gebhart/patrepeval huggingface dataset:
N-Alkylated 2-aminotetralins: central dopamine-receptor stimulating activity (1979)

In order to define the structural requirements of N-substituents of 2-aminotetralins as central dopamine receptor agonists, a series of N-alkyl- and N,N-dialkyl-substituted 2-amino-5-hydroxy- and 2-amino-5-methoxytetralins have been synthesized and evaluated. The compounds were tested biochemically and behaviorally for dopaminergic activity. From the biochemical data it is concluded that an n-propyl group on the nitrogen is optimal for activity. The corresponding N-ethyl-substituted compounds are slightly less active, while the absence of N-ethyl or N-propyl groups give almost inactive compounds. It could be demonstrated that this is due to steric and not to lipophilic factors. It is suggested that a possible requirement for a potent agonist is that one of it N substituents must fit into a receptor cavity which, because of its size, can maximally accommodate an n-propyl but also smaller groups like ethyl or methyl. The active compounds appeared to give a similar relative pre- and postsynaptic stimulation and had also similar activities for the limbic system and for striatum. None of the compounds listed seemed to have central noradrenaline- or serotonin-receptor stimulating activity.
Effects of Adenosine Deaminase Inhibitors on Lymphocyte‐mediated Cytolysis (1985)

Four compounds that inhibit adenosine deaminase, erythro-9-(2-hydroxy-3-nonyl)adenine, 2'-deoxycoformycin, coformycin, and 9-(1-hydroxy-2-octyl)adenine have been studied in an in vitro lymphocyte-mediated cytolysis assay. At low concentration (congruent to 10 microM) these agents enhance the activities of a number of inhibitory purine nucleosides, including adenosine and 2'-deoxyadenosine. The LMC-inhibitory activity of Ado but not dAdo is further enhanced by 5-iodotubercidin, uridine, 4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone, or L-homocysteine and is antagonized by theophylline. The inhibition of LMC by Ado and dAdo is increased by nitrobenzyl-thioinosine. Lymphocyte-mediated cytolysis was inhibited by EHNA or HOA alone (IC50 congruent to 150 microM), but not by dCF and CF (even at 400 microM). Inhibition of LMC by EHNA, HOA, Ado, or dAdo could not be attributed to changes in nucleoside 5'-triphosphate or S-adenosylhomocysteine levels. Inhibition of LMC by Ado appears to be related to increases in lymphocyte cAMP levels, while the mechanism of action of dAdo remains obscure. Lymphocyte-mediated cytolysis may be inhibited by EHNA and HOA through modulation of cAMP metabolism.
Organocatalytic Redox Deracemization of Cyclic Benzylic Ethers Enabled by An Acetal Pool Strategy (2017)

The first redox deracemization of a series of cyclic benzylic ethers, including 6H-benzo[c]chromenes, isochromans, and 1H-isochromenes, is described. An "acetal pool" strategy was adopted to harmonize the complete oxidation of secondary ethers with imidodiphosphoric acid catalyzed asymmetric transfer hydrogenation. The synthetic utility of the process was demonstrated by the effective deracemization of biologically active molecules of interest that are difficult to prepare by other methods.
A Genome-Wide Screen Reveals Functional Gene Clusters in the Cancer Genome and Identifies EphA2 as a Mitogen in Glioblastoma (2006)

A novel genome-wide screen that combines patient outcome analysis with array comparative genomic hybridization and mRNA expression profiling was developed to identify genes with copy number alterations, aberrant mRNA expression, and relevance to survival in glioblastoma. The method led to the discovery of physical gene clusters within the cancer genome with boundaries defined by physical proximity, correlated mRNA expression patterns, and survival relatedness. These boundaries delineate a novel genomic interval called the functional common region (FCR). Many FCRs contained genes of high biological relevance to cancer and were used to pinpoint functionally significant DNA alterations that were too small or infrequent to be reliably identified using standard algorithms. One such FCR contained the EphA2 receptor tyrosine kinase. Validation experiments showed that EphA2 mRNA overexpression correlated inversely with patient survival in a panel of 21 glioblastomas, and ligand-mediated EphA2 receptor activation increased glioblastoma proliferation and tumor growth via a mitogen-activated protein kinase-dependent pathway. This novel genome-wide approach greatly expanded the list of target genes in glioblastoma and represents a powerful new strategy to identify the upstream determinants of tumor phenotype in a range of human cancers.
Enhancement by novel anti-methicillin-resistant Staphylococcus aureus compound HT61 of the activity of neomycin, gentamicin, mupirocin and chlorhexidine: in vitro and in vivo studies (2012)

We demonstrate that HT61, developed as a topical agent, acts as an enhancer that accelerates the activities of other antimicrobial agents against both MSSA and MRSA.
Controlling Streptococcus mutans and Staphylococcus aureus biofilms with direct current and chlorhexidine (2017)

Microbial biofilms formed on biomaterials are major causes of chronic infections. Among them, Gram-positive bacteria Streptococcus mutans and Staphylococcus aureus are important pathogens causing infections associated with dental caries (tooth-decay) and other medical implants. Unfortunately, current antimicrobial approaches are ineffective in disrupting established biofilms and new methods are needed to improve the efficacy. In this study, we report that the biofilm cells of S. mutans and S. aureus can be effectively killed by low-level direct current (DC) and through synergy in concurrent treatment with DC and chlorhexidine (CHX) at low concentrations. For example, after treatment with 28 µA/cm<sup>2</sup> DC and 50 µg/mL CHX for 1 h, the viability of biofilm cells was reduced by approximately 4 and 5 logs for S. mutans and S. aureus, respectively. These results are useful for developing more effective approaches to control pathogenic biofilms.
Multilineage Differentiation from Human Embryonic Stem Cell Lines (2001)

Stem cells are unique cell populations with the ability to undergo both self-renewal and differentiation. A wide variety of adult mammalian tissues harbors stem cells, yet "adult" stem cells may be capable of developing into only a limited number of cell types. In contrast, embryonic stem (ES) cells, derived from blastocyst-stage early mammalian embryos, have the ability to form any fully differentiated cell of the body. Human ES cells have a normal karyotype, maintain high telomerase activity, and exhibit remarkable long-term proliferative potential, providing the possibility for unlimited expansion in culture. Furthermore, they can differentiate into derivatives of all three embryonic germ layers when transferred to an in vivo environment. Data are now emerging that demonstrate human ES cells can initiate lineage-specific differentiation programs of many tissue and cell types in vitro. Based on this property, it is likely that human ES cells will provide a useful differentiation culture system to study the mechanisms underlying many facets of human development. Because they have the dual ability to proliferate indefinitely and differentiate into multiple tissue types, human ES cells could potentially provide an unlimited supply of tissue for human transplantation. Though human ES cell-based transplantation therapy holds great promise to successfully treat a variety of diseases (e.g., Parkinson's disease, diabetes, and heart failure) many barriers remain in the way of successful clinical trials.
Recent Developments in the Maytansinoid Antitumor Agents (2004)

Maytansine and its congeners have been isolated from higher plants, mosses and from an Actinomycete, Actinosynnema pretiosum. Many of these compounds are antitumor agents of extraordinary potency, yet phase II clinical trials with maytansine proved disappointing. The chemistry and biology of maytansinoids has been reviewed repeatedly in the late 1970s and early 1980s; the present review covers new developments in this field during the last two decades. These include the use of maytansinoids as "warheads" in tumor-specific antibodies, preliminary metabolism studies, investigations of their biosynthesis at the biochemical and genetic level, and ecological issues related to the occurrence of such typical microbial metabolites in higher plants.
HIV does not replicate in naive CD4 T cells stimulated with CD3/CD28. (1997)

In this report, we demonstrate that the T cell tropic strain of HIV, LAI, does not replicate in naive CD4 T cells stimulated by cross-linking CD3 and CD28. In contrast, LAI replicates well in memory CD4 T cells stimulated in the same way. Unlike this physiologically relevant stimulation, PHA stimulates productive LAI replication in both naive and memory T cells. These studies were conducted with highly purified (FACS-isolated) subsets of CD4 T cells identified by expression of both CD45RA and CD62L. Remixing of purified T cells showed that naive T cells do not suppress LAI replication in memory T cells and that memory T cells do not restore LAI expression in naive T cells. The suppression of productive LAI replication in naive T cells is not due to differential expression of viral coreceptors, nor is it due to inhibition of activation of the important HIV transcription factors, nuclear factor-kappaB and activator protein-1. The inherent resistance of naive T cells to productive HIV infection, coupled with their proliferative advantage as demonstrated here, provides a sound basis for proposed clinical therapies using ex vivo expansion and reinfusion of CD4 T cells from HIV-infected adults.
Generation of high-contrast subpicopulses by single-stage 110-fold compression of YAG:Nd3+laser pulses (1987)

The optimal conditions for the compression of pulses from a cw YAG:Nd3 + laser with active mode locking were achieved by the use of a single-mode fiber waveguide and a diffraction grating compressor. The pulses compressed from 60 psec to 550 fsec were of high quality: there were no wide wings or a pedestal. This 110-fold compression was the maximum value for single-stage compression schemes in the spectral range of positive dispersion of group velocities in waveguides.
Mutation of l7Rn3 Shows That Odz4 Is Required for Mouse Gastrulation (2004)

A mouse homolog of the Drosophila pair-rule gene Odd Oz (Odz4) maps to the critical region of the l7Rn3 locus on mouse chromosome 7. Here we show that Odz4 is an excellent candidate for this allelic series because (1) it spans the entire critical region, (2) the phenotypes correlate with embryonic expression, (3) the complex genetic inheritance of the alleles is consistent with complex transcriptional regulation, and (4) one allele has a mutation in a conserved amino acid. Odz4 uses five alternate promoters that encode both secreted and membrane-bound proteins. Intragenic complementation of the l7Rn3 alleles is consistent with these multiple-protein isoforms. Further, the allelic series shows that Odz4 is required to establish the anterior-posterior axis of the gastrulating mouse embryo and is necessary later for mesoderm-derived tissues such as somites, heart, and skeleton. Sequencing of RT-PCR products from five of the six alleles reveals a nonconservative amino acid change in the l7Rn3(m4) allele. This amino acid is important evolutionarily, as it is conserved to Drosophila. Together, our data indicate that Odz4 is mutated in the l7Rn3 allele series and performs roles in the mouse brain, heart, and embryonic patterning similar to those of its Drosophila counterpart.
Interferon action: two distinct pathways for inhibition of protein synthesis by double-stranded RNA. (1978)

Double-stranded RNA inhibits protein synthesis in at least two ways. It activates a protein kinase that blocks peptide chain initiation by phosphorylating the peptide chain initiation factor eIF-2 and also activates an endonuclease that inactivates different mRNAs at different rates. The protein kinase and the endonuclease have been partially purified from interferon-treated Ehrlich ascites tumor cells. The 2',5'-oligoadenylates [pppA(2'p5'A)n], found found earlier to be mediators in the activation of the endonuclease by double-stranded RNA, are not mediators in the activation of the protein kinase by double-stranded RNA.
Paternal age and maternal age are risk factors for miscarriage; results of a multicentre European study (2002)

The risk of an adverse pregnancy outcome is highest if both partners are advanced in age.
Ytterbium Triflate Catalyzed Reactions of Epoxide with Nitrogen Heterocycles Under Solvent-Free Condition (2003)

Abstract Ytterbium triflate was found to effectively catalyze the reaction of epoxides with nitrogen heterocycles. The reactions afforded hydroxyl alkylated products in high yields.
Primer: Immunity and Autoimmunity (2008)

For nonimmunologists, a daunting and rapidly evolving immunologic vocabulary, our incomplete understanding of both normal and abnormal immune function, and multiple interrelated complex immune cellular pathways can be a barrier to using basic immunology to understand and improve care for patients with type 1 diabetes. Our task in this review is to introduce current immune concepts specifically relevant to type 1 diabetes. Because our understanding is not complete, as evidenced perhaps by our lack of standard immunotherapy to prevent type 1 diabetes, we can only provide a partial framework. Perhaps the simplest framework (which may be wrong) is to consider the development of type 1 diabetes as the balance between regulatory and effector T lymphocytes. We know that in the absence of a major portion of regulatory T lymphocytes in a rare syndrome caused by mutation of the FOXP3 gene, most infants (even neonates) develop type 1 diabetes. Central to the development of type 1 diabetes are T lymphocytes with specific T-cell receptors that recognize islet molecules. When a T-cell is activated through its receptor, it can orchestrate protection from infection or autoimmunity, depending on the target. Other T-cells can suppress or enhance autoimmunity (either in general or only for T lymphocytes in islets). The activation of a T-cell involves multiple different cell types and genes, as we will discuss.

The modern era of immunology began with the clonal selection theory independently expressed by David W. Talmage and Sir Frank Macfarlane Burnet (1,2). The clonal selection theory postulates that a foreign antigen entering the body binds to one unique antibody selected from an unlimited repertoire of antibodies formed early in the organism's life. This explains how the immune system is able to recognize and respond to a virtually inestimable number of foreign antigens.

The immune system is a …
Proteotoxicity and the Contrasting Effects of Oxaloacetate and Glycerol on Caenorhabditis elegans Life Span: A Role for Methylglyoxal? (2010)

Because accumulation of altered proteins is the most common biochemical symptom of aging, it is at least possible that such proteotoxicity may cause aging and influence life span. The life span of the nematode worm Caenorhabditis elegans is strongly influenced by changes in the intracellular concentration of methylglyoxal (MG), a putative source of much age-related proteotoxicity and organelle, cellular, and molecular dysfunction. Glycerol has recently been shown to shorten, whereas oxaloacetate has been found to extend, life span in C. elegans. It is suggested here that glycerol and oxaloacetate exert opposing effects on MG formation in C. elegans. It is proposed that, if not secreted by aquaporin, glycerol is converted to glycerol phosphate and then to dihydroxyacetone phosphate (DHAP) via a reaction requiring nicotinamide adenine dinucleotide (NAD(+)). This inhibits operation of the glycerol phosphate cycle in which DHAP is converted into glycerol phosphate, which concomitantly regenerates NAD(+) from NADH, thereby ensuring glycolytic oxidation of glyceraldehyde-3-phosphate (G3P). Because DHAP and G3P spontaneously decompose into MG, and NAD(+) is required for conversion of G3P into phosphoglycerate, the glycerol-induced increased DHAP formation and decreased NAD(+) availability will increase the potential for MG generation. In contrast, oxaloacetate may decrease MG generation by stimulating the operation of the malate-oxaloacetate shuttle, in which oxaloacetate is converted to malate, which regenerates NAD(+) from NADH. By the ensuing G3P oxidation, increased NAD(+) availability will decrease the potential for MG formation. It should be noted that mitochondria are involved in the operation of the above cycle/shuttles and that increased NAD(+) availability also stimulates those sirtuin activities that increase mitogenesis and mitochondrial activity via effects on signal transduction and gene expression, which frequently accompany dietary restriction-induced life span extension.
Effects of nitric oxide synthase inhibitors on murine infection with Mycobacterium tuberculosis (1995)

We have recently demonstrated that the macrophage L-arginine-dependent cytotoxic pathway effectively kills the virulent Erdman strain of Mycobacterium tuberculosis in vitro via the generation of toxic reactive nitrogen intermediates by the enzyme nitric oxide synthase. This report demonstrates that two distinct inhibitors of nitric oxide synthase (aminoguanidine and NG-monomethyl-L-arginine) render similar deleterious effects on tuberculous infection in mice, as assessed by mortality, bacterial burden, and pathological tissue damage, thus confirming the importance of reactive nitrogen intermediates in resistance against M. tuberculosis.
Roles of MinC and MinD in the site-specific septation block mediated by the MinCDE system of Escherichia coli (1992)

The proper placement of the cell division site in Escherichia coli requires the site-specific inactivation of potential division sites at the cell poles in a process that requires the coordinate action of the MinC, MinD, and MinE proteins. In the absence of MinE, the coordinate expression of MinC and MinD leads to a general inhibition of cell division. MinE gives topological specificity to the division inhibition process, so that the septation block is restricted to the cell poles. At normal levels of expression, both MinC and MinD are required for the division block. We show here that, when expressed at high levels, MinC acts as a division inhibitor even in the absence of MinD. The division inhibition that results from MinC overexpression in the absence of MinD is insensitive to the MinE topological specificity factor. The results suggest that MinC is the proximate cause of the septation block and that MinD plays two roles in the MinCDE system--it activates the MinC-dependent division inhibition mechanism and is also required for the sensitivity of the division inhibition system to the MinE topological specificity factor.
Trainable rule‐based algorithm for the measurement of joint space width in digital radiographic images of the knee (2000)

The progression of osteoarthritis (OA) can be monitored by measuring the minimum joint space width (mJSW) between the edges of the femoral condyle and the tibial plateau on radiographs of the knee. This is generally performed by a trained physician using a graduated magnifying lens and is prone to the subjectivity and variation associated with observer measurement. We have developed software that performs this measurement automatically on digitized radiographs. The test data consisted of 180 digitized radiographs of the knee (90 duplicate acquisitions) from 18 normal (nonarthritic) subjects and 38 images from 10 subjects with OA. These were digitized and manually cropped so that the images were free of nonanatomical structures and the knee was approximately centered. The software first determined the edge of the femoral condyle on 400 microm pixel subsampled images. Contours marking the location of the tibial plateau in the medial compartment were found on 100 microm images using the femoral edge as a reference. The algorithm was trained using an independent but similar data set and using a jackknife approach with the test data. The results were compared to contours drawn by a trained reader and the duplicate acquisitions were used to measure the reproducibility of the mJSW measurement. The reproducibility was 0.16 mm and 0.18 mm for normal and osteoarthritic knees, respectively, representing an improvement of approximately a factor of 2 over manual measurement. The algorithm also showed excellent agreement with the hand-drawn contours and with mJSW determined by the manual method.
Subcellular localization of protein kinase C δ and ε affects transcriptional and post-transcriptional processes in four-cell mouse embryos (2005)

During mouse preimplantation development, two isozymes of protein kinase C (PKC), delta and epsilon, transiently localize to nuclei at the early four-cell stage. In order to study their functions at this stage, we altered the subcellular localization of these isozymes (ratio of nuclear to cytoplasmic concentrations) with peptides that specifically activate or inhibit translocation of each isozyme. The effects of altering nuclear concentration of each isozyme on transcription (5-bromouridine 5'-triphosphate (BrUTP) incorporation), amount and distribution of small nuclear ribonucleoproteins (snRNPs), nucleolar dynamics (immunocytochemistry for Smith antigen (Sm) protein) and the activity of embryonic alkaline phosphatase (EAP; histochemistry) were examined. We found that nuclear concentration of PKC epsilon correlated with total mRNA transcription. Higher nuclear concentrations of both PKC delta and epsilon decreased storage of snRNPs in Cajal bodies and decreased the number of nucleoli, but did not affect the nucleoplasmic concentration of snRNPs. Inhibiting translocation of PKC delta out of the nucleus at the early four-cell stage decreased cytoplasmic EAP activity, whereas inhibiting translocation of PKC epsilon increased EAP activity slightly. These results indicate that translocation of PKC delta and epsilon in and out of nuclei at the early four-cell stage in mice can affect transcription or message processing, and that sequestration of these PKC in nuclei can also affect the activity of a cytoplasmic protein (EAP).
Introduce Satisfy Policies into Semaphore in WRK (2009)

This paper describes an improved semaphore with policies in Windows operating system. We introduce policies to help operating system kernel select next process (or thread) in the waiting list queue to satisfy. The paper present live policies: first in first out (FIFO), first in last out (FILO), highest priority first out (HPFO), lowest priority first out (LPFO) and random. We discuss the design and implement of semaphore with policies in windows research kernel (WRK), and the results are the same as expected.
A bispecific antibody against human IgE and human FcγRII that inhibits antigen‐induced histamine release by human mast cells and basophils (2004)

The bispecific antibody described here is the prototype of similar molecules that could be used in new therapeutic approaches of allergic diseases based on the coaggregation of activating receptors, such as FcepsilonRI, with inhibitory receptors, such as FcgammaRIIB, that are constitutively expressed by mast cells and basophils.