gebhart/patrepeval huggingface dataset:
Characterization of hybridization between synthetic oligodeoxynuclotides and RNA in living cells (1995)

Cells internalized synthetic oligonucleotides (oligos) in culture. The hybridization of these molecules to target RNA in the living cell was subsequently detected and characterized after fixation of the cells, with or without previous detergent extraction. Hybridized oligo was distinguished from free oligo in the cell using an in situ reverse transcription technique. This assay exploited the ability of the hybridized oligo to prime synthesis of a specific cDNA strand; unhybridized oligo present in the cell could not act as a primer for reverse transcription. Phosphorothioate and fluorochrome-labeled phosphodiester oligo dT were found to enter cells rapidly and hybridize to poly (A) RNA within 30 min. Hybrids containing phosphorothioate oligo dT were detectable in cells after up to 4 h of efflux time. Phosphodiester bonded oligo dT containing covalently-linked fluorochromes appeared more stable in the cell than unmodified phosphodiester oligo dT; hybrids containing these oligos could be detected in cells as long as 18h after efflux began. The in situ transcription assay was also sensitive enough to detect hybridization of anti-actin oligos to actin mRNA in the cell. It is probable, therefore, that this assay can be used to help assess the efficacy of antisense oligos by their hybridization to a target mRNA in cells or tissues; hybridized oligos are more likely to induce a specific antisense effect. Additionally, this assay will help to identify probes that would be useful as stable hybridization tags to follow RNA movement in living cells.
Using empirical methods to assess the risks of mercury accumulation in fish from lakes receiving acid rain (1995)

Abstract It has been hypothesized that concentrations of mercury ([Hg]) in fish increase with increasing acidic deposition. Our investigation suggests that this hypothesis is false for three species of fish from Ontario lakes. Across Ontario, Canada, slightly lower average [Hg] in Lake Trout, Walleye and Northern Pike (controlled for fish length) were associated with regions receiving progressively greater rates of sulphate deposition. We also observed that lake concentration of dissolved organic carbon ([DOC]), not pH, alkalinity or sulphate ion concentration, was the strongest correlate of this residual fish Hg contamination. Path analysis also determined a net reduction in fish [Hg] at higher rates of sulphate deposition. However, this analysis indicated a far more complex web of interactions between sulphate deposition, water chemistry and fish [Hg] than simple correlation analysis could define. Path analysis provided empirical evidence in support of several previously described mechanisms interacting simultaneously to influence fish Hg accumulation. Based on these empirical observations, an alternate hypothesis is proposed whereby increasing sulphate deposition results in lower [DOC] levels in lakes which, in turn, cause a decline in fish Hg contamination.
Structure and mechanism of the reversible photoswitch of a fluorescent protein (2005)

Proteins that can be reversibly photoswitched between a fluorescent and a nonfluorescent state bear enormous potential in diverse fields, such as data storage, in vivo protein tracking, and subdiffraction resolution light microscopy. However, these proteins could hitherto not live up to their full potential because the molecular switching mechanism is not resolved. Here, we clarify the molecular photoswitching mechanism of asFP595, a green fluorescent protein (GFP)-like protein that can be transferred from a nonfluorescent "off" to a fluorescent "on" state and back again, by green and blue light, respectively. To this end, we establish reversible photoswitching of fluorescence in whole protein crystals and show that the switching kinetics in the crystal is identical with that in solution. Subsequent x-ray analysis demonstrated that upon the absorption of a green photon, the chromophore isomerizes from a trans (off) to a cis (on) state. Molecular dynamics calculations suggest that isomerization occurs through a bottom hula twist mechanism with concomitant rotation of both bonds of the chromophoric methine ring bridge. This insight into the switching mechanism should facilitate the targeted design of photoswitchable proteins. Reversible photoswitching of the protein chromophore system within intact crystals also constitutes a step toward the use of fluorescent proteins in three-dimensional data recording.
Enabling Blockchain Innovations with Pegged Sidechains (2014)

Since the introduction of Bitcoin[Nak09] in 2009, and the multiple computer science and electronic cash innovations it brought, there has been great interest in the potential of decentralised cryptocurrencies. At the same time, implementation changes to the consensuscritical parts of Bitcoin must necessarily be handled very conservatively. As a result, Bitcoin has greater difficulty than other Internet protocols in adapting to new demands and accommodating new innovation. We propose a new technology, pegged sidechains, which enables bitcoins and other ledger assets to be transferred between multiple blockchains. This gives users access to new and innovative cryptocurrency systems using the assets they already own. By reusing Bitcoin’s currency, these systems can more easily interoperate with each other and with Bitcoin, avoiding the liquidity shortages and market fluctuations associated with new currencies. Since sidechains are separate systems, technical and economic innovation is not hindered. Despite bidirectional transferability between Bitcoin and pegged sidechains, they are isolated: in the case of a cryptographic break (or malicious design) in a sidechain, the damage is entirely confined to the sidechain itself. This paper lays out pegged sidechains, their implementation requirements, and the work needed to fully benefit from the future of interconnected blockchains.
Some 7-Substituted 4-Aminoquinoline Derivatives (1946)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSome 7-Substituted 4-Aminoquinoline DerivativesAlexander R. Surrey and Henry F. HammerCite this: J. Am. Chem. Soc. 1946, 68, 1, 113–116Publication Date (Print):January 1, 1946Publication History Published online1 May 2002Published inissue 1 January 1946https://doi.org/10.1021/ja01205a036RIGHTS & PERMISSIONSArticle Views1423Altmetric-Citations75LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (479 KB) Get e-Alertsclose Get e-Alerts
Simple method for concentration of bacteria from large volumes of tap water (1980)

Membrane adsorption-elution techniques have made it possible to concentrate and detect small numbers of viruses in large volumes of water and wastewater, but no such methods are available for quantitative recovery of bacteria. A number of waterborne disease outbreaks of "unknown etiology" in the United States are suspected to have been caused by pathogens present in numbers too small to be detected by currently available methodology. The present study reports on the use of positively charged depth filters for the concentration and detection of bacteria in large volumes of tap water. In this method, dechlorinated tap water was passed, under positive pressure, through positively charged filter media (Zetaplus, 05S). More than 90% of seeded bacteria adsorbed to these filters at ambient pH levels. Adsorbed bacteria were eluted by passing a small volume of Trypticase soy broth in the direction opposite of the influent flow. By this method, Escherichia coli and Salmonella serovar B organisms in 20 liters of tap water were concentrated in a final volume of 50 ml, with an average recovery efficiency of greater than or equal to 30%.
2-Triazole-Substituted Adenosines:  A New Class of Selective A3Adenosine Receptor Agonists, Partial Agonists, and Antagonists (2006)

"Click chemistry" was explored to synthesize two series of 2-(1,2,3-triazolyl)adenosine derivatives (1-14). Binding affinity at the human A(1), A(2A), and A(3)ARs (adenosine receptors) and relative efficacy at the A(3)AR were determined. Some triazol-1-yl analogues showed A(3)AR affinity in the low nanomolar range, a high ratio of A(3)/A(2A) selectivity, and a moderate-to-high A(3)/A(1) ratio. The 1,2,3-triazol-4-yl regiomers typically showed decreased A(3)AR affinity. Sterically demanding groups at the adenine C2 position tended to reduce relative A(3)AR efficacy. Thus, several 5'-OH derivatives appeared to be selective A(3)AR antagonists, i.e., 10, with 260-fold binding selectivity in comparison to the A(1)AR and displaying a characteristic docking mode in an A(3)AR model. The corresponding 5'-ethyluronamide analogues generally showed increased A(3)AR affinity and behaved as full agonists, i.e., 17, with 910-fold A(3)/A(1) selectivity. Thus, N(6)-substituted 2-(1,2,3-triazolyl)adenosine analogues constitute a novel class of highly potent and selective nucleoside-based A(3)AR antagonists, partial agonists, and agonists.
Ophthalmic arachidonylethanolamide decreases intraocular pressure in normotensive rabbits (1995)

Arachidonylethanolamide (AEA) was the first anandamide to be identified as an endogenous ligand for the cannabinoid receptor of porcine brain. Since cannabinoids have shown some value in the reduction of ocular hypertension, the title compound was evaluated in normotensive rabbits as a possible topically applied agent for reducing intraocular pressure. AEA was dissolved in an aqueous solution of 2-hydroxy-propyl-beta-cyclodextrin. Single eyedrops (25 microliters) containing 3.13, 6.25, 31.25, 62.5 or 125.0 micrograms of AEA were instilled unilaterally into eyes of normotensive albino and pigmented rabbits. The intraocular pressures (IOPs) of these rabbits were then measured at fixed time intervals. The effect of AEA on IOP in treated and untreated (contralateral) eyes was similar in both types of rabbits. Administration of 31.25 micrograms of AEA caused an immediate IOP reduction in the treated eyes. AEA doses of 62.5 micrograms caused an initial increase and subsequent decrease of IOP in the treated eyes. In the untreated eyes, a marginal ocular hypotensive response of limited duration occurred immediately after administration of AEA at doses 31.25 or 62.5 micrograms. A significant increase (without subsequent decrease below baseline) in IOP occurred in treated eyes after a dose of 125.0 micrograms. The lowest dose (3.13 micrograms) did not have an effect on IOP. This study constitutes the first published demonstration that topical, unilateral administration of AEA significantly decreases IOP in normotensive albino and pigmented rabbits. Although the mechanism of action by which this compound produces its hypotensive effect in the eye is not known, the results suggest that AEA may prove useful in the investigation of glaucoma therapy.
Biomimetic Hydrogels with VEGF Induce Angiogenic Processes in Both hUVEC and hMEC (2010)

Angiogenesis is the process by which new blood vessels arise from the pre-existing vasculature. Human endothelial cells are known to be involved in three key cellular processes during angiogenesis: increased cell proliferation, degradation of the extracellular matrix during cell migration, and the survival of apoptosis. The above processes depend upon the presence of growth factors, such as vascular endothelial growth factor isoform 165 (VEGF(165)) that is released from the extracellular matrix as it is being degraded or secreted from activated endothelial cells. Thus, the goal of the current study is to develop a system with a backbone of polyethylene glycol (PEG) and grafted angiogenic signals to compare the initial angiogenic response of human umbilical vein endothelial cells (hUVEC) or human microvascular endothelial cells (hMEC). Adhesion ligands (PEG-RGDS) for cell attachment and PEG-modified VEGF(165) (PEG-VEGF(165)) are grafted into the hydrogels to encourage the angiogenic response. Our data suggest that our biomimetic system is equally effective in stimulating proliferation, migration, and survival of apoptosis in hMEC as compared to the response to hUVEC.
The nutritional quality of foods advertised on UK children's TV (2006)

With the increasing trend of childhood obesity, concerns have been raised about the influence of food advertising on children's eating habits. This paper describes a content analysis of food advertising on UK terrestrial children's television and of the nutritional quality of the food products advertised.
A functional study of miR-124 in the developing neural tube (2007)

Neural development is a highly orchestrated process that entails precise control of gene expression. Although microRNAs (miRNAs) have been implicated in fine-tuning gene networks, the roles of individual miRNAs in vertebrate neural development have not been studied in vivo. We investigated the function of the most abundant neuronal miRNA, miR-124, during spinal cord development. Neither inhibition nor overexpression of miR-124 significantly altered the acquisition of neuronal fate, suggesting that miR-124 is unlikely to act as a primary determinant of neuronal differentiation. Two endogenous targets of miR-124, laminin gamma 1 and integrin beta1, were identified, both of which are highly expressed by neural progenitors but repressed upon neuronal differentiation. Thus miR-124 appears to ensure that progenitor genes are post-transcriptionally inhibited in neurons.
LEAFY COTYLEDON1-LIKE Defines a Class of Regulators Essential for Embryo Development (2002)

Arabidopsis LEAFY COTYLEDON1 (LEC1) is a critical regulator required for normal development during the early and late phases of embryogenesis that is sufficient to induce embryonic development in vegetative cells. LEC1 encodes a HAP3 subunit of the CCAAT binding transcription factor. We show that the 10 Arabidopsis HAP3 (AHAP3) subunits can be divided into two classes based on sequence identity in their central, conserved B domain. LEC1 and its most closely related subunit, LEC1-LIKE (L1L), constitute LEC1-type AHAP3 subunits, whereas the remaining AHAP3 subunits are designated non-LEC1-type. Similar to LEC1, L1L is expressed primarily during seed development. However, suppression of L1L gene expression induced defects in embryo development that differed from those of lec1 mutants, suggesting that LEC1 and L1L play unique roles in embryogenesis. We show that L1L expressed under the control of DNA sequences flanking the LEC1 gene suppressed genetically the lec1 mutation, suggesting that the LEC1-type B domains of L1L and LEC1 are critical for their function in embryogenesis. Our results also suggest that LEC1-type HAP3 subunits arose from a common origin uniquely in plants. Thus, L1L, an essential regulator of embryo development, defines a unique class of plant HAP3 subunits.
Many novel mammalian microRNA candidates identified by extensive cloning and RAKE analysis (2006)

MicroRNAs are 20- to 23-nucleotide RNA molecules that can regulate gene expression. Currently > 400 microRNAs have been experimentally identified in mammalian genomes, whereas estimates go up to 1000 and beyond. Here we show that many more mammalian microRNAs exist. We discovered novel microRNA candidates using two approaches: testing of computationally predicted microRNAs by a modified microarray-based detection system, and cloning and sequencing of large numbers of small RNAs from different human and mouse tissues. Together these efforts experimentally identified 348 novel mouse and 81 novel human microRNA candidate genes. Most novel microRNAs candidates are not conserved beyond mammals, and ~10% are taxon-specific. Our analyses indicate that the entire microRNA repertoire is not remotely exhausted.
Reproductive Functions in Young Fathers and Grandfathers (1982)

Testicular functions were investigated in 23 grandfathers [60--88 yr old; 67 +/- 7.8 (mean +/- SD)], i.e. men with fertility proven earlier in life. They were recruited from a nonpatient population and led an active life, most of them with a permanent partner. The grandfathers were compared with a group of 20 unrelated healthy fathers, 24--37 years old (29.2 +/- 3.2). Whereas sperm density was higher in the older group, there were no significant differences in ejaculate volume and sperm morphology between the younger and older men. Sperm motility and seminal fructose, however, decreased with age. The fertilizing capacity of sperm as assessed in the heterologous ovum penetration test using zona pellucida-free hamster eggs did not decrease significantly with age. Whereas the basal serum testosterone and estradiol levels were not different between the younger and older men, the response to 2 days of hCG stimulation decreased significantly with age. This decrease was observed in older men whether they had frequent or infrequent sexual activity. Basal serum LH and FSH levels were elevated in the older men. The LH response to GnRH stimulation relative to basal; values was significantly reduce, while FSH responses did not change with age. We conclude that sperm counts and fertilizing capacity of sperm are not negatively influenced by old age, at least not in men with sustained sexual activity. However, the pituitary as well as the testis show signs of decreased endocrine reserve capacity in old age.
Three-item Direct Observation Screen (TIDOS) for autism spectrum disorder (2013)

We compared ratings on the Three-Item Direct Observation Screen test for autism spectrum disorders completed by pediatric residents with the Social Communication Questionnaire parent reports as an augmentative tool for improving autism spectrum disorder screening performance. We examined three groups of children (18–60 months) comparable in age (18–24 month, 24–36 month, 36–60 preschool subgroups) and gender distribution: n = 86 with Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.) autism spectrum disorders; n = 76 with developmental delay without autism spectrum disorders; and n = 97 with typical development. The Three-Item Direct Observation Screen test included the following (a) Joint Attention, (b) Eye Contact, and (c) Responsiveness to Name. The parent Social Communication Questionnaire ratings had a sensitivity of .73 and specificity of .70 for diagnosis of autism spectrum disorders. The Three-Item Direct Observation Screen test item Joint Attention had a sensitivity of .82 and specificity of .90, Eye Contact had a sensitivity of .89 and specificity of .91, and Responsiveness to Name had a sensitivity of .67 and specificity of .87. In the Three-Item Direct Observation Screen test, having at least one of the three items positive had a sensitivity of .95 and specificity of .85. Age, diagnosis of autism spectrum disorder, and developmental level were important factors affecting sensitivity and specificity. The results indicate that augmentation of autism spectrum disorder screening by observational items completed by trained pediatric-oriented professionals can be a highly effective tool in improving screening performance. If supported by future population studies, the results suggest that primary care practitioners will be able to be trained to use this direct procedure to augment screening for autism spectrum disorders in the community.
Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors (2007)

Many of the defining characteristics of human subtypes were conserved among the mouse models. Although no single mouse model recapitulated all the expression features of a given human subtype, these shared expression features provide a common framework for an improved integration of murine mammary tumor models with human breast tumors.
The dual kinase complex FAK-Src as a promising therapeutic target in cancer (2010)

Focal adhesion kinase (FAK) and steroid receptor coactivator (Src) are intracellular (nonreceptor) tyrosine kinases that physically and functionally interact to promote a variety of cellular responses. Plenty of reports have already suggested an additional central role for this complex in cancer through its ability to promote proliferation and anoikis resistance in tumor cells. An important role for the FAK/Src complex in tumor angiogenesis has also been established. Furthermore, FAK and Src have been associated with solid tumor metastasis through their ability to promote the epithelial mesenchymal transition. In fact, a strong correlation between increased FAK/Src expression/phosphorylation and the invasive phenotype in human tumors has been found. Additionally, an association for FAK/Src with resistances to the current anticancer therapies has already been established. Currently, novel anticancer agents that target FAK or Src are under development in a broad variety of solid tumors. In this article we will review the normal cellular functions of the FAK/Src complex as an effector of integrin and/or tyrosine kinase receptor signaling. We will also collect data about their role in cancer and we will summarize the most recent data from the FAK and Src inhibitors under clinical and preclinical development. Furthermore, the association of both these proteins with chemotherapy and hormonal therapy resistances, as a rationale for new combined therapeutic approaches with these novel agents, to abrogate treatment associated resistances, will also be reviewed.
Phosphorylation of P20 is associated with the actions of insulin in rat skeletal and smooth muscle (1999)

Although a large number of protein kinases/phosphatases involved in insulin's actions have been characterized recently, relatively few of the downstream phosphoproteins have been identified. We have employed two-dimensional gel electrophoresis-based proteome analysis to investigate the insulin-evoked phosphorylation cascade in rat soleus muscle. Insulin reproducibly increased phosphorylation of a 20-kDa protein with a pI value of 6.0, which was identified subsequently as a phospho-isoform of P20, a small heat-shock-related protein. The adenylyl cyclase activator, forskolin, decreased phosphorylation of this P20 isoform and increased phosphorylation of another two P20 isoforms, with pI values of 5.9 and 5.6. Two-dimensional peptide mapping revealed that the phospho-peptides of these three P20 isoforms are different. In contrast to its action in soleus muscle, insulin decreased phosphorylation of the P20 isoform with pI 6.0 and increased phosphorylation of the two isoforms with pI values of 5.9 and 5.6 in vascular smooth muscle. This effect is similar to that induced by vasodilatory stimuli, suggesting that insulin could exert its vasodilatory action by affecting phosphorylation of P20. In summary, these results demonstrate that insulin differently modulates phosphorylation of P20 in skeletal and smooth muscle, and suggest that P20 could be a potential modulator of insulin's functions in these tissues.