gebhart/patrepeval huggingface dataset:
Inhibition of plasminogen activator inhibitor-1 binding to endocytosis receptors of the low-density-lipoprotein receptor family by a peptide isolated from a phage display library (2006)

The functions of the serpin PAI-1 (plasminogen activator inhibitor-1) are based on molecular interactions with its target proteases uPA and tPA (urokinase-type and tissue-type plasminogen activator respectively), with vitronectin and with endocytosis receptors of the low-density-lipoprotein family. Understanding the significance of these interactions would be facilitated by the ability to block them individually. Using phage display, we have identified the disulfide-constrained peptide motif CFGWC with affinity for natural human PAI-1. The three-dimensional structure of a peptide containing this motif (DVPCFGWCQDA) was determined by liquid-state NMR spectroscopy. A binding site in the so-called flexible joint region of PAI-1 was suggested by molecular modelling and validated through binding studies with various competitors and site-directed mutagenesis of PAI-1. The peptide with an N-terminal biotin inhibited the binding of the uPA-PAI-1 complex to the endocytosis receptors low-density-lipoprotein-receptor-related protein 1A (LRP-1A) and very-low-density-lipoprotein receptor (VLDLR) in vitro and inhibited endocytosis of the uPA-PAI-1 complex in U937 cells. We conclude that the isolated peptide represents a novel approach to pharmacological interference with the functions of PAI-1 based on inhibition of one specific molecular interaction.
Semiconductor Nanowires: From Self‐Organization to Patterned Growth (2006)

The synthesis of semiconductor nanowires has been studied intensively worldwide for a wide spectrum of materials. Such low-dimensional nanostructures are not only interesting for fundamental research due to their unique structural and physical properties relative to their bulk counterparts, but also offer fascinating potential for future technological applications. Deeper understanding and sufficient control of the growth of nanowires are central to the current research interest. This Review discusses the various growth processes, with a focus on the vapor-liquid-solid process, which offers an opportunity for the control of spatial positioning of nanowires. Strategies for position-controlled and nanopatterned growth of nanowire arrays are reviewed and demonstrated by selected examples as well as discussed in terms of larger-scale realization and future prospects. Issues on building up nanowire-based electronic and photonic devices are addressed at the end of the Review, accompanied by a brief survey of recent progress demonstrated so far on the laboratory level.
Evaluation of Systemic Follistatin as an Adjuvant to Stimulate Muscle Repair and Improve Motor Function in Pompe Mice (2010)

Due to the lack of acid alpha-glucosidase (GAA) activity, Pompe mice develop glycogen storage pathology and progressive skeletal muscle dysfunction with age. Applying either gene or enzyme therapy to reconstitute GAA levels in older, symptomatic Pompe mice effectively reduces glycogen storage in skeletal muscle but provides only modest improvements in motor function. As strategies to stimulate muscle hypertrophy, such as by myostatin inhibition, have been shown to improve muscle pathology and strength in mouse models of muscular dystrophy, we sought to determine whether these benefits might be similarly realized in Pompe mice. Administration of a recombinant adeno-associated virus serotype 8 vector encoding follistatin, an inhibitor of myostatin, increased muscle mass and strength but only in Pompe mice that were treated before 10 months of age. Younger Pompe mice showed significant muscle fiber hypertrophy in response to treatment with follistatin, but maximal gains in muscle strength were achieved only when concomitant GAA administration reduced glycogen storage in the affected muscles. Despite increased grip strength, follistatin treatment failed to improve rotarod performance. These findings highlight the importance of treating Pompe skeletal muscle before pathology becomes irreversible, and suggest that adjunctive therapies may not be effective without first clearing skeletal muscle glycogen storage with GAA.
Actions of the Opioid Antagonist, Nalmefene, and Congeners on Reperfusion Cardiac Arrhythmias and Regional Left Coronary Blood Flow (1990)

Opioid antagonists have been shown to prevent the occurrence of lethal arrhythmias following coronary reperfusion. In this study, we have examined the effect of a new, long-lasting, potent opioid antagonist, nalmefene, and congeners in the prevention of reperfusion arrhythmias in dogs. Nalmefene given at a dose of 1 mg/kg i.v. reduced the incidence of reperfusion arrhythmias significantly when compared to the saline control. Neither N-methyl nalmefene, a quaternary analog that does not cross the blood brain barrier, nor (+) nalmefene, an isomer with no anti-opioid actions, provided any protection against reperfusion arrhythmias. Regional myocardial blood flow profiles, during and after coronary occlusion, were not different between the nalmefene- and saline-treated groups. We conclude that nalmefene prevents the occurrence of reperfusion-induced arrhythmias by blocking opioid receptors in the brain.
Identification of a novel nuclear speckle‐type protein, SPOP (1997)

A novel antigen recognized by serum from a scleroderma patient was identified by expression cloning from the HeLa cell cDNA library. The cloned cDNA encoded a 374-amino acid protein with a relative molecular mass of 47,000 and a predicted amino acid sequence 62.7% identical to the hypothetical protein of Caenorhabditis elegans, T16H12.5. The deduced amino acid sequence had a typical POZ domain and an unidentified region conserved during evolution. No zinc finger or RNA recognition motifs were found in this clone. The 2 kbp mRNA encoding the novel clone SPOP (speckle-type POZ protein) was found to be expressed in all human tissues examined. HA-tagged SPOP, transfected and overexpressed in COS7 cells, exhibited a discrete speckled pattern in the nuclei and was co-localized with the splicing factor, snRNP B'/B. Deletion analysis revealed that both the POZ domain and the evolutionarily conserved region at the amino-terminus are required for the nuclear speckled accumulation of SPOP.
Mechanistic studies on .beta.-ketoacyl thiolase from Zoogloea ramigera: identification of the active-site nucleophile as Cys89, its mutation to Ser89, and kinetic and thermodynamic characterization of wild-type and mutant enzymes (1989)

Thiolase proceeds via covalent catalysis involving an acetyl-S-enzyme. The active-site thiol nucleophile is identified as Cys89 by acetylation with [14C]acetyl-CoA, rapid denaturation, tryptic digestion, and sequencing of the labeled peptide. The native acetyl enzyme is labile to hydrolytic decomposition with t 1/2 of 2 min at pH 7, 25 degrees C. Cys89 has been converted to the alternate nucleophile Ser89 by mutagenesis and the C89S enzyme overproduced, purified, and assessed for activity. The Ser89 enzyme retains 1% of the Vmax of the Cys89 enzyme in the direction of acetoacetyl-CoA thiolytic cleavage and 0.05% of the Vmax in the condensation of two acetyl-CoA molecules. A covalent acetyl-O-enzyme intermediate is detected on incubation with [14C]acetyl-CoA and isolation of the labeled Ser89-containing tryptic peptide. Comparisons of the Cys89 and Ser89 enzymes have been made for kinetic and thermodynamic stability of the acetyl enzyme intermediates both by isolation and by analysis of [32P]CoASH/acetyl-CoA partial reactions and for rate-limiting steps in catalysis with trideuterioacetyl-CoA.
Comprehensive analysis of the Corynebacterium glutamicum transcriptome using an improved RNAseq technique (2013)

The comprehensive transcriptome map of C. glutamicum established in this study represents a major step forward towards a complete definition of genetic elements (e.g. promoter regions, gene starts and stops, 5'-UTRs, RBSs, transcript starts and ends) and provides the ideal basis for further analyses on transcriptional regulatory networks in this organism. The methods developed are easily applicable for other bacteria and have the potential to be used also for quantification of transcriptomes, replacing microarrays in the near future.
Screening for novel quorum-sensing inhibitors to interfere with the formation of Pseudomonas aeruginosa biofilm (2011)

The objective of this study was to screen for novel quorum-sensing inhibitors (QSIs) from traditional Chinese medicines (TCMs) that inhibit bacterial biofilm formation. Six of 46 active components found in TCMs were identified as putative QSIs based on molecular docking studies. Of these, three compounds inhibited biofilm formation by Pseudomonas aeruginosa and Stenotrophomonas maltophilia at a concentration of 200 µM. A fourth compound (emodin) significantly inhibited biofilm formation at 20 µM and induced proteolysis of the quorum-sensing signal receptor TraR in Escherichia coli at a concentration of 3-30 mM. Emodin also increased the activity of ampicillin against P. aeruginosa. Therefore, emodin might be suitable for development into an antivirulence and antibacterial agent.
A protein tyrosine phosphatase-like protein from baculovirus has RNA 5′-triphosphatase and diphosphatase activities (1998)

The superfamily of protein tyrosine phosphatases (PTPs) includes at least one enzyme with an RNA substrate. We recently showed that the RNA triphosphatase domain of the Caenorhabditis elegans mRNA capping enzyme is related to the PTP enzyme family by sequence similarity and mechanism. The PTP most similar in sequence to the capping enzyme triphosphatase is BVP, a dual-specificity PTP encoded by the Autographa californica nuclear polyhedrosis virus. Although BVP previously has been shown to have modest tyrosine and serine/threonine phosphatase activity, we find that it is much more potent as an RNA 5'-phosphatase. BVP sequentially removes gamma and beta phosphates from the 5' end of triphosphate-terminated RNA, leaving a 5'-monophosphate end. The activity was specific for polynucleotides; nucleotide triphosphates were not hydrolyzed. A mutant protein in which the active site cysteine was replaced with serine was inactive. Three other dual-specificity PTPs (VH1, VHR, and Cdc14) did not exhibit detectable RNA phosphatase activity. Therefore, capping enzyme and BVP are members of a distinct PTP-like subfamily that can remove phosphates from RNA.
A novel mechanism of factor VIII protection by von Willebrand factor from activated protein C–catalyzed inactivation (2002)

The protective effect of von Willebrand factor (VWF) toward activated protein C (APC)-catalyzed inactivation of factor VIII (FVIII) has been attributed mainly to inhibition of FVIII binding to phospholipid. In the present study, we demonstrated that VWF-mediated FVIII protection from APC also results from direct inhibition of FVIII binding to APC. Inhibition of FVIII binding to anhydro-APC by VWF would be consistent with partial or complete overlap of the FVIII binding sites for APC and VWF. We examined, therefore, the inhibitory effects of 6 synthetic peptides spanning residues 1996 to 2028 around the previously localized APC binding region (FVIII residues 2009-2018). Peptide 2009 to 2018 inhibited FVIII binding to anhydro-APC by 83% (50% inhibition, 55 microM). Similarly, peptide 2013 to 2022 inhibited FVIII binding to VWF by 84% (50% inhibition, 25 microM). It was also found that peptides 2009 to 2018 and 2013 to 2022 optimally bound to anhydro-APC and VWF, respectively. A rabbit antipeptide IgG, raised against peptide 2009 to 2022, blocked the binding of both anhydro-APC and VWF to FVIII. This immunoglobulin G inhibited proteolytic cleavage of FVIII by APC. Our results indicate that the essential regions for the binding of APC and VWF to FVIII overlap and that the protective effect of VWF on APC-catalyzed FVIII inactivation includes competitive inhibition of APC binding to FVIII by VWF.
The tenascin family of ECM glycoproteins: Structure, function, and regulation during embryonic development and tissue remodeling (2000)

The determination of animal form depends on the coordination of events that lead to the morphological patterning of cells. This epigenetic view of development suggests that embryonic structures arise as a consequence of environmental influences acting on the properties of cells, rather than an unfolding of a completely genetically specified and preexisting invisible pattern. Specialized cells of developing multicellular organisms are surrounded by a complex extracellular matrix (ECM), comprised largely of different collagens, proteoglycans, and glycoproteins. This ECM is a substrate for tissue morphogenesis, lends support and flexibility to mature tissues, and acts as an epigenetic informational entity in the sense that it transduces and integrates intracellular signals via distinct cell surface receptors. Consequently, ECM-receptor interactions have a profound influence on major cellular programs including growth, differentiation, migration, and survival. In contrast to many other ECM proteins, the tenascin (TN) family of glycoproteins (TN-C, TN-R, TN-W, TN-X, and TN-Y) display highly restricted and dynamic patterns of expression in the embryo, particularly during neural development, skeletogenesis, and vasculogenesis. These molecules are reexpressed in the adult during normal processes such as wound healing, nerve regeneration, and tissue involution, and in pathological states including vascular disease, tumorigenesis, and metastasis. In concert with a multitude of associated ECM proteins and cell surface receptors that include members of the integrin family, TN proteins impart contrary cellular functions, depending on their mode of presentation (i.e., soluble or substrate-bound) and the cell types and differentiation states of the target tissues. Expression of tenascins is regulated by a variety of growth factors, cytokines, vasoactive peptides, ECM proteins, and biomechanical factors. The signals generated by these factors converge on particular combinations of cis-regulatory elements within the recently identified TN gene promoters via specific transcriptional activators or repressors. Additional complexity in regulating TN gene expression is achieved through alternative splicing, resulting in variants of TN polypeptides that exhibit different combinations of functional protein domains. In this review, we discuss some of the recent advances in TN biology that provide insights into the complex way in which the ECM is regulated and how it functions to regulate tissue morphogenesis and gene expression.
Mage-3 and Influenza-Matrix Peptide-Specific Cytotoxic T Cells Are Inducible in Terminal Stage HLA-A2.1+ Melanoma Patients by Mature Monocyte-Derived Dendritic Cells (2000)

Dendritic cell (DC) vaccination, albeit still in an early stage, is a promising strategy to induce immunity to cancer. We explored whether DC can expand Ag-specific CD8+ T cells even in far-advanced stage IV melanoma patients. We found that three to five biweekly vaccinations of mature, monocyte-derived DC (three vaccinations of 6 x 106 s.c. followed by two i.v. ones of 6 and 12 x 106, respectively) pulsed with Mage-3A2.1 tumor and influenza matrix A2. 1-positive control peptides as well as the recall Ag tetanus toxoid (in three of eight patients) generated in all eight patients Ag-specific effector CD8+ T cells that were detectable in blood directly ex vivo. This is the first time that active, melanoma peptide-specific, IFN-gamma-producing, effector CD8+ T cells have been reliably observed in patients vaccinated with melanoma Ags. Therefore, our DC vaccination strategy performs an adjuvant role and encourages further optimization of this new immunization approach.
In vitro susceptibility studies of vancomycin-resistant Enterococcus faecalis (1989)

Vancomycin resistance exhibited by Enterococcus faecalis isolates V583, V586, and V587 is described. The vancomycin MICs ranged from 32 to 64 micrograms/ml. Although resistant to vancomycin, the isolates were susceptible to teicoplanin (MIC, less than or equal to 0.5 micrograms/ml). Such a glycopeptide susceptibility profile has not been previously described for E. faecalis. Time kill studies showed that vancomycin resistance adversely affected the synergistic activity that vancomycin and aminoglycoside combinations usually demonstrate against enterococci. However, the ability to detect vancomycin resistance varied with the susceptibility testing method used. Whereas broth microdilution, broth macrodilution, and agar dilution methods detected resistance, disk-agar diffusion and the AutoMicrobic system Gram-Positive GPS-A susceptibility card (Vitek Systems Inc., Hazelwood, Mo.) did not. To detect vancomycin resistance reliably and establish the incidence of such E. faecalis isolates, adjustments in some susceptibility testing methods may be necessary.
Morphable memory system (2010)

Phase Change Memory (PCM) is emerging as a scalable and power efficient technology to architect future main memory systems. The scalability of PCM is enhanced by the property that PCM devices can store multiple bits per cell. While such Multi-Level Cell (MLC) devices can offer high density, this benefit comes at the expense of increased read latency, which can cause significant performance degradation. This paper proposes Morphable Memory System (MMS), a robust architecture for efficiently incorporating MLC PCM devices in main memory. MMS is based on observation that memory requirement varies between workloads, and systems are typically over-provisioned in terms of memory capacity. So, during a phase of low memory usage, some of the MLC devices can be operated at fewer bits per cell to obtain lower latency. When the workload requires full memory capacity, these devices can be restored to high density MLC operation to have full main-memory capacity. We provide the runtime monitors, the hardware-OS interface, and the detailed mechanism for implementing MMS. Our evaluations on an 8-core 8GB MLC PCM-based system show that MMS provides, on average, low latency access for 95% of all memory requests, thereby improving overall system performance by 40%.
Video services on copper (2002)

It is noted that video services may be provided over twisted wire pairs provided that the digital video is sufficiently compressed and provided that the bit rate achieved on copper is sufficiently high. Recent advances in digital video coding have resulted in an international standard for video coding at about 1.5 Mb/s with quality sufficient for many business and residential services. It is further noted that advances in transmission technology offer the possibility of megabit and higher bit rates over a single wire pair. Together these advances can be used to provide video services over existing telephone interoffice facilities and distribution loop plants.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Targeted Delivery of Small Interfering RNA: Approaching Effective Cancer Therapies (2008)

Three of the primary requirements for the development of effective dual-targeting therapeutic modalities for the treatment of cancer are the tumor-targeted delivery of the therapeutic molecules of interest to the tumor site(s) in the body (both primary and metastatic), passage of the molecular therapeutic through the cell membrane, and targeting specifically a growth or apoptotic pathway. However, lack of efficient targeted delivery, low transfection efficiency, instability to nucleases, poor tissue penetration, and nonspecific immune stimulation have hindered the translation of small interfering RNA (siRNA) into clinical applications. The development of a systemically administered, tumor-specific immunoliposome nanocomplex with high transfection efficiency could overcome these limitations and thus realize the potential of siRNAs to become effective anticancer clinical modalities.
Gene Expression Patterns of Th2 Inflammation and Intercellular Communication in Asthmatic Airways (2010)

Asthma is canonically thought of as a disorder of excessive Th2-driven inflammation in the airway, although recent studies have described heterogeneity with respect to asthma pathophysiology. We have previously described distinct phenotypes of asthma based on the presence or absence of a three-gene "Th2 signature" in bronchial epithelium, which differ in terms of eosinophilic inflammation, mucin composition, subepithelial fibrosis, and corticosteroid responsiveness. In the present analysis, we sought to describe Th2 inflammation in human asthmatic airways quantitatively with respect to known mediators of inflammation and intercellular communication. Using whole-genome microarray and quantitative real-time PCR analysis of endobronchial biopsies from 27 mild-to-moderate asthmatics and 13 healthy controls with associated clinical and demographic data, we found that asthmatic Th2 inflammation is expressed over a variable continuum, correlating significantly with local and systemic measures of allergy and eosinophilia. We evaluated a composite metric describing 79 coexpressed genes associated with Th2 inflammation against the biological space comprising cytokines, chemokines, and growth factors, identifying distinctive patterns of inflammatory mediators as well as Wnt, TGF-β, and platelet-derived growth factor family members. This integrated description of the factors regulating inflammation, cell migration, and tissue remodeling in asthmatic airways has important consequences for the pathophysiological and clinical impacts of emerging asthma therapeutics targeting Th2 inflammation.
Diffuse Optical Tomography of Cerebral Blood Flow, Oxygenation, and Metabolism in Rat during Focal Ischemia (2003)

Diffuse optical tomography (DOT) is an attractive approach for evaluating stroke physiology. It provides hemodynamic and metabolic imaging with unique potential for continuous noninvasive bedside imaging in humans. To date there have been few quantitative spatial-temporal studies of stroke pathophysiology based on diffuse optical signatures. The authors report DOT images of hemodynamic and metabolic contrasts using a rat middle cerebral artery occlusion (MCAO) stroke model. This study used a novel DOT device that concurrently obtains coregistered images of relative cerebral blood volume (rCBV), tissue-averaged hemoglobin oxygen saturation (Sto(2)), and relative cerebral blood flow (rCBF). The authors demonstrate how these hemodynamic measures can be synthesized to calculate an index of the oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen consumption (CMRo(2)). Temporary (60-minute) MCAO was performed on five rats. Ischemic changes, averaged over the 60 minutes of occlusion, were as follows: rCBF = 0.42 +/- 0.04, rCBV = 1.02 +/- 0.04, DeltaSto(2) = -11 +/- 2%, rOEF = 1.39 +/- 0.06 and rCMRo(2) = 0.59 +/- 0.07. Although rOEF increased in response to decreased blood flow, rCMRo(2) decreased. The sensitivity of this method of DOT analysis is discussed in terms of assumptions about baseline physiology, and the diffuse optical results are compared with positron emission tomography, magnetic resonance imaging, and histology observations in the literature.