gebhart/patrepeval huggingface dataset:
Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, 1994: THE ALLOMETRIC APPROACH FOR INTERSPECIES SCALING OF PHARMACOKINETICS AND TOXICITY OF ANTI‐CANCER DRUGS (1995)

1. The rationale for extrapolation or 'scaling' across animal species is based on their underlying anatomical, physiological and biochemical similarities. 2. Research carried out in the 19th and early 20th century resulted in Benedict's famous 'mouse-to-elephant' graph which showed that the log of the basal metabolic rate plotted against the log of bodyweight (W) produced a straight line with a slope of 0.76. Since then it has become apparent that a number of other physiological variables (Y) exhibit a similar relationship which can be represented by the general allometric equation, Y = alpha W beta; where beta is the slope of the log-log plot and alpha is the intercept on the y axis. 3. The major pharmacokinetic parameters such as clearance and volume of distribution of many drugs are also related to W in a similar manner. 4. This empirical approach does not require a strong mathematical background and offers a relatively simple method of predicting the kinetics of anti-cancer drugs in patients from pre-clinical animal data. 5. The occurrence of major qualitative and quantitative differences in the metabolism of drugs between species is probably the single greatest complicating factor in the use of animals as predictors of drug toxicity and kinetics in patients. 6. Despite this, the allometric approach is useful for allowing the estimation of a more appropriate starting dose for some drugs in a Phase I trial, which might result in potential savings in escalation steps and maximize the chance that the dose which an individual receives has the potential for therapeutic value.
Distributed Fault Detection and Estimation for Cooperative Adaptive Cruise Control System in a Platoon (2015)

   Wireless vehicle to vehicle communication in a vehicle platoon is proposed in intelligent transportation systems to increase safety of the transportation system and assist drivers for improved decision making. However, similar to any networked system, cooperative connected vehicles in a platoon are vulnerable to malfunction due to failures in network communication. In addition to the possible data corruption, sensor and actuator faults can have significant effects on the control strategy for cruise control. This paper considers a platoon of connected vehicles equipped with cooperative adaptive cruise control and presents a reconstructive method based on sliding mode observer to estimate and reconstruct the faults in the sensors and actuators of vehicles.
Properties of a baculovirus mutant defective in the protein phosphatase gene (1995)

Autographa california nuclear polyhedrosis virus (AcMNPV) contains a gene, ptp, encoding a protein tyrosine/serine phosphatase, BV-PTP. To investigate the biological function of ptp in the baculoviral replication cycle, we constructed a recombinant baculovirus, vPTPdel, in which the catalytically active site of BV-PTP was deleted. Although the vPTPdel mutant was viable in cell culture, it was partially defective in occluded virus production in SF-21 but not TN-368 cell lines. SF-21 cells infected with vPTPdel were heterogeneous in their ability to support occluded virus production. These results suggest that BV-PTP functions in a cell line-specific and possibly a cell cycle-specific fashion. The yield of occlusion bodies, infectivity (concentration of virus causing 50% mortality) and virulence (the time at which 50% of the cells died) of vPTPdel appeared to be normal in insect larvae. We identified a 35-kDa phosphoprotein as a potential target of the BV-PTP in SF-21 cells.
The Role of Hepatic AMPK in Metabolic Adaptation under High‐Protein Diet (2015)

High protein diets are recognized to reduce food intake and body fat gain. As hepatic AMPK is involved in the transduction of both amino acid signals and energy sensing, we tested the hypothesis that high protein diets can affect metabolism via this pathway. We, therefore, compared the metabolic responses of wild type and liver‐specific AMPK‐KO mice to a low, normal and high protein diet. 24 wild–type (WT) and 24 liver specific AMPK‐KO (KO) C57BL/6 mice were respectively split in 3 groups (N=8/group) fed during 3 weeks on a low (5%, LP) normal (14%, NP) and high (55%, HP) protein diet. Food intake was measured, body composition was followed by Dual energy X‐ray absorptiometry and changes in the rates of glucose and lipid oxidation were assessed by indirect calorimetry following ingestion of a calibrated test meal. No difference in fat mass gain or food intake was observed between WT and KO mice under LP and HP diet but KO mice tended to eat more and to gain less fat mass when fed the NP diet. Results from indirect calorimetry showed that in KO mice fed the HP and LP diets the increase in glucose oxidation and decrease in lipid oxidation induced by ingestion of the test meal were of lower amplitude than in WT mice. Under NP diet, the responses were of the same amplitude but occurred with a delay of ~2 hours. This study suggests that consequences of the knockout of liver AMPK on energy homeostasis depend on the protein content of the diet; we observed no significant effect under LP and HP despite significant alterations of post‐meal glucose and lipid metabolism. In contrast, we observed reduced energy efficiency under NP diet associated with delayed changes in fuel oxidations after meal ingestion.
Organic Nanoparticles: Mechanism of Electron Transfer to Indigo Nanoparticles (2014)

Abstract Organic nanoparticles are attracting many significant applications in bio‐imaging and nanomedicine. However, in comparison with intensive studies of metal and inorganic nanoparticles, the research of organic nanoparticles is still at a very early stage due to their complex physical and chemical properties. Most recently, there are increasingly significant interests in developing nano‐capacitors and nano‐scale energy storage and sensor devices based on organic materials. Herein, we report for the first time the kinetics and mechanism of electron transfer to individual organic nanoparticles, using indigo nanoparticles as a model system, via analysis of the charge transferred in the reduction of individual organic nanoparticles. We conclude the indigo nanoparticles display irreversible (slow) electron transfer kinetics and that the charge transfer is the rate‐determining step in the reductive dissolution of the nanoparticles; protonation and detachment of molecules from the nanoparticles occurs after this rate‐determining step. The transfer coefficient, α , of the electron transfer is found to be 0.25±0.05, whilst the rate constant ( k 0 ) is determined as the composite parameter ${k^0 \exp \left( {{{0.25F} \over {RT}}E_{\rm{f}}^{\rm{{\rm \theta} }} } \right)}$ , where ${E_{\rm{f}}^{\rm{{\rm \theta} }} }$ is the formal potential, which is found to have the value of 1.7×10 −8 m s −1 . Given the high importance of the electron transfer mechanism for organic nanomaterials, this report may have great significance on future research of organic nanomaterials for diverse applications.
Ethanol Enhances Agonist-Induced Fast Desensitization in Nicotinic Acetylcholine Receptors (1994)

The reversible decline of the nicotinic acetylcholine receptor's response to acetylcholine during prolonged exposure to acetylcholine is known as desensitization. Here, we studied ethanol's modulation of fast agonist-induced desensitization of the nicotinic acetylcholine receptor in postsynaptic membrane vesicles from Torpedo using a fast kinetic technique: pulsed quenched flow. Preincubation of the vesicles with various concentrations of acetylcholine at 4 degrees C for times ranging from 80 ms to 1.5 s caused fast desensitization, which was revealed as a decreased 86Rb+ influx when the vesicles were subsequently briefly exposed to a saturating concentration of acetylcholine in 86RbCl. Acetylcholine-induced fast desensitization had a maximum observed rate, kdmax, of 6.8 s-1, a half-effect concentration, KD, of 157 microM, and a Hill coefficient of 1.4. Increasing the ethanol concentration up to 1.0 M causes a linear increase in kdmax, such that 1.0 M ethanol doubles the rate. Ethanol (1 M) also decreased KD 10-fold without changing the Hill coefficient. We consider a modified sequential model to interpret our data. Two acetylcholine molecules bind sequentially to the receptor's resting state to form a pre-open (closed) state, which then opens and, at very high acetylcholine concentrations, is inhibited. A priori fast desensitization might occur from any of these acetylcholine-occupied states. If we assume fast desensitization to occur solely from the pre-open state, our data predict an excessively large action of ethanol on the fast desensitization rate constant (> 200-fold increase in the desensitization rate constant at 1 M ethanol). When we assume fast desensitization to occur from all states, ethanol is seen to have two actions.(ABSTRACT TRUNCATED AT 250 WORDS)
SAA, AN APOPROTEIN OF HDL: ITS STRUCTURE AND FUNCTION* (1982)

The putative precursor of amyloid protein AA appears in serum as an apoprotein (apoSAA) of heavier HDL fractions of lipoproteins found in humans and mice. ApoSAA is found by precipitation with specific anti-AA antibodies to be on a particle that also carries apoA-I and some C-apoproteins. In endotoxin-treated mice a lipoprotein fraction with about 2 moles of apoSAA to 1 mole of apoA-I can be isolated, an apoSAA-carrying subset of HDL being thus suggested. In mice, rapid clearance from plasma of native apoSAA compared to apoA-I suggests a special function for apoSAA. The C-terminal amino acid portion of apoSAA may play a role in this function.
Purification, molecular cloning, and sequence analysis of sucrose-6 <sup>F</sup> -phosphate phosphohydrolase from plants (2000)

Sucrose-6(F)-phosphate phosphohydrolase (SPP; EC ) catalyzes the final step in the pathway of sucrose biosynthesis and is the only enzyme of photosynthetic carbon assimilation for which the gene has not been identified. The enzyme was purified to homogeneity from rice (Oryza sativa L.) leaves and partially sequenced. The rice leaf enzyme is a dimer with a native molecular mass of 100 kDa and a subunit molecular mass of 50 kDa. The enzyme is highly specific for sucrose 6(F)-phosphate with a K(m) of 65 microM and a specific activity of 1250 micromol min(-1) mg(-1) protein. The activity is dependent on Mg(2+) with a remarkably low K(a) of 8-9 microM and is weakly inhibited by sucrose. Three peptides from cleavage of the purified rice SPP with endoproteinase Lys-C showed similarity to the deduced amino acid sequences of three predicted open reading frames (ORF) in the Arabidopsis thaliana genome and one in the genome of the cyanobacterium Synechocystis sp. PCC6803, as well as cDNA clones from Arabidopsis, maize, and other species in the GenBank database of expressed sequence tags. The putative maize SPP cDNA clone contained an ORF encoding a 420-amino acid polypeptide. Heterologous expression in Escherichia coli showed that this cDNA clone encoded a functional SPP enzyme. The 260-amino acid N-terminal catalytic domain of the maize SPP is homologous to the C-terminal region of sucrose-phosphate synthase. A PSI-BLAST search of the GenBank database indicated that the maize SPP is a member of the haloacid dehalogenase hydrolase/phosphatase superfamily.
Studying connectivity and brain development with combinatorial Brainbow labels (2013)

Frontiers Events is a rapidly growing calendar management system dedicated to the scheduling of academic events. This includes announcements and invitations, participant listings and search functionality, abstract handling and publication, related events and post-event exchanges. Whether an organizer or participant, make your event a Frontiers Event!
Multimodal video search techniques: late fusion of speech-based retrieval and visual content-based retrieval (2004)

This paper describes multimodal systems for ad-hoc search constructed by IBM for the TRECVID 2003 benchmark of search systems for broadcast video. These systems all use a late fusion of independently developed speech-based and visual content-based retrieval systems and outperform our individual retrieval systems on both manual and interactive search tasks. For the manual task, our best system used a query-dependent linear weighting between speech-based and image-based retrieval systems. This system has mean average precision (MAP) performance 20% above our best unimodal system for manual search. For the interactive task, where the user has full knowledge of the query topic and the performance of the individual search systems, our best system used an interlacing approach. The user determines the (subjectively) optimal weights A and B for the speech-based and image-based systems, where the multimodal result set is aggregated by combining the top A documents from system A followed by top B documents of system B and then repeating this process until the desired result set size is achieved. This multimodal interactive search has MAP 40% above our best unimodal interactive search system.
Next-Generation Sequencing: A New Revolution in Molecular Diagnostics? (2009)

In 1980, Fred Sanger and Walter Gilbert were awarded the Nobel Prize in Chemistry for discovering novel ways for sequencing nucleic acids. In 2003, the human genome sequence was published, an effort that involved more than 3000 scientists from 6 countries. The work took 13 years to complete, at a cost of nearly $3 billion. Only 6 years later, nucleic acid sequencing technologies have advanced to a stage in which a human genome can be sequenced within weeks at a cost of $50 000 or less. These new sequencing technologies are about a million times more efficient than standard Sanger sequencing. Now, people are talking about the $1000 genome, and there is an X Prize worth $10 million for sequencing 100 human genomes within 10 days at a cost of <$10 000 per genome. International organizations are sequencing thousands of cancer genomes to find novel genetic changes, and individuals with money are paying for genomewide association studies in hopes of preventing diseases to which they are predisposed.

Although the technologies for high-throughput sequencing are here and although they are being perfected in terms of accuracy and reduced costs, many questions are being raised. Some of these questions are explored below with leading scientists from academia and industry.

Karl V. Voelkerding2 : Calculating the cost for sequencing a human genome needs to incorporate the level of sequencing “completeness” or “coverage” that will be required to accurately characterize both sequence and structural variation. Reagent and wet bench labor costs for sequencing a human genome should approach $5000 or less within three to five years, depending on the technology. It is difficult to price the costs for bioinformatic analysis, currently a lengthy and extensive process that varies depending on the questions being asked. New computational algorithms will definitely streamline this process. Beyond …
<i>IN VIVO</i> EFFECTS OF LYMPHOCYTES SENSITIZED <i>IN VITRO</i> AGAINST TUMOR CELLS* (1976)

Experiments are reported on immunotherapy of lethal lung metastasis by lymphocytes sensitized in culture against a syngenic tumor. We used the Lewis lung carcinoma (3LL) which had originated in a C57Bl mouse. C57Bl mice were footpad inoculated with tumor cells. Seven days liter, the tumor-bearing leg was amputated, and the animals were inoculated with syngenic lymphocytes which had been sensitized on monolayers of 3LL-tumor cells. The sensitized lymphocytes significantly reduced the development of lethal lung metastasis of the 3LL-tumor cells.
American canine hepatozoonosis (2003)

Abstract American canine hepatozoonosis is an emerging, tick-transmitted infection of domestic dogs caused by a recently recognized species of apicomplexan parasite, Hepatozoon americanum . The known definitive host of the protozoan is the Gulf Coast tick, Amblyomma maculatum . Presently recognized intermediate hosts include the domestic dog and the coyote, Canis latrans . Laboratory-reared larval or nymphal A. maculatum can be infected readily by feeding to repletion on a parasitemic intermediate host; sporogony requires 35–40 days. Transmission of infection to the dog has been produced experimentally by oral administration of mature oocysts or oocyst-containing ticks. Canine disease follows experimental exposure in 4–6 weeks and is characterized by systemic illness, extreme neutrophilic leukocytosis, muscle and bone pain, and proliferation of periosteal bone. Histopathological findings include multifocal skeletal and cardiac myositis associated with escape of mature merozoites from within the host-cell environment. There is also rapid onset of periosteal activation and osteogenesis and, less frequently, glomerulopathy and amyloidosis. Sequential stages of development of H. americanum in both the dog and the tick have been elucidated. Gamonts potentially infectious to ticks have been observed in peripheral blood leukocytes of the dog in as few as 28 days after exposure to oocysts. Young coyotes experimentally exposed to a canine strain of H. americanum acquired disease indistinguishable from that of similarly exposed young dogs.
Safety Assessment of Stearyl Heptanoate and Related Stearyl Alkanoates as Used in Cosmetics (2012)

Stearyl heptanoate is an ester of stearyl alcohol and heptanoic acid that functions in cosmetics as a skin conditioning agent and is in the general class of chemicals called stearyl alkanoates. Stearyl caprylate, stearyl palmitate, stearyl stearate, stearyl behenate, and stearyl olivate are stearyl alkanoates with similar chemical structures, toxicokinetics, and functions in cosmetics. These water-insoluble stearyl alkanoates, when metabolized, yield stearyl alcohol and a corresponding fatty acid. The available information supports the safety of all of the related stearyl alkanoates. The Expert Panel concluded that stearyl heptanoate, stearyl caprylate, stearyl palmitate, stearyl stearate, stearyl behenate, and stearyl olivate are safe in the present practices of use and concentration.
STIMULUS FUNCTION IN SIMULTANEOUS DISCRIMINATION<sup>1</sup> (1968)

In discrimination learning, the negativity of the stimulus correlated with nonreinforcement (S-) declines after 100 training trials while the stimulus correlated with reinforcement (S+) is paradoxically more positive with lesser amounts of discrimination training. Training subjects on two simultaneous discrimination tasks revealed a within-subjects overlearning reversal effect, where a more-frequently presented discrimination problem was better learned in reversal than was a discrimination problem presented less frequently during training.
DC power bus modeling in high-speed digital designs including conductor and dielectric losses (2002)

Power bus design is a critical aspect in high-speed digital circuit designs. A circuit extraction approach based on a mixed-potential integral equation formulation is presented herein to model arbitrary multilayer power bus structures including vertical discontinuities associated with surface mount (SMT) decoupling capacitor interconnects. Both conductor and dielectric losses are incorporated, and included into the first principles formulation. The agreement of modeling and measurements demonstrates its effectiveness and utilization in power bus designs.
Detection of Syphilitic Hearing Loss (1978)

Syphilis can cause sensorineural hearing loss that is potentially treatable. To determine the incidence of positive serological findings in patients with sensorineural hearing loss, the rapid plasma reagin card test (RPRCT) and the FTA-ABS test were performed in a study group composed of patients with sensorineural hearing loss of obscure origin. Of the 306 patients with sensorineural hearing loss, 20 (6.5%) demonstrated a positive FTA-ABS as compared with two of 100 (2%) of the control group. Considerable variation was found in the rate of the false-negative and the biological false-positive RPRCT as performed by our hospital and state laboratories when compared with the results of the FTA-ABS test. Syphilis should be considered in any patient with sensorineural hearing loss of obscure origin, despite a negative history for syphilis. The FTA-ABS is the preferred test to exclude hearing loss of syphilitic origin.
The altered gene profile of human osteosarcoma cell after knock-down of double functional gene apurinic/apyrimidinic endonuclease (2007)

Objective To explore the molecular mechanism of inhibited malignant phenotype by knock-down of apurinic/apyrimidinic endonuclease(APE1) in human osteosarcoma cell HOS,as well as the possible interacting molecules among APE1.Methods Knock-down of APE1 by synthesized APE1 siRNA in HOS cell was identified first by Western blotting and AP endonuclease assay,then the gene profile was determined with GEArray~(TM) series Human CancerPathwayFinder gene array.Results The specific knock-down of APE1 was found in HOS cell transfected with APE1 siRNA,and its inhibited rate was 91.5%.Six biological pathways of the gene array were involved in HOS cell after knock-down of APE1,but the cell cycle pathway was less influenced.Forty-two out of 96 genes were altered(43.8%),in which only CDK4,FGFR2,KAI1 and NCAM were increased,38 others were decreased.Conclusion The knock-down of APE1 was detected to be involved in all the pathways including cell cycle and DNA repair,apoptosis,signal transduction,adhesion,angiogenesis,invasion and metastasis.These findings are significant to further elucidate APE1 role in tumor genesis and to provide experimental evidence for gene therapy targeting APE1 gene in the future.
High-l CMB power spectrum from ACBAR: New results, observation status, and future prospects (2005)

We present new measurements of the temperature anisotropy in the cosmic microwave background using Arcminute Cosmology Bolometer Array Receiver (ACBAR). Significant improvements in sensitivity over previous data release were achieved by a combination of more efficient analysis techniques and the inclusion of more data. Together with the CBI measurements at lower photon frequencies, and the WMAP results on large angular scales, the joint ACBAR/CBI/WMAP power spectrum represents the current best knowledge of the temperature anisotropy between l=2 and 3000. Cosmological implications, current status of the instrument, and prospects for further improvements will be discussed.
Improved output beam quality in large aperture semiconductor lasers by modification of transverse gain and index profiles (2003)

Summary form only given. High brightness, high power semiconductor lasers have attracted considerable attention for applications such as free-space communications and pumping fiber lasers. Most techniques used to increase the brightness of large aperture semiconductor lasers require complex processing techniques and are difficult to realise in mass production. A simple approach is to optimise the performance of conventional broad area lasers (BALs). This has mainly focused on improving the quality of the epitaxial material, thus reducing the tendency for filament formation at high output powers. However, even with uniform active regions, BALs oscillate on many high order transverse modes and suffer from self-focusing and filamentation at high power densities. One way of overcoming this problem is to tailor the transverse gain or refractive index profiles to favour fundamental mode oscillation. In addition, elimination of intense filaments at the laser facet should increase the maximum output power attainable by increasing the catastrophic optical mirror damage limit. We have investigated two techniques to tailor the gain and refractive index profiles in large aperture semiconductor lasers. We have also compared our experimental results with numerical simulations, obtaining good agreement, and indicating that tailoring of the transverse gain and index profiles are very attractive techniques to control the optical field at high output powers in large aperture devices.