gebhart/patrepeval huggingface dataset:
Specificity in the biosynthesis of the universal tRNA nucleoside N6-threonylcarbamoyl adenosine (t6A)—TsaD is the gatekeeper (2020)

<i>N</i><sup>6</sup>-threonylcarbamoyl adenosine (t<sup>6</sup>A) is a nucleoside modification found in all kingdoms of life at position 37 of tRNAs decoding ANN codons, which functions in part to restrict translation initiation to AUG and suppress frameshifting at tandem ANN codons. In Bacteria the proteins TsaB, TsaC (or C2), TsaD, and TsaE, comprise the biosynthetic apparatus responsible for t<sup>6</sup>A formation. TsaC(C2) and TsaD harbor the relevant active sites, with TsaC(C2) catalyzing the formation of the intermediate threonylcarbamoyladenosine monophosphate (TC-AMP) from ATP, threonine, and CO<sub>2</sub>, and TsaD catalyzing the transfer of the threonylcarbamoyl moiety from TC-AMP to A<sub>37</sub> of substrate tRNAs. Several related modified nucleosides, including hydroxynorvalylcarbamoyl adenosine (hn<sup>6</sup>A), have been identified in select organisms, but nothing is known about their biosynthesis. To better understand the mechanism and structural constraints on t<sup>6</sup>A formation, and to determine if related modified nucleosides are formed via parallel biosynthetic pathways or the t<sup>6</sup>A pathway, we carried out biochemical and biophysical investigations of the t<sup>6</sup>A systems from <i>E. coli</i> and <i>T. maritima</i> to address these questions. Using kinetic assays of TsaC(C2), tRNA modification assays, and NMR, our data demonstrate that TsaC(C2) exhibit relaxed substrate specificity, producing a variety of TC-AMP analogs that can differ in both the identity of the amino acid and nucleotide component, whereas TsaD displays more stringent specificity, but efficiently produces hn<sup>6</sup>A in <i>E. coli</i> and <i>T. maritima</i> tRNA. Thus, in organisms that contain modifications such as hn<sup>6</sup>A in their tRNA, we conclude that their origin is due to formation via the t<sup>6</sup>A pathway.
Effect of higher-order statistics of images on signal detection performance of human observers (1991)

Recent work has shown that a linear discriminant model derived from the work of Harold Hotelling can account for a significant body of psychophysical data. 1-3 This model utilizes only the first- and second-order statistics of the image and is insensitive to the shape of the grey level histogram. A natural question is whether the human observer is also insensitive to the shape of the histogram or whether human observer performance is sensitive to higher-order statistics in a image. To answer this question, a psychophysical study was conducted. The images viewed by human observers were simulated ones with inhomogeneous, random backgrounds, and Poisson noise. The mean, variance, and autocorrelation function of the images were controlled to be the same for all images. The grey level histograms of half of the images were designed to be distinctly non-Gaussian, while the other half had Gaussian histograms. Thus the first- and second-order statistics were constant, and only higher-orders were variable. Our results indicate that human detectability is independent of the shape of the grey level histograms, and that the Hotelling observer remains a good predictor of human performance in spite of this variability.
Matryoshka: Hiding Secret Communication in Plain Sight (2016)

We want to enable a pair of communicating users to exchange secret messages while hiding the fact that secret communication is taking place. We propose a linguistic steganography approach, where each human message is hidden in another human-like message. A hard open question is how to keep the steganographic message small -- existing related tools tend to blow up its size, thereby revealing the use of steganography. We encrypt by compressing each message, mapping it to a plausible sequence of words (using a language model), and letting the human user edit the outcome to produce a human-like message; we decrypt with a Viterbi-like state decoder. Our approach aims in producing text that a human can edit and fix with minimal effort. As a first step, we build a prototype of our system that helps users encrypt English messages (into English messages), and we report on first experiments on Mechanical Turk.
Characterization of Neoagarooligosaccharide Hydrolase BpGH117 from a Human Gut Bacterium Bacteroides plebeius (2021)

α-Neoagarobiose (NAB)/neoagarooligosaccharide (NAO) hydrolase plays an important role as an exo-acting 3,6-anhydro-α-(1,3)-L-galactosidase in agarose utilization. Agarose is an abundant polysaccharide found in red seaweeds, comprising 3,6-anhydro-L-galactose (AHG) and D-galactose residues. Unlike agarose degradation, which has been reported in marine microbes, recent metagenomic analysis of <i>Bacteroides plebeius</i>, a human gut bacterium, revealed the presence of genes encoding enzymes involved in agarose degradation, including α-NAB/NAO hydrolase. Among the agarolytic enzymes, <i>Bp</i>GH117 has been partially characterized. Here, we characterized the exo-acting α-NAB/NAO hydrolase <i>Bp</i>GH117, originating from <i>B. plebeius</i>. The optimal temperature and pH for His-tagged <i>Bp</i>GH117 activity were 35 °C and 9.0, respectively, indicative of its unique origin. His-tagged <i>Bp</i>GH117 was thermostable up to 35 °C, and the enzyme activity was maintained at 80% of the initial activity at a pre-incubation temperature of 40 °C for 120 min. <i>K<sub>m</sub></i> and <i>V<sub>max</sub></i> values for NAB were 30.22 mM and 54.84 U/mg, respectively, and <i>k<sub>cat</sub>/K<sub>m</sub></i> was 2.65 s<sup>-1</sup> mM<sup>-1</sup>. These results suggest that His-tagged <i>Bp</i>GH117 can be used for producing bioactive products such as AHG and agarotriose from agarose efficiently.
DELVING INTO THE WITTIG REACTION-STEREOCHEMISTRY AND MECHANISM. STEREOCHEMICAL IDIOSYNCRASIES AND MECHANISTIC IMPLICATIONS1 (1986)

Abstract Non-stabilized triphenylphosphorus ylides bearing anionic groups can react with aldehydes to give alkene mixtures anomalously enriched in the E isomer [ref. 7]. To explain this phenomenon, we sought to study both cis and trans oxaphosphetane (OP) intermediates at low temperature. The observation of both intermediates was achieved for the first time by the use of high-field H-1, P-31, and C-13 NMR spectroscopy in various instances. We have monitored some Wittig reactions in detail via NMR-based kinetic measurements of OP's and alkenes. In certain cases, OP's equilibrate, presumably by reaction reversal to aldehyde and ylide, to introduce a measure of thermodynamic control into the Wittig reaction. Thermodynamic control accounts for a large portion of the excess E stereoselectivity observed in going from a triphenyl to trialkyl (i.e., butyl) phosphorus ylide. Quenching experiments with HBr and the deprotonation of erythro and threo beta-hydroxyphosphonium salts are also discussed. Attempts to investigate reactions of stabilized and semi-stabilized ylides in an analogous manner were not fruitful.
A Hundred Years of Insulin Innovation: When Science Meets Technology (2021)

The story of insulin development is a remarkable example of what can be accomplished in medicine when academic science meets translational biotechnology. The foundation was laid 100 years ago this year with the discovery of insulin in Toronto in 1921, prompting a Nobel Prize in 1923.

The discovery made by Banting and Best (1) was so spectacular and of such importance for many people that it immediately led to collaboration with industry partners, most notably Eli Lilly in the U.S. and what became Novo Nordisk in Europe. One of the founding fathers of Novo Nordisk, Dr. August Krogh, was himself a Nobel Prize laureate. Krogh understood the scientific significance of the insulin discovery and partnered with people skilled in medicine as well as in technological development and upscaling. In the following decades, academic discoveries such as insulin crystallization (2) and binding of zinc (3) and protamine (4) immediately translated to benefits on insulin product characteristics that are of importance even today. Seminal discoveries in academia in the 1950s and 1960s unraveled the amino acid sequence as well as the secondary, tertiary, and quaternary insulin structures. These academic endeavors were led by Nobel Laureates Sanger (5) and Hodgkin (6), respectively. …
LiOH promoted allomerization of pyropheophorbide a. A convenient synthesis of 132-oxopyropheophorbide a and its unusual enolization (1998)

Treatment of pyropheophorbide a with aqueous LiOH–THF gave the corresponding enolate, which on in situ oxidation produced the corresponding 132-oxo derivative in 79% yield; prolonged autoxidation gave purpurin-18 and purpurin-5 as major products and a mechanism for the formation of 12-formyl derivative from 132-oxopyropheophorbide a under unusual enolization is discussed; the electronic absorption spectroscopy data of the enolic intermediates showed a considerable perturbation in the π-systems of the macrocycle.
Supplementary Figure 5 from A Novel Epigenetic Signature for Early Diagnosis in Lung Cancer (2023)

&lt;p&gt;Heatmap representing the patients' methylation profile for the four genes involved in the prediction model and Nomogram for prediction of cancer risk, constructed using the coefficients of our combined logistic regression model as weights.&lt;/p&gt;
Foxp4 Is Dispensable for T Cell Development, but Required for Robust Recall Responses (2012)

Transcription factors regulate T cell fates at every stage of development and differentiation. Members of the Foxp family of forkhead transcription factors are essential for normal T lineage development; Foxp3 is required for T regulatory cell generation and function, and Foxp1 is necessary for generation and maintenance of naïve T cells. Foxp4, an additional member of the Foxp family, is highly homologous to Foxp1 and has been shown to dimerize with other Foxp proteins. We report the initial characterization of Foxp4 in T lymphocytes. Foxp4 is expressed in both thymocytes and peripheral CD4(+) and CD8(+) T cells. We used a CD4Cre mediated approach to evaluate the cell autonomous role for Foxp4 in murine T lymphocytes. T cell development, peripheral cellularity and cell surface phenotype are normal in the absence of Foxp4. Furthermore, Foxp3(+) T regulatory cells develop normally in Foxp4 deficient animals and naïve Foxp4 deficient CD4 T cells can differentiate to inducible T regulatory cells in vitro. In wild-type T cells, expression of Foxp4 increases following activation, but deletion of Foxp4 does not affect T cell proliferative responses or in vitro effector T cell differentiation. In vivo, despite effective control of Toxoplasma gondii and acute lymphocytic choriomeningitis virus infections, effector cytokine production during antigen specific recall responses are reduced in the absence of Foxp4. We conclude that Foxp4 is dispensable for T cell development, but necessary for normal T cell cytokine recall responses to antigen following pathogenic infection.
Cholesterol Accumulation in Heterotransplanted Renal Cell Cancer (1983)

To date there have been no in vivo studies of the known propensity of human renal cell cancer (RCC) to accumulate large amounts of cholesterol. Caki-1, a human RCC line, was grown in the cheek pouches of immunosuppressed golden Syrian hamsters. Analysis of cholesterol levels revealed 2 to 4 times as much cholesterol in the heterotransplants as in any of the host tissues. After intraperitoneal injection of tumor-bearing hamsters with 4-14C-cholesterol, the tumors accumulated less radioactivity than did hamster liver and no more radioactivity than did hamster kidney or cheek pouch. It appears that accumulation of cholesterol by human RCC is not dependent on extensive uptake of extracellular cholesterol. Instead, an intrinsic defect in the cellular regulation of cholesterol synthesis and efflux is more likely to be responsible.
Network medicine links SARS-CoV-2/COVID-19 infection to brain microvascular injury and neuroinflammation in dementia-like cognitive impairment (2021)

Our results suggest significant mechanistic overlap between AD and COVID-19, centered on neuroinflammation and microvascular injury. These results help improve our understanding of COVID-19-associated neurological manifestations and provide guidance for future development of preventive or treatment interventions, although causal relationship and mechanistic pathways between COVID-19 and AD need future investigations.
Verschluss von Nahtinsuffizienzen und iatrogenen Perforationen am oberen Gastrointestinaltrakt mittels endoskopischer Naht am Menschen (2010)

Einleitung: Nahtinsuffizienzen oder iatrogene Perforationen am oberen Gastrointestinaltrakt sind eine schwierige klinische Herausforderung. Die chirurgische Revision ist die Standardtherapie, ist aber mit hoher Invasivität und einer Gesamtmortalität von bis zu 30% verbunden. Endoskopische Verfahren wie Clipping, endoskopische Nahtverfahren und Stenteinlage sind noch nicht ausreichend etabliert.
Synthesis, Antidepressant Evaluation and Docking Studies of Long‐Chain Alkylnitroquipazines as Serotonin Transporter Inhibitors (2013)

Twelve alkyl analogues (1-12) of the high-affinity serotonin transporter (SERT) inhibitor 6-nitroquipazine (6-NQ) were synthesized and studied using in vitro radioligand competition binding assays to determine their binding affinity (Ki ). The putative antidepressant activity of five of the binders with the highest SERT binding affinities was studied by the forced swim and locomotor activity mouse tests. The three-dimensional (3D) structures of 8 and 9 were determined using NOE NMR technique. Flexible docking of the compounds was undertaken to illustrate the binding of the compounds in the SERT model. Our results showed that several of the 6-NQ analogues are high-affinity SERT inhibitors and indicated that the octyl (8), decyl (10) and dodecyl (12) 6-NQ analogues exhibit moderate antidepressant activity.
Novel interleukin 2 (IL-2) receptor appears to mediate IL-2-induced activation of natural killer cells. (1988)

A novel IL-2 receptor, distinct from the Tac protein, has been identified on the surface of purified human natural killer (NK) cells by chemical cross-linking of 125I-IL-2. This protein is approximately 70,000 D in size (p70) and appears to be identical to the recently recognized second subunit of the human high affinity IL-2 receptor complex. Scatchard analysis of 125I-IL-2 binding to purified NK cells revealed approximately 2,300 p70 binding sites per cell with an apparent dissociation constant of 200 pM, a value intermediate between the previously recognized high and low affinity forms of the human IL-2 receptor. The monoclonal anti-Tac antibody did not inhibit the cross-linking of 125I-IL-2 to the p70 binding sites present on NK cells. Functionally, the addition of high concentrations of recombinant IL-2 to the enriched NK cells promoted a rapid augmentation of cytolytic activity and a more delayed increase in cellular proliferation. Anti-Tac effectively blocked the IL-2-induced proliferative response in these cells, but failed to alter the enhancement of cytotoxicity. Analysis of NK cytoplasmic RNA isolated at various time points after IL-2 stimulation revealed the rapid induction of c-myb and Tac gene expression that was also not inhibited by the anti-Tac antibody. These findings suggest that IL-2 binding to the p70 receptor constitutively expressed on the surface of NK cells may mediate both the development of increased cytolytic activity and rapid changes in gene expression. The activation of the Tac gene may in turn permit the formation of the high affinity IL-2 receptor complex (comprised of at least the Tac and p70 proteins) that appears to transduce the requisite signals involved in NK cell proliferation.
Les web services sémantiques, automate et intégration. I. Introduction, éléments et scénarios, découverte de services web (2009)

National audience
A Hyperdense Semantic Domain for Discontinuous Behavior in Physical System Models (2013)

Abstract. Multiple time models have been proposed for the formalization of hybrid dynamic system behavior. The superdense notion of time is a well-known time model for describing event-based systems where several events can occur simultaneously. Hyperreals provide a domain for defining the semantics of hybrid models that is elegantly aligned with first principles in physics. This paper discusses the value of both time models and shows how approximating di↵erent physical e↵ects is best expressed over di↵erent domains. Finally, the formalization and interaction of two types of discontinuities observed in hybrid systems, mythical modes and pinnacles, are explored. This analysis helps specify semantics that combine continuous-time behavior with discontinuities in the computational system. 1
Model for predicting the photoreactions and relative quantum yields of transition metal and organometallic complexes. II. Cobalt(III) and rhodium(III) (1973)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTModel for predicting the photoreactions and relative quantum yields of transition metal and organometallic complexes. II. Cobalt(III) and rhodium(III)Jeffrey I. ZinkCite this: Inorg. Chem. 1973, 12, 5, 1018–1024Publication Date (Print):May 1, 1973Publication History Published online1 May 2002Published inissue 1 May 1973https://pubs.acs.org/doi/10.1021/ic50123a010https://doi.org/10.1021/ic50123a010research-articleACS PublicationsRequest reuse permissionsArticle Views89Altmetric-Citations21LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Hypotensive mechanism of [Leu13]motilin in dogs in vivo and in vitro (1998)

The effects of [Leu 13 ]motilin were examined in vivo after its intravenous administration into anesthetized dogs and in vitro with isolated preparations of canine mesenteric artery. [Leu 13 ]Motilin (0.1-10 nmol·kg -1 , i.v.) induced both strong and clustered phasic contractions in the gastric antrum and duodenum. At doses of over 1 nmol·kg -1 , [Leu 13 ]motilin also produced transient decreases in arterial blood pressure, left ventricular pressure, maximum rate of rise of left ventricular pressure, and total peripheral resistance, and an increase in aortic blood flow and heart rate. A selective motilin antagonist, GM-109 (Phe-cyclo[Lys-Tyr(3-tBu)-betaAla]betatrifluoroacetate), completely abolished the gastric antrum and duodenal motor responses induced by [Leu 13 ]motilin. In contrast, hypotension induced by [Leu 13 ]motilin (1 nmol·kg -1 ) was unchanged in the presence of GM-109. In isolated mesenteric artery preparations precontracted with U-46619 (10 -7 M), [Leu 13 ]motilin (10 -8 -10 -5 M) induced an endothelium-dependent relaxation, and this was inhibited by a pretreatment with N omega -nitro-L-arginine, a competitive inhibitor of NO synthase (10 -4 M). A high dose (10 -4 M) of GM-109 slightly decreased [Leu 13 ]motilin-induced relaxation, and shifted the concentration-response curve of [Leu 13 ]motilin to the right. However, the pA 2 value (4.09) of GM-109 for [Leu 13 ]motilin in the present study was conspicuously lower than that previously demonstrated in the rabbit duodenum (7.37). These results suggest that [Leu 13 ]motilin induces hypotension via the endothelial NO-dependent relaxation mechanism and not through the receptor type that causes upper gastrointestinal contractions.Key words: motilin, gastrointestinal motility, hypotension, hemodynamics, anesthetized dog, mesenteric artery, endothelium, nitric oxide.
Human homologs of TU transposon sequences: polypurine/polypyrimidine sequence elements that can alter DNA conformation in vitro and in vivo. (1986)

We previously have shown that homologs of the outer domain segment of the inverted repeat termini (IVR-OD) of the sea urchin TU transposons are conserved among multiple eucaryotic species, including humans. We report here that two cloned human DNA IVR-OD homologs, Hut2 and Hut17, consist of a series of tandem repeats of the trimer AGG/TCC, forming segments (313 and 221 base pairs in length, respectively) of polypurine/polypyrimidine (pPu/pPy or "Puppy") asymmetry in the two DNA strands; these are punctuated at certain sites with variant trimers, which are different for the two clones. Sequences homologous to the Hut2 pPu/pPy tract exist at multiple sites in the DNA of a wide variety of eucaryotes. Hybridization of human DNA with a Hut2 probe or with a previously described chicken DNA pPu/pPy sequence indicates that pPu/pPy sequences can be grouped into families distinguishable by the extent of their homology with each probe at different hybridization stringencies. Moreover, particular pPu/pPy tracts show species-specific differences in their distribution. Both the Hut2 and Hut17 pPu/pPy tracts are cleaved by S1 nuclease when tested on supercoiled plasmids. Most if not all of the 313-base-pair Hut2 pPu/pPy tract is also sensitive to S1 in its native location in HeLa cell chromatin, indicating that the sequence contains conformational information that can be expressed in vivo. This view is supported by evidence that exogenously derived Hut2 pPu/pPy tracts introduced into mouse L cells and integrated in chromatin can assume an S1-sensitive conformation.
Latrophilin-2 repels Teneurin-3+ hippocampal axons during target selection (2020)

Spatial- and object-related signals are preferentially processed through the medial and lateral hippocampal networks (MHN and LHN), respectively1,2. MHN comprises interconnected medial entorhinal cortex, proximal CA1 (pCA1), and distal subiculum (dSub), whereas the LHN comprises interconnected lateral entorhinal cortex, distal CA1, and proximal subiculum3,4. Previously, we showed that Teneurin-3 (Ten3) has matching expression in all interconnected regions of the MHN and is required in both CA1 and subiculum for the precise pCA1->dSub axon targeting through homophilic attraction5. Can matching gene expression in interconnected nodes of the LHN also contribute to hippocampal network assembly? Here, we discovered that latrophilin-2 (Lphn2), an adhesion GPCR known to bind teneurins6-8, has matching expression in the LHN that is complementary to Ten3. Viral-genetic perturbations in vivo revealed that Ten3+ pCA1 axons are repelled by ectopic expression of Lphn2 in dSub, and ectopically invade proximal subiculum deleted for Lphn2. Simultaneous subiculum deletion of Lphn2 and Ten3 causes Ten3+ pCA1 axon mistargeting reflecting loss of both repulsion and attraction. Our findings demonstrate that Lphn2 acts as a repulsive ligand for Ten3+ axons, identify Ten3 as a receptor for both repulsive and attractive ligands in the same axon during target choice, and reveal how a Ten3->Ten3, Lphn2->Lphn2 rule directs the precise assembly of functional hippocampal networks.