gebhart/patrepeval huggingface dataset:
TGFβ/BMP activate the smooth muscle/bone differentiation programs in mesoangioblasts (2004)

Mesoangioblasts are vessel-derived stem cells that can be induced to differentiate into different cell types of the mesoderm such as muscle and bone. The gene expression profile of four clonal derived lines of mesoangioblasts was determined by DNA micro-array analysis: it was similar in the four lines but different from 10T1/2 embryonic fibroblasts, used as comparison. Many known genes expressed by mesoangioblasts belong to response pathways to developmental signalling molecules, such as Wnt or TGFbeta/BMP. Interestingly, mesoangioblasts express receptors of the TGFbeta/BMP family and several Smads and, accordingly, differentiate very efficiently into smooth muscle cells in response to TGFbeta and into osteoblasts in response to BMP. In addition, insulin signalling promotes adipogenic differentiation, possibly through the activation of IGF-R. Several Wnts and Frizzled, Dishevelled and Tcfs are expressed, suggesting the existence of an autocrine loop for proliferation and indeed, forced expression of Frzb-1 inhibits cell division. Mesoangioblasts also express many neuro-ectodermal genes and yet undergo only abortive neurogenesis, even after forced expression of neurogenin 1 or 2, MASH or NeuroD. Finally, mesoangioblasts express several pro-inflammatory genes, cytokines and cytokine receptors, which may explain their ability to be recruited by tissue inflammation. Our data define a unique phenotype for mesoangioblasts, explain several of their biological features and set the basis for future functional studies on the role of these cells in tissue histogenesis and repair.
Normal Frequency and Excitation Statistics in Rooms: Model Experiments with Electric Waves (1987)

Etude experimentale de la reponse d'une salle a l'aide d'un modele analogique hyperfrequence
Characterization of novel reverse transcriptase encoding human endogenous retroviral sequences similar to type A and type B retroviruses: differential transcription in normal human tissues (1993)

The polymerase chain reaction was used to amplify genomic DNA and reverse-transcribed RNA from human lymphocytes, using primers derived from conserved regions within the retroviral reverse transcriptase. Sequencing of 33 cloned amplification products revealed that a variety of sequences with similarity to mouse mammary tumor virus, mouse intracisternal A particle, and human endogenous retrovirus K10 were detected with this primer pair. The sequences were divided into six subgroups, with a nucleotide sequence dissimilarity of about 25% between the subgroups. Members within five of the subgroups were most closely related to human endogenous retrovirus K10 and mouse mammary tumor virus, whereas sequences of the sixth subgroup also showed similarity to mouse intracisternal A particle. Ten of the sequences had open reading frames with preference for silent mutations at conserved sites. Southern blot analysis showed that some HML (human endogenous MMTV-like) subgroups (HML-4 and HML-5) were present in a few copies (about 5), whereas others (HML-1 to HML-3 and HML-6) were present in at least 10 to 20 copies per genome. Northern (RNA) blot analysis revealed that several of the subgroups are differentially expressed in human normal tissues. A complex pattern of transcripts from about 12 to 1.4 kb was found in several of the tissues tested. However, the most abundant expression was detected in lung (all subgroups), skeletal muscle (HML-4 and HML-5), placenta (HML-2 and HML-5), and kidney (HML-2, HML-3 and HML-5). Expression of reverse transcriptase sequences in human tissues may have biological consequences. The described sequences are similar to elements which cause carcinoma and are immunoregulatory in mice. It remains to be seen whether human sequences also have such functions.
Role of alpha 4-integrins in lymphocyte homing to mucosal tissues in vivo. (1994)

Lymphocyte recirculation through different organs is thought to be regulated by adhesion molecules ("homing receptors") recognizing tissue-specific vascular addressins on endothelium. Here we show that the alpha 4/beta 7-integrin has a key role in the migration of mouse lymphocytes to mucosal sites. Homing to Peyer's patches but not to peripheral lymph nodes is inhibited by Fab fragments of mAb PS/2 against the alpha 4-integrin chain, by mAb DATK32 recognizing a combinatorial epitope on the alpha 4/beta 7-integrin, and by mAb FIB30 against the beta 7-chain. The Abs significantly reduce homing of lymphocytes to the intestine, as well. The migration of immunoblasts to gut and gut-associated lymphoid tissue also involves the alpha 4/beta 7-integrin heterodimer. Another anti-alpha 4 Ab, R1-2, which blocks lymphocyte binding to Peyer's patches in the Stamper-Woodruff frozen section assay and lymphocyte adhesion to VCAM-1 and fibronectin, has only minor effects on lymphocyte traffic in vivo. Anti-VCAM-1 Ab as well as the fibronectin peptide CS-1 are without influence on the migration to Peyer's patches or intestine, in contrast to Ab against the mucosal addressin MAdCAM-1. Thus, homing to gut-associated sites is regulated by the alpha 4/beta 7-integrin heterodimer interacting with the vascular addressin, MAdCAM-1, and not with fibronectin or VCAM-1 as counterstructures. Inhibition of homing to Peyer's patches and intestine by the anti-integrin Abs studied was only partial. L-selectin also participates in the homing of small lymphocytes to mucosal sites, especially Peyer's patches, but does not contribute substantially to the localization of blasts into the intestinal wall. The results support a major, but not exclusive role of the alpha 4/beta 7-integrin in lymphocyte traffic to mucosal sites.
Characterizations of Collagen Fibers for Biodegradable Films Production (2006)

Elaboration of films containing fibers of crude, insoluble, collagen is intended to be investigated, since collagen partial insolubility and fibrous structure could result in films with improved mechanical properties. The purpose of this work was to determine some chemical and physical-chemical characteristics of collagen fibers obtained from bovine hide. The material showed a high protein content of about 86%, and only moderate solubility at low pH. Protein denaturation was observed when collagen fibers dispersed in water were heated above 50 o C. Denaturation temperature decreased with acidification of the dispersion, indicating lower thermal stability of the protein at low pH.
3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV–infected mice (2020)

Pathogenic coronaviruses are a major threat to global public health, as exemplified by severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and the newly emerged SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). We describe herein the structure-guided optimization of a series of inhibitors of the coronavirus 3C-like protease (3CLpro), an enzyme essential for viral replication. The optimized compounds were effective against several human coronaviruses including MERS-CoV, SARS-CoV, and SARS-CoV-2 in an enzyme assay and in cell-based assays using Huh-7 and Vero E6 cell lines. Two selected compounds showed antiviral effects against SARS-CoV-2 in cultured primary human airway epithelial cells. In a mouse model of MERS-CoV infection, administration of a lead compound 1 day after virus infection increased survival from 0 to 100% and reduced lung viral titers and lung histopathology. These results suggest that this series of compounds has the potential to be developed further as antiviral drugs against human coronaviruses.
Finding similar questions in large question and answer archives (2005)

There has recently been a significant increase in the number of community-based question and answer services on the Web where people answer other peoples' questions. These services rapidly build up large archives of questions and answers, and these archives are a valuable linguistic resource. One of the major tasks in a question and answer service is to find questions in the archive that a semantically similar to a user's question. This enables high quality answers from the archive to be retrieved and removes the time lag associated with a community-based system. In this paper, we discuss methods for question retrieval that are based on using the similarity between answers in the archive to estimate probabilities for a translation-based retrieval model. We show that with this model it is possible to find semantically similar questions with relatively little word overlap.
Dyskinesias after neural transplantation in Parkinson's disease: what do we know and what is next? (2010)

Since the 1980 s, when cell transplantation into the brain as a cure for Parkinson's disease hit the headlines, several patients with Parkinson's disease have received transplantation of cells from aborted fetuses with the aim of replacing the dopamine cells destroyed by the disease. The results in human studies were unpredictable and raised controversy. Some patients showed remarkable improvement, but many of the patients who underwent transplantation experienced serious disabling adverse reactions, putting an end to human trials since the late 1990 s. These side effects consisted of patients' developing troublesome involuntary, uncontrolled movements in the absence of dopaminergic medication, so-called off-phase, graft-induced dyskinesias. Notwithstanding the several mechanisms having been proposed, the pathogenesis of this type of dyskinesias remained unclear and there was no effective treatment. It has been suggested that graft-induced dyskinesias could be related to fiber outgrowth from the graft causing increased dopamine release, that could be related to the failure of grafts to restore a precise distribution of dopaminergic synaptic contacts on host neurons or may also be induced by inflammatory and immune responses around the graft. A recent study, however, hypothesized that an important factor for the development of graft-induced dyskinesias could include the composition of the cell suspension and specifically that a high proportion of serotonergic neurons cografted in these transplants engage in nonphysiological properties such as false transmitter release. The findings from this study showed serotonergic hyperinnervation in the grafted striatum of two patients with Parkinson's disease who exhibited major motor recovery after transplantation with fetal mesencephalic tissue but later developed graft-induced dyskinesias. Moreover, the dyskinesias were significantly attenuated by administration of a serotonin agonist, which activates the inhibitory serotonin autoreceptors and attenuates transmitter release from serotonergic neurons, indicating that graft-induced dyskinesias were caused by the dense serotonergic innervation engaging in false transmitter release. Here the implications of the recent findings for the development of new human trials testing the safety and efficacy of cell transplantation in patients with Parkinson's disease are discussed.
The Ulip family phosphoproteins (1998)

The search for intracellular phosphoproteins implicated in the regulation of neuronal differentiation led to the identification of Ulip1, a mammalian protein related to the Caenorhabditis elegans unc-33 gene product [Byk, T., Dobransky, T., Cifuentes-Diaz, C. & Sobel, A. (1996) J. Neurosc. 16, 688-701]. The expression level and phosphorylation pattern of Ulip1 were shown to be strongly regulated during development and neuronal differentiation. We have isolated three additional complete coding sequences for members of the Ulip family in the mouse, Ulips 2-4, all preferentially expressed in the nervous system. Furthermore, two Ulip sequences, Ulips A and Ulips B, could be identified in C. elegans. The Ulip family is highly conserved throughout evolution (more than 96 % for Ulips 1-3 and 92.5 % for Ulip4 between mouse and human) and the various members of the family within a single species display about 75% similarity. Sequence comparisons further reveal several highly similar domains and subdomains, including a 32-amino-acid region highly conserved from a bacterial hydantoinase to human Ulips. Two-dimensional immunoblot analysis of in vitro translated Ulips 1-4 demonstrates the existence, for each Ulip protein, of several, most probably differentially phosphorylated forms, in agreement with the presence of conserved phosphorylation consensus sites within their sequences. The expression of Ulips 1-4 mRNAs is differentially regulated during development and nerve-growth-factor-induced neuronal differentiation of PC12 cells. Our results indicate a differential, possibly complementary role of phosphoproteins of the highly conserved Ulip family in the control of neuronal differentiation, in relation with the development and plasticity of the nervous system.
In Vitro Selection of Highly Modified Cyclic Peptides That Act as Tight Binding Inhibitors (2012)

There is a great demand for the discovery of new therapeutic molecules that combine the high specificity and affinity of biologic drugs with the bioavailability and lower cost of small molecules. Small, natural-product-like peptides hold great promise in bridging this gap; however, access to libraries of these compounds has been a limitation. Since ribosomal peptides may be subjected to in vitro selection techniques, the generation of extremely large libraries (>10(13)) of highly modified macrocyclic peptides may provide a powerful alternative for the generation and selection of new useful bioactive molecules. Moreover, the incorporation of many non-proteinogenic amino acids into ribosomal peptides in conjunction with macrocyclization should enhance the drug-like features of these libraries. Here we show that mRNA-display, a technique that allows the in vitro selection of peptides, can be applied to the evolution of macrocyclic peptides that contain a majority of unnatural amino acids. We describe the isolation and characterization of two such unnatural cyclic peptides that bind the protease thrombin with low nanomolar affinity, and we show that the unnatural residues in these peptides are essential for the observed high-affinity binding. We demonstrate that the selected peptides are tight-binding inhibitors of thrombin, with K(i)(app) values in the low nanomolar range. The ability to evolve highly modified macrocyclic peptides in the laboratory is the first crucial step toward the facile generation of useful molecular reagents and therapeutic lead molecules that combine the advantageous features of biologics with those of small-molecule drugs.
Tim-3: An Activation Marker and Activation Limiter of Innate Immune Cells (2013)

Tim-3 was initially identified on activated Th1, Th17, and Tc1 cells and induces T cell death or exhaustion after binding to its ligand, Gal-9. The observed relationship between dysregulated Tim-3 expression on T cells and the progression of many clinical diseases has identified this molecule as an important target for intervention in adaptive immunity. Recent data have shown that it also plays critical roles in regulating the activities of macrophages, monocytes, dendritic cells, mast cells, natural killer cells, and endothelial cells. Although the underlying mechanisms remain unclear, dysregulation of Tim-3 expression on these innate immune cells leads to an excessive or inhibited inflammatory response and subsequent autoimmune damage or viral or tumor evasion. In this review, we focus on the expression and function of Tim-3 on innate immune cells and discuss (1) how Tim-3 is expressed and regulated on different innate immune cells; (2) how it affects the activity of different innate immune cells; and (3) how dysregulated Tim-3 expression on innate immune cells affects adaptive immunity and disease progression. Tim-3 is involved in the optimal activation of innate immune cells through its varied expression. A better understanding of the physiopathological role of the Tim-3 pathway in innate immunity will shed new light on the pathogenesis of clinical diseases, such as autoimmune diseases, chronic viral infections, and cancer, and suggest new approaches to intervention.
Rodent Aβ(1–42) exhibits oxidative stress properties similar to those of human Aβ(1–42): Implications for proposed mechanisms of toxicity (2004)

Alzheimer's disease is a neurodegenerative disorder associated with aging and cognitive decline. Amyloid beta peptide (1-42) [Abeta(1-42)] is a primary constituent of senile plaques - a hallmark of Alzheimer's disease - and has been implicated in the pathogenesis of the disease. Previous studies have shown that methionine residue 35 of beta(1-42) may play a critical role in Abeta(1-42)-mediated oxidative stress and neurotoxicity. Several additional mechanisms of neurotoxicity have been proposed, including the role of Cu(II) binding and reduction to produce hydrogen peroxide and the role of peptide aggregation. It has been reported that rodent Abeta is less likely to form larger beta-sheet structures, and consequently, large aggregates. As a consequence of the lack of deposition of the peptide in rodent brain, rodent Abeta has been proposed to be non-toxic. Additionally, the sequence of the rodent variety of Abeta(1-42) contains three amino acid substitutions compared to the human sequence. These substitutions include the shift of arginine 5, trysosine 10, and histidine 13 to glycine, phenylalanine, and arginine, respectively. This shift in sequence within the Cu(II) binding region of the peptide results in a decrease in the ability of the rodent Abeta peptide to reduce Cu(II) to Cu(I) compared to the human Abeta peptide. As a result of the effect of the amino acid variations on the ability of the rodent peptide to reduce Cu(II) to Cu(I) compared to the human peptide, the rodent beta has been proposed to lack oxidative stress properties. In this study, the oxidative stress and neurotoxic properties of rodent beta(1-42) [Abeta(1-42)Rat] were evaluated and compared to those of human Abeta(1-42). Both human Abeta(1-42) and beta(1-42)Rat were found to have a significant effect on neuronal DNA fragmentation, loss of neuritic networks, and cell viability. beta(1-42) Rat was found to cause a significant increase in both protein oxidation and lipid peroxidation, similar to Abeta(1-42), both of which were inhibited by the lipid-soluble, chain breaking antioxidant vitamin E, suggesting that reactive oxygen species play a role in the Abeta-mediated toxicity. Taken together, these results suggest that Cu(II) reduction may not play a critical role inbeta(1-42)Rat-induced oxidative stress, and that the oxidative stress exhibited by this peptide may be a consequence of the presence of methionine 35, similar to the findings associated with the native human beta(1-42) peptide.
Herpesviruses and heparan sulfate: an intimate relationship in aid of viral entry (2001)

Heparan sulfate proteoglycansGlycosaminoglycan chains on cell surface proteoglycans provide initial docking sites for the binding to eukaryotic cells of various viruses and other microorganisms.The ubiquitously expressed glycosaminoglycan heparan sulfate is particularly important in this regard, at least for viruses.Often, binding of a viral protein to heparan sulfate is only the first step in a cascade of interactions between virus and cell that is required for viral entry into the cell and the initiation of infection.The steps that occur after binding of virus to heparan sulfate may require the interaction of other viral proteins with other cell surface molecules.Several of the human herpesviruses, the focus of this Perspective, can make their initial contact with cells by binding to cell surface heparan sulfate.One member of this group, herpes simplex virus type 1 (HSV-1), can also bind to specific sites in heparan sulfate to trigger the fusion between viral envelope and cell membrane that is required for viral entry.
Antidepressant analgesia in rheumatoid arthritis. (1988)

Forty-seven patients with definite rheumatoid arthritis (RA) were treated in a 32 week, double blind, crossover trial of amitriptyline, desipramine, trazodone, and placebo. All drug regimens produced significant changes on pain measures relative to baseline, but only amitriptyline exceeded placebo. Amitriptyline was associated with a significant reduction in the number of painful/tender joints. Our study supports the efficacy of a moderate dose of amitriptyline as an adjunct drug for the treatment of pain in both depressed and nondepressed patients with RA.
Biodistribution of adeno-associated virus serotype 9 (AAV9) vector after intrathecal and intravenous delivery in mouse (2014)

Adeno-associated virus serotype 9 (AAV9)-mediated gene transfer has been reported in central nervous system (CNS) and peripheral tissues. The current study compared the pattern of expression of Green Fluorescent Protein (GFP) across the mouse CNS and selected peripheral tissues after intrathecal (i.t.) or intravenous (i.v.) delivery of equivalent doses of single-stranded AAV9 vector. After i.t. delivery, GFP immunoreactivity (-ir) was observed in spinal neurons, primary afferent fibers and corresponding primary sensory neurons at all spinal levels. Robust transduction was seen in small and large dorsal root ganglion (DRG) neurons as well as trigeminal and vagal primary afferent neurons. Transduction efficiency in sensory ganglia was substantially lower in i.v. treated mice. In brain, i.v. delivery yielded GFP-immunoreactivity (-ir) primarily in spinal trigeminal tract, pituitary, and scattered isolated neurons and astrocytes. In contrast, after i.t. delivery, GFP-ir was widespread throughout CNS, with greater intensity and more abundant neuropil-like staining at 6 weeks compared to 3 weeks. Brain regions with prominent GFP-ir included cranial nerve nuclei, ventral pons, cerebellar cortex, hippocampus, pituitary, choroid plexus, and selected nuclei of midbrain, thalamus and hypothalamus. In cortex, GFP-ir was associated with blood vessels, and was seen in both neurons and astrocytes. In the periphery, GFP-ir in colon and ileum was present in the enteric nervous system in both i.v. and i.t. treated mice. Liver and adrenal cortex, but not adrenal medulla, also showed abundant GFP-ir after both routes of delivery. In summary, i.t. delivery yielded higher transduction efficiency in sensory neurons and the CNS. The observation of comparable gene transfer to peripheral tissues using the two routes indicates that a component of i.t. delivered vector is redistributed from the subarachnoid space to the systemic circulation.
MIMO transmission over a time-varying TDD channelusing SVD (2001)

Multiple input, multiple output (MIMO) systems using singular value decomposition (SVD) require channel state information (CSI) at both the transmitter and the receiver. Operation over a time division multiplexing (TDD) channel avoids the requirement of a feedback channel but the CSI must be updated some 3.36 times faster than the update rate in the feedback mode. Hence, the TDD mode can only be applied to channels facing a very low Doppler frequency, or using very short frames.
Clinical Pharmacology of Tranexamic Acid (1987)

Tranexamic acid (AMCA) is a potent antifibrinolytic drug occurring in two isomeric forms; the antifibrinolytic potency resides in the transisomeric form. The main action of AMCA is blocking of the lysine-binding sites of the plasminogen molecule, which are of importance for the binding to fibrin. This prevents activation of plasminogen by plasminogen activator also absorbed to fibrin. AMCA can be administered perorally or intravenously and is excreted into the urine. It enters tissues and fluids in various concentrations and crosses the placenta. There is no evidence of a thrombogenic effect of AMCA, but in accordance with its action, it prolongs dissolution of fibrin deposits already formed. AMCA is a drug of high clinical value for the treatment of bleedings due to both systemic and local fibrinolysis.