gebhart/patrepeval huggingface dataset:
Receptor binding and biological potency of several split forms (conversion intermediates) of human proinsulin. Studies in cultured IM-9 lymphocytes and in vivo and in vitro in rats. (1985)

The biological activities of several derivatives of human proinsulin (HPI) containing peptide bond cleavages or peptide deletions in the connecting peptide region were examined in vivo in rats and in several in vitro systems. The two derivatives which were tested in vivo, split (32-33)HPI and des-(64,65)HPI, both demonstrated greater potency in lowering blood glucose than did intact HPI. The receptor binding affinities of split (65-66)HPI, des-(57-65)HPI, des-(64,65)HPI, des-(33-56)HPI, des-(31,32)HPI, split (32-33)HPI, and split (56-57)HPI were examined in cultured IM-9 lymphocytes, freshly isolated rat adipocytes, and purified rat liver membranes and were compared to the binding of intact HPI and insulin. In these systems, HPI averaged approximately 1% of the activity of insulin. Modification of proinsulin in the connecting peptide region near the A-chain of insulin to form split (65-66)HPI, des-(57-65)HPI, des-(64,65)HPI, or des-(33-56)HPI resulted in an increase in affinity for receptor binding ranging from 11 to 27-fold over that of intact HPI. In contrast, modifications near the B-chain of insulin to form either des-(31,32)HPI or split (32-33)HPI resulted in roughly a 5-fold increase in affinity, whereas a cleavage within the connecting peptide to form split (56-57)HPI showed only a 2-fold increase in affinity as compared to intact HPI. The biological potencies of these materials were examined in isolated rat adipocytes. At high concentrations (10(-7) M), each derivative produced the same maximal response. At lower concentrations, differences in the relative potencies paralleled the differences in receptor binding affinity previously noted.
Fungal saprobes and pathogens as endophytes of rice (Oryza sativaL.) (1992)

summary Fungal endophytes have been isolated from inside the leaf blades, leaf sheaths, and roots of six‐week‐old plants as well as from seeds and ten‐day‐old seedlings of Oryza sativa (L.). The fungi isolated can be grouped in two categories; one containing organisms known mainly to be saprotrophic and the other comprising potential pathogens. Of the former Alternaria alternata (Fr.) Keissler and Epicoccum purpurascens Ehrenb. ex. Schlecht preferentially colonize the leaf blades of their host, whereas Cladosporium tenuissimum Cooke seems more generally distributed between leaf blades and leaf sheaths. Fusarium equiseti (Cords) Sacc., F. oxysporum Schecht and Phoma sorghina (Sacc. Boerema) are latent in their hosts without causing disease symptoms. A. alternata, E. purpurascens, F, equiseti. and Nigraspora oryzae have also been frequently isolated from seeds and young seedlings and can be considered seed‐borne. Principal components analysis has shown a marked tissue specificity among rice endophytes. Leaf sheaths of the rice varieties grown under dry conditions are colonized by endophyte communities different from those of the wet cultivars.
Charge Density and Molecular Weight of Polyphosphoramidate Gene Carrier Are Key Parameters Influencing Its DNA Compaction Ability and Transfection Efficiency (2010)

A series of polyphosphoramidates (PPAs) with different molecular weights (MWs) and charge densities were synthesized and examined for their DNA compaction ability and transfection efficiency. A strong correlation was observed between the transfection efficiency of PPA/DNA nanoparticles and the MW and net positive charge density of the PPA gene carriers in three different cell lines (HeLa, HEK293, and HepG2 cells). An increase in MW and net positive charge density of PPA carrier yielded higher DNA compaction capacity, smaller nanoparticles with higher surface charges, and higher complex stability against challenges by salt and polyanions. These favorable physicochemical properties of nanoparticles led to enhanced transfection efficiency. PPA/DNA nanoparticles with the highest complex stability showed comparable transfection efficiency as PEI/DNA nanoparticles likely by compensating the low buffering capacity with higher cellular uptake and affording higher level of protection to DNA in endolysosomal compartment. The differences in transfection efficiency were not attributed by any difference in cytotoxicity among the carriers, as all nanoparticles showed a minimal level of cytotoxicity under the transfection conditions. Using PPA as a model system, we demonstrated the structural dependence of transfection efficiency of polymer gene carrier. These results offer more insights into nanoparticle engineering for nonviral gene delivery.
Clumping factor B (ClfB), a new surface‐located fibrinogen‐binding adhesin of Staphylococcus aureus (1998)

The surface-located fibrinogen-binding protein (clumping factor; ClfA) of Staphylococcus aureus has an unusual dipeptide repeat linking the ligand binding domain to the wall-anchored region. Southern blotting experiments revealed several other loci in the S. aureus Newman genome that hybridized to a probe comprising DNA encoding the dipeptide repeat. One of these loci is analysed here. It also encodes a fibrinogen-binding protein, which we have called ClfB. The overall organization of ClfB is very similar to that of ClfA, and the proteins have considerable sequence identity in the signal sequence and wall attachment domains. However, the A regions are only 26% identical. Recombinant biotinylated ClfB protein bound to fibrinogen in Western ligand blots. ClfB reacted with the alpha- and beta-chains of fibrinogen in the ligand blots in contrast to ClfA, which binds exclusively to the gamma-chain. Analysis of proteins released from the cell wall of S. aureus Newman by Western immunoblotting using antibody raised against the recombinant A region of ClfB identified a 124 kDa protein as the clfB gene product. This protein was detectable only on cells that were grown to the early exponential phase. It was absent from cells from late exponential phase or stationary phase cultures. Using a clfB mutant isolated by allelic replacement alone and in combination with a clfA mutation, the ClfB protein was shown to promote (i) clumping of exponential-phase cells in a solution of fibrinogen, (ii) adherence of exponential-phase bacteria to immobilized fibrinogen in vitro, and (iii) bacterial adherence to ex vivo human haemodialysis tubing, suggesting that it could contribute to the pathogenicity of biomaterial-related infections. However, in wild-type exponential-phase S. aureus Newman cultures, ClfB activity was masked by the ClfA protein, and it did not contribute at all to interactions of cells from stationary-phase cultures with fibrinogen. ClfB-dependent bacterial adherence to immobilized fibrinogen was inhibited by millimolar concentrations of Ca2+ and Mn2+, which indicates that, like ClfA, ligand binding by ClfB is regulated by a low-affinity inhibitory cation binding site.
Generation of mutant mice via the CRISPR/Cas9 system using FokI-dCas9 (2015)

Genome editing, which introduces mutations in genes of interest using artificial DNA nucleases such as the ZFN, TALEN, and CRISPR/Cas9 systems in living cells, is a useful tool for generating mutant animals. Although CRISPR/Cas9 provides advantages over the two other systems, such as an easier vector construction and high efficiency of genome editing, it raises concerns of off-target effects when single guide RNA (gRNA) is used. Recently, FokI-dCas9 (fCas9), a fusion protein comprised of the inactivated mutant form of Cas9 and the DNA nuclease domain of FokI, has been developed. It enables genome editing with reduced risks of off-target effects in mammalian cultured cell lines, as fCas9 requires gRNAs to bind opposite strands with an appropriate distance between them. Here, we demonstrated that fCas9 efficiently generates living mutant mice through microinjection of its mRNA and gRNAs into zygotes. A comparison of the relative efficiencies of genome editing using fCas9 and other modified Cas9s showed that these mutagenesis efficiencies are similar when the targets of two gRNAs are separated by an appropriate distance, suggesting that in addition to the ease of vector construction, fCas9 exhibit high efficiency in producing mutant mice and in reducing risks of off-target effects.
Chemical Strategies for Functional Proteomics (2002)

With complete genome sequences now available for several prokaryotic and eukaryotic organisms, biological researchers are charged with the task of assigning molecular and cellular functions to thousands of predicted gene products. To address this problem, the field of proteomics seeks to develop and apply methods for the global analysis of protein expression and protein function. Here we review a promising new class of proteomic strategies that utilizes synthetic chemistry to create tools and assays for the characterization of protein samples of high complexity. These approaches include the development of chemical affinity tags to measure the relative expression level and post-translational modification state of proteins in cell and tissue proteomes. Additionally, we discuss the emerging field of activity-based protein profiling, which aims to synthesize and apply small molecule probes that monitor dynamics in protein function in complex proteomes.
A Twisted Dimeric Perylene Diimide Electron Acceptor for Efficient Organic Solar Cells (2014)

A novel solution-processable twisted dimeric perylene diimide (IDT-2PDI) with a bulky fused-ring indacenodithiophene as a bridge is developed as an electron acceptor for organic solar cells (OSCs). Poly(3-hexylthiophene) (P3HT):IDT-2PDI based OSCs have power conversion efficiencies (PCEs) up to 2.61% with a high fill factor of 0.668, and benzodithiophene-diketopyrrolopyrrole (BDT-2DPP):IDT-2PDI based OSCs exhibit a promising PCE of 3.12%.
RECOVERY OF CO2 WITH LACTATE INFUSION DURING REST AND EXERCISE -??? THE LACTATE CLAMP??? (2002)

As a follow up to a larger study examining training induced changes in gluconeogenic capacity, we employed an exogenous Na-lactate:lactic acid (70:30) infusion during periods of rest and exercise in moderately active subjects. Others have previously shown that RER decreases during rest with Na-lactate infusion due to the generation of HCO3−. Presumably the introduction of Na+ with lacate increases the NaHCO3 content of blood and thus the body HCO3− pool. The increased HCO3− pool leads to decreased pulmonary CO2 elimination and consequently a decrease in RER or 13C-tracer infusion. Purpose: To determine the recovery of CO2 during a Na-lactate/lactic acid infusion to accurately quantify substrate oxidation. Methods: Subjects were studied during 90-minutes of rest and 90-minutes of exercise (55% VO2peak) with a primed-continuous infusion of NaH13CO3. Subjects were studied once with a Na-lactate/lactic acid infusion (LAC) and once without (CON). Results: Lactate infusion during rest averaged (± SEM) 2.98 ± 0.13 mg/kg/min and raised blood lactate to an average of 3.3 ± 0.1 mmol (CON= 0.8 ± 0.03 mmol) During exercise exogenous lactate infusion averaged 2.8 ± 0.2 mg/kg/min and resulted in lactate levels of 2.9 ± 0.2 mmol (CON = 1.5 mmol). Resting plasma HCO3− concentrations were increased during LAC compared to CON (14.5 ± 0.7 vs. 11.4 ± 0.3 mmol). During exercise HCO3− increased to 22.8 ± 0.8 mmol during LAC, but did not change in CON (10.8 ± 0.3 mmol). During rest tracer measured HCO3− recovery averaged 69.8 and 66.7% during CON and LAC respectively. During exercise HCO3− recovery was 77.1 and 82.4% during CON and LAC respectively. VCO2 was not significantly different during rest (CON = 2.86 ± 0.1 and LAC = 2.84 ± 0.1 ml/kg/min) or exercise (CON = 25.3 ± 0.7 and LAC = 25.2 ± 0.7 ml/kg/min). However, VO2 was elevated during LAC in rest (CON = 3.33 ± 0.1 and LAC = 3.84 ± 0.1 ml/kg/min) and exercise (CON = 28.5 ± 0.9 and LAC = 29.3 ± 0.8 ml/kg/min). Subsequently, LAC resulted in a decreased RER during rest (CON= 0.87 ± 0.0 and LAC = 0.75 ± 0.01) and exercise (CON = 0.90 ± 0.01 and LAC = 0.87 ± 0.01). Conclusion: HCO3− recovery and CO2 was similar during CON and LAC trials. However, O2 consumption was greater resulting in a decreased RER. Thus, tracer measured oxidation rates should not change due to CO2 retention despite increased plasma HCO3− concentration. Supported by NIH DK-19577 and AR-42906.
Conservation of the Duchenne Muscular Dystrophy Gene in Mice and Humans (1987)

A portion of the Duchenne muscular dystrophy (DMD) gene transcript from human fetal skeletal muscle and mouse adult heart was sequenced, representing approximately 25 percent of the total, 14-kb DMD transcript. The nucleic acid and predicted amino acid sequences from the two species are nearly 90 percent homologous. The amino acid sequence that is predicted from this portion of the DMD gene indicates that the protein product might serve a structural role in muscle, but the abundance and tissue distribution of the messenger RNA suggests that the DMD protein is not nebulin.
Key role of poly-γ-dl-glutamic acid in immune evasion and virulence of Staphylococcus epidermidis (2005)

Coagulase-negative staphylococci, with the leading species Staphylococcus epidermidis, are the predominant cause of hospital-acquired infections. Treatment is especially difficult owing to biofilm formation and frequent antibiotic resistance. However, virulence mechanisms of these important opportunistic pathogens have remained poorly characterized. Here we demonstrate that S. epidermidis secretes poly-γ-DL-glutamic acid (PGA) to facilitate growth and survival in the human host. Importantly, PGA efficiently sheltered S. epidermidis from key components of innate host defense, namely antimicrobial peptides and neutrophil phagocytosis, and was indispensable for persistence during device-related infection. Furthermore, PGA protected S. epidermidis from high salt concentration, a key feature of its natural environment, the human skin. Notably, PGA was synthesized by all tested strains of S. epidermidis and a series of closely related coagulase-negative staphylococci, most of which are opportunistic pathogens. Our study presents important novel biological functions for PGA and indicates that PGA represents an excellent target for therapeutic maneuvers aimed at treating disease caused by S. epidermidis and related staphylococci.
Translocation Down syndrome. (2002)

Cytogenetic investigations carried on 1021 cases of Down syndrome revealed translocation in 46 cases. The most frequent was of t(14;21) and t(21;21) types. Most of the translocation DS cases (n = 31) were born to younger mother's (< 25 years), when compared to pure trisomy 21 DS cases. Parental karyotypes, family history and parental ages has helped us greatly in offering genetic counseling, prenatal diagnosis and estimating the risk for the next conception.
Structure determination of tunicaminyl uracil, a degradation product of tunicamycin. (1979)

Tunicaminyl uracil, C15H23N3O10, was obtained by the hydrolysis of tunicamycin with 3 N HCl at 100° for 3hr. By a combination of chemical and spectrometric methods, its structure was determined to be 1-β-(10'-amino-6', 10'-dideoxy-L-galacto-D-allo-undecodialdo-7', 11'-pyranose-1', 4'-furanosyl)-uracil (I).
Error characterization of flight trajectories reconstructed using Structure from Motion (2013)

This research assesses the accuracy of Structure from Motion algorithms in replicating aircraft flight trajectories in real world coordinate systems. Structure from Motion techniques can be used to estimate aircraft trajectory and attitude by estimating the position and pose of a camera mounted on the airframe from a series of images taken with that camera. The scale and coordinate systems associated with these pose estimates are arbitrary but can be tied to a real world coordinate system and scale with knowledge of terrain features or aircraft INU/GPS measurements. As a result, Structure from Motion techniques hold great promise for use in image based Simultaneous Localization and Mapping (SLAM); however, the error associated with these techniques must be understood for incorporation into a robust navigation system. The error in the Structure from Motion trajectory reconstruction is affected by feature matching methods, camera geometry and algorithm parameters as well as the method used to convert from reconstruction coordinates to real world coordinates. Methods of using inertial and geographic measurement data to associate a scale and real world coordinate system with the trajectory estimates are developed and compared. The reconstructed flight trajectory output by Structure from Motion is compared to the actual flight trajectory to characterize errors using both simulation and flight test data in a variety of flight regimes.
Thermal annealing effects of dangling bonds in hydrogenated polymorphous silicon (2008)

We investigate the effect of thermal annealing on the density of thermally induced native dangling bonds existing in the amorphous network and created during sample preparation in hydrogenated polymorphous silicon (pm-Si:H) by means of electron spin resonance (ESR). The decay curve of the ESR signal intensity associated with dangling bonds is fitted by a stretched exponential function. The dispersion parameter β and the characteristic time τ are deduced and compared to those for hydrogenated amorphous silicon (a-Si:H). The results are discussed in terms of rapid hydrogen motion associated with the peculiar structure of pm-Si:H.
Crizotinib inALK-Rearranged Inflammatory Myofibroblastic Tumor (2010)

Inflammatory myofibroblastic tumor (IMT) is a distinctive mesenchymal neoplasm characterized by a spindle-cell proliferation with an inflammatory infiltrate. Approximately half of IMTs carry rearrangements of the anaplastic lymphoma kinase (ALK) locus on chromosome 2p23, causing aberrant ALK expression. We report a sustained partial response to the ALK inhibitor crizotinib (PF-02341066, Pfizer) in a patient with ALK-translocated IMT, as compared with no observed activity in another patient without the ALK translocation. These results support the dependence of ALK-rearranged tumors on ALK-mediated signaling and suggest a therapeutic strategy for genomically identified patients with the aggressive form of this soft-tissue tumor. (Funded by Pfizer and others; ClinicalTrials.gov number, NCT00585195.).
High levels of HER-2 expression alter the ability of epidermal growth factor receptor (EGFR) family tyrosine kinase inhibitors to inhibit EGFR phosphorylation in vivo. (2001)

The epidermal growth factor receptor (EGFR) and HER-2 tyrosine kinases have been implicated in the development, progression, and severity of several human cancers and are attractive targets for therapeutic intervention. SU11925 was developed as a small molecule inhibitor of the tyrosine kinase activity of both EGFR and HER-2. In cellular assays, SU11925 exhibited similar potency against EGFR and HER-2, inhibiting EGF-stimulated EGFR autophosphorylation in A431 (human epidermoid carcinoma) cells with an IC(50) of 30 nM and HER-2 phosphorylation in SK-OV-3TP5 (human ovarian carcinoma) cells with an IC(50) of 38 nM. In contrast to its similar activity against the two targets in cellular assays, approximately 10-fold higher plasma concentrations of SU11925 were required to inhibit HER-2 phosphorylation in HER-2-overexpressing tumors compared with EGFR phosphorylation in EGFR-overexpressing tumors in vivo. Consistent with the proposed mechanism of action of this inhibitor, SU11925 inhibited the s.c. growth of EGFR- and HER-2-dependent tumors in athymic mice at doses that produced substantial inhibition of target receptor phosphorylation in vivo. An unexpected finding from these studies was that higher plasma concentrations of SU11925 were required to inhibit EGFR phosphorylation in vivo in tumors that also express high levels of HER-2 than in tumors that express EGFR alone. This observation, which suggests that it is more difficult to inhibit EGFR phosphorylation in vivo in cells that express high levels of HER-2, was confirmed with ZD1839 (Iressa), a selective EGFR inhibitor that also targets the tyrosine kinase catalytic site. The potential clinical implications of this observation are discussed.
Cell Migration Is Regulated by AGE-RAGE Interaction in Human Oral Cancer Cells In Vitro (2014)

Advanced glycation end products (AGEs) are produced in an irreversible non-enzymatic reaction of carbohydrates and proteins. Patients with diabetes mellitus (DM) are known to have elevated AGE levels, which is viewed as a risk factor of diabetes-related complications. In a clinical setting, it has been shown that patients with oral cancer in conjunction with DM have a higher likelihood of cancer metastasis and lower cancer survival rates. AGE-RAGE (a receptor of AGEs) is also correlated with metastasis and angiogenesis. Recent studies have suggested that the malignancy of cancer may be enhanced by glyceraldehyde-derived AGEs; however, the underlying mechanism remains unclear. This study examined the apparently close correlation between AGE-RAGE and the malignancy of SAS oral cancer cell line. In this study, AGEs increased ERK phosphorylation, enhanced cell migration, and promoted the expression of RAGE, MMP2, and MMP9. Using PD98059, RAGE antibody, and RAGE RNAi to block RAGE pathway resulted in the inhibition of ERK phosphorylation. Cell migration, MMP2 and MMP9 expression were also reduced by this treatment. Our findings demonstrate the importance of AGE-RAGE with regard to the malignancy of oral cancer, and help to explain the poor prognosis of DM subjects with oral cancer.
PEG- and Peptide-Grafted Aliphatic Polyesters by Click Chemistry (2005)

Novel aliphatic polyesters with pendent acetylene groups were prepared by controlled ring-opening polymerization and subsequently used for grafting poly(ethylene glycol) and oligopeptide moieties by the Cu(I)-catalyzed addition of azides and alkynes, a type of "click" chemistry. These aliphatic polyesters possess an acetylene graft density that can be tailored by ring-opening copolymerization of alpha-propargyl-delta-valerolactone (1) with epsilon-caprolactone. Since the mild conditions associated with the click reaction are shown to be compatible with the polyester backbone, this method is a generally useful means for grafting numerous types of functionality onto aliphatic polyesters. The amphiphilic graft polyesters prepared in this study are shown to be biocompatible by in vitro cytotoxicity evaluation, suggesting their suitability for a range of biomaterial applications.