gebhart/patrepeval huggingface dataset:
Synthesis of 5-Substituted Pyrimidines via Formaldehyde Addition1 (1959)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of 5-Substituted Pyrimidines via Formaldehyde Addition1Richard E. Cline, Robert M. Fink, and Kay FinkCite this: J. Am. Chem. Soc. 1959, 81, 10, 2521–2527Publication Date (Print):May 1, 1959Publication History Published online1 May 2002Published inissue 1 May 1959https://pubs.acs.org/doi/10.1021/ja01519a056https://doi.org/10.1021/ja01519a056research-articleACS PublicationsRequest reuse permissionsArticle Views1349Altmetric-Citations182LEARN 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
ACME dissociation: a versatile cell fixation-dissociation method for single-cell transcriptomics (2021)

Single-cell sequencing technologies are revolutionizing biology, but they are limited by the need to dissociate live samples. Here, we present ACME (ACetic-MEthanol), a dissociation approach for single-cell transcriptomics that simultaneously fixes cells. ACME-dissociated cells have high RNA integrity, can be cryopreserved multiple times, and are sortable and permeable. As a proof of principle, we provide single-cell transcriptomic data of different species, using both droplet-based and combinatorial barcoding single-cell methods. ACME uses affordable reagents, can be done in most laboratories and even in the field, and thus will accelerate our knowledge of cell types across the tree of life.
PEI–PEG–Chitosan‐Copolymer‐Coated Iron Oxide Nanoparticles for Safe Gene Delivery: Synthesis, Complexation, and Transfection (2009)

Gene therapy offers the potential of mediating disease through modification of specific cellular functions of target cells. However, effective transport of nucleic acids to target cells with minimal side effects remains a challenge despite the use of unique viral and non-viral delivery approaches. Here we present a non-viral nanoparticle gene carrier that demonstrates effective gene delivery and transfection both in vitro and in vivo. The nanoparticle system (NP-CP-PEI) is made of a superparamagnetic iron oxide nanoparticle (NP), which enables magnetic resonance imaging, coated with a novel copolymer (CP-PEI) comprised of short chain polyethylenimine (PEI) and poly(ethylene glycol) (PEG) grafted to the natural polysaccharide, chitosan (CP), which allows efficient loading and protection of the nucleic acids. The function of each component material in this nanoparticle system is illustrated by comparative studies of three nanoparticle systems of different surface chemistries, through material property characterization, DNA loading and transfection analyses, and toxicity assessment. Significantly, NP-CP-PEI demonstrates an innocuous toxic profile and a high level of expression of the delivered plasmid DNA in a C6 xenograft mouse model, making it a potential candidate for safe in vivo delivery of DNA for gene therapy.
A Molecular Beacon-Based Duplex Real-Time Polymerase Chain Reaction Assay for Simultaneous Detection of Escherichia coli O157:H7 and Listeria monocytogenes in Milk and Milk Products (2009)

In this study, a real-time polymerase chain reaction assay based on two specific molecular beacons tagged with different reporter dyes was designed and developed for Escherichia coli O157:H7 and Listeria monocytogenes in such a way that each pathogen could be detected simultaneously in a single tube and differentiated. The duplex assay was developed by targeting the rfb gene of E. coli O157:H7 and the hly gene of L. monocytogenes using the homemade master reaction mix. The detection limit of the assay in reconstituted nonfat dried milk (11%) spiked with the two targeted pathogens at different levels was 1 and 3 log colony forming units/mL of each with and without enrichment (6 h) of the sample. The assay was quantifiable for both pathogens over 5 logs with respective regression coefficient 0.9852 (E. coli O157:H7) and 0.9812 (L. monocytogenes). The application of the developed assay on 60 market samples, including 20 samples of two popular Indian indigenous products (10 each of Kulfi and Paneer), revealed three samples involving one each of raw milk, kulfi, and paneer found to be positive for E. coli O157:H7, while one sample of raw milk was positive for L. monocytogenes. The performance of the assay was validated using commercially available individual detection kits for both pathogens, which further authenticated the results by detecting the same samples positive. These assays were set up rigorously in a closed system, therefore enabling rapid, highly specific, and sensitive detection of E. coli O157:H7 and L. monocytogenes in dairy food samples.
The adult hip (1998)

This major two-volume reference provides comprehensive coverage of the evaluation and surgical management of problems of the hip. It begins with a thorough review of clinically relevant basic science, including the anatomy and biomechanics of the hip, the biomaterials used in hip reconstruction, the sequelae of wear, and the biology of bone autografts and allografts. A section on clinical science covers the clinical and radiological evaluation of the hip, the pathology of the hip, osteonecrosis of the hip and related disorders, perioperative considerations, surgical anatomy, and surgical approaches to the hip. Subsequent sections provide complete information on all current surgical procedures, including arthroscopy, resection arthroplasty, arthrodesis, osteotomy, total hip arthroplasty, complex total hip arthroplasty, procedures for the treatment of sepsis, and revision total hip arthroplasty. Complementing the text are more than 1,300 full-color and black-and-white illustrations, including drawings by a noted medical illustrator
[The effect of C 1 esterase inhibitor on ischemia: reperfusion injury in the rat brain]. (2001)

The results of this study provided the first evidence that C 1 INH reduced polymorphonuclear leukocytes(PMN) accumulation and reperfusion damage in the brain.
Autoimmune concepts of multiple sclerosis as a basis for selective immunotherapy: From pipe dreams to (therapeutic) pipelines (2004)

Autoimmune T and B cell responses to CNS antigen(s) are thought to drive the pathogenesis of multiple sclerosis (MS), and thus are logical targets for therapy. Indeed, several immunomodulatory agents, including IFN-beta 1b, IFN-beta 1a, glatiramer acetate, and mitoxantrone, have had beneficial clinical effects in different forms of MS. However, because the available treatments are only partially effective, MS therapy needs to be further improved. Selective (antigen-specific) immunotherapies are especially appealing because in theory they combine maximal efficacy with minimal side effects. Indeed, several innovative immunotherapies have been successfully applied in experimental autoimmune encephalomyelitis. For example, autoreactive T cells can be selectively targeted by means of antigen, T cell receptor, or activation markers. However, experimental autoimmune encephalomyelitis is far from being a perfect approximation of MS because MS is more heterogeneous and the target antigen(s) is (are) not known. Further advances in MS therapy will depend on our growing understanding of the pathogenesis of this still incurable disease.
Mutation screening and association study of RNASEL as a prostate cancer susceptibility gene (2005)

To date, germline mutations have been found in three candidate genes for hereditary prostate cancer: ELAC2 at 17p11, RNASEL at 1q25 and MSR1 at 8p22. RNASEL, encoding the 2',5'-oligoadenylate-dependant RNase L, seems to have rare mutations in different ethnicities, such as M1I in Afro-Americans, E265X in men of European descent and 471delAAAG in Ashkenazi Jews. In order to evaluate the relevance of RNASEL in the German population, we sequenced its open reading frame to determine the spectrum and frequency of germline mutations. The screen included 303 affected men from 136 Caucasian families, of which 45 met the criteria for hereditary prostate cancer. Variants were analysed using a family-based association test, and genotyped in an additional 227 sporadic prostate cancer patients and 207 controls. We identified only two sib pairs (1.4% of our families) cosegregating conspicuous RNASEL variants with prostate cancer: the nonsense mutation E265X, and a new amino-acid substitution (R400P) of unknown functional relevance. Both alleles were also found at low frequencies (1.4 and 0.5%, respectively) in controls. No significant association of polymorphisms (I97L, R462Q and D541E) was observed, neither in case-control analyses nor by family-based association tests. In contrast to previous reports, our study does not suggest that common variants (i.e. R462Q) modify disease risk. Our results are not consistent with a high penetrance of deleterious RNASEL mutations. Due to the low frequency of germline mutations present in our sample, RNASEL does not have a significant impact on prostate cancer susceptibility in the German population.
Efficient parallel algorithms for chordal graphs (1988)

The author gives efficient parallel algorithms for recognizing chordal graphs, finding a maximum clique and a maximum independent set in a chordal graph, finding an optimal coloring of a chordal graph, finding a breadth-first search tree and a depth-first search tree of a chordal graph, recognizing interval graphs, and testing interval graphs for isomorphism. The key to the results is an efficient parallel algorithm for finding a perfect elimination ordering.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Contribution of oxygen-derived free radicals to experimental necrotizing enterocolitis. (1988)

Oxygen-derived free radicals, particularly superoxide anion, are considered important mediators of intestinal injury induced by ischemia/reperfusion based on the protective effects of superoxide dismutase and allopurinol. A role for free radicals was investigated in a model of necrotizing enterocolitis (NEC) which was initiated by a luminal, as opposed to a vascular, insult. Intestinal loops of weanling rabbits received either saline (control loops) or a solution of 10 mg/ml casein and 50 mg/ml calcium gluconate acidified to pH 4 with proprionic acid (treated loops). When the animals were sacrificed 3 hours later, severe damage was noted in the treated loops, which included blunting of villi and edema, with all animals surviving. At 16 hours only 5 of 8 rabbits survived, and 3 had hemorrhagic necrosis. Control loops were normal in each case. Intravenous infusion of superoxide dismutase (4 mg/kg/hr), commencing 15 minutes after NEC induction, totally prevented intestinal injury. On the other hand, pretreatment with allopurinol, an inhibitor of xanthine oxidase, for 2 days (30 and 60 mg/kg by mouth) was not protective against intestinal damage. A cellular infiltration in treated loops was not histologically evident in the majority of animals at 3 hours after treatment, a finding confirmed by the minimal accumulation of 111In-labeled leukocytes in damaged and intact intestinal tissue. These results suggest that superoxide generated locally from sources other than xanthine oxidase play a critical and early role in experimental NEC and that superoxide dismutase may prove to be an effective therapy in this devastating neonatal disease.
TRANSCARBOXYLASE, II. PURIFICATION AND PROPERTIES OF METHYLMALONYL-OXALOACETIC TRANSCARBOXYLASE (1961)

cytidylic acid, and uridylic acid.The molar ratios were 1.17 4 0.03, 1.00, 1.21 i 0.06, and k 0.07, respectively.The sugar present was determined by chromatographing the above HCl hydroly- sate and a control mixture of sugars on Whatman #1 paper using a mixture of butanol, ethanol, and ammonia."lThe sugar had an Rf characteristic of ribose.Summary.-The evidence presented indicates that the bacteriophage f2 contains RNA and not DNA as its nucleic acid.The evidence is based primarily on the analysis of purified material but also on the distribution of the two types of nucleic acid synthesized after infection.Although f2 is an extremely small phage, there is a compensating large yield per bacterium (about 10,000 P.F.U.).Therefore, the synthesis of phage materials can be followed and the phage itself readily purified.In its general features such as adsorption and intracellular growth, f2 resembles the DNA bacteriophages.Further studies on the biology and chemistry of f2 are in progress.We gratefully acknowledge our indebtedness to Dr. M. Jesaitis for advice
Synthesis and biological evaluation of new Donepezil-like Thiaindanones as AChE inhibitors (2008)

Pharmacomodulations of previously reported thiaindanones related to donepezil were achieved with the aim to enhance their AChE inhibitory activity. Condensation of the cyclopentane carbonyl group into hydrazone or cyanolefine derivatives, as well as its hydrogenation and the subsequent substitution of the resulting hydroxyl group led to new 2-(4-benzylpiperazin-1-yl)-N-(1,3-dibromo-6-hydroxy-5,6-dihydro-4H-cyclopenta[c]thien-4-yl) acetamides. The in vitro evaluation of this new series, according to the method of Ellman, shows however that it conserved only partially the biological activity. The best compound remains the alcohol 11 (IC(50) = 0.40 microM, against 0.02 microM for donepezil).
Functional characterization of chondroitin sulfate proteoglycans of brain: interactions with neurons and neural cell adhesion molecules. (1993)

Ng-CAM and N-CAM are cell adhesion molecules (CAMs), and each CAM can bind homophilically as demonstrated by the ability of CAM-coated beads (Covaspheres) to self-aggregate. We have found that the extent of aggregation of Covaspheres coated with either Ng-CAM or N-CAM was strongly inhibited by the intact 1D1 and 3F8 chondroitin sulfate proteoglycans of rat brain, and by the core glycoproteins resulting from chondroitinase treatment of the proteoglycans. Much higher concentrations of rat chondrosarcoma chondroitin sulfate proteoglycan (aggrecan) core proteins had no significant effect in these assays. The 1D1 and 3F8 proteoglycans also inhibited binding of neurons to Ng-CAM when mixtures of these proteins were adsorbed to polystyrene dishes. Direct binding of neurons to the proteoglycan core glycoproteins from brain but not from chondrosarcoma was demonstrated using an assay in which cell-substrate contact was initiated by centrifugation, and neuronal binding to the 1D1 proteoglycans was specifically inhibited by the 1D1 monoclonal antibody. Different forms of the 1D1 proteoglycan have been identified in developing and adult brain. The early postnatal form (neurocan) was found to bind neurons more effectively than the adult proteoglycan, which represents the C-terminal half of the larger neurocan core protein. Our results therefore indicate that certain brain proteoglycans can bind to neurons, and that Ng-CAM and N-CAM may be heterophilic ligands for neurocan and the 3F8 proteoglycan. The ability of these brain proteoglycans to inhibit adhesion of cells to CAMs may be one mechanism to modulate cell adhesion and migration in the nervous system.
Interleukin-2 can induce suppression of human natural killer cell cytotoxicity. (1989)

By interaction with monocytes, interleukin-2 (IL-2) suppressed natural killer (NK) cell cytotoxicity (NKCC) of human, Percoll-fractionated, low-density mononuclear cells. The NK-suppressive effect of IL-2 was independent of de novo formation of prostaglandins or protein since it was unaffected by treatment with indomethacin and cycloheximide, respectively. A monoclonal antibody to the p55 (beta) moiety of the IL-2 receptor (anti-Tac/anti-CD25) blocked IL-2-induced NKCC suppression but did not affect the NK-enhancing effect of the lymphokine. We conclude that IL-2 exerts a monocyte-dependent, IL-2 beta-receptor mediated suppressive influence on human NK cells.
Fast HPLC determination of serum free fatty acids in the picomole range (1993)

We developed a method for determining individual free fatty acids in serum by using a modified one-step Dole extraction, derivatization, and a new high-performance liquid chromatographic (HPLC) separation. Sample handling is minimized to a single transfer of the fatty acids (upper layer of the Dole extract), which are readily derivatized at 85 degrees C with p-bromophenacyl bromide without significant hydrolysis of esterified fatty acids. The derivatization mixture is directly injected into the HPLC apparatus. The new method, which uses C6 (3-microns particle) column material and an isocratic acetonitrile-water eluent, separates nearly to baseline 12 of the physiologically most abundant long-chain fatty acids (C12-C22) in < 20 min with a detection limit of approximately 2 pmol. It is therefore suitable for routine analysis even with basic HPLC equipment and can easily analyze a series of 10-20 samples in about 2 h including extraction until first results are available. The method is also applicable to other matrices than serum, e.g., for determination of precursor fatty acids such as arachidonic acid in platelets or of fatty acid patterns liberated by lipases or phospholipases A1/A2 in test systems.
Activation of Caspase-12, an Endoplastic Reticulum (ER) Resident Caspase, through Tumor Necrosis Factor Receptor-associated Factor 2-dependent Mechanism in Response to the ER Stress (2001)

When accumulation of a malfolded protein in the endoplastic reticulum (ER) is induced by various adverse conditions, such as hypoxia, glucose starvation, and perturbation of calcium homeostasis, cells respond to the stress by increasing transcription of genes encoding ER molecular chaperones, a process known as unfolded protein response. The signaling is initiated by IRE1s, ER stress sensors. Alternatively, excessive stress to the ER results in apoptosis. Caspase-12 is known to be essential for this ER stress-induced apoptosis. In this study, we analyzed the detailed regulatory mechanisms of IRE1s during ER stress. We identified c-Jun N-terminal inhibitory kinase (JIK) as a binding partner of IRE1alpha, and JIK was seen to modulate IRE1alpha-TRAF2 (tumor necrosis factor receptor-associated factor 2) complex formation and the resultant alteration to c-Jun N-terminal kinase signaling from IRE1s in response to ER stress. We also demonstrated that TRAF2 interacts with procaspase-12 and promotes the clustering of procaspase-12 and its activation by cleavage in response to ER stress. These results indicate that TRAF2 plays crucial roles not only in the signaling of the c-Jun N-terminal kinase pathway but also in activation of caspase-12 to transduce signals from IRE1s. Thus, we provide a missing link in the ER stress-induced apoptosis-signaling pathway, one which connects the stress sensor molecule IRE1 and the activation of caspase-12.
Post soft breakdown conduction in SiO/sub 2/ gate oxides (2002)

The post Soft Breakdown (SBD) conduction in ultra-thin SiO/sub 2/ films is studied using a Quantum Point Contact model which also applies to hard breakdown. The main experimental characteristics of the post-SBD conduction are correctly explained. The role of holes and electrons is also discussed.
Post-transcriptional regulation of lipoprotein receptors by the E3-ubiquitin ligase inducible degrader of the low-density lipoprotein receptor (2012)

Transcriptional induction of IDOL by liver X receptor defines a new post-transcriptional pathway for controlling LDLR abundance and LDL uptake independent of sterol regulatory element binding proteins. Targeting IDOL activity may offer a novel therapeutic approach complementary to statins for treating cardiovascular disease.
Eph receptors inactivate R-Ras through different mechanisms to achieve cell repulsion (2006)

Eph receptor tyrosine kinases regulate the spatial organization of cells within tissues. Central to this function is their ability to modulate cell shape and movement in response to stimulation by the ephrin ligands. The EphB2 receptor was reported to inhibit cell-matrix adhesion by phosphorylating tyrosine 66 in the effector domain of R-Ras, a Ras family protein known to regulate cell adhesion and motility. Here, we further characterize the role of R-Ras downstream of both EphA and EphB receptors. Our data show that besides inhibiting R-Ras function through phosphorylation, Eph receptors can reduce R-Ras activity through the GTPase-activating protein, p120RasGAP. By using R-Ras mutants that cannot be inactivated by p120RasGAP and/or cannot be phosphorylated at tyrosine 66, we show that the two forms of R-Ras negative regulation - through increased GTP hydrolysis and phosphorylation - differentially contribute to various ephrin-mediated responses. Retraction of the COS cell periphery depends only on R-Ras inactivation through p120RasGAP. By contrast, both reduced R-Ras GTP levels and tyrosine 66 phosphorylation contribute to the ephrin inhibitory effects on COS cell migration and to ephrin-dependent growth cone collapse in primary neurons. Therefore, Eph receptors can regulate R-Ras in two different ways to achieve cell repulsion.
Identification of a central regulator of stationary‐phase gene expression in Escherichia coli (1991)

During carbon-starvation-induced entry into stationary phase, Escherichia coli cells exhibit a variety of physiological and morphological changes that ensure survival during periods of prolonged starvation. Induction of 30-50 proteins of mostly unknown function has been shown under these conditions. In an attempt to identify C-starvation-regulated genes we isolated and characterized chromosomal C-starvation-induced csi::lacZ fusions using the lambda placMu system. One operon fusion (csi2::lacZ) has been studied in detail. csi2::lacZ was induced during transition from exponential to stationary phase and was negatively regulated by cAMP. It was mapped at 59 min on the E. coli chromosome and conferred a pleiotropic phenotype. As demonstrated by two-dimensional gel electrophoresis, cells carrying csi2::lacZ did not synthesize at least 16 proteins present in an isogenic csi2+ strain. Cells containing csi2::lacZ or csi2::Tn10 did not produce glycogen, did not develop thermotolerance and H2O2 resistance, and did not induce a stationary-phase-specific acidic phosphatase (AppA) as well as another csi fusion (csi5::lacZ). Moreover, they died off much more rapidly than wild-type cells during prolonged starvation. We conclude that csi2::lacZ defines a regulatory gene of central importanc e for stationary phase E. coli cells. These results and the cloning of the wild-type gene corresponding to csi2 demonstrated that the csi2 locus is allelic with the previously identified regulatory genes katF and appR. The katF sequence indicated that its gene product is a novel sigma factor supposed to regulate expression of catalase HPII and exonuclease III (Mulvey and Loewen, 1989). We suggest that this novel sigma subunit of RNA polymerase defined by csi2/katF/appR is a central early regulator of a large starvation/stationary phase regulon in E. coli and propose 'rpoS' ('sigma S') as appropriate designations.