gebhart/patrepeval huggingface dataset:
Expression and characterization of a second L‐amino acid deaminase isolated from Proteus mirabilis in Escherichia coli (2011)

L-amino acid deaminases catalyze the deamination of natural L-amino acids. Two types of L-amino acid deaminase have been identified in Proteus species. One exhibits high levels of activity toward a wide range of aliphatic and aromatic L-amino acids, typically L-phenylalanine, whereas the other acts on a relatively narrow range of basic L-amino acids, typically L-histidine. In this study, we cloned, expressed, and characterized a second amino acid deaminase, termed Pm1, from P. mirabilis KCTC 2566. Homology alignment of the deduced amino acid sequence of Pm1 demonstrated that the greatest similarity (96%) was with the L-amino acid deaminase (LAD) of P. vulgaris, and that homology with Pma was relatively low (72%). Also, similar to LAD, Pm1 was most active on L-histidine, indicating that Pm1 belongs to the second type of amino acid deaminase. In agreement with this conclusion, the V(max) and K(m) values of Pm1 were 119.7 (μg phenylpyruvic acid/mg/min) and 31.55 mM phenylalanine, respectively, values lower than those of Pma. The Pml deaminase will be very useful industrially in the preparation of commercially valuable materials including urocanic acid and α-oxoglutarate.
SHOX mutations detected by FISH and direct sequencing in patients with short stature (2003)

Height is the result of interactions of several factors including those of genetic origin. About 3% of people have short stature and in most of them the cause is unknown.1 Recently, the SHOX gene (short stature homeobox containing gene), mapped on the pseudoautosomal region (PAR1) of the X and Y chromosomes, has been specifically associated with the short stature of patients with Turner syndrome or with Leri-Weill dyschondrosteosis (LWD).2–7 Few data have been reported on the relationship between SHOX mutations and idiopathic short stature. Rao et al 2 reported one change among 91 patients with idiopathic short stature, and Binder et al 8 found a mutation in one out of 68 patients. The largest study was recently published by Rappold et al ,9 who found a frequency of 2.4% of SHOX mutations using fluorescence in situ hybridisation (FISH) on 150 patients and single strand conformational polymorphism analysis (SSCP) on 750 patients.

We report a study carried out on 56 patients with short stature of unknown origin detecting SHOX mutations in seven (12.5%) by using FISH and direct sequencing analyses.

### Patients

Fifty-six patients, 33 females and 23 males, with a mean age of 12.2 years (range 5-18 years) entered this study. All patients were unrelated, coming from different regions of central and southern Italy. In order to exclude patients with dyschondrosteosis or other diseases associated with short stature, we used the following criteria: (1) height at or below the 3rd centile; (2) absence of obvious skeletal abnormalities on physical examination; (3) absence of other diseases on physical examination and routine analyses; (4) normal bone age; (5) normal hGH values using a polyclonal in house RIA (lower detection limit 0.1 ng/μl, mean intra-assay coefficient of variation 6.9%, and mean interassay coefficient 9.5%); and (6) normal karyotype in 16 metaphases …
APRIL/TRDL-1, a tumor necrosis factor-like ligand, stimulates cell death. (2000)

We have examined the activity of a new member of the tumor necrosis factor (TNF) family identified through Expressed Sequence Tag database searching using TNFalpha protein as the search query. We have termed this protein TNF-related death ligand-la (TRDL-1alpha). Traditional cDNA library screening identified two additional splice variants designated TRDL-1beta and TRDL-1gamma that differed from TRDL-1alpha by the deletion of two small regions within the protein coding region. TRDL-1alpha is identical in sequence to the recently described molecule, APRIL, that may induce cell proliferation. We found, however, that purified, FLAG-tagged TRDL-1alpha caused Jurkat cell death with kinetics that paralleled FasL. In vitro binding experiments demonstrated that TRDL-1alpha coprecipitated Fas and HVEM and suggested TRDL-1alpha as an alternate ligand for these receptors. TRDL-1 localized to chromosome 17p13.3 and its expression was widespread in normal tissues. Examination of 48 tumor samples revealed high levels of TRDL-1 expression in several tumors, including those from the gastrointestinal tract. Expression of TRDL-1 in COS-1 cells confirmed membrane association of TRDL-1, typical of TNF family members.
Large-scale quantum computation in an anharmonic linear ion trap (2009)

We propose a large-scale quantum computer architecture by stabilizing a single large linear ion chain in a very simple trap geometry. By confining ions in an anharmonic linear trap with nearly uniform spacing between ions, we show that high-fidelity quantum gates can be realized in large linear ion crystals under the Doppler temperature based on coupling to a near-continuum of transverse motional modes with simple shaped laser pulses.
Clinical consequences of cytochrome P450 2C9 polymorphisms (2005)

The gene coding for the cytochrome P450 (CYP) enzyme 2C9 (CYP2C9) carries numerous inherited polymorphisms. Those coding for R144C (*2) and I359L (*3) amino acid substitutions have both significant functional effects and appreciable high population frequencies, and their in vivo consequences have been studied in humans with regard to drug metabolism. This review summarizes present knowledge about the pharmacokinetics, drug responses, and outcomes of clinical studies in individuals with different CYP2C9 genotypes. Tentative estimates of how CYP2C9 genotyping might be applied to dose adjustments in clinical therapy were based on dose-related pharmacokinetic parameters such as clearance or trough drug concentrations. Mean clearances in homozygous carriers of the *3 allele were below 25% of that of the wild type for S -warfarin, tolbutamide, glipizide, celecoxib, and fluvastatin. In the more frequent heterozygous carriers (genotype *1/*3), the clearances were between 40% and 75%. In these cases in which individual dosages are derived from clinical drug effects, such as for the oral anticoagulants, the pharmacogenetics-based dose adjustments showed a good correlation with the genotype-specific empirically derived doses. In addition to its role in pharmacokinetics, CYP2C9 contributes to the metabolism of fatty acids, prostanoids, and steroid hormones, and it may catalyze potentially toxic bioactivation reactions. However, our current understanding of the role of CYP2C9 in biotransformation of endogenous signaling molecules and in drug toxicity is relatively meager.
Chromosomal organization of adrenergic receptor genes. (1990)

The adrenergic receptors (ARs) (subtypes alpha 1, alpha 2, beta 1, and beta 2) are a prototypic family of guanine nucleotide binding regulatory protein-coupled receptors that mediate the physiological effects of the hormone epinephrine and the neurotransmitter norepinephrine. We have previously assigned the genes for beta 2- and alpha 2-AR to human chromosomes 5 and 10, respectively. By Southern analysis of somatic cell hybrids and in situ chromosomal hybridization, we have now mapped the alpha 1-AR gene to chromosome 5q32----q34, the same position as beta 2-AR, and the beta 1-AR gene to chromosome 10q24----q26, the region where alpha 2-AR is located. In mouse, both alpha 2- and beta 1-AR genes were assigned to chromosome 19, and the alpha 1-AR locus was localized to chromosome 11. Pulsed field gel electrophoresis has shown that the alpha 1- and beta 2-AR genes in humans are within 300 kilobases (kb) and the distance between the alpha 2- and beta 1-AR genes is less than 225 kb. The proximity of these two pairs of AR genes and the sequence similarity that exists among all the ARs strongly suggest that they are evolutionarily related. Moreover, they likely arose from a common ancestral receptor gene and subsequently diverged through gene duplication and chromosomal duplication to perform their distinctive roles in mediating the physiological effects of catecholamines. The AR genes thus provide a paradigm for understanding the evolution of such structurally conserved yet functionally divergent families of receptor molecules.
Lipiodol-based emulsions used for transarterial chemoembolization and drug delivery: Effects of composition on stability and product quality (2019)

Transarterial chemoembolization with emulsion-based formulations using doxorubicin hydrochloride (DOX) and Lipiodol® is the golden standard for the loco-regional treatment of unresectable hepatocellular carcinoma (HCC). However, from a pharmaceutical quality perspective these emulsions are poorly characterized. In this study, clinically relevant Lipiodol®-based emulsions were characterized in terms of emulsion stability, continuous phase classification and droplet-size distribution. Also, the solubility of DOX in the different emulsion components and the distribution of DOX to the lipid phase were investigated. These are key features to investigate due to the claimed tumor–seeking properties of Lipiodol®. The in vitro release of DOX was studied in a miniaturized dialysis method and an empirical release model was applied to adjust for the passage of DOX across the dialysis membrane. The most stable emulsion (>72 h) was classified as water-in-oil (w/o), had the highest distribution of DOX to the lipid phase (20%) and an aqueous-to-lipid phase ratio of 1:4. The composition of the aqueous phase was a mixture (v/v) of iohexol (85%) and water (15%). Emulsions containing iohexol and a high aqueous-to-lipid phase ratio (1:2–1:4) displayed prolonged in vitro release profiles of DOX. This study further emphasizes the medical need to standardize these emulsion-based drug delivery systems.
Design and Synthesis of Isoxazole Containing Bioisosteres of Epibatidine as Potent Nicotinic Acetylcholine Receptor Agonists. (1999)

An efficient synthesis of isoxazole containing isosteres of epibatidine is described. The synthesis proceeded from N-tert-butoxycarbonyl (Boc)-exo-2-(methoxycarbonyl)-7-azabicyclo[2.2.1]heptane (9). Compound 9 was reacted with the dilithium salt of an appropriately substituted oxime in tetrahydrofuran (THF). Cyclodehydration of the resultant beta-keto oxime and deprotection of the N-Boc group in 5 N aqueous HCl afforded the isoxazole containing isosteres of epibatidine (6-8). The binding affinities of these compounds were determined at the nicotinic acetylcholine receptor for the displacement of [3H]cystisine. The unsubstituted isoxazole containing isostere (6) showed the lower binding potency compared to the 3'-methylisoxazole isostere (7). Substitution with a phenyl group at the 3'-position of the isoxazole significantly reduced the binding potency. The in vivo toxicological studies of these analogs were also performed. The LD50 of the analogs ranged in the order: Me > H > Ph.
Copper and Manganese Induce Yeast Apoptosis via Different Pathways (2007)

Metal ions are essential as well as toxic to the cell. The mechanism of metal-induced toxicity is not well established. Here, for the first time we studied two essential nutritional elements, copper and manganese, for their apoptotic effects in yeast Saccharomyces cerevisiae. Although beneficial at subtoxic levels, we demonstrated that at moderately toxic levels, both metals induce extensive apoptosis in yeast cells. At even higher concentrations, necrosis takes over. Furthermore, we investigated the molecular pathways mediating Cu- and Mn-mediated apoptotic action. Mitochondria-defective yeast exhibit a much reduced apoptotic marker expression and better survival under Cu and Mn stress, indicating mitochondria are involved in both Cu- and Mn-induced apoptosis. Reactive oxygen species (ROS) are generated in high amounts in Cu- but not in Mn-induced cell death, and Cu toxicity can be alleviated by overexpression of superoxide dismutase 2, suggesting ROS mediate Cu but not Mn toxicity. Yeast metacaspase Yca1p is not involved in Cu-induced apoptosis, although it plays an important role in the Mn-induced process. A genetic screen identified Cpr3p, a yeast cyclophilin D homologue, as mediating the Cu-induced apoptotic program. Cpr3p mutant seems to eliminate Cu-induced apoptosis without affecting ROS production, while leaving necrosis intact. These results may provide important insight into a detailed understanding at the molecular and cellular level of metal toxicity and metal accumulation diseases.
Biosynthesis of 1‐alkenes in higher plants (1987)

Uneven numbered 1-alkenes, such as 1-pentadecene, 1-heptadecene, 1,8-heptadecadiene, 1,8,11-heptadecatriene and 1,8,11,14-heptadecatetraene are the predominant hydrocarbons in germinating safflower (Carthamus tinctorius L.). According to their chain length and positions of double bonds they are derived from palmitic, stearic, oleic, linoleic or linolenic acid, respectively. This has been proved by administration of synthetic alpha-, beta-, or gamma-deuterated 12-phenyldodecanoic acids to germinating safflower. Mass spectrometric analysis of the resulting deuterium-labelled 11-phenyl-1-undecenes shows that only a single hydrogen from C-3 and carbon dioxide from C-1 of the precursor fatty acid is lost during vinyl group formation. A strong isotope effect (kH/kD greater than or equal to 10) during the conversion of racemic 12-phenyl[3-2h]dodecanoic acid to 11-phenyl-1-[2-2H]undecene is consistent with an initial enzymatic attack on a non-activated hydrogen at C-3 accompanied by simultaneous fragmentation into the respective 1-alkene and carbon dioxide. Mechanisms, based on ionic or radical abstraction of a hydrogen from C-3 of the fatty acid, followed by decarboxylation are discussed. The results are applicable to the formation of various vinylic substituents in natural products such as porphyrins, acetylenic hydrocarbons, pheromones from marine brown algae and terpenoids.
Hydrodynamic stability of swimming in ostraciid fishes: role of the carapace in the smooth trunkfishLactophrys triqueter(Teleostei:Ostraciidae) (2003)

The hydrodynamic bases for the stability of locomotory motions in fishes are poorly understood, even for those fishes, such as the rigid-bodied smooth trunkfish Lactophrys triqueter, that exhibit unusually small amplitude recoil movements during rectilinear swimming. We have studied the role played by the bony carapace of the smooth trunkfish in generating trimming forces that self-correct for instabilities. The flow patterns, forces and moments on and around anatomically exact, smooth trunkfish models positioned at both pitching and yawing angles of attack were investigated using three methods: digital particle image velocimetry (DPIV), pressure distribution measurements, and force balance measurements. Models positioned at various pitching angles of attack within a flow tunnel produced well-developed counter-rotating vortices along the ventro-lateral keels. The vortices developed first at the anterior edges of the ventro-lateral keels, grew posteriorly along the carapace, and reached maximum circulation at the posterior edge of the carapace. The vortical flow increased in strength as pitching angles of attack deviated from 0 degrees, and was located above the keels at positive angles of attack and below them at negative angles of attack. Variation of yawing angles of attack resulted in prominent dorsal and ventral vortices developing at far-field locations of the carapace; far-field vortices intensified posteriorly and as angles of attack deviated from 0 degrees. Pressure distribution results were consistent with the DPIV findings, with areas of low pressure correlating well with regions of attached, concentrated vorticity. Lift coefficients of boxfish models were similar to lift coefficients of delta wings, devices that also generate lift through vortex generation. Furthermore, nose-down and nose-up pitching moments about the center of mass were detected at positive and negative pitching angles of attack, respectively. The three complementary experimental approaches all indicate that the carapace of the smooth trunkfish effectively generates self-correcting forces for pitching and yawing motions--a characteristic that is advantageous for the highly variable velocity fields experienced by trunkfish in their complex aquatic environment. All important morphological features of the carapace contribute to producing the hydrodynamic stability of swimming trajectories in this species.
Nitrogen fixation island and rhizosphere competence traits in the genome of root-associated Pseudomonas stutzeri A1501 (2008)

The capacity to fix nitrogen is widely distributed in phyla of Bacteria and Archaea but has long been considered to be absent from the Pseudomonas genus. We report here the complete genome sequencing of nitrogen-fixing root-associated Pseudomonas stutzeri A1501. The genome consists of a single circular chromosome with 4,567,418 bp. Comparative genomics revealed that, among 4,146 protein-encoding genes, 1,977 have orthologs in each of the five other Pseudomonas representative species sequenced to date. The genome contains genes involved in broad utilization of carbon sources, nitrogen fixation, denitrification, degradation of aromatic compounds, biosynthesis of polyhydroxybutyrate, multiple pathways of protection against environmental stress, and other functions that presumably give A1501 an advantage in root colonization. Genetic information on synthesis, maturation, and functioning of nitrogenase is clustered in a 49-kb island, suggesting that this property was acquired by lateral gene transfer. New genes required for the nitrogen fixation process have been identified within the nif island. The genome sequence offers the genetic basis for further study of the evolution of the nitrogen fixation property and identification of rhizosphere competence traits required in the interaction with host plants; moreover, it opens up new perspectives for wider application of root-associated diazotrophs in sustainable agriculture.
A Novel PAAD-containing Protein That Modulates NF-κB Induction by Cytokines Tumor Necrosis Factor-α and Interleukin-1β (2002)

PAAD domains are found in diverse proteins of unknown function and are structurally related to a superfamily of protein interaction modules that includes death domains, death effector domains, and Caspase activation and recruitment domains. Using bioinformatics strategies, cDNAs were identified that encode a novel protein of 110 kDa containing a PAAD domain followed by a putative nucleotide-binding (NACHT) domain and several leucine-rich repeat domains. This protein thus resembles Cryopyrin, a protein implicated in hereditary hyperinflammation syndromes, and was termed PAN2 for PAAD and NACHT-containing protein 2. When expressed in HEK293 cells, PAN2 suppressed NF-kappaB induction by the cytokines tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta), suggesting that this protein operates at a point of convergence in these two cytokine signaling pathways. This PAN2-mediated suppression of NF-kappaB was evident both in reporter gene assays that measured NF-kappaB transcriptional activity and electromobility shift assays that measured NF-kappaB DNA binding activity. PAN2 also suppressed NF-kappaB induction resulting from overexpression of several adapter proteins and protein kinases involved in the TNF or IL-1 receptor signal transduction, including TRAF2, TRAF6, RIP, IRAK2, and NF-kappaB-inducing kinase as well as the IkappaB kinases IKKalpha and IKKbeta. PAN2 also inhibited the cytokine-mediated activation of IKKalpha and IKKbeta as measured by in vitro kinase assays. Furthermore, PAN2 association with IKKalpha was demonstrated by co-immunoprecipitation assays, suggesting a direct effect on the IKK complex. These observations suggest a role for PAN2 in modulating NF-kappaB activity in cells, thus providing the insights into the potential functions of PAAD family proteins and their roles in controlling inflammatory responses.
Translocation t(3;22)(q23;q11) in three patients with diffuse large B cell lymphoma. (1990)

In our series of 134 patients with a diagnosis of non-Hodgkin's lymphoma (NHL) and clonal chromosomal abnormalities, three were found to show an identical t(3;22)(q28;q11) translocation. All were old patients with isolated lymphadenomegaly and diffuse large noncleaved cell lymphoma. All expressed a B cell immunophenotype, and all entered a complete remission when treated with aggressive chemotherapy. This translocation could, therefore, delineate a particular subtype of diffuse large cell NHL.
Synthesis of trans-3'-methylnicotine (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of trans-3'-methylnicotineMark Cushman and Neal Castagnoli Jr.Cite this: J. Org. Chem. 1972, 37, 8, 1268–1271Publication Date (Print):April 1, 1972Publication History Published online1 May 2002Published inissue 1 April 1972https://doi.org/10.1021/jo00973a046RIGHTS & PERMISSIONSArticle Views344Altmetric-Citations32LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (567 KB) Get e-Alerts Get e-Alerts
Magnetic resonance imaging of brain tumors: measurement of T1. Work in progress. (1984)

Longitudinal relaxation times (T1) of 20 brain tumors were calculated in vivo using a whole-body magnetic resonance unit with a 0.15-T resistive magnet. Images employing standard inversion recovery pulse sequences with different intervals between the 180 degrees pulse and selective excitation pulses were compared on every point of the 256 X 256 pixel matrix. Tumor, white matter, and gray matter were sampled from each patient from the computed T1 image for T1 measurement. Astrocytomas, neurinomas, and metastatic tumors showed longer T1 values than did meningiomas. Lipomas had the shortest T1s. It is concluded that it is difficult to predict histological types of brain tumors by the measurement of T1 alone because of the wide variation in relaxation times, but measurement of T1 can be helpful in differentiating brain tumors when additional information about the patient's condition is known.