gebhart/patrepeval huggingface dataset:
The Resistance of Retroviral Vectors Produced from Human Cells to Serum Inactivation In Vivo and In Vitro Is Primate Species Dependent (1999)

The ability to deliver genes as therapeutics requires an understanding of the vector pharmacokinetics similar to that required for conventional drugs. A first question is the half-life of the vector in the bloodstream. Retroviral vectors produced in certain human cell lines differ from vectors produced in nonhuman cell lines in being substantially resistant to inactivation in vitro by human serum complement (F. L. Cosset, Y. Takeuchi, J. L. Battini, R. A. Weiss, and M. K. Collins, J. Virol. 69:7430-7436, 1995). Thus, use of human packaging cell lines (PCL) may produce vectors with longer half-lives, resulting in more-efficacious in vivo gene therapy. However, survival of human PCL-produced vectors in vivo following systemic administration has not been explored. In this investigation, the half-lives of retroviral vectors packaged by either canine D17 or human HT1080 PCL were measured in the bloodstreams of macaques and chimpanzees. Human PCL-produced vectors exhibited significantly higher concentrations of circulating biologically active vector at the earliest time points measured (>1, 000-fold in chimpanzees), as well as substantially extended half-lives, compared to canine PCL-produced vectors. In addition, the circulation half-life of human PCL-produced vector was longer in chimpanzees than in macaques. This was consistent with in vitro findings which demonstrated that primate serum inactivation of vector produced from human PCL increased with increasing phylogenetic distance from humans. These results establish that in vivo retroviral vector half-life correlates with in vitro resistance to complement. Furthermore, these findings should influence the choice of animal models used to evaluate retroviral-vector-based therapies.
Selective Intermolecular Amination of CH Bonds at Tertiary Carbon Centers (2013)

C-H insertion: A method for intermolecular amination of tertiary CH bonds is described that uses limiting amounts of substrate and a convenient phenol-derived nitrogen source. Structure-selectivity and mechanistic studies suggest that steric interaction between the substrate and active oxidant is the principal determinant of product selectivity.
Rock: A High-Performance Sparc CMT Processor (2009)

Rock, Sun's third-generation chip-multithreading processor, contains 16 high-performance cores, each of which can support two software threads. Rock uses a novel checkpoint-based architecture to support automatic hardware scouting under a load miss, speculative out-of-order retirement of instructions, and aggressive dynamic hardware parallelization of a sequential instruction stream. It is also the first processor to support transactional memory in hardware.
1,5-Disubstituted 1,2,3-Triazolylation at C1, C2, C3, C4, and C6 of Pyranosides: A Metal-Free Route to Triazolylated Monosaccharides and Triazole-Linked Disaccharides (2013)

A pair of easily accessible vinyl sulfones derived from styrene epoxide and monotosylated glycerol were reacted with six different azidopyranosides having an azido group at C1, C2, C3, C4, C6, and at the terminal position of an exocylic chain attached to C1. The reaction was performed mostly in water at elevated temperature without any metal catalyst to afford regioselectively 1,5-disubstituted triazolylated pyranosides in high yields. Another set of exocyclic vinyl sulfones prepared from 3-O-methylated- and 3-O-benzylated glucofuranosides as well as 3-O-benzylated allofuranoside were also subjected to 1,3-dipolar cycloaddition reactions with six azidopyranosides under similar reaction conditions to generate a series of 1,5-disubstituted triazole-linked disaccharides. The synthesis of all 1,5-disubstituted triazolylated monosaccharides as well as all 1,5-disubstituted triazole linked disaccharides are reported for the first time. Steric bulk around the azido and vinyl sulfone groups plays a significant role in deciding the outcome of the reactions. This powerful and practical route has the potential to be exploited for the synthesis of complex 1,5-disubstituted 1,2,3-triazolylated carbohydrates.
Combinatorial manipulation of three key active site residues in glycinamide ribonucleotide transformylase (1997)

The enzyme glycinamide ribonucleotide transformylase (EC 2.1.2.2) has previously been shown to have three key polar active site residues important for catalysis: N106, H108 and D144. Mutations of any of these three residues lead to substantially decreased catalytic activity, although none of them are completely irreplaceable. In order to determine whether any alternative arrangement of amino acids at these three positions could lead to an active protein, all three of these residues were simultaneously subjected to saturation site-directed mutagenesis. The resulting combinatorial library of mutant genes was screened for those encoding active proteins using functional complementation. Glycinamide ribonucleotide transformylase was found to be capable of tolerating no more than one mutation amongst these key residues, since the only proteins found to be sufficiently active to allow growth of auxotrophic cells on selective media were the wild-type and enzymes containing a single mutation to one of these residues. It seems likely that no enzymes containing two or more mutations of these three residues possess significant catalytic activity. The combinatorial approach used could prove to be quite useful in protein engineering and protein evolution experiments.
The Polysaccharide Capsule of Bacteroides fragilis Subspecies fragilis: Immunochemical and Morphologic Definition (1976)

A large-molecular-weight capsular polysaccharide was isolated from strains of Bacteroides fragilis subspecies fragilis. By means of electron microscopy and staining with ruthenium red, the thick polysaccharide capsule was also visualized. With use of a radioactive antigen-binding assay, antibody to this capsular polysaccharide was demonstrated in antisera prepared in rabbits to each of eight strains of B. fragilis fragilis. Antibody of similar specificity was not found in antisera prepared to Bacteroides melaninogenicus or to strains of Bacteroides fragilis subspecies vulgatus and Bacteroides fragilis subspecies distasonis; such antibody was found in antisera to only one of two strains of Bacteroides fragilis subspecies thetaiotaomicron. The radioactive antigen-binding assay is a sensitive test for the detection of antibody to capsular polysaccharide. This polysaccharide antigen may form the basis of a serogrouping system for B. fragilis.
Cancer-associated IDH2 mutants drive an acute myeloid leukemia that is susceptible to Brd4 inhibition (2013)

Somatic mutations in the isocitrate dehydrogenase (IDH) genes IDH1 and IDH2 occur frequently in acute myeloid leukemia (AML) and other cancers. These genes encode neomorphic proteins that produce the presumed oncometabolite 2-hydroxyglutarate (2-HG). Despite the prospect of treating AML and other cancers by targeting IDH mutant proteins, it remains unclear how these mutants affect tumor development and maintenance in vivo, and no cancer models exist to study the action of IDH2 mutants in vivo. We show that IDH2 mutants can cooperate with oncogenic Flt3 or Nras alleles to drive leukemia in mice by impairing the differentiation of cells of the myeloid lineage. Pharmacologic or genetic inhibition of IDH2 triggers the differentiation and death of AML cells, albeit only with prolonged IDH2 inhibition. In contrast, inhibition of the bromodomain-containing protein Brd4 triggers rapid differentiation and death of IDH2 mutant AML. Our results establish a critical role for mutant IDH2 in leukemogenesis and tumor maintenance and identify an IDH-independent strategy to target these cancers therapeutically.
Gas vesicles (1994)

The gas vesicle is a hollow structure made of protein. It usually has the form of a cylindrical tube closed by conical end caps. Gas vesicles occur in five phyla of the Bacteria and two groups of the Archaea, but they are mostly restricted to planktonic microorganisms, in which they provide buoyancy. By regulating their relative gas vesicle content aquatic microbes are able to perform vertical migrations. In slowly growing organisms such movements are made more efficiently than by swimming with flagella. The gas vesicle is impermeable to liquid water, but it is highly permeable to gases and is normally filled with air. It is a rigid structure of low compressibility, but it collapses flat under a certain critical pressure and buoyancy is then lost. Gas vesicles in different organisms vary in width, from 45 to > 200 nm; in accordance with engineering principles the narrower ones are stronger (have higher critical pressures) than wide ones, but they contain less gas space per wall volume and are therefore less efficient at providing buoyancy. A survey of gas-vacuolate cyanobacteria reveals that there has been natural selection for gas vesicles of the maximum width permitted by the pressure encountered in the natural environment, which is mainly determined by cell turgor pressure and water depth. Gas vesicle width is genetically determined, perhaps through the amino acid sequence of one of the constituent proteins. Up to 14 genes have been implicated in gas vesicle production, but so far the products of only two have been shown to be present in the gas vesicle: GvpA makes the ribs that form the structure, and GvpC binds to the outside of the ribs and stiffens the structure against collapse. The evolution of the gas vesicle is discussed in relation to the homologies of these proteins.
Hydrolysis of Milk Protein by a Bacillus licheniformis Protease Specific for Acidic Amino Acid Residues (1997)

ABSTRACT A serine protease, which preferentially cleaves peptide bonds at the carboxylic site of Glu and Asp was evaluated with milk proteins as substrate. The enzyme hydrolyzed casein almost 10 times more efficiently than whey protein. In the casein assay, whey protein did not inhibit the protease, but the enzyme activity in a chromogenic assay was severely inhibited by one whey protein, β‐lactoglobulin. Capillary electrophoresis of β‐lactoglobulin hydrolysate revealed a peptide profile corresponding to the numbers of susceptible bonds, The enzyme may provide advantages in preparation of functional protein fractions and in cheese ripening.
Blue and green light emission from new soluble alternating copolymers (1997)

Visible‐light‐emitting alternating copolymers consisting of two different repeat units have been investigated. The synthesis and optical characterization of PDHFPPV (top in Figure) and PDHEMPV (bottom in Figure) are described. It is shown that these soluble copolymers can be used as the active layer in light‐emitting diodes, just like the corresponding homopolymers. magnified image
Quest for alternatives (1987)

La mise en evidence de l'influence negative des refrigerants de type CFC (chlorofluorocarbones) sur la couche d'ozone de l'atmosphere a pousse les industriels a rechercher des fluides frigorigenes pouvant remplacer notamment les fluides R11 et R12. Ces produits de remplacement doivent repondre a des criteres physiques et thermodynamique precis. Les auteurs etudient systematiquement tous les composes derives du methane et de l'ethane par substitution d'un ou de plusieurs hydrogenes par des atomes de chlore ou de fluor
Fisher Kernels on Visual Vocabularies for Image Categorization (2007)

Within the field of pattern classification, the Fisher kernel is a powerful framework which combines the strengths of generative and discriminative approaches. The idea is to characterize a signal with a gradient vector derived from a generative probability model and to subsequently feed this representation to a discriminative classifier. We propose to apply this framework to image categorization where the input signals are images and where the underlying generative model is a visual vocabulary: a Gaussian mixture model which approximates the distribution of low-level features in images. We show that Fisher kernels can actually be understood as an extension of the popular bag-of-visterms. Our approach demonstrates excellent performance on two challenging databases: an in-house database of 19 object/scene categories and the recently released VOC 2006 database. It is also very practical: it has low computational needs both at training and test time and vocabularies trained on one set of categories can be applied to another set without any significant loss in performance.
Regulation of membrane peptides by the Pseudomonas plasmid alk regulon (1979)

Pseudomonas putida strains carrying the plasmid alk genes will grow on n-alkanes. Induced alk+ strains contain membrane activities for alkane hydroxylation and dehydrogenation of aliphatic primary alcohols. P. putida cytoplasmic and outer membranes can be separated by sucrose gradient centrifugation after disruption of cells by either mild detergent lysis or passage through a French press. Both the membrane component of alkane hydroxylase and membrane alcohol dehydrogenase fractionated with the cytoplasmic membrane. Induction of the alk regulon resulted in the appearance of at least three new plasmid-determined cytoplasmic membrane peptides of about 59,000 (59K), 47,000 (47K), and 40,000 (40K) daltons as well as the disappearance of a pair of chromosomally encoded outer membrane peptides of about 43,000 daltons. The 40K peptide is the membrane component of alkane hydroxylase and the product of the plasmid alkB gene because the alkB1029 mutation altered the properties of alkane hydroxylase in whole cells, reduced its thermal stability in cell extracts, and led to increased electrophoretic mobility of the inducible 40K peptide. These results are consistent with a model for vectorial oxidation of n-alkanes in the cytoplasmic membrane of P. putida.
Hybrid fiber Bragg grating/long period fiber grating sensor for strain/temperature discrimination (1996)

We demonstrate a novel sensor which uses the difference in strain and temperature response of fiber Bragg gratings and a long period fiber grating to discriminate between strain and temperature induced wavelength shifts. Sensor interrogation is performed entirely on the fiber Bragg grating reflection signals. Strain and temperature were simultaneously measured to /spl plusmn/9 μstrain and /spl plusmn/1.5/spl deg/C over a wide range of conditions.
Benzyl Alcohol Attenuates the Pain of Lidocaine Injections and Prolongs Anesthesia (1994)

Benzyl alcohol is itself an effective anesthetic and can reduce the pain of injection for lidocaine without adversely affecting its anesthetic properties.
P‐60: LCD Smear Elimination by Scanning Ray Angle into a Light Guide (2004)

Abstract LCD moving image smear can be eliminated without power loss by sequentially modulating segmented illuminators at the edge of a wedge light guide.
Two Dimensional Photoinduced Electron Transfer (PET) Fluorescence Sensor for Saccharides (1995)

Abstract The cooperative binding of two boronic acid moieties has been utilized to create a two dimensional fluorescence sensor for saccharides. The photoinduced electron transfer switching mechanism has been used to provide information of saccharide concentration while the excimer emission changes of the pyrene moieties provide the nature of the complex.
Evaluation of phase I/II clinical trials in prostate cancer with dendritic cells and PSMA peptides (1998)

The responses observed in the phase I and II clinical trials were significant and of long duration. The partial-responder group included patients who continued to respond from phase I, as well as those who started to respond during the phase II trial.
In vivo properties of an anti-GnRH Spiegelmer: An example of an oligonucleotide-based therapeutic substance class (2002)

Spiegelmers are high-affinity l-enantiomeric oligonucleotide ligands that display high resistance to enzymatic degradation compared with d-oligonucleotides. The target binding properties of Spiegelmers can be designed by an in vitro-selection process starting from a random pool of oligonucleotides. Applying this method, a Spiegelmer with high affinity (K(D) = 20 nM) for the peptide hormone, gonadotropin-releasing hormone (GnRH) was isolated. The Spiegelmer acts as an antagonist to GnRH in Chinese hamster ovary cells stably expressing the human GnRH receptor, and its activity is unchanged by linking to 40-kDa polyethylene glycol. In a castrated rat model the Spiegelmer further demonstrated strong GnRH antagonist activity, which is more pronounced and persists longer with the polyethylene glycol-linked derivative. Furthermore, in rabbits the anti-GnRH Spiegelmer was shown to have a very low, possibly negligible immunogenic potential. These studies suggest that Spiegelmers could be of substantial interest in the development of new pharmaceutical approaches against GnRH and other targets.
An overview of herbal supplement utilization with particular emphasis on possible interactions with dental drugs and oral manifestations. (2003)

Herbal medication in the United States is a popular form of therapy. This paper provides an overview of the utilization of herbal supplements with particular emphasis on possible interactions with oral health drugs and oral manifestations. Herbal supplements are regulated by the Dietary Supplement Health and Education Act (DSHEA), which limits their regulation by the U.S Food and Drug Administration (FDA). A number of studies indicate that there is a progressive increase in the utilization of herbal supplements. The majority of consumers of these products are white, middle-aged women who have some college education. Many of the consumers use pharmaceutical drugs concurrently, but most do not inform their health-care providers about their use of herbal supplements. Various herbal supplements have been reported or are suspected to interact with certain oral health drugs, the most important one being 1) bromelain, cayenne, chamomile, feverfew, dong quai, eleuthro/Seberian ginseng, garlic, ginkgo, ginger, ginseng and licorice interacting with aspirin; 2) aloe latex, ephedra, ginseng, rhubarb, cascara sagrada, licorice, and senna interacting with corticosteriods; 3) kava, St. John's wort, chamomile, and valerian interacting with central nervous system (CNS) depressant drugs; and 4) herbs acting on the gastrointestinal system, altering the absorption of several orally administered drugs. Further, the use of some herbal supplements has been reported to be associated with oral manifestations, including aphthous ulcers, lip and tongue irritation, and swelling with feverfew; gingival bleeding with feverfew and ginkgo; tongue numbness with echinacea; xerostomia with St. John's wort; oral and lingual dyskinesia with kava; and salivation with yohimbe. These potential effects of herbal supplements in conjunction with factors related to regulation restrictions suggest that the use of these products may be associated with various adverse reactions that can affect oral health and treatment. Dental hygienists should inform themselves about herbal supplements in order to offer appropriate oral health care to individuals who take these substances.
Qualitative and Quantitative Analysis of the Binding of GII.4 Norovirus Variants onto Human Blood Group Antigens (2011)

Noroviruses (NoVs) are one of the leading causes of gastroenteritis in children and adults. For the last 2 decades, genogroup II genotype 4 (GII.4) NoVs have been circulating worldwide. GII.4 NoVs can be divided into variants, and since 2002 they have circulated in the population before being replaced every 2 or 3 years, which raises questions about the role of their histo-blood group antigen (HBGA) ligands in their evolution. To shed light on these questions, we performed an analysis of the interaction between representative GII.4 variants and HBGAs, and we determined the role of selected amino acids in the binding profiles. By mutagenesis, we showed that there was a strict structural requirement for the amino acids, directly implicated in interactions with HBGAs. However, the ablation of the threonine residue at position 395 (ΔT395), an epidemiological feature of the post-2002 variants, was not deleterious to the binding of the virus-like particle (VLP) to the H antigen, while binding to A and B antigens was severely hampered. Nevertheless, the ΔT395 VLPs gained the capacity to bind to the Lewis x and sialyl-Lewis x antigens in comparison with the wild-type VLP, demonstrating that amino acid residues outside the HBGA binding site can modify the binding properties of NoVs. We also analyzed the attachment of baculovirus-expressed VLPs from six variants (Bristol, US95/96, Hunter, Yerseke, Den Haag, and Osaka) that were isolated from 1987 to 2007 to phenotyped saliva samples and synthetic HBGAs. We showed that the six variants could all attach to saliva of secretors irrespective of the ABO phenotype and to oligosaccharides characteristic of the secretor phenotype. Interestingly, Den Haag and Osaka variants additionally bound to carbohydrates present in the saliva of Lewis-positive nonsecretors. The carbohydrate binding profile and the genetic and mutagenesis analysis suggested that GII.4 binding to Lewis x and sialyl-Lewis x antigens might be a by-product of the genetic variation of the amino acids located in the vicinity of the binding site. Analysis of the binding properties for the six variants by surface plasmon resonance showed that only post-2002 variants (i.e., Hunter, Yerseke, Den Haag, and Osaka) presented strong binding to A and B antigens, suggesting that the GII.4 evolution could be related to an increased affinity for HBGAs for the post-2002 variants. The combination of increased affinity for ABH antigens and of a newly acquired ability to recognize glycans from Lewis-positive nonsecretors could have contributed to the epidemiological importance of strains such as the Den Haag GII.4 subtype.
Human iPS cellâ€“derived alveolar epithelium repopulates lung extracellular matrix (2013)

The use of induced pluripotent stem cells (iPSCs) has been postulated to be the most effective strategy for developing patient-specific respiratory epithelial cells, which may be valuable for lung-related cell therapy and lung tissue engineering. We generated a relatively homogeneous population of alveolar epithelial type II (AETII) and type I (AETI) cells from human iPSCs that had phenotypic properties similar to those of mature human AETII and AETI cells. We used these cells to explore whether lung tissue can be regenerated in vitro. Consistent with an AETII phenotype, we found that up to 97% of cells were positive for surfactant protein C, 95% for mucin-1, 93% for surfactant protein B, and 89% for the epithelial marker CD54. Additionally, exposing induced AETII to a Wnt/β-catenin inhibitor (IWR-1) changed the iPSC-AETII-like phenotype to a predominantly AETI-like phenotype. We found that of induced AET1 cells, more than 90% were positive for type I markers, T1α, and caveolin-1. Acellular lung matrices were prepared from whole rat or human adult lungs treated with decellularization reagents, followed by seeding these matrices with alveolar cells derived from human iPSCs. Under appropriate culture conditions, these progenitor cells adhered to and proliferated within the 3D lung tissue scaffold and displayed markers of differentiated pulmonary epithelium.