gebhart/patrepeval huggingface dataset:
X-ray Absorption Spectroscopy Study of Cu0.25V2O5 and Zn0.25V2O5 Aerogel-Like Cathodes for Lithium Batteries (2004)

Vanadium pentoxide materials prepared through sol−gel processes (xerogel, aerogel, and aerogel-like) act as excellent intercalation hosts for lithium as well as polyvalent cations. The large lithium insertion capacity of these materials makes them attractive for use as cathodes in high-capacity lithium batteries. The local structural modifications resulting from low dopant concentration (copper and zinc) in V2O5 aerogel-like material have been investigated by X-ray absorption spectroscopy (XAS). To study the structural sites of the polyvalent ions, extended X-ray absorption fine structure (EXAFS) spectra have been recorded at the vanadium, zinc, and copper K edges. The EXAFS analysis shows that the vanadium atomic environment is almost the same for Cu0.25V2O5 and Zn0.25V2O5. Furthermore, the doping metals (Cu and Zn) are found to be in the same site. Copper and zinc are 4-fold coordinated by almost-coplanar oxygens. This suggests a preferred site for the doping metal (M) and the same interaction between the vanadium and the doping metals. M−O first-shell distances are shorter for the copper compared to those for the zinc, and we have found higher disorder in the Zn0.25V2O5 compound compared to that in Cu0.25V2O5. No interactions between metal−metal sites were found because the metal doping level was too small.
Antioxidants reduce endoplasmic reticulum stress and improve protein secretion (2008)

Protein misfolding in the endoplasmic reticulum (ER) contributes to the pathogenesis of many diseases. Although oxidative stress can disrupt protein folding, how protein misfolding and oxidative stress impact each other has not been explored. We have analyzed expression of coagulation factor VIII (FVIII), the protein deficient in hemophilia A, to elucidate the relationship between protein misfolding and oxidative stress. Newly synthesized FVIII misfolds in the ER lumen, activates the unfolded protein response (UPR), causes oxidative stress, and induces apoptosis in vitro and in vivo in mice. Strikingly, antioxidant treatment reduces UPR activation, oxidative stress, and apoptosis, and increases FVIII secretion in vitro and in vivo. The findings indicate that reactive oxygen species are a signal generated by misfolded protein in the ER that cause UPR activation and cell death. Genetic or chemical intervention to reduce reactive oxygen species improves protein folding and cell survival and may provide an avenue to treat and/or prevent diseases of protein misfolding.
Process vs resource‐oriented Petri net modeling of automated manufacturing systems (2010)

Abstract Since the 1980s, Petri nets (PN) have been widely used to model automated manufacturing systems (AMS) for analysis, performance evaluation, simulation, and control. They are mostly based on process‐oriented modeling methods and thus termed as process‐oriented PN (POPN) in this paper. The recent study of deadlock avoidance problems in AMS led to another type of PN called resource‐oriented PN (ROPN). This paper, for the first time, compares these two modeling methods and resultant models in terms of modeling power, model complexity for analysis and control, and some critical properties. POPN models the part production processes straightforwardly, while ROPN is more compact and effective for deadlock resolution. The relations between these two models are investigated. Several examples are used to illustrate them. Copyright © 2010 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society
-Amyloid Oligomers Induce Phosphorylation of Tau and Inactivation of Insulin Receptor Substrate via c-Jun N-Terminal Kinase Signaling: Suppression by Omega-3 Fatty Acids and Curcumin (2009)

Both insulin resistance (type II diabetes) and beta-amyloid (Abeta) oligomers are implicated in Alzheimer's disease (AD). Here, we investigate the role of Abeta oligomer-induced c-Jun N-terminal kinase (JNK) activation leading to phosphorylation and degradation of the adaptor protein insulin receptor substrate-1 (IRS-1). IRS-1 couples insulin and other trophic factor receptors to downstream kinases and neuroprotective signaling. Increased phospho-IRS-1 is found in AD brain and insulin-resistant tissues from diabetics. Here, we report Abeta oligomers significantly increased active JNK and phosphorylation of IRS-1 (Ser616) and tau (Ser422) in cultured hippocampal neurons, whereas JNK inhibition blocked these responses. The omega-3 fatty acid docosahexaenoic acid (DHA) similarly inhibited JNK and the phosphorylation of IRS-1 and tau in cultured hippocampal neurons. Feeding 3xTg-AD transgenic mice a diet high in saturated and omega-6 fat increased active JNK and phosphorylated IRS-1 and tau. Treatment of the 3xTg-AD mice on high-fat diet with fish oil or curcumin or a combination of both for 4 months reduced phosphorylated JNK, IRS-1, and tau and prevented the degradation of total IRS-1. This was accompanied by improvement in Y-maze performance. Mice fed with fish oil and curcumin for 1 month had more significant effects on Y-maze, and the combination showed more significant inhibition of JNK, IRS-1, and tau phosphorylation. These data indicate JNK mediates Abeta oligomer inactivation of IRS-1 and phospho-tau pathology and that dietary treatment with fish oil/DHA, curcumin, or a combination of both has the potential to improve insulin/trophic signaling and cognitive deficits in AD.
Induction of the Transcriptional Repressor Yin Yang-1 by Vascular Cell Injury (2001)

Yin Yang-1 (YY1) is a multifunctional transcription factor that can repress the expression of many growth factor, hormone, and cytokine genes implicated in atherogenesis. YY1 expression is activated in rat vascular smooth muscle cells shortly after injury. YY1 DNA binding activity paralleled elevated protein levels in the nucleus. Smooth muscle cell injury triggered the rapid extracellular release of immunoreactive fibroblast growth factor-2 (FGF-2). YY1 induction after injury was blocked by neutralizing antibodies directed against FGF-2. This growth factor increased YY1 mRNA and protein expression and stimulated YY1 binding and transcriptional activity. Overexpression of YY1 inhibited smooth muscle cell replication. Immunohistochemical analysis demonstrated YY1 staining in medial smooth muscle cells, coincident with FGF-2 expression. Proliferating cell nuclear antigen staining, in contrast, was confined mainly to the atherosclerotic intima. This is the first demonstration that YY1 is induced by either injury or FGF-2, is differentially expressed in normal and diseased human arteries, and that its overexpression inhibits vascular smooth muscle but not endothelial cell replication.
Immunology in the clinic review series; focus on cancer: glycolipids as targets for tumour immunotherapy (2011)

Research into aberrant glycosylation and over-expression of glycolipids on the surface of the majority of cancers, coupled with a knowledge of glycolipids as functional molecules involved in a number of cellular physiological pathways, has provided a novel area of targets for cancer immunotherapy. This has resulted in the development of a number of vaccines and monoclonal antibodies that are showing promising results in recent clinical trials.
Expression of tetanus toxin Fragment C in tobacco chloroplasts (2003)

Fragment C (TetC) is a non-toxic 47 kDa polypeptide fragment of tetanus toxin that can be used as a subunit vaccine against tetanus. Expression of TetC in Escherichia coli and yeast was dependent on the availability of synthetic genes that were required to improve translation efficiency and stabilize the mRNA. To explore the feasibility of producing TetC in tobacco leaves, we attempted expression of both the bacterial high-AT (72.3% AT) and the synthetic higher-GC genes (52.5% AT) in tobacco chloroplasts. We report here that the bacterial high-AT mRNA is stable in tobacco chloroplasts. Significant TetC accumulation was obtained from both genes, 25 and 10% of total soluble cellular protein, respectively, proving the versatility of plastids for expression of unmodified high-AT and high-GC genes. Mucosal immunization of mice with the plastid- produced TetC induced protective levels of TetC antibodies. Thus, expression of TetC in chloroplasts provides a potential route towards the development of a safe, plant-based tetanus vaccine for nasal and oral applications.
Genes controlling fertilization-independent seed development in Arabidopsis thaliana (1999)

We have cloned two genes, FIS1 and FIS2, that control both fertilization independent seed development and postpollination embryo development in Arabidopsis. These genes confer female gametophytic phenotypes. FIS2 encodes a protein with a C2H2 zinc-finger motif and three putative nuclear localization signals, indicating that it is likely to be a transcription factor. FIS1 encodes a protein with homology to the Drosophila Polycomb group gene Enhancer-of-zeste and is identical to the recently described Arabidopsis gene MEDEA. FIS1 is a protein with a number of putative functional domains, including the SET domain present in Enhancer-of-zeste-related proteins. Comparison of the position of the lesions in the fis1 and medea mutant alleles indicates that fis1 is a null allele producing a truncated polypeptide lacking all the protein domains whereas the deduced protein from medea lacks only the SET domain. We present a model of the role of FIS1 and FIS2 gene products in seed development.
Platelet factor 4 is a negative autocrine in vivo regulator of megakaryopoiesis: clinical and therapeutic implications (2007)

Platelet factor 4 (PF4) is a negative regulator of megakaryopoiesis in vitro. We have now examined whether PF4 regulates megakaryopoiesis in vivo by studying PF4 knockout mice and transgenic mice that overexpress human (h) PF4. Steady-state platelet count and thrombocrit in these animals was inversely related to platelet PF4 content. Growth of megakaryocyte colonies was also inversely related to platelet PF4 content. Function-blocking anti-PF4 antibody reversed this inhibition of megakaryocyte colony growth, indicating the importance of local PF4 released from developing megakaryocytes. The effect of megakaryocyte damage and release of PF4 on 5-fluorouracil-induced marrow failure was then examined. Severity of thrombocytopenia and time to recovery of platelet counts were inversely related to initial PF4 content. Recovery was faster and more extensive, especially in PF4-overexpressing mice, after treatment with anti-PF4 blocking antibodies, suggesting a means to limit the duration of such a chemotherapy-induced thrombocytopenia, especially in individuals with high endogenous levels of PF4. We found that approximately 8% of 250 healthy adults have elevated (> 2 times average) platelet PF4 content. These individuals with high levels of platelet PF4 may be especially sensitive to developing thrombocytopenia after bone marrow injury and may benefit from approaches that block the effects of released PF4.
Regulatory squelching (1994)

An important function of transcription factors may be to sequester coactivators or corepressors of transcription. In this manner transcription factors could regulate in trans the activity of promoters to which they do not bind. This may be of widespread significance as a mechanism to control cell cycle-dependent and differentiation-specific transcriptional activity within eukaryotic cells. Therefore squelching in vivo may be important than hitherto appreciated.
Characterization of Hydraulically-Induced Shale Fracture Network Using an Analytical/Semi-Analytical Model (2009)

Abstract A model describing hydraulic fracture network growth is presented in this paper. The model is fully constrained by accounting for mechanical interactions between injected fluid and fracture walls and among nearby fractures and by satisfying observation data including wellbore pressure and microseismic event distribution. It may be solved analytically or semi-analytically, depending on whether a quasi-steady approximation is made. The mathematical framework of the model is first discussed to certain detail. The model is then applied to a Barnett Shale case to illustrate the procedures of characterizing a hydraulically induced fracture network via inverse modeling and predicting the growth of the fracture network using forward modeling. Detailed information including fluid pressure, fracture width, fracture permeability, fracture volume and the surface area of fracture walls are also obtained during the course of modeling. It is further applied to carry out parameter sensitivity analysis. Its potential in realtime applications is also discussed.
Transcranial Magnetic Stimulation: A Neurochronometrics of Mind (2003)

The mainstays of brain imaging techniques have been positron emission tomography (PET), functional magnetic resonance imaging (fMRI), magnetoencephalography (MEG), and event-related potentials (ERPs). These methods all record direct or indirect measures of brain activity and correlate the activity patterns with behavior. But to go beyond the correlations established by these techniques and prove the necessity of an area for a given function, cognitive neuroscientists need to be able to reverse engineer the brain -- i.e., to selectively remove components from information processing and assess their impact on the output. This book is about transcranial magnetic stimulation (TMS), a technique that emerged during the same period as neuroimaging and has made it possible to reverse engineer the human brain's role in behavioral and cognitive functions. The subject areas that can be studied using TMS run the gamut of cognitive psychology -- attention, perception, awareness, eye movements, action selection, memory, plasticity, language, numeracy, and priming. The book presents an overview of historical attempts at magnetic brain stimulation, ethical considerations of the technique's use, basic technical and practical information, the results of numerous TMS studies, and a discussion of the future of TMS in the armamentarium of cognitive neuropsychology.
Decisions With Uncertainty: The Glass Half Full (2013)

Each of us makes important decisions involving uncertainty in domains in which we are not experts, such as retirement planning, medical treatment, and precautions against severe weather. Often, reliable information about uncertainty is available to us, although how effectively we incorporate it into the decision process remains in question. Previous research suggests that people are error-prone when reasoning with probability. However, recent research in weather-related decision making is more encouraging. Unlike earlier work that compares people’s decisions with a rational standard, this research compares decisions made by people with and without uncertainty information. The results suggest that including specific numeric uncertainty estimates in weather forecasts increases trust and gives people a better idea of what to expect in terms of both the range of possible outcomes and the amount of uncertainty in the particular situation, all of which benefit precautionary decisions. However, the advantage for uncertainty estimates depends critically on how they are expressed. It is crucial that the expression is compatible with both the decision task and cognitive processes of the user.
Window-consistent replication for real-time applications (2002)

Two widely-studied approaches for structuring fault-tolerant services are the state-machine and the primary-backup replication schemes. For a large class of soft and hard real-time applications, the degree of consistency among servers can be exploited to design replication protocols with predictable timing behavior. This is particularly useful in applications such as automated process control, in which one can trade off the quality or precision for timely availability of data. This paper presents the architecture and prototype implementation of a primary-backup replication service that employs window consistency semantics between the primary data repository and the backups. A client registers a data object with the service by declaring the consistency requirements for the data, in terms of a time window. The primary ensures that each backup site maintains a version of the object that was valid on the primary within the preceding time window by scheduling update messages to the backups. Decoupling the transmission of updates to the backups from the processing of client requests permits the primary to handle a higher rate of operations and provide more timely service to clients. The non-blocking semantics free the client from waiting for updates to the backups to complete. Furthermore, real-time scheduling of update messages can guarantee controlled inconsistency between the primary and backup repositories.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Immunogenicity of Liposomal Model Membranes Sensitized with Dinitrophenylated Phosphatidylethanolamine Derivatives Containing Different Length Spacers (1979)

Abstract The immunogenicity of liposomes sensitized with dinitrophenylated (DNP) phosphatidylethanolamine (PE) derivatives, differing in the length of the spacer linking DNP to PE, has been examined. The magnitude of the anti-DNP response of mice was influenced by the number of methylene and amino groups interposed between DNP and the amino function of PE; generally, derivatives containing very short or long spacers were less effective immunogens than those of intermediate length. The epitope density of the derivative in the lipid bilayers, but not the dose, also affected the relative immunogenicity of the different derivatives. Incorporation of lipid A, which has been previously demonstrated to enhance liposomal immunogenicity, increased the response to those derivatives that elicited antibodies in the absence of this polyclonal B cell mitogen; however, the relative immunogenicity of the derivatives was not significantly altered. A good correlation was observed between the ability to bind low affinity IgG and IgM antibodies in vitro (determined by complement-dependent glucose release from liposomes) and in vivo immunogenicity. These results suggest that the ability of sensitized liposomes to elicit a response requires the extension of the antigenic determinant away from the surface of the lipid bilayer.
Molecular imaging of integrin αvβ6 expression in living subjects. (2014)

Integrins, a family of cell adhesion molecules composed of α and β heterodimeric subunits, are involved in a wide range of cell-extracellular matrix and cell-cell interactions. The study of integrin family members as targets for molecular imaging and therapy has been generally limited with the exception of integrin αvβ3. vβ6, a member of the integrin family, is expressed at low or undetectable levels in normal tissues, but is widely upregulated during many pathological and physiological processes, especially cancer and fibrosis, making it a promising target for molecular imaging. Noninvasive and quantitative imaging of integrin vβ6 expression would be very useful for disease diagnosis, treatment monitoring, and prognosis assessment. Although various molecular probes have been developed for positron emission tomography and single-photon emission computed tomography imaging of integrin vβ6 expression in preclinical animal models, further research efforts are required to optimize integrin vβ6-targeting probes for future potential clinical applications in the fields of oncology and beyond.
Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA (2011)

In vitro-transcribed mRNA has great therapeutic potential to transiently express the encoded protein without the adverse effects of viral and DNA-based constructs. Mammalian cells, however, contain RNA sensors of the innate immune system that must be considered in the generation of therapeutic RNA. Incorporation of modified nucleosides both reduces innate immune activation and increases translation of mRNA, but residual induction of type I interferons (IFNs) and proinflammatory cytokines remains. We identify that contaminants, including double-stranded RNA, in nucleoside-modified in vitro-transcribed RNA are responsible for innate immune activation and their removal by high performance liquid chromatography (HPLC) results in mRNA that does not induce IFNs and inflammatory cytokines and is translated at 10- to 1000-fold greater levels in primary cells. Although unmodified mRNAs were translated significantly better following purification, they still induced high levels of cytokine secretion. HPLC purified nucleoside-modified mRNA is a powerful vector for applications ranging from ex vivo stem cell generation to in vivo gene therapy.
BLyS: Member of the Tumor Necrosis Factor Family and B Lymphocyte Stimulator (1999)

The tumor necrosis factor (TNF) superfamily of cytokines includes both soluble and membrane-bound proteins that regulate immune responses. A member of the human TNF family, BLyS (B lymphocyte stimulator), was identified that induced B cell proliferation and immunoglobulin secretion. BLyS expression on human monocytes could be up-regulated by interferon-γ. Soluble BLyS functioned as a potent B cell growth factor in costimulation assays. Administration of soluble recombinant BLyS to mice disrupted splenic B and T cell zones and resulted in elevated serum immunoglobulin concentrations. The B cell tropism of BLyS is consistent with its receptor expression on B-lineage cells. The biological profile of BLyS suggests it is involved in monocyte-driven B cell activation.
Inhibitory Effects of Expanded GAA·TTC Triplet Repeats from Intron I of the Friedreich Ataxia Gene on Transcription and Replicationin Vivo (1998)

Friedreich ataxia (FRDA) is associated with the expansion of a GAA. TTC triplet repeat in the first intron of the frataxin gene, resulting in reduced levels of frataxin mRNA and protein. To investigate the mechanisms by which the intronic expansion produces its effect, GAA.TTC repeats of various lengths (9 to 270 triplets) were cloned in both orientations in the intron of a reporter gene. Plasmids containing these repeats were transiently transfected into COS-7 cells. A length- and orientation-dependent inhibition of reporter gene expression was observed. RNase protection and Northern blot analyses showed very low levels of mature mRNA when longer GAA repeats were transcribed, with no accumulation of primary transcript. Replication of plasmids carrying long GAA.TTC tracts (approximately 250 triplets) was greatly inhibited in COS-7 cells compared with plasmids carrying (GAA.TTC)9 and (GAA.TTC)90. Replication inhibition was five times greater for the plasmid whose transcript contains (GAA)230 than for the plasmid whose transcript contains (UUC)270. Our in vivo investigation revealed that expanded GAA.TTC repeats from intron I of the FRDA gene inhibit transcription rather than post-transcriptional RNA processing and also interfere with replication. The molecular basis for these effects may be the formation of non-B DNA structures.