gebhart/patrepeval huggingface dataset:
Abstract 3148: Implication of highly cytotoxic natural killer cells for esophageal cancer treatment (2015)

Abstract Natural killer cell-based immunotherapy is a potential treatment for esophageal cancer due to the cytotoxic effect of NK cell and minimal side effects. Natural Killer Activation and Expansion System (NKAES) is our unique system that capable to produce highly cytotoxic and highly proliferative NK cells. Previous studies showed that NKAES-generated NK cells exerted high cytotoxicity on various types of leukemic cell lines and soft tissue cancer cell lines. Our study focuses on the feasibility of NKAES-generated NK cell immunotherapy for esophageal cancer. To generate NKAES-generated NK, peripheral blood mononuclear cell (PBMC) is co-cultured with feeder cells (genetically modified K562 leukemic cell) in presence of interleukin 2. The feeder cells express 4-1BB ligands and membrane bound interleukin 15, which enhance NK responsiveness to interleukin 2, NK activation, NK proliferation and NK survival. Our NK cytotoxicity assay results indicate that seven esophageal cancer cell lines (TE1, TE2, TE3, TE4, TE5, KYSE110 and KYSE30) are highly sensitive to NKAES-generated NK cells. We further compared the cytotoxicity between resting NK, IL-2 activated NK, and NKAES-generated NK on these cell lines. We found that NKAES-generated NK produced the strongest cytotoxicity on these cancer cell lines. NK cytotoxicity is strongly depending on the expression of NK Group 2 Member D (NKG2D) ligands. During cancer metastasis, NKG2D ligands are shedded off by metalloproteinase, which contributes to immune evasion. Interestingly, a previous study showed that a colorectal cancer cell line was sensitive to NK cytotoxicity in early phase of EMT. We further investigated this phenomena in esophageal cancer. To study this, we successfully established an in vitro model, in which stimulated EMT event in esophageal cancer cell lines by using GSK3β inhibitor and epithelial growth factor (EGF). Astonishingly, beside EMT features, we observed that surface NKG2D ligand expression was higher in EMTed esophageal cancer cells compared with control. In addition, EMTed esophageal cancer cells were much sensitive to NKAES-generated NK cytotoxicity. The difference of NK sensitivity was insignificant in IL-2 activated NK. These findings suggest that early EMT event is a crucial checkpoint to prevent further progression that ultimately lead to cancer metastasis, and NK Immunosurveillance is important in this checkpoint. As a conclusion, NKAES-generated NK cells are capable to exert high cytotoxic effect on esophageal cancer cells as well as to establish a strong checkpoint to prevent the progression of EMT event. Citation Format: Kee Siang Lim, Ley Fang Kua, Kosaku Mimura, Kensuke Shiraishi, Wee Joo Chng, Wei Peng Yong, Dario Campana, Koji Kono. Implication of highly cytotoxic natural killer cells for esophageal cancer treatment. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3148. doi:10.1158/1538-7445.AM2015-3148
Structural and Functional Evidence for Bacillus subtilis PaiA as a Novel N1-Spermidine/Spermine Acetyltransferase (2005)

Bacillus subtilis PaiA has been implicated in the negative control of sporulation as well as production of degradative enzymes. PaiA shares recognizable sequence homology with N-acetyltransferases, including those that can acetylate spermidine/spermine substrates. We have determined the crystal structure of PaiA in complex with CoA at 1.9 A resolution and found that PaiA is a member of the N-acetyltransferase superfamily of enzymes. Unexpectedly, we observed the binding of an oxidized CoA dimer in the active site of PaiA, and the structural information suggests the substrates of the enzyme could be linear, positively charged compounds. Our biochemical characterization is also consistent with this possibility, since purified PaiA possesses N1-acetyltransferase activity toward polyamine substrates including spermidine and spermine. Further, conditional overexpression of PaiA in bacteria results in increased acetylation of endogenous spermidine pools. Thus, our structural and biochemical analyses indicate that PaiA is a novel N-acetyltransferase capable of acetylating both spermidine and spermine. In this way, the pai operon may function in regulating intracellular polyamine concentrations and/or binding capabilities. In addition to preventing toxicity due to polyamine excess, this function may also serve to regulate expression of certain bacterial gene products such as those involved in sporulation.
Pharmacological and therapeutic effects of Peganum harmala and its main alkaloids (2013)

Wild Syrian rue (Peganum harmala L. family Zygophyllaceae) is well-known in Iran and various parts of this plant including, its seeds, bark, and root have been used as folk medicine. Recent years of research has demonstrated different pharmacological and therapeutic effects of P. harmala and its active alkaloids, especially harmine and harmaline. Analytical studies on the chemical composition of the plant show that the most important constituents of this plant are beta-carboline alkaloids such as harmalol, harmaline, and harmine. Harmine is the most studied among these naturally occurring alkaloids. In addition to P. harmala (Syrian rue), these beta-carbolines are present in many other plants such as Banisteria caapi and are used for the treatment of different diseases. This article reviews the traditional uses and pharmacological effects of total extract and individual active alkaloids of P. harmala (Syrian rue).
The Sphincter of Oddi is a Boundary for Bacterial Colonisation in the Feline Biliary Tract (1990)

The autochthonous microbial flora of the gastrointestinal and biliary system were studied in ten cats using standard bacteriological cultures and electron microscopic techniques. The most common organisms isolated from the gastrointestinal tract were streptococci, anaerobes and coliform bacteria. A spiral organism was identified in the feline stomach and duodenum. The bile and the biliary system were entirely sterile except in one cat. Bacteria were isolated from the sphincter of Oddi. Electron microscopy confirmed that bacteria had colonised in the thick mucous layer in the gastrointestinal tract and the sphincter of Oddi. No bacteria could be found above the sphincter by electron microscopy. The sphincter of Oddi is hence the natural boundary and probably serves as a physical barrier to the upward migration of bacteria from the colonised gastrointestinal tract to the uncolonised biliary system. The cat may be a suitable animal model for bacteriological studies of the biliary system in the human.
Neutral Beam Dump Utilizing Cathodic ARC Titanium Evaporation (2011)

Unlike tokamaks, where the neutral beam shine through is rarely an issue, open magnetic systems with neutral beam injection oftentimes suffer from incomplete beam capture, which necessitates the handling of the shine through power load and beam particle recycling. The cathodic arc gettering, which provides high evaporation rate coupled with a fast time response, is a powerful and versatile technique for depositing clean getter films in vacuum. A compact neutral beam dump utilizing the titanium arc gettering was developed for a field-reversed configuration plasma sustained by 1 MW, 20–40 keV neutral hydrogen beams. The beam dump is capable of handling large, pulsed gas loads, has a high sorption capacity, and is robust and reliable. The beam recycling coefficient, measured under the beam particle flux density of 5 × 1017 H/(cm2s) sustained for 3–10 ms, is ~ 0.7. The use of the beam dump allows to reduce the recycling of the shine through neutral beam by factor of 3–5, as well as to improve the vacuum conditions in the machine.
Half-Half Transposals (2002)

Most readers will be familiar with split-word transposals such as HORSEHOER in which the letters of the first half of the words are repeated in the second half in a different order. The current exercise is similar, but different in that it concerns pairs of words rather than a single word. I set out to find pairs of words (such as ISOL.ATED and SOLIDATE) in which the letters of the first half of the first word, rearranged, form the letters of the first half of the second word; and the letters of the second half of the first word, rearranged, form the letters of the second half of the second word.
Integration Preferences of Wildtype AAV-2 for Consensus Rep-Binding Sites at Numerous Loci in the Human Genome (2010)

Adeno-associated virus type 2 (AAV) is known to establish latency by preferential integration in human chromosome 19q13.42. The AAV non-structural protein Rep appears to target a site called AAVS1 by simultaneously binding to Rep-binding sites (RBS) present on the AAV genome and within AAVS1. In the absence of Rep, as is the case with AAV vectors, chromosomal integration is rare and random. For a genome-wide survey of wildtype AAV integration a linker-selection-mediated (LSM)-PCR strategy was designed to retrieve AAV-chromosomal junctions. DNA sequence determination revealed wildtype AAV integration sites scattered over the entire human genome. The bioinformatic analysis of these integration sites compared to those of rep-deficient AAV vectors revealed a highly significant overrepresentation of integration events near to consensus RBS. Integration hotspots included AAVS1 with 10% of total events. Novel hotspots near consensus RBS were identified on chromosome 5p13.3 denoted AAVS2 and on chromsome 3p24.3 denoted AAVS3. AAVS2 displayed seven independent junctions clustered within only 14 bp of a consensus RBS which proved to bind Rep in vitro similar to the RBS in AAVS3. Expression of Rep in the presence of rep-deficient AAV vectors shifted targeting preferences from random integration back to the neighbourhood of consensus RBS at hotspots and numerous additional sites in the human genome. In summary, targeted AAV integration is not as specific for AAVS1 as previously assumed. Rather, Rep targets AAV to integrate into open chromatin regions in the reach of various, consensus RBS homologues in the human genome.
Hyaluronan Fragments Act as an Endogenous Danger Signal by Engaging TLR2 (2006)

Upon tissue injury, high m.w. hyaluronan (HA), a ubiquitously distributed extracellular matrix component, is broken down into lower m.w. (LMW) fragments, which in turn activate an innate immune response. In doing so, LMW HA acts as an endogenous danger signal alerting the immune system of a breach in tissue integrity. In this report, we demonstrate that LMW HA activates the innate immune response via TLR-2 in a MyD88-, IL-1R-associated kinase-, TNFR-associated factor-6-, protein kinase Czeta-, and NF-kappaB-dependent pathway. Furthermore, we show that intact high m.w. HA can inhibit TLR-2 signaling. Finally, we demonstrate that LMW HA can act as an adjuvant promoting Ag-specific T cell responses in vivo in wild-type but not TLR-2(null) mice.
Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy (2017)

Early results of this study suggest that Lenti-D gene therapy may be a safe and effective alternative to allogeneic stem-cell transplantation in boys with early-stage cerebral adrenoleukodystrophy. Additional follow-up is needed to fully assess the duration of response and long-term safety. (Funded by Bluebird Bio and others; STARBEAM ClinicalTrials.gov number, NCT01896102 ; ClinicalTrialsRegister.eu number, 2011-001953-10 .).
Divergent Signaling Pathways in Phagocytic Cells during Sepsis (2006)

Neutrophil accumulation in the lung plays a pivotal role in the pathogenesis of acute lung injury during sepsis. Directed movement of neutrophils is mediated by a group of chemoattractants, especially CXC chemokines. Local lung production of CXC chemokines is intensified during experimental sepsis induced by cecal ligation and puncture (CLP), as reflected by rising levels of MIP-2 and cytokine-induced neutrophil chemoattractant-1 in bronchoalveolar lavage fluids. Alveolar macrophages are primed and blood neutrophils are down-regulated for production of MIP-2 and cytokine-induced neutrophil chemoattractant production in response to LPS and C5a. Under these conditions of stimulation, activation of MAPKs (p38, p42/p44) occurs in sham neutrophils but not in CLP neutrophils, while under the same conditions phosphorylation of p38 and p42/p44 occurs in both sham and CLP alveolar macrophages. These data indicate that, under septic conditions, there is impaired signaling in neutrophils and enhanced signaling in alveolar macrophages, resulting in CXC chemokine production, and C5a appears to play a pivotal role in this process. As a result, CXC chemokines increase in lung, setting the stage for neutrophil accumulation in lung during sepsis.
Nucleotide sequence of the EcoRI E fragment of adenovirus 2 genome (1981)

The entire nucleotide sequence of the Ad.2 EcoRI E fragment has been determined using the Maxam and Gilbert method. This sequence of 2222 bp, which maps between coordinate 83.4 and 89.7 contains information relative to the early 3 region and to the fiber gene. Altogether with fragment EcoRI D which has been recently sequenced, they cover the entire Early 3 region in which several mRNA were mapped. The aminoacid sequence of the 16K and 14K protein is deduced. The localization of the 14.5K mRNA directing the synthesis of the third E3 known protein is discussed, as well as the hypothetical existence of three other early 3 proteins, which would have a molecular weight of 11K. The initiator ATG triplet of the fiber protein has been found at coordinate 86.1, it is followed up to the end of the fragment by an open reading frame allowing deduction of 80% of the aminoacid sequence of this protein. Sequences known to be frequently present at the border of exon sequence were used to tentatively localize the additional "Z" late leader.
Effect of External Stenting and Systemic Hypertension on Intimal Hyperplasia in Rat Vein Grafts (2000)

OBJECTIVE: Overdistention of vein grafts in arterial circulation and systemic hypertension are thought to be influential risk factors contributing to vein graft failures. This study tested the effects of external stenting in preventing systemic hypertension and overdistention of the rat vein graft in the long term. METHODS: Jugular vein grafts were interposed into the carotid artery of normotensive (n = 39) and two-kidney, one-clip hypertensive (n = 30) rats. Jugular vein grafts wrapped with 1.5-mm-diameter polyester stents were used in normotensive (n = 26) and hypertensive (n = 25) rats. The vein grafts were harvested at 1, 2, 4, 8, 12, and 24 weeks after the grafting procedure. The neointimal area and wall thickness were measured by computerized planimetry, and Ki-67 immunohistochemistry was used to detect replicative smooth muscle cells in the graft wall. RESULTS: In each group, intimal hyperplasia was apparent at 1 week and increased gradually to 24 weeks. The number of Ki-67-positive cells was most increased at 2 weeks after the grafting procedure and gradually decreased thereafter. The numbers of Ki-67-positive cells and the extent of intimal hyperplasia were not significantly different between normotensive and hypertensive rats. Both neointima formation and cell proliferation in the graft wall were significantly reduced by external stenting as compared with the results with unstented grafts. CONCLUSION: Systemic hypertension by itself is not a risk factor for intimal hyperplasia and experimental vein graft failure in the long term. External stenting is effective against intimal hyperplasia, and it is possible to reduce the subsequent atherosclerotic change of the vein graft wall and improve the long-term patency of the vein graft with external stenting.
A radio-frequency nonequilibrium atmospheric pressure plasma operating with argon and oxygen (2006)

A capacitively coupled, atmospheric pressure plasma has been developed that produces a high concentration of reactive species at a gas temperature below 300°C. The concentration of ground-state oxygen atoms produced by the discharge was measured by NO titration, and found to equal 1.2vol%, or 1.2±0.4×1017cm−3, using 6.0vol% O2 in argon at 150W∕cm3. The ozone concentration determined at the same conditions was 4.3±0.5×1014cm−3. A model of the gas phase reactions was developed and yielded O atom and O3 concentrations in agreement with experiment. This plasma source etched Kapton® at 5.0μm∕s at 280°C and an electrode-to-sample spacing of 1.5cm. This fast etch rate is attributed to the high O atom flux generated by the plasma source.
The distribution of interleukin-2 receptor bearing lymphocytes in multiple sclerosis: evidence for a key role of activated lymphocytes. (1985)

The identification of T cells in the brain using monoclonal antibodies has suggested a role for T cells in the pathogenesis of multiple sclerosis (MS). In the present study the monoclonal antibody anti-Tac, shown to react with interleukin-2 (IL-2) receptors expressed on activated T cells, was used to determine levels of recently activated T cells in blood, cerebrospinal fluid (CSF) and brain sections from MS patients at different stages of disease. The CSF of MS patients contained much higher numbers of IL-2 receptor positive lymphocytes (up to 67%) than blood cells from the same patients, or the CSF of patients with non-inflammatory neurological diseases. In histological sections of the brain of MS patients with active disease, perivascular lymphocytes expressing IL-2 receptors were detected, as were lymphocytes containing IL-2. In contrast, these were absent in brain sections from patients with chronic MS, secondary demyelination or from normal controls. These observations in CSF and brain suggest that in multiple sclerosis, T-cell activation is occurring within the CNS and not in peripheral lymphoid tissue.
Randomized controlled trial of transdermal secretin on behavior of children with autism (2005)

Previous trials of secretin for the treatment of autism have utilized a single or double dose administered intravenously. This is a report of a double-blind, randomized, controlled crossover trial of transdermally applied secretin in 15 children diagnosed with autism or pervasive developmental delay. Secretin or placebo was applied daily, in ointment form, to the backs of the children in randomized, successive 4 week periods with an intermediate 6 week washout period. Behavioral outcomes were measured by parents and teachers using the Autism Treatment Evaluation Checklist. Overall, there were no statistically significant differences in speech, sociability, sensory, and health scores for treatment versus placebo periods. In addition, there were no differences in such scores for children with a history of diarrhea. Severity of autism was significantly greater at baseline in children receiving concomitant medications. Improvement in speech was found during the treatment phase of the trial (p=0.0479 for secretin versus placebo) only in children not using other medications.
Cyclic gas bursts: are they a ‘usual’ feature of Lake Nyos and other gas-bearing lakes? (1992)

The physical conditions in Lake Nyos and other stratified lakes, which are charged from below with gas, favour the creation of gas accumulations in solution in lake water. If in the case of strong stratification the gas influx rate is higher than its transport rate through the stratification to the surface, a hazardous situation will build up. It is then inevitable that gas bursts will take place, normally as “fountain-limnic eruptions”. They may or may not be disastrous. Water stratification will survive these bursts in a modified form. Thus, cyclic gas bursts of this kind are in a sense pre-programmed, probably with a ‘stochastic’ frequency. This particular hazard, which comes on top of other hazards associated with zones of crustal weakness, can only be eliminated by controlled degassing of these lakes.
Epitope Mapping of the Hemagglutinin Molecule of A/(H1N1)pdm09 Influenza Virus by Using Monoclonal Antibody Escape Mutants (2014)

The first influenza pandemic of the 21st century occurred in 2009 with the emergence of a novel virus originating with swine influenza, A(H1N1)pdm09. Although HA of A(H1N1)pdm09 has a common origin (1918 H1N1) with seasonal H1N1, the antigenic divergence of HA between the seasonal H1N1 and A(H1N1)pdm09 viruses gave rise to the influenza pandemic in 2009. To take precautions against the antigenic drift of the A(H1N1)pdm09 virus in the near future, it is important to identify its precise antigenic structure. To obtain various mutants that are not neutralized by MAbs, it is important to neutralize several plaque-cloned parent viruses rather than only a single parent virus. We characterized 599 escape mutants that were obtained by neutralizing four parent viruses of A(H1N1)pdm09 in the presence of 16 MAbs. Consequently, we were able to determine the details of the antigenic structure of HA, including a novel epitope.
Two-codon insertion mutagenesis of plasmid genes by using single-stranded hexameric oligonucleotides. (1985)

An efficient method for introducing two codons into a cloned gene has been applied to studying functional regions of the pBR322-encoded tetracycline-resistance gene and beta-lactamase (ampicillin-resistance) gene. Single-stranded hexameric linkers are inserted into a preexisting cohesive end restriction site to create a new (six-base recognition) restriction site. Insertion mutations are enriched by using biochemical selection or are selected by using a kanamycin-resistance cassette (biological selection). Phenotypes of insertion mutations isolated in the tetracycline-resistance gene support the hypothesis that it is comprised of two domains connected by a central hinge. Mutations in the beta-lactamase gene are temperature sensitive and demonstrate altered sensitivity to various beta-lactams and inhibitors.
Global Mapping of the Yeast Genetic Interaction Network (2004)

A genetic interaction network containing approximately 1000 genes and approximately 4000 interactions was mapped by crossing mutations in 132 different query genes into a set of approximately 4700 viable gene yeast deletion mutants and scoring the double mutant progeny for fitness defects. Network connectivity was predictive of function because interactions often occurred among functionally related genes, and similar patterns of interactions tended to identify components of the same pathway. The genetic network exhibited dense local neighborhoods; therefore, the position of a gene on a partially mapped network is predictive of other genetic interactions. Because digenic interactions are common in yeast, similar networks may underlie the complex genetics associated with inherited phenotypes in other organisms.
Adaptive prediction, tracking and power adjustment for frequency non-selective fast fading channels (1999)

Previously, the authors introduced a novel algorithm for long range prediction of fading channels. This algorithm finds the linear minimum mean squared error (MMSE) estimate of the future fading coefficients given a fixed number of previous observations. In this paper, we show that the superior performance of this algorithm is due to its lower sampling rate relative to the conventional (data rate) methods of fading prediction. We also enhance the algorithm by an adaptive prediction and tracking method that increases accuracy and maintains the robustness of long-term prediction as the physical channel parameters vary. Finally, we show that large improvements in the bit error rate (BER) are possible when the proposed prediction method is used. In particular, analysis of the channel inversion with threshold technique is presented to demonstrate that the BER can be reduced to the level of and beyond the additive white Gaussian noise (AWGN) channel.