gebhart/patrepeval huggingface dataset:
Recombinant murine IL-5 induces high rate IgA synthesis in cycling IgA-positive Peyer's patch B cells. (1988)

Recent studies have shown that purified IL-5 from T cell lines and clones enhances IgA synthesis in LPS-triggered splenic B cell cultures, and that this effect is augmented by IL-4. In this study we have examined the ability of rIL-5 and rIL-4 to support spontaneous Ig synthesis in normal Peyer's patch (PP) B cell cultures. The rIL-4 supported proliferation of the HT-2 and in vivo adapted BCL-1 cell lines, increased Ia expression on normal spleen B cells, co-stimulated splenic B cell proliferation in the presence of anti-mu and enhanced IgG1 synthesis in LPS triggered splenic B cell cultures. The rIL-5 supported BCL-1 proliferation, co-stimulated splenic B cell proliferation in the presence of dextran sulfate, and increased IgA synthesis in LPS-stimulated splenic B cell cultures. Markedly enhanced IgA responses occurred in PP B cell, but not splenic B cell cultures supplemented with rIL-5 in the absence of an added B cell trigger. However, rIL-4 alone did not enhance IgA synthesis or increase the IgA synthesis of PP B cell cultures stimulated with rIL-5. The rIL-5 receptive PP B cells were present in the blast cell subpopulation, inasmuch as a low density fraction isolated on Percoll gradients accounted for the enhanced IgA synthesis. Further, cell cycle analysis of whole PP B cells using propidium iodide in conjunction with staining for surface B220, demonstrated that approximately 12 to 16% of the B cells were in the S and G2/M stages of cell cycle, the remainder being in Go + G1. The surface IgM+ B cells were predominantly in Go + G1, whereas the sIgA+ B cell subpopulation was enriched for cells in the S and G2/M compartments. The PP B cell subset responsible for enhanced IgA synthesis in the presence of rIL-5 was sIgA-positive because FACS-depletion of the sIgA+ B cells resulted in the total loss of rIL-5 enhanced IgA synthesis. Further, when PP B cells were enriched for sIgA+ B cells by cell sorting, these cells responded to rIL-5 with increased IgA synthesis in a dose-dependent manner. When the actual numbers of IgA secreting cells were assessed in PP B cell cultures with supplemental rIL-5, no significant increase in total IgA-producing cells was noted when compared with B cells cultured without rIL-5.(ABSTRACT TRUNCATED AT 400 WORDS)
Causes of a Negative Ethanol Gelation Test in Diffuse Intravascular Coagulation (1974)

Summary The clinical value of the ethanol gelation test (EGT) in diagnosing diffuse intravascular coagulation (DIC) has been questioned because of the occasional finding of a negative test, while other laboratory data pointed to DIC. Therefore, the behaviour of the EGT during thrombin infusions in rabbits was studied, with special reference to the fibrinogen level and activation of fibrinolysis. Fibrinolytic activity was inhibited or induced by synchronous infusion of epsilon-aminocaproic acid or plasmin respectively. The results obtained show that apart from severe depletion of fibrinogen strong activation of fibrinolysis can cause a negative EGT during thrombin infusions in rabbits. This phenomenon could not be ascribed to high levels of fibrin degradation products (fdp); it might be due to plasmin digestion of fibrin monomers. In vitro studies with human plasma confirmed that the EGT becomes negative at a fibrinogen level of less than 20 mg per 100 ml or by plasmin activity in the presence of a normal fibrinogen level. Whereas a positive EGT is highly specific for DIC, these studies show that a negative EGT does not exclude the presence of DIC.
Benefit of combination therapy in epilepsy: A review of the preclinical evidence with levetiracetam (2008)

Levetiracetam (Keppra) is an antiepileptic drug (AED) characterized by a novel mechanism of action, unique profile of activity in seizure models, and broad-spectrum clinical efficacy. The present report critically reviews several preclinical studies focused on combination therapy with levetiracetam and other anticonvulsants in various seizure and epilepsy models. Administration of levetiracetam together with many different clinically used AEDs or other anticonvulsants generally enhances their protective activity and, among existing AEDs, this was particularly prevalent with valproate. The protective activity of other AEDs was also enhanced by levetiracetam, which seems to be a universal finding that is independent of seizure model or drug combination studied. However, particularly strong enhancement was observed when levetiracetam was combined with agents either enhancing GABAergic or reducing glutamatergic neurotransmission. Importantly, these combinations were not associated with exacerbation of side effects or pharmacokinetic interactions. Based on the available preclinical data, it appears that combination treatment with levetiracetam and other anticonvulsants provides additional therapeutic benefit that may be attributed to its novel and distinct mechanism of action. Moreover, combinations of levetiracetam with clinically used AEDs that enhance GABAergic inhibition may be considered for rational polytherapy, which is often necessary in drug-resistant patients.
Engineering biosynthesis of the anticancer alkaloid noscapine in yeast (2016)

Noscapine is a potential anticancer drug isolated from the opium poppy Papaver somniferum, and genes encoding enzymes responsible for the synthesis of noscapine have been recently discovered to be clustered on the genome of P. somniferum. Here, we reconstitute the noscapine gene cluster in Saccharomyces cerevisiae to achieve the microbial production of noscapine and related pathway intermediates, complementing and extending previous in planta and in vitro investigations. Our work provides structural validation of the secoberberine intermediates and the description of the narcotoline-4'-O-methyltransferase, suggesting this activity is catalysed by a unique heterodimer. We also reconstitute a 14-step biosynthetic pathway of noscapine from the simple alkaloid norlaudanosoline by engineering a yeast strain expressing 16 heterologous plant enzymes, achieving reconstitution of a complex plant pathway in a microbial host. Other engineered yeasts produce previously inaccessible pathway intermediates and a novel derivative, thereby advancing protoberberine and noscapine related drug discovery.
'Smart' Cane for the Visually Impaired: Design and Controlled Field Testing of an Affordable Obstacle Detection System (2010)

Visually challenged persons face great difficulty in independent mobility and use the white cane as a mobility aid to detect close-by obstacles on the ground. However, the cane has two major limitations: 1. It can only detect obstacles up to knee-level. Hence, the user cannot detect raised obstacles like elevated bars and frequently collides with them. 2. The cane can only detect obstacles within 1m from the user. Also, obstacles like moving vehicles cannot be detected until dangerously close to the person. Almost 90% of the blind persons live in developing countries, with a majority below poverty line. Current devices available internationally are unaffordable. In this work the authors present the design and usability features of a low-cost knee-above obstacle detection system and report results from controlled field experiments.
DIFFERENTIAL EXPRESSION OF ??-GAL EPITOPES (Gal??1???3Gal??1???4GlcNAc-R) ON PIG AND MOUSE ORGANS (2000)

Expression of alpha-gal epitopes in pig organs is many fold higher than in mouse organs. The abundance of these epitopes in pigs raises the question of whether pigs can properly develop without expression of alpha-gal epitopes.
Simultaneous activation of SHR and ATHB8 expression defines switch to preprocambial cell state in Arabidopsis leaf development (2010)

The processes underlying the formation of leaf vascular networks have long captured the attention of developmental biologists, especially because files of elongated vascular-precursor procambial cells seem to differentiate from apparently equivalent, isodiametric ground cells. In Arabidopsis leaves, ground cells that have been specified to vascular fate engage expression of ARABIDOPSIS THALIANA HOMEOBOX8 (ATHB8). While definition of the transcriptional state of ATHB8-expressing ground cells would be particularly informative, no other genes have been identified whose expression is initiated at this stage. Here we show that expression of SHORT-ROOT (SHR) is activated simultaneously with that of ATHB8 in leaf development. Congruence between SHR and ATHB8 expression domains persists under conditions of manipulated vein patterning, suggesting that inception of expression of SHR and ATHB8 identifies transition to a preprocambial cell state that presages vein formation. Our observations further characterize the molecular identity of cells at anatomically inconspicuous stages of leaf vein development.
Serine 363 Is Required for Nociceptin/Orphanin FQ Opioid Receptor (NOPR) Desensitization, Internalization, and Arrestin Signaling (2012)

We determined the role of carboxyl-terminal regulation of NOPR (nociceptin, orphanin FQ receptor) signaling and function. We mutated C-terminal serine and threonine residues and examined their role in NOPR trafficking, homologous desensitization, and arrestin-dependent MAPK signaling. The NOPR agonist, nociceptin, caused robust NOPR-YFP receptor internalization, peaking at 30 min. Mutation of serine 337, 346, and 351, had no effect on NOPR internalization. However, mutation of C-terminal threonine 362, serine 363, and threonine 365 blocked nociceptin-induced internalization of NOPR. Furthermore, point mutation of only Ser-363 was sufficient to block NOPR internalization. Homologous desensitization of NOPR-mediated calcium channel blockade and inhibition of cAMP were also shown to require Ser-363. Additionally, NOPR internalization was absent when GRK3, and Arrestin3 were knocked down using siRNA, but not when GRK2 and Arrestin2 were knocked down. We also found that nociceptin-induced NOPR-mediated JNK but not ERK signaling requires Ser-363, GRK3, and Arrestin3. Dominant-positive Arrestin3 but not Arrestin2 was sufficient to rescue NOPR-S363A internalization and JNK signaling. These findings suggest that NOPR function may be regulated by GRK3 phosphorylation of Ser-363 and Arrestin3 and further demonstrates the complex nature of G-protein-dependent and -independent signaling in opioid receptors.
Acetylsalicylic acid reduces perfusion deficit in ischemic injured brain in rats (2003)

Acetylsalicylic acid (ASA) is an antiplatelet agent which has been used in treatment and prevention of stroke in humans. In the present study, the effects of ASA on perfusion deficits in the brain have been studied in an embolic model of stroke. Data showed that perfusion deficits were observed in all rats sacrificed immediately after middle cerebral artery (MCA) occlusion. Treatment with ASA significantly reduced perfusion deficits 1 h but not 3 h after the MCA occlusion. These findings thus support that ASA is useful agent in treatment and prevention of stroke, and show that its mechanism of action is likely through the reopening of cerebral microvessels.
Impact of Acute Lung Injury and Acute Respiratory Distress Syndrome After Traumatic Brain Injury in the United States (2012)

Our analysis demonstrates that ARDS/ALI is common after TBI. Despite an overall reduction of in-hospital mortality, ARDS/ALI carries a higher risk of in-hospital death after TBI.
Mammary-Derived Growth Inhibitor Protein and Messenger Ribonucleic Acid Concentrations in Different Physiological States of the Gland (1992)

Expression of mammary-derived growth inhibitor in tissue from lactating and involuting bovine mammary glands was investigated. Seventeen lactating, pregnant (220 to 272 d in gestation) cows were divided in two groups of 8 and 9 cows each. Cows of the first group were slaughtered while in lactation. Cows of the second group (9 involuting cows) were slaughtered at 13 to 52 d following sudden cessation of milking. High concentrations of mammary-derived growth inhibitor (.63% of the total protein) were detected in mammary tissue of lactating cows. Mammary-derived growth inhibitor (less than .10% of the total protein) was dramatically reduced during most of the involution period (13 to 45 d following cessation of milking). Mammary-derived growth inhibitor was again detected (.28% of the total protein) during the last stage of the involution (46 to 53 d after cessation of milking), which coincided with colostrum formation. When steady state concentrations of mammary-derived growth inhibitor mRNA were examined, the results obtained mirrored those obtained at the protein concentration. These data suggest that regulation of mammary-derived growth inhibitor occurs via modulation of the steady state concentration of its mRNA. Furthermore, there is a strong correlation between mammary-derived growth inhibitor expression and lactation in dairy cows.
The genetic contribution to canine personality (2005)

The domestic dog may be exceptionally well suited for behavioral genetic studies owing to its population history and the striking behavior differences among breeds. To explore to what extent and how behavioral traits are transmitted between generations, heritabilities and genetic correlations for behavioral traits were estimated in a cohort containing over 10,000 behaviorally tested German shepherd and Rottweiler dogs. In both breeds, the pattern of co-inheritance was found to be similar for the 16 examined behavioral traits. Furthermore, over 50% of the additive genetic variation of the behavioral traits could be explained by one underlying principal component, indicating a shared genetic component behind most of the examined behavioral traits. Only aggression appears to be inherited independently of the other traits. The results support a genetic basis for a broad personality trait previously named shyness-boldness dimension, and heritability was estimated to be 0.25 in the two breeds. Therefore, breeds of dogs appear to constitute a valuable resource for behavioral genetic research on the normal behavioral differences in broad personality traits.
Stimulation of rat oxyntic gland mucosal growth by epidermal growth factor (1980)

Epidermal growth factor (EGF) inhibits gastric acid secretion, but its effects on the growth of gut mucosa have not been examined. Fasted male rats were given six injections of EGF (10 micrograms/kg) over a 48-h period. The animals were killed and the incorporation of [3H]thymidine into various tissues was examined and compared to rats treated with NaCl, pentagastrin, and EGF plus secretin. EGF and pentagastrin significantly increased DNA synthesis of the oxyntic gland mucosa. Pentagastrin, but not EGF, stimulated DNA synthesis of duodenal and colonic mucosa as well. Neither peptide altered skin DNA synthesis. Secretin inhibited the effects of pentagastrin but not EGF. Chronic administration of EGF (5 days) caused significant increases in oxyntic gland mucosal DNA, RNA, and protein content. These results not only demonstrate that EGF is a trophic agent for the oxyntic gland mucosa but lend further support to the hypothesis that acid secretion and mitogenesis are the result of two separate mechanisms.
Receptor Modulation by FcγRI-Specific Fusion Proteins Is Dependent on Receptor Number and Modified by IgG (2001)

The high-affinity IgG receptor, FcgammaRI (CD64), is constitutively expressed exclusively on professional APCs. Human FcgammaRI binds monomeric IgG with high affinity and is, therefore, saturated in vivo. The binding of IgG to FcgammaRI causes receptor recycling, while Abs that cross-link FcgammaRI cause rapid down-modulation of surface FcgammaRI. Because studies performed in the absence of ligand may not be representative of FcgammaRI modulation in vivo, we investigated the ability of FcgammaRI-cross-linking Abs and non-cross-linking derivatives to modulate FcgammaRI in the presence and absence of ligand. In the absence of ligand mAb H22 and wH22xeGFP, an enhanced green fluorescent protein (eGFP)-labeled fusion protein of H22, cross-linked and rapidly down-modulated surface FcgammaRI on the human myeloid cell line, U937, and its high FcgammaRI-expressing subclone, 10.6. This effect was dependent on the concentration of fusion protein and the level of FcgammaRI expression and correlated with internalization of both wH22xeGFP and FcgammaRI, itself, as assessed by confocal microscopy. A single-chain Fv version, sFv22xeGFP, which does not cross-link FcgammaRI, was unable to modulate FcgammaRI in the absence of IgG. However, if ligand was present, treatment with either monovalent or cross-linking fusion protein led to intracellular receptor accumulation. These findings suggest at least two alternate mechanisms of internalization that are influenced by ligand and demonstrate the physiologic potential of FcgammaRI to transport a large antigenic load into APCs for processing. These studies may lead to the development of better FcgammaRI-targeted vaccines, as well as therapies to down-modulate FcR involved in autoimmune diseases.
Theory of Dielectric Optical Waveguides (1974)

The asymmetric slab waveguide weakly guiding optical fibers coupled mode theory applications of the coupled mode theory coupled power theory theory of the directional coupler grating-assisted direction couplers approximate and numerical methods nonlinear effects.
Structural Phosphoprotein M2-1 of the Human Respiratory Syncytial Virus Is an RNA Binding Protein (2000)

The structural phosphoprotein M2-1 of human respiratory syncytial virus (HRSV) Long strain shows RNA binding capacity in three different assays that detect RNA-protein complexes: cross-linking, gel retardation, and Northern-Western assays. It is able to bind HRSV leader RNA specifically with cooperative kinetics, with an apparent K(d) of at least 90 nM. It also binds to long RNAs with no sequence specificity. The RNA binding domain has been located between amino acid residues 59 and 85, at the NH(2) terminus of the protein. This region contains the phosphorylatable amino acid residues threonine 56 and serine 58, whose modification decreases the binding capacity of M2-1 protein to long RNAs.
MicroRNA-like off-target transcript regulation by siRNAs is species specific (2009)

siRNAs mediate sequence-specific gene silencing in cultured mammalian cells but also silence unintended transcripts. Many siRNA off-target transcripts match the guide-strand "seed region," similar to the way microRNAs match their target sites. The extent to which this seed-matched, microRNA-like, off-target silencing affects the specificity of therapeutic siRNAs in vivo is currently unknown. Here, we compare microRNA-like off-target regulations in mouse liver in vivo with those seen in cell culture for a series of therapeutic candidate siRNAs targeting Apolipoprotein B (APOB). Each siRNA triggered regulation of consistent microRNA-like off-target transcripts in mouse livers and in cultured mouse liver tumor cells. In contrast, there was only random overlap between microRNA-like off-target transcripts from cultured human and mouse liver tumor cells. Therefore, siRNA therapeutics may trigger microRNA-like silencing of many unintended targets in vivo, and the potential toxicities caused by these off-target gene regulations cannot be accurately assessed in rodent models.
Piezoelectric properties in perovskite 0.948(K0.5Na0.5)NbO3–0.052LiSbO3 lead-free ceramics (2006)

Lead-free piezoelectric ceramics, with the nominal composition of 0.948(K0.5Na0.5)NbO3–0.052LiSbO3 (KNN-LS5.2), were synthesized by conventional solid-state sintering, and the piezoelectric and electromechanical properties were characterized as a function of temperature. The Curie temperature of the KNN based perovskite material was found to be 368°C with an orthorhombic-tetragonal polymorphic phase transition (TO-T) temperature at approximately ∼35°C. The room temperature dielectric permittivity (ε33T∕ε0) and loss were found to be 1380 and 2%, respectively, with piezoelectric properties of k33∼62% and d33∼265pC∕N and k31∼30% and d31∼−116pC∕N. The temperature dependence of the properties mimicked the compositional variation seen in the proximity of a morphotropic phase boundary [e.g., lead zirconate titanate (PZT)], with a maxima in the dielectric and piezoelectric properties and a corresponding “softening” of the elastic properties. Unlike that found for PZT-type materials, the modified KNN material exhibited characteristics of both “soft” and “hard” piezoelectricities owing to the distinctly different domain states associated with orthorhombic and tetragonal phases.
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of an Orally Active Novel Camptothecin Analog, DRF‐1042, in Refractory Cancer Patients in a Phase I Dose Escalation Study (2004)

The objective of this study was to characterize the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetics, and antitumor effects of DRF-1042, a novel camptothecin analog, in refractory solid tumor patients. DRF-1042 was given for 5 consecutive days for 2 weeks, repeated every 3 weeks at 1.5 to 270 mg/m(2). Adverse events were monitored following NCI-CTC. Pharmacokinetics of lactone and total forms were determined using validated high-performance liquid chromatography (HPLC) and noncompartmental methods. Efficacy was evaluated applying World Health Organization (WHO) criteria. The 1st course was used to determine DLT and MTD. Twenty-five patients received 73 courses of therapy. Myelosuppression and diarrhea were DLTs. MTD was 120 mg/m(2)/day. AUC increased approximately linearly with dose. The t(1/2) for lactone and total forms was 9.9 and 29 hours, respectively. AUCs correlated significantly with nadir leucopenia and grade 4 diarrhea. Two complete responses (CRs) and 2 partial responses (PRs) were observed. In addition, 4 stable diseases were observed. The recommended phase II dose is 80 mg/m(2)/day.
Synthesis of 5,6‐dihydro‐8‐methoxy‐4H‐imidazo[4,5,1‐ij]quinolines and some related ring systems (1968)

Abstract Reduction of amides of 8‐amino‐6‐methoxyquinoline over platinum oxide in glacial acetic acid at room temperature affords 2‐substituted‐5,6‐dihydro‐8‐methoxy‐4 H ‐imidazo [4,5,1‐ ij ]‐quinolines (I). The method could not be utilized for urea or carbamate derivatives of 8‐amino‐6‐methoxyquinoline. 2‐Amino derivatives of I were prepared through the chloro compound obtained from 5,6‐dihydro‐8‐methoxy‐4 H ‐imidazo[4,5,1‐ ij ]quinolin‐2(1 H )‐one, (IV). Several related ring systems have also been prepared.
Tomographic optical breast imaging guided by three-dimensional mammography (2003)

We introduce a modified Tikhonov regularization method to include three-dimensional x-ray mammography as a prior in the diffuse optical tomography reconstruction. With simulations we show that the optical image reconstruction resolution and contrast are improved by implementing this x-ray-guided spatial constraint. We suggest an approach to find the optimal regularization parameters. The presented preliminary clinical result indicates the utility of the method.
Pretreatment With Citrulline Improves Gut Barrier After Intestinal Obstruction in Mice (2011)

Pretreatment with citrulline was able to preserve barrier integrity and also modulated the immune response that might have affected BT decrease.
SNPs by AFLP (SBA): a rapid SNP isolation strategy for non-model organisms (2003)

Despite the great potential of single nucleotide polymorphism (SNP) markers in evolutionary studies, in particular for inferring population genetic parameters, SNP analysis has almost exclusively been limited to humans and 'genomic model' organisms, due to the lack of available sequence data in non-model organisms. Here, we describe a rapid and cost effective method to isolate candidate SNPs in non-model organisms. This SNP isolation strategy consists basically in the direct sequencing of amplified fragment length polymorphism bands. In a first application of this method, 10 unique DNA fragments that contained 24 SNPs were discovered in 11.11 kb of sequenced genomic DNA of a non-model species, the brown trout (Salmo trutta).