gebhart/patrepeval huggingface dataset:
Stabilizing biocatalysts (2013)

The area of biocatalysis itself is in rapid development, fueled by both an enhanced repertoire of protein engineering tools and an increasing list of solved problems. Biocatalysts, however, are delicate materials that hover close to the thermodynamic limit of stability. In many cases, they need to be stabilized to survive a range of challenges regarding temperature, pH value, salt type and concentration, co-solvents, as well as shear and surface forces. Biocatalysts may be delicate proteins, however, once stabilized, they are efficiently active enzymes. Kinetic stability must be achieved to a level satisfactory for large-scale process application. Kinetic stability evokes resistance to degradation and maintained or increased catalytic efficiency of the enzyme in which the desired reaction is accomplished at an increased rate. However, beyond these limitations, stable biocatalysts can be operated at higher temperatures or co-solvent concentrations, with ensuing reduction in microbial contamination, better solubility, as well as in many cases more favorable equilibrium, and can serve as more effective templates for combinatorial and data-driven protein engineering. To increase thermodynamic and kinetic stability, immobilization, protein engineering, and medium engineering of biocatalysts are available, the main focus of this work. In the case of protein engineering, there are three main approaches to enhancing the stability of protein biocatalysts: (i) rational design, based on knowledge of the 3D-structure and the catalytic mechanism, (ii) combinatorial design, requiring a protocol to generate diversity at the genetic level, a large, often high throughput, screening capacity to distinguish 'hits' from 'misses', and (iii) data-driven design, fueled by the increased availability of nucleotide and amino acid sequences of equivalent functionality.
Ball‐Milling‐Induced Amorphization of Zeolitic Imidazolate Frameworks (ZIFs) for the Irreversible Trapping of Iodine (2013)

The I2-sorption and -retention properties of several existing zeolitic imidazolate frameworks (ZIF-4, -8, -69) and a novel framework, ZIF-mnIm ([Zn(mnIm)2 ]; mnIm=4-methyl-5-nitroimidazolate), have been characterised using microanalysis, thermogravimetric analysis and X-ray diffraction. The topologically identical ZIF-8 ([Zn(mIm)2]; mIm=2-methylimidazolate) and ZIF-mnIm display similar sorption abilities, though strikingly different guest-retention behaviour upon heating. We discover that this guest retention is greatly enhanced upon facile amorphisation by ball milling, particularly in the case of ZIF-mnIm, for which I2 loss is retarded by as much as 200 °C. It is anticipated that this general approach should be applicable to the wide range of available metal-organic framework-type materials for the permanent storage of harmful guest species.
Urine is Necessary to Provoke Bladder Inflammation in Protamine Sulfate Induced Urothelial Injury (2008)

Bladder inflammation in this experimental model of urothelial injury was not due to protamine sulfate alone. The association of protamine sulfate and urine was necessary to trigger the inflammatory cascade. Thus, urine indeed has an important role in the development of bladder inflammation in an environment of higher urothelial permeability.
Frequent <i>hSNF5/INI1</i> Germline Mutations in Patients with Rhabdoid Tumor (2011)

Our results show a high proportion of germline mutations in patients with RT that can be found at any age and up to 60% in the youngest patients. Genetic counseling is recommended given the low but actual risk of familial recurrence.
104. Nitration of 4-chloro- and 4-hydroxy-quinaldine (1945)

B. E. Halcrow and W. O. Kermack, J. Chem. Soc., 1945, 415 DOI: 10.1039/JR9450000415
Iso-surface Extraction and Optimization Method Based on Marching Cubes (2009)

Iso-surface extraction is a standard visualization method for scalar data. A widely used iso-surface extraction algorithm is called Marching Cubes algorithm(MC). Based on the analysis of the MC algorithms used in the construction of value surface, it is proposed that the related point search algorithm and mid-point of linear interpolation improve the reconstruction rate and visualization. The selection of data points can be judged by the angle. Replacing the polygon vertex by the midpoint between two adjacent sample points, performing a smooth process in this vector field as well, would accelerate this reconstruction procedure and return a more smooth surface.
The countercurrent principle in invasion and metastasis of cancer cells. Recent insights on the roles of chemokines (2004)

Chemokine production by cancer cells constitutes a duality. Leukocyte recruitment under the pressure of chemokines may be beneficial for the host or for the tumor. Here, the emphasis will be on the detrimental effects of chemokines in tumor biology. A decade ago, the countercurrent principle of tumor-derived chemokine and peritumoral protease production was formulated to explain chemokine expression as a selective advantage for specific tumors and as a phenotype of invasive and metastasizing cancer cells. Chemoattracted leukocytes may provide trophic factors and produce invasion and metastasis-promoting proteinases. On the basis of the consensus sequence glutamic acid-leucine-arginine (ELR) preceding the canonical cysteine-any amino acid-cysteine (CXC), ELR-positive CXC chemokines, such as interleukin-8 and granulocyte chemotactic protein-2, are angiogenic and thus instruct the host to feed the tumor and bring the vessels into closer contact with the tumor cells. These mechanisms may enhance lymphogenic and hematogenic metastasis. Recent research and proofs of this countercurrent concept are here reviewed and compared. In addition, we discuss how alterations in chemokine ligand and receptor expression profiles may contribute to tumor growth, invasion, metastasis and immune evasion. These comparisons imply practical consequences for future cancer diagnosis and therapy. The implications include methods to diminish metastasis by inhibiting angiogenic CXC chemokine ligands and receptors, therapeutic combinations of chemokine overexpression with antigenic stimuli and co-treatment with angiostatic chemokines and tumor antigens.
Detection of basal cell carcinoma using color and histogram measures of semitranslucent areas (2009)

Texture and color analysis measures, especially smoothness, may afford automatic detection of BCC images with semitranslucency.
Dissecting the role of the CRMP2–neurofibromin complex on pain behaviors (2017)

Neurofibromatosis type 1 (NF1), a genetic disorder linked to inactivating mutations or a homozygous deletion of the Nf1 gene, is characterized by tumorigenesis, cognitive dysfunction, seizures, migraine, and pain. Omic studies on human NF1 tissues identified an increase in the expression of collapsin response mediator protein 2 (CRMP2), a cytosolic protein reported to regulate the trafficking and activity of presynaptic N-type voltage-gated calcium (Cav2.2) channels. Because neurofibromin, the protein product of the Nf1 gene, binds to and inhibits CRMP2, the neurofibromin-CRMP2 signaling cascade will likely affect Ca channel activity and regulate nociceptive neurotransmission and in vivo responses to noxious stimulation. Here, we investigated the function of neurofibromin-CRMP2 interaction on Cav2.2. Mapping of >275 peptides between neurofibromin and CRMP2 identified a 15-amino acid CRMP2-derived peptide that, when fused to the tat transduction domain of HIV-1, inhibited Ca influx in dorsal root ganglion neurons. This peptide mimics the negative regulation of CRMP2 activity by neurofibromin. Neurons treated with tat-CRMP2/neurofibromin regulating peptide 1 (t-CNRP1) exhibited a decreased Cav2.2 membrane localization, and uncoupling of neurofibromin-CRMP2 and CRMP2-Cav2.2 interactions. Proteomic analysis of a nanodisc-solubilized membrane protein library identified syntaxin 1A as a novel CRMP2-binding protein whose interaction with CRMP2 was strengthened in neurofibromin-depleted cells and reduced by t-CNRP1. Stimulus-evoked release of calcitonin gene-related peptide from lumbar spinal cord slices was inhibited by t-CNRP1. Intrathecal administration of t-CNRP1 was antinociceptive in experimental models of inflammatory, postsurgical, and neuropathic pain. Our results demonstrate the utility of t-CNRP1 to inhibit CRMP2 protein-protein interactions for the potential treatment of pain.
Fast retrieval of cursive handwriting (1996)

This paper presents an indexing method that can be used to search a large collection of cursive handwriting. The basic idea is to segment each cursive string into a set of strokes. Each of these strokes can be described with a set of features and, thus, can be stored as points in the feature space. The Karhuraen-Lor%e transform is then used to minimize the number of features used (data dimensionality) and thus the index size. Feature vectors are stored in an R-tree. Similarity search can be performed by executing a few range queries and then applying a simple voting algorithm to the output to select the strings that are most similar to the query. The proposed index can support similarity queries as well as substring mat thing. It is resilient to the kind of errors that result from the segmentation process, namely, stroke insertion/deletion and m-n substitution. The proposed index achieves substantial saving in search time over the sequential search. Moreover, it improves the matching rate up to 46~0 over the the sequential search.
Cardiovascular disease in type 2 diabetes mellitus: current management guidelines. (2003)

Cardiovascular disease is the most prevalent and detrimental complication of diabetes mellitus. The incidence of cardiovascular mortality in diabetic subjects without a clinical history of previous cardiac events is as high as the incidence in nondiabetic subjects with a history of myocardial infarction. This inordinate increase in the risk of coronary events in diabetic patients is attributed to multiple factors, including glycation and oxidation of proteins and increased prevalence of classic risk factors of coronary disease, such as hypertension, obesity, and dyslipidemia. Despite advances in the management of cardiovascular disease, a large proportion of diabetic subjects continue to have uncontrolled hyperglycemia, hypertension, and dyslipidemia. In addition, certain medical interventions with established efficacy in the general population do not appear to be appropriate for diabetic subjects. Recently published clinical trials of managing coronary risk factors indicate that more stringent goals of therapy should be set for diabetic patients. In this communication, some of these landmark studies are reviewed and some practical guidelines of management are suggested.
T Cell Activation-Induced Mitochondrial Hyperpolarization Is Mediated by Ca2+- and Redox-Dependent Production of Nitric Oxide (2003)

Activation, proliferation, or programmed cell death of T lymphocytes is regulated by the mitochondrial transmembrane potential (Deltapsi(m)) through controlling ATP synthesis, production of reactive oxygen intermediates (ROI), and release of cell death-inducing factors. Elevation of Deltapsi(m) or mitochondrial hyperpolarization is an early and reversible event associated with both T cell activation and apoptosis. In the present study, T cell activation signals leading to mitochondrial hyperpolarization were investigated. CD3/CD28 costimulation of human PBL elevated cytoplasmic and mitochondrial Ca(2+) levels, ROI production, and NO production, and elicited mitochondrial hyperpolarization. Although T cell activation-induced Ca(2+) release, ROI levels, and NO production were diminished by inositol 1,4,5-triphosphate receptor antagonist 2-aminoethoxydiphenyl borane, superoxide dismutase mimic manganese (III) tetrakis (4-benzoic acid) porphyrin chloride, spin trap 5-diisopropoxyphosphoryl-5-methyl-1-pyrroline-N-oxide, and NO chelator carboxy-2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide, mitochondrial hyperpolarization was selectively inhibited by carboxy-2-phenyl-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide (-85.0 +/- 10.0%; p = 0.008) and, to a lesser extent, by 2-aminoethoxydiphenyl borane. Moreover, NO precursor (Z)-1-[2-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate diethylenetriamine elicited NO and ROI production, Ca(2+) release, transient ATP depletion, and robust mitochondrial hyperpolarization (3.5 +/- 0.8-fold; p = 0.002). Western blot analysis revealed expression of Ca-dependent endothelial NO synthase and neuronal NO synthase isoforms and absence of Ca-independent inducible NO synthase in PBL. CD3/CD28 costimulation or H(2)O(2) elicited severalfold elevations of endothelial NO synthase and neuronal NO synthase expression, as compared with beta-actin. H(2)O(2) also led to moderate mitochondrial hyperpolarization; however, Ca(2+) influx by ionomycin or Ca(2+) release from intracellular stores by thapsigargin alone failed to induce NO synthase expression, NO production, or Deltapsi(m) elevation. The results suggest that T cell activation-induced mitochondrial hyperpolarization is mediated by ROI- and Ca(2+)-dependent NO production.
Model-driven development: a metamodeling foundation (2003)

Metamodeling is an essential foundation for MDD, but there's little consensus on the precise form it should take and role it should play. The authors analyze the underlying motivation for MDD and then derive a concrete set of requirements that a supporting infrastructure should satisfy. They discuss why the traditional "language definition" interpretation of metamodeling isn't a sufficient foundation and explain how it can be extended to unlock MDD's full potential.
Optoacoustic effect in dense layers of oriented carbon nanotubes: Its use for measuring the optical absorption coefficient and the film thickness (2006)

The optoacoustic effect is used to measure the coefficient of light absorption at a wavelength of 0.53 μm by a dense layer of oriented carbon nanotubes on a quartz substrate. The value of the absorption coefficient is found to be equal to 3 × 106 m−1. This value is compared with the theoretical estimates and the estimate obtained from the reflection coefficient with the use of the Kramers-Kronig relation. With the coefficient of light absorption being known, the optoacoustic effect allows one to measure the film thickness at any point without destroying the film.
Architecture of high-speed 22-bit floating-point digital signal processor (2005)

A high-speed floating-point DSP(MSM6992) has been successfully developed as a second-generation DSP. The DSP employs a 22-bit(16E6) floating-point data format and realizes a 100-ns instruction cycle as well as an arithmetic capability of 20- MFLOPS. Furthermore, the DSP features an excellent expandability and allows the expansion of both the program and data memories up to a maximum of 64K words. In addition, the DSP enables flexible system constructions, including multi-DSP systems. The DSP is implemented by a 2µm CMOS process and contains 125K transistors within a single chip. The dimensions of the chip are 12.7 × 10.6mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> and its power dissipation is 400mW. The chip is packaged in a 132-pin PGA. This paper describes the architecture of the high-speed floating-point DSP and its VLSI implementation.
The Androgen Receptor Is Significantly Associated with Vascular Endothelial Growth Factor and Hypoxia Sensing via Hypoxia-Inducible Factors HIF-1a, HIF-2a, and the Prolyl Hydroxylases in Human Prostate Cancer (2005)

These findings confirm the relationship between hypoxia and the androgen receptor in prostate cancer, and show for the first time, the role of HIF-2a in this disease process. They provide clinical evidence to support the recent cell line findings that androgens may regulate VEGF levels through the activation of HIF in androgen-sensitive tumors. Inhibition of both the HIF pathways may provide new therapeutic options in the management of this disease.
Inhibition of Thrombosis by a Selective Fibrinogen Receptor Antagonist without Effect on Bleeding Time (1994)

Membrane glycoprotein alpha IIb beta 3 on platelets plays a pivotal role in hemostasis by mediating RGD-(arginine-glycine-aspartic acid)-dependent platelet adhesion and aggregation. Antagonists of alpha IIb beta 3 ligand binding function, such as antibodies, snake venom peptides, or synthetic RGD-containing peptides can completely inhibit platelet aggregation in vitro and cause significant prolongation of bleeding times when injected into experimental animals. The in vitro and in vivo properties of an alpha IIb beta 3 specific RGD-containing peptide 2G (G(Pen)GHRGDLRCA) were compared to two non-specific RGD-containing peptides 1N (G(Pen)GRGDTPCA) and 2H (GRGDSPDG). All three peptides have similar IC50 values in human platelet aggregation (14-22 microM) and ELISA-based alpha IIb beta 3 receptor assays (0.2-0.3 microM) but show different inhibitory activity (IC50 values) in the alpha v beta 5 (2G = 10 microM; 1N = 0.06 microM; 2H = 0.05 microM) and alpha 5 beta 1 receptor assays (2G = 8.3 microM; 1N = 0.06 microM; 2H = 0.04). The alpha IIb beta 3 specific peptide 2G had no effect on monolayers of human saphenous vein endothelial cells while 1N and 2H caused many cells to detach and contract. Peptides 2G and 1N inhibited ADP-stimulated ex vivo platelet aggregation in dogs in a dose dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)
Flavonoids Inhibit Estrogen Binding to Rat Alpha-Fetoprotein (1998)

There is considerable interest in the role(s) of plant-derived compounds such as bioflavonoids in regulating steroid hormone action in mammals, and in particular, the possible effects of the bioflavonoids on the growth of steroid-dependent breast and prostate tumors and on possible abnormal development of steroid-sensitive tissues. Studies of the hormone-like actions of bioflavonoids often use fetal or neonatal rats, which contain high levels of serum alpha-fetoprotein (AFP), a protein that binds estradiol with a Kd approximately 5 x 10(-9) M. Interaction of bioflavonoids with AFP could affect the availability of estrogens to estrogen-responsive cells, as well as the actions of bioflavonoids. These considerations motivated us to study the effect of several flavonoids (quercetin, rutin, naringenin, chrysin, apigenin, kaempferol, myricetin, morin, fisetin) and isoflavonoids (daidzein, genistein) on estrogen binding to rat AFP. We found that naringenin, a flavanone, and quercetin and kaempferol, flavonols, inhibit estrogen binding to AFP with apparent Kds of about 5 x 10(-7) M. To our surprise, the two isoflavonoids, daidzein and genistein, have Kds of about 5 x 10(-6) M for AFP. This 10-fold [correction of 1Q-fold] difference in affinity for AFP between flavonoids and isoflavonoids suggests that AFP has a specificity for the flavonoid structure. Moreover, the affinities of bioflavonoids for rat AFP are sufficiently high to suggest that flavonoids and isoflavonoids could modulate estradiol and estrone binding to rat AFP in vivo, when present at dietary levels. Additionally, the potency of the plant estrogens may be altered by binding to AFP. The flavonoids that we tested have different hydroxyl and glucoside substituents on the A, B, and C rings, which allows us to define some of the spatial requirements for binding to AFP. We find that 5,7-hydroxyl groups in ring A and a 4'-hydroxyl group in ring B are important for binding to AFP. This information, combined with molecular modeling studies, may elucidate the molecular basis for recognition of flavonoids and estrogens by AFP. Also, these findings indicate that the flavonoid levels in the diet need to be considered in studies of the effects of various xenobiotics and endocrine manipulations on experimental animals, particularly during development when serum estrogen binding protein concentrations are often elevated. Finally, bioflavonoids should be useful tools for understanding the variety of estrogen actions initiated by different structural classes of estrogens.
Peripheral blood MicroRNAs distinguish active ulcerative colitis and Crohnʼs disease (2010)

Peripheral blood miRNAs can be used to distinguish active CD and UC from healthy controls. The data support the evidence that CD and UC are associated with different circulating immune cells types and that the differential expression of peripheral blood miRNAs may form the basis of future diagnostic tests for inflammatory bowel disease.
Clockworks: a multimedia bibliography of works useful for the study of the human/machine interface in SF (1993)

About This volume Introduction A List of Works Useful for the Study of The Human/Machine Interface in SF Reference Works Anthologies and Collections Fiction and Poetry Literary Criticism Stage, Screen, and Television Drama Stage, Screen, and Television Drama Criticism Graphic and Plastic Arts Music Background Reading Author Index Title Index Keywords and Theme Index
Full‐scale dynamic response of an RC building under weak seismic motions using earthquake recordings, ambient vibrations and modelling (2009)

Abstract In countries with a moderate seismic hazard, the classical methods developed for strong motion prone countries to estimate the seismic behaviour and subsequent vulnerability of existing buildings are often inadequate and not financially realistic. The main goals of this paper are to show how the modal analysis can contribute to the understanding of the seismic building response and the good relevancy of a modal model based on ambient vibrations for estimating the structural deformation under weak earthquakes. We describe the application of an enhanced modal analysis technique (frequency domain decomposition) to process ambient vibration recordings taken at the Grenoble City Hall building (France). The frequencies of ambient vibrations are compared with those of weak earthquakes recorded by the French permanent accelerometric network (RAP) that was installed to monitor the building. The frequency variations of the building under weak earthquakes are shown to be less (∼2%) and therefore ambient vibration frequencies are relevant over the elastic domain of the building. The modal parameters extracted from ambient vibrations are then used to determine the 1D lumped‐mass model in order to reproduce the inter‐storey drift under weak earthquakes and to fix a 3D numerical model that could be used for strong earthquakes. The correlation coefficients between data and synthetic motion are close to 80 and 90% in horizontal directions, for the 1D and 3D modelling, respectively. Copyright © 2009 John Wiley & Sons, Ltd.