gebhart/patrepeval huggingface dataset:
Grafting of thrombopoietin‐mimetic peptides into cystine knot miniproteins yields high‐affinity thrombopoietin antagonists and agonists (2006)

Thrombopoietin is the primary regulator of platelet production. We exploited two naturally occurring miniproteins of the inhibitor cystine knot family as stable and rigid scaffolds for the incorporation of peptide sequences that have been shown to act as high-affinity thrombopoietin antagonists. Several miniproteins that antagonistically block thrombopoietin-mediated receptor activation were identified using a microscale reporter assay. Covalent miniprotein dimerization yielded potent bivalent c-Mpl receptor agonists with EC(50) values in the low nanomolar or picomolar range. One selected miniprotein-derived thrombopoietin agonist was almost as active as natural thrombopoietin with regard to stimulation of megakaryocyte colony formation from human bone marrow mononuclear cells, and elicited doubling of platelet counts in mice. Our data suggest that dimeric cystine knot miniproteins have considerable potential for the future development of small and stable receptor agonists. This approach may provide a promising strategy for pharmaceutical interference with other receptors activated by ligand-induced dimerization.
Urokinase-type plasminogen activator is induced in migrating capillary endothelial cells. (1987)

Cellular migration is an essential component of invasive biological processes, many of which have been correlated with an increase in plasminogen activator production. Endothelial cell migration occurs in vivo during repair of vascular lesions and angiogenesis, and can be induced in vitro by wounding a confluent monolayer of cells. By combining the wounded monolayer model with a substrate overlay technique, we show that cells migrating from the edges of an experimental wound display an increase in urokinase-type plasminogen activator (uPA) activity, and that this activity reverts to background levels upon cessation of movement, when the wound has closed. Our results demonstrate a direct temporal relationship between endothelial cell migration and uPA activity, and suggest that induction of uPA activity is a component of the migratory process.
An Assessment of the Continuous Neutron Source Using a Low-Energy Electron Accelerator (1997)

The performance of a continuous neutron source using an electron accelerator was evaluated by computer simulation codes (EGS4 and MCNP) in terms of neutron yield, neutron flux distribution, neutron spectrum, and heat distribution. Electrons with energies from 10 to 100 MeV were injected into a tungsten converter in order to generate photons by bremsstrahlung. When the photon irradiated a heavy water (D2O) target, neutrons were produced by photonuclear reaction in the (D2O) target. This type of source was optimized for target geometry and electron energy from the point of neutron yield. The neutron spectrum was found to have two characteristic peaks, at the low-energy (thermal) region and the high-energy (million-electron-volt) region. The maximum photoneutrons per 1000 MeV of electron energy was 0.56 at the electron energy of 30 MeV. In the case of irradiation by a 30-MeV, 33-mA continuous electron beam, the maximum thermal neutron flux was on the order of 1011 cm−2·s−1.
Preparation of superconducting Y-Ba-Cu-O films by a reactive plasma evaporation method (1988)

Y-Ba-Cu-O superconducting films were prepared by a reactive plasma evaporation method, in which mixed powders were coevaporated in a thermal radio-frequency Ar+O2 plasma and the ternary composition controlled high-temperature metallic vapors were codeposited onto a substrate. The deposition rate was much more than 10 μm/min, which is several orders of magnitude higher than those reported by the other methods previously. The structure of the prepared films was identified as an orthorhombic oxygen-deficient perovskite phase and some films showed the preferred orientation of (001). The as-deposited film without post-annealing showed a superconducting transition temperature Tcm (midpoint) of 94 K.
AN INTRODUCTION TO TRP CHANNELS (2005)

The aim of this review is to provide a basic framework for understanding the function of mammalian transient receptor potential (TRP) channels, particularly as they have been elucidated in heterologous expression systems. Mammalian TRP channel proteins form six-transmembrane (6-TM) cation-permeable channels that may be grouped into six subfamilies on the basis of amino acid sequence homology (TRPC, TRPV, TRPM, TRPA, TRPP, and TRPML). Selected functional properties of TRP channels from each subfamily are summarized in this review. Although a single defining characteristic of TRP channel function has not yet emerged, TRP channels may be generally described as calcium-permeable cation channels with polymodal activation properties. By integrating multiple concomitant stimuli and coupling their activity to downstream cellular signal amplification via calcium permeation and membrane depolarization, TRP channels appear well adapted to function in cellular sensation. Our review of recent literature implicating TRP channels in neuronal growth cone steering suggests that TRPs may function more widely in cellular guidance and chemotaxis. The TRP channel gene family and its nomenclature, the encoded proteins and alternatively spliced variants, and the rapidly expanding pharmacology of TRP channels are summarized in online supplemental material.
Dexamethasone protection from TNF-alpha-induced cell death in MCF-7 cells requires NF-kappaB and is independent from AKT (2006)

NF-kappaB, but not PI3K/Akt activation, is required for the Dex protective effect against TNF-alpha-mediated cell death, and correlates with lack of degradation of the anti-apoptotic protein c-IAP1.
Induction of Systemic Resistance in Cucumber by Plant Growth-Promoting Rhizobacteria: Duration of Protection and Effect of Host Resistance on Protection and Root Colonization (1995)

Two plant growth-promoting rhizobacteria, Pseudomonas putida strain 89B-27 and Serratia marcescens strain 90-166, which previously induced systemic resistance (ISR) in cucumber 'Straight 8' against anthracnose caused by Colletotrichum orbiculare, were used to determine the duration of ISR in cucumber. ISR activity induced by strain 89B-27 occurred at the first-leaf stage, increased over time, and was maintained at least to the fifth-leaf stage. With strain 90-166, ISR was less stable, occurring at the second-, fourth-, and fifth-leaf stages. Cultivar specificity of ISR and colonization capacity of the two strains were studied in one resistant and three susceptible cucumber cultivars under greenhouse conditions. Strain 89B-27 induced systemic resistance in all three, whereas strain 90-166 induced systemic resistance in two of the three susceptible cultivars. Both strains failed to induce resistance in the resistant cultivar. Root colonization patterns of strains 89B-27 and 90-166 also differed. Populations of strain 89B-27 declined at a consistent rate over time, dropping from log 10 8.2 CFU/g fresh weight of roots 1 week after planting to log 10 3.2 CFU/g fresh weight of roots by 4 weeks after planting. In contrast, populations of strain 90-166 declined rapidly from log 10 7.4 CFU/g fresh weight of roots 2 weeks after inoculation and then decreased more slowly to log 10 3.2 CFU/g fresh weight of roots by 4 weeks after planting. There was no relationship between ISR activity and populations of the two strains on roots. ISR increased over time, while populations of the bacteria decreased.
Identification and characterization of the transferrin receptor from Neisseria meningitidis (1988)

Expression of the meningococcal transferrin receptor, detected by assay with human transferrin conjugated to peroxidase, was regulated by the level of iron in the medium. The transferrin receptor was identified by SDS-PAGE and Western blot analysis, as a 71,000 molecular weight iron-regulated outer membrane protein in Neisseria meningitidis B16B6. Growth studies with iron-deficient cells and competition binding experiments demonstrated that the meningococcal receptor was species-specific for human transferrin. Reciprocal competitive binding experiments and limited proteolysis of intact cells indicated that the transferrin and lactoferrin receptors are distinct.
Important Aspects concerning the Quantification of Biomolecules by Time-of-Flight Secondary-Ion Mass Spectrometry (1996)

Fundamental aspects regarding the use of time-of-flight secondary-ion mass spectrometry (TOF-SIMS) as a quantitative tool for the analysis of organic compounds are reported. The following factors are discussed: (1) the use of Poisson's law to correct for dead-time in single-ion data collection; (2) practical considerations concerning the analysis of “real world” samples; and (3) the effect of the etching process on the reproducibility of the intensity ratio (analyte/internal standard) of Ag-cationized species. To evaluate the importance of these factors, we used cocaine and cyclosporin A (CsA) as analytes because they show protonated and Ag-cationized species, respectively, in their SIMS spectra. Correction for detector dead-time using Poisson's law of single-ion counting expanded the dynamic range for cocaine by ∼2 orders of magnitude. For analyses requiring only a small dynamic range (i.e., CsA), the correction improved the % RSD of the slope from 2.43 to 0.87%. The maximum secondary-ion (SI) yield of CsA (Ag-cationized species) occurs at a CsA concentration ∼3 orders of magnitude higher than the therapeutic levels in blood (25–2000 ng/mL). It is discussed how this problem should be addressed. Analysis of variance (ANOVA) indicates that Ag substrates must be etched under identical conditions to obtain quantitative results when species requiring cationization are being analyzed.
Preconditioning full waveform inversion with phase‐encoded Hessian (2010)

Full waveform inversion (FWI) has received an increasing amount of attention thanks to its ability to provide a high‐resolution velocity model of the subsurface. The computational cost still presents a challenge, however, and the convergence rate of the FWI problem is usually very slow without proper preconditioning of the gradient. While preconditioners based on the Gauss‐Newton Hessian matrix can provide significant improvements in the convergence of FWI, computation of the Hessian matrix itself has been considered highly impractical due to its cost in computational time and storage requirements. In this paper, we design preconditioners based on an approximate Gauss‐Newton Hessian matrix obtained using the phase‐encoding method. The new method requires only 2Ns forward simulations compared to Ns(Nr+ 1) forward simulations required in conventional approaches, where Ns and Nr are the numbers of sources and receivers, respectively. We apply the diagonal of the phase‐encoded Gauss‐Newton Hessian to both sequential‐source FWI and encoded simultaneous‐source FWI. Numerical examples using a truncated Marmousi2 model demonstrate that the phase‐encoded Gauss‐Newton Hessian improves the convergence of the FWI significantly.
Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry (2007)

Electron transfer dissociation (ETD) is a recently introduced mass spectrometric technique that provides a more comprehensive coverage of peptide sequences and posttranslational modifications. Here, we evaluated the use of ETD for a global phosphoproteome analysis. In all, we identified a total of 1,435 phosphorylation sites from human embryonic kidney 293T cells, of which 1,141 ( approximately 80%) were not previously described. A detailed comparison of ETD and collision-induced dissociation (CID) modes showed that ETD identified 60% more phosphopeptides than CID, with an average of 40% more fragment ions that facilitated localization of phosphorylation sites. Although our data indicate that ETD is superior to CID for phosphorylation analysis, the two methods can be effectively combined in alternating ETD and CID modes for a more comprehensive analysis. Combining ETD and CID, from this single study, we were able to identify 80% of the known phosphorylation sites in >1,000 phosphorylated peptides analyzed. A hierarchical clustering of the identified phosphorylation sites allowed us to discover 15 phosphorylation motifs that have not been reported previously. Overall, ETD is an excellent method for localization of phosphorylation sites and should be an integral component of any strategy for comprehensive phosphorylation analysis.
αPix Stimulates p21-activated Kinase Activity through Exchange Factor-dependent and -independent Mechanisms (1999)

Activation of p21-activated kinases (Paks) is achieved through binding of the GTPases Rac or Cdc42 to a conserved domain in the N-terminal regulatory region of Pak. Additional signaling components are also likely to be important in regulating Pak activation. Recently, a family of Pak-interacting guanine nucleotide exchange factors (Pix) have been identified and which are good candidates for regulating Pak activity. Using an active, truncated form of alphaPix (amino acids 155-545), we observe stimulation of Pak1 kinase activity when alphaPix155-545 is co-expressed with Cdc42 and wild-type Pak1 in COS-1 cells. This activation does not occur when we co-express a Pak1 mutant unable to bind alphaPix. The activation of wild-type Pak1 by alphaPix155-545 also requires that alphaPix155-545 retain functional exchange factor activity. However, the Pak1(H83,86L) mutant that does not bind Rac or Cdc42 is activated in the absence of GTPase by alphaPix155-545 and by a mutant of alphaPix155-545 that no longer has exchange factor activity. Pak1 activity stimulated in vitro using GTPgammaS-loaded Cdc42 was also enhanced by recombinant alphaPix155-545 in a binding-dependent manner. These data suggest that Pak activity can be modulated by physical interaction with alphaPix and that this specific effect involves both exchange factor-dependent and -independent mechanisms.
Alleviation of mechanical and thermal allodynia by CGRP8-37 in a rodent model of chronic central pain (2000)

CGRP(8-37) is a truncated version of calcitonin gene-related peptide (CGRP) that binds to the CGRP receptor with similar affinity but does not activate the receptor and is a highly selective CGRP receptor antagonist. CGRP and activation of its receptor appear to play a role in peripheral inflammatory and neuropathic models of pain although there is considerable controversy. The aim of this study was to examine possible anti-nociceptive effects of CGRP(8-37) on a model of chronic central neuropathic pain known to develop weeks after spinal hemisection. Adult male Sprague-Dawley rats were given a spinal hemisection (N=34) or a sham surgery (N=10) at the T13 spinal segment. An externally accessible PE-10 intrathecal catheter that terminated at T13 was used for drug delivery. Animals were allowed to recover for 4 weeks at which time the hemisected animals displayed mechanical and thermal allodynia bilaterally, in both forelimbs and hindlimbs. CGRP(8-37) was delivered just prior to a testing session in 1, 5, 10, or 50 nM doses in artificial cerebral spinal fluid in 10 microl volumes. CGRP(8-37) was effective in alleviating mechanical and thermal allodynia in a dose-dependent manner (P<0.05). The 50 nM dose was most efficacious for both forelimb and hindlimb responses (P<0.05). The period of efficacy was 10 min to onset for a duration of 20 min. Post-drug washout responses were not statistically significant compared to pre-drug responses. The sham control groups demonstrated no statistically significant difference at any dose of CGRP(8-37) when compared to pre-surgical baseline values. In conclusion, CGRP(8-37) is effective in abolishing mechanical and thermal allodynia produced by spinal hemisection. Consequently, the CGRP receptor may play a role in chronic central neuropathic pain and offers a novel therapeutic approach to managing chronic central pain.
Use of human GH in elderly patients with accidental hip fracture (2000)

A 6 week treatment with hGH (20 microg/kg per day) of otherwise healthy patients after an accidental hip fracture may be of benefit if given to subjects older than 75 years of age. The rate of return to the pre-fracture living situation in subjects of this age treated with hGH was significantly increased when compared with the placebo-treated group. The treatment intervention was well tolerated and no safety issues were recorded.
Identification of chitin as a structural component of Giardia cysts (1985)

The intestinal parasite Giardia lamblia is a significant cause of diarrheal disease, which is perpetuated by the infective cyst form of the parasite. Although a rational approach to the control of giardiasis would be to inhibit cyst formation, nothing is known of the chemical composition of the cyst wall or of its biosynthesis. In these studies, we have shown that chitin is a major structural component of G. lamblia and G. muris cyst walls. This conclusion is based on the finding that chitinase specifically destroys the cyst wall, as revealed by electron microscopy. The presence of chitin was also shown directly by lectin binding studies. Of 12 lectins with diverse carbohydrate recognition specificity, only the N-acetylglucosamine-specific lectins wheat germ agglutinin, succinylated wheat germ agglutinin, and tomato lectin bound to cyst walls, as shown by fluorescence microscopy and cytochemistry. Wheat germ agglutinin binding was completely abolished by treatment of the cysts with purified chitinase. This effect was specific since it could be prevented by incubating the enzyme with chitin before treatment of the cysts. Treatment of cysts with N-acetyl-beta-glucosaminidase partially inhibited wheat germ agglutinin binding, whereas other glycosidases and proteases had no effect. These findings indicate that chitin is a major structural component of Giardia cyst walls and raise the possibility that inhibitors of chitin synthesis may be of use in preventing encystation and thus controlling spread of the disease.
30 kVA LF/VLF power amplifier module (2002)

A high reliability RF power amplifier module (PAM) has been developed for high power LF/VLF transmit systems applications. The PAM is intended for operation in the 14 to 160 kHz frequency range for driving highly reactive loads. It uses a full-bridge configuration of high power field effect transistors (FETs). The PAM replaces four of the current 7.5 kVA modules developed for airborne applications resulting in a reduction in parts count, increased efficiency and increased power output. The new PAM provides efficiencies greater than 90 percent when operating into a reactive load of 70 degree phase angles and greater than 98 percent when operating into a resistive load. A low inductance power and RF interconnect bus structure is employed along with metal oxide semiconductor field effect transistor (MOSFET) power hybrid switching assemblies to minimize switching losses and reduce voltage transients. Protection features have been provided to preclude over current, over temperature and loss of the low voltage power on the RF input drive from causing damage or erroneous operation. Remote control and monitoring is provided through an EIA RS-485 bus interface, allowing RF output control and reporting of status conditions. The RF and control interfaces utilize opto-isolators to provide noise immunity for operation in high noise environments. Cooling is provided by means of a forced air, high performance heat sink assembly resulting in low operating temperatures and high efficiency. The PAM provides an output of thirty kVA into a resistive or reactive load when operating from a 330 V DC source and can be combined with additional modules to form a transmitter power amplifier capable of delivering up to 2 MW to an antenna system.
Enhancing immune responses by targeting antigen to DC (2009)

mAb that recognise various cell surface receptors have been used to deliver antigen to DC and thereby elicit immune responses. The encouraging data obtained in mouse models suggests that this immunisation strategy is efficient and could lead to clinical trials. We discuss a number of issues pertinent to this vaccination approach. These include which molecules are the best targets for delivering antigen to DC, which DC subtypes should be targeted, the types of immune responses to be generated and whether additional adjuvants are required. Finally, we discuss some progress towards targeting antigen to human DC.
Weight Loss and Survival in HIV-Positive Patients in the Era of Highly Active Antiretroviral Therapy (2002)

Weight loss and wasting have long been established as strong predictors of mortality in HIV-infected patients. Today, despite the effectiveness of highly active antiretroviral therapy (HAART), there is evidence that HIV-related wasting is still an important comorbidity in many patients. We conducted a study to determine if wasting is still associated with decreased survival in patients receiving HAART and which parameter (weight, fat-free mass [FFM], body cell mass [BCM], or fat mass [FM]) is most strongly associated with mortality. The study population consisted of 678 HIV-positive participants enrolled in the Nutrition for Healthy Living study. Weight, FFM, BCM, and FM were assessed for all participants at 6-month intervals. At each follow-up visit, percent losses of each parameter were calculated from values at baseline and the previous visit. Cox proportional hazards models were used to estimate and compare the relative risks of death for each parameter, adjusting for potential confounders such as HAART use, body mass index, and CD4 cell counts. In analyses examining the parameters separately and together in the same model, weight loss emerged as the strongest independent predictor of mortality. Weight loss of >or=10% from baseline or the previous visit was significantly associated with a four- to sixfold increase in mortality compared with maintenance or gaining of weight. Even one episode of weight loss of >or=3% from baseline or >or=5% from the previous visit was predictive of mortality. In summary, despite the apparent benefits of HAART use on HIV-related survival, weight loss remains an independent predictor of mortality. In addition, FFM or BCM estimated using bioelectrical impedance analysis does not add further prognostic value over weight loss.
Prostate Specific Antigen Decreases After Withdrawal of Antiandrogen Therapy with Bicalutamide or Flutamide in Patients Receiving Combined Androgen Blockade (1997)

For patients with stage D2 prostate cancer and disease progression or an increasing PSA concentration, withdrawal of antiandrogen therapy with bicalutamide or flutamide may result in a PSA response. The time to PSA response is longer with bicalutamide than with flutamide. The clinical significance of the antiandrogen withdrawal phenomenon is unknown.
A Single Free Cysteine Residue and Disulfide Bond Contribute to the Thermostability ofAspergillus saitoi1,2-α-Mannosidase (2005)

Aspergillus saitoi 1,2-alpha-mannosidase contains three conserved cysteine residues (Cys334, Cys363, and Cys443). We showed that Cys334 and Cys363 are involved in a disulfide bond, and that Cys443 contains a free thiol group. The cysteines were not essential for the activity analyzed by site-directed mutagenesis and kinetics. The substitution at each cysteine residue greatly destabilized the enzyme. The T(m) values of WT, C443A, C443G, C443S, and C443T were 55.8, 51.9, 50.2, 50.0, and 52.8 degrees C respectively. The specific activity of these mutants was almost equal to that of WT. Introducing Asp, Leu, Met, or Val at position 443 caused partial denaturation, although the enzymes had some activity. C443F, C443I, C443N, and C443Y were not secreted. These results suggest that the hydrophilic and large side chain causes the destabilization. Molecular modelling showed that the Cys443 residue is buried and surrounded by a hydrophobic environment. Cys334 and Cys363 form a disulfide bond, and Cys443 is involved in a hydrophobic interaction to stabilize the enzyme.