gebhart/patrepeval huggingface dataset:
Sulfated Cyclocarya paliurus polysaccharides markedly attenuates inflammation and oxidative damage in lipopolysaccharide-treated macrophage cells and mice (2017)

Natural polysaccharides and their modified derivatives are crucial supplements to the prevention of inflammation. This study aimed to evaluate the effect of sulfated modification on the anti-inflammatory and anti-oxidative activities of Cyclocarya paliurus polysaccharides (CP). A sulfated CP, S-CP<sub>1-4</sub> was obtained using chlorosulfonic acid-pyridine method. The chemical components and FT-IR spectrum confirmed that sulfated group was synthesized to the polysaccharide chains successfully. S-CP<sub>1-4</sub> was found to inhibit nitric oxide production, phagocytic activity and the release of interleukin (IL)-6 and IL-1β in lipopolysaccharide-treated macrophage cells, RAW 264.7. S-CP<sub>1-4</sub> significantly decreased the secretion of IL-6 and TNF-α and the thymus and spleen indexes, and increased the production of IL-10 in lipopolysaccharide-treated mice. S-CP<sub>1-4</sub> could better protect the liver by inhibiting the activities of alanine aminotransferase and aspartate aminotransferase, and malondialdehyde level while increasing the superoxide dismutase activity and total anti-oxidative capacity. These results suggested that S-CP<sub>1-4</sub> may be an effective anti-inflammatory agent, and sulfated modification may be a reliable method for the development of food supplements.
Synthesis and antimalarial effects of N2-aryl-N4-[(dialkylamino)alkyl]- and N4-aryl-N2-[(dialkylamino)alkyl]-2,4-quinazolinediamines (1981)

A series of N2(and N4)-aryl-N4(and N2)-[(dialkylamino)alkyl]-2,4-quinazolinediamines has been synthesized for antimalarial evaluation. Condensation of the appropriate 2,4-dichloroquinazoline (IV) with the requisite N,N-dialkylalkylenediamine afforded a series of 2-chloro-N-[(dialkylamino)alkyl]-4-quinazolinamines (V) which were condensed with the appropriate arylamine to provide the corresponding N2-aryl-N4-[(dialkylamino)alkyl]-2,4-quinazolinediamines (VI). Hydrolysis of 2,4-dichloroquinazoline to 2-chloro-4-quinazolinol was followed by condensation with the appropriate N,N-dialkylalkylenediamine to give an array of 2-[[(dialkylamino)alkyl]amino]-4-quinazolinols (IXa). Chlorination with phosphorus oxychloride and condensation with a requisite arylamine provided the N2-[(dialkylamino)alkyl]-N4-phenyl-2,4-quinazolinediamines (X). Antimalarial activity was general among the N2-aryl-N4-[(dialkylamino)alkyl]-2,4-quinazolinediamines (VI), while the reverse isomers were of lower activity. Phototoxic liability precluded clinical evaluation of a member of the series.
HUMAN IMMUNITY TO THE MENINGOCOCCUS (1969)

Susceptibility to systemic meningococcal disease is related to a selective deficiency of humoral antibodies to pathogenic strains of meningococci. In a study of the age-specific incidence of meningococcal meningitis in the United States, it was found that the proportion of individuals with serum bactericidal activity to meningococci of serogroups A, B, and C was reciprocally related to the incidence of disease. The prevalence of bactericidal activity was highest at birth and among adults, and lowest in infants between 6 and 24 months of age. Sera from 51 of 54 prospective cases of meningococcal disease among military recruits were deficient in antibodies to homologous and heterologous strains of pathogenic meningococci as determined by serum bactericidal activity and indirect immunofluorescence. Such sera, however, could support the bactericidal activity of purified human gamma globulin (Cohn fraction II), and such individuals could respond immunologically to infection with meningococci. The implication is that susceptible persons are deficient in antimeningococcal antibodies because they have not received significant exposure to meningococcal antigens in the past. The fate of individuals who lack bactericidal antibodies to pathogenic meningococci was determined during an outbreak of group C meningitis among military recruits. The incidence of disease was found to be primarily associated with the incidence of exposure of susceptibles to the pathogenic strains. Whereas 81.5% of the presumed susceptibles acquired a meningococcal strain, only 24.1% acquired an organism similar to the prevalent disease-producing strains. Of the exposed susceptibles, 38.5% developed systemic meningococcal disease.
Stimulation of Oct‐4 Activity by Ewing's Sarcoma Protein (2005)

The Oct-4 gene encodes a transcription factor that is expressed in embryonic stem (ES) cells and germ cells. Oct-4 is known to function as a transcriptional activator of genes involved in maintaining an undifferentiated totipotent state and possibly in preventing expression of genes activated during differentiation. In addition, it is a putative proto-oncogene and a critical player in the genesis of human testicular germ cell tumors. Although much effort has gone toward characterizing Oct-4, there is still little known about the molecular mechanisms and the proteins that regulate Oct-4 function. To identify cofactors that control Oct-4 function in vivo, we used a recently developed bacterial two-hybrid screening system and isolated a novel ES cell-derived cDNA encoding Ewing's sarcoma protein (EWS). EWS is a proto-oncogene and putative RNA-binding protein involved in human cancers. By using glutathione-S-transferase (GST) pull-down assays, we were able to confirm the interaction between Oct-4 and EWS in vitro, and moreover, coimmunoprecipitation and colocalization studies have shown that these proteins also associate in vivo. We have mapped the EWS-interacting region to the POU domain of Oct-4. In addition, three independent sites on EWS are involved in binding to Oct-4. In this study, we report that Oct-4 and EWS are coexpressed in the pluripotent mouse and human ES cells. Consistent with its ability to bind to and colocalize with Oct-4, ectopic expression of EWS enhances the transactivation ability of Oct-4. Moreover, a chimeric protein generated by fusion of EWS (1-295) to the GAL4 DNA-binding domain significantly increases promoter activity of a reporter containing GAL4 DNA-binding sites, suggesting the presence of a strong activation domain within EWS. Taken together, our results suggest that Oct-4-mediated transactivation is stimulated by EWS.
Hedgehog-Producing Cancer Cells Respond to and Require Autocrine Hedgehog Activity (2011)

A number of Smoothened (SMO) pathway antagonists are currently undergoing clinical trials as anticancer agents. These drugs are proposed to attenuate tumor growth solely through inhibition of Hedgehog (HH), which is produced in tumor cells but acts on tumor stromal cells. The pivotal argument underlying this model is that the growth-inhibitory properties of SMO antagonists on HH-producing cancer cells are due to their off-target effects. Here, we show that the tumorigenic properties of such lung cancer cells depend on their intrinsic level of HH activity. Notably, reducing HH signaling in these tumor cells decreases HH target gene expression. Taken together, these results question the dogma that autocrine HH signaling plays no role in HH-dependent cancers, and does so without using SMO antagonists.
Purification, Functionalization, and Bioconjugation of Carbon Nanotubes (2011)

Bioconjugation of carbon nanotubes (CNTs) with biomolecules promises exciting applications such as biosensing, nanobiocomposite formulation, design of drug vector systems, and probing protein interactions. Pristine CNTs, however, are virtually water-insoluble and difficult to evenly disperse in a liquid matrix. Therefore, it is necessary to attach molecules or functional groups to their sidewalls to enable bioconjugation. Both noncovalent and covalent procedures can be used to conjugate CNTs with a target biomolecule for a specific bioapplication. This chapter presents a few selected protocols that can be performed at any wet chemistry laboratory to purify and biofunctionalize CNTs. The preparation of CNTs modified with metallic nanoparticles, especially gold, is also described since biomolecules can bind and self-organize on the surfaces of such metal-decorated CNTs.
An active twenty-amino-acid-residue peptide derived from the inhibitor protein of the cyclic AMP-dependent protein kinase (1985)

Digestion with Staphylococcus aureus V8 proteinase of the inhibitor protein of the cyclic AMP-dependent protein kinase results in the sequential formation of three active inhibitory peptides. The smallest active peptide has the sequence Thr-Thr-Tyr-Ala-Asp-Phe-Ile-Ala-Ser-Gly-Arg-Thr-Gly-Arg-Arg-Asn-Ala-Ile- His-Asp . This 20-amino-acid-residue peptide has 20-40% of the activity of the native molecule and a Ki of 0.2 nM. Inhibition, as a minimum, appears to be based upon the inhibitor protein containing the recognition sequences that dictate protein-substrate-specificity. This inhibitory peptide also has sequence homology with the phosphorylation site for a protein kinase other than the cyclic AMP-dependent enzyme.
En-face coherence imaging using galvanometer scanner modulation (1998)

We introduce a novel optical path-modulation technique for a low-coherence interferometric imaging system based on transverse scanning of the target with a galvanometric scanning-mirror pair. The path modulation arises when the beam that is incident upon one of the scanning mirrors does not fall on its axis of rotation. The method is demonstrated by the production of en-face low-coherence images of different objects such as a fiber-optic tip and a human retina invivo .
Mode of disulfide bond formation of a heat‐stable enterotoxin (STh) produced by a human strain of enterotoxigenic Escherichia coli (1987)

To determine the modes of three disulfide linkages in the heat-stable enterotoxin (STh) produced by a human strain of enterotoxigenic Escherichia coli, we synthesized STh(6-18), which consists of 13 amino acid residues and has the same intramolecular disulfide linkages as native STh [(1985) FEBS Lett. 181, 138-142], by stepwise and selective formation of disulfide bonds using different types of removable protecting groups for the Cys residues. Synthesis of the peptide with different modes of disulfide bond formation provided three peptides consistent with standard STh(6-18) in their physicochemical and biological properties, thereby indicating that the disulfide bonds in STh(6-18) are Cys-Cys-Glu-Leu-Cys-Cys-Asn-Pro-Ala-Cys-Thr-Gly-Cys.
Free primary alcohols in oils and waxes from germs, kernels and other components of nuts, seeds, fruits and cereals (1991)

Abstract The composition of free primary alcohols in oils and waxes obtained from the germ, kernel, seed coat, shell and skin (peel) of various nuts, seeds, fruits and cereals and from the chrysalis of silkworm was examined. These alcohols are usually present in small amounts, along with large quantities of hydrocarbons, esters and glycerides in oils and waxes. Thus, it is necessary to remove hydrocarbons, esters and glycerides to analyze the alcohols. We found that preparative reverse‐phase thin‐layer chromatography (TLC) was the best way to isolate alcohols from oils and waxes. Gas liquid chromatography (GLC) then detected hexacosanol, octacosanol and triacontanol in the oils and waxes. Octacosanol usually was the predominant alcohol. Relationships between the organs from nuts, seeds, fruits and cereals and the contents of octacosanol are suggested. For example, degermed kernels contained two times more octacosanol than the germ, and the skin coat and shell contained one‐half and one‐fortieth the octacosanol of the germ, respectively.
Oligocarbonate Molecular Transporters: Oligomerization-Based Syntheses and Cell-Penetrating Studies (2009)

A new family of guanidinium-rich molecular transporters featuring a novel oligocarbonate backbone with 1,7-side chain spacing is described. Conjugates can be rapidly assembled irrespective of length in a one-step oligomerization strategy that can proceed with concomitant introduction of probes (or by analogy drugs). The new transporters exhibit excellent cellular entry as determined by flow cytometry and fluorescence microscopy, and the functionality of their drug delivery capabilities was confirmed by the delivery of the bioluminescent small molecule probe luciferin and turnover by its intracellular target enzyme.
Metabolic Control Analysis of Aspergillus nigerl‐Arabinose Catabolism (2005)

A mathematical model of the L-arabinose/D-xylose catabolic pathway of Aspergillus niger was constructed based on the kinetic properties of the enzymes. For this purpose L-arabinose reductase, L-arabitol dehydrogenase and D-xylose reductase were purified using dye-affinity chromatography, and their kinetic properties were characterized. For the other enzymes of the pathway the kinetic data were available from the literature. The metabolic model was used to analyze flux and metabolite concentration control of the L-arabinose catabolic pathway. The model demonstrated that flux control does not reside at the enzyme following the intermediate with the highest concentration, L-arabitol, but is distributed over the first three steps in the pathway, preceding and following L-arabitol. Flux control appeared to be strongly dependent on the intracellular L-arabinose concentration. At 5 mM intracellular L-arabinose, a level that resulted in realistic intermediate concentrations in the model, flux control coefficients for L-arabinose reductase, L-arabitol dehydrogenase and L-xylulose reductase were 0.68, 0.17 and 0.14, respectively. The analysis can be used as a guide to identify targets for metabolic engineering aiming at either flux or metabolite level optimization of the L-arabinose catabolic pathway of A. niger. Faster L-arabinose utilization may enhance utilization of readily available organic waste containing hemicelluloses to be converted into industrially interesting metabolites or valuable enzymes or proteins.
Mechanistic Basis for Coding End Sequence Effects in the Initiation of V(D)J Recombination (1999)

V(D)J recombination is directed by recombination signal sequences. However, the flanking coding end sequence can markedly affect the frequency of the initiation of V(D)J recombination in vivo. Here we demonstrate that the coding end sequence effect can be qualitatively and quantitatively recapitulated in vitro with purified RAG proteins. We find that coding end sequence specifically affects the nicking step, which is the first biochemical step in RAG-mediated cleavage. The subsequent hairpin formation step is not affected by the coding end sequence. Furthermore, the coding end sequence effect can be ablated by prenicking the substrate, indicating that the coding end effect is specific to the nicking step. In reactions in which both 12- and 23-substrates are present, a suboptimal coding end sequence on one signal can slow down hairpin formation at the partner signal, a result consistent with models in which coordination between the signals occurs at the hairpin formation step. The coding end sequence effect on nicking and the coupling of the 12- and 23-substrates explains how hairpin formation can be rate limiting for some 12/23 pairs, whereas nicking can be rate limiting when low-efficiency coding end sequences are involved.
Increased cytotoxic potential of microglia from ALS‐transgenic mice (2004)

Amyotrophic lateral sclerosis is a fatal, adult-onset motor neuron disease. A subset of cases is caused by mutations of superoxide dismutase 1 (SOD1) gene. The mechanisms how the mutations in this ubiquitous enzyme mediate the highly selective motor neuron degeneration, however, remain poorly understood. Recent results from transgenic animal models suggest a "non-cell autonomous" mechanism; i.e., cells other than neurons play an active role in motor neuron death. To investigate a possible effect of mtSOD1 on microglial cells, we compared primary cultured microglia from mtSOD1-transgenic mice and nontransgenic litter controls at neonatal (3 days) and adult (60 days) age. We found that mtSOD1 expression increases the production of TNF-alpha and attenuates IL-6-release by LPS-activated adult microglia. Neonatal microglia, however, showed no differences. Our findings suggest an increased cytotoxic potential of adult mtSOD1 microglia, which only becomes apparent after microglial activation.
The neuroprotective function of vascular endothelial growth factor (VEGF). (2005)

The vascular endothelial growth factor (VEGF) is known mainly as the potent angiogenic and vascular permeability-enhancing factor. Both processes are very effective in hypoxia. The latest studies show that VEGF has neurotrophic and neuroprotective as well as angiogenic properties. It exerts neuroprotective actions directly through the inhibition of programmed cell death (PCD), or apoptosis and the stimulation of neurogenesis. VEGF is also a mediator of multiple processes including angiogenesis, enhancing blood brain barrier permeability for glucose, antioxidants activation, which indirectly result in neuroprotection. VEGF prevents neurons from death under critical conditions such as hypoxia, glucose deprivation through binding to the specific receptors, which are also expressed on the surface of neuronal cells. The increased expression of VEGFR-2/flk-1/KDR receptors on neurons subjected to hypoxia, glucose deprivation provides evidence that these receptors are mainly involved in neuroprotective effects of VEGF. Furthermore, binding to these receptors triggers the phosphatidyloinositol 3-kinase (PI3K) /Akt signal transduction system and, in consequence, leads to the inhibition of PCD by activating antiapoptotic proteins through the transcription factor NFkappaB and inhibiting proapoptotic signaling by Bad, caspase-9, caspase-3, and other effectors. Promotion of neuronal cells proliferation by VEGF is also associated with the increased expression of VEGFR-2 receptors and up-regulation of E2F family transcription factors, cyclin D1, cyclin E, and cdc25. It is known that the amount and types of VEGF isoforms influence its action. At least six isoforms of VEGF proteins are formed as a result of alternative mRNA splicing and it is unknown which of them and in what proportion occur in the nervous system in physiology and pathophysiology. It seems to be very essential to find out the mechanisms responsible for specific patterns of VEGF isoforms and their receptors expression in different pathologies of the nervous system. Maybe such knowledge will provide new perspectives in VEGF therapy.
Retrodirective arrays for wireless communications (2002)

This article reports the recent progress in active and passive retrodirective arrays using phase-conjugation techniques. The arrays presented here are designed for wireless communications in microwave bands and have other features in addition to self-phasing aspects such that they can be applied to practical communication systems. The reliance on purely analog circuitry offers system simplicity and high-speed response. The self-beam-steering feature potentially offers the improvement of communication link gain between an interrogator and a retrodirective array, reducing the burden on transmitting and receiving amplifiers. By implementing a receiving function, it has been demonstrated that retrodirective arrays can also be used in bidirectional communications in either a full or semiduplex manner, initiating a new class of transceiver architecture.
Acidic Lipids Associated with the Local Mechanism of Calcification (1976)

Two current areas of research on hard tissues have focused upon acidic lipids associated with the local mechanism of calcification and the presence of matrix vesicles as the loci for initial mineralization. Data which show that acidic phospholipids are a component of the vesicle membrane provide a common denominator between these two areas. Furthermore, studies on vertebrate, microbial and synthetic lipoprotein calcification indicate that acidic phospholipids play a pivotal role in the local mechanism. Through a sequence of initial Ca2++ binding followed by desolvation and ion concentration, the acidic phospholipid rich membrane provides an environment in which calcification can be facilitated. A proposed mechanism includes in additon to Ca2++ binding, the formation of (CaHPO4)2 dimers and their condensation into a Ca9 (PO4)6 unit bound to the membrane. The bound unit functions as a nucleus for the formation of additonal units to form an amorphous calcium phosphate cluster. Conversion to crystalline apatite would require dehydration of the environment, either by mineral build up exceeding the hydrophobic domain or by breakdown of the membrane.
Interaction of HP1 and Brg1/Brm with the Globular Domain of Histone H3 Is Required for HP1-Mediated Repression (2009)

The heterochromatin-enriched HP1 proteins play a critical role in regulation of transcription. These proteins contain two related domains known as the chromo- and the chromoshadow-domain. The chromo-domain binds histone H3 tails methylated on lysine 9. However, in vivo and in vitro experiments have shown that the affinity of HP1 proteins to native methylated chromatin is relatively poor and that the opening of chromatin occurring during DNA replication facilitates their binding to nucleosomes. These observations prompted us to investigate whether HP1 proteins have additional histone binding activities, envisioning also affinity for regions potentially occluded by the nucleosome structure. We find that the chromoshadow-domain interacts with histone H3 in a region located partially inside the nucleosomal barrel at the entry/exit point of the nucleosome. Interestingly, this region is also contacted by the catalytic subunits of the human SWI/SNF complex. In vitro, efficient SWI/SNF remodeling requires this contact and is inhibited in the presence of HP1 proteins. The antagonism between SWI/SNF and HP1 proteins is also observed in vivo on a series of interferon-regulated genes. Finally, we show that SWI/SNF activity favors loading of HP1 proteins to chromatin both in vivo and in vitro. Altogether, our data suggest that HP1 chromoshadow-domains can benefit from the opening of nucleosomal structures to bind chromatin and that HP1 proteins use this property to detect and arrest unwanted chromatin remodeling.
Transdiscal Lumbar Sympathetic Block (1997)

Neurolytic lumbar sympathetic block was performed with the needle advanced through the intervertebral disc. With this technique, the risk of genitofemoral neuritis, the most common complication after neurolytic lumbar sympathetic block, was reduced because the needle does not penetrate the psoas muscle, through which the genitofemoral nerve passes.