gebhart/patrepeval huggingface dataset:
Attenuation of Zinc Finger Nuclease Toxicity by Small-Molecule Regulation of Protein Levels (2009)

Zinc finger nucleases (ZFNs) have been used successfully to create genome-specific double-strand breaks and thereby stimulate gene targeting by several thousand fold. ZFNs are chimeric proteins composed of a specific DNA-binding domain linked to a non-specific DNA-cleavage domain. By changing key residues in the recognition helix of the specific DNA-binding domain, one can alter the ZFN binding specificity and thereby change the sequence to which a ZFN pair is being targeted. For these and other reasons, ZFNs are being pursued as reagents for genome modification, including use in gene therapy. In order for ZFNs to reach their full potential, it is important to attenuate the cytotoxic effects currently associated with many ZFNs. Here, we evaluate two potential strategies for reducing toxicity by regulating protein levels. Both strategies involve creating ZFNs with shortened half-lives and then regulating protein level with small molecules. First, we destabilize ZFNs by linking a ubiquitin moiety to the N-terminus and regulate ZFN levels using a proteasome inhibitor. Second, we destabilize ZFNs by linking a modified destabilizing FKBP12 domain to the N-terminus and regulate ZFN levels by using a small molecule that blocks the destabilization effect of the N-terminal domain. We show that by regulating protein levels, we can maintain high rates of ZFN-mediated gene targeting while reducing ZFN toxicity.
Molecular Cocrystals of Carboxylic Acids. XV. Preparation and Characterization of Heterocyclic Base Adducts With a Series of Carboxylic Acids, and the Crystal Structures of the Adducts of 2-Aminopyrimidine With 2,6-Dihydroxybenzoic Acid, 4-Aminobenzoic Acid, Phenoxyacetic Acid, (2,4-Dichlorophenoxy) (1994)

The molecular adducts of the heterocyclic base 2-aminopyrimidine with the aromatic and aromatic aliphatic carboxylic acids salicylic acid, 2,6-dihydroxybenzoic acid and 4-aminobenzoic acid, phenoxyacetic acid, (2,4-dichlorophenoxy)acetic acid, and (3,4-dichlorophenoxy)acetic acid have been prepared, and their interactive modes characterized by single-crystal X-ray diffraction methods. In addition, the complexes with (4-chlorophenoxy)acetic acid, (2,3-dichlorophenoxy)acetic acid, (4-chloro-2-methylphenoxy)acetic acid and (2,4,5- trichlorophenoxy)acetic acid have been characterized by analytical methods, including infrared spectroscopy. Except for the phenoxyacetic acid adduct (2:1), all form 1:1 molecular associations in which the carboxylic acid shows a variable tendency to protonate the hetero nitrogen of the base. The 1:1 complex of 2-aminopyridine with 2,6-dihydroxybenzoic acid has also been characterized by single-crystal X-ray diffraction.
Detection of specific DNA sequences by fluorescence amplification: a color complementation assay. (1989)

We have developed a color complementation assay that allows rapid screening of specific genomic DNA sequences. It is based on the simultaneous amplification of two or more DNA segments with fluorescent oligonucleotide primers such that the generation of a color, or combination of colors, can be visualized and used for diagnosis. Color complementation assay obviates the need for gel electrophoresis and has been applied to the detection of a large and small gene deletion, a chromosomal translocation, an infectious agent, and a single-base substitution. DNA amplification with fluorescent oligonucleotide primers has also been used to multiplex and discriminate five different amplified DNA loci simultaneously. Each primer set is conjugated to a different dye, and the fluorescence of each dye respective to its amplified DNA locus is scored on a fluorometer. This method is valuable for DNA diagnostics of genetic, acquired, and infectious diseases, as well as in DNA forensics. It also lends itself to complete automation.
Comparison of the effect of multiwavelength light produced by a cluster of semiconductor diodes and of each individual diode on mast cell number and degranulation in intact and injured skin (1990)

Intact skin and partial thickness wounds in adult male Wistar rats were irradiated by pulsed, monochromatic light of different spectral wavelength peaks simultaneously and the effects on mast cell number and degranulation were assessed. The light was produced by a Biotherapy 3ML (Omega Universal Technologies) device utilizing a 21 semiconductor diode cluster probe emitting 6 different wavelengths in the red and near infrared part of the spectrum simultaneously, only one of the wavelengths (820 nm) being coherent. The duration of treatment was 4 minutes. The average power density, distributed over the surface area of the probe (19.62 cm2) was 45 mW/cm2. The average energy density at the wound site was 10.8 J/cm2. The effect of each of the wavelengths incorporated in the cluster probe was then examined separately. The average power density for each single probe was 120 mW/cm2, except for the 820 nm diode which was 400 mW/cm2. The average energy density was maintained at 10.8 J/cm2 as with the cluster probe. After 2 hours the rats were killed and the skin was removed, processed for light microscopy, and stained with toluidine blue to identify the mast cells. The numbers of the intact and degranulated mast cells were counted in 100 high power fields (i.e., over a total area of 20 mm2) in each irradiated specimen and compared to the sham-irradiated and untreated groups. To avoid bias, the slides examined were coded and evaluated blind. In intact skin, the cluster probe irradiation was followed by a statistically significant increase in the total number of mast cells compared to the sham-irradiated group, but the percentage of the degranulated mast cells was not affected. In the partial thickness wound, the cluster probe irradiation was also followed by a statistically significant increase in the total number of mast cells compared to the sham-irradiated group; however, there was, in addition, a significant increase in the percentage of degranulated mast cells. Concerning the single probes, only the 660, 820, 940, and 950 nm wavelength emitters produced statistically significant increases in both mast cell number and degranulation in partial thickness wounds. However, when intact skin was irradiated with probes emitting these wavelengths, although the total number of mast cells was increased significantly, there was no change in degranulation compared with the sham-irradiated group. The effects observed were less than those of the cluster probe. No significant differences were found between the 870 and 880 nm wavelength-irradiated, sham-irradiated, and untreated groups in either intact or injured skin.(ABSTRACT TRUNCATED AT 400 WORDS)
Oligosaccharides from human milk influence growth-related characteristics of intestinally transformed and non-transformed intestinal cells (2007)

Human milk oligosaccharides (HMO) are considered to influence the composition of the gut microflora in breastfed infants. We investigated direct effects of milk HMO fractions or individual oligosaccharides on proliferation, differentiation and apoptosis in transformed human intestinal cells (HT-29 and Caco-2) and non-transformed small intestinal epithelial crypt cells of fetal origin (human intestinal epithelial cells; HIEC). We observed growth inhibition induced by neutral and acidic HMO fractions in HT-29, Caco-2 and HIEC cells in a dose dependent manner. However, the effects varied between cell lines, i.e. HT-29 and Caco-2 cells were more sensitive than HIEC cells. In HT-29, all 16 individual neutral and acidic oligosaccharides except from the two fucosyllactoses had an inhibitory effect on cell growth. Regarding the induction of differentiation in HT-29 and HIEC cells a threshold concentration was observed at 7.5 mg/ml for neutral and acidic HMO fractions. Among individual oligosaccharides, only sialyllactoses induced differentiation in HT-29 and HIEC cells; no effect neither of fractions nor of individual oligosaccharides was found in Caco-2 cells. A strong induction of apoptosis was only detected in HT-29 and HIEC cells for neutral oligosaccharide but not for acidic fractions. HMO were shown to induce growth inhibition in intestinal cells through two different mechanisms, by suppressing cell cycle progression through induction of differentiation and/or by influencing apoptosis. As the development and maturation of digestive and absorptive processes depend on differentiation our experiments show that oligosaccharides are effective at influencing various stages in gastrointestinal development in vitro.
Sequence-Selective DNA Cleavage by a Chimeric Metallopeptide (2003)

A chimeric metallopeptide derived from the sequences of two structurally superimposable motifs was designed as an artificial nuclease. Both DNA recognition and nuclease activity have been incorporated into a small peptide sequence. P3W, a 33-mer peptide comprising helices alpha2 and alpha3 from the engrailed homeodomain and the consensus EF-hand Ca-binding loop binds one equivalent of lanthanides or calcium and folds upon metal binding. The conditional formation constants (in the presence of 50 mM Tris) of P3W for Eu(III) (K(a) = (2.1 +/- 0.1) x 10(5) M(-1)) and Ce(IV) (K(a) = (2.6 +/- 0.1) x 10(5) M(-1)) are typical of isolated EF-hand peptides. Circular dichroism studies show that 1:1 CeP3W is 26% alpha-helical and EuP3W is up to 40% alpha-helical in the presence of excess metal. The predicted helicity of the folded peptide based on helix length and end effects is about 50%, showing the metallopeptides are significantly folded. EuP3W has considerably more secondary structure than our previously reported chimeras (Welch, J. T.; Sirish, M.; Lindstrom, K. M.; Franklin, S. J. Inorg. Chem. 2001, 40, 1982-1984). Eu(III)P3W and Ce(IV)P3W nick supercoiled DNA at pH 6.9, although EuP3W is more active at pH 8. CeP3W cleaves linearized, duplex DNA as well as supercoiled plasmid. The cleavage of a 5'-(32)P-labeled 121-mer DNA fragment was followed by polyacrylamide gel electrophoresis. The cleavage products are 3'-OPO(3) termini exclusively, suggesting a regioselective or multistep mechanism. In contrast, uncomplexed Ce(IV) and Eu(III) ions produce both 3'-OPO(3) and 3'-OH, and no evidence of 4'-oxidative cleavage termini with either metal. The complementary 3'-(32)P-labeled oligonucleotide experiment also showed both 5'-OPO(3) and 5'-OH termini were produced by the free ions, whereas CeP3W produces only 5'-OPO(3) termini. In addition to apparent regioselectivity, the metallopeptides cut DNA with modest sequence discrimination, which suggests that the HTH motif binds DNA as a folded domain and thus cleaves selected sequences. The de novo artificial nuclease LnP3W represents the first small, underivatized peptide that is both active as a nuclease and sequence selective.
Transposition of a reconstructed Harbinger element in human cells and functional homology with two transposon-derived cellular genes (2008)

Ancient, inactive copies of transposable elements of the PIF/Harbinger superfamily have been described in vertebrates. We reconstructed components of the Harbinger3_DR transposon in zebrafish, including a transposase and a second, transposon-encoded protein that has a Myb-like trihelix domain. The reconstructed Harbinger transposon shows efficient cut-and-paste transposition in human cells and preferentially inserts into a 15-bp consensus target sequence. The Myb-like protein is required for transposition and physically interacts with the N-terminal region of the transposase via its C-terminal domain. The Myb-like protein enables transposition in part by promoting nuclear import of the transposase, by directly binding to subterminal regions of the transposon, and by recruiting the transposase to the transposon ends. We investigated the functions of two transposon-derived human proteins: HARBI1, a domesticated transposase-derived protein, and NAIF1, which contains a trihelix motif similar to that described in the Myb-like protein. Physical interaction, subcellular localization, and DNA-binding activities of HARBI1 and NAIF1 suggest strong functional homologies between the Harbinger3_DR system and their related, host-encoded counterparts. The Harbinger transposon will serve as a useful experimental system for transposon biology and for investigating the enzymatic functions of domesticated, transposon-derived cellular genes.
Self-seeding-based 10Gb/s over 25km optical OFDM transmissions utilizing face-to-face dual-RSOAs at gain saturation (2014)

Self-seeded passive optical networks (PONs) are currently attracting extensive research interest. In this paper, a novel self-seeded PON transmitter is, for the first time, proposed and experimentally demonstrated, which incorporates two face-to-face-positioned reflective semiconductor optical amplifiers (RSOAs) operating at their gain saturation regions: one RSOA directly driven by an upstream electrical signal and the other RSOA biased at a fixed current. Detailed experimental explorations are undertaken of the dynamic performance characteristics of the proposed transmitter. It is shown that, in comparison with previously reported self-seeded transmitters each employing a reflective mirror and a single electrical signal-driven RSOA, the proposed transmitter has a number of salient advantages including, considerably narrowed optical signal spectra, up to 16dB reduction in RINs of intensity-modulated optical signals, and residual intensity modulation crosstalk suppression as high as 10.7dB. The aforementioned features enable experimental demonstrations of real-time self-seeded 10Gb/s optical OFDM (OOFDM) transmitters. In particular, by making use of two low-cost RSOAs having their 3-dB modulation bandwidths as small as 1.125GHz, 10Gb/s over 25km adaptive OOFDM transmissions with power penalties of 0.6dB are experimentally achieved in the simple self-seeded IMDD PON systems.
Perceived Impact of Spasticity Is Associated with Spatial and Temporal Parameters of Gait in Multiple Sclerosis (2012)

Background. Spasticity is prevalent and disabling in persons with multiple sclerosis (MS), and the development of the Multiple Sclerosis Spasticity Scale-88 (MSSS-88) provides an opportunity for examining the perceived impact of spasticity and its association with gait in this population. Purpose. This study examined the association between the perceived impact of spasticity and spatio-temporal parameters of gait in persons with MS. Methods. The sample included 44 adults with MS who completed the MSSS-88 and 4 walking trials on a 26-foot GAITRite(TM) electronic walkway for measurement of spatio-temporal components of gait including velocity, cadence, base of support, step time, single support, double support, and swing phase. Results. The overall MSSS-88 score was significantly associated with velocity (r = -0.371), cadence (r = -0.306), base of support (r = 0.357), step time (r = 0.305), single leg support (r = -0.388), double leg support (r = 0.379), and swing phase (r = -0.386). Conclusions. The perceived impact of spasticity coincides with alterations of the spatio-temporal parameters of gait in MS. This indicates that subsequent interventions might target a decrease in spasticity or its perceived impact as an approach for improving mobility in MS.
The Development of A Spatial Heterodyne Spectrometer For Raman Spectroscopy (2012)

Raman spectroscopy is a valuable tool for molecular analysis and is currently being investigated for a wide range of applications, including standoff planetary measurements. NASA has stated a desire for small, space-flight capable instruments with minimal or no moving parts that can be used to analyze minerals and detect organic molecules and biomarkers on other planets. Raman spectroscopy is an ideal technique for this application and a standoff instrument would allow measurements to be made at a much greater range than is now possible. Existing Raman systems are not optimal for standoff planetary measurements because they are too large and heavy, contain moving parts, have low light throughput and have a limited ability to measure extended objects. This thesis discusses the development of a new type of Raman spectrometer for planetary applications called the Spatial Heterodyne Raman Spectrometer (SHRS). The SHRS is based on a Michelson interferometer, but the SHRS uses stationary diffraction gratings in place of mirrors and requires no moving parts. The SHRS does not require long focal length optics to achieve high spectral resolution, which makes the SHRS intrinsically small. The SHRS measures all wavelengths simultaneously and can be coupled with a pulsed laser source and gated detector for measurements in high ambient light conditions. The SHRS system boasts an expanded etendue because it does not have an entrance slit and has a large acceptance angle (up to 10 degrees). This allows the system to maintain high sensitivity when making standoff measurements of large area samples using defocused laser excitation. This is important for photosensitive samples where a larger laser spot size might reduce photodegradation. It is also useful for heterogeneous samples where measuring a larger area would be more representative of the sample as a whole. This dissertation will introduce the theories of Raman spectroscopy and spatial heterodyne spectroscopy, discuss the use of Raman spectroscopy for planetary studies, describe the development of the SHRS, and show how the SHRS can be used for wide area standoff measurements.
The PAN module: the N‐terminal domains of plasminogen and hepatocyte growth factor are homologous with the apple domains of the prekallikrein family and with a novel domain found in numerous nematode proteins (1999)

Based on homology search and structure prediction methods we show that (1) the N-terminal N domains of members of the plasminogen/hepatocyte growth factor family, (2) the apple domains of the plasma prekallikrein/coagulation factor XI family, and (3) domains of various nematode proteins belong to the same module superfamily, hereafter referred to as the PAN module. The patterns of conserved residues correspond to secondary structural elements of the known three-dimensional structure of hepatocyte growth factor N domain, therefore we predict a similar fold for all members of this superfamily. Based on available functional informations on apple domains and N domains, it is clear that PAN modules have significant functional versatility, they fulfill diverse biological functions by mediating protein-protein or protein-carbohydrate interactions.
Estimation of skeletal muscle mass by bioelectrical impedance analysis (2000)

The purpose of this study was to develop and cross-validate predictive equations for estimating skeletal muscle (SM) mass using bioelectrical impedance analysis (BIA). Whole body SM mass, determined by magnetic resonance imaging, was compared with BIA measurements in a multiethnic sample of 388 men and women, aged 18-86 yr, at two different laboratories. Within each laboratory, equations for predicting SM mass from BIA measurements were derived using the data of the Caucasian subjects. These equations were then applied to the Caucasian subjects from the other laboratory to cross-validate the BIA method. Because the equations cross-validated (i.e., were not different), the data from both laboratories were pooled to generate the final regression equation SM mass (kg) = [(Ht<SUP>2</SUP>/ <IT>R</IT> x 0.401) + (gender x 3.825) + (age x -0. 071)] + 5.102 where Ht is height in centimeters; R is BIA resistance in ohms; for gender, men = 1 and women = 0; and age is in years. The r(2) and SE of estimate of the regression equation were 0.86 and 2.7 kg (9%), respectively. The Caucasian-derived equation was applicable to Hispanics and African-Americans, but it underestimated SM mass in Asians. These results suggest that the BIA equation provides valid estimates of SM mass in healthy adults varying in age and adiposity.
High Level Views in Object-Oriented Systems using Formal Concept Analysis (2018)

Within object-oriented there are different meaningful dependencies between different objects. These dependencies reveal ``contracts, ``collaborations and ``relationships between classes, methods, packages and any development unit in the systems. In most of the cases, these dependencies are not explicit in the code. This problem is due to inadequate or out-of-date documentation and mechanisms such as dynamic binding, inheritance and polymorphism that obscure the presence of existing dependencies. These dependencies play an important part in implicit contracts between the various software artifacts of the system. It is therefore essential that a developer, who has to make changes or extensions to an object-oriented system, understands the dependencies among the classes. Lack of understanding increases the risk that seemingly innocuous changes break the implicit existing contracts in the system. In short, implicit, undocumented dependencies lead to ``fragile systems that are difficult to extend or modify correctly. In this thesis we develop an approach —- based on a methodology and a tool support —- to recover this implicit information and generate ``high-level views of a system at different abstraction levels, using a formal clustering technique called Formal Concept Analysis (FCA). With these views, we help to build the first mental model of a system. Thus the implicit or lost information is made explicit and we are able to find uses of coding styles, possible bottlenecks and weakpoints of a system, identify eventual contracts between the entities, ``patterns based on the dependencies and —- if possible —- propose possible solutions to correct problems in the code. With this approach we also evaluate which are the advantages and disadvantages of using a clustering technique in software reverse engineering
Essential Oil ofEugenia melanadeniaKrug et Urb. from Cuba (2003)

Abstract The chemical composition of the essential oil obtained from the leaves of Eugenia melanadenia Krug et Urb. from Cuba was examined by combined GC/MS. The oil was characterized by the presence of 1,8-cineole (45.3%), terpinen-4-ol (10.6%), p-cymene (8.2%), β-eudesmol (7.0%) and α-terpineol (6.7%) as major constituents.
Solid polymer electrolytes: materials designing and all-solid-state battery applications: an overview (2008)

Polymer electrolytes are promising materials for electrochemical device applications, namely, high energy density rechargeable batteries, fuel cells, supercapacitors, electrochromic displays, etc. The area of polymer electrolytes has gone through various developmental stages, i.e. from dry solid polymer electrolyte (SPE) systems to plasticized, gels, rubbery to micro/nano-composite polymer electrolytes. The polymer gel electrolytes, incorporating organic solvents, exhibit room temperature conductivity as high as ∼10−3 S cm−1, while dry SPEs still suffer from poor ionic conductivity lower than 10−5 S cm−1. Several approaches have been adopted to enhance the room temperature conductivity in the vicinity of 10−4 S cm−1 as well as to improve the mechanical stability and interfacial activity of SPEs. In this review, the criteria of an ideal polymer electrolyte for electrochemical device applications have been discussed in brief along with presenting an overall glimpse of the progress made in polymer electrolyte materials designing, their broad classification and the recent advancements made in this branch of materials science. The characteristic advantages of employing polymer electrolyte membranes in all-solid-state battery applications have also been discussed.