gebhart/patrepeval huggingface dataset:
The gal Genes for the Leloir Pathway of Lactobacillus casei 64H (1998)

The gal genes from the chromosome of Lactobacillus casei 64H were cloned by complementation of the galK2 mutation of Escherichia coli HB101. The pUC19 derivative pKBL1 in one complementation-positive clone contained a 5.8-kb DNA HindIII fragment. Detailed studies with other E. coli K-12 strains indicated that plasmid pKBL1 contains the genes coding for a galactokinase (GalK), a galactose 1-phosphate-uridyltransferase (GalT), and a UDP-galactose 4-epimerase (GalE). In vitro assays demonstrated that the three enzymatic activities are expressed from pKBL1. Sequence analysis revealed that pKBL1 contained two additional genes, one coding for a repressor protein of the LacI-GalR-family and the other coding for an aldose 1-epimerase (mutarotase). The gene order of the L. casei gal operon is galKETRM. Because parts of the gene for the mutarotase as well as the promoter region upstream of galK were not cloned on pKBL1, the regions flanking the HindIII fragment of pKBL1 were amplified by inverse PCR. Northern blot analysis showed that the gal genes constitute an operon that is transcribed from two promoters. The galKp promoter is inducible by galactose in the medium, while galEp constitutes a semiconstitutive promoter located in galK.
A Low Temperature Drifting Acoustic Wave Pressure Sensor with an Integrated Vacuum Cavity for Absolute Pressure Sensing (2020)

In this paper we demonstrate a novel acoustic wave pressure sensor, based on an aluminum nitride (AlN) piezoelectric thin film. It contains an integrated vacuum cavity, which is micro-fabricated using a cavity silicon-on-insulator (SOI) wafer. This sensor can directly measure the absolute pressure without the help of an external package, and the vacuum cavity gives the sensor a very accurate reference pressure. Meanwhile, the presented pressure sensor is superior to previously reported acoustic wave pressure sensors in terms of the temperature drift. With the carefully designed dual temperature compensation structure, a very low temperature coefficient of frequency (TCF) is achieved. Experimental results show the sensor can measure the absolute pressure in the range of 0 to 0.4 MPa, while the temperature range is from 20 °C to 220 °C with a TCF of -14.4 ppm/°C. Such a TCF is only about half of that of previously reported works.
Isolation and characterization of different activated forms of factor VIII, the human antihemophilic A factor (1989)

Factor VIII was purified 1200-fold from commercial concentrates (Centre National de Transfusion Sanguine) by immunoaffinity chromatography using an anti-(80-kDa light chain) monoclonal antibody. The different molecular forms isolated were subsequently separated and analyzed using Fast Protein Liquid Chromatography and sodium dodecyl sulphate polyacrylamide gel electrophoresis analysis. The different factor-VIII forms obtained, consisted of 80-kDa light chains, each being associated with one more-or-less fragmented heavy chain ranging over 90-210 kDa. The specific activity of these different forms was 7000 U/mg. At different stages of activation of factor VIII by thrombin, various forms were separated and identified. Activated complexes were found to result from the association of the 70-kDa light chain (generated from the 80-kDa light chain) with heavy chains ranging over 90-210 kDa. Two different thrombin activation steps were characterized. The first step corresponding to the cleavage of the 80-kDa light chain led to a sixfold increase in the procoagulant activity, and yielded a stable activated intermediate form. Compared with normal factor VIII, the ratio of von Willebrand activity to factor-VIII activity, measured in the activated fractions, decreased, indicating that von Willebrand factor dissociates from factor VIII after proteolysis of the light chain by thrombin. In the second step, the 90-kDa heavy chain was cleaved into two polypeptides of 45 kDa and 50 kDa, which were associated with the 70-kDa proteolyzed light chain, generating the final activated complex (45-50-70 kDa). The new intermediate forms we described imply a new scheme for the multistep activation process of factor VIII.
Oriloc: prediction of replication boundaries in unannotated bacterial chromosomes (2000)

A program called Oriloc has been developed for the prediction of bacterial replication origins. The method builds on the fact that there are compositional asymmetries between the leading and the lagging strand for replication. The program works with unannotated sequences in fasta format and therefore uses glimmer 2.0 outputs to discriminate between codon positions so as to increase the signal/noise ratio.
Sodium/Calcium Exchange: Its Physiological Implications (1999)

The Na+/Ca2+ exchanger, an ion transport protein, is expressed in the plasma membrane (PM) of virtually all animal cells. It extrudes Ca2+ in parallel with the PM ATP-driven Ca2+ pump. As a reversible transporter, it also mediates Ca2+ entry in parallel with various ion channels. The energy for net Ca2+ transport by the Na+/Ca2+ exchanger and its direction depend on the Na+, Ca2+, and K+ gradients across the PM, the membrane potential, and the transport stoichiometry. In most cells, three Na+ are exchanged for one Ca2+. In vertebrate photoreceptors, some neurons, and certain other cells, K+ is transported in the same direction as Ca2+, with a coupling ratio of four Na+ to one Ca2+ plus one K+. The exchanger kinetics are affected by nontransported Ca2+, Na+, protons, ATP, and diverse other modulators. Five genes that code for the exchangers have been identified in mammals: three in the Na+/Ca2+ exchanger family (NCX1, NCX2, and NCX3) and two in the Na+/Ca2+ plus K+ family (NCKX1 and NCKX2). Genes homologous to NCX1 have been identified in frog, squid, lobster, and Drosophila. In mammals, alternatively spliced variants of NCX1 have been identified; dominant expression of these variants is cell type specific, which suggests that the variations are involved in targeting and/or functional differences. In cardiac myocytes, and probably other cell types, the exchanger serves a housekeeping role by maintaining a low intracellular Ca2+ concentration; its possible role in cardiac excitation-contraction coupling is controversial. Cellular increases in Na+ concentration lead to increases in Ca2+ concentration mediated by the Na+/Ca2+ exchanger; this is important in the therapeutic action of cardiotonic steroids like digitalis. Similarly, alterations of Na+ and Ca2+ apparently modulate basolateral K+ conductance in some epithelia, signaling in some special sense organs (e.g., photoreceptors and olfactory receptors) and Ca2+-dependent secretion in neurons and in many secretory cells. The juxtaposition of PM and sarco(endo)plasmic reticulum membranes may permit the PM Na+/Ca2+ exchanger to regulate sarco(endo)plasmic reticulum Ca2+ stores and influence cellular Ca2+ signaling.
Repulsive axon guidance molecule Slit3 is a novel angiogenic factor (2009)

Slits are large, secreted repulsive axon guidance molecules. Recent genetic studies revealed that the Slit3 is dispensable for neural development but required for non-neuron-related developmental processes, such as the genesis of the diaphragm and kidney. Here we report that Slit3 potently promotes angiogenesis, a process essential for proper organogenesis during embryonic development. We observed that Slit3 is expressed and secreted by both endothelial cells and vascular smooth muscle cells in vasculature and that the Slit cognate receptors Robo1 and Robo4 are universally expressed by endothelial cells, suggesting that Slit3 may act in paracrine and autocrine manners to regulate endothelial cells. Cellular function studies revealed that Slit3 stimulates endothelial-cell proliferation, promotes endothelial-cell motility and chemotaxis via interaction with Robo4, and accelerates endothelial-cell vascular network formation in vitro with a specific activity comparable with vascular endothelial growth factor. Furthermore, Slit3 stimulates neovessel sprouting ex vivo and new blood vessel growth in vivo. Consistent with these observations, the Slit3 knockout mice display disrupted angiogenesis during embryogenesis. Taken together, our studies reveal that the repulsive axon guidance molecule Slit3 is a novel and potent angiogenic factor and functions to promote angiogenesis in coordinating organogenesis during embryonic development.
Small Molecule Shape-Fingerprints (2005)

The optimal overlap between two molecular structures is a useful measure of shape similarity. However, it usually requires significant computation. This work describes the design of shape-fingerprints: binary bit strings that encode molecular shape. Standard measures of similarity between two shape-fingerprints are shown to be an excellent surrogate for similarity based on volume overlap but several orders of magnitude faster to compute. Consequently, shape-fingerprints can be used for clustering of large data sets, evaluating the diversity of compound libraries, as descriptors in SAR and as a prescreen for exact shape comparison against large virtual databases. Our results show that a small set of shapes can be used to build these fingerprints and that this set can be applied universally.
FOXA1 Expression in Breast Cancer—Correlation with Luminal Subtype A and Survival (2007)

FOXA1 expression correlates with luminal subtype A breast cancer and it is significant predictor of cancer-specific survival in patients with ER-positive tumors. Prognostic ability of FOXA1 in these low-risk breast cancers may prove to be useful in clinical treatment decisions.
Developments in the pharmacotherapeutic management of osteoporosis (2006)

During the last two decades, several medications have been granted a marketing authorisation for the management of osteoporosis. Bisphosphonates are the most widely prescribed drugs in this area, worldwide. Alendronate and risedronate are given daily or weekly and have demonstrated their ability to reduce fracture rates at the spine and hip. Ibandronate has demonstrated spine antifracture efficacy with intervals between dosings greater than weekly. New developments in this class include intravenous administration of ibandronate or zoledronate, once every three months or once yearly. Raloxifene, a selective estrogen-receptor modulator, reduces spine fractures and, in post-hoc analyses, non-spine fractures in high-risk subjects. New selective estrogen-receptor modulators, including lasofoxifene, bazedoxifene and arzoxifene, are expected to demonstrate antifracture efficacy at the hip level, whilst retaining the extra-skeletal benefits (such as in the breast) that are obtained with raloxifene. The peptides from the parathyroid hormone family are potent stimulators of bone formation. Teriparatide (1 - 34 amino acid fragment of the parathyroid hormone) reduces spine and non-spine fractures, an effect that is sustained for up to 30 months after the withdrawal of treatment. The intact hormone (1 - 84 amino acids) showed similar results on spine fractures, and more data are requested to evaluate its effect on non-spine or hip fractures. Strontium ranelate is suggested to be the first medication to uncouple bone formation from bone resorption. It has shown antifracture efficacy at all sites in a large number of postmenopausal women. New developments include: denosumab, an antibody against receptor activator of NF-kappaB ligand (RANKL); a cytokine that is responsible for osteoclastogenesis; and inhibitors of cathepsin K, a cysteine protease that is involved in the cleavage of collagen.
Raman Spectroscopic Study on the Copper(II) Binding Mode of Prion Octapeptide and Its pH Dependence (1999)

The cellular form of prion protein is a precursor of the infectious isoform, which causes fatal neurodegenerative diseases through intermolecular association. One of the characteristics of the prion protein is a high affinity for Cu(II) ions. The site of Cu(II) binding is considered to be the N-terminal region, where the octapeptide sequence PHGGGWGQ repeats 4 times in tandem. We have examined the Cu(II) binding mode of the octapeptide motif and its pH dependence by Raman and absorption spectroscopy. At neutral and basic pH, the single octapeptide PHGGGWGQ forms a 1:1 complex with Cu(II) by coordinating via the imidazole N pi atom of histidine together with two deprotonated main-chain amide nitrogens in the triglycine segment. A similar 1:1 complex is formed by each octapeptide unit in (PHGGGWGQ)2 and (PHGGGWGQ)4. Under weakly acidic conditions (pH approximately 6), however, the Cu(II)-amide- linkages are broken and the metal binding site of histidine switches from N pi to N tau to share a Cu(II) ion between two histidine residues of different peptide chains. The drastic change of the Cu(II) binding mode on going from neutral to weakly acidic conditions suggests that the micro-environmental pH in the brain cell regulates the Cu(II) affinity of the prion protein, which is supposed to undergo pH changes in the pathway from the cell surface to endosomes. The intermolecular His(N tau)-Cu(II)-His(N tau) bridge may be related to the aggregation of prion protein in the pathogenic form.
Regulation of transforming growth factor beta receptors in H-ras oncogene-transformed rat intestinal epithelial cells. (1995)

We have reported that over expression of the H-ras oncogene causes resistance to growth inhibition by transforming growth factor beta 1 (TGF-beta 1) and a time-dependant switch of type II to type I TGF-beta receptor expression in the rat intestinal epithelial cell line IEC-18 (J. Filmus, J. Zhao, and R. N. Buick, Oncogene, 7: 521-526, 1992). Here, we investigate the possible mechanisms involved in H-ras-mediated regulation of TGF-beta receptors in an IEC-18 cell clone expressing H-ras, conditional on the activity of a dexamethasone-sensitive promoter. The switch from type II to type I receptor expression in response to H-ras expression has a requirement for de novo RNA synthesis. In addition, accumulation of TGF-beta receptor type II mRNA is approximately 5-fold lower in ras-expressing cells compared to control cells. Nuclear run-on experiments suggest that the down-regulation of type II receptor mRNA by H-ras oncogene is based, at least in part, on reduced transcription. We have also analyzed the consequences of H-ras expression on the properties of the TGF-beta receptors. Type I and II in IEC-18 cells and type I receptors in ras-transformed cells have similar characteristics in terms of binding affinities for TGF-beta 1 (or TGF-beta 2) turnover rates and glycosylation states. Notably, the type I receptors in ras-transformed cells are not capable of ligand-induced internalization. Although H-ras expression in IEC-18 cells causes resistance to TGF-beta-mediated growth inhibition, the cells remain responsive to TGF-beta 1 stimulation of fibronectin expression. These results are discussed in the context of the knowledge of TGF-beta receptor complexity and signal transduction, and with reference to the potential role for loss of TGF-beta-mediated negative growth regulation in malignant transformation.
Therapeutic Effects of ALT-803, an IL-15 Superagonist, in Combination with Anti-CD20 Chimeric Antigen Receptor Modified Expanded Natural Killer Cells Against Burkitt Lymphoma (BL) (2016)

Our group has successfully modified expanded peripheral blood Natural Killer cells (exPBNK) with an anti-CD20 CAR to target rituximab sensitive/resistant CD20+ BL cells in vitro and in NSG mice (Chu/Cairo, et al, Can Imm Res 2015). However, the short lifespan/persistence of adoptively transferred NK cells has limited the therapeutic efficacy of these CAR NK cells. ALT-803 (Altor BioScience Corporation) is a superagonist of an IL-15 variant bound to an IL-15RαSu-Fc fusion with enhanced IL-15 biological activity (Zhu et al. 2009 J Immunol), longer half-life, better lymphoid tissue retention, increased potency, less toxicity (Han, et al. Cytokine. 2011). ALT-803 is currently in several clinical trials including refractory indolent non-Hodgkin's lymphoma (NCT02384954). To determine if ALT-803 promotes exPBNK persistence and significantly enhances the cytotoxicity of anti-CD20 CAR exPBNK against CD20+ BL. PBMCs were expanded with lethally irradiated K562-mbIL21-41BBL cells (Lee et al, PLoS One, 2012). CD56+CD3- exPBNK cells were isolated using Miltenyi NK cell isolation kit. Anti-CD20-4-1BB-CD3ζ mRNA (CAR mRNA) was produced in vitro and nucleofected into exPBNK as we have previously described (Chu/Cairo et al, Can Imm Res 2015). ALT-803 was generously provided by Altor BioScience Corporation. ExPBNK were cultured with 0.35 or 3.5ng/ml ALT-803. NK proliferation, NK receptors expression and cytotoxicity were examined (Chu/Cairo, et al, ASH 2014). NK resistant BL cells Raji and Daudi were used as target cells. Different doses of ALT-803 or IgG were added to the culture medium of purified expanded exPBNK. Proliferation assays were performed at day 3, 7, 11, and 17. ALT-803 significantly promoted exPBNK proliferation and persistence compared to IgG in vitro in a dose-dependent manner. Similar to IL-15, ALT-803 induced exPBNK proliferation by increasing the phosphorylation of Akt, Stat3/5 and p38 MAPK but not mTOR nor ERK1/2. ALT-803 significantly enhanced exPBNK cytotoxicity against Raji (p<0.001) and Daudi (p<0.001) in part by increasing the activating receptors' expression such as NKG2D, NKp30, NKp44, and NKp46. Further more, we demonstrated that the in vitro cytotoxicity of anti-CD20 CAR exPBNK was significantly enhanced by ALT-803 against Raji and Daudi compared to mock-electroporated exPBNK maintained in ALT803 medium (p<0.001) and compared to anti-CD20 CAR modified exPBNK maintained in medium without ALT803 (p<0.01) (Fig. 1). Additionally, we observed that the combination of anti-CD20 CAR NK and ALT-803 reduced tumor burden in Raji xenografted mice. ALT-803 significantly enhanced in vitro cytotoxicity and in vitro persistence of exPBNK and significantly enhanced anti-CD20 CAR exPBNK cytotoxicity against NK resistant BL. Further in vivo effects of ALT-803 on CAR exPBNK using humanized BL NSG mice are under investigation.
Does Intradiscal Electrothermal Therapy Denervate and Repair Experimentally Induced Posterolateral Annular Tears in an Animal Model? (2003)

Vascular granulation tissue and posterior annular neo-innervation was observed in the experimentally induced posterolateral annular lesion. IDET delivered at 90C in the sheep consistently heated the posterior annulus and the nucleus to a temperature normally associated with coagulation of nociceptors and collagen contraction. IDET did not denervate the posterior annular lesion. Thermal necrosis was observed within the inner annulus and adjacent nucleus from 6 weeks after IDET. The reported benefits from IDET appear to be related to factors other than denervation and repair.
Palmitoylation of the human β2-adrenergic receptor (1989)

We report that a cysteine residue in the human beta 2-adrenergic receptor (beta 2AR) is covalently modified by thioesterification with palmitic acid. By site-directed mutagenesis of the receptor, we have identified Cys341 in the carboxyl tail of the protein as the most likely site of palmitoylation. Mutation of Cys341 to glycine results in a nonpalmitoylated form of the receptor that exhibits a drastically reduced ability to mediate isoproterenol stimulation of adenylyl cyclase. The functional impairment of this mutated beta 2AR is also reflected in a markedly reduced ability to form a guanyl nucleotide-sensitive high affinity state for agonists, characteristic of wild-type receptor. These results indicate that post-translational modification by palmitate of beta 2AR may play a crucial role in the normal coupling of the receptor to the adenylyl cyclase signal transduction system.
Naturally occurring porcine relaxins and large-scale preparation of the B29 hormone (1985)

Porcine ovaries were collected from pregnant sows under conditions designed to keep autolysis to an absolute minimum. During the extraction the tissues were never allowed to warm up to 0 degree C until submerged in 1.6 N HCl. Isolation and fractionation of the various relaxin forms became possible by application of CM-cellulose chromatography at pH 5.5 and 7.8, gel filtration, and high-performance liquid chromatography. The new isolation procedure has made it possible to isolate and identify LeuB32 relaxin. Also, [Leu-PheA0]B29 relaxin was identified and the existence of a [Leu-PheA0]B32 relaxin may be deduced from our data. Controlled digestion of B-chain-extended relaxins with carboxypeptidase A led to the large-scale production of homogeneous B29 relaxin, a suitable starting material for controlled chemical modification of porcine relaxin.
Influence of Meal Ingestion Time on Pharmacokinetics of Orally Administered Levodopa in Parkinsonian Patients (1987)

The influence of meal ingestion time on rate and extent of oral levodopa absorption was evaluated in a group of 17 patients, after administration of their usual second daily dose of levodopa plus carbidopa (Sinemet 10:1) or benserazide (Madopar 4:1). Standard meals were consumed by the patients after they had fasted 15-17 h, on one occasion 30 min before ingestion of the levodopa "study dose" and, at another time, 2 h after ingestion of the same dose. This study dose, ranging from 50 to 250 mg levodopa, was given to the patients at 11 a.m., 4 h after their first morning dose. Time to peak plasma levodopa concentration increased threefold (from 45 +/- 23 to 134 +/- 76 min, p less than 0.001), when levodopa was administered after meals. Area under the 6-h plasma concentration-time curve for levodopa was decreased in 10 subjects, unchanged in three and higher in four after ingestion of meals, the latter finding probably resulting from an erratic absorption even at fasting. On the whole, levodopa absorption proved significantly lower (p less than 0.01), on the average 15%. Similarly, peak plasma levodopa concentrations were lower in 12 patients, unchanged in two, and higher in three, with an overall significant decrease (p less than 0.001) of 30% on the average. The data confirm the importance of meal ingestion time in relation to levodopa dose as a determinant of drug absorption.
Regional infusion of urokinase into occluded lower-extremity bypass grafts: long-term clinical results. (1989)

The initial outcome, long-term patency rate, and rate of limb salvage were studied in patients after regional urokinase infusion for treatment of thrombosed lower-extremity grafts. Seventy-one infusions were performed in 53 patients. Complete clot lysis occurred in 75% of grafts, with establishment of antegrade blood flow in 66%. Variables that favorably influenced clot lysis and the reestablishment of antegrade blood flow through the graft were a short duration of occlusion and a suprainguinal graft position. The median duration of patency after infusion and adjunctive therapy was 162 days, with 75% limb salvage at 301 days. No statistically significant variables that influenced the length of patency were identified. These long-term patency results are inferior to the reported results in suprainguinal grafts after reoperation. They appear similar to reported results for occluded infrainguinal grafts treated with thrombectomy and patch grafting.