gebhart/patrepeval huggingface dataset:
Pheromonal regulation and sequence of the Saccharomyces cerevisiae SST2 gene: a model for desensitization to pheromone. (1987)

Strains of both haploid mating types containing sst2 mutations are altered in response to pheromone; MATa sst2 cells are supersensitive to alpha-factor, and MAT alpha sst2 cells are supersensitive to a-factor. This phenotype suggests that SST2 encodes a component of the pheromone response pathway that is common to both mating types. We have cloned the SST2 gene by isolation of multicopy plasmids that complement the sst2-1 mutation. One such plasmid contained a 4.5-kilobase HindIII fragment that was able to complement the sst2-1 mutation in high or low copy number, integrated at the SST2 locus, and resulted in an sst2 phenotype when disrupted, indicating that this fragment contained the SST2 gene. We identified the functional region of the complementing DNA fragment by transposon mutagenesis. Sequencing of this fragment identified an open reading frame encoding 698 amino acids at a position that correlated well with the functional region. Expression of an Sst2-beta-galactosidase fusion was haploid specific and induced by exposure to pheromone. We discuss a model in which induction of the SST2 product results in inhibition of a component of the pheromone response pathway, resulting in desensitization to pheromone.
Remodeling and Enhancing Schmidt Reaction Pathways in Hexafluoroisopropanol (2016)

The effect of carrying out two variations of the Schmidt reaction with ketone electrophiles in hexafluoroisopropanol (HFIP) solvent has been studied. When TMSN3 is reacted with ketones in the presence of triflic acid (TfOH) promoter, tetrazoles are obtained as the major products. This observation is in contrast to established methods, which usually lead to amides or lactams arising from formal NH insertion as the major products. The full product profiles of several examples of this reaction are also reported and found to include mechanistically interesting products (e.g., double ring expansion). Application of TfOH promoter in HFIP was also found to promote the reaction of a hydroxyalkyl azide with a ketone, which affords lactams following nucleophilic opening of initially formed iminium ether more efficiently than previously reported methods.
Effect of swainsonine on stimulation and cell cycle progression of human lymphocytes. (1989)

The indolizidine alkaloid swainsonine (SW) is an inhibitor of lysosomal alpha-mannosidase reported to have antimetastatic activity in animal models. The cells grown in its presence develop truncated (hybrid) surface oligosaccharides that may alter their functional properties dependent on interactions of various ligands with membrane receptors. In the present study we observe that SW enhances stimulation of human lymphocytes induced by suboptimal concentration of concanavalin A. The enhancement is manifested by an increased proportion of cells undergoing transition from G0 (G1Q) to G1 and progressing through the cell cycle (S + G2 + M). In contrast, SW suppresses stimulation of lymphocytes by phytohemagglutinin, and the degree of suppression is greater when measured by the number of cells progressing through the cell cycle (S + G2 + M) than by the proportion of cells entering G1 phase. The suppression remains evident even when SW is added 12 h after phytohemagglutinin, suggesting that SW modifies membrane receptors that develop in G1 and are necessary for cell entrance to S phase. The modification of receptors by SW thus up-regulates stimulation by concanavalin A and down-regulates stimulation by phytohemagglutinin. SW has no effect on lymphocyte stimulation induced by OKT3 monoclonal antibody or on the progression of cells from three leukemic cell lines, HL-60, L1210, and MOLT-4, through the cell cycle. The present data are compatible with the possibility that the reported suppression of the growth of metastatic mouse tumors by SW may be due to the immunomodulatory properties of this alkaloid.
Performance of an electro-optic waveguide modulator fabricated using a deoxyribonucleic-acid-based biopolymer (2006)

An electro-optic (EO) planar waveguide modulator using a deoxyribonucleic acid (DNA)-based biopolymer for both the waveguide core and cladding layers has been fabricated and its performance evaluated. A cross-linked DNA-surfactant biopolymer was used for the top and bottom cladding layers and the core layer was a cross-linked DNA-surfactant biopolymer with 3wt% Disperse Red 1. The EO coefficient r33 was induced through contact poling. The fabricated device was found to exhibit EO modulating behavior. Using an estimated value of r33=0.5pm∕V, a sine-squared fit to the modulating data was obtained with Vπ=263V±10%.
Small Molecule Inhibitor of NRF2 Selectively Intervenes Therapeutic Resistance in KEAP1-Deficient NSCLC Tumors (2016)

Loss of function mutations in Kelch-like ECH Associated Protein 1 (KEAP1), or gain-of-function mutations in nuclear factor erythroid 2-related factor 2 (NRF2), are common in non-small cell lung cancer (NSCLC) and associated with therapeutic resistance. To discover novel NRF2 inhibitors for targeted therapy, we conducted a quantitative high-throughput screen using a diverse set of ∼400 000 small molecules (Molecular Libraries Small Molecule Repository Library, MLSMR) at the National Center for Advancing Translational Sciences. We identified ML385 as a probe molecule that binds to NRF2 and inhibits its downstream target gene expression. Specifically, ML385 binds to Neh1, the Cap 'N' Collar Basic Leucine Zipper (CNC-bZIP) domain of NRF2, and interferes with the binding of the V-Maf Avian Musculoaponeurotic Fibrosarcoma Oncogene Homologue G (MAFG)-NRF2 protein complex to regulatory DNA binding sequences. In clonogenic assays, when used in combination with platinum-based drugs, doxorubicin or taxol, ML385 substantially enhances cytotoxicity in NSCLC cells, as compared to single agents. ML385 shows specificity and selectivity for NSCLC cells with KEAP1 mutation, leading to gain of NRF2 function. In preclinical models of NSCLC with gain of NRF2 function, ML385 in combination with carboplatin showed significant antitumor activity. We demonstrate the discovery and validation of ML385 as a novel and specific NRF2 inhibitor and conclude that targeting NRF2 may represent a promising strategy for the treatment of advanced NSCLC.
The Soluble Wnt Receptor Frizzled8CRD-hFc Inhibits the Growth of Teratocarcinomas In vivo (2007)

Wnt signaling is important for normal cell proliferation and differentiation, and mutations in pathway components are associated with human cancers. Recent studies suggest that altered wnt ligand/receptor interactions might also contribute to human tumorigenesis. Therefore, agents that antagonize wnt signaling at the extracellular level would be attractive therapeutics for these cancers. We have generated a soluble wnt receptor comprising the Frizzled8 cysteine-rich domain (CRD) fused to the human Fc domain (F8CRDhFc) that exhibits favorable pharmacologic properties in vivo. Potent antitumor efficacy was shown using the mouse mammary tumor virus-Wnt1 tumor model under dosing conditions that did not produce detectable toxicity in regenerating tissue compartments. In vitro, F8CRDhFc inhibited autocrine wnt signaling in the teratoma cell lines PA-1, NTera-2, Tera-2, and NCCIT. In vivo, systemic administration of F8CRDhFc significantly retarded the growth of tumor xenografts derived from two of these cell lines, PA-1 and NTera-2. Pharmacodynamic markers of wnt signaling, identified by gene expression analysis of cultured teratoma cells, were also modulated in the tumor xenografts following treatment with F8CRDhFc. Additionally, these markers could be used as indicators of treatment efficacy and might also be useful in identifying patients that would benefit from the therapeutic agent. This is the first report showing the efficacy of a soluble wnt receptor as an antitumor agent and suggests that further development of wnt antagonists will have utility in treating human cancer.
Cytokine production and inflammation drive autophagy in the tumor microenvironment (2011)

Recently, we proposed a new paradigm for understanding the role of the tumor microenvironment in breast cancer onset and progression. In this model, cancer cells induce oxidative stress in adjacent fibroblasts. This, in turn, results in the onset of stromal autophagy, which produces recycled nutrients to "feed" anabolic cancer cells. However, it remains unknown how autophagy in the tumor microenvironment relates to inflammation, another key driver of tumorigenesis. To address this issue, here we employed a well-characterized co-culture system in which cancer cells induce autophagy in adjacent fibroblasts via oxidative stress and NFκB-activation. We show, using this co-culture system, that the same experimental conditions that result in an autophagic microenvironment, also drive in the production of numerous inflammatory mediators (including IL-6, IL-8, IL-10, MIP1a, IFNg, RANTES (CCL5) and GMCSF). Furthermore, we demonstrate that most of these inflammatory mediators are individually sufficient to directly induce the onset of autophagy in fibroblasts. To further validate the in vivo relevance of these findings, we assessed the inflammatory status of Cav-1 (-/-) null mammary fat pads, which are a model of a bonafide autophagic microenvironment. Notably, we show that Cav-1 (-/-) mammary fat pads undergo infiltration with numerous inflammatory cell types, including lymphocytes, T-cells, macrophages and mast cells. Taken together, our results suggest that cytokine production and inflammation are key drivers of autophagy in the tumor microenvironment. These results may explain why a loss of stromal Cav-1 is a powerful predictor of poor clinical outcome in breast cancer patients, as it is a marker of both (1) autophagy and (2) inflammation in the tumor microenvironment. Lastly, hypoxia in fibroblasts was not sufficient to induce the full-blown inflammatory response that we observed during the co-culture of fibroblasts with cancer cells, indicating that key reciprocal interactions between cancer cells and fibroblasts may be required.
Hyperbranched Conjugated Polyelectrolyte Bilayers for Solar-Cell Applications (2007)

Cationically and anionically charged hyperbranched conjugated polyelectrolytes (HB-CPEs) PNMe3+ and PSO3- have been synthesized via the Heck coupling method using A3 + B2 type approach. Both HB-CPEs are highly fluorescent and soluble in polar organic solvents allowing processing to electrostatic adsorption. TiO2 hybrid solar cells have been fabricated with the HB-CPEs as sensitizers. The self-assembled bilayer HB-CPE films show higher overall efficiencies when compared to their respective monolayers
Adenovirus type 5 packaging domain is composed of a repeated element that is functionally redundant (1990)

Previous analyses have demonstrated that adenovirus DNA is packaged into virions in vivo in a polar, left-to-right fashion. The packaging of viral DNA is dependent on cis-acting elements at the left end of the genome. In this report, we describe a genetic analysis of the sequences that are required for efficient packaging of adenovirus type 5 (Ad5) DNA. Our results demonstrate that the Ad5 packaging domain (nucleotides 194 to 358) is composed of at least five distinct elements that are functionally redundant. An AT-rich repeated sequence motif, the A repeat, is located in four of five of these regions; the fifth region is also AT rich. The efficiency of viral packaging depends on the number of individual A repeats that are present in the viral genome. The deletion of the entire packaging domain resulted in the loss of virus viability. A virus that contains a multimerized oligonucleotide corresponding to A repeat II in place of the packaging domain could package viral DNA, although with reduced efficiency compared with that of the wild-type virus. Our results also suggest that the spacing of specific sequences at the left end of the Ad5 genome are important for enhancer region function in vivo.
A Human SPT3-TAFII31-GCN5-L Acetylase Complex Distinct from Transcription Factor IID (1998)

In yeast, SPT3 is a component of the multiprotein SPT-ADA-GCN5 acetyltransferase (SAGA) complex that integrates proteins with transcription coactivator/adaptor functions (ADAs and GCN5), histone acetyltransferase activity (GCN5), and core promoter-selective functions (SPTs) involving interactions with the TATA-binding protein (TBP). In particular, yeast SPT3 has been shown to interact directly with TBP. Here we report the molecular cloning of a cDNA encoding a human homologue of yeast SPT3. Amino acid sequence comparisons between human SPT3 (hSPT3) and its counterparts in different yeast species reveal three highly conserved domains, with the most conserved 92-amino acid N-terminal domain being 25% identical with human TAFII18. Despite the significant sequence similarity with TAFII18, native hSPT3 is not a bona fide TAFII because it is not associated in vivo either with human TBP/TFIID or with a TFIID-related TBP-free TAFII complex. However, we present evidence that hSPT3 is associated in vivo with TAFII31 and the recently described longer form of human GCN5 (hGCN5-L) in a novel human complex that has histone acetyltransferase activity. We propose that the human SPT3-TAFII31-GCN5-L acetyltransferase (STAGA) complex is a likely homologue of the yeast SAGA complex.
Modern Communication Systems: Principles and Applications (1994)

From the Publisher:
The modern telecommunication age is here. We live in a world of cordless phones, electronic mail (e-mail), mobile cellular telephones, cable TV, satellite TV, inexpensive long-distance, national and international communications via fiber optic cables and satellites, personal computers (PC), data communications networks, and intelligent telecommunication systems.
The Evolution of Video Magnification Technology (1996)

Closed-circuit television (CCTV) systems are the product of a long line of technological advances in several fields, including optics, electrical signal processing, and video display technology. Many different models are now on the market, and more advanced ones are frequently introduced. This article traces the development of early CCTV systems, examines CCTVs that are on the market today, and speculates on video magnification technology of the future, which will make extensive use of computer-related technology.
Polyelectrolyte Interlayer for Ultra-Sensitive Organic Transistor Humidity Sensors (2013)

We demonstrate low-voltage, flexible, transparent pentacene humidity sensors with ultrahigh sensitivity, good reliability, and fast response/recovery behavior. The excellent performances of these devices are derived from an inserted polyelectrolyte (poly[2-(methacryloyloxy)ethyltrimethylammonium chloride-co-3-(trimethoxysilyl)propyl methacrylate] (poly(METAC-co-TSPM)) interlayer, which releases free Cl- ions in the electrolyte dielectric layer under humid conditions and boosts the electrical current in the transistor channel. This has led to extreme device sensitivity, such that electrical signal variations exceeding 7 orders of magnitude have been achieved in response to a 15% change in the relative humidity level. The new sensors exhibit a fast responsivity and a stable performance toward changes in humidity levels. Furthermore, the humidity sensors, mounted on flexible substrates, provided low voltage (<5 V) operation while preserving the unique ultrasensitivity and fast responsivity of these devices. We believe that the strategy of utilizing the enhanced ion motion in an inserted polyelectrolyte layer of an OFET structure can potentially improve sensor technologies beyond humidity-responsive systems.
Anti-Inflammatory Therapy for Diabetic Retinopathy (2011)

Diabetic retinopathy (DR) is one of the most common complications of diabetes. This devastating disease is a leading cause of blindness in people of working age in industrialized countries and affects the daily lives of millions of people. Despite tight glycemic control, blood pressure control and lipid-lowering therapy, the number of DR patients keeps growing and therapeutic approaches are limited. Moreover, there are significant limitations and side effects associated with the current therapies. Thus, there is a great need for development of new strategies for prevention and treatment of DR. Studies have shown that DR has prominent features of chronic, subclinical inflammation. This article focuses on the role of inflammation in DR and summarizes the progress of studies of anti-inflammatory strategies for DR.
Mutation rate of the CDKN2 gene in malignant gliomas. (1994)

The CDKN2 gene encodes p16, a protein controlling the cell cycle. CDKN2 is deleted in a relevant number of tumor cell lines, but results of the studies in primary tumors are contradictory. We have investigated by using quantitative polymerase chain reaction and single-strand conformation polymorphism analysis the structure of exon 2 of CDKN2 in 32 malignant gliomas. In 11 tumors the amount of amplified material was 21% of that of controls and in 8 tumors it was 42.3%, suggesting the presence of homozygous and hemizygous deletions of the CDKN2 gene, respectively. However, no abnormality could be detected by single-strand conformation polymorphism analysis. The data confirm in primary gliomas that homozygous deletions are a mechanism of CDKN2 inactivation and suggest that another gene in the vicinity could be targeted by mutations.
Two-photon voltage imaging using a genetically encoded voltage indicator (2013)

Voltage-sensitive fluorescent proteins (VSFPs) are a family of genetically-encoded voltage indicators (GEVIs) reporting membrane voltage fluctuation from genetically-targeted cells in cell cultures to whole brains in awake mice as demonstrated earlier using 1-photon (1P) fluorescence excitation imaging. However, in-vivo 1P imaging captures optical signals only from superficial layers and does not optically resolve single neurons. Two-photon excitation (2P) imaging, on the other hand, has not yet been convincingly applied to GEVI experiments. Here we show that 2P imaging of VSFP Butterfly 1.2 expresssing pyramidal neurons in layer 2/3 reports optical membrane voltage in brain slices consistent with 1P imaging but with a 2-3 larger ΔR/R value. 2P imaging of mouse cortex in-vivo achieved cellular resolution throughout layer 2/3. In somatosensory cortex we recorded sensory responses to single whisker deflections in anesthetized mice at full frame video rate. Our results demonstrate the feasibility of GEVI-based functional 2P imaging in mouse cortex.
Spatio-temporal Saliency Detection in Dynamic Scenes Using Local Binary Patterns (2014)

Visual saliency detection is an important step in many computer vision applications, since it reduces further processing steps to regions of interest. Saliency detection in still images is a well-studied topic. However, videos scenes contain more information than static images, and this additional temporal information is an important aspect of human perception. Therefore, it is necessary to include motion information in order to obtain spatio-temporal saliency map for a dynamic scene. In this paper, we introduce a new spatio-temporal saliency detection method for dynamic scenes based on dynamic textures computed with local binary patterns. In particular, we extract local binary patterns descriptors in two orthogonal planes (LBP-TOP) to describe temporal information, and color features are used to represent spatial information. The obtained three maps are finally fused into a spatio-temporal saliency map. The algorithm is evaluated on a dataset with complex dynamic scenes and the results show that our proposed method outperforms state-of-art methods.
Stimulation of the human CTP:phosphoethanolamine cytidylyltransferase gene by early growth response protein 1 (2008)

Change in phosphoethanolamine pool size in tumor tissues is an important indicator of tumor prognosis and drug therapy efficacy. Phosphoethanolamine is the substrate of the regulatory enzyme CTP:phosphoethanolamine cytidylyltransferase (ECT) in the de novo biosynthesis of phosphatidylethanolamine (PE). Metabolic labeling with [14C]ethanolamine revealed a reduced ECT activity in MCF-7 breast cancer cells, which led to an accumulation of phosphoethanolamine and a decrease in PE synthesis in comparison with MCF-10A mammary epithelial cells. The enhanced ECT activity in MCF-10A cells was due to significantly elevated CTP:phosphoethanolamine cytidylyltransferase gene (PCYT2) expression, at the level of promoter activity, mRNA, and protein content. The early growth response protein 1 (EGR1) could account for most of the elevated ECT activity in MCF-10A cells relative to MCF-7 cells, as evidenced by promoter-luciferase reporter assays, gel-shift analyses, and by alterations in the EGR1 gene expression. In MCF-7 cells, EGR1 is present at lower levels and the basal PCYT2 promoter activity is maintained by proximal CAAT and GC regions and by elevated nuclear NFkappaB activity. Together, these data demonstrate that EGR1 is an important transcriptional stimulator of the human PCYT2 and that conditions that modify EGR1 also affect the function of ECT and consequently PE synthesis.
Blood Group B Degrading Activity ofRuminococcus gnavusα-Galactosidase (2004)

Ruminococcus gnavus is a Gram positive, nonspore-forming obligate anaerobe normally found in the human alimentary tract. In culture, this organism constitutively produces a 1-3 alpha-galactosidase. We fractionated and characterized this enzyme demonstrating hydrolysis of the B epitope on erythrocyte membranes and seroconversion to H epitope (blood type O). Since the enzyme yield was low, cell suspension studies could not be performed. Instead, hydrolysis of the B membrane epitope was studied with an ELISA. A highly purified enzyme product was analyzed for characteristics such as pH, ionic strength, and temperature optimum. Activity in red cell preservative solutions and in the presence of type B plasma was also demonstrated. Ruminococcus gnavus a 1-3 alpha-galactosidase has potential application in the enzymatic conversion of type B to O packed red blood cell units.
Hepatitis C Virus Nonstructural Protein 5A (NS5A) Is an RNA-binding Protein (2005)

Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) has been shown to antagonize numerous cellular pathways, including the antiviral interferon-alpha response. However, the capacity of this protein to interact with the viral polymerase suggests a more direct role for NS5A in genome replication. In this study, we employed two bacterially expressed, soluble derivatives of NS5A to probe for novel functions of this protein. We find that NS5A has the capacity to bind to the 3'-ends of HCV plus and minus strand RNAs. The high affinity binding site for NS5A in the 3'-end of plus strand RNA maps to the polypyrimidine tract, an element known to be essential for genome replication and infectivity. NS5A has a preference for single-stranded RNA containing stretches of uridine or guanosine. Values for the equilibrium dissociation constants for high affinity binding sites were in the 10 nM range. Two-dimensional gel electrophoresis followed by Western blotting revealed the presence of unphosphorylated NS5A in Huh-7 cells stably expressing the subgenomic replicon. Moreover, RNA immunoprecipitation and NS5A pull-down experiments showed the capacity of replicon-derived NS5A to bind to synthetic RNA and the HCV genome, respectively. Deletion of all of the casein kinase II phosphorylation sites in NS5A supported stable replication of a subgenomic replicon in Huh-7. However, this derivative could not be labeled with inorganic phosphate, suggesting that extensive phosphorylation of NS5A is not required for the replication functions of NS5A. The discovery that NS5A is an RNA-binding protein defines a new functional target for development of agents to treat HCV infection and a new structural class of RNA-binding proteins.