gebhart/patrepeval huggingface dataset:
Inhibition of radiation-induced G2 delay potentiates cell death by apoptosis and/or the induction of giant cells in colorectal tumor cells with disrupted p53 function. (1997)

We have previously identified a p53-independent apoptotic response that is delayed until 48-72 h after irradiation of colorectal adenoma and carcinoma cells. Because the delay appears to be in part due to a transient G2 cell cycle arrest, the importance of this checkpoint in the mechanism of ionizing radiation (IR)-induced death of colorectal tumor cells was investigated. An adenoma cell line with (282Arg-->Trp) mutant p53 (S/RG/C2) and a carcinoma cell line (PC/JW/FI) lacking p53 protein treated with 5 Gy IR in the presence of 1.5 mm caffeine (CAF) reduced IR-induced G2 arrest and increased the level of apoptosis (1.5-1.6-fold) 24 h after treatment. Increased IR apoptotic cell death with CAF significantly reduced IR cell survival over a 7-day period in S/RG/C2 and PC/JW/FI. To investigate whether CAF radiosensitization correlated with lack of wild-type (wt) p53, we studied transfected derivatives of an adenoma-derived cell line (PC/AA/C1), in which the endogenous wt p53 activity was disrupted by the expression of a dominant negative (273Arg-->His) p53 mutant protein (designated AA/273p53/B). This p53-defective cell line was also radiosensitized by CAF, whereas the vector control (AA/PCMV/D), which retained wt p53 activity, was not. In addition, as with the S/RG/C2 and PC/JW/FI cell lines, the 7-day IR cell survival was reduced significantly in AA/273p53/B compared with the vector control cell line. This suggests that radiosensitization by CAF and increased cell death is dependent on loss of wt p53 function. Interestingly, radiosensitization of the AA/273p53/B cell line was not associated with accelerated apoptosis but correlated with increased polyploid giant cells, which have been associated with disruption of cell cycle checkpoints and genomic instability. These results demonstrate that G2 checkpoint inhibition with CAF leads to preferential IR cell killing in cell lines in which wt p53 is inactivated and that this increased cell killing is not necessarily dependent on increased IR-induced apoptosis.
Interleukins in the Control of Osteoclast Differentiation (1998)

To maintain homeostasis of bone, the production of osteoblasts and osteoclasts is tightly regulated. At the local level, hormones and cytokines control formation of osteoclasts from hemopoietic precursors by acting upon osteoblastic-stromal cells and in some cases also upon cells of the immune system. Osteoblasts regulate osteoclast formation by providing physical support and cytokines such as M-CSF and IL-11, which promote osteoclast differentiation. Osteoblasts are also a source of IL-18, which limits osteoclast formation. The requirement of contact between osteoblasts and hemopoietic cells for successful osteoclast formation led to a concept of a membrane-anchored stromal cell molecule that programs osteoclast differentiation. This mechanism has been highlighted by the discovery of osteoprotegerin (OPG), a soluble tumor necrosis factor (TNF) family member that inhibits osteoclast formation. The ligand for OPG is a novel transmembrane TNF receptor superfamily member, the osteoclast differentiating factor (ODF). The recognition of the osteoprotegerin/osteoprotegerin-ligand axis will lead to new insights into the control of osteoclast differentiation by interleukins.
Reduction in Atherosclerotic Lesion Size in Pigs by αVβ3 Inhibitors Is Associated With Inhibition of Insulin-Like Growth Factor-I–Mediated Signaling (1999)

Insulin-like growth factor-I (IGF-I) is a potent stimulant of smooth muscle cell (SMC) migration and proliferation and has been implicated in the development of experimental atherosclerotic lesions. Because optimal stimulation of SMC in vitro by IGF-I requires ligand occupancy of alphaVbeta3, these studies were conducted to determine whether alphaVbeta3 antagonists would result in a change in lesion size and whether they could alter IGF-I-mediated actions. Clamps were placed on the carotid and femoral arteries of normal pigs that had been fed a high-cholesterol diet for 4 weeks. alphaVbeta3 inhibitors (SC-69000, SC-65811) (10(-6) mol/L) or saline were infused for 2 weeks into the peristenotic area. Lesion area, the number of SMC layers, and proliferating cell nuclear antigen positive cells were determined in a 1.2-mm segment of each artery. Lesion areas were 304 788+/-113 453 micron(2) (saline), compared with 149 799+/-35 456 micron(2) (SC-69000) (P<0.01). Lesion areas in arteries treated with SC-64258, a compound that does not bind to alphaVbeta3, were 310 284+/-160 467 micron(2), P=not significant. In a second experiment, lesion areas were 110 391+/-17 347 micron(2) (saline) and 59 533+/-17 568 micron(2) (SC-65811, P<0.001). Neointimal SMC layers were reduced by SC-65811 from 7.4+/-4.5 to 3.0+/-0.4 (P<0.001). To determine whether IGF-I action was altered, IGF binding protein-5, which is synthesized in response to IGF-I, was analyzed. IGF-I binding protein-5 mRNA abundance was reduced by 67+/-8% in the 6 lesions treated with SRL-69000 compared with saline controls (P<0.001). We conclude that alphaVbeta3 antagonists block the development of lesions in pigs that have been induced by a high-cholesterol diet and stenosis, and the effect of these compounds is associated with their ability to inhibit IGF-I-mediated signaling.
Diagnosis and treatment of systemic lupus erythematosus. (1993)

Many CNS disorders involve an inflammatory response that is orchestrated by cells of the innate immune system: macrophages, neutrophils, and microglia (the endogenous CNS immune cell). Hence, there is considerable interest in anti-inflammatory strategies that target these cells. Microglia express Kv1.3 (KCNA3) channels, which we showed previously are important for their proliferation and the NADPH-mediated respiratory burst. Here, we demonstrate the potential for targeting Kv1.3 channels to control CNS inflammation. Rat microglia express Kv1.2, Kv1.3, and Kv1.5 transcripts and protein, but only a Kv1.3 current was detected. When microglia were activated with lipopolysaccharide or a phorbol ester, only the Kv1.3 transcript (but not protein) expression changed. Using a Transwell cell-culture system that allows separate drug treatment of microglia or neurons, we found that activated microglia killed postnatal hippocampal neurons through a process that requires Kv1.3 channel activity in microglia but not in neurons. A major neurotoxic molecule in this model was peroxynitrite, which is formed from superoxide and nitric oxide; thus, it is significant that Kv1.3 channel blockers reduced the respiratory burst, but not nitric oxide production, by the activated microglia. In addressing the biochemical pathway affected by Kv1.3 channel activity, we found that Kv1.3 acts via a different cellular mechanism from the broad-spectrum drug minocycline, which is often used in animal models of neuroinflammation. That is, the dose-dependent reduction in neuron killing by minocycline corresponded with a reduction in p38 mitogen-activated protein kinase activation in microglia; however, none of the Kv1.3 blockers affected p38 activation.
Wavelet Transform for Rabbit EEG with Vagus Nerve Electric Stimulation (2006)

Vagus nerve electric stimulation is a new method for preventing and treating epilepsy, pain disorders and depression with a subcutaneous surgically implanted device. The mechanisms of action of implanted stimulation device are still unknown. And the vagus nerve electric stimulator has several operating and stimulation parameters with the programming wand or the magnet. We had finished designing a new vagus nerve electric stimulator for the epilepsy last year. In order to analysis and detect the effects on the brain characteristics with these operation and the electrical activation, the rabbits are implanted the device. Then the EEG is used for recording the brain functional activity of the rabbit with the stimulator. Moreover the wavelet transform is employed to classify and separate the EEG signals into different spectral components. The delta, theta, alpha and beta waves are obtained to better understand the stimulation effects on the brain. The results demonstrated that the new device is safe and has excellent potential role for the epilepsy treatment.
Human Osteoblast Precursors Produce Extracellular Adenosine, Which Modulates Their Secretion of IL-6 and Osteoprotegerin (2006)

Our findings show that HCC1 and primary BMS cells produce adenosine, express CD73 and all four adenosine receptor subtypes. In HCC1 cells, adenosine has a potent stimulatory action on IL-6 secretion but an inhibitory action on OPG expression. These data show for the first time that adenosine may be an important regulator of progenitor cell differentiation and hence an important local contributor to the regulation of bone formation and resorption.
Cyclometalated Complexes of Platinum and Palladium with N-(4-Chlorophenyl)-α-benzoylbenzylideneamine. In Vitro Cytostatic Activity, DNA Modification, and Interstrand Cross-Link Studies (1996)

In the present paper we report the synthesis and structural IR and 1H and 13C NMR characterization of four platinum(II) and palladium(II) cyclometalated complexes of the formula [Pd(4-ClC6H4NC(COC6H5)C6H4)X]2, where X = OAc (2) or Cl (3), and [Pt(4-ClC6H4NC(COC6H5)C6H4)X]2, where X = Cl (4) or OAc (5). The acetate-bridged compounds 2 and 5 have an open-book structure. The chloro-bridged compounds 3 and 4 have an unfolded structure. Complex 2 crystallizes in the centrosymmetric triclinic space group P1̄, with Z = 2. Unit cell parameters are as follows: a = 11.765(3) Å, b = 12.862(4) Å, c = 15.022(5) Å, α = 84.08(2)°, β = 78.56(2)°, γ = 83.13(2)°. All these compounds were screened against MDA-MB 468 (breast carcinoma) and HL-60 (leukemic) tumor cells. The low IC50 values of compound 5 (1.05 μM) and of compound 4 (1.58 μM) against MDA-MB 468 and of 0.82 μM (5) and 1.37 μM (4) against HL-60 relative to cis-DDP (2.67 and 2.07 μM, respectively) and other cyclometalated compounds suggest that the synthesized compounds may be regarded as having potential antitumor properties. The data suggest that the antiproliferative activity of compound 5 may correlate with its covalent binding to DNA and the induction of important modifications on the helix.
Solution Structure of Physiological Cu(His)2: Novel Considerations into Imidazole Coordination (2009)

A disagreement on the mode of histidine binding to copper and the structure of [Cu(2+)(His)(2)] in solution still exists. Spectroscopic data in solution support a six-coordinate species with N4O2 donor atoms, while X-ray crystallography reveals five-coordinate N(3)O(2) donor atoms. We modified [Cu(2+)(His)(2)] in solution using diethyl pyrocarbonate (DEPC) and monitored the products spectrophotometrically and by mass spectrometry. Our spectrophotometric study indicates the presence of a free imidazole in the [Cu(2+)(His)(2)] complex in solution. Mass spectral characterization of a DEPC-modified [Cu(2+)(His)(2)] complex yielded a peak at 587.8 amu corresponding to three DEPC adducts. Taken together, our data indicate that the [Cu(2+)(His)(2)] complex in solution exists as a neutral five-coordinate structure with N3O2 donor atoms.
Antimicrobial activity of monocaprin: a monoglyceride with potential use as a denture disinfectant (2006)

Monocaprin is a 1-monoglyceride of capric acid that has antimicrobial activity against enveloped viruses, certain bacteria, and the yeast Candida albicans. Solutions containing monocaprin were formulated and tested in vitro against a number of micro-organisms, including species found in the oral cavity and common pathogenic species. The antimicrobial activity of monocaprin was tested with strains growing on a surface as well as in the planktonic phase. Micro-organisms tested were: Streptococcus mutans, Candida albicans, Lactobacillus sp., Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Two sets of dilutions were prepared for each test strain; one to be inoculated with the micro-organism growing in the planktonic phase and the other with the same strain growing on a filter paper disk. Control solutions were also prepared to find out if any of the excipients were affecting the microbicidal effect of monocaprin. Test strains growing on the filter paper surface were less sensitive to monocaprin than the same strain growing in its planktonic phase. C. albicans was the micro-organism that was most sensitive to monocaprin, but S. mutans also showed appreciable sensitivity. The indication that monocaprin may have potential as a topical agent against Candida was tested in an open study of denture disinfection in 32 patients attending a geriatric daycare centre. A significant, but short-term, reduction in counts of Candida on the fitting surface of full dentures was observed.
The prostate‐specific antigen gene and the human glandular kallikrein‐1 gene are tandemly located on chromosome 19 (1989)

Using a prostate-specific antigen cDNA as a hybridization probe, clones containing the kallikrein genes encoding prostate-specific antigen, human glandular kallikrein-1 and pancreas/kidney kallikrein were isolated from a human genomic library. Clones containing the prostate-specific antigen gene and the human glandular kallikrein-1 gene overlap and span a region of about 36 kb. The two genes are aligned in a head to tail orientation at a mutual distance of 12 kb. Southern blot analysis of DNA from a panel of human-hamster hybrid cells with specific probes revealed the genes to be situated on chromosome 19. Assuming that the pancreas/kidney kallikrein gene is located in the same cluster, the distance to the prostate-specific antigen gene and the human glandular kallikrein gene must be at least 15 kb.
Chlorotrimethylsilane-Mediated Synthesis of 2-Aryl-1-chloro-1-heteroarylalkenes (2007)

The condensation of (chloromethyl)heterarenes with aro­matic aldehydes was investigated, resulting in a simple and flexi­ble general procedure for the synthesis of 2-aryl-1-chloro-1-heteroarylalkenes. The best reaction conditions were found to be heating in N,N-dimethylformamide in the presence of chlorotri­methylsilane as a promoter and water-scavenger.
Structure-function analysis of synthetic and recombinant derivatives of transforming growth factor alpha. (1988)

Transforming growth factor alpha (TGF-alpha) is a 50-amino-acid peptide that stimulates cell proliferation via binding to cell surface receptors. To identify the structural features of TGF-alpha that govern receptor-ligand interactions, we prepared synthetic peptide fragments and recombinant mutant proteins of TGF-alpha. These TGF-alpha derivatives were tested in receptor binding and mitogenesis assays. Synthetic peptides representing the N terminus, the C terminus, or the individual disulfide constrained rings of TGF-alpha did not exhibit receptor-binding or mitogenic activity. Replacement of the cysteines with alanines at positions 8 and 21, 16 and 32, and 34 and 43 or at positions 8 and 21 and 34 and 43 yielded inactive mutant proteins. However, mutant proteins containing substitutions or deletions in the N-terminal region retained significant biologic activity. Conservative amino acid changes at residue 29 or 38 or both and a nonconservative amino acid change at residue 12 had little effect on binding or mitogenesis. However, nonconservative amino acid changes at residues 15, 38, and 47 produced dramatic decreases in receptor binding (23- to 71-fold) and mitogenic activity (38- to 125-fold). These studies indicate that at least three distinct regions of TGF-alpha contribute to biologic activity.
In vivo diagnosis of murine pancreatic intraepithelial neoplasia and early-stage pancreatic cancer by molecular imaging (2011)

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with poor patient outcome often resulting from late diagnosis in advanced stages. To date methods to diagnose early-stage PDAC are limited and in vivo detection of pancreatic intraepithelial neoplasia (PanIN), a preinvasive precursor of PDAC, is impossible. Using a cathepsin-activatable near-infrared probe in combination with flexible confocal fluorescence lasermicroscopy (CFL) in a genetically defined mouse model of PDAC we were able to detect and grade murine PanIN lesions in real time in vivo. Our diagnostic approach is highly sensitive and specific and proved superior to clinically established fluorescein-enhanced imaging. Translation of this endoscopic technique into the clinic should tremendously improve detection of pancreatic neoplasia, thus reforming management of patients at risk for PDAC.
Tandem duplication of chromosomal segments is common in ovarian and breast cancer genomes (2012)

The application of paired-end next generation sequencing approaches has made it possible to systematically characterize rearrangements of the cancer genome to base-pair level. Utilizing this approach, we report the first detailed analysis of ovarian cancer rearrangements, comparing high-grade serous and clear cell cancers, and these histotypes with other solid cancers. Somatic rearrangements were systematically characterized in eight high-grade serous and five clear cell ovarian cancer genomes and we report here the identification of > 600 somatic rearrangements. Recurrent rearrangements of the transcriptional regulator gene, TSHZ3, were found in three of eight serous cases. Comparison to breast, pancreatic and prostate cancer genomes revealed that a subset of ovarian cancers share a marked tandem duplication phenotype with triple-negative breast cancers. The tandem duplication phenotype was not linked to BRCA1/2 mutation, suggesting that other common mechanisms or carcinogenic exposures are operative. High-grade serous cancers arising in women with germline BRCA1 or BRCA2 mutation showed a high frequency of small chromosomal deletions. These findings indicate that BRCA1/2 germline mutation may contribute to widespread structural change and that other undefined mechanism(s), which are potentially shared with triple-negative breast cancer, promote tandem chromosomal duplications that sculpt the ovarian cancer genome.
Using Peripheral Blood Mononuclear Cells to Determine a Gene Expression Profile of Acute Ischemic Stroke (2005)

This study demonstrated an altered gene expression profile in PBMCs during acute ischemic stroke. Some genes with altered expression were consistent with an adaptive response to central nervous system ischemia.
Kinetics of dilute acid hydrolysis of cellulose originating from municipal solid wastes (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTKinetics of dilute acid hydrolysis of cellulose originating from municipal solid wastesIlan A. Malester, Michal Green, and Gedaliah ShelefCite this: Ind. Eng. Chem. Res. 1992, 31, 8, 1998–2003Publication Date (Print):August 1, 1992Publication History Published online1 May 2002Published inissue 1 August 1992https://pubs.acs.org/doi/10.1021/ie00008a023https://doi.org/10.1021/ie00008a023research-articleACS PublicationsRequest reuse permissionsArticle Views697Altmetric-Citations50LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Improved production of ethanol and n-butanol in immobilized cell bioreactors (1989)

The US Department of Energy, Energy Conversion and Utilization Technology Division, includes a Biocatalysis Program which has sponsored research on a series of novel bioreactors. It was determined that high-cell density, biomass retention or cell recycle were essential factors in the successful operation and improved economics of the bioreactors. One such bioreactor system has been used for ethanol production by Saccharomyces cerevisiae and Zymomonas mobilis in both CSTR and fluidized-bed bioreactors. Higher productivity and lower product inhibition levels were observed using Zymomonas, and further studies concentrated on this bacterium. Using Zymomonas cells encapsulated in 1.0 to 1.5 mm {kappa}-carrageenan beads with cell densities of 15 to 50 g/L, a 98% stoichiometric yield of ethanol from glucose was obtained, along with specific productivities as high as 600 g/L/h and overall productivities as high 180 g/L/h in fluidized-bed bioreactors up to 2.5-m tall. Another bioreactor has been used for the production of n-butanol by Clostridium acetobutylicum encapsulated in alginate beads. This bioreactor uses oleyl alcohol or trioctyl phosphine oxide as a continuous extractant for the cytotoxic n-butanol. Product extraction can be carried out in an external loop or in situ, and product recovered by distillation. By recycling the cells, the cell densitymore » increased from 1.4 to 22.3 g/L, the dilution rate increased from 0.03 to 0.48 h{sup {minus}1}, and the butanol productivity has been increased from 0.4 to 6.3 g/L/h. 10 refs.« less
Active micro-mixers utilizing moving wall structures activated pneumatically by buried side chambers (2006)

In this study, a new active micro-mixer utilizing moving wall structures has been demonstrated. Rapid and reliable fabrication techniques involving standard SU-8 lithography and a polydimethylsiloxane (PDMS) replication process were employed for the formation of this micro chip device. The moving wall structures are activated pneumatically by buried side chambers which deform the channel walls and generate a rapid mixing of the confluent sample streams. The deformation of the moving wall structure can be controlled by the applied air pressure. A maximum deformation of 96.5 µm (about 96.5% of the channel width) can be achieved at an applied pressure of 50 psi for a wall structure with a width of 50 µm and a thickness of 100 µm. In this study, two pairs of moving wall structures were used for active mixing of the samples. Two dynamic operation modes, namely symmetric and asymmetric wall activation, are employed to alternately perturb the flow field and to generate a significant mixing effect. Mixing efficiency as high as 93.6% and 96.4%, respectively, can be achieved for these two modes. The effect of the operation frequency was also investigated. Experimental results indicate that the mixing efficiency increases with increasing operation frequency. However, once the operation frequency is higher than the frequency response of the device, the mixing efficiency drops sharply since the moving wall cannot be completely deflected within one actuation cycle. A numerical simulation was employed to investigate the mixing mechanism and to identify how the moving wall affected the sample flow field. Numerical data are in reasonable agreement with the experimental data with a variation less than 5%. Experimental results and numerical data indicate that the developed chip device can mix two confluent samples successfully. The development of active micro-mixers is a crucial component in many microfluidic applications.