gebhart/patrepeval huggingface dataset:
Abstract B49: Role of RAS palmitoyl-acyltransferase DHHC9 in hematopoiesis and NRAS leukemogenesis (2014)

Abstract Hyperactivation of RAS is common in human cancer, including hematological malignancies. Most oncogenic RAS proteins have been difficult to target. Identification of alternative targets that block RAS signaling is critical to develop therapies for RAS-related cancer. The biological activity of RAS proteins relies upon post-translational modifications (PTMs) that anchor RAS to cellular membranes. Protein palmitoylation regulates the membrane targeting, subcellular trafficking, and functions of proteins. We have previously examined the importance of PTMs in NRAS leukemogenesis and found for the first time that palmitoylation is essential for NRAS leukemogenesis. These studies suggest that targeting RAS palmitoylation may be an effective therapy for cancers involving RAS proteins that rely on palmitoylation for plasma membrane binding. In the previous studies, we blocked NRAS palmitoylation by mutating the palmitoylation site in NRAS. Therapeutic intervention of RAS palmitoylation requires targeting enzymes that mediate RAS palmitoylation. The reaction of protein S-palmitoylation is catalyzed by a family DHHC protein palmitoyl-acyltransferases (PATs). Thus far 24 mamalian PATs have been identified. It has been shown that DHHC9 (a 364-amino acid protein encoded by ZDHHC9, an X-linked gene), is the ortholog of yeast Ras2 PAT and constitute a mammalian PAT with specificity for H- and NRAS in vitro. Increased expression of DHHC9 has been found in various cancer. Here we investigate the role of DHHC9 in hematopoiesis and NRAS leukemogenesis in vivo. We found that ectopic expression of DHHC9 in mouse bone marrow cells hinders hematopoiesis, but is incapable of inducing hematological malignancies in mice. We also found that frequency of lineage-specific populations and hematopoietic stem cell phenotype were similar in mice with knockout alleles of ZDHHC9 as that of wild type mice, suggesting that DHHC9 is dispensable for normal hematopoiesis. Expression of oncogenic NRAS in bone marrow cells from ZDHHC9 knockout mice still induced leukemia but the mice survived longer that the wild type control mice. These results suggest that DHHC9 plays a role in the pathogenesis of NRAS-induced leukemia, but it is not the only PATs for RAS palmitoylation. We are identifying additional RAS PATs and developing cancer therapies targeting RAS palmitoylation. Citation Format: Ping Liu, Bo Jiao, Maurine Linder, Ruibao Ren. Role of RAS palmitoyl-acyltransferase DHHC9 in hematopoiesis and NRAS leukemogenesis. [abstract]. In: Proceedings of the AACR Special Conference on RAS Oncogenes: From Biology to Therapy; Feb 24-27, 2014; Lake Buena Vista, FL. Philadelphia (PA): AACR; Mol Cancer Res 2014;12(12 Suppl):Abstract nr B49. doi: 10.1158/1557-3125.RASONC14-B49
Effect of Action Potential Duration and Conduction Velocity Restitution and Their Spatial Dispersion on Alternans and the Stability of Arrhythmias (2002)

Alternans and arrhythmia dynamics are affected by the spatial dispersion of APD restitution as well as CV restitution, not simply the slope of APD restitution. Therefore, a direct link of the APD restitution slope to alternans and arrhythmia dynamics in rabbit heart does not exist. Designing antiarrhythmic drugs to alter only the restitution slope may not be appropriate.
Retailer's Response to Alternate Manufacturer's Incentives Under a Single‐Period, Price‐Dependent, Stochastic‐Demand Framework* (2005)

ABSTRACT This article considers the joint development of the optimal pricing and ordering policies of a profit‐maximizing retailer, faced with (i) a manufacturer trade incentive in the form of a price discount for itself or a rebate directly to the end customer; (ii) a stochastic consumer demand dependent upon the magnitude of the selling price and of the trade incentive, that is contrasted with a riskless demand, which is the expected value of the stochastic demand; and (iii) a single‐period newsvendor‐type framework. Additional analysis includes the development of equal profit policies in either form of trade incentive, an assessment of the conditions under which a one‐dollar discount is more profitable than a one‐dollar rebate, and an evaluation of the impact upon the retailer‐expected profits of changes in either incentive or in the degree of demand uncertainty. A numerical example highlights the main features of the model. The analytical and numerical results clearly show that, as compared to the results for the riskless demand, dealing with uncertainty through a stochastic demand leads to (i) (lower) higher retail prices if additive (multiplicative) error, (ii) lower (higher) pass throughs if additive (multiplicative) error, (iii) higher claw backs in both error structures wherever applicable, and (iv) higher rebates to achieve equivalent profits in both error structures.
On the mechanism of the hypolipidemic effect of sulfur-substituted hexadecanedioic acid (3-thiadicarboxylic acid) in normolipidemic rats (1993)

The mechanism behind the hypolipidemic effect of the sulfur-substituted non-beta-oxidizable fatty acid analogue 1,10 bis(carboxymethylthio)decane, also known as 3-thiadicarboxylic acid, was studied in normolipidemic rats. Treatment with 3-thiadicarboxylic acid markedly decreased plasma levels of free fatty acids, triglycerides, and cholesterol. This was accompanied by a corresponding reduction in very low density lipoprotein (VLDL)-triglyceride and low density lipoprotein (LDL)-cholesterol levels (by 46% and 42%, respectively), whereas the decrease in high density lipoprotein (HDL)-cholesterol levels was less pronounced (16%). However, the composition of the various plasma lipoprotein fractions was essentially unchanged. Fatty acid oxidation in both mitochondria and peroxisomes was stimulated in parallel; the activities of ATP:citrate lyase and fatty acid synthase, two key enzymes in fatty acid synthesis, were inhibited. Hepatic triglyceride biosynthesis was retarded, as indicated by a decrease in the liver triglyceride content along with a 30% reduction of hepatic VLDL-triglyceride secretion. This was accompanied by a 50% inhibition of phosphatidate phosphohydrolase. The activities of plasma lipoprotein lipase as well as hepatic lipase were somewhat higher (18%) in treated animals, suggesting a slight increase in the clearance potential of triglyceride-rich lipoproteins. The cholesterol-lowering effect was accompanied by a considerable reduction (75%) in HMG-CoA reductase activity and a less pronounced inhibition of cholesterol 7 alpha-hydroxylase (52%), and acyl-CoA:cholesterol acyltransferase (25%) activities. The present data suggest that the hypotriglyceridemic and hypocholesterolemic properties of sulfur-substituted fatty acid analogues are primarily due to effects on triglyceride and cholesterol synthesis.
Experimental Analysis of Dynamic Algorithms for the Single Source Shortest Path Problem. (1997)

In this paper we propose the first experimental study of the fully dynamic single source shortest paths problem on directed graphs with positive real edge weights. In particular, we perform an experimental analysis of three different algorithms: Dijkstra&apos;s algorithm, and the two output bounded algorithms proposed by Ramalingam and Reps in [31] and by Frigioni, Marchetti-Spaccamela and Nanni in [18], respectively. The main goal of this paper is to provide a first experimental evidence for: (a) the effectiveness of dynamic algorithms for shortest paths with respect to a traditional static approach to this problem; (b) the validity of the theoretical model of output boundedness to analyze dynamic graph algorithms. Beside random generated graphs, useful to capture the &quot;asymptotic&quot; behavior of algorithms, we also develope experiments by considering a widely used graph from the real world, i.e., the Internet graph. Work partially supported by the ESPRIT Long Term Research Project...
Management of Segmental Defects by the Ilizarov Intercalary Bone Transport Method (1992)

Seventeen patients with segmental skeletal defects were managed with the Ilizarov intercalary bone transport method, whereby an osseous defect is eliminated by elongating one fragment. On average, the regenerate new bone length measured 5.14 cm, corresponding to the creation of new osseous tissue equaling 13.7% of the bone's original length (range, 4.2%-35%). The average time in fixation was 9.6 months, including 4.8 months to transport the bone fragment throughout the limb. Numerous complications were encountered, most commonly wire-site sepsis and fixator instability. No serous nerve or vessel complications occurred. All but one patient eventually healed, although six patients required bone grafts, five at the target site and one at the level of the regenerate. Most of the difficulties encountered were due to a lack of technical knowledge with the method.
Cyclin D1/Cyclin-Dependent Kinase 4 Interacts with Filamin A and Affects the Migration and Invasion Potential of Breast Cancer Cells (2010)

Cyclin D1 belongs to a family of proteins that regulate progression through the G1-S phase of the cell cycle by binding to cyclin-dependent kinase (cdk)-4 to phosphorylate the retinoblastoma protein and release E2F transcription factors for progression through cell cycle. Several cancers, including breast, colon, and prostate, overexpress the cyclin D1 gene. However, the correlation of cyclin D1 overexpression with E2F target gene regulation or of cdk-dependent cyclin D1 activity with tumor development has not been identified. This suggests that the role of cyclin D1 in oncogenesis may be independent of its function as a cell cycle regulator. One such function is the role of cyclin D1 in cell adhesion and motility. Filamin A (FLNa), a member of the actin-binding filamin protein family, regulates signaling events involved in cell motility and invasion. FLNa has also been associated with a variety of cancers including lung cancer, prostate cancer, melanoma, human bladder cancer, and neuroblastoma. We hypothesized that elevated cyclin D1 facilitates motility in the invasive MDA-MB-231 breast cancer cell line. We show that MDA-MB-231 motility is affected by disturbing cyclin D1 levels or cyclin D1-cdk4/6 kinase activity. Using mass spectrometry, we find that cyclin D1 and FLNa coimmunoprecipitate and that lower levels of cyclin D1 are associated with decreased phosphorylation of FLNa at Ser2152 and Ser1459. We also identify many proteins related to cytoskeletal function, biomolecular synthesis, organelle biogenesis, and calcium regulation whose levels of expression change concomitant with decreased cell motility induced by decreased cyclin D1 and cyclin D1-cdk4/6 activities.
Production of Biodiesel from Algae Oils (2008)

Abstract A macroalga (Cladophora fracta) and a microalga (Chlorella protothecoides) samples were used in this work. Most current research on oil extraction is focused on microalgae to produce biodiesel from algal oil. The biodiesel from algal oil in itself is not significantly different from biodiesel produced from vegetable oils. Algal oils, as well as vegetable oils, are all highly viscous, with viscosities ranging 10–20 times those of no. 2 diesel fuel. Transesterification of the oil to its corresponding fatty ester is the most promising solution to the high viscosity problem. Fatty acid (m)ethyl esters produced from natural oils and fats is called biodiesel. Generally, methanol has been mostly used to produce biodiesel as it is the least expensive alcohol. The oil proportion from the lipid fractions of Chlorella protothecoides is considerable higher than that of Cladophora fracta. The higher heating value of Chlorella protothecoides (25.1 MJ/kg) also is higher than that of Cladophora fracta (21.1 MJ/kg). The average polyunsaturated fatty acids of Chlorella protothecoides (62.8%) also are higher than those of Cladophora fracta (50.9%).
Establishment and Characterization of an Estrogen-Producing Human Ovarian Granulosa Tumor Cell Line (1984)

Cells designated HTOG and HTOT were established by long-term culture from a human ovarian granulosa cell and a theca cell tumor, respectively. The HTOG line grew well forming colonies and multilayered rapidly without contact inhibition; serial passages of HTOG were performed over 100 times successively within 25 months. HTOG were spindle cells, polygonal or spherical in shape, revealed neoplastic and pleomorphic features, and produced estrone (E1) and 17 beta-estradiol (E2). The chromosome number varied considerably and showed hyperploidy; the modal chromosome number was in the hypertriploid-tetraploid range. When HTOG cells were heterotransplanted into the subcutis of BALB/c nude mice, they produced a sarcomatous diffuse type of granulosa cell tumors. In contrast, HTOT cells grew slowly while forming monolayers and underwent five successive passages in about 100 days, but a theca cell tumor line could not be established. HTOT cells were fibroblastic in shape and also produced E1 and E2. The majority of the cells showed diploidy and karyologic normality.
Simultaneous Real-Time Detection of Initiator- and Effector-Caspase Activation by Double Fluorescence Resonance Energy Transfer Analysis (2005)

Fluorescence resonance energy transfer (FRET) with green fluorescent protein (GFP) variants has become widely used for biochemical research. In order to expand the choice of fluorescent range in FRET analysis, we designed various color versions of the FRET-based probes for caspase activity, in which the substrate sequence of the caspase was sandwiched by donor and acceptor fluorescent proteins, and studied the potential of these color versions as fluorescent indicators. Six color versions were constructed by a combination of cyan fluorescent protein (CFP), GFP, yellow fluorescent protein (YFP), and DsRed. Real-time monitoring in single cells revealed that all probes could detect caspase activation during tumor necrosis factor (TNF)-alpha-induced cell death as a fluorescent change. GFP-DsRed and YFP-DsRed were as sensitive as CFP-YFP, and CFP-DsRed also showed a large fluorescent change. By using two probes, CFP-DsRed and YFP-DsRed, we carried out simultaneous multi-FRET analysis and revealed that the initiator- and effector-caspases were activated almost simultaneously in TNF-alpha-induced cell death. These findings may give experimental bases for the development of novel techniques to analyze multi-events simultaneously in single cells by using FRET probes in combination.
The development of 3D X-ray micro-tomography with sub 100 micron resolution for medical, industrial and biological applications (1989)

Apparatus has been developed for the acquisition of 3D X-ray commuted tomography images in cone-beam geometry. The equipment consists of a microfocal X-ray source operating at photon energies of up to 30 kVp with a focal spot size of 10 mu m, a computer-controlled stage for rotating the object, a 2D multi-wire gas proportional X-ray counter and a microcomputer to control image acquisition. Projection data were generated by rotating the object in discrete steps around a single axis until of the order of 100 2D projection images of the object were collected. The projection images were transferred to a VAX 11/750 computer for subsequent 3D reconstruction using a convolution and back-projection algorithm. The reconstructed data were displayed as transaxial, sagittal and coronal planes through the object. The specification of the acquisition hardware is discussed and some projection images together with the corresponding 3D reconstruction of the object are shown with pixel sizes smaller than 100 mu m.
Biomechanical Factors Associated with Tibial Stress Fracture in Female Runners (2006)

These data indicate that a history of TSF in runners is associated with increases in dynamic loading-related variables.
Angiotensin IV-mediated pulmonary artery vasorelaxation is due to endothelial intracellular calcium release (2000)

Angiotensin (ANG) IV stimulation of pulmonary artery (PA) endothelial cells (PAECs) but not of PA smooth muscle cells (PASMCs) resulted in significant increased production of cGMP in PASMCs. ANG IV receptors are not present in PASMCs, and PASMC nitric oxide synthase activity was not altered by ANG IV. ANG IV caused a dose-dependent vasodilation of U-46619-precontracted endothelium-intact but not endothelium-denuded PAs, and this response was blocked by the ANG IV receptor antagonist divalinal ANG IV but not by ANG II type 1 and 2 receptor blockers. ANG IV receptor-mediated increased intracellular Ca(2+) concentration ([Ca(2+)](i)) release from intracellular stores in PAECs was blocked by divalinal ANG IV as well as by the G protein, phospholipase C, and phosphoinositide (PI) 3-kinase inhibitors guanosine 5'-O-(2-thiodiphosphate), U-73122, and LY-294002, respectively, and was regulated by both PI 3-kinase- and ryanodine-sensitive Ca(2+) stores. Basal and ANG IV-mediated vasorelaxation of endothelium-denuded PAs was restored by exogenous PAECs but not by exogenous PAECs pretreated with the intracellular Ca(2+) chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM. These results demonstrate that ANG IV-mediated vasodilation of PAs is endothelium dependent and regulated by [Ca(2+)](i) release through receptor-coupled G protein-phospholipase C-PI 3-kinase signaling mechanisms.
Integrins α2β1 and α4β1 Can Mediate SA11 Rotavirus Attachment and Entry into Cells (2000)

Most mammalian rotaviruses contain tripeptide amino acid sequences in outer capsid proteins VP4 and VP7 which have been shown to act as ligands for integrins alpha2beta1 and alpha4beta1. Peptides containing these sequences and monoclonal antibodies directed to these integrins block rotavirus infection of cells. Here we report that SA11 rotavirus binding to and infection of K562 cells expressing alpha2beta1 or alpha4beta1 integrins via transfection is increased over virus binding to and infection of cells transfected with alpha3 integrin or parent cells. The increased binding and growth were specifically blocked by a monoclonal antibody to the transfected integrin subunit but not by irrelevant antibodies. In our experiments, integrin activation with phorbol ester did not affect virus binding to cells. However, phorbol ester treatment of K562 parent and transfected cells induced endogenous gene expression of alpha2beta1 integrin, which was detectable by flow cytometry 16 h after treatment and quantitatively correlated with the increased level of SA11 virus growth observed after this time. Virus binding to K562 cells treated with phorbol ester 24 h previously and expressing alpha2beta1 was elevated over binding to control cells and was specifically blocked by the anti-alpha2 monoclonal antibody AK7. Virus growth in alpha4-transfected K562 cells which had also been induced to express alpha2beta1 integrin with phorbol ester occurred at a level approaching that in the permissive MA104 cell line. We therefore have demonstrated that two integrins, alpha2beta1 and alpha4beta1, are capable of acting as cellular receptors for SA11 rotavirus.
Electronic transport of n-type CdSe quantum dot films: Effect of film treatment (2006)

Solid films of CdSe colloidal quantum dots are conductive when reduced by electrochemistry. The dark conductivity and the photoconductivity of these n-type CdSe nanocrystalline solids have been investigated as a function of film treatment. When the films are treated with NaOH, a carrier mobility of ∼10−2cm2∕Vs and a charging/discharging time of ∼10ms are obtained. Under an excitation intensity of ∼0.75mW∕cm2, a significant photoconductivity of ∼10−3Scm−1 has been observed. The high mobility allowed demonstrating the operation of a field effect transistor.
Darstellung und spektroskopische Charakterisierung von bindungsisomeren Halogenorhodanoosmaten(IV) (1986)

Abstract Durch oxydativen Ligandenaustausch an trans‐[OsCl 4 BrI] 2− bzw. tr.‐[OsCl 4 I 2 ] 2− mit (SCN) 2 in CH 2 Cl 2 , durch Substitution von [OsCl 5 I] 2− mit SCN − bzw. [OsCl 5 (NCS)] 2− mit F − in Toluol und Reaktion von [OsF 5 Cl] 2− mit (SCN) 2 in CH 2 Cl 2 lassen sich die folgenden Bindungsisomeren darstellen: tr.‐[OsF 4 Cl(NCS)] 2− /tr.‐[OsF 4 Cl(SCN)] 2− ,tr.‐[OsFCl 4 (NCS)] 2− /tr.‐[OsFCl 4 (SCN)] 2− , tr.‐[OsCl 4 Br(NCS)] 2− /tr.‐[OsCl 4 Br(SCN)] 2− , tr.‐[OsCl 4 I(NCS)] 2− /tr.‐[OsCl 4 I(SCN)] 2− ,tr.‐[OsCl 4 (NCS) 2 ] 2− /tr.‐[OsCl 4 (NCS)(SCN) ] 2− /tr.‐[OsCl 4 (SCN) 2 ] 2− , [OsBr 5 (NCS)] 2− /[OsBr 5 (SCN)] 2− und tr.‐[OsBr 4 (NCS)(SCN)] 2− . Alle Verbindungen werden durch Ionenaustauschchromatographie an DEAE‐Cellulose in reiner Form isoliert. In den IR‐ und Ramanspektren liegen ν CN(S) , ν CS(N) und δ NCS stets bei höheren Frequenzen als ν CN(N) , ν CS(S) und δ SCN . Die durch Spin‐Bahn‐Kopplung und niedrige Symmetrie (D 4h , C 4v ) aufgespaltenen Intrakonfigurations‐übergänge werden bei 10 K als schwache Banden in den Bereichen 600, 1000 und 2000 nm registriert. Die OO‐Übergänge ergeben sich aus der Schwingungsfeinstruktur und werden in einigen Fällen durch elektronische Ramanbanden gleicher Frequenz bestätigt. Die mit ζ(Os IV ) = 3200 cm −1 und den berechneten Racah‐Parametern B abgeleiteten Energieniveaus stimmen mit den Schwerpunkten der für D 4h ‐ und C 4v ‐Symmetrie erwarteten und gefundenen Multipletts gut überein.
ChemInform Abstract: Small‐Molecule PROTACS: New Approaches to Protein Degradation (2016)

Abstract Review: [42 refs.
Determination of the precise location and orientation of the Escherichia coli dnaE gene (1984)

The minimal region required for expression of the dnaE gene of Escherichia coli has been determined relative to a detailed restriction endonuclease map. This has been accomplished by analysis of Bal 31 exonuclease-generated deletions from the termini of the E. coli DNA contained in plasmid pMWE303 , a plasmid that we have previously demonstrated to contain the dnaE gene (M. M. Welch and C. S. McHenry , J. Bacteriol . 152:351-356, 1982). The competence of these deletion-containing plasmids in expressing the alpha subunit of DNA polymerase III holoenzyme has been determined by their ability both to complement a dnaE mutant and to direct the synthesis of a complete alpha subunit. The carboxyl-terminal coding region of dnaE has been identified through the detection of partial alpha polypeptides encoded by plasmids containing deletions from one end of the gene. This approach has permitted the precise determination of both termini of the dnaE gene and the determination of the orientation of the gene within the E. coli chromosome.