gebhart/patrepeval huggingface dataset:
Bulk flow and diffusion in the cerebrospinal fluid system of the goat (1962)

Ventriculocisternal perfusions were carried out on chronically prepared, unanesthetized goats. Measurements were made of steady-state rates at which inulin, fructose, creatinine, urea, K, Na, and labeled water (TOH) were removed from perfusion fluid at various hydrostatic and osmotic pressures. The ventricular system is virtually impermeable to inulin. Inulin is removed from subarachnoid spaces by bulk absorption at rates which vary linearly with hydrostatic pressure. Net absorption ceases at –15 cm H 2 O. Rate of net formation of cerebrospinal fluid (CSF) is equal to inulin clearance plus the difference between outflow and inflow rates; normally it averages 0.16 cm 3 min –1 and is essentially independent of hydrostatic pressures in the range –10 to +30 cm H 2 O. Net rate of formation is linearly related to total osmotic pressure differences between plasma and CSF. The coefficient of osmotic flow is greater than that measured from diffusion of TOH, as in other porous membranes. Passive permeability characteristics resemble those of the vasopressin-treated toad bladder.
Synthesis of Some New Imidazoles and Related Purine Derivatives (2000)

Treatment of 5-(amino)imidazole-4-carbonitrile 1 with a mixture of acetic anhydride and acetic acid afforded, the unexpected 5-(acetylamino)imidazole-4-(N-acetyl)carboxamide 2, but upon reacting 1 with acetic anhydride for a short time, the 5-(diacetylamino)imidazole-4-carbonitrile 4 was obtained. Reaction of 2 and 4 with hydrazine hydrate gave the condensation products 6 and 8a respectively. Upon reacting 2 with methylamine and hydroxylamine, the 5-(amino)imidazole derivative 7 was afforded, but reaction of 4 with the same reagents gave products 8b and 11 respectively. Cyclization of 2 and 4 in alkaline medium was carried out to afford the 2-methylpurin-6(1H)-one derivative 13. Treatment of the latter product with phosphoryl chloride, followed by reaction with some cyclic 2T amines and amino acids gave the 6-substituted purines 15-17. Moreover, when 1 was allowed to react with alkyl isocyanate the urea derivatives 19 were afforded. Also, the 8-substituted purines 20 and were obtained from 19.
Home automation in the wild (2011)

Visions of smart homes have long caught the attention of researchers and considerable effort has been put toward enabling home automation. However, these technologies have not been widely adopted despite being available for over three decades. To gain insight into this state of affairs, we conducted semi-structured home visits to 14 households with home automation. The long term experience, both positive and negative, of the households we interviewed illustrates four barriers that need to be addressed before home automation becomes amenable to broader adoption. These barriers are high cost of ownership, inflexibility, poor manageability, and difficulty achieving security. Our findings also provide several directions for further research, which include eliminating the need for structural changes for installing home automation, providing users with simple security primitives that they can confidently configure, and enabling composition of home devices.
Carbamazepine in manic-depressive illness: a new treatment (1980)

The authors evaluated carbamazepine (Tegretol), a drug of choice for treatment of temporal lobe epilepsy, in a double-blind placebo-controlled trial in patients with manic-depressive illness. Seven of 9 manic patients had a partial to marked response; several also showed relapses when placebo was substituted and improvement when carbamazepine was reinstituted. Five of 13 depressed patients showed significant improvement in depression ratings; 3 additional patients experienced partial relapse when placebo was substituted. Carbamazepine might also have prophylactic as well as acute efficacy in patients with both phases of manic-depressive illness, including some patients who do not respond to lithium. Therapeutic effects were achieved with 600-1600 mg/day at blood levels of 8-12 microgram/ml with relatively few side effects. Carbamazepine may prove to be a useful additional treatment for affective illness.
Ionizing radiation and aging: rejuvenating an old idea (2009)

This paper reviews the contemporary evidence that radiation can accelerate aging, degenerative health effects and mortality. Around the 1960s, the idea that ionizing radiation caused premature aging was dismissed as the radiation-induced health effects appeared to be virtually confined to neoplasms. More recently, radiation has become associated with a much wider spectrum of age-related diseases, including cardiovascular disease; although some diseases of old age, such as diabetes, are notably absent as a radiation risk. On the basis of recent research, is there a stronger case today to be made linking radiation and aging? Comparison is made between the now-known biological mechanisms of aging and those of radiation, including oxidative stress, chromosomal damage, apoptosis, stem cell exhaustion and inflammation. The association between radiation effects and the free-radical theory of aging as the causative hypothesis seems to be more compelling than that between radiation and the nutrient-sensing TOR pathway. Premature aging has been assessed by biomarkers in calorie restriction studies; yet, biomarkers such as telomere erosion and p16(INK4a) are ambiguous for radiation-induced aging. Some animal studies suggest low dose radiation may even demonstrate hormesis health benefits. Regardless, there is virtually no support for a life span extending hypothesis for A-bomb survivors and other exposed subjects.
Biochemical and pharmacological effects of the fermentation-derived antitumor agent, (alphaS,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (AT-125). (1979)

Abstract (αS,5S)-α-Amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (AT-125; α-amino-3-chloro-2-isoxazoline-5-acetic acid; U-42126; NSC 163501) is a fermentation-derived amino acid antimetabolite with significant antitumor activity. It has been shown previously to act in mammalian cells as a glutamine antagonist. In the present studies, AT-125 has been shown to exhibit sex-related toxicity towards mice; females are considerably more sensitive than males. Further, especially in male mice, toxicity appears to be age related, younger animals being more sensitive. Similar effects have been observed previously with another antitumor agent, 3-deazauridine, suggesting common biochemical mechanisms of action. Coadministration of testosterone with AT-125 alleviates the toxicity of the agent and, in L1210 leukemic mice, allows administration of higher doses and a resulting enhanced therapeutic activity. Cytidine triphosphate synthetase, a glutamine-dependent amidotransferase and the primary locus of 3-deazauridine activity, was also shown to be inhibited strongly by AT-125 (Ki 2 × 10−6m). The effects of AT-125 on L1210 cell ribonucleotide pools (elevation of uridine triphosphate levels, decreases in cytidine triphosphate and guanosine triphosphate levels) were consistent with such inhibition and also suggested that inhibition of another glutamine-dependent enzyme, xanthosine monophosphate aminase, might be important in the action of this agent. Further support for such a hypothesis was provided when it was observed that a combination of cytosine and guanosine ribonucleosides (or deoxyribonucleosides) acted synergistically in reversing the growth-inhibitory activity of AT-125 towards L1210 cells in culture.
AST Critical Propulsion and Noise Reduction Technologies for Future Commercial Subsonic Engines: Separate-Flow Exhaust System Noise Reduction Concept Evaluation (2000)

This report describes the work performed by General Electric Aircraft Engines (GEAE) and Allison Engine Company (AEC) on NASA Contract NAS3-27720 AoI 14.3. The objective of this contract was to generate quality jet noise acoustic data for separate-flow nozzle models and to design and verify new jet-noise-reduction concepts over a range of simulated engine cycles and flight conditions. Five baseline axisymmetric separate-flow nozzle models having bypass ratios of five and eight with internal and external plugs and 11 different mixing-enhancer model nozzles (including chevrons, vortex-generator doublets, and a tongue mixer) were designed and tested in model scale. Using available core and fan nozzle hardware in various combinations, 28 GEAE/AEC separate-flow nozzle/mixing-enhancer configurations were acoustically evaluated in the NASA Glenn Research Center Aeroacoustic and Propulsion Laboratory. This report describes model nozzle features, facility and data acquisition/reduction procedures, the test matrix, and measured acoustic data analyses. A number of tested core and fan mixing enhancer devices and combinations of devices gave significant jet noise reduction relative to separate-flow baseline nozzles. Inward-flip and alternating-flip core chevrons combined with a straight-chevron fan nozzle exceeded the NASA stretch goal of 3 EPNdB jet noise reduction at typical sideline certification conditions.
Cell sheet technology and cell patterning for biofabrication (2009)

We have developed cell sheet technology as a modern method for the fabrication of functional tissue-like and organ-like structures. This technology allows for a sheet of interconnected cells and cells in full contact with their natural extracellular environment to be obtained. A cell sheet can be patterned and composed according to more than one cell type. The key technology of cell sheet engineering is that a fabricated cell sheet can be harvested and transplanted utilizing temperature-responsive surfaces. In this review, we summarize different aspects of cell sheet engineering and provide a survey of the application of cell sheets as a suitable material for biofabrication and clinics. Moreover, since cell micropatterning is a key tool for cell sheet engineering, in this review we focus on the introduction of our approaches to cell micropatterning and cell co-culture to the principles of automation and how they can be subjected to easy robotics programming. Finally, efforts towards making cell sheet technology suitable for biofabrication and robotic biofabrication are also summarized.
Theory of Tackiness (1999)

We show that the interplay between surface roughness on micron scale and air suction can yield tack energies much higher than thermodynamic surface energies. Our model provides a quantitative interpretation of highly nonlinear force-versus-separation curves which are usually observed when adhesion forces and energies are high.
Methylene blue prevents retinal damage in an experimental model of ischemic proliferative retinopathy (2016)

Perinatal asphyxia induces retinal lesions, generating ischemic proliferative retinopathy, which may result in blindness. Previously, we showed that the nitrergic system was involved in the physiopathology of perinatal asphyxia. Here we analyze the application of methylene blue, a well-known soluble guanylate cyclase inhibitor, as a therapeutic strategy to prevent retinopathy. Male rats (n = 28 per group) were treated in different ways: 1) control group comprised born-to-term animals; 2) methylene blue group comprised animals born from pregnant rats treated with methylene blue (2 mg/kg) 30 and 5 min before delivery; 3) perinatal asphyxia (PA) group comprised rats exposed to perinatal asphyxia (20 min at 37°C); and 4) methylene blue-PA group comprised animals born from pregnant rats treated with methylene blue (2 mg/kg) 30 and 5 min before delivery, and then the pups were subjected to PA as above. For molecular studies, mRNA was obtained at different times after asphyxia, and tissue was collected at 30 days for morphological and biochemical analysis. Perinatal asphyxia produced significant gliosis, angiogenesis, and thickening of the inner retina. Methylene blue treatment reduced these parameters. Perinatal asphyxia resulted in a significant elevation of the nitrergic system as shown by NO synthase (NOS) activity assays, Western blotting, and (immuno)histochemistry for the neuronal isoform of NOS and NADPH-diaphorase activity. All these parameters were also normalized by the treatment. In addition, methylene blue induced the upregulation of the anti-angiogenic peptide, pigment epithelium-derived factor. Application of methylene blue reduced morphological and biochemical parameters of retinopathy. This finding suggests the use of methylene blue as a new treatment to prevent or decrease retinal damage in the context of ischemic proliferative retinopathy.
Synthesis of poly-3-hydroxyalkanoates is a common feature of fluorescent pseudomonads (1989)

The fluorescent pseudomonads are classified as a group, one characteristic of which is that they do not accumulate poly-3-hydroxybutyrate (PHB) during nutrient starvation in the presence of excess carbon source. In this paper we show that prototype strains from this subclass, such as Pseudomonas aeruginosa, Pseudomonas putida, and Pseudomonas fluorescens, do accumulate poly-3-hydroxyalkanoates (PHA) when grown on fatty acids. These PHAs are composed of medium-chain-length (C6 to C12) 3-hydroxy fatty acids. The ability to form these polyesters does not depend on the presence of plasmids. A specificity profile of the enzymes involved in the biosynthesis of PHA was determined by growing Pseudomonas oleovorans on fatty acids ranging from C4 to C18. In all cases, PHAs were formed which contained C6 to C12 3-hydroxy fatty acids, with a strong preference for 3-hydroxyoctanoate when Ceven fatty acids were supplied and 3-hydroxynonanoate when Codd fatty acids were the substrate. These results indicate that the formation of PHAs depends on a specific enzyme system which is distinct from that responsible for the synthesis of PHB. While the fluorescent pseudomonads are characterized by their inability to make PHB, they appear to share the capacity to produce PHAs. This characteristic may be helpful in classifying pseudomonads. It may also be useful in the optimization of PHA production for biopolymer applications.
Generalized penetration depth for penalty-based six-degree-of-freedom haptic rendering (2008)

SUMMARY Existing penalty-based haptic rendering approaches are based on the penetration depth estimation in strictly translational sense and cannot properly take object rotation into account. We propose a new six-degree-of-freedom (6-DOF) haptic rendering algorithm which is based on determining the closest-point projection of the inadmissible configuration onto the set of admissible configurations. Energy is used to define a metric on the configuration space. Once the projection is found the 6-DOF wrench can be computed from the generalized penetration depth. The space is locally represented with exponential coordinates to make the algorithm more efficient. Examples compare the proposed algorithm with the existing approaches and show its advantages.
A Laplace transform pair model for spectral reconstruction (1982)

A four-parameter Laplace transform pair model, which accurately reconstructs an experimental bremsstrahlung spectrum from attenuation data, is presented. Computed spectral values with both aluminum and copper attenuators generally agree with experimental 70-kVp data to better than 2%. Reconstructed spectra at other kVp's also show good agreement with published data.
Electrical properties of LaAlO3/Si and Sr0.8Bi2.2Ta2O9/LaAlO3/Si structures (2001)

Lanthanum aluminate (LaAlO3) films were deposited on Si(100) substrates by evaporating single-crystal pellets in vacuum using an electron-beam gun. Then, they were annealed in N2 ambience at 700 °C for 10 min using an electric furnace. X-ray diffraction analysis showed that the LaAlO3 films were amorphous even after the annealing process. No hysteretic characteristics were observed in the capacitance–voltage (C–V) measurement and the dielectric constant of the LaAlO3 films was estimated to be 21–25. It was also found that the leakage current density decreased by about three orders of magnitude after the annealing process. On these films, Sr0.8Bi2.2Ta2O9 films with 210 nm thickness were deposited by a sol–gel method. All samples annealed in O2 atmosphere at temperatures ranging from 650 to 750 °C showed hysteretic C–V characteristics, and the memory window width in the sample annealed at 750 °C for 30 min was about 3.0 V for a voltage sweep of ±10 V. It was also found that the capacitance values biased in the hysteresis loop were unchanged over 12 h.
Constrained Peptides: Models of Bioactive Peptides and Protein Substructures (1992)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
An in vivo structure-function study of armadillo, the beta-catenin homologue, reveals both separate and overlapping regions of the protein required for cell adhesion and for wingless signaling. (1996)

Armadillo, the Drosophila homologue of vertebrate beta-catenin, plays a pivotal role both in Wingless signaling and in assembly of adherens junctions. We performed the first in vivo structure-function study of an adherens junction protein, by generating and examining a series of Armadillo mutants in the context of the entire animal. We tested each mutant by assaying its biological function, its ability to bind proteins that normally associate with Armadillo in adherens junctions, its cellular localization, and its pattern of phosphorylation. We mapped the binding sites for DE-cadherin and alpha-catenin. Although these bind to Armadillo independently of each other, binding of each is required for the function of adherens junctions. We identified two separate regions of Armadillo critical for Wingless signaling. We demonstrated that endogenous Armadillo accumulates in the nucleus and provide evidence that it may act there in transducing Wingless signal. We found that the Arm repeats, which make up the central two-thirds of Armadillo, differ among themselves in their functional importance in different processes. Finally, we demonstrated that Armadillo's roles in adherens junctions and Wingless signaling are independent. We discuss the potential biochemical role of Armadillo in each process.
β1-Adrenergic Receptor Association with PSD-95 (2000)

The beta(1)-adrenergic receptor (beta(1)AR) is the most abundant subtype of beta-adrenergic receptor in the mammalian brain and is known to potently regulate synaptic plasticity. To search for potential neuronal beta(1)AR-interacting proteins, we screened a rat brain cDNA library using the beta(1)AR carboxyl terminus (beta(1)AR-CT) as bait in the yeast two-hybrid system. These screens identified PSD-95, a multiple PDZ domain-containing scaffolding protein, as a specific binding partner of the beta(1)AR-CT. This interaction was confirmed by in vitro fusion protein pull-down and blot overlay experiments, which demonstrated that the beta(1)AR-CT binds specifically to the third PDZ domain of PSD-95. Furthermore, the full-length beta(1)AR associates with PSD-95 in cells, as determined by co-immunoprecipitation experiments and immunofluorescence co-localization studies. The interaction between beta(1)AR and PSD-95 is mediated by the last few amino acids of the beta(1)AR, and mutation of the beta(1)AR carboxyl terminus eliminated the binding and disrupted the co-localization of the beta(1)AR and PSD-95 in cells. Agonist-induced internalization of the beta(1)AR in HEK-293 cells was markedly attenuated by PSD-95 co-expression, whereas co-expression of PSD-95 has no significant effect on either desensitization of the beta(1)AR or beta(1)AR-induced cAMP accumulation. Furthermore, PSD-95 facilitated the formation of a complex between the beta(1)AR and N-methyl-d-aspartate receptors, as assessed by co-immunoprecipitation. These data reveal that PSD-95 is a specific beta(1)AR binding partner that modulates beta(1)AR function and facilitates physical association of the beta(1)AR with synaptic proteins, such as the N-methyl-d-aspartate receptors, which are known to be regulated by beta(1)AR stimulation.
Gene Expression in the Mammalian Cochlea: A Study of Multiple Vector Systems (2001)

Successful delivery of genes to the inner ear has been demonstrated using a variety of vectors and animal models. As our understanding of the molecular pathophysiology of hearing and balance disorders increases, the delivery of genes is becoming central to our ability to manipulate the function of the inner ear. This study evaluates the efficacy of gene transfer and the distribution of three different vector types within the inner ear. Adenovirus vectors, herpes virus vectors and liposomes carrying a plasmid with the green fluorescent protein or beta galactosidase marker genes and a CMV promoter were introduced into the inner ear of 3-month-old mice. The temporal bones and brain were then removed from the animals and examined for transgene expression. Distribution of staining in the treated ear was compared with distribution of staining in the contralateral inner ear. Staining for T cell markers was also carried out to determine inner ear immune response to gene transfer. Herpes virus vectors appear to target neurons most efficiently. Liposome vectors were least efficient in terms of gene transfer. Adenovirus vectors accomplished gene transfer to the widest variety of inner ear cells including auditory and vestibular hair cells. Newer generation adenovirus vectors promise less immune reaction and toxicity than traditional vectors and will be useful for both research and future clinical applications.
CD38 knockout suppresses tumorigenesis in mice and clonogenic growth of human lung cancer cells (2017)

The ectodomain of the plasma membrane ectoenzyme CD38 functions as both an NAD glycohydrolase and an ADP-ribosyl cyclase by catalyzing, respectively, the conversion of NAD to nicotinamide and ADP-ribose or cyclic ADP-ribose. CD38 is attracting particular attention in cancer therapy. An anti-CD38 monoclonal antibody (daratumumab) was approved for treatment of patients with multiple myeloma. However, the role of CD38 in non-hematological malignancies has not been explored. Previously, we reported that ADP-ribose-acceptor hydrolase (ARH)-1 deficiency in mice was associated with tumor development. In the present study, we found that in wild-type and ARH1-deficient mice deletion of the CD38 gene reduced tumor formation. Significant reductions in tumor number were observed in lymphomas, adenocarcinomas and hemangio/histolytic sarcomas. Consistent with a role for CD38 in tumorigenesis, CRISPR/Cas9-based knockout of CD38 in A549 human adenocarcinoma cells inhibited anchorage-independent cell growth, cell invasion and xenograft growth in nude mice. CD38 mRNA and protein expression were evaluated in human lung cancer cell lines and in human lung cancer specimens. CD38 overexpression in tumor cells was identified in 11 of 27 patient samples. In addition, some human lung cancer cell lines had dramatically higher CD38 mRNA and protein expression than normal cells. Consistent with these observations, search of the Oncomine database showed that some human lung adenocarcinomas had higher CD38 mRNA levels compared to normal lung tissues. In total, our data are consistent with the conclusion that CD38 plays a role in murine and human lung tumorigenesis and that anti-CD38 treatment may have therapeutic potential in lung cancer.
Parallel Tempering: Theory, Applications, and New Perspectives (2008)

We review the history of the parallel tempering simulation method. From its origins in data analysis, the parallel tempering method has become a standard workhorse of physiochemical simulations. We discuss the theory behind the method and its various generalizations. We mention a selected set of the many applications that have become possible with the introduction of parallel tempering and we suggest several promising avenues for future research. 1