gebhart/patrepeval huggingface dataset:
Regulated expression of a repressor protein: FadR activates iclR (1996)

The control of the glyoxylate bypass operon (aceBAK) of Escherichia coli is mediated by two regulatory proteins, IclMR and FadR. IclMR is a repressor protein which has previously been shown to bind to a site which overlaps the aceBAK promoter. FAR is a repressor/activator protein which participates in control of the genes of fatty acid metabolism. A sequence just upstream of the iclR promoter bears a striking resemblance to FadR binding sites found in the fatty acid metabolic genes. The in vitro binding specificity of FadR, determined by oligonucleotide selection, was in good agreement with the sequences of these sites. The ability of FadR to bind to the site associated with iclR was demonstrated by gel shift and DNase I footprint analyses. Disruption of FadR or inactivation of the FadR binding site of iclR decreased the expression of an iclR::lacZ operon fusion, indicating that FadR activates the expression of iclR. It has been reported that disruption of fadR increases the expression of aceBAK. We observed a similar increase when we inactivated the FadR binding site of an iclR+ allele. This result suggests that FadR regulates aceBAK indirectly by altering the expression of IclR.
Dietary supplementation with melatonin reduces levels of amyloid beta‐peptides in the murine cerebral cortex (2004)

Melatonin levels decrease with aging in mice. Dietary supplementation with melatonin has recently been shown to result in a significant rise in levels of endogenous melatonin in the serum and all other tissue samples tested. Herein, the effects of dietary melatonin on brain levels of nitric oxide synthase, synaptic proteins and amyloid beta-peptides (Abeta) were determined in mice. Melatonin supplementation did not significantly change cerebral cortical levels of nitric oxide synthase or synaptic proteins such as synaptophysin and SNAP-25. Increased brain melatonin concentrations however, led to a significant reduction in levels of toxic cortical Abeta of both short and long forms which are involved in amyloid depositions and plaque formation in Alzheimer's diseases. Thus, melatonin supplementation may retard neurodegenerative changes associated with brain aging. Depletion of melatonin in the brain of aging mice may in part account for this adverse change.
Natural Foam Stabilizing and Bittering Compounds Derived from Hops (1998)

Various naturally occurring hop resin acids have been isolated by preparative HPLC from hops and hop products. Two resin acids have been tentatively identified by nuclear magnetic resonance techniques to be the minor constituent α-acids, adprehumulone and prehumulone. The isomerized derivative of the former considerably improved the foam stability and lacing of a commercial brand of beer. Dihydro-α-acids have previously been shown to occur and form in hops and hop products. Two of the dihydroiso-α-acids have been isolated by preparative HPLC, and dihydroisohumulone has also been shown to substantially improve foam stability and lacing of various brands of commercial beer as compared with the iso-α-acids.
Nonpeptide angiotensin II receptor antagonists. Synthesis and biological activity of benzimidazoles (1993)

A series of substituted 2-butylbenzimidazoles bearing a biphenylylmethyl moiety at the 1-position was prepared via three synthetic routes and evaluated for angiotensin II (AII) receptor antagonistic activity (in vitro and in vivo). Binding affinity was determined using bovine adrenal cortical membrane. Substitution at the 4-, 5-, or 6-position reduced the affinity relative to that of the unsubstituted compound (13a). However, most of the compounds with a substituent at the 7-position showed binding affinity comparable to that of DuP 753 (losartan). In functional studies, a carboxyl group was found to be very important for antagonistic activity against AII. Comparison of 2-butyl-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]- 1H-benzimidazole-4-, -5-, -6-, and -7-carboxylic acids (15a-d) in an AII-induced rabbit aortic ring contraction assay clearly demonstrated the importance of the substitutional position of the carboxyl group. In an in vivo assay, oral administration of benzimidazole-7-carboxylic acids caused long-lasting inhibition of the AII-induced pressor response in rats. The optimum substituent at the 7-position of the benzimidazole ring was found to be a carboxyl or an ester group. The representative compound, 2-butyl-1-[[2'- (1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxy lic acid (15d, CV-11194), inhibited the specific binding of [125I]AII to bovine adrenal cortical membrane with an IC50 value of 5.5 x 10(-7) M. The AII-induced contraction of rabbit aortic strips was antagonized by CV-11194 (IC50 value, 5.5 x 10(-11) M), while the compound had no effect on the contraction induced by norepinephrine or KCl. Orally administered CV-11194 at doses of 0.3-10 mg/kg dose-dependently inhibited the AII-induced pressor response in rats and dogs. CV-11194 at 1 mg/kg po reduced blood pressure in spontaneously hypertensive rats (SHR). The three-dimensional molecular structure of CV-11194 was determined by X-ray diffraction.
Hydrogen Production by Catalytic Decomposition of Methane (2001)

Traditionally, hydrogen is produced by reforming or partial oxidation of methane to produce synthesis gas, followed by the water-gas shift reaction to convert CO to CO2 and produce more hydrogen, followed in turn by a purification or separation procedure. This paper presents results for the catalytic decomposition of undiluted methane into hydrogen and carbon using nanoscale, binary, Fe−M (M = Pd, Mo, or Ni) catalysts supported on alumina. All of the supported Fe−M binary catalysts reduced methane decomposition temperature by 400−500 °C relative to noncatalytic thermal decomposition and exhibited significantly higher activity than Fe or any of the secondary metals (Pd, Mo, and Ni) supported on alumina alone. At reaction temperatures of approximately 700−800 °C and space velocities of 600 mL g-1 h-1, the product stream was comprised of over 80 volume % of hydrogen, with the balance being unconverted methane. No CO, CO2, or C2 and higher hydrocarbons were observed in the product gas. High-resolution SEM and TEM characterization indicated that almost all carbon produced in the temperature range of 700−800 °C is in the form of potentially useful multiwalled nanotubes. At higher temperatures (>900 °C), hydrogen production decreases and carbon is deposited on the catalyst in the form of amorphous carbon, carbon flakes, and carbon fibers. In the noncatalytic thermal decomposition mode, at temperatures above 900 °C, graphitic carbon film is deposited everywhere in the reactor. Thus, the morphology of the carbon produced may be the controlling parameter in catalytic decomposition of methane. The efficient removal of the carbon from the catalyst surface in the form of nanotubes may be the key factor influencing catalyst performance.
Molecular imaging of tumor angiogenesis using αvβ3-integrin targeted multimodal quantum dots (2008)

Molecular imaging of angiogenesis is urgently needed for diagnostic purposes such as early detection, monitoring of (angiostatic) therapy and individualized therapy. Multimodality molecular imaging is a promising and refined technique to study tumor angiogenesis, which has so far been largely unexplored due to the lack of suitable multimodal contrast agents. Here, we report on the application of a novel alphavbeta3-specific quantum dot-based nanoparticle, which has been optimized for both optical and magnetic resonance detection of tumor angiogenesis. Upon intravenous injection of RGD-pQDs in tumor-bearing mice, intravital microscopy allowed the detection of angiogenically activated endothelium at cellular resolution with a small scanning window and limited penetration depth, while magnetic resonance imaging was used to visualize angiogenesis at anatomical resolution throughout the entire tumor. Fluorescence imaging allowed whole-body investigation of angiogenic activity. Using these quantum dots and the aforementioned imaging modalities, the angiogenic tumor vasculature was readily detected with the highest angiogenic activity occurring in the periphery of the tumor. This nanoparticle may be employed for multimodality imaging of a variety of diseases that are accompanied by activation of endothelial cells. Furthermore, the current technology might be developed for molecular imaging of other pathophysiological processes.
Nanostructured supramolecular arrays based on dendrimers using DNA: Design, synthesis and biological evaluation. (2005)

This dissertation describes a series of experiments that synthesize and characterize a new type of supramolecular array. These molecules are based on dendrimers linked together with complementary DNA oligonucleotides. The arrays have a good range of applications including cancer cell specific drug targeting. Three specific studies were designed to test the hypothesis that complementary DNA oligonucleotides would self-assemble different single-functional dendrimers to form functional supramolecular clusters. First, in order to produce a library of functionalized dendrimers, generation 5 polyamidoamine (PAMAM) dendrimers were first partially acetylated, then conjugated with either imaging agents (fluorochromes; FITC, 6-TAMRA, and AF488) or targeting molecules (folic acid). The molecular characteristics of each functionalized dendrimers were characterized by UV-Vis, NMR, GPC, HPLC, and MALDI-TOF MS to ascertain their molar extinction, degree of functionalization, molecular weight and molecular weight distribution. Secondly, a synthetic method to covalently attach DNA oligonucleotides to the partially acetylated dendrimers was developed based on phosphoramidate chemistry. This chemistry was then applied to attach three sets of complementary oligonucleotides of different lengths (34, 50, 66 bases-long) to partially acetylated generation 7 and 5 PAMAM dendrimers. The size and the shape of the DNA-linked nanostructure were characterized by dynamic light scattering (DLS) and atomic force microscopy (AFM). Finally, we extended our strategy of DNA-based assembly to the construction of dimers of different single-functionalized dendrimers designed for cancer cell specific targeting. Three different batches of DNA-linked dendrimers consisting of imaging dendrimers (G5-FITC, G5-6-TAMRA, or G5-AF488) coupled to targeting dendrimer (G5-FA) consistently targeted KB cells overexpressing the high affinity folate receptor with maximum binding at 100 nM and an apparent binding affinity of &sim; 50 nM and internalized into the cells after 1 hour incubation at 37&deg;C <italic>in vitro</italic>. Preliminary <italic>in vivo </italic> experiments using SCID mice showed that the clusters accumulated in tumor cells expressing folic acid receptors 16 and 48 hours after injection. These results confirmed our hypothesis and demonstrated our ability to design and produce supramolecular arrays of dendrimers using DNA duplex formation. This DNA-linked dendrimer supramolecular array provides a potential platform for developing combinatorial targeted therapeutics in the future.
CELP coding based on mel-cepstral analysis (2002)

We propose a CELP coder based on mel-cepstral analysis. In the coder, since the transfer functions of perceptual weighting and postfiltering are defined through mel-cepstral coefficients, the effects of perceptual weighting and postfiltering should fit with the characteristics of the human auditory sensation. We use a basic CELP structure without adaptive codebook, and the subjective speech quality of the proposed coder in terms of the opinion equivalent Q is measured and compared with that of the conventional CELP coder. It is shown that the improvement of more than 1.8 dB is achieved by the proposed coder over the conventional CELP coder.
[Evaluation of indices indicating elderly long-term care need in municipalities]. (2004)

Hours of Care Need correlate well with the Odds Ratio and also with Care Compensation which represents long-term care insurance service expenses. The results clearly indicate that the 3 indices represent the status of care need of the elderly in these districts, even with conservative estimates, after 2002. It is suggested that Hours of Care Need and the Odds Ratio are appropriate as indices to evaluate preventive care programs in municipalities.
Improving the Oral Bioavailability of the Iron Chelator HBED by Breaking the Symmetry of the Intramolecular H-Bond Network (2000)

Physicochemical analysis and Monte Carlo simulations were used to identify structural features which prevent oral absorption of HBED, a potent iron chelator. In water the dominant conformations of HBED involve the hydrophobic collapse of the two aromatic rings. These conformations are favored in polar media because they expose the polar phenolic hydroxy groups to the solvent and partially shield the nonpolar aromatic rings. In a less polar solvent such as chloroform, a symmetrical H-bond network between the carboxylates and the amines dominates the conformational space. This leads to the exposure of the phenolic hydroxy groups to the solvent, which is unfavorable for solvation. The low solubility of HBED in nonpolar solvents was confirmed experimentally by determination of the partition coefficients in octanol, chloroform, and cyclohexane and may explain the poor membrane permeability of this compound. The high conformational stability which disfavors partitioning into phospholipids is mainly due to the symmetrical H-bond network. Potentiometric titrations of a monoester of HBED in MeOH/water indicate that the protonation sequence was changed compared to that of the parent compound, suggesting that the symmetrical H-bond network was disrupted. Conformational analysis in chloroform confirmed that, in contrast to HBED, no symmetric interaction between the carboxylate and the nitrogen amines is possible in the half-ester and a variety of conformations which allow partial shielding of the polar phenolic OH groups are energetically possible. This theoretical model predicting a better solubility of the half-esters in nonpolar solvents was supported by the large increase in the partition coefficients in octanol, chloroform, and cyclohexane measured experimentally. The high absorbability predicted by physicochemical and computer simulation methods was corroborated by in vivo experiments in marmoset monkeys where the monoethyl ester derivative of HBED was well-absorbed orally while the parent compound was nearly ineffective in the same model.
Raman spectroscopy of synovial fluid as a tool for diagnosing osteoarthritis (2009)

For many years, viscosity has been the primary method used by researchers in rheumatology to assess the physiochemical properties of synovial fluid in both normal and osteoarthritic patients. However, progress has been limited by the lack of methods that provide multiple layers of information, use small sample volumes, and are rapid. Raman spectroscopy was used to assess the biochemical composition of synovial fluid collected from 40 patients with clinical evidence of knee osteoarthritis (OA) at the time of elective surgical treatment. Severity of knee osteoarthritis was assessed by a radiologist using Kellgren/Lawrence (K/L) scores from knee joint x rays, while light microscopy and Raman spectroscopy were used to examine synovial fluid (SF) aspirates (2 to 10 microL), deposited on fused silica slides. We show that Raman bands used to describe protein secondary structure and content can be used to detect changes in synovial fluid from osteoarthritic patients. Several Raman band intensity ratios increased significantly in spectra collected from synovial fluid in patients with radiological evidence of moderate-to-severe osteoarthritis damage. These ratios can be used to provide a "yes/no" damage assessment. These studies provide evidence that Raman spectroscopy would be a suitable candidate in the evaluation of joint damage in knee osteoarthritis patients.
Single-cell analyses of circulating tumor cells. (2015)

Circulating tumor cells (CTCs) are a population of tumor cells mediating metastasis, which results in most of the cancer related deaths. The number of CTCs in the peripheral blood of patients is rare, and many platforms have been launched for detection and enrichment of CTCs. Enumeration of CTCs has already been used as a prognosis marker predicting the survival rate of cancer patients. Yet CTCs should be more potential. Studies on CTCs at single cell level may help revealing the underlying mechanism of tumorigenesis and metastasis. Though far from developed, this area of study holds much promise in providing new clinical application and deep understanding towards metastasis and cancer development.
Selective, covalent modification of β-tubulin residue Cys-239 by T138067, an antitumor agent with in vivo efficacy against multidrug-resistant tumors (1999)

Microtubules are linear polymers of alpha- and beta-tubulin heterodimers and are the major constituents of mitotic spindles, which are essential for the separation of chromosomes during mitosis. Here we describe a synthetic compound, 2-fluoro-1-methoxy-4-pentafluorophenylsulfonamidobenzene (T138067), which covalently and selectively modifies the beta1, beta2, and beta4 isotypes of beta-tubulin at a conserved cysteine residue, thereby disrupting microtubule polymerization. Cells exposed to T138067 become altered in shape, indicating a collapse of the cytoskeleton, and show an increase in chromosomal ploidy. Subsequently, these cells undergo apoptosis. Furthermore, T138067 exhibits cytotoxicity against tumor cell lines that exhibit substantial resistance to vinblastine, paclitaxel, doxorubicin, and actinomycin D. T138067 is also equally efficacious in inhibiting the growth of sensitive and multidrug-resistant human tumor xenografts in athymic nude mice. These observations suggest that T138067 may be clinically useful for the treatment of multidrug-resistant tumors.
Expression of Putative Fatty Acid Transporter Genes Are Regulated by Peroxisome Proliferator-activated Receptor α and γ Activators in a Tissue- and Inducer-specific Manner (1998)

Regulation of gene expression of three putative long-chain fatty acid transport proteins, fatty acid translocase (FAT), mitochondrial aspartate aminotransferase (mAspAT), and fatty acid transport protein (FATP), by drugs that activate peroxisome proliferator-activated receptor (PPAR) alpha and gamma were studied using normal and obese mice and rat hepatoma cells. FAT mRNA was induced in liver and intestine of normal mice and in hepatoma cells to various extents only by PPARalpha-activating drugs. FATP mRNA was similarly induced in liver, but to a lesser extent in intestine. The induction time course in the liver was slower for FAT and FATP mRNA than that of an mRNA encoding a peroxisomal enzyme. An obligatory role of PPARalpha in hepatic FAT and FATP induction was demonstrated, since an increase in these mRNAs was not observed in PPARalpha-null mice. Levels of mAspAT mRNA were higher in liver and intestine of mice treated with peroxisome proliferators, while levels in hepatoma cells were similar regardless of treatment. In white adipose tissue of KKAy obese mice, thiazolidinedione PPARgamma activators (pioglitazone and troglitazone) induced FAT and FATP more efficiently than the PPARalpha activator, clofibrate. This effect was absent in brown adipose tissue. Under the same conditions, levels of mAspAT mRNA did not change significantly in these tissues. In conclusion, tissue-specific expression of FAT and FATP genes involves both PPARalpha and -gamma. Our data suggest that among the three putative long-chain fatty acid transporters, FAT and FATP appear to have physiological roles. Thus, peroxisome proliferators not only influence the metabolism of intracellular fatty acids but also cellular uptake, which is likely to be an important regulatory step in lipid homeostasis.
Nine-Year Longitudinal Study of Antibodies to Variant Antigens on the Surface ofPlasmodium falciparum-Infected Erythrocytes (1999)

PfEMP1 is an antigenically variable molecule which mediates the adhesion of parasitized erythrocytes to a variety of cell types and which is believed to constitute an important target for naturally acquired protective immune responses in malaria. For 9 years we have monitored individuals living in an area of low-intensity, seasonal, and unstable malaria transmission in eastern Sudan, and we have used this database to study the acquisition, specificity, and duration of the antibody response to variant parasitized erythrocyte surface antigens. Both the levels and the spectrum of reactivity of these antibodies varied considerably among individuals, ranging from low levels of antibodies recognizing only few parasitized erythrocyte surface antigens to high levels of broad-specificity antibodies. In general, episodes of clinical malaria were associated with increases in the levels of parasitized erythrocyte surface-specific antibodies that subsided within months of the attack. This response was often, but not always, specific for the antigenic variants expressed by the parasite isolate causing disease. Our study provides evidence that Palciparum falciparum malaria is associated with a short-lived, variant-specific antibody response to PfEMP1-like antigens exposed on the surface of parasitized erythrocytes. Furthermore, our data suggest that the antigenic repertoires of variant antigens expressed by different parasite isolates show considerable overlapping, at least under Sahelian conditions of low-intensity, seasonal, and unstable malaria transmission. Finally, we demonstrate the existence of persistent differences among individuals in the capacity to mount antibody responses to variant surface antigens.
Cytokines Induce Indoleamine 2,3-Dioxygenase Expression in Human Atheroma-Associated Cells: Implications for PersistentChlamydophila pneumoniaeInfection (2002)

This study shows that vascular smooth muscle cells express significantly higher levels of gamma interferon-inducible indoleamine 2,3-dioxygenase (IDO) activity than endothelium or mononuclear cells. Since IDO activity is linked to persistent Chlamydophila pneumoniae infection, our results suggest that smooth muscle cells may be an important reservoir of that organism in atherosclerosis.
Inclusive Innovation Path Design of the New-Type Urbanization Development in Multiple-Block-Joint Impoverished Regions (2014)

Defining the multiple-block-joint impoverished regions which is an important strategic plan to fight the anti-poverty battle, were made by Central Committee and State Council in a new period. It is of great significance to achieve the political stability, national solidarity, border consolidation, social harmony, ecological security, build moderately prosperous society and realize the great rejuvenation of the Chinese dream. New urbanization, as a national grand strategy, not only facilitate promoting the economic and social structure adjustment, enhancing sustainable development dynamic, but also conducive to helping the poor get rid of poverty. This paper, based on the current situation of these regions and the correlation between the region and new urbanization, examines the problems and analyses the reasons in the process of the urbanization by combining static description and dynamic analysis together, at last discusses the routes to promote the urbanization in these regions from the perspective of inclusive innovation.