gebhart/patrepeval huggingface dataset:
Engineering subtilisin BPN′ for site‐specific proteolysis (1989)

A combination of protein engineering and substrate optimization was used to create variants of the serine protease, subtilisin BPN', which efficiently and specifically cleave a designed target sequence in a fusion protein. The broad substrate specificity of wild-type subtilisin BPN' is greatly restricted by substitution of the catalytic histidine-containing of the catalytic histidine 64 with alanine (H64A) so that certain histidine-containing substrates are preferentially hydrolysed (Carter, P., Wells, J.A. Science 237:394-399, 1987). The catalytic efficiency, (kcat/Km), of this H64A variant was increased almost 20-fold by judicious choice of substrate and by installing three additional mutations which increase the activity of wild-type subtilisin. The most favorable substrate sequence identified was introduced as a linker in a fusion protein between a synthetic IgG binding domain of Staphylococcus aureus protein A and Escherichia coli alkaline phosphatase. The fusion protein (affinity purified on an IgG column) was cleaved by the prototype H64A enzyme and its improved variant, efficiently and exclusively at the target site, to liberate an alkaline phosphatase product of the expected size and N-terminal sequence. Several features of H64A variants of subtilisin make them attractive for site-specific proteolysis of fusion proteins: they have exquisite substrate specificity on the N-terminal side of the cleavage site and yet are broadly specific on the C-terminal side; they can be produced in large quantities and remain highly active even in the presence of detergents, reductants (modest concentrations), protease inhibitors, at high temperatures, or when specifically immobilized on a solid support.
Continuous culture studies on the synthesis of capsular polysaccharide by Klebsiella pneumoniae K1 (1994)

The synthesis of capsular polysaccharide by Klebsiella pneumoniae K1 was investigated in a minimal salts medium by continuous culture. The organism produced larger amounts of polysaccharide under nitrogen-limited conditions than under carbon-limited conditions. The synthesis of polysaccharide was dependent not only on the availability of excess carbon, but also on growth rate. The rate of polysaccharide synthesis was greatest at low dilutions, low temperature (30 degrees C) and at neutral pH. Prolonged growth in nitrogen-limited culture resulted in the development of non-mucoid variants, possibly due to a selective growth advantage over mucoid cells. The non-mucoid isolate was more susceptible to some bacteriophages, possibly due to the reduction nor absence of capsular polysaccharide.
Design, Synthesis and Some uses of Receptor-Specific Agonists and Antagonists of Vasopressin and Oxytocin (1993)

Selective agonists and antagonists are powerful tools for studies on AVP and OT receptors and on the physiological and pathophysiological roles of AVP and OT. Here we show how some of these peptides and their radiolabelled derivatives were designed. We also present examples of the currently available cyclic and linear OT and AVP agonists and antagonists from our laboratories.
A framework for predictive modeling of anatomical deformations (2001)

A framework for modeling and predicting anatomical deformations is presented, and tested on simulated images. Although a variety of deformations can be modeled in this framework, emphasis is placed on surgical planning, and particularly on modeling and predicting changes of anatomy between preoperative and intraoperative positions, as well as on deformations induced by tumor growth. Two methods are examined. The first is purely shape-based and utilizes the principal modes of co-variation between anatomy and deformation in order to statistically represent deformability. When a patient's anatomy is available, it is used in conjunction with the statistical model to predict the way in which the anatomy will/can deform. The second method is related, and it uses the statistical model in conjunction with a biomechanical model of anatomical deformation. It examines the principal modes of co-variation between shape and forces, with the latter driving the biomechanical model, and thus predicting deformation. Results are shown on simulated images, demonstrating that systematic deformations, such as those resulting from change in position or from tumor growth, can be estimated very well using these models. Estimation accuracy will depend on the application, and particularly on how systematic a deformation of interest is.
Glioblastoma Therapy Can Be Augmented by Targeting IDH1-Mediated NADPH Biosynthesis (2016)

NADPH is a critical reductant needed in cancer cells to fuel the biosynthesis of deoxynucleotides and antioxidants and to sustain stress-survival responses after radiation-induced DNA damage. Thus, one rational strategy to attack cancer cells is to target their heavy reliance on NADPH. Here, we report that the isocitrate dehydrogenase IDH1 is the most strongly upregulated NADPH-producing enzyme in glioblastoma (GBM). IDH1 silencing in GBM cells reduced levels of NADPH, deoxynucleotides, and glutathione and increased their sensitivity to radiation-induced senescence. Rescuing these metabolic restrictions was sufficient to reverse IDH1-mediated radiosensitization. In a murine xenograft model of human GBM, we found that IDH1 silencing significantly improved therapeutic responses to fractionated radiotherapy, when compared with either treatment alone. In summary, our work offers a mechanistic rationale for IDH1 inhibition as a metabolic strategy to improve the response of GBM to radiotherapy. <i>Cancer Res; 77(4); 960-70. ©2016 AACR</i>.
Transient 2D-IR Spectroscopy:  Snapshots of the Nonequilibrium Ensemble during the Picosecond Conformational Transition of a Small Peptide (2003)

The technique of transient two-dimensional infrared (T2D-IR) spectroscopy is introduced, which extends the advantage of 2D-IR spectroscopy to the investigation of a transient species with picosecond time resolution. The conformational change of a small cyclic peptide is studied in the amide-I spectral range, which is induced by means of a photoswitch integrated into the peptide backbone. Substantial changes are found in the transient 2D-IR spectra at times when the transient 1D spectra show only a minor time dependence, illustrating the information gain accessible from 2D-IR spectroscopy. In contrast to 1D spectroscopy, 2D-IR can distinguish between homogeneous and inhomogeneous broadening. The homogeneous contribution to the total width of the amide-I band changes during the course of the conformational transition, a result that is interpreted in terms of the manner in which the peptide samples its conformational space.
Compact slit-based couplers for metal-dielectric-metal plasmonic waveguides (2012)

We introduce compact wavelength-scale slit-based structures for coupling free space light into metal-dielectric-metal (MDM) subwave-length plasmonic waveguides. We first show that for a single slit structure the coupling efficiency is limited by a trade-off between the light power coupled into the slit, and the transmission of the slit-MDM waveguide junction. We next consider a two-section slit structure, and show that for such a structure the upper slit section enhances the coupling of the incident light into the lower slit section. The optimized two-section slit structure results in ∼ 2.3 times enhancement of the coupling into the MDM plasmonic waveguide compared to the optimized single-slit structure. We finally consider a symmetric double-slit structure, and show that for such a structure the surface plasmons excited at the metal-air interfaces are partially coupled into the slits. Thus, the coupling of the incident light into the slits is greatly enhanced, and the optimized double-slit structure results in ∼ 3.3 times coupling enhancement compared to the optimized single-slit structure. In all cases the coupler response is broadband.
Improved silencing properties using small internally segmented interfering RNAs (2007)

RNA interference is mediated by small interfering RNAs (siRNAs) that upon incorporation into the RNA-induced silencing complex (RISC) can target complementary mRNA for degradation. Standard siRNA design usually feature a 19-27 base pair contiguous double-stranded region that is believed to be important for RISC incorporation. Here, we describe a novel siRNA design composed of an intact antisense strand complemented with two shorter 10-12 nt sense strands. This three-stranded construct, termed small internally segmented interfering RNA (sisiRNA), is highly functional demonstrating that an intact sense strand is not a prerequisite for RNA interference. Moreover, when using the sisiRNA design only the antisense strand is functional in activated RISC thereby completely eliminating unintended mRNA targeting by the sense strand. Interestingly, the sisiRNA design supports the function of chemically modified antisense strands, which are non-functional within the context of standard siRNA designs. This suggests that the sisiRNA design has a clear potential of improving the pharmacokinetic properties of siRNA in vivo.
HYDROPROCESSING LIGNIN AND LIGNIN MODEL COMPOUNDS: PRODUCTS, KINETICS, AND CATALYST AGING (1991)

Abstract The hydroprocessing reactions of kraft lignin and four of its model compounds, o-hydroxydiphenylmethane (OHD), diphenylmethane (DPM), 4-phenoxyphenol (PP), and 4-methylguaiacol (MG) were studied over a sulfided CoMo/γ-Al2O3 catalyst. The reactions of OHD were also studied over sulfided Ni-Mo/γ-Al2O3, Ni-W/γ-Al2O3, and Ni-Mo/zeolite catalysts. Reaction pathways, kinetics, and catalyst deactivation were resolved. Experiments with the actual kraft lignin substrate showed that catalytic hydroprocessing led to higher yields of single-ring products and lower yields of light gas compared to hydropyrolysis alone. The CoMo/γ-Al2O3 catalyst increased the selectivity to non-coking monophenolics and hydrocarbon products. The model compound results permitted interpretation. The hydroxyl substituents on OHD and PP directed bond cleavage strongly. The atom linking the two aromatic rings remained almost exclusively with the unsubstituted ring after cleavage. The substituent increased reactivity by at least an order of magnitude. The catalytic reactions of OHD, DPM, and PP were 103-104 times faster than their thermal reactions. Deoxygenation was appreciable in these reactions and in the catalytic hydroprocessing of MG. Collectively, these results suggest that the improved activity and selectivity in catalytic lignin liquefaction is due to enhancement of link cleavage and the transformation of coking dioxygen-substituted phenolic coke pecursors (e.g., catechols and guaiacols) to non-coking phenols. Hydrotreating catalysts with alumina supports appear suitable for lignin conversion. The highly active and rapidly deactivating zeolite-supported hydrotreating catalyst afforded a complex mixture of products. Regeneration of the alumina-supported catalysts would be required. Notes ∗Correspondence Additional informationNotes on contributorsPeter M. Train Present Address: Amoco Oil Company, Research and Development, P. O. Box 3011, Naperville, IL 60566.
Fast and Robust Classification using Asymmetric AdaBoost and a Detector Cascade (2001)

This paper develops a new approach for extremely fast detection in do-mains where the distribution of positive and negative examples is highly skewed (e.g. face detection or database retrieval). In such domains a cascade of simple classifiers each trained to achieve high detection rates and modest false positive rates can yield a final detector with many desir-able features: including high detection rates, very low false positive rates, and fast performance. Achieving extremely high detection rates, rather than low error, is not a task typically addressed by machine learning al-gorithms. We propose a new variant of AdaBoost as a mechanism for training the simple classifiers used in the cascade. Experimental results in the domain of face detection show the training algorithm yields sig-nificant improvements in performance over conventional AdaBoost. The final face detection system can process 15 frames per second, achieves over 90 % detection, and a false positive rate of 1 in a 1,000,000. 1
Smart-Cut® process using metallic bonding:Application to transfer of Si, GaAs, InP thin films (1999)

The ability to obtain thin films using the Smart-Cut® process combined with metallic bonding is demonstrated. New structures have been realised from thin films of Si, GaAs or InP bonded to silicon substrates via metallic layers.
Importance of replication in microarray gene expression studies: Statistical methods and evidence from repetitive cDNA hybridizations (2000)

We present statistical methods for analyzing replicated cDNA microarray expression data and report the results of a controlled experiment. The study was conducted to investigate inherent variability in gene expression data and the extent to which replication in an experiment produces more consistent and reliable findings. We introduce a statistical model to describe the probability that mRNA is contained in the target sample tissue, converted to probe, and ultimately detected on the slide. We also introduce a method to analyze the combined data from all replicates. Of the 288 genes considered in this controlled experiment, 32 would be expected to produce strong hybridization signals because of the known presence of repetitive sequences within them. Results based on individual replicates, however, show that there are 55, 36, and 58 highly expressed genes in replicates 1, 2, and 3, respectively. On the other hand, an analysis by using the combined data from all 3 replicates reveals that only 2 of the 288 genes are incorrectly classified as expressed. Our experiment shows that any single microarray output is subject to substantial variability. By pooling data from replicates, we can provide a more reliable analysis of gene expression data. Therefore, we conclude that designing experiments with replications will greatly reduce misclassification rates. We recommend that at least three replicates be used in designing experiments by using cDNA microarrays, particularly when gene expression data from single specimens are being analyzed.
The Effect of Organic Ligand Binding on the Growth of CdSe Nanoparticles Probed by Ab Initio Calculations (2004)

First principles electronic structure simulations are used to study the atomistic detail of the interaction between organic surfactant molecules and the surfaces of CdSe semiconductor nanoparticles. These calculations provide insights into the relaxed atomic geometry of organics bound to semiconductor surfaces at the nanoscale as well as the electronic charge transfer between surface atoms and the organics. We calculate the binding energy of phosphine oxide, phosphonic and carboxylic acids, and amine ligands to a range of CdSe nanoparticle facets. The dominant binding interaction is between oxygen atoms in the ligands and cadmium atoms on the nanoparticle surfaces. The most strongly bound ligands are phosphonic acid molecules, which bind preferentially to the facets forming the sides of CdSe nanorods. The calculated relative binding strengths of ligands to different facets support the hypothesis that these binding energies control the relative growth rates of different facets, and therefore the resulting geometry of the nanoparticles.
Oscillations and Sparsening of Odor Representations in the Mushroom Body (2002)

In the insect olfactory system, oscillatory synchronization is functionally relevant and reflects the coherent activation of dynamic neural assemblies. We examined the role of such oscillatory synchronization in information transfer between networks in this system. The antennal lobe is the obligatory relay for olfactory afferent signals and generates oscillatory output. The mushroom body is responsible for formation and retrieval of olfactory and other memories. The format of odor representations differs significantly across these structures. Whereas representations are dense, dynamic, and seemingly redundant in the antennal lobe, they are sparse and carried by more selective neurons in the mushroom body. This transformation relies on a combination of oscillatory dynamics and intrinsic and circuit properties that act together to selectively filter and synthesize the output from the antennal lobe. These results provide direct support for the functional relevance of correlation codes and shed some light on the role of oscillatory synchronization in sensory networks.
Two-dimensional color-code quantum computation (2011)

We describe in detail how to perform universal fault-tolerant quantum computation on a two-dimensional color code, making use of only nearest neighbor interactions. Three defects (holes) in the code are used to represent logical qubits. Triple-defect logical qubits are deformed into isolated triangular sections of color code to enable transversal implementation of all single logical qubit Clifford group gates. Controlled-NOT (CNOT) is implemented between pairs of triple-defect logical qubits via braiding.
Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid (2004)

Glutathione (GSH) significantly declines in the aging rat liver. Because GSH levels are partly a reflection of its synthetic capacity, we measured the levels and activity of gamma-glutamylcysteine ligase (GCL), the rate-controlling enzyme in GSH synthesis. With age, both the catalytic (GCLC) and modulatory (GCLM) subunits of GCL decreased by 47% and 52%, respectively (P < 0.005). Concomitant with lower subunit levels, GCL activity also declined by 53% (P < 0.05). Because nuclear factor erythroid2-related factor 2 (Nrf2) governs basal and inducible GCLC and GCLM expression by means of the antioxidant response element (ARE), we hypothesized that aging results in dysregulation of Nrf2-mediated GCL expression. We observed an approximately 50% age-related loss in total (P < 0.001) and nuclear (P < 0.0001) Nrf2 levels, which suggests attenuation in Nrf2-dependent gene transcription. By using gel-shift and supershift assays, a marked reduction in Nrf2/ARE binding in old vs. young rats was noted. To determine whether the constitutive loss of Nrf2 transcriptional activity also affects the inducible nature of Nrf2 nuclear translocation, old rats were treated with (R)-alpha-lipoic acid (LA; 40 mg/kg i.p. up to 48 h), a disulfide compound shown to induce Nrf2 activation in vitro and improve GSH levels in vivo. LA administration increased nuclear Nrf2 levels in old rats after 12 h. LA also induced Nrf2 binding to the ARE, and, consequently, higher GCLC levels and GCL activity were observed 24 h after LA injection. Thus, the age-related loss in GSH synthesis may be caused by dysregulation of ARE-mediated gene expression, but chemoprotective agents, like LA, can attenuate this loss.
Novel Glass Fiber‐Reinforced Composites Having a UV and Peroxy Curable Fluoropolymer Matrix (2003)

Abstract Novel glass fiber‐reinforced composites were prepared from E‐glass fibers and perfluoropolyether (PFPE), polyurethane acrylate, and methacrylate resins. The PFPE resins were synthesized by a two‐step process and formulated with reactive acrylic diluents obtaining two compositions with different viscosity and fluorine content. These formulations were photocrosslinked by UV‐A radiation and characterized by tensile and dynamic‐mechanical properties as well as by impact resistance. The two UV cured fluoropolymer compositions are high modulus (&gt; 1 GPa), polyphasic materials characterized by a fracture toughness higher than conventional polymer matrices, like epoxies and unsaturated polyesters. Unidirectional laminate composites were also prepared by hand lay‐up and crosslinked both photochemically and thermally. Mechanical characterization of glass fiber‐reinforced composites was carried out by tensile tests and shear adhesion measurements, showing a good fluoropolymer‐glass adhesion strength (ca. 9 MPa). Surface characterization of composites by static contact angle measurements allowed the calculation of the total surface tension γ s according to Wu's harmonic mean approximation. Surface tension is very low (&lt; 20 mN/m) suggesting a preferential stratification of PFPE segments at the material‐air interface. magnified image
Psoriasis: Proceedings of the International Symposium—Stanford University 1971 (1972)

This volume is devoted solely to the deliberations of the International Symposium on Psoriasis which was held in June of 1971. It is remarkable that the papers given by an outstanding group of international experts could be published by December 1971. In it one can find almost everything currently known about psoriasis; yet as the dedication states, "To those who wait with hope for discoveries that will lessen their sufferings from psoriasis," we must know more and undoubtedly will as years pass by. Drs. Farber and Cox are congratulated strongly for their willingness and ability to undertake the development and ultimate fruition of this great meeting. The 460 pages of text are written by more than 75 authors and comprise 51 chapters divided as follows: 20 chapters dealing with the clinical manifestations of psoriasis, 15 with biological approaches and 16 with therapy and complications. Unfortunately, no subject index is offered,
Machine learning based lithographic hotspot detection with critical-feature extraction and classification (2009)

In this paper, we present a fast and accurate lithographic hotspot detection flow with a novel MLK (Machine Learning Kernel), based on critical feature extraction and classification. In our flow, layout binary image patterns are decomposed/analyzed and critical lithographic hotspot related features are defined and employed for low noise MLK supervised training. Combining novel critical feature extraction and MLK supervised training procedure, our proposed hotspot detection flow achieves over 90% detection accuracy on average and much smaller false alarms (10% of actual hotspots) compared with some previous work [9, 13], without CPU time overhead.
Bacteriophage SPO1-induced macromolecular synthesis in minicells of Bacillus subtilis (1975)

SPO1 bacteriophage injects its DNA into minicells produced by Bacillus subtilis CU403 divIVB1. The injected DNA is partially degraded to small trichloracetic acid-precipitable material and trichloroacetic acid-soluble material. The injected DNA is not replicated; however, it serves as a template for RNA and protein synthesis. The RNA produced specifically hybridizes to SPO1 DNA, and the amount of RNA hybridized can be reduced by competition with RNA isolated at all stages of the phage cycle from infected nucleate cells of the B. subtilis CU403 divIVB1. An unrelated phage, SPP1, also induces phage-specific RNA in infected minicells. Translation occurs in SPO1-infected minicells resulting in at least eight proteins which have been separated by gel electrophoresis, and two of these proteins have mobilities similar to proteins found only in infected B. subtilis CU403 divIVB1 nucleate cells. A large proportion of the polypeptide material synthesized in infected minicells is very small and heterogeneous in size.