gebhart/patrepeval huggingface dataset:
eIF2α Phosphorylation-Dependent Translation in CA1 Pyramidal Cells Impairs Hippocampal Memory Consolidation without Affecting General Translation (2010)

Protein synthesis inhibitor antibiotics are widely used to produce amnesia, and have been recognized to inhibit general or global mRNA translation in the basic translational machinery. For instance, anisomycin interferes with protein synthesis by inhibiting peptidyl transferase or the 80S ribosomal function. Therefore, de novo general or global protein synthesis has been thought to be necessary for long-term memory formation. However, it is unclear which mode of translation-gene-specific translation or general/global translation-is actually crucial for the memory consolidation process in mammalian brains. Here, we generated a conditional transgenic mouse strain in which double-strand RNA-dependent protein kinase (PKR)-mediated phosphorylation of eIF2alpha, a key translation initiation protein, was specifically increased in hippocampal CA1 pyramidal cells by the chemical inducer AP20187. Administration of AP20187 significantly increased activating transcription factor 4 (ATF4) translation and concomitantly suppressed CREB-dependent pathways in CA1 cells; this led to impaired hippocampal late-phase LTP and memory consolidation, with no obvious reduction in general translation. Conversely, inhibition of general translation by low-dose anisomycin failed to block hippocampal-dependent memory consolidation. Together, these results indicated that CA1-restricted genetic manipulation of particular mRNA translations is sufficient to impair the consolidation and that consolidation of memories in CA1 pyramidal cells through eIF2alpha dephosphorylation depends more on transcription/translation of particular genes than on overall levels of general translation. The present study sheds light on the critical importance of gene-specific translations for hippocampal memory consolidation.
Preparation of 2- and 4-Substituted Quinolines from 1-(2-Quinolyl)- and 1-(4-Quinolyl)-pyridinium Salts (1964)

Heating of 1-(4-quinolyl)- or 1-(2-quinolyl)-pyridinium salt with various nucleophilic reagents (amine hydrochloride, hydroxyamine hydrochloride, phenols, thiophenols, phosphorus pentachloride, etc.) generally results in exchange reaction between the pyridinium group and the reagent in a considerably good yield. Some side reaction also occurs but this reaction can be used fairly extensively for the synthesis of 4- or 2-substituted quinolines.
Legacy System Modernization Strategies (2001)

Abstract : Modernization of legacy enterprise systems introduces many challenges due to the size, complexity, and frailty of the legacy systems. Size and complexity issues often dictate that these systems are incrementally modernized, and new functionality is incrementally deployed before the modernization effort is concluded. This in turn requires that legacy components operate side by side with modernized components in an operation system, introducing additional problems. In this report we discuss some alternative development approaches for incrementally modernizing legacy systems, including consideration of the advantages and disadvantages of each approach. These development alternatives can be mapped against the peculiarities of a particular modernization effort to recommend an appropriate approach.
BitShred (2011)

The sheer volume of new malware found each day is growing at an exponential pace. This growth has created a need for automatic malware triage techniques that determine what malware is similar, what malware is unique, and why. In this paper, we present BitShred, a system for large-scale malware similarity analysis and clustering, and for automatically uncovering semantic inter- and intra-family relationships within clusters. The key idea behind BitShred is using feature hashing to dramatically reduce the high-dimensional feature spaces that are common in malware analysis. Feature hashing also allows us to mine correlated features between malware families and samples using co-clustering techniques. Our evaluation shows that BitShred speeds up typical malware triage tasks by up to 2,365x and uses up to 82x less memory on a single CPU, all with comparable accuracy to previous approaches. We also develop a parallelized version of BitShred, and demonstrate scalability within the Hadoop framework.
Sugars modulate an unusual mode of control of the cell-wall invertase gene ( Incw 1) through its 3′ untranslated region in a cell suspension culture of maize (1999)

We show here that a cell-wall invertase encoded by the Incw1 gene is regulated at both the transcriptional and posttranscriptional levels by sugars in a heterotrophic cell suspension culture of maize. The Incw1 gene encoded two transcripts: Incw1-S (small) and Incw1-L (large); the size variation was attributable to different lengths in the 3' untranslated region. Both metabolizable and nonmetabolizable sugars induced Incw1-L RNA apparently by default. However, only the metabolizable sugars, sucrose and D-glucose, were associated with the increased steady-state abundance of Incw1-S RNA, the concomitant increased levels of INCW1 protein and enzyme activity, and the downstream metabolic repression of the sucrose synthase gene, Sh1. Conversely, nonmetabolizable sugars, including the two glucose analogs 3-O-methylglucose and 2-deoxyglucose, induced greater steady-state levels of the Incw1-L RNA, but this increase did not lead to either an increase in the levels of the INCW1 protein/enzyme activity or the repression of the Sh1 gene. We conclude that sugar sensing and the induction of the Incw1 gene is independent of the hexokinase pathway. More importantly, our results also suggest that the 3' untranslated region of the Incw1 gene acts as a regulatory sensor of carbon starvation and may constitute a link between sink metabolism and cellular translation in plants.
Recommendation as classification: using social and content-based information in recommendation (1998)

Recommendation systems make suggestions about arti-facts to a user. For instance, they may predict whether a user would be interested in seeing a particular movie. Social recomendation methods collect ratings of arti-facts from many individuals and use nearest-neighbor techniques to make recommendations to a user concern-ing new artifacts. However, these methods do not use the significant amount of other information that is of-ten available about the nature of each artifact-- such as cast lists or movie reviews, for example. This paper presents an inductive learning approach to recommen-dation that is able to use both ratings information and other forms of information about each artifact in pre-dicting user preferences. We show that our method outperforms an existing social-filtering method in the domain of movie recommendations on a dataset of more than 45,000 movie ratings collected from a community of over 250 users.
Synthesis and Biochemical Evaluation of Thiochromanone Thiosemicarbazone Analogues as Inhibitors of Cathepsin L (2012)

A series of 36 thiosemicarbazone analogues containing the thiochromanone molecular scaffold functionalized primarily at the C-6 position were prepared by chemical synthesis and evaluated as inhibitors of cathepsins L and B. The most promising inhibitors from this group are selective for cathepsin L and demonstrate IC50 values in the low nanomolar range. In nearly all cases, the thiochromanone sulfide analogues show superior inhibition of cathepsin L as compared to their corresponding thiochromanone sulfone derivatives. Without exception, the compounds evaluated were inactive (IC50 > 10000 nM) against cathepsin B. The most potent inhibitor (IC50 = 46 nM) of cathepsin L proved to be the 6,7-difluoro analogue 4. This small library of compounds significantly expands the structure-activity relationship known for small molecule, nonpeptidic inhibitors of cathepsin L.
Oncolytic adenoviruses coated with MHC-I tumor epitopes for a new oncolytic vaccine platform (2015)

Meeting abstracts Oncolytic adenoviruses (OAds) demonstrated great potential for the treatment of cancer in many pre-clinical studies. The pre-existing immunity and their immunodominance, however, still limit the success of oncolytic virotherapy in cancer patients. Thus, a transition from oncolytic
Synthesis of Lysine Anhydride (1946)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of Lysine AnhydrideEphraim Katchalski, Isaac Grossfeld, and Max FrankelCite this: J. Am. Chem. Soc. 1946, 68, 5, 879–880Publication Date (Print):May 1, 1946Publication History Published online1 May 2002Published inissue 1 May 1946https://pubs.acs.org/doi/10.1021/ja01209a053https://doi.org/10.1021/ja01209a053research-articleACS PublicationsRequest reuse permissionsArticle Views353Altmetric-Citations14LEARN 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
Purine Nucleosides and Nucleotides Unequivocally in the Syn Conformation: Guanosine and 5′-GM P with 8-tert-Butyl and 8-( α-Hydroxyisopropyl) Substituents (1978)

Direct alkylation via a free radical reaction was utilized to prepare 8-tert-butylguanosine-5′- phosphate; this was dephosphorylated with alkaline phosphatase to give the parent nucleoside. The 8- (α-hydroxyisopropyl) derivatives of 5′-GMP and guanosine were prepared in an analogous manner. The foregoing products, which are necessarily in the syn conformation about the glycosidic bond because of the bulky 8-substituents (van der Waals’ radii 3.5-4 Å), were characterized by elementary analysis, UV spectra and 1 HNMR spectroscopy. The changes in chemical shifts of H (1′), H (2′) and H (3′) of each of the foregoing derivatives, relative to those for guanosine and 5′-GMP, were consistent with their being in the syn conformation and, furthermore, pointed to guanosine and 5′-GMP being predominantly anti, in aqueous medium or DMSO. They also demonstrated that, contrary to the prevailing opinion, 8-bromo-5′-GMP and 8-bromoguanosine are not necessarily ex­clusively in the syn conformation in solution. While 8-bromoadenosine-5′-phosphate was slowly dephosphorylated by snake venom 5′-nucleoti- dase, the 8-tert-butyl and 8-(α-hydroxyisopropyl) derivatives of 5′-GMP were fully resistant to this enzyme.
Ultrafine Particles Cross Cellular Membranes by Nonphagocytic Mechanisms in Lungs and in Cultured Cells (2005)

High concentrations of airborne particles have been associated with increased pulmonary and cardiovascular mortality, with indications of a specific toxicologic role for ultrafine particles (UFPs; particles < 0.1 microm). Within hours after the respiratory system is exposed to UFPs, the UFPs may appear in many compartments of the body, including the liver, heart, and nervous system. To date, the mechanisms by which UFPs penetrate boundary membranes and the distribution of UFPs within tissue compartments of their primary and secondary target organs are largely unknown. We combined different experimental approaches to study the distribution of UFPs in lungs and their uptake by cells. In the in vivo experiments, rats inhaled an ultrafine titanium dioxide aerosol of 22 nm count median diameter. The intrapulmonary distribution of particles was analyzed 1 hr or 24 hr after the end of exposure, using energy-filtering transmission electron microscopy for elemental microanalysis of individual particles. In an in vitro study, we exposed pulmonary macrophages and red blood cells to fluorescent polystyrene microspheres (1, 0.2, and 0.078 microm) and assessed particle uptake by confocal laser scanning microscopy. Inhaled ultrafine titanium dioxide particles were found on the luminal side of airways and alveoli, in all major lung tissue compartments and cells, and within capillaries. Particle uptake in vitro into cells did not occur by any of the expected endocytic processes, but rather by diffusion or adhesive interactions. Particles within cells are not membrane bound and hence have direct access to intracellular proteins, organelles, and DNA, which may greatly enhance their toxic potential.
A novel rear-end collision warning system using neural network ensemble (2016)

Negligence of a driver or a sudden stop of a forward vehicle can cause rear-end collision. In this paper, we propose a new situation assessment algorithm to determine collision probability to prevent the rear-end collision. The proposed algorithm consists of two phases: coarse assessment and fine assessment. In the coarse assessment, the algorithm selects a target vehicle with the highest possibility of collision by using fuzzy logic. In fine assessment, it determines collision probability based on a statistical approach considering driving maneuvers; it models the driving maneuvers to enable the driver to operate the vehicle in conditions toward the collision and calculates the collision probability as the ratio between the total driving maneuvers and the driving maneuvers in possible collisions. To reduce the simulation time complexity, we adapt a neural network. Since there exist variance of widths for different vehicles, we also apply neural network ensemble to cope with the variance. Numerical evaluation of the proposed method is provided through simulations and practical tests.
Purification of High Molecular Weight Urokinase from Human Urine and Comparative Study of Two Active Forms of Urokinase (1983)

An improved method for the purification of high molecular weight urokinase to homogeneity from human urine was established. A yield of 32% with a 3,100-fold purification was obtained by Hyflo Super-Cel treatment, heat treatment at 60 degrees C for 10 hr, serial column chromatography on DEAE-Sepharose CL-6B and O-[3-(p-sulfophenylamino)-2-hydroxypropyl]-cellulose (SFOP-cellulose), and gel filtration on Ultrogel AcA 54. The low molecular weight form of urokinase was also purified to homogeneity by chromatography on hydroxyl apatite and gel filtration on Sephadex G-75 after the SFOP-cellulose column step. The high molecular weight urokinase had only one isoelectric form with a pI of 9.7, whereas the low molecular weight form had six isoelectric subforms with pI values between 9.4 and 6.4. The absorption coefficients at 280 nm of both urokinase forms were 13.61 and 13.50, respectively. Fibrinolytic and esterolytic activities of the two urokinase forms were compared in various assay methods.
Photopolarimeter using two modulated optical rotators (1977)

The basic compensator-analyzer-polarimeter is automated by inserting two modulated optical rotators, one in front of the compensator and the other between the compensator and the analyzer. The modulated optical rotators (e.g., two series-connected Faraday cells) are excited by the same ac source to produce sinusoidal optical rotations of the same frequency, generally of different amplitudes, that are mutally in or 180 degrees out of phase. We show that, when the radiation leaving this generalized polarimeter (which is of constant polarization) is linearly detected, limited Fourier analysis of the resulting signal yields the four Stokes parameters of the incident radiation.
An integrated 16-channel CMOS time to digital converter (1994)

An integrated 16-channel Time to Digital Converter (TDC) for use in the NA48 experiment at CERN has been developed in a 1 /spl mu/m CMOS technology. The resolution is 156ns and the total time history is 204.8 ms. Buffering of up to 128 hits is done in on-chip FIFOs. The chip area is 25 mm/sup 2/. The vernier circuit consists of a 16-tap voltage-controlled delay chain controlled by a Delay Locked Loop (DLL). Read out is possible at 40 MHz. JTAG/IEEE 1149.1 protocol has been incorporated to allow in-site testing of the chip. The JTAG data path is also used to access internal control and status registers.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Achievable rate of MIMO channels with data-aided channel estimation and perfect interleaving (2001)

The achievable rate of a coherent coded modulation digital communication system with data-aided channel estimation and a discrete equiprobable symbol alphabet is derived under the assumption that the system operates on a flat fading multiple-input/multiple-output channel and uses a perfect interleaver to combat the bursty nature of the channel. It is shown that linear minimum mean square error channel estimation directly follows from the derivation and links average mutual information to the channel dynamics. Based on the assumption that known training symbols are transmitted, the achievable rate of the system is optimized with respect to the amount of training information needed.
Griffiths effects and quantum critical points in dirty superconductors without spin-rotation invariance: One-dimensional examples (2001)

We introduce a strong-disorder renormalization group (RG) approach suitable for investigating the quasiparticle excitations of disordered superconductors in which the quasiparticle spin is not conserved. We analyze one-dimensional models with this RG and with elementary transfer matrix methods. We find that such models with broken spin rotation invariance generically lie in one of two topologically distinct localized phases. Close enough to the critical point separating the two phases, the system has a power-law divergent low-energy density of states (with a nonuniversal continuously varying power law) in either phase, due to quantum Griffiths singularities. This critical point belongs to the same infinite-disorder universality class as the one-dimensional particle-hole symmetric Anderson localization problem, while the Griffiths phases in the vicinity of the transition are controlled by lines of strong (but not infinite) disorder fixed points terminating in the critical point.
Sphingosine-1-Phosphate-Induced Nociceptor Excitation and Ongoing Pain Behavior in Mice and Humans Is Largely Mediated by S1P3 Receptor (2013)

The biolipid sphingosine-1-phosphate (S1P) is an essential modulator of innate immunity, cell migration, and wound healing. It is released locally upon acute tissue injury from endothelial cells and activated thrombocytes and, therefore, may give rise to acute post-traumatic pain sensation via a yet elusive molecular mechanism. We have used an interdisciplinary approach to address this question, and we find that intradermal injection of S1P induced significant licking and flinching behavior in wild-type mice and a dose-dependent flare reaction in human skin as a sign of acute activation of nociceptive nerve terminals. Notably, S1P evoked a small excitatory ionic current that resulted in nociceptor depolarization and action potential firing. This ionic current was preserved in "cation-free" solution and blocked by the nonspecific Cl(-) channel inhibitor niflumic acid and by preincubation with the G-protein inhibitor GDP-β-S. Notably, S1P(3) receptor was detected in virtually all neurons in human and mouse DRG. In line with this finding, S1P-induced neuronal responses and spontaneous pain behavior in vivo were substantially reduced in S1P(3)(-/-) mice, whereas in control S1P(1) floxed (S1P(1)(fl/fl)) mice and mice with a nociceptor-specific deletion of S1P(1)(-/-) receptor (SNS-S1P(1)(-/-)), neither the S1P-induced responses in vitro nor the S1P-evoked pain-like behavior was altered. Therefore, these findings indicate that S1P evokes significant nociception via G-protein-dependent activation of an excitatory Cl(-) conductance that is largely mediated by S1P(3) receptors present in nociceptors, and point to these receptors as valuable therapeutic targets for post-traumatic pain.
Human platelet cGI-PDE: expression in yeast and localization of the catalytic domain by deletion mutagenesis (1996)

Cyclic adenosine monophosphate (cAMP) is an important modulator of platelet responses to agonists. Cyclic nucleotide phosphodiesterase (PDE) controls intracellular cAMP concentrations by hydrolyzing it to AMP. The major PDE activity in platelets is PDE3A (cyclic guanosine monophosphate [cGMP]-inhibited PDE). To obtain structural information on platelet PDE3A, we cloned the enzyme cDNA from a human erythroleukemia cell (HEL) library since the cell line expresses many platelet proteins. This clone consists of 87% of the full-length human myocardial PDE3A cDNA, spanning from nucleotides 456 to 4606, and is identical in sequence. The nucleotide coding for the N terminal 179 amino acid sequence (nt 1-536) as well as four other cDNAs (nt 1459-1632, nt 1765-1986, nt 2152-2538, and nt 2978-3375) obtained by RT-PCR of platelet RNA are also identical to the myocardial sequences, indicating that the HEL, myocardial, and platelet PDE3As are the same. Northern blot analysis of HEL cell RNA detected two mRNAs of 7.5 and 4.4 kb. Four new deletion mutants are reported. PDE 3A delta 1 and PDE 3A delta 2, encoding amino acids 665 to 1141 and amino acids 679 to 1141, respectively, were expressed in a PDE-deficient yeast. They displayed PDE activities of 172 and 79 pmol/mg/min, respectively. PDE 3A delta 3 and PDE 3A delta 4, encoding amino acids 686 to 1141 and 700 to 1141, had no detectable PDE activity. All mutant proteins were expressed as determined by Western blot analysis. These findings localize the PDE3A catalytic domain to within amino acid residues 679 to 1141.
Dipeptidyl peptidase IV activity in commercial solutions of human serum albumin (2013)

Due to the heterogeneous nature of commercial human serum albumin (cHSA), other components, such as the protease dipeptidyl peptidase IV (DPP-IV), possibly contribute to the therapeutic effect of cHSA. Here, we provide evidence for the first time that DPP-IV activity contributes to the formation of aspartate-alanine diketopiperazine (DA-DKP), a known immunomodulatory molecule from the N terminus of human albumin. cHSA was assayed for DPP-IV activity using a specific DPP-IV substrate and inhibitor. DPP-IV activity was assayed at 37 and 60°C because cHSA solutions are pasteurized at 60°C. DPP-IV activity in cHSA was compared with other sources of albumin such as a recombinant albumin (rHSA). In addition, the production of DA-DKP was measured by negative electrospray ionization/liquid chromatography mass spectrometry (ESI(-)/LCMS). Significant levels of DPP-IV activity were present in cHSA. This activity was abolished using a specific DPP-IV inhibitor. Fully 70 to 80% DPP-IV activity remained at 60°C compared with the 37°C incubate. No DPP-IV activity was present in rHSA, suggesting that DPP-IV activity is present only in HSA produced using the Cohn fractionation process. The formation of DA-DKP at 60°C was observed with the DPP-IV inhibitor significantly decreasing this formation. DPP-IV activity in cHSA results in the production of DA-DKP, which could account for some of the clinical effects of cHSA.