gebhart/patrepeval huggingface dataset:
Lysophosphatidic acid‐regulated mitogenic ERK signaling in androgen‐insensitive prostate cancer PC‐3 cells (2002)

Advanced and recurrent prostate tumors contain elevated levels of activated extracellular signal-regulated kinases 1 and 2 (ERK) in comparison to early-stage or benign specimens, and inhibition of ERK activation attenuates growth factor-dependent proliferation of prostate cells, suggesting a potential regulatory role for ERK in prostate tumorigenesis. Factors responsible for ERK activation in prostate cells are not well defined. Here, we show positive cooperative interaction between the G protein-coupled lysophosphatidic acid (LPA) and tyrosine kinase epidermal growth factor (EGF) receptors in androgen-insensitive prostate cancer PC-3 cells. Pre-treatment of the PC-3 cells with LPA decreases the dose of EGF required to elicit maximal activation of EGFR. Furthermore, treatment with LPA alone induces the rapid (maximal signal within 2 min) tyrosine phosphorylation of EGFR, and subsequent (maximal signal after 5 min) activation of ERK, suggesting that EGFR activation precedes ERK phosphorylation and may constitute a required component for signal relay from the LPA receptor to ERK. Accordingly, we show that inhibition of EGFR kinase activity attenuates the LPA-regulated ERK activation. In addition, we find that the LPA-regulated tyrosine phosphorylation of EGFR and activation of ERK are attenuated by batimastat, a generic inhibitor of matrix metalloproteinases (MMP). However, unlike the situation in fibroblasts, we find that the LPA-induced transactivation of EGFR in PC-3 cells is not mediated by shedding of heparin-binding EGF. Together, our data show that LPA and EGF cooperate to induce mitogenic signaling in prostate cancer cells in an MMP-regulated activation of the ERK pathway.
Analysis of Cell-free Epstein-Barr Virus-associated RNA in the Plasma of Patients with Nasopharyngeal Carcinoma (1999)

Chen et al. (1) and Nawroz et al. (2) have reported that tumor-derived DNA is detectable in the plasma and serum of cancer patients and have opened up a new molecular approach for the early detection of malignancy. It is not known, however, whether circulating tumor-derived RNA is also present in plasma, because of the lability of RNA. To address this possibility, we used nasopharyngeal carcinoma (NPC) as a model system and attempted to detect Epstein-Barr virus (EBV)-latent gene transcripts in cell-free plasma samples from NPC patients.

NPC constitutes one of the commonest cancers in Hong Kong and Southern China (3). Previous studies have indicated that EBV is consistently detected in all undifferentiated NPC cases and is present in all cancer cells (3). Latent EBV infection is an early event in the development of this cancer (4). These findings suggested that the EBV genome and latency products may serve as potential markers for the screening and diagnosis of this cancer. Among the EBV-latent genes, the small EBV-encoded RNAs (EBERs) are expressed in all NPC cases and are the most abundant latency-associated transcripts in NPC cells (∼105 to 106 …
Multiwavelength achromatic metasurfaces by dispersive phase compensation (2015)

The replacement of bulk refractive optical elements with diffractive planar components enables the miniaturization of optical systems. However, diffractive optics suffers from large chromatic aberrations due to the dispersion of the phase accumulated by light during propagation. We show that this limitation can be overcome with an engineered wavelength-dependent phase shift imparted by a metasurface, and we demonstrate a design that deflects three wavelengths by the same angle. A planar lens without chromatic aberrations at three wavelengths is also presented. Our designs are based on low-loss dielectric resonators, which introduce a dense spectrum of optical modes to enable dispersive phase compensation. The suppression of chromatic aberrations in metasurface-based planar photonics will find applications in lightweight collimators for displays, as well as chromatically corrected imaging systems.
Benzopyrimido‐pyrrolo‐oxazine‐dione CFTR inhibitor (R)‐BPO‐27 for antisecretory therapy of diarrheas caused by bacterial enterotoxins (2016)

Secretory diarrheas caused by bacterial enterotoxins, including cholera and traveler's diarrhea, remain a major global health problem. Inappropriate activation of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel occurs in these diarrheas. We previously reported that the benzopyrimido-pyrrolo-oxazinedione (R)-BPO-27 inhibits CFTR chloride conductance with low-nanomolar potency. Here, we demonstrate using experimental mouse models and human enterocyte cultures the potential utility of (R)-BPO-27 for treatment of secretory diarrheas caused by cholera and Escherichia coli enterotoxins. (R)-BPO-27 fully blocked CFTR chloride conductance in epithelial cell cultures and intestine after cAMP agonists, cholera toxin, or heat-stable enterotoxin of E. coli (STa toxin), with IC<sub>50</sub> down to ∼5 nM. (R)-BPO-27 prevented cholera toxin and STa toxin-induced fluid accumulation in small intestinal loops, with IC<sub>50</sub> down to 0.1 mg/kg. (R)-BPO-27 did not impair intestinal fluid absorption or inhibit other major intestinal transporters. Pharmacokinetics in mice showed >90% oral bioavailability with sustained therapeutic serum levels for >4 h without the significant toxicity seen with 7-d administration at 5 mg/kg/d. As evidence to support efficacy in human diarrheas, (R)-BPO-27 blocked fluid secretion in primary cultures of enteroids from human small intestine and anion current in enteroid monolayers. These studies support the potential utility of (R)-BPO-27 for therapy of CFTR-mediated secretory diarrheas.-Cil, O., Phuan, P.-W., Gillespie, A. M., Lee, S., Tradtrantip, L., Yin, J., Tse, M., Zachos, N. C., Lin, R., Donowitz, M., Verkman, A. S. Benzopyrimido-pyrrolo-oxazine-dione CFTR inhibitor (R)-BPO-27 for antisecretory therapy of diarrheas caused by bacterial enterotoxins.
High-Performance Size-Based Microdevice for the Detection Of Circulating Tumor Cells from Peripheral Blood in Rectal Cancer Patients (2013)

Since individualized therapy becomes more and more important in the treatment of rectal cancer, an accurate and effective approach should be established in the clinical settings to help physicians to make their decisions. Circulating tumor cells (CTCs), originated from either primary or metastatic cancer, could provide important information for diagnosis and monitoring of cancer. However, the implication and development of CTCs are limited due to the extreme rarity of these tumor cells. In this study we fabricated a simple and high-performance microfluidic device, which exploited numerous filtered microchannels in it to enrich the large-sized target tumor cells from whole blood. A very high CTC capture efficiency (average recovery rate: 94%) was obtained in this device at the optimum flow rate of 0.5 mL/h and channel height of 5 µm. Additionally, we used this device for detecting CTCs in 60 patients with rectal cancer. The CTC counts of rectal cancer patients were significantly higher than those in healthy subjects. Furthermore, the CTC counts detected by this device were significantly higher than those by EpCAM bead-based method for rectal cancer patients with various stage. Especially, for localized rectal cancer patients, the positive rates of samples with more than 3 CTCs per 5 mL blood by use of microdevice vs. EpCAM-based ones were 100% vs. 47%, respectively. Thus, this device provides a new and effective tool for accurate identification and measurement of CTCs in patients with rectal cancer, and has broad potential in clinical practice.
Synthesis of L-tartaric Acid Derivatives (2008)

Chiral ligands,(4R,5R)-2,2-dimethyl-5-[(4-pyridineamino)carbonyl]-1,3-dioxolane-4-formate and(4R,5R)-2,2-dimethyl-N,N′-di(pyridine-4-yl)-1,3-dioxolane-4,5-bisformamide,were synthesized from L-tartaric acid.The structures were characterized by 1H NMR,IR and MS.
Different Babesia canis isolates, different diseases (1997)

Using surface immunofluorescence isolate-specific antigens were detected on the membrane of erythrocytes infected with Babesia parasites. In addition, the strains reacted differently with Plasmagel in that the European isolate (B.c. canis) could be purified on Plasmagel effectively, whereas infected erythrocytes of the South-African isolate (B.c. rossi) could not. Experimental infection of dogs with Babesia canis isolates from geographically different areas revealed different pathology. The European isolate obtained from France exhibited transient parasitaemia, usually below 1%, associated with low PCV values and congestion of internal organs. Clinical disease was correlated with an effect on the coagulation system, and not with peripheral parasitaemia. Infection of dogs with South-African-derived isolate induced high parasitaemia usually much higher than 1%, which required chemotherapeutic treatment. In these animals clinical disease was correlated with peripheral parasitaemia and not with parameters of the coagulation system. The results show that the etiology of disease caused by these isolates of B.c. canis and B.c. rossi is different. This might have implications for the development of vaccines against these infections.
PiCANet: Learning Pixel-Wise Contextual Attention for Saliency Detection (2018)

Contexts play an important role in the saliency detection task. However, given a context region, not all contextual information is helpful for the final task. In this paper, we propose a novel pixel-wise contextual attention network, i.e., the PiCANet, to learn to selectively attend to informative context locations for each pixel. Specifically, for each pixel, it can generate an attention map in which each attention weight corresponds to the contextual relevance at each context location. An attended contextual feature can then be constructed by selectively aggregating the contextual information. We formulate the proposed PiCANet in both global and local forms to attend to global and local contexts, respectively. Both models are fully differentiable and can be embedded into CNNs for joint training. We also incorporate the proposed models with the U-Net architecture to detect salient objects. Extensive experiments show that the proposed PiCANets can consistently improve saliency detection performance. The global and local PiCANets facilitate learning global contrast and homogeneousness, respectively. As a result, our saliency model can detect salient objects more accurately and uniformly, thus performing favorably against the state-of-the-art methods.
The Role of Coinhibitory Signaling Pathways in Transplantation and Tolerance (2012)

Negative costimulatory molecules, acting through so-called inhibitory pathways, play a crucial role in the control of T cell responses. This negative "second signal" opposes T cell receptor activation and leads to downregulation of T cell proliferation and promotes antigen specific tolerance. Much interest has focused upon these pathways in recent years as a method to control detrimental alloresponses and promote allograft tolerance. However, recent experimental data highlights the complexity of negative costimulatory pathways in alloimmunity. Varying effects are observed from molecules expressed on donor and recipient tissues and also depending upon the activation status of immune cells involved. There appears to be significant overlap and redundancy within these systems, rendering this a challenging area to understand and exploit therapeutically. In this article, we will review the literature at the current time regarding the major negative costimulation pathways including CTLA-4:B7, PD-1:PD-L1/PD-L2 and PD-L1:B7-1, B7-H3, B7-H4, HVEM:BTLA/CD160, and TIM-3:Galectin-9. We aim to outline the role of these pathways in alloimmunity and discuss their potential applications for tolerance induction in transplantation.
SFRP2 Regulates Cardiomyogenic Differentiation by Inhibiting a Positive Transcriptional Autofeedback Loop of Wnt3a (2007)

Wnts comprise a family of 20 lipid-modified glycoproteins in mammals and play critical roles during embryological development and organogenesis of several organ systems, including the heart. They are required for mesoderm formation and have been implicated in promoting cardiomyogenic differentiation of mammalian embryonic stem cells, but the underlying mechanisms regulating Wnt signaling during cardiomyogenesis remain poorly understood. In this report, we show that in a pluripotent mouse embryonal carcinoma stem cell line, SFRP2 inhibits cardiomyogenic differentiation by regulating Wnt3a transcription. SFRP2 inhibited early stages of cardiomyogenesis, preventing mesoderm specification and maintaining the cells in the undifferentiated state. Using a gain- and loss-of-function approach, we demonstrate that although addition of recombinant SFRP2 decreased Wnt3a transcription and cardiomyogenic differentiation, silencing of Sfrp2 led to enhanced Wnt3a transcription, mesoderm formation, and increased cardiomyogenesis. We show that the inhibitory effects of SFRP2 on Wnt transcription are secondary to interruption of a positive feedback effect of Wnt3a on its own transcription. Wnt3a increased its own transcription via the canonical pathway and TCF4 family of transcription factors, and the inhibitory effects of SFRP2 on Wnt3a transcription were associated with disruption of downstream canonical Wnt signaling. The inhibitory effects of Sfrp2 on Wnt3a expression identify Sfrp2 as a "checkpoint gene," which exerts its control on cardiomyogenesis through regulation of Wnt3a transcription.
A Family of acr -Coregulated Mycobacterium tuberculosis Genes Shares a Common DNA Motif and Requires Rv3133c ( dos R or dev R) for Expression (2003)

Previous work has shown that the divergently transcribed Mycobacterium tuberculosis genes acr (hspX, Rv2031c) and acg (Rv2032) are induced under conditions of shallow standing culture and low oxygen and intracellularly within macrophages. We used a combination of computational and experimental methods to identify promoters for eight additional genes that are regulated in a similar manner and that comprise an acr-coregulated promoter (ACP) family. Transcriptional regulation of these ACP family members was evaluated by using a plasmid-based promoter-green fluorescent protein fusion system and flow cytometry. All promoters showed increased expression in shallow standing versus shaking cultures, in low- versus high-oxygen conditions, and intracellularly within macrophages versus extracellularly in tissue culture medium. However, there were quantitative differences in expression among promoters and among conditions for each promoter. A conserved 18-bp palindromic sequence motif was identified in all ACPs by Gibbs sampling-based computational analyses. Two such motifs overlap regions in the acr and acg promoters that were previously shown to be required for their expression. In addition, we found that 5% carbon dioxide was required for growth of Mycobacterium bovis BCG under microaerophilic (1.3% O(2)) culture conditions and fully prevented the growth cessation typically associated with rapid removal of oxygen. These findings are likely to be relevant to the in vivo environment and will contribute to our understanding of the pathogenesis of tuberculosis infection.
EGF-CFC proteins are essential coreceptors for the TGF-β signals Vg1 and GDF1 (2003)

The TGF-beta signals Nodal, Activin, GDF1, and Vg1 have been implicated in mesoderm induction and left-right patterning. Nodal and Activin both activate Activin receptors, but only Nodal requires EGF-CFC coreceptors for signaling. We report that Vg1 and GDF1 signaling in zebrafish also depends on EGF-CFC proteins, but not on Nodal signals. Correspondingly, we find that in Xenopus Vg1 and GDF1 bind to and signal through Activin receptors only in the presence of EGF-CFC proteins. These results establish that multiple TGF-beta signals converge on Activin receptor/EGF-CFC complexes and suggest a more widespread requirement for coreceptors in TGF-beta signaling than anticipated previously.
LSD Increases Primary Process Thinking via Serotonin 2A Receptor Activation (2017)

<b>Rationale:</b> Stimulation of serotonin 2A (5-HT2A) receptors by lysergic acid diethylamide (LSD) and related compounds such as psilocybin has previously been shown to increase primary process thinking - an ontologically and evolutionary early, implicit, associative, and automatic mode of thinking which is typically occurring during altered states of consciousness such as dreaming. However, it is still largely unknown whether LSD induces primary process thinking under placebo-controlled, standardized experimental conditions and whether these effects are related to subjective experience and 5-HT2A receptor activation. Therefore, this study aimed to test the hypotheses that LSD increases primary process thinking and that primary process thinking depends on 5-HT2A receptor activation and is related to subjective drug effects. <b>Methods:</b> Twenty-five healthy subjects performed an audio-recorded mental imagery task 7 h after drug administration during three drug conditions: placebo, LSD (100 mcg orally) and LSD together with the 5-HT2A receptor antagonist ketanserin (40 mg orally). The main outcome variable in this study was primary index (PI), a formal measure of primary process thinking in the imagery reports. State of consciousness was evaluated using the Altered State of Consciousness (5D-ASC) rating scale. <b>Results:</b> LSD, compared with placebo, significantly increased primary index (<i>p</i> < 0.001, Bonferroni-corrected). The LSD-induced increase in primary index was positively correlated with LSD-induced disembodiment (<i>p</i> < 0.05, Bonferroni-corrected), and blissful state (<i>p</i> < 0.05, Bonferroni-corrected) on the 5D-ASC. Both LSD-induced increases in primary index and changes in state of consciousness were fully blocked by ketanserin. <b>Conclusion:</b> LSD induces primary process thinking via activation of 5-HT2A receptors and in relation to disembodiment and blissful state. Primary process thinking appears to crucially organize inner experiences during both dreams and psychedelic states of consciousness.
Expression, Purification, Characterization, and Reconstitution of the Large and Small Subunits of Yeast Acetohydroxyacid Synthase (1999)

Acetohydroxyacid synthase (AHAS, EC 4.1.3.18) catalyzes the first step in the biosynthesis of the branched-chain amino acids. In bacteria, the enzyme has a large subunit containing the catalytic machinery and a small subunit with a regulatory role. In eucaryotes, the evidence for a regulatory subunit is largely indirect and circumstantial. We investigated the possibility that the yeast open reading frame YCL009c is an AHAS small subunit. Analysis of the DNA sequence shows that it contains all the appropriate transcription, translation and regulatory signals. YCL009c was shown to be expressed in yeast and the protein localized in mitochondria where it undergoes removal of a transit peptide targeting sequence. This putative small subunit protein (ilv6) and the catalytic subunit of yeast AHAS (ilv2) were each overexpressed in Escherichia coli and purified to near homogeneity. Reconstitution studies showed that the ilv6 protein stimulates the catalytic activity of the ilv2 protein by up to 7-fold (from 6.8 +/- 0.7 to 49.0 +/- 1.8 U/mg) and confers upon it sensitivity to inhibition by valine (Ki = 0.16 +/- 0.02 mM). Valine inhibition is partially reversed by ATP. The reconstitution is favored by high concentrations of potassium phosphate ( approximately 1 M) and at neutral pH. Under optimal conditions for reconstitution, a dissociation constant for the subunits of 70 +/- 7 nM was determined. Valine inhibition is partial, resulting in a specific activity that is similar to that of the ilv2 protein alone. However, measurements of the Km for substrate rule out the possibility that valine inhibition is accomplished by dissociation of the subunits.
dNTP Modified at Triphosphate Residues: Substrate Properties Towards DNA Polymerases and Stability in Human Serum (1998)

Substrate and terminating substrate properties of dNTP with phosphate groups replaced by phosphonates at alpha-, gamma-, beta, gamma-, and alpha, beta, gamma-positions towards different human DNA polymerases and retroviral reverse transcriptases are reviewed. Substitution of the phosphate group by the phosphonate at any of the three phosphate positions of dNTP increased their stability towards dephosphorylating enzymes of human blood. In some cases hydrophobicity of these compounds was markedly enhanced.
Rapid induction of a specific nuclear mRNA precursor by thyroid hormone. (1984)

Administration of thyroid hormone to the thyroidectomized rat results in a rapid and dramatic increase in the relative amount of hepatic mRNA coding for spot 14--a translational product with an approximate Mr of 17,500 and isoelectric point of 4.9. We have now isolated a cDNA clone containing sequences homologous to this thyroid hormone-responsive mRNA. Two distinct mRNA species that differed by 200 nucleotides in length were found to be capable of hybridizing to the cDNA probe. Both mRNA species were proportionally elevated in relative concentration in rats with increasing plasma levels of thyroid hormone. The earliest change in the levels of mature mRNA occurred at 20 minutes following thyroid hormone treatment of the thyroidectomized rat. Analysis of nuclear RNA revealed a single higher molecular weight species that was homologous to spot 14 mRNA. An increase in the nuclear level of this putative precursor occurred by 10 minutes following thyroid hormone administration, a time preceding the earliest change in mature mRNA. Thus, thyroid hormone appears to act at least in part at a nuclear level in altering the cellular concentration of this mRNA species. The rapidity of this change suggests that it may reflect a direct response to the binding of thyroid hormone to its nuclear receptor.
Personalized Awareness and Safety with Mobile Phones as Sources and Sinks (2008)

Today’s mobile phones are equipped with an increasing set of sensors including GPS, accelerometers, cameras, and more that makes them ideal source nodes in urban sensing applications. The growing displays and internet connectivity also makes these phones excellent sinks of just-in-time information, including information from other sensors deployed in the infrastructure. Exploiting these features, our personalized safety and awareness system tries to enhance personal safety of users around the clock through a collection of services that process personal and aggregate community data to track, escort, flag, supervise behaviors and help users coordinate to enhance the collective safety of the group. Designed for individuals and groups that operate on campuses and beyond, it intends to make campuses safer, by going beyond the processing of individual location data and by providing services based on the application of intelligent behavior sensing algorithms and collaborative models to aggregate sensor data. I.
Characteristics of Analgesia Induced by Adenosine Triphosphate (1987)

Adenosine triphosphate (ATP) injected intravenously in mice was found to have dose-dependent analgesic activity in the hot plate and phenylquinone-induced stretching assays. ATP prolonged the hot plate latency (ED50 value of 1 (0.7-1.4) mg/kg) and inhibited phenylquinone-induced writhing (ED50 value of 0.4 (0.31-0.52) mg/kg). Low doses of ATP produced a potent antinociceptive effect without any significant depression of locomotor activity. Treatment of mice for either 4 days or 14 days with ATP did not result in development of physical dependence on or tolerance to ATP. The analgesic action of ATP was not antagonized by naloxone at 1 and 5 mg/kg. ATP analgesia was antagonized, in a dose-related fashion, by Ca++ ion injected intracerbroventricularly which may indicate that Ca++ plays a role in ATP-induced antinociception.