gebhart/patrepeval huggingface dataset:
The Role of GM1 and Other Gangliosides in Neuronal Differentiation Overview and New Findingsa (1998)

The pronounced increases in gangliosides belonging to the gangliotetraose family during the neurite outgrowth phase of neuronal differentiation have suggested a functional requirement for these substances related to process extension, arborization, and possibly synaptogenesis. Support for this hypothesis has come from a variety of experimental paradigms utilizing neuroblastoma cell lines, primary neuronal cultures, and observations on the developing nervous system. We have recently observed that differentiation of both primary neurons and neuroblastoma cells by Ca(2+)-elevating stimulants is characterized by upregulation of GM1 in the nuclear membrane. Immunostaining revealed these Ca(2+)-induced neurites to have axonal characteristics. Recent work has indicated that nuclear GM1 facilitates efflux of nuclear Ca2+, thereby contributing to the reduced level of nuclear Ca2+ that characterizes the differentiated neuron. Thus, while GM1 is generally recognized as a pluripotent molecule with several modulatory roles in the plasma membrane of developing and mature neurons, regulation of Ca2+ flux across the nuclear membrane is proposed as another critical function of this ganglioside in neuronal development, with special relevance to axonogenesis.
A Theoretical Justification for Single Molecule Peptide Sequencing (2015)

The proteomes of cells, tissues, and organisms reflect active cellular processes and change continuously in response to intracellular and extracellular cues. Deep, quantitative profiling of the proteome, especially if combined with mRNA and metabolite measurements, should provide an unprecedented view of cell state, better revealing functions and interactions of cell components. Molecular diagnostics and biomarker discovery should benefit particularly from the accurate quantification of proteomes, since complex diseases like cancer change protein abundances and modifications. Currently, shotgun mass spectrometry is the primary technology for high-throughput protein identification and quantification; while powerful, it lacks high sensitivity and coverage. We draw parallels with next-generation DNA sequencing and propose a strategy, termed fluorosequencing, for sequencing peptides in a complex protein sample at the level of single molecules. In the proposed approach, millions of individual fluorescently labeled peptides are visualized in parallel, monitoring changing patterns of fluorescence intensity as N-terminal amino acids are sequentially removed, and using the resulting fluorescence signatures (fluorosequences) to uniquely identify individual peptides. We introduce a theoretical foundation for fluorosequencing and, by using Monte Carlo computer simulations, we explore its feasibility, anticipate the most likely experimental errors, quantify their potential impact, and discuss the broad potential utility offered by a high-throughput peptide sequencing technology.
The Bone Regenerative Effect of Platelet‐Derived Growth Factor‐BB Delivered With a Chitosan/Tricalcium Phosphate Sponge Carrier (2000)

The results of this study support the use of chitosan/TCP sponges as a delivery system for growth factors and demonstrate that PDGF-BB loaded onto chitosan/TCP sponge carriers has an osteogenic effect on bone regeneration in vivo.
Evidence for a role of the ileum in the control of nitrogen homeostasis via the regulation of arginine metabolism (2011)

As arginine plays a key role in the regulation of liver ureagenesis, we hypothesised that a modulation of enzymes involved in arginine metabolism within the intestine contributes to the regulation of N homeostasis according to protein supply. Our aim was to study the influence of variations in protein or amino acid (AA) supply on intestinal arginase, glutaminase, ornithine aminotransferase (OAT), argininosuccinate lyase and argininosuccinate synthetase. We evaluated in vivo in rats the responses of these enzymes to short-term (ST, 16 h) and long-term (LT, 15 d) variations in dietary protein (10, 17 or 25 % protein diet). In addition, in order to test whether these responses could involve a direct action of AA on the gene expression and activity of these enzymes, Caco-2/TC7 cells were cultured for 3 d with increasing AA concentrations. In vivo, in the ST, both high- and low-protein diets increased arginase activity in the intestinal mucosa (ST25 %: 46 (sem 2) μmol/g per min and ST10 %: 46 (sem 2) μmol/g per min v. ST17 %: 36 (sem 3) μmol/g per min, P < 0.05). In the LT, OAT expression was increased in the LT10 % group (+277 %, P < 0.05) compared with the LT17 % group. Caco-2/TC7 cells showed inverse relationships between AA supply and arginase (P = 0.058) and OAT (P = 0.035) expressions. The present study demonstrates the regulation of intestinal arginase and OAT expressions in response to protein supply. Our in vitro experiments further indicate a direct AA-induced regulation of the mRNA abundance of these enzymes. In situations of limited protein supply, this regulation would increase intestinal arginine catabolism and, possibly via a decrease in arginine portal release, decrease hepatic AA oxidation, thus promoting N sparing.
Modern antipsychotic drugs: a critical overview (2005)

Conventional antipsychotic drugs, used for a half century to treat a range of major psychiatric disorders, are being replaced in clinical practice by modern "atypical" antipsychotics, including aripiprazole, clozapine, olanzapine, quetiapine, risperidone and ziprasidone among others. As a class, the newer drugs have been promoted as being broadly clinically superior, but the evidence for this is problematic. In this brief critical overview, we consider the pharmacology, therapeutic effectiveness, tolerability, adverse effects and costs of individual modern agents versus older antipsychotic drugs. Because of typically minor differences between agents in clinical effectiveness and tolerability, and because of growing concerns about potential adverse long-term health consequences of some modern agents, it is reasonable to consider both older and newer drugs for clinical use, and it is important to inform patients of relative benefits, risks and costs of specific choices.
Phosphorus 31-nuclear magnetic resonance spectroscopy of rat liver during simple storage or continuous hypothermic perfusion. (1992)

The adenosine triphosphate (ATP) content and intracellular pH (pHi) of isolated rat liver before, during, and after cold preservation in either University of Wisconsin lactobionate solution (UW) (n = 10) or Euro-Collins solution (EC), (n = 8) were monitored with phosphorus 31 nuclear magnetic resonance. The 31P nuclear magnetic resonance spectra were obtained on a 4.7 T system operating at 81 MHz. Fructose metabolism, liver enzyme release, oxygen consumption, and rat survival after liver transplantation were also evaluated. During simple cold storage (SCS) the ATP level declined to undetectable levels with both preservation solutions whereas the pHi declined to approximately 7.0. In contrast, during continuous hypothermic perfusion (CHP), hepatic ATP levels remained measurable during the 24-hour EC preservation and actually increased significantly (p > 0.01) during UW preservation. After reperfusion at 37 degrees C with Krebs lactate, the livers in SCS treated with EC differed significantly from the UW-treated livers in terms of their ATP level and pHi and their response to a fructose challenge. In contrast, livers undergoing CHP demonstrated similar behaviors with both solutions. These results demonstrate an increase in the hepatic ATP content during CHP, which occurs with UW but is not seen with EC. On the other hand, only livers that were simply stored with UW achieved significant survival after transplantation, whereas CHP livers were affected by vascular damage as demonstrated by fatal thrombosis after transplantation. These data suggest that ATP content is not the only determinant of good liver function. A system of hypothermic perfusion might further improve liver preservation efficacy should injury to the vascular endothelium be avoided.
Disturbances in growth control and gene expression in a C3H/10T1/2 cell line that stably overproduces protein kinase C. (1989)

We have utilized a retroviral expression vector to construct a series of C3H/10T1/2 murine fibroblast cell lines that stably overexpress a full length cDNA encoding rat protein kinase C beta 1 (PKC). These cell lines contain 3-11 fold greater PKC enzyme activity than parental cells or control cells that carry an integrated vector lacking the cDNA insert. 10T1/2-PKC-4, a line with an 11-fold increase in PKC activity, is morphologically altered, grows to 4-fold higher saturation density, and has decreased adhesiveness when compared to control cells. These cells also show constitutive and inducible alterations in the levels of two PKC-regulated genes, phorbin and TPA-R1. However, 10T1/2-PKC-4 cells do not have a transformed morphology, are incapable of growth in soft agar, and are non-tumorigenic in nude mice. When 10T1/2-PKC-4 cells are cultured in 2.5% calf serum and 100 ng ml-1 TPA, numerous large, dense foci appear 2-3 weeks after the cells reach confluence. TPA is required for focus formation, and control cells do not form foci under the same conditions. However, when such foci are isolated and grown in the absence of TPA, the cells closely resemble later passage 10T1/2-PKC-4 cells. Therefore, the events leading to focus formation appear to be reversible. The 10T1/2-PKC-4 cell line should be valuable for more precisely defining molecular events relevant to tumor promotion and multistage carcinogenesis.
Structure–Property Relationships of a Class of Carbamate‐Based Fatty Acid Amide Hydrolase (FAAH) Inhibitors: Chemical and Biological Stability (2009)

Cyclohexylcarbamic acid aryl esters are a class of fatty acid amide hydrolase (FAAH) inhibitors, which includes the reference compound URB597. The reactivity of their carbamate fragment is involved in pharmacological activity and may affect their pharmacokinetic and toxicological properties. We conducted in vitro stability experiments in chemical and biological environments to investigate the structure-stability relationships in this class of compounds. The results show that electrophilicity of the carbamate influences chemical stability, as suggested by the relation between the rate constant of alkaline hydrolysis (log k(pH9)) and the energy of the lowest unoccupied molecular orbital (LUMO). Introduction of small electron-donor substituents at conjugated positions of the O-aryl moiety increased the overall hydrolytic stability of the carbamate group without affecting FAAH inhibitory potency, whereas peripheral non-conjugated hydrophilic groups, which favor FAAH recognition, helped decrease oxidative metabolism in the liver.
Catecholaminergic Polymorphic Ventricular Tachycardia Is Caused by Mutation-Linked Defective Conformational Regulation of the Ryanodine Receptor (2010)

A single point mutation within the RyR2 sensitizes the channel to agonists and reduces the threshold of luminal [Ca(2+)] for activation, primarily mediated by defective interdomain interaction within the RyR2.
Quantitative evaluation of blood-brain barrier permeability following middle cerebral artery occlusion in rats (1996)

A sensitive quantitative fluorescence method was used to explore the time course and regional pattern of blood-brain barrier (BBB) opening after transient middle cerebral artery occlusion (MCAo). Male Sprague-Dawley rats were anesthetized with halothane and subjected to 2 h of temporary MCAo by retrograde insertion of an intraluminal nylon suture, coated with poly-L-lysine, through the external carotid artery into the internal carotid artery and MCA. Damage to the BBB was judged by extravasation of Evans Blue (EB) dye, which was administered either 2, 3, 24 or 48 h after onset of MCAo. Fluorometric quantitation of EB was performed 1 or 2 h later in six brain regions. Cerebral infarction volumes were quantitated from histopathological material at 72 h. EB extravasation first became grossly visible in the ipsilateral caudoputamen and neocortex following 3 h of MCAo, was grossly unapparent at 24-26 h, and was maximal at 48-50 h. Fluorescence quantitation confirmed that BBB opening was absent at 2-3 h but present at all later times. In the hemisphere ipsilateral to MCAo, a 179% mean increase in extravasation of EB (compared to sham rats) was measured at 4 h, 407% at 5 h, 311% at 26 h and 264% at 50 h. (in each case, P < 0.05 vs. sham). The volume of infarcted tissue at 72 h in this model was 163.6 +/- 7.7 mm3. Our results indicate that an initial, acute disruption of the BBB occurs between 3 and 5 h following MCAo, and that a later, more widespread increase in regional BBB permeability is present at 48 h. Regional measurement of Evans Blue extravasation offers a precise means of quantitating BBB disruption in focal cerebral ischemia; this method will be of considerable utility in assessing the BBB-protective properties of pharmacological agents.
Cobalt‐Catalyzed Cross‐Coupling Reaction between Functionalized Primary and Secondary Alkyl Halides and Aliphatic Grignard Reagents (2008)

Abstract The coupling of primary and secondary unactivated alkyl bromides with alkyl‐Grignard reagents was performed in good yields under mild conditions by using a new catalytic system: consisting of cobalt chloride and tetramethylethylenediamine (CoCl 2 ⋅2 LiI, 4 TMEDA). The reaction is very chemoselective since ketone, ester and nitrile functions are tolerated.
Rapid Simultaneous Diagnosis of Infections with Respiratory Syncytial Viruses A and B, Influenza Viruses A and B, and Human Parainfluenza Virus Types 1, 2, and 3 by Multiplex Quantitative Reverse Transcription–Polymerase Chain Reaction–Enzyme Hybridization Assay (Hexaplex) (1998)

A multiplex quantitative reverse transcription-polymerase chain reaction-enzyme hybridization assay (Hexaplex; Prodesse, Milwaukee) was developed and used to rapidly detect and quantitate RNA of respiratory syncytial viruses A and B, influenza viruses A and B, and human parainfluenza virus types 1, 2, and 3 in nasal wash specimens in a single test. Primers and probes originated from highly conserved regions of each viral genome. Six and a half primer pairs were mixed for the simultaneous detection and quantitation of RNA from seven different respiratory viruses. We tested 109 clinical samples with this assay. Twenty-nine virus culture-positive samples were all positive by Hexaplex. Samples from 40 symptomatic patients were negative by virus culture, but eight of these were positive by Hexaplex. Forty samples from asymptomatic children were negative by both virus culture and Hexaplex. No cross-reactions were noted among 17 different respiratory viruses with use of this assay. Hexaplex was 100% sensitive (95% confidence interval [CI], 0.88-1.0) and 98% specific (95% CI, 0.97-0.99). All eight "false-positive" Hexaplex results (in comparison with negative viral culture results) were for symptomatic patients with low numbers of virus RNA copies. This finding suggests that Hexaplex may be more sensitive than virus culture. Our data demonstrate that Hexaplex is a rapid, sensitive, and specific quantitative test for the diagnosis of infections with these seven common respiratory viruses.
Corn (Zea mays L.) Yield Prediction Using Multispectral and Multidate Reflectance (2003)

Yield predictive models based on multiple sampling dates may explain more yield variability than models based on a single sampling date. This study determined the influence of two approaches (multiple regression of either soil and crop multispectral and multidate reflectance or variables developed during principal‐component analysis of reflectance data) on corn ( Zea mays L.) yield predictions. Research was conducted in 1999, 2000, and 2001. Corn yield data from two 65‐ha fields were collected with a yield monitor, and crop and soil radiance [green, red, and near‐infrared (NIR) wavebands] was measured three times (April–May, July, and August–September). Relative radiance (reflectance) was determined by dividing the measured radiance by the radiance at invariant target. Stepwise multiple regression based on reflectance or principal components was used to develop predictive equations. Multiple‐regression models based on 2 yr of reflectance data were biased and provided poor estimates of yield whereas a model based on variables developed during principal‐component analysis of reflectance data measured in the spring and summer of 1999 and 200 was unbiased and explained 45% of the corn yield variability in 2001. Differences between these models were attributed to multicollinearity of the data. Models that included data from two or three sampling dates generally explained more yield variability than models that used only one sampling date. Reflectance measured early in the season provided information about soil water and color while reflectance measured in August and September provided information about plant conditions.
Fimbriae of Bacteroides nodosus: protein engineering of the structural subunit for the production of an exogenous peptide (1989)

The pattern of sequence variation between Bacteroides nodosus fimbrial subunits of different serotypes suggests a degree of flexibility, which might be exploited for protein engineering approaches for the expression of other peptides. We have tested this using the well-characterized peptide epitope from VP1 of foot-and-mouth disease virus (FMDV), residues 144-159: LRGDLQVLAQKVARTL (strain 01-BFS). Using bacterial codon usage, several oligonucleotides were designed for the substitution of this sequence internally at hypervariable regions of the fimbrial subunit (aligned for maximum homology), and for its addition at the carboxyterminus with a diglycine spacer as a flexible hinge. Following site-directed mutagenesis in phage M13, the modified genes were placed under PL promoter control and placed in a broad host range vector. Analysis of the variant proteins expressed in E. coli showed that these substitutions affected, to varying extents, recognition by both anti-fimbrial and anti-FMDV antibodies, indicating that hypervariable region 2 is a major antigenic determinant of the fimbrial subunit and that local stereochemical effects can influence antibody binding to the FMDV peptide antigenic determinant. In Pseudomonas aeruginosa, viable transformants could only be obtained with the mutant gene encoding the carboxy-terminal graft. These cells provided fimbrial preparations comprised of the modified subunit. This then constitutes the prototype for the development of a general expression system for the production of vaccine epitopes and other bioactive peptides. Furthermore, there is considerable scope for further modification of the system, for example by engineering specific chemical or protease cleavage sites for release of the grafted peptide. Alternatively, the fimbriae themselves may serve as a useful supramolecular carrier or adjuvant for immune provocation.
Characterization of Continued Antibacterial Therapy After Diagnosis of Hospital‐Onset Clostridium difficile Infection: Implications for Antimicrobial Stewardship (2012)

A majority of patients with CDI continued to receive antibacterial agents after their CDI diagnosis, although the interhospital range was large. Compared with patients who did not continue therapy, hospital length of study, mortality, and subsequent admissions among patients who continued their antibacterial therapy remained significantly higher after adjusting for confounders. The adverse outcomes associated with continued therapy likely reflect the severity of the underlying primary infection and/or a poorer response to CDI therapy, suggesting an opportunity for antimicrobial stewardship programs to make important contributions to patient care.
Timing of paternal Pgk-1 expression in embryos of transgenic mice (1991)

In mouse development, the paternal allele of the X-linked gene Pgk-1 initiates expression on day 6, two days later than the maternal allele, which is activated on day 4. The different timing of expression of the maternal and paternal alleles may be determined by (i) imprinting of the chromosome region in which the gene resides, but not aimed specifically at the Pgk-1 gene; (ii) gene specific imprinting, acting on Pgk-1 irrespective of the chromosomal localization of the gene; (iii) an interplay between embryo cell differentiation, timing of X-inactivation and Pgk-1 expression, without the involvement of imprinting at the Pgk-1 locus itself (Fundele R., Illmensee, K., Jagerbauer, E. M., Fehlau, M. and Krietsch, W. K. (1987) Differentiation 35, 31-36). Our findings in transgenic mouse lines, carrying Pgk-1 on autosomes, indicate the importance of the X chromosomal location for the delayed expression of the paternal Pgk-1 allele, and are in agreement with the first of the explanations listed above. We propose that the late activation of the paternal Pgk-1 locus is a consequence of imprinting targeted at, and centered around, the X chromosome controlling element.
Approach for satellite slant pathremote sensing (1998)

It is theoretically and experimentally shown how angular smoothing of the sky brightness temperature caused by the radiometer antenna pattern can be used in conjunction with the spectral characteristics of the amplitude scintillations of a beacon receiver to allow unambiguous determination of the wind speed of a turbulent layer and its height, helping in the estimation of the refractive index structure constant (Cn2).
AI-Assisted Pipeline for Dynamic Generation of Trustworthy Health Supplement Content at Scale (2018)

Although geospatial question answering systems have received increasing attention in recent years, existing prototype systems struggle to properly answer qualitative spatial questions. In this work, we propose a unique framework for answering qualitative spatial questions, which comprises three main components: a geoparser that takes the input questions and extracts place semantic information from text, a reasoning system which is embedded with a crisp reasoner, and finally, answer extraction, which refines the solution space and generates final answers. We present an experimental design to evaluate our framework for point-based cardinal direction calculus (CDC) relations by developing an automated approach for generating three types of synthetic qualitative spatial questions. The initial evaluations of generated answers in our system are promising because a high proportion of answers were labelled correct.
Human motion signatures: analysis, synthesis, recognition (2003)

Human motion is the composite consequence of multiple elements, including the action performed and a motion signature that captures the distinctive pattern of movement of a particular individual. We develop an algorithm that is capable of extracting these motion elements and recombining them in novel ways. The algorithm analyzes motion data spanning multiple subjects performing different actions. The analysis yields a generative motion model that can synthesize new motions in the distinctive styles of these individuals. Our algorithms can also recognize people and actions from new motions by comparing motion signatures and action parameters.