gebhart/patrepeval huggingface dataset:
Directed Evolution of β-Glucosidase A from Paenibacillus polymyxa to Thermal Resistance (2000)

The beta-glucosidase encoded by the bglA gene from Paenibacillus polymyxa has a half-life time of 15 min at 35 degrees C and no detectable activity at 55 degrees C. We have isolated random mutations that enhance the thermoresistance of the enzyme. Following a directed evolution strategy, we have combined some of the isolated mutations to obtain a beta-glucosidase with a half-life of 12 min at 65 degrees C, in the range of resistance of thermophilic enzymes. No significant alteration of the kinetic parameters of the enzyme was observed. One of the mutants isolated in the screening for thermoresistant beta-glucosidase had the same resistance to denaturation as the wild type. This mutation caused the accumulation of enzyme in E. coli, probably due to its lower turnover. The structural changes responsible for the properties of the mutant enzymes have been analyzed. The putative causes increasing thermoresistance are as follows: the formation of an extra salt bridge, the replacement of an Asn residue exposed to the solvent, stabilization of the hydrophobic core, and stabilization of the quaternary structure of the protein.
Isolation of the Oleaginous Yeasts from the Soil and Studies of Their Lipid-Producing Capacities (2009)

D-xylose is one of the most abundant pentose sugars in nature. To isolate oleaginous yeasts that can utilize xylose from diverse soil samples, soils from a litchi orchard, longan orchard, carambola orchard, and woods were collected, yeasts were isolated by the glycerol enrichment and their xylose-assimilating capacities were measured. A subset of these isolates was grown in nitrogen-limited media and then screened for potential oleaginous yeasts by the Sudan Black B staining, after which their lipid-producing capacities were studied. There were 13 strains of oleaginous yeasts identified, and a rapid microbiological assay was provided to exploit microbial lipids that may one day be used as biodiesels or cocoa butter substitute.
Computational Scattering Models for Elastic and Electromagnetic Waves in Particulate Media (2021)

Numerical models were developed to simulate the propagation of elastic and electromagnetic waves in an arbitrary, dense dispersion of spherical particles. The scattering interactions were modeled with vector multipole fields using pure-orbital vector spherical harmonics, and solved using the full vector form of the boundary conditions. Multiple scattering was simulated by translating the scattered wave fields from one particle to another with the use of translational addition theorems, summing the multiple-scattering contributions, and recalculating the scattering in an iterative fashion to a convergent solution. The addition theorems were rederived in this work using an integral method, and were shown to be numerically equivalent to previously published theorems. Both ordered and disordered collections of up to 5,000 spherical particles were used to demonstrate the ability of the scattering models to predict the spatial and frequency distributions of the transmitted waves. The results of the models show they are qualitatively correct for many particle configurations and material properties, displaying predictable phenomena such as refractive focusing, mode conversion, and photonic band gaps. However, the elastic wave models failed to converge for specific frequency regions, possibly due to resonance effects. Additionally, comparison of the multiple-scattering simulations with those using only single-particle scattering showed the multiple-scattering computations are quantitatively inaccurate. The inaccuracies arise from nonconvergence of the translational addition theorems, introducing errors into the translated fields, which minimize the multiple-scattering contributions and bias the field amplitudes towards single-scattering contributions. The addition theorems are shown to converge very slowly, and to exhibit plateaus in convergence behavior that can lead to false indications of convergence. The theory and algorithms developed for the models are broad-based, and can accommodate a variety of structures, compositions, and wave modes. The generality of the approach also lends itself to the modeling of static fields and currents. Suggestions are presented for improving and implementing the models, including extension to nonspherical particles, efficiency improvements for the algorithms, and specific applications in a variety of fields.
Humoral Immunity to Adeno-Associated Virus Type 2 Vectors following Administration to Murine and Nonhuman Primate Muscle (2000)

Adeno-associated virus (AAV) is being developed as a vector capable of conferring long-term gene expression, which is useful in the treatment of chronic diseases. In most therapeutic applications, it is necessary to readminister the vector. This study characterizes the humoral immune response to AAV capsid proteins following intramuscular injection and its impact on vector readministration. Studies of mice and rhesus monkeys demonstrated the formation of neutralizing antibodies to AAV capsid proteins that persisted for over 1 year and then diminished, but this did not prevent the efficacy of vector readministration. More-detailed studies strongly suggested that the B-cell response was T cell dependent. This was further evaluated with a blocking antibody to human CD4, primatized for clinical trials, in a biologically compatible mouse in which the endogenous murine CD4 gene was functionally replaced with the human counterpart. Transient pharmacologic inhibition of CD4 T cells with CD4 antibody prevented an antivector response long after the effects of the CD4 antibody diminished; readministration of vector without diminution of gene expression was possible. Our studies suggest that truly durable transgene expression (i.e., prolonged genetic engraftment together with vector readministration) is possible with AAV in skeletal muscle, although it will be necessary to transiently inhibit CD4 T-cell function to avoid the activation of memory B cells.
An Antimesothelin-Monomethyl Auristatin E Conjugate with Potent Antitumor Activity in Ovarian, Pancreatic, and Mesothelioma Models (2014)

Mesothelin (MSLN) is an attractive target for antibody-drug conjugate therapy because it is highly expressed in various epithelial cancers, with normal expression limited to nondividing mesothelia. We generated novel antimesothelin antibodies and conjugated an internalizing one (7D9) to the microtubule-disrupting drugs monomethyl auristatin E (MMAE) and MMAF, finding the most effective to be MMAE with a lysosomal protease-cleavable valine-citrulline linker. The humanized (h7D9.v3) version, αMSLN-MMAE, specifically targeted mesothelin-expressing cells and inhibited their proliferation with an IC50 of 0.3 nmol/L. Because the antitumor activity of an antimesothelin immunotoxin (SS1P) in transfected mesothelin models did not translate to the clinic, we carefully selected in vivo efficacy models endogenously expressing clinically relevant levels of mesothelin, after scoring mesothelin levels in ovarian, pancreatic, and mesothelioma tumors by immunohistochemistry. We found that endogenous mesothelin in cancer cells is upregulated in vivo and identified two suitable xenograft models for each of these three indications. A single dose of αMSLN-MMAE profoundly inhibited or regressed tumor growth in a dose-dependent manner in all six models, including two patient-derived tumor xenografts. The robust and durable efficacy of αMSLN-MMAE in preclinical models of ovarian, mesothelioma, and pancreatic cancers justifies the ongoing phase I clinical trial.
Jahn-Teller instability in dissipative quantum systems (2010)

We consider the steady states of a harmonic oscillator coupled so strongly to a two-level system (a qubit) that the rotating wave approximation cannot be made. The Hamiltonian version of this model is known as the $E\ensuremath{\bigotimes}\ensuremath{\beta}$ Jahn-Teller model. The semiclassical version of this system exhibits a fixed-point bifurcation, which in the quantum model leads to a ground state with substantial entanglement between the oscillator and the qubit. We show that the dynamical bifurcation survives in a dissipative quantum description of the system, amidst an even richer bifurcation structure. We propose an experimental implementation of this model based on a superconducting cavity: a superconducting junction in the central conductor of a coplanar waveguide.
Vascular endothelial growth factor prolongs survival in a transgenic mouse model of ALS (2004)

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease associated with the death of motor neurons in the spinal cord and brainstem. The cause of ALS is unknown and there is no cure. This study demonstrates, for the first time, that vascular endothelial growth factor (VEGF) delays progression of symptoms and prolongs survival in a Cu/Zn superoxide dismutase (SOD1) transgenic mouse model of ALS. These observations suggest that VEGF or related compounds, might be of value in the treatment of ALS patients.
Emergence of protease inhibitor resistance mutations in human immunodeficiency virus type 1 isolates from patients and rapid screening procedure for their detection (1996)

Patient human immunodeficiency virus type 1 (HIV-1) isolates that are resistant to protease inhibitors may contain amino acid substitutions L10I/V, M46L/I, G-48V, L63P, V82A/F/T, I84V, and L90M in the protease gene. Substitutions at positions 82 and/or 90 occur in variants that display high levels of resistance to certain protease inhibitors. Nucleotide substitutions at these two sites also lead to the loss of two HindII restriction enzyme digestion sites, and these changes make possible a rapid procedure for the detection of drug-resistant variants in patients on protease inhibitor therapy. This procedure was used to detect the emergence of mutated viruses at various times after the initiation of therapy with the HIV-1 protease inhibitor indinavir. The method includes viral RNA isolation from plasma and reverse transcription PCR amplification of the protease gene with fluorescence-tagged primers. The PCR product is digested with HindII, the cleavage products are separated on a urea-acrylamide gel in a DNA sequencer, and the extent of cleavage is automatically analyzed with commercially available software. In viruses from 34 blood samples from four patients, mutations leading to an amino acid change at residue 82 appeared as early as 6 weeks after the start of therapy and persisted throughout the course of the study period (48 weeks). Mutations leading to double substitutions at residues 82 and 90 were seen at a lower frequency and appeared later than the change at position 82. The changes detected by restriction enzyme cleavage were confirmed by DNA sequencing of the cloned protease genes by reverse transcription PCR amplification of viral RNA from isolates in plasma. In addition to the changes at positions 82 and 90, we have identified M46L/I, G48V, and I54V substitutions in isolates derived from indinavir-treated patients. HindII analysis of uncloned, PCR-amplified DNA offers a rapid screening procedure for the detection of virus isolates containing mutations at amino acid residues 82 and 90 in the HIV-1 protease gene. By using other restriction enzymes, the same method can be used to detect additional protease drug-resistant variants and is generally applicable for the detection of mutations.
Towards an integrated information environment with open hypermedia systems (1993)

This paper examines open hypermedia systems, and presents the case that such systems provide a step forward for dealing with large, dynamic data editing and version control. Some attempts to provide solutions to these problems are presented and discussed.
Mitochondrial Dysfunction in Friedreich's Ataxia: From Pathogenesis to Treatment Perspectives (2002)

Friedreich's ataxia (FRDA), the most common inherited ataxia, is an autosomal recessive degenerative disorder caused by a GAA triplet expansion or point mutations in the FRDA gene on chromosome 9q13. The FRDA gene product, frataxin, is a widely expressed mitochondrial protein, which is severely reduced in FRDA patients. The demonstration that deficit of frataxin in FRDA is associated with mitochondrial iron accumulation, increased sensitivity to oxidative stress, deficit of respiratory chain complex activities and in vivo impairment of cardiac and skeletal muscle tissue energy metabolism, has established FRDA as a "new" nuclear encoded mitochondrial disease. Pilot studies have shown the potential effect of antioxidant therapy based on idebenone or coenzyme Q10 plus Vitamin E administration in this condition and provide a strong rationale for designing larger randomized clinical trials.
A single amino acid substitution makes ERK2 susceptible to pyridinyl imidazole inhibitors of p38 MAP kinase (1998)

Mitogen-activated protein (MAP) kinases are serine/threonine kinases that mediate intracellular signal transduction pathways. Pyridinyl imidazole compounds block pro-inflammatory cytokine production and are specific p38 kinase inhibitors. ERK2 is related to p38 in sequence and structure, but is not inhibited by pyridinyl imidazole inhibitors. Crystal structures of two pyridinyl imidazoles complexed with p38 revealed these compounds bind in the ATP site. Mutagenesis data suggested a single residue difference at threonine 106 between p38 and other MAP kinases is sufficient to confer selectivity of pyridinyl imidazoles. We have changed the equivalent residue in human ERK2, Q105, into threonine and alanine, and substituted four additional ATP binding site residues. The single residue change Q105A in ERK2 enhances the binding of SB202190 at least 25,000-fold compared to wild-type ERK2. We report enzymatic analyses of wild-type ERK2 and the mutant proteins, and the crystal structure of a pyridinyl imidazole, SB203580, bound to an ERK2 pentamutant, I103L, Q105T, D106H, E109G. T110A. These ATP binding site substitutions induce low nanomolar sensitivity to pyridinyl imidazoles. Furthermore, we identified 5-iodotubercidin as a potent ERK2 inhibitor, which may help reveal the role of ERK2 in cell proliferation.
Human placental 11 beta-hydroxysteroid dehydrogenase: evidence for and partial purification of a distinct NAD-dependent isoform. (1993)

Excess glucocorticoids impair fetal growth and cause teratogenesis. Placental 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) catalyzes the inactivation of cortisol to cortisone, preventing the high maternal cortisol levels from reaching the fetal circulation and thus preserving the low cortisol fetal environment. In previous work, an NADP-dependent isoform of 11 beta HSD has been purified from rat liver, a cDNA isolated, and the human homolog cloned. However, much evidence suggests tissue-specific 11 beta HSD activities that cannot be explained by the liver-type isoform. Therefore, we have partially purified human placental 11 beta HSD and compared it to the enzyme in rat liver. Human placental subcellular fractions exhibited NAD-dependent 11 beta HSD activity, but showed little activity with NADP. The enzyme had a pH optimum of 7-8.5 (peak, 7.7), was only sparingly soluble in detergents (solubility with Triton X-100 was very poor), and exhibited little latency or change in pH profile in detergent solution. By contrast, rat liver 11 beta HSD was exclusively NADP dependent and was easily solubilized by a wide range of detergents (including Triton X-100), revealing substantial latency and altered pH profile [optimum of 10, becoming 7-10 (peak, 9.5) in detergent]. These data do not merely reflect species differences, as rat placental 11 beta HSD was similar to the human placental isoform. AMP affinity chromatography, which was completely without affinity for rat liver 11 beta HSD, achieved a 1000-fold purification of human placental 11 beta HSD. This had Km values for corticosterone (mean +/- SE, 14 +/- 1 nM) and cortisol (approximately 55 nM) that were over 100 times lower than that for liver 11 beta HSD. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis allowed identification of a band (apparent mol wt, 40,000) that correlated consistently with human placental 11 beta HSD activity (contrasting with a mol wt of 34,000 for rat liver 11 beta HSD). Thus, the NAD-dependent human placental 11 beta HSD is distinct from the previously characterized rat liver isoform and may be the product of a separate gene.
Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain interpretation (1991)

The purpose of the study was to examine intercenter variability in the interpretation of Gram-stained vaginal smears from pregnant women. The intercenter reliability of individual morphotypes identified on the vaginal smear was evaluated by comparing them with those obtained at a standard center. A new scoring system that uses the most reliable morphotypes from the vaginal smear was proposed for diagnosing bacterial vaginosis. This scoring system was compared with the Spiegel criteria for diagnosing bacterial vaginosis. The scoring system (0 to 10) was described as a weighted combination of the following morphotypes: lactobacilli, Gardnerella vaginalis or bacteroides (small gram-variable rods or gram-negative rods), and curved gram-variable rods. By using the Spearman rank correlation to determine intercenter variability, gram-positive cocci had poor agreement (0.23); lactobacilli (0.65), G. vaginalis (0.69), and bacteroides (0.57) had moderate agreement; and small (0.74) and curved (0.85) gram-variable rods had good agreement. The reliability of the 0 to 10 scoring system was maximized by not using gram-positive cocci, combining G. vaginalis and bacteroides morphotypes, and weighting more heavily curved gram-variable rods. For comparison with the Spiegel criteria, a score of 7 or higher was considered indicative of bacterial vaginosis. The standardized score had improved intercenter reliability (r = 0.82) compared with the Spiegel criteria (r = 0.61). The standardized score also facilitates future research concerning bacterial vaginosis because it provides gradations of the disturbance of vaginal flora which may be associated with different levels of risk for pregnancy complications.
Oxygen sensing characteristics of individual ZnO nanowire transistors (2004)

Individual ZnO nanowire transistors are fabricated, and their sensing properties are investigated. The transistors show a carrier density of 2300μm−1 and mobility up to 6.4cm2∕Vs, which are obtained from the ISD−VG curves. The threshold voltage shifts in the positive direction and the source-drain current decreases as ambient oxygen concentration increases. However, the opposite occurs when the transistors are under illumination. Surface adsorbates on the ZnO nanowires affect both the mobility and the carrier density. Our data are helpful in understanding the sensing mechanism of the gas sensors.
A Computational Approach to Edge Detection (1986)

This paper describes a computational approach to edge detection. The success of the approach depends on the definition of a comprehensive set of goals for the computation of edge points. These goals must be precise enough to delimit the desired behavior of the detector while making minimal assumptions about the form of the solution. We define detection and localization criteria for a class of edges, and present mathematical forms for these criteria as functionals on the operator impulse response. A third criterion is then added to ensure that the detector has only one response to a single edge. We use the criteria in numerical optimization to derive detectors for several common image features, including step edges. On specializing the analysis to step edges, we find that there is a natural uncertainty principle between detection and localization performance, which are the two main goals. With this principle we derive a single operator shape which is optimal at any scale. The optimal detector has a simple approximate implementation in which edges are marked at maxima in gradient magnitude of a Gaussian-smoothed image. We extend this simple detector using operators of several widths to cope with different signal-to-noise ratios in the image. We present a general method, called feature synthesis, for the fine-to-coarse integration of information from operators at different scales. Finally we show that step edge detector performance improves considerably as the operator point spread function is extended along the edge.
Implantation of neutral atoms into liquid helium by laser sputtering (1993)

We have developed a new method for producing a high density of neutral atoms in liquid helium; laser sputtering within liquid helium. When we irradiate samples immersed in liquid helium with a pulsed laser, a large number of clusters are introduced into the liquid. When we further irradiate these clusters with an additional pulse laser, the clusters are sputtered and decomposed, which results in the creation of a high density of isolated atoms in the liquid. For alkaline earth atoms this method is demonstrated, and the results of laser spectroscopy are given.
Genetics and regulation of heme iron transport in Shigella dysenteriae and detection of an analogous system in Escherichia coli O157:H7 (1995)

Shigella species can use heme as the sole source of iron. In this work, the heme utilization locus of Shigella dysenteriae was cloned and characterized. A cosmid bank of S. dysenteriae serotype 1 DNA was constructed in an Escherichia coli siderophore synthesis mutant incapable of heme transport. A recombinant clone, pSHU12, carrying the heme utilization system of S. dysenteriae was isolated by screening on iron-poor medium supplemented with hemin. Transposon insertional mutagenesis and subcloning identified the region of DNA in pSHU12 responsible for the phenotype of heme utilization. Minicell analysis indicated that a 70-kDa protein encoded by this region was sufficient to allow heme utilization in E. coli. Synthesis of this protein, designated Shu (Shigella heme uptake), was induced by iron limitation. The 70-kDa protein is located in the outer membrane and binds heme, suggesting it is the S. dysenteriae heme receptor. Heme iron uptake was found to be TonB dependent in E. coli. Transformation of an E. coli hemA mutant with the heme utilization subclone, pSHU262, showed that heme could serve as a source of porphyrin as well as iron, indicating that the entire heme molecule is transported into the bacterial cell. DNA sequences homologous to shu were detected in strains of S. dysenteriae serotype 1 and E. coli O157:H7.
Studies on segmented polyetherurethane for biomedical application: Effects of composition and hard-segment content on biocompatibility (1998)

Segmented polyetherurethane (SPEU) materials based on polytetramethylene oxide (PTMO, Mw 1000 and 2000) with various hard-segment contents were synthesized and their biocompatibilities studied via different tests. The static contact angle data reveal that the higher hard-segment-content SPEU material possesses a lower contact angle, implying that the surface of the higher hard-segment-content SPEU is more hydrophilic than its low hard-segment-content SPEU counterpart. The catalyst- and additive-free PTMO-based SPEU materials in this study possess neither a hemolytic nor a cytotoxic response that could be considered non toxic for biomedical applications. By using L-929 cell lines, a cell-seeding test indicated that the higher hard-segment-content SPEU material possesses quicker cell attachment and proliferation behaviors. In vitro platelet adhesion tests indicated that the lower hard-segment-content SPEU possesses less platelet adhesion than the high hard-segment-content SPEU material. Both ex vivo canine artery-artery (A-A) and arterio-venous (A-V) shunting tests revealed that the extent of platelet adhesion reaction is less for lower hard-segment content SPEU. In addition, the blood compatibility of SPEU material synthesized from PTMO 1000 excels over PTMO 2000 SPEU material by near the same levels as the hard-segment-content SPEU.