gebhart/patrepeval huggingface dataset:
Heat shock factor 1 regulates lifespan as distinct from disease onset in prion disease (2008)

Prion diseases are fatal, transmissible, neurodegenerative diseases caused by the misfolding of the prion protein (PrP). At present, the molecular pathways underlying prion-mediated neurotoxicity are largely unknown. We hypothesized that the transcriptional regulator of the stress response, heat shock factor 1 (HSF1), would play an important role in prion disease. Uninoculated HSF1 knockout (KO) mice used in our study do not show signs of neurodegeneration as assessed by survival, motor performance, or histopathology. When inoculated with Rocky Mountain Laboratory (RML) prions HSF1 KO mice had a dramatically shortened lifespan, succumbing to disease approximately 20% faster than controls. Surprisingly, both the onset of home-cage behavioral symptoms and pathological alterations occurred at a similar time in HSF1 KO and control mice. The accumulation of proteinase K (PK)-resistant PrP also occurred with similar kinetics and prion infectivity accrued at an equal or slower rate. Thus, HSF1 provides an important protective function that is specifically manifest after the onset of behavioral symptoms of prion disease.
Use of a Peptide Derived from Foot-and-Mouth Disease Virus for the Noninvasive Imaging of Human Cancer: Generation and Evaluation of 4-[18F]Fluorobenzoyl A20FMDV2 for In vivo Imaging of Integrin αvβ6 Expression with Positron Emission Tomography (2007)

Expression of the epithelial-specific integrin alphavbeta6 is low or undetectable in most adult tissues but may be increased during wound healing and inflammation and is up-regulated dramatically by many different carcinomas, making alphavbeta6 a promising target for the in vivo detection of cancer using noninvasive imaging. In addition, alphavbeta6 is recognized as promoting invasion and correlates with aggressive behavior of human cancers and thus agents that recognize alphavbeta6 specifically in vivo will be an essential tool for the future management of alphavbeta6-positive cancers. Recently, we identified the peptide NAVPNLRGDLQVLAQKVART (A20FMDV2), derived from foot-and-mouth disease virus, as a potent inhibitor of alphavbeta6. Using flow cytometry and ELISA, we show that this peptide is highly selective, inhibiting alphavbeta6-ligand binding with a IC50 of 3 nmol/L, an activity 1,000-fold more selective for alphavbeta6 than for other RGD-directed integrins (alphavbeta3, alphavbeta5, and alpha5beta1). A20FMDV2 was radiolabeled on solid-phase using 4-[18F]fluorobenzoic acid, injected into mice bearing both alphavbeta6-negative and alphavbeta6-positive (DX3puro/DX3purobeta6 cell lines) xenografts and imaged using a small animal positron emission tomography (PET) scanner. Rapid uptake (<30 min) and selective retention (>5 h) of radioactivity in the alphavbeta6-positive versus the alphavbeta6-negative tumor, together with fast renal elimination of nonspecifically bound activity, resulted in specific imaging of the alphavbeta6-positive neoplasm. These data suggest that PET imaging of alphavbeta6-positive tumors is feasible and will provide an important new tool for early detection and improved management of many types of cancers.
celB, a gene coding for a bifunctional cellulase from the extreme thermophile "Caldocellum saccharolyticum" (1990)

"Caldocellum saccharolyticum" is an obligatory anaerobic thermophilic bacterium. A gene from this organism, designated celB, has been cloned in Escherichia coli as part of a bacteriophage lambda gene library. This gene produces a thermostable cellulase that shows both endoglucanase and exoglucanase activities on test substrates and is able to degrade crystalline cellulose to glucose. The sequence of celB has homology with both exo- and endoglucanases described by others. It appears to have a central domain without enzymatic activity which is joined to the enzymatic domains by runs of amino acids rich in proline and threonine (PT boxes). Deletion analysis shows that the exoglucanase activity is located in the amino-terminal domain of the enzyme and that endoglucanase activity is located in the carboxy-terminal domain. There are internal transcriptional and translational start sites within the gene. The intact gene has been cloned into a temperature-inducible expression vector, pJLA602, and overexpressed in E. coli. Polyacrylamide gel electrophoresis showed that celB produced a protein with a molecular weight of 118,000 to 120,000. A number of smaller proteins with activity against carboxymethyl cellulose and 4-methyl umbelliferyl-beta-D-cellobioside were also produced. These are believed to be the result of alternative translational start sites and/or proteolytic degradation products of the translated gene product.
Interference compensation technique for multilevel flash memory (2011)

Multilevel cell flash memory devices are gaining popularity because it can increase the memory capacity by storing two or more bits to a single cell. However, when the number of levels of a cell increases, the inter-cell interference which shifts cell (threshold) voltage becomes more critical. Thereare two approaches to alleviate the errors caused by the voltage shift. One is the error correcting codes, and the other is the signal processing methods. We focus on signal processing methods to reduce the cell to cell interference which causes the voltage shift, and propose algorithms which reduce the voltage shift effects by classfying and compensating erratic cells. The simulation results show that the proposed algorithms are effective for interference reduction.
A Monomeric Derivative of the Cellular Transcription Factor CREB Functions as a Constitutive Activator (1994)

The mammalian transcriptional activator CREB binds as a dimer to a broad spectrum of inducible promoters. CREB activity is modulated by several signalling agents (protein kinase A [PKA], Ca2+, and transforming growth factor beta) and via functional interactions with cell-specific transcription factors. In addition, CREB can activate transcription constitutively and repress the activity of several other transcriptional activators. The mechanisms that allow CREB to act in such a malleable manner and the role that CREB dimerization might play in this are poorly understood. To probe the latter issue, we have created monomeric forms of CREB by fusing CREB to the DNA-binding domain of a protein (B-cell specific activator protein [BSAP]) that binds to DNA as a monomer. Remarkably, monomeric CREB acts as a potent, constitutive activator under conditions in which native CREB is inducible by PKA. Thus, CREB contains constitutive activation regions that are unable to function in native CREB. Two glutamine-rich domains that are important for native, PKA-inducible CREB activity are required for the constitutive activity of monomeric CREB. In contrast, two elements within the kinase-inducible domain of CREB are dispensable for constitutive activity. We discuss our results in relation to inducible and constitutive CREB activity and the potential modes of action of other activators that directly interact with CREB.
Induction of neutralization antibodies in mice by Dengue-2 envelope DNA vaccines. (2009)

We demonstrated that most of our DNA vaccine candidates could induce antibody responses and partial protection against DEN-2 virus in mice. These results provide valuable information for the design and construction of a tetravalent DEN DNA vaccine.
Functional Analysis of TRAIL Receptors Using Monoclonal Antibodies (1999)

mAbs were generated against the extracellular domain of the four known TNF-related apoptosis-inducing ligand (TRAIL) receptors and tested on a panel of human melanoma cell lines. The specificity of the mAb permitted a precise evaluation of the TRAIL receptors that induce apoptosis (TRAIL-R1 and -R2) compared with the TRAIL receptors that potentially regulate TRAIL-mediated apoptosis (TRAIL-R3 and -R4). Immobilized anti-TRAIL-R1 or -R2 mAbs were cytotoxic to TRAIL-sensitive tumor cells, whereas tumor cells resistant to recombinant TRAIL were also resistant to these mAbs and only became sensitive when cultured with actinomycin D. The anti-TRAIL-R1 and -R2 mAb-induced death was characterized by the activation of intracellular caspases, which could be blocked by carbobenzyloxy-Val-Ala-Asp (OMe) fluoromethyl ketone (zVAD-fmk) and carbobenzyloxy-Ile-Glu(OMe)-Thr-Asp (OMe) fluoromethyl ketone (zIETD-fmk). When used in solution, one of the anti-TRAIL-R2 mAbs was capable of blocking leucine zipper-human TRAIL binding to TRAIL-R2-expressing cells and prevented TRAIL-induced death of these cells, whereas two of the anti-TRAIL-R1 mAbs could inhibit leucine zipper-human TRAIL binding to TRAIL-R1:Fc. Furthermore, use of the blocking anti-TRAIL-R2 mAb allowed us to demonstrate that the signals transduced through either TRAIL-R1 or TRAIL-R2 were necessary and sufficient to mediate cell death. In contrast, the expression of TRAIL-R3 or TRAIL-R4 did not appear to be a significant factor in determining the resistance or sensitivity of these tumor target cells to the effects of TRAIL.
NADPH oxidase 2-derived reactive oxygen species in spinal cord microglia contribute to peripheral nerve injury-induced neuropathic pain (2010)

Increasing evidence supports the notion that spinal cord microglia activation plays a causal role in the development of neuropathic pain after peripheral nerve injury; yet the mechanisms for microglia activation remain elusive. Here, we provide evidence that NADPH oxidase 2 (Nox2)-derived ROS production plays a critical role in nerve injury-induced spinal cord microglia activation and subsequent pain hypersensitivity. Nox2 expression was induced in dorsal horn microglia immediately after L5 spinal nerve transection (SNT). Studies using Nox2-deficient mice show that Nox2 is required for SNT-induced ROS generation, microglia activation, and proinflammatory cytokine expression in the spinal cord. SNT-induced mechanical allodynia and thermal hyperalgesia were similarly attenuated in Nox2-deficient mice. In addition, reducing microglial ROS level via intrathecal sulforaphane administration attenuated mechanical allodynia and thermal hyperalgesia in SNT-injured mice. Sulforaphane also inhibited SNT-induced proinflammatory gene expression in microglia, and studies using primary microglia indicate that ROS generation is required for proinflammatory gene expression in microglia. These studies delineate a pathway involving nerve damage leading to microglial Nox2-generated ROS, resulting in the expression of proinflammatory cytokines that are involved in the initiation of neuropathic pain.
Aerobraking and aerocapture for planetary missions (1980)

The paper examines the utilization of aerodynamic forces to capture a vehicle into a closed orbit and/or to modify an orbit. Attention is given to two techniques: aerobraking which uses drag during successive passes through the upper atmosphere to circularize a highly elliptical orbit, and aerocapture which transfers a vehicle into a closed stable orbit from a hyperbolic flyby trajectory. Sample missions employing both techniques are discussed.
Drug Absorption Behavior after Periocular Injections. (1999)

The purpose of this study was to investigate the absorption behavior of an ophthalmic drug injected in rabbit periocular tissues. After intracapsular, retrobulbar and palpebral conjunctival injections of 150 microl and 50 microl fluorescein isothiocyanate dextran (FITC-dextran, average molecular weight 11000), leakage of the dye into the tear fluid was dependent on the injection route and volume. After periocular injections (50 microl) of tilisolol, as a model beta-blocker, the concentrations in the tear fluid, blood, aqueous humor and vitreous body were determined by HPLC. Slight drug leakage was observed in the tear fluid after injections. The periocular injections showed a faster absorption and a higher area under the concentration-time curve (AUC) in the plasma and a lower AUC in the aqueous humor than those observed in instillation. They also showed a higher ratio of AUC of tilisolol in the vitreous body to AUC in the aqueous humor than that observed in the instillation. Among the periocular injections, retrobulbar injection showed the highest concentrations in the plasma and the lowest in the aqueous humor and vitreous body, while intracapsular injection showed the lowest in the plasma and the highest in the aqueous humor and vitreous body. Although the periocular injections showed a rapid systemic absorption of drug by a rich topical vasculature, it might be an effective approach to deliver the drug to the periocular tissues and vitreous body.
Peroxynitrite Generated at the Level Produced by Spinal Cord Injury Induces Peroxidation of Membrane Phospholipids in Normal Rat Cord: Reduction by a Metalloporphyrin (2005)

The goal of the present study was to determine in vivo whether peroxynitrite, at the concentration and duration produced by SCI, contributes to membrane lipid peroxidation (MLP) after traumatic spinal cord injury (SCI) and the capability of a broad spectrum scavenger of reactive species, Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), to reduce MLP. This was accomplished by administering a peroxynitrite donor 3-morpholinosydnonimine (SIN-1) into the gray matter of an uninjured rat spinal cord through a microdialysis fiber to generate ONOO at the SCI-elevated levels. The resulting MLP was characterized by measuring the productions of extracellular malondialdehyde and of intracellular 4-hydroxynonenal. We demonstrated that extracellular SIN- 1 administration significantly increased the concentration of malondialdehyde (p < 0.001) and the numbers of hydroxynonenal-positive cells (p < 0.001) as compared to a control group in which ACSF was administered. Simultaneous administration of MnTBAP through a second microdialysis fiber significantly reduced SIN-1-induced malondialdehyde production (p < 0.001) and the numbers of HNE-positive cells (p < 0.001). There was no significant difference between MnTBAP-treated and ACSF-controls (p = 0.3). These results demonstrate in vivo that (1) SCI-produced levels of peroxynitrite sufficient to cause MLP, and therefore that peroxynitrite is an agent of secondary damage after acute SCI; (2) MnTBAP can efficiently reduce SIN-1-induced MLP.
A.S.P.E.N. Parenteral Nutrition Safety Consensus Recommendations (2014)

Parenteral nutrition (PN) serves as an important therapeutic modality that is used in adults, children, and infants for a variety of indications. The appropriate use of this complex therapy aims to maximize clinical benefit while minimizing the potential risk for adverse events. Despite being classified and acknowledged as a high-alert medication,1 only 58% of organizations have precautions in place to prevent errors and patient harm associated with PN.2 Complications can occur as a result of the therapy and as the result of the PN process. The American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) Parenteral Nutrition Safety Consensus Recommendations are based on practices that are generally accepted to minimize errors with PN therapy. However, the broad range of healthcare settings in which PN administration occurs—from critical care to home care—raises the potential for disparities to exist in the knowledge and skills of the healthcare professionals responsible for PN prescribing, review, preparation (including compounding, labeling, and dispensing), and administration. Regardless of the setting or the number of patients treated in a given facility, the classification of PN as a high-alert medication requires all healthcare organizations to develop evidence-based policies and procedures related to PN. With these concepts in mind, the A.S.P.E.N. Parenteral Nutrition Safety Task Force developed the A.S.P.E.N. Parenteral Nutrition Safety Consensus Recommendations, available online in the Journal of Parenteral and Enteral Nutrition (JPEN) in late 2013 and published in March …
Multidrug (pleiotropic) resistance in doxorubicin-selected variants of the human sarcoma cell line MES-SA. (1985)

The emergence of drug-resistant tumor cells is a major limiting factor in cancer chemotherapy. There is little information about the nature of such resistant variants among human cancer cell populations. Doxorubicin (DOX)-resistant sublines of the human sarcoma cell line MES-SA were selected by continuous in vitro exposure to DOX. Stepwise increases in DOX concentration produced variants which were 25- and 100-fold resistant to DOX. These sublines displayed marked cross-resistance to daunorubicin, dactinomycin, mitoxantrone, colchicine, vincristine, vinblastine, and etoposide and moderate resistance to mitomycin C and melphalan. Cross-resistance was not observed, however, to methotrexate, 5-fluorouracil, bleomycin, carmustine, or cisplatin. DOX resistance in these cell lines appeared to be stable despite long periods of growth in drug-free medium. Two additional marker chromosomes were identified in the 100-fold resistant variant, which indicated clonal selection during drug exposure, but no double minute chromosomes or homogeneously staining regions were noted. Doxorubicin accumulation in the DOX-resistant cells was reduced by approximately 50% compared to that of the sensitive MES-SA cells, as a result of enhanced efflux of DOX from the resistant cells. There was no evidence of appreciable DOX metabolism by either the sensitive or resistant cells. These studies demonstrate marked DOX resistance and multidrug resistance arising in a human sarcoma line during exposure to DOX. The pleiotropic nature of this resistance is similar to that described in other models. Decreased drug accumulation due to enhanced drug efflux is identified as a major mechanism of resistance in these cells, although other factors may also be involved.
Chloramphenicol-Sensitive Escherichia coli Strain Expressing the Chloramphenicol Acetyltransferase ( cat ) Gene (2001)

An Escherichia coli strain (strain CM2555) bearing the chloramphenicol acetyltransferase (cat) gene was found to be sensitive to chloramphenicol. We demonstrate that the cat gene is efficiently expressed in strain CM2555. Our results suggest that decreased levels of acetyl coenzyme A in cat-expressing CM2555 cells in the presence of chloramphenicol may cause the bacterium to be sensitive to this antibiotic.
Wnt signaling: an essential regulator of cardiovascular differentiation,morphogenesis and progenitor self-renewal (2008)

Emerging evidence indicates that Wnt signaling regulates crucial aspects of cardiovascular biology (including cardiac morphogenesis, and the self-renewal and differentiation of cardiac progenitor cells). The ability of Wnt signaling to regulate such diverse aspects of cardiovascular development rests on the multifarious downstream and tangential targets affected by this pathway. Here, we discuss the roles for Wnt signaling in cardiac and vascular development, and focus on the emerging role of Wnt signaling in cardiovascular morphogenesis and progenitor cell self-renewal.
Combining Microdialysis, NanoLC-MS, and MALDI-TOF/TOF To Detect Neuropeptides Secreted in the Crab, Cancer borealis (2008)

Microdialysis is a useful technique for sampling neuropeptides in vivo, and decapod crustaceans are important model organisms for studying how these peptides regulate physiological processes. However, to date, no microdialysis procedure has been reported for sampling neuropeptides from crustaceans. Here we report the first application of microdialysis to sample neuropeptides from the hemolymph of the crab, Cancer borealis. Microdialysis probes were implanted into the pericardial region of live crabs, and the resulting dialysates were desalted, concentrated, and analyzed by LC-ESI-QTOF and MALDI-TOF/TOF mass spectrometry. Analysis of in vitro microdialysates of hemolymph revealed more neuropeptides and fewer protein fragments than hemolymph prepared by typical analysis methods. Mass spectra of in vivo dialysates displayed neuropeptides from 10 peptide families, including the RFamide, allatostatin, and orcokinin families. In addition, GAHKNYLRFa, SDRNFLRFa, and TNRNFLRFa were sequenced from hemolymph dialysates. The detection of these neuropeptides in the hemolymph suggests that they are functioning as hormones as well as neuromodulators. In vivo microdialysis offers the capability to further study these and other neuropeptides in crustacean hemolymph, complementing current tissue-based studies and extending our knowledge of hormonal regulation of physiological states.
Essential requirement for Wnt signaling in proliferation of adult small intestine and colon revealed by adenoviral expression of Dickkopf-1 (2003)

Whereas the adult gastrointestinal epithelium undergoes tremendous self-renewal through active proliferation in crypt stem cell compartments, the responsible growth factors regulating this continuous proliferation have not been defined. The exploration of physiologic functions of Wnt proteins in adult organisms has been hampered by functional redundancy and the necessity for conditional inactivation strategies. Dickkopf-1 (Dkk1) is a potent secreted Wnt antagonist that interacts with Wnt coreceptors of the LRP family. To address the contribution of Wnt signaling to gastrointestinal epithelial proliferation, adenoviral expression of Dkk1 was used to achieve stringent, conditional, and reversible Wnt inhibition in adult animals. Adenovirus Dkk1 (Ad Dkk1) treatment of adult mice repressed expression of the Wnt target genes CD44 and EphB2 within 2 days in both small intestine and colon, indicating an extremely broad role for Wnt signaling in the maintenance of adult gastrointestinal gene expression. In parallel, Ad Dkk1 markedly inhibited proliferation in small intestine and colon, accompanied by progressive architectural degeneration with the loss of crypts, villi, and glandular structure by 7 days. Whereas decreased Dkk1 expression at later time points (>10 days) was followed by crypt and villus regeneration, which was consistent with a reversible process, substantial mortality ensued from colitis and systemic infection. These results indicate the efficacy of systemic expression of secreted Wnt antagonists as a general strategy for conditional inactivation of Wnt signaling in adult organisms and illustrate a striking reliance on a single growth factor pathway for the maintenance of the architecture of the adult small intestine and colon.
Prospects for increasing starch and sucrose yields for bioethanol production (2008)

In the short term, the production of bioethanol as a liquid transport fuel is almost entirely dependent on starch and sugars from existing food crops. The sustainability of this industry would be enhanced by increases in the yield of starch/sugar per hectare without further inputs into the crops concerned. Efforts to achieve increased yields of starch over the last three decades, in particular via manipulation of the enzyme ADPglucose pyrophosphorylase, have met with limited success. Other approaches have included manipulation of carbon partitioning within storage organs in favour of starch synthesis, and attempts to manipulate source-sink relationships. Some of the most promising results so far have come from manipulations that increase the availability of ATP for starch synthesis. Future options for achieving increased starch contents could include manipulation of starch degradation in organs in which starch turnover is occurring, and introduction of starch synthesis into the cytosol. Sucrose accumulation is much less well understood than starch synthesis, but recent results from research on sugar cane suggest that total sugar content can be greatly increased by conversion of sucrose into a non-metabolizable isomer. A better understanding of carbohydrate storage and turnover in relation to carbon assimilation and plant growth is required, both for improvement of starch and sugar crops and for attempts to increase biomass production in second-generation biofuel crops.