gebhart/patrepeval huggingface dataset:
Resveratrol inhibits the proliferation of normal human keratinocytes in vitro (2001)

Resveratrol, a phytoalexin found in grapes and other plants, is a potent antioxidant, anti-inflammatory, and antiproliferative agent that is thought to have chemopreventive properties with respect to carcinogenesis. However, the antiproliferative effects of resveratrol have been described primarily for cultured tumor cells and its effects on the proliferation of normal cells are not clear. We evaluated the viability and proliferation of cultured normal human keratinocytes (KCs) exposed to resveratrol (0.25-100 microM) for different lengths of time (5-72 h) by means of (3)H-thymidine incorporation, direct cell counts, and a tetrazolium-based formazan reaction. The first two methods indicated that resveratrol, even at low concentrations, induced a time-and concentration-dependent inhibition of KC proliferation. However, formazan production was actually increased at moderate resveratrol concentrations (10 microM) and diminished only at higher concentrations. Even brief exposure (5 h) of KCs to resveratrol resulted in a concentration-dependent elevation in formazan production. This was blocked by ionomycin but was not dependent on Ca(2+). We conclude that resveratrol, even at submicromolar concentrations, inhibits the proliferation of normal human KCs in vitro and, at higher concentrations (40-100 microM), is cytotoxic to these cells. J. Cell. Biochem. Suppl. 36: 55-62, 2001.
Structure and Expression of H-type GDP-L-Fucose:β-D-Galactoside 2-α-L-Fucosyltransferase Gene (FUT1) (1997)

The expression of the ABO antigens on erythrocyte membranes is regulated by H gene (FUT1)-encoded alpha(1,2)fucosyltransferase activity. We have examined the expression of the FUT1 in several tumor cell lines, including erythroid lineage and normal bone marrow cells, by Northern blot and/or reverse transcription-polymerase chain reaction (RT-PCR) analyses. RT-PCR indicated that bone marrow cells, erythroleukemic cells (HEL), and highly undifferentiated leukemic cells (K562) that have erythroid characteristics expressed the FUT1 mRNA while four leukemic cell lines did not. The FUT1 mRNA was also demonstrated in gastric, colonic, and ovarian (MCAS) cancer cell lines by RT-PCR. Northern blot analysis indicated that a 4. 0-kilobase FUT1 transcript was expressed in some of these tumor cell lines. Rapid amplification of 5' cDNA end (RACE) analysis suggested that the FUT1 transcript had several forms generated by two distinct transcription start sites and alternative splicing. The results of RT-PCR using specific primers for each starting exon suggested that two transcription initiation sites (exon 1A and exon 2A) of the FUT1 were identified in gastric cancer cells and in ovarian cancer cells. Only exon 1A was identified as a transcription start site in another gastric cancer cell line, two colonic cancer cell lines, and in K562 cells, whereas only exon 2A was identified in HEL cells and in bone marrow cells. These two transcription start sites were located 1.8 kilobases apart. Therefore, two distinct promoters appeared to be present in the FUT1. The distinct promoters of the FUT1 and alternative splicing of the FUT1 mRNA may be associated with time- and tissue-specific expression of the FUT1.
Engineered Respiro-Fermentative Metabolism for the Production of Biofuels and Biochemicals from Fatty Acid-Rich Feedstocks (2010)

Although lignocellulosic sugars have been proposed as the primary feedstock for the biological production of renewable fuels and chemicals, the availability of fatty acid (FA)-rich feedstocks and recent progress in the development of oil-accumulating organisms make FAs an attractive alternative. In addition to their abundance, the metabolism of FAs is very efficient and could support product yields significantly higher than those obtained from lignocellulosic sugars. However, FAs are metabolized only under respiratory conditions, a metabolic mode that does not support the synthesis of fermentation products. In the work reported here we engineered several native and heterologous fermentative pathways to function in Escherichia coli under aerobic conditions, thus creating a respiro-fermentative metabolic mode that enables the efficient synthesis of fuels and chemicals from FAs. Representative biofuels (ethanol and butanol) and biochemicals (acetate, acetone, isopropanol, succinate, and propionate) were chosen as target products to illustrate the feasibility of the proposed platform. The yields of ethanol, acetate, and acetone in the engineered strains exceeded those reported in the literature for their production from sugars, and in the cases of ethanol and acetate they also surpassed the maximum theoretical values that can be achieved from lignocellulosic sugars. Butanol was produced at yields and titers that were between 2- and 3-fold higher than those reported for its production from sugars in previously engineered microorganisms. Moreover, our work demonstrates production of propionate, a compound previously thought to be synthesized only by propionibacteria, in E. coli. Finally, the synthesis of isopropanol and succinate was also demonstrated. The work reported here represents the first effort toward engineering microorganisms for the conversion of FAs to the aforementioned products.
Convection cooling of microelectronic chips (2003)

Mixed natural/forced convective heat transfer in a channel with heating elements is reported. Three microelectronic chps provided the heating surfaces. An experimental study was performed to determine the influence of the Reynolds number and Grashof number on the Nusselt number. Real-time holographic interferometry with an optical crystal as the storage medium was used to visualize heat transfer from microelectronic chips. The results show that the influence of natural convection is usually negligible, even for small Reynolds numbers.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Self-organized propagation of dislocations in GaN films during epitaxial lateral overgrowth (2000)

Dislocation propagation and defect evolution in GaN films formed by epitaxial lateral overgrowth (ELO) are examined by transmission electron microscopy. A novel effect that induces self-organized propagation of preexisting dislocations in ELO films is evaluated. This propagation forms dislocations into bundle structures along the stripes of masks used for ELO. The dislocation bundling gives rise to crystallographic tilting in the overgrown region on the mask and leads to a total reduction of threading dislocation density in the film.
Controlled Delivery of Sonic Hedgehog Morphogen and Its Potential for Cardiac Repair (2013)

The morphogen Sonic hedgehog (Shh) holds great promise for repair or regeneration of tissues suffering ischemic injury, however clinical translation is limited by its short half-life in the body. Here, we describe a coacervate delivery system which incorporates Shh, protects it from degradation, and sustains its release for at least 3 weeks. Shh released from the coacervate stimulates cardiac fibroblasts to upregulate the expression of multiple trophic factors including VEGF, SDF-1α, IGF-1, and Shh itself, for at least 48 hours. Shh coacervate also demonstrates cytoprotective effects for cardiomyocytes in a hydrogen peroxide-induced oxidative stress environment. In each of these studies the bioactivity of the Shh coacervate is enhanced compared to free Shh. These results warrant further investigation of the in vivo efficacy of Shh coacervate for cardiac repair.
Association of subclinical hypercortisolism with type 2 diabetes mellitus: a case-control study in hospitalized patients (2005)

In hospitalized patients, SH is associated with T2D.
DNA-binding and transcriptional regulatory properties of hepatic leukemia factor (HLF) and the t(17;19) acute lymphoblastic leukemia chimera E2A-HLF. (1994)

The t(17;19) translocation in acute lymphoblastic leukemias results in creation of E2A-hepatic leukemia factor (HLF) chimeric proteins that contain the DNA-binding and protein dimerization domains of the basic leucine zipper (bZIP) protein HLF fused to a portion of E2A proteins with transcriptional activation properties. An in vitro binding site selection procedure was used to determine DNA sequences preferentially bound by wild-type HLF and chimeric E2A-HLF proteins isolated from various t(17;19)-bearing leukemias. All were found to selectively bind the consensus sequence 5'-GTTACGTAAT-3' with high affinity. Wild-type and chimeric HLF proteins also bound closely related sites identified previously for bZIP proteins of both the proline- and acidic amino acid-rich (PAR) and C/EBP subfamilies; however, E2A-HLF proteins were significantly less tolerant of certain deviations from the HLF consensus binding site. These differences were directly attributable to loss of an HLF ancillary DNA-binding domain in all E2A-HLF chimeras and were further exacerbated by a zipper mutation in one isolate. Both wild-type and chimeric HLF proteins displayed transcriptional activator properties in lymphoid and nonlymphoid cells on reporter genes containing HLF or C/EBP consensus binding sites. But on reporter genes with nonoptimal binding sites, their transcriptional properties diverged and E2A-HLF competitively inhibited activation by wild-type PAR proteins. These findings establish a spectrum of binding site-specific transcriptional properties for E2A-HLF which may preferentially activate expression of select subordinate genes as a homodimer and potentially antagonize expression of others through heteromeric interactions.
Characterization of a Mutated IgA2 Antibody of the m(1) Allotype against the Epidermal Growth Factor Receptor for the Recruitment of Monocytes and Macrophages (2012)

IgA antibodies constitute an important part of the mucosal immune system, but their immunotherapeutic potential remains rather unexplored, in part due to biotechnological issues. For example, the IgA2m(1) allotype carries an unusual heavy and light chain pairing, which may confer production and stability concerns. Here, we report the generation and the biochemical and functional characterization of a P221R-mutated IgA2m(1) antibody against the epidermal growth factor receptor (EGFR). Compared with wild type, the mutated antibody demonstrated heavy chains covalently linked to light chains in monomeric as well as in joining (J)-chain containing dimeric IgA. Functional studies with wild type and mutated IgA2m(1) revealed similar binding to EGFR and direct effector functions such as EGFR down-modulation and growth inhibition. Furthermore, both IgA molecules triggered similar levels of indirect tumor cell killing such as antibody-dependent cell-mediated cytotoxicity (ADCC) by isolated monocytes, activated polymorphonuclear cells, and human whole blood. Interestingly, the dimeric IgA antibodies demonstrated higher efficiency in direct as well as in indirect effector mechanisms compared with their respective monomeric forms. Both wild type and mutated antibody triggered effective FcαRI-mediated tumor cell killing by macrophages already at low effector to target cell ratios. Interestingly, also polarized macrophages mediated significant IgA2-mediated ADCC. M2 macrophages, which have been described as promoting tumor growth and progression, may convert to ADCC-mediating effector cells in the presence of EGFR-directed antibodies. In conclusion, these results provide further insight into the immunotherapeutic potential of recombinant IgA antibodies for tumor immunotherapy and suggest macrophages as an additional effector cell population.
D-Type Cyclin-Dependent Kinase Activity in Mammalian Cells (1994)

D-type cyclin-dependent kinase activities have not so far been detected in mammalian cells. Lysis of rodent fibroblasts, mouse macrophages, or myeloid cells with Tween 20 followed by precipitation with antibodies to cyclins D1, D2, and D3 or to their major catalytic partner, cyclin-dependent kinase 4 (cdk4), yielded kinase activities in immune complexes which readily phosphorylated the retinoblastoma protein (pRb) but not histone H1 or casein. Virtually all cyclin D1-dependent kinase activity in proliferating macrophages and fibroblasts could be attributed to cdk4. When quiescent cells were stimulated by growth factors to enter the cell cycle, cyclin D1-dependent kinase activity was first detected in mid G1, reached a maximum near the G1/S transition, and remained elevated in proliferating cells. The rate of appearance of kinase activity during G1 phase lagged significantly behind cyclin induction and correlated with the more delayed accumulation of cdk4 and formation of cyclin D1-cdk4 complexes. Thus, cyclin D1-associated kinase activity was not detected during the G0-to-G1 transition, which occurs within the first few hours following growth factor stimulation. Rodent fibroblasts engineered to constitutively overexpress either cyclin D1 alone or cyclin D3 together with cdk4 exhibited greatly elevated cyclin D-dependent kinase activity, which remained absent in quiescent cells but rose to supraphysiologic levels as cells progressed through G1. Therefore, despite continued enforced overproduction of cyclins and cdk4, the assembly of cyclin D-cdk4 complexes and the appearance of their kinase activities remained dependent upon serum stimulation, indicating that upstream regulators must govern formation of the active enzymes.
Structural Comparison of Three Types of Staphylococcal Cassette Chromosome mec Integrated in the Chromosome in Methicillin-Resistant Staphylococcus aureus (2001)

The beta-lactam resistance gene mecA of Staphylococcus aureus is carried by a novel mobile genetic element, designated staphylococcal cassette chromosome mec (SCCmec), identified in the chromosome of a Japanese methicillin-resistant S. aureus (MRSA) strain. We now report identification of two additional types of mecA-carrying genetic elements found in the MRSA strains isolated in other countries of the world. There were substantial differences in the size and nucleotide sequences between the elements and the SCCmec. However, new elements shared the chromosomal integration site with the SCCmec. Structural analysis of the new elements revealed that they possessed all of the salient features of the SCCmec: conserved terminal inverted repeats and direct repeats at the integration junction points, conserved genetic organization around the mecA gene, and the presence of cassette chromosome recombinase (ccr) genes responsible for the movements of SCCmec. The elements, therefore, were considered to comprise the SCCmec family of staphylococcal mobile genetic elements together with the previously identified SCCmec. Among 38 epidemic MRSA strains isolated in 20 countries, 34 were shown to possess one of the three typical SCCmec elements on the chromosome. Our findings indicated that there are at least three distinct MRSA clones in the world with different types of SCCmec in their chromosome.
Plasma PCSK9 Concentrations Correlate with LDL and Total Cholesterol in Diabetic Patients and Are Decreased by Fenofibrate Treatment (2008)

We conclude that this decrease in PCSK9 explains at least in part the LDL cholesterol-lowering effects of fenofibrate. Fenofibrate might be of interest to further reduce cardiovascular risk in patients already treated with a statin.
Folate-Targeted Therapies for Cancer (2010)

ADVERTISEMENT RETURN TO ISSUEPREVPerspectiveNEXTFolate-Targeted Therapies for CancerWei Xia and Philip S. Low*View Author Information Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907*To whom correspondence should be addressed. Phone: +1-765-494-5273. Fax: +1-765-494-5272. E-mail: [email protected]Cite this: J. Med. Chem. 2010, 53, 19, 6811–6824Publication Date (Web):July 28, 2010Publication History Received26 April 2010Published online28 July 2010Published inissue 14 October 2010https://pubs.acs.org/doi/10.1021/jm100509vhttps://doi.org/10.1021/jm100509vreview-articleACS PublicationsCopyright © 2010 American Chemical SocietyRequest reuse permissionsArticle Views9043Altmetric-Citations391LEARN 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 SUBJECTS:Cancer therapy,Cells,Conjugate acid-base pairs,Nutrition,Organic compounds Get e-Alerts
Digital material fabrication using mask‐image‐projection‐based stereolithography (2013)

Purpose The purpose of this paper is to present a mask‐image‐projection‐based stereolithography (MIP‐SL) process that can combine two base materials with various concentrations and structures to produce a solid object with desired material characteristics. Stereolithography is an additive manufacturing process in which liquid photopolymer resin is cross‐linked and converted to solid. The fabrication of digital material requires frequent resin changes during the building process. The process presented in this paper attempts to address the related challenges in achieving such fabrication capability. Design/methodology/approach A two‐channel system design is presented for the multi‐material MIP‐SL process. In such a design, a coated thick film and linear motions in two axes are used to reduce the separation force of a cured layer. The material cleaning approach to thoroughly remove resin residue on built surfaces is presented for the developed process. Based on a developed testbed, experimental studies were conducted to verify the effectiveness of the presented process on digital material fabrication. Findings The proposed two‐channel system can reduce the separation force of a cured layer by an order of magnitude in the bottom‐up projection system. The developed two‐stage cleaning approach can effectively remove resin residue on built surfaces. Several multi‐material designs have been fabricated to highlight the capability of the developed MIP‐SL process. Research limitations/implications A proof‐of‐concept testbed has been developed. Its building speed and accuracy can be further improved. The tests were limited to the same type of liquid resins. In addition, the removal of trapped air is a challenge in the presented process. Originality/value This paper presents a novel and a pioneering approach towards digital material fabrication based on the stereolithography process. This research contributes to the additive manufacturing development by significantly expanding the selection of base materials in fabricating solid objects with desired material characteristics.
Molecular Cloning and Characterization of an Insecticidal Toxin from Pseudomonas taiwanensis (2010)

An insecticidal toxin gene, tccC, was cloned from the recently discovered novel species Pseudomonas taiwanensis using degenerate PCR and genomic walking. The DNA sequence of the tccC gene (2,940 bp) has an open reading frame encoding 980 amino acids with a calculated molecular weight of 107.93 kDa. The amino acid sequence alignment showed the highest sequence identity (41.2%) with the insecticidal toxin from Pseudomonas entomophila. To examine the insecticidal functionality of the tccC gene product, TccC was heterologously expressed in Escherichia coli as a recombinant His6 fusion protein and purified by immobilized metal ion-affinity chromatography. The recombinant TccC was fed to Drosophila larvae at a concentration of 350 ppm, which induced about 60% mortality within 72 h. The recombinant TccC was stable at pH 7.0 and at 37 °C. When the pH was less than 5.0 or greater than 9.0, or temperature was greater than 55 °C, less than 20% Drosophila larvae mortality was observed. These results prove that Pseudomonas taiwanensis could be used as a source for developing novel biopesticides.
A 32 K ASIC synchronous RAM using a two-transistor basic cell (1989)

A 32 K synchronous RAM using a two-transistor basic cell has been developed for use with a 100 K compact gate array. The basic cell consists of only two transfer gates and a storage capacitor and thus results in a very dense memory array. The RAM operates as a static RAM during system operations and provides both serial and parallel data ports. It can be reconfigured into 1 K*32, 2 K*16, 4 K*8, etc. depending on the system needs. An access time of 40 ns was achieved for a test chip at an operating power of 175 mW.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Molecular characterization of properdin deficiency type III: dysfunction produced by a single point mutation in exon 9 of the structural gene causing a tyrosine to aspartic acid interchange (1996)

Inherited properdin deficiency is an X-linked recessive disorder clinically manifested by susceptibility to meningococcal disease. Deficiency of properdin is characterized by complete absence (type I), very low level presence (type II), or the presence of a dysfunctional properdin protein in serum as found in one Dutch family (type III). To better understand the dysfunctional protein on the molecular level, samples from three members of the Dutch family were analyzed by direct genomic sequencing. The sequence of the complete gene, including 10 exons and 9 introns, covering about 6500 bases was determined. The dysfunctional properdin was found to be caused by a single T to G mutation in exon 9, which gives rise to a substitution of a tyrosine by an aspartic acid residue at position 387. This change to a hydrophilic amino acid affects the function of the properdin molecule, although the oligomerization of dysfunctional properdin molecules was similar to that of normal properdin. In binding studies with C3b and properdin in serum, no properdin deposition was detected with the type III deficient serum. Inhibition studies with different decapeptides revealed distinct inhibitory sequences, and indicated also that the part of properdin containing the type III mutation was not directly involved in the binding to C3b. The mutation most likely causes conformational changes that make the properdin molecule dysfunctional by affecting its binding to C3b.
Apoptin, a protein derived from chicken anemia virus, induces p53-independent apoptosis in human osteosarcoma cells. (1995)

Previously, we have shown that the chicken anemia virus-derived VP3 ("apoptin") protein induces apoptosis in chicken mononuclear cells. Here, we report that apoptin also induces apoptosis in human osteosarcoma cells, regardless of whether they expressed wild-type, mutant p53, or no p53 at all. Moreover, the nuclear location of apoptin appears to be important for its optimal induction of apoptosis. The fact that apoptin can induce p53-independent apoptosis in human tumor cells makes apoptin a potential candidate for treatment of frequently occurring types of cancer cells that do not contain functional p53.