gebhart/patrepeval huggingface dataset:
SMG6 is the catalytic endonuclease that cleaves mRNAs containing nonsense codons in metazoan (2008)

Messenger RNAs harboring nonsense codons (or premature translation termination codons [PTCs]) are degraded by a conserved quality-control mechanism known as nonsense-mediated mRNA decay (NMD), which prevents the accumulation of truncated and potentially harmful proteins. In Drosophila melanogaster, degradation of PTC-containing messages is initiated by endonucleolytic cleavage in the vicinity of the nonsense codon. The endonuclease responsible for this cleavage has not been identified. Here, we show that SMG6 is the long sought NMD endonuclease. First, cells expressing an SMG6 protein mutated at catalytic residues fail to degrade PTC-containing messages. Moreover, the SMG6-PIN domain can be replaced with the active PIN domain of an unrelated protein, indicating that its sole function is to provide endonuclease activity for NMD. Unexpectedly, we found that the catalytic activity of SMG6 contributes to the degradation of PTC-containing mRNAs in human cells. Thus, SMG6 is a conserved endonuclease that degrades mRNAs terminating translation prematurely in metazoa.
Arylation Reactions of Alkynes: The Sonogashira Reaction (2009)

This chapter contains sections titled: Introduction Palladium-Catalyzed Reactions: Ligands and Reaction Protocols Alternative Metal Catalysts Mechanism of the Sonogashira Reaction Concluding Remarks References
Immunologic Reconstitution in the Acquired Immunodeficiency Syndrome (1985)

Although effective therapies are available for many of the infections and tumors that occur in patients with the acquired immunodeficiency syndrome (AIDS), no therapy exists for the underlying immunodeficiency. Three approaches used to treat this immunodeficiency have included wholescale immune replacement through lymphocyte transfers, bone marrow transplantation, and thymic implantation; immunologic enhancement with biologic-response modifiers, such as gamma interferon, interleukin-2, and some drugs; and antiretroviral therapy. Because of the persistence of the etiologic virus, both immune replacement and enhancement will probably be ineffective unless effective strategies are developed against the virus. Agents that have shown antiviral activity in vitro which are currently in clinical trials include suramin, heteropolyanion-23 (HPA-23), ribavirin, and alpha interferon. Foscarnet and monoclonal antibodies have yet to enter clinical trials in the United States. It is still too early to tell if any of the antiviral agents will prove of value in the management of patients with AIDS.
Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors (2010)

The reported results could lead to the development of an inexpensive, easy-to-use, portable, non-invasive tool that overcomes many of the deficiencies associated with the currently available diagnostic methods for cancer.
Solution Structure of Prosurvival Mcl-1 and Characterization of Its Binding by Proapoptotic BH3-only Ligands (2004)

The B cell lymphoma-2 (Bcl-2) homologs myeloid cell leukemia-1 (Mcl-1) and A1 are prosurvival factors that selectively bind a subset of proapoptotic Bcl homology (BH) 3-only proteins. To investigate the molecular basis of the selectivity, we determined the solution structure of the C-terminal Bcl-2-like domain of Mcl-1. This domain shares features expected of a prosurvival Bcl-2 protein, having a helical fold centered on a core hydrophobic helix and a surface-exposed hydrophobic groove for binding its cognate partners. A number of residues in the binding groove differentiate Mcl-1 from its homologs, and in contrast to other Bcl-2 homologs, Mcl-1 has a binding groove in a conformation intermediate between the open structures characterized by peptide complexes and the closed state observed in unliganded structures. Mutagenesis of potential binding site residues was used to probe the contributions of groove residues to the binding properties of Mcl-1. Although mutations in Mcl-1 had little impact on binding, a single mutation in the BH3-only ligand Bad enabled it to bind both Mcl-1 and A1 while retaining its binding to Bcl-2, Bcl-xL, and Bcl-w. Elucidating the selective action of certain BH3-only ligands is required for delineating their mode of action and will aid the search for effective BH3-mimetic drugs.
Role of early region 3 (E3) in pathogenesis of adenovirus disease. (1989)

The cotton rat Sigmodon hispidus has provided an animal model of adenovirus pneumonia that permits investigation of the viral gene products required to produce the disease and the molecular mechanisms effecting the damage. This study was carried out to test the hypothesis that early region 3 (E3) of the adenovirus genome plays a critical role in pathogenesis of the virus's disease process even though none of its gene products are essential for its replication. Mutants whose E3 region is largely deleted (i.e., H2dl801 and H5dl327) replicated like wild-type virus in the cotton rats' lungs, but the lymphocyte and macrophage/monocyte inflammatory response was markedly increased. Viruses containing mutations that ablated production of the 19-kDa glycoprotein had the same effect as H2dl801 and H5dl327. However, mutants with deletions in the other E3 open reading frames, some of which encode known proteins, did not differ from wild-type virus in their pathogenic properties. The 19-kDa glycoprotein markedly reduces expression of the class I major histocompatibility complex antigens on the surface of infected cells. A complete correlation was found between those mutants that had increased pathogenic effects and those that lost the ability to reduce transport of the class I major histocompatibility complex antigens to surface of infected cells (i.e., all mutants unable to express the 19-kDa glycoprotein). H5sub304, which has a deletion between 83.2 and 85.1 map units in the E3B region and expresses the 19-kDa glycoprotein, did not increase the extent of pneumonia but qualitatively changed the inflammatory response in that increased numbers of polymorphonuclear leukocytes accumulated, often in small foci.
Porphyrins with Exocyclic Rings. 14.1 Synthesis of Tetraacenaphthoporphyrins, a New Family of Highly Conjugated Porphyrins with Record-Breaking Long-Wavelength Electronic Absorptions (2000)

The Soret band for porphyrins is usually observed in the near-ultraviolet at approximately 400 nm, and few examples of "nonexpanded" porphyrins with this major absorption band at values above 500 nm have previously been reported in the literature. Ring fusion with aromatic ring systems such as naphthalene, anthracene, or phenanthrene generally only produces minor bathochromic shifts to this diagnostic absorption band. In this paper, the synthesis of a series of tetraacenaphthoporphyrins and their metal chelates is reported. The compact nature of the acenaphthylene ring system allows the introduction of meso substituents using the Lindsey methodology. meso-Tetraphenylporphyrin 10a shows the presence of a Soret band at 556 nm, while p-methoxy and p-nitro substituents in 10f and 10g, respectively, further shift this band to 560 and 570 nm. Addition of TFA produces the corresponding dications with slightly higher wavelength Soret bands at 565, 573, and 588 nm. These values compare to 525 nm for the dication of tetraacenaphthylene 8, which lacks the meso-aryl substituents, indicating that steric crowding and its resulting distortion of the macrocyclic conformation is responsible for a significant albeit minor portion of these shifts. The nickel(II), copper(II), and zinc chelates of 10a produce Soret bands at 528, 545, and 558 nm, respectively, demonstrating that the trend for increasing red shifts in metalloporphyrins across the periodic table is retained for this series. The lead(II) chelate 19d gave an additional "hyper" shift that brought the Soret band to 604 nm. A similar red shift could be achieved by introducing four phenylethynyl substituents at the meso positions, and this highly conjugated porphyrin (20) also showed a Soret band at 604 nm, while the corresponding dication afforded this absorption band at 629 nm. The essentially additive "hyper" shift due to lead chelation brought the Soret band for the related lead(II) complex 22d to 642 nm. These effects are by far the largest ever observed for true porphyrins and demonstrate that the Soret band can be fined tuned to virtually any part of the visible spectrum.
Effect of Positive End-Expiratory Pressure on Intra-abdominal Pressure (1991)

Massive elevation of intra-abdominal pressure (IAP) causes renal, cardiovascular, and respiratory dysfunction. Positive end-expiratory pressure (PEEP) markedly increases the detrimental effect of IAP on the cardiovascular system. The purpose of this study was to determine the effect of PEEP on IAP. In 15 patients requiring mechanical ventilation, IAP was measured, after 15-minute equilibration intervals, at PEEP levels of 0, 5, 10, and 15 cm H2O. Parametric analysis with multiple paired t tests and nonparametric analysis with Spearman's rho and Kendall's tau tests were used to determine correlation between PEEP and IAP. All patients were male. The mean age was 39 years (range, 18-77). Ten patients had just had laparotomy. No correlation was found between PEEP and IAP. We conclude that PEEP of 15 cm H2O or less has no effect on IAP, and we discuss the clinical implications.
Pds1p, an inhibitor of anaphase in budding yeast, plays a critical role in the APC and checkpoint pathway(s). (1996)

We report the isolation and characterization of pds1 mutants in Saccharomyces cerevisiae. The initial pds1-1 allele was identified by its inviability after transient exposure to microtubule inhibitors and its precocious dissociation of sister chromatids in the presence of these microtubule inhibitors. These findings suggest that pds1 mutants might be defective in anaphase arrest that normally is imposed by a spindle-damage checkpoint. To further examine a role for Pds1p in anaphase arrest, we compared the cell cycle arrest of pds1 mutants and PDS1 cells after: (a) the inactivation of Cdc16p or Cdc23p, two proteins that are required for the degradation of mitotic cyclins and are putative components of the yeast anaphase promoting complex (APC); (b) the inactivation of Cdc20p, another protein implicated in the degradation of mitotic cyclins; and (c) the inactivation of Cdc13 protein or gamma irradiation, two circumstances that induce a DNA-damage checkpoint. Under all these conditions, anaphase is inhibited in PDS1 cells but not in pds1 mutants. From these results we suggest that Pds1 protein is an anaphase inhibitor in PDS1 cells but not in pds1 mutants. From these results we suggest that Pds1 protein is an anaphase inhibitor that plays a critical role in the control of anaphase by both APC and checkpoints. We also show that pds1 mutants exit mitosis and initiate new rounds of cell division after gamma irradiation and Cdc13p inactivation but no after nocodazole-treatment or inactivation of Cdc16p, Cdc20p or Cdc23p function. Therefore, in the DNA-damage checkpoint, Pds1p is required for the inhibition of cytokinesis and DNA replication as well as anaphase. The role of Pds1 protein in anaphase inhibition and general cell cycle regulation is discussed.
The Treatment of Pulmonary Diseases and Respiratory‐Related Conditions with Inhaled (Nebulized or Aerosolized) Glutathione (2007)

Reduced glutathione or simply glutathione (gamma-glutamylcysteinylglycine; GSH) is found in the cytosol of most cells of the body. GSH in the epithelial lining fluid (ELF) of the lower respiratory tract is thought to be the first line of defense against oxidative stress. Inhalation (nebulized or aerosolized) is the only known method that increases GSH's levels in the ELF. A review of the literature was conducted to examine the clinical effectiveness of inhaled GSH as a treatment for various pulmonary diseases and respiratory-related conditions. This report also discusses clinical and theoretical indications for GSH inhalation, potential concerns with this treatment, its presumed mechanisms of action, optimal doses to be administered and other important details. Reasons for inhaled GSH's effectiveness include its role as a potent antioxidant, and possibly improved oxygenation and host defenses. Theoretical uses of this treatment include Farmer's lung, pre- and postexercise, multiple chemical sensitivity disorder and cigarette smoking. GSH inhalation should not be used as a treatment for primary lung cancer. Testing for sulfites in the urine is recommended prior to GSH inhalation. Minor side effects such as transient coughing and an unpleasant odor are common with this treatment. Major side effects such as bronchoconstriction have only occurred among asthma patients presumed to be sulfite-sensitive. The potential applications of inhaled GSH are numerous when one considers just how many pulmonary diseases and respiratory-related conditions are affected by deficient antioxidant status or an over production of oxidants, poor oxygenation and/or impaired host defenses. More studies are clearly warranted.
Nucleosides. 5. Synthesis of guanine and formycin B derivatives as potential inhibitors of purine nucleoside phosphorylase (1993)

In an effort to develop potent human purine nucleoside phosphorylase (PNP) inhibitors as immunosuppressive and chemotherapeutic agents, several 8-aminoguanine derivatives were synthesized and evaluated as potential PNP inhibitors. These studies were designed to investigate the hydrophobic effect of a substituent on the N-9 of the purine heterocycle and/or the C-5' positions. Compounds such as 8-aminoguanosine, guanosine, formycin B, and 8-aminoacyclovir containing a p-(fluorosulfonyl)benzoyl moiety were synthesized. The affinity of these compounds to erythrocytic PNP was determined and none of these compounds showed a better affinity than those of the parent compounds. However, we found that the effect of hydrophobicity at the N-9 and the C-5' positions might play an important role in binding to the active site of PNP. Thus, 8-amino-5'-deoxy-5'-(phenylthio)guanosine (19) was found to be the best inhibitor in this series of compounds with a Ki = 0.45 microM.
Variability of Heparins and Heterogeneity of Low Molecular Weight Heparins (2007)

Chemical and physical characteristics, building blocks, constitutive disaccharides, sulfation degree, and biological activities of heparins (UFHs) and of low molecular weight heparins (LMWHs) obtained by different depolymerization processes are examined comparatively in terms of structure characteristics, content of 1,6-anhydro rings, and other fingerprints. The heterogeneity of different LMWHs depends on different manufacturing processes and on particular specifications of pharmacopoeias. The reported examples prove that the variability among samples of LMWHs manufactured by the same process is quite limited. Most of the variability is derived from the parent UFH. In contrast, fingerprint groups and residues are specific to the depolymerization process and their extent can be roughly controlled through the process parameters.
Viscoelastic Evaluation of a Surfactant Gel for Hydraulic Fracturing (2011)

Abstract A new viscoelastic surfactant-based fluid was developed as an alternative to conventional fracturing fluids. The surfactant gel structure can be formed by adding a combination of cationic and anionic surfactants to water. This technology enables a clean fluid that can be prepared in fresh water, brines, or even produced waters without requiring biocides. Also, the cationic surfactant in the system functions as a temporary clay control agent or KCl replacement. The objective of this study is to evaluate the proppant suspension ability of the system, and its dependence on total surfactant concentration (TSC), cationic/anionic surfactant ratio (C/A), and temperature. Elastic and viscous properties (G’ and G") of twelve different formulae were measured using an oscillatory rheometer. Static and dynamic proppant settling tests were conducted at 2- to 4-ppg concentrations. Three proppant types were selected that had the same size, but different densities and shapes. Based on the experimental results obtained, the apparent viscosity of the surfactant gel was found to be a strong function of the TSC and temperature, while it has a weak dependence on C/A ratio. The viscous regime increased with increasing temperature and increasing TSC, while the elastic regime increased only with increasing C/A ratio. C/A ratio was found to be the primary parameter that affects proppant suspension. Only the formulae that had C/A ratio higher than 1.5 and TSC greater than 30 gpt displayed good proppant suspension properties. For these systems, proppant shape didn't affect the settling velocity. The viscous regime region was not affected by increasing the breaker concentration, but the values of G’ and G" decreased with increasing breaker concentration. Viscosity reduction profile was affected greatly by temperature and TSC, but C/A ratio did not have any significant effect. Results obtained can be used to better design hydraulic fracturing treatments.
Tamsulosin and the Intraoperative Floppy Iris Syndrome (2009)

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Gene profiling of Graffi murine leukemia virus-induced lymphoid leukemias: identification of leukemia markers and Fmn2 as a potential oncogene (2010)

The Graffi murine leukemia virus induces a large spectrum of leukemias in mice and thus provides a good model to compare the transcriptome of all types of leukemias. We analyzed the gene expression profiles of both T and B leukemias induced by the virus with DNA microarrays. Given that we considered that a 4-fold change in expression level was significant, 388 probe sets were associated to B, to T, or common to both leukemias. Several of them were not yet associated with lymphoid leukemia. We confirmed specific deregulation of Fmn2, Arntl2, Bfsp2, Gfra2, Gpm6a, and Gpm6b in B leukemia, of Nln, Fbln1, and Bmp7 in T leukemias, and of Etv5 in both leukemias. More importantly, we show that the mouse Fmn2 induced an anchorage-independent growth, a drastic modification in cell shape with a concomitant disruption of the actin cytoskeleton. Interestingly, we found that human FMN2 is overexpressed in approximately 95% of pre-B acute lymphoblastic leukemia with the highest expression levels in patients with a TEL/AML1 rearrangement. These results, surely related to the role of FMN2 in meiotic spindle maintenance, suggest its important role in leukemogenesis. Finally, we propose a new panel of genes potentially involved in T and/or B leukemias.
Multicenter Retrospective Study on the Utilization of FEIBA in France in Patients with Factor VIII and Factor IX Inhibitors (1997)

Factor VIII or factor IX replacement is frequently impossible in inhibitor-developing hemophiliacs, because of the level of the inhibitor titer. Activated prothrombin complex concentrates are one of the available options to treat the bleeding episodes in such patients. However, the efficacy of these products and the associated thrombogenic risk, particularly in prolonged administration such as employed during surgeries, are important concerns for hemophilia care providers. We performed a multicenter retrospective study to evaluate the use of FEIBA (Factor Eight Bypassing Activity) in France, and data is presented on 433 bleeding episodes, including surgical procedures, concerning 60 patients from 15 hemophilia centers. The efficacy was judged as good or excellent in 352 episodes (81.3%), poor in 73 episodes (16.9%) and non-existent in 8 episodes (1.8%). Minor and major surgical procedures were successfully performed using FEIBA as a second-line therapy after human or porcine factor VIII, and in some occasions FEIBA was utilized as the only substitution product. The tolerance was assessed as good in 428 episodes (98.8%), but in 5 cases adverse effects were reported. Only 3 patients out of 52 regularly evaluated (5.8%) were HIV-seropositive, and for two of them the seroconversion occurred prior to the first use of FEIBA. In contrast, 80.4% of the patients were HCV-seropositive. An anamnestic response after the administration of FEIBA was noted in 31.5% of cases. This study points out the main features of the use of FEIBA in France, and particularly the low HIV seroprevalence in the patients treated. The good efficacy and the excellent tolerance still confer to this product a place to consider in the therapeutic options for the treatment of inhibitor-developing hemophiliacs or in acquired hemophilia.
Regulation of Plasminogen Receptor Expression on Monocytoid Cells by β1-Integrin-dependent Cellular Adherence to Extracellular Matrix Proteins (1996)

Plasminogen binding sites function to arm cell surfaces with the proteolytic activity of plasmin, critical for degradation of extracellular matrices. We have assessed the effects of adhesion of the representative monocytoid cell lines, THP-1 and U937, to purified extracellular matrix proteins on their expression of plasminogen receptors. After adhesion to immobilized fibronectin, adherent and nonadherent subpopulations of cells were separated. Plasminogen binding to the nonadherent population of cells increased 3-fold, whereas binding to the adherent population decreased by 60%. These changes were due to differences in the plasminogen binding capacities of the cells, while the affinities of the cells for plasminogen were unchanged. The up-regulation of receptor expression in the nonadherent cell population was: 1) induced rapidly and reversibly, 2) independent of new protein synthesis, 3) required an interaction between adherent and nonadherent cell populations, and 4) associated with an enhanced ability of the cells to promote plasminogen activation and to degrade fibronectin. Other immobilized adhesive proteins, laminin and vitronectin, also supported up-regulation of plasminogen receptors in the nonadherent cells. Carboxypeptidase B treatment eliminated the increment in the plasminogen binding capacity of the nonadherent cells, suggesting that the increase in binding was due to exposure of new carboxyl-terminal lysyl residues on the cell surfaces. Furthermore, both the adherence of the cells and up-regulation of plasminogen binding sites was abolished by beta1-integrin monoclonal antibodies. These results suggest that proteins found in extracellular matrices have the capacity to modulate the expression of plasminogen binding sites, thus regulating local proteolysis and cell migration.