gebhart/patrepeval huggingface dataset:
Increased Matrix Metalloproteinase Activity and Selective Upregulation in LV Myocardium From Patients With End-Stage Dilated Cardiomyopathy (1998)

Background —One of the hallmarks of dilated cardiomyopathy (DCM) is left ventricular (LV) remodeling. The matrix metalloproteinases (MMPs) are a family of enzymes that contribute to extracellular remodeling in several disease states. Additionally, a family of inhibitors called tissue inhibitors of MMPs (TIMPs) has been shown to exist and to tightly regulate MMP activity. However, the types of MMPs and TIMPs expressed within the normal and DCM LV myocardium and the relation to MMP activity remain unexplored. Methods and Results —Relative LV myocardial MMP activity was determined in the normal (n=8) and idiopathic DCM (n=7) human LV myocardium by substrate zymography. Relative LV myocardial abundance of interstitial collagenase (MMP-1), stromelysin (MMP-3), 72 kD gelatinase (MMP-2), 92 kD gelatinase (MMP-9), TIMP-1, and TIMP-2 were measured with quantitative immunoblotting. LV myocardial MMP zymographic activity increased with DCM compared with normal (984±149 versus 413±64 pixels, P &lt;.05). With DCM, LV myocardial abundance of MMP-1 decreased to 16±6% ( P &lt;.05), MMP-3 increased to 563±212% ( P &lt;.05), MMP-9 increased to 422±64% ( P &lt;.05), and MMP-2 was unchanged when compared with normal. LV myocardial abundance of TIMP-1 and TIMP-2 increased by &gt;500% with DCM. A high-molecular-weight immunoreactive band for both TIMP-1 and TIMP-2, suggesting a TIMP/MMP complex, was increased &gt;600% with DCM. Conclusions —This study demonstrated increased LV myocardial MMP activity and evidence for independent regulatory mechanisms of MMP and TIMP expression with DCM. These findings suggest that selective inhibition of MMP species within the LV myocardium may provide a novel therapeutic target in patients with DCM.
A silent bomb: The risk of anthrax as a weapon of mass destruction (2003)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Telomere-bound TRF1 and TRF2 stall the replication fork at telomeric repeats (2004)

Vertebrate telomeres consist of tandem repeats of T2AG3 and associated proteins including the telomeric DNA-binding proteins, TRF1 and TRF2. It has been proposed that telomeres assume two interswitchable states, the open state that is accessible to various trans-acting factors and the closed state that excludes those factors. TRF1 and TRF2 are believed to promote the formation of the closed state. However, little is known about how those two states influence DNA replication. We analyzed the effects of TRF1 and TRF2 on telomeric replication both in vitro and in vivo. By exploiting the in vitro replication system of linear SV40 DNA, we found that telomeric repeats are a poor replication template. Moreover, the addition of recombinant TRF1 and TRF2 significantly stalled the replication fork progression at telomeric repeats. When TRF1 was overexpressed in HeLa cells, cells with 4N DNA content were accumulated. Furthermore, cytological analyses revealed that the replication focus overlapped with telomere signals at a significantly higher frequency in TRF1-overexpressing cells than in control cells. The results suggest that TRF1 and TRF2 exert inhibitory effects on replication fork progression.
Energetics of Formation of Sixteen Triple Helical Complexes Which Vary at a Single Position Within a Purine Motif (1995)

The association constants for the formation of sixteen purine purine pyrimidine triple helical complexes which vary at a single common position (Z . XY where Z = A, G, C, T and XY = AT, GC, CG, TA) were determined by quantitative DNAse I footprint titration. The sequence context in which the sixteen pairings Z . XY were studied is 5'-d(AGGGGAGGGGXGGGA)-3' within a 648 base pair DNA fragment. The association constants for the purine-rich oligonucleotides 5'-d(TGGGZGGGGTGGGGT)-3' ranged from 2.7 x 10^5 (Z . XY = G . TA) to 8.9 x 10^7 M^(-1) (Z . XY = T . AT) at 37 degrees C, pH 7,4, 50 mM tris acetate, 10 mM NaCl, and 3 mM MgCl_2. For the sequences studied, T . AT is more stable than T . CG, T . GC, and T . TA by greater than or equal to 1.2 kcal mol^(-1); A . AT is more stable than A . CG, A . GC, and A . TA by greater than or equal to 1.2 kcal mol^(-1); and G . GC is more stable than G . AT, G . CG, and G . TA by greater than or equal to 2.1 kcal mol^(-1). The triplet T . CG is greater than or equal to 1.5 kcal mol^(-1) more stable than the other three bases opposite a CG base pair.
Human-induced pluripotent stem cells from blood cells of healthy donors and patients with acquired blood disorders (2009)

Human induced pluripotent stem (iPS) cells derived from somatic cells hold promise to develop novel patient-specific cell therapies and research models for inherited and acquired diseases. We and others previously reprogrammed human adherent cells, such as postnatal fibroblasts to iPS cells, which resemble adherent embryonic stem cells. Here we report derivation of iPS cells from postnatal human blood cells and the potential of these pluripotent cells for disease modeling. Multiple human iPS cell lines were generated from previously frozen cord blood or adult CD34(+) cells of healthy donors, and could be redirected to hematopoietic differentiation. Multiple iPS cell lines were also generated from peripheral blood CD34(+) cells of 2 patients with myeloproliferative disorders (MPDs) who acquired the JAK2-V617F somatic mutation in their blood cells. The MPD-derived iPS cells containing the mutation appeared normal in phenotypes, karyotype, and pluripotency. After directed hematopoietic differentiation, the MPD-iPS cell-derived hematopoietic progenitor (CD34(+)CD45(+)) cells showed the increased erythropoiesis and gene expression of specific genes, recapitulating features of the primary CD34(+) cells of the corresponding patient from whom the iPS cells were derived. These iPS cells provide a renewable cell source and a prospective hematopoiesis model for investigating MPD pathogenesis.
In vivo flow cytometry: A new method for monitoring circulating cancer cells (2004)

We present a new method for detecting fluorescently labeled circulating cells in vivo. We use this method to monitor the depletion kinetics of circulating prostate cancer cells with different metastatic potential in two different hosts.
UGT1A7 and UGT1A9 Polymorphisms Predict Response and Toxicity in Colorectal Cancer Patients Treated with Capecitabine/Irinotecan (2005)

These data strongly suggest that UGT1A7 and/or UGT1A9 genotypes may be predictors of response and toxicity in CRC patients treated with capecitabine plus irinotecan. Specifically, patients with genotypes conferring low UGT1A7 activity and/or the UGT1A9 (dT)(9/9) genotype may be particularly likely to exhibit greater antitumor response with little toxicity.
Dry Gas Seal System Design Standards For Centrifugal Compressor Applications. (2002)

Dry gas seals have been applied in process gas centrifugal compressors for more than 20 years. Over 80 percent of centrifugal gas compressors manufactured today are equipped with dry gas seals. Despite the 20-year trend of increasing dry gas seal applications, an industry accepted standard for gas seal support system design does not exist. The American Petroleum Institute (API) has only recently addressed gas seal system design in its Standard 614 (1999). This paper proposes a set of gas seal system design standards for process gas centrifugal compressors on the basis of safety, reliability, and economics. This paper presents the philosophy of one centrifugal compressor and dry gas seal original equipment manufacturer (OEM) in regard to gas seal system design standards. These standards are based on over 20 years of experience in the area of gas seal system design, drawing from actual field experience of thousands of compressors. The reader shall recognize, however, that numerous gas seal system design philosophies can be applied to achieve the same system objectives.
Cloning of Four Plant Viruses from Small Quantities of Double-Stranded RNA (1989)

The first strand and second strand synthesis were basically that of Gubler and Hoffman with the omission of mung bean nuclease digestion. After second strand synthesis, the DNA was size-fractionated on a Sepharose CL-4B column, C-tailed, annealed to G-tailed pBR322/pUC9, and Escherichia coli DH1/DH5a cells transformed. No differences in length of cDNA and size of inserts was observed when heat- and DMSO-denaturation were used. However, use of MeHg yielded greater incorporation of 32 P-dATP into first strand when compared to the boiling method of denaturation
Phosphorylation of eIF4E by Mnk-1 enhances HSV-1 translation and replication in quiescent cells (2004)

Although the activity of the translation initiation factor eIF4F is regulated in part by translational repressors (4E-BPs) that prevent incorporation of eIF4E, the cap-binding protein, into the initiation complex, the contribution of eIF4E phosphorylation to translational control remains controversial. Here, we demonstrate that the herpes simplex virus-1 (HSV-1) ICP0 gene product, a multifunctional transactivator of viral gene expression with ubiquitin E3 ligase activity that is important for vegetative replication and reactivation of latent infections, is required to stimulate phosphorylation of eIF4E as well as 4E-BP1, and promote assembly of eIF4F complexes in infected cells. Furthermore, 4E-BP1 is degraded by the proteasome in an ICP0-dependent manner, establishing that the proteasome can control 4E-BP1 steady-state levels. Preventing eIF4E phosphorylation by inhibiting the eIF4E kinase mnk-1 dramatically reduced viral replication and the translation of viral polypeptides in quiescent cells, providing the first evidence that phosphorylation of eIF4E by mnk-1 is critical for viral protein synthesis and replication. Thus, in marked contrast to many viruses that inactivate eIF4F, HSV-1 stimulates eIF4F complex assembly in quiescent, differentiated cells; moreover, this is important for viral replication, and may be crucial for HSV-1 to initiate its productive growth cycle in resting cells, such as latently infected neurons.
PD‐1 inhibits T‐cell receptor induced phosphorylation of the ZAP70/CD3ζ signalosome and downstream signaling to PKCθ (2004)

Engagement of the immunoinhibitory receptor, programmed death-1 (PD-1) attenuates T-cell receptor (TCR)-mediated activation of IL-2 production and T-cell proliferation. Here, we demonstrate that PD-1 modulation of T-cell function involves inhibition of TCR-mediated phosphorylation of ZAP70 and association with CD3zeta. In addition, PD-1 signaling attenuates PKCtheta activation loop phosphorylation in a cognate TCR signal. PKCtheta has been shown to be required for T-cell IL-2 production. A phosphorylated PD-1 peptide, corresponding to the C-terminal immunoreceptor tyrosine-switch motif (ITSM), acts as a docking site in vitro for both SHP-2 and SHP-1, while the phosphorylated peptide containing the N-terminal PD-1 immunoreceptor tyrosine based inhibitory motif (ITIM) associates only with SHP-2.
Silver Nanodisks (2002)

Flat silver nanocrystals have been synthesized by using a soft chemical procedure that involves mixing two reverse micellar solutions. The resulting “nanodisks” display highly anisotropic optical properties attributed to their shape anisotropy. A dark-field TEM image of such a nanodisk, illustrating its single crystal nature, is shown in the Figure.
Polymer Microscopy, 3rd ed. (2009)

ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewPolymer Microscopy, 3rd ed.Karen I. WineyView Author Information University of PennsylvaniaCite this: J. Am. Chem. Soc. 2009, 131, 9, 3408Publication Date (Web):February 17, 2009Publication History Published online17 February 2009Published inissue 11 March 2009https://pubs.acs.org/doi/10.1021/ja900764thttps://doi.org/10.1021/ja900764tbook-reviewACS PublicationsCopyright © 2009 American Chemical SocietyRequest reuse permissionsArticle Views538Altmetric-Citations-LEARN 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:Imaging,Microscopy,Polymer morphology,Polymers Get e-Alerts
Astrocytes attenuate oligodendrocyte death in vitro through an α6 integrin‐laminin–dependent mechanism (2001)

Oligodendrocyte (OL) death occurs in many disorders of the CNS, including multiple sclerosis and brain trauma. Factors reported to induce OL death include deprivation of growth factors, elevation of cytokines, oxidative stress, and glutamate excitotoxicity. Because astrocytes produce a large amount of growth factors and antioxidants and are a major source of glutamate uptake, we tested the hypothesis that astrocytes may have a protective role for OL survival. We report that when OLs from the adult mouse brain were initiated into tissue culture, DNA fragmentation and chromatin condensation resulted, indicative of apoptosis. OL death was significantly reduced in coculture with astrocytes, but not with fibroblasts, which provided a similar monolayer of cells as astrocytes. The protection of OL demise by astrocytes was not reproduced by its conditioned medium and was not accounted for by several neurotrophic factors. In contrast, interference with the alpha(6) integrin subunit, but not the alpha(1), alpha(2), alpha(3), alpha(4), alpha(5), or alpha(v) integrin chains, negated astrocyte protection of OLs. Furthermore, a function-blocking antibody to alpha(6)beta(1) integrin reduced the ability of astrocytes to promote OL survival. The extracellular matrix ligand for alpha(6)beta(1) is laminin, which is expressed by astrocytes. Significantly, neutralizing antibodies to laminin-2 and laminin-5 inhibited the astrocyte mediation of OL survival. These results implicate astrocytes in promoting OL survival through a mechanism involving the interaction of alpha(6)beta(1) integrin on OLs with laminin on astrocytes. Enhancing this interaction may provide for OL survival in neurological injury.
Genetic stability of Borrelia burgdorferi recovered from chronically infected immunocompetent mice (1994)

Persistent infection with Borrelia burgdorferi in the presence of a vigorous host immune response has been demonstrated in humans and in animal models of Lyme disease. Long-term persistence of B. burgdorferi was documented recently in our studies of BALB/c and C3H mice infected with cloned and uncloned strains of B. burgdorferi. From mice inoculated with the cloned strain, 11 isolates were recovered from the skin, bladder, and blood after 1 year of infection. Analysis of the genes encoding the major outer surface proteins (OspA and OspB) by restriction digestion and DNA sequencing showed no evidence of point mutations or other small genetic alterations after 1 year. Genomic macrorestriction analysis of whole B. burgdorferi showed no loss or gross alterations of the plasmids encoding OspA, OspB, or OspC. However, in two isolates, loss of a 38-kb plasmid encoding outer surface protein D was noted. Our studies suggest that loss or alteration of the genes encoding OspA and OspB is not a common occurrence during persistent spirochetal infection and that other possible mechanisms, including invasion of immunologically privileged sites, should be actively explored.
1,2-Cyclomethylencarboxylic monoamide hydroxamic derivatives. A novel class of non-amino acid angiotensin converting enzyme inhibitors (1993)

A series of monoamidic derivatives of cis- and trans-1,2-cyclohexanedicarboxylic and 1,2-cyclopentanedicarboxylic acids bearing either a carboxylic, sulfhydrylic, or hydroxamic group in the side chain were synthesized and evaluated in vitro for their inhibitory activity against angiotensin converting enzyme. The compounds were designed as potential ACE inhibitors of novel structure, assuming that a monoamidic residue of an 1,2-cyclomethylenedicarboxylic acid could be an alternative structure to the acylproline moiety, the carboxyl-terminal portion common to various ACE inhibitors. The most active compounds were found in the hydroxamic derivatives of cyclohexane series; within this series of derivatives a marked increase of potency was caused by alkylation of the amidic nitrogen with a methyl or ethyl group. Therefore enantiomers of the selected hydroxamic derivatives of cis- and trans-1,2-cyclohexanedicarboxylic acid were prepared by two different chiral synthetic routes and evaluated in vitro for their ACE inhibitor potencies. The active enantiomers both of the cis series (21a, 21c) and trans series (16b, 16d) were found to have all R configuration at the C-2 and R or S configuration at the C-1, while in the classical ACE inhibitors S configuration at the terminal carboxylate (corresponding to the C-1 of our compounds) is strictly required for activity. The most potent compound of the series was (1S,2R)-cis-2[[[2-(hydroxyamino)-2-oxoethyl]methylamino]carbonyl] cyclohexanecarboxylic acid (21a) with an IC50 value of 7.0 nM compared with the value of 3.0 nM for captopril. Further 21a was shown to be highly selective and competitive ACE inhibitor. These results indicate that this non-amino acid structure of inhibitors meets the ACE active site requirements for the binding. The binding compatibility of the most active compounds with a model of ACE active site was evaluated by molecular modeling techniques.
Fabrication of Microfluidic Reactors and Mixing Studies for Luciferase Detection (2008)

We report the detection of luciferase by implementing a bioluminescent assay in microfluidic reactors. The reactors were fabricated in poly(methyl methacrylate) by hot embossing using a mold master with the reactor layouts made by high-precision micromilling. The overall fabrication process was simple to implement and had a quick turnaround time with low cost. Two reactors, one with smooth channels (called reactor I) and the other with staggered herringbone mixers (called reactor II), were studied for the bioluminescent assay. The assay was implemented by introducing a sample and an assay solution into the reactors and then mixing took place to achieve the enzymatic reactions. We found that the mixing efficiency in reactor II was 17.8 times higher than reactor I. Theoretical analysis of the experimental results indicated that the required channel length of mixing was linearly proportional to the flow rate. A calibration curve for luciferase was obtained for both reactors. We found that the detection sensitivity of reactor II was 3 times higher than reactor I. The limit of detection in reactor II was determined to be 0.14 microg/mL luciferase. The device was further exploited to determine the concentration of luciferase samples obtained from in vitro protein expression.
WASP and WAVE family proteins: key molecules for rapid rearrangement of cortical actin filaments and cell mov (2001)

Reorganization of cortical actin filaments plays critical roles in cell movement and pattern formation. Recently, the WASP and WAVE family proteins WASP and N-WASP, and WAVE1, WAVE2 and WAVE3 have been shown to regulate cortical actin filament reorganization in response to extracellular stimuli. These proteins each have a verprolin-homology (V) domain, cofilin-homology (C) domain and an acidic (A) region at the C-terminus, through which they activate the Arp2/3 complex, leading to rapid actin polymerization. N-WASP is usually present as an inactive form in which the VCA region is masked. Cooperative binding of Cdc42 and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)) exposes the VCA region, activating N-WASP. In addition to this activation mechanism, WISH also activates N-WASP independently of Cdc42 and PtdIns(4,5)P(2), by binding to the proline-rich region of N-WASP. N-WASP activation induces formation of filopodia in vivo. In contrast, the ubiquitously expressed form of WAVE2 is activated downstream of Rac, leading to formation of lamellipodia. In this case, IRSp53 transmits a signal from Rac to WAVE2 through formation of a ternary Rac-IRSp53-WAVE2 complex. Thus, N-WASP, which is activated downstream of Cdc42 or independently by WISH, induces formation of filopodia and WAVE2, which is activated via IRSp53 downstream of Rac, induces formation of lamellipodia.
Regulation of fibrillar collagen types I and III and basement membrane type IV collagen gene expression in pressure overloaded rat myocardium. (1990)

Left ventricular hypertrophy is based on cardiac myocyte growth. The hypertrophic process can be considered heterogeneous based on whether it also includes a remodeling and accumulation of fibrillar types I and III collagens that are responsible for impaired myocardial stiffness. In the heart, the messenger RNA (mRNA) for fibrillar collagen types I and III has been detected only in cardiac fibroblasts, whereas mRNA for basement membrane collagen type IV is present in both fibroblasts and myocytes. We studied the early and long-term expression of these collagenous proteins in rat myocardium after abdominal aortic banding with renal ischemia. Complementary DNA probes for rat pro-alpha 2 (I), mouse type III and mouse type IV collagens, and chicken beta-actin were used. Northern and dot blot analysis on total RNA extracted from left ventricular tissue indicated a sixfold increase in steady-state levels of mRNA for collagen type I on day 3 of abdominal aortic banding, which had declined to control levels by day 7 where it remained rather constant at 4 and 8 weeks. Type III collagen showed a similar pattern of gene expression after banding. mRNA levels for type IV collagen, on the other hand, were elevated on day 1 after banding, returning to control at day 7 and remaining constant. Actin mRNA levels also increased on day 1 of banding, followed by a rapid return to control levels. Monospecific antibody to types I and III collagens and immunofluorescent light microscopy on frozen sections of the myocardium revealed that at 1 week after banding, the distribution and density of these collagens were similar to those of control animals.(ABSTRACT TRUNCATED AT 250 WORDS)