gebhart/patrepeval huggingface dataset:
Structural and dynamic aspects of binding of a prototype lexitropsin to the decadeoxyribonucleotide d(CGCAATTGCG)2 deduced from high-resolution proton NMR studies (1988)

Structural and dynamic properties of the self-complementary decadeoxyribonucleotide d(CGCAATTGCG)2 and the interaction between a prototype lexitropsin, or information-reading oligopeptide, and the decadeoxyribonucleotide are deduced by using high-resolution 1H NMR techniques. The nonexchangeable and imino proton resonances of d(CGCAATTGCG)2 have been completely assigned by two-dimensional NMR studies. The decadeoxyribonucleotide exists as a right-handed B-DNA. In the 1H NMR spectrum of the 1:1 complex, the selective chemical shifts and removal of degeneracy of AH2(4), AH2(5), T-CH3(6), and T-CH3(7) due to the anisotropy effects of the heterocyclic moieties of the ligand, and with lesser effects at the flanking base sites C(3) and G(8), locate the drug centrally in the decadeoxyribonucleotide. This conclusion is supported by plots of individual chemical shift changes across the decadeoxyribonucleotide. Similarly, imino protons IV and V experience larger shifts and II and III smaller shifts in accord with this conclusion while drug complexation permits the detection of imino proton I. Strong nuclear Overhauser effects (NOEs) between pyrrole H5 and AH2(5), and weaker NOEs to AH1'(5), TH3'(6), and AH2'(5), firmly locate the ligand in the minor groove. Intraligand NOEs between the adjacent heterocyclic moieties indicate that the lexitropsin is subject to propeller twisting about the N6-C9 bond in both the bound and free forms. Nuclear Overhauser effect spectroscopy (NOESY) and correlated spectroscopy (COSY) experiments also indicate that the removal of degeneracy of the C16 methylene protons upon complexation may arise from restricted rotation about the C15-N9, C15-C16, and C16-C17 bonds. Specific hydrogen bonds between amide NH groups on the concave face of the ligand (N4H, N6H, N9H) and adenine N3 or thymine O2 on the floor of the minor groove are in accord with displacement of the hydration shell by the drug. NOE measurements on the decadeoxyribonucleotide in the 1:1 complex confirm it exists as a right-handed helix and belongs to the B family. Exchange NMR effects permit an estimate of a rate of approximately equal to 44 s-1 for the two-site exchange of the lexitropsin between two equivalent sites on the decamer with delta G++ approximately equal to 70 +/- 5 kJ mol-1 at 294 K. Alternative mechanisms for this exchange process are considered.
Effect of DNA Secondary Structure on Human Telomerase Activity (1998)

Telomeres are specialized DNA-protein complexes located at the chromosome ends. The guanine-rich telomeric sequences have the ability to form G-quadruplex structures under physiological ionic conditions in vitro. Human telomeres are maintained through addition of TTAGGG repeats by the enzyme telomerase. To determine a correlation between DNA secondary structure and human telomerase, telomerase activity in the presence of various metal cations was monitored. Telomerase synthesized a larger proportion of products corresponding to four, five, eight, and nine full repeats of TTAGGG in 100 mM K+ and to a lesser extent in 100 mM Na+ when a d(TTAGGG)3 input primer was used. A more even product distribution was observed when the reaction mixture contained no added Na+ or K+. Increasing concentrations of Cs+ resulted in a loss of processivity but not in the distinct manner observed in K+. When the input primer contained 7-deaza-dG, the product distribution resembled that of reactions without K+ even in the presence of 100 mM K+. Native polyacrylamide gel electrophoresis indicated that d(TTAGGG)4, d(TTAGGG)5, d(TTAGGG)8, and d(TTAGGG)9 formed compact structures in the presence of K+. The oligonucleotide d(TTAGGG)4 had a UV spectrum characteristic of that of the G-quadruplex only in the presence of K+ and Na+. A reasonable explanation for these results is that four, five, eight, and nine repeats of TTAGGG form DNA secondary structures which promote dissociation of the primer from telomerase. This suggests that telomerase activity in cells can be modulated by the secondary structure of the DNA template. These findings are of probable relevance to the concept of telomerase as a therapeutic target for drug design.
Signal Transduction by the Chemokine Receptor CXCR3 (2001)

Hepatic stellate cells (HSC) and glomerular mesangial cells (MC) are tissue-specific pericytes involved in tissue repair, a process that is regulated by members of the chemokine family. In this study, we explored the signal transduction pathways activated by the chemokine receptor CXCR3 in vascular pericytes. In HSC, interaction of CXCR3 with its ligands resulted in increased chemotaxis and activation of the Ras/ERK cascade. Activation of CXCR3 also stimulated Src phosphorylation and kinase activity and increased the activity of phosphatidylinositol 3-kinase and its downstream pathway, Akt. The increase in ERK activity was inhibited by genistein and PP1, but not by wortmannin, indicating that Src activation is necessary for the activation of the Ras/ERK pathway by CXCR3. Inhibition of ERK activation resulted in a decreased chemotactic and mitogenic effect of CXCR3 ligands. In MC, which respond to CXCR3 ligands with increased DNA synthesis, CXCR3 activation resulted in a biphasic stimulation of ERK activation, a pattern similar to the one observed in HSC exposed to platelet-derived growth factor, indicating that this type of response is related to the stimulation of cell proliferation. These data characterize CXCR3 signaling in pericytes and clarify the relevance of downstream pathways in the modulation of different biologic responses.
Coded aperture imaging with uniformly redundant arrays (1978)

Uniformly redundant arrays (URA) have autocorrelation functions with perfectly flat sidelobes. The URA combines the high-transmission characteristics of the random array with the flat sidelobe advantage of the nonredundant pinhole arrays. This gives the URA the capability to image low-intensity, low-contrast sources. Furthermore, whereas the inherent noise in random array imaging puts a limit on the obtainable SNR, the URA has no such limit. Computer simulations show that the URA with significant shot and background noise is vastly superior to random array techniques without noise. Implementation permits a detector which is smaller than its random array counterpart.
Increased remineralization of tooth enamel by milk containing added casein phosphopeptide-amorphous calcium phosphate (2006)

Casein phosphopeptide amorphous calcium phosphate nano-complexes (CPP-ACP) in chewing gum, lozenges and mouthrinses have been shown to re-mineralize enamel subsurface lesions in human in situ experiments. The aim of this double-blind, randomized clinical study was to investigate the capacity of CPP-ACP added to bovine milk to re-mineralize enamel subsurface lesions in situ. Ten subjects drank milk containing either 2.0 or 5.0 g CPP-ACP/l or a control milk whilst wearing removable appliances with enamel slabs containing subsurface demineralized lesions. Each 200 ml milk sample was consumed once a day for each weekday over three consecutive weeks. After each treatment and one weeks rest the subjects crossed over to the other treatments. At the completion of the treatments the enamel slabs were removed and remineralization determined using microradiography and microdensitometry. The results demonstrated that all three milk samples re-mineralized enamel subsurface lesions. However, the milk samples containing CPP-ACP produced significantly greater remineralization than the control milk. The re-mineralizing effect of CPP-ACP in milk was dose-dependent with 2.0 and 5.0 g CPP-ACP/l producing an increase in mineral content of 70 and 148%, respectively, relative to the control milk. The differences in remineralization following exposure to the three milk samples were all statistically significant (P<0.001). In conclusion, this study shows that the addition of 2.0-5.0 g CPP-ACP/l to milk substantially increases its ability to re-mineralize enamel subsurface lesions.
Myocardial Perfusion Patterns Related to Thrombolysis in Myocardial Infarction Perfusion Grades After Coronary Angioplasty in Patients With Acute Anterior Wall Myocardial Infarction (1996)

Despite no obstructive lesion of the vessel, TIMI 2 is caused by advanced microvascular damage and is a highly specific, although not sensitive, predictor of poor functional outcomes in patients with acute myocardial infarction. TIMI 3 does not necessarily indicate myocardial salvage, and detection of MCE no reflow in these patients is particularly useful for the prediction of functional outcome.
Workload orchestration and optimization for software defined environments (2014)

The software defined environment (SDE) provides a powerful programmable interface to a cloud infrastructure through an abstraction of compute, network, and storage resources. A workload refers to the application to be deployed in such an infrastructure. To take advantage of the SDE interface, the workload is described using a declarative workload definition language and is then deployed in the infrastructure through an automated workload orchestration and optimization layer. This paper describes the architecture and algorithms that make up this layer. Given a definition of the workload, including the virtual components of the application and their resource needs, as well as other meta-information relating to factors such as performance, availability, and privacy, the function of the workload orchestration and optimization layer is to map virtual resources to physical resources and realize such a mapping in the infrastructure. This mapping, known as placement, is optimized so that the infrastructure is efficiently utilized, and the workload requirements are satisfied. We present the overall architecture of the workload orchestration and optimization runtime. We focus on the workload placement problem and describe our optimization framework. Then, we consider a real application, IBM Connections, as a use-case to demonstrate the orchestration and optimization functionalities.
Clostridium difficile diarrhea: pathogenesis, epidemiology, and treatment. (1994)

Clostridium difficile, the bacterium responsible for antibiotic-associated diarrhea and colitis, has become a significant cause of morbidity and prolonged hospital stays, largely because of the increasing use of broad-spectrum antibiotics. This gram-positive organism, which can lay dormant in its spore form in the environment for extended periods of time, proliferates in the colon when the normal colonic flora is compromised by antibiotic use. C. difficile produces intestinal inflammation and diarrhea through the elaboration of two protein exotoxins, toxin A and toxin B. The spectrum of clinical manifestations ranges from mild diarrhea that resolves with the cessation of the offending antibiotic, to fulminant pseudomembranous colitis complicated by megacolon and perforation. Our ability to meet the challenge offered by this organism has been enhanced by the development of new diagnostic modalities as well as the development of new therapeutic regimens. Through further investigation of the structure and function of toxins A and B and further study of the interaction of C. difficile with the normal colonic flora, advances will continue to be made in the prevention and treatment of antibiotic-associated colitis.
UPT demo on integrated wireline and wireless testbed (2002)

This paper describes a Universal Personal Telecommunication (UPT) demonstration on an integrated wireline and wireless testbed at GTE Laboratories in Massachusetts. The integrated testbed allows us to investigate the support of UPT services in the wireline and wireless networks. This paper first describes the service concept and the key characteristics of UPT service. The integrated wireline and wireless testbed (especially the UPT-related components) and the information flow sequences among the network elements in the integrated testbed are described next. Finally, the issues that will be investigated during the next phase of the testbed effort are discussed.
Engineering Approaches for the Detection and Control of Orthopaedic Biofilm Infections (2005)

Artificial joints are subject to chronic infections associated with bacterial biofilms, which only can be eradicated by the traumatic removal of the implant followed by sustained intravenous antibiotic therapy. We have adopted an engineering approach to develop electrical-current-based approaches to bacterial eradication and microelectromechanical systems that could be embedded within the implanted joint to detect the presence of bacteria and to provide in situ treatment of the infection before a biofilm can form. In the former case we will examine the combined bactericidal effects of direct and indirect electrical fields in combination with antibiotic therapy. In the latter case, bacterial detection will occur by developing a microelectromechanical-systems-based biosensor that can "eavesdrop" on bacterial quorum-sensing-based communication systems. Treatment will be effected by the release of a cocktail of pharmaceutical reagents contained within integral reservoirs associated with the implant, including a molecular jamming signal that competitively binds to the bacteria's quorum sensing receptors (which will "blind" the bacteria, preventing the production of toxins) and multiple high dose antibiotics to eradicate the planktonic bacteria. This approach is designed to take advantage of the relatively high susceptibility to antibiotics that planktonic bacteria display compared with biofilm envirovars. Here we report the development of a generic microelectromechanical systems biosensor that measures changes in internal viscosity in a base fluid triggered by a change in the external environment.
Techniques in Facial Fat Grafting (2008)

According to the author, autologous fat transplantation is an ideal technique to correct facial atrophy, providing a stable and potentially long lasting alternative to "off the shelf" fillers. Structural augmentation with fat involves multilayer blunt fat infiltration designed around concepts of volume expansion and resultant tissue shifting. The author has found that retention varies in different parts of the face and fat seems to "take" best in areas in which fat atrophy is the problem, such as in the cheek, periorbital area, and mandible. When fat is being used to replace bony remodeling or mucosal atrophy (both occur in the perioral area), retention can be unpredictable.
CD95 triggers Orai1-mediated localized Ca2+entry, regulates recruitment of protein kinase C (PKC) β2, and prevents death-inducing signaling complex formation (2011)

The death receptor CD95 plays a pivotal role in immune surveillance and immune tolerance. Binding of CD95L to CD95 leads to recruitment of the adaptor protein Fas-associated death domain protein (FADD), which in turn aggregates caspase-8 and caspase-10. Efficient formation of the CD95/FADD/caspase complex, known as the death-inducing signaling complex (DISC), culminates in the induction of apoptosis. We show that cells exposed to CD95L undergo a reorganization of the plasma membrane in which the Ca(2+) release-activated Ca(2+) channel Orai1 and the endoplasmic reticulum-resident activator stromal interaction molecule 1 colocalize with CD95 into a micrometer-sized cluster in which the channel elicits a polarized entry of calcium. Orai1 knockdown and expression of a dominant negative construct (Orai1E106A) reveal that on CD95 engagement, the Orai1-driven localized Ca(2+) influx is fundamental to recruiting the Ca(2+)-dependent protein kinase C (PKC) β2 to the DISC. PKCβ2 in turn transiently holds the complex in an inactive status, preventing caspase activation and transmission of the apoptotic signal. This study identifies a biological role of Ca(2+) and the Orai1 channel that drives a transient negative feedback loop, introducing a lag phase in the early steps of the CD95 signal. We suggest that these localized events provide a time of decision to prevent accidental cell death.
Association study of polymorphisms in the glutamate transporter genes SLC1A1, SLC1A3, and SLC1A6 with schizophrenia (2007)

Based on the glutamatergic dysfunction hypothesis for schizophrenia pathogenesis, we have been performing systematic association studies of schizophrenia with the glutamate receptor and transporter genes. We report here association studies of schizophrenia with three glutamate transporter genes SLC1A1, SLC1A3, and SLC1A6 encoding the glutamate transporters EAAT3, EAAT1, and EAAT4, respectively. We initially performed the screening of the total 25 single nucleotide polymorphisms (SNPs) distributed in the three gene regions using 100 out of 400 Japanese cases and 100 out of 420 Japanese controls. After controlling the false discovery rate (FDR) at level 0.05, we observed significant associations of schizophrenia with a genotype of SNP4 (rs2097837, P = 0.007) and with haplotypes of SNP2-SNP5 (P = 7.5 x 10(-5)) and SNP3-SNP5 (P = 9.0 x 10(-4)) in the SLC1A6 region. The haplotype of SNP2-SNP5 of SLC1A6 even showed marginally significant association with the disease in the full-size sample (400 cases and 420 controls, P = 0.031). We concluded that at least one susceptibility locus for schizophrenia may be located within or nearby SLC1A6, whereas SLC1A1 and SLC1A3 are unlikely to be major susceptibility genes for schizophrenia in the Japanese population.
Interaction of Chemokine Receptor CCR5 with its Ligands: Multiple Domains for HIV-1 gp120 Binding and a Single Domain for Chemokine Binding (1997)

CCR5 is a chemokine receptor expressed by T cells and macrophages, which also functions as the principal coreceptor for macrophage (M)-tropic strains of HIV-1. To understand the molecular basis of the binding of chemokines and HIV-1 to CCR5, we developed a number of mAbs that inhibit the various interactions of CCR5, and mapped the binding sites of these mAbs using a panel of CCR5/CCR2b chimeras. One mAb termed 2D7 completely blocked the binding and chemotaxis of the three natural chemokine ligands of CCR5, RANTES (regulated on activation normal T cell expressed and secreted), macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta, to CCR5 transfectants. This mAb was a genuine antagonist of CCR5, since it failed to stimulate an increase in intracellular calcium concentration in the CCR5 transfectants, but blocked calcium responses elicited by RANTES, MIP-1alpha, or MIP-1beta. This mAb inhibited most of the RANTES and MIP-1alpha chemotactic responses of activated T cells, but not of monocytes, suggesting differential usage of chemokine receptors by these two cell types. The 2D7 binding site mapped to the second extracellular loop of CCR5, whereas a group of mAbs that failed to block chemokine binding all mapped to the NH2-terminal region of CCR5. Efficient inhibition of an M-tropic HIV-1-derived envelope glycoprotein gp120 binding to CCR5 could be achieved with mAbs recognizing either the second extracellular loop or the NH2-terminal region, although the former showed superior inhibition. Additionally, 2D7 efficiently blocked the infectivity of several M-tropic and dual-tropic HIV-1 strains in vitro. These results suggest a complicated pattern of HIV-1 gp120 binding to different regions of CCR5, but a relatively simple pattern for chemokine binding. We conclude that the second extracellular loop of CCR5 is an ideal target site for the development of inhibitors of either chemokine or HIV-1 binding to CCR5.
Local automatic load control for electric vehicle smart charging systems extensible via OCPP using compact submeters (2017)

There are many challenges in implementing grid aware electric vehicle charging systems with local load control. New opportunities for innovative load control were created as a result of changes to the National Electric Code (NEC) for automatic load control definitions for EV charging infrastructure. Stakeholders in optimised dispatch of EV charging assets include the end users (EV drivers), site owner/operators, facility managers and utilities. NEC definition changes allow for `over subscription' of more EV charging stations than can be continuously supported if the total load at any time is within the supply system safey limit. Local load control can be implemented via compact submeter(s) with locally hosted control algorithms with direct communication to the managed EVSEs. Larger groups of EVSEs can be managed as a constrained system via network connections, or meshes of smaller nodes, with cloud based control algorithms coordinating local control nodes. This paper is constrained to only AC charging, from grid to vehicle, in a modestly sized system, extensible to larger meshes of EV charging stations.
Three-phase shifting method for full range spectral optical coherence tomography (2006)

A three-phase shifting method is introduced to spectral OCT to eliminate mirror image and autocorrelation noise inherent in spectral OCT signal, thus improves the measurable range of spectral OCT by a factor of 2. The feasibility of such method is demonstrated using a mirror like object. Comparison between two-phase and three-phase shifting methods is performed using a 1mm slab as the object. An intact porcine cornea tissue in vitro is also used to show the potential of this method for biological imaging.
Amplification of the gli gene in childhood sarcomas. (1989)

The gli gene, originally identified by its amplified copy number in cells from a human malignant glioma, has a predicted translation product that contains five tandem DNA-binding zinc finger motifs related to those of Krüppel, a developmentally important Drosophila segmentation gene. Because of the potential importance of overproduction of this protein in neoplastic development, we examined DNAs from 29 cases of childhood sarcoma for evidence of amplification of the gli gene. In one of the 13 rhabdomyosarcomas studied, genomic DNA restriction fragments containing the gli gene were amplified approximately 30-fold, and expression of the 4.0-kilobase gli mRNA transcript was identified. The tumor with gli gene amplification lacked the usual histological features of alveolar or embryonal rhabdomyosarcoma; however, ultrastructural analysis of tumor cells established in culture revealed attenuated sarcomeres, resembling those found in primitive rhabdomyoblasts. Cytogenetic analysis of this cell line disclosed double-minute chromatin bodies, with no apparent rearrangements in the region of the gli locus on the long arm of chromosome 12, bands q13 to q14.3. A 15-fold level of gli amplification and gli mRNA transcripts were also detected in an established cell line from a patient with a rare form of osteosarcoma characterized by multipotential histological features. A similar level of gli gene amplification was observed in cryopreserved primary tumor cells from this patient, confirming that gene amplification took place during tumor development and not during in vitro cell culture. Amplified gli sequences were cytogenetically localized by in situ hybridization to a homogeneously staining region contained on a derivative chromosome 7. Of eight osteosarcomas and seven Ewing's sarcomas with typical histopathological features, none had detectable rearrangements or amplification of gli sequences. Thus, gli gene amplification in childhood sarcomas appears restricted to tumors with primitive histopathological features, perhaps reflecting overproduction of a gene product able to influence gene expression during early mesenchymal cell development.