gebhart/patrepeval huggingface dataset:
Vulnerability of Central Neurons to Secondary Insults afterIn VitroMechanical Stretch (2004)

Mild traumatic brain injuries are of major public health significance. Neurons in such injuries often survive the primary mechanical deformation only to succumb to subsequent insults. To study mechanisms of vulnerability of injured neurons to secondary insults, we used an in vitro model of sublethal mechanical stretch. Stretch enhanced the vulnerability of the neurons to excitotoxic insults, causing nuclear irregularities, DNA fragmentation, and death suggestive of apoptosis. However, the DNA degradation was not attributable to classical (caspase mediated) or caspase-independent apoptosis. Rather, it was associated with profound stretch-induced mitochondrial dysfunction and the overproduction of reactive oxygen species (ROS). Sublethally stretched neurons produced surprisingly high levels of ROS, but these in isolation were insufficient to kill the cells. To be lethal, the ROS also needed to combine with nitric oxide (NO) to form the highly reactive species peroxynitrite. Peroxynitrite was not produced after stretch alone and arose only after combining stretch with an insult capable of stimulating NO production, such as NMDA or an NO donor. This explained the exquisite sensitivity of sublethally stretched neurons to a secondary NMDA insult. ROS scavengers and NO synthase (NOS) inhibitors prevented cell death and DNA degradation. Moreover, inhibiting neuronal NOS activation by NMDA using peptides that perturb NMDA receptor-postsynaptic density-95 interactions also reduced protein nitration and cell death, indicating that the reactive nitrogen species produced were neuronal in origin. Our data explain the mechanism of enhanced vulnerability of sublethally injured neurons to secondary excitotoxic insults and highlight the importance of secondary mechanisms to the ultimate outcome of neurons in mild neurotrauma.
Discovery of a Potent, Selective, and Efficacious Class of Reversible α-Ketoheterocycle Inhibitors of Fatty Acid Amide Hydrolase Effective as Analgesics (2004)

Fatty acid amide hydrolase (FAAH) degrades neuromodulating fatty acid amides including anandamide (endogenous cannabinoid agonist) and oleamide (sleep-inducing lipid) at their sites of action and is intimately involved in their regulation. Herein we report the discovery of a potent, selective, and efficacious class of reversible FAAH inhibitors that produce analgesia in animal models validating a new therapeutic target for pain intervention. Key to the useful inhibitor discovery was the routine implementation of a proteomics-wide selectivity screen against the serine hydrolase superfamily ensuring selectivity for FAAH coupled with systematic in vivo examinations of candidate inhibitors.
Effects of Right and Left Cardiosympathetic Nerve Stimulation on Blood Flow in the Major Coronary Arteries of the Anaesthetized Dog (1969)

Journal Article Effects of Right and Left Cardiosympathetic Nerve Stimulation on Blood Flow in the Major Coronary Arteries of the Anaesthetized Dog Get access Gordon Ross, Gordon Ross From the Departments of Physiology and Thoracic Surgery, U.C.L.A. School of Medicine, Los Angeles, California, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Donald G. Mulder Donald G. Mulder From the Departments of Physiology and Thoracic Surgery, U.C.L.A. School of Medicine, Los Angeles, California, U.S.A. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 3, Issue 1, January 1969, Pages 22–29, https://doi.org/10.1093/cvr/3.1.22 Published: 01 January 1969 Article history Received: 22 April 1968 Published: 01 January 1969
Synthetic Strategies towards Well‐Defined Complex Polymeric Architectures through Covalent Chemistry (2014)

Abstract Macromolecular architecture is a key factor determining the materials properties of polymers. Exploration of novel structural arrangements has become a viable means to develop advanced functional nanomaterials. Recent developments in polymer chemistry have forged robust synthetic platforms for innovative polymeric materials with highly regulated structures, functionalities, and compositions. This review summarizes the latest synthetic strategies for well‐defined polymer architectures through covalent chemistry, with the focus on four main types of well‐defined macromolecular constructs.
Appearance and localization of acetylcholinesterase in embryos of the leech Helobdella triserialis (1981)

The appearance and localization of acetylcholinesterase (AchE) were studied during embryonic development of the leech Helobdella triserialis. Use of a histochemical stain showed that AchE is present in the polar plasms of the uncleaved leech egg. in the course of the first two cleavages, the AchE is transmitted along with the polar plasms mainly to the D blastomere, precursor of mesoderm and ectoderm. At these early developmental stages, AchE also lines the cleavage furrows between the blastomeres. At later stages, AchE is present in the parental meso- and ectoteloblasts and their daughter stem cells that form the germinal bands. At the completion of germinal band coalescence, AchE is present in the rostral and caudal regions of the germinal plate. Thus, the presence of AchE in the early phase of embryogenesis precedes the formation of any nervous tissue. In the late phase of embryogenesis, once the embryo has reached the stage of body closure and a nervous system is present, the distribution of AchE is that characteristic of the adult leech: AchE is localized in the neuropil of the segmental ganglia of the ventral nerve cord and in the musculature of the body wall. Therefore, at this still quite immature stage, the embryonic nervous system has taken on not only the morphological but also some of the neurochemical characteristics of the adult leech.
Effect of Diet‐induced Obesity on Acute Pancreatitis Induced by Administration of Interleukin‐12 Plus Interleukin‐18 in Mice (2009)

Obesity is associated with increased severity of acute pancreatitis (AP). We recently developed a model of AP induced by administration of interleukin (IL)-12+IL-18, two cytokines that are elevated in patients with AP. In this model, severe AP develops in obese leptin-deficient ob/ob mice compared to lean littermates. In the present report, we evaluated the pancreatic response of diet-induced obesity (DIO) mice to IL-12+IL-18. Body weight loss and adipose tissue necrosis were more severe and prolonged in cytokine-injected DIO compared to lean mice. Edematous AP developed in lean mice, whereas DIO mice developed necrotizing AP. Obese DIO mice developed more severe hypocalcemia, increased liver damage and a heightened acute-phase response compared to lean mice, although leukopenia and thrombocytopenia were of comparable severity in lean and DIO mice. Serum levels of IL-6, IL-10, and IL-22 were significantly higher in DIO compared to lean mice, whereas interferon-gamma and tumor necrosis factor-alpha did not differ between the two groups. In conclusion, obesity induced by high-fat diet is associated with increased disease severity and duration in the model of AP induced by administration of IL-12+IL-18.
Quantifying Adenovirus-Neutralizing Antibodies by Luciferase Transgene Detection: Addressing Preexisting Immunity to Vaccine and Gene Therapy Vectors (2003)

The presence of various levels of anti-adenovirus serotype 5 (Ad5)-neutralizing antibodies in humans is thought to contribute to the inconsistent clinical results obtained so far in diverse gene transfer and vaccination studies and might preclude universal dosing with recombinant Ad5. Prescreening of individuals eligible for Ad5 or alternative serotype treatment and subsequently tailoring the vector dose might aid in ensuring the consistency of clinical parameters. For this purpose, a qualified Ad neutralization assay is required. Here we have tested the different protocols used to date to determine anti-Ad neutralizing activity. Based on simplicity, speed, high throughput, sensitivity, and robustness, we propose a qualified assay in which Ad neutralization is monitored by luciferase reporter gene expression.
Efficient reconstruction of nonrigid shape and motion from real-time 3D scanner data (2009)

We present a new technique for reconstructing a single shape and its nonrigid motion from 3D scanning data. Our algorithm takes a set of time-varying unstructured sample points that capture partial views of a deforming object as input and reconstructs a single shape and a deformation field that fit the data. This representation yields dense correspondences for the whole sequence, as well as a completed 3D shape in every frame. In addition, the algorithm automatically removes spatial and temporal noise artifacts and outliers from the raw input data. Unlike previous methods, the algorithm does not require any shape template but computes a fitting shape automatically from the input data. Our reconstruction framework is based upon a novel topology-aware adaptive subspace deformation technique that allows handling long sequences with complex geometry efficiently. The algorithm accesses data in multiple sequential passes, so that long sequences can be streamed from hard disk, not being limited by main memory. We apply the technique to several benchmark datasets, significantly increasing the complexity of the data that can be handled efficiently in comparison to previous work.
Maximizing the response of selection with a predefined rate of inbreeding. (1997)

A method was derived that maximizes the genetic level of selected animals while constraining their average coancestry to a predefined value. The average coancestry of the selected parents equals the inbreeding level in the next generation, so that rates of inbreeding were controlled. When this method was applied for several generations of selection, stable rates of genetic gain were attained, which indicates that the method could control the short- and long-term effects of selection on inbreeding. At equal rates of inbreeding, genetic gains were 21 to 60% greater than that with selection for BLUP-EBV, because of increased selection differentials. The difference was larger when the desirable rate of inbreeding was smallest. Selection with a constraint on inbreeding required only EBV of, and relationships between, the selection candidates and is therefore easy to apply in practice. The optimal solution is expressed in genetic contributions of selection candidates to the next generation, which is equivalent to numbers of offspring per candidate. These optimal numbers of offspring may be difficult to attain because of female reproductive limitations. The optimal method could be adapted to situations with additional reproductive constraints. The method can also be used to constrain the variance of response by restricting the average prediction error variance of the selected animals.
Periostin‐like‐factor in osteogenesis (2008)

Periostin-like-factor (PLF), an isoform related to Periostin, is expressed in bone, heart, and vascular smooth muscle cells. PLF was detected by immunostaining in mesenchymal cells in the periosteum and in osteoblasts lining trabecular bone, suggesting that PLF has a role in osteogenesis. PLF has a signal peptide and is also secreted from osteoblasts in vitro. To study the function of PLF in osteogenesis, we assessed the effect of PLF on osteoblast proliferation and differentiation in vitro and bone formation in vivo. First, to examine whether PLF regulates osteoblast proliferation in vitro, the CyQUANT cell proliferation assay was performed. PLF over-expression by adenovirus resulted in a significantly higher rate of cell proliferation compared to controls. This finding suggests that PLF promotes osteoblast proliferation in vitro. Second, to test whether PLF mediates osteoblast differentiation in vitro, differentiation markers of osteoblasts, were assessed, including alkaline phosphatase staining and activity, von Kossa staining and calcium deposition. Over-expression of PLF resulted in higher expression and activity of alkaline phosphatase and higher amounts of mineralization and calcium deposition compared to controls. These data suggest that PLF promotes osteoblast differentiation in vitro. Third, to investigate the role of PLF in bone formation in vivo, PLF adenovirus was injected into 6-week-old rat femur bone marrow. Over-expression of PLF resulted in increased bone formation within the marrow cavity. Lastly, in a model of fracture healing, PLF expression is robustly upregulated in callus osteoblasts at post-fracture days 7 and 14. Taken together, these findings suggests that PLF induces bone formation in vivo. We conclude that PLF stimulates bone formation in vivo possibly by promoting osteoblast proliferation and differentiation.
Novel putative protein tyrosine phosphatases identified by the polymerase chain reaction (1990)

Protein tyrosine phosphatases (PTPases) are a family of enzymes that specifically dephosphorylate phosphotyrosyl residues in selected protein substrates. To more fully understand the regulatory role of protein tyrosine phosphorylation and dephosphorylation in cellular signal transduction, characterization of PTPases is essential. Using the polymerase chain reaction and degenerate oligonucleotide primers corresponding to conserved amino acid sequences within the catalytic domain of PTPases, we have identified 11 PTPase-related human liver cDNA sequences. Five of these have not been described previously. These results indicate that, like protein tyrosine kinases, PTPases may also comprise a gene family with a large number of members.
Toxoid of Pseudomonas aeruginosa exotoxin A generated by deletion of an active-site residue (1988)

Glutamic acid-553 of Pseudomonas aeruginosa exotoxin A (ETA), identified previously as an active-site residue, was deleted by oligonucleotide-directed mutagenesis of the cloned toxin gene in Escherichia coli. The purified mutant toxin was stable, fully immunoreactive, and capable of blocking toxin receptors. ADP-ribosyltransferase and cytotoxic activities were at least 10(6)-fold lower than those of wild-type ETA, and injection of mice with 50 micrograms (equivalent to 400 lethal doses of ETA) produced no ill effects. The mutant toxin elicited high levels of neutralizing anti-ETA antibodies in mice, which protected against a challenge with 100 micrograms of authentic ETA (greater than 600 lethal doses). The mutant protein has the attributes of a toxoid and may be useful as a component of vaccines for individuals at risk for infection by P. aeruginosa.
Design Principles, Biomechanical Data and Clinical Experience with a Polycentric Knee Offering Controlled Stance Phase Knee Flexion (1997)

Published quarterly by the AAOP, JPO: Journal of Prosthetics and Orthotics provides information on new devices, fitting and fabrication techniques, and patient management experiences. The focus is on prosthetics and orthotics, with timely reports from related fields such as orthopaedic research, occupational therapy, physical therapy, orthopaedic surgery, amputation surgery, physical medicine, biomedical engineering, psychology, ethics, and gait analysis. Each issue contains research-based articles reviewed and approved by a highly qualified editorial board, and two Academy self-study quizzes offering a total of two CEUs.
Protective Immunity against Eimeria acervulina following In Ovo Immunization with a Recombinant Subunit Vaccine and Cytokine Genes (2004)

A purified recombinant protein from Eimeria acervulina (3-1E) was used to vaccinate chickens in ovo against coccidiosis both alone and in combination with expression plasmids encoding the interleukin 1 (IL-1), IL-2, IL-6, IL-8, IL-15, IL-16, IL-17, IL-18, or gamma interferon (IFN-gamma) gene. When used alone, vaccination with 100 or 500 mug of 3-1E resulted in significantly decreased oocyst shedding compared with that in nonvaccinated chickens. Simultaneous vaccination of the 3-1E protein with the IL-1, -15, -16, or -17 gene induced higher serum antibody responses than 3-1E alone. To evaluate protective intestinal immunity, vaccinated birds were challenged with live E. acervulina oocysts 14 days posthatch, and fecal-oocyst shedding and body weight gain were determined as parameters of coccidiosis. Chickens vaccinated with 3-1E protein showed significantly lower oocyst shedding and normal body weight gain than nonvaccinated and infected controls. Simultaneous immunization with 3-1E and the IL-2, -15, -17, or -18 or IFN-gamma gene further reduced oocyst shedding compared with that achieved with 3-1E alone. These results provide the first evidence that in ovo vaccination with the recombinant 3-1E Eimeria protein induces protective intestinal immunity against coccidiosis, and this effect was enhanced by coadministration of genes encoding immunity-related cytokines.
Chemically-Sensitive Imaging in Tapping Mode by Chemical Force Microscopy:  Relationship between Phase Lag and Adhesion (1998)

Tapping mode atomic force microscopy has been used to record phase-lag images of patterned self-assembled monolayer (SAM) surfaces in alcohol−water solutions using probe tips functionalized with SAMs that terminate in distinct chemical groups. We find that phase contrast between chemically distinct monolayer regions and adhesion forces are directly correlated: increasing adhesion forces lead to increases in the phase lag. Data recorded in alcohol−water mixtures have been analyzed using a driven oscillator model and show that differences in phase shift between distinct regions of the patterned SAMs can be quantitatively related to differences in the work of adhesion, Wst. Because the adhesion forces are readily interpretable on the basis of surface chemical functionality, our results demonstrate that intermittent contact or tapping mode force microscopy can be used to image samples with chemical sensitivity. The implications and potential applications of this new form of chemical force microscopy are discussed.
Neuregulin-1 Reverses Long-Term Potentiation at CA1 Hippocampal Synapses (2005)

Neuregulin-1 (NRG-1) has been identified genetically as a schizophrenia susceptibility gene, but its function in the adult brain is unknown. Here, we show that NRG-1beta does not affect basal synaptic transmission but reverses long-term potentiation (LTP) at hippocampal Schaffer collateral-->CA1 synapses in an activity- and time-dependent manner. Depotentiation by NRG-1beta is blocked by two structurally distinct and selective ErbB receptor tyrosine kinase inhibitors. Moreover, ErbB receptor inhibition increases LTP at potentiated synapses and blocks LTP reversal by theta-pulse stimuli. NRG-1beta selectively reduces AMPA, not NMDA, receptor EPSCs and has no effect on paired-pulse facilitation ratios. Live imaging of hippocampal neurons transfected with receptors fused to superecliptic green fluorescent protein, as well as quantitative analysis of native receptors, show that NRG-1beta stimulates the internalization of surface glutamate receptor 1-containing AMPA receptors. This novel regulation of LTP by NRG-1 has important implications for the modulation of synaptic homeostasis and schizophrenia.
Hematopoietic lineage- and stage-restricted expression of the ETS oncogene family member PU.1 (1993)

The ETS oncogene family member PU.1 is a transcriptional activator that is dysregulated by Friend erythroleukemia virus insertion. Northern analysis found that PU.1 is highly expressed in cells of myeloid and B- lymphoid origin, but not expressed at all in a number of nonhematopoietic tissues. Interferon-gamma and retinoic acid downregulated PU.1 expression in marrow macrophages. In situ immunohistochemistry found that PU.1 is expressed only in early granulocytic and erythroid cells and megakaryocytes, but not in mature erythroid cells, mature granulocytes, endothelial cells, or osteocytes. Thus, its expression pattern makes PU.1 a candidate for a genetic determinant of lineage commitment and stage progression in blood cell development. It also lends insight into how PU.1 might play a role in Friend virus erythroleukemia.
Monosodium [1-hydroxy-2-(1H-imidazol-3-ium-4-yl)ethane-1,1-diyl]bis(phosphonate) tetrahydrate (monosodium isozoledronate) (2002)

The title compound, Na(+).C(5)H(9)N(2)O(7)P(2)(-).4H(2)O, is an isomer of zoledronate, a potent bone antiresorptive bisphosphonate drug having significant activity against several parasitic protozoa. The crystal structure of isozoledronate consists of bisphosphonate dimers coordinated by two Na(+) ions. The dimers are held together through an extensive hydrogen-bonding network. The crystals exhibit non-merohedral twinning that roughly superimposes the a and b axes, and inverts the c axis.
Hydrogen sulfide is involved in the chilling stress response in Vitis vinifera L. (2013)

Hydrogen sulfide (H&lt;sub&gt;2&lt;/sub&gt;S) is an important signaling molecule involved in several stress-resistance processes in plants, such as drought and heavy metal stresses. However, little is known about the roles of H&lt;sub&gt;2&lt;/sub&gt;S in responses to chilling stress. In this paper, we demonstrated that chilling stress enhance the H&lt;sub&gt;2&lt;/sub&gt;S levels, the H&lt;sub&gt;2&lt;/sub&gt;S synthetase (L-/D-cysteine desulfhydrase, L/DCD) activities, and the expression of L/DCD gene in &lt;em&gt;Vitis vinifera&lt;/em&gt; L. ‘F-242’. Furthermore, the seedlings were treated with sodium hydrosulﬁde (NaHS, a H&lt;sub&gt;2&lt;/sub&gt;S donor) and hypotaurine (HT, a H&lt;sub&gt;2&lt;/sub&gt;S scavenger) at 4°C to examine the effects of exogenous H&lt;sub&gt;2&lt;/sub&gt;S on grape. The results revealed that the high activity of superoxide dismutase and enhanced expression of &lt;em&gt;VvICE1&lt;/em&gt; and &lt;em&gt;VvCBF3&lt;/em&gt; genes, but low level of super oxide anion radical, malondialdehyde content and cell membrane permeability were detected after addition of NaHS. In contrast, HT treatment displayed contrary effect under the chilling temperature. Taken together, these data suggested that H&lt;sub&gt;2&lt;/sub&gt;S might be directly involved in the cold signal transduction pathway of grape.
Neotectonic deformation of the central Chile margin: Deepwater forearc basin formation in response to hot spot ridge and seamount subduction (2002)

Underlying the midslope Valparaiso Terrace, the Valparaiso Basin constitutes a unique and prominent deepwater forearc basin on the central Chile margin. The basin contains a 3–3.5 km thick sediment fill of late Cenozoic age. The seismic‐stratigraphic architecture of the Valparaiso Basin fill shows that margin‐wide subsidence above the underthrusting Juan Fernández Ridge, an aseismic volcanic swell crested with seamounts on the Nazca plate, characterized the basin evolution. Contemporaneously with margin subsidence and seaward rotation of the upper slope and shelf, the outer part of the forearc was deformed by thrust faulting above the leading flank of underthrusting seamounts that rotated the middle slope to a more horizontal attitude and formed seaward‐vergent outer forearc highs. Subsidence of the margin above the underthrusting Juan Fernández Ridge is ascribed to processes of subduction erosion, enhanced by factors related to subduction of the ridge, that caused dismemberment of upper plate material along the shallow aseismic part of the plate interface and transfer of material to the downgoing Nazca plate. Accelerated midslope subsidence, 55–75 km landward of the trench, coincides with the seaward limit of interplate seismicity, suggesting that enhanced basal erosion is related to the transition from aseismic to stick slip subduction behavior. Since subduction of the Juan Fernández Ridge began near 33°S ∼10 Ma ago, the Chile Trench north of 33°S is inferred to have retreated ∼3 km/Myr, and the midslope Valparaiso Basin subsided ∼0.3–0.5 km/Myr, approximating analogous Neogene rates for the Peruvian margin.