gebhart/patrepeval huggingface dataset:
Synthesis of Mixed Monolayer-Protected Gold Clusters from Thiol Mixtures:  Variation in the Tail Group, Chain Length, and Solvent (2003)

We present a systematic study on the synthesis of mixed monolayer-protected clusters (MMPCs) from mixtures of alkanethiols. Our results show that solvation-driven thermodynamic preferential adsorption of precursor ligands governs monolayer composition of MMPCs. In the mixed system HO(CH2)nSH/ CH3(CH2)mSH (n = m or n ≠ m) in toluene, adsorption of the polar component is largely favored because of the poorer solvation of polar tail groups in toluene compared to tetrahydrofuran (THF). When MMPCs are generated from the mixed system HO(CH2)nSH/CH3(CH2)mSH (n = m) in THF, the tail group effect is much less. The MMPC synthesis in THF solutions containing HO(CH2)nSH/CH3(CH2)mSH (n ≠ m) shows large thermodynamic control, which promotes a preferential adsorption of the thiols with a longer alkyl chain onto the surface of clusters. Transmission electron microscopy (TEM) and UV−vis spectroscopy data suggest that the average core dimension of MPCs generated from alkanethiols in THF is slightly smaller than that of MPCs generated from alkanethiols in toluene under the same conditions.
Anti-tumor activity of an antibiotic peptide derived from apoprotein E. (2005)

ApoE 133-162 has anti-tumor activity, probably through perturbation and formation of ion-permeable "pores" in membranes.
RNase G-Dependent Degradation of theenomRNA Encoding a Glycolysis Enzyme Enolase inEscherichia coli (2002)

Escherichia coli RNase G, encoded by the rng gene, is involved in the processing of 16S rRNA and degradation of the adhE mRNA encoding a fermentative alcohol dehydrogenase. In a search for the intracellular target RNAs of RNase G other than the 16S rRNA precursor and adhE mRNA, total cellular proteins from rng+ and rng::cat cells were compared by two-dimensional gel electrophoresis. The amount of enolase encoded by the eno gene reproducibly increased two- to three-fold in the rng::cat mutant strain compared with the rng+ parent strain. Rifampicin chase experiments showed that the half-life of the eno mRNA was some 3 times longer in the rng::cat mutant than in the wild type. These results indicate that the eno mRNA was a substrate of RNase G in vivo, in addition to 16S rRNA precursor and adhE mRNA.
Non-Nutritive Bioactive Food Constituents of Plants: Lycopene, Lutein and Zeaxanthin (2003)

Lycopene, lutein, and zeaxanthin are major carotenoids in human blood and tissues but unlike beta-carotene do not contribute to vitamin A supply. These carotenoids are efficient antioxidants quenching singlet molecular oxygen which is formed in photooxidative processes and thus may contribute to the prevention of light-exposed tissue, skin and eyes, from light-induced damage. Increasing lycopene intake by daily consumption of tomato paste over a period of ten weeks provides protection against erythema formation following UV-irradiation. Lycopene and other carotenoids may be used as oral sun protectants and contribute to the maintenance of skin health. The yellow color of the macula lutea is due to the presence of the carotenoid pigments lutein and zeaxanthin. These macula carotenoids are suggested to play a role in protection against light-dependent damage. Filtering of blue light and scavenging of reactive intermediates generated in photooxidation are considered to be the underlying protective mechanisms. Epidemiological studies provide evidence that an increased consumption of lutein is associated with a lowered risk for age-related macular degeneration, a disease with increasing incidence in the elderly.
Distribution of costameric proteins in normal human ventricular and atrial cardiac muscle. (2010)

In the mature heart, the intercalated disc and costameres provide the cell-cell and cell-matrix junctions respectively. Intercalated disc is situated at the bipolar ends of the cardiomyocytes and the myofibrils are anchored at this structure. The costameres mediate integration with the extracellular matrix that covers individual cardiomyocytes laterally. Costameres are considered as "proteic machinery" that appears to comprise two protein complexes: the dystrophin-glycoprotein complex (DGC) and the vinculin-talin-integrin system. There are structural differences between atrial and ventricular myocytes, but there have been relatively few studies that have analyzed costameres and focal adhesion function in cardiac cells. Our previous study carried out only on atrial myocytes, demonstrated that the DGC and talin-vinculin-integrin complexes had a costameric distribution that, unlike skeletal muscle, it localized only on the I band. We performed a further immunohistochemical analysis extending also the evaluation to the normal human cardiac muscle fibers obtained from ventricle and interventricular septum, in order to define the distribution and the spatial relationship between the proteins of the two complexes also in the other heart districts. Immunoconfocal microscopy of cardiac tissue revealed the costameric distribution of DGC and of vinculin-talin-integrin system, the association of all tested proteins in intercalated disks, in disagreement with other Authors, and in T-tubule with irregular spokelike extensions penetrating toward the center of the cell. Moreover, our data showed that all tested proteins colocalize between each other.
Thermally-Actuated Microfluidic Systems (2008)

A new system concept has been developed for microfluidic devices in which thermal actuation is used to achieve most or all fluid and reaction control functions (e.g., valves, pumps, mixers, separators, heaters, and coolers). Thermal actuation makes it possible to incorporate the fluid-containing components in a module that can be physically separated from the actuation elements, making the fluid-bearing module disposable. The actuation elements are embedded in a reusable module, reducing the complexity and cost of the disposable unit. The thermally-actuated valve is central to the system design, and has been well characterized. Thermal-actuation concepts for other fluid-handling functions have been developed and, in most cases, demonstrated. The approach is scalable from microchip to microtiter-plate formats. It can also be integrated into existing microchip technologies to expand functionality. Prototypes have been built and tested in combination with a DNA array for diagnostics of infectious diseases.
Making (anti)sense of non-coding sequence conservation (1997)

A substantial fraction of vertebrate mRNAs contain long conserved blocks in their untranslated regions as well as long blocks without silent changes in their protein coding regions. These conserved blocks are largely comprised of unique sequence within the genome, leaving us with an important puzzle regarding their function. A large body of experimental data shows that these regions are associated with regulation of mRNA stability. Combining this information with the rapidly accumulating data on endogenous antisense transcripts, we propose that the conserved sequences form long perfect duplexes with antisense transcripts. The formation of such duplexes may be essential for recognition by post-transcriptional regulatory systems. The conservation may then be explained by selection against the dominant negative effect of allelic divergence.
Conformation of two non‐immunosuppressive FK506 analogs when bound to FKBP by isotope‐filtered NMR (1992)

The 3D structure of two unlabeled FK506 analogs, (R)- and (S)-[18-OH]ascomycin, when bound to [U-13C,15N]FKBP were determined by isotope-filtered 2D NMR experiments. The structures for the R and S isomers that bind tightly to FKBP but lack immunosuppressive activity are compared to each other and to the conformation of the potent immunosuppressant, ascomycin, when bound to FKBP. The results are interpreted in terms of calcineurin binding to the FKBP/ascomycin complex.
Rapid decrease in tumor perfusion following VEGF blockade predicts long-term tumor growth inhibition in preclinical tumor models (2012)

Vascular endothelial growth factor (VEGF) is a key upstream mediator of tumor angiogenesis, and blockade of VEGF can inhibit tumor angiogenesis and decrease tumor growth. However, not all tumors respond well to anti-VEGF therapy. Despite much effort, identification of early response biomarkers that correlate with long-term efficacy of anti-VEGF therapy has been difficult. These difficulties arise in part because the functional effects of VEGF inhibition on tumor vessels are still unclear. We therefore assessed rapid molecular, morphologic and functional vascular responses following treatment with aflibercept (also known as VEGF Trap or ziv-aflibercept in the United States) in preclinical tumor models with a range of responses to anti-VEGF therapy, including Colo205 human colorectal carcinoma (highly sensitive), C6 rat glioblastoma (moderately sensitive), and HT1080 human fibrosarcoma (resistant), and correlated these changes to long-term tumor growth inhibition. We found that an overall decrease in tumor vessel perfusion, assessed by dynamic contrast-enhanced ultrasound (DCE-US), and increases in tumor hypoxia correlated well with long-term tumor growth inhibition, whereas changes in vascular gene expression and microvessel density did not. Our findings support previous clinical studies showing that decreased tumor perfusion after anti-VEGF therapy (measured by DCE-US) correlated with response. Thus, measuring tumor perfusion changes shortly after treatment with VEGF inhibitors, or possibly other anti-angiogenic therapies, may be useful to predict treatment efficacy.
Improving Ethanol Tolerance of Escherichia coli by Rewiring Its Global Regulator cAMP Receptor Protein (CRP) (2013)

A major challenge in bioethanol fermentation is the low tolerance of the microbial host towards the end product bioethanol. Here we report to improve the ethanol tolerance of E. coli from the transcriptional level by engineering its global transcription factor cAMP receptor protein (CRP), which is known to regulate over 400 genes in E. coli. Three ethanol tolerant CRP mutants (E1- E3) were identified from error-prone PCR libraries. The best ethanol-tolerant strain E2 (M59T) had the growth rate of 0.08 h(-1) in 62 g/L ethanol, higher than that of the control at 0.06 h(-1). The M59T mutation was then integrated into the genome to create variant iE2. When exposed to 150 g/l ethanol, the survival of iE2 after 15 min was about 12%, while that of BW25113 was <0.01%. Quantitative real-time reverse transcription PCR analysis (RT-PCR) on 444 CRP-regulated genes using OpenArray® technology revealed that 203 genes were differentially expressed in iE2 in the absence of ethanol, whereas 92 displayed differential expression when facing ethanol stress. These genes belong to various functional groups, including central intermediary metabolism (aceE, acnA, sdhD, sucA), iron ion transport (entH, entD, fecA, fecB), and general stress response (osmY, rpoS). Six up-regulated and twelve down-regulated common genes were found in both iE2 and E2 under ethanol stress, whereas over one hundred common genes showed differential expression in the absence of ethanol. Based on the RT-PCR results, entA, marA or bhsA was knocked out in iE2 and the resulting strains became more sensitive towards ethanol.
Inducible inactivation of hepatic LRP gene by cre-mediated recombination confirms role of LRP in clearance of chylomicron remnants. (1998)

The multifunctional low density lipoprotein (LDL) receptor-related protein (LRP) has been postulated to participate in a number of diverse physiological and pathological processes ranging from the homeostasis of plasma lipoproteins, atherosclerosis, and fibrinolysis to neuronal regeneration and survival. It has not been possible to demonstrate in vivo the physiological significance of LRP for each of these complex processes by a conventional gene knockout approach because LRP is essential for embryonic development. Here we have used the Cre/loxP recombination system to achieve inducible, tissue-specific and quantitative disruption of the LRP gene in adult mice. Inactivation of LRP in the livers of LDL receptor-deficient mice resulted in the accumulation of cholesterol-rich remnant lipoproteins in the circulation. In normal animals, this caused a compensatory upregulation of the LDL receptor in the liver. Conditional gene targeting has thus allowed us to isolate a specific physiological function of LRP for in vivo analysis and has provided unequivocal evidence for another LDL receptor-independent cholesterol clearance pathway in liver.
Heterogeneous T-cell response to MAGE-A10(254-262): high avidity-specific cytolytic T lymphocytes show superior antitumor activity. (2001)

MAGE-encoded antigens, which are expressed by tumors of many histological types but not in normal tissues, are suitable candidates for vaccine-based immunotherapy of cancers. Thus far, however, T-cell responses to MAGE antigens have been detected only occasionally in cancer patients. In contrast, by using HLA/peptide fluorescent tetramers, we have observed recently that CD8(+) T cells specific for peptide MAGE-A10(254-262) can be detected frequently in peptide-stimulated peripheral blood mononuclear cells from HLA-A2-expressing melanoma patients and healthy donors. On the basis of these results, antitumoral vaccination trials using peptide MAGE-A10(254-262) have been implemented recently. In the present study, we have characterized MAGE-A10(254-262)-specific CD8(+) T cells in polyclonal cultures and at the clonal level. The results indicate that the repertoire of MAGE-A10(254-262)-specific CD8(+) T cells is diverse both in terms of clonal composition, efficiency of peptide recognition, and tumor-specific lytic activity. Importantly, only CD8(+) T cells able to recognize the antigenic peptide with high efficiency are able to lyse MAGE-A10-expressing tumor cells. Under defined experimental conditions, the tetramer staining intensity exhibited by MAGE-A10(254-262)-specific CD8(+) T cells correlates with efficiency of peptide recognition so that "high" and "low" avidity cells can be separated by FACS. Altogether, the data reported here provide evidence for functional diversity of MAGE-A10(254-262)-specific T cells and will be instrumental for the monitoring of peptide MAGE-A10(254-262)-based clinical trials.
Blocking Tumor Cell Migration and Invasion with Biphenyl Isoxazole Derivative KRIBB3, a Synthetic Molecule That Inhibits Hsp27 Phosphorylation (2005)

Cell migration is a prerequisite for cancer invasion and metastasis, suggesting cell motility as a potential therapeutic target for cancer treatment. A synthetic library was screened to identify inhibitors of tumor cell migration. From this, we discovered that CAC-1098 (aurintricarboxylic acid) and CBI-0997 (5-(2,4-dimethoxy-5-ethylphenyl)-4-(4-bromophenyl) isoxazole) inhibited migration of MDA-MB-231 cells with IC50 = 5 and 50 nM, respectively. We synthesized KRIBB3 (5-(5-ethyl-2-hydroxy-4-methoxyphenyl)-4-(4-methoxyphenyl) isoxazole) by replacing the bromide group of CBI-0997 with a methoxyl group. Like CBI-0997, KRIBB3 has anti-migratory and anti-invasive activities in MDA-MB-231 cells. Because KRIBB3 has a better drug-like structure, we focused our effort on further understanding its anti-migratory mechanism. Biotinyl-KRIBB3 was synthesized as an affinity probe for identification of KRIBB3-binding proteins. Using affinity chromatography, we identified Hsp27 as a target protein of KRIBB3 in vitro. Treatment of MDA-MB-231 cells with phorbol 12-myristate 13-acetate induced protein kinase C-dependent phosphorylation of Hsp27 and tumor cell migration. In contrast, treatment of MDA-MB-231 cells with KRIBB3 blocked phorbol 12-myristate 13-acetate-induced phosphorylation of Hsp27 and tumor cell migration. Furthermore, overexpression of Hsp27 antagonized the inhibitory effect of KRIBB3 on tumor cell invasion, and knockdown of Hsp27 using small interfering RNA inhibited tumor cell migration. Overall, our results demonstrate that KRIBB3 inhibits tumor cell migration and invasion by blocking protein kinase C-dependent phosphorylation of Hsp27 through its direct binding to Hsp27.
Treatment of Hematologic Malignancies with Immunotoxins and Antibody-Drug Conjugates (2011)

To enable antibodies to function as cytotoxic anticancer agents, they are modified either via attachment to protein toxins or highly potent, low-molecular-weight drugs. Such molecules, termed immunotoxins and antibody-drug conjugates, respectively, represent a second revolution in antibody-mediated cancer therapy. Thus, highly toxic compounds are delivered to the interior of cancer cells based on antibody specificity for cell-surface target antigens.
Effect of laser phase noise in Sagnac interferometers (1993)

A theoretical analysis of the responsivity and the noise caused by backscattering in a Sagnac interferometer used as a sensor for reciprocal measurands, such as acoustic waves, is presented. Both Rayleigh backscattering and reflections from splices are taken into account. The noise power is found to increase proportionally to the source coherence time, and a noise equivalent phase shift in the range of 0.1*10/sup -6/ rad r.m.s./Hz/sup 1/2/ is predicted for typical fibers and diode lasers. Experimentally, a noise equivalent phase shift of 2.5*10/sup -7/ rad r.m.s./Hz/sup 1/2/ at 10 kHz was observed, with a detector current of 3 mu A.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Respiratory Syncytial Virus–Induced Activation of Nuclear Factor–κB in the Lung Involves Alveolar Macrophages and Toll‐Like Receptor 4–Dependent Pathways (2002)

The transcription factor nuclear factor (NF)-kappaB controls the expression of numerous respiratory syncytial virus (RSV)-inducible inflammatory and immunomodulatory genes. Using a BALB/c mouse model, the present article shows that RSV potently and specifically activates NF-kappaB in vivo, a process that involves nuclear translocation of the subunits RelA, p50, and c-Rel in the lung. By depletion of alveolar macrophages (AMs) in BALB/c mice and use of C3H/HeJ mice lacking a functional Toll-like receptor (TLR)-4 signaling pathway, we demonstrate the existence of distinct but sequentially integrated RSV-inducible early NF-kappaB responses in the lung. The first response occurs early after RSV inoculation, is AM and TLR4 dependent, and is viral replication independent, whereas the second response involves epithelial cells and/or inflammatory cells, is TLR4 independent, and requires viral replication. NF-kappaB may be considered a central activator of not only inflammatory but also innate immune responses to RSV.
ATR and H2AX Cooperate in Maintaining Genome Stability under Replication Stress (2008)

Chromosomal abnormalities are frequently caused by problems encountered during DNA replication. Although the ATR-Chk1 pathway has previously been implicated in preventing the collapse of stalled replication forks into double-strand breaks (DSB), the importance of the response to fork collapse in ATR-deficient cells has not been well characterized. Herein, we demonstrate that, upon stalled replication, ATR deficiency leads to the phosphorylation of H2AX by ATM and DNA-PKcs and to the focal accumulation of Rad51, a marker of homologous recombination and fork restart. Because H2AX has been shown to play a facilitative role in homologous recombination, we hypothesized that H2AX participates in Rad51-mediated suppression of DSBs generated in the absence of ATR. Consistent with this model, increased Rad51 focal accumulation in ATR-deficient cells is largely dependent on H2AX, and dual deficiencies in ATR and H2AX lead to synergistic increases in chromatid breaks and translocations. Importantly, the ATM and DNA-PK phosphorylation site on H2AX (Ser(139)) is required for genome stabilization in the absence of ATR; therefore, phosphorylation of H2AX by ATM and DNA-PKcs plays a pivotal role in suppressing DSBs during DNA synthesis in instances of ATR pathway failure. These results imply that ATR-dependent fork stabilization and H2AX/ATM/DNA-PKcs-dependent restart pathways cooperatively suppress double-strand breaks as a layered response network when replication stalls.
Differential utilization of poly(rC) binding protein 2 in translation directed by picornavirus IRES elements (1999)

The translation of picornavirus genomic RNAs occurs by a cap-independent mechanism that requires the formation of specific ribonucleoprotein complexes involving host cell factors and highly structured regions of picornavirus 5' noncoding regions known as internal ribosome entry sites (IRES). Although a number of cellular proteins have been shown to be involved in picornavirus RNA translation, the precise role of these factors in picornavirus internal ribosome entry is not understood. In this report, we provide evidence for the existence of distinct mechanisms for the internal initiation of translation between type I and type II picornavirus IRES elements. In vitro translation reactions were conducted in HeLa cell cytoplasmic translation extracts that were depleted of the cellular protein, poly(rC) binding protein 2 (PCBP2). Upon depletion of PCBP2, these extracts possessed a significantly diminished capacity to translate reporter RNAs containing the type I IRES elements of poliovirus, coxsackievirus, or human rhinovirus linked to luciferase; however, the addition of recombinant PCBP2 could reconstitute translation. Furthermore, RNA electrophoretic mobility-shift analysis demonstrated specific interactions between PCBP2 and both type I and type II picornavirus IRES elements; however, the translation of reporter RNAs containing the type II IRES elements of encephalomyocarditis virus and foot-and-mouth disease virus was not PCBP2 dependent. These data demonstrate that PCBP2 is essential for the internal initiation of translation on picornavirus type I IRES elements but is dispensable for translation directed by the structurally distinct type II elements.
Divalent–Anion Salt Effects in Polyelectrolyte Multilayer Depositions (2012)

We systematically investigate the effects of divalent anions on the assembly of polyelectrolyte multilayers by fabricating polystyrene sulfonate (PSS)/polyallylamine hydrochloride (PAH) multilayer films from aqueous solutions containing SO(4)(2-), HPO(4)(2-), or organic dicarboxylate dianions. The chosen concentrations of these anions (i.e., ≤0.05 M) allow us to isolate their effects on the assembly process from those of the polyelectrolyte solubility or solution ionic strength (maintained constant at μ = 1.00 M by added NaCl). Compared to a control film prepared from solutions containing only Cl(-) anions, stratified multilayers deposited in the presence of dianions exhibit increased UV absorbance, thickness, and roughness. From the dependence of film properties on the solution concentration of SO(4)(2-) and number of polyelectrolyte layers deposited, we derive a generic model for the PSS/PAH multilayer formation that involves adsorption of PAH aggregates formed in solution via electrostatic interactions of PAH with bridging dianions. Experiments using HPO(4)(2-) and organic dicarboxylate species of varying structure indicate that the separation, rigidity, and angle between the discrete negatively charged sites in the dianion govern the formation of the PAH aggregates, and therefore also the properties of the multilayer film. A universal linear relationship between film UV absorbance and thickness is observed among all dianion types or concentrations, consistent with the model.