gebhart/patrepeval huggingface dataset:
Detection and Characterisation of Transforming Growth Factor-Beta in Porcine Colostrum (1998)

Porcine colostrum and milk collected at different stages of lactation were assessed for transforming growth factor-beta (TGF-beta) activity using an epithelial cell bio-assay. A high level of TGF-beta activity was recorded in all colostrum samples after transient acidification treatment, ranging between 126 and 260 ng/ml for samples collected at the time of parturition and 73 ng/ml for the sample collected 12 h after parturition. Without transient acidification treatment TGF-beta activity was detected only in 2 samples collected at the time of parturition (12 ng/ml) and 12 h after parturition (9 ng/ml), respectively. TGF-beta activity was undetectable in milk collected 5 days after parturition. These results suggest that TGF-beta exists mainly in latent form in porcine colostrum and the concentration declines rapidly as lactation proceeds. After enrichment with cation exchange chromatography a low level of TGF-beta activity was detected in porcine milk. Further separation by size exclusion chromatography revealed two molecular mass forms of TGF-beta in both colostrum and milk samples, a major peak of about 80 kD and a minor peak of about 25 kD representing latent and active forms of TGF-beta, respectively. A further experiment showed that the latent form of TGF-beta in colostrum can be activated at pH 3.5 or less. It is speculated that TGF-beta found in the colostrum may play a physiological role in regulating postnatal adaptation of the gastro-intestinal tract in newborns.
JAK2, Ras, and Raf Are Required for Activation of Extracellular Signal-regulated Kinase/Mitogen-activated Protein Kinase by Growth Hormone (1995)

Protein-tyrosine kinases (PTKs) of the JAK family have been characterized on the basis of their ability to mediate the rapid induction of transcription of interferon-responsive genes through the stimulation of a class of latent cytoplasmic transcription factors known as signal transducers and activators of transcription (STATs). STAT activation, which has been described as being Ras-independent, requires tyrosine phosphorylation, but STAT transactivating activity is enhanced by phosphorylation on serine as well, probably by extracellular signal-regulated kinase/mitogen-activated protein kinase(s) (ERK/MAPK). STATs can be activated upon binding of ligands to receptor PTKs, to G-protein-linked receptors, and to cytokine receptors. Whether JAKs are required for the activation of signaling pathways other than that leading to STAT activation is not known. The binding of growth hormone (GH) to its receptor (GHR) activates JAK2 and STATs as well as ERK/MAP kinases. We have used a transient transfection system in 293 cells to evaluate the requirement for JAK2 in the activation of ERK2/MAPK by GH. We found that JAK2 is required for GH-simulated activation of ERK2/MAPK. Employing the transient expression of dominant negative forms of H-Ras and Raf-1, we determined that the GHR/JAK2-mediated activation of ERK2/MAPK is dependent on both Ras and Raf. Thus, JAK protein-tyrosine kinases may represent a common component in the activation of the ERK2/MAPK and STAT signaling pathways, which appear to bifurcate upstream of Ras activation but converge with ERK/MAPK phosphorylation of STATs.
Abuse Liability Of Intravenous Lisdexamfetamine Dimesylate [LDX; NRP104] (2006)

s: Abstracts of Papers Accepted for Presentation at the Annual Meeting of the Society for Developmental and Behavioral Pediatrics: Poster Session, Sunday, September 17, 2006, 6: 00 p.m. - 7: 00 p.m.: Abstract # 45
Paclitaxel synergizes with exposure time adjusted CD22-targeting immunotoxins against B-cell malignancies (2017)

CD22-targeted recombinant immunotoxins (rIT) are active in hairy cell leukemia or acute lymphoblastic leukemia (ALL), but not in mantle cell lymphoma (MCL) patients. The goal was to enhance rIT efficacy in vivo and to define a strong combination treatment. Activity of Moxetumomab pasudotox (Moxe) and LR combined with paclitaxel was tested against MCL cell lines in vitro and as bolus doses or continuous infusion in xenograft models. In the KOPN-8 ALL xenograft, Moxe or paclitaxel alone was active, but all mice died from leukemia; when combined, 60% of the mice achieved a sustained complete remission. Against MCL cells in vitro, LR was more active than Moxe and the cells had to be exposed to rIT for more than 24 hours for them to die. To maintain high blood levels in vivo, LR was administered continuously by 7-day pumps achieving a well-tolerated steady plasma concentration of 45 ng/ml. In JeKo-1 xenografts, continuously administered LR was 14-fold more active than bolus doses and the combination with paclitaxel additionally improved responses by 135-fold. Maintaining high rIT-plasma levels greatly improves responses in the JeKo-1 model and paclitaxel substantially enhances bolus and continuously infused rIT, supporting a clinical evaluation against B-cell malignancies.
Correcting temperature-sensitive protein folding defects. (1997)

Recently, we found that different low molecular weight compounds, all known to stabilize proteins in their native conformation, are effective in correcting the temperature-sensitive protein folding defect associated with the deltaF508 cystic fibrosis transmembrane regulator (CFTR) protein. Here we examined whether the folding of other proteins which exhibit temperature-sensitive folding defects also could be corrected via a similar strategy. Cell lines expressing temperature-sensitive mutants of the tumor suppressor protein p53, the viral oncogene protein pp60src, or a ubiquitin activating enzyme E1, were incubated at the nonpermissive temperature (39.5 degrees C) in the presence of glycerol, trimethylamine N-oxide or deuterated water. In each case, the cells exhibited phenotypes similar to those observed when the cells were incubated at the permissive temperature (32.5 degrees C), indicative that the particular protein folding defect had been corrected. These observations, coupled with our earlier work and much older studies in yeast and bacteria, indicate that protein stabilizing agents are effective in vivo for correcting protein folding abnormalities. We suggest that this type of approach may prove to be useful for correcting certain protein folding abnormalities associated with human diseases.
Dose‐range and dose‐frequency study of recombinant human interleukin‐1 receptor antagonist in patients with rheumatoid arthritis (1996)

These preliminary data suggest that rHuIL-1Ra may be safely administered by subcutaneous injection to RA patients. The frequency of dosing appears to be important in determining clinical response, with daily administration providing the most benefit. A placebo-controlled trial is in progress to further assess the clinical usefulness and to better define appropriate doses of rHuIL-1Ra in patients with RA.
cAMP- but not Ca(2+)-regulated Cl- conductance in the oviduct is defective in mouse model of cystic fibrosis (1995)

Defective adenosine 3',5'-cyclic monophosphate (cAMP)-mediated Cl- transport in cystic fibrosis (CF) reflects defects in the cystic fibrosis transmembrane conductance regulator (CFTR). A moderate level of CFTR mRNA expression has been found in rodent and human oviductal epithelium, but unlike other CFTR-expressing tissues, the oviduct in CF patients is apparently normal. The present study was carried out to investigate the relative magnitude of the cAMP- and intracellular Ca2+ (Cai2+)-regulated Cl- secretion in primary cultures of the oviduct from normal and CF mice generated by targeted disruption of the murine CF gene. Normal oviductal epithelium exhibited a basal equivalent short-circuit current (Ieq) of 20.3 +/- 1.7 muA/cm2. CF oviduct exhibited a lower basal Ieq of 4.5 +/- 1.9 muA/cm2. In normal mice, forskolin (10(-5) M, apical) elicited a slowly developing sustained rise in Ieq, whereas ionomycin (5 x 10(-6) M, apical) and ATP (10(-4) M, apical) induced larger increases in Ieq consisting of a prompt, transient response followed by a slowly decreasing component. The Ieq response to forskolin was totally abolished in CF mouse oviducts, but the magnitudes of the peak Ieq responses to ionomycin and ATP were not different from normal. The time courses of the ionomycin- and ATP-evoked responses, however, were significantly more transient in CF than in normal oviducts. These results demonstrate that CF mouse oviduct exhibits defective cAMP- but not Cai(2+)-mediated Cl- secretion. The relatively high level of functional expression of the alternative Cai(2+)-activated Cl- secretory pathway in the mouse oviduct may contribute to the absence of major pathology in the CF oviduct.
Spontaneous hemolytic uremic syndrome triggered by complement factor H lacking surface recognition domains (2007)

Factor H (FH) is an abundant serum glycoprotein that regulates the alternative pathway of complement-preventing uncontrolled plasma C3 activation and nonspecific damage to host tissues. Age-related macular degeneration (AMD), atypical hemolytic uremic syndrome (aHUS), and membranoproliferative glomerulonephritis type II (MPGN2) are associated with polymorphisms or mutations in the FH gene (Cfh), suggesting the existence of a genotype-phenotype relationship. Although AMD and MPGN2 share pathological similarities with the accumulation of complement-containing debris within the eye and kidney, respectively, aHUS is characterized by renal endothelial injury. This pathological distinction was reflected in our Cfh association analysis, which demonstrated that although AMD and MPGN2 share a Cfh at-risk haplotype, the haplotype for aHUS was unique. FH-deficient mice have uncontrolled plasma C3 activation and spontaneously develop MPGN2 but not aHUS. We show that these mice, transgenically expressing a mouse FH protein functionally equivalent to aHUS-associated human FH mutants, regulate C3 activation in plasma and spontaneously develop aHUS but not MPGN2. These animals represent the first model of aHUS and provide in vivo evidence that effective plasma C3 regulation and the defective control of complement activation on renal endothelium are the critical events in the molecular pathogenesis of FH-associated aHUS.
Color pixels classification in an hybrid color space (2002)

We describe a new approach for color image segmentation which is considered as a problem of pixels classification. The algorithm is applied to classify pixels of soccer color images in order to recognize the team of players. The color pixels classification algorithm is achieved in a new color space, the hybrid color space, which is determined thanks to a supervised learning scheme. This space is defined by the set of the three most discriminating color features selected among a set of classical color features.
Fiber gratings in lasers and amplifiers (1997)

The emergence of UV-written fiber gratings, both short and long period, as a reliable fiber technology has revolutionized the field of active fiber devices. The advantageous properties of spectral selectivity, low insertion loss, and component ruggedness have made devices possible that would not be viable without their use. The use of fiber gratings in conjunction with erbium-doped fiber amplifiers (EDFAs), fiber lasers, and with semiconductor diode lasers is reviewed.
Nucleophilic 18F-Fluorination of Heteroaromatic Iodonium Salts with No-Carrier-Added [18F]Fluoride (2007)

Diaryliodonium salts containing the 2-thienyl group as an example of an electron-rich heteroaromatic moiety proved to be very potent precursors for the nucleophilic, regioselective no-carrier-added (nca) radiofluorination of various arenes. It even allowed the nucleophilic introduction of nca [18F]fluoride into electron-rich arene compounds in one step. The influences of the substitution pattern, of counteranions, and of different reaction conditions were studied. Effects of counterions could be explained by the influence of solvent on ion pair separation of precursor salts. Different aryl(2-thienyl)iodonium salts were used as precursors, where the homoaromatic group systematically varied from bearing electron-deficient to electron-rich substituents. Relative rates of exchange kinetics correlated linearly with Hammett constants of the appropriate substituents confirming a nucleophilic aromatic substitution reaction of high reactivity and low selectivity.
ACS Chemical Neuroscience Molecule Spotlight on Telcagepant (MK-0974) (2011)

Telcagepant (MK-0974) is a novel calcitonin gene-related peptide (CGRP) receptor antagonist currently undergoing clinical trials for migraine (http://www.merck.com/research/pipeline/home.html). MK-0974 is currently being studied in phase III clinical trials.
Decision tree-based triphones are robust and practical for mandarian speech recognition (1999)

In this paper, we describe The Attribute Logic Engine (ALE) and enhancements to it that enable it to serve as a complete grammatical infrastructure for applications such as spoken language translation. We indicate how ALE was expanded and combined with off-the-shelf speech components to develop an application that translates English speech to German speech. The translation operates by way of a semantic representation based on typed feature structures, with information on thematic roles (“who did what to whom”) and agreement information that can be used to guide search in less restricted domains and map expressions to more felicitous (but semantically equivalent) constructions in the target language than a more literal, surface-oriented method would admit.
Amino acid variations at a single residue in an autoimmune peptide profoundly affect its properties: T-cell activation, major histocompatibility complex binding, and ability to block experimental allergic encephalomyelitis. (1991)

Myelin basic protein (MBP) or helper T cells reactive against MBP induce an autoimmune disease, experimental allergic encephalomyelitis, in B10.PL and PL/J inbred mice. In both strains, virtually the entire repertoire of MBP-specific T cells recognize an N-terminal peptide fragment in the context of the I-Au molecule encoded by the major histocompatibility complex (MHC) and utilize a very limited set of T-cell receptor genes. To delineate the nature of the trimolecular complex, consisting of the T-cell receptor, MBP-peptide fragment, and MHC molecule (I-Au), we have synthesized 13 variants of the 9-mer N-terminal immunodominant peptide differing at residue 4 and studied their immune recognition in vitro and in vivo. These substitutions have a striking range of effects on T-cell activation, ability to bind to the MHC molecule, and initiation of immune responses in vivo. An understanding of the autoimmune peptide/MHC/T-cell receptor interactions allowed us to design variant 9-mer peptides that have high affinity for an MHC molecule and are effective in blocking experimental allergic encephalomyelitis, possibly through two distinct mechanisms, peripheral T-cell tolerance and the inhibition of binding of the encephalitogenic peptide to the MHC molecules.
Communications: Telephone nets go digital: Digital communication links promise flexible, economical telephone services for both home and office (1983)

Digital communication links promise flexible, economical telephone services for both home and office. As integrated-services digital networks (ISDNs) are implemented during the 1980s and 1990s, any telephone user will be able, for a fee, to access such digital services as facsimile transmission, teleconferencing, and eventually even video conferencing. The bandwidths available to residential users will begin to increase in the next few years from the present few kilobits per second to 80 to 144 kb/s. Businesses will have access to digital communications that are much more flexible and economical than those available today. Already some limited steps towards ISDNs have been taken, and a number of digital services will be available in the next few years. Ultimately the new network will encompass most telecommunications, supplanting current analog networks.
A Novel Alternatively Spliced Fibroblast Growth Factor Receptor 3 Isoform Lacking the Acid Box Domain Is Expressed during Chondrogenic Differentiation of ATDC5 Cells (2001)

To determine the role of fibroblast growth factor (FGF).FGF receptor (FGFR) signaling in chondrogenesis, we analyzed the gene expression of alternatively spliced FGFRs during chondrogenic differentiation of ATDC5 cells in vitro. Two isoforms of FGFR3 were expressed in these cells. One was the complete form of FGFR3 (FGFR3) already reported, and the other was a novel one that lacks the acid box domain (FGFR3DeltaAB). The gene of FGFR3DeltaAB was expressed in undifferentiated ATDC5 cells. In contrast, the transcripts of FGFR3 were not detectable in undifferentiated cells but increased during cellular condensation, which is an obligatory step for chondrogenic differentiation. FGFR1 and FGFR2 expression was higher than that of FGFR3 in undifferentiated cells. The gene expression of cell cycle inhibitor p21 was induced during cell condensation and correlated best with the expression of FGFR3 among the FGFR isoforms expressed. The differential expression of FGFR3 isoforms during chondrogenesis suggests that these isoforms may play different roles in the regulation of growth and differentiation in chondrocytes. To define the mitogenic response of FGFR3DeltaAB and FGFR3 to FGFs, their cDNAs were stably transfected into mouse BaF3 pro-B cells. FGFR3 preferentially mediates the mitogenic response to FGF1 and poor response to FGF2. In contrast, FGFR3DeltaAB mediated a higher mitogenic response to FGF2 as well as to FGF1. In addition, FGFR3DeltaAB responds to FGF1 at lower concentrations of heparin than FGFR3 does. These results suggest that the acid box plays an important role in the regulation of FGFR3 to mediate biological activities in response to FGFs.
Induced Pluripotent Stem Cells for Regenerative Medicine (2014)

With the discovery of induced pluripotent stem (iPS) cells, it is now possible to convert differentiated somatic cells into multipotent stem cells that have the capacity to generate all cell types of adult tissues. Thus, there is a wide variety of applications for this technology, including regenerative medicine, in vitro disease modeling, and drug screening/discovery. Although biological and biochemical techniques have been well established for cell reprogramming, bioengineering technologies offer novel tools for the reprogramming, expansion, isolation, and differentiation of iPS cells. In this article, we review these bioengineering approaches for the derivation and manipulation of iPS cells and focus on their relevance to regenerative medicine.
cAMP receptor protein–cAMP plays a crucial role in glucose–lactose diauxie by activating the major glucose transporter gene in Escherichia coli (1997)

The inhibition of beta-galactosidase expression in a medium containing both glucose and lactose is a typical example of the glucose effect in Escherichia coli. We studied the glucose effect in the lacL8UV5 promoter mutant, which is independent of cAMP and cAMP receptor protein (CRP). A strong inhibition of beta-galactosidase expression by glucose and a diauxic growth were observed when the lacL8UV5 cells were grown on a glucose-lactose medium. The addition of isopropyl beta-D-thiogalactoside to the culture medium eliminated the glucose effect. Disruption of the crr gene or overproduction of LacY also eliminated the glucose effect. These results are fully consistent with our previous finding that the glucose effect in wild-type cells growing in a glucose-lactose medium is not due to the reduction of CRP-cAMP levels but is due to the inducer exclusion. We found that the glucose effect in the lacL8UV5 cells was no longer observed when either the crp or the cya gene was disrupted. Evidence suggested that CRP-cAMP may not enhance directly the lac repressor action in vivo. Northern blot analysis revealed that the mRNA for ptsG, a major glucose transporter gene, was markedly reduced in a delta crp or delta cya background. The constitutive expression of the ptsG gene by the introduction of a multicopy plasmid restored the glucose effect in delta cya or delta crp cells. We conclude that CRP-cAMP plays a crucial role in inducer exclusion, which is responsible for the glucose-lactose diauxie, by activating the expression of the ptsG gene.
Neocortical Transplants in the Mammalian Brain Lack a Blood-Brain Barrier to Macromolecules (1987)

In order to determine whether the blood-brain barrier was present in transplants of central nervous tissue, fetal neocortex, which already possesses blood-brain and blood-cerebrospinal fluid barriers to protein, was grafted into the undamaged fourth ventricle or directly into the neocortex of recipient rats. Horseradish peroxidase or a conjugated human immunoglobulin G-peroxidase molecule was systemically administered into the host. These proteins were detected within the cortical transplants within 2 minutes regardless of the age of the donor or postoperative time. At later times these compounds, which normally do not cross the blood-brain barrier, inundated the grafts and adjacent host brain and also entered the cerebrospinal fluid. Endogenous serum albumin detected immunocytochemically in untreated hosts had a comparable although less extensive distribution. Thus, transplants of fetal central nervous tissue have permanent barrier dysfunction, probably due to microvascular changes, and are not integrated physiologically within the host. Blood-borne compounds, either systemically administered or naturally occurring, which should never contact normal brain tissue, have direct access to these transplants and might affect neuronal function.
T-bet negatively regulates autoimmune myocarditis by suppressing local production of interleukin 17 (2006)

Experimental autoimmune myocarditis (EAM) appears after infectious heart disease, the most common cause of dilated cardiomyopathy in humans. Here we report that mice lacking T-bet, a T-box transcription factor required for T helper (Th)1 cell differentiation and interferon (IFN)-gamma production, develop severe autoimmune heart disease compared to T-bet+/+ control mice. Experiments in T-bet-/- IL-4-/- and T-bet-/- IL-4Ralpha-/- mice, as well as transfer of heart-specific Th1 and Th2 cell lines, showed that autoimmune heart disease develops independently of Th1 or Th2 polarization. Analysis of T-bet-/- IL-12Rbeta1-/- and T-bet-/- IL-12p35-/- mice then identified interleukin (IL)-23 as critical for EAM pathogenesis. In addition, T-bet-/- mice showed a marked increase in production of the IL-23-dependent cytokine IL-17 by heart-infiltrating lymphocytes, and in vivo IL-17 depletion markedly reduced EAM severity in T-bet-/- mice. Heart-infiltrating T-bet-/- CD8+ but not CD8- T cells secrete IFN-gamma, which inhibits IL-17 production and protects against severe EAM. In contrast, T-bet-/- CD8+ lymphocytes completely lost their capacity to release IFN-gamma within the heart. Collectively, these data show that severe IL-17-mediated EAM can develop in the absence of T-bet, and that T-bet can regulate autoimmunity via the control of nonspecific CD8+ T cell bystander functions in the inflamed target organ.