more mental health treatment than subjects without a comorbid eating disorder. These findings have important implications for the assessment and treatment of these comorbid body image disorders.
Antiviral Activities of Methylated Nordihydroguaiaretic Acids. 1. Synthesis, Structure Identification, and Inhibition of Tat-Regulated HIV Transactivation (1998)

Nordihydroguaiaretic acid (NDGA, meso-1) possesses four phenolic hydroxyl groups. Treatment of NDGA with 0.50-4.1 equiv of dimethyl sulfate and 3.0-6.0 equiv of potassium carbonate in acetone at 56 degrees C gave nine methylated products. Eight of those mono-, di-, tri-, and tetra-O-methylated NDGAs were isolated in pure form, and their structures were identified unambiguously by spectroscopic methods. A preparative amount of tetramethyl NDGA M4N (10) was obtained in 99% yield from NDGA by use of 4.1 equiv of dimethyl sulfate for the methylation. Among the eight different methylated NDGAs (2-6 and 8-10), tetra-O-methyl-NDGA (10) showed the strongest anti-HIV activity (IC50 11 microM). Chemically synthesized 3'-O-methyl-NDGA ((+/-)-2) showed identical anti-HIV activity (IC50 25 microM) to the lignan isolated from Creosote Bush. Lignans with methylated catecholic hydroxyl groups can be produced in large quantities with low cost. At drug concentrations below 30 microM tetramethyl NDGA (10) was a stronger anti-HIV agent than mono- and dimethylated NDGAs.
Alterations of Sodium Channel Kinetics and Gene Expression in the Postinfarction Remodeled Myocardium (2001)

Our findings raise the possibility that the increase in the slow component of I(Na) in post-MI remodeled myocytes is secondary to the increased expression of NaCh I. Additional studies are required to address these questions and to characterize the functional role of the NaCh I subtypes in cardiac myocytes.
Creatine Kinase MB Isoforms in Patients with Skeletal Muscle Injury: Ramifications for Early Detection of Acute Myocardial Infarction (1992)

We measured total creatine kinase (CK), CK-MB isoenzyme, and the MB isoforms in 202 serum and plasma samples from nine groups of patients and normal individuals: 39 with acute myocardial infarction (MI), divided according to time between the onset of chest pain and blood collection (1-6 h, 7-12 h, and 13-48 h); 26 with chest pain for whom an MI was ruled out, sampled at admission; 17 undergoing bypass surgery or cardiac catheterization, sampled within 6 h after either procedure; 17 with acute skeletal muscle injury, sampled within 8 h after injury; 30 marathon runners immediately after a race; 17 runners and other athletes > 12 h after training or a race; 12 with cerebral injury or seizures, sampled at admission; 8 with closed head injury, sampled at admission; and 38 normal subjects. CK-MB (relative index) and MB isoforms (MB2/MB1) were respectively increased in 15% and 75% of MI patients 1-6 h after onset, 94% and 94% after 7-12 h, and 88% and 8% after 12 h, and in 87% and 82% of cardiac surgery patients. MB isoforms were increased in most patients with acute skeletal muscle trauma and in subjects examined after exercise, but were within normal limits in patients for whom MI was ruled out, patients with cerebral trauma, and normal individuals. The relative index of MB/total CK was normal in essentially all individuals in the last groups, including those with acute skeletal muscle trauma. We concluded that the CK-MB isoform ratio is increased in both acute skeletal muscle injury and MI. The isoform ratio is most useful for distinguishing recent from old (> 12 h) injury.
Characterization of the 56‐kDa subunit of yeast trehalose‐6‐phosphate synthase and cloning of its gene reveal its identity with the product of CIF1, a regulator of carbon catabolite inactivation (1992)

Trehalose-6-phosphate synthase is the key enzyme for biosynthesis of trehalose, the major soluble carbohydrate in resting cells of yeast. This enzyme was purified from a strain of Saccharomyces cerevisiae lacking vacuolar proteases. It was found to be a multimeric protein of 630 kDa. Monoclonal antibodies were raised against its smallest subunit (56 kDa) and used for screening a yeast cDNA library. This yielded an immunopositive cDNA clone of 1.7 kb, containing an open reading frame of 1485 base pairs. Its sequence, called TPS1 (for trehalose-6-phosphate synthase), was represented by a single gene in the yeast genome and was found to be almost identical with the recently sequenced CIF1, a gene important for carbon catabolite inactivation, believed to be allelic with FDP1. A mutant obtained by disruption of TPS1 had a very low activity of trehalose-6-phosphate synthase, indicating that TPS1 is an important component of the enzyme. The mutant also showed a growth defect when transferred from glycerol to glucose, a phenotype similar to that of the cif1 and fdp1 mutants deficient in carbon catabolite inactivation. Thus, the smallest subunit of the biosynthetic enzyme trehalose-6-phosphate synthase appears to have, in addition, a central regulatory role in the carbohydrate metabolism of yeast.
26.7 A 10mm3 syringe-implantable near-field radio system on glass substrate (2016)

We present a millimeter-scale near-field radio system for ultra-low-power (ULP) healthcare sensor nodes. It is specifically designed for `syringe implantation' which minimizes invasiveness of implantation. Designing a millimeter-scale wireless node for implanted healthcare is challenging because: 1) the antenna is constrained to the diameter of the syringe needle, which significantly constrains the link distance through RF. 2) The energy/power are strictly limited by the millimeter-scale form-factor where thin-film batteries can source only <;10μAh and sustain <;50μA peak current. Recent works [1-4] have demonstrated near-field transceivers for millimeter-scale implants. Passive backscatter radios consume low power but they are only operable at very short distances (e.g., 3.5cm) due to excessive path loss and self-jamming at the reader [1-2]. Although active radios can provide >10cm distance, their high power consumption (45mW [3]) and/or large antenna size (2.3cm×2.4cm [4]) make them impractical for implanted healthcare applications.
A floating, offshore satellite launching facility (1997)

This paper describes a concept for a floating, offshore satellite launching facility capable of meeting present and future lift-off needs while providing for greater environmental acceptability, improved safety, and economic competitiveness with coastal, land-based systems. The paper pertains only to information- and communications-type satellite payloads and their attendant systems. However, the floating facility concept discussed herein can be scaled up and expanded to handle the largest of systems.
Electron irradiation slows down wound repair in rat skin: a morphological investigation (1994)

To date, there have been few morphological investigations of the effect of electron radiation on the healing of skin wounds in rats. The present morphological study examines the wound repair process in electron-irradiated rat skin by electron microscopy. Standardized, full-thickness, incisional wounds were made in the lower dorsal skin of animals which had been locally irradiated with 9.6 Gy electron radiation 7 days previously. The irradiation dose was maximal at 3 mm depth. Twenty-four rats were used in the investigation; 12 were irradiated and 12 sham-irradiated. Three rats from each experimental group were killed at 1, 3, 7 and 14-day time intervals after wounding. The morphological effect of electron irradiation on the repair of each wound was investigated by light microscopy (LM) and scanning electron microscopy (SEM). New granulation tissue visualized by SEM was quantified using computerized image analysis. The results suggest that a single, partial-body, controlled depth dose of electron irradiation delays wound repair. LM showed that there is a depression of the inflammatory cell and tissue exudate response, slowing of epithelial migration, and a decrease in fibroblast representation, together with a delay in the formation of collagen bundles. Granulation tissue formation was impaired up to 7 days post-wounding, but was restored to around control values by day 14, indicating that healing was delayed. However, as the healing of normal tissue was not prevented, this study supports a preoperative role for the use of low-dose electron irradiation therapy for the treatment of electron-sensitive superficial pathologies in surgical practice.
Regulation of G1/S transition by cyclins D2 and D3 in hematopoietic cells. (1993)

Identification of the genes that control passage through the G1 phase of the cell cycle in mammalian cells is of particular interest because virtually all external events that regulate proliferation act primarily or exclusively during G1. Cyclins are likely to play a key role in controlling cell cycle progression, although their role during G1 in higher eukaryotic cells is unclear. In the hematopoietic cell line 32Dcl3, both cyclins D2 and D3 were expressed in proliferating cells, while cyclin D1 was undetectable. Expression of D2, and to a lesser extent D3, was interleukin 3 (IL-3) dependent and declined rapidly in the absence of this growth factor. To investigate the potential role of D cyclins in regulating cell growth, cell lines overexpressing either D2 or D3 were generated by transfection. Constitutive overexpression of either D2 or D3 did not affect cell viability, rate of cell proliferation, or dependence on IL-3 for growth. However, the distribution of cells through the cell cycle was dramatically altered, with both cyclins causing an increase in the fraction of cells in S phase, apparently related to a shortening of G1. Also, when deprived of IL-3, D3-overexpressing cells failed to arrest in G1, and apoptotic cell death in the absence of IL-3 was delayed. These results suggest a role for cyclins D2 and D3 in controlling passage of hematopoietic cells through G1 in the presence of growth factors and in effecting G1 arrest in the absence of growth factors.