gebhart/patrepeval huggingface dataset:
Use of porous aluminosilicate pellets for drug delivery (2005)

Three pelletized porous aluminosilicate ceramics were obtained commercially and their potential to act as extended release drug delivery systems was assessed. The pellets were drug loaded using a vacuum impregnation technique. Factors such as the concentration of the loading solution and the porosity and bulk density of the ceramic influenced the drug loading. The release of drug from the pellets was extended as the drug was entrapped within their porous interior. The rate of release was influenced by the porous microstructure of the pellets and the physicochemical properties of the drug. Extrusion-spheronization was used to prepare pellets similar to the porous ceramics. The pellet formulations contained an aluminosilicate clay mineral (kaolin or halloysite), ethylcellulose 100 cps, ethanol and varying quantities of sucrose. The latter two components acted as pore forming agents. Diltiazem HCl was loaded into the pellets and its release was extended. The release rate could be modified by changing the quantity of sucrose included in the initial formulation, as this influenced the porous microstructure of the pellets. In halloysite-based products the release was further extended due to entrapment of the drug within the halloysite microtubules. Porous kaolin-based pellets were also prepared by cryopelletization. This involved freezing droplets of an aqueous suspension containing kaolin, sodium silicate solution and sodium lauryl sulphate. The resulting pellets were freeze-dried, which removed ice from them to leave pores behind. The pellets gave extended drug release with the release rate being influenced by the porous microstructure of the pellets and their microclimate pH.
MathPad 2 (2004)

We present mathematical sketching , a novel, pen-based, modeless gestural interaction paradigm for mathematics problem solving. Mathematical sketching derives from the familiar pencil-and-paper process of drawing supporting diagrams to facilitate the formulation of mathematical expressions; however, with a mathematical sketch, users can also leverage their physical intuition by watching their hand-drawn diagrams animate in response to continuous or discrete parameter changes in their written formulas. Diagram animation is driven by implicit associations that are inferred, either automatically or with gestural guidance, from mathematical expressions, diagram labels, and drawing elements. The modeless nature of mathematical sketching enables users to switch freely between modifying diagrams or expressions and viewing animations. Mathematical sketching can also support computational tools for graphing, manipulating and solving equations; initial feedback from a small user group of our mathematical sketching prototype application, MathPad 2 , suggests that it has the potential to be a powerful tool for mathematical problem solving and visualization.
The reactions of estrogens with benzeneseleninic anhydride and hexamethyldisilazane (1982)

Reaction of estrone and 17-ethynylestradiol with benzeneseleninic anhydride and hexamethyldisilazane gave predominantly the respective 4-phenylselenoimines, together with smaller amounts of the corresponding 2-substituted derivatives. Reductive acetylation of these compounds gave high yields of the 4- and 2-acetamidoderivatives of 3-acetoxyestrone and 3,17-diacetoxy-17-ethylnylestradiol respectively. Under similar conditions 4-bromoestrone gave the 2-phenylselenoimine which was then converted into 2-acetamido-3-acetoxy-4-bromoestra-1,3,5(10)-trien-17-one. This on hydrogenolysis furnished 2-acetamido-3-acetoxyestra-1,3,5(10)trien-17β-ol. A possible mechanistic rationalisation of these results is proposed.
Transcranial Alternating Current Stimulation Enhances Individual Alpha Activity in Human EEG (2010)

Non-invasive electrical stimulation of the human cortex by means of transcranial direct current stimulation (tDCS) has been instrumental in a number of important discoveries in the field of human cortical function and has become a well-established method for evaluating brain function in healthy human participants. Recently, transcranial alternating current stimulation (tACS) has been introduced to directly modulate the ongoing rhythmic brain activity by the application of oscillatory currents on the human scalp. Until now the efficiency of tACS in modulating rhythmic brain activity has been indicated only by inference from perceptual and behavioural consequences of electrical stimulation. No direct electrophysiological evidence of tACS has been reported. We delivered tACS over the occipital cortex of 10 healthy participants to entrain the neuronal oscillatory activity in their individual alpha frequency range and compared results with those from a separate group of participants receiving sham stimulation. The tACS but not the sham stimulation elevated the endogenous alpha power in parieto-central electrodes of the electroencephalogram. Additionally, in a network of spiking neurons, we simulated how tACS can be affected even after the end of stimulation. The results show that spike-timing-dependent plasticity (STDP) selectively modulates synapses depending on the resonance frequencies of the neural circuits that they belong to. Thus, tACS influences STDP which in turn results in aftereffects upon neural activity.The present findings are the first direct electrophysiological evidence of an interaction of tACS and ongoing oscillatory activity in the human cortex. The data demonstrate the ability of tACS to specifically modulate oscillatory brain activity and show its potential both at fostering knowledge on the functional significance of brain oscillations and for therapeutic application.
Growth Hormone and Dexamethasone Stimulate Lipolysis and Activate Adenylyl Cyclase in Rat Adipocytes by Selectively Shifting Gi 2 to Lower Density Membrane Fractions (1999)

GH, in the presence of glucocorticoid, produces a delayed increase in lipolysis in rat adipose tissue, but the biochemical mechanisms that account for this action have not been established. Other lipolytic agents rapidly activate adenylyl cyclase (AC) and the resulting production of cAMP initiates a chain of reactions that culminates in the activation of hormone-sensitive lipase. We compared responses of segments of rat epididymal fat or isolated adipocytes to 30 ng/ml GH and 0.1 μg/ml dexamethasone (Dex) with 0.1 ng/ml isoproterenol (ISO), which evoked a similar increase in lipolysis. All measurements were made during the fourth hour after the addition of GH+Dex or immediately after the addition of ISO to cells or tissues that had been preincubated for 3 h without hormone. Although no significant increases in cAMP were discernible in homogenates of GH+Dex-treated tissues, RP-cAMPS (RP-adenosine 3′5′-phosphothioate), a competitive inhibitor of cAMP, was equally effective in decreasing lipolysis induced by GH+Dex or ISO. The proportion of PKA that was present in the active form was determined by measuring the incorporation of 32P from[γ -32P]ATP into kemptide in the absence and presence of saturating amounts of cAMP. GH+Dex and ISO produced similar increases in protein kinase A activity in tissue extracts. Treatment with GH+Dex did not change the total forskolin-stimulated AC present in either a crude membrane pellet sedimented at 16K × g or a less dense membrane pellet sedimented at 100K × g, but doubled the AC activity in the 16K pellet when assayed in the absence of forskolin. To evaluate possible effects on G proteins, pellets obtained from centrifugation of adipocyte homogenates at 16K × g and 100K × g were solubilized and subjected to PAGE and Western analysis. GH+Dex decreased Giα2 by 44% (P < 0.02) in the 16K pellets and increased it by 52% (P < 0.01) in the 100K pellets. Gsα in the 16K pellet was unaffected by GH+Dex and was decreased (P < 0.05) in the 100K pellet. Sucrose density fractionation of the 16K pellets revealed a similar GH+Dex-dependent shift of Giα2 to less dense fractions as determined by both Western analysis and[ 32P]NAD ribosylation catalyzed by pertussis toxin. No such changes were seen in the distribution of Gsα or 5′-nucleotidase. Colchicine (100 μm) blocked the GH+Dex-dependent shift of Giα2 from the 16K to the 100K pellet and blocked the lipolytic effects of GH+Dex, but not those of ISO. We conclude that by modifying the relationship between AC and Giα2, GH+Dex relieves some inhibition of cAMP production and consequently increases lipolysis.
Mean Field Multi-Agent Reinforcement Learning (2018)

Existing multi-agent reinforcement learning methods are limited typically to a small number of agents. When the agent number increases largely, the learning becomes intractable due to the curse of the dimensionality and the exponential growth of agent interactions. In this paper, we present \emph{Mean Field Reinforcement Learning} where the interactions within the population of agents are approximated by those between a single agent and the average effect from the overall population or neighboring agents; the interplay between the two entities is mutually reinforced: the learning of the individual agent's optimal policy depends on the dynamics of the population, while the dynamics of the population change according to the collective patterns of the individual policies. We develop practical mean field Q-learning and mean field Actor-Critic algorithms and analyze the convergence of the solution to Nash equilibrium. Experiments on Gaussian squeeze, Ising model, and battle games justify the learning effectiveness of our mean field approaches. In addition, we report the first result to solve the Ising model via model-free reinforcement learning methods.
Mouse anti-ceramide antiserum: a specific tool for the detection of endogenous ceramide (2001)

Ceramide is a pivotal molecule in signal transduction and an essential structural component of the epidermal permeability barrier. The epidermis is marked by a high concentration of ceramide and by a unique spectrum of ceramide species: Besides the two ceramide structures commonly found in mammalian tissue, N-acylsphingosine and N-2-hydroxyacyl-sphingosine, six additional ceramides differing in the grade of hydroxylation of either the sphingosine base or the fatty acid have been identified in the epidermis. Here we report on the characterization of an IgM-enriched polyclonal mouse serum against ceramide. In dot blot assays with purified epidermal lipids the antiserum bound to a similar extent to N-acyl-sphingosine (ceramide 2), N-acyl-4-hydroxysphinganine (ceramide 3), and N-(2-hydroxyacyl)-sphingosine (ceramide 5), whereas no specific reaction was detected with glycosylceramides, sphingomyelin, free sphingosine, phospholipids, or cholesterol. In contrast, a monoclonal IgM antibody, also claimed to be specific for ceramide, was shown to bind specifically to sphingomyelin and therefore was not further investigated. In thin-layer chromatography immunostaining with purified lipids a strong and highly reproducible reaction of the antiserum with ceramide 2 and ceramide 5 was observed, whereas the reaction with ceramide 1 and ceramide 3 was weaker and more variable. Ceramide 2 and ceramide 5 were detected in the nanomolar range at serum dilutions of up to 1:100 by dot blot and thin-layer immunostaining. In thin-layer chromatography immunostaining of crude lipid extracts from human epidermis, the antiserum also reacted with N-(2-hydroxyacyl)-4-hydroxysphinganine (ceramide 6) and N-(2-hydroxyacyl)-6-hydroxysphingosine (ceramide 7). Furthermore, the suitability of the antiserum for the detection of endogenous ceramide by immunolight microscopy was demonstrated on cryoprocessed human skin tissue. Double immunofluorescence labeling experiments with the anti-ceramide antiserum and the recently described anti-glucosylceramide antiserum (Brade et al., 2000, Glycobiology 10, 629) showed that both lipids are concentrated in separate epidermal sites. Whereas anti-ceramide stained the dermal and basal epidermal cells as well as the corneocytes, anti-glucosylceramide staining was concentrated in the stratum granulosum. In conclusion, the specificity and sensitivity of the reagent will enable studies on the subcellular distribution and biological functions of endogenous ceramide.
Crystal Structure of Human Liver Δ4-3-Ketosteroid 5β-Reductase (AKR1D1) and Implications for Substrate Binding and Catalysis (2008)

AKR1D1 (steroid 5beta-reductase) reduces all Delta(4)-3-ketosteroids to form 5beta-dihydrosteroids, a first step in the clearance of steroid hormones and an essential step in the synthesis of all bile acids. The reduction of the carbon-carbon double bond in an alpha,beta-unsaturated ketone by 5beta-reductase is a unique reaction in steroid enzymology because hydride transfer from NADPH to the beta-face of a Delta(4)-3-ketosteroid yields a cis-A/B-ring configuration with an approximately 90 degrees bend in steroid structure. Here, we report the first x-ray crystal structure of a mammalian steroid hormone carbon-carbon double bond reductase, human Delta(4)-3-ketosteroid 5beta-reductase (AKR1D1), and its complexes with intact substrates. We have determined the structures of AKR1D1 complexes with NADP(+) at 1.79- and 1.35-A resolution (HEPES bound in the active site), NADP(+) and cortisone at 1.90-A resolution, NADP(+) and progesterone at 2.03-A resolution, and NADP(+) and testosterone at 1.62-A resolution. Complexes with cortisone and progesterone reveal productive substrate binding orientations based on the proximity of each steroid carbon-carbon double bond to the re-face of the nicotinamide ring of NADP(+). This orientation would permit 4-pro-(R)-hydride transfer from NADPH. Each steroid carbonyl accepts hydrogen bonds from catalytic residues Tyr(58) and Glu(120). The Y58F and E120A mutants are devoid of activity, supporting a role for this dyad in the catalytic mechanism. Intriguingly, testosterone binds nonproductively, thereby rationalizing the substrate inhibition observed with this particular steroid. The locations of disease-linked mutations thought to be responsible for bile acid deficiency are also revealed.
Corneal angiogenic privilege: angiogenic and antiangiogenic factors in corneal avascularity, vasculogenesis, and wound healing (an American Ophthalmological Society thesis). (2006)

Corneal angiogenic privilege is an active process involving the production of antiangiogenic factors to counterbalance the proangiogenic factors (which are upregulated after wound healing even in the absence of new vessels). Our finding that the potent antiangiogenic factors, angiostatin and endostatin, are colocalized with several MMPs during wound healing suggests that MMPs may be involved in the elaboration of these antiangiogenic molecules by proteolytic processing of substrates within the cornea.
Using neural networks for non-intrusive monitoring of industrial electrical loads (2002)

The success of demand side energy control in industries, mines and commercial buildings depends on factors like the energy sensitivity and awareness of the organisation as well as an accurate and effective measurement and monitoring of its electrical energy consumption. Demand side energy control also forms an important part in the research programs of many research organisations. Reliable data on energy consumption is therefore imperative for effective research in this field, as well as for the successful implementation of demand side management. Traditional load research instrumentation has involved intrusive techniques that require the installation of sensors on each of the individual components of the total load. A non-intrusive appliance load monitor is proposed in this paper to determine the energy consumption of individual appliances turning on or off or operating under continuously varying load conditions. This monitoring system, which is implemented by network pattern identification technology, is based on detailed analysis of the current and voltage of the total load, as measured at the interface of the power source. The approach has been developed to simplify the collection of energy consumption data by utilities, but also has other applications. It is called nonintrusive to contrast it with previous techniques for gathering appliance data, which require placing sensors on individual appliances, and hence an intrusion onto the energy consumer's properly.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Biological defence mechanism in the pathogenesis of prolonged cerebral vasospasm in the patients with ruptured intracranial aneurysms. (1986)

We examined the relationship between the biological protective mechanisms of scavengers and free radicals that are elicited by subarachnoid hemorrhage (SAH) in the pathogenesis of prolonged vasospasm following ruptured intracranial aneurysm. The study included 25 patients treated by early surgery (within 72 hours after SAH). Lipid peroxides concentrations and the activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH-px) in the cerebrospinal fluid (CSF) were measured. The concentration of lipid peroxides increased significantly more (p less than 0.05) during the first 4 days after SAH in patients with symptomatic vasospasm than in those without. Patients with symptomatic vasospasm had a marked decrease in SOD activity on Days 3 and 4 followed by a gradual decrease, whereas the patients without spasm showed little change (difference between the groups, p less than 0.05). There was a significant difference in catalase activity reversal to SOD activity, but no difference in GSH-px activity. Thus, correlation was close between the increased lipid peroxides concentration and the decrease in SOD activity in CSF (p less than 0.05), suggesting an important mechanism in the pathogenesis of vasospasm.
Position of ester groups in the lipid A backbone of lipopolysaccharides obtained from Salmonella typhimurium. (1983)

Lipopolysaccharides extracted from the heptoseless mutant of Salmonella typhimurium G30/C21 were hydrolyzed with either 0.1 N HCl at 100 degrees C or treated twice with 20 mM sodium acetate, pH 4.5, at 100 degrees C for 45 min and finally purified by preparative thin layer chromatography to yield a structural series of mono- and diphosphoryl lipid A, respectively. Positive ion fast atom bombardment mass spectrometry of the diphosphoryl lipid A TLC-3 (a highly acylated major band) showed a major component with (M + H)+ ion of mass 1798, which fragmented to yield a (M - H2PO4)+ ion of mass 1700. Cleavage at the glycosidic bond gave rise to an oxonium ion fragment of mass 1087. In conjunction with other studies, this establishes the molecular formula and Mr of the major component to be C94H178N2O25P2 and 1797.2 (as the free acid), respectively. Similar analysis of monophosphoryl lipid A TLC-3 produced an (M + H)+ peak at m/z 1718, (M + Na)+ adduct peak at m/z 1740, and a fragment of mass 1087. The spectrum of monophosphoryl lipid A TLC-5 was devoid of the m/z 1087 peak and instead contained the phosphorylated oxonium ion of mass 876. This fragment ion is assigned as the distal subunit, and these results show that the distal subunit of the major lipid A TLC-3 contains two hydroxymyristoyl, one myristoyl, and one lauroyl residues, whereas the reducing end subunit contains two hydroxymyristoyl groups. A revised structure of the lipid A backbone in lipopolysaccharides of S. typhimurium is proposed.
Oil shale retorting processes: A technical overview (1984)

The challenge facing the oil shale industry is to devise a simple and efficient retorting process that operates at low cost. This will require a thorough understanding of the important physical and chemical processes that occur during retorting, mathematical modeling to analyze the complex interactions, and sophisticated engineering to design a retorting process having the minimum cost. Retorting processes can be classified into two groups, one using hot gas as the heat transfer medium and one using hot solid material. The authors have constructed mathematical models of two generic processes from each of these groups to represent state-of-the-art processes as well as those under development. The models are based on detailed reaction kinetics, thermodynamics, and process physics. Using these models, they have calculated the process characteristics and the complete mass and energy balances for 50,000-barrel/day shale oil plants. They made comparisons of these four processes to illustrate their advantages and disadvantages. The comparisons include retort vessel volume, heat exchange capacity, power requirements, water requirements, and waste gas volume. The results indicate no present easy choice of a best process. Oil shale process technology is neither highly developed nor mature, and substantial improvements can be expected from further research and development,more » and from industrial experience. The hot gas processes can be viewed as first-generation technology, and the hot solid processes, if they can be successfully developed, may be second-generation technology.« less
Lateral vacuum microelectronic logic gate design (1991)

A detailed calculation of static electric fields and electron trajectories is used for designs of vacuum microelectronic NOR and NAND logic gates based on a wedge-shaped field emission cathode. A basic pentode device that permits a compact physical layout has lateral electron trajectories and a field emission wedge-shaped cathode. Electric fields at the cathode surface are calculated using a special zooming technique based on a 1600-point spatial matrix. Cathode current is calculated using the Fowler-Nordheim equation form but with constants adjusted to match available experimental data. The gates modeled are direct-coupled-vacuum-microelectronic logic (DCVML) capable of large fan-in and fan-out. The basic pentode device modeled with a 1 mu m cathode-to-extraction grid spacing has total layout dimension of 17 mu m. The pentode device geometry greatly reduces a major problem of high grid current by making use of two deflector electrodes. The deflectors also provide trajectory confinement to reduce the device size.
Herpes Simplex Encephalitis (1982)

Continuing evaluations of antiviral agents for treatment of herpes simplex encephalitis (HSE) provided an opportunity to collect clinical data from 113 patients in whom the diagnosis was proved by viral isolation. Occurrence of HSE was in all ages and in both sexes and was nonseasonal. Characteristically, patients had behavioral changes, fever, confusion, speech disturbances, and, less frequently, seizures. The EEG was the most useful neurodiagnostic aid followed by technetium and computed axial tomographic scans. Employing a logistic regression model for variable selection, the diagnosis could be predicted by clinical findings and neurodiagnostic tests in 83% of the proved cases, but the evidence in 25% was falsely positive. There was evidence of localization by either clinical or neurodiagnostic assessment in all patients with proved disease. Among patients wtih negative findings for HSE, similar focal findings predominated in all but a few. The CSF and brain scans were normal in many patients with proved HSE. This extensive clinical experience in patients wtih diagnosis proved by viral isolation shows that diagnosis cna be confirmed only by brain biopsy.