gebhart/patrepeval huggingface dataset:
Insight into the Role of Low Molecular Weight Phosphotyrosine Phosphatase (LMW-PTP) on Platelet-derived Growth Factor Receptor (PDGF-r) Signaling (2002)

Low molecular weight phosphotyrosine phosphatase (LMW-PTP) is an enzyme involved in platelet-derived growth factor-induced mitogenesis and cytoskeleton rearrangement. Our previous results demonstrated that LMW-PTP is able to bind and dephosphorylate activated platelet-derived growth factor receptor (PDGF-r), thus inhibiting cell proliferation. Here we revisit the role of LMW-PTP on activated PDGF-r dephosphorylation. We demonstrate that LMW-PTP preferentially acts on cell surface PDGF-r, excluding the internalized activated receptor pool. Many phosphotyrosine phosphatases act by site-selective dephosphorylation on several sites of PDGF-r, but until now, there has been no evidence of a direct involvement of a specific phosphotyrosine phosphatase in the dephosphorylation of the 857 kinase domain activation tyrosine. Here we report that LMW-PTP affects the kinase activity of the receptor through the binding and dephosphorylation of Tyr-857 and influences many of the signal outputs from the receptor. In particular, we demonstrate a down-regulation of phosphatidylinositol 3-kinase, Src homology phosphatase-2, and phospholipase C-gamma1 binding but not of MAPK activation. In addition, we report a slight action of LMW-PTP on Tyr-716, which directs MAPK activation through Grb2 binding. On the basis of these results, we propose a key role for LMW-PTP in PDGF-r down-regulation through the dephosphorylation of the activation loop Tyr-857, thus determining a general negative regulation of all downstream signals, with the exception of those elicited by internalized receptors.
Actinonin, a Naturally Occurring Antibacterial Agent, Is a Potent Deformylase Inhibitor (2000)

Peptide deformylase (PDF) is essential in prokaryotes and absent in mammalian cells, thus making it an attractive target for the discovery of novel antibiotics. We have identified actinonin, a naturally occurring antibacterial agent, as a potent PDF inhibitor. The dissociation constant for this compound was 0.3 x 10(-)(9) M against Ni-PDF from Escherichia coli; the PDF from Staphylococcus aureus gave a similar value. Microbiological evaluation revealed that actinonin is a bacteriostatic agent with activity against Gram-positive and fastidious Gram-negative microorganisms. The PDF gene, def, was placed under control of P(BAD) in E. coli tolC, permitting regulation of PDF expression levels in the cell by varying the external arabinose concentration. The susceptibility of this strain to actinonin increases with decreased levels of PDF expression, indicating that actinonin inhibits bacterial growth by targeting this enzyme. Actinonin provides an excellent starting point from which to derive a more potent PDF inhibitor that has a broader spectrum of antibacterial activity.
Hyperprogressive Disease in Patients With Advanced Non–Small Cell Lung Cancer Treated With PD-1/PD-L1 Inhibitors or With Single-Agent Chemotherapy (2018)

Our study suggests that HPD is more common with PD-1/PD-L1 inhibitors compared with chemotherapy in pretreated patients with NSCLC and is also associated with high metastatic burden and poor prognosis in patients treated with PD-1/PD-L1 inhibitors. Additional studies are needed to determine the molecular mechanisms involved in HPD.
Study of a new ytterbium doped phosphate laser glass (2002)

Physical, and spectral properties of a new com-mercial ytterbium doped phosphate laser glass with big size, NEW/Yb, was researched. Assessing from thermal mechani-cal property, nonlinear property, crystalline phase, micro defects and spectroscopic properties of NEW/Yb and Kigre’s QX/Yb glasses, it is found that thermal-optical properties and glass internal quality of NEW/Yb glass are superior to QX/Yb glass. For NEW/Yb, the emission cross-section and fluorescent lifetime have a value of 0.53×10 pm2 and 2.2 ms, which are higher than those of QX/Yb.
Development and Analysis of Retroviral Vectors Expressing Human Factor VIII as a Potential Gene Therapy for Hemophilia A (1995)

To develop a potential gene therapy strategy for the treatment of hemophilia A, we constructed several retroviral vectors expressing a B-domain-deleted factor VIII (FVIII) cDNA. We confirmed previous reports that when the FVIII cDNA is inserted into a retroviral vector, the vector mRNA is decreased resulting in significantly (100- to 1,000-fold) lower vector titers. In an attempt to overcome this inhibition we pursued two independent strategies. First, site-directed mutagenesis was employed to change the structure of a putative 1.2-kb FVIII RNA inhibitory sequence (INS). Second, the FVIII gene was transcribed from a retroviral vector containing a 5' intron. Results demonstrated that the intron increased FVIII expression up to 20-fold and viral titer up to 40-fold but conservative mutagenesis of the putative FVIII INS region failed to yield a significant increase in FVIII expression or titer. Using the improved FVIII splicing vector, we transduced a variety of cell types and were able to demonstrate relatively high FVIII expression (10-60 ng of FVIII/10(6) cells/24 hr). These results underscore the usefulness of these transduced cell types for potential in vivo delivery of FVIII.
Analysis of temporal noise in CMOS photodiode active pixel sensor (2001)

Temporal noise sets the fundamental limit on image sensor performance, especially under low illumination and in video applications. In a CCD image sensor, temporal noise is primarily due to the photodetector shot noise and the output amplifier thermal and 1/f noise. CMOS image sensors suffer from higher noise than CCDs due to the additional pixel and column amplifier transistor thermal and 1/f noise. Noise analysis is further complicated by the time-varying circuit models, the fact that the reset transistor operates in subthreshold during reset, and the nonlinearity of the charge to voltage conversion, which is becoming more pronounced as CMOS technology scales. The paper presents a detailed and rigorous analysis of temporal noise due to thermal and shot noise sources in CMOS active pixel sensor (APS) that takes into consideration these complicating factors. Performing time-domain analysis, instead of the more traditional frequency-domain analysis, we find that the reset noise power due to thermal noise is at most half of its commonly quoted kT/C value. This result is corroborated by several published experimental data including data presented in this paper. The lower reset noise, however, comes at the expense of image lag. We find that alternative reset methods such as overdriving the reset transistor gate or using a pMOS transistor can alleviate lag, but at the expense of doubling the reset noise power. We propose a new reset method that alleviates lag without increasing reset noise.
Materials for Non-Viral Gene Delivery (2001)

▪ Abstract Novel therapeutic strategies can be envisioned based on altering the expression level of target genes involved in cellular processes and disease progression; however, our ability to efficiently manipulate gene expression is limited. Non-viralbased gene therapy provides a relatively safe approach to increase or decrease the expression of a specific gene using DNA or antisense sequences; however, synthetic systems are required to direct plasmids and oligonucleotides to a specific tissue and to enhance cellular uptake and intracellular trafficking. Numerous materials are being developed that interact with DNA to enhance its properties (e.g. stability, charge density) and thus direct its biodistribution and facilitate cellular interactions. The development of synthetic delivery systems to manipulate gene expression efficiently is a powerful tool that will ultimately lead to novel therapeutic strategies for the treatment of numerous disorders.
Thermal unfolding of human high-density apolipoprotein A-1: implications for a lipid-free molten globular state. (1996)

Apolipoprotein A-1 (apoA-1) in complex with high-density lipoprotein is critically involved in the transport and metabolism of cholesterol and in the pathogenesis of atherosclerosis. We reexamined the thermal unfolding of lipid-free apoA-1 in low-salt solution at pH approximately 7, by using differential scanning calorimetry and circular dichroism. At protein concentrations <5 mg/ml, thermal unfolding of apoA-1 is resolved as an extended peak (25 degrees C-90 degrees C) that can be largely accounted for by a single reversible non-two-state transition with midpoint Tm 57 +/- 1 degree C, calorimetric enthalpy deltaH(Tm)= 200 +/- 20 kcal/mol (1 kcal = 4.18 kJ), van't Hoff enthalpy deltaHv(Tm) approximately 32.5 kcal/mol, and cooperativity deltaHv(Tm)/deltaH(Tm) approximately 0.16. The enthalpy deltaH(Tm) can be accounted for by melting of the alpha-helical structure that is inferred by CD to constitute approximately 60% of apoA-1 amino acids. Farand near-UV CD spectra reveal noncoincident melting of the secondary and tertiary structural elements and indicate a well-defined secondary structure but a largely melted tertiary structure for apoA-1 at approximately 37 degrees C and pH 7. This suggests a molten globular-like state for lipid-free apoA-1 under near-physiological conditions. Our results suggest that in vivo lipid binding by apoA-1 may be mediated via the molten globular apolipoprotein state in plasma.
Smart grid: An electricity market perspective (2011)

A vision of the smart grid as an agent of economic value creation is needed to understand the paradigm shift that will be unfolding over the next few decades in the electricity market. This paper presents one such vision of the smart grid from an electricity market perspective and discusses its technical underpinnings. In contrast with the current mix of traditional and renewable resources, the smart grid is envisioned to be ultimately based on 100% renewable resources with end-to-end direct transactions between producers and consumers facilitated by one or more connectivity provider(s) much the same way e-commerce and other business transactions and interactions take place over the internet. These connectivity provider(s) will provide all necessary infrastructure for transmission and distribution of energy as well as the relevant information and data exchanges. Trading of power and various services based on allied information will enjoy internet-like market transparency and ease of execution.
Selective Localization of Carbon Black in Immiscible Polymer Blends: A Useful Tool To Design Electrical Conductive Composites (1994)

peer reviewed
The biomechanics of percutaneous needle insertion. (2008)

Emphasis has been placed on improving patient outcomes in healthcare management. Significant patient morbidity and mortality exists from inappropriate procedural technique and percutaneous catheter needle insertion procedures have been linked to medical complications. Healthcare trainees learn these procedures through trial and error and most existing simulators are synthetic tissue based and lack in-vivo force feedback. We seek to utilize the Blue DRAGON instrument positioning system coupled with a force sensor to determine true forces experienced by a needle as it is passed through animal and human tissues in an effort to design a percutaneous needle insertion simulator that affords the learner with the experience of the true force feedback. Acquiring force displacement measurements of needle insertion is the first step towards development of a computational model of the phenomena. The computational model may be further incorporated into a medical haptic simulator that provides physically based force feedback to the user.
A General Method for Site-specific Incorporation of Unnatural Amino Acids into Proteins (1989)

A new method has been developed that makes it possible to site-specifically incorporate unnatural amino acids into proteins. Synthetic amino acids were incorporated into the enzyme beta-lactamase by the use of a chemically acylated suppressor transfer RNA that inserted the amino acid in response to a stop codon substituted for the codon encoding residue of interest. Peptide mapping localized the inserted amino acid to a single peptide, and enough enzyme could be generated for purification to homogeneity. The catalytic properties of several mutants at the conserved Phe66 were characterized. The ability to selectively replace amino acids in a protein with a wide variety of structural and electronic variants should provide a more detailed understanding of protein structure and function.
Recognition Specificity of Neoglycopolymers Prepared by Ring-Opening Metathesis Polymerization (1996)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTRecognition Specificity of Neoglycopolymers Prepared by Ring-Opening Metathesis PolymerizationKathleen H. Mortell, Ross V. Weatherman, and Laura L. KiesslingView Author Information Department of Chemistry, University of WisconsinMadison Madison, Wisconsin 53706 Cite this: J. Am. Chem. Soc. 1996, 118, 9, 2297–2298Publication Date (Web):March 6, 1996Publication History Received25 October 1995Published online6 March 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/ja953574qhttps://doi.org/10.1021/ja953574qrapid-communicationACS PublicationsCopyright © 1996 American Chemical SocietyRequest reuse permissionsArticle Views1536Altmetric-Citations235LEARN 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-AlertscloseSupporting Info (2)»Supporting Information Supporting Information SUBJECTS:Carbohydrates,Chemical specificity,Ligands,Polymers,Reaction products Get e-Alerts
Oxygen Tolerance Study of Photoinduced Electron Transfer–Reversible Addition–Fragmentation Chain Transfer (PET-RAFT) Polymerization Mediated by Ru(bpy)3Cl2 (2014)

This study reports a highly efficient photoredox catalyst, Ru(bpy)3Cl2, capable of controlling the polymerization of methacrylates, acrylates, and acrylamides in the presence of thiocarbonylthio compounds via a photoinduced electron transfer–reversible addition–fragmentation chain (PET-RAFT) process. This polymerization technique was performed in a closed vessel in the presence or absence of air. Online Fourier transform near-infrared spectroscopy (FTNIR) was employed to monitor the monomer conversions of methyl methacrylate, methyl acrylate, and N,N′-dimethylacrylamide in the presence or absence of air. Interestingly, after an induction period, the polymerization proceeded in the presence of air to yield well-defined polymers (PDI < 1.20). The polymers were characterized by 1H NMR, UV–vis spectroscopy, and gel permeation chromatography. Excellent end-group retention was also demonstrated by NMR, UV–vis, and successive chain extensions of the resulting homopolymers to yield diblock and multiblock copolymers (decablock copolymers).
Isolation, characterization and properties of the oversulphated chondroitin sulphate proteoglycan from squid skin with peculiar glycosaminoglycan sulphation pattern (1992)

Oversulphated chondroitin sulphate proteoglycan from squid skin was isolated from 4 M guanidine hydrochloride extract by ion-exchange chromatography, gel chromatography and density gradient centrifugation. The proteoglycan had Mr 3.5 x 10(5), contained on average six oversulphated chondroitin sulphate chains (Mr 4 x 10(4)) bound on a polypeptide of Mr 2.8 x 10(4), and oligosaccharides consisting of both hexosamines, glucuronic acid, sulphates and fucose as the only neutral monosaccharide. The major amino acids of the proteoglycan protein core are glycine (corresponding to about one third of the total amino acids), aspartic acid/asparagine and serine, together amounting to 50% of the total. The proteoglycan was resistant to the proteolytic enzymes V8 protease, trypsin (treated with diphenylcarbamoyl chloride), alpha-chymotrypsin and pronase, while it was completely degraded by papain and to a large extent by collagenase. Pretreated proteoglycan with chondroitinase AC was degraded by pronase to a large extent and slightly by V8 protease and trypsin. The proteoglycan did not interact with hyaluronic acid and did not form self-aggregates. Oversulphated chondroitin sulphate chains were composed of unusual sulphated disaccharide units which were isolated and characterized by HPLC. In particular, it contained 2-acetamido-2-deoxy-3-O-(alpha-L-threo-4-enopyranosyluronic acid)-D-galactose 4-sulphate (delta di-4S) and disulphated disaccharides (delta di-diS) [90% 2-acetamido-2-deoxy-3-O-(alpha-L-threo-4-enopyranosyluronic acid 2/3-sulphate)-D-galactose 6-sulphate (delta di-diSD) and 10% 2-acetamido-2-deoxy-3-O-(alpha-L-threo-4-enopyranosyluronic acid 2/3-sulphate)-D-galactose 4-sulphate (delta di-diSK)] as the major disaccharides, significant amounts of trisulphated disaccharides (delta di-triS) and small amounts of 2-acetamido-2-deoxy-3-O-(alpha-L-threo-4-enopyranosyluronic acid)-D-galactose 6-sulphate (delta di-6S) and 2-acetamido-2-deoxy-3-O-(alpha-L-threo-4-enopyranosyluronic acid)-D-galactose (delta di-OS). Trisulphated disaccharides contained sulphate groups at C-4 and C-6 of the galactosamine and at C-2 or C-3 of the glucuronic acid. By HPLC analysis of a pure preparation of oversulphated chondroitin sulphate, it was found that it contains glucose, galactose, mannose and fucose most likely as branches.
Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates (2005)

We report seven patients, six from a single institution, who developed subacute limbic encephalitis initially considered of uncertain aetiology. Four patients presented with symptoms of hippocampal dysfunction (i.e. severe short-term memory loss) and three with extensive limbic dysfunction (i.e. confusion, seizures and suspected psychosis). Brain MRI and [(18)F]fluorodeoxyglucose (FDG)-PET complemented each other but did not overlap in 50% of the patients. Combining both tests, all patients had temporal lobe abnormalities, five with additional areas involved. In one patient, FDG hyperactivity in the brainstem that was normal on MRI correlated with central hypoventilation; in another case, hyperactivity in the cerebellum anticipated ataxia. All patients had abnormal CSF: six pleocytosis, six had increased protein concentration, and three of five examined had oligoclonal bands. A tumour was identified and removed in four patients (mediastinal teratoma, thymoma, thymic carcinoma and thyroid cancer) and not treated in one (ovarian teratoma). An immunohistochemical technique that facilitates the detection of antibodies to cell surface or synaptic proteins demonstrated that six patients had antibodies to the neuropil of hippocampus or cerebellum, and one to intraneuronal antigens. Only one of the neuropil antibodies corresponded to voltage-gated potassium channel (VGKC) antibodies; the other five (two with identical specificity) reacted with antigens concentrated in areas of high dendritic density or synaptic-enriched regions of the hippocampus or cerebellum. Preliminary characterization of these antigens indicates that they are diverse and expressed on the neuronal cell membrane and dendrites; they do not co-localize with VGKCs, but partially co-localize with spinophilin. A target autoantigen in one of the patients co-localizes with a cell surface protein involved in hippocampal dendritic development. All patients except the one with antibodies to intracellular antigens had dramatic clinical and neuroimaging responses to immunotherapy or tumour resection; two patients had neurological relapse and improved with immunotherapy. Overall, the phenotype associated with the novel neuropil antibodies includes dominant behavioural and psychiatric symptoms and seizures that often interfere with the evaluation of cognition and memory, and brain MRI or FDG-PET abnormalities less frequently restricted to the medial temporal lobes than in patients with classical paraneoplastic or VGKC antibodies. When compared with patients with VGKC antibodies, patients with these novel antibodies are more likely to have CSF inflammatory abnormalities and systemic tumours (teratoma and thymoma), and they do not develop SIADH-like hyponatraemia. Although most autoantigens await characterization, all share intense expression by the neuropil of hippocampus, with patterns of immunolabelling characteristic enough to suggest the diagnosis of these disorders and predict response to treatment.
Synthesis and biological evaluation of dipeptidyl and tripeptidyl polyoxin and nikkomycin analogs as anticandidal prodrugs (1991)

Nine analogues (1-5, 9-12) of the peptidyl nucleoside antibiotics nikkomycin and polyoxin were synthesized and tested for their biological properties against different strains of the pathogenic yeast Candida albicans. The tripeptidyl series of analogues (1-5) was designed to behave as prodrugs, releasing a toxic moiety upon enzymatic hydrolysis inside the cell. The dipeptidyl series (9-12) was designed as double-targeted drugs, being themselves toxic and releasing a toxic amino acid upon hydrolysis. All the analogues were prepared by coupling suitably protected amino acid p-nitrophenyl esters to 1-(5'-amino-5'-deoxy-alpha-D-allofuranuronosyl)uracil (UPOC) or the corresponding polyoxins and nikkomycins, with subsequent removal of the protecting group. Improved coupling yields were observed when DMSO was used as the solvent. Products were purified with use of reversed-phase HPLC and, in one case, diastereomeric products (compound 11) were resolved by using this procedure. One of the tripeptidyl nikkomycins behaved as a prodrug but none of the compounds, as measured by in vitro testing, proved more effective than nikkomycin as an anticandidal agent.
Look who's talking: discovering dependencies between virtual machines using CPU utilization (2010)

A common problem experienced in datacenters and utility clouds is the lack of knowledge about the mappings of the services being offered to or run by external users to the sets of virtual machines (VMs) realizing them. This makes it difficult to manage VM ensembles to attain provider goals like minimizing the resources consumed by certain services or reducing the power drawn by datacenter machines. This paper presents the 'Look Who's Talking' (LWT) set of methods and framework for identifying inter-VM dependencies. LWT does not require services to be modified, or middleware or operating systems to be instrumented, but instead, operates in management VMs with privileged access to hypervisor-level information about current machine use. The current implementation of LWT has been integrated into the Xen hypervisor running across a small-scale prototype datacenter, for which experimental measurements show that it can effectively identify dependencies between VMs with an average of 97.15% overall accuracy rate, with zero knowledge of or modifications to applications or workloads and with minimal effect on system performance.