gebhart/patrepeval huggingface dataset:
Modulation of Antibody Pharmacokinetics by Chemical Polysialylation (2008)

Chemical coupling of a variety of polymers to therapeutic proteins has been studied as a way of improving their pharmacokinetics and pharmacodynamics in vivo. Conjugates have been shown to possess greater stability, lower immunogenicity, and a longer blood circulation time due to the chemicophysical properties of these hydrophilic long chain molecules. Naturally occurring colominic acid (polysialic acid, PSA) has been investigated as an alternative to synthetic polymers such as poly(ethylene glycol) (PEG) due to its lower toxicity and natural metabolism. Antibodies and their fragments are a good example of the types of proteins which benefit from pharmacokinetic engineering. Here, we chemically attached differing amounts and differing lengths of short (11 kDa) and longer (22 kDa) chain colominic acid molecules to the antitumor monoclonal antibody H17E2 Fab fragment. Different coupling ratios and lengths were seen to alter the electrophoretic mobility of the Fab fragment but have a minor effect on the antibody immunoreactivity toward the placental alkaline phosphatase (PLAP) antigen. Polysialylation generally increased Fab fragment blood half-life resulting in higher tumor uptake in a KB human tumor xenograft mouse model. One H17E2 Fab-PSA conjugate had over a 5-fold increase in blood exposure and over a 3-fold higher tumor uptake with only a marginal decrease in tumor/blood selectivity ratio compared to the unconjugated Fab. This conjugate also had a blood bioavailability approaching that of a whole immunoglobulin.
3D colonic polyp segmentation using dynamic deformable surfaces (2004)

An improved 3D method for colonic polyp segmentation was developed based on previous 2D method. The method is based on combination of 3D knowledge-guided intensity adjustment, fuzzy clustering, and dynamic deformable surfaces. After intensity adjustment and fuzzy clustering, a deformable surface is employed to locate the polyp boundaries. The surface is also dynamically maintained to preserve the resolution and topology. The deformable surface is operated on a sub-volume of the data set and driven by image forces, balloon forces and internal spline forces. Compared to previous 2D method, the improved method produces much smoother polyp boundaries, and 3D features can be derived from the segmentation, such as 3D aspect ratio, curvatures, and polyp wall thickness etc. The computer segmentations were validated with manual segmentations. Preliminary results showed that the average volume overlap percentage among 25 polyp detections was 80.6%.
Many Random Sequences Functionally Replace the Secretion Signal Sequence of Yeast Invertase (1987)

In the process of protein secretion, amino-terminal signal sequences are key recognition elements; however, the relation between the primary sequence of an amino-terminal peptide and its ability to function as an export signal remains obscure. The limits of variation permitted for functional signal sequences were determined by replacement of the normal signal sequence of Saccharomyces cerevisiae invertase with essentially random peptide sequences. Since about one-fifth of these sequences can function as an export signal the specificity with which signal sequences are recognized must be very low.
Embryonic Pig Pancreatic Tissue Transplantation for the Treatment of Diabetes (2006)

These results emphasize the importance of selecting embryonic tissue of the correct gestational age for optimal growth and function and for reduced immunogenicity, and provide a proof of principle for the therapeutic potential of E42 embryonic pig pancreatic tissue transplantation in diabetes.
The immunostimulating complex (ISCOM) is an efficient mucosal delivery system for respiratory syncytial virus (RSV) envelope antigens inducing high local and systemic antibody responses (1998)

ISCOM is an efficient mucosal delivery system for RSV envelope proteins as measured by antibody responses in respiratory tract secretions and in sera of mice following two intranasal (i.n.) administrations. Intranasally administered RSV ISCOMs induced high levels of IgA antibodies both in the upper respiratory tract and in the lungs. In the lungs, a prominent and long-lasting IgA response was recorded, which still persisted 22 weeks after the second i.n. immunization when the experiment ended. Subcutaneous (s.c.) immunization only induced low IgA titres in the upper respiratory tract and no measurable response to RSV was found in the lungs. Differences were also noticed in serum between the i.n. and s.c. modes of immunization. ISCOMs given intranasally induced earlier, higher and longer lasting IgM and IgG1 serum anti-RSV antibody responses than those induced by the s.c. mode of administration. A low serum IgE response was only detectable at 2 weeks after i.n. immunization with ISCOMs and after s.c. immunization with an inactivated virus, but no IgE response was detectable after s.c. injection of ISCOMs. The serum IgA response was more pronounced following s.c. injection of inactivated virus than after i.n. application of ISCOMs, and a clear-cut booster effect was obtained with a second immunization. Virtually no serum IgA response was detected after the s.c. administration of ISCOMs. In conclusion, the high immune responses induced by RSV ISCOMs in the respiratory tract and serum after i.n. administration indicate prominent mucosal delivery and adjuvant properties of the ISCOMs, warranting further studies.
Clinical usefulness of color doppler ultrasound in patients with endometrial hyperplasia and carcinoma (2002)

TV-CDU may be more useful in differentiating between EH and EC than measuring endometrial thickness by transvaginal gray-scale sonography. For patients with EC, the detection of intratumoral blood flow may be helpful in distinguishing between low-grade and high-grade tumors and predicting myometrial invasion. However, intratumoral blood flow analysis using RI, PI, or PSV may not be useful for predicting tumor spread before surgery.
AtBXL1, a novel higher plant (Arabidopsis thaliana) putative beta‐xylosidase gene, is involved in secondary cell wall metabolism and plant development (2003)

To investigate mechanisms involved in cell wall development, an Arabidopsis T-DNA insertion mutant collection was screened to identify mutants with beta-glucuronidase fusion gene expression in tissues undergoing secondary cell wall thickening. This promoter-trapping strategy allowed the isolation of a transformant containing the GUS coding sequence inserted 700 bp upstream of the ATG of a putative beta-xylosidase gene. The transformant has no phenotype as the expression of the gene was not disrupted by the insertion. The analysis of the predicted protein, AtBXL1, suggests its targeting to the extracellular matrix and its involvement in cell wall metabolism through a putative activity towards xylans. The 2-kb promoter sequence of AtBXL1 was fused to the GUS coding sequence and introduced into wild-type Arabidopsis thaliana. GUS expression was shown to be restricted to tissues undergoing secondary cell wall formation. Beta-xylosidase activity was associated with the cell wall-enriched fraction of different organs of wild-type plants. The level of activity correlates with transcript accumulation of AtBXL1 and other AtBXL1-related genes. Transgenic plants expressing the AtBXL1 cDNA in antisense orientation were generated. Lines exhibiting the highest decrease in AtBXL1 transcript accumulation and beta-xylosidase activity had phenotypic alterations. This newly identified gene is proposed to be involved in secondary cell wall hemicellulose metabolism and plant development.
Sildenafil for Psychotropic-Induced Sexual Dysfunction in 31 Women and 61 Men (2000)

Ninety-two outpatients (31 women, 61 men) who were treated with oral sildenafil for psychotropic-induced sexual dysfunction (PISD) completed ratings of their sexual functioning pre- and posttreatment. Both women and men reported significant improvements (p = .001) in all domains of sexual functioning, with 88% reporting improvement in overall sexual satisfaction. Significant improvements were reported regardless of psychotropic medication type. However, patients taking selective serotonin re-uptake inhibitors reported less improvement in arousal, libido, and overall sexual satisfaction than did other patients, whereas patients taking benzodiazepines reported significantly more improvement in libido and overall sexual satisfaction. Oral sildenafil may be an effective treatment for PISD.
Occurrence of Amphoterin (HMG1) as an Endogenous Protein of Human Platelets that Is Exported to the Cell Surface upon Platelet Activation (2000)

Amphoterin (HMG1) is a 30-kD heparin-binding protein which is functionally associated with the outgrowth of cytoplasmic processes in developing neurones. Amphoterin has been shown to mediate adhesive and proteolytic interactions at the leading edge of motile cells. Recently it was shown that inhibition of amphoterin interactions with its cell surface receptor (RAGE) suppresses tumour growth and metastasis. In this work we have identified amphoterin polypeptide and its mRNA in human platelets. Amphoterin had a cytoplasmic localisation in resting platelets according to subcellular fractionation studies and immunogold electronmicroscopy. After platelet activation, part of amphoterin was associated with the external surface of plasma membrane. Externalisation of amphoterin during platelet activation was also detected in immunofluorescence studies. Amphoterin was detectable in human serum (0.2 ng/ml) but not in plasma. Resting platelets treated with PGI2 and forskolin bound to immobilised recombinant amphoterin independently of divalent cations. The binding induced a spicular morphology in platelets, and was effectively inhibited by heparin. Amphoterin-binding protein components on the platelet surface were not identified, but amphoterin bound to phosphatidylserine and sulfatide in lipid binding assays. Our results suggest that amphoterin is an endogenous protein in human platelets, which is exported to the cell surface during platelet activation. Interaction of amphoterin with the platelet surface may be mediated by sulfoglycolipids and phospholipids.
Platelet-derived microvesicles transfer tissue factor to monocytes but not to neutrophils (2004)

Activated platelets are known to adhere to both blood monocytes and neutrophils, and this adhesion is mainly mediated by the surface exposure of the platelet granule protein CD62P. Platelets as well as platelet-derived microvesicles (PMV) have also been shown to contain and to transfer tissue factor (TF), the most important initiator of intravascular thrombin and fibrin formation, to monocytes. However, the role of neutrophils for gathering platelet-derived TF is controversial. Here we studied the interaction of PMV with monocytes and neutrophils using a whole blood system. Platelet-rich plasma (PRP) obtained from citrated human blood was incubated with collagen (5 microg/ml, 15 min) and the platelets were removed by centrifugation (5 min at 5000 x g). After incubating the PMV-containing plasma for further 30 min with a sediment of red and white bloods cells that had been obtained after PRP preparation, monocytes and neutrophils were analysed by flow cytometry for the surface exposure of the platelet-specific antigen CD42a and TF. Compared to a control with non-activated PRP, there was a significant increase in the number of both CD42a-positive monocytes and neutrophils. In contrast, there was no change in the number of TF-positive neutrophils, but a more than 2-fold increase in the number of TF-positive monocytes. The changes in CD42a on monocytes and neutrophils as well as the changes in TF on monocytes could be significantly reduced by an anti-CD62P antibody or by removal of PMV from the plasma samples. The data indicate that the transfer of TF to monocytes is not simply an CD62P-mediated adhesion of platelets or PMV to monocytes, but may involve other not yet identified mechanisms.
Biosynthesis of prodiginines. 13C resonance assignments and enrichment patterns in nonyl-, cyclononyl-, methylcyclodecyl-, and butylcycloheptylprodiginine produced by actinomycete cultures supplemented with 13C-labeled acetate and 15N-labeled nitrate (1978)

Resonances in the 13 C nmr spectra of nonylprodiginine, cyclononylprodiginine, methylcyclodecylprodiginine, and butylcycloheptylprodiginine were assigned using information from the literature, from high resolution spectra and double irradiation experiments, and from 13 C– 15 N couplings observed in samples of nonylprodiginine enriched with 15 N. Supplementation of cultures with sodium [1- 13 C]- and [1,2- 13 C]acetate gave 13 C-enriched prodiginines and the labeling patterns were established from 13 C nmr spectra. These indicated that rings A and B were formed in a similar manner to rings A and B in prodigiosin and other prodiginine pigments. Ring C and the C2-alkyl substituent were derived in part from acetate units that were condensed in a linear 12- or 14-carbon chain. The same pattern of acetate assembly has been found in ail actinomycete prodiginines examined.
Mechanism of porphobilinogen synthase. Requirement of Zn2+ for enzyme activity. (1980)

The role of metal ions in the mechanism of action of bovine liver porphobilinogen synthase was investigated. Studies with chelating agents were consistent with a requirement of metal ions for enzyme activity, and the use of 8-hydroxyquinoline-5-sulfonic acid suggested that Zn2+ was present in the enzyme. The low activity detected in metal-free apoporphobilinogen synthase was attributed to adventitious metal ions. Addition of Zn2+ to the apoenzyme completely restored enzyme activity if the essential sulfhydryl groups on the enzyme were first reduced with sulfhydryl reagents. It does not follow necessarily from this observation that Zn2+ forms a bond with a sulfhydryl group in the enzyme. However, we also observed that Zn2+ did not bind to the enzyme unless the essential cysteinyl residues were reduced. We have concluded that the octameric enzyme contains 4 g atoms of Zn2+/mol from our enzyme activity measurements and binding studies. Alkylation of the enzyme resulted in a marked reduction in the binding of Zn2+ to the enzyme. These observations are consistent with the suggestion that the interaction of the Zn2+ ions with the enzyme occurs with sulfhydryl groups at the active site. It appears that Zn2+ does not participate in substrate binding nor in the maintenance of the quaternary structure of the enzyme. Possible mechanistic roles for Zn2+ in porphobilinogen synthase are discussed. It should be noted that Cd2+ was the only other element found which restored activity to the apoenzyme.
Biotin-Labeled Riboprobes to Study RNA-Binding Proteins (1996)

Most of the methods available to detect and study RNA-binding proteins use a radioactively labeled component. We describe a nonradioactive modification of the Northwestern assay using biotinylated riboprobes. The method detects binding of biotinylated RNA to proteins fixed on nitrocellulose. Proteins are first separated by SDS-polyacrylamide gel electrophoresis (PAGE), transferred to the nitrocellulose membrane, and renatured. Therefore, generation of variant proteins and the analysis of their RNA-binding capacity can be quickly accomplished. The biotinylated riboprobes are stable and easy to handle, permitting the processing of large numbers of samples in a short time. Chemiluminescence is generated with streptavidin-conjugated peroxidase and luminol-luciferin. This method has been successfully applied to the study of poliovirus RNA-binding proteins.
Casting inorganic structures with DNA molds (2014)

We report a general strategy for designing and synthesizing inorganic nanostructures with arbitrarily prescribed three-dimensional shapes. Computationally designed DNA strands self-assemble into a stiff "nanomold" that contains a user-specified three-dimensional cavity and encloses a nucleating gold "seed." Under mild conditions, this seed grows into a larger cast structure that fills and thus replicates the cavity. We synthesized a variety of nanoparticles with 3-nanometer resolution: three distinct silver cuboids with three independently tunable dimensions, silver and gold nanoparticles with diverse cross sections, and composite structures with homo- and heterogeneous components. The designer equilateral silver triangular and spherical nanoparticles exhibited plasmonic properties consistent with electromagnetism-based simulations. Our framework is generalizable to more complex geometries and diverse inorganic materials, offering a range of applications in biosensing, photonics, and nanoelectronics.
Overcoming the restriction barrier to plasmid transformation and targeted mutagenesis in Bifidobacterium breve UCC2003 (2008)

In silico analysis of the Bifidobacterium breve UCC2003 genome predicted two distinct loci, which encode three different restriction/modification systems, each comprising a modification methylase and a restriction endonuclease. Based on sequence homology and observed protection against restriction we conclude that the first restriction endonuclease, designated BbrI, is an isoschizomer of BbeI, the second, BbrII, is a neoschizomer of SalI, while the third, BbrIII, is an isoschizomer of PstI. Expression of each of the B. breve UCC2003 methylase-encoding genes in B. breve JCM 7017 established that BbrII and BbrIII are active and restrict incoming DNA. By exploiting knowledge on restriction/modification in B. breve UCC2003 we successfully increased the transformation efficiency to a level that allows the reliable generation of mutants by homologous recombination using a non-replicative plasmid.
Intrinsic and Rashba spin-orbit interactions in graphene sheets (2006)

Starting from a microscopic tight-binding model and using second-order perturbation theory, we derive explicit expressions for the intrinsic and Rashba spin-orbit interaction induced gaps in the Dirac-like low-energy band structure of an isolated graphene sheet. The Rashba interaction parameter is first order in the atomic carbon spin-orbit coupling strength $\ensuremath{\xi}$ and first order in the external electric field $E$ perpendicular to the graphene plane, whereas the intrinsic spin-orbit interaction which survives at $E=0$ is second order in $\ensuremath{\xi}$. The spin-orbit terms in the low-energy effective Hamiltonian have the form proposed recently by Kane and Mele. Ab initio electronic structure calculations were performed as a partial check on the validity of the tight-binding model.
AKT-1, -2, and -3 are expressed in both normal and tumor tissues of the lung, breast, prostate, and colon. (2001)

Our data show that both normal and tumor tissues express all three of the AKT isoforms and indicate that tumorigenesis does not involve a dramatic shift in the RNA expression patterns of the three AKT isoforms.
Engineering split intein DnaE from Nostoc punctiforme for rapid protein purification (2012)

We report the engineering of a DnaE intein able to catalyze rapid C-terminal cleavage in the absence of N-terminal cleavage. A single mutation in DnaE intein from Nostoc punctiforme PCC73102 (NpuDnaE), Asp118Gly, was introduced based on sequence alignment with a previously engineered C-terminal cleaving intein mini-MtuRecA. This mutation was able to both suppress N-terminal cleavage and significantly elevate C-terminal cleavage efficiency. Molecular modeling suggests that in NpuDnaE Asp118 forms a hydrogen bond with the penultimate Asn, preventing its spontaneous cyclization prior to N-terminal cleavage. Mutation of Asp118 to Gly essentially abolishes this restriction leading to subsequent C-terminal cleavage in the absence of N-terminal cleavage. The Gly118 NpuDnaE mutant exhibits rapid thio-dependent C-terminal cleavage kinetics with 80% completion within 3 h at room temperature. We used this newly engineered intein to develop both column-free and chromatography-based protein purification methods utilizing the elastin-like-polypeptide and chitin-binding protein as removable purification tags, respectively. We demonstrate rapid target protein purification to electrophoretic purity at yields up to 84 mg per liter of Escherichia coli culture.
Characterization of unique amphipathic antimicrobial peptides from venom of the scorpion Pandinus imperator (2001)

Two novel antimicrobial peptides have been identified and characterized from venom of the African scorpion Pandinus imperator. The peptides, designated pandinin 1 and 2, are α-helical polycationic peptides, with pandinin 1 belonging to the group of antibacterial peptides previously described from scorpions, frogs and insects, and pandinin 2 to the group of short magainin-type helical peptides from frogs. Both peptides demonstrated high antimicrobial activity against a range of Gram-positive bacteria (2.4–5.2μM), but were less active against Gram-negative bacteria (2.4–38.2μM), and only pandinin 2 affected the yeast Candida albicans. Pandinin 2 also demonstrated strong haemolytic activity (11.1–44.5μM) against sheep erythrocytes, in contrast with pandinin 1, which was not haemolytic. CD studies and a high-resolution structure of pandinin 2 determined by NMR, showed that the two peptides are both essentially helical, but differ in their overall structure. Pandinin 2 is composed of a single α-helix with a predominantly hydrophobic N-terminal sequence, whereas pandinin 1 consists of two distinct α-helices separated by a coil region of higher flexibility. This is the first report of magainin-type polycationic antimicrobial peptides in scorpion venom. Their presence brings new insights into the mode of action of scorpion venom and also opens new avenues for the discovery of novel antibiotic molecules from arthropod venoms.
Use of ultra stable UNCG tetraloop hairpins to fold RNA structures: thermodynamic and spectroscopic applications (1995)

RNA molecules of > 20 nucleotides have been the focus of numerous recent NMR structural studies. Several investigators have used the UNCG family of hairpins to ensure proper folding. We show that th UUCG hairpin has a minimum requirement of a two base-pair stem. Hairpins with a CG loop closing base pair and an initial 5'CG or 5'GC base pair have a melting temperature approximately 55 degrees C in 10 mM sodium phosphate. The high stability of even such small hairpins suggests that the hairpin can serve as a nucleation site for folding. For high resolution NMR work, the UNCG loop family (UACG in particular) provides excellent spectroscopic markers in one-dimensional exchangeable spectra, in two-dimensional COSY spectra and in NOESY spectra that clearly define it as forming a hairpin. This allows straightforward initiation of chemical shift assignments.
Radiolabeling of Nanoshells with 64 Cu and 111 In for PET and SPECT Imaging in Rats (2009)

Here we report for the first time the radioactive labeling of gold nanoshells with 64 Cu and 111 In. A conjugation method was developed to link nanoshells with the radioactive tags. The resulting conjugates showed good labeling efficiency and stability in PBS and serum for in vivo imaging applications. The circulation of 64 Cunanoshells and 111 In-nanoshells in mice were determined by dynamic light scattering and their blood clearance in rats were determined in terms of radioactive counting. By PET/CT and SPECT/CT imaging, we monitored the in vivo distribution of 64 Cu-nanoshells and 111 In-nanoshells in nude rats with a head and neck squamous cell carcinoma xenograft at various time points after their intravenous injection. PET and SPECT images of the rats showed that both of the labeled nanoshells accumulated in the tumor. PET images with 64 Cu showed better resolution and were therefore, more promising for future applications.