gebhart/patrepeval huggingface dataset:
Structured design (1974)

The HIPO Hierarchy chart is being used as an aid during general systems design. The considerations and techniques presented here are useful for evaluating alternatives for thos portions of the system that will be programmed on a computer. The charting technique used here depicts more details about the interfaces than the HIPO Hierarchy chart. This facilitates consideration during general program design of each individual connection and its associated passed parameters. The resulting design can be documented with the HIPO charts. (if the designer decides to have more than one function in any module, the structure chart should show them in the same block. However, the HIPO Hierarchy chart would still show all the functions in separate blocks.) The output of the general program design is the input for the detailed module design. The HIPO input-process-output chart is useful for describing and designing each module.
Amyloid precursor protein processing and Aβ 42 deposition in a transgenic mouse model of Alzheimer disease (1997)

The PDAPP transgenic mouse, which overexpresses human amyloid precursor protein (APP717V-->F), has been shown to develop much of the pathology associated with Alzheimer disease. In this report, levels of APP and its amyloidogenic metabolites were measured in brain regions of transgenic mice between 4 and 18 months of age. While absolute levels of APP expression likely contribute to the rate of amyloid beta-peptide (Abeta) deposition, regionally specific factors also seem important, as homozygotic mice express APP levels in pathologically unaffected regions in excess of that measured in certain amyloid plaque-prone regions of heterozygotic mice. Regional levels of APP and APP-beta were nearly constant at all ages, while A beta levels dramatically and predictably increased in brain regions undergoing histochemically confirmed amyloidosis, most notably in the cortex and hippocampus. In hippocampus, A beta concentrations increase 17-fold between the ages of 4 and 8 months, and by 18 months of age are over 500-fold that at 4 months, reaching an average level in excess of 20 nmol of A beta per g of tissue. A beta1-42 constitutes the vast majority of the depositing A beta species. The similarities observed between the PDAPP mouse and human Alzheimer disease with regard to A beta42 deposition occurring in a temporally and regionally specific fashion further validate the use of the model in understanding processes related to the disease.
The Influence of Sulphur-Containing Amino Acids on the Biosynthesis of High-Sulphur Wool Proteins (1970)

The sulphur content of wool can vary within the range of about 2·7-4·2% depending on the diet of the sheep. The lower limit may represent a limiting fundamental structure for wool as it has not been possible to produce wool of sulphur content lower than 2·7% during sulphur-deprivation experiments. There is a highly significant linear relationship between the sulphur content of wool and its content of high-sulphur proteins. The major part of this variation in sulphur content is due to alterations in the extent of biosynthesis of proteins of extremely high sulphur content having about one-third of the amino acid residues presen1, as half cystine. The biosynthesis of these proteins may be under separate metabolic control for they can be produced at maximum rate under conditions where the synthesis of other highsulphur proteins is partly inhibited by a sulphur-deficient diet or by high levels of DL-methionine supplementation
Co-design of hardware and algorithms for real-time optimization (2014)

It is difficult or impossible to separate the performance of an optimization solver from the architecture of the computing system on which the algorithm is implemented. This is particularly true if measurements from a physical system are used to update and solve a sequence of mathematical optimization problems in real-time, such as in control, automation, signal processing and machine learning. In these real-time optimization applications the designer has to trade off computing time, space and energy against each other, while satisfying constraints on the performance and robustness of the resulting cyber-physical system. This paper is an informal introduction to the issues involved when designing the computing hardware and a real-time optimization algorithm at the same time, which can result in systems with efficiencies and performances that are unachievable when designing the sub-systems independently. The co-design process can, in principle, be formulated as a sequence of uncertain and non-smooth optimization problems. In other words, optimizers might be used to design optimizers. Before this can become a reality, new systems theory and numerical methods will have to be developed to solve these co-design problems effectively and reliably.
Isolation of Alcohol Oxidase and Two Other Methanol Regulatable Genes from the Yeast Pichia pastoris (1985)

The oxidation of methanol follows a well-defined pathway and is similar for several methylotrophic yeasts. The use of methanol as the sole carbon source for the growth of Pichia pastoris stimulates the expression of a family of genes. Three methanol-responsive genes have been isolated; cDNA copies have been made from mRNAs of these genes, and the protein products from in vitro translations have been examined. The identification of alcohol oxidase as one of the cloned, methanol-regulated genes has been made by enzymatic, immunological, and sequence analyses. Methanol-regulated expression of each of these three isolated genes can be demonstrated to occur at the level of transcription. Finally, DNA subfragments of two of the methanol-responsive genomic clones from P. pastoris have been isolated and tentatively identified as containing the control regions involved in methanol regulation.
Water-Soluble Polyion Complex Associates of DNA and Poly(ethylene glycol)−Poly(l-lysine) Block Copolymer (1997)

Complex formation of poly(ethylene glycol)-poly(L-lysine) (PEG-PLL) AB type block copolymer with salmon testes DNA or Col E1 plasmid DNA in aqueous milieu was studied. The PLL segment of PEG-PLL interacts with nucleic acid through an electrostatic force to form a water-soluble complex associate with a diameter of ca. 50 nm. PEG segments surrounding the core of the polyion complex prevented the complex from precipitation even under stoichiometric conditions, at which the unit ratio of L-lysine in PEG-PLL and phosphate in the DNA is equal. The profile of the thermal melting curve revealed a higher stabilization of DNA structure in PEG-PLL/DNA complexes compared to that in the complex made from DNA and PLL homopolymer with the same molecular weight as the PLL segment in PEG-PLL. This stabilizing effect on the DNA structure may be due to the compartmentalization of DNA into the microenvironment of PEG with low permittivity. The reversible nature of the PEG-PLL/DNA complex was further verified through the addition of polyanion [poly-(L-aspartic acid)]: Poly(L-aspartic acid) replaced DNA in the complex with PEG-PLL, resulting in the release of free DNA in the medium. Furthermore, the PEG-PLL/DNA complex showed high resistance against DNase I attack, suggesting DNA protection through the segregation into the core of the associate having PEG palisade.
Scientific and Regulatory Reasons for Delay and Denial of FDA Approval of Initial Applications for New Drugs, 2000-2012 (2014)

Several potentially preventable deficiencies, including failure to select optimal drug doses and suitable study end points, accounted for significant delays in the approval of new drugs. Understanding the reasons for previous failures is helpful to improve the efficiency of clinical development for new drugs.
Determination of VFA production rate in the rumen of sheep fed different levels of intake (2001)

Six wethers received a diet containing 70% alfalfa hay and 30% ground maize in eight equal meals at three-hour intervals. The diet (9.8 MJ ME/kg DMI) was offered at 90% of ad libitum intake (high intake : HI) and 45% of ad libitum intake (low intake : LI) in a 2 x 2 crossover design. Each sheep received successively 5 intraruminal VFA solutions infused continuously during 24 hours. The first infusion (II) considered as control treatment consisted of a solution of [l-13C]-propionate (7 mmol/d). The four other solutions were isoenergetic (1.9 MJ ME/kg DMI) mixtures of non-labelled propionate (C3) and butyrate (C4) in different levels : 0.9 mol C4/kg DMI (12); 0.6 mol C4 + 0.45 mol C3/kg DMI (13); 0.3 mol C4 + 0.9 mol C3/kg DMI (14); 1.35 mol C3/kg DMI (15). Irrespective of the intake level the ruminai production rate of individual VFA was on average 1.4 times higher when estimated by the tracer method compared to the non-tracer method. Ruminai VFA production rates estimated by the non-tracer method appeared reasonable (67% of ME intake) and overestimated with the tracer method (120% of ME intake). However, irrespective of the technique the ruminai production rates of VFA were in mean 1.7 fold for animals fed at HI than those fed at LI.
Repetitive DNA sequence of Mycobacterium tuberculosis: analysis of differential hybridization pattern with other mycobacteria. (1988)

In order to generate specific DNA probes for Mycobacterium tuberculosis, restriction fragment length analysis was carried out with some of the mycobacterial species that fall within the tuberculosis complex. The presence of specific bands of 5.6 kb and 4.8 kb was revealed in the AluI DNA digest of M. tuberculosis. The hybridization profile of the 5.6-kb AluI DNA sequence, as judged by the Southern blot and dot blot hybridization experiments, revealed the presence of this sequence in M. tuberculosis H37Rv, M. tuberculosis H37Ra, M. bovis BCG as multiple copy and M. kansasii as single copy but this sequence was not present in M. avium, M. smegmatis, or M. vaccae genomes. Genomic clones corresponding to the 5.6-kb AluI fragment from M. tuberculosis H37Rv library made in the lambda gt11 expression vector were isolated.
Alternating Bioactivity of Polymeric Layer-by-Layer Assemblies:  Anticoagulation vs Procoagulation of Human Blood (2002)

The layer-by-layer assembly between cationic chitosan and anionic dextran sulfate was analyzed quantitatively by a quartz crystal microbalance technique in the absence and presence of 0.2, 0.5, and 1 M NaCl in the polymer solution. The apparent film thickness increased upon increasing the NaCl concentration. The anti- versus procoagulant activity of these films against whole human blood was studied by the immersion of a substrate into blood for 30 min incubation time at 37 degrees C. The substrate was coated with films of varying NaCl concentrations and assembly step numbers. There was a critical concentration for the alternating activity; above a concentration of 0.5 M NaCl, both anti- and procoagulation could be observed on the dextran sulfate and chitosan surfaces, respectively. The underlying layer of the assembly was necessary for this alternating activity; after a five-step assembly, the activity was realized. The adsorption of a cationic dye (methylene blue) onto the films revealed that the anionic-charge density derived from dextran sulfate on the film surface was linearly increased with increased NaCl concentration. There was a critical charge density of the dextran sulfate for the anticoagulant activity. An assembly was also constructed from a combination of chitosan and heparin, but the activity was different from that of the former system; strong anticoagulant activity was observed even on the chitosan surface. We suggest that the polymer species and/or the assembly conditions are key factors for realizing the alternating bioactivities of films prepared by the layer-by-layer assembly.
Triphenylene-Based Discotic Liquid Crystals as Self-Assembled Monolayers (1999)

A series of ω-thiol-substituted 2,3,6,7,10,11-hexaalkoxytriphenylenes was synthesised for the purpose of forming self-assembled monolayers (SAMs) on gold in which the self-organizing, discogenic headgroups have a known orientation. In principle, these headgroups can be oriented either with their short axes perpendicular (disc “face-on”) on their short axes parallel (disc “edge-on”) to the surface, depending on the number and position of the tethering points. To obtain a “face-on” orientation of the headgroups a trithiol (three points of attachment) was synthesized and to obtain an “edge-on” orientation both monothiol and ortho-dithiol derivatives (one or two points of attachment) were made. Within the SAMs it was expected that the headgroups of the “face-on” discogen would self-organize into a hexagonal array and those of the “edge-on” discogens into columns that would run parallel to the surface. The kinetics of formation and the structures of the monolayers were characterized by contact angle measurements, ellipsometry, and scanning tunneling microscopy (STM). In the case of the SAMs obtained from the “edge-on” materials, these confirmed that the desired orientation of the headgroups had been achieved. STM images of a SAM obtained from one of the “edge-on” materials also clearly showed the desired organization of the headgroups into columnar aggregates running parallel to the surface. Clearer STM images were obtained after the SAM had been immersed into a solution of TNF (trinitrofluorenone), a compound known to interdigitate between the triphenylene nuclei. In the case of the SAMs obtained from the “face-on” material, scanning tunneling microscopy gave no indication of the expected hexagonal ordering and ellipsometry suggested that these systems form multilayer rather than monolayer structures.
2-D shape blending (1993)

This paper presents an algorithm for determiningthe paths along which corresponding vertices travel in a 2-D shape blending. Rather than considering the vertex paths explicitly, the algorithm defines the intermediate shapes by interpolating the intrinsic definitions of the initial and final shapes. The algorithm produces shape blends which generally are more satisfactory than those produced using linear or cubic curve paths. Particularly, the algorithm can avoid the shrinkage that normally occurs when rotating rigid bodies are linearly blended, and avoids kinks in the blend when there were none in the key polygons.
A comparison of a food frequency questionnaire with a 24-hour recall for use in an epidemiological cohort study: results from the biomarker-based Observing Protein and Energy Nutrition (OPEN) study (2003)

Because of severe attenuation, the FFQ cannot be recommended as an instrument for evaluating relations between absolute intake of energy or protein and disease. Although this attenuation is lessened in analyses of energy-adjusted protein, it remains substantial for both FFQ and multiple 24HR. The utility of either of these instruments for detecting important but moderate relative risks (between 1.5 and 2.0), even for energy-adjusted dietary factors, is questionable.
THE BRAIN’S RECORD OF AUDITORY AND VISUAL EXPERIENCE (1963)

Journal Article THE BRAIN'S RECORD OF AUDITORY AND VISUAL EXPERIENCE: A FINAL SUMMARY AND DISCUSSION Get access WILDER PENFIELD, WILDER PENFIELD Search for other works by this author on: Oxford Academic PubMed Google Scholar PHANOR PEROT PHANOR PEROT Search for other works by this author on: Oxford Academic PubMed Google Scholar Brain, Volume 86, Issue 4, December 1963, Pages 595–696, https://doi.org/10.1093/brain/86.4.595 Published: 01 December 1963
Biosafety, Antioxidant Status, and Metabolites in Urine after Consumption of Dried Cranberry Juice in Healthy Women:  A Pilot Double-Blind Placebo-Controlled Trial (2007)

This study assessed the effect of an 8 week consumption of dried cranberry juice (DCJ) on 65 healthy young women. Basic biochemical and hematological parameters, antioxidant status, presence of metabolites in urine, and urine ex vivo antiadherence activity were determined throughout the trial. A 400 mg amount of DCJ/day had no influence on any parameter tested. A 1200 mg amount of DCJ/day resulted in a statistically significant decrease in serum levels of advanced oxidation protein products. This specific protective effect against oxidative damage of proteins is described here for the first time. Urine samples had an inhibitory effect on the adhesion of uropathogenic Escherichia coli strains, but no increase in urine acidity was noted. Hippuric acid, isomers of salicyluric and dihydroxybenzoic acids, and quercetin glucuronide were identified as the main metabolites. In conclusion, cranberry fruits are effective not only in the prevention of urinary tract infection but also for the prevention of oxidative stress.
Practical HPLC Methodology and Applications (1993)

Liquid Chromatography as a Research Tool The Chromatogram and What Contributes to It Approaching the Problem Developing the Separation Considerations for Proper Operation of a Liquid Chromatograph Gradient Elution Chromatography Experiment 1: Demonstrating the Fundamentals Experiment 2: Normal-Phase Chromatography Experiment 3: Effect of Column Length and Recycle Experiment 4: Gel Permeation Chromatography Using Dual Detectors (UV and RI) Experiment 5: Developing a Reverse Phase Chromatographic Separation Experiment 6: Quantitation Experiment 7: Monitoring Kinetics Experiment 8: Preparative Liquid Chromatography Experiment 9: Analysis of Essential Oils (Steam Distillates) Experiment 10: Gradient Elution Index.
The Tumor Suppressor, PTEN/MMAC1, Dephosphorylates the Lipid Second Messenger, Phosphatidylinositol 3,4,5-Trisphosphate (1998)

Phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) is a key molecule involved in cell growth signaling. We demonstrated that overexpression of PTEN, a putative tumor suppressor, reduced insulin-induced PtdIns(3,4,5)P3 production in human 293 cells without effecting insulin-induced phosphoinositide 3-kinase activation. Further, transfection of the catalytically inactive mutant of PTEN (C124S) caused PtdIns(3,4,5)P3 accumulation in the absence of insulin stimulation. Purified recombinant PTEN catalyzed dephosphorylation of PtdIns(3,4,5)P3, specifically at position 3 on the inositol ring. PTEN also exhibited 3-phosphatase activity toward inositol 1,3,4,5-tetrakisphosphate. Our results raise the possibility that PTEN acts in vivo as a phosphoinositide 3-phosphatase by regulating PtdIns(3,4,5)P3 levels. As expected, the C124S mutant of PTEN was incapable of catalyzing dephosphorylation of PtdIns(3,4,5)P3 consistent with the mechanism observed in protein-tyrosine phosphatase-catalyzed reactions.
Latent Herpes Simplex Virus (1972)

The unscarified eyes of 14 male New Zealand albino rabbits were infected with herpes simplex virus. Most eyes (26 of 28) exhibited recurrent ocular infection. Four to nine months after original infection and between episodes of recurrence, all animals were killed. Conjunctiva, nictitating membrane, lacrimal gland, cornea, iris, preganglionic trigeminal nerve, trigeminal ganglia, and brain tissue containing the trigeminal nerve nucleus were removed from each animal and tested for virus. Herpes simplex virus was recovered only from trigeminal ganglia and only from those portions maintained as organ cultures. Nineteen of 26 ganglia (73%) were positive. These results are consistent with the theory that sensory ganglia act as reservoirs of herpes simplex virus between attacks of overt disease.
A complex from cultured Chinese hamster ovary cells containing nine aminoacyl‐tRNA synthetases (1985)

The size distribution of the 20 aminoacyl-tRNA synthetases from wild-type Chinese hamster ovary (CHO) cells and from the mutant cell line tsH1, containing a temperature-sensitive leucyl-tRNA synthetase, was determined by gel filtration. Nine aminoacyl-tRNA synthetases, specific for arginine, aspartic acid, glutamic acid, glutamine, isoleucine, leucine, lysine, methionine and proline, which coeluted as high-Mr entities (Mr approximately 1.2 X 10(6)), were further co-purified to yield a multienzyme complex, the polypeptide composition of which was identical to that previously determined for the complex from rabbit liver. Immunoprecipitates obtained from crude extracts of wild-type and tsH1 mutant cells, using specific antibodies directed to the lysyl-tRNA or methionyl-tRNA synthetase components of the complex, displayed the same polypeptide compositions as that of the purified complex, thereby establishing the heterotypic nature of this complex. Although the activity of leucyl-tRNA synthetase from the mutant cells, grown at a permissive temperature, was low compared to that from the wild-type, the polypeptide of Mr 129 000, corresponding to this enzyme, was present in similar amounts and occurred exclusively as a component of the high-Mr complex. Finally, we report that attempts to demonstrate phosphorylation of the components of the complex from cultured CHO, HeLa and C3 cells were unsuccessful.
Increased Excitatory Synaptic Activity and Local Connectivity of Hippocampal CA1 Pyramidal Cells in Rats With Kainate-Induced Epilepsy (2004)

Formation of local excitatory circuits may contribute to epileptogenesis. We tested the hypothesis that epileptogenesis is associated with increased recurrent excitation in the hippocampal CA1 area of rats with kainate-induced epilepsy. Whole cell recordings were obtained during focal flash photolysis of caged glutamate, which served as a focal excitant to activate local pyramidal cells and to study possible connections between neurons. Kainate-treated rats with spontaneous seizures were studied months after status epilepticus and were compared with saline-injected control rats. Experiments were done in isolated CA1 minislices and in bicuculline to block GABA A receptors. Spontaneous excitatory postsynaptic currents (sEPSCs) were present in 42% of the CA1 pyramidal cells from controls and 62% from kainate-treated rats. The frequency of sEPSCs in the kainate group was significantly higher than that in the control group, but mean amplitude was not different. Flash photolysis of caged glutamate on the somatodendritic area of CA1 pyramidal neurons caused a burst of action potentials. Local excitatory connections between CA1 pyramidal cells were found in 4 of 48 neurons (8%) in slices from control animals, but in significantly more neurons (12 of 37; 32%) from rats with kainate-induced epilepsy exhibited interconnections ( P &lt; 0.001). Photoactivation of glutamate on recorded CA1 pyramidal cells in the kainate group sometimes caused afterdischarges, but not in controls. The kainate-treated rats with pyramidal cells that responded to photostimulaltion with repetitive EPSCs appeared to have experienced more severe seizures. These data provide new electrophysiological evidence for the formation of recurrent excitatory circuits in the CA1 area of rats with kainate-induced epilepsy.
Modeling DNA in Aqueous Solutions: Theoretical and Computer Simulation Studies on the Ion Atmosphere of DNA (1996)

This article provides a review of current theoretical and computational studies of the ion atmosphere of DNA as related to issues of both structure and function. Manning's elementary yet elegant concept of "counterion condensation" is revisited and shown to be well supported by current state-of-the-art molecular simulations. Studies of the ion atmosphere problem based on continuum electrostatics, integral equation methods, Monte Carlo simulation, molecular dynamics, and Brownian dynamics are considered. Grand canonical Monte Carlo and non-linear Poisson Boltzmann studies have recently focussed on the determination and significance of the index of non-ideality in solution known as the "preferential interaction coefficient," for which the relevant current literature is cited. The review concludes with a survey of applications to ligand binding problems involving drug-DNA and protein-DNA interactions.