gebhart/patrepeval huggingface dataset:
Stimulation of homology-directed gene targeting at an endogenous human locus by a nicking endonuclease (2009)

Homologous recombination (HR) is a highly accurate mechanism of DNA repair that can be exploited for homology-directed gene targeting. Since in most cell types HR occurs very infrequently (approximately 10(-6) to 10(-8)), its practical application has been largely restricted to specific experimental systems that allow selection of the few cells that become genetically modified. HR-mediated gene targeting has nonetheless revolutionized genetics by greatly facilitating the analysis of mammalian gene function. Recent studies showed that generation of double-strand DNA breaks at specific loci by designed endonucleases greatly increases the rate of homology-directed gene repair. These findings opened new perspectives for HR-based genome editing in higher eukaryotes. Here, we demonstrate by using donor DNA templates together with the adeno-associated virus (AAV) Rep78 and Rep68 proteins that sequence- and strand-specific cleavage at a native, predefined, human locus can also greatly enhance homology-directed gene targeting. Our findings argue for the development of other strategies besides direct induction of double-strand chromosomal breaks to achieve efficient and heritable targeted genetic modification of cells and organisms. Finally, harnessing the cellular HR pathway through Rep-mediated nicking expands the range of strategies that make use of AAV elements to bring about stable genetic modification of human cells.
Folding in two-dimensional off-lattice models of proteins (1999)

Off-lattice proteinlike models are constructed in two dimensions so that their native states are close to an on-lattice target. The Hamiltonian involves the Lennard-Jones and harmonic interactions. The native states of these sequences are determined with a high degree of certainty through Monte Carlo processes. The sequences are characterized thermodynamically and kinetically. It is shown that the rank-ordering-based scheme of the assignment of contact energies typically fails in off-lattice models even though it generates high stability of on-lattice sequences. Similar to the on-lattice case, Go-like modeling, in which the interaction potentials are restricted to the native contacts in a target shape, gives rise to good folding properties. Involving other contacts deteriorates these properties.
Phi 29 DNA polymerase active site. The conserved amino acid motif “Kx3NSxYG” is involved in template-primer binding and dNTP selection (1993)

phi 29 DNA polymerase shares with other alpha-like DNA polymerases several regions of amino acid similarity. Among them, the conserved region characterized by the amino acid motif "Kx3NSxYG" has been proposed to form part of the polymerization active site of alpha-like DNA polymerases. Mutants in phi 29 DNA polymerase residue Tyr390 of this conserved motif had been previously described to be affected in DNA-dependent dNTP binding. In this paper, the functional significance of this conserved motif is further studied by the analysis of mutants in conserved residues Asn387, Ser388, and Gly391. Residue Phe393 of phi 29 DNA polymerase has also been selected as target for site-directed mutagenesis because of its conservation within the group of alpha-like DNA polymerases from genomes that replicate by a protein-priming mechanism. Mutant N387Y was shown to be affected both in initiation and polymerization reactions, showing 3-fold higher Km value for dATP and more than 11-fold lower Vmax value than the wild-type enzyme in the initiation reaction; moreover, it was affected in enzyme-DNA translocation. Mutant S388G retained initiation and polymerization activities; interestingly, this mutation significantly increased the efficiency of dNTP incorporation in non-templated reactions. Mutation Gly391 to Asp abolished template-primer binding as shown by gel retardation assays; this mutant was drastically affected in template-dependent dNTP incorporation both in initiation and polymerization reactions, but the efficiency of the non-templated phi 29 terminal protein-deoxynucleotidylation was higher than with the wild-type protein. Mutation Phe393 to Tyr severely decreased initial binding to template-primer DNA molecules, resulting in a reduced activity in DNA primer-dependent polymerization reactions but not in phi 29 terminal protein-dependent ones.
The Nantucket Quakers' Message as an Alternative to Benjamin Franklin's Message to the French Revolution (2000)

Benjamin Franklin lived in France from 1778 to 1785. He was successful in drawing the country into the American Independence war against Britain in 1778. He became the idol of future French revolutionaries, and remained so even after his death in 1790. The French revolutionaries also admired American Quakers, but they mistook Benjamin Franklin for a Quaker, which he was not. From 1786, American Quakers from Nantucket settled down in Dunkerque, in France. In February 1791, together with Jean de Marsillac, a French Quaker from Congenies, they brought a petition in favour of a non-violent revolution. But Mirabeau, who was President of the National Assembly, was a great admirer of Benjamin Franklin. He did not take the Quakers' petition seriously, and historians afterwards forgot about this message. Benjamin Franklin indirectly originated from Nantucket through his mother Abiah Folger. He was a relative of many Nantucket Quakers who went to Dunkerque. So, the two messages brought to France during the French revolution came from Nantucket, directly or indirectly. They are complementary to each other, but the second one still remains to be discovered.
X-chromosome inactivation and epigenetic fluidity in human embryonic stem cells (2008)

With the potential to give rise to all somatic cell types, human embryonic stem cells (hESC) have generated enormous interest as agents of cell replacement therapy. One potential limitation is their safety in vivo. Although several studies have focused on concerns over genomic stability ex vivo, few have analyzed epigenetic stability. Here, we use tools of the epigenetic phenomenon, X-chromosome inactivation (XCI), to investigate their epigenetic properties. Among 11 distinct hESC lines, we find a high degree of variability. We show that, like mouse ESC, hESC in principle have the capacity to recapitulate XCI when induced to differentiate in culture (class I lines). However, this capacity is seen in few hESC isolates. Many hESC lines have already undergone XCI (class II and III). Unexpectedly, there is a tendency to lose XIST RNA expression during culture (class III). Despite losing H3-K27 trimethylation, the inactive X of class III lines remains transcriptionally suppressed, as indicated by Cot-1 RNA exclusion. We conclude that hESC lines are subject to dynamic epigenetic reprogramming ex vivo. Given that XCI and cell differentiation are tightly linked, we consider implications for hESC pluripotency and differentiation potential.
Developmental regulation of a murine T-cell-specific tyrosine kinase gene, Tsk. (1993)

Protein-tyrosine kinases have been implicated in signal transduction in T lymphocytes after stimulation of many cell-surface molecules, including the T-cell antigen receptor, CD4, CD8, CD2, CD5, and CD28. Yet the identities of many of these tyrosine kinases remain unknown. We have isolated a murine tyrosine kinase gene, called Tsk for T-cell-specific kinase, that appears to be exclusively expressed in T lymphocytes. The Tsk cDNA clone encodes a polypeptide of 70 kDa, which is similar in sequence to both the src and abl families of tyrosine kinases. Sequence comparisons also indicate that Tsk contains one src-homology region 2 domain and one src-homology 3 domain but lacks the negative regulatory tyrosine (src Tyr-527) common to src-family kinases. In addition, Tsk expression is developmentally regulated. Steady-state Tsk mRNA levels are 5- to 10-fold higher in thymocytes than in peripheral T cells and increase in the thymus during mouse development from neonate to adult. Furthermore, Tsk is expressed in day 14 fetal thymus, suggesting a role for Tsk in early T-lymphocyte differentiation.
Calcitonin and CGRP inhibit gastrointestinal transit via distinct neuronal pathways (1988)

This study compares the central nervous system effects of rat calcitonin and rat calcitonin gene-related peptide (CGRP) on gastrointestinal transit in freely moving rats. Calcitonin and CGRP (0.01-1.0 nmol) injected into the lateral cerebral ventricle significantly inhibited gastric emptying and small bowel transit but did not affect large bowel transit. These biological actions were abolished by ganglionic blockade with chlorisondamine but not by noradrenergic blockade with bretylium. Truncal vagotomy abolished the inhibitory effects of CGRP but not those of calcitonin. Neither adrenalectomy nor hypophysectomy prevented the inhibitory actions of calcitonin and CGRP on gastric emptying and small bowel transit. Intraperitoneal administration of calcitonin and CGRP (1 nmol) produced inhibition of gastric emptying only, and this was not abolished by ganglionic blockade. These results indicate that calcitonin and CGRP exhibit similar central nervous system effects, producing inhibition of gastric emptying and small bowel transit but not altering large bowel transit. Calcitonin inhibits gastrointestinal transit via nonvagal, nonnoradrenergic autonomic efferents, yet CGRP inhibits gastrointestinal transit via vagal efferent fibers.
Expression of herpes simplex virus 1 glycoprotein B by a recombinant vaccinia virus and protection of mice against lethal herpes simplex virus 1 infection. (1987)

The herpes simplex virus 1 (HSV-1) strain F gene encoding glycoprotein gB was isolated and modified at the 5' end by in vitro oligonucleotide-directed mutagenesis. The modified gB gene was inserted into the vaccinia virus genome and expressed under the control of a vaccinia virus promoter. The mature gB glycoprotein produced by the vaccinia virus recombinant was glycosylated, was expressed at the cell surface, and was indistinguishable from authentic HSV-1 gB in terms of electrophoretic mobility. Mice immunized intradermally with the recombinant vaccinia virus produced gB-specific neutralizing antibodies and were resistant to a lethal HSV-1 challenge.
PD-1 up-regulation is correlated with HIV-specific memory CD8+ T-cell exhaustion in typical progressors but not in long-term nonprogressors (2007)

The immunoreceptor PD-1 is significantly up-regulated on exhausted CD8+ T cells during chronic viral infections such as HIV-1. However, it remains unknown whether PD-1 expression on CD8+ T cells differs between typical progressors (TPs) and long-term nonprogressors (LTNPs). In this report, we examined PD-1 expression on HIV-specific CD8+ T cells from 63 adults with chronic HIV infection. We found that LTNPs exhibited functional HIV-specific memory CD8+ T cells with markedly lower PD-1 expression. TPs, in contrast, showed significantly up-regulated PD-1 expression that was closely correlated with a reduction in CD4 T-cell number and an elevation in plasma viral load. Importantly, PD-1 up-regulation was also associated with reduced perforin and IFN-gamma production, as well as decreased HIV-specific effector memory CD8+ T-cell proliferation in TPs but not LTNPs. Blocking PD-1/PD-L1 interactions efficiently restored HIV-specific CD8+ T-cell effector function and proliferation. Taken together, these findings confirm the hypothesis that high PD-1 up-regulation mediates HIV-specific CD8+ T-cell exhaustion. Blocking the PD-1/PD-L1 pathway may represent a new therapeutic option for this disease and provide more insight into immune pathogenesis in LTNPs.
CHARACTERISTICS OF PORK WITH DOCOSAHEXAENOIC ACID SUPPLEMENTED IN THE DIET (2002)

ABSTRACT The omega‐3 fatty acid, docosahexaenoic acid (DHA) was added to the basal diet of market pigs at 0, 0.125 and 0.250 kg/pig for 22–42 days. There were three consecutive pens per block with 10 blocks for a total of 30 pens assigned to each treatment group. No differences were found in off‐flavor, juiciness, and overall flavor of the semimembranosus muscle and cured bacon among the three treatment groups. Furthermore, weight loss during storage and cooking did not differ among the three treatments. Objective evaluation results for oxidative rancidity did not differ between hams from control pigs and those from pigs receiving 0.250 kg/pig DHA. Shear force of cured bacon did not differ among the three treatments. These data suggest that DHA, when fed at 0.125 and 0.250 kg/pig, causes no adverse effects on carcass characteristics, sensory attributes, and tenderness of market size pigs.
<title>Integration of polymer electro-optic devices on nonplanar silicon-integrated circuits</title> (1995)

To demonstrate the feasibility of integrating polymer electro-optic devices on Si circuitry, we have vertically integrated a demonstration slab phase modulator on nonplanar VLSI circuitry. Optical loss measurements for waveguides fabricated on planarized circuits demonstrate that more practical devices like channel phase and Mach-Zehnder amplitude modulators can easily be integrated onto the circuits.
Feeding Strategies for Premature Infants: Beneficial Outcomes of Feeding Fortified Human Milk Versus Preterm Formula (1999)

Although the study does not allow a comparison of FHM with unfortified human milk, the data suggest that the unique properties of human milk promote an improved host defense and gastrointestinal function compared with the feeding of formula. The benefits of improved health (less sepsis and necrotizing enterocolitis) associated with the feeding of FHM outweighed the slower rate of growth observed, suggesting that the feeding of FHM should be promoted actively in premature infants.
Simultaneous Saccharification and Fermentation of Dilute Acid Pretreated Red Algae (Gelidiella acerosa) for Bioethanol Production (2014)

Studies on the production of bioethanol from red algae (Gelidiella acerosa) by dilute acid pretreatment and simultaneous saccharification and fermentation were performed. The non-cellulosic compounds were significantly reduced during dilute acid pretreatment. Results obtained in simultaneous saccharification and fermentation showed that the ethanol yield was affected by the changes in pretreatment, liquid to solid ratio, enzyme concentration, and pH. Kinetic study was also performed with experimental value to analyze the production rate and their actual means of production process. The maximum 91.62% of theoretical yield of ethanol was obtained at 36 h of simultaneous saccharification and fermentation under optimized conditions.
Standard Numbering Scheme for Class B β-Lactamases (2001)

Unlike for classes A and B, a standardized amino acid numbering scheme has not been proposed for the class C (AmpC) β-lactamases, which complicates communication in the field. Here, we propose a scheme developed through a collaborative approach that considers both sequence and structure, preserves traditional numbering of catalytically important residues (Ser<sup>64</sup>, Lys<sup>67</sup>, Tyr<sup>150</sup>, and Lys<sup>315</sup>), is adaptable to new variants or enzymes yet to be discovered and includes a variation for genetic and epidemiological applications.
KnowRob: A knowledge processing infrastructure for cognition-enabled robots (2013)

Autonomous service robots will have to understand vaguely described tasks, such as “set the table” or “clean up”. Performing such tasks as intended requires robots to fully, precisely, and appropriately parameterize their low-level control programs. We propose knowledge processing as a computational resource for enabling robots to bridge the gap between vague task descriptions and the detailed information needed to actually perform those tasks in the intended way. In this article, we introduce the KnowRob knowledge processing system that is specifically designed to provide autonomous robots with the knowledge needed for performing everyday manipulation tasks. The system allows the realization of “virtual knowledge bases”: collections of knowledge pieces that are not explicitly represented but computed on demand from the robot’s internal data structures, its perception system, or external sources of information. This article gives an overview of the different kinds of knowledge, the different inference mechanisms, and interfaces for acquiring knowledge from external sources, such as the robot’s perception system, observations of human activities, Web sites on the Internet, as well as Web-based knowledge bases for information exchange between robots. We evaluate the system’s scalability and present different integrated experiments that show its versatility and comprehensiveness.
Elevated thiobarbituric acid-reactive substances and antioxidant enzyme activity in the brain in Alzheimer's disease (1995)

We determined levels of thiobarbituric acid-reactive substances (TBARS), a measure of lipid peroxidation, and the activity of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GSSG-R), and catalase (CAT) in the amygdala, hippocampus, pyriform cortex, superior and middle temporal gyri, inferior parietal lobule, middle frontal gyrus, occipital pole, and cerebellum of 13 Alzheimer's disease (AD) and 10 control brains. Levels of TBARS were elevated in all AD brain regions except the middle frontal gyrus, and elevation levels reached statistical significance in the hippocampus and pyriform cortex and marginal significance in the amygdala of AD subjects compared with age-matched controls. Significant elevation of GSH-Px activity was present in AD hippocampus compared with control. Moderate but statistically insignificant elevations of GSH-Px activity also were present in the amygdala and pyriform cortex in AD. GSSG-R activity was significantly elevated in the amygdala and hippocampus in AD subjects compared with controls. CAT activity was significantly elevated in AD hippocampus and superior and middle temporal gyri. SOD levels were elevated in all brain regions in AD patients compared with controls, although none of these elevations reached statistical significance. Antioxidant enzyme activities were significantly elevated where lipid peroxidation was most pronounced, suggesting a compensatory rise in antioxidant activity in response to increased free radical formation. This study supports the concept that the brain in AD is under increased oxidative stress and demonstrates that the oxidative changes are most pronounced in the medial temporal lobe, where histopathologic alterations are most severe.
Activation of the spinal sigma‐1 receptor enhances NMDA‐induced pain via PKC‐ and PKA‐dependent phosphorylation of the NR1 subunit in mice (2008)

The results of this study suggest that the activation of spinal Sig-1 R enhances NMDA-induced pain via PKC- and PKA-dependent phosphorylation of the NMDA receptor NR 1 subunit.
Collagen fibrillar networks as skeletal frameworks. A demonstration by cell-maceration/scanning electron microscope method. (1988)

A cell-maceration/scanning electron microscope (SEM) method was employed to demonstrate the arrangement of the collagen fibrillar network of various tissues. Immersion of fixed tissues in NaOH (25 degrees C) for 3-7 days, followed by rinsing in distilled water successfully removed the cellular elements, exposing collagen fibrils which were identified as such by transmission electron microscopy in their natural locations. SEM observations of the preparations are able to demonstrate the three-dimensional architecture of collagen fibrils much more precisely than other methods, including the silver impregnation method. Collagen fibrils, forming sheaths for housing individual cardiac myocytes, fused together, thus ensuring an equal stretch of contiguous myocytes and preventing the slippage of adjacent cells. Individual skeletal muscle fibers and nerve fibers were ensheathed by the meshwork of collagen fibrils running in two opposite helices. Such structures seem to play an important role in resisting the stretching impetus. At the epithelial-connective tissue junction of the tongue and fingertip skin, interwoven collagen fibrils formed numerous microridges which probably provide a broad anchorage for the epithelium. In the intestinal mucosa, the collagen fibrillar network immediately below the basal laminae of the villous epithelium possessed heterogeneous pores. As the collagen fibrillar network shows morphological features specific to individual organs and tissues, it is suggested that such formations not only constitute the skeletal framework but also provide those cells which are housed there with a microenvironment suitable for their activities.
Routes of clearance of radioactive water from the rabbit vitreous. (1984)

The movement of water to and from the vitreous across the retina and pigment epithelium is important in relation to an understanding of such conditions as retinal detachment and its surgical cure, central serous retinopathy, and retinal oedema. Experiments were carried out to determine the main routes for removal of water injected into the vitreous and to see if the removal could be explained on the basis of diffusion or whether bulk flow was also implicated. 25 microCi of 3H2O in 25 microliter were injected into a central position in the vitreous humour of living rabbits under general anaesthesia. For 9 animals blood was collected from one of the 4 vortex veins draining the choroid and the radioactivity in the samples measured. For another 6 rabbits similarly injected the radioactivity in samples of aqueous humour was determined. The percentage of injectate recovered from the vortex vein blood ranged between 13% and 38%, mean 25 +/- 3%. The percentage of injectate recovered from the aqueous humour ranged between 1.2% and 5.2%, mean 2.8 +/- 0.6%. Analysis of the time course of isotope activity in the samples revealed a mean transit time from the mid vitreous to the choroid of 32 +/- 2 minutes, and from the mid vitreous to the anterior chamber of 84 +/- 3 minutes. By means of a computer model it was calculated that diffusion alone could effect this transfer; if active transport were involved in the transport of 3H2O to the choroid, this was not a limiting factor under the conditions of the experiment.
Identification of an Amplified, Highly Expressed Gene in a Human Glioma (1987)

A gene, termed gli, was identified that is amplified more than 50-fold in a malignant glioma. The gene is expressed at high levels in the original tumor and its derived cell line and is located at chromosome 12 position (q13 to q14.3). The gli gene is a member of a select group of cellular genes that are genetically altered in primary human tumors.
Inactivation of Bacillus coagulans Spores by Pressure-assisted Thermal Processing (2010)

Food sterilization has traditionally been associated with thermal processing at ≥121°C to ensure elimination of pathogenic spore-forming bacteria. Thermal processing alone tends to adversely affect the product’s freshness and quality attributes. Pressure-assisted thermal processing (PATP) offers new opportunities to overcome these limitations by treatment of foods at lower temperatures. This study was conducted to examine the lethality of PATP against the spores of Bacillus coagulans (an acid-tolerant spoilage bacterium) in a commercial tomato juice. The spores were suspended in deionized water, added to the samples (tomato juice at pH 4.2) at 108 CFU/ml, and treated at 600 MPa and temperatures of up to 105°C for various holding times (≤1.5 min). The viable numbers of spores were subsequently determined on tripticase soy and nutrient agars. A PATP treatment at 100°C for 2 min was found to be sufficient to inactivate the B. coagulans spores to an undetectable level (≤10 CFU/ml). The decimal reduction time (D-value) of the spores under these conditions was determined as 30 s. These findings demonstrate the efficacy of PATP treatment against heat and pressure-resistant bacterial spores; however, the level of inactivation will depend on the process conditions and composition of the suspending medium.