gebhart/patrepeval huggingface dataset:
Mechanisms of cell death induced by suicide genes encoding purine nucleoside phosphorylase and thymidine kinase in human hepatocellular carcinoma cells in vitro (2001)

For gene therapy of hepatocellular carcinoma (HCC), the Escherichia coli purine nucleoside phosphorylase (PNP)/fludarabine suicide gene system may be more useful than the herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system as a result of a stronger bystander effect. To analyze the molecular mechanisms involved in PNP/fludarabine-mediated cell death in human HCC cells in comparison with HSV-tk/GCV, we transduced human HCC cells of the cell lines, HepG2 and Hep3B, with PNP or HSV-tk using adenoviral vectors, followed by prodrug incubation. Both systems predominantly induced apoptosis in HepG2 and Hep3B cells. PNP/fludarabine induced strong p53 accumulation and a more rapid onset of apoptosis in p53-positive HepG2 cells as compared with p53-negative Hep3B cells, but efficiency of tumor cell killing was similar in both cell lines. In contrast, HSV-tk/GCV-induced apoptosis was reduced in p53-negative Hep3B cells as compared with p53-positive HepG2 cells. HSV-tk/GCV, but not PNP/fludarabine, caused up-regulation of Fas in p53-positive HepG2 cells and of Fas ligand (FasL) in both HCC cell lines. These results demonstrate cell line-specific differences in response to treatment with PNP/fludarabine and HSV-tk/GCV, respectively, and indicate that PNP/fludarabine may be superior to HSV-tk/GCV for the treatment of human HCC because of its independence from p53 and the Fas/FasL system.
Regulatory Elements That Control Transcription Activation and Unsaturated Fatty Acid-mediated Repression of the Saccharomyces cerevisiae OLE1 Gene (1996)

In Saccharomyces cerevisiae, unsaturated fatty acids are formed from saturated acyl-CoA precursors by Ole1p, a delta-9 fatty acid desaturase. OLE1 mRNA levels are differentially regulated by the addition of saturated or unsaturated fatty acids to the growth medium. One component of this regulation system involves the control of OLE1 transcription. Saturated fatty acids induce a 1.6-fold increase in transcription activity, whereas a large family of unsaturated fatty acids repress OLE1 transcription as much as 60-fold. A deletion analysis of OLE1 promoter::lacZ fusion reporter genes identified a 111-base pair (bp) fatty acid-regulated (FAR) region approximately 580 bp upstream of the start codon that is essential for transcription activation and unsaturated fatty acid repression. Deletion of an 88-bp sequence within that region resulted in a complete loss in transcription activation and unsaturated fatty acid regulation. The 111-bp FAR element strongly activates transcription and confers unsaturated fatty acid regulation on a heterologous CYC1 promoter test plasmid. Essential elements required for unsaturated fatty acid repression of OLE1 were found in the 5 and 3 region of the 111-bp sequence. The FAR element-mediated activation and fatty acid repression of transcription was found to be closely tied to fatty acyl-CoA metabolism. Two fatty acid activation genes, FAA1 and FAA4, were found to be essential for unsaturated fatty acid repression of OLE1 through the FAR sequences. Disruption of either gene results in reduced levels of unsaturated fatty acid repression; disruption of both genes completely blocks the regulatory response. Acyl-CoA binding protein (ACBP) plays a role in determining the level of FAR element activated transcription. Disruption of the ACBP gene causes a >5-fold activation of OLE1 transcription and a similar increase in OLE1 mRNA levels. Unsaturated fatty acid repression of OLE1 transcription, however, is not affected by the disrupted ACBP gene. These studies show that promoter elements responsible for unsaturated fatty acid-mediated transcription repression are tightly linked to OLE1 activation sequences and that OLE1 transcription levels are closely tied to acyl-CoA metabolism.
β-catenin signaling and cancer (1999)

Since its discovery as a protein associated with the cytoplasmic region of E-cadherin, beta-catenin has been shown to perform two apparently unrelated functions: it has a crucial role in cell-cell adhesion in addition to a signaling role as a component of the Wnt/wg pathway. Wnt/wg signaling results in beta-catenin accumulation and transcriptional activation of specific target genes during development. It is now apparent that deregulation of beta-catenin signaling is an important event in the genesis of a number of malignancies, such as colon cancer, melanoma, hepatocellular carcinoma, ovarian cancer, endometrial cancer, medulloblastoma pilomatricomas, and prostate cancer. beta-catenin mutations appear to be a crucial step in the progression of a subset of these cancers, suggesting an important role in the control of cellular proliferation or cell death. The APC/beta-catenin pathway is highly regulated and includes players such as GSK3-beta, CBP, Groucho, Axin, Conductin, and TCF. c-MYC and cyclin D1 were recently identified as a key transcriptional targets of this pathway and additional targets are likely to emerge. Published 1999 John Wiley & Sons, Inc.
5‐3: 3‐Stacked Top‐Emitting White OLEDs with Super‐Wide Color Gamut and High Efficiency (2019)

A set of top‐emitting OLED with wide‐color gamut and high‐efficiency were successfully fabricated by using 3‐stacked B/RG/B tandem structure and color filter. Optimization of MgAg and Indium Zinc Oxide (IZO) composite structure made the devices with IZO served as capping layer almost identical to the devices with conventional organic capping layer. On the whole, they exhibited 90% color gamut coverage of the ultra‐high definition display standard BT.2020, while maintaining high efficiency of red 15.5 cd/A, green 26.6 cd/A, blue 3.5 cd/A. The impressive properties make them applicable to a variety of occasions, such as the medium‐sized notebook monitors, emerging high‐specification virtual and augmented reality (VR/AR) technologies, and special medical displays.
Functional beverage of Garcinia mangostana (mangosteen) enhances plasma antioxidant capacity in healthy adults (2014)

This study was to investigate the absorption and antioxidant effect of a mangosteen-based functional beverage in humans. The beverage contained mangosteen, aloe vera, green tea, and multivitamins. A randomized, double-blind, placebo-controlled clinical trial was conducted with generally healthy male and female subjects between 18 and 60 years of age. Ten men and 10 women participated in this study. Participants were randomly divided into two groups, treatment and placebo group. Participants received either a daily single dose (245 mL) of the beverage or a placebo. Blood samples were collected from each participant at time points 0, 1, 2, 4, and 6 h. The plasma samples were analyzed by LC/MS for α-mangostin and vitamins B2 and B5. Results indicated that the three analytes were bioavailable, with observed C max at around 1 h. The antioxidant capacity measured with the oxygen radical absorbance capacity (ORAC) assay was increased with a maximum effect of 60% after 1 h, and the elevated antioxidant level lasted at least 6 h. This study demonstrated the bioavailability of α-mangostin and B vitamins from a xanthone-rich beverage and the mechanisms of the increase in plasma antioxidant may be direct effects from antioxidants, enhancement of endogenous antioxidant activity through activation of Nrf2 pathway, and synergism of the antioxidants.
Hydrogen sulfide and its possible roles in myocardial ischemia in experimental rats (2006)

The role of hydrogen sulfide (H(2)S) in myocardial infarction (MI) has not been previously studied. We therefore investigated the effect of H(2)S in a rat model of MI in vivo. Animals were randomly divided into three groups (n = 80) and received either vehicle, 14 micromol/kg of sodium hydrosulfide (NaHS), or 50 mg/kg propargylglycine (PAG) everyday for 1 wk before surgery, and the treatment was continued for a further 2 days after MI when the animals were killed. The mortality was 35% in vehicle-treated, 40% in PAG-treated, and 27.5% in NaHS-treated (P < 0.05 vs. vehicle) groups. Infarct size was 52.9 +/- 3.5% in vehicle-treated, 62.9 +/- 7.6% in PAG-treated, and 43.4 +/- 2.8% in NaHS-treated (P < 0.05 vs. vehicle) groups. Plasma H(2)S concentration was significantly increased after MI (59.2 +/- 7.16 microM) compared with the baseline concentration (i.e., 38.2 +/- 2.07 microM before MI; P < 0.05). Elevated plasma H(2)S after MI was abolished by treatment of animals with PAG (39.2 +/- 5.02 microM). We further showed for the first time cystathionine-gamma-lyase protein localization in the myocardium of the infarct area by using immunohistochemical staining. In the hypoxic vascular smooth muscle cells, we found that cell death was increased under the stimuli of hypoxia but that the increased cell death was attenuated by the pretreatment of NaHS (71 +/- 1.2% cell viability in hypoxic vehicle vs. 95 +/- 2.3% in nonhypoxic control; P < 0.05). In conclusion, endogenous H(2)S was cardioprotective in the rat model of MI. PAG reduced endogenous H(2)S production after MI by inhibiting cystathionine-gamma-lyase. The results suggest that H(2)S might provide a novel approach to the treatment of MI.
S 6. Furochromones. Part I. The synthesis of Khellin (1949)

R. A. Baxter, G. R. Ramage and J. A. Timson, J. Chem. Soc., 1949, S30 DOI: 10.1039/JR9490000S30
Kinetics and Stereochemistry of CO Substitution Reactions of Half-Open Chromocene Carbonyls(II) : Reactions of Cp$(\eta^{5}-2,4-Me_{2}C_{5}H_{5})$CrCO and Phosphines (1993)

The CO substitution reactions in the complex, CrCO with were investigated spectrophotometrically at various temperatures. For the reaction rates, it was suggested that the CO substitution reaction took place by first-order (dissociative) pathway. Activation parameters in decaline are kcal/mol, cal/mol·k. Unusually low value of , suggested an -U conversion of the pentadienyl ligand. At various temperature, the rates of reaction for the Cp(pdl)CrCO complexes increase in the order -CrCO CrCO )CrCO, which can be attributed to the usual steric acceration or electronic influence for the ligand substitution of metal complexes. This suggestion was confirmed by the extended-Huckel molecular orbital (EHMO) calculations, which revealed that the energy of transition state is about 4.93 kcal/mol lower than that of [Cp(S- transition state, and the arrangement of the overlap populations between Cr and the carbon of CO is CrCO > Cp()CrCO > Cp(2,4-)CrCO.
Effects of protein kinase inhibitors and protein phosphatase inhibitors on cyclic AMP‐dependent down‐regulation of vesicular monoamine transport in pheochromocytoma PC12 cells (1995)

Cyclic AMP down-regulates vesicular monoamine transport in PC12 cells and thereby decreased catecholamine reuptake from the extracellular fluid. We examined the effects of protein kinase inhibitors and protein phosphatase inhibitors on this cAMP action. Treatment of cells with a protein kinase inhibitor, K252a, increased vesicular amine transport and cellular amine uptake, thereby antagonizing the regulatory action of cAMP. In contrast, a protein phosphatase inhibitor, okadaic acid, had the opposite effect on the amine transport, i.e. it enhanced the cAMP action. These results suggest the involvement of a protein phosphorylation process in the cAMP-dependent modulation of vesicular monoamine transport.
Investigational C-C chemokine receptor 2 antagonists for the treatment of autoimmune diseases (2008)

Although there is growing evidence for a great therapeutic potential of CCR2 blockade in autoimmune diseases, especially well documented in experimental animal models, so far clinical trials with CCR2 antagonists in humans have been moderately encouraging or even disappointing, indicating a need to further elucidate the complex system of chemokine interactions.
Characterization of the genomic sequence of type V (or 3a) hepatitis C virus isolates and PCR primers for specific detection (1993)

We have identified four new hepatitis C virus (HCV) isolates whose genomic RNA could be amplified by PCR using primers from the 5' untranslated region (UTR), but the RNA could not be detected with genotype I to IV (or types 1a, 1b, 2a and 2b respectively)-specific core region-derived primers. We compared the nucleotide sequences of the new isolates from positions 65 to 1850 (3' end of 5' UTR, C, E1 and 5' end of E2/NS1) and 8276 to 9394 (3' end of NS5 and 3' UTR) with those for genotypes I to IV. The four isolates had the following characteristics: (i) the overall nucleotide sequence similarity between the four isolates was 95 to 96%, compared to 73 to 74%, 73%, 70% or 69 to 70% against genotypes I, II, III or IV, respectively; (ii) the sequence similarity to other reported 'type V (3a)' isolates was 88 to 100%; (iii) the hypervariable region 1 [(HVR)-1] was present but HVR-2 was absent within the E2/NS1 region; (iv) only one in-frame termination codon was present for the presumed polyprotein; (v) the 3'UTR preceding a terminal poly(U) stretch was significantly shorter than in genotype I to IV isolates. We classified the four isolates as genotype V (3a), and searched for uniquely conserved nucleotide sequences that could be used for type-specific PCR. A core region-derived primer pair (no. 104V: 5' CGTAAAACTTCT GAACGGTC, sense and no. 339: 5' GCTGAGCCCA GGACCGGTCT, antisense) was identified and successfully used to diagnose genotype V (3a) HCV infection.
Contemporary murine models in preclinical astrocytoma drug development (2014)

Despite 6 decades of research, only 3 drugs have been approved for astrocytomas, the most common malignant primary brain tumors. However, clinical drug development is accelerating with the transition from empirical, cytotoxic therapy to precision, targeted medicine. Preclinical animal model studies are critical for prioritizing drug candidates for clinical development and, ultimately, for their regulatory approval. For decades, only murine models with established tumor cell lines were available for such studies. However, these poorly represent the genomic and biological properties of human astrocytomas, and their preclinical use fails to accurately predict efficacy in clinical trials. Newer models developed over the last 2 decades, including patient-derived xenografts, genetically engineered mice, and genetically engineered cells purified from human brains, more faithfully phenocopy the genomics and biology of human astrocytomas. Harnessing the unique benefits of these models will be required to identify drug targets, define combination therapies that circumvent inherent and acquired resistance mechanisms, and develop molecular biomarkers predictive of drug response and resistance. With increasing recognition of the molecular heterogeneity of astrocytomas, employing multiple, contemporary models in preclinical drug studies promises to increase the efficiency of drug development for specific, molecularly defined subsets of tumors.
Photo‐Induced Solid‐State Crosslinking of Electrospun Poly(vinyl alcohol) Fibers (2005)

Abstract Summary: Poly(vinyl alcohol) (PVA) was derivatized by polymer analogous reaction with thienyl acryloyl chloride and processed to submicrometer fibers by electrospinning from aqueous solution. Water solubility of otherwise water‐soluble PVA fibers was reduced considerably by UV crosslinking of thienyl acrylate modified PVA fibers in the solid state. Water stability of these crosslinked fibers was proven by water steam test at 95 °C. UV/Vis spectrum of PVA‐Thio fibers irradiated for different periods at 300 nm. magnified image UV/Vis spectrum of PVA‐Thio fibers irradiated for different periods at 300 nm.
Leveraging Endogenous ADAR for Programmable Editing on RNA (2019)

Abstract Nucleic acid editing carries enormous potential for biological research and the development of therapeutics. Current tools for DNA or RNA editing rely on introducing exogenous proteins into living organisms, which is subject to potential risks or technical barriers due to possible aberrant effector activity, delivery limits and immunogenicity. Here, we report a programmable approach that employs a short RNA to leverage endogenous ADAR (Adenosine Deaminase Acting on RNA) proteins for targeted RNA editing. We engineered an RNA that is partially complementary to the target transcript to recruit native ADAR1 or ADAR2 to change adenosine to inosine at a specific site. We designated this new method as LEAPER ( L everaging E ndogenous A DAR for P rogrammable E diting on R NA) and the ADAR-recruiting RNA as arRNA. arRNA, either expressed from plasmid or viral vector, or synthesized as an oligonucleotide, could achieve desirable editing. LEAPER has a manageable off-target rate on the targeted transcripts and rare global off-targets. We demonstrated that LEAPER could restore p53 function by repairing a specific cancer-relevant point mutation. Moreover, LEAPER could apply to a broad spectrum of cell types including multiple human primary cells, and it restored the α-L-iduronidase catalytic activity in Hurler syndrome patient-derived primary fibroblasts without evoking innate immune responses. As a single molecule system akin to RNAi, LEAPER enables precise and efficient RNA editing, offering the transformative potential for basic research and therapeutics.
Disrupted splenic architecture, but normal lymph node development in mice expressing a soluble lymphotoxin-β receptor–IgG1 fusion protein (1996)

Early in ontogeny, the secondary lymphoid organs become populated with numerous cells of mesodermal origin which forms both the lymphoid and stromal elements. The critical receptor/ligand interactions necessary for lymphoid organogenesis to occur are for the most part unknown. Although lymphotoxin-alpha (LT alpha) has been shown to be required for normal lymph node, Peyer's patch, and splenic development, it is unclear if soluble LT alpha 3, and/or cell-bound lymphotoxin-alpha beta (LT alpha beta) mediate these developmental events. Here we report that blocking LT alpha beta/lymphotoxin-beta receptor (LT beta R) interaction in vivo by generating mice which express a soluble LT beta R-Fc fusion protein driven by the human cytomegalovirus promoter results in an array of anatomic abnormalities affecting both the spleen and Peyer's patches, but not the lymph nodes. These results demonstrate that surface LT alpha beta ligand plays a critical role in normal lymphoid organ development.
Phase separation of a yeast prion protein promotes cellular fitness (2018)

Despite the important role of prion domains in neurodegenerative disease, their physiological function has remained enigmatic. Previous work with yeast prions has defined prion domains as sequences that form self-propagating aggregates. Here, we uncovered an unexpected function of the canonical yeast prion protein Sup35. In stressed conditions, Sup35 formed protective gels via pH-regulated liquid-like phase separation followed by gelation. Phase separation was mediated by the N-terminal prion domain and regulated by the adjacent pH sensor domain. Phase separation promoted yeast cell survival by rescuing the essential Sup35 translation factor from stress-induced damage. Thus, prion-like domains represent conserved environmental stress sensors that facilitate rapid adaptation in unstable environments by modifying protein phase behavior.
Handbook of nanoscience, engineering, and technology (2003)

In his 1959 address, There is Plenty of Room at the Bottom, Richard P. Feynman speculated about manipulating materials atom by atom and challenged the technical community find ways of manipulating and controlling things on a small scale. This visionary challenge has now become a reality, with recent advances enabling atomistic-level tailoring and control of materials.


Exemplifying Feynman’s vision, Handbook of Nanoscience, Engineering, and Technology, Third Edition continues to explore innovative nanoscience, engineering, and technology areas. Along with updating all chapters, this third edition extends the coverage of emerging nano areas even further. Two entirely new sections on energy and biology cover nanomaterials for energy storage devices, photovoltaics, DNA devices and assembly, digital microfluidic lab-on-a-chip, and much more. This edition also includes new chapters on nanomagnet logic, quantum transport at the nanoscale, terahertz emission from Bloch oscillator systems, molecular logic, electronic optics in graphene, and electromagnetic metamaterials. 


With contributions from top scientists and researchers from around the globe, this color handbook presents a unified, up-to-date account of the most promising technologies and developments in the nano field. It sets the stage for the next revolution of nanoscale manufacturing—where scalable technologies are used to manufacture large numbers of devices with complex functionalities.
Molecular Determinants of Recognition for the Intestinal Peptide Carrier (1997)

Computer-aided conformational analysis was used to characterize the pharmacophore for the intestinal peptide carrier. The active analog approach to pharmacophore building was applied as implemented in the SYBYL software package. Conformational analysis and MOPAC calculations were used to determine the lowest energy conformation of carrier substrates, as well as the conformations of compounds that displayed a common pharmacophoric geometry (i.e., inhibitors and inactive structural analogs). A pharmacophore map was calculated, and based on structural mutualities and functional topology, three substrate groups were suggested: compounds that bind to the transporter and are transferred across the membrane; compounds that show affinity for the peptide carrier (i.e., known to inhibit transport of substrates) but are not transferred across the membrane; and compounds that contain the pharmacophoric geometry but show no affinity for the carrier. Affinity for the peptide transporter can be diminished or abolished in either of three ways: esterification of the free carboxylic acid moiety; introduction of a second negative group; and intramolecular steric hindrance of the free carboxylic acid by either side chains with a positively charged nitrogen function or groups capable of hydrogen bond formation.
Safety and antitumor activity of recombinant soluble Apo2 ligand (1999)

TNF and Fas ligand induce apoptosis in tumor cells; however, their severe toxicity toward normal tissues hampers their application to cancer therapy. Apo2 ligand (Apo2L, or TRAIL) is a related molecule that triggers tumor cell apoptosis. Apo2L mRNA is expressed in many tissues, suggesting that the ligand may be nontoxic to normal cells. To investigate Apo2L's therapeutic potential, we generated in bacteria a potently active soluble version of the native human protein. Several normal cell types were resistant in vitro to apoptosis induction by Apo2L. Repeated intravenous injections of Apo2L in nonhuman primates did not cause detectable toxicity to tissues and organs examined. Apo2L exerted cytostatic or cytotoxic effects in vitro on 32 of 39 cell lines from colon, lung, breast, kidney, brain, and skin cancer. Treatment of athymic mice with Apo2L shortly after tumor xenograft injection markedly reduced tumor incidence. Apo2L treatment of mice bearing solid tumors induced tumor cell apoptosis, suppressed tumor progression, and improved survival. Apo2L cooperated synergistically with the chemotherapeutic drugs 5-fluorouracil or CPT-11, causing substantial tumor regression or complete tumor ablation. Thus, Apo2L may have potent anticancer activity without significant toxicity toward normal tissues.