gebhart/patrepeval huggingface dataset:
Idiopathic Pulmonary Fibrosis — A Sticky Business (2011)

Pulmonary fibrosis comprises a spectrum of disease phenotypes, including familial and idiopathic forms. Current research suggests that pulmonary fibrosis is a “two-hit” disease: a genetic predisposition to abnormal alveolar epithelial-cell regulation of the cell cycle and apoptosis combined with environmental stressors, including exposure to known fibrogenic materials (e.g., asbestos, silica, and cigarette smoke).1 Indeed, the identification of mutations in genes expressed in alveolar epithelia in association with pulmonary fibrosis — such as the surfactant proteins A and C (SPA and SPC, respectively)2,3 — and genes associated with cell stability — such as telomerase4 (hTERT and hTER) . . .
Strong Enhancement of Recombinant Cytosine Deaminase Activity inBifidobacterium longumfor Tumor-Targeting Enzyme/Prodrug Therapy (2007)

In our previous studies, a strain of the nonpathogenic, anaerobic, intestinal bacterium, Bifidobacterium longum (B. longum), was found to be localized selectively and to proliferate within solid tumors after systemic administration. In addition, B. longum transformed with the shuttle-plasmid encoding the cytosine deaminase (CD) gene expressed active CD, which deaminated the prodrug 5-fluorocytosine (5-FC) to the anticancer agent 5-fluorouracil (5-FU). We also reported antitumor efficacy with the same plasmid in several animal experiments. In this study, we constructed a novel shuttle-plasmid, pAV001-HU-eCD-M968, which included the mutant CD gene with a mutation at the active site to increase the enzymatic activity. In addition, the plasmid-transformed B. longum produces mutant CD and strongly increased (by 10-fold) its 5-FC to 5-FU enzymatic activity. The use of B. longum harboring the new shuttle-plasmid increases the effectiveness of our enzyme/prodrug strategy.
Arterial gene therapy: a molecular biological perspective for the treatment of arterial ischemia. (1997)

Since most cells do not naturally incorporate foreign DNA, strategies for arterial gene transfer have generally relied on agents designed to augment cellular DNA uptake such as liposomes, viral vectors, and protein conjugates. However, even when DNA has been successfully introduced into a cell, the likelihood of gene expression remains uncertain because the transgene has to escape lysosomal degradation, be transferred to the nucleus for transcription of mRNA, and be exported to the cytoplasm for translation and/or post-translation modification of the protein product. Transfection efficiency represents the final index of this regulatory sequence. The extent to which this compromises human gene therapy for cardiovascular disease depends in part on the presence or absence of a signal sequence permitting active secretion of the gene product. The implication of these issues is discussed with regard to restenosis and angiogenesis.
Secretion of matrix metalloproteinase‐9 by the proinflammatory cytokine, IL‐1β: a role for the dual signalling pathways, Akt and Erk (2003)

Taken together, our results suggest that IL-1beta stimulation of cells activates MMP-9 secretion by the activation of the dual signalling pathways, the PI3K-Akt and MEK1-Erk and constitutive activation of these pathways were sufficient to induce MMP-9 secretion.
Adeno-Associated Virus-Mediated Transduction of VEGF165 Improves Cardiac Tissue Viability and Functional Recovery After Permanent Coronary Occlusion in Conscious Dogs (2006)

We have previously shown that VEGF165 gene delivery into ischemic skeletal muscle exerts not only proangiogenic, but also remarkable antiapoptotic and proregenerative activity. The aim of this study was to determine whether recombinant adeno-associated virus (rAAV)-mediated gene delivery of VEGF165 into cardiac muscle, during acute myocardial infarction, exerts a protective effect to promote long-term functional recovery. Acute infarction of the anterior LV wall was induced in 12 chronically instrumented dogs by permanent occlusion of the LAD coronary artery. Four hours after occlusion, rAAV-VEGF165 or rAAV-LacZ (n=6 each; 5x10(12) viral particles per animal) was directly injected with an echo-guided needle into the dysfunctional cardiac wall. LV and arterial pressure, dP/dtmax, and ejection fraction were not significantly different between the two groups over time. In contrast, in the infarcted region, at four weeks after infarction, fractional shortening was 75+/-18% and -3+/-15% of baseline and length-pressure area was 54+/-15% and 0.8+/-15% of baseline in VEGF165 versus LacZ, respectively (P<0.05). Histological analysis of the border regions showed a marked increase in the number of alpha-SMA-positive arterioles (68+/-2.8 versus 100+/-3.8 vessels per microscopic field in LacZ and VEGF165 group, respectively; P<0.05). In both groups, the receptor VEGFR-2 was diffusely expressed on the surviving cardiomyocytes and, consistently, myocardial viability was significantly improved in the VEGF165-treated group, with several troponin T-expressing cardiomyocytes displaying nuclear positivity for the proliferation marker PCNA. Altogether, our results indicate that VEGF165 gene delivery exerts a marked beneficial action by enhancing both arteriologenesis and cardiomyocyte viability in infarcted myocardium.
Sacroiliac joint innervation and pain. (1999)

The present paper reviews current knowledge on the innervation of the human sacroiliac joint (SIJ). We conclude, based on a recent anatomic study on adult cadavers, with fetal correlation, that the joint is predominantly, if not entirely, innervated by sacral dorsal rami. This conclusion is in agreement with patterns of referred pain reported by asymptomatic volunteers upon direct SIJ capsular stimulation and with a reduction in pain in patients treated for (presumptive) SIJ pain by injection of an anesthetic into the SIJ. We also present preliminary data suggesting that the periarticular tissues of the SIJ, like those of other synovial joints, contain mechanoreceptors and nociceptors that function to inform the central nervous system about the state of the joint.
Overexpression of Akt/PKB modulates N‐myristoyltransferase activity in cancer cells (2009)

N-myristoyltransferase (NMT) catalyses the myristoylation reaction. Since NMT activity is elevated in various cancers and activated Akt/PKB leads to cell survival, we were interested in studying if activation of Akt/PKB has any effect on NMT. Overexpression of constitutively active Akt/PKB in HepG2 cells (HepG2-CA-Akt/PKB) led to an approximately 50% reduction of NMT compared with parental HepG2 cells. Reduced NMT activity in HepG2-CA-Akt/PKB was found to be due to the NMT1 phosphorylation. We determined NMT activity in various human breast cancer cell lines with differing metastatic potentials and pseudo-normal breast cells (HBL-100). Tumourigenic or metastatic breast cancer cell lines such as MDA-MB-231, MDA-MB-435, and Hs 578T displayed reduced NMT activity. Western blot analysis revealed that NMT1 is phosphorylated in these breast cancer cells. Furthermore, patients' breast cancer tissue array revealed strong positivity and high intensity for NMT in malignant breast tissues compared with normal breast cells. A gradation in the NMT staining was observed for grade I, II, and III infiltrating ductal carcinoma breast tissues. These studies demonstrate that overexpression of Akt/PKB results in NMT1 phosphorylation and that NMT1 is phosphorylated in breast cancer cells. Immunohistochemical analysis suggests that NMT may prove to be an added diagnostic biomarker for breast cancer.
Subcellular distribution of daptomycin given alone or with tobramycin in renal proximal tubular cells (1994)

Previous studies in experimental animals showed that daptomycin, a lipopeptide antibiotic, protects against aminoglycoside nephrotoxicity (C. A. Wood, H. C. Finkbeiner, S. J. Kohlhepp, P. W. Kohnen, and D. N. Gilbert, Antimicrob. Agents Chemother. 33:1280-1285, 1989; D. Beauchamp, M. Pellerin, P. Gourde, M. Pettigrew, and M. G. Bergeron, Antimicrob. Agents Chemother. 34:139-147, 1990). In order to better understand the mechanism involved in this protective effect, the subcellular distribution of daptomycin was investigated in the proximal tubular cells of animals treated with daptomycin alone or in combination with tobramycin. A first group of female Sprague-Dawley rats received a single intravenous injection of daptomycin at a dose of 100 mg/kg of body weight and were killed at 10 min, 1 h, or 24 h after the injection. Other groups of rats were treated during 10 days with saline (NaCl, 0.9%), tobramycin at dosages of 20 mg/kg/12 h, daptomycin at dosages of 10 mg/kg/12 h, or the combination tobramycin-daptomycin at the same dosages. At the time of sacrifice, the renal cortex of the right kidney of each animal was dissected, and small blocks of tissue were fixed, dehydrated, and embedded in Araldite 502 epoxy resin. The subcellular distribution of daptomycin and tobramycin was determined on ultrathin sections by immunogold labeling. Ten minutes after the injection of daptomycin alone, gold particles were seen over the brush border membrane and on the membranes of the endocytic vacuoles of proximal tubular cells. One hour after the injection, a similar distribution was seen and numerous gold particles were found over the lysosomes of proximal tubular cells. The results suggest that daptomycin might protect against aminoglycoside nephrotoxicity by interfering with the interaction between the aminoglycoside and phospholipids inside the lysosomes of proximal tubular cells.
Characterization of Genes and Proteins Involved in Excision Repair of Human Cells (1987)

To extend our knowledge of the excision repair system in mammalian cells we have focussed on the isolation of genes and proteins involved in this process. For the purification and characterization of human repair proteins the microneedle injection assay technique is utilized. This system is based on the transient correction of the excision repair defect of xeroderma pigmentosum (XP) fibroblasts (scored as increase of ultraviolet (u.v.)-induced unscheduled DNA synthesis (UDS) upon microinjection of crude extracts from complementing XP or normal cells. Specific correction is observed in fibroblasts of all (9) excision-deficient XP complementation groups. The XP-A and G correcting factors were found to be proteins and several purification steps (including (NH4)2SO4 fractionation, chromatography of phosphocellulose, heparin and u.v.-irradiated DNA-cellulose) have been worked out for the XP-A correcting protein. The microinjection system was also used for the introduction of (partially) purified repair enzymes of lower organisms. Micrococcus luteus endonuclease and bacteriophage T4 endonuclease V were able to correct all XP complementation groups tested, in marked contrast to the more sophisticated Escherichia coli uvrABC complex injected with uvrD. Photoreversal of dimers could be registered after introduction of the yeast photoreactivating enzyme in repair-competent, XP-variant, XP-C and XP-I fibroblasts (monitored as decrease of (residual) UDS). Remarkably, no effect was noticed in XP-A, D, E and H, suggesting that something prevents dimers in these cells from being monomerized by the injected enzyme. Using DNA-mediated gene transfer we have cloned a human gene (designated ERCC-1) that compensates for the excision defect of the u.v. and mitomycin C-sensitive Chinese hamster ovary cell (CHO) mutant 43-3B (complementation group 2). Characterization of this gene and its cDNA revealed the following features: (1) ERCC-1 corrects the full spectrum of repair deficiencies in mutants of complementation group 2. No correction is observed in mutants of the other CHO complementation groups. (2) The ERCC-1 gene has a size of 15 X 10(3) base-pairs (bp) and consists of 10 exons, one of which appears to be differentially spliced. (3) It encodes two largely identical mRNAs, which differ in the presence or absence of a 72 bp coding exon, situated in the 3' half of the mRNA. Only the cDNA of the large transcript is able to confer repair proficiency to 43-3B cells. No effect of u.v. treatment is found at the level of ERCC-1 transcription in HeLa cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Methylation of CLDN6, FBN2, RBP1, RBP4, TFPI2, and TMEFF2 in esophageal squamous cell carcinoma (2009)

In the development and progression of cancer, tumor suppressor genes may be silenced by mechanisms such as methylation. Thus the discovery of new genes silenced by methylation may uncover new tumor suppressor genes, and improve our understanding of cancer biology. In this study we investigated the methylation of 19 genes in esophageal squamous cell carcinoma. Methylation was measured in 10 of these genes in esophageal squamous cell carcinoma cell lines: CDH13, CLDN6, C16orf62, FBN2, FNBP1, ID4, RBP1, RBP4, TFPI2 and TMEFF2. To determine if there was a correlation between DNA methylation and gene silencing, each cell line was cultured with or without the demethylating drug 5-aza-2'-deoxycytidine (aza-dC). For 6 genes (CLDN6, FBN2, RBP1, RBP4, TFPI2 and TMEFF2) there was an association between reduction of methylation and increase in mRNA expression in the demethylated cell lines. The frequency of the methylation of these 6 genes in esophageal squamous cell carcinoma resection specimens was also investigated. All 6 genes showed more frequent methylation in the tumor than the matched proximal resection margin of uninvolved esophagus. There was a significant difference in the frequency of methylation and in the extent of the methylation between the cancer and the margin tissues for CLDN6, FBN2, TFPI2 and TMEFF2 (P=0.0007, P=0.0048 P=0.0002 and P<0.0001, respectively). This is the first report of gene silencing by methylation of CLDN6, FBN2, RBP4, TFPI2 and TMEFF2 in esophageal squamous cell carcinoma.
Zygaria: Storage Performance as a Managed Resource (2006)

Large-scale storage systems often hold data for multiple applications and users. A problem in such systems is isolating applications and users from each other to prevent their workloads from interacting in unexpected ways. Another is ensuring that each application receives an appropriate level of performance. As part of the solution to these problems, we have designed a hierarchical I/O scheduling algorithm to manage performance resources on an underlying storage device. Our algorithm uses a simple allocation abstraction: an application or user has a corresponding pool of throughput, and manages throughput within its pool by opening sessions. The algorithm ensures that each pool and session receives at least a reserve rate of throughput and caps usage at a limit rate, using hierarchical token buckets and EDF I/O scheduling. Once it has fulfilled the reserves of all active sessions and pools, it shares unused throughput fairly among active sessions and pools such that they tend to receive the same amount. It thus combines deadline scheduling with proportional-style resource sharing in a novel way. We assume that the device performs its own low-level head scheduling, rather than modeling the device in detail. Our implementation shows the correctness of our algorithm, imposes little overhead on the system, and achieves throughput nearly equal to that of an unmanaged device.
Centertrack: an IP overlay network for tracking DoS floods (2000)

Finding the source of forged Internet Protocol (IP) datagrams in a large, high-speed network is difficult due to the design of the IP protocol and the lack of sufficient capability in most high-speed, highcapacity router implementations. Typically, not enough of the routers in such a network are capable of performing the packet forwarding diagnostics required for this. As a result, tracking-down the source of a flood-type denial-of-service (DoS) attack is usually difficult or impossible in these networks. CenterTrack is an overlay network, consisting of IP tunnels or other connections, that is used to selectively reroute interesting datagrams directly from edge routers to special tracking routers. The tracking routers, or associated sniffers, can easily determine the ingress edge router by observing from which tunnel the datagrams arrive. The datagrams can be examined, then dropped or forwarded to the appropriate egress point. This system simplifies the work required to determine the ingress adjacency of a flood attack while bypassing any equipment which may be incapable of performing the necessary diagnostic functions. 1
Transitions in human atrial and ventricular myosin light-chain isoenzymes in response to cardiac-pressure-overload-induced hypertrophy (1982)

1. The light-chain subunits of human atrial and ventricular cardiac muscle were examined by two-dimensional polyacrylamide-gel electrophoresis and limited proteolytic digestion. The light-chain patterns in the normal right and left atria were identical. 2. Myosin preparations isolated from right or left atria that had been subjected to cardiac-pressure-overload-induced hypertrophy also contained ventricular light-chain subunits. These were identified by peptide mapping in sodium dodecyl sulphate. 3. Ventricular light chain-2 was the major species in hypertrophied atria, although light chain-1 subsequently appeared in severe pressure-overload-hypertrophied cases. Evidence is presented for the existence of more than one form of ventricular light chain-2. 4. The transition from atrial to ventricular myosin light chains correlated with the degree of pressure-overload hypertrophy in 83 examples of surgically excised atria. 5. The adult atrial light chain-1 was shown to be homologous to the human foetal ventricular light chain-1 [Price, Littler & Cummins (1980) Biochem. J. 191, 571-580] by peptide mapping. 6. A scheme of atrial/ventricular myosin light-chain isoenzyme transitions is discussed in relation to changing contractile properties in cardiac muscle, together with implications for the role of light-chain subunits.
Subsite Mapping of an Acidic Amino Acid-Specific Endopeptidase from Streptomyces griseus, GluSGP, and Protease V8 (1991)

The substrate specificities of an acidic amino acid-specific endopeptidase of Streptomyces griseus, GluSGP, and protease V8 [EC 3.4.21.19] were investigated with peptide p-nitroanilide substrates which have a Glu residue at the P1 position. GluSGP and protease V8 favored Pro and Leu residues at S2, respectively, while the S3 subsite of GluSGP preferred Phe over either Ala or Leu. The S3 subsite of protease V8 preferred Leu over either Ala or Phe. The best substrates for GluSGP and for protease V8 were Boc-Ala-Phe-Pro-Glu-pNA with a Km value of 0.41 mM (0.1 M Tris-HCl, pH 8.8) and Boc-Ala-Leu-Leu-Glu-pNA with a Km value of 0.25 mM (0.1 M phosphate, pH 7.8), respectively. The kcat/Km values for these substrates obtained with GluSGP were about one hundred to twenty thousand times larger than those obtained with protease V8. Protease V8 exhibited a single optimal pH of around 8 for the hydrolysis of Boc-Ala-Ala-Leu-Glu-pNA and Boc-Ala-Leu-Leu-Asp-pNA.
Sucrose accumulation in salt-stressed cells of agp gene deletion-mutant in cyanobacterium Synechocystis sp. PCC 6803 (2003)

The agp gene encoding the ADP-glucose pyrophosphorylase is involved in cyanobacterial glycogen synthesis and glucosylglycerol formation.By in vitro DNA recombination technology, a mutant with partial deletion of agp gene in the cyanobacterium Synechocystis sp.PCC 6803 was constructed.This mutant could not synthesize glycogen or the osmoprotective substance glucosylglycerol.In the mutant cells grown in the medium containing 0.9 M NaCl for 96 h, no glucosylglycerol was detected and the total amount of sucrose was 29 times of that of in wild-type cells.Furthermore, the agp deletion mutant could tolerate up to 0.9 M salt concentration.Our results suggest that sucrose might act as a similar potent osmoprotectant as glucosylglycerol in cyanobacterium Synechocystis sp.
UNC569, a Novel Small-Molecule Mer Inhibitor with Efficacy against Acute Lymphoblastic Leukemia In Vitro and In Vivo (2020)

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Although survival rates have improved, patients with certain biological subtypes still have suboptimal outcomes. Current chemotherapeutic regimens are associated with short- and long-term toxicities and novel, less toxic therapeutic strategies are needed. Mer receptor tyrosine kinase is ectopically expressed in ALL patient samples and cell lines. Inhibition of Mer expression reduces pro-survival signaling, increases chemosensitivity, and delays development of leukaemia in vivo suggesting that Mer tyrosine kinase inhibitors are excellent candidates for targeted therapies. Brain and spinal tumors are the second most common malignancies in childhood. Multiple chemotherapy approaches and radiation have been attempted, yet overall survival remains dismal. Mer is also abnormally expressed in atypical teratoid/rhabdoid tumors (ATRT), providing a rationale for targeting Mer as a therapeutic strategy. We have previously described UNC569, the first small molecule Mer inhibitor. This manuscript describes the biochemical and biological effects of UNC569 in ALL and ATRT. UNC569 inhibited Mer activation and downstream signaling through ERK1/2 and AKT, determined by western blot analysis. Treatment with UNC569 reduced proliferation/survival in liquid culture, decreased colony formation in methylcellulose/soft agar, and increased sensitivity to cytotoxic chemotherapies. MYC transgenic zebrafish with T-ALL were treated with UNC569 (4 µM for 2 weeks). Fluorescence was quantified as indicator of the distribution of lymphoblasts, which express Mer and enhanced green fluorescent protein. UNC569 induced >50% reduction in tumor burden compared to vehicle- and mock-treated fish. These data support further development of Mer inhibitors as effective therapies in ALL and ATRT.
Spatial contrast sensitivity in patients with multiple sclerosis. (1985)

Contrast sensitivity tests a basic visual function which is not examined by conventional visual acuity testing or visual evoked responses. It is frequently abnormal in patients with multiple sclerosis. The lack of relationship between VERs and SCSF implies that contrast sensitivity measures aspects of the visual system not examined by the conventional electrophysiological technique, probably visual function situated beyond the anterior visual pathway. It is therefore a useful complementary diagnostic test for patients with multiple sclerosis. Both VER and spatial contrast sensitivity separately detect a high proportion of patients with multiple sclerosis. When used in combination, the two techniques give a yield which approaches 100%. Contrast sensitivity testing as used here is cumbersome and time-consuming. Use of fewer spatial frequencies and/or adaptation of VER techniques for estimation of a contrast threshold may be more applicable for clinical use.
Convex optimization based time-domain broadband beamforming with sidelobe control (2007)

An approach to time-domain broadband beamforming with sidelobe control is proposed. The array response is expressed as a linear function of the finite impulse response filters tap weights. The filters are designed by minimizing beamformer output power while maintaining the distortionless response in the direction of the desired signal and guaranteeing the sidelobes to be below some given threshold values. Norm constraint on tap weights is also imposed to improve the robustness of the beamformer. Computationally efficient convex formulation for the beamformer design problem is derived using second-order cone programming. Simulation results demonstrate the satisfactory performance of the proposed approach.