gebhart/patrepeval huggingface dataset:
Antibacterial activity of lactoferrin and a pepsin-derived lactoferrin peptide fragment (1993)

Although the antimicrobial activity of lactoferrin has been well described, its mechanism of action has been poorly characterized. Recent work has indicated that in addition to binding iron, human lactoferrin damages the outer membrane of gram-negative bacteria. In this study, we determined whether bovine lactoferrin and a pepsin-derived bovine lactoferrin peptide (lactoferricin) fragment have similar activities. We found that both 20 microM bovine lactoferrin and 20 microM lactoferricin release intrinsically labeled [3H]lipopolysaccharide ([3H]LPS) from three bacterial strains, Escherichia coli CL99 1-2, Salmonella typhimurium SL696, and Salmonella montevideo SL5222. Under most conditions, more LPS is released by the peptide fragment than by whole bovine lactoferrin. In the presence of either lactoferrin or lactoferricin there is increased killing of E. coli CL99 1-2 by lysozyme. Like human lactoferrin, bovine lactoferrin and lactoferricin have the ability to bind to free intrinsically labeled [3H]LPS molecules. In addition to these effects, whereas bovine lactoferrin was at most bacteriostatic, lactoferricin demonstrated consistent bactericidal activity against gram-negative bacteria. This bactericidal effect is modulated by the cations Ca2+, Mg2+, and Fe3+ but is independent of the osmolarity of the medium. Transmission electron microscopy of bacterial cells exposed to lactoferricin show the immediate development of electron-dense "membrane blisters." These experiments offer evidence that bovine lactoferrin and lactoferricin damage the outer membrane of gram-negative bacteria. Moreover, the peptide fragment lactoferricin has direct bactericidal activity. As lactoferrin is exposed to proteolytic factors in vivo which could cleave the lactoferricin fragment, the effects of this peptide are of both mechanistic and physiologic relevance.
Annealing of ZrAl[sub x]O[sub y] Ultrathin Films on Si in a Vacuum or in O[sub 2] (2001)

films deposited on Si were submitted to thermal annealings in a vacuum or an oxygen atmosphere. Elemental compositions as functions of depth were established using ion beam techniques such as Rutherford backscattering spectrometry and narrow nuclear resonance profiling. In addition, chemical composition profiles were obtained by angle-resolved X-ray photoelectron spectroscopy. The as-deposited film is amorphous, has an abrupt interface with the Si substrate, and its chemical composition is a double oxide with approximate stoichiometry Atomic transport and chemical reaction induced by thermal annealing were investigated by the above mentioned techniques and by low energy ion scattering spectroscopy. We have observed that Al, O, and Si migrate during annealing, whereas Zr is essentially immobile. Oxygen from the gas phase was heavily incorporated into the oxide films during annealing in mostly in exchange for previously existing oxygen. © 2001 The Electrochemical Society. All rights reserved.
Phospholipid-anchored and transmembrane versions of either decay-accelerating factor or membrane cofactor protein show equal efficiency in protection from complement-mediated cell damage. (1991)

Decay-accelerating factor (DAF) is a glycosyl-phosphatidylinositol (GPI)-anchored membrane protein that protects cells from complement-mediated damage by regulation of the C3 convertase. To investigate the role of the GPI anchor in the function of DAF, the cDNA encoding human DAF was expressed by transfection in Chinese hamster ovary (CHO) cells. Testing of these DAF transfectants in an antibody plus human complement-mediated cytotoxicity assay demonstrated that DAF protects these cells from cytotoxicity, and that the level of protection increases with expression of surface DAF. A cDNA construct encoding a transmembrane version of DAF (DAF-TM) protects CHO transfectants from cytotoxicity with equal efficiency to DAF. This DAF-TM construct used the TM and cytoplasmic domains of membrane cofactor protein (MCP); an alternate TM version of DAF constructed with the TM and cytoplasmic domains of HLA-B44 showed equivalent protection. The protection from cytotoxicity involved a decrease in the deposition of C3 on the cell, consistent with the effect of DAF on the C3 convertase. A second pair of anchor variants, MCP and a GPI-anchored construct, MCP-PI, were also equivalent in their complement protection. The equivalent function of GPI-anchored and TM versions of a protein was not expected based on the hypothesized increased lateral mobility of GPI-anchored proteins, which should confer a functional advantage in contacting ligand, in this case, C3b or C4b, on the cell surface. These data suggest either that GPI-anchored and TM versions of a protein have equal lateral mobility in the membrane, or else that increased lateral mobility is not advantageous to DAF or MCP in carrying out their complement inhibitory roles. Furthermore, DAF and MCP demonstrated approximately equal protection of cells from complement-mediated cytotoxicity, suggesting that DAF and MCP provide overlapping levels of protection to cells against damage mediated by the complement system.
Physical and Functional Interaction between the Y-Box Binding Protein YB-1 and Human Polyomavirus JC Virus Large T Antigen (1999)

Y-box binding protein YB-1 is a member of a family of DNA and RNA binding proteins which have been shown to affect gene expression at both the transcriptional and translational levels. We have previously shown that YB-1 modulates transcription from the promoters of the ubiquitous human polyomavirus JC virus (JCV). Here we investigate the physical and functional interplay between YB-1 and the viral regulatory protein large T antigen (T-antigen), using JCV as a model system. Results of mobility band shift assays demonstrated that the efficiency of binding of YB-1 to a 23-bp single-stranded viral target sequence was significantly increased when T-antigen was included in the binding reaction mixture. Affinity chromatography and coimmunoprecipitation assays demonstrated that YB-1 and T-antigen physically interact with each other. Additionally, results of transcription studies demonstrated that these two proteins interact functionally on the JCV early and late gene promoters. Whereas ectopic expression of YB-1 and T-antigen results in synergistic transactivation of the viral late promoter, YB-1 alleviates T-antigen-mediated transcriptional suppression of the viral early promoter activity. Furthermore, we have localized, through the use of a series of deletion mutants, the sequences of these proteins which are important for their interaction. The T-antigen-interacting region of YB-1 is located in the cold shock domain of YB-1 and its immediate flanking sequences, and the YB-1-interacting domain of T-antigen maps to the carboxy-terminal half of T-antigen. Results of transient transfection assays with various YB-1 mutants and T-antigen expression constructs confirm the specificity of the functional interaction between YB-1 and T-antigen. Taken together, these data demonstrate that the cellular factor YB-1 and the viral regulatory protein T-antigen interact both physically and functionally and that this interaction modulates transcription from the JCV promoters.
PRC1 controls spindle polarization and recruitment of cytokinetic factors during monopolar cytokinesis (2012)

The central spindle is a postanaphase array of microtubules that plays an essential role in organizing the signaling machinery for cytokinesis. The model by which the central spindle organizes the cytokinetic apparatus is premised on an antiparallel arrangement of microtubules, yet cells lacking spindle bipolarity are capable of generating a distal domain of ectopic furrowing when forced into mitotic exit. Because protein regulator of cytokinesis (PRC1) and kinesin family member 4A (KIF4A) are believed to play a principal role in organizing the antiparallel midzone array, we sought to clarify their roles in monopolar cytokinesis. Although both factors localized to the distal ends of microtubules during monopolar cytokinesis, depletion of PRC1 and KIF4A displayed different phenotypes. Cells depleted of PRC1 failed to form a polarized microtubule array or ectopic furrows following mitotic exit, and recruitment of Aurora B kinase, male germ cell Rac GTPase-activating protein, and RhoA to the cortex was impaired. In contrast, KIF4A depletion impaired neither polarization nor ectopic furrowing, but it did result in elongated spindles with a diffuse distribution of cytokinetic factors. Thus, even in the absence of spindle bipolarity, PRC1 appears to be essential for polarizing parallel microtubules and concentrating the factors responsible for contractile ring assembly, whereas KIF4A is required for limiting the length of anaphase microtubules.
Synthetic Polymers Seeded with Chondrocytes Provide a Template for New Cartilage Formation (1991)

A new approach for tissue creation using synthetic biocompatible and biodegradable polymers as templates onto which cells are seeded is presented. This report concerns the generation of homogeneous plates of stable mature cartilage in vivo. The delivery of chondrocytes on synthetic polymers configured to provide a large surface area for cell attachment and thus to allow cell function and survival by diffusion of nutrients has resulted in the creation of macroscopic plates of up to 100 mg of new cartilage subcutaneously in 19 of 21 animals. The approximate dimensions and configuration of the original templates were maintained as new cartilage was formed and the polymers resorbed.
Structure and chance (1995)

Software errors abound in the world of computing. Sophisticated computer programs rank high on the list of the most complex systems ever created by humankind. The complexity of a program or a set of interacting programs makes it extremely difficult to perform offline verification of run-time behavior. Thus, the creation and maintenance of program code is often linked to a process of incremental refinement and ongoing detection and correction of errors. To be sure, the detection and repair of program errors is an inescapable part of the process of software development. However, run-time software errors may be discovered in fielded applications days, months, or even years after the software was last modified—especially in applications composed of a plethora of separate programs created and updated by different people at different times. In such complex applications, software errors are revealed through the run-time interaction of hundreds of distinct processes competing for limited memory and CPU resources. Software developers and support engineers responsible for correcting software problems face difficult challenges in tracking down the source of run-time errors in complex applications. The information made available to engineers about the nature of a failure often leaves open a wide range of possibilities that must be sifted through carefully in searching for an underlying error.
Nerve invasion distance is dependent on laminin γ2 in tumors of pancreatic cancer (2009)

The distance of nerve invasion is an important prognostic factor in pancreatic cancer. The extracellular matrix (ECM) of nerve, mainly composed of laminin, collagen IV and anchoring fibrils, might affect nerve invasion. However, this relationship has not been demonstrated. Our study aimed at discovering the promoting factor of nerve invasion within the tumoral ECM. An animal model was established to evaluate the distance of nerve invasion in murine sciatic nerves by intraneural injection of 6 human pancreatic cancer cell lines. mRNA expression of laminins and anchoring fibrils was compared to the distance of nerve invasion for each cancer cell line. A target molecule provided the strong association between mRNA expression and the distance of nerve invasion. To evaluate the role of a target molecule in nerve invasion, protein expression and function were examined using an animal model and surgical cases. Cancer cells with high laminin gamma2 mRNA and protein expression in their basement membranes were associated with long nerve invasion. Knockdown of laminin gamma2 in cancer cells significantly shortened nerve invasion in the animal model. In 75 patients with pancreatic cancer, a large distance of nerve invasion was associated with high expression levels of laminin gamma2 mRNA and basement membranous deposition of laminin gamma2 protein. Our results indicate that laminin gamma2 plays an important role in nerve invasion. The measurement of the nerve invasion distance in our mouse nerve invasion model is useful for evaluating the molecular mechanisms of nerve invasion.
Molecular Properties of ClpAP Protease of Escherichia coli:  ATP-Dependent Association of ClpA and ClpP (1998)

The ClpAP protease from Escherichia coli consists of the ATP-binding regulatory component, ClpA (subunit Mr 84 165), and the proteolytic component, ClpP (subunit Mr 21 563). Our hydrodynamic studies demonstrate that the predominant forms of these proteins in solution correspond to those observed by electron microscopy. ClpP and proClpP(SA), which in electron micrographs appear to have subunits arranged in rings of seven subunits, were found by ultracentrifugation to have s20,w values of 12.2 and 13.2 S and molecular weights of 300 000 and 324 000 +/- 3000, respectively, indicating that the native form of each consists of two such rings. The two intact rings of ClpP were separated in the presence of >/= 0.1 M sulfate at low temperatures, suggesting that ring-ring contacts are polar in nature and more easily disrupted than subunit contacts within individual rings. Sedimentation equilibrium analysis indicated that ClpA purified without nucleotide exists as an equilibrium mixture of monomers and dimers with Ka = (1.0 +/- 0.2) x 10(5) M-1 and that, upon addition of MgATP or adenosine 5'-O-(3-thiotriphosphate), ClpA subunits associated to a form with Mr 505 000 +/- 5000, consistent with the hexameric structure seen by electron microscopy. Sedimentation velocity and gel-filtration analysis showed that the nucleotide-promoted hexamer of ClpA (s20,w = 17.2 S) binds tightly to ClpP producing species with s20,w values of 21 and 27 S (f/f0 = 1.5 and 1.8, respectively), consistent with electron micrographs of ClpAP that show a single tetradecamer of ClpP associated with either one or two ClpA hexamers [Kessel et al. (1995) J. Mol. Biol. 250, 587-594]. Under assay conditions in the presence of ATP and Mg2+, the apparent dissociation constant of hexameric ClpA and tetradecameric ClpP was approximately 4 +/- 2 nM. By the method of continuous variation, the optimal ratio of ClpA to ClpP in the active complex was 2:1. The specific activities of limiting ClpA and ClpP determined in the presence of an excess of the other component indicated that the second molecule of ClpA provides very little additional activation of ClpP.
Phytoalexin Detoxification: Importance for Pathogenicity and Practical Implications (1989)

Beneficial microbes in the microbiome of plant roots improve plant health. Induced systemic resistance (ISR) emerged as an important mechanism by which selected plant growth–promoting bacteria and fungi in the rhizosphere prime the whole plant body for ...Read More
Online motion correction for diffusion‐weighted imaging using navigator echoes: Application to RARE imaging without sensitivity loss (2001)

This article describes the first application of true online motion correction to diffusion-weighted RARE imaging. Two orthogonal navigator echoes were acquired and zeroth and first-order phase corrections applied in less than 8 ms between a diffusion-weighted magnetization preparation and data acquisition using the RARE sequence. The zeroth-order phase correction was realized by pulsing the system's B(0)-coil: the first-order error corrected with appropriate magnetic field gradient pulses. Online correction ensured that no irreversible signal loss could occur in the imaging experiment. Diffusion-weighted images of the brain were obtained from healthy volunteers. EGG-triggered acquisition was applied at 400 ms after the R-wave. Data were acquired on a matrix of 256 x 256 with a RARE factor of 16 and a b-value of 804 smm(-2). The images obtained with online motion correction showed a remarkably high image quality, while those acquired without motion correction were severely degraded by artifacts.
>1.3-Tb/s VCSEL-Based On-Board Parallel-Optical Transceiver Module for High-Density Optical Interconnects (2017)

This paper gives a detailed description of a >1.3-Tb/s VCSEL-based on-board parallel-optical transceiver module for high-density optical interconnects. The optical module integrates a 28-Gb/s × 24-channel transmitter and receiver into one package with a 1-in <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> footprint, thereby yielding a data rate density as high as 1.34 Tb/s/in <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . A unique module design is developed to utilize the whole top surface for thermal dissipation and the bottom surface for optical and electrical interfaces. The heat dissipation characteristics are studied in simulations and experiments. A test system of 24-channel optical loop-back link is built to evaluate the performance when operating all 24 channels by 28.05-Gb/s 2 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">31</sup> -1 PRBS bit streams simultaneously. With a total power consumption of 9.1 W, the optical module can be operated within the operating case temperature under a practical air cooling condition. When operating all 24 channels simultaneously, a total jitter margin at BER of 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-12</sup> is larger than 0.4 U.I. at a monitor channel. The measured jitter margin is consistent regardless of any channel operation.
Gamma Interferon Expression in CD8+T Cells Is a Marker for Circulating Cytotoxic T Lymphocytes That Recognize an HLA A2-Restricted Epitope of Human Cytomegalovirus Phosphoprotein pp65 (2001)

Antigen-specific CD8(+) T cells with cytotoxic activity are often critical in immune responses to infectious pathogens. To determine whether gamma interferon (IFN-gamma) expression is a surrogate marker for cytotoxic T lymphocytes (CTL), human cytomegalovirus-specific CTL responses were correlated with CD8(+) T-cell IFN-gamma expression determined by cytokine flow cytometry. A strong positive correlation was observed between specific lysis of peptide-pulsed targets in a (51)Cr release assay and frequencies of peptide-activated CD8(+) T cells expressing IFN-gamma at 6 h (r(2) = 0.72) or 7 days (r(2) = 0.91). Enumeration of responding cells expressing perforin, another marker associated with CTL, did not improve this correlation. These results demonstrate that IFN-gamma expression can be a functional surrogate for identification of CTL precursor cells.
Copy number variation at theFCGRlocus includesFCGR3A, FCGR2CandFCGR3Bbut notFCGR2AandFCGR2B (2009)

Human Fcgamma receptors (FcgammaRs) are glycoproteins that bind the Fc region of IgG. The genes encoding the low-affinity FcgammaRs are located on chromosome 1q23-24. Beside single nucleotide polymorphisms (SNPs), gene copy number variation (CNV) is now being recognized as an important indicator for inter-individual differences. Recent studies on identifying CNV in the human genome suggest large areas at chromosome 1q23-24 to be involved, and CNV in this region has been associated with manifestations of systemic autoimmune disease. To study both SNPs and CNV of the low-affinity FcgammaRs in one assay, we have developed a Multiplex Ligation-dependent Probe Amplification (MLPA) assay. A novel CNV for FCGR3A was observed. Similar to FCGR3B and FCGR2C, a gene-dosage effect of FCGR3A was found, that seemed to correlate nicely with the FcgammaRIIIa expression on NK cells. Next, we delineated the approximate boundaries of CNV at the FCGR locus. Variation in co-segregation of neighboring FCGR genes was limited to four variants, with patterns of Mendelian inheritance. No CNV of the FCGR2A and FCGR2B genes was observed in over 600 individuals. In conclusion, we report a novel CNV of the FCGR3A gene that correlates with FcgammaRIIIa expression and function on NK cells. Only FCGR3A, FCGR2C and FCGR3B show CNV, in contrast to FCGR2A and FCGR2B.
Multiple sources of the impedance cardiogram based on 3-D finite difference human thorax models (1995)

Two 3-D electrical models of the human thorax, each consisting of 216,000 control volumes, were constructed based upon MR images taken at end diastole and end systole. Using the finite difference method, the contributions of various sources to the impedance cardiogram were studied for the traditional band electrode configuration. The contributions were categorized into three areas: 1) the structural changes between end diastole and end systole, 2) the flow-induced blood resistivity changes in major arteries and veins, and 3) the lung resistivity variation due to the lung blood volume change. Based on the models, Zo and delta Z between end diastole and end systole were 24.4 omega and -0.132 omega, as compared with the measurements of 21.8 omega and -0.123 omega made on the same subject from whom the images were taken. Arterial and venous blood resistivity changes caused approximately 57% of the total impedance change. The lung resistivity change and the structural changes contributed 39% and 4%, respectively. The structural changes inside the thorax included the dimensional changes of blood vessels, the blood volume changes of the heart chambers, and heart movement. Although the net impedance change due to the structural changes was relatively small, the individual variation of various factors was large, with significant cancellation occurring. The results suggest that the thoracic impedance cardiographic signal is a mixed representation of many inseparable factors and may not be reliable for the stroke volume calculation. Also, the O-wave, which is clinically observed in various cardiac conditions, may be linked to the diastolic blood flow in the central veins.
Bivalirudin in percutaneous coronary intervention (2006)

Bivalirudin is a member of the direct thrombin inhibitor group of anticoagulants. It has been evaluated as an alternative to unfractionated and low-molecular-weight heparins in the settings of percutaneous coronary intervention (PCI) and acute coronary syndrome (ACS). Results of clinical trials to date suggest bivalirudin is a viable alternative to the use of a heparin combined with a glycoprotein (GP) IIb/IIIa inhibitor in these settings. Thrombin has a central role in coagulation and platelet activation in ACS and during PCI. Its direct inhibition is an attractive target for therapy in these settings. Bivalirudin is a 20 amino acid polypeptide hirudin analog. It displays bivalent and reversible binding to the thrombin molecule, inhibiting its action. Direct inhibition of thrombin with bivalirudin has theoretical pharmacokinetic and pharmacodynamic advantages over the indirect anticoagulants. A reduction in rates of bleeding without loss of anti-thrombotic efficacy has been a consistent finding across multiple clinical trials. There may be economic benefits to the use ofbivalirudin if it permits a lower rate of use of the GP IIb/IIIa inhibitors. This article reviews the pharmacology of bivalirudin and clinical trial evidence to date. There are now data from multiple clinical trials and meta-analyses in the setting of ACS and PCI. Early results from the acute catheterization and urgent intervention strategy (ACUITY) trial are discussed.