gebhart/patrepeval huggingface dataset:
Enhanced Cardiomyocyte DNA Synthesis During Myocardial Hypertrophy in Mice Expressing a Modified TSC2 Transgene (2000)

Tuberous sclerosis complex (TSC) is a rare genetic disorder characterized by the appearance of benign tumors in multiple organs, including the heart. Disease progression is accompanied by homozygous mutation at 1 of 2 loci (designated TSC1 or TSC2), leading to the suggestion that these genes function as tumor suppressors. In this study, we generated a series of TSC2 cDNAs in which one or more structural motifs were deleted, with the hope that expression of the modified gene product would override the growth-inhibitory activity of the endogenous TSC2 gene product. Several of the modified cDNAs enhanced growth rate, increased endocytosis, and promoted aberrant protein trafficking when expressed in NIH-3T3 cells, thereby mimicking phenotypes typical of TSC2-deficient cells. Surprisingly, targeted expression of the most potent TSC2 cDNA to the heart did not perturb cardiac development. However, the level of cardiomyocyte DNA synthesis in adult transgenic mice was elevated >35-fold during isoproterenol-induced hypertrophy compared with their nontransgenic siblings. These results suggest that alteration of TSC2 gene activity in combination with beta-adrenergic stimulation can reactivate the cell cycle in a limited number of terminally differentiated adult cardiomyocytes.
The lipofuscin component A2E selectively inhibits phagolysosomal degradation of photoreceptor phospholipid by the retinal pigment epithelium (2002)

Daily phagocytosis of spent photoreceptor outer segments is a critical maintenance function performed by the retinal pigment epithelium (RPE) to preserve vision. Aging RPE accumulates lipofuscin, which includes N-retinylidene-N-retinylethanolamine (A2E) as the major autofluorescent component. We studied the effect of physiological levels of A2E in RPE cultures on their ability to phagocytose outer segments. A2E localized to lysosomes in cultured RPE as well as in human RPE in situ. A2E-loaded RPE cells in culture bound and internalized identical numbers of outer segments as control RPE indicating that A2E does not alter early steps of phagocytosis. A2E-loaded RPE degraded outer segment proteins efficiently but, strikingly, failed to completely digest phospholipids within 24 h. Because of the circadian rhythm of RPE phagocytosis in the eye, a delay in lipid degradation would likely result in a build up of undigested material in RPE that could contribute to the development of age-related macular degeneration.
Tumour targeting of humanised cross-linked divalent-fab′ antibody fragments: a clinical phase I/II study (2002)

Antibody engineering has made it possible to design antibodies with optimal characteristics for delivery of radionuclides for tumour imaging and therapy. A humanised divalent-Fab' cross-linked with a bis-maleimide linker referred to as humanised divalent-Fab' maleimide was produced as a result of this design process. It is a humanised divalent antibody with no Fc, which can be produced in bacteria and has enhanced stability compared with F(ab')(2). Here we describe a clinical study in patients with colorectal cancer using humanised divalent-Fab' maleimide generated from the anti-carcinoembryonic antigen antibody A5B7 radiolabelled with iodine-131. Ten patients received an i.v. injection of iodine-131-labelled A5B7 humanised divalent-Fab' maleimide, and positive tumour images were obtained by gamma camera imaging in eight patients with known lesions, and one previously undetected lesion was identified. True negative results were obtained in two patients without tumour. Area under the curve analysis of serial blood gamma counting and gamma camera images showed a higher tumour to blood ratio compared to A5B7 mF(ab')(2) used previously in the clinic, implying this new molecule may be superior for radioimmunotherapy. MIRD dose calculations showed a relatively high radiation dose to the kidney, which may limit the amount of activity that could be administered in radioimmunotherapy. However the reduction in immunogenicity was also a major advantage for A5B7 humanised divalent-Fab' maleimide over murine versions of this antibody suggesting that humanised divalent-Fab' maleimide should be a useful vehicle for repeated therapies.
Problems in Adapting a Glucose-Oxidase Electrochemical Sensor into an Implantable Glucose-Sensing Device (1982)

Taking into account the analytic patterns of different types of glucose-oxidase electrochemical sensors, the specific problems which have to be solved for such a sensor to be implantable are outlined. Of particular interest is the lifetime of enzymatic membrane and the dependence of the sensor responses to oxygen concentration and hydrodynamics.
Anti–Prostate Stem Cell Antigen Monoclonal Antibody 1G8 Induces Cell Death In vitro and Inhibits Tumor Growth In vivo via a Fc-Independent Mechanism (2005)

Prostate stem cell antigen (PSCA), a 123-amino acid cell surface glycoprotein, is highly expressed in both local and metastatic prostate cancers as well as in a large proportion of bladder and pancreatic cancers. PSCA overexpression correlates with a high risk of recurrence after primary therapy for prostate cancer. We have reported previously that anti-PSCA monoclonal antibody (mAb) 1G8 inhibits tumor growth, prevents metastasis, and prolongs the survival of mice inoculated with human prostate cancer cell lines and xenografts. The current study was undertaken to elucidate the mechanism of action of anti-PSCA antibody therapy. In particular, we asked whether antitumor activity resulted from recruitment of an immune response or a direct effect on the tumor cell itself. In vitro assays show that both intact 1G8 and F(ab')2 fragments of 1G8 induce prostate cancer cell death. The anti-PSCA antibody-induced cell death is caspase independent and requires antigen cross-linking. These results were confirmed in in vivo models in which both 1G8 and F(ab')2 fragments were able to inhibit prostate tumor formation and growth equally. These results suggest that the anti-PSCA mAb 1G8 acts by a direct, Fc-independent mechanism to inhibit prostate tumor growth both in vitro and in vivo.
Dynamic programming and influence diagrams (1990)

The concept of a super value node is developed to extend the theory of influence diagrams to allow dynamic programming to be performed within this graphical modeling framework. The operations necessary to exploit the presence of these nodes and efficiently analyze the models are developed. The key result is that by representing value function separability in the structure of the graph of the influence diagram, formulation is simplified and operations on the model can take advantage of the separability. From the decision analysis perspective, this allows simple exploitation of separability in the value function of a decision problem. This allows algorithms to be designed to solve influence diagrams that automatically recognize the opportunity for applying dynamic programming. From the decision processes perspective, influence diagrams with super value nodes allow efficient formulation and solution of nonstandard decision process structures. They also allow the exploitation of conditional independence between state variables.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Mechanisms for electrical stimulation of excitable tissue. (1994)

Electric fields excite electrically active tissue by several mechanisms. A long, straight, uniform fiber is polarized by an activating function, proportional to the axial gradient of the axial electric field. During unipolar anodal stimulation, the activating function results in two areas of depolarization (virtual cathodes) that are responsible for anode-make stimulation. During unipolar cathodal stimulation, the virtual anodes can be exploited to produce unidirectional propagation and physiological recruitment of axons. Anode-break stimulation of nerves arises from the intrinsic properties of the sodium channel kinetics; cathode-break stimulation in nerves is anode-break stimulation at a virtual anode. The activating function applies to magnetic stimulation as well as to electric stimulation. Other important mechanisms of stimulation arise if the fiber is terminated, nonuniform, or curved. In the brain, cortical neurons are excited when the electric field is directed from the dendrites toward the axon. Possible mechanisms for cortical excitation are the impedance mismatch between the axon and dendritic tree, and the axon bending as it enters the white matter. Transcranial magnetic stimulation differs from transcranial electric stimulation because during magnetic stimulation the electric field is parallel to the brain surface, whereas during electric stimulation the electric field has components both parallel and perpendicular to the brain surface. Cardiac tissue can be represented by use of the bidomain model. This model predicts that a point-source stimulus results in adjacent areas of depolarized and hyperpolarized tissue. The presence of virtual anodes during cathodal stimulation is analogous to the creation of virtual anodes along a one-dimensional fiber by the activating function. Anode- and cathode-break stimulation both occur in cardiac tissue, but the mechanism may be different than for nerve and may depend on diffusion of depolarization into a previously hyperpolarized region. Electrical stimulation of cardiac tissue can cause reentry through a critical point mechanism. Two mechanisms for defibrillation have been hypothesized: (1) the relatively high junctional resistance between cardiac cells causes each cell to be depolarized on one side and hyperpolarized on the other; and (2) the fiber tracts within the heart behave like individual fibers, with fiber curvature providing a mechanism for polarization. Similarities among nerve, brain, and cardiac stimulation are emphasized.
Phenotypic features of smooth muscle cells during the evolution of experimental carotid artery intimal thickening. Biochemical and morphologic studies. (1991)

Balloon catheter denudation of rat carotid artery that results in significant medial damage is followed by marked intimal smooth muscle cell (SMC) proliferation associated with limited endothelial regrowth. In this report we demonstrate that: (a) SMC of the carotid media, preceding their intimal proliferation, develop a cytoskeletal profile and morphology consistent with a de-differentiated SMC phenotype; and (b) both medial and intimal SMC subsequently revert to a cytoskeletal profile and morphology reflecting incomplete but significant re-differentiation toward normal SMC phenotype. Specifically, early after balloon injury, SMC of the media and those that have migrated into the intima contain decreased amounts of actin, desmin, and tropomyosin and increased amounts of vimentin; moreover, beta-actin becomes the dominant actin isoform, whereas alpha-actin decreases as compared with that found in normal medial SMC. Late after balloon injury, actin is still less abundant, however, desmin, tropomyosin, and vimentin return toward normal values and both medial and intimal SMC again show a predominance of alpha-actin, although the endothelium does not regenerate over the central surface of intimal thickening in this model. The SMC surface to volume ratio significantly decreases early after balloon injury, whereas it is not significantly different late after balloon injury as compared with that of SMC of the normal carotid media. We demonstrate, furthermore that: (c) adjacent luminal SMC are interconnected by gap junctions and develop focal tight junctions, a feature not reported previously to occur in smooth muscle; these cells however do not form any well defined membrane specialization with the leading edge of endothelium, supporting the view that presence of modified SMC on the luminal surface of chronically denuded vessels is not responsible for the cessation of endothelial regrowth.
Delivering stable high-quality video (2016)

Dynamic adaptive streaming over HTTP (DASH) is a simple, but effective, technology for video streaming over the Internet. It provides adaptive streaming while being highly scalable at the side of the content providers. However, the mismatch between TCP and the adaptive bursty nature of DASH traffic results in underperformance of DASH streams in busy networks. This paper describes a networking architecture based on the Software Defined Networking (SDN) paradigm. Controllers in the network with a broad overview on the network activity provide two mechanisms for adaptation assistance: explicitly signaling target bitrates to DASH players and dynamic traffic control in the network. We evaluate how each of these mechanisms can contribute to the delivery of a stable and high quality stream. It shows that our architecture improves the quality of experience by doubling the video bitrate and reducing disturbing quality switches. As such, this paper contributes insights on how to implement DASH-aware networking that also enables internet service providers, network administrators, and end-users to configure their networks to their requirements.
Dielectric breakdown in a simplified parallel model (1998)

The growth of streamer trees in insulating fluids (a submicrosecond process that triggers high-voltage breakdown) has been simulated with a combination of parallel-coding tools. Large grids and arrays display well the multifractal, self-avoiding character of the streamer trees. Three physical cases have been approximated by different power-law weightings of the statistical growth filter: dense anode trees, in the uniform field; sparse cathode trees (a rarer experimental case); and ultrasparse anode trees (seen in some fluids of higher viscosity). The model is contained in a software package that is written in Fortran 90 with data parallel extensions for distributed execution. These extensions encapsulate an underlying, invisible message-passing environment, thus enabling the solution of memory-intensive problems on a group of limited-memory processors. Block partitioning creates processes of reasonable size, which operate in parallel like small copies of the original code. The user needs only to express his model in transparent array-directed commands; parallel interfacing between blocks is handled invisibly. Breakdown is performed in parallel in each of the local blocks. Results are presented for experiments run on eight and nine nodes of the IBM SP2, and four and eight nodes of the SGI Onyx and Origin, three examples of multiple-processor machines. Display is carried out in three dimensions. Timing of the growth can be shown by color banding or by frame animation of the results. The adequacy of the growth rules and size scaling are tested by comparing the simulations against snapshots from high-voltage discharge events.
A Storable Encapsulated Bilayer Chip Containing a Single Protein Nanopore (2007)

A robust, portable chip containing a single protein nanopore would be a significant development in the practical application of stochastic sensing technology. Here, we describe a chip in which a single alpha-hemolysin (alphaHL) pore in a planar phospholipid bilayer is sandwiched between two layers of agarose gel. These encapsulated nanopore chips remain functional after storage for weeks. The detection of the second messenger inositol 1,4,5-trisphosphate (IP3) was demonstrated with a chip containing a genetically engineered alphaHL pore as the sensor element.
Immunotherapeutic approaches in ocular inflammatory diseases. (2006)

This comprehensive review discusses immunotherapeutic approaches to ocular inflammatory diseases, updates information provided in the literature, and presents clinical experiences with an emphasis on autoimmune uveitis at the National Eye Institute, United States. Current medical and surgical therapeutic approaches, including medications such as corticosteroids, anti-metabolites, alkylating agents, calcineurin and purine synthesis inhibitors, biologics as well as some anti-infectious agents, are reviewed along with new modalities and experimental approaches. Most immunosuppressive therapies have significant adverse effects. Physicians must be familiar with the pharmacology of the available drugs and aware of the philosophies behind the treatment.
Human macrophage metalloelastase gene expression in colorectal carcinoma and its clinicopathologic significance (2001)

Human macrophage metalloelastase (HME), also referred as matrix metalloproteinase 12, has been shown to convert plasminogen into angiostatin, an essential inhibitor of tumor angiogenesis. The current study was designed to investigate the association of HME mRNA expression with disease progression of in patients with colorectal carcinoma.
Requirement for Src Family Protein Tyrosine Kinases in G 2 for Fibroblast Cell Division (1995)

The protein tyrosine kinase c-Src is transiently activated at the transition from the G2 phase to mitosis in the cell cycle of mammalian fibroblasts. Fyn and Yes, the other members of the Src family present in fibroblasts, were also found to be activated at mitosis. In cells microinjected with a neutralizing antibody specific for Src, Fyn, and Yes (anti-cst.1) during G2, cell division was inhibited by 75 percent. The block occurred before nuclear envelope breakdown. Antibodies specific for phosphatidylinositol-3 kinase alpha and phospholipase C-gamma 1 had no effect. Microinjection of the Src homology 2 (SH2) domain of Fyn was also inhibitory. Functional redundancy between members of the Src family was observed; a Src-specific antibody had no effect in NIH 3T3 cells but inhibited cell division in fibroblasts in which the only functional Src family kinase was Src itself. Thus, Src family kinases and proteins associating with their SH2 domains are required for entry into mitosis.
Zinc(II) coordination domain mutants of T4 gene 32 protein (1992)

Gene 32 protein (g32P), the replication accessory single-stranded nucleic acid binding protein from bacteriophage T4, contains 1 mol of Zn(II)/mol of protein. Zinc coordination provides structural stability to the DNA-binding core domain of the molecule, termed g32P-(A+B) (residues 22-253). Optical absorption studies with the Co(II)-substituted protein and 113Cd NMR spectroscopy of 113Cd(II)-substituted g32P-(A+B) show that the metal coordination sphere in g32P is characterized by approximately tetrahedral ligand symmetry and ligation by the Cys-S- atoms of Cys77, Cys87, and Cys90. These studies predicted the involvement of a fourth protein-derived non-thiol ligand to complete the tetrahedral complex, postulated to be His81 on the basis of primary structure prediction and modeling [Giedroc, D.P., Johnson, B.A., Armitage, I.M., & Coleman, J.E. (1989) Biochemistry 28, 2410-2418]. To test this model, we have employed site-directed mutagenesis to substitute each of the two histidine residues in g32P (His64 and His81), accompanied by purification and structural characterization of these single-site mutant proteins. We show that g32P's containing any of three substitutions at residue 64 (H64Q, H64N, and H64L) are isolated from Escherichia coli in a Zn(II)-free form [less than or equal to 0.03 g.atom Zn(II)]. All derivatives show extremely weak affinity for the ssDNA homopolymer poly(dT). All are characterized by a far-UV-CD spectrum reduced in negative intensity relative to the wild-type protein. These structural features parallel those found for the known metal ligand mutant Cys87----Ser87 (C87S) g32P. In contrast, g32P-(A+B) containing a substitution of His81 with glutamine (H81Q), alanine (H81A) or cysteine (H81C), contains stoichiometric Zn(II) as isolated and binds to polynucleotides with an affinity comparable to the wild-type g32P-(A+B). Spin-echo 1H NMR spectra recorded for wild-type and H81Q g32P-(A+B) as a function of pH allow the assignment of His81 ring proteins to delta = 6.81 and 6.57 ppm, respectively, at pH 7.8, corresponding to the C and D histidyl protons of 1H-His-g32P-(A+B) [Pan, T., Giedroc, D.P., & Coleman, J.E. (1989) Biochemistry 28, 8828-8832]. These resonances shift downfield as the pH is reduced from 7.8 to 6.6 without metal dissociation, a result incompatible with His81 donating a ligand to the Zn(II) in wild-type g32P. Likewise, Cys81 in Zn(II) H81C g32P is readily reactive with 5,5'-dithiobis(2-nitrobenzoic acid), unlike metal ligands Cys77, Cys87, and Cys90.(ABSTRACT TRUNCATED AT 400 WORDS)
Development of low field nuclear magnetic resonance microcoils (2005)

A miniaturized spiral Helmholtz rf coil was fabricated using standard photolithography and electroplating. A commercial 0.6 T superconductive magnet was used to test the coil performance for both nuclear magnetic resonance (NMR) spectroscopy and imaging applications. NMR spectra of water, methanol, and 1-propanol were obtained as well as static and flow images of a water phantom. The spectral resolution was sufficient to allow chemical identification. Additionally, the viscosity of water was estimated from the experimental velocity profile and was equal to the expected value of 1 cP. Results obtained demonstrated the prospect of using the Helmholtz rf coil as part of a portable low-field NMR system for applications in analytical chemistry and process measurements in industrial settings.
A mechanistic study of the Mitsunobu esterification reaction (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA mechanistic study of the Mitsunobu esterification reactionD. L. Hughes, R. A. Reamer, J. J. Bergan, and E. J. J. GrabowskiCite this: J. Am. Chem. Soc. 1988, 110, 19, 6487–6491Publication Date (Print):September 1, 1988Publication History Published online1 May 2002Published inissue 1 September 1988https://doi.org/10.1021/ja00227a032RIGHTS & PERMISSIONSArticle Views4241Altmetric-Citations149LEARN 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 InReddit PDF (627 KB) Get e-Alerts Get e-Alerts
Pharmacomechanical thrombolysis and angioplasty in the management of clotted hemodialysis grafts: early and late clinical results. (1991)

The results of pharmacomechanical thrombolysis and angioplasty of 121 thrombosed hemodialysis grafts were reviewed. The initial pharmacomechanical method (used in 65 cases) employed clot maceration with hook-shaped catheters and clot lacing with highly concentrated urokinase. The current technique (used in 56 cases) consisted of pulsed-spray injection of urokinase into the clot. All fully treated grafts (117 cases) underwent complete or near-complete thrombolysis, and 93% remained patent after 1 day. Mean time for pulsed-spray lysis was 46 minutes +/- 21. One patient (less than 1%) had gastrointestinal bleeding and received a transfusion; minor complications occurred in 3% of patients. Primary and secondary graft patency rates for both methods at 1 year were 26% and 51%, respectively. While graft age and results of angioplasty did not influence future graft patency, shorter intervals between graft thromboses was predictive of earlier subsequent graft failure. Results suggest that pharmacomechanical thrombolysis and angioplasty provide rapid, consistent, and safe recanalization of clotted hemodialysis grafts and represent a promising additional therapeutic approach to long-term graft management.