gebhart/patrepeval huggingface dataset:
Cellular Manipulation of Human Embryonic Stem Cells by TAT-PDX1 Protein Transduction (2005)

Human embryonic stem cells (hESCs) are an in vitro model system for the study of human early development and a potential source for cell-based therapies. An efficient strategy for cellular manipulation of hESCs may be highly valuable for the analysis of gene function involved in human embryogenesis and the development of cell-based therapies via induced differentiation into particular cell types. However, plasmid transfection of hESCs has low efficiency and viral transduction may not be the method of choice for cell-based therapies due to genome integration. To overcome these limitations, we applied protein transduction technology that can transfer proteins into cells via direct penetration across the lipid bilayer. Here, we show that the FITC dye fused to the TAT protein transduction domain (PTD) was efficiently transferred into hESCs. In addition, the PDX1 transcription factor, which plays a central role in pancreatic development, was transferred into hESCs as a fusion form of TAT PTD. The transduced TAT-PDX1 activated its downstream target genes and induced insulin protein production in hESCs. These results demonstrate that protein transduction could be used in the cellular manipulation of hESCs and would provide a significant breakthrough for basic and therapeutic research in hESCs.
Surface kinetic roughening caused by dental erosion: An atomic force microscopy study (2008)

Surface kinetic roughening takes place both in case of growth and erosion processes. Teeth surfaces are eroded by contact with acid drinks, such as those used to supplement mineral salts during sporting activities. Calcium-phosphate based (CPP-ACP) pastes are known to reduce the erosion process, and to favour the enamel remineralization. In this study we used atomic force microscopy (AFM) to investigate the surface roughening during dental erosion, and the mechanisms at the basis of the protection role exerted by a commercial CPP-ACP paste. We found a statistically significant difference (p&amp;lt;0.01) in the roughness of surfaces exposed and not exposed to the acid solutions. The treatment with the CPP-ACP paste determined a statistically significant reduction of the roughness values. By interpreting the AFM results in terms of fractal scaling concepts and continuum stochastic equations, we showed that the protection mechanism of the paste depends on the chemical properties of the acid solution.
Efficiency of Transduction by Recombinant Sindbis Replicon Virus Varies Among Cell Lines, Including Mosquito Cells and Rat Sensory Neurons (1996)

Recombinant alphaviruses have been used as vehicles for delivery and expression of heterologous genes in mammalian, avian and insect cell lines. We have used a Sindbis replicon virus (Sinreplac) able to express the E. coli lacZ gene to compare the efficiency of transduction in one insect, six mammalian cell lines and cultured rat dorsal neurons which apparently express beta-galactosidase over a 30-day time period. Results show that different cell lines were transduced with varying degrees of efficiency and that this efficiency could be improved in some cell lines by packaging the replicon with a helper derived from a more neurovirulent strain of Sindbis.
COBRA: a sensitive and quantitative DNA methylation assay (1997)

We report here on a quantitative technique called COBRA to determine DNA methylation levels at specific gene loci in small amounts of genomic DNA. Restriction enzyme digestion is used to reveal methylation-dependent sequence differences in PCR products of sodium bisulfite-treated DNA as described previously. We show that methylation levels in the original DNA sample are represented by the relative amounts of digested and undigested PCR product in a linearly quantitative fashion across a wide spectrum of DNA methylation levels. In addition, we show that this technique can be reliably applied to DNA obtained from microdissected paraffin-embedded tissue samples. COBRA thus combines the powerful features of ease of use, quantitative accuracy, and compatibility with paraffin sections.
IP Version 6 Addressing Architecture (1995)

This document specifies an Internet standards track protocol for the Internet community, and requests discussion and suggestions for improvements.
Experimental Campylobacter jejuni Infection in Humans (1988)

Two strains of Campylobacter jejuni ingested by 111 adult volunteers, in doses ranging from 8 x 10(2) to 2 x 10(9) organisms, caused diarrheal illnesses. Rates of infection increased with dose, but development of illness did not show a clear dose relation. Resulting illnesses with strain A3249 ranged from a few loose stools to dysentery, with an average of five diarrheal stools and a volume of 509 mL. Infection with strain 81-176 was more likely to cause illness, and these illnesses were more severe, with an average of 15 stools and 1484 mL of total stool volume. All patients had fecal leukocytes. The dysenteric nature of the illness indicates that the pathogenesis of C. jejuni infection includes tissue inflammation. Ill volunteers developed a serum antibody response to the C. jejuni group antigen and were protected from subsequent illness but not infection with the same strain.
EFFECTS OF INSULIN‐LIKE GROWTH FACTOR‐BINDING PROTEIN 2 AND AN IGF‐TYPE I RECEPTOR‐BLOCKING ANTIBODY ON APOPTOSIS IN HUMAN TERATOCARCINOMA CELLS IN VITRO (2001)

Human teratocarcinoma cells (Tera-2) deprived of serum undergo programmed cell death which can be counteracted by simultaneous addition of IGF-I or IGF-II. This protective effect of IGFs was specific in the sense that both addition of IGF-binding protein-2, and blocking of the IGF-type I receptor by a specific antibody, both resulted in an increased apoptotic rate.
Synthesis of a Large Precursor to Ribosomal RNA in a Mutant of Escherichia coli (1973)

A mutant of E. coli, isolated by Kindler and Hofschneider as a strain defective in RNase III activity, forms a 30S precursor of ribosomal RNA ("30S pre-rRNA"). The half-life of the 30S pre-rRNA in growing cells at 30 degrees , estimated by the rate of specific (3)[H]uridine incorporation, is about 1 min. In rifampicin-treated cells, the RNA is metabolized to mature rRNA with a half-life of about 2 min. The 30S pre-rRNA has been highly purified. DNA-RNA hybridization tests demonstrate that it contains both 16S and 23S rRNA sequences. Also, in cultures treated with rifampicin, the cleavage products of radioactive 30S pre-rRNA include 25S and 17.5S RNA species, destined to becomes 23S and 16S rRNA. Thus, each 30S chain probably contains one 16S and one 23S RNA sequence, as well as additional sequences. Two independent techniques indicate that the additional portions account for about 27% of the total lenght: (1) By comparison to the sedimentation rate and electrophoretic mobility of marker RNAs, the 30S pre-RNA has an apparent molecular weight of 2.3 x 10(6) +/- 5%, or 28% more than the sum of 16S and 23S rRNA; (2) 27% of the 30S pre-rRNA is not competed away from hybridization by mature 16S and 23S rRNA.Thus, bacteria appear to make a pre-rRNA similar in some respects to that observed in eukaryotes; though in normal E. coli cells, the pre-rRNA is ordinarily cleaved endonucleolytically during its formation.
Genetics of survival in mice: subregions of the major histocompatibility complex. (1990)

In this study of murine survival, 422 F1 hybrids between DBA/2J (D2) female mice and C57BL/10 (B10) background H-2 congenic male mice (11 strains), 88 F1 hybrids between B10 female mice and B10 background H-2 congenic male mice (3 strains), and 532 control mice from the 11 parental B10 background H-2 congenic mice were bred over a period of 2 yr. Toward the end of the breeding period there was documentation of Sendai infection in the mouse rooms. All analyses were done separately for the two sexes. Although it did not appear that an unusually high number of mice died during the time the colony was infected with Sendai, there was a highly significant tendency for mice who were younger at the time of the Sendai infection to have shorter survival than mice who were older at that time point. The effect of birth date on survival was approximately as significant as the effect of strain on survival. Hence all analyses of genetic effects on survival were either done within subsets of mice born in the same quarter of a particular year or else included date of birth variables in survival models. Of the 18 possible comparisons of pairs of strains which overlapped in birth dates and differed only in the D end of H-2, five were associated with highly significant survival differences. Of the 11 pairs of strains which overlapped in birth date and differed only in the K end of H-2, none was associated with significant survival differences.(ABSTRACT TRUNCATED AT 250 WORDS)
More than a sidekick: the IL-6 family cytokine IL-11 links inflammation to cancer (2010)

IL-11, a member of the IL-6 family of cytokines, exerts pleiotropic activities by stimulating hemopoiesis and thrombopoiesis, regulating macrophage differentiation, and conferring mucosal protection in the intestine. These effects are mediated by a multimeric complex comprising the ligand-binding IL-11Rα and the ubiquitously expressed gp130R β-subunit, which together, trigger intracellular signaling and engagement of Stat3. In turn, activated Stat3 promotes cell survival and proliferation as well as immune responses associated with inflammatory diseases and tumor progression. IL-6 and IL-11 compete for interaction with gp130, resulting in tissue-specific functions depending on the expression patterns of their respective α-subunit receptors. Although traditionally, IL-6 has been associated with aberrant Stat3 activation and associated pathologies, here, we discuss newly emerging roles for IL-11 in linking inflammation to cancer progression. We propose that in light of the recurrence of persistent STAT3 activation and elevated IL-11 expression in inflammation-associated gastrointestinal cancers in humans, inhibition of Stat3 or pharmacologically, more amenable upstream molecules such as IL-11 may represent novel, therapeutic targets.
Bacillus subtilis natto: a non-toxic source of poly-γ-glutamic acid that could be used as a cryoprotectant for probiotic bacteria (2013)

It is common practice to freeze dry probiotic bacteria to improve their shelf life. However, the freeze drying process itself can be detrimental to their viability. The viability of probiotics could be maintained if they are administered within a microbially produced biodegradable polymer - poly-γ-glutamic acid (γ-PGA) - matrix. Although the antifreeze activity of γ-PGA is well known, it has not been used for maintaining the viability of probiotic bacteria during freeze drying. The aim of this study was to test the effect of γ-PGA (produced by B. subtilis natto ATCC 15245) on the viability of probiotic bacteria during freeze drying and to test the toxigenic potential of B. subtilis natto. 10% γ-PGA was found to protect Lactobacillus paracasei significantly better than 10% sucrose, whereas it showed comparable cryoprotectant activity to sucrose when it was used to protect Bifidobacterium breve and Bifidobacterium longum. Although γ-PGA is known to be non-toxic, it is crucial to ascertain the toxigenic potential of its source, B. subtilis natto. Presence of six genes that are known to encode for toxins were investigated: three component hemolysin (hbl D/A), three component non-haemolytic enterotoxin (nheB), B. cereus enterotoxin T (bceT), enterotoxin FM (entFM), sphingomyelinase (sph) and phosphatidylcholine-specific phospholipase (piplc). From our investigations, none of these six genes were present in B. subtilis natto. Moreover, haemolytic and lecithinase activities were found to be absent. Our work contributes a biodegradable polymer from a non-toxic source for the cryoprotection of probiotic bacteria, thus improving their survival during the manufacturing process.
Thickness dependence of spin torque ferromagnetic resonance in Co75Fe25/Pt bilayer films (2014)

The spin Hall angle of Pt in Co75Fe25/Pt bilayer films was experimentally investigated by means of the spin-torque ferromagnetic resonance and the modulation of damping measurements. By comparing the present results with the Ni80Fe20/Pt system, we found that the ferromagnetic layer underneath the Pt one greatly affects the estimation of the spin Hall angle. We also discuss the spin diffusion length of Pt and the ferromagnetic thickness dependence of the Gilbert damping coefficient.
The use of film dosimetry of the penumbra region to improve the accuracy of intensity modulated radiotherapy (2004)

Accurate measurements of the penumbra region are important for the proper modeling of the radiation beam for linear accelerator-based intensity modulated radiation therapy. The usual data collection technique with a standard ionization chamber artificially broadens the measured beam penumbrae due to volume effects. The larger the chamber, the greater is the spurious increase in penumbra width. This leads to inaccuracies in dose calculations of small fields, including small fields or beam segments used in IMRT. This source of error can be rectified by the use of film dosimetry for penumbra measurements because of its high spatial resolution. The accuracy of IMRT calculations with a pencil beam convolution model in a commercial treatment planning system was examined using commissioning data with and without the benefit of film dosimetry of the beam penumbrae. A set of dose-spread kernels of the pencil beam model was calculated based on commissioning data that included beam profiles gathered with a 0.6-cm-i.d. ionization chamber. A second set of dose-spread kernels was calculated using the same commissioning data with the exception of the penumbrae, which were measured with radiographic film. The average decrease in the measured width of the 80%-20% penumbrae of various square fields of size 3-40 cm, at 5 cm depth in water-equivalent plastic was 0.27 cm. Calculations using the pencil beam model after it was re-commissioned using film dosimetry of the penumbrae gave better agreement with measurements of IMRT fields, including superior reproduction of high dose gradient regions and dose extrema. These results show that accurately measuring the beam penumbrae improves the accuracy of the dose distributions predicted by the treatment planning system and thus is important when commissioning beam models used for IMRT.
The CYP2 A gene subfamily: species differences, regulation, catalytic activities and role in chemical carcinogenesis (1995)

The CYP2A subfamily has been characterized in several mammalian species including mouse, rat, rabbit, hamster, cattle and human. Marked species differences have been demonstrated in the catalytic activities and regulation of this subfamily. In humans, the CYP2A genes are found as a cluster on the long arm of chromosome 19 with the CYP2B and CYP2F genes. Marked interindividual differences in expression of the CYP2A6 gene was found in livers analyzed in vitro and in humans phenotyped in vivo by using coumarin, a specific substrate for the enzyme. Efforts are underway to determine the existence of mutant and variant CYP2A6 alleles in the human population. Since CYP2A6 is able to metabolically-activate chemical carcinogens and is expressed in extrahepatic tissue, it will be of interest to determine whether genetic differences in expression of the gene is associated with cancer risk.
High-Dose [131I]Tositumomab (anti-CD20) Radioimmunotherapy and Autologous Hematopoietic Stem-Cell Transplantation for Adults ≥ 60 Years Old With Relapsed or Refractory B-Cell Lymphoma (2007)

Myeloablative RIT and ASCT is a safe and effective therapeutic option for older adults with relapsed B-NHL.
Structure and functional characterization of the atypical human kinase haspin (2009)

The protein kinase haspin/Gsg2 plays an important role in mitosis, where it specifically phosphorylates Thr-3 in histone H3 (H3T3). Its protein sequence is only weakly homologous to other protein kinases and lacks the highly conserved motifs normally required for kinase activity. Here we report structures of human haspin in complex with ATP and the inhibitor iodotubercidin. These structures reveal a constitutively active kinase conformation, stabilized by haspin-specific inserts. Haspin also has a highly atypical activation segment well adapted for specific recognition of the basic histone tail. Despite the lack of a DFG motif, ATP binding to haspin is similar to that in classical kinases; however, the ATP gamma-phosphate forms hydrogen bonds with the conserved catalytic loop residues Asp-649 and His-651, and a His651Ala haspin mutant is inactive, suggesting a direct role for the catalytic loop in ATP recognition. Enzyme kinetic data show that haspin phosphorylates substrate peptides through a rapid equilibrium random mechanism. A detailed analysis of histone modifications in the neighborhood of H3T3 reveals that increasing methylation at Lys-4 (H3K4) strongly decreases substrate recognition, suggesting a key role of H3K4 methylation in the regulation of haspin activity.
Inhibitory effects of tibial nerve stimulation on bladder neurophysiology in rats (2016)

Tibial nerve stimulation (TNS) is a form of peripheral neuromodulation which has been found effective in treating overactive bladder symptoms, with lesser side effects than first line pharmacotherapy. Despite its widespread clinical use, the underlying mechanism of action is not fully understood. Our aim was to study its effect on the bladder neurophysiology and the trigger mechanism of voiding in the overactive detrusor, simulated by acetic acid (AA) instillation. In urethane anaesthetized male Wistar rats, the tibial nerve was stimulated for 30 min at 5 Hz, pulse width 200 µs and amplitude approximately three times the threshold to induce a slight toe movement. The pressure at which a voiding contraction was triggered (pthres) did not change significantly between the pre- and post-TNS measurements in AA induced detrusor overactivity. It was found that TNS significantly reversed the effects of AA irritation by increasing the bladder compliance and the bladder volume at pthres, as well as suppressed the threshold afferent nerve activity. The slope of the linear relationship between pressure and the afferent activity increased after AA instillation and decreased significantly after stimulation. In addition to its well-known central inhibitory mechanisms, this study has demonstrated that TNS improves bladder storage capacity by delaying the onset of voiding, via an inhibitory effect on the bladder afferent signaling at the peripheral level.
Acetylcholine release by a stimulus train lowers atrial fibrillation threshold (1987)

This study was designed to evaluate the importance of local release of autonomic neuromediators when electrical stimuli are applied to the right atrium to measure the atrial fibrillation threshold (AFT). Experiments were performed in 16 open-chest dogs anesthetized with alpha-chloralose. The dogs were denervated by bilateral transection of the stellates and cervical vagi. The AFT was determined in 11 dogs by delivering either a train of stimuli (14 pulses, 4 ms, 100 Hz) or a single stimulus (10 ms) to the right atrium during its vulnerable period. In eight dogs, beta-adrenergic blockade with timolol (0.1 mg/kg) had no effect on the AFT determined with either method. Atropine (0.2 mg/kg), given after timolol, significantly increased the train-of-pulses AFT from 4.7 +/- 0.4 to 32.3 +/- 4.6 mA (P less than 0.001). The single-pulse AFT increased from 16.5 +/- 1.5 to 17.8 +/- 1.5 mA (P less than 0.05). Atropine had a similar effect on the AFT when it was given in the absence of timolol (n = 3). In five additional dogs, a monophasic action potential was recorded while a 10-mA train was delivered to the atrium during its absolute refractory period. There was marked shortening of the monophasic action potential duration (55 +/- 6 ms) in the first beat after the train. The shortening was totally abolished by atropine (0.2 mg/kg). The results suggest that a train of stimuli liberates local stores of acetylcholine, which cause a shortening of atrial repolarization time and a profound decrease in the current necessary to evoke fibrillation.
Cerebral Anoxic Attacks in Sleep Apnea Syndrome (1989)

In a 52-year-old man who presented with an obstructive sleep apnea (OSAS) syndrome, we observed cerebral anoxic attacks during rapid eye movement (REM) sleep. Polysomnography showed that the attacks were due to severe hypoxia provoked by apneas lasting up to 220 s. Electroencephalogram (EEG) and clinical features clearly differentiate cerebral anoxic attacks from epileptic seizures. The length of apneas in our patient is very unusual, indicating an impairment of the mechanism terminating apneas. The cause of this impairment is unknown. However, this case report documents a possible pathogenetic mechanism other than heart arrhythmias responsible for sudden death or coma arising during sleep.
N-recognin/Ubc2 interactions in the N-end rule pathway (1993)

The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. In the yeast Saccharomyces cerevisiae, substrates of the N-end rule pathway are targeted for degradation by a complex that includes the 225-kDa N-recognin, encoded by UBR1, and the 20-kDa ubiquitin-conjugating enzyme encoded by UBC2. We report that both physical stability and functional activity of the N-recognin.Ubc2 complex require the presence of a highly acidic 23-residue region at the C terminus of Ubc2. Ubc2-C88A, an inactive variant of Ubc2 in which the active-site Cys-88 has been replaced by Ala, is shown to retain the affinity for N-recognin. Expression of Ubc2-C88A inhibits the N-end rule pathway, apparently as a result of competition between Ubc2 and Ubc2-C88A for binding to N-recognin. The two-hybrid (interaction cloning) technique was used to identify a approximately 170-residue C-terminal fragment of the 1,950-residue N-recognin as a Ubc2-interacting domain. We also show that the level of UBR1 mRNA decreases upon overexpression of UBC2. This effect of UBC2 is observed with cells whose UBR1 is expressed from an unrelated promoter but is not observed if UBR1 contains a frameshift mutation, or if the Ubc2 protein lacks its C-terminal acidic region. The N-recognin.Ubc2 complex appears to regulate the expression of N-recognin through changes in the metabolic stability of its mRNA.