gebhart/patrepeval huggingface dataset:
Abstract 1837: Cellular glutathione is an essential mediator of the enhancing effect of plant polyphenolic antioxidants on vitamin D-induced differentiation of acute myeloid leukemia cells (2012)

Abstract Acute myeloid leukemia (AML) is an aggressive malignancy with poor prognosis. Differentiation therapy may provide an alternative AML treatment, based on the induction of leukemic blasts to mature. The hormonal form of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D), is a powerful inducer of monocytic differentiation of AML cells in vitro; however, it causes severe hypercalcemia in vivo at pharmacologically effective doses. We have previously shown that various plant polyphenolic antioxidants (PAOx), such as carnosic acid (CA), curcumin (CUR), and silibinin (SIL), strongly potentiate the differentiation of AML cells induced by a low, near physiologic dose of 1,25D (1 nM). Further, we have demonstrated that a functionally active transcription factor Nrf2 is required for the differentiation-enhancing effect of CA; however, the mechanism whereby Nrf2 contributes to this effect was unclear. Here we show that similar to CA, CUR and SIL transactivated the Nrf2 response element (antioxidant response element; ARE), induced Nrf2/ARE-responsive gene products, such as NADP(H)-quinone oxidoreductase, thioredoxin reductase-1 and the α-glutamylcysteine synthetase heavy subunit (≥GCSh), and elevated the total glutathione content in human AML cells (HL60 and U937). Interestingly, 1,25D markedly potentiated these effects of PAOx. Stable expression of dominant negative Nrf2 (dnNrf2) abolished the differentiation-enhancing effects of all the PAOx tested. Importantly, such inhibitory action of dnNrf2 was mimicked by treatment of untransfected cells with non-cytotoxic concentrations of L-buthionine-sulfoximine (BSO), the specific inhibitor of αGCS. Glutathione depletion in BSO-treated cells was associated with attenuation of both the transactivation of the transcription factor activating protein-1 (AP-1) and elevation of protein levels of the vitamin D receptor (VDR) and retinoid X receptor alpha (RXRα) induced by 1,25D/PAOx combinations. This may account for the reduction in the extent of 1,25D/PAOx-induced differentiation observed following BSO treatment. Collectively, our data suggest that cooperative elevation of glutathione levels by PAOx and 1,25D, as a result of Nrf2/ARE-dependent induction of αGCS, may mediate the enhancing effects of PAOx on 1,25D-induced differentiation of AML cells. These findings may provide a mechanistic basis for the therapy and/or prevention of AML using combinations of vitamin Dand plant antioxidants. (This research was supported by the Israel Science Foundation grant 635/11 to both M.D. and Y.S., and by the NIH-NCI grant RO1-CA117942-04 to both G.P.S. and M.D.). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1837. doi:1538-7445.AM2012-1837
Effects of spatial restriction on streamers in white oil (2014)

Streamer propagation guided within PTFE tubes were investigated in an 8 cm point-plane gap in white oil. Both positive and negative polarities were studied with a near step voltage of 50-400 kV. Streamers in a free volume were compared with those in tubes. Within tubes, branching of streamers is suppressed, and interaction between streamers and tube wall may occur. For positive streamers, the guiding tube slightly accelerates streamers and reduces acceleration voltage. However, for negative streamers the tube significantly increases the velocity and drastically decreases the acceleration voltage. Possibly, streamer propagation is governed by the streamers tip-field. When the interaction between streamers and the tube wall appears, the electric field at the streamer tip is increased. This leads to an increase in streamer velocity. The mechanism of streamer propagation is discussed.
Molecular-beam epitaxy of CdTe on large area Si(100) (1991)

We have grown CdTe directly on 2‐ and 5‐in. diam Si(100) by molecular‐beam epitaxy and characterized the layers by in situ reflection high‐energy electron diffraction, double crystal x‐ray diffraction, scanning electron microscopy, transmission electron microscopy, and low‐temperature photoluminescence. The films are up to 10‐μm thick and mirror‐like over their entire surface. Even on 5‐in. diam wafers, the structural and thickness uniformity is excellent. Two domains, oriented 90° apart, are observed in the CdTe films on oriented Si(100) substrates, whereas single‐domain films are grown on Si(100) titled 6° or 8° toward [011]. The layers on misoriented substrates have better morphology than those on oriented Si(100), and the substrate tilt also eliminates twinning in the CdTe layers. First attempts to grow HgCdTe on Si(100 with a CdTe buffer layer have produced up to 10‐μm thick layers with cutoff wavelengths between 5 and 10‐μm and with an average full width at half‐maximum of the double‐crystal x‐ray diffraction peaks of 200 arc s.
Toward the defined and xeno-free differentiation of functional human pluripotent stem cell-derived retinal pigment epithelial cells. (2011)

We have developed a progressive differentiation protocol for the production of functional RPE-like cells from hESCs and hiPSCs. Our results demonstrate that putative hESC-RPE and hiPSC-RPE express genes and proteins characteristic for RPE cells, as well as being able to phagocytose POS and secrete PEDF. Furthermore, our results show that RPE-like cells can be differentiated in xeno-free and defined culture conditions, which is mandatory for Good Manufacturing Practice-production of these cells for clinical use.
Sequence-specific inhibition of microRNA via CRISPR/CRISPRi system (2014)

Here, we report a convenient and efficient miRNA inhibition strategy employing the CRISPR system. Using specifically designed gRNAs, miRNA gene has been cut at a single site by Cas9, resulting in knockdown of the miRNA in murine cells. Using a modified CRISPR interference system (CRISPRi), inactive Cas9 can reversibly prevent the expression of both monocistronic miRNAs and polycistronic miRNA clusters. Furthermore, CRISPR/CRISPRi is also capable of suppressing genes in porcine cells.
Angiotensin II Receptors in Normal and Failing Human Hearts* (1989)

To demonstrate the existence and help clarify the function of angiotensin II (Ang II) receptors in the human heart, we characterized the cardiac Ang II receptor and examined the levels and distribution of ventricular Ang II receptors in normal (n = 6) and failing (n = 14) hearts. Ang II receptors were characterized using the Ang II receptor agonist [125I]Ang II. Cardiac [125I]Ang II-binding sites were of high affinity (Kd, approximately 1 nmol/L) and low capacity (Bmax, approximately 3 fmol/mg membrane protein) and were pharmacologically specific [IC50 values for Ang II, [Sar1,Ile8]Ang II, and Ang III were 1.2, 3.0, and 400 nmol/L, respectively; the inactive Ang II metabolite Ang-(1-5), at a concentration of 1 mumol/L, inhibited [125I]Ang II binding by less than 10%]. These characteristics of cardiac [125I]Ang II-binding sites are similar to those of previously characterized mammalian heart Ang II receptors. In normal adult donor hearts (n = 5), Ang II receptor density in the left ventricle [LV, 2.90 +/- 1.40 (+/- SE) fmol/mg] was similar to that in the right ventricle (RV, 3.82 +/- 1.10 fmol/mg). The ventricular Ang II receptor density in adult patients with idiopathic (LV, 1.77 +/- 0.35 fmol/mg; RV, 1.58 +/- 0.29 fmol/mg; n = 8) or dilated cardiomyopathy (LV, 2.00 +/- 0.58 fmol/mg; RV, 2.56 +/- 0.52 fmol/mg n = 5) was similar to that in the normal heart. Ventricular Ang II receptors, localized by autoradiography using the Ang II receptor antagonist [125I]-[Sar1,Ile8]Ang II, were consistently found in the myocardium, cardiac adrenergic nerves, and coronary vessels of normal and failing ventricles. In human ventricles Ang II receptor levels were not correlated with age. Because ventricular Ang II receptor density in a normal neonatal human heart and that in a heart from an adolescent patient with idiopathic cardiomyopathy were more than 10-fold and more than 5-fold higher, respectively, than in normal adult ventricles, we investigated whether postnatal changes occur in ventricular Ang II receptors in rats. In male and female rats ventricular Ang II receptor density was about 2-fold higher in 1-day-old rats compared to that in 10-day-old or peripubertal rats. These data suggest developmental regulation of ventricular Ang II receptors. Our findings suggest that direct and neural angiotensinergic inputs to the myocardium play a role in the regulation of cardiac function in man and that these inputs are preserved in the failing heart.
Preparation of Antimicrobial Compounds by Hydrolysis of Oleuropein from Green Olives1 (1973)

Oleuropein, an intensely bitter glucoside, was isolated from green olives. Hydrolysis products obtained from oleuropein in sufficient quantity for further tests were: (i) β-3,4-dihydroxyphenylethyl alcohol prepared by acid hydrolysis of oleuropein; (ii) elenolic acid obtained by methanolysis of oleuropein, isolation of the intermediate acetal, and subsequent acid hydrolysis; and (iii) oleuropein aglycone formed by the action of β-glucosidase on the parent glucoside. Mass spectral verification of the isolated compounds and ultraviolet absorption data are given. Oleuropein and its aglycone had similar threshold levels for detection of bitterness, whereas elenolic acid and β-3,4-dihydroxyphenylethyl alcohol were not judged to be bitter.
Functional asymmetry in cohesin binding belies inherent symmetry of the dockerin module: insight into cellulosome assembly revealed by systematic mutagenesis (2008)

The cellulosome is an intricate multi-enzyme complex, known for its efficient degradation of recalcitrant cellulosic substrates. Its supramolecular architecture is determined by the high-affinity intermodular cohesin-dockerin interaction. The dockerin module comprises a calcium-binding, duplicated 'F-hand' loop-helix motif that bears striking similarity to the EF-hand loop-helix-loop motif of eukaryotic calcium-binding proteins. In the present study, we demonstrate by progressive truncation and alanine scanning of a representative type-I dockerin module from Clostridium thermocellum, that only one of the repeated motifs is critical for high-affinity cohesin binding. The results suggest that the near-symmetry in sequence and structure of the repeated elements of the dockerin is not essential to cohesin binding. The first calcium-binding loop can be deleted entirely, with almost full retention of binding. Likewise, significant deletion of the second repeated segment can be achieved, provided that its calcium-binding loop remains intact. Essentially the same conclusion was verified by systematically mutating the highly conserved residues in the calcium-binding loop. Mutations in one of the calcium-binding loops failed to disrupt cohesin recognition and binding, whereas a single mutation in both loops served to reduce the affinity significantly. The results are mutually compatible with recent crystal structures of the type-I cohesin-dockerin heterodimer, which demonstrate that the dockerin can bind in an equivalent manner to its cohesin counterpart through either its first or second repeated motif. The observed plasticity in cohesin-dockerin binding may facilitate cellulosome assembly in vivo or, alternatively, provide a conformational switch that promotes access of the tethered cellulosomal enzymes to their polysaccharide substrates.
A comprehensive classification of invasive procedures for treating the local complications of acute pancreatitis based on visualization, route, and purpose. (2011)

This article describes the development and validation of a comprehensive classification for the wide range of procedures used to treat the local complications of acute pancreatitis. It has substantial inter-rater reliability and high acceptability, which should enhance communication between clinicians and facilitate comparison between procedures.
The Last Mile: High-Assurance and High-Speed Cryptographic Implementations (2020)

We develop a new approach for building cryptographic implementations. Our approach goes the last mile and delivers assembly code that is provably functionally correct, protected against side-channels, and as efficient as hand-written assembly. We illustrate our approach using ChaCha20-Poly1305, one of the two ciphersuites recommended in TLS 1.3, and deliver formally verified vectorized implementations which outperform the fastest non-verified code.We realize our approach by combining the Jasmin framework, which offers in a single language features of high-level and low-level programming, and the EasyCrypt proof assistant, which offers a versatile verification infrastructure that supports proofs of functional correctness and equivalence checking. Neither of these tools had been used for functional correctness before. Taken together, these infrastructures empower programmers to develop efficient and verified implementations by "game hopping", starting from reference implementations that are proved functionally correct against a specification, and gradually introducing program optimizations that are proved correct by equivalence checking.We also make several contributions of independent interest, including a new and extensible verified compiler for Jasmin, with a richer memory model and support for vectorized instructions, and a new embedding of Jasmin in EasyCrypt.
Phosphorylation of Serine 337 of NF-κB p50 Is Critical for DNA Binding (2003)

It has been demonstrated that phosphorylation of the p50 subunit of NF-kappaB is required for efficient DNA binding, yet the specific phospho-residues of p50 have not been determined. In this study, we substituted all of the serine and conserved threonine residues in the p50 Rel homology domain and identified three serine residues, Ser65, Ser337, and Ser342, as critical for DNA binding without affecting dimerization. Although substitution with negatively charged aspartic acid at each of these positions failed to restore DNA binding, substitution with threonine, a potential phospho-acceptor, retained DNA binding for residues 65 and 337. In particular, Ser337, in a consensus site for protein kinase A (PKA) and other kinases, was shown to be phosphorylated both in vitro and in vivo. Importantly, phosphorylation of Ser337 by PKA in vitro dramatically increased DNA binding of p50. This study shows for the first time that the DNA binding ability of NF-kappaB p50 subunit is regulated through phosphorylation of residue Ser337, which has implications for both positive and negative control of NF-kappaB transcription.
Removal and Recovery of Phosphorus from Water by Means of Adsorption onto Orange Waste Gel and Pectic Acid Gel Loaded with Zirconium (2009)

リンを吸着・除去するためにリン酸イオンに対して親和性が高いジルコニウム（IV）イオンを担持させた架橋ペクチン酸およびけん化処理したみかん搾汁残渣の吸着剤を調製した．ジルコニウム（IV）イオンを上記の吸着剤に担持した結果，飽和吸着量はそれぞれの吸着剤に対して0.25および0.70 mmol/gであった．リン酸イオンの吸着を行うと，ジルコニウム（IV）担持みかん搾汁残渣吸着剤を用いた場合，pH 1–4において100%吸着した．一方，ジルコニウム（IV）担持の架橋ペクチン酸の吸着剤はpH 1以上でpHの上昇と共に吸着率が減少する傾向が見られた．リン酸イオンの飽和吸着量はジルコニウム（IV）担持架橋ペクチン酸およびけん化みかん搾汁残渣吸着剤については，それぞれ0.25および3.40 mmol/gであった．吸着したリン酸イオンは0.2 Mの水酸化ナトリウム水溶液を用いて100%の溶離ができ，リン酸イオンのみの選択的な吸着・溶離・濃縮の繰り返し使用が可能であった．
F.M.-C.W. Delft atmospheric research radar (1980)

At the Delft University of Technology a high-resolution S-band f.m.-c.w. radar system for remote sensing of the troposphere has been built to extend knowledge about layered and turbulent structures in clear air and to investigate the reflectivity levels of hydrometeors. Design considerations and performance characteristics of the radar are given. Separate antennas for transmitting and receiving on one fully steerable mount are used. The signal processing is performed with a minicomputer and uses microprogramming to a large extent. Preliminary results are given to illustrate the potentials of the radar.
A computationally efficient solution to the simultaneous localisation and map building (SLAM) problem (2002)

The theoretical basis of the solution to the simultaneous localisation and map building (SLAM) problem where an autonomous vehicle starts in an unknown location in an unknown environment and then incrementally build a map of landmarks present in this environment while simultaneously using this map to compute absolute vehicle location is well understood. Although a number of SLAM implementations have appeared in the literature, the need to maintain the knowledge of the relative relationships between all the landmark location estimates contained in the map makes SLAM computationally intractable in implementations containing more than few tens of landmarks. In this paper, the theoretical basis and a practical implementation of a computationally efficient solution to SLAM is presented. The paper shows that it is indeed possible to remove a large percentage of the landmarks from the map without making the map-building process statistically inconsistent. Furthermore, it is shown that the efficiency of the SLAM can be maintained by judicious selection of landmarks, to be preserved in the map, based on their information content.
A Low-Diameter Unstructured P2P Overlay and Corresponding Search Algorithm (2009)

Unstructured peer-to-peer networks are frequently used as the overlay in various middleware toolkits for emerging applications, from content distribution to query result caching to distributed collaboration. There are two main aspects in unstructured P2P system researches: (1) How to build a scalable and robust topology and (2) how to present a low cost and more efficient query algorithm. Though normally a search algorithm is independent of the topology, a good topology can greatly improve the performance of the search algorithm. However, most unstructured P2P systems can not combine the robustness with the efficiency and searching accuracy. The main contribution of the paper is to combine the researches on both topology and search algorithm. At first, a low-diameter unstructured P2P overlay called MPO with small world and power-law characteristics is presented. Detailed experiments show that current popular search algorithms can obtain better performances in MPO. Then, a new search algorithm based on the overlay is presented. We compared the new algorithm with popular search algorithms in the unstructured P2P systems. The results show that the algorithm is better than others in MPO according to several parameters. Thus, we draw a conclusion that the combination of the new search algorithm and the MPO has better performances than that of other search algorithm and other overlay.
Dietary supplementation of 3-hydroxy-3-methylbutyrate improves catch-up growth in underfed lambs (1994)

National audience
The elusive factor Xa receptor: failure to detect transcripts that correspond to the published sequence of EPR-1 (2000)

The coagulation protease factor Xa induces cellular responses implicated in cardiovascular and inflammatory disease. Effector-cell protease receptor 1 (EPR-1) is a functionally characterized receptor of factor Xa, and the EPR-1 complementary DNA (cDNA) was published. Remarkably, the cDNA encoding an inhibitor of apoptosis, survivin, is reportedly identical to that of EPR-1 except for a few nucleotide differences and its orientation opposite to EPR-1. To isolate the EPR-1 cDNA and gene, we surveyed gene databases for expressed sequence tags (ESTs) that could be derived from EPR-1. All ESTs with strong homology to EPR-1/survivin were derived from survivin and could not encode EPR-1. By polymerase chain reaction and Southern blot hybridization, EPR-1 was not detectable in the human or murine genome, but survivin was. Our data suggest that EPR-1 is either highly cell-specific or the published EPR-1 cDNA includes sequences from clones derived from survivin messenger RNA. The means by which factor Xa mediates its cellular effects requires further evaluation.
Damage in hydrogen plasma implanted silicon (2001)

The damage and defects created in silicon by hydrogen plasma immersion ion implantation (PIII) are not the same as those generated by conventional beamline ion implantation due to the difference in the ion energy distribution and lack of mass selection in PIII. Defect generation must be well controlled because damage in the implanted and surface zones can easily translate into defects in the silicon-on-insulator structures synthesized by the PIII/wafer bonding/ion-cut process. The defect formation and its change with annealing temperature were investigated experimentally employing channeling Rutherford backscattering spectrometry, secondary ion mass spectrometry, and atomic-force microscopy. We also calculated the damage energy density of the three dominant hydrogen species in the plasma (H+, H2+, and H3+) as well as displacement of silicon atoms in the silicon wafer. H2+ creates the most damage because its damage energy density is very close to the silicon threshold energy. The effects of atmospheric gaseous impurities unavoidably coimplanted from the overlying plasma are also modeled. Even though their concentration is usually small in the plasma, our results indicate that these gaseous impurities lead to significant silicon atom displacement and severe damage in the implanted materials.
Waiting for JAK inhibitor safety data (2022)

The US Food and Drug Administration (FDA) has recently added a new 'black box warning' on all currently approved Janus kinase (JAK) inhibitors indicated for the treatment of arthritis and other inflammatory conditions based on results from the ORAL Surveillance study of tofacitinib versus tumour necrosis factor alpha inhibitors in rheumatoid arthritis. This is a warning difficult to ignore because the data, being from a randomised controlled trial, are of high fidelity and hard to reproach. It is especially problematic because safety data for all the other JAK inhibitors will be pending for several years. So how might we proceed, without being bound by our stasis? The lack of absolute certainty seems to require a pragmatic approach to the routine care use of JAK inhibitors. The patients who were at greatest risk were older and had other risk factors for the corresponding adverse events, in keeping with effect modification. This highlights the need to focus on risk stratification when tailoring therapy. In this viewpoint, we propose a simple illustration to guide clinical decision-making. First, identify general risk factors for venous thromboembolic event (VTE), major adverse cardiac event (MACE) and cancer (age>65 years and smoking) and whether there is a previous history of VTE, MACE or cancer. Then, evaluate risk based on the number of other risk factors for VTE and the number of other risk factors for MACE. Ultimately, 'treat-to-target' will in the end always be 'treat-to-agreement'. As we have done in the past, and will do in the future, the optimal treatment strategy will have to be tailored based on individual patient risk factors and preferences in a shared-decision process.
Hepatic vein waveform and splenomegaly predict improvement of prothrombin time after splenectomy in hepatitis C virus‐related cirrhotic patients (2012)

Prothrombin time and total bilirubin improve in approximately half of cirrhotic patients within a year after splenectomy. HVWF type I and splenomegaly may be predictive factors for improvement in prothrombin time after splenectomy in patients with cirrhosis due to hepatitis C.