gebhart/patrepeval huggingface dataset:
The beginnings of mucin biosynthesis: The crystal structure of UDP-GalNAc:polypeptide α- N -acetylgalactosaminyltransferase-T1 (2004)

UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferases (ppGaNTases) initiate the formation of mucin-type, O-linked glycans by catalyzing the transfer of alpha-N-acetylgalactosamine from UDP-GalNAc to Ser or Thr residues of core proteins to form the Tn antigen (GalNAc-alpha-1-O-Ser/Thr). ppGaNTases are unique among glycosyltransferases in containing a C-terminal lectin domain. We present the x-ray crystal structure of a ppGaNTase, murine ppGaNTase-T1, and show that it folds to form distinct catalytic and lectin domains. The association of the two domains forms a large cleft in the surface of the enzyme that contains a Mn2+ ion complexed by invariant D209 and H211 of the "DXH" motif and by invariant H344. Each of the three potential lectin domain carbohydrate-binding sites (alpha, beta, and gamma) is located on the active-site face of the enzyme, suggesting a mechanism by which the transferase may accommodate multiple conformations of glycosylated acceptor substrates. A model of a mucin 1 glycopeptide substrate bound to the enzyme shows that the spatial separation between the lectin alpha site and a modeled active site UDP-GalNAc is consistent with the in vitro pattern of glycosylation observed for this peptide catalyzed by ppGaNTase-T1. The structure also provides a template for the larger ppGaNTase family, and homology models of several ppGaNTase isoforms predict dramatically different surface chemistries consistent with isoform-selective acceptor substrate recognition.
High-Throughput TILLING for Functional Genomics (2003)

Targeting-induced local lesions in genomes (TILLING) is a general strategy for identifying induced point mutations that can be applied to almost any organism. Here, we describe the basic methodology for high-throughput TILLING. Gene segments are amplified using fluorescently tagged primers, and products are denatured and reannealed to form heteroduplexes between the mutated sequence and its wild-type counterpart. These heteroduplexes are substrates for cleavage by the endonuclease CEL I. Following cleavage, products are analyzed on denaturing polyacrylamide gels using the LI-COR DNA analyzer system. High-throughput TILLING has been adopted by the Arabidopsis TILLING Project (ATP) to provide allelic series of point mutations for the general Arabidopsis community.
ISOLATION AND IDENTIFICATION OF ENDOPHYTIC BACTERIA OF BANANAS IN KENYA (2012)

This study was conducted with the aim of isolating and identifying banana endophytic bacteria on the basis of their potential  as biological  fertilizer. Banana  materials were  collected from five different geographical regions to enhance diversity. Isolation of bacteria was done using five (5) different isolation media  and the isolates were characterized on the basis of their morphology, biochemical and molecular characteristics. A total of 214 bacterial isolates were obtained and characterized. Microorganism profiling was done using MALDI-TOF/MS and the isolates were clustered into 53 genotypes. Based on their functional characteristics, 43 isolates were selected for 16S rRNA gene sequencing. The 43 strains showed varied levels of positive nitrogenase activity as measured by the acetylene reduction assay and 37 strains were observed to solubilize phosphates by the formation of visible dissolution halos on agar plates (NBRIP medium). Siderophore  production of the isolates was determined using Chrome Azurol  S (CAS) agar plates and  all the isolates were observed to be positive for siderophore production with  3  strains showing distinctively high level of production. Using the 16S rRNA gene sequencing, the 43 strains were identified as Serratia spp. (17 strains), Pseudomonas spp. (12 strains), Enterobacter spp. (4 strains), Rahnella spp. (4 strains), Raoultella spp. (2  strains), Bacillus spp. (1 strain),  Klebsiella spp. (1 strain),  Yersinia spp. (1 strain) and Ewingella spp. (1 strain).  In  conclusion, banana endophytic bacteria were successfully isolated and identified, and  some of the isolates  showed  potential  of being  biological  fertilizers. However, greenhouse and field investigations are necessary to confirm this potentiality.
Pharmacokinetic Equivalence of Stable—Isotope‐Labeled and Unlabeled Drugs. Phenobarbital in Man (1982)

Stable isotope labeling of drugs has been used in human metabolism studies because it eliminates the risk of radiation exposure accompanying use of radioactive tracers. The labeled drug can be measured by gas-chromatographic mass spectrometry (GCMS). However, if reliable pharmacokinetic data are to be obtained, one has to be certain the rate of metabolism of labeled and unlabeled drug is the same, i.e., there is no kinetic isotope effect. To evaluate this for phenobarbital (PB), three humans were infused with a 1:1 mixture of phenobarbital and 1,3-15N2-2-13C-PB. Serum was collected at regular intervals. Concentrations of labeled and unlabeled phenobarbital were determined by GCMS. Within each subject, there was no trend for concentrations of labeled phenobarbital to be higher or lower than concentrations of unlabeled phenobarbital (P greater than 0.90 for all three subjects). There was no difference in the zero time intercepts, distribution and elimination time constants and half-lives, volumes of distribution and central compartment, or clearance of the two forms of phenobarbital. Thus, no isotope effect was found. Published data on other labeled drugs and the likelihood of encountering an isotope effect based on type of isotope and its location in the molecule are discussed.
The Slow-Releasing Hydrogen Sulfide Donor, GYY4137, Exhibits Novel Anti-Cancer Effects In Vitro and In Vivo (2011)

The slow-releasing hydrogen sulfide (H₂S) donor, GYY4137, caused concentration-dependent killing of seven different human cancer cell lines (HeLa, HCT-116, Hep G2, HL-60, MCF-7, MV4-11 and U2OS) but did not affect survival of normal human lung fibroblasts (IMR90, WI-38) as determined by trypan blue exclusion. Sodium hydrosulfide (NaHS) was less potent and not active in all cell lines. A structural analogue of GYY4137 (ZYJ1122) lacking sulfur and thence not able to release H₂S was inactive. Similar results were obtained using a clonogenic assay. Incubation of GYY4137 (400 µM) in culture medium led to the generation of low (<20 µM) concentrations of H₂S sustained over 7 days. In contrast, incubation of NaHS (400 µM) in the same way led to much higher (up to 400 µM) concentrations of H₂S which persisted for only 1 hour. Mechanistic studies revealed that GYY4137 (400 µM) incubated for 5 days with MCF-7 but not IMR90 cells caused the generation of cleaved PARP and cleaved caspase 9, indicative of a pro-apoptotic effect. GYY4137 (but not ZYJ1122) also caused partial G₂/M arrest of these cells. Mice xenograft studies using HL-60 and MV4-11 cells showed that GYY4137 (100-300 mg/kg/day for 14 days) significantly reduced tumor growth. We conclude that GYY4137 exhibits anti-cancer activity by releasing H₂S over a period of days. We also propose that a combination of apoptosis and cell cycle arrest contributes to this effect and that H₂S donors should be investigated further as potential anti-cancer agents.
A set of operating system mechanisms to support multi-media applications (2003)

The operating system of a terminal in a multimedia communication network needs mechanisms to manipulate the network interface and to direct the information flow. Some approaches and hardware support that can provide these capabilities are reported. These include a connector object to control the information exchange among the network interface and the voice, data, and image peripherals and the concept of an active device to provide uniform interfaces among information sources and sinks involved in a multimedia application. Voice, data, and image are packetized and transmitted on a single network. Packet streams of different media are multiplexed into a multimedia virtual circuit, which maintains the temporal relationship among the different information streams. Schemes to manage resources, such as network bandwidth and memory buffers to support multimedia applications, are also reported.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Deletion of the Braun Lipoprotein-Encoding Gene and Altering the Function of Lipopolysaccharide Attenuate the Plague Bacterium (2012)

Braun (murein) lipoprotein (Lpp) and lipopolysaccharide (LPS) are major components of the outer membranes of Enterobacteriaceae family members that are capable of triggering inflammatory immune responses by activating Toll-like receptors 2 and 4, respectively. Expanding on earlier studies that demonstrated a role played by Lpp in Yersinia pestis virulence in mouse models of bubonic and pneumonic plague, we characterized an msbB in-frame deletion mutant incapable of producing an acyltransferase that is responsible for the addition of lauric acid to the lipid A moiety of LPS, as well as a Δlpp ΔmsbB double mutant of the highly virulent Y. pestis CO92 strain. Although the ΔmsbB single mutant was minimally attenuated, the Δlpp single mutant and the Δlpp ΔmsbB double mutant were significantly more attenuated than the isogenic wild-type (WT) bacterium in bubonic and pneumonic animal models (mouse and rat) of plague. These data correlated with greatly reduced survivability of the aforementioned mutants in murine macrophages. Furthermore, the Δlpp ΔmsbB double mutant was grossly compromised in its ability to disseminate to distal organs in mice and in evoking cytokines/chemokines in infected animal tissues. Importantly, mice that survived challenge with the Δlpp ΔmsbB double mutant, but not the Δlpp or ΔmsbB single mutant, in a pneumonic plague model were significantly protected against a subsequent lethal WT CO92 rechallenge. These data were substantiated by the fact that the Δlpp ΔmsbB double mutant maintained an immunogenicity comparable to that of the WT strain and induced long-lasting T-cell responses against heat-killed WT CO92 antigens. Taken together, the data indicate that deletion of the msbB gene augmented the attenuation of the Δlpp mutant by crippling the spread of the double mutant to the peripheral organs of animals and by inducing cytokine/chemokine responses. Thus, the Δlpp ΔmsbB double mutant could provide a new live-attenuated background vaccine candidate strain, and this should be explored in the future.
Aromatic steroids. Part I. Oxidation products of 3-methoxyoestra-1,3,5(10)-trien-17β-yl acetate (1968)

Re-examination of chromium trioxide oxidations of 3-methoxyoestra-1,3,5-(10)-trien-17β-yl acetate (1; R1= OAc, ⋯ H, R2= H2) has shown that the neutral products are a ketol (IV; R1= OAc, ⋯ H, R2= Me, R3= OH, R4= H2), a 6-oxo-derivative (I; R1= OAc, ⋯ H, R2= O), a hydroxy-dione (IV; R1= O, R2= Me, R3= OH, R4= H2), and a mixture of a hydroxy-dione (IV; R1= OAc, ⋯ H, R2= Me, R3= OH, R4= O) and a hydroxy-trione (IV; R1= R4= O, R2= Me, R3= OH). Evidence is presented that the 9-hydroxy-group of the ketol has a β-configuration rather than the α-configuration previously assigned. Acids from the oxidation include C-seco-acids (III; R = OAc, ⋯ H) and (III; R = O), and structures (VII) and (VIII) for lactones derived from the latter acid have been proposed.
Pregnancy and Interferon-Tau Induce Conjugation of Bovine Ubiquitin Cross-Reactive Protein to Cytosolic Uterine Proteins1 (1998)

Conceptus-derived interferon-tau (IFN-tau) induces bovine endometrial ubiquitin cross-reactive protein (UCRP) mRNA and protein on Days 15-21 of pregnancy. Bovine UCRP retains the Leu-Arg-Gly-Gly C-terminal sequence of ubiquitin that ligates to and directs degradation of cytosolic proteins. The objectives of the present experiments were to determine whether UCRP became conjugated to endometrial cytosolic proteins during early pregnancy and in response to recombinant bovine (rbo) IFN-tau. Ubiquitin (8 kDa), UCRP (17 kDa), and conjugates thereof (> or = 30 kDa) were quantitated using Western blotting and densitometry. Endometrial ubiquitin and its conjugates did not differ between Day 18 pregnant and nonpregnant cows, or between control and rboIFN-tau-treated (25 nM) explant cultures (Day 14; nonpregnant). Bovine UCRP was induced in endometrium from pregnant as compared with nonpregnant cows. Conjugation of endometrial proteins to UCRP was induced in pregnant as compared to nonpregnant cows. Recombinant boIFN-tau induced UCRP and its conjugates in cultured endometrial explants from nonpregnant cows. It is concluded that UCRP, in response to rboIFN-tau, becomes conjugated to endometrial cytosolic proteins during early pregnancy. The regulation of uterine proteins by UCRP may be integral to the maintenance of early pregnancy in ruminants.
Phreatic and vadose cements in the Teritary Bluff Formation of Grand Cayman Island, British West Indies (1984)

ABSTRACT The Oligocene-Miocene Bluff Formation, which crops out on the eastern part of Grand Cayman Island, has been subjected to an exceedingly complex diagenetic history. Cavities formed during subaerial exposure, as a result of leaching of skeletal allochems and dissolution of the host rock. At a later stage of diagenesis many of these cavities were filled or partly filled by a complex sequence of dolomite and calcite cements. Such cements document the passage of the rocks from the phreatic zone to the vadose zone, and provide a record of highly variable pore-water chemistry. While the formation sediments were in the mixed marine-meteoric zone and the freshwater phreatic zone, limpid dolomite or zoned dolomite and coarse, sparry calcite formed. However, once the rocks reached the vadose zone, complex, zoned, dolomite-calcite microstalactites formed. In some cavities this phase of cementation was followed by the emplacement of terra rossa and/or microbreccia. Although distinct successions of cements can be documented for most cavities, the actual succession varies greatly from cavity to cavity, even though the cavities may be very close together. The cement fabrics are distinct. Recognition of similar fabrics in ancient rocks would provide an indication of proximity to surfaces that had been subaerially exposed. CIMENTS PHREATIQUES ET VADOSES DANS LA FORMATION DE BLUFF D'AGE TERTIAIRE DE L'ILE GRAND CAYMAN, ANTILLES BRITANNIQUES RESUME La formation de Bluff, d'age oligo-miocene, affleure dans la partie est de l'ile Grand Cayman. L'histoire diagenetique de cette formation apparait particulierement complexe. Lors d'une phase d'exposition aerienne, des cavites se formerent par lessivage des allochems et dissolution de la roche encaissante. Dans un stade ulterieur, une sequence complexe de ciments dolomitiques et calcitiques se developpa dans beaucoup de ces cavites. Cette sequence temoigne du passage des roches de la zone phreatique a la zone vadose et represente un enregistrement de la chimie tres variable de l'eau intersticielle. Dans la zone mixte a eau meteorique et marine ainsi que dans la zone phreatique a eau douce, de la dolomite limpide ou zonee et de la sparite se formerent. Des microstalactites zonees a dolomite et calcite, plus complexes, se developperent ensuite dans la zone vadose. Dans certaines cavites, cette phase de cimentation fut suivie par le depot de terra rosa et/ou de microbreche. Bien que la sequence de formation des ciments puisse etre documentee pour la plupart des cavites, cette sequence apparait tres variable d'une cavite a l'autre, meme lorsque celles-ci sont tres proches. Les caracteristiques de ce ciment apparaissant particulieres, la reconnaissance de caracteristiques semblables dans des roches anciennes serait une indication de la proximite d'une surface erosionnelle. Traduit par B. Collot
The hepatitis C virus enigma (2009)

Hepatitis C virus (HCV) has a high propensity to establish chronic infection with end-stage liver disease. The high turnover of virus particles and high transcription error rates due to lack of proof-reading function of the viral polymerase imply that HCV exists as quasispecies, thus enabling the virus to evade the host immune response. Clearance of the virus is characterized by a multispecific, vigorous and persistent T-cell response, whereas T-cell responses are weak, narrow and transient in patients who develop chronic infection. At present, standard treatment is a combination of pegylated interferon-alpha and ribavirin, with a sustained viral response rate of 40-80%, depending on genotype. The mechanisms for the observed synergistic effects of the two drugs are still not known in detail, but in addition to direct antiviral mechanisms, the immunomodulatory effects of both drugs seem to be important, with a shift from Th2- to Th1-cytokine profiles in successfully treated patients. This article describes virus-host relations in the natural course of HCV infection and during treatment.
Histone Acetylation, Chromatin Remodelling and Nucleotide Excision Repair: Hint from the Study on MFA2 in Saccharomyces cerevisiae (2005)

Nucleotide excision repair (NER) is a sophisticated repair pathway that the cell utilizes to remove a broad range of DNA damage to help maintain the functional integrity of the genome. In the context of DNA packaged into chromosomes it is clear that the NER machinery does not repair all regions with equal efficiency. Recently, we found after UV that histone acetylation and chromatin remodelling were activated. UV irradiation triggers genome-wide histone hyperacetylation at both histone H3 and H4. However, in nucleosomes at the repressed MFA2 promoter only histone H3, but not histone H4, is hyperacetylated following UV. This Gcn5p-mediated histone H3 hyperacetylation enables efficient NER at MFA2. Chromatin in this promoter also becomes more accessible after UV. This is not dependent on Gcn5p, yet it is partially dependent on Swi2p. In later repair times both events gradually return to the pre-UV state. The post-UV histone modifications and chromatin remodelling at the repressed MFA2 promoter do not activate MFA2 transcription, nor do they require damage recognition by Rad4p or Rad14p. These experiments indicate early events are triggered in chromatin in response to UV treatment, and they are likely needed for efficient NER.
An Aqueous-Based Surface Modification of Poly(dimethylsiloxane) with Poly(ethylene glycol) to Prevent Biofouling (2005)

We report a simple modification of poly(dimethylsiloxane) (PDMS) surfaces with poly(ethylene glycol) (PEG) through the adsorption of a graft copolymer, poly(l-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) from aqueous solution. In this approach, the PDMS surface was treated with oxygen plasma, followed by immersion into aqueous solution containing PLL-g-PEG copolymers. Due to the hydroxyl/carboxylic groups generated on the PDMS surface after oxygen plasma, the polycationic PLL backbone is attracted to the negatively charged surface and PEG side chains exhibit an extended structure. The PEG/aqueous interface generated in this way revealed a near-perfect resistance to nonspecific protein adsorption as monitored by means of optical waveguide lightmode spectroscopy (OWLS) and fluorescence microscopy.
Progress in the Development of Topiramate for Treating Alcohol Dependence: From a Hypothesis to a Proof‐of‐Concept Study (2004)

Advances in neuroscientific knowledge have evoked interest in developing effective medications for the treatment of alcohol dependence. Pharmacological approaches that involve the use of relatively specific medications at a particular neuronal target to modulate corticomesolimbic dopamine neuronal activity, the critical pathway for expression of the reinforcing effects of abused drugs, have yielded modest efficacy in the treatment of alcohol dependence. A new approach is needed. Because corticomesolimbic dopamine neurons interact with a variety of neurotransmitters that modulate its effects in the nucleus accumbens, it might be possible to more reliably control these dopaminergic effects with a medication that acted contemporaneously on more than one neuromodulator of dopamine function. Additionally, because alcohol use results in neuronal adaptations due to sensitization, the chances of effective therapy might be bolstered by administering a medication that also has utility with mitigating its chronic effects. My proposed conceptual framework suggests that a medication that facilitates inhibitory gamma-aminobutyric acid-A input and antagonizes excitatory glutaminergic afferents to the nucleus accumbens would have pharmacotherapeutic potential in treating the alcohol dependence syndrome because these effects would act contemporaneously to suppress corticomesolimbic dopamine release. Through similar effects, topiramate might also aid chronic drinkers to wean themselves off alcohol and might ameliorate the symptoms of alcohol withdrawal. This commentary highlights the scientific concepts and clinical evidence for the development of topiramate in the treatment of alcohol dependence.
Pharmacokinetics of a Testosterone Gel in Healthy Postmenopausal Women (2006)

Administration of testosterone gel to postmenopausal women raised total and free testosterone concentrations in proportion to the administered dose without affecting estradiol levels. A 4.4-mg dose raised testosterone levels into the mid- to high-normal range. Previous estrogen therapy had no significant effect on testosterone pharmacokinetics over this short duration.
The genome of Eucalyptus grandis (2014)

Eucalypts are the world's most widely planted hardwood trees. Their outstanding diversity, adaptability and growth have made them a global renewable resource of fibre and energy. We sequenced and assembled >94% of the 640-megabase genome of Eucalyptus grandis. Of 36,376 predicted protein-coding genes, 34% occur in tandem duplications, the largest proportion thus far in plant genomes. Eucalyptus also shows the highest diversity of genes for specialized metabolites such as terpenes that act as chemical defence and provide unique pharmaceutical oils. Genome sequencing of the E. grandis sister species E. globulus and a set of inbred E. grandis tree genomes reveals dynamic genome evolution and hotspots of inbreeding depression. The E. grandis genome is the first reference for the eudicot order Myrtales and is placed here sister to the eurosids. This resource expands our understanding of the unique biology of large woody perennials and provides a powerful tool to accelerate comparative biology, breeding and biotechnology.
PD-L1 expression on immune cells, but not on tumor cells, is a favorable prognostic factor for head and neck cancer patients (2016)

To investigate the expression of programmed death-ligand 1 (PD-L1) and immune checkpoints and their prognostic value for resected head and neck squamous cell cancer (HNSCC). PD-L1 expression on tumor cells (TC) and tumor-infiltrating immune cells (IC), abundance of tumor-infiltrating lymphocytes (TILs), and expression of the immune checkpoints were investigated in 402 HNSCC patients. PD-L1 expression on TC and IC was categorized into four groups according to the percentage of PD-L1-positive cells. PD-L1 positivity was defined as ≥5% of cells based on immunohistochemistry. High PD-L1 expression on IC, but not TC, was an independent favorable prognostic factor for RFS and OS adjusted for age, gender, smoking, stage, and HPV. High frequencies of CD3<sup>+</sup> or CD8<sup>+</sup> TILs, Foxp3<sup>+</sup> T<sub>reg</sub>s, and PD-1<sup>+</sup> TILs were strongly associated with favorable prognosis. PD-L1 was exclusively expressed on either TC or IC. Transcriptome analysis demonstrated that IC3 expressed higher levels of the effector T cell markers than TC3, suggesting that PD-L1 expression is regulated via an adaptive IFNγ-mediated mechanism. High PD-L1 expression on IC, but not TC, and high abundance of PD-1<sup>+</sup> T cells and Foxp3<sup>+</sup> T<sub>reg</sub>s are favorable prognostic factors for resected HNSCC. This study highlights the importance of comprehensive assessment of both TC and IC.