gebhart/patrepeval huggingface dataset:
The effect of silica‐containing calcium‐phosphate particles on human osteoblasts in vitro (2003)

There is an ongoing need for more effective and less costly bone substitutes. It has previously been proposed that silica-containing bioactive glass would be more effective as a bone repair material because of its physiochemical properties. Three newly synthesized silica-containing bioactive glass formulations, HA-31 (25%), HA-11 (50%), and HA-13 (75%), were tested as biocompatible substrates for the continued proliferation and phenotype expression of human bone cells in vitro. Two currently available bioactive glasses (BioGlass(R), Hydroxyapatite) served as comparisons. The biocompatibility of these bioglasses, as well as their osteoconductive properties, was assessed by employing primary cultures of human osteoblasts and human synoviocytes for 4 days. The results obtained demonstrated that the three new bioglasses enhanced the proliferative response of osteoblasts compared with osteoblasts cultured alone. Reverse Transcription Polymerase Chain Reaction (RT-PCR) analysis indicated that osteoblasts retained their phenotypic expression by continued expression of collagen type I and alkaline phosphatase. The newly synthesized preparations of silica-containing bioactive glass did not induce stimulation of proinflammatory markers iNOS and IL-1beta in synoviocytes. In conclusion, the newly synthesized silica-containing bioactive glasses are biocompatible substrate for bone-forming osteoblasts. However, the formulations tested did not show significant advantage over the currently available bioactive glasses in vitro.
Inhibition of the mitochondrial permeability transition by cyclosporin A during long time frame experiments: relationship between pore opening and the activity of mitochondrial phospholipases (1995)

Inhibition of the mitochondrial permeability transition pore by cyclosporin A or trifluoperazine is transient on the time scale of cell injury studies (hours). However, these agents act synergistically and produce long-lasting inhibition when used in combination. The cause of this synergism has been investigated from the perspective of the known action of trifluoperazine as an inhibitor of mitochondrial phospholipase A2. Free fatty acids, which are phospholipase reaction products, facilitate pore opening in a concentration-dependent manner (I50 approximately 2 nmol/mg of mitochondrial protein). Endogenous and exogenous fatty acids are similarly effective. Fatty acids of differing structure are also similarly effective, but long-chain alcohols and alkanes are ineffective. Free fatty acids accumulate in cyclosporin A-treated mitochondria when Ca2+ plus tert-butyl hydroperoxide or Ca2+ plus N-ethylmaleimide is present, but do not accumulate when Ca2+ plus inorganic phosphate is present. In the presence of cyclosporin A, bovine serum albumin markedly delays pore opening induced by tert-butyl hydroperoxide or N-ethylmaleimide, but has little effect on pore opening induced by inorganic phosphate, which is subject to long-lasting inhibition by cyclosporin A without trifluoperazine. Free fatty acid accumulation is thus a factor which limits pore inhibition by cyclosporin A. However, trifluoperazine has no effect on free fatty acid accumulation in intact, cyclosporin-inhibited mitochondria and thus does not act by inhibiting phospholipases. Comparing the actions of free fatty acids, trifluoperazine, long-chain acyl cations, and other effectors on the pore suggests that a more negative membrane surface potential favors pore opening and a more positive potential favors a closed pore. Expected surface potential effects of trifluoperazine can explain the synergism between this compound and cyclosporin A as pore inhibitors. Surface potential may influence the pore through the voltage-sensing element which responds to transmembrane potential. The present data also suggest that long-lived, solute-selective forms of the pore exist when it is opened in the presence of inhibitors. The implications of these findings for pore regulation and for the use of cyclosporin A to identify pore opening as a component of cell injury mechanisms are discussed.
Optimizing and Learning for Super-resolution (2006)

In multiple-image super-resolution, a high resolution image is estimated from a number of lower-resolution images. This involves computing the parameters of a generative imaging model (such as geometric and photometric registration, and blur) and obtaining a MAP estimate by minimizing a cost function including an appropriate prior. We consider the quite general geometric registration situation modelled by a plane projective transformation, and make two novel contributions: (i) in previous approaches the MAP estimate has been obtained by fir st computing and fixing the registration, and then computing the super-re solution image with this registration. We demonstrate that superior estim ates are obtained by optimizing over both the registration and image; (ii) the parameters of the edge preserving prior are learnt automatically from the data, rather than being set by trial and error. We show examples on a number of real sequences including multiple stills, digital video, and DVDs of movies.
Comparisons of repetitive- and single-insult ischaemia (1994)

Single- and repetitive-insult ischaemia have been used with the gerbil to model human stroke and the impact of anti-ischaemic agents. It is currently not well-established whether the duration of an ischaemic insult, or single vs repetitive insults may have different behavioural consequences. In this study, groups of gerbils were given either single- or repetitive-insult ischaemia of either 3, 6 or 9 min cumulative duration. As the cumulative duration of ischaemia was increased, the degree of brain damage correspondingly increased and performance in a water maze task was progressively more impaired. However, no behavioural or brain-damage differences were found between groups of animals which received comparable durations of single- or repetitive-insult ischaemia. Significant mortality was observed in the group receiving three 3 min ischaemic insults, suggesting that the repetitive ischaemia technique may be limited to brief periods of occlusion. We conclude that there are no grounds for distinguishing between the single- and repetitive-ischaemia paradigms when employing cumulative durations up to 9 min.
A Time–Kill Evaluation of Clarithromycin and Azithromycin against Two Extracellular Pathogens and the Development of Resistance (1999)

Clarithromycin and azithromycin elicited a concentration-independent bacteriostatic effect against H. influenzae and S. aureus at concentrations at least two times the MIC. In addition, concentrations maintained above the MIC prevented changes in the susceptibility of H. influenzae and S. aureus to both macrolides.
Changes in protein conformation and stability accompany complex formation between human C1 inhibitor and C1.lovin.s (1985)

The fluorescence spectrum of C1 inhibitor (C1-Inh) in aqueous buffer has a maximum at 324 nm which shifts to 358 nm in 6.0 M guanidinium chloride (GdmC1), indicating that fluorescent tryptophans are buried in the native protein. When titrated with GdmC1, the fluorescence intensity, polarization, and emission maximum of C1-Inh and C1-s exhibited clear transitions which were more prominent than those of the enzyme-inhibitor complex. Two of the variables (intensity and emission maximum) suggest biphasic unfolding of C1-Inh. Differential absorption measurements and sodium iodide quenching of intrinsic fluorescence were consistent with a net increase in the exposure of tryptophans and tyrosines upon complex formation. This reaction, i.e., complex formation, was also accompanied by an increase in the ability to enhance the fluorescence of the hydrophobic probe 8-anilino-1-naphthalenesulfonate. Fluorescence assays of heat denaturation showed transitions at 40 and 52 degrees C for C1-s and at 60 degrees C for C1-Inh whereas there was no detectable melting transition for the complex. Similarly, differential scanning calorimetric measurements revealed transitions at 42, 52, and 62 degrees C for C1-s and one transition at 60 degrees C for C1-Inh, with no major transitions detectable for the complex. The ratio of the calorimetric enthalpy to the apparent van't Hoff enthalpy for thermal unfolding of C1-Inh was 1.6. Taken together, these results suggest that C1-Inh and C1-s are each composed of at least two independently unfolding domains and that complex formation, which involves conformational change, yields a protein substantially more stable than either component alone.
Nicotinic Receptor Binding Site Probed with Unnatural Amino Acid Incorporation in Intact Cells (1995)

The nonsense codon suppression method for unnatural amino acid incorporation has been applied to intact cells and combined with electrophysiological analysis to probe structure-function relations in the nicotinic acetylcholine receptor. Functional receptors were expressed in Xenopus oocytes when tyrosine and phenylalanine derivatives were incorporated at positions 93, 190, and 198 in the binding site of the alpha subunit. Subtle changes in the structure of an individual side chain produced readily detectable changes in the function of this large channel protein. At each position, distinct features of side chain structure dominated the dose-response relation, probably by governing the agonist-receptor binding.
Inheritance and Linkage of theRps7Gene for Resistance to Phytophthora Rot of Soybean (1992)

An Rps allele in the Harosoy cultivar of soybean (Glycine max) for resistance to races 16, 18, and 19 of Phytophthora megasperma f. sp. glycinea was shown to be at a new locus, designated Rps7, which is linked 12.5±2.7 map units from Rps1 in Linkage Group 10
A Biophysical Model of CRISPR/Cas9 Activity for Rational Design of Genome Editing and Gene Regulation (2016)

The ability to precisely modify genomes and regulate specific genes will greatly accelerate several medical and engineering applications. The CRISPR/Cas9 (Type II) system binds and cuts DNA using guide RNAs, though the variables that control its on-target and off-target activity remain poorly characterized. Here, we develop and parameterize a system-wide biophysical model of Cas9-based genome editing and gene regulation to predict how changing guide RNA sequences, DNA superhelical densities, Cas9 and crRNA expression levels, organisms and growth conditions, and experimental conditions collectively control the dynamics of dCas9-based binding and Cas9-based cleavage at all DNA sites with both canonical and non-canonical PAMs. We combine statistical thermodynamics and kinetics to model Cas9:crRNA complex formation, diffusion, site selection, reversible R-loop formation, and cleavage, using large amounts of structural, biochemical, expression, and next-generation sequencing data to determine kinetic parameters and develop free energy models. Our results identify DNA supercoiling as a novel mechanism controlling Cas9 binding. Using the model, we predict Cas9 off-target binding frequencies across the lambdaphage and human genomes, and explain why Cas9's off-target activity can be so high. With this improved understanding, we propose several rules for designing experiments for minimizing off-target activity. We also discuss the implications for engineering dCas9-based genetic circuits.
Electrical stimulation enhances peripheral nerve regeneration after crush injury in rats (2013)

Injured peripheral nerves have the ability to regenerate; however, there is conflicting evidence with regard to whether electrical stimulation (ES) accelerates or hinders neural regeneration. To study the effect of ES on peripheral nerve regeneration following nerve crush injury, 54 Wistar rats were randomly divided into three groups (n=18/group); the control, crush and crush+ES group. Four weeks after surgery, the sciatic functional index (SFI), compound muscle action potential (CMAP) conduction velocity and amplitude in the regenerated nerve, nerve histomorphometry, and levels of myelin protein zero (P0) mRNA and protein at the crush site were assessed. The rats exposed to crush+ES had a significantly increased CMAP conduction velocity, enhanced myelin sheath thickness and increased P0 mRNA and protein levels compared with the rats exposed to crush alone. However, the CMAP amplitude and axonal diameter were similar in the crush and crush+ES rats. Findings of this study demonstrated that the application of ES (3 V, 0.1 ms, 20 Hz, 1 h) immediately after nerve injury accelerates remyelination and may provide a therapeutic clinical strategy.
Stable Production of a Human Growth Hormone Antagonist from CHO Cells Adapted to Serum-Free Suspension Culture (1999)

Human growth hormone (hGH) is a polypeptide with 191 amino acids and a molecular mass of 22 kDa. An hGH analogue was created with a single amino acid substitution (glycine[G] 120 to arginine[R]) in the third alpha-helix of the hGH molecule. This hGH analogue, named hGHG120R, was found to be an hGH antagonist. It is a parenteral drug candidate for treating conditions in which hGH levels are abnormally high, as found in type I diabetics. Previously, a genetically engineered anchorage-dependent mouse L cell line was created that produced and secreted hGHG120R in culture media (Dulbecco's modified Eagle's medium, DMEM) supplemented with 5% NuSerum IV. A multistep downstream process was developed to purify hGHG120R. The process consisted of cell clarification, salt precipitation, membrane ultrafiltration, size exclusion chromatography, reversed phase high-performance liquid chromatography, phase separation, and lyophilization. Here, we present the development of a superior eukaryotic system using a proper combination of genetic elements, cell line, and media formulation. This system is suitable for the large-scale production of the recombinant protein and is superior to the previously developed system in that it increases the specific production rate and at the same time eases the burden of the purification process, in both time and efficiency. Dihydrofolate reductase mutant (DHFR-) Chinese hamster ovary (CHO) cells were used that were stably transfected with an expression vector in which the hGHG120R gene is driven by the relatively strong human cytomegalovirus-early gene regulatory region. The hGHG120R tested to be biologically active. These cells were then adapted to grow in suspension in CHO-S-SFM (serum-free media). High cell densities, typically 2.0 x 10(6) cells/mL were obtained from spinner flask cultures. Partial purification of hGHG120R from CHO cell cultured media revealed that the level of impurities in SFM was significantly lower than the serum-supplemented DMEM. This suggests that the salt precipitation and the SEC step need not be employed in the purification of hGHG120R from SFM. This would result in a reduction of the operating time by 50 h and boost the recovery yield of hGHG120R to 75%.
III-V/SOI Vertical Cavity Laser with In-plane Output into a Si Waveguide (2015)

We experimentally demonstrate an optically-pumped III-V-on-SOI hybrid vertical-cavity laser that outputs light into an in-plane Si waveguide, using CMOS-compatible processes. The laser operates ∼1.49 µm with a side-mode suppression ratio of ~27 dB and has a similar threshold as long-wavelength VCSELs.
Cost-efficient high-throughput HLA typing by MiSeq amplicon sequencing (2014)

The workflow presented proved to be a cost-efficient alternative to Sanger sequencing for high-throughput HLA typing. Despite the focus on cost efficiency, resolution exceeds the current standards of Sanger typing for donor registration.
Machines Tuning Machines: Configuring Distributed Stream Processors with Bayesian Optimization (2015)

Modern distributed computing frameworks such as Apache Hadoop, Spark, or Storm distribute the workload of applications across a large number of machines. Whilst they abstract the details of distribution they do require the programmer to set a number of configuration parameters before deployment. These parameter settings (usually) have a substantial impact on execution efficiency. Finding the right values for these parameters is considered a difficult task and requires domain, application, and framework expertise. In this paper, we propose a machine learning approach to the problem of configuring a distributed computing framework. Specifically, we propose using Bayesian Optimization to find good parameter settings. In an extensive empirical evaluation, we show that Bayesian Optimization can effectively find good parameter settings for four different stream processing topologies implemented in Apache Storm resulting in significant gains over a parallel linear approach.
Emerging Influence of the Intestinal Microbiota during Allogeneic Hematopoietic Cell Transplantation: Control the Gut and the Body Will Follow (2015)

The intestinal microbiota has many critical roles in maintaining gastrointestinal epithelial and gastrointestinal systemic immune homeostasis. This review provides insight into how allogeneic hematopoietic cell transplantation (HCT) and its associated complications and supportive care therapies affect the microbiota. Additionally, the review discusses how preservation and restoration of the microbiota might be advantageous in decreasing HCT-related morbidity and mortality.
Single-chain urokinase-type plasminogen activator bound to its receptor is relatively resistant to plasminogen activator inhibitor type 1 (1996)

Urokinase-type plasminogen activator (uPA) is synthesized as single-chain protein (scuPA) with little intrinsic activity. scuPA is activated when it is converted to two-chain urokinase (tcuPA) by plasmin or when it binds as a single-chain molecule to its cellular receptor (uPAR). Previous data indicate that complexes between scuPA and its receptor have somewhat higher affinity for plasminogen than does tcuPA. The current study indicates that plasminogen activator activity of scuPA bound to recombinant, soluble uPAR (suPAR) is also fivefold less sensitive to inhibition by plasminogen activator type 1 (PAI-1) than is soluble or receptor-bound tcuPA. Binding of PaI-1 to suPAR/scuPA complexes is totally reversible and can be overcome by increasing the concentration of plasminogen, suggesting a competitive mechanism of inhibition (Ki = 18 nmol/L). Binding of scuPA to suPAR also retards its cleavage by plasmin. These results indicates that binding of single-chain urokinase to its receptor promotes its activity, retards its inhibition, and protects it from conversion to a two-chain form of the enzyme, a step that may precede its inactivation and clearance from cell surfaces. These results are consistent with a physiologic role for receptor-bound single-chain urokinase as a cellular plasminogen activator.
Treatment Strategies for Pulmonary Arterial Hypertension (2010)

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Development of high-affinity 5-HT3 receptor antagonists. 1. Initial structure-activity relationship of novel benzamides (1992)

This report describes the development of novel benzamides which are orally active, highly potent, specific antagonists of 5-HT3 receptors. Described in this first report are the structure-activity relationships that led to novel structures with improved potency and selectivity. From this series of compounds, (S)-28 was identified and selected for further evaluation as a 5-HT3 receptor antagonist. Compared with 5-HT3 antagonists such as GR 38032F, BRL 43694, and metoclopramide, (S)-28 was most active in (a) inhibiting binding to 5-HT3 receptor binding sites in rat entorhinal cortex with an Ki value of 0.19 nM and (b) blocking cisplatin-induced emesis in the ferret with an ED50 value determined to be 9 micrograms/kg po.
A soluble deletion mutant of the human complement receptor type 1, which lacks the C4b binding site, is a selective inhibitor of the alternative complement pathway (1996)

The human complement receptor type 1 (CR1, CD35), is a single-chain glycoprotein consisting of 30 repeating homologous protein domains known as short consensus repeats (SCR) followed by transmembrane and cytoplasmic domains. The SCR themselves, considered in groups of seven, form long homologous repeats (LHR) which have been designated LHR-A, -B, -C, and -D for the most common human allotype of CR1. A soluble deletion mutant of CR1 which lacks the first seven N-terminal SCR (LHR-A) as well as the transmembrane and cytoplasmic domains was produced and characterized. The resulting protein, designated sCR1[desLHR-A], lacks the C4b binding site found in LHR-A, but retains the two C3b binding sites found in LHR-B and -C, respectively. The functional activities of sCR1[desLHR-A] were quantitatively compared in vitro to those of soluble complement receptor type 1 (sCR1) which has been shown to retain all known functions of the native cell surface receptor. sCR1[desLHR-A] and sCR1 competed equally for the binding of dimeric C3b to erythrocyte CR1. sCR1[desLHR-A] and sCR1 were similar in their capacity to serve as a cofactor in the factor I-mediated degradation of the C3b and C4b alpha chains. sCR1[desLHR-A] and sCR1 were comparable in their capacity to inhibit erythrocyte lysis and anaphylatoxin production mediated by the alternative complement pathway. sCR1[desLHR-A], however, was significantly less effective an inhibitor of erythrocyte lysis and anaphylatoxin production than sCR1 under conditions which allow classical pathway activation. These results demonstrate sCR1[desLHR-A] to be a selective inhibitor of the alternative complement pathway in vitro.
Activation of Sphingosine Kinase by Tumor Necrosis Factor-α Inhibits Apoptosis in Human Endothelial Cells (1999)

Human umbilical vein endothelial cells (HUVEC), like most normal cells, are resistant to tumor necrosis factor-alpha (TNF)-induced apoptosis in spite of TNF activating sphingomyelinase and generating ceramide, a known inducer of apoptosis. Here we report that TNF activates another key enzyme, sphingosine kinase (SphK), in the sphingomyelin metabolic pathway resulting in production of sphingosine-1-phosphate (S1P) and that S1P is a potent antagonist of TNF-mediated apoptosis. The TNF-induced SphK activation is independent of sphingomyelinase and ceramidase activities, suggesting that TNF affects this enzyme directly other than through a mass effect on sphingomyelin degradation. In contrast to normal HUVEC, in a spontaneously transformed endothelial cell line (C11) TNF stimulation failed to activate SphK and induced apoptosis as characterized by morphological and biochemical criteria. Addition of exogenous S1P or increasing endogenous S1P by phorbol ester markedly protected C11 cell line from TNF-induced apoptosis. Conversely, N, N-dimethylsphingosine, an inhibitor of SphK, profoundly sensitized normal HUVEC to killing by TNF. Thus, we demonstrate that the activation of SphK by TNF is an important signaling for protection from the apoptotic effect of TNF in endothelial cells.
Extracting surfaces from fuzzy 3D-ultrasound data (1995)

Rendering 3D models from 3D-ultrasonic data is a complicated task due to the noisy, fuzzy nature of ultrasound imaging containing a lot of artifacts, speckle etc.In the method presented in this paper we first apply several filtering techniques (low-pass, mathematical morphology, multi-resolution analysis) to separate the areas of low coherency containing mostly noise and speckle from those of useful information.Our novel BLTP filtering can be applied at interactive times on-the-fly under user control & feed-back.Goal of this processing is to create a 'region-of-interest' (ROI) mask, whereas the data itself remains unaltered.Secondly, we examine several alternatives to the original Levoy contouring method.Finally we introduce an improved surface-extraction volume rendering procedure, applied on the original data within the ROI areas for visualizing high quality images within a few seconds on a normal workstation, or even on a PC, thus making the complete system suitable for routine clinical applications.