gebhart/patrepeval huggingface dataset:
Structurally distinct disintegrins contortrostatin and multisquamatin differentially regulate platelet tyrosine phosphorylation. (1994)

Tyrosine phosphorylation of multiple platelet proteins is regulated by the integrin alpha IIb beta 3. In order to further examine integrin-regulated tyrosine phosphorylation, we have used small Arg-Gly-Asp-containing snake venom proteins (termed disintegrins) that inhibit platelet aggregation to competitively block the agonist-induced binding of fibrinogen to alpha IIb beta 3. One structurally unique disintegrin, contortrostatin (which appears to be a disulfide-linked dimer of 13.5 kDa with two Arg-Gly-Asp sites), was found to trigger signaling events typically mediated by fibrinogen cross-linking of alpha IIb beta 3, as demonstrated by tyrosine phosphorylation of the tyrosine kinase pp72syk and a 140-kDa protein. Contortrostatin and another disintegrin, multisquamatin (a monomer of 5.7 kDa with a single Arg-Gly-Asp site), did not affect thrombin-induced platelet shape change, secretion, or integrin-independent tyrosine phosphorylation; however, they inhibited aggregation and aggregation-dependent tyrosine phosphorylation of numerous proteins, including the focal adhesion kinase pp125FAK. Our results suggest that structurally distinct disintegrins have varying effects on tyrosine phosphorylation; while monomeric multisquamatin and dimeric contortrostatin both inhibit aggregation-dependent tyrosine phosphorylation, contortrostatin also possesses a unique functional activity that allows it to activate an intracellular signaling pathway leading to tyrosine phosphorylation. This activity may be involved in the function of this snake venom protein on hemostasis.
Manipulation of host signalling pathways by anthrax toxins (2007)

Infectious microbes face an unwelcoming environment in their mammalian hosts, which have evolved elaborate multicelluar systems for recognition and elimination of invading pathogens. A common strategy used by pathogenic bacteria to establish infection is to secrete protein factors that block intracellular signalling pathways essential for host defence. Some of these proteins also act as toxins, directly causing pathology associated with disease. Bacillus anthracis, the bacterium that causes anthrax, secretes two plasmid-encoded enzymes, LF (lethal factor) and EF (oedema factor), that are delivered into host cells by a third bacterial protein, PA (protective antigen). The two toxins act on a variety of cell types, disabling the immune system and inevitably killing the host. LF is an extraordinarily selective metalloproteinase that site-specifically cleaves MKKs (mitogen-activated protein kinase kinases). Cleavage of MKKs by LF prevents them from activating their downstream MAPK (mitogen-activated protein kinase) substrates by disrupting a critical docking interaction. Blockade of MAPK signalling functionally impairs cells of both the innate and adaptive immune systems and induces cell death in macrophages. EF is an adenylate cyclase that is activated by calmodulin through a non-canonical mechanism. EF causes sustained and potent activation of host cAMP-dependent signalling pathways, which disables phagocytes. Here I review recent progress in elucidating the mechanisms by which LF and EF influence host signalling and thereby contribute to disease.
Interaction between the acceptor end of tRNA and the T box stimulates antitermination in the Bacillus subtilis tyrS gene: a new role for the discriminator base (1994)

The Bacillus subtilis tyrS gene is a member of a group of gram-positive aminoacyl-tRNA synthetase and amino acid biosynthesis genes which are regulated by transcription antitermination. Each gene in the group is specifically induced by limitation for the appropriate amino acid. This response is mediated by interaction of the cognate tRNA with the mRNA leader region to promote formation of an antiterminator structure. The tRNA interacts with the leader by codon-anticodon pairing at a position designated the specifier sequence which is upstream of the antiterminator. In this study, an additional site of possible contact between the tRNA and the leader was identified through covariation of leader mRNA and tRNA sequences. Mutations in the acceptor end of tRNA(Tyr) could suppress mutations in the side bulge of the antiterminator, in a pattern consistent with base pairing. This base pairing may thereby directly affect the formation and/or function of the antiterminator. The discriminator position of the tRNA, an important identity determinant for a number of tRNAs, including tRNA(Tyr), was shown to act as a second specificity determinant for assuring response to the appropriate tRNA. Furthermore, overproduction of an unchargeable variant of tRNA(Tyr) resulted in antitermination in the absence of limitation for tyrosine, supporting the proposal that uncharged tRNA is the effector in this system.
The optical–mechanical analogy in general relativity: New methods for the paths of light and of the planets (1996)

The optical–mechanical analogy involves the expression of geometrical optics and particle mechanics in the same mathematical language. In this paper, an especially simple version of the optical–mechanical analogy is extended to general relativity. A variational principle for the trajectories of photons and particles is obtained which is applicable to a broad class of metrics. This permits us to cast the exact equations of motion for both massive and massless particles into the form of Newtonian mechanics. The new equations of motion are illustrated by applications to the Schwarzschild metric.
Error control coding (2001)

The basic goal in digital communications is to transport bits of information without losing too much information along the way. The level of information loss that is tolerable/acceptable varies for different applications. The loss is measured in terms of the bit error rate, or BER. An interesting application that employs error control coding is a system with a storage medium such as a hard disk drive or a compact disc (CD). We can think of the channel as a block that causes errors to occur when a signal passes through it. Regardless of the error source, we can describe the problem as follows: when the transmitted signal arrives at the receiver after passing through the channel, the received data will have some bits that are in error. The system designer would like to incorporate ways to detect and correct these errors. The field that covers such digital processing techniques is known as error control coding.
Differential signaling via surface IgM is associated with VH gene mutational status and CD38 expression in chronic lymphocytic leukemia (2003)

The mutational status of tumor immunoglobulin V(H) genes is providing a powerful prognostic marker for chronic lymphocytic leukemia (CLL), with patients having tumors expressing unmutated V(H) genes being in a less favorable subset. However, the biologic differences correlating with V(H) gene status that could determine the clinical course of the disease are unknown. Here we show that differing responses to IgM ligation are closely associated with V(H) gene status. Specifically, 80% of cases with unmutated V(H) genes showed increased global tyrosine phosphorylation following IgM ligation, whereas only 20% of samples with mutated V(H) genes responded (P =.0002). There was also an association between response to IgM ligation and expression of CD38 (P =.015). The Syk kinase, critical for transducing B-cell receptor (BCR)- derived signals, was constitutively present in all CLL samples, and there was a perfect association between global phosphorylation and induction of phosphorylation/activation of Syk. Nonresponsiveness to anti-IgM could be circumvented by ligation of IgD (10 of 15 samples tested) or the BCR-associated molecule CD79alpha (12 of 15 samples tested). These results suggest that multiple mechanisms underlie nonresponsiveness to anti-IgM in CLL and that retained responsiveness to anti-IgM contributes to the poor prognosis associated with the unmutated subset of CLL. The prognostic power of the in vitro response to IgM ligation remains to be determined in a large series, but the simple technology involved may present an alternative or additional test for predicting clinical course.
SUBBAND-BASED PARAMETER OPTIMIZATION IN NOISE REDUCTION SCHEMES BY MEANS OF OBJECTIVE PERCEPTUAL QUALITY MEASURES (2006)

In general, noise reduction schemes for application in hearing-aids or car environments have parameters that are determined by technical distance measures or heuristically based on infor-mal listening by the algorithm developers. In [1] we have shown that quality measures based on psychoacoustic models are better suited to optimize single parameters in terms of the best subjec-tive overall quality than pure technical measures like, e.g., the signal-to-noise ratio. In other words, a test-bench based on ob-jective quality measures and several typical noise types can sup-port the search for the best-sounding noise reduction algorithms and their internal parameter settings. However, if the algorithms becomemore complex, e.g., because of frequency-dependent pa-rameters, a single broadband measure might not be feasible to assess optimal settings because of the high dimensionality of the parameter space. In this case a subband-based perceptual quality measure might be feasible. In this study, we exemplarily apply subband-based quality prediction to parameter optimization in a noise reduction algorithm based on auditory filters. 1.
State-of-the-art EUV materials and processes for the 7nm node and beyond (2017)

Extreme ultraviolet lithography (EUVL, λ = 13.5 nm) being the most likely candidate to manufacture electronic devices for future technology nodes is to be introduced in high volume manufacturing (HVM) at the 7 nm logic node, at least at critical lithography levels. With this impending introduction, it is clear that excellent resist performance at ultra-high printing resolutions (below 20 nm line/space L/S) is ever more pressing. Nonetheless, EUVL has faced many technical challenges towards this paradigm shift to a new lithography wavelength platform. Since the inception of chemically amplified resists (CARs) they have been the base upon which state-of-the art photoresist technology has been developed from. Resist performance as measured in terms of printing resolution (R), line edge roughness (LER), sensitivity (D or exposure dose) and exposure latitude (EL) needs to be improved but there are well known trade-off relationships (LRS trade-off) among these parameters for CARs that hamper their simultaneous enhancement. Here, we present some of the most promising EUVL materials tested by EUV interference lithography (EUV-IL) with the aim of resolving features down to 11 nm half-pitch (HP), while focusing on resist performance at 16 and 13 nm HP as needed for the 7 and 5 nm node, respectively. EUV-IL has enabled the characterization and development of new resist materials before commercial EUV exposure tools become available and is therefore a powerful research and development tool. With EUV-IL, highresolution periodic images can be printed by the interference of two or more spatially coherent beams through a transmission-diffraction grating mask. For this reason, our experiments have been performed by EUV-IL at Swiss Light Source (SLS) synchrotron facility located at the Paul Scherrer Institute (PSI). Having the opportunity to test hundreds of EUVL materials from vendors and research partners from all over the world, PSI is able to give a global update on some of the most promising materials tested.
Quantized Peak-Based Impulsive Noise Blanking in Power-Line Communications (2014)

Impulsive-noise (IN) over power-line channels can cause serious performance degradations. As such, many IN mitigation techniques have been proposed in the literature, the most common of which is the blanking technique. The conventional way to implement this technique, however, requires prior knowledge about the IN characteristics to identify the optimal blanking threshold (OBT). When such knowledge cannot be obtained, the performance deteriorates rapidly. To alleviate this, we propose a lookup table (LUT)-based algorithm with uniform quantization to utilize estimates of the peak-to-average power ratio at the receiver to determine the OBT. To fully evaluate the performance of the proposed method, we investigate the impact of quantization bits on the system performance in terms of signal-to-noise ratio (SNR) and symbol error rate under various IN scenarios. The results reveal that a 5-bit LUT is sufficient to achieve a gain of up to 3-dB SNR improvement relative to the conventional blanking method. It will also be shown that to maintain good performance, the resolution of quantization must be increased especially when the IN probability of occurrence is relatively high.
Metabolic compartmentalization in the human cortex and hippocampus: evidence for a cell- and region-specific localization of lactate dehydrogenase 5 and pyruvate dehydrogenase (2007)

These observations reveal a metabolic segregation, not only at the cellular but also at the regional level, that support the notion of metabolic compartmentalization between astrocytes and neurons, whereby lactate produced by astrocytes could be oxidized by neurons.
Retrospective review of colorectal cancer specimens in individuals younger than age 50 for microsatellite instability testing and DNA mismatch repair enzyme expression. (2011)

392 Background: Data from studies performed at tertiary referral centers suggest that the yield of patients with the underlying defect in hereditary non-polyposis colon cancer (HNPCC) could be improved by screening every colon cancer for the phenotypic expression of the MMR defect by immunohistochemistry (IHC) and/or an assay for microsatellite instability (MSI). We propose to determine the incidence of microsatellite unstable colon cancers and the incidence of absence of expression of DNA MMR enzymes in de-identified colorectal cancer specimens from patients under the age of 50 who have presented to Winthrop University Hospital over the past ten years. This incidence will be compared with those suggested by recent large retrospective studies in tertiary care centers. Methods: Immunoperoxidase staining for MLH1, MSH2, MSH6 and PMS2 were performed on formalin-fixed tissue. MSI assays were performed on microdissected DNA from paraffin-embedded tissue blocks. All cases were tested with five mononucleotide repeat markers (BAT-25, BAT-26, NR-21, NR-24 and MONO-27) and two pentanucleotide repeat markers (Penta C and Penta D). Tumor samples in which two or more altered monoclonal repeat markers were found out of five were classified as MSI-H. Results: Screening for expression of DNA mismatch repair enzymes and MSI in an enriched selected (by age <50) population of colorectal cancer patients resulted in detection of 7/51 (14%) specimens that were MSI-H and 7/61 (12%) that were “positive” for lack of expression of at least one DNA mismatch repair enzyme. Conclusions: Our results are similar to those reported in the literature in unselected series of patients with colorectal cancer. IHC staining or MSI analysis alone may be insufficient in selecting those colorectal cancer patients that should be referred for genetic testing for HNPCC. However, screening of an unselected population with both these modalities should have a low but clinically significant yield. Since other research have shown that traditional criteria such as the Bethesda guidelines are inadequate, we support the use of both measures prospectively in all colorectal cancer patients. No significant financial relationships to disclose.
Nicotinic Acetylcholine Receptor α3 mRNA in Rat Visual System After Monocular Deprivation (1997)

In situ hybridization was used to examine effects of monocular enucleation on nicotinic acetylcholine receptor subunit cc3 mRNA in the rat dLGNand visual cortex. After 28 days postoperative, there were no significant differences in α3 mRNA density between the contralateral (deprived) and ipsilateral (non-deprived) sides. The lack of obvious effects of visual deprivation on α3 mRNA density suggests that other factors, possibly intrinsic to dLGNand visual cortex, govern the postnatal expression of α3 mRNA.
Preparation of Gelatinous Reversible Addition−Fragmentation Chain Transfer Agents “RAFT Gel” via Chemoselective Polycondensations of a Dicarboxylic Acid Containing a Mercapto Group and Diols (2010)

The results of the model reactions with ethanol or 2-propanethiol and acetic acid showed that the dehydration condensation of the ethanol reaction was chemoselective and that thioesterification did not occur under the conditions used. We synthesized polyesters with pendant mercapto groups by dehydration polycondensations of diols and TMA, and as with the model reactions, esterification proceeded chemoselectively and thioesterification did not occur. The pendant mercapto-containing polyesters had Mns >1.0 × 104. We also demonstrated that the pendant mercapto groups could be chemically modified by glycosylation or cross-linked by TCDI to synthesize a gelatinous RAFT agent as a first example, which acted as a RAFT agent in a radical polymerization to afford poly(methyl methacrylate) with a narrow molecular weight distribution (Mn = 8.5 × 104, Mw/Mn = 1.47). These procedures could be used to produce new types of polyesters from monomers that differ in chirality and functionality and also nanoscale-reactive media containing RAFT agent as a cross-linker for controlled radical polymerization of vinyl monomers.
Synthesis and physicochemical properties of oligonucleotides built with either<i>α</i>-L or<i>β</i>-L nucleotides units and covalently linked to an acridine derivative (1991)

Modified deoxynucleosides 2′-deoxy- β-L-uridine, β-L-thymidine, α-L-thymidine, 2′-deoxy-β-L-adenosine and 2′-deoxy-α-L-adenosine were synthesized and assembled as homooligomers, respectively: octa-β-L-deoxyuridylates, octa β-L and α-L-thymidylates and tetra β-L and α-L-deoxyadenylates. These unnatural oligomers were then substituted with an acridine derivative. The binding studies of these modified oligonucleotides with D-ribo- and D-deoxyribopoly nucleotides were carried out by absorption spectros copy. While β-L-d(Up)8m5Acr, β-L-d(Tp)8m5Acr, α;-L- (Tp)8m5Acr, did not interact with poly(rA) and poly(dA), β-L-d(Up)4m5Acr, and α-L-d(Ap)4m5Acr, did form double and triple helices with poly(rU) and poly(dT), respectively. Their stability towards nuclease digestion was studied through comparison with that of octa-β-D thymidylate and tetra β-D-deoxyadenylate covalently linked to an acridine derivative. One endonuclease (nuclease P1 from Penicillium citrinum) and two exonucleases (a 3′-exonuclease from Crotalus durissus venom and a 5′-exonuclease extracted from calf thymus) were employed. β-L- and α-L-oligomers demonstrate a high resistance toward nuclease digestion.
The Footprints of Gut Microbial–Mammalian Co-Metabolism (2011)

Gut microbiota are associated with essential various biological functions in humans through a "network" of microbial-host co-metabolism to process nutrients and drugs and modulate the activities of multiple pathways in organ systems that are linked to different diseases. The microbiome impacts strongly on the metabolic phenotypes of the host, and hence, metabolic readouts can give insights into functional metagenomic activity. We applied an untargeted mass spectrometry (MS) based metabonomics approach to profile normal Wistar rats exposed to a broad spectrum β-lactam antibiotic imipenem/cilastatin sodium, at 50 mg/kg/daily for 4 days followed by a 14-day recovery period. In-depth metabolic phenotyping allowed identification of a panel of 202 urinary and 223 fecal metabolites significantly related to end points of a functional metagenome (p < 0.05 in at least one day), many of which have not been previously reported such as oligopeptides and carbohydrates. This study shows extensive gut microbiota modulation of host systemic metabolism involving short-chain fatty acids, tryptophan, tyrosine metabolism, and possibly a compensatory mechanism of indole-melatonin production. Given the integral nature of the mammalian genome and metagenome, this panel of metabolites will provide a new platform for potential therapeutic markers and mechanistic solutions to complex problems commonly encountered in pathology, toxicology, or drug metabolism studies.
Epigenetic editing of the Dlg4/PSD95 gene improves cognition in aged and Alzheimer’s disease mice (2017)

The Dlg4 gene encodes for post-synaptic density protein 95 (PSD95), a major synaptic protein that clusters glutamate receptors and is critical for plasticity. PSD95 levels are diminished in ageing and neurodegenerative disorders, including Alzheimer's disease and Huntington's disease. The epigenetic mechanisms that (dys)regulate transcription of Dlg4/PSD95, or other plasticity genes, are largely unknown, limiting the development of targeted epigenome therapy. We analysed the Dlg4/PSD95 epigenetic landscape in hippocampal tissue and designed a Dlg4/PSD95 gene-targeting strategy: a Dlg4/PSD95 zinc finger DNA-binding domain was engineered and fused to effector domains to either repress (G9a, Suvdel76, SKD) or activate (VP64) transcription, generating artificial transcription factors or epigenetic editors (methylating H3K9). These epi-editors altered critical histone marks and subsequently Dlg4/PSD95 expression, which, importantly, impacted several hippocampal neuron plasticity processes. Intriguingly, transduction of the artificial transcription factor PSD95-VP64 rescued memory deficits in aged and Alzheimer's disease mice. Conclusively, this work validates PSD95 as a key player in memory and establishes epigenetic editing as a potential therapy to treat human neurological disorders.
Steric Hindrance and Short Wave Length Bands in the Ultraviolet Spectra of Some Naphthalene and Diphenyl Derivatives<sup>1</sup> (1948)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSteric Hindrance and Short Wave Length Bands in the Ultraviolet Spectra of Some Naphthalene and Diphenyl Derivatives1R. A. Friedel, Milton Orchin, and Leslie ReggelCite this: J. Am. Chem. Soc. 1948, 70, 1, 199–204Publication Date (Print):January 1, 1948Publication History Published online1 May 2002Published inissue 1 January 1948https://pubs.acs.org/doi/10.1021/ja01181a057https://doi.org/10.1021/ja01181a057research-articleACS PublicationsRequest reuse permissionsArticle Views250Altmetric-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 InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts