gebhart/patrepeval huggingface dataset:
Delay time sensitivity analysis of multi-generation BiCMOS digital circuits (1997)

The speed sensitivity of BiCMOS circuits to changes in the key MOS/BJT device parameters is analysed. The study takes into account the changes in the forward transit time, the knee current, the collector resistance, the base resistance, and the current gain of the bipolar transistor and the channel length and width, threshold voltage, and oxide thickness of the MOS transistor. The relationships between the key process parameters and the overall speed sensitivity are reported. The analysis also covers the effects of the output load capacitance, scaling the technology, and the quality of the bipolar device on the delay sensitivity. Sensitivity coefficients are defined and generated for the conventional BiCMOS circuit as well as two recently reported circuits designed for low-voltage operation. A method to calculate the worst case speed degradation for a given set of device and process parameters&apos; tolerances is described. HSPICE is used to generate the numerical results for the three technologies (5 V, 0.8 µm), (3.3 V, 0.5 µm), and (2.2 V, 0.2 µm).
Bypass graft disease: analysis of proliferative activity in human aorto-coronary bypass grafts. (2002)

1. Proliferation occured at low level. While proliferation may play an important role in early lesions our data imply low proliferation activity in advanced graft lesions. Other mechanism like production and deposition of extracellular matrix (ECM) in the neointima are responsible for the lumen reduction of bypass grafts. 2. The high portion of unidentified cells may represent SMC or other cell types at different stages of differentiation; this requires further investigation. 3. The identification of proliferating macrophages and T-lymphocytes implicate an inflammatory component in the development of human bypass graft lesions.
Degradation of Agar by a Gram-negative Bacterium (1975)

An agar-degrading bacterium, having a guanine-cytosine content of 50-5 mol% has been isolated from sewage. This Gram-negative rod grew well in a simple salts medium containing various carbohydrates. Growing bacteria dissolved gels and suspensions of agar and agarose rapidly, but did not attack cross-linked agars. Agarase was cell-bound in exponentially growing cultures but was released into the medium at stationary phase. Both cell extracts and culture filtrates released reducing sugars from agar solutions and prevented them from gelling. Gels were not dissolved by enzyme solutions, but the turbidity and iodine-binding properties of the agar were decreased.
Who killed my battery? (2012)

Despite the growing popularity of mobile web browsing, the energy consumed by a phone browser while surfing the web is poorly understood. We present an infrastructure for measuring the precise energy used by a mobile browser to render web pages. We then measure the energy needed to render financial, e-commerce, email, blogging, news and social networking sites. Our tools are sufficiently precise to measure the energy needed to render individual web elements, such as cascade style sheets (CSS), Javascript, images, and plug-in objects. Our results show that for popular sites, downloading and parsing cascade style sheets and Javascript consumes a significant fraction of the total energy needed to render the page. Using the data we collected we make concrete recommendations on how to design web pages so as to minimize the energy needed to render the page. As an example, by modifying scripts on the Wikipedia mobile site we reduced by 30% the energy needed to download and render Wikipedia pages with no change to the user experience. We conclude by estimating the point at which offloading browser computations to a remote proxy can save energy on the phone.
The mechanism of action of retigabine (ezogabine), a first‐in‐class K+channel opener for the treatment of epilepsy (2012)

The pharmacologic profile of retigabine [RTG (international nonproprietary name); ezogabine, EZG (U.S. adopted name)], is different from all currently approved antiepileptic drugs (AEDs). Its primary mechanism of action (MoA) as a positive allosteric modulator of KCNQ2-5 (K(v) 7.2-7.5) ion channels defines RTG/EZG as the first neuronal potassium (K(+)) channel opener for the treatment of epilepsy. KCNQ2-5 channels are predominantly expressed in neurons and are important determinants of cellular excitability, as indicated by the occurrence of human genetic mutations in KCNQ channels that underlie inheritable disorders including, in the case of KCNQ2/3, the syndrome of benign familial neonatal convulsions. In vitro pharmacologic studies demonstrate that the most potent action of RTG/EZG is at KCNQ2-5 channels, particularly heteromeric KCNQ2/3. Furthermore, mutagenesis and modeling studies have pinpointed the RTG/EZG binding site to a hydrophobic pocket near the channel gate, indicating how RTG/EZG can stabilize the open form of KCNQ2-5 channels; the absence of this site in KCNQ1 also provides a clear explanation for the inbuilt selectivity RTG/EZG has for potassium channels other than the KCNQ cardiac channel. KCNQ channels are active at the normal cell resting membrane potential (RMP) and contribute a continual hyperpolarizing influence that stabilizes cellular excitability. The MoA of RTG/EZG increases the number of KCNQ channels that are open at rest and also primes the cell to retort with a larger, more rapid, and more prolonged response to membrane depolarization or increased neuronal excitability. In this way, RTG/EZG amplifies this natural inhibitory force in the brain, acting like a brake to prevent the high levels of neuronal action potential burst firing (epileptiform activity) that may accompany sustained depolarizations associated with the initiation and propagation of seizures. This action to restore physiologic levels of neuronal activity is thought to underlie the efficacy of RTG/EZG as an anticonvulsant in a broad spectrum of preclinical seizure models and in placebo-controlled trials in patients with partial epilepsy. In this article, we consider the pharmacologic characteristics of RTG/EZG at the receptor, cellular, and network levels as a means of understanding the novel and efficacious MoA of this new AED as defined in both preclinical and clinical research.
Growth and activities of sulphate-reducing bacteria in gut contents of healthy subjects and patients with ulcerative colitis (1991)

During fermentation in the human large intestine, terminal oxidative processes may involve the activities of dissimilatory sulphate-reducing bacteria (SRB). Approximately 50% of healthy individuals harbour significant populations of SRB in faeces. In mixed culture, growth of SRB in vitro was modulated by sulphate availability, with sulphated polysaccharides such as mucin, chondroitin sulphate and carrageenan causing increased growth rates and sulphide production when compared with starch, pectin and arabino-galactan. Rates of H2S production were higher among SRB isolated from patients with ulcerative colitis in contrast to those present in healthy volunteers. The majority (up to 92%) of SRB in faecal samples belonged to the genus Desulfovibrio. In vitro studies demonstrated that compared to isolates from healthy subjects. Desulfovibrio desulfuricans from colitic individuals were better able to adapt to high dilution rates, which may be associated with the disease. These findings indicate that the metabolic capabilities of SRB isolated from the human large intestine are not uniform and may respond to the type of substrate available in the gut as well as the rate of passage of digesta.
Quantitative Whole Body Biodistribution of Fluorescent-Labeled Agents by Non-Invasive Tomographic Imaging (2011)

When small molecules or proteins are injected into live animals, their physical and chemical properties will significantly affect pharmacokinetics, tissue penetration, and the ultimate routes of metabolism and clearance. Fluorescence molecular tomography (FMT) offers the ability to non-invasively image and quantify temporal changes in fluorescence throughout the major organ systems of living animals, in a manner analogous to traditional approaches with radiolabeled agents. This approach is best used with biotherapeutics (therapeutic antibodies, or other large proteins) or large-scaffold drug-delivery vectors, that are minimally affected by low-level fluorophore conjugation. Application to small molecule drugs should take into account the significant impact of fluorophore labeling on size and physicochemical properties, however, the presents studies show that this technique is readily applied to small molecule agents developed for far-red (FR) or near infrared (NIR) imaging. Quantification by non-invasive FMT correlated well with both fluorescence from tissue homogenates as well as with planar (2D) fluorescence reflectance imaging of excised intact organs (r² = 0.996 and 0.969, respectively). Dynamic FMT imaging (multiple times from 0 to 24 h) performed in live mice after the injection of four different FR/NIR-labeled agents, including immunoglobulin, 20-50 nm nanoparticles, a large vascular imaging agent, and a small molecule integrin antagonist, showed clear differences in the percentage of injected dose per gram of tissue (%ID/g) in liver, kidney, and bladder signal. Nanoparticles and IgG1 favored liver over kidney signal, the small molecule integrin-binding agent favored rapid kidney and bladder clearance, and the vascular agent, showed both liver and kidney clearance. Further assessment of the volume of distribution of these agents by fluorescent volume added information regarding their biodistribution and highlighted the relatively poor extravasation into tissue by IgG1. These studies demonstrate the ability of quantitative FMT imaging of FR/NIR agents to non-invasively visualize and quantify the biodistribution of different agents over time.
PEP-FOLD: an online resource for de novo peptide structure prediction (2009)

Rational peptide design and large-scale prediction of peptide structure from sequence remain a challenge for chemical biologists. We present PEP-FOLD, an online service, aimed at de novo modelling of 3D conformations for peptides between 9 and 25 amino acids in aqueous solution. Using a hidden Markov model-derived structural alphabet (SA) of 27 four-residue letters, PEP-FOLD first predicts the SA letter profiles from the amino acid sequence and then assembles the predicted fragments by a greedy procedure driven by a modified version of the OPEP coarse-grained force field. Starting from an amino acid sequence, PEP-FOLD performs series of 50 simulations and returns the most representative conformations identified in terms of energy and population. Using a benchmark of 25 peptides with 9-23 amino acids, and considering the reproducibility of the runs, we find that, on average, PEP-FOLD locates lowest energy conformations differing by 2.6 A Calpha root mean square deviation from the full NMR structures. PEP-FOLD can be accessed at http://bioserv.rpbs.univ-paris-diderot.fr/PEP-FOLD.
Point Set Topology Extraction for Branch and Crown-level Species Classification (2010)

Contextually-based distance and proximity functions derived from the axioms of point set topology are applied at the branch and crown-level for species differentiation between eastern hemlock (Tsuga canadensis) and eastern white pine (Pinus strobus). Point set topology is a branch of mathematics that offers methods to describe the connectivity and orientation of spatial objects and therefore allows object grouping based on spatial characteristic metrics unlike traditional fixed distance measures imposed from a global metric. Local neighborhood membership functions based on topological space are robust to variation in object sizes within a fixed image resolution and are therefore useful for describing spatial characteristics in highly variable objects such as tree morphology. We investigated the utility of topological space for describing branch-level needle orientations and crown-level patterns of high and low spectral intensity clusters. Branch-level measures of orientations within topologically-derived neighborhoods resulted in a classification accuracy of 96 percent for hemlock and pine; this represents a 23 percentage point (pp) improvement over traditional spectral feature classification. A crown-level species feature extraction and classification methodology that incorporated a local Getis (Gi *) statistic contour analysis produced species discrimination results that were improved by 8 pp for an overall accuracy of 85 percent over traditional color and shape-based feature classification.
Demonstration of two molecular forms of dipeptidyl peptidase IV in normal human serum. (1983)

The heterogeneity of dipeptidyl peptidase IV (EC 3.4.14.5) was investigated in normal human serum. Thin-layer analytical isoelectric focusing revealed the presence of multiple molecular forms of the enzyme, their isoelectric points being in the pH range of 3.30-4.25. The maximum of enzyme activity appeared around pH 3.50. After treatment with neuraminidase the pI shifted to 4.70-5.40 with two maxima at pH 5.00 and 5.15. The Triton X-100 solubilized as well as the papain-treated-Triton X-100 solubilized enzyme from the whole human adult jejunal biopsy were also found to be heterogeneous. They focused--both before and after neuraminidase treatment--at pH values different from those of the enzyme of normal human serum. There was almost no pI shift after neuraminidase treatment of the intestinal enzyme from adult enterobiopsy. Electrophoresis in continuous polyacrylamide gradient gels as well as gel chromatography on Bio-Gel A-1.5m revealed two molecular forms of dipeptidyl peptidase IV in normal human serum. The estimated relative molecular mass of the major enzyme form was 250 000 in both the separation techniques used. On the other hand, the apparent relative molecular mass of the minor enzyme form was 450 000 as assessed by gradient gel electrophoresis, and 550 000, when estimated by gel chromatography. The Km values for glycyl-L-proline-4-nitroanilide as substrate with the major and minor forms of the serum enzyme were 1.60 +/- 0.39 X 10(-4) mol/l and 1.60 +/- 0.13 X 10(-4) mol/l, respectively. Our results indicate that the dipeptidyl peptidase IV in normal human serum is a heterogeneous enzyme as far as its charge and molecular size are concerned.
A model for the prediction of thresholds, loudness, and partial loudness (1997)

A loudness model for steady sounds is described having the following stages: 1) a fixed filter representing transfer through the outer ear; 2) a fixed filter representing transfer through the middle ear; 3) calculation of an excitation pattern from the physical spectrum; 4) transformation of the excitation pattern to a specific loudness pattern; 5) determination of the area under the specific loudness pattern, which gives overall loudness for a given ear; and 6) summation of loudness across ears. The model differs from earlier models in the following areas: 1) the assumed transfer function for the outer and middle ear; 2) the way that excitation patterns are calculated; 3) the way that specific loudness is related to excitation for sounds in quiet and in noise; and (4) the way that binaural loudness is calculated from monaural loudness. The model is based on the assumption that sounds at absolute threshold have a small but finite loudness. This loudness is constant regardless of frequency and spectral content. It is also assumed that a sound at masked threshold has the same loudness as a sound at absolute threshold. The model accounts well for recent measures of equal-loudness contours, which differ from earlier measures because of improved control over bias effects. The model correctly predicts the relation between monaural and binaural threshold and loudness. It also correctly accounts for the threshold and loudness of complex sounds as a function of bandwidth.
A Novel Cation-Sensing Mechanism in Osteoblasts Is a Molecular Target for Strontium (2004)

We found that strontium stimulated SRE-luc activity in HEK-293 cells transfected with full-length CASR but not in cells expressing the alternatively spliced CASR construct lacking exon 5. In contrast, we found that MC3T3-E1 osteoblasts that lack CASR as well as osteoblasts derived from CASR null mice respond to millimolar concentrations of strontium. The response to strontium in osteoblasts was nonadditive to a panel of extracellular cations, including aluminum, gadolinium, and calcium, suggesting a common mechanism of action. In contrast, neither the CASR agonist magnesium nor the calcimimetic NPS-R568 activated SRE activity in osteoblasts, but the response to these agonists was imparted by transfection of CASR into these osteoblasts, consistent with the presence of distinct cation-sensing mechanisms. Co-expression of the dominant negative Galphaq(305-359) minigene also inhibited cation-stimulated SRE activity in osteoblasts lacking known CASR. These findings are consistent with strontium activation of a novel Galphaq-coupled extracellular cation-sensing receptor in osteoblasts with distinct cation specificity.
Discovery of a Novel, Potent, and Src Family-selective Tyrosine Kinase Inhibitor (1996)

Here, we have studied the activity of a novel protein-tyrosine kinase inhibitor that is selective for the Src family of tyrosine kinases. We have focused our study on the effects of this compound on T cell receptor-induced T cell activation, a process dependent on the activity of the Src kinases Lck and FynT. This compound is a nanomolar inhibitor of Lck and FynT, inhibits anti-CD3-induced protein-tyrosine kinase activity in T cells, demonstrates selectivity for Lck and FynT over ZAP-70, and preferentially inhibits T cell receptor-dependent anti-CD3-induced T cell proliferation over non-T cell receptor-dependent phorbol 12-myristate 13-acetate/interleukin-2 (IL-2)-induced T cell proliferation. Interestingly, this compound selectively inhibits the induction of the IL-2 gene, but not the granulocyte-macrophage colony-stimulating factor or IL-2 receptor genes. This compound offers a useful new tool for examining the role of the Lck and FynT tyrosine kinases versus ZAP-70 in T cell activation as well as the role of other Src family kinases in receptor function.
Structural Definition of a Neutralization-Sensitive Epitope on the MERS-CoV S1-NTD (2019)

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged into the human population in 2012 and has caused substantial morbidity and mortality. Potently neutralizing antibodies targeting the receptor-binding domain (RBD) on MERS-CoV spike (S) protein have been characterized, but much less is known about antibodies targeting non-RBD epitopes. Here, we report the structural and functional characterization of G2, a neutralizing antibody targeting the MERS-CoV S1 N-terminal domain (S1-NTD). Structures of G2 alone and in complex with the MERS-CoV S1-NTD define a site of vulnerability comprising two loops, each of which contain a residue mutated in G2-escape variants. Cell-surface binding studies and in vitro competition experiments demonstrate that G2 strongly disrupts the attachment of MERS-CoV S to its receptor, dipeptidyl peptidase-4 (DPP4), with the inhibition requiring the native trimeric S conformation. These results advance our understanding of antibody-mediated neutralization of coronaviruses and should facilitate the development of immunotherapeutics and vaccines against MERS-CoV.
Clostridium septicum alpha-toxin is proteolytically activated by furin (1997)

Clostridium septicum alpha-toxin is secreted as an inactive 46,450-Da protoxin. The protoxin is activated by proteolytic cleavage near the C terminus, which eventually causes the release of a 45-amino-acid fragment. Proteoytic activation and loss of the propeptide allow alpha-toxin to oligomerize and form pores on the plasma membrane, which results in colloidal-osmotic lysis. Activation may be accomplished in vitro by cleavage with trypsin at Arg367 (J. Ballard, Y. Sokolov, W. L. Yuan, B. L. Kagan, and R. K. Tweten, Mol. Microbiol. 10:627-634, 1993), which is located within the sequence KKRRGKR367S. A conspicuous feature of this site is a recognition site (RGKR) for the eukaryotic protease furin. Pro-alpha-toxin (AT[pro]) that was digested with trypsin or recombinant soluble furin yielded the 41,327-Da active form (AT[act]). A mutated alpha-toxin in which the furin consensus site was altered to KKRSGSRS at the cleavage site (AT[SGSR]) was cleaved and activated by trypsin but not by furin. In cytotoxicity assays, wild-type Chinese hamster ovary (CHO) and furin-deficient CHO (FD11) cells were killed by AT(pro) but not by AT(SGSR). Both cell types were killed by AT(SGSR) that was preactivated with trypsin. Propidium iodide uptake assays revealed that FD11 cells were approximately 22% less sensitive to AT(pro) than were CHO cells. AT(pro)-induced cell lysis of FD11 cells, assessed by propidium iodide uptake, was partially prevented by leupeptin (5 mM) and completely prevented by antipain (2.5 mM). The inhibition by antipain suggested the presence of cysteine or serine proteases that could also activate AT(pro). These findings demonstrate that furin is involved in the activation of C. septicum alpha-toxin on the cell surface but that alternate eukaryotic proteases can also activate the toxin. Regardless of the activating protease, the furin consensus site appears to be essential for the activation of alpha-toxin on the cell surface.
Ranibizumab versus Verteporfin for Neovascular Age-Related Macular Degeneration (2006)

Ranibizumab was superior to verteporfin as intravitreal treatment of predominantly classic neovascular age-related macular degeneration, with low rates of serious ocular adverse events. Treatment improved visual acuity on average at 1 year. (ClinicalTrials.gov number, NCT00061594 [ClinicalTrials.gov].).
Carbon nanopipettes for cell probes and intracellular injection (2007)

We developed integrated, carbon-based pipettes with nanoscale dimensions (CNP) that can probe cells with minimal intrusion, inject fluids into the cells, and concurrently carry out electrical measurements. Our manufacturing technique does not require cumbersome nanoassembly and is amenable to mass production. Using CNPs, we demonstrate the injection of reagents into cells with minimal intrusion and without inhibiting cell growth.
Surface analysis of machined versus sandblasted and acid-etched titanium implants. (2001)

Initially, implant surface analyses were performed on 10 machined implants and on 10 sandblasted and acid-etched implants. Subsequently, sandblasted and acid-etched implant cytotoxicity (using L929 mouse fibroblasts), morphologic differences between cells (osteoblast-like cells MG63) adhering to the machined implant surfaces, and cell anchorage to sandblasted and acid-etched implant surfaces were evaluated. Results indicated that acid etching with 1% hydrofluoric acid/30% nitric acid after sandblasting eliminated residual alumina particles. The average roughness (Ra) of sandblasted and acid-etched surfaces was about 2.15 microns. Cytotoxicity tests showed that sandblasted and acid-etched implants had non-cytotoxic cellular effects and appeared to be biocompatible. Scanning electron microscopic examination showed that the surface roughness produced by sandblasting and acid etching could affect cell adhesion mechanisms. Osteoblast-like cells adhering to the machined implants presented a very flat configuration, while the same cells adhering to the sandblasted and acid-etched surfaces showed an irregular morphology and many pseudopodi. These morphologic irregularities could improve initial cell anchorage, providing better osseointegration for sandblasted and acid-etched implants.