gebhart/patrepeval huggingface dataset:
Double-stranded RNA specifically disrupts gene expression during planarian regeneration (1999)

Metazoan regeneration is one of the least understood fundamental problems of biology. The lack of progress in understanding this phenomenon at the molecular level has been due to the poor regenerative abilities of the genetic organisms used for developmental studies, as well as the difficulties encountered with molecular and genetic manipulations of the commonly studied vertebrate models (the urodele amphibians). Here, we demonstrate that introduction of double-stranded RNA selectively abrogates gene function in planarians, a classic model of regeneration. The ability to eliminate gene function in a regenerating organism such as the planarian overcomes previous experimental limitations and opens the study of animal regeneration to unprecedented levels of molecular detail.
BAFF/APRIL Inhibition Decreases Selection of Naive but Not Antigen-Induced Autoreactive B Cells in Murine Systemic Lupus Erythematosus (2011)

BAFF inhibition is a new B cell-directed therapeutic strategy for autoimmune disease. Our purpose was to analyze the effect of BAFF/APRIL availability on the naive and Ag-activated B cell repertoires in systemic lupus erythematosus, using the autoreactive germline D42 H chain (glD42H) site-directed transgenic NZB/W mouse. In this article, we show that the naive Vκ repertoire in both young and diseased glD42H NZB/W mice is dominated by five L chains that confer no or low-affinity polyreactivity. In contrast, glD42H B cells expressing L chains that confer high-affinity autoreactivity are mostly deleted before the mature B cell stage, but are positively selected and expanded in the germinal centers (GCs) as the mice age. Of these, the most abundant is VκRF (Vκ16-104*01), which is expressed by almost all IgG anti-DNA hybridomas derived from the glD42H mouse. Competition with nonautoreactive B cells or BAFF/APRIL inhibition significantly inhibited selection of glD42H B cells at the late transitional stage, with only subtle effects on the glD42H-associated L chain repertoire. However, glD42H/VκRF-encoded B cells were still vastly overrepresented in the GC, and serum IgG anti-DNA Abs arose with only a slight delay. Thus, although BAFF/APRIL inhibition increases the stringency of negative selection of the naive autoreactive B cell repertoire in NZB/W mice, it does not correct the major breach in B cell tolerance that occurs at the GC checkpoint.
High-Density Directional Display for Generating Natural Three-Dimensional Images (2006)

A high-density directional display can produce natural three-dimensional(3-D) images by projecting a large number of directional images using directional rays. When the angle pitch of the directional rays is 0.2/spl deg//spl sim/0.4/spl deg/, more than two directional rays passing through a point in 3-D space enter the viewer's eye simultaneously so that the viewer's eye can focus on that point. No discrepancy appears between the convergence function and the accommodation function so that the display does not induce visual fatigue. Two different system configurations are presented: a projection configuration and a thin configuration. A prototype display based on the projection configuration was constructed. The prototype display displayed 64 directional images with directional rays having a horizontal angle pitch of 0.34/spl deg/. The screen size was 9.2 in. The preliminary experimental results showed that a viewer could focus on 3-D images produced by the prototype display.
The Role of Anticonvulsant Drugs in Anxiety Disorders (2007)

Antiepileptic drugs (AEDs) have been successfully used in the treatment of mood disturbances, leading clinicians and researchers to investigate their use in other psychiatric disorders. This article reviews the literature about the potential efficacy of AEDs in anxiety disorders. An updated MEDLINE search (January 1970 to September 2006) using the terms "panic disorder," "agoraphobia," "posttraumatic stress disorder," "obsessive-compulsive disorder," "generalized anxiety disorder," "social phobia," "phobia," "carbamazepine," "phenobarbital," "phenytoin," "valproate," "lamotrigine," "topiramate," "vigabatrin," "tiagabine," "gabapentin," "levetiracetam," and "pregabalin" showed more than 70 articles and 38 published studies. Only articles published in English were reviewed. We have assigned level 1 of evidence to meta-analysis and replicated randomized controlled trials, level 2 to at least 1 randomized controlled trial, level 3 to uncontrolled trials with 10 or more subjects, and level 4 to anecdotal case reports. The strongest evidence has been demonstrated for pregabalin in social phobia and generalized anxiety disorder, lamotrigine in posttraumatic stress disorder, and gabapentin in social anxiety. The available data about gabapentin in panic disorder are somewhat mixed, and more definitive conclusion would require additional studies. This review suggests that AEDs can be an alternative treatment in some anxiety disorders. Further investigation is needed to determine in what circumstances they should be used in individuals who are partially responsive or nonresponsive to conventional therapy.
ON THE MECHANISMS WHEREBY EDTA, EGTA, DPTA, OXALATE, DESFERRIOXAMINE, AND 1,10-PHENANTHROLINE AFFECT CONTRACTILITY OF RAT UTERUS (1965)

The effects of EDTA on rat uterine horns were studied and found to consist of contraction followed by relaxation, and inhibition of subsequent contraction in response to acetylcholine. An hypothesis was formulated to explain these actions. The contraction is attributed to complexing and consequent decrease in the activity of magnesium in or near the membrane, accompanied by unstabilization of the membrane following removal of calcium from sites at which it exerts a stabilizing action. The relaxation is attributed to similar complexing of membrane calcium bound to other sites from which it is released during excitation to cause contraction. Na 4 EDTA was much more effective in evoking contractions than Na 2 EDTA; this is attributed to the competition between hydrogen and magnesium.Experiments in which ions in the bathing medium were varied supported this general hypothesis. Furthermore, MgEDTA was found to produce only relaxation, while CaEDTA was found to produce little or no effect; mixtures had intermediate effects. The calcium-depleted membrane was found to compete effectively with CaEDTA for its calcium. Similar studies were carried out with DTPA (diethylenetriaminepentaacetic acid) and similar results obtained. DTPA was more dependent than EDTA on a high pH, as expected from the greater affinity of this material for hydrogen ions. EGTA (ethylene bisglycol (β-aminoethylether) tetraacetic acid), a substance with equivalent ability to complex calcium and less ability to complex magnesium relative to EDTA or DTPA, was ineffective in evoking contraction unless magnesium was omitted from the medium; however, it did inhibit responses to subsequent acetylcholine. None of these complexing agents produced significant contractions when strontium was substituted for calcium.Other complexing agents unrelated to EDTA were studied as well. Desferrioxamine (DFO) caused contractions when added at a pH of 9 or more. It had little inhibitory action on acetylcholine-evoked contractions. Oxalate was relatively ineffective in evoking contraction or inhibition of responses to acetylcholine. Both these sets of findings are compatible with the hypotheses for EDTA when considered in the light of the complexometric characteristics of DFO and oxalate. 1,10-Phenanthroline, which complexes neither magnesium nor calcium effectively, evoked no contractions, but did inhibit contractions in response to other agents by a mechanism apparently unrelated to calcium.
Genetic and Functional Dissection of ARMS2 in Age-Related Macular Degeneration and Polypoidal Choroidal Vasculopathy (2013)

Age-related maculopathy susceptibility 2(ARMS2) was suggested to be associated with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in multiple genetic studies in Caucasians and Japanese. To date, no biological properties have been attributed to the putative protein in nAMD and PCV. The complete genes of ARMS2 and HTRA1 including all exons and the promoter region were assessed using direct sequencing technology in 284 unrelated mainland northern Chinese individuals: 96 nAMD patients, 92 PCV patients and 96 controls. Significant associations with both nAMD and PCV were observed in 2 polymorphisms of ARMS2 and HTRA1 rs11200638, with different genotypic distributions between nAMD and PCV (p<0.001). After adjusting for rs11200638, ARMS2 rs10490924 remained significantly associated with nAMD and PCV (p<0.001). Then we overexpressed wild-type ARMS2 and ARMS2 A69S mutation (rs10490924) in RF/6A cells and RPE cells as in vitro study model. Cell proliferation, attachment, migration and tube formation were analyzed for the first time. Compare with wild-type ARMS2, A69S mutation resulted in a significant increase in proliferation and attachment but inhibited cell migration. Moreover, neither wild-type ARMS2 nor A69S mutation affected tube formation of RF/6A cells. There is a strong and consistent association of the ARMS2/HTRA1 locus with both nAMD and PCV, suggesting the two disorders share, at least partially, similar molecular mechanisms. Neither wild-type ARMS2 nor A69S mutation had direct association with neovascularisation in the pathogenesis of AMD.
Polymer capture by electro-osmotic flow of oppositely charged nanopores (2008)

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A randomized evaluation of betrixaban, an oral factor Xa inhibitor, for prevention of thromboembolic events after total knee replacement (EXPERT) (2008)

Betrixaban is an oral direct inhibitor of factor Xa (FXa) being developed for the prevention of venous thromboembolism (VTE). Its antithrombotic effects had not been previously tested in patients. This exploratory clinical trial in the US and Canada randomized 215 patients undergoing elective total knee replacement (TKR) in a 2:2:1 ratio to receive post-operative betrixaban 15 mg or 40 mg p.o. bid or enoxaparin 30 mg s.c. q12h, respectively, for 10-14 days. The betrixaban dosage was blinded, but enoxaparin was not. Primary efficacy outcome was the incidence of VTE, consisting of deep-vein thrombosis (DVT) on mandatory unilateral (operated leg) venography, symptomatic proximal DVT, or pulmonary embolism (PE) through Day 10-14. Safety outcomes included major and clinically significant non-major bleeds through 48 h after treatment. All efficacy and bleeding outcomes were adjudicated by a blinded independent central adjudication committee. Of 214 treated patients, 175 (82%) were evaluable for primary efficacy. VTE incidence was 14/70 (20%; 95% CI: 11, 31) for betrixaban 15 mg, 10/65 (15%; 95% CI: 8, 27) for betrixaban 40 mg, and 4/40 (10%; 95% CI: 3, 24) for enoxaparin. No bleeds were reported for betrixaban 15 mg, 2 (2.4%) clinically significant non-major bleeds with betrixaban 40 mg, and one (2.3%) major and two (4.6%) clinically significant non-major bleeds with enoxaparin. A dose- and concentration-dependent effect of betrixaban on inhibition of thrombin generation and anti-Xa levels was observed. Betrixaban demonstrated antithrombotic activity and appeared well tolerated in knee replacement patients at the doses studied.
Minnesota's Groundwater Protection Act: A Response to Federal Inaction (1990)

At common law, the question of what is surface water arises when unwanted surface water is diverted by one landowner onto the land of another.Surface water is defined as "waters from rain
The 3′ untranslated region of a soybean cytosolic glutamine synthetase (GS1) affects transcript stability and protein accumulation in transgenic alfalfa (2006)

Higher plants assimilate nitrogen in the form of ammonia through the concerted activity of glutamine synthetase (GS) and glutamate synthase (GOGAT). The GS enzyme is either located in the cytoplasm (GS1) or in the chloroplast (GS2). Glutamine synthetase 1 is regulated in different plants at the transcriptional level and there are some reports of regulation at the level of protein stability. Here we present data that clearly establish that GS1 in plants is also regulated at the level of transcript turnover and at the translational level. Using a Glycine max (soybean) GS1 transgene, with and without its 3' untranslated region (UTR), driven by the constitutive CaMV 35S promoter in Medicago sativa (alfalfa) and Nicotiana tabacum (tobacco), we show that the 3' UTR plays a major role in both transcript turnover and translation repression in both the leaves and the nodules. Our data suggest that the 3' UTR mediated turnover of the transcript is regulated by a nitrogen metabolite or carbon/nitrogen ratios. We also show that the 3' UTR of the gene for the soybean GS1 confers post-transcriptional regulation on a reporter gene. Our dissection of post-transcriptional and translational levels of regulation of GS in plants shows that the situation in plants strongly resembles that in other organisms where GS is regulated at almost all levels. Multistep regulation of GS shows the high priority given by organisms to regulating and ensuring optimal control of nitrogen substrates and preventing overproduction of glutamine and drainage of the glutamate pool.
Rapid Quantification of Molecular Diversity for Selective Database Acquisition (1997)

There is an increasing need to expand the structural diversity of the molecules investigated in lead-discovery programs. One way in which this can be achieved is by acquiring external datasets that will enhance an existing database. This paper describes a rapid procedure for the selection of external datasets using a measure of structural diversity that is calculated from sums of pairwise intermolecular structural similarities.
A New Protein-Protein Interaction Sensor Based on Tripartite Split-GFP Association (2013)

Monitoring protein-protein interactions in living cells is key to unraveling their roles in numerous cellular processes and various diseases. Previously described split-GFP based sensors suffer from poor folding and/or self-assembly background fluorescence. Here, we have engineered a micro-tagging system to monitor protein-protein interactions in vivo and in vitro. The assay is based on tripartite association between two twenty amino-acids long GFP tags, GFP10 and GFP11, fused to interacting protein partners, and the complementary GFP1-9 detector. When proteins interact, GFP10 and GFP11 self-associate with GFP1-9 to reconstitute a functional GFP. Using coiled-coils and FRB/FKBP12 model systems we characterize the sensor in vitro and in Escherichia coli. We extend the studies to mammalian cells and examine the FK-506 inhibition of the rapamycin-induced association of FRB/FKBP12. The small size of these tags and their minimal effect on fusion protein behavior and solubility should enable new experiments for monitoring protein-protein association by fluorescence.
Thrombolytic and Pharmacokinetic Properties of a Recombinant Chimeric Plasminogen Activator Consisting of a Fibrin Fragment D-Dimer Specific Humanized Monoclonal Antibody and a Truncated Single-Chain Urokinase (1992)

A recombinant chimeric plasminogen activator consisting of a humanized monoclonal antibody specific for cross-linked human fibrin (MA-15C5Hu) and a 32 kDa single-chain urokinase-type plasminogen activator (scu-PA-32k) comprising amino acids Leu144-Leu411, MA-15C5Hu/scu-PA-32k, was previously found to have a 12-fold higher fibrinolytic potency than recombinant scu-PA-32k towards a human plasma clot in a human plasma milieu in vitro (Vandamme et al., Eur J Biochem 1992; 205: 139-46). Therefore, the thrombolytic and pharmacokinetic properties of MA-15C5Hu/scu-PA-32k were compared with those of recombinant single-chain urokinase-type plasminogen activator (scu-PA) in 3 different venous thrombosis models in vivo. In hamsters with a pulmonary embolus consisting of a human plasma clot, the thrombolytic potency (% lysis per dose in mg/kg administered) of MA-15C5Hu/scu-PA-32k was 23-fold higher than that of scu-PA (p less than 0.0005). In rabbits with a jugular vein clot prepared from human plasma, the thrombolytic potency of MA-15C5Hu/scu-PA-32k was 11-fold higher than that of scu-PA (p = 0.012). In baboons with an autologous whole blood clot in the femoral vein, the chimera had a 5-fold higher thrombolytic potency than scu-PA. In all three animal species, the clearance of the chimera was 10- to 27-fold reduced as compared to scu-PA. The specific thrombolytic activity (% lysis per micrograms/ml steady-state plasma u-PA antigen) was increased up to 7-fold with MA-15C5Hu/scu-PA-32k as compared with scu-PA, which is indicative of targeting of the chimera to the clot. No fibrinogen breakdown or alpha 2-antiplasmin depletion was observed during thrombolysis with the chimera. Thus, MA-15C5Hu/scu-PA-32k constitutes a recombinant chimeric plasminogen activator with a significantly enhanced thrombolytic potency in 3 different animal models of venous thrombosis.
Crystal Structure of an RNA 16-mer Duplex R(GCAGAGUUAAAUCUGC)2 with Nonadjacent G(Syn)·A+(Anti) Mispairs (1999)

G.A mispairs are one of the most common noncanonical structural motifs of RNA. The 1.9 A resolution crystal structure of the RNA 16-mer r(GCAGAGUUAAAUCUGC)2 has been determined with two isolated or nonadjacent G.A mispairs. The molecule crystallizes with one duplex in the asymmetric unit in space group R3 and unit cell dimensions a = b = c = 49.24 A and alpha = beta = gamma = 51.2 degrees. It is the longest known oligonucleotide duplex at this resolution and isomorphous to the 16-mer duplex with the C.A+ mispairs [Pan, et al., (1998) J. Mol. Biol. 283, 977-984]. The C.A+ mispair behaves like a wobble pair while the G.A+ does not. The G.A mispairs are protonated at N1 of the adenines as in the C.A+ mispairs, and two hydrogen bonds in the G(syn).A+(anti) conformation are formed. The syn guanine is stabilized by an intranucleotide hydrogen bond between the 2-amino and the 5'-phosphate groups. The G(syn).A+(anti) conformation can provide a different surface for recognition in the grooves compared to other G.A hydrogen bonding schemes. The major groove is widened between the two mispairs allowing access to ligands. One of the 3-fold axes is occupied by a sodium ion and a water molecule, while a second is occupied by another water molecule.
Characterization of magnetic nanoparticles using programmed quadrupole magnetic field-flow fractionation (2010)

Quadrupole magnetic field-flow fractionation is a relatively new technique for the separation and characterization of magnetic nanoparticles. Magnetic nanoparticles are often of composite nature having a magnetic component, which may be a very finely divided material, and a polymeric or other material coating that incorporates this magnetic material and stabilizes the particles in suspension. There may be other components such as antibodies on the surface for specific binding to biological cells, or chemotherapeutic drugs for magnetic drug delivery. Magnetic field-flow fractionation (MgFFF) has the potential for determining the distribution of the magnetic material among the particles in a given sample. MgFFF differs from most other forms of field-flow fractionation in that the magnetic field that brings about particle separation induces magnetic dipole moments in the nanoparticles, and these potentially can interact with one another and perturb the separation. This aspect is examined in the present work. Samples of magnetic nanoparticles were analysed under different experimental conditions to determine the sensitivity of the method to variation of conditions. The results are shown to be consistent and insensitive to conditions, although magnetite content appeared to be somewhat higher than expected.
Frequency-tuning for control of parametrically resonant mass sensors (2005)

Parametric resonance based mass sensing leads to increased sensitivity over other resonant methods. In this work, we present a frequency-tuning approach to measure mass change in an ultra-sensitive mass sensor. This scheme drives the oscillator using an electrical signal with fixed frequency and tunes the parametric resonance frequency to match the driving frequency by feeding back a dc offset to the sensor. Instead of monitoring frequency shift of the oscillation in a micro-oscillator, mass change in the sensor can be detected by measuring the shift in dc offset, making the sensor amenable to closed-loop control. This scheme and the prototype mass sensor with a mass of ∼30ng and a first mode harmonic resonance frequency of ∼83kHz has been built and experimentally characterized. Good correlation between parametric resonance frequency and dc offset has been shown and the noise floor is less than 1 pg. The sensor is used to track water content variation in a humidity-testing chamber and shows increased efficiency over open loop operation.
Responses of spinothalamic tract neurons to mechanical and thermal stimuli in an experimental model of peripheral neuropathy in primates (1992)

1. An experimental peripheral neuropathy (EPN) was induced in three monkeys (Macaca fascicularis) by ligation of spinal nerve L7. Behavioral responses to innocuous mechanical stimuli were tested before and after the surgery. Two weeks after the nerve ligation, the activity of spinothalamic tract (STT) neurons was recorded on both sides of the spinal cord with the animal under general anesthesia. Responses of the STT neurons to the following stimuli applied to the skin were recorded: graded mechanical stimuli (brush, press, pinch and squeeze), von Frey filaments of different bending forces (0.077-19.05 g), 5-s heat stimuli ranging from 39 to 53 degrees C, and 15 s cold stimuli (32-8 degrees C). 2. Innocuous mechanical stimulation of the foot did not evoke hindlimb withdrawal in the animals before surgery. Within 24-48 h after nerve ligation, the animals showed hindlimb withdrawal to the same innocuous stimuli. This behavior was more pronounced on the side of the ligation than on the sham-operated side and more frequent during the second week after the surgery. 3. Responses of 51 STT neurons recorded on the side of the ligation (EPN all group) were compared with responses of 33 STT cells recorded on the sham-operated side (control group) and with records from STT neurons in unoperated animals obtained earlier (reference group). Neurons from the EPN all group were divided into two sets according to their rostrocaudal location (EPN R, rostral to L6/7 border, n = 40; EPN C, caudal to L6/7 border, n = 11). 4. Neurons from the EPN all and EPN R groups had significantly higher background frequencies than those from the control and reference groups. Innocuous brush stimuli evoked mean discharge frequencies of approximately 35 Hz in EPN R neurons and only approximately 15 Hz in both control and reference groups. Increased responsiveness of EPN R neurons to innocuous stimuli was also demonstrated by lower thresholds and higher discharge frequencies to von Frey filament stimulation and by discriminative analysis of the responses evoked by graded mechanical stimuli. 5. The responses of the EPN R neurons to heat stimulation of the skin showed decreased thresholds and increased responses to suprathreshold stimuli, resulting in a significant leftward shift of the stimulus-response curve compared with both reference and control groups. The neurons from the control group showed responses comparable to reference group values. 6. Neurons from the reference group tested with the cooling stimuli showed no evoked response above background.(ABSTRACT TRUNCATED AT 400 WORDS)