gebhart/patrepeval huggingface dataset:
Pegylation of Antimicrobial Peptides Maintains the Active Peptide Conformation, Model Membrane Interactions, and Antimicrobial Activity while Improving Lung Tissue Biocompatibility following Airway Delivery (2012)

Antimicrobial peptides (AMPs) have therapeutic potential, particularly for localized infections such as those of the lung. Here we show that airway administration of a pegylated AMP minimizes lung tissue toxicity while nevertheless maintaining antimicrobial activity. CaLL, a potent synthetic AMP (KWKLFKKIFKRIVQRIKDFLR) comprising fragments of LL-37 and cecropin A peptides, was N-terminally pegylated (PEG-CaLL). PEG-CaLL derivatives retained significant antimicrobial activity (50% inhibitory concentrations [IC(50)s] 2- to 3-fold higher than those of CaLL) against bacterial lung pathogens even in the presence of lung lining fluid. Circular dichroism and fluorescence spectroscopy confirmed that conformational changes associated with the binding of CaLL to model microbial membranes were not disrupted by pegylation. Pegylation of CaLL reduced AMP-elicited cell toxicity as measured using in vitro lung epithelial primary cell cultures. Further, in a fully intact ex vivo isolated perfused rat lung (IPRL) model, airway-administered PEG-CaLL did not result in disruption of the pulmonary epithelial barrier, whereas CaLL caused an immediate loss of membrane integrity leading to pulmonary edema. All AMPs (CaLL, PEG-CaLL, LL-37, cecropin A) delivered to the lung by airway administration showed limited (<3%) pulmonary absorption in the IPRL with extensive AMP accumulation in lung tissue itself, a characteristic anticipated to be beneficial for the treatment of pulmonary infections. We conclude that pegylation may present a means of improving the lung biocompatibility of AMPs designed for the treatment of pulmonary infections.
Hot electron transport in suspended multilayer graphene (2010)

We study hot electron transport in short-channel suspended multilayer graphene devices created by a distinct experimental approach. For devices with semitransparent contact barriers, a dip of differential conductance $(dI/dV)$ has been observed at source-drain bias ${V}_{d}=0$, along with anomalies at higher ${V}_{d}$ likely induced by optical-phonon scattering. For devices with low-contact barriers, only the $dI/dV$ dip at ${V}_{d}=0$ is observed, and we find a well-fit logarithmic dependence of $dI/dV$ on both the bias ${V}_{d}$ and the temperature $T$. The logarithmic ${V}_{d}$ dependence is explained with the hot electron effect and the logarithmic $T$ dependence could be attributed to the weak localization in two dimensions.
An efficient in vitro translation system from mammalian cells lacking the translational inhibition caused by eIF2 phosphorylation (2008)

In vitro translation systems are used to investigate translational mechanisms and to synthesize proteins for characterization. Most available mammalian cell-free systems have reduced efficiency due to decreased translation initiation caused by phosphorylation of the initiation factor eIF2alpha on Ser51. We describe here a novel cell-free protein synthesis system using extracts from cultured mouse embryonic fibroblasts that are homozygous for the Ser51 to- Ala mutation in eIF2alpha (A/A cells). The translation efficiency of a capped and polyadenylated firefly luciferase mRNA in A/A cell extracts was 30-fold higher than in wild-type extracts. Protein synthesis in extracts from A/A cells was active for at least 2 h and generated up to 20 microg/mL of luciferase protein. Additionally, the A/A cell-free system faithfully recapitulated the selectivity of in vivo translation for mRNA features; translation was stimulated by a 5'-end cap (m7GpppN) and a 3'-end poly(A) tail in a synergistic manner. The system also showed similar efficiencies of cap-dependent and IRES-mediated translation (EMCV IRES). Significantly, the A/A cell-free system supported the post-translational modification of proteins, as shown by glycosylation of the HIV type-1 gp120 and cleavage of the signal peptide from beta-lactamase. We propose that cell-free systems from A/A cells can be a useful tool for investigating mechanisms of mammalian mRNA translation and for the production of recombinant proteins for molecular studies. In addition, cell-free systems from differentiated cells with the Ser51Ala mutation should provide a means for investigating cell type-specific features of protein synthesis.
Some social factors of software engineering (2005)

While the importance of 'people factors' in software engineering has been recognised for over 25 years, few specific factors, and their impact on software engineering, have been identified. 'People factors' covers a wide and diverse set of issues. In this paper we focus on social factors, i.e. factors that arise from the various interactions that need to take place in order to develop software. We draw on three different studies we have conducted over the last 10 years to identify three specific factors and their impact on software development.
Characterization of fast‐tumbling isotropic bicelles by PFG diffusion NMR (2015)

Small isotropic bicelles are versatile membrane mimetics, which, in contrast to micelles, provide a lipid bilayer and are at the same time suitable for solution-state NMR studies. The lipid composition of the bilayer is flexible allowing for incorporation of various head groups and acyl chain types. In bicelles, lipids are solubilized by detergents, which are localized in the rim of the disk-shaped lipid bilayer. Bicelles have been characterized by a broad array of biophysical methods, pulsed-field gradient NMR (PFG NMR) being one of them. PFG NMR can readily be used to measure diffusion coefficients of macromolecules. It is thus employed to characterize bicelle size and morphology. Even more importantly, PFG NMR can be used to study the degree of protein association to membranes. Here, we present the advances that have been made in producing small, fast-tumbling isotropic bicelles from a variety of lipids and detergents, together with insights on the morphology of such mixtures gained from PFG NMR. Furthermore, we review approaches to study protein-membrane interaction by PFG NMR. Copyright © 2015 John Wiley & Sons, Ltd.
Assessing Exposure to Cosmic Radiation during Long-haul Flights (2000)

The assessment of exposure to cosmic radiation on board aircraft is one of the concerns of organizations responsible for radiation protection. Cosmic-particle flux increases with altitude and latitude and depends on solar activity. To illustrate the effect of these parameters, exposure has been estimated on several airlines operating subsonic and supersonic aircraft on transatlantic, Siberian and transequatorial routes. Measurements have been made with a tissue-equivalent proportional counter using the microdosimetric technique. This type of system provides the absorbed dose, the ambient dose equivalent, the mean quality factor, and the dose distribution as a function of lineal energy. Data were collected at maximum solar activity in 1991-1992 and at minimum activity in 1996-1998. The lowest mean dose rate measured was 3 microSv h(-1) during a Paris-Buenos Aires flight in 1991. The highest rates were 6.6 microSv h(-1) during a Paris-Tokyo flight on a Siberian route and 9.7 microSv h(-1) on Concorde in 1996-1997. The mean quality factor is around 1.8. The corresponding annual effective dose, based on 700 h of flight for subsonic aircraft and 300 h for Concorde, can be estimated at between 2 mSv for the least-exposed routes and 5 mSv for the more-exposed routes.
Autosomal recessive inheritance of congenital goiter in Afrikander cattle (1985)

Congenital goiter was reported in a number of herds of Afrikander cattle in the 1950's. Some affected animals were assembled and maintained as a closed herd. Although considerable biochemical research into the nature of the disease has been conducted, no definitive report has described the mode of inheritance of the defect. This paper presents the results of breeding studies that indicate the defect is inherited as an autosomal recessive. Southern blot analysis of the thyroglobulin gene confirms this finding. In addition, serum levels of TSH (thyroid stimulating hormone, thyrotropin), T3 (3,4,3'-tri-iodothyronine), T4 (thyroxine), rT3 (3,3',5'-tri-iodothyronine), and DIT (diiodotyrosine) of goitrous animals are compared with normal animals.
An efficient algorithm for a generalized joint replenishment problem (1997)

textabstractIn most multi-item inventory systems, the ordering costs consist of a major cost and a minor cost for each item included. Applying for every individual item a cyclic inventory policy, where the cycle length is a multiple of some basic cycle time, reduces the major ordering costs. An efficient algorithm to determine the optimal policy of this type is discussed in this paper. It is shown that this algorithm can be used for deterministic multi-item inventory problems, with general cost rate functions and possibly service level constraints, of which the well-known joint replenishment problem is a special case. Some useful results in determining the optimal control parameters are derived, and worked out for piecewise linear cost rate functions. Numerical results for this case show that the algorithm significantly outperforms other solution methods, both in the quality of the solution as in the running time.
Glyphosate Resistance by Engineering the Flavoenzyme Glycine Oxidase (2009)

Glycine oxidase from Bacillus subtilis is a homotetrameric flavoprotein of great potential biotechnological use because it catalyzes the oxidative deamination of various amines and d-isomer of amino acids to yield the corresponding alpha-keto acids, ammonia/amine, and hydrogen peroxide. Glyphosate (N-phosphonomethylglycine), a broad spectrum herbicide, is an interesting synthetic amino acid: this compound inhibits 5-enolpyruvylshikimate-3-phosphate synthase in the shikimate pathway, which is essential for the biosynthesis of aromatic amino acids in plants and certain bacteria. In recent years, transgenic crops resistant to glyphosate were mainly generated by overproducing the plant enzyme or by introducing a 5-enolpyruvylshikimate-3-phosphate synthase insensitive to this herbicide. In this work, we propose that the enzymatic oxidation of glyphosate could be an effective alternative to this important biotechnological process. To reach this goal, we used a rational design approach (together with site saturation mutagenesis) to generate a glycine oxidase variant more active on glyphosate than on the physiological substrate glycine. The glycine oxidase containing three point mutations (G51S/A54R/H244A) reaches an up to a 210-fold increase in catalytic efficiency and a 15,000-fold increase in the specificity constant (the k(cat)/K(m) ratio between glyphosate and glycine) as compared with wild-type glycine oxidase. The inspection of its three-dimensional structure shows that the alpha2-alpha3 loop (comprising residues 50-60 and containing two of the mutated residues) assumes a novel conformation and that the newly introduced residue Arg(54) could be the key residue in stabilizing glyphosate binding and destabilizing glycine positioning in the binding site, thus increasing efficiency on the herbicide.
Zeta Potential Altering System for Increased Fluid Recovery, Production, and Fines Control (2007)

Abstract This paper presents a new zeta potential altering system that is based on an inner salt developed to enhance the water flowback recovery on borate and slick-water frac jobs. The system also aids in the control of fines. The mechanism of this system is to modify the zeta potential on particles such as frac sand from -50 mV, or coal from -28 mV, to more neutral values. This modification helps increase the potential for particle agglomeration and changes in the sand pack in the fracture to increase fluid recovery and production. Results from lab studies have shown that the flow rate ratio for a 2% KCl solution through sand packs (treated/not treated) increased up to 45% when treated with 6.0 gal of chemical per 1,000 lb of frac sand. Similar results were obtained on conductivity tests using ceramic proppant, improving conductivity from 7,150 mD-ft to 11,387 mD-ft at 2,000 psi closure stress. This new system does not interfere with fracturing fluid rheological profiles for borate systems and improves friction reducing characteristics in slick-water systems. The system was tested in the field on a slick-water job, where the additive was mixed in the blender tub.
Condylomata of the uterine cervix and koilocytosis of cervical intraepithelial neoplasia. (1981)

In 202 women with koilocytotic atypia in cervical smears, 136 had predominantly small condylomata of the uterine cervix, and 66 had cervical intraepithelial neoplasia (CIN) of varying degree either with koilocytosis of the neoplasia or associated with condylomata. Koilocytosis correlated well with the histological diagnosis of condylomata, but occasionally it obscured the cytological evidence of CIN. Human papilloma virus particles were found in the cells of condylomata in 10 cases and in those of CIN II with koilocytosis in two cases of 21 examined ultrastructurally. There was evidence that the condyloma of the uterine cervix is a well-defined morphological entity and also that cytopathie changes similar to those seen in condylomata are present in some cases of CIN.
Mutations affecting somite formation and patterning in the zebrafish, <i>Danio rerio</i> (1996)

Somitogenesis is the basis of segmentation of the mesoderm in the trunk and tail of vertebrate embryos. Two groups of mutants with defects in this patterning process have been isolated in our screen for zygotic mutations affecting the embryonic development of the zebrafish (Danio rerio). In mutants of the first group, boundaries between individual somites are invisible early on, although the paraxial mesoderm is present. Later, irregular boundaries between somites are present. Mutations in fused somites (fss) and beamter (bea) affect all somites, whereas mutations in deadly seven (des), after eight (aei) and white tail (wit) only affect the more posterior somites. Mutants of all genes but wit are homozygous viable and fertile. Skeletal stainings and the expression pattern of myoD and snail1 suggest that anteroposterior patterning within individual somites is abnormal. In the second group of mutants, formation of the horizontal myoseptum, which separates the dorsal and ventral part of the myotome, is reduced. Six genes have been defined in this group (you-type genes). you-too mutants show the most severe phenotype; in these the adaxial cells, muscle pioneers and the primary motoneurons are affected, in addition to the horizontal myoseptum. The horizontal myoseptum is also missing in mutants that lack a notochord. The similarity of the somite phenotype in mutants lacking the notochord and in the you-type mutants suggests that the genes mutated in these two groups are involved in a signaling pathway from the notochord, important for patterning of the somites.
Multilocus genetic determinants of LDL particle size in coronary artery disease families. (1996)

Recent interest in atherosclerosis has focused on the genetic determinants of low-density lipoprotein (LDL) particle size, because of (i) the association of small dense LDL particles with a three-fold increased risk for coronary artery disease (CAD) and (ii) the recent report of linkage of the trait to the LDL receptor (chromosome 19). By utilizing nonparametric quantitative sib-pair and relative-pair analysis methods in CAD families, we tested for linkage of a gene or genes controlling LDL particle sizes with the genetic loci for the major apolipoproteins and enzymes participating in lipoprotein metabolism. We confirmed evidence for linkage to the LDL receptor locus (P=.008). For six candidate gene loci, including apolipoprotein(apo)B, apoAII, apo(a), apoE-CI-CII, lipoprotein lipase, and high-density lipoprotein-binding protein, no evidence for linkage was observed by sib-pair linkage analyses (P values ranged from .24 to .81). However, in addition, we did find tentative evidence for linkage with the apoAI-CIII-AIV locus (chromosome 11) (P=.06) and significant evidence for linkage of the cholesteryl ester transfer protein locus (chromosome 16) (P=.01) and the manganese superoxide dismutase locus (chromosome 6) (P=.001), thus indicating multilocus determination of this atherogenic trait.
SeSAMe: reducing artifactual detection of DNA methylation by Infinium BeadChips in genomic deletions (2018)

We report a new class of artifacts in DNA methylation measurements from Illumina HumanMethylation450 and MethylationEPIC arrays. These artifacts reflect failed hybridization to target DNA, often due to germline or somatic deletions and manifest as incorrectly reported intermediate methylation. The artifacts often survive existing preprocessing pipelines, masquerade as epigenetic alterations and can confound discoveries in epigenome-wide association studies and studies of methylation-quantitative trait loci. We implement a solution, P-value with out-of-band (OOB) array hybridization (pOOBAH), in the R package SeSAMe. Our method effectively masks deleted and hyperpolymorphic regions, reducing or eliminating spurious reports of epigenetic silencing at oft-deleted tumor suppressor genes such as CDKN2A and RB1 in cases with somatic deletions. Furthermore, our method substantially decreases technical variation whilst retaining biological variation, both within and across HM450 and EPIC platform measurements. SeSAMe provides a light-weight, modular DNA methylation data analysis suite, with a performant implementation suitable for efficient analysis of thousands of samples.
ncdDetect2: improved models of the site-specific mutation rate in cancer and driver detection with robust significance evaluation (2018)

Supplementary data are available at Bioinformatics online.
Bioactive Contaminants Leach from Disposable Laboratory Plasticware (2008)

Disposable plasticware such as test tubes, pipette tips, and multiwell assay or culture plates are used routinely in most biological research laboratories. Manufacturing of plastics requires the inclusion of numerous chemicals to enhance stability, durability, and performance. Some lubricating (slip) agents, exemplified by oleamide, also occur endogenously in humans and are biologically active, and cationic biocides are included to prevent bacterial colonization of the plastic surface. We demonstrate that these manufacturing agents leach from laboratory plasticware into a standard aqueous buffer, dimethyl sulfoxide, and methanol and can have profound effects on proteins and thus on results from bioassays of protein function. These findings have far-reaching implications for the use of disposable plasticware in biological research.
The Split-Apply-Combine Strategy for Data Analysis (2011)

Many data analysis problems involve the application of a split-apply-combine strategy, where you break up a big problem into manageable pieces, operate on each piece independently and then put all the pieces back together. This insight gives rise to a new R package that allows you to smoothly apply this strategy, without having to worry about the type of structure in which your data is stored. The paper includes two case studies showing how these insights make it easier to work with batting records for veteran baseball players and a large 3d array of spatio-temporal ozone measurements.
Membrane Binding of Plasmid DNA and Endocytic Pathways Are Involved in Electrotransfection of Mammalian Cells (2011)

Electric field mediated gene delivery or electrotransfection is a widely used method in various studies ranging from basic cell biology research to clinical gene therapy. Yet, mechanisms of electrotransfection are still controversial. To this end, we investigated the dependence of electrotransfection efficiency (eTE) on binding of plasmid DNA (pDNA) to plasma membrane and how treatment of cells with three endocytic inhibitors (chlorpromazine, genistein, dynasore) or silencing of dynamin expression with specific, small interfering RNA (siRNA) would affect the eTE. Our data demonstrated that the presence of divalent cations (Ca(2+) and Mg(2+)) in electrotransfection buffer enhanced pDNA adsorption to cell membrane and consequently, this enhanced adsorption led to an increase in eTE, up to a certain threshold concentration for each cation. Trypsin treatment of cells at 10 min post electrotransfection stripped off membrane-bound pDNA and resulted in a significant reduction in eTE, indicating that the time period for complete cellular uptake of pDNA (between 10 and 40 min) far exceeded the lifetime of electric field-induced transient pores (∼10 msec) in the cell membrane. Furthermore, treatment of cells with the siRNA and all three pharmacological inhibitors yielded substantial and statistically significant reductions in the eTE. These findings suggest that electrotransfection depends on two mechanisms: (i) binding of pDNA to cell membrane and (ii) endocytosis of membrane-bound pDNA.
Preclinical antitumor activity of SST0116CL1: A novel heat shock protein 90 inhibitor (2014)

4-Amino substituted resorcino-isoxazole (SST0116CL1) (property of Sigma-Tau Research Switzerland S.A.) is a potent, second generation, small-molecule heat shock protein 90 inhibitor (Hsp90i). SST0116CL1 binds to the ATP binding pocket of Hsp90, and interferes with Hsp90 chaperone function thus resulting in client protein degradation and tumor growth inhibition. The aim of the study was to assess SST0116CL1 in various solid and haematological tumors. The antitumor properties of SST0116CL1 were assessed using in vitro cell proliferation and client protein degradation assays and in vivo different tumor xenograft models. Pharmacokinetic (PK) data were also generated in tumor-bearing mice to gain an understanding of optimal dosing schedules and regimens. SST0116CL1 was shown to inhibit recombinant Hsp90α and to induce the destabilization of different client proteins, often overexpressed and constitutively activated in different types of hematological or solid human tumors. In preclinical in vivo studies, it was revealed to induce antitumor effects in murine models of leukemia and of gastric and ovarian carcinoma. A modulation of PD biomarkers in terms of downregulation of Hsp90 client proteins in tumor-bearing mice was found. SST0116CL1 is a new clinical candidate for cancer therapy. The antitumor property of SST0116CL1, likely due to direct inhibition of the Hsp90 enzymatic activity, may prove to be a critical attribute as the compound enters phase I clinical trials.
The photodynamic occlusion of choroidal vessels using benzoporphyrin derivative (1994)

We used benzoporphyrin derivative-monoacid (BPD-MA), a new photosensitizing agent, in photodynamic therapy (PDT) to occlude choroidal vessels in the rabbit. Using BPD-MA, seven dutch-belted rabbit eyes were photodynamically treated to achieve acute choroidal vessel closure. Fundoscopy, fluorescein angiography (FA), and histology were performed 1 hour, 1 day, 3 days, 7 days, 14 days, 21 days, and 28 days after PDT. On FA, PDT-treated spots remained nonperfused until day 3 when gradual reperfusion from the periphery began to appear. By day 28 the area of PDT appeared completely reperfused. Histology of lesions showed acute damage to choroidal vascular endothelial cells and retinal pigment epithelial (RPE) cells. Over subsequent days, recovery of RPE cells and regeneration of large choroidal vascular endothelial cells occurred. In addition, retinal degeneration occurred gradually over the 28 days of follow-up. Since current argon laser therapy of retinal neovascularization causes immediate retinal damage, the ability to occlude choroidal vessels without inducing acute thermal damage holds promise for treating clinical pathologic conditions that feature abnormal neovascularization, such as age-related macular degeneration and diabetic retinopathy.