gebhart/patrepeval huggingface dataset:
The Effect of Ascorbic Acid on the Pharmacokinetics of Levodopa in Elderly Patients with Parkinson Disease (2004)

Levodopa (LD) is one of the most effective drugs for clinical symptoms in patients with Parkinson disease (PD). Most PD patients are advanced in age and may have trouble with LD absorption because aging influences drug absorption processes. Previous reports have indicated that ascorbic acid (AsA) can reduce LD dosage without losing its effectiveness. The current study sought to determine whether AsA affects LD absorption in elderly PD patients. Sixty-seven elderly PD patients took a tablet orally containing 100 mg LD and 10 mg carbidopa following an overnight fast. Plasma LD concentrations were determined at 6 points up to 3 hours, using high-performance liquid chromatography with electrochemical detection. The area under the curve (AUC), peak drug concentration (Cmax), and time to peak drug concentration (Tmax) were calculated. The pharmacokinetic evaluation was repeatedly performed 1 week later in the same way except for adding 200 mg AsA to the tablet. The changes in AUC, Cmax, and Tmax between the tests were evaluated. Significant changes in these parameters were not observed when analyzed using data from all patients. However, significant increases in AUC and Cmax, and a significant reduction in Tmax by adding AsA were observed in 25 patients with baseline AUC < or =2500 ng.hour/mL. In conclusion, AsA can improve LD absorption in elderly PD patients with poor LD bioavailability. LD therapy in combination with AsA may be one of the strategies for PD treatment.
Necrotic enteritis in broilers: an updated review on the pathogenesis (2011)

Clostridium perfringens-induced necrotic enteritis and related subclinical disease have become economically significant problems for the broiler industry. Fortunately, scientific interest in this topic has grown: new C. perfringens virulence factors have been discovered and new insight gained about the pathogenesis of necrotic enteritis. It has been shown that alpha toxin, for a long time thought to be the key virulence factor, is not essential for the development of the disease. Moreover, it is now clearly established that only certain C. perfringens strains are capable of inducing necrotic enteritis under specific conditions that predispose to the disease and they constitute only a minority in the intestinal tract of healthy chickens. A novel pore-forming toxin, NetB, has been identified in these virulent avian C. perfringens strains. Using a gene knockout mutant, it has been shown that NetB is a critical virulence factor in the pathogenesis of necrotic enteritis in broilers. In addition to toxin production, other factors have been described that contribute to the ability of certain C. perfringens strains to cause necrotic enteritis in broilers. It has been suggested that proteolytic enzymes play an important role in the initial stages of necrotic enteritis since the villi are first affected at the level of the basement membrane and the lateral domain of the enterocytes. In field outbreaks of necrotic enteritis, a single clone of C. perfringens is dominant in intestines of all affected birds, as opposed to the mixture of different C. perfringens strains that can be isolated from healthy bird intestines. It has been proposed that bacteriocin production is responsible for the dominance of a single strain in necrotic enteritis cases. Furthermore, it has been shown that virulent strains are more able to adhere to extracellular matrix molecules than non-virulent strains. The current knowledge on the pathogenesis of the disease has been summarized in this short review.
Novel production method and in‐vitro cell compatibility of porous Ti‐6Al‐4V alloy disk for hard tissue engineering (2007)

Porous metals are attractive due to its unique physical, mechanical, and new bone tissue ingrowth properties. In the present study, the production of highly porous Ti-6Al-4V parts by powder metallurgical technology and subsequently it's uses in in vitro bone tissue engineering is described. A space-holder method using carbamide with different particle size to produce parts with porosities between 35 and 70% were applied. The compressive strength and Young's modulus of porous Ti-6Al-4V were determined. Results indicated that stress and Young's modulus decrease with increasing porosity and pore size. The porous parts are characterized by scanning electron microscopy. Furthermore, study was to investigate the effects of three different porosities of porous Ti-6Al-4V (35, 50, and 70%) on proliferation, differentiation, and cell-matrix interaction of mouse osteoblast-like cells, MC-3T3. Results showed that the cell proliferation was significantly (p < 0.05) higher on 70% porous Ti-6Al-4V. However, synthesis of different types of extra cellular matrix proteins was also more abundant on 70% porous Ti-6Al-4V than 35 and 50% porous Ti-6Al-4V disk except some specific proteins. An increase in alkaline phosphate activity was significantly (p < 0.05) higher on 70 and 50% porous Ti-6Al-4V disk after 12 days of MC-3T3 cells incubation. Above all, results indicated that porosity (nearly 70%) of porous Ti-6Al-4V topography affects proliferation and differentiation of osteoblast-like MC-3T3 cells. The results showed that this novel process is a promise to fabricate porous biomaterials for bone implants.
Interposed proportional sharing for a storage service utility (2004)

This paper develops and evaluates new share-based scheduling algorithms for differentiated service quality in network services, such as network storage servers. This form of resource control makes it possible to share a server among multiple request flows with probabilistic assurance that each flow receives a specified minimum share of a server's capacity to serve requests. This assurance is important for safe outsourcing of services to shared utilities such as Storage Service Providers.Our approach interposes share-based request dispatching on the network path between the server and its clients. Two new scheduling algorithms are designed to run within an intermediary (e.g., a network switch), where they enforce fair sharing by throttling request flows and reordering requests; these algorithms are adaptations of Start-time Fair Queuing (SFQ) for servers with a configurable degree of internal concurrency. A third algorithm, Request Windows (RW), bounds the outstanding requests for each flow independently; it is amenable to a decentralized implementation, but may restrict concurrency under light load. The analysis and experimental results show that these new algorithms can enforce shares effectively when the shares are not saturated, and that they provide acceptable performance isolation under saturation. Although the evaluation uses a storage service as an example, interposed request scheduling is non-intrusive and views the server as a black box, so it is useful for complex services with no internal support for differentiated service quality.
14-3-3 Proteins Act as Negative Regulators of the Mitotic Inducer Cdc25 inXenopusEgg Extracts (1998)

Cdc25, the dual-specificity phosphatase that dephosphorylates the Cdc2-cyclin B complex at mitosis, is highly regulated during the cell cycle. In Xenopus egg extracts, Cdc25 is associated with two isoforms of the 14-3-3 protein. Cdc25 is complexed primarily with 14-3-3epsilon and to a lesser extent with 14-3-3zeta. The association of these 14-3-3 proteins with Cdc25 varies dramatically during the cell cycle: binding is high during interphase but virtually absent at mitosis. Interaction with 14-3-3 is mediated by phosphorylation of Xenopus Cdc25 at Ser-287, which resides in a consensus 14-3-3 binding site. Recombinant Cdc25 with a point mutation at this residue (Cdc25-S287A) is incapable of binding to 14-3-3. Addition of the Cdc25-S287A mutant to Xenopus egg extracts accelerates mitosis and overrides checkpoint-mediated arrests of mitotic entry due to the presence of unreplicated and damaged DNA. These findings indicate that 14-3-3 proteins act as negative regulators of Cdc25 in controlling the G2-M transition.
Modulating responsiveness of human TLR7 and 8 to small molecule ligands with T‐rich phosphorothiate oligodeoxynucleotides (2006)

Toll-like receptors (TLR) 7 and 8 are closely related members of the TLR family of pathogen-associated molecular pattern recognition receptors and have an important function in activation of innate immune responses upon viral infection. TLR7 can be activated selectively by the guanosine analogue loxoribine, whereas the imidazoquinoline derivative Resiquimod (R-848) activates both TLR7 and TLR8. We demonstrate that co-incubation of R-848 with thymidine homopolymer oligodeoxynucleotides (ODN) significantly increased activity of R-848 on TLR8-expressing HEK 293 cells, but abolished TLR7-mediated signaling. Similarly, the combination of loxoribine and thymidine ODN redirected the stimulatory effect of loxoribine away from TLR7, and toward TLR8. This alteration in ligand specificity was demonstrated both in TLR-transfected HEK cells, and also in human PBMC, with a corresponding change in cytokine production away from IFN-alpha secretion by TLR7-expressing plasmacytoid DC and toward IL-12, TNF-alpha and IFN-gamma secretion by TLR8-expressing monocytes and NK cells. These results demonstrate an unexpected plasticity in the ligand specificities of TLR7 and TLR8, and suggest a novel sequence-selective interaction between these receptors and synthetic phosphorothioate ODN.
FlyingDrosophilastabilize their vision-based velocity controller by sensing wind with their antennae (2014)

Flies and other insects use vision to regulate their groundspeed in flight, enabling them to fly in varying wind conditions. Compared with mechanosensory modalities, however, vision requires a long processing delay (~100 ms) that might introduce instability if operated at high gain. Flies also sense air motion with their antennae, but how this is used in flight control is unknown. We manipulated the antennal function of fruit flies by ablating their aristae, forcing them to rely on vision alone to regulate groundspeed. Arista-ablated flies in flight exhibited significantly greater groundspeed variability than intact flies. We then subjected them to a series of controlled impulsive wind gusts delivered by an air piston and experimentally manipulated antennae and visual feedback. The results show that an antenna-mediated response alters wing motion to cause flies to accelerate in the same direction as the gust. This response opposes flying into a headwind, but flies regularly fly upwind. To resolve this discrepancy, we obtained a dynamic model of the fly's velocity regulator by fitting parameters of candidate models to our experimental data. The model suggests that the groundspeed variability of arista-ablated flies is the result of unstable feedback oscillations caused by the delay and high gain of visual feedback. The antenna response drives active damping with a shorter delay (~20 ms) to stabilize this regulator, in exchange for increasing the effect of rapid wind disturbances. This provides insight into flies' multimodal sensory feedback architecture and constitutes a previously unknown role for the antennae.
Advancing Crop Transformation in the Era of Genome Editing (2016)

Plant transformation has enabled fundamental insights into plant biology and revolutionized commercial agriculture. Unfortunately, for most crops, transformation and regeneration remain arduous even after more than 30 years of technological advances. Genome editing provides novel opportunities to enhance crop productivity but relies on genetic transformation and plant regeneration, which are bottlenecks in the process. Here, we review the state of plant transformation and point to innovations needed to enable genome editing in crops. Plant tissue culture methods need optimization and simplification for efficiency and minimization of time in culture. Currently, specialized facilities exist for crop transformation. Single-cell and robotic techniques should be developed for high-throughput genomic screens. Plant genes involved in developmental reprogramming, wound response, and/or homologous recombination should be used to boost the recovery of transformed plants. Engineering universal Agrobacterium tumefaciens strains and recruiting other microbes, such as Ensifer or Rhizobium, could facilitate delivery of DNA and proteins into plant cells. Synthetic biology should be employed for de novo design of transformation systems. Genome editing is a potential game-changer in crop genetics when plant transformation systems are optimized.
Human peripheral blood monocyte-derived macrophages produce haemolytically active C3 in vitro. (1983)

The third component of complement (C3) synthesized by human monocyte-derived macrophages has been shown to have the same size and sub-unit structure as serum C3, but haemolytic activity has not been demonstrated. Human monocyte-derived macrophages were cultured from days 4 to 7 in medium without serum, and the conditioned medium was dialysed to remove inhibitors of the C3 assay and concentrated to enhance detection of low amounts of C3. Using these techniques C3 activity was detected routinely. The amount of C3 was 3.4 x 10(7) effective C3 molecules/ml of concentrated tissue culture medium (range 1.0-7.5 x 10(7)), and the number of C3 molecules synthesized by each cell was 4.4 x 10(5), assuming that each cell synthesized C3. The specific activity of the C3 synthesized by the monocytes was the same as the specific activity of C3 that had been purified from serum and then incubated with the cells and processed in the same manner as the monocyte media. Synthesis as the basis for the presence of the C3 activity in the medium was indicated by an inhibition of production of the C3 activity of 66 +/- 16% by cycloheximide, 2 micrograms/ml. Thus, human blood monocytes that migrate into areas of inflammation can mature into cells capable of producing C3 which can participate in the complement sequence and thus potentiate inflammation.
Advances in polymers for anti-biofouling surfaces (2008)

Self-assembling polymers and nanostructured polymer thin films are being actively explored as advanced coatings for marine and biomedical applications. This review highlights recent advances in the design and synthesis of polymers that can resist fouling by biomolecules, cells and organisms. Current understanding of the mechanisms of anti-biofouling activity is also discussed.
Effects of Epibrassinolide and Abscisic Acid on Sorghum Plants Growing under Soil Water Deficit. I. Effects on growth and survival. (1994)

Spray treatment with 22R, 23R epibrassinolide (EBR, 0.1 ppm) increased the length and dry weight of both the top and root of sorghum plants under various soil water conditions, although the extent of growth promotion was small. Under well-watered conditions, abscisic acid treatment (ABA, 50 ppm) inhibited top growth but promoted root growth. However, under water-stressed conditions, ABA-treated plants grew at a higher rate than control and EBR-treated plants. The accelerated growth of ABA-treated plants was apparent both in the top and the root. Treatment with 0.1 ppm EBR + 50 ppm ABA inhibited growth even more than ABA treatment under well-watered conditions, but it increased the growth rate more than ABA alone under water stressed conditions. Treatment with EBR + ABA promoted root growth to a larger extent even than ABA treatment. From the above results, it was concluded that EBR increased the effects of ABA both under well-watered and water stressed conditions. Treatment with EBR and ABA increased the survival ability of plant and leaf under severe drought. This effect of ABA was also enhanced by EBR. Thus, synergistic interaction between ABA and EBR was observed in almost all aspects examined.
Identification of the active site residues in dipeptidyl peptidase IV by affinity labeling and site-directed mutagenesis (1992)

The active site of dipeptidyl peptidase IV (DPPIV) was examined by chemical modification and site-directed mutagenesis. Purified DPPIV was covalently modified with [3H]diisopropyl fluorophosphate (DFP). The radiolabeled DPPIV was digested with lysyl endopeptidase, and the peptides were separated by high-performance liquid chromatography. A single 3H-containing peptide was obtained and analyzed for amino acid sequence and radioactivity distribution. A comparison of the determined sequence with the predicted primary structure of DPPIV [Ogata, S., Misumi, Y., & Ikehara, Y. (1989) J. Biol. Chem. 264, 3596-3601] revealed that [3H]DFP was bound to Ser631 within the sequence Gly629-Trp-Ser-Tyr-Gly633, which corresponds to the consensus sequence Gly-X-Ser-X-Gly proposed for serine proteases. To further identify the essential residues in the active-site sequence, we modified the DPPIV cDNA by site-directed mutagenesis to encode its variants. Expression of the mutagenized cDNAs in COS-1 cells demonstrated that any single substitution of Gly629, Ser631, or Gly633 with other residues resulted in the complete loss of the enzyme activity and DFP binding. Although substitution of Trp630----Glu or Tyr632----Phe caused no effect on the enzyme activity, that of Tyr632----Leu or Gly abolished the activity. These results indicate that the sequence Gly-X-Ser-(Tyr)-Gly is essential for the expression of the DPPIV activity.
Comparison of spatial firing characteristics of units in dorsal and ventral hippocampus of the rat (1994)

The septal and temporal poles of the hippocampus differ markedly in their anatomical and neurochemical organization. Although it is well established that the internal representation of space is a fundamental function of hippocampal neurons, most of what is known about spatial coding in the hippocampus of freely moving animals has come from recordings from the dorsal one-third (largely for technical convenience). The present study therefore compared the spatial selectivity of CA1 neurons in the dorsal and ventral hippocampi of rats during performance of a food reinforced, random search task in a square chamber containing simple visual landmarks. Neural activity was recorded in the dorsal and ventral hippocampi of opposite hemispheres in the same rats, in many cases simultaneously. As in dorsal hippocampus, ventral CA1 units could be classified as "complex spike" (pyramidal) cells or "theta" interneurons. Both dorsal and ventral theta cells fired at relatively high rates and with low spatial selectivity in the apparatus. Of the population of complex spike cells in the ventral hippocampus, a significantly smaller number had "place fields" than in the dorsal hippocampus, and the average spatial selectivity was of significantly lower resolution than that found among dorsal hippocampal complex spike cells. Thus, a septotemporal difference of spatial selectivity was found in the CA1 field of the rat hippocampus, complementing many other anatomical and neuropharmacological studies. A number of possible functional interpretations can be suggested from these results, including a computational advantage of representing space at different scales or a preeminence of essentially nonspatial information processing in the ventral hippocampus.
Characterisation of unipolar waveform alternation in acutely ischaemic porcine myocardium (1986)

The relation between electrical alternans recorded in acutely ischaemic myocardium, ventricular arrhythmias, and changes in the activation sequence was studied. Sixty three unipolar electrograms, simultaneously recorded from the epicardial surface of the in situ porcine heart during 6 min periods of coronary occlusion, were converted to a digital format and analysed by computer. The time integrals of the electrograms during their QRS complex, ST segment, and T wave were measured. Unipolar waveform alternation was then quantified by subtracting the values obtained for two consecutive beats showing alternans. The spatial distribution of unipolar waveform alternation was illustrated by isoarea difference maps. Isochronal maps of the local excitation detected on each electrogram were constructed. Of 52 occlusions in 27 preparations, unipolar waveform alternation was detected in 42 and was promptly followed by ventricular arrhythmias in 37. The magnitude of unipolar waveform alternation increased from the margin to the inner portion of the ischaemic zone but its correlation with activation delay was poor, and there was no change in the activation sequence. These results suggest that beat to beat alternation of the unipolar waveform is related to changes in the action potential configuration rather than to changes in the activation sequence. Furthermore, unipolar waveform alternation appears to be associated with the development of early post-occlusion ventricular arrhythmias.
Effects of duodenal fat, protein or mixed‐nutrient infusions on epigastric sensations during sustained gastric distension in healthy humans (2002)

Duodenal fat modulates sensory and motor responses to gastric distension and raises plasma cholecystokinin compared with glucose. The effects of protein (also releasing cholecystokinin), or mixed nutrients (with a balanced macronutrient composition), on gastrointestinal sensations in relation to gastric relaxation and plasma cholecystokinin concentrations are not known. The aim of this study was therefore to compare the effects of duodenal infusion of fat, protein or mixed nutrients during sustained gastric distension (mimicking the intragastric presence of food) on these parameters. In 10 healthy subjects, gastric distension to fullness was maintained for 90 min, while gastric volume, sensations and plasma cholecystokinin were monitored during duodenal infusion of isotonic saline or nutrients (2 kcal min-1). During saline infusion, all parameters remained unchanged for 90 min. Initially, only lipid increased plasma cholecystokinin, gastric volume and scores for sensations. Cholecystokinin and gastric volume responses to protein and mixed nutrients were delayed and not associated with significant changes in sensations. In conclusion, the intensity of gastrointestinal sensations is related to, but not entirely explained by, the magnitude in intragastric volume and plasma cholecystokinin changes. Our results offer new insights into the role of dietary nutrient composition in gastrointestinal sensations, and may have implications for the dietary management of digestive symptoms.
Phytochrome B Is Not Detectable in the hy3 Mutant of Arabidopsis, Which Is Deficient in Responding to End-of-Day Far-Red Light Treatments (1991)

Journal Article Phytochrome B Is Not Detectable in the hy3 Mutant of Arabidopsis, Which Is Deficient in Responding to End-of-Day Far-Red Light Treatments Get access Akira Nagatani, Akira Nagatani 1The Laboratory of Plant Biological Regulation, Frontier Research Program, RIKEN InstituteHirosawa 2-1, Wako City, Saitama, 351-01 Japan Search for other works by this author on: Oxford Academic Google Scholar Joanne Chory, Joanne Chory 2Plant Biology Laboratory, The Salk Institute for Biological StudiesSan Diego, California 92138, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar Masaki Furuya Masaki Furuya 1The Laboratory of Plant Biological Regulation, Frontier Research Program, RIKEN InstituteHirosawa 2-1, Wako City, Saitama, 351-01 Japan Search for other works by this author on: Oxford Academic Google Scholar Plant and Cell Physiology, Volume 32, Issue 7, October 1991, Pages 1119–1122, https://doi.org/10.1093/oxfordjournals.pcp.a078177 Published: 01 October 1991 Article history Received: 20 September 1991 Accepted: 26 September 1991 Published: 01 October 1991