gebhart/patrepeval huggingface dataset:
Direct cytochemical localization of catalytic subunits dissociated from cAMP-dependent protein kinase in Reuber H-35 hepatoma cells. II. Temporal and spatial kinetics. (1982)

The activation of cyclic AMP-dependent protein kinase has been found to be the predominant mode by which cyclic AMP (cAMP) leads to alterations of a large variety of cellular functions. The activation of the kinase results in the release of the catalytic subunit which as the free enzyme possesses phosphotransferase activity for a variety of specific protein substrates. Using a sensitive and specific cytofluorometric technique we monitored the appearance of free catalytic subunit in Reuber H35 hepatoma cells in culture after incubation with N6-1'-O-dibutyryl-cyclic AMP (DBcAMP), 8-bromoadenosine-3':5'-cyclic monophosphate (8-BrcAMP), and glucagon. The cytochemical method employs the heat-stable inhibitor of the free catalytic subunit which has been conjugated to fluorescein isothiocyanate (F:PKI) and was validated as described in the companion paper (Fletcher and Byus. 1982. J. Cell Biol. 93:719-726). Here we studied the temporal and spatial kinetics of the free catalytic subunit following activation of cAMP-dependent protein kinase by increasing concentrations of DBcAMP,8-BrcAMP, and glucagon. Under similar conditions protein kinase activation was also assessed biochemically in H35 cell supernatants by assaying the protein kinase activity ratio. Incubation of the hepatoma cells with DBcAMP (0.1 mM) led to an increase in the activity ratio from 0.2 in control cultures to a value of nearly 1.0 within a 1- to 2-h period. During this same period using the F:PKI probe, a significant increase in cytoplasmic and nucleolar fluorescence indicative of the release of the free catalytic subunit was coincidentally observed. In contrast to the rapid appearance of catalytic subunit in the cytoplasm and nucleolus of the cell within 5-15 min of the addition of DBcAMP, discernible nucleoplasmic fluorescence did not occur until after 1 h. H35 cell cultures incubated with 8-BrcAMP (0.01-1.0 mM) exhibited a more rapid activation of the protein kinase measured cytochemically compared to the cells treated with DBcAMP. Cultures incubated with 8-BrcAMP had significantly increased cytoplasmic and nucleolar fluorescence compared to unstimulated cells within 1 min of the addition of the analogue and reached a maximal level within 15 min. By employing a microspectrophotometer a distinct dose-dependent increase in cellular fluorescence (i.e., free catalytic subunit) was observed as the concentration of 8-BrcAMP was increased from 0.01 to 1.0 mM at 1, 5, 15, and 60 min following stimulation. The addition of glucagon (10(-6) M) to the culture also led to the activation of cAMP-dependent protein kinase as determined by an increase in the activity ratio. This increase was paralleled throughout the incubation period by a marked elevation in cytoplasmic and nucleolar fluorescence. The results reported herein suggest that both cyclic nucleotide analogues and a polypeptide hormone lead to the activation of cAMP-dependent protein kinase in similar intracellular compartments in Reuber H35 hepatoma cells...
Altered Localization of p120 Catenin During Epithelial to Mesenchymal Transition of Colon Carcinoma Is Prognostic for Aggressive Disease (2005)

We examined the expression and localization of p120 catenin (p120ctn) as a consequence of the epithelial to mesenchymal transition (EMT) of highly differentiated colon carcinoma cells (LIM1863 cells). This unique line grows in suspension as spheroids and undergoes an EMT within 24 hours following stimulation with transforming growth factor-beta and tumor necrosis factor-alpha. Although p120ctn expression remains stable during the EMT, its localization shifts from cell-cell junctions to the cytoplasm. Interestingly, a marked decrease in RhoA activation coincident with E-cadherin loss occurs during the EMT and correlates with the formation of a p120ctn/RhoA complex. Use of RNA interference showed that p120ctn reduction results in increased RhoA activity and a significant decrease in the motility of post-EMT cells. To determine the relevance of these findings to colorectal cancer progression, we assessed p120ctn expression by immunohistochemistry in 557 primary tumors. Of note, we observed that 53% of tumors presented cytoplasmic staining for p120ctn, and statistical analysis revealed that this localization is predictive of poor patient outcome. Cytoplasmic p120ctn correlated with later-stage tumors, significantly reduced 5- and 10-year survival times and a greater propensity for metastasis to lymph nodes compared with junctional p120ctn. We also confirmed that altered localization of p120ctn corresponded with loss or cytoplasmic localization of E-cadherin. These alterations in E-cadherin are also associated with a significant reduction in patient survival time and an increase in tumor stage and lymph node metastasis. These data provide a compelling argument for the importance of both p120ctn and the EMT itself in the progression of colorectal carcinoma.
Mathematical Modeling of Yarn Dynamics in a Generalized Twisting System (2016)

Twisting is an important process to form a continuous yarn from short fibres and to determine the structure and properties of the resultant yarn. This paper proposes a new theoretical model of yarn dynamics in a generalized twisting system, which deals with two important phenomena simultaneously, that is, twist generation and twist propagation. Equations of yarn motion are established and the boundary value problems are numerically solved by Newton-Raphson method. The simulation results are validated by experiments and a good agreement has been demonstrated for the system with a moving rigid cylinder as the twisting element. For the first time, influences of several parameters on the twisting process have been revealed in terms of twist efficiency of the moving rigid cylinder, propagation coefficients of twist trapping and congestion. It was found that the wrap angle and yarn tension have large influence on the twisting process, and the yarn torsional rigidity varies with the twisting parameters.
Exploring Librarians’ Teaching Roles through Metaphor (2021)

As librarians’ instructional roles continue to evolve, metaphor can be a powerful tool through which to reflect on and at times to reframe librarians’ evolving educational roles and pedagogical approaches, as they consider beliefs and assumptions about teaching and learning and about their unfolding work and identities. This article explores this potential by examining professional documents on librarians’ teaching, discussing empirical research on metaphor as a tool for teacher development, examining metaphors that librarians have sometimes used to describe their pedagogical work, and sharing the author’s experiences facilitating a librarian workshop on metaphor and librarians’ teaching roles.
Geometric Means in a Novel Vector Space Structure on Symmetric Positive‐Definite Matrices (2007)

In this work we present a new generalization of the geometric mean of positive numbers on symmetric positive‐definite matrices, called Log‐Euclidean. The approach is based on two novel algebraic structures on symmetric positive‐definite matrices: first, a lie group structure which is compatible with the usual algebraic properties of this matrix space; second, a new scalar multiplication that smoothly extends the Lie group structure into a vector space structure. From bi‐invariant metrics on the Lie group structure, we define the Log‐Euclidean mean from a Riemannian point of view. This notion coincides with the usual Euclidean mean associated with the novel vector space structure. Furthermore, this means corresponds to an arithmetic mean in the domain of matrix logarithms. We detail the invariance properties of this novel geometric mean and compare it to the recently introduced affine‐invariant mean. The two means have the same determinant and are equal in a number of cases, yet they are not identical in general. Indeed, the Log‐Euclidean mean has a larger trace whenever they are not equal. Last but not least, the Log‐Euclidean mean is much easier to compute.
Arabidopsis mutant analysis and gene regulation define a nonredundant role for glutamate dehydrogenase in nitrogen assimilation. (1996)

Glutamate dehydrogenase (GDH) is ubiquitous to all organisms, yet its role in higher plants remains enigmatic. To better understand the role of GDH in plant nitrogen metabolism, we have characterized an Arabidopsis mutant (gdh1-1) defective in one of two GDH gene products and have studied GDH1 gene expression. GDH1 mRNA accumulates to highest levels in dark-adapted or sucrose-starved plants, and light or sucrose treatment each repress GDH1 mRNA accumulation. These results suggest that the GDH1 gene product functions in the direction of glutamate catabolism under carbon-limiting conditions. Low levels of GDH1 mRNA present in leaves of light-grown plants can be induced by exogenously supplied ammonia. Under such conditions of carbon and ammonia excess, GDH1 may function in the direction of glutamate biosynthesis. The Arabidopsis gdh-deficient mutant allele gdh1-1 cosegregates with the GDH1 gene and behaves as a recessive mutation. The gdh1-1 mutant displays a conditional phenotype in that seedling growth is specifically retarded on media containing exogenously supplied inorganic nitrogen. These results suggest that GDH1 plays a nonredundant role in ammonia assimilation under conditions of inorganic nitrogen excess. This notion is further supported by the fact that the levels of mRNA for GDH1 and chloroplastic glutamine synthetase (GS2) are reciprocally regulated by light.
Natural language processing: State of the art and prospects for significant progress, a workshop sponsored by the National Library of Medicine (2013)

Natural language processing (NLP) is crucial for advancing healthcare because it is needed to transform relevant information locked in text into structured data that can be used by computer processes aimed at improving patient care and advancing medicine. In light of the importance of NLP to health, the National Library of Medicine (NLM) recently sponsored a workshop to review the state of the art in NLP focusing on text in English, both in biomedicine and in the general language domain. Specific goals of the NLM-sponsored workshop were to identify the current state of the art, grand challenges and specific roadblocks, and to identify effective use and best practices. This paper reports on the main outcomes of the workshop, including an overview of the state of the art, strategies for advancing the field, and obstacles that need to be addressed, resulting in recommendations for a research agenda intended to advance the field.
FTY720 (fingolimod) efficacy in an animal model of multiple sclerosis requires astrocyte sphingosine 1-phosphate receptor 1 (S1P <sub>1</sub> ) modulation (2010)

Sphingosine 1-phosphate (S1P), a lysophospholipid, has gained relevance to multiple sclerosis through the discovery of FTY720 (fingolimod), recently approved as an oral treatment for relapsing forms of multiple sclerosis. Its mechanism of action is thought to be immunological through an active phosphorylated metabolite, FTY720-P, that resembles S1P and alters lymphocyte trafficking through receptor subtype S1P(1). However, previously reported expression and in vitro studies of S1P receptors suggested that direct CNS effects of FTY720 might theoretically occur through receptor modulation on neurons and glia. To identify CNS cells functionally contributing to FTY720 activity, genetic approaches were combined with cellular and molecular analyses. These studies relied on the functional assessment, based on clinical score, of conditional null mouse mutants lacking S1P(1) in CNS cell lineages and challenged by experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. All conditional null mutants displayed WT lymphocyte trafficking that responded normally to FTY720. In marked contrast, EAE was attenuated and FTY720 efficacy was lost in CNS mutants lacking S1P(1) on GFAP-expressing astrocytes but not on neurons. In situ hybridization studies confirmed that astrocyte loss of S1P(1) was the key alteration in functionally affected mutants. Reductions in EAE clinical scores were paralleled by reductions in demyelination, axonal loss, and astrogliosis. Receptor rescue and pharmacological experiments supported the loss of S1P(1) on astrocytes through functional antagonism by FTY720-P as a primary FTY720 mechanism. These data identify nonimmunological CNS mechanisms of FTY720 efficacy and implicate S1P signaling pathways within the CNS as targets for multiple sclerosis therapies.
Caudal Cruciate Ligament Damage in Dogs with Cranial Cruciate Ligament Rupture (2010)

In dogs with CCLR, cruciate ligament pathology typically involves both the CCL and CaCL. As the severity of synovitis and the extent of CaCL damage are related, this observation supports the hypothesis that stifle synovitis may contribute to CCL and CaCL degeneration and subsequent damage.
Low-Voltage Origami-Paper-Based Electrophoretic Device for Rapid Protein Separation (2014)

We present an origami paper-based electrophoretic device (oPAD-Ep) that achieves rapid (∼5 min) separation of fluorescent molecules and proteins. Due to the innovative design, the required driving voltage is just ∼10 V, which is more than 10 times lower than that used for conventional electrophoresis. The oPAD-Ep uses multiple, thin (180 μm/layer) folded paper layers as the supporting medium for electrophoresis. This approach significantly shortens the distance between the anode and cathode, and this, in turn, accounts for the high electric field (>1 kV/m) that can be achieved even with a low applied voltage. The multilayer design of the oPAD-Ep enables convenient sample introduction by use of a slip layer as well as easy product analysis and reclamation after electrophoresis by unfolding the origami paper and cutting out desired layers. We demonstrate the use of oPAD-Ep for simple separation of proteins in bovine serum, which illustrates its potential applications for point-of-care diagnostic testing.
Feasibility, Utility, and Limitations of a Rapid Community Behavioral Diagnosis for Social Distancing During the 2020 Coronavirus Pandemic (2020)

In a situation where local community action is paramount for reducing coronavirus transmission, this RCBD process is feasible and useful for informing local health promotion.
Development of Spontaneous Synaptic Transmission in the Rat Spinal Cord (1998)

Dorsal root afferents form synaptic connections on motoneurons a few days after motoneuron clustering in the rat lumbar spinal cord, but frequent spontaneous synaptic potentials are detected only after birth. To increase our understanding of the mechanisms underlying the differentiation of synaptic transmission, we examined the developmental changes in properties of spontaneous synaptic transmission at early stages of synapse formation. Spontaneous postsynaptic currents (PSCs) and tetrodotoxin (TTX)-resistant miniature PSCs (mPSCs) were measured in spinal motoneurons of embryonic and postnatal rats using whole cell patch-clamp recordings. Spontaneous PSC frequencies were higher than mPSC frequencies in both embryonic and postnatal motoneurons, suggesting that even at embryonic stages, when action-potential firing rate was low, presynaptic action potentials played an important role in triggering spontaneous PSCs. After birth, the twofold increase in spontaneous PSC frequency was attributed to an increase in action-potential-independent quantal release rather than to a higher rate of action-potential firing. In embryonic motoneurons, the fluctuations in peak amplitude of spontaneous PSCs were normally distributed around single peaks with modal values similar to those of mPSCs. These data indicated that early in synapse differentiation spontaneous PSCs were primarily composed of currents generated by quantal release. After birth, mean mPSC amplitude increased by 50% but mean quantal current amplitude did not change. Synchronous, multiquantal release was apparent in postnatal motoneurons only in high-K+ extracellular solution. Comparison of the properties of miniature excitatory and inhibitory postsynaptic currents (mEPSCs and mIPSCs) demonstrated that mean mEPSC frequency was higher than mIPSC frequency, suggesting that either excitatory synapses outnumbered inhibitory synapses or that the probability of excitatory transmitter release was higher than the release of inhibitory neurotransmitters. The finding that mIPSC duration was several-fold longer than mEPSC duration implied that despite their lower frequency, inhibitory currents could modulate motoneuron synaptic integration by shunting incoming excitatory inputs for prolonged time intervals.
Strain and temperature characterization of LPGs written by CO2 laser in pure silica LMA photonic crystal fibers (2015)

This paper reports on the writing of long period gratings (LPGs) in a six-ring pure silica solid core, and large mode area photonic crystal fiber (fiber core diameter ρ = 10.1 μm) using a CO2 laser system, and the characterization of their strain and temperature sensitivities. Temperature and strain sensitivities in the order of −19.6 pm/°C and −88 pm/μɛ, respectively, were obtained, which were comparable or surpassed values of the similar photonic crystal fiber (PCF)-based LPG or sensor configurations found in the literature.
Printing Ultrasensitive Artificially Intelligent Sensors Array with a Single Self‐Propelled Droplet Containing Nanoparticles (2016)

The fabrication and implementation of artificially intelligent sensor arrays has faced serious technical and/or cost‐effectiveness challenges. Here, a new printing method is presented to produce a fully functional array of sensors based on monolayer‐capped gold nanoparticles. The proposed printing technique is based on the so‐called self‐propelled antipinning ink droplet, from which evaporative deposition takes place along the path of motion. By applying actuating forces, different deposition line patterns with different thicknesses and morphology from a single droplet are generated. The functionality of the produced sensors is demonstrated by their ability to detect different representative volatile organic compounds (VOCs) belonging to different chemical families, including alcohols, alkanes, ethers, and aromatics, and under extremely different humidity levels resembling those encountered in real‐world conditions. The results show that the sensors exhibit ultrasensitive sensing features, with an ability to detect and differentiate between different VOCs at low ppb levels. Additionally, the results show that the sensors are able to accurately predict VOC concentrations, viz. enable quantification capabilities, while nevertheless being inexpensive, do not need complicated and expensive printing equipment and prepatterning processes, allow low voltage operation, and provide a platform for multifunctional applications.
Structural basis of AMPK regulation by small molecule activators (2013)

AMP-activated protein kinase (AMPK) plays a major role in regulating cellular energy balance by sensing and responding to increases in AMP/ADP concentration relative to ATP. Binding of AMP causes allosteric activation of the enzyme and binding of either AMP or ADP promotes and maintains the phosphorylation of threonine 172 within the activation loop of the kinase. AMPK has attracted widespread interest as a potential therapeutic target for metabolic diseases including type 2 diabetes and, more recently, cancer. A number of direct AMPK activators have been reported as having beneficial effects in treating metabolic diseases, but there has been no structural basis for activator binding to AMPK. Here we present the crystal structure of human AMPK in complex with a small molecule activator that binds at a site between the kinase domain and the carbohydrate-binding module, stabilising the interaction between these two components. The nature of the activator-binding pocket suggests the involvement of an additional, as yet unidentified, metabolite in the physiological regulation of AMPK. Importantly, the structure offers new opportunities for the design of small molecule activators of AMPK for treatment of metabolic disorders.
Comparison between Tube Ileostomy and Loop Ileostomy as a Diversion Procedure (2012)

Aim. Loop ileostomy has high complication rates and causes much patient inconvenience. This study was performed to compare the outcome of tube versus loop ileostomy in management of ileal perforations. Patients and Methods. From July 2008 to July 2011, all patients with ileal perforation on laparotomy where a defunctioning proximal protective loop ileostomy was considered advisable were chosen for study. Patients were randomly assigned to undergo either tube ileostomy or classical loop ileostomy as the diversion procedure. Tube ileostomy was constructed in the fashion of feeding jejunostomy, with postoperative saline irrigation. Results. A total of 60 diversion procedures were performed over the period with 30 for each of tube and loop ileostomy. Typhoid and tuberculosis formed the most common etiology for ileal perforation. The complication rate of tube ileostomy was 33%. Main complications related to tube ileostomy were peritubal leak, tube blockage. In patients with loop, overall complications in 53% majority were peristomal skin irritation and wound infection following ileostomy closure. Two patients developed obstruction following ileostomy closure which needed reoperation. Conclusions. Tube ileostomy is effective and feasible as a diversion procedure and has reduced morbidity. It can be used as an alternative to loop ileostomy.
Self-Assembly of Designed Antimicrobial Peptides in Solution and Micelles (1997)

Hydrophobic interactions are responsible for stabilizing leucine zippers in peptides containing heptad repeats. The effects of substituting leucine by phenylalanine and alanine by glycine on the self-assembly of coiled-coils were examined in minimalist antimicrobial peptides designed to form amphipathic alpha-helices. The secondary structure of these peptides was monitored in solution and in diphosphocholine (DPC) micelles using circular dichroism spectroscopy. The leucine peptides (KLAKLAK)3 and (KLAKKLA)n (n = 3, 4) become alpha-helical with increasing concentrations of salt, peptide, and DPC. The aggregation state and equilibrium constant for self-association of the peptides were measured by sedimentation equilibrium. The glycine peptide (KLGKKLG)3 does not self-associate. The leucine peptides and phenylalanine peptides (KFAKFAK)3 and (KFAKKFA)n (n = 3, 4) are in a monomer-tetramer equilibrium in solution, with the phenylalanine zippers being 2-4 kcal/mol less stable than the equivalent leucine zippers. Thermodynamic parameters for the association reaction were calculated from the temperature dependence of the association constants. Leucine zipper formation has DeltaCp = 0, whereas phenylalanine zipper formation has a small negative DeltaCp, presumably due to the removal of the larger surface area of phenylalanine from water. Self-association of the peptides is coupled to formation of a hydrophobic core as detected using 1-anilino-naphthalene-8-sulfonate fluorescence. Carboxyfluorescein-labeled peptides were used to determine the aggregation state of (KLAKKLA)3 and (KLGKKLG)3 in DPC micelles. (KLAKKLA)3 forms dimers, and (KLGKKLG)3 is a monomer. Aggregation appears to correlate with the cytotoxicity of these peptides.