gebhart/patrepeval huggingface dataset:
Adaptive fuzzy logic control of discrete-time dynamical systems (2002)

This paper demonstrates tracking control of a class of unknown nonlinear dynamical systems using a discrete-time fuzzy logic controller (FLC). Designing a discrete-time FLC is significant because almost all FLCs are implemented on digital computers. A repeatable design algorithm and a stability proof are presented for an adaptive fuzzy logic controller that uses basis vectors based on the fuzzy system, unlike most standard adaptive control approaches which use basis vectors depending on the unknown plant (e.g. a tediously computed "regression matrix"). The authors select an e-modification sort of approach to adapt the fuzzy system parameters. Using this adaptive fuzzy logic controller, the authors prove uniform ultimate boundedness of the closed-loop signals and that the controller achieves tracking. In fact, the fuzzy system designed is a model-free universal fuzzy controller that works for any system in the given class of systems.
The Nature of Genetic Influences on Behavior: Lessons From “Simpler” Organisms (2006)

Substantial advances have been made in recent years in the understanding of the genetic basis of behavior in "simpler" organisms, especially the mouse and the fruit fly Drosophila. The authors examine the degree of similarity between the genetic underpinnings of psychiatric illness and genetic influences on behavior in such simpler organisms. Six topics are reviewed: 1) the extent of natural genetic variation, 2) the multigenic nature of natural variation, 3) the impact of individual genes on multiple traits, 4) gene-environment interactions, 5) genetic effects on the environment, and 6) gene-by-sex interactions. The results suggest that the pattern of results emerging in psychiatric genetics is generally consistent with the findings of behavioral genetics in simpler organisms. Across the animal kingdom, individual differences in behavior are nearly always influenced by genetic factors which, in turn, result from a substantial number of individual genes, each with a small effect. Nearly all genes that affect behavior influence multiple phenotypes. The impact of individual genes can be substantially modified by other genes and/or by environmental experiences. Many animals alter their environment, and the nature of that alteration is influenced by genes. For some behaviors, the pathway from genes to behavior differs meaningfully in males and females. With respect to the broad patterns of genetic influences on behavior, Homo sapiens appears to be typical of other animal species.
CB1 Cannabinoid Receptors Modulate Kinase and Phosphatase Activity During Extinction of Conditioned Fear in Mice (2004)

Cannabinoid receptors type 1 (CB1) play a central role in both short-term and long-term extinction of auditory-cued fear memory. The molecular mechanisms underlying this function remain to be clarified. Several studies indicated extracellular signal-regulated kinases (ERKs), the phosphatidylinositol 3-kinase with its downstream effector AKT, and the phosphatase calcineurin as potential molecular substrates of extinction behavior. To test the involvement of these kinase and phosphatase activities in CB1-dependent extinction of conditioned fear behavior, conditioned CB1-deficient mice (CB1(-/-)) and wild-type littermates (CB1(+/+)) were sacrificed 30 min after recall of fear memory, and activation of ERKs, AKT, and calcineurin was examined by Western blot analysis in different brain regions. As compared with CB1(+/+), the nonreinforced tone presentation 24 h after auditory-cued fear conditioning led to lower levels of phosphorylated ERKs and/or calcineurin in the basolateral amygdala complex, ventromedial prefrontal cortex, dorsal hippocampus, and ventral hippocampus of CB1(-/-). In contrast, higher levels of phosphorylated p44 ERK and calcineurin were observed in the central nucleus of the amygdala of CB1(-/-). Phosphorylation of AKT was more pronounced in the basolateral amygdala complex and the dorsal hippocampus of CB1(-/-). We propose that the endogenous cannabinoid system modulates extinction of aversive memories, at least in part via regulation of the activity of kinases and phosphatases in a brain structure-dependent manner.
Human Psychometric and Taste Receptor Responses to Steviol Glycosides (2012)

Steviol glycosides, the sweet principle of Stevia Rebaudiana (Bertoni) Bertoni, have recently been approved as a food additive in the EU. The herbal non-nutritive high-potency sweeteners perfectly meet the rising consumer demand for natural food ingredients in Europe. We have characterized the organoleptic properties of the most common steviol glycosides by an experimental approach combining human sensory studies and cell-based functional taste receptor expression assays. On the basis of their potency to elicit sweet and bitter taste sensations, we identified glycone chain length, pyranose substitution, and the C16 double bond as the structural features giving distinction to the gustatory profile of steviol glycosides. A comprehensive screening of 25 human bitter taste receptors revealed that two receptors, hTAS2R4 and hTAS2R14, mediate the bitter off-taste of steviol glycosides. For some test substances, e.g., stevioside, we observed a decline in sweet intensity at supra-maximum concentrations. This effect did not arise from allosteric modulation of the hTAS1R2/R3 sweet taste receptor but might be explained by intramolecular cross-modal suppression between the sweet and bitter taste component of steviol glycosides. These results might contribute to the production of preferentially sweet and least bitter tasting Stevia extracts by an optimization of breeding and postharvest downstream processing.
Photoremovable Protecting Groups in Organic Synthesis (1980)

The applications of light-sensitive protecting groups which can be removed by photolysis in the synthesis of organic compounds are reviewed. The use of groups such as 2-nitrobenzyl, benzyloxycarbonyl, 3-nitrophenyl, phenacyl, 3,5-dimethoxybenzoinyl, and 2, 4-dinitrobenzenesulphenyl for the blocking of various functional groups is reviewed with particular emphasis on their application in syntheses involving polyfunctional molecules. The methods for the incorporation of the protecting group, subsequent synthetic steps, and the final removal of the employed protecting group are illustrated with specific examples. The important applications of these groups in carbohydrate chemistry, nucleotide synthesis, and peptide synthesis on polymeric supports are discussed. 1. Introduction 2. 2-Nitrobenzyl and Related Groups 2.1. 2-Nitrobenzyl and α-Substituted 2-Nitrobenzyl Groups 2.2. 2-Nitrobenzyloxycarbonyl and α-Substituted 2-Nitrobenzyloxycarbonyl Groups 2.3. 2-Nitrophenylethyleneglycol Group 3. Benzyloxycarbonyl and Related Groups 3.1. Benzyloxycarbonyl Group 3.2. 3,5-Dimethoxybenzyloxycarbonyl Group 3.3. α,α-Dimethyl-3,5-dimethoxybenzyloxycarbonyl Group 4. 3-Nitrobenzyl and Related Groups 4.1. 3-Nitrophenyloxy and 3,5-Dinitrophenyloxy Groups 4.2. 3-Nitrophenyloxycarbonyl Group 5. Phenacyl Groups 5.1. 4-Methoxyphenacyl Group 5.2. α-Methylphenacyl Group 6. 3,5-Dimethoxybenzoinyl Groups 7. 2,4-Dinitrobenzenesulphenyl Group 8. Other Miscellaneous Groups 9. Specific Applications 9.1. Carbohydrate Synthesis 9.2. Nucleotide Synthesis 9.3. Polymer-Based Peptide Synthesis 10. Conclusions
Marching cubes: A high resolution 3D surface construction algorithm (1987)

We present a new algorithm, called marching cubes , that creates triangle models of constant density surfaces from 3D medical data. Using a divide-and-conquer approach to generate inter-slice connectivity, we create a case table that defines triangle topology. The algorithm processes the 3D medical data in scan-line order and calculates triangle vertices using linear interpolation. We find the gradient of the original data, normalize it, and use it as a basis for shading the models. The detail in images produced from the generated surface models is the result of maintaining the inter-slice connectivity, surface data, and gradient information present in the original 3D data. Results from computed tomography (CT), magnetic resonance (MR), and single-photon emission computed tomography (SPECT) illustrate the quality and functionality of marching cubes . We also discuss improvements that decrease processing time and add solid modeling capabilities.
A Dominant-Negative Inhibitor of CREB Reveals that It Is a General Mediator of Stimulus-Dependent Transcription of c-fos (1998)

Several studies have characterized the upstream regulatory region of c-fos, and identified cis-acting elements termed the cyclic AMP (cAMP) response elements (CREs) that are critical for c-fos transcription in response to a variety of extracellular stimuli. Although several transcription factors can bind to CREs in vitro, the identity of the transcription factor(s) that activates the c-fos promoter via the CRE in vivo remains unclear. To help identify the trans-acting factors that regulate stimulus-dependent transcription of c-fos via the CREs, dominant-negative (D-N) inhibitor proteins that function by preventing DNA binding of B-ZIP proteins in a dimerization domain-dependent fashion were developed. A D-N inhibitor of CREB, termed A-CREB, was constructed by fusing a designed acidic amphipathic extension onto the N terminus of the CREB leucine zipper domain. The acidic extension of A-CREB interacts with the basic region of CREB forming a coiled-coil extension of the leucine zipper and thus prevents the basic region of wild-type CREB from binding to DNA. Other D-N inhibitors generated in a similar manner with the dimerization domains of Fos, Jun, C/EBP, ATF-2, or VBP did not block CREB DNA binding activity, nor did they inhibit transcriptional activation of a minimal promoter containing a single CRE in PC12 cells. A-CREB inhibited activation of CRE-mediated transcription evoked by three distinct stimuli: forskolin, which increases intracellular cAMP; membrane depolarization, which promotes Ca2+ influx; and nerve growth factor (NGF). A-CREB completely inhibited cAMP-mediated, but only partially inhibited Ca2+- and NGF-mediated, transcription of a reporter gene containing 750 bp of the native c-fos promoter. Moreover, glutamate induction of c-fos expression in primary cortical neurons was dependent on CREB. In contrast, induction of c-fos transcription by UV light was not inhibited by A-CREB. Lastly, A-CREB attenuated NGF induction of morphological differentiation in PC12 cells. These results suggest that CREB or its closely related family members are general mediators of stimulus-dependent transcription of c-fos and are required for at least some of the long-term actions of NGF.
Role of Insulin Resistance in Human Disease (1988)

Resistance to insulin-stimulated glucose uptake is present in the majority of patients with impaired glucose tolerance (IGT) or non-insulin-dependent diabetes mellitus (NIDDM) and in approximately 25% of nonobese individuals with normal oral glucose tolerance. In these conditions, deterioration of glucose tolerance can only be prevented if the beta-cell is able to increase its insulin secretory response and maintain a state of chronic hyperinsulinemia. When this goal cannot be achieved, gross decompensation of glucose homeostasis occurs. The relationship between insulin resistance, plasma insulin level, and glucose intolerance is mediated to a significant degree by changes in ambient plasma free-fatty acid (FFA) concentration. Patients with NIDDM are also resistant to insulin suppression of plasma FFA concentration, but plasma FFA concentrations can be reduced by relatively small increments in insulin concentration. Consequently, elevations of circulating plasma FFA concentration can be prevented if large amounts of insulin can be secreted. If hyperinsulinemia cannot be maintained, plasma FFA concentration will not be suppressed normally, and the resulting increase in plasma FFA concentration will lead to increased hepatic glucose production. Because these events take place in individuals who are quite resistant to insulin-stimulated glucose uptake, it is apparent that even small increases in hepatic glucose production are likely to lead to significant fasting hyperglycemia under these conditions. Although hyperinsulinemia may prevent frank decompensation of glucose homeostasis in insulin-resistant individuals, this compensatory response of the endocrine pancreas is not without its price. Patients with hypertension, treated or untreated, are insulin resistant, hyperglycemic, and hyperinsulinemic. In addition, a direct relationship between plasma insulin concentration and blood pressure has been noted. Hypertension can also be produced in normal rats when they are fed a fructose-enriched diet, an intervention that also leads to the development of insulin resistance and hyperinsulinemia. The development of hypertension in normal rats by an experimental manipulation known to induce insulin resistance and hyperinsulinemia provides further support for the view that the relationship between the three variables may be a causal one.(ABSTRACT TRUNCATED AT 400 WORDS)
Vasculogenesis and angiogenesis in embryonic-stem-cell-derived embryoid bodies (1988)

Embryonic stem cells (ESC) have been established previously from the inner cell mass cells of mouse blastocysts. In suspension culture, they spontaneously differentiate to blood-island-containing cystic embryoid bodies (CEB). The development of blood vessels from in situ differentiating endothelial cells of blood islands, a process which we call vasculogenesis, was induced by injecting ESC into the peritoneal cavity of syngeneic mice. In the peritoneum, fusion of blood islands and formation of an in vivo-like primary capillary plexus occurred. Transplantation of ESC and ESC-derived complex and cystic embryoid bodies (ESC-CEB) onto the quail chorioallantoic membrane (CAM) induced an angiogenic response, which was directed by nonyolk sac endoderm structures. Neither yolk sac endoderm from ESC-CEB nor normal mouse yolk sac tissue induced angiogenesis on the quail CAM. Extracts from ESC-CEB stimulated the proliferation of capillary endothelial cells in vitro. Mitogenic activity increase during in vitro culture and differentiation of ESC. Almost all growth factor activity was associated with the cells. The ESC-CEB derived endothelial cell growth factor bound to heparin-sepharose. The identification of acidic fibroblast growth factor (FGF)in heparin-sepharose-purified material was accomplished by immunoblot experiments involving antibodies against acidic and basic FGF. We conclude that vasculogenesis, the development of blood vessels from in situ differentiating endothelial cells, and angiogenesis, the sprouting of capillaries from preexisting vessels are very early events during embryogenesis which can be studied using ESC differentiating in vitro. Our results suggest that vasculogenesis and angiogenesis are differently regulated.
Meta-Analysis of the Effect of Insulin Lispro on Severe Hypoglycemia in Patients With Type 1 Diabetes (1998)

The results of this meta-analysis demonstrate that in type 1 diabetic patients, the frequency of severe hypoglycemia can be reduced by taking insulin lispro as compared with regular human insulin therapy.
Proto-TAI: Quick Design Prototyping Using Tangible Assisted Interfaces (2014)

In the real world, we use our innate manual dexterity to create and manipulate 3D objects. Conventional virtual design tools largely neglect this skill by imposing non-intuitive 2D control mechanisms for interacting with 3D design models. Their usage is thus cumbersome, time consuming and requires training. We propose a novel design paradigm that combines users’ manual dexterity with the physical affordances of non-instrumented and ordinary objects to support virtual 3D design constructions. We demonstrate this paradigm through Proto-TAI, a quick prototyping application where 2D shapes are assembled into 3D representations of ideated design concepts. Here, users can create 2D shapes in a pen-based sketch medium and use expressive handheld movements of a planar proxy to configure the shapes in 3D space. The proxy provides a metaphorical means for possessing and controlling the shapes. Here, a depth sensor and computer vision algorithms track the proxy’s spatial movement. The 3D design prototype constructed in our system can be fabricated using a laser cutter and physically assembled on-the-fly. Our system has vast implications in many design and assembly contexts, and we demonstrate its usability and efficacy through user studies and evaluations.
Nox4 NAD(P)H Oxidase Mediates Hypertrophy and Fibronectin Expression in the Diabetic Kidney (2005)

Renal hypertrophy and extracellular matrix accumulation are early features of diabetic nephropathy. We investigated the role of the NAD(P)H oxidase Nox4 in generation of reactive oxygen species (ROS), hypertrophy, and fibronectin expression in a rat model of type 1 diabetes induced by streptozotocin. Phosphorothioated antisense (AS) or sense oligonucleotides for Nox4 were administered for 2 weeks with an osmotic minipump 72 h after streptozotocin treatment. Nox4 protein expression was increased in diabetic kidney cortex compared with non-diabetic controls and was down-regulated in AS-treated animals. AS oligonucleotides inhibited NADPH-dependent ROS generation in renal cortical and glomerular homogenates. ROS generation by intact isolated glomeruli from diabetic animals was increased compared with glomeruli isolated from AS-treated animals. AS treatment reduced whole kidney and glomerular hypertrophy. Moreover, the increased expression of fibronectin protein was markedly reduced in renal cortex including glomeruli of AS-treated diabetic rats. Akt/protein kinase B and ERK1/2, two protein kinases critical for cell growth and hypertrophy, were activated in diabetes, and AS treatment almost abolished their activation. In cultured mesangial cells, high glucose increased NADPH oxidase activity and fibronectin expression, effects that were prevented in cells transfected with AS oligonucleotides. These data establish a role for Nox4 as the major source of ROS in the kidneys during early stages of diabetes and establish that Nox4-derived ROS mediate renal hypertrophy and increased fibronectin expression.
Cowpea mosaic virus chimeric particles bearing the ectodomain of matrix protein 2 (M2E) of the influenza a virus: Production and characterization (2009)

The epitope presentation system for ectodomain of M2-protein of influenza A virus (M2e) based on Cowpea Mosaic Virus (CPMV) was constructed for expression in plants Vigna unguiculata. CPMV is widely used as a vector for production of immunogenic chimeric virus particles (CVPs) bearing epitopes of different infectious human and animal pathogens. To produce chimeric CPMV virus particles in plants, two binary vectors were constructed bearing modified gene coding for S-coat protein of CPMV with insertions of M2e epitopes of human influenza and bird influenza viruses. Antigenic and immunogenic properties of CVPs obtained were investigated in mice immunization experiments and it was shown that they can induce anti-M2e IgG production and partial protection mice against challenge with low doses of flu virus. However, low infectivity and immunogenicity of CPMV chimeric particles indicate the need for further optimization of plant virus-based systems for M2e-epitopes presentation to use plants as a possible source of flu vaccines.
Immediate S-100B and Neuron-Specific Enolase Plasma Measurements for Rapid Evaluation of Primary Brain Damage in Alcohol-Intoxicated, Minor Head-Injured Patients (2002)

The neuroproteins S-100B and neuron-specific enolase (NSE) released into the circulation are suggested to be reliable markers for primary brain damage. However, safe identification of relevant post-traumatic complications after minor head injury (MHI) is often hampered by acute intoxication of the patients. The objective of this study was to determine the diagnostic validity of immediate plasma measurements of S-100B and NSE in comparison with neurological examinations and cerebral computed tomography (CCT) findings in alcohol-intoxicated MHI patients. One hundered thrity-nine MHI individuals were enrolled in this prospective study during Munich's Oktoberfest 2000. Plasma levels of S-100B and NSE as well as serum alcohol and glucose values were determined by fully automated assays immediately after admission. The results were compared with Glasgow Coma Scale score, a brief neurological examination, and the CCT findings. Without being influenced by alcohol, median S-100B levels of the CCT+ group were significantly increased compared with those of the CCT- group (P < 0.001). NSE, alcohol, and glucose levels showed no significant group differences. As calculated by the ROC analysis, a cutoff value of 0.21 ng/mL with an area under the curve of 0.864 clearly differentiates between CCT+ and CCT- patients at a sensitivity of 100%, a specificity of 50.0%, and a positive likelihood ratio of 2.0. Although acute alcohol intoxication did not confound plasma measurements of S-100B and NSE, only S-100B levels below the cutoff level of 0.21 ng/mL seem to indicate absence of primary brain damage. Thus, in addition to routine neurological examinations, S-100B measurements immediately after admission might help to reduce CCT scans in alcohol-intoxicated patients early after MHI.
RETRACTED: Hierarchical Organization of Guidance Receptors: Silencing of Netrin Attraction by Slit Through a Robo/DCC Receptor Complex (2001)

Axonal growth cones that cross the nervous system midline change their responsiveness to midline guidance cues: They become repelled by the repellent Slit and simultaneously lose responsiveness to the attractant netrin. These mutually reinforcing changes help to expel growth cones from the midline by making a once-attractive environment appear repulsive. Here, we provide evidence that these two changes are causally linked: In the growth cones of embryonic Xenopus spinal axons, activation of the Slit receptor Roundabout (Robo) silences the attractive effect of netrin-1, but not its growth-stimulatory effect, through direct binding of the cytoplasmic domain of Robo to that of the netrin receptor DCC. Biologically, this hierarchical silencing mechanism helps to prevent a tug-of-war between attractive and repulsive signals in the growth cone that might cause confusion. Molecularly, silencing is enabled by a modular and interlocking design of the cytoplasmic domains of these potentially antagonistic receptors that predetermines the outcome of their simultaneous activation.
Spermidine/spermine N 1 ‐acetyltransferase — the turning point in polyamine metabolism (1993)

Polyamines are thought to have several vital roles in cell growth and differentiation. The highly regulated polyamine metabolic pathway provides cells with the ability to finely control the intracellular concentration of these ubiquitous polycations. Although earlier studies of regulation of polyamine content were concentrated on the biosynthetic reactions, recently the importance of the catabolic processes, particularly the highly regulated acetylation step in polyamine degradation, has become apparent. This work has led to an understanding of how a cell may, in a tightly controlled manner, facilitate the breakdown, excretion, cycling, and/or intracellular shuttling of the polyamines. This myriad of possibilities appears to be regulated initially at a single rate-limiting enzymatic step, the N1-acetylation of spermidine or spermine, by spermidine/spermine N1-acetyltransferase (SSAT). Recent cloning of the human SSAT gene has facilitated a more detailed study of this enzyme. SSAT appears to have a role in the determination of tumor sensitivity to a new class of antineoplastic agents. The further study of SSAT and the associated polyamine metabolism should provide a better understanding of the regulation and function of these cations.