gebhart/patrepeval huggingface dataset:
The diversity of FtsY‐lipid interactions (2010)

The bacterial signal recognition particle (SRP) receptor FtsY forms a complex with the SRP Ffh to target nascent polypeptide chains to the bacterial inner membrane. How FtsY interacts with lipids and associates to the membrane is unclear. Here, we show that vesicle binding leads to partial protection against proteolytic degradation and a change in secondary structure, which differs depending on whether the lipids are simple mixtures of zwitterionic and anionic lipids, mimics of Escherichia coli lipids, or lysolipids. Lipid binding alters the stability of FtsY. Thermal unfolding of FtsY in buffer shows two transitions, one occurring at approximately 60 degrees C and the other at approximately 90 degrees C. The thermal intermediate accumulating between 60 and 90 degrees C has structural features in common with the state induced by binding to E. coli lipids. E. coli lipid extract induces a single transition around 70 degrees C, anionic lipids have no effect while cooperative unfolding is completely removed in lysolipids. Thus, the lipid environment profoundly influences the dynamic properties of FtsY, leading to three different kinds of FtsY-lipid interactions with different effects on structure, proteolytic protection, and stability, and is driven both by hydrophobic and electrostatic interactions. Trypsin digestion experiments highlight the central role of the N-domain in lipid contacts, whereas the A- and G-domains appear to play a more minor part.
Inhibition of Cell Surface Export of Group A Streptococcal Anchorless Surface Dehydrogenase Affects Bacterial Adherence and Antiphagocytic Properties (2005)

Surface dehydrogenase (SDH) is an anchorless, multifunctional protein displayed on the surfaces of group A Streptococcus (GAS) organisms. SDH is encoded by a single gene, sdh (gap or plr) that is essential for bacterial survival. Hence, the resulting nonfeasibility of creating a knockout mutant is a major limiting factor in studying its role in GAS pathogenesis. An insertion mutagenesis strategy was devised in which a nucleotide sequence encoding a hydrophobic tail of 12 amino acids ((337)IVLVGLVMLLLS(348)) was added at the 3' end of the sdh gene, successfully creating a viable mutant strain (M1-SDH(HBtail)). In this mutant strain, the SDH(HBtail) protein was not secreted in the medium but was retained in the cytoplasm and to some extent trapped within the cell wall. Hence, SDH(HBtail) was not displayed on the GAS surface. The mutant strain, M1-SDH(HBtail), grew at the same rate as the wild-type strain. The SDH(HBtail) protein displayed the same GAPDH activity as the wild-type SDH protein. Although the whole-cell extracts of the wild-type and mutant strains showed similar GAPDH activities, cell wall extracts of the mutant strain showed 5.5-fold less GAPDH activity than the wild-type strain. The mutant strain, M1-SDH(HBtail), bound significantly less human plasminogen, adhered poorly to human pharyngeal cells, and lost its innate antiphagocytic activity. These results indicate that the prevention of the cell surface export of SDH affects the virulence properties of GAS. The anchorless SDH protein, thus, is an important virulence factor.
Fluorination of Boronic Acids Mediated by Silver(I) Triflate (2009)

A regiospecific Ag-mediated fluorination reaction of aryl- and alkenylboronic acids and esters is reported. The fluorination reaction uses commercially available reagents, does not require the addition of exogenous ligands, and can be performed on a multigram scale. This report discloses the first practical reaction sequence from arylboronic acid to aryl fluorides.
Fluctuations of Intracellular Iron Modulate Elastin Production (2004)

Production of insoluble elastin, the major component of elastic fibers, can be modulated by numerous intrinsic and exogenous factors. Because patients with hemolytic disorders characterized with fluctuations in iron concentration demonstrate defective elastic fibers, we speculated that iron might also modulate elastogenesis. In the present report we demonstrate that treatment of cultured human skin fibroblasts with low concentration of iron 2-20 microm (ferric ammonium citrate) induced a significant increase in the synthesis of tropoelastin and deposition of insoluble elastin. Northern blot and real-time reverse transcription-PCR analysis revealed that treatment with 20 microm iron led to an increase of approximately 3-fold in elastin mRNA levels. Because treatment with an intracellular iron chelator, desferrioxamine, caused a significant decrease in elastin mRNA level and consequent inhibition of elastin deposition, we conclude that iron facilitates elastin gene expression. Our experimental evidence also demonstrates the existence of an opposite effect, in which higher, but not cytotoxic concentrations of iron (100-400 microm) induced the production of intracellular reactive oxygen species that coincided with a significant decrease in elastin message stability and the disappearance of iron-dependent stimulatory effect on elastogenesis. This stimulatory elastogenic effect was reversed, however, in cultures simultaneously treated with high iron concentration (200 microm) and the intracellular hydroxyl radical scavenger, dimethylthiourea. Thus, presented data, for the first time, demonstrate the existence of two opposite iron-dependent mechanisms that may affect the steady state of elastin message. We speculate that extreme fluctuations in intracellular iron levels result in impaired elastic fiber production as observed in hemolytic diseases.
Highly scattering optical transmission polymer and its application for LCD displays (2002)

We have developed a highly scattering optical transmission (HSOT) polymer, and have succeeded in applying it to a highly efficient backlight in liquid crystal displays (LCDs). In the present work, a multiple scattering modeling simulation has been developed. Also the effects of adjacent particles inside the HSOT polymer are demonstrated. Although Mie scattering theory is based on the assumption that there exists one particle, light scattering intensity profiles are extended by adjacent particles in measurement data. In order to improve the multiple scattering modeling simulation, light scattering intensity profiles calculated by Mie scattering theory are modified by using the experimental correction function. It follows that the numerical calculation improved by taking account of the adjacent particles has precisely reproduced multiple scattering phenomena inside the HSOT polymer. Based upon the results of multiple scattering analysis, an optimal design has been developed and applied to an LCD backlight system. By altering the internal particle condition, uniformity of color and brightness on the top face of the backlight can has been achieved
Consumers' Perceptions of Speciality Foods and the Rural Mail Order Business (1997)

Many rural-based farm and food businesses are relatively small but successful

companies. They face severe constraints in terms of finance, marketing and distribution. However, marketing food by mail order presents the opportunity for these firms to gain access to national or even international markets. The achievement of commercial success requires that these companies become marketing oriented. Thus, the critical issue for these firms is to identify the needs of existing or potential customers.

The objectives of the paper are to establish a profile of the characteristics,

behaviour and attitudes of mail order customers.
Use of a Chimeric Adenovirus Vector Enhances BMP2 Production and Bone Formation (2002)

Recombinant adenoviral vectors have potential for the treatment of a variety of musculoskeletal defects and such gene therapy systems have been a recent research focus in orthopedic surgery. In studies reported here, two different adenovirus vectors have been compared for their ability to transduce human bone marrow mesenchymal stem cells (hBM-MSCs) and elicit bone formation in vivo. Vectors consisted either of standard adenovirus type 5 (Ad5) vector or a chimeric adenovirus type 5 vector that contains an adenovirus type 35 fiber (Ad5F35), which has been recently demonstrated to bestow a different cellular tropism, and a complete cDNA encoding human bone morphogenetic 2 (BMP2). Studies were also conducted to compare the transduction efficiency of these vectors using enhanced green fluorescent protein (GFP). hBM-MSCs transduced with Ad5F35 vectors had higher levels of transgene expression than those transduced with Ad5 vectors. The results also demonstrate that hBM-MSCs lack the coxsackie-adenovirus receptor (CAR), which is responsible for cellular adsorption of Ad5. Therefore, the data suggest that Ad5 virus adsorption to hBM-MSCs is inefficient. Ad5BMP2- or Ad5F35BMP2-transduced hBM-MSCs were also compared in an in vivo heterotopic bone formation assay. Mineralized bone was radiologically identified only in muscle that received the Ad5F35BMP2 transduced hBM-MSCs. In summary, Ad5F35BMP2 can efficiently transduce hBM-MSCs leading to enhanced bone formation in vivo.
Molecular breakdown: a comprehensive view of anaplastic lymphoma kinase (ALK)‐rearranged non‐small cell lung cancer (2017)

Most anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancers (NSCLCs) show good clinical response to ALK inhibitors. However, some ALK-rearranged NSCLC patients show various primary responses with unknown reasons. Previous studies focused on the clinical aspects of ALK fusions in small cohorts, or were conducted in vitro and/or in vivo to investigate the function of ALK. One of the suggested theories describes how echinoderm microtubule-associated protein-like 4 (EML4)-ALK variants play a role towards different sensitivities in ALK inhibitors. Until now, there has been no integrated comprehensive study that dissects ALK at the molecular level in a large scale. Here, we report the largest extensive molecular analysis of 158 ALK-rearranged NSCLCs and have investigated these findings in a cell line construct experiment. We discovered that NSCLCs with EML4-ALK short forms (variant 3/others) had more advanced stage and frequent metastases than cases with the long forms (variant 1/others) (p = 0.057, p < 0.05). In vitro experiments revealed that EML4-ALK short forms show lower sensitivity to ALK inhibitors than do long forms. Clinical analysis also showed a trend for the short forms showing worse PFS. Interestingly, we found that breakpoints of ALK are evenly distributed mainly in intron 19 and almost all of them undergo a non-homologous end-joining repair to generate ALK fusions. We also discovered four novel somatic ALK mutations in NSCLC (T1151R, R1192P, A1280V, and L1535Q) that confer primary resistance; all of them showed strong resistance to ALK inhibitors, as G1202R does. Through targeted deep sequencing, we discovered three novel ALK fusion partners (GCC2, LMO7, and PHACTR1), and different ALK fusion partners showed different intracellular localization. With our findings that the EML4-ALK variants, new ALK somatic mutations, and novel ALK-fusion partners may affect sensitivity to ALK inhibitors, we stress the importance of targeted therapy to take the ALK molecular profiling into consideration. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Mesoscale simulations of hydrodynamic squirmer interactions (2010)

The swimming behavior of self-propelled microorganisms is studied by particle-based mesoscale simulations. The simulation technique includes both hydrodynamics and thermal fluctuations that are both essential for the dynamics of microswimmers. The swimmers are modeled as squirmers, i.e., spherical objects with a prescribed tangential surface velocity, where the focus of thrust generation can be tuned from pushers to pullers. For passive squirmers (colloids), we show that the velocity autocorrelation function agrees quantitatively with the Boussinesq approximation. Single active squirmers show a persistent random-walk behavior, determined by forward motion, lateral diffusion, and orientational fluctuations, in agreement with theoretical predictions. For pairs of squirmers, which are initially swimming in parallel, we find an attraction for pushers and a repulsion for pullers, as expected. The hydrodynamic force between squirmer pairs is calculated as a function of the center-to-center distances d(cm) and is found to be consistent with a logarithmic distance dependence for d(cm) less than about two sphere diameters; here, the force is considerably stronger than expected from the far-field expansion. The dependence of the force strength on the asymmetry of the polar surface velocity is obtained. During the collision process, thermal fluctuations turn out to be very important and to strongly affect the postcollision velocity directions of both squirmers.
Maturation of wild-type and mutated frataxin by the mitochondrial processing peptidase (1998)

Frataxin is a mitochondrial protein deficient in Friedreich ataxia (FRDA) and which is associated with abnormal intramitochondrial iron handling. We identified the mitochondrial processing peptidase beta (MPPbeta) as a frataxin protein partner using the yeast two-hybrid assay. In in vitro assays, MPPbeta binds frataxin which is cleaved by the reconstituted MPP heterodimer. MPP cleavage of frataxin results in an intermediate form (amino acids 41-210) that is processed further to the mature form. In vitro and in vivo experiments suggest that two C-terminal missense mutations found in FRDA patients modulate interaction with MPPbeta, resulting in a slower maturation process at the normal cleavage site. The slower processing rate of frataxin carrying such missense mutations may therefore contribute to frataxin deficiency, in addition to an impairment of its function.
Variable-dimension vector quantization of speech spectra for low-rate vocoders (2002)

Optimal vector quantization of variable-dimension vectors in principle is feasible by using a set of fixed dimension VQ codebooks. However, for typical applications, such a multi-codebook approach demands a grossly excessive and impractical storage and computational complexity. Efficient quantization of such variable-dimension spectral shape vectors is the most challenging and difficult encoding task required in an important family of low bit-rate vocoders. The authors introduce a simple and effective formulation of variable-dimension vector quantization (VDVQ) which quantizes variable-dimension vectors using a single universal codebook having fixed dimension yet covering the entire range of input vector dimensions under consideration. This VDVQ technique is applied to quantize variable-dimension spectral shape vectors leading to a high quality speech coder at the low bit-rate of 2.5 kb/s. The combination of a universal spectral codebook and structured VQ reduces storage and computational complexity, yet delivers a high quantization efficiency and enhanced perceptual quality of the coded speech.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Characterization of the human trophoblast-leukocyte antigenic molecules defined by a monoclonal antibody. (1986)

The murine monoclonal antibody H316 recognizes cell surface glycoproteins shared in expression by human trophoblast and peripheral blood leukocytes. It is also strongly expressed by many human tumor cell types, including choriocarcinoma and teratocarcinoma. The H316 antigenic determinant from these different cell types is carried on two wheat germ agglutinin-reactive glycoproteins of approximately 65,000 and 55,000 m.w. The antigenicity is not dependent on N-linked glycosylation. Biochemical fractionation procedures suggest that the molecules are related to each other, are not associated through intermolecular disulfide bonds, but do exhibit intramolecular disulfide interactions. These glycoproteins demonstrate m.w. heterogeneity between different cell lines and individual trophoblast membrane preparations. Such properties suggest that H316 molecules may be representative of TLX antigens (trophoblast-leukocyte common antigens), which have been suggested to influence maternofetal immunogenetic interactions.
Expression of Bacillus thuringiensis delta-endotoxin genes during vegetative growth (1990)

Bacillus thuringiensis delta-endotoxin (crystal protein) genes are normally expressed only during sporulation. It is possible to produce crystal protein during vegetative growth by placing B. thuringiensis crystal protein genes downstream of a strong vegetative promoter. By removing a possible transcriptional terminator of the tetracycline resistance gene of pBC16 and inserting a multiple cloning site, delta-endotoxin genes can be cloned downstream from the tetracycline resistance gene promoter. This construct allows for readthrough transcription from the strong vegetative promoter. Crystal protein is then produced during vegetative growth as well as during sporulation in both B. thuringiensis and Bacillus megaterium. This construct also allows for production of delta-endotoxin in B. thuringiensis strains that do not normally produce delta-endotoxin because of a defect in sporulation.
Induction of thromboxane release from macrophages by anaphylatoxic peptide C3a of complement and synthetic hexapeptide C3a 72-77. (1983)

Guinea pig peritoneal macrophages were examined for their response to homologous anaphylatoxic peptide C3a of complement. C3a caused the release of considerable amounts of thromboxane A2 from macrophages maintained in serum-free culture for up to 12 hr. Preincubation of C3a with the Fab portion of a monoclonal anti-C3a IgG abrogated its stimulatory capacity. C3a desarg was found to be rather ineffective in eliciting thromboxane release. Hexapeptide C3a 72-77, comprising the C-terminal amino acids of human C3a, proved also to stimulate the cyclooxygenation pathway of macrophage arachidonic acid metabolism, following the same routes of receptor-ligand interactions (rapid onset of activation, low dose, and cumulative desensitization) as proven for other anaphylatoxin-cell interactions. This novel effect of anaphylatoxins C3a and C3a 72-77 could contribute to inflammatory reactions in which macrophages play a role.
Skeletal Accelerations Measured during Different Exercises (1993)

Exercise is often suggested as a means of reducing the effects of osteoporosis in post-menopausal women. In response to an increase in physical activity, bone mass can be increased and several studies have investigated the effectiveness of different exercises in increasing bone mass. In this study we have attempted to quantify the effect of different exercises by measuring the accelerations produced during various exercises. Accelerations have been measured at the ankle of normal subjects during a series of impulsive (walking, running and walking up and down stairs) and non-impulsive (cycling) exercises. Accelerations were measured using an accelerometer attached to a stiff cuff which straps around the ankle. Signals from the accelerometer are amplified and recorded using a specially developed portable data-logging system. THe principal parameters measured were the maximum change of acceleration (peak to peak) and the rate of change of acceleration. From the results it was observed that running and walking up and down stairs produced the highest peak-to-peak change (running = 8.08 g; walking downstairs = 8.11 g) and rate of change of acceleration (running = 2.14 g/s; walking downstairs = 2.07 g/s). By contrast, a non-impulsive exercise such as cycling produced relatively low values of peak-to-peak change (2.24 g) and rate of change (0.23 g/s) of acceleration.
The fibrinogenolytic activity of purified tryptase from human lung mast cells. (1985)

The capacity of purified tryptase from human lung mast cells to metabolize human fibrinogen, fibrin, and plasminogen was evaluated. Tryptase (5 micrograms/ml) inactivated the thrombin-induced clotting activity of fibrinogen (100 micrograms/ml) with essentially similar t 1/2 values of 4.6 min in the absence of heparin and 5.8 min in the presence of heparin (20 micrograms/ml) that were not appreciably different than with lysine-Sepharose-purified plasmin (5 micrograms/ml). Fibrinogen treated with tryptase together with heparin lost all detectable clotting activity by 4 hr at 37 degrees C, whereas fibrinogen treated with tryptase alone resulted in destruction of only 80% of fibrinogen clotting equivalents after 16 hr. Tryptase alone was observed to cleave only the alpha-chains of fibrinogen by electrophoresis of tryptase-treated, denatured, and reduced fibrinogen in polyacrylamide gradient gels. Tryptase together with heparin cleaved first the alpha-chain and then the beta-chain, the latter cleavage corresponding to complete loss of fibrinogen clotting activity by 4 hr. No fibrinogen fragments with anticoagulant activity were generated by tryptase. In contrast, plasmin left no residual clotting activity after 4 hr of incubation and generated fibrinogen fragments with anticoagulant activity. Plasmin sequentially cleaved the alpha, beta, and gamma subunits of fibrinogen. Tryptase alone (6 micrograms/ml) or together with heparin (20 micrograms/ml) failed to activate plasminogen (0.6 mg/ml) after a 60-min incubation at 37 degrees C. Addition of urokinase to tryptase-treated or untreated plasminogen resulted in essentially identical plasmin activities (0.32 and 0.34 U/ml, respectively), indicating that tryptase neither activates nor destroys plasminogen. Tryptase (700 ng) also failed to substantially solubilize cross-linked fibrin (2.6 micrograms) or the corresponding amount of fibrinogen bound to plastic microtiter plates with or without heparin. The failure to solubilize fibrinogen and, possibly, fibrin is consistent with the observation that the apparent m.w. by SDS polyacrylamide gel electrophoresis of unreduced fibrinogen is not appreciably altered by prior treatment with tryptase, even though cleavage of alpha-and beta-chains is revealed after reduction. Fibrinogenolysis by tryptase complements other mast cell mediators with anticoagulant properties such as heparin and suggests a significant prevention of coagulation by activated mast cells.
Intramolecular cyclization of the antimicrobial peptide Polybia‐MPI with triazole stapling: influence on stability and bioactivity (2017)

Cationic antimicrobial peptides have attracted increasing attention as a novel class of antibiotics to treat infectious diseases caused by pathogenic bacteria. However, susceptibility to protease is a shortcoming in their development. Cyclization is one approach to increase the proteolytic resistance of peptides. Therefore, to improve the proteolytic resistance of Polybia-MPI, we have synthesized the MPI cyclic analogs C-MPI-1 (i-to-i+4) and C-MPI-2 (i-to-i+6) by copper(I)-catalyzed azide-alkyne cycloaddition. Compared with MPI, C-MPI-1 displayed sustained antimicrobial activity and had enhanced anti-trypsin resistance, while C-MPI-2 displayed no antimicrobial activity. The relationship between peptide structure and bioactivity was further investigated by probing the secondary structure of the peptides by circular dichroism. This showed that C-MPI-1 adopted an α-helical structure in aqueous solution and, interestingly, had increased α-helical conformation in 30 mM sodium dodecyl sulfate and 50% trifluoroethyl alcohol compared with MPI. C-MPI-2 that was not α-helical in structure, suggesting that the propensity for α-helix conformation may play an important role in cyclic peptide design. In addition, scanning electron microscopy, propidium iodide uptake, and membrane permeabilization assays indicated that MPI and the optimized analog C-MPI-1 had membrane-active action modes, indicating that the peptides would not be susceptible to conventional resistance mechanisms. Our study provides additional insight into the influence of intramolecular cyclization at various positions on peptide structure and biological activity. In conclusion, the design and synthesis of cyclic analogs via click chemistry offer a new strategy for the development of stable antimicrobial agents. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.