gebhart/patrepeval huggingface dataset:
Up-regulation of the cAMP/PKA pathway inhibits proliferation, induces differentiation, and leads to apoptosis in malignant gliomas. (1998)

Manipulation of signal transduction pathways has been increasingly used to modulate tumor growth. We have investigated the effects of up-regulation of the cAMP/protein kinase A (PKA) pathway in cell lines and primary cultures of malignant gliomas. The malignant glioma cell line A-172 was treated with agonistic cAMP analogs dibutyryl cyclic AMP (dcAMP) and 8-bromo-cyclic AMP (8-Br-cAMP), an adenylate cyclase activator (forskolin), and a phosphodiesterase inhibitor (3-isobutyl-1-methyl-xanthene [IBMX]). Proliferation was determined by 3H-thymidine assay. Differentiation was measured by morphologic changes, glial fibrillary acidic protein (GFAP) content, and invasion potential. Apoptosis was measured quantitatively by the TUNEL method, which labels DNA fragments using terminal transferase. Agonistic cAMP analogs, forskolin, and IBMX were found to decrease proliferation in A-172 cells after 24 hours. Treatment with 8-Br-cAMP for 24 hours caused an increase in GFAP and decrease in invasion. Apoptosis was induced after 48 hours in the presence of synergistic cAMP analogs for the Type II PKA isozyme, but not Type I PKA isozyme. Activation of PKA by increasing cAMP levels (forskolin, IBMX) or directly by cAMP analogs correlated with decreased proliferation, increased differentiation, and induction of apoptosis in A-172 cells. Modulation of the cAMP/PKA pathway may thus represent a possible target site for treating malignant gliomas.
Intracavernous Injection of Papaverine as a Diagnostic and Therapeutic Method in Erectile Failure (1984)

The effect of intracavernous injection of papaverine (ICIP) has been investigated in 45 men: 6 normally potent volunteers, 10 psychogenic, and 29 organic impotent males. The first two groups obtained erections within 10 minutes, lasting from 1 to 4 hours, after injection of 80 mg of papaverine. Those belonging to the organic group experienced delayed, weaker and shorter erections, related to various degrees of arterial and/or venous and neurologic lesions. Haemodynamic and radiologic studies done concomitantly, showed a strong vasodilation in the penile arteries (even when pathologic) and a diminished outflow from the cavernous bodies. Subsequently, a pilot study was performed in a series of 63 patients suffering from various degrees of angiogenic impotence, in order to study the therapeutic effect of repeated intracavernous injections of papaverine completed by intracavernous infusion of heparinized saline. Erections improved significantly in 66% of the patients with a mean follow up of one year.
Prevention of Alzheimer's Disease Pathology by Cannabinoids: Neuroprotection Mediated by Blockade of Microglial Activation (2005)

Alzheimer's disease (AD) is characterized by enhanced beta-amyloid peptide (betaA) deposition along with glial activation in senile plaques, selective neuronal loss, and cognitive deficits. Cannabinoids are neuroprotective agents against excitotoxicity in vitro and acute brain damage in vivo. This background prompted us to study the localization, expression, and function of cannabinoid receptors in AD and the possible protective role of cannabinoids after betaA treatment, both in vivo and in vitro. Here, we show that senile plaques in AD patients express cannabinoid receptors CB1 and CB2, together with markers of microglial activation, and that CB1-positive neurons, present in high numbers in control cases, are greatly reduced in areas of microglial activation. In pharmacological experiments, we found that G-protein coupling and CB1 receptor protein expression are markedly decreased in AD brains. Additionally, in AD brains, protein nitration is increased, and, more specifically, CB1 and CB2 proteins show enhanced nitration. Intracerebroventricular administration of the synthetic cannabinoid WIN55,212-2 to rats prevent betaA-induced microglial activation, cognitive impairment, and loss of neuronal markers. Cannabinoids (HU-210, WIN55,212-2, and JWH-133) block betaA-induced activation of cultured microglial cells, as judged by mitochondrial activity, cell morphology, and tumor necrosis factor-alpha release; these effects are independent of the antioxidant action of cannabinoid compounds and are also exerted by a CB2-selective agonist. Moreover, cannabinoids abrogate microglia-mediated neurotoxicity after betaA addition to rat cortical cocultures. Our results indicate that cannabinoid receptors are important in the pathology of AD and that cannabinoids succeed in preventing the neurodegenerative process occurring in the disease.
Detecting Illumination in Images (2007)

In this paper we present a surprisingly simple yet powerful method for detecting illumination—determining which pixels are lit by different lights—in images. Our method is based on the chromagenic camera, which takes two pictures of each scene: one is captured as normal and the other through a coloured filter. Previous research has shown that the relationship between the colours, the RGBs, in the filtered and unfiltered images depends strongly on the colour of the light and this can be used to estimate the colour of the illuminant. While chromagenic illuminant estimation often works well it can and does fail and so is not itself a direct solution to the illuminant detection problem. In this paper we dispense with the goal of illumination estimation and seek only to use the chromagenic effect to find out which parts of a scene are illuminated by the same lights. The simplest implementation of our idea involves a combinatorial search. We precompute a dictionary of possible illuminant relations—that might map RGBs to filtered counterparts—from which we select a small number 𝑚 corresponding to the number of distinct lights we think might be present. Each pixel, or region, is assigned the relation from this 𝑚-set that best maps filtered to unfiltered RGB. All 𝑚-sets are tried in turn and the one that has the minimum prediction error over all is found. At the end of this search process each pixel or region is assigned an integer between 1 and 𝑚 indicating which of the m lights are thought to have illuminated the region. Our simple search algorithm is possible when 𝑚 = 2 (and 𝑚 = 3) and for this case we present experiments that show our method does a remarkable job in detecting illumination in images: if the 2 lights are shadow and non- shadow, we find the shadows almost effortlessly. Compared to ground truth data, our method delivers close to optimal performance.
L-Dopa in Legume Seeds: A Chemical Barrier to Insect Attack (1973)

Seeds of the genus Mucuna display both a remarkable immunity to attack by seed-eating insects and an unustially high concentration of free L-dopa. When seed powders or pure L-dopa were incorporated into artificial diets and fed to southern armyworm larvae, mortality increased, and abnormal pupae and adults resulted. At higher concentrations L-dopa acted as a feeding repellent.
Human cellular restriction factors that target HIV-1 replication (2009)

Recent findings have highlighted roles played by innate cellular factors in restricting intracellular viral replication. In this review, we discuss in brief the activities of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G), bone marrow stromal cell antigen 2 (BST-2), cyclophilin A, tripartite motif protein 5 alpha (Trim5alpha), and cellular microRNAs as examples of host restriction factors that target HIV-1. We point to countermeasures encoded by HIV-1 for moderating the potency of these cellular restriction functions.
Semi-invasive EM attack on FPGA RO PUFs and countermeasures (2011)

It is often argued that Physical Unclonable Functions (PUFs) are resistant against invasive and semi-invasive attacks since these attacks would damage the underlying PUF structure resulting in a different PUF response. In this paper, we demonstrate exemplarily that this assumption does not hold for a Ring Oscillator (RO) PUF implemented on a Xilinx Spartan 3 FPGA, where we were able to perform a semi-invasive attack. We present analysis methods to identify ring oscillator frequencies and to map them to their corresponding oscillators. We practically prove that it is possible to recover the generated RO PUF response bits with this approach. To harden RO PUFs against side-channel analysis, we also propose a RO PUF concept not leaking useful information through the side-channel of electro-magnetic radiation.
Understanding tubulin–Taxol interactions: Mutations that impart Taxol binding to yeast tubulin (2003)

We have successfully used mutagenesis to engineer Taxol (paclitaxel) binding activity in Saccharomyces cerevisiae tubulin. Taxol, a successful antitumor agent, acts by promoting tubulin assembly and stabilizing microtubules. Several structurally diverse antimitotic compounds, including the epothilones, compete with Taxol for binding to mammalian microtubules, suggesting that Taxol and these compounds share an overlapping binding site. However, Taxol has no effect on tubulin or microtubules from S. cerevisiae, whereas epothilone does. After considering data on Taxol binding to mammalian tubulin and recent modeling studies, we have hypothesized that differences in five key amino acids are responsible for the lack of Taxol binding to yeast tubulin. After changing these amino acids to those found in mammalian brain tubulin, we observed Taxol-related activity in yeast tubulin comparable to that in mammalian tubulin. Importantly, this experimental system can be used to reveal tubulin interactions with Taxol, the epothilones, and other Taxol-like compounds.
Hydroxylated Phytosiderophore Species Possess an Enhanced Chelate Stability and Affinity for Iron(III) (2000)

Graminaceous plant species acquire soil iron by the release of phytosiderophores and subsequent uptake of iron(III)-phytosiderophore complexes. As plant species differ in their ability for phytosiderophore hydroxylation prior to release, an electrophoretic method was set up to determine whether hydroxylation affects the net charge of iron(III)-phytosiderophore complexes, and thus chelate stability. At pH 7.0, non-hydroxylated (deoxymugineic acid) and hydroxylated (mugineic acid; epi-hydroxymugineic acid) phytosiderophores form single negatively charged iron(III) complexes, in contrast to iron(III)-nicotianamine. As the degree of phytosiderophore hydroxylation increases, the corresponding iron(III) complex was found to be less readily protonated. Measured pKa values of the amino groups and calculated free iron(III) concentrations in presence of a 10-fold chelator excess were also found to decrease with increasing degree of hydroxylation, confirming that phytosiderophore hydroxylation protects against acid-induced protonation of the iron(III)-phytosiderophore complex. These effects are almost certainly associated with intramolecular hydrogen bonding between the hydroxyl and amino functions. We conclude that introduction of hydroxyl groups into the phytosiderophore skeleton increases iron(III)-chelate stability in acid environments such as those found in the rhizosphere or the root apoplasm and may contribute to an enhanced iron acquisition.
Evaluation of a new enzyme-linked immunosorbent assay for the determination of neopterin. (2005)

The above mentioned neopterin assay as an alternative method to other ELISA kits and the HPLC is highly suited for automation and was especially evaluated as a simple, rapid and reproducible version for the Behring ELISA Processor BEP III during this study.
Prognostic significance of plasma vascular endothelial growth factor levels in patients with hormone-refractory prostate cancer treated on Cancer and Leukemia Group B 9480. (2001)

Although these data are exploratory and need to be confirmed in an independent data set, they suggest that VEGF may have clinical significance in patients with HRPC.
Homozygous Deletions and Recurrent Amplifications Implicate New Genes Involved in Prostate Cancer (2008)

Prostate cancer cell lines provide ideal in vitro systems for the identification and analysis of prostate tumor suppressors and oncogenes. A detailed characterization of the architecture of prostate cancer cell line genomes would facilitate the study of precise roles of various genes in prostate tumorigenesis in general. To contribute to such a characterization, we used the GeneChip 500K single nucleotide polymorphic (SNP) array for analysis of genotypes and relative DNA copy number changes across the genome of 11 cell lines derived from both normal and cancerous prostate tissues. For comparison purposes, we also examined the alterations observed in the cell lines in tumor/normal pairs of clinical samples from 72 patients. Along with genome-wide maps of DNA copy number changes and loss of heterozygosity for these cell lines, we report previously unreported homozygous deletions and recurrent amplifications in prostate cancers in this study. The homozygous deletions affected a number of biologically important genes, including PPP2R2A and BNIP3L identified in this study and CDKN2A/CDKN2B reported previously. Although most amplified genomic regions tended to be large, amplifications at 8q24.21 were of particular interest because the affected regions are relatively small, are found in multiple cell lines, are located near MYC, an oncogene strongly implicated in prostate tumorigenesis, and are known to harbor SNPs that are associated with inherited susceptibility for prostate cancer. The genomic alterations revealed in this study provide an important catalog of positional information relevant to efforts aimed at deciphering the molecular genetic basis of prostate cancer.
Circulating tumor antigen-specific regulatory T cells in patients with metastatic melanoma (2007)

Although it is accepted that regulatory T cells (T regs) contribute to cancer progression, most studies in the field consider nonantigen-specific suppression. Here, we show the presence of tumor antigen-specific CD4(+) T regs in the blood of patients with metastatic melanoma. These CD4(+) T regs recognize a broad range of tumor antigens, including gp100 and TRP1 (melanoma tissue differentiation antigens), NY-ESO-1 (cancer/testis antigen) and survivin (inhibitor of apoptosis protein (IAP) family antigen). These tumor antigen-specific T regs proliferate in peripheral blood mononuclear cells (PBMC) cultures in response to specific 15-mer peptides, produce preferentially IL-10 and express high levels of FoxP3. They suppress autologous CD4(+)CD25(-) T cell responses in a cell contact-dependent manner and thus share properties of both naturally occurring regulatory T cells and type 1 regulatory T cells. Such tumor antigen-specific T regs were not detected in healthy individuals. These tumor antigen-specific T regs might thus represent another target for immunotherapy of metastatic melanoma.
Phasing and matching units for the CFA (2002)

Crossed field antenna (CFA) theory and applications are widely discussed. The electrical characteristics of the two inputs of the CFA are very important and have to be analyzed and studied carefully. This analysis is considered in detail. In addition, a phasing and matching unit which are inserted between the transmitter and the CFA antenna are designed and executed to fulfil the analysis of this non-resonant antenna.
Genomewide Association Studies and Common Disease — Realizing Clinical Utility (2012)

Interview with Dr. David Hunter on genomewide association studies and their potential clinical utility in common diseases. (13:08)Download The value of GWAS for finding therapies for complex disease may seem dubious. But even if genetic variants confer modest risk and subtly alter biologic function, drugs mimicking their activity can have much more powerful effects. GWAS data analysis could identify key leads.
Desynchronization of epileptiform activity by extracellular current pulses in rat hippocampal slices. (1994)

1. A single cathodic current pulse applied in the somatic CA1 region of the hippocampus was found to induce a large decrease in the amplitude of the population spike. 2. Intracellular recordings showed intense cellular firing suggesting the amplitude decrease could not be attributed to a decrease in neuronal firing. 3. Simultaneous intracellular and extracellular potentials were recorded to analyse the synchronization of neuronal firing in the CA1 region. Action potentials were synchronized with the first population spike but this synchronization decreased with subsequent spikes. Histograms of the phase of the action potentials displayed a normal distribution. 4. Histograms of the phases of the action potentials following the application of the 'singular stimulus' (one producing a singular response) revealed a uniform distribution of the phases suggesting that the neuronal population was desynchronized. 5. This desynchronization effect of the singular stimulus was verified by double intracellular recordings. The simultaneous firing of two neurons could be desynchronized by the application of the singular stimulus. 6. These findings indicate that it is possible to desynchronize a neuronal pool with the application of a single current pulse. In addition, the results show that it is possible for a neuronal population to fire a large number of action potentials with no resulting evoked potentials in the extracellular space.
Remdesivir Inhibits SARS-CoV-2 in Human Lung Cells and Chimeric SARS-CoV Expressing the SARS-CoV-2 RNA Polymerase in Mice (2020)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the novel viral disease COVID-19. With no approved therapies, this pandemic illustrates the urgent need for broad-spectrum antiviral countermeasures against SARS-CoV-2 and future emerging CoVs. We report that remdesivir (RDV) potently inhibits SARS-CoV-2 replication in human lung cells and primary human airway epithelial cultures (EC<sub>50</sub> = 0.01 μM). Weaker activity is observed in Vero E6 cells (EC<sub>50</sub> = 1.65 μM) because of their low capacity to metabolize RDV. To rapidly evaluate in vivo efficacy, we engineered a chimeric SARS-CoV encoding the viral target of RDV, the RNA-dependent RNA polymerase of SARS-CoV-2. In mice infected with the chimeric virus, therapeutic RDV administration diminishes lung viral load and improves pulmonary function compared with vehicle-treated animals. These data demonstrate that RDV is potently active against SARS-CoV-2 in vitro and in vivo, supporting its further clinical testing for treatment of COVID-19.
420. A reaction of certain diazosulphonates derived from β-naphthol-1-sulphonic acid. Part XIII. Fission of the naphthalene nucleus and subsequent closure in two directions (1935)

F. M. Rowe, W. C. Dovey, B. Garforth, E. Levin, J. D. Pask and A. T. Peters, J. Chem. Soc., 1935, 1796 DOI: 10.1039/JR9350001796
Detection of Epstein-Barr virus-encoded small RNA 1 and latent membrane protein 1 in synovial lining cells from rheumatoid arthritis patients (1997)

Several investigators have demonstrated an association between Epstein-Barr virus (EBV) and the pathogenesis of rheumatoid arthritis (RA). However, there is no direct evidence that this virus exists in the synovial cells of patients with RA. We attempted to detect EBV in synovial cells from RA patients. Specimens of synovial tissues from 34 patients with RA and from 20 patients with osteoarthritis (OA), and from one patient with psoriatic arthritis as controls, were examined for evidence of the EBV by in situ hybridization. The specimens were also tested by immunoperoxidase staining for expression of the CD21 molecule (EBV receptor), EBV nuclear antigen (EBNA)-2 and latent membrane protein (LMP)-1. EBV-encoded small RNA-1 (EBER) was demonstrated in synovial lining cells from eight (23.5%) out of 34 RA patients but in none of 20 OA patients (P < 0.05) nor in the one psoriatic arthritis patient. Interestingly, EBER localized in synovial lining cells that were located at the apex of villus proliferating lesions. Furthermore, LMP-1 was also detected in synovial lining cells at the top of villus lesions. Nevertheless, CD19 and CD21 molecules, and EBNA-2 were not demonstrated in such lesions. The incidence of EBV-positive in synovial lining cells with severely infiltrated lymphocytes tended to be higher than that in moderately infiltrated ones. This is the first evidence that EBV exists in chronically inflamed synovial lining cells of human joints in RA.
Conserved terminal hairpin sequences of histone mRNA precursors are not involved in duplex formation with the U7 RNA but act as a target site for a distinct processing factor. (1989)

The hairpin loop structure and the downstream spacer element of histone mRNA precursors are both needed for efficient 3' end formation in vivo and in vitro. Though generally considered as a single processing signal, these two motifs are involved in different types of interaction with the processing machinery. Whereas RNA duplex formation between the downstream spacer element and the U7 small nuclear RNA is essential for processing, we show here that base pairing between the histone stem-loop structure and the U7 RNA is not relevant. Our experiments demonstrate that a processing factor other than the U7 RNA makes contact with the highly conserved hairpin structure of the histone precursor. The recognition of the target site by the processing factor is structure and sequence specific. Prevention of this interaction results in an 80% decrease of 3' cleavage efficiency in vitro. The hairpin binding factor is Sm-precipitable and can be partially separated from the U7 small nuclear ribonucleoprotein particle on a Mono Q column.
Lung Cancer That Harbors an HER2 Mutation: Epidemiologic Characteristics and Therapeutic Perspectives (2013)

This study, the largest to date dedicated to HER2-mutated NSCLC, reinforces the importance of screening for HER2 mutations in lung adenocarcinomas and suggests the potential efficacy of HER2-targeted drugs in this population.
Oncolytic viruses for the therapy of brain tumors and other solid malignancies a review (2003)

In spite of significant advances in the understanding of molecular processes in tumor biology that have led to the development of oncologic therapeutic strategies, the prognosis for several types of tumors (such as brain, pancreas, or hepatic malignancies) remains dismal. Without question, a strong need exists for continued investigations in new agents and new therapeutic regimens. The realization that several genes used by viruses in their lytic life cycle interact and/or complement the function of genes employed by cells in cellular events linked to cell cycle progression, apoptosis, and/or metabolism immediately suggests the development of treatment strategies wherein viral mutants could be employed as selective anticancer agents. Such viruses (designated as oncolytic viruses) can selectively grow in tumor cells, produce viral progeny in those cells, lyse them and release this progeny that can then infect additional cells in the tumor mass. A theoretical advantage of oncolytic viruses (OV) is that their numbers should augment within the tumor mass, a property that is lacking with drugs or radiation treatments. Additionally, Ovs' mode of tumor killing differs from standard anticancer agents, providing the possibility for synergistic interactions in multimodal tumor therapies. In this review, we will describe the development of OVs and briefly review the life cycle of their wild-type (wt) counterparts. We will also summarize published results from OV clinical trials and attempt to provide a perspective on research in this area.